ArchiveTo observe the clinical efficacy and safety of aripiprazole tablets combined with magnesium valproate sustained-release tablets in the treatment of patients with bipolar disorder (BD).
BD patients were divided into control group and treatment group according to treatment regimen. The control group was given oral magnesium valproate sustained-release tablets with an initial dose of 0.25 g per time, bid. After 1-2 weeks, the dose was adjusted to 0.75-1.5 g·d-1 according to the patient’s condition. On the basis of the treatment for the control group, the treatment group was additionally given oral aripiprazole tablets, 5 mg per time, bid. After 2 weeks of medication, the dose was appropriately adjusted to 10 mg per time, bid, according to the patient’s tolerance. Both groups received treatment for 8 weeks. The efficacy, clinical symptom scores, cognitive function, sleep quality, 5-hydroxytryptamine(5-HT), quality of life and adverse drug reactions were compared between the two groups.
A total of 92 cases were enrolled, including 44 in the control group and 48 in the treatment group. After treatment, the clinical efficacy rates in the control group and treatment group were 72.73% (32 cases/44 cases) and 91.67% (44 cases/48 cases), respectively; the Hamilton depression rating scale (HAMD) scores were (7.07±1.38) and (6.38±1.35) points, respectively; the Bipolar disorder rating scale (BRMS) scores were (8.68±2.01) and (7.65±1.16) points, respectively; the positive and negative syndrome scale (PANSS) scores were (52.07±8.97) and (45.27±8.12) points, respectively; the Wisconsin card sorting test (WCST) scores were (51.57±5.66) and (54.13±5.43) points, respectively; the Hopkins Verbal learning test-revised (HVLT-R) scores were (26.27±3.64) and (28.02±3.50) points, respectively; the continuous performance test (CPT) scores were (1.86±0.63) and (2.13±0.57) points, respectively; sleep efficiency rates were (85.45±2.48)% and (89.17±1.17)%, respectively; wakefulness frequency were (3.39±0.81) and (2.92±0.77) times, respectively; 5-HT levels were (52.29±8.23) and (58.09±8.06) ng·L-1, respectively. Comparisons between the two groups for all the aforementioned indicators showed statistically significant differences (P<0.05, P<0.01, P<0.001). The overall adverse drug reaction rates in the control group and treatment group were 11.36% (5 cases/44 cases) and 14.58% (7 cases/48 cases), respectively (P>0.05).
The combination therapy regimen of aripiprazole tablets and magnesium valproate sustained-release tablets can effectively alleviate clinical symptoms in patients with BD, improve cognitive function and sleep quality, enhance overall quality of life and demonstrate good safety profiles.
To observe the clinical efficacy and safety of budesonide/glycopyrrolate bromide/formoterol fumarate inhalation aerosol combined with theophylline sustained-release tablets in patients with severe chronic obstructive pulmonary disease (COPD) complicated by bronchiectasis (BE).
Patients with BE complicated with severe COPD admitted to our hospital were divided into control group and treatment group based on the treatment method. The control group received theophylline sustained-release tablets (oral, twice daily, 0.1 g per dose), while the treatment group received budesonide/glycopyrrolate/formoterol fumarate aerosol (oral inhalation, twice daily, two puffs per dose) combined with theophylline sustained-release tablets (oral, twice daily, 0.1 g per dose). Both groups were treated for 12 weeks. Inflammatory factor levels, pulmonary ventilation function indicators and clinical efficacy were compared between the two groups, and safety was evaluated.
A total of 133 patients were enrolled, including 71 in treatment group and 62 in control group. Propensity score matching (PSM) was performed at 1∶1 ratio, resulting in 50 patients in each group. After treatment, the total clinical effective rates in control group and treatment group were 80.00% (40 cases/50 cases) and 92.00% (46 cases /50 cases), respectively, with statistically significant difference (P<0.05). After treatment, the levels of C-reactive protein (CRP) in treatment group and control group were (13.85±2.43) and (27.54±3.71) mg·L-1, respectively; tumor necrosis factor-alpha (TNF-α) levels were (50.54±4.28) and (59.37±4.61) pg·mL-1, respectively; interleukin-6 (IL-6) levels were (42.30±4.71) and (56.42±5.24) pg·mL-1, respectively; interleukin-8 (IL-8) levels were (15.71±2.63) and (17.88±3.11) pg·mL-1, respectively; interleukin-18 (IL-18) levels were (59.42±6.25) and (78.62±7.09) pg·mL-1, respectively. Differences in the above indicators between the two groups were statistically significant (all P<0.05). After treatment, the forced expiratory volume in 1 second (FEV1) in treatment group and control group were (2.64±0.37) and (2.06±0.32) L, respectively; forced vital capacity (FVC) were (2.82±0.30) and (2.04±0.27) L, respectively; FEV1/FVC were (65.68±5.94)% and (54.83±5.55)%, respectively. Differences in the above indicators between the two groups were statistically significant (all P<0.05). The main adverse drug reactions in treatment group were nausea, headache, rash and gastrointestinal discomfort; those in control group were nausea, insomnia, gastrointestinal discomfort and rash. The total incidence of adverse drug reactions was 10.00% in treatment group and 8.00% in control group, with no statistically significant difference (P>0.05).
For patients with BE combined with severe COPD, the regimen of budesonide/glycopyrronium bromide/formoterol fumarate inhalation aerosol combined with theophylline sustained-release tablets demonstrates favorable clinical advantages. It can effectively reduce inflammatory factors in patients and improve their ventilation function.
To investigate the clinical efficacy and safety of atorvastatin calcium tablets in patients with type 2 diabetes cardiomyopathy.
Patients with type 2 diabetic cardiomyopathy admitted to our hospital were divided into treatment group and control group according to the treatment methods. The control group received conventional therapy, while the treatment group was administered atorvastatin calcium tablets at 20 mg·d-1, orally for 4 weeks. The heart function, blood lipids, blood glucose, autophagy-related proteins and the relative expression levels of phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway-related mRNA were compared between the two groups, along with a safety evaluation.
A total of 198 patients were included, with 104 in treatment group and 94 in control group. After 4 weeks of treatment, the total clinical effective rate of treatment group was 92.31% (96 cases/104 cases), significantly higher than control group’s 80.85% (76 cases/94 cases) (P<0.05). After treatment, the left ventricular end diastolic diameter of treatment group and control group were (54.41±3.87) and (58.62±3.44) mm, respectively; the left ventricular end diastolic volume were (115.63±8.06) and (121.53±9.88) mL, respectively; the left ventricular end systolic diameter were (30.34±3.52) and (34.84±3.46) mm, respectively; the left ventricular end systolic volume were (69.72±6.32) and (76.57±6.24) mL, respectively; the left ventricular ejection fraction were (52.30±5.53)% and (48.52±4.21)%, respectively; the total cholesterol were (4.48±1.32) and (5.92±1.76) mmol·L-1, respectively; triglycerides were (1.75±0.52) and (2.38±0.57) mmol·L-1, respectively; low-density lipoprotein cholesterol were (2.49±0.65) and (3.32±1.21) mmol·L-1, respectively; high-density lipoprotein cholesterol were (1.02±0.26) and (0.80±0.21) mmol·L-1, respectively; the levels of benzyl chloride 1 were (3.28±0.43) and (2.62±0.41) ng·mL-1, respectively; the levels of autophagy related gene 7 were (6.38±1.07) and (4.60±0.86) ng· mL-1, respectively; the relative expression levels of PI3K mRNA were 0.68±0.25 and 0.94±0.28, respectively; the relative expression levels of Akt mRNA were 0.58±0.27 and 0.95±0.30, respectively; the relative expression levels of mTOR mRNA were 0.66±0.31 and 0.98±0.32, respectively. The above indicators in treatment group were statistically significant compared with control group (all P<0.05). The adverse drug reactions in treatment group include liver dysfunction, gastrointestinal reactions and muscle pain; the control group had abnormal liver function and gastrointestinal reactions. The total incidence of adverse drug reactions in treatment group was 5.77% (6 cases/104 cases), while in control group was 3.19% (3 cases/94 cases). There was no statistically significant difference between the two groups (all P>0.05).
Atorvastatin tablets can significantly improve cardiac structure and function, and regulate blood lipid levels in patients with type 2 diabetic cardiomyopathy. Additionally, it exerts cardioprotective effects by promoting autophagosome formation and downregulating the activity of the PI3K/Akt/mTOR pathway.
To observe the clinical efficacy and safety of tocilizumab injection combined with iguratimod tablets in the treatment of elderly patients with rheumatoid arthritis (RA) complicated with interstitial pneumonia.
Elderly patients with RA complicated with interstitial pneumonia in our hospital were divided into control group and treatment group according to the treatment methods. The control group was given iguratimod tablets 25 mg bid, orally after breakfast and dinner, for a total of 12 weeks on the basis of the conventional treatment plan. The treatment group was given tocilizumab injection 8 mg·kg-1 intravenously every 4 weeks on the basis of control group. When abnormal liver enzymes, decreased neutrophil count, or decreased platelet count occurred, the dose of tocilizumab injection was reduced to 4 mg·kg-1, for a total of 12 weeks. The clinical efficacy, lung function and inflammatory response indicators of the two groups were compared, and the safety was evaluated.
A total of 84 cases were included in this study, with 39 cases in control group and 45 cases in treatment group. After treatment, the overall clinical response rates were 74.36% (29 cases /39 cases) in control group and 91.11% (41 cases /45 cases) in treatment group, respectively. The overall clinical response rate of treatment group was statistically significant higher than control group (P<0.05). After treatment, the levels of vital capacity (VC) in control group and treatment group were (2.25±0.34) and (2.38±0.30) L, respectively; the levels of forced expiratory volume in 1 second (FEV1) were (2.71±0.39) and (2.85±0.36) L, respectively; the high-resolution CT (HRCT) scores were (1.59±0.68) and (1.49±0.59) points, respectively. There was no statistically significant difference in the above indicators between the two groups (all P>0.05). After treatment, the levels of interleukin-6 (IL-6) in control group and treatment group were (13.27±1.95) and (12.05±1.72) pg·mL-1, respectively; the levels of rapid C-reactive protein (CRP) were (16.09±2.44) and (14.83±2.15) mg·L-1, respectively; the levels of matrix metalloproteinase-3 (MMP-3) were (60.32±9.59) and (55.61±8.27) μg·mL-1, respectively; the levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) were (86.79±14.58) and (79.83±13.27) pg·mL-1, respectively. All the aforementioned indicators in treatment group were statistically significant lower than control group (P<0.05, P<0.01). The main adverse drug reactions in control group were elevated aminotransferase, leukopenia and upper abdominal pain. The main adverse drug reactions in treatment group were elevated aminotransferase, leukopenia, decreased neutrophil count and upper abdominal pain. The total incidence of adverse drug reactions was 7.69% in control group and 11.11% in treatment group, with no statistically significant difference (P>0.05).
Tocilizumab injection combined with iguratimod tablets is effective in the treatment of elderly patients with RA complicated with interstitial pneumonia, and can effectively improve their clinical symptoms, serum marker levels, and lung function, reduce inflammatory responses, and has good safety.
To observe the efficacy and safety of bifidobacterium triple viable capsule in patients with type Ⅲ prostatitis.
Patients with type Ⅲ prostatitis in the hospital were retrospectively selected and divided into treatment group and control group. The two groups of patients both took sertraline tablets 0.05 g, once daily. Patients in control group were given oral administration of 0.2 mg of tamsulosin sustained release capsule once a day, while patients in treatment group received oral administration of 0.42 g of bifidobacterium triple viable capsule twice a day on the basis of control group. Both groups were treated for 4 weeks. The efficacy, clinical symptoms scores, urodynamic parameters and inflammatory factors were compared between the two groups, and the safety was evaluated.
A total of 200 patients were enrolled, including 97 cases in control group and 103 cases in treatment group. After 4 weeks of treatment, the total effective rate in treatment group was 88.35% (91 cases/103 cases), which was statistical significant higher than 79.38% (77cases/97 cases) in control group (P>0.05). After treatment, the scores of the pain domain of the national institutes of health chronic prostatitis symptom index (NIH-CPSI) in treatment group and control group were (4.37±1.42) and (5.04±1.56) point, respectively; the self-rating depression scale (SDS) scores were (38.20±5.38) and (40.63±5.54) point, respectively; the levels of interleukin-6 (IL-6) were (5.93±1.08) and (6.30±1.27) pg·mL-1, respectively; the levels of interleukin-10 (IL-10) were (6.21±1.37) and (6.62±1.49) pg·mL-1, respectively; and the levels of cyclooxygenase-2 (COX-2) were (9.46±2.66) and (10.26±2.02) ng·mL-1, respectively. There were statistical significant differences in the above indicators between treatment and control group (all P<0.05). The main adverse drug reactions in treatment group included dizziness, nausea and vomiting, and diarrhea, whereas dizziness and diarrhea occurred in control group. The overall incidence of adverse drug reactions was 4.85% (5 cases/103 cases) in treatment group and 2.06% (2 cases/97 cases) in control group, with no statistically significant difference between the two groups (P>0.05).
Bifidobacterium triple viable capsule in the treatment of type Ⅲ prostatitis can improve the pain symptom and depression, and regulate the levels of inflammatory factors, and it has good safety.
To observe the clinical efficacy and safety of the application of bromhexine hydrochloride injection combined with high-flow nasal cannula oxygen therapy in children with severe pneumonia complicated with type I respiratory failure.
Children with severe pneumonia complicated with type I respiratory failure who were treated in our hospital were collected and divided into control group and treatment group based on the treatment methods. The control group received conventional oxygen therapy on the basis of conventional treatment, while the treatment group was given bromhexine hydrochloride and glucose injection (2~4 mg each time, qd, intravenous drip) combined with high-flow nasal cannula oxygen therapy on the basis of conventional treatment. Both groups were treated for 7 days. The clinical efficacy, respiratory and circulatory indicators, and inflammatory indicators of the two groups were compared, and safety was evaluated.
A total of 94 children were included, including 49 in control group and 45 in treatment group. After treatment, the overall clinical response rates were 75.51% (37 cases/49 cases) in control group and 91.11% (41 cases /45 cases) in treatment group, demonstrating a statistically significant difference (P<0.05). After treatment, the arterial partial pressure of oxygen (PaO2) levels of control group and treatment group were (75.43±7.71) and (80.35±8.63) mmHg, respectively; the percutaneous oxygen saturation (SpO2) levels were (94.16±2.06)% and (95.31±2.33)%, respectively; the PaO2/FiO2 levels were 327.08±34.36 and 342.40±33.53, respectively; the respiratory rate (RR) levels were (30.16±3.39) and (28.33±3.03) time·min-1, respectively; the lactate levels were (2.66±0.43) and (2.38±0.34) mmol·L-1, respectively; the interleukin-6 (IL-6) levels were (14.45±3.37) and (12.64±3.31) pg·mL-1, respectively; the white blood cell (WBC) levels were (7.94±2.13) and (7.07±1.87) ×109·L-1, respectively; the neutrophil percentage (NEUT%) levels were (55.36±8.25)% and (51.58±7.43)%, respectively; the procalcitonin (PCT) levels were (0.17±0.04) and (0.15±0.04) ng·mL-1, respectively, all differences between the two groups were statistically significant (P<0.05, P<0.01). The main adverse drug reactions in control group were facial skin damage, nasal mucosa damage and abdominal distension; the main adverse drug reactions in treatment group were nausea, vomiting, facial skin damage and nasal mucosa damage. The total incidence of adverse drug reactions in control group and treatment group were 14.29% (7 cases/49 cases) and 11.11% (5 cases/45 cases), respectively, with no statistically significant difference (P>0.05).
The treatment plan of bromhexine hydrochloride and glucose injection combined with high-flow nasal cannula oxygen therapy for children with severe pneumonia complicated with type Ⅰ respiratory failure is effective. It can significantly improve clinical symptoms, shorten the time of symptom relief, improve respiratory and circulatory indicators, reduce inflammatory indicators, promote the absorption of pneumonia, improve treatment comfort, shorten hospital stay and has good safety.
To observe the clinical efficacy and safety of programmed death-1 (PD-1) inhibitors (tislelizumab injection or sintilimab injection) combined with the capecitabine tablet and oxaliplatin for injection regimen (XELOX) as first-line treatment in patients with advanced gastric signet-ring cell carcinoma (SRCC)
Patients with SRCC were enrolled and divided into control group and treatment group using a random number table. The control group received the XELOX regimen, 130 mg·m-2 intravenous oxaliplatin for injection on day 1, and oral 1 000 mg·m-2 capecitabine tablets twice daily from days 1 to 14, repeated every 21 days. The treatment group received an intravenous infusion of tislelizumab injection or sintilimab injection 200 mg per dose prior to the XELOX regimen, also administered every 21 days. Both groups were treated for 6 cycles. Clinical efficacy, tumor markers, immune function, clinical scores, safety and long-term prognosis were compared between the two groups.
A total of 82 patients were included, with 41 cases in each group. The levels of carcinoembryonic antigen (CEA) in treatment and control group were (6.46±1.03) and (7.00±0.94) ng·mL-1, respectively; the levels of carbohydrate antigen 19-9 (CA19-9) were (18.62±3.36) and (20.58±3.52) U·mL-1, respectively; vascular endothelial growth factor (VEGF) were (33.57±5.56) and (36.15±5.03) ng·mL-1, respectively; CD3+ T cells were (62.31±5.71)% and (59.50±6.10)%, respectively; CD4+ T cells were (47.56±5.93)% and (44.91±4.84)%, respectively; European organisation for research and treatment of cancer quality of life questionnaire core 30 (QLQ-C30) score were (60.15±11.01) and (55.02±9.46) points, respectively; and revised piper fatigue scale (RPFS) score were (5.05±0.89) and (5.49±0.84) points, respectively; the levels of CA72-4 were (34.07±3.74) and (36.23±3.01) U·mL-1, respectively; the CD4+/CD8+ ratios were 1.99±0.35 and 1.75±0.37, respectively; the differences of above indicators between two groups were all statistically significant (P<0.05, P<0.01). Adverse drug reactions in both groups were gradeⅠorⅡand resolved after drug discontinuation. The incidence of adrenal dysfunction in the treatment group was 14.63% (6 cases/41 cases), which was significantly higher than that in the control group (0%) (P<0.05). The median survival time was 38 months in the treatment group and 28 months in the control group (P<0.05).
PD-1 inhibitors (tislelizumab or sintilimab injection) combined with the XELOX regimen as first-line therapy can enhance the efficacy in patients with advanced SRCC, significantly improve quality of life and long-term survival benefits, and exhibit a favorable safety profile. This therapeutic advantage may be attributed to the regimen’s effect on downregulating tumor markers and improving immune function.
To explore the potential mechanism of cinnamaldehyde in alleviating nerve injury in rats with traumatic brain injury (TBI).
Rats were randomly divided into sham group (only craniotomy), model group(TBI model), experimental-L group (TBI+25 mg·kg-1 cinnamaldehyde), experimental-H group (TBI+75 mg·kg-1 cinnamaldehyde), miR-NC group (TBI+miR-NC lentivirus+75 mg·kg-1 cinnamaldehyde) and miR-27a-3p inhibitor group (TBI+miR-27a-3p inhibitor lentivirus+75 mg·kg-1 cinnamaldehyde). After treatment, real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of miR-27a-3p; the Morris water maze test was used to assess memory function; immunofluorescence assay was used to detect the expression of ionized calcium-binding adapter molecule 1 (Iba-1); Western blot was used to detect the expression of related proteins in brain tissues; and the dual-luciferase reporter gene assay was used to verify the binding of miR-27a-3p to BCL2/adenovirus E1B 19kDa interacting protein 3-like (BNIP3L).
The relative expression levels of miR-27a-3p in the sham group, model group, experimental-L group, experimental-H group, miR-NC group and miR-27a-3p inhibitor group were 1.00±0.08, 0.40±0.03, 0.52±0.08, 0.76±0.08, 0.73±0.09 and 0.18±0.02, respectively; the escape latency times were (11.19±0.75), (26.06±1.47), (23.59±1.39), (14.95±1.71), (15.37±0.77) and (24.91±1.96) s, respectively; the Iba-1 fluorescence intensities were (1 189.50±113.68), (2 958.70±279.29), (2 287.05±271.69), (1 916.55±205.44), (1 935.57±164.54) and (2 564.52±333.05) a.u., respectively; the relative expression levels of autophagy-related gene 5 (ATG5) protein were 0.32±0.03, 0.94±0.07, 0.71±0.09, 0.50±0.08, 0.53±0.07 and 0.85±0.09, respectively; the relative expression levels of Beclin-1 autophagy regulator (Beclin-1) protein were 0.35±0.03, 0.95±0.13, 0.75±0.12, 0.49±0.05, 0.48±0.07 and 0.73±0.10, respectively; the relative expression levels of Parkin RBR domain E3 ubiquitin protein ligase (Parkin) protein were 0.29±0.04, 0.64±0.08, 0.51±0.09, 0.41±0.04, 0.43±0.05 and 0.62±0.07, respectively. For the above indicators, there were all statistically significant differences when comparing the model group with the sham group, the experimental-L and experimental-H groups with the model group, and the miR-27a-3p inhibitor group with the miR-NC group (P<0.05, P<0.01, P<0.001). The dual-luciferase reporter gene assay confirmed the targeted binding of miR-27a-3p to BNIP3L.
Cinnamaldehyde may regulate autophagy through the miR-27a-3p/BNIP3L axis, improve neurological function, alleviate neuroinflammation and exert neuroprotective effects on TBI-induced brain injury.
To investigate the ameliorative effects of curculigoside on rats with aortic dissection by the inhibition of the reactive oxygen species /NOD-like receptor thermal protein domain associated protein 3 (ROS/NLRP3) pathway.
Rats were randomly divided into control group, model group, low-dose experimental group (50 mg·kg-1 curculigoside), high-dose experimental group (100 mg·kg-1 curculigoside) and combination group (100 mg·kg-1 curculigoside and 1.75 mg·mL-1 trimethylamine N-oxide), with 12 rats in each group. The rat model of aortic dissection was established by intragastric administration of 0.1 g·kg-1 β-aminopropionitrile (BAPN). Cardiac blood was collected, and the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay (ELISA). hematoxylin-eosin (HE) staining and Van Gieson staining were used to evaluate histopathological changes and the degree of elastic fiber rupture. Reactive oxygen species (ROS) levels were detected using 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) staining. The mRNA expression levels of matrix metalloproteinase 9 (MMP-9) and matrix metalloproteinase 2 (MMP-2) in aortic tissues were measured by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). The protein expression levels of apoptosis-associated speck-like protein containing a CARD (ASC), NLR family pyrin domain-containing 3 (NLRP3) and caspase-1 in aortic tissues were detected by Western blotting.
The IL-6 levels in the low-dose experimental group, high-dose experimental group, control group, model group and combination group were (49.06±4.98), (37.18±3.81), (35.62±3.63), (72.34±7.33) and (50.03±5.08) pg·mL-1, respectively; the TNF-α levels were (25.63±2.64), (16.35±1.71), (15.31±1.62), (42.06±4.23) and (26.15±2.64) pg·mL-1, respectively; the degrees of elastic fiber rupture were 2.01±0.22, 0.85±0.09, 0±0, 3.22±0.34 and 1.85±0.19, respectively; the ROS levels were 358.62±36.64, 203.11±20.15, 186.34±19.11, 588.64±60.03 and 361.24±37.24, respectively; the relative mRNA expression levels of MMP-9 were 1.67±0.18, 1.15±0.12, 1.02±0.11, 2.45±0.26 and 1.72±0.19, respectively; the relative mRNA expression levels of MMP-2 were 1.88±0.19, 1.24±0.14, 0.98±0.10, 2.85±0.30 and 1.91±0.20, respectively; the relative protein expression levels of Caspase-1 were 0.85±0.09, 0.55±0.06, 0.44±0.05, 1.24±0.13 and 0.88±0.10, respectively; the relative protein expression levels of ASC were 0.97±0.10, 0.64±0.08, 0.55±0.06, 1.48±0.16 and 0.89±0.09, respectively; and the relative protein expression levels of NLRP3 were 0.64±0.08, 0.35±0.05, 0.25±0.03, 1.02±0.11 and 0.72±0.09, respectively. Compared with the control group, the above indicators in the model group were significantly different (all P<0.05); compared with the model group, the above indicators in the high-dose experimental group were significantly different (all P<0.05); and compared with the high-dose experimental group, the above indicators in the combination group were significantly different (all P<0.05).
Curculigoside can effectively ameliorate BAPN-induced aortic injury in rats. Its protective mechanism against the development of aortic dissection may be associated with the inhibition of the ROS/NLRP3 signaling pathway.
To investigate the effects of celastrol (Cel) on airway remodeling factors, collagen synthesis and degradation in lung fibroblasts of chronic obstructive pulmonary disease (COPD) rats by regulating the neurogenic locus notch homolog protein (Notch) pathway.
A total of 30 rats were randomly divided into 3 groups: animal control group (normal feeding), animal model group (COPD rat model established by smoke exposure combined with lipopolysaccharide tracheal instillation) and animal experimental group (intraperitoneal injection of 0.01 mg·kg-1 Cel after successful modeling). The bronchial fibroblasts (BF) cells were isolated from rats in the animal model group and randomly divided into cell control group (no treatment), cell experimental group (2 μmol·L-1 Cel) and inhibitor group [1 mmol·L-1 valproic acid (VPA)]. Pulmonary function was assessed in rats using invasive pulmonary function testing methods; Western blot was used to detect the expression of Notch signaling pathway-related proteins in each group of cells; real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect mRNA expression of airway remodeling-related factors; enzyme-linked immunosorbent assay (ELISA) was used to detect the contents of matrixmetalloproteinase-1 (MMP-1) and tissue inhibitors of metalloproteinase-1 (TIMP-1) in each group of cells.
The forced vital capacity (FVC) of rats in animal control group, animal model group and animal experimental group were (6.74±0.87), (3.28±0.51) and (4.94±0.83) mL, respectively; the forced expiratory volume in 0.1 second (FEV0.1) were (3.94±0.45), (1.05±0.16) and (2.41±0.37) mL, respectively; the peak expiratory flow (PEF) were (28.09±4.60), (16.63±3.21) and (21.55±4.02) L·min-1, respectively. Significant differences were observed in the above indicators between animal control group and animal model group, and between animal model group and animal experimental group (P<0.01, P<0.001). The relative expression levels of (Notch1) protein in cell control group, cell experimental group and inhibitor group were 1.00±0.19, 0.12±0.02 and 0.38±0.06, respectively; the relative expression levels of Notch1 receptor intracellular binding domain (NICD1) protein were 1.00±0.17, 0.72±0.12 and 0.85±0.13, respectively; the relative expression levels of serrated typical Notch ligand 1 (Jagged1) protein were 1.00±0.15, 0.71±0.11 and 0.84±0.12, respectively; the relative expression levels of hair and enhancer of split 1 (Hes1) protein were 1.00±0.11, 0.69±0.08 and 0.81±0.09, respectively; the relative expression levels of MMP-9 mRNA were 1.00±0.16, 0.59±0.08 and 0.73±0.11, respectively; the relative expression levels of type Ⅰ collagen(ColⅠ) mRNA were 1.00±0.14, 0.67±0.09 and 0.86±0.14, respectively; the relative expression levels of α-smoth muscle actin (α-SMA) mRNA were 1.00±0.16, 0.41±0.07 and 0.78±0.13, respectively; the relative expression levels of transforming growth factor-β (TGF-β) mRNA were 1.00±0.18, 0.53±0.09 and 0.75±0.14, respectively; the contents of MMP-1 were (1.19±0.17), (0.80±0.15) and (1.06±0.15) ng·mL-1, respectively; the contents of tissue inhibitor of protease-1 (TIMP-1) were (219.78±30.24), (131.94±18.15) and (167.51±21.01) ng·mL-1, respectively. There were all statistically significant differences in the above indicators between cell control group and cell experimental group, as well as between cell experimental group and inhibitor group (P<0.05, P<0.01, P<0.001).
Celastrol can effectively improve lung function and pulmonary pathological damage in COPD rats, reduce the levels of inflammatory cells and inflammatory factors, and improve the imbalance of airway remodeling-related factors and collagen synthesis/degradation in BF cells, which may be related to its inhibition of Notch signaling activation.
To investigate the effects and mechanism of nobiletin (NOB) on slow transit constipation (STC) in rats through dopamine receptor D2 (DRD2).
A total of 70 SD rats were randomly divided into blank group, model group, experimental-L, M, H group, AAV9-NC group and AAV9-DRD2 group, with 10 rats in each group. STC model was established with 15 mg·kg-1 compound diphenoxylate by intragastric administration except in blank group. In experimental-L, M, H group, 0.1, 0.2, 0.4 g·kg-1 NOB was administered intragastricly. On the basis of experimental-M group, AAV9-NC group and AAV9-DRD2 group were given AAV9-NC and AAV9-DRD2 100 μL, respectively. Weight and fecal indexes of rats were detected. The expression levels of DRD2 was detected by quantitative real time polymerase chain reaction. Vasoactive intestinal peptide (VIP) and nitric oxide (NO) levels were detected by enzyme-linked immunosorbent assay. Levels of AMP-activated protein kinase (AMPK)/endothelial nitric oxide synthase (eNOS) signaling pathway related proteins were detected by Western blot.
The fecal water content in blank, model, and experimental-L, M, H groups were (35.24±5.25)%, (24.76±3.47)%, (28.38±2.77)%, (32.76±3.49)% and (33.32±4.34)% , respectively; the fecal quantity were (53.20±5.25), (42.40±4.55), (47.10±5.36), (49.50±5.10) and (50.10±5.04) grains, respectively. Compared model group with blank group, and compared experimental-L, -M, -H groups with model group, the above indicators showed statistically significant differences (P<0.05, P<0.01, P<0.001). The relative expression levels of DRD2 mRNA in blank, model and experimental-L, M, H groups were 1.00±0.12, 2.95±0.47, 2.73±0.49, 2.17±0.35 and 2.08±0.32, respectively. The relative expression levels of DRD2 mRNA in the experimental-M and experimental-H groups were significantly lower than those in the model group (all P<0.001), with no significant difference between the two groups (P>0.05); therefore, experimental-M was selected for subsequent experiments. The VIP levels of blank group, model group, experimental-M group, AAV9-NC group and AAV9-DRD2 group were (43.15±4.52), (64.42±7.64), (51.68±5.37), (49.25±4.44) and (56.84±6.41) ng·L-1, respectively; NO levels were (6.84±0.71), (11.68±1.37), (9.28±0.93), (9.35±0.97) and (10.45±1.03) μmol·L-1, respectively; the relative expression levels of AMPK protein were 1.00±0.15, 2.42±0.34, 1.68±0.17, 1.55±0.18 and 1.94±0.21, respectively; the relative expression levels of eNOS protein were 1.00±0.11, 3.18±0.35, 2.28±0.23, 2.35±0.27 and 2.95±0.33, respectively. Compared model group with blank group, compared experimental-M group with model group, and compared AAV9-DRD2 group with AAV9-NC group, the above indicators all showed statistically significant differences (all P<0.05).
NOB can improve STC in rats, possibly by down-regulating DRD2 expression, regulating VIP and NO levels, and inhibiting the AMPK/eNOS signaling pathway.
To explore the effects and mechanism of shionone on ulcerative colitis in rats based on the extracellular regulated protein kinase (ERK)/NOD-like receptor protein 3 (NLRP3)/interleukin (IL)-1β signaling pathway.
A total of 60 rats were randomly divided into normal group, model group, experimental-L group, experimental-H group and activator group by random number table method, with 12 rats in each group. The normal group was given drinking water without dextran sulfate sodium, while the other groups were fed with drinking water containing 5% dextran sulfate sodium for 10 days to establish ulcerative colitis rat models. After modeling, rats were administered for 7 days. The experimental-L and -H groups were intragastrically given 50 and 100 mg·kg-1 shionone daily, respectively; the activator group was intragastrically given 100 mg·kg-1 shionone daily combined with intraperitoneal injection of 4 mg·kg-1 ERK activator RO 67-7476; the normal group and model group were intragastrically given and intraperitoneally injected with equal volumes of normal saline daily. Disease activity index was analyzed; the levels of IL-17 and IL-23 in colon tissue were detected by enzyme-linked immunosorbent assay (ELISA); colonic histopathological changes were observed by hematoxylin-eosin (HE) staining; intestinal mucosa was detected by Alcian blue-periodic acid-Schiff (AB-PAS) staining; the relative expression levels of phosphorylated (p)-ERK, NLRP3 and IL-1β proteins were determined by Western blot.
Rats in the model group showed severe colonic tissue damage, characterized by disappearance of intestinal mucosa, blurred epithelial cell structure, gland atrophy, inflammatory cell infiltration, lamellar necrosis of the colonic mucosal layer and decreased number of goblet cells. The disease activity index scores in the normal group, model group, experimental-L group, experimental-H group and activator group were (0.12±0.02), (2.98±0.34), (1.76±0.19), (0.55±0.07) and (2.69±0.29) points, respectively; the levels of IL-17 in colon tissue were (24.64±2.74), (39.78±4.27), (32.92±3.65), (26.13±2.85) and (37.85±3.98) pg·mL-1, respectively; the levels of IL-23 in colon tissue were (14.25±1.73), (28.47±3.04), (22.14±2.42), (15.96±1.87) and (26.95±2.94) pg·mL-1, respectively; the histopathological scores of colon tissue were (0±0), (3.73±0.39), (2.49±0.28), (1.24±0.15) and (3.61±0.38) points, respectively; the p-ERK/ERK in colon tissue were 0.32±0.04, 0.81±0.09, 0.58±0.07, 0.36±0.05 and 0.77±0.08, respectively; the relative expression levels of NLRP3 protein were 1.03±0.11, 2.05±0.23, 1.64±0.18, 1.24±0.14 and 1.95±0.22, respectively; the relative expression levels of IL-1β protein were 1.05±0.11, 1.96±0.22, 1.58±0.17, 1.21±0.13 and 1.91±0.21, respectively. Statistical significance was observed in the above indicators when comparing the normal group with the model group, comparing the model group with the experimental-L, H groups and comparing the experimental-H group with the activator group (all P<0.05).
Shionone has protective effects on rats with ulcerative colitis by inhibiting the ERK/NLRP3/IL-1β signaling pathway.
To explore the mechanism of action by which icariin regulates the loss of immune tolerance to immune thrombocytopenia (ITP) through the microRNA (miRNA)-98-5p-mediated adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/Unc-51-like autophagy-activating kinase 1 (ULK1) signaling pathway.
The ITP model was established by intraperitoneal injection of guinea pig anti-mouse platelet serum into mice. Another 12 normal mice were taken as the control group. The mice with successful modeling were divided into model group, the experimental-low group, the experimental-high group and the positive drug group. The experimental-low and experimental-high groups and the positive drug group were gavaged with 1.25, 5.00 mg·kg-1 icariin and 9.1 mg·kg-1 prednisone acetate, respectively, after the mice were modeled. The levels of platelets (PLT) and hemoglobin (Hb) were detected by automatic blood analyzer; the levels of thrombopoietin (TPO) and inflammatory factors were detected by enzyme-linked immunosorbent assay; the pathological damage of spleen tissue was detected by hematoxylin-eosin staining; megakaryocytes were observed with sternum bone marrow smears; the relative expression level of miRNA-98-5p was detected by real-time fluorescence quantitative polymerase chain reaction; and the protein relative expression levels of the AMPK/mTOR/ULK1 signaling pathway was detected by Western blotting.
The PLT levels in control group, model group, experimental-low group, experimental-high group and positive drug group were (1 504.56±166.99), (752.68±80.33), (862.95±98.33), (1 212.35±134.23) and (1 363.23±155.33)×10·L-1, respectively; the Hb levels were (151.33±18.96), (124.11±13.56), (138.32±14.02), (145.33±16.88) and (149.22±16.02) g·L-1, respectively; the TPO levels were (12.05±1.33), (5.86±0.78), (6.62±0.96), (7.85±0.92) and (9.66±0.89) pg·mL-1, respectively; the levels of interleukin-6 (IL-6) were (18.96±2.33), (44.33±5.39), (39.25±4.46), (32.32±4.33) and (22.98±3.78) ng·L-1, respectively; the levels of IL-10 were (42.15±6.48), (23.12±3.56), (26.89±3.99), (31.02±4.65) and (33.66±4.86) ng·L-1, respectively; the levels of tumor necrosis factor-α(TNF-α) were (31.02±4.65), (77.36±8.98), (67.65±7.88), (60.52±7.34) and (40.56±5.99) ng·L-1, respectively; the levels of interferon-gamma (IFN-γ) were (4.33±0.68), (8.33±0.96), (7.35±0.89), (6.02±0.81) and (5.86±0.75) ng·L-1, respectively; the relative expression levels of miRNA-98-5p were 1.00±0.16, 1.78±0.21, 1.51±0.18, 1.22±0.16 and 1.15±0.15, respectively; the relative expression levels of phosphorylated (p)-AMPK/AMPK were 1.00±0.14, 1.81±0.28, 1.60±0.19, 1.31±0.16 and 1.25±0.21, respectively; the relative expression levels of p-mTOR/β-actin were 1.00±0.16, 0.48±0.07, 0.59±0.09, 0.79±0.12 and 0.82±0.14, respectively; the relative expression levels of p-ULK1/β-actin were 1.00±0.15, 0.42±0.06, 0.53±0.09, 0.89±0.14 and 0.93±0.16, respectively. There were statistically significant differences when comparing the above indicators of model group with those of control group, and also when comparing the above indicators of the experimental-low, experimental-high groups and positive drug group with those of model group (P<0.05, P<0.01, P<0.001).
Icariin regulates the loss of immune tolerance in rats with ITP, inhibits autophagy, and thus elevates platelet levels by down-regulating the expression of miRNA-98-5p and modulating the AMPK/mTOR/ULK1 signaling pathway.
To investigate the effects of bicalutamide (BIC) on the malignant biological behavior of prostate cancer LNCaP cells through cadherin 7 (CDH7), and to explore its possible mechanism of action.
This study was divided into two parts, animal experiment and cell experiment. In animal experiment, 30 Balb/c male nude mice were randomly divided into animal blank control group (daily gavage of 10 mL·kg-1 0.5% carboxymethyl cellulose sodium solution), animal positive control group (daily gavage of 10 mL·kg-1 enzalutamide) and animal experimental group (daily gavage of 25 mg·kg-1 BIC), with 10 nude mice in each group. All mice were treated with subcutaneous injection of LNCaP cell suspension to establish a xenograft model and each group was continuously treated for 28 days. The tumor volume of nude mice in each group was recorded every 7 days; tumor tissues were collected 24 h after drug withdrawal; the expression of proliferating cell nuclear antigen (PCNA) protein was detected by immunohistochemistry. In cell experiment, LNCaP cells were divided into cell blank control group (normal culture, no treatment), cell positive control group (treated with enzalutamide 1 μM), cell experimental group (treated with BIC 50 μM), oe-NC group (transfected with oe-NC plasmid and then treated with BIC 50 μM), and oe-CDH7 group (transfected with oe-CDH7 plasmid and then treated with BIC 50 μM). The relative expression levels of CDH7 mRNA in cells was detected by real-time fluorescence quantitative polymerase chain reaction method. The cell invasion ability and apoptosis rate were detected by Transwell assay and terminal-deoxynucleotidyl transferase mediated nick end labeling method, respectively. The activities of superoxide dismutase (SOD) and the levels of malondialdehyde (MDA) were detected by enzyme-linked immunosorbent assay. The relative expression levels of CDH7 and proteins related to relevant pathways were detected by Western blot.
In animal experiments, the tumor volume on day 21 of animal blank control group, animal positive control group and animal experimental group were (622.30±131.15), (411.90±72.07) and (467.40±63.92) mm3, respectively; the tumor volumes on day 28 were (1 189.50±225.95), (729.40±142.90) and (688.60±89.07) mm3, respectively; and the relative expression levels of PCNA protein were 1.00±0.11, 0.28±0.09 and 0.33±0.07, respectively. There were statistically significant differences compared animal positive control group or animal experimental group with the control group (all P<0.001). In cell experiments, the relative expression levels of CDH7 mRNA in the cell blank control group, cell positive control group, cell experimental group, oe-NC group and oe-CDH7 group were 1.00±0.16, 0.35±0.07, 0.40±0.05, 0.37±0.05 and 3.12±0.34, respectively; the number of cell invasions were (134.26±24.97), (57.63±11.53), (66.34±11.84), (61.17±9.12) and (98.08±15.88) pieces, respectively; the MDA levels were (126.94±20.81), (257.63±46.19), (239.21±29.32), (244.35±38.46) and (187.79±25.35) pg·mL-1, respectively; the apoptosis rates were (4.54±0.87)%, (53.27±6.14)%, (47.13±7.15)%, (51.76±9.59)% and (17.49±3.48) %, respectively; the relative expression levels of extracellular signal-regulated kinase 1/2 (ERK1/2) protein were 1.00±0.12, 0.44±0.06, 0.39±0.05, 0.41±0.03 and 0.67±0.11, respectively. Compared cell positive control group, or cell experimental group with cell blank control group, compared oe-CDH7 group with oe-NC group, the above indicators were all statistically significantly different (all P<0.001).
BIC could inhibit the invasion of prostate cancer LNCaP cells and promote their apoptosis through CDH7, and the mechanism of action may be related to the inhibition of mitogen-activated protein kinase (MAPK)-ERK signaling pathway activation.
To investigate the mechanism of peiminine (PEI) affects pain and cartilage injury in rats with knee osteoarthritis (KOA) by regulating the peroxisome proliferator-activated receptor gamma (PPARγ)/cellular sloan kettering institute(c-SKI) signaling pathway through a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5).
The KOA model was established in rats by intra-articular injection of sodium iodoacetate. The rats were divided into control group, model group, experimental group (intraperitoneal injection of 3.5 mg·kg-1 PEI) and ADAMTS-5 overexpression group (tail vein injection of oe-ADAMTS-5 plasmid). The pain threshold of rats was measured using the mechanical stimulation method; the pathological injury of the rat knee joint was examined by hematoxylin-eosin (HE) staining; the protein levels of ADAMTS-5, matrix metalloproteinase (MMP)-3, MMP-13 and proteins in the PPARγ/c-SKI signaling pathway in rat knee joint tissues were detected by Western blot; the protein level of collagen type Ⅱ alpha 1 chain (Col2α1) in rat knee joint tissues was determined by immunohistochemistry; the levels of inflammatory factors in rat serum were measured using corresponding commercial kits.
The pain thresholds in control group, model group and experimental group were (19.15±2.87), (7.10±1.03) and (13.69±1.27) g, respectively; the relative expression levels of ADAMTS-5 were 1.00±0.16, 1.77±0.21 and 1.35±0.18, respectively; Col2α1 levels in control, model, experimental, and ADAMTS-5 overexpression groups were 1.00±0.10, 0.28±0.04, 0.76±0.13 and 0.58±0.06, respectively; the relative expression levels of MMP-3 were 1.00±0.15, 2.11±0.36, 1.62±0.22 and 1.83±0.25, respectively; the relative expression levels of MMP-13 were 1.00±0.18, 1.98±0.28, 1.27±0.16 and 1.45±0.19, respectively; the tumor necrosis factor-alpha (TNF-α) levels were (62.74±6.93), (159.37±26.40), (98.08±14.09) and (124.43±17.79) pg·mL-1, respectively; the interleukin (IL)-4 levels were (75.62±11.54), (19.56±2.59), (53.28±6.34) and (41.67±5.31) pg·mL-1, respectively; IL-6 levels were (42.65±9.77), (133.84±13.22), (84.19±11.71) and (105.24±18.19) pg·mL-1, respectively; IL-10 levels were (98.06±24.50), (23.42±10.61), (64.72±20.96) and (38.09±12.86) pg·mL-1, respectively; the relative expression levels of PPARγ were 1.00±0.13, 0.39±0.07, 0.73±0.09 and 0.51±0.08, respectively; the relative expression levels of c-SKI were 1.00±0.17, 0.32±0.05, 0.86±0.15 and 0.44±0.09, respectively. The above indicators in model group were statistically significantly different from those in control group, those in experimental group were statistically significantly different from those in model group, and those in ADAMTS5 overexpression group were statistically significantly different from those in experimental group (all P<0.05).
PEI inhibits inflammatory cytokine levels, alleviates bone fibrosis, and improves bone injury in KOA rats, thereby relieving joint pain, possibly by downregulating ADAMTS-5 expression to activate the PPARγ/c-SKI signaling pathway.
To evaluate the safety and bioequivalence of two formulations of agomelatine tablets in healthy Chinese subjects.
A randomized, open-label, two-treatment, four-period, two-sequence, fully replicated crossover bioequivalence study was conducted under both fasting and fed conditions. Each subject received a single 25 mg dose of the test (T) product or reference (R) product agomelatine tablet in both fasting and fed conditions. Plasma concentration of agomelatine was determined by the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The main pharmacokinetic parameters were derived using WinNonlin 8.3 software.
A total of 128 subjects were enrolled, 64 in the fasting group and 64 in the fed group. The primary pharmacokinetic(PK) parameters of the test and reference formulations under fasting condition were as follows: Cmax were (25.55±29.65) and (26.59±28.04) ng·mL-1, AUC0-t were (28.59±26.66) and (29.33±26.98) ng·h·mL-1, AUC0-∞ were (29.13±26.96) and (29.62±27.17) ng·h·mL-1. The primary pharmacokinetic parameters of the test and reference formulations under fed condition were as follows: Cmax were (26.26±23.29) and (28.97±34.82) ng·mL-1, AUC0-t were (35.75±27.67) and (36.91±32.59) ng·h·mL-1, AUC0-∞ were (36.15±27.89) and (37.14±32.69) ng·h·mL-1. Under both fasting and post-meal conditions, the 90% confidence interval of the geometric mean ratio (GMR) of the main PK parameters of the test formulation of agomelatine tablets compared to the reference formulation fell within the range of 80%-125%.
The test formulations and reference formulations of agomelatine are bioequivalent under both fasting and fed conditions.
To evaluate the bioequivalence and safety profile of ezetimibe and atorvastatin calcium tablets (10 mg/10 mg) in healthy subjects.
This study utilized a single-center, randomized, open-label, four-period replicate crossover design. A total of 36 participants were enrolled for both fasting and fed state evaluations. Subjects, following a randomization plan, were administered orally either a single tablet of the test (T) or reference (R) formulation on the designated dosing day of each period. An 8-day washout interval separated treatment periods. Quantification of plasma levels for free ezetimibe, total ezetimibe (sum of free ezetimibe and its glucuronide conjugates) and atorvastatin were performed employing validated high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters were analyzed using Phoenix WinNonlin 8.2 software, and the bioequivalence evaluation was conducted.
Fasting state was as following: pharmacokinetic metrics Cmax of ezetimibe for T and R formulations were (6.35±3.22) and (7.04±3.20) ng·mL-1; AUC0-t were (107.10±46.61) and (109.67±50.23) ng·h·mL-1; AUC0-∞ were (114.88±49.96) and (117.14±50.74) ng·h·mL-1. The 90% confidence intervals for the geometric mean ratio of Cmax, AUC0-t and AUC0-∞ were 84.11%-98.34%, 94.60%-106.44% and 93.52%-105.82%, respectively, all in the range of 80.00%-125.00%. Pharmacokinetic metrics Cmax of total ezetimibe for T and R formulations were (67.01±35.70) and (71.82±30.91) ng·mL-1; AUC0-t were (605.29±255.51) and (615.90±270.21) ng·h·mL-1; AUC0-∞ were (655.81±268.02) and (676.04±279.18) ng·h·mL-1. The 90% confidence intervals for the geometric mean ratio of Cmax, AUC0-t and AUC0-∞ were 85.32%-97.52%, 92.35%-103.46% and 91.43%-102.13%, all in the range of 80.00%-125.00%. Pharmacokinetic metrics Cmax of atorvastatin for T and R formulations were (4.28±2.50) and (4.06±2.40) ng·mL-1; AUC0-t were (24.24±18.91) and (22.12±10.80) ng·h·mL-1; AUC0-∞were (23.86±12.05) and (23.44±10.98) ng·h·mL-1. The individual coefficient of variation for Cmax with the one-sided 95% upper confidence limit below the zero boundary value. The geometric mean ratio for Cmax was 1.06, falling within the acceptance range 0.80-1.25. The 90% confidence intervals for the geometric mean ratios of AUC0-t and AUC0-∞ were 97.11%-109.14% and 97.24%-104.00%, all in the range of 80.00%-125.00%. The pharmacokinetic parameters of active ingredients in the fed group were as follows: for ezetimibe, the Cmax values of the test and reference preparations were (12.50±8.43) and (12.10±10.20) ng·mL-1, respectively; the AUC0-t values were (115.66±61.86) and (114.91±61.10) ng·h·mL-1, respectively; and the AUC0-∞ values were (127.40±66.49) and (128.37±66.73) ng·h·mL-1, respectively. The one-sided 95% upper confidence limit for ezetimibe Cmax was <0, with a GMR of 1.09, within the range of 0.80-1.25. The 90% confidence intervals for the geometric mean ratios of AUC0-t and AUC0-∞ were 93.63%-107.27% and 91.07%-108.13%, respectively, both within 80.00%-125.00%. For total ezetimibe, the Cmax values of the test and reference preparations were (102.02±50.21) and (95.10±48.31) ng·mL-1, respectively; the AUC0-t values were (660.62±342.67) and (645.43±290.84) ng·h·mL-1, respectively; the AUC0-∞ values were (728.80±356.15) and (711.88±301.04) ng·h·mL-1, respectively. The one-sided 95% upper confidence limit for total ezetimibe Cmax was <0, with a GMR of 1.08, within the range of 0.80-1.25. The 90% confidence intervals for the geometric mean ratios of AUC0-t and AUC0-∞ were 95.12%-106.95% and 95.27%-107.60%, respectively, both within 80.00%-125.00%. For atorvastatin, the Cmax values of the test and reference preparations were (1.79±0.80) and (1.83±0.87) ng·mL-1, respectively; the AUC0-t values were (19.09±6.85) and (18.24±6.29) ng·h·mL-1, respectively; and the AUC0-∞ values were (21.25±6.97) and (20.34±6.84) ng·h·mL-1, respectively. The 90% confidence intervals for the geometric mean ratios of Cmax, AUC0-t and AUC0-∞ were 91.25%-106.96%, 99.81%-108.09% and 100.22%-108.73%, respectively, all falling within the range of 80.00%-125.00%.
The test formulation of ezetimibe and atorvastatin calcium tablets met bioequivalence criteria relative to the reference product in healthy subjects under both fasting and fed (high-fat meal) conditions.
To observe the clinical efficacy and safety of optimized clinical procedures combined with N-acetylcysteine (NAC) tablets in the diagnosis and treatment of testicular torsion.
Patients diagnosed with testicular torsion in our hospital from January 2020 to January 2022 were enrolled as control group and received routine diagnosis and treatment. Patients treated from January 2023 to January 2024 who underwent optimized clinical procedures combined with postoperative oral NAC tablets were enrolled as treatment group. The treatment group implemented optimized clinical procedures (including health education, fast track pathway, simplified evaluation and surgical preparation, etc.) and started oral NAC tablets on the second day after surgery (200 mg each time, 3 times daily, for 1 consecutive week). The two groups were compared in terms of time from symptom onset to hospital arrival (T1), time from hospital arrival to surgery start (T2), total ischemia time (T3), orchiectomy rate and testicular atrophy rate at 6 months postoperatively.
T1 in treatment group and control group were 8.00 (5.00, 12.00) and 62.00 (51.00, 72.00) min, respectively; T2 were 52.00 (48.00, 57.00) and 109.00 (85.00, 135.50) min, respectively; and T3 were 60.00 (56.00, 64.00) and 171.50 (149.00, 199.00) min, respectively. The differences in the above indicators between the two groups were statistically significant (all P<0.001). The orchiectomy rate was 65.00% in treatment group and 82.00% in control group, with a statistically significant difference (P<0.001, RR=0.78, 95%CI: 0.66-0.91). At 6 months postoperatively, among patients who underwent testicular salvage, the testicular atrophy rate was 11.43% in treatment group and 33.33% in control group, with a statistically significant difference (P<0.05, RR=0.30, 95%CI: 0.10-0.94). Multivariate logistic regression analysis showed that the combined intervention was an independent protective factor for reducing orchiectomy rate (P=0.001, OR=0.31, 95%CI: 0.15-0.64). In terms of safety, only 3 (3.00%) patients in treatment group reported mild nausea, with no serious adverse drug reactions; no related adverse reactions occurred in control group.
The application of optimized clinical procedures combined with N-acetylcysteine tablets shows significant clinical benefits in the treatment of testicular torsion, helping to shorten treatment time, reduce testicular injury, improve testicular survival rate, and exhibits a favorable safety profile.
To construct a clinical pharmacist intervention strategy for tislelizumab injection in the treatment of advanced non-small cell lung cancer (NSCLC) and evaluate its practical effects.
Patients with advanced NSCLC admitted to our hospital were divided into control group and treatment group. The control group received routine pharmaceutical care, while the treatment group received a clinical pharmacist intervention strategy. Therapeutic efficacy, incidence of immune-related adverse events (irAEs), incidence of grade ≥3 irAEs, treatment-related drug withdrawal rate, medication adherence, quality of life and satisfaction with pharmaceutical care were compared between the two groups.
A total of 106 patients were included, including 53 in control group and 53 in treatment group. After treatment, the objective response rates (ORR) of treatment group and control group were 47.17% and 28.30%, respectively; the disease control rates (DCR) were 60.38% and 39.62%, respectively. The above indicators in treatment group were statistically significantly higher than those in control group (all P<0.05). The incidences of irAEs in treatment group and control group were 39.62% and 60.38%, respectively; the incidences of irAEs≥grade 3 were 13.21% and 30.19%, respectively; the treatment-related discontinuation rates were 9.43% and 24.53%, respectively. The above indicators in treatment group were statistically significantly lower than those in control group (all P<0.05). After treatment, the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–lung cancer 13 (EORTC QLQ-LC13) scores for treatment group and control group were (50.15±9.06) and (53.94±7.19) points, respectively, with treatment group statistically significantly lower than control group (P<0.05). The satisfaction rate of pharmaceutical services in treatment group was 90.57%, statistically significantly higher than control group’s 75.47% (P<0.05).
The clinical pharmacist intervention strategy can improve medication adherence to tislelizumab injection, reduce immune-related adverse events and treatment interruption, improve quality of life, and enhance satisfaction with pharmaceutical care, thereby contributing to better clinical outcomes.
To explore the prescription rationality of compound dextromethorphan hydrobromide syrup and the review effectiveness of the rational drug use system in pediatric outpatient and emergency departments, clarify the key medication risk points and system shortcomings, and provide data support and practical evidence for optimizing the safety prevention and control process of pediatric medication.
A retrospective study was conducted to collect prescriptions of compound dextromethorphan hydrobromide syrup in the outpatient and emergency departments of our hospital from January to December 2024. The mode of system screening combined with manual review was adopted, and an age-weight dual-dimensional evaluation criteria was established with reference to drug instructions and relevant clinical guidelines. The irrational prescriptions were classified and analyzed, and statistical analysis was performed using Excel 2010 and SPSS 23.0 software.
A total of 74 905 prescriptions of this preparation were issued throughout the year. System screening identified 527 positive irrational prescriptions, among which 357 were confirmed as true positive irrational prescriptions after manual review, with a system precision rate of 67.74% (357 prescriptions /527 prescriptions) and a false positive rate of 32.26% (170 prescriptions /527 prescriptions), and the overall irrational prescription rate was 0.48% (357 prescriptions /74 905 prescriptions). The core issues of irrational prescriptions primarily include drug interactions, duplicate medication, inappropriate dosage and administration, and unsuitable indications, accounting for 29.41% (105 prescriptions/357 prescriptions), 26.05% (93 prescriptions /357 prescriptions), 29.41% (105 prescriptions /357 prescriptions) and 16.81% (60 prescriptions /357 prescriptions), respectively. 98.24% (167 prescriptions /170 prescriptions) of false positive prescriptions were from overweight patients, indicating defects in the single-dimensional judgment logic of the system; the true positive rate of nighttime prescriptions 75.56% (250 prescriptions /357 prescriptions) was higher than 65.05% (255 prescriptions/392 prescriptions) of daytime prescriptions.
The medication risks of compound dextromethorphan hydrobromide syrup in children are characterized by age concentration and vary among different age groups, and the rational drug use system has efficiency shortcomings. It is necessary to optimize the age-weight dual-dimensional judgment system, implement hierarchical prevention and control, source intervention and system upgrading, so as to effectively improve the level of pediatric medication safety, and provide reference for the clinical standardized management of this preparation and the optimization of rational drug use system.
To extract severe cutaneous adverse reactions (SCAR) associated with commonly used anti-influenza virus drugs from the US Food and Drug Administration (FDA) adverse event reporting system (FAERS) database, analyze the epidemiological characteristics of SCAR to provide a reference for safe clinical medication, and explore the underlying molecular mechanisms using network pharmacology.
Reports from January 2004 to December 2024 in FAERS database were collected, in which oseltamivir, peramivir, zanamivir and baloxavir marboxil were the primary suspected drugs and SCAR was the preferred term (PT). The reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) methods were used to mine and analyze adverse drug event (ADE) signals. Targets of commonly used anti-influenza virus drugs and SCAR were extracted, a protein-protein interaction network was constructed, and enrichment analysis was performed.
A total of 263 cases (1.90%) of SCAR related to commonly used anti-influenza virus drugs were collected. Females (55.13%) accounted for a higher proportion than males (35.36%). Positive signals were detected for all drugs except peramivir, with the association strength in descending order, baloxavir marboxil [n=42, ROR 1.75, information component(IC)0.8], zanamivir (n=53, ROR 1.61, IC 0.68) and oseltamivir (n=208, ROR 1.34, IC 0.42). The top 5 PT by frequency were blister, erythema multiforme, drug eruption, toxic epidermal necrolysis and acute generalized exanthematous pustulosis. Network pharmacology analysis showed that the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway may be a key pathway underlying SCAR induced by commonly used anti-influenza virus drugs.
Baloxavir marboxil, oseltamivir and zanamivir carry a risk of SCAR, with baloxavir marboxil and zanamivir showing higher signal intensity, while oseltamivir had the highest number of reports. Close monitoring of skin symptoms in female patients is recommended from 3 days after administration to guard against the occurrence of SCAR. Anti-influenza virus drugs may induce SCAR by regulating the JAK-STAT signaling pathway, which provides insights for further research.
Sitafloxacin, a fourth-generation fluoroquinolone antibacterial agent, exerts potent antibacterial activity against gram-negative and gram-positive bacteria, atypical pathogens and anaerobic bacteria. It also remains effective against fluoroquinolone-resistant strains, methicillin-resistant Staphylococcus aureus, penicillin-insensitive Streptococcus pneumoniae and Enterococcus. It is widely used clinically for treating infectious diseases such as upper and lower respiratory tract infections, genitourinary infections, oral infections and otitis media. Sitafloxacin shows linear pharmacokinetic characteristics within the dose range of 50-200 mg. It is rapidly absorbed after oral administration, widely distributed in various tissues and organs throughout the body, and mainly excreted in the urine as unchanged form. Commonly reported adverse events include diarrhea, nausea and abnormal liver function. In recent years, studies have found that sitafloxacin is also effective against multidrug-resistant pathogens causing ventilator-associated pneumonia, hospital-acquired pneumonia, tuberculosis, Mycoplasma genitalium infections in men, Mycobacterium abscessus infection periodontal infection, Helicobacter pylori infections and refractory Mycobacterium skin infections. However, further clinical studies are still needed to evaluate its efficacy and safety, and pharmacokinetic studies should be conducted in special populations such as the elderly and those with hepatic impairment. This article systematically reviews the pharmacological mechanism, antibacterial activity, pharmacokinetic/pharmacodynamic characteristics and recent advances in clinical research of sitafloxacin, aiming to provide a reference basis for the safe and effective clinical use of sitafloxacin.
Laryngopharyngeal reflux disease (LPRD) is one of the diseases widely recognized and highly valued by otorhinolaryngologists in recent years. Its symptoms are changeable and its signs are complex, which brings challenges to clinical diagnosis, especially the lack of specific signs and laboratory examination results, which leads to clinical diagnosis relying on patients’ chief complaints and signs. Western medicine mainly uses proton pump inhibitors to intervene. After treatment, the improvement of symptoms is obviously earlier than that of signs, and there is no unified diagnosis and treatment standard at home and abroad. With the continuous deepening of traditional Chinese medicine research (TCM), TCM can provide treatment through syndrome differentiation and external therapies such as acupoint application and acupuncture. The decrease of recurrence rate and decreased adverse drug reactions not only improves the clinical efficacy, but also brings new ideas for the diagnosis and treatment of LPRD.