ArchiveTo investigate relative factors of coagulation abnormalities induced by eravacycline injection in elderly patients.
Elderly patients (age ≥ 65 years) who received eravacycline for infection were enrolled. The patients were divided into the abnormal coagulation group and the normal coagulation group based on whether there was prolongation of prothrombin time (PT) by more than 3 seconds and/or a decrease in fibrinogen to ≤ 1.5 g·L-1. The clinical data, medication prescribed, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, and nutrition risk screening 2002 (NRS2002) score before treatment were recorded. The incidence of coagulation abnormalities after eravacycline injection treatment was statistically analyzed. Comorbidities, baseline liver, kidney function, coagulation function, SOFA, APACHE Ⅱ and NRS2002 scores were compared between normal coagulation group and abnormal coagulation group. Logistic regression analyses were performed for further exploration.
A total of 84 elderly patients were enrolled. At 1 week of eravacycline injection treatment, 33 patients developed coagulation abnormalities, with an incidence rate of 39.29% (33 cases/84 cases). The proportion of chronic liver disease of normal coagulation group and abnormal coagulation group were 6.00% (3 cases /51 cases) and 24.24% (8 cases /33 cases), respectively; the proportion of combined antithrombotic drugs were 68.00% (34 cases /51 cases) and 45.45% (15 cases /33 cases), respectively; baseline levels of white blood cell count were 8.30 (4.55, 12.41) and 11.40 (7.08, 13.88) ×109·L-1, respectively; total bilirubin (TBIL) levels were 14.00 (10.80, 19.83) and 23.50 (14.70, 46.90) umol·L-1, respectively; direct bilirubin (DBIL) levels were 5.98 (3.69, 9.60) and 9.50 (6.20, 25.05) umol·L-1, respectively; C-reactive protein (CRP) levels were 57.91 (22.43, 97.33) and 69.20 (33.87, 86.54) mg·L-1, respectively; interleukin-6 (IL-6) levels were 43.11 (22.26, 106.98) and 91.12 (24.30, 181.60) pg·mL-1, respectively; PT were 12.90 (11.95, 15.00) and 14.40 (12.80, 15.70) s, respectively; activated partial thromboplastin time (APTT) were 31.50 (28.35, 34.00) and 34.10 (30.70, 37.95) s, respectively; international normalized ratio (INR) were 1.13 (1.05, 1.29) and 1.27 (1.13, 1.36), respectively. The differences of above indicators between the two groups were all statistically significant (all P<0.05). Regression analysis showed that TBIL was associated with eravacycline injection-induced coagulation abnormalities in elderly patients, with an odds ratio (OR) of 1.04 (P<0.05). Among the 62 patients who received eravacycline injection for more than 1 week, 27 developed coagulation abnormalities by the end of treatment, with an incidence rate of 43.55% (27 cases/62 cases). The proportion of chronic kidney disease of normal coagulation group and abnormal coagulation group were 29.41% (10 cases/35 cases) and 59.26% (16 cases/27 cases), respectively; the proportion of combined antithrombotic drugs were 70.59% (24 cases /35 cases) and 40.74% (11 cases /27 cases), respectively; baseline APACHE Ⅱ scores were (14.82±6.62) and (19.68±6.38) point, respectively; NRS2002 scores were 4.00 (3.00, 4.00) and 5.00 (3.50,7.00) point, respectively; CRP levels were 57.62 (21.48, 83.29) and 88.11 (49.11, 149.80) mg·L-1, respectively; IL-6 levels were 26.45 (13.58, 78.82) and 99.32 (43.79, 191.57) pg·mL-1, respectively; APTT were 30.30 (28.10, 33.15) and 33.90 (28.90, 36.40) s, respectively; platelet levels were 176.50 (120.25, 225.50) and 132.00 (81.00, 195.00) ×109·L-1, respectively. The differences of above indicatiors between the two groups were all statistically significant (all P<0.05). Regression analysis showed that the NRS2002 score was associated with eravacycline-induced coagulation abnormalities in elderly patients, with an OR of 2.04 (P<0.05). The incidence of coagulation abnormalities increases with the prolongation of eravacycline injection treatment. The dosage of eravacycline of normal coagulation group and abnormal coagulation group were (0.78±0.14) and (0.84±0.17) mg·kg-1, the difference between the two groups was not statistically significant (P>0.05)
Coagulation abnormalities may occur in elderly patients treated with eravacycline injection. Total bilirubin level and NRS2002 score are risk factors for coagulation abnormalities. Coagulation indicators should be closely monitored during treatment.
To evaluate the efficacy and safety of a 12-week regimen of coblopasvir hydrochloride capsules combined with sofosbuvir tablets in patients with chronic hepatitis C (CHC).
CHC patients who visited our hospital and received a 12-week regimen of coblopasvir hydrochloride capsules combined with sofosbuvir tablets were enrolled as the study subjects. All patients received oral coblopasvir hydrochloride capsules (60 mg) and sofosbuvir tablets (400 mg) once daily for 12 weeks. Some patients with genotype 3b additionally received ribavirin tablets for 12 weeks at a dose of 1 000 mg·d-1 for those weighing < 75 kg and 1 200 mg·d-1 for those weighing ≥ 75 kg. Hepatitis C virus (HCV) ribonucleic acid and relevant laboratory indicators were measured before and after treatment. The sustained virological response at 12 weeks post-treatment (SVR12) rate was observed in all patients. Changes in liver and renal function before and after treatment were compared, and safety was evaluated.
A total of 110 CHC patients were enrolled. After treatment, 97.27% (107 cases/110 cases) of patients achieved SVR12. Specifically, the SVR12 rate was 93.33% (14 cases/15 cases) in patients with decompensated cirrhosis, 92.86% (13 cases/14 cases) in patients with genotype 3b CHC, 87.50% (7 cases/8 cases) in patients with moderate-to-severe renal impairment, and 83.33% (5 cases/6 cases) in genotype 3b patients receiving ribavirin combination therapy. The alanine aminotransferase levels before and after treatment were 58.70 (31.85, 100.45) and 20.60 (13.30, 31.33) U·L-1, respectively; the aspartate aminotransferase levels were 52.75 (28.68, 82.13) and 23.30 (17.78, 33.73) U·L-1, respectively; the total bilirubin levels were 13.90 (9.60, 20.25) and 11.70 (8.78, 18.85) μmol·L-1, respectively; the albumin levels were 42.80 (38.10, 45.30) and 45.10 (42.13, 46.73) g·L-1, respectively. After treatment, the aforementioned indicators showed statistically significant differences compared to before treatment (P<0.05, P<0.001). The estimated glomerular filtration rates before and after treatment were 102.09 (87.66, 108.68) and 99.23 (84.00, 104.28) mL·min-1, respectively, with no statistically significant difference (P>0.05). The main adverse drug reactions were fatigue (6.36%), decreased appetite (4.55%), abdominal distension (1.82%) and abdominal pain (1.82%). The overall incidence of adverse drug reactions was 10.91% (12 cases/110 cases), and the incidence in patients with decompensated cirrhosis was 13.33% (2 cases/15 cases). No serious adverse drug reaction occurred.
The 12-week regimen of coblopasvir hydrochloride capsules combined with sofosbuvir tablets demonstrated favorable efficacy and high safety in real-world CHC patients, including those with genotype 3b, decompensated cirrhosis, or moderate-to-severe renal impairment.
To investigate the influencing factors of the steady-state concentration/dose ratio (C/D) for milnacipran tablets based on therapeutic drug monitoring (TDM), with the goal of promoting individualized use of this medication.
Inpatients who underwent milnacipran TDM were included in this study. General information, including gender, age, body mass index (BMI) and serum creatinine levels were collected through the medical record system. Additionally, dosage and comedication data were recorded. The analysis of these data was conducted using SPSS 23.0.
A total of 156 patients with steady-state concentrations determined by milnacipran TDM were included in the analysis. The steady-state concentration of milnacipran was found to be 95.52 (67.34, 126.97) ng·mL-1, C/D was 0.95 (0.71, 1.24) ng·mL-1·mg-1·d. Multiple linear regression analysis indicated that renal function statistically significantly influenced C/D (P<0.05). C/D ratio in patients with renal insufficiency and patients with normal insufficiency were 1.16 (0.79,1.50) and 0.92 (0.64,1.08) ng·mL-1·mg-1·d, with statisticaly significant difference (P<0.05).
The factors influencing milnacipran’s C/D are complex; therefore, for patients with renal insufficiency, regular monitoring of serum drug concentrations is recommended to ensure both safety and efficacy in its use.
To observe the clinical efficacy and safety of fumarate furosemide tablets combined with mosapride tablets in the treatment of refractory non erosive gastroesophageal reflux disease (rNERD).
The rNERD patients admitted to our hospital were divided into control group (oral administration of 20 mg fumarate fumarate tablets, qd) and treatment group (addition of mosapride citrate tablets, taken before meals, 5 mg each time, tid) according to the treatment method, with a treatment course of 8 weeks. Compared the clinical symptoms, esophageal motility indicators, gastrointestinal hormone indicators, quality of life and clinical efficacy of two groups, and conducted safety evaluation.
A total of 120 patients were included, with 59 in control group and 61 in treatment group. After treatment, the gastroesophageal reflux disease scale (Gerd Q) scores of treatment group and control group were (6.89±1.29) and (7.56±1.64) points, respectively; the gastroesophageal reflux disease symptom frequency scale (FSSG) scores were (7.95±1.71) and (9.00±2.24) points, respectively; the lower esophageal sphincter pressure (LESP) were (22.19±4.33) and (19.67±4.38) mmHg, respectively; the pepsinogen Ⅰ (PG Ⅰ) levels were (121.21±26.75) and (111.57±20.28) pg·mL-1, respectively; the pepsinogen Ⅱ (PG Ⅱ) levels were (13.58±3.17) and (15.12±3.57) pg·mL-1, respectively; the gastrin (GAS) levels were (72.16±11.23) and (67.97±10.94) pg·mL-1, respectively; the scores of the gastroesophageal reflux disease quality of life scale (GERD-QOL) were (32.82±7.24) and (29.75±5.37) points, respectively. The differences in the above indicators were all statistically significant between the two groups (P<0.05, P<0.01). The total clinical effective rate of treatment group was 90.16% (55 cases/61 cases), which was significantly higher than 76.27% (45 cases/59 cases) in control group (P<0.05). The adverse drug reactions in control group mainly included diarrhea, constipation and nausea; treatment group included diarrhea, constipation and dry mouth. The total incidence of adverse drug reactions in treatment group and control group were 8.20% (5 cases/61 cases) and 6.78% (4 cases/59 cases), respectively, with no statistically significant difference (P>0.05).
The combination of vonoprazan fumarate tablets and mosapride citrate tablets has a synergistic effect in the treatment of rNERD, which can effectively improve the clinical symptoms and quality of life of rNERD. Its mechanism of action may be related to multiple effects such as synergistic improvement of esophageal motility and regulation of gastrointestinal hormone levels, and the combination regimen has good safety.
To evaluate the application effect of roxadustat capsules combined with recombinant human erythropoietin (rHuEPO) for injection in hemodialysis patients with renal anemia.
Patients with renal anemia undergoing hemodialysis were randomly divided into control group and treatment group using a random number table method. The control group received treatment with rHuEPO injection, intravenous injection of 120-150 IU·kg-1, 2-3 times a week; the treatment group was administered roxadustat capsules orally after meals (100 mg for patients weighing <60 kg, 120 mg for patients weighing ≥60 kg) on the basis of the control group, 3 times per week. Both groups were treated continuously for 3 months. Iron metabolism indicators, anemia indicators and inflammatory factors were compared between the two groups. Clinical efficacy and adverse drug reactions were also assessed.
A total of 148 patients were enrolled in this study, including 70 cases in treatment group and 68 cases in control group. After treatment, the overall clinical effective rates of treatment group and control group were 95.71% (67 cases/70 cases) and 83.82% (57 cases/68 cases), respectively, with a statistically significant difference (P<0.05). After treatment, the serum iron (SI) levels of treatment group and control group were (15.98±4.04) and (13.41±3.72) μmol·L-1, respectively; the transferrin saturation (TSAT) levels were (35.23±5.03)% and (29.38±4.94)%, respectively; the serum ferritin (SF) levels were (284.69±31.41) and (219.57±28.47) μg·L-1, respectively; the hemoglobin (Hb) levels were (97.57±11.16) and (91.09±9.84) g·L-1, respectively; the hematocrit (Hct) levels were (34.62±4.09)% and (28.34±3.47)%, respectively; the red blood cell (RBC) counts were (3.41±0.74) and (2.77±0.61)×1012·L-1, respectively; the interleukin-6 (IL-6) levels were (58.02±6.19) and (64.23±7.63) ng·L-1, respectively; and the tumor necrosis factor-α (TNF-α) levels were (111.02±12.54) and (120.63±15.29) ng·L-1, respectively. There were statistically significant differences in all the above indicators between treatment group and control group (all P<0.05). Adverse drug reactions in treatment group included dizziness, fever, elevated blood pressure, nausea and vomiting, diarrhea and abnormal liver function, while those in control group included dizziness, fever, elevated blood pressure, nausea and vomiting, diarrhea and abnormal liver function. The total incidence of adverse drug reactions in treatment and control groups were 17.14% (12 cases/70 cases) and 19.12% (13 cases/68 cases), respectively, with no statistically significant difference (P>0.05).
Roxadustat capsules combined with rHuEPO solution for injection can improve iron metabolism and anemia status, reduce inflammatory factor levels, and do not increase the risk of adverse drug reactions in hemodialysis patients with renal anemia.
To observe the clinical efficacy and safety of denosumab injection combined with teriparatide injection in patients with osteoporotic fractures after percutaneous kyphoplasty (PKP).
Patients with osteoporotic fractures treated with PKP in our hospital were divided into treatment group and control group according to different medication regimens. On the basis of conventional treatment, the control group was subcutaneously injected with teriparatide injection at a dose of 20 μg once daily for consecutive 12 months. The treatment group was additionally subcutaneously injected with denosumab injection on the basis of the control group’s regimen, at a dose of 60 mg once every 6 months, with a total of 2 administrations. The clinical efficacy, bone mineral density (BMD), bone metabolism indicators, pain relief and functional recovery status and incidence of refracture, and safety evaluation were compared between the two groups.
A total of 108 patients were enrolled, including 53 in control group and 55 in treatment group. After treatment, the total effective rate was 90.91% (50 cases/55 cases) in treatment group and 75.47% (40 cases /53 cases) in control group; lumbar vertebrae L2-4 BMD levels were (0.88±0.13) and (0.82±0.11) g·cm-2, respectively; femoral neck BMD levels were (0.81±0.14) and (0.75±0.13) g·cm-2, respectively; greater trochanter BMD levels were (0.69±0.08) and (0.65±0.08) g·cm-2, respectively; total hip BMD levels were (0.85±0.16) and (0.78±0.16) g·cm-2, respectively; the receptor activator of nuclear factor-κB ligand (RANKL) levels were (4.82±1.24) and (5.53±1.29) pg·mL-1, respectively; total procollagen type Ⅰ N-terminal propeptide (T-P1NP) levels were (44.93±9.12) and (40.58±8.95) ng·mL-1, respectively; β-cross-linked C-telopeptide of type 1 collagen (β-CTX) levels were (0.38±0.08) and (0.43±0.07) ng·mL-1, respectively; N-terminal midfragment of osteocalcin (N-MID) levels were (19.32±2.97) and (17.93±2.59) ng·mL-1, respectively; the visual analog scale (VAS) scores were (1.88±0.66) and (2.16±0.55) points, respectively; the oswestry disability index (ODI) scores were (10.83±1.73) and (12.12±2.89) points, respectively; the incidence of refracture within 1 year of treatment was 0% (0 cases/55 cases) and 9.43% (5 cases /53 cases). The aforementioned indicators showed statistically significant differences between the two groups (P<0.05, P<0.01). The main adverse drug reactions in treatment group include nausea, muscle pain and injection site reactions; the control group included nausea, muscle pain, palpitations and injection site reactions, and both groups had mild adverse drug reactions. The total incidence of adverse drug reactions in treatment group and control group were 12.73% (7 cases/55 cases) and 9.43% (5 cases/53 cases), respectively, with no statistically significant difference (P>0.05).
Denosumab injection combined with teriparatide injection in the treatment of patients with osteoporotic fractures after PKP surgery can significantly improve clinical efficacy and bone density, promote bone formation, reduce the recurrence of fractures, and has favorable safety.
To observe the clinical efficacy and safety of folic acid tablets combined with vitamin B6 tablets as an adjuvant therapy for obese patients with polycystic ovary syndrome (PCOS).
Obese PCOS patients admitted to our hospital were divided into treatment group and control group according to the medication plan. The control group was treated with ethinylestradiol and cyproterone acetate tablets (taken orally before bedtime every night), metformin hydrochloride tablets (0.25 g, taken orally before breakfast and dinner), and orlistat capsules (60 mg, twice a day). The treatment group was treated with folic acid tablets (5 mg, once a day) and vitamin B6 tablets (10 mg, once a day) in addition to control group. Compare clinical efficacy, glucose metabolism indicators, reproductive endocrine hormones, mean ovarian volume (MOV), mean number of follicles (MFN), inflammatory factors, serum homocysteine (Hcy), triglyceride (TG) levels and body measurement parameters between two groups, and evaluate their safety.
A total of 150 patients were included, with 73 in treatment group and 77 in control group. The total effective rates of treatment and control group were 90.41% (66 cases/73 cases) and 77.92% (60 cases/77 cases), respectively, and the difference was statistically significant (P<0.05). After treatment, the fasting plasma glucose (FPG) levels of treatment group and control group were (4.42±0.58) and (4.66±0.53) mmol·L-1, respectively; the fasting insulin (FINS) levels were (9.16±1.77) and (10.03±2.06) mIU·L-1, respectively; the homeostatic model assessment of insulin resistance (HOMA-IR) levels were 1.80±0.46 and 2.08±0.65, respectively; the anti-Müllerian hormone (AMH) levels were (4.03±1.19) and (4.63±1.32) ng·mL-1, respectively; the inhibin B (INHB) levels were (102.33±14.54) and (108.81±17.63) pg·mL-1, respectively; the MOV levels were (7.36±1.88) and (6.77±1.24) cm3, respectively; the numbers of MFN were (8.89±1.86) and (8.24±1.45) cell, respectively; the interleukin-6 (IL-6) levels were (16.87±3.22) and (18.34±3.67) pg·mL-1, respectively; the tumor necrosis factor-alpha (TNF-α) levels were (10.19±3.06) and (11.83±3.22) pg·mL-1, respectively; the Hcy levels were (14.78±3.52) and (16.16±3.64) μmol·L-1, respectively; the TG levels were (3.49±0.61) and (4.15±0.66) mmol·L-1, respectively; the body mass index (BMI) levels were (31.09±3.06) and (32.16±3.17) kg·m-2, respectively; the body fat percentages were (31.42±3.24)% and (32.89±3.38)%, respectively; and the waist-to-hip ratio (WHR) levels were 0.92±0.21 and 1.01±0.26, respectively. There were statistically significant differences in the above indicators between treatment group and control group (P<0.05, P<0.01). The adverse drug reactions in treatment group were gastrointestinal discomfort, while those in control group were headache. The overall incidence rates of adverse drug reactions in treatment and control groups were 1.37% (1 case/73 cases) and 2.60% (2 cases/77 cases), respectively, with no statistically significant difference (P>0.05).
The adjuvant treatment of PCOS with folic acid combined with vitamin B6 tablets has good clinical efficacy and safety. It can significantly reduce the levels of serum Hcy in patients and improve the insulin resistance status and lipid metabolism of patients.
To observe the clinical efficacy and safety of local infiltration of levobupivacaine injection combined with tranexamic acid injection in patients undergoing posterior lumbar interbody fusion.
Patients undergoing posterior lumbar interbody fusion surgery in our hospital were divided into treatment group and control group based on the local infiltration medication regimen postoperatively. The control group received 20 mL of normal saline for local infiltration, and the treatment group received 20 mL of a mixed solution containing levobupivacaine injection (concentration 0.25%, 37.5 mg diluted to 15 mL) and tranexamic acid injection (concentration 10%, 0.2 g diluted to 5 mL). The two groups were compared in terms of visual analogue scale (VAS) scores at rest and during activity at 2, 6, 12, 24 and 48 hours postoperatively, postoperative rescue analgesia rate, serum inflammatory markers, stress indicators at 24 hours postoperatively, postoperative recovery indicators, and safety evaluation was conducted.
A total of 92 patients were finally enrolled, with 48 in control group and 44 in treatment group. After treatment, the resting VAS scores at 48 hours postoperatively in control group and treatment group were (1.75±0.44) and (1.55±0.50) points, respectively; the activity VAS scores were (2.54±0.50) and (2.32±0.47) points, respectively; the interleukin-6 (IL-6) levels at 24 hours postoperatively were (57.02±5.15) and (54.23±4.52) pg·mL-1, respectively; the tumor necrosis factor-α (TNF-α) levels were (34.12±5.40) and (30.88±5.13) pg·mL-1, respectively; the S100 calcium-binding protein B (S100β) levels were (110.78±9.66) and (104.13±10.54) pg·mL-1, respectively; the serum cortisol (Cor) levels were (95.87±14.69) and (89.43±13.73) ng·mL-1, respectively; the norepinephrine (NE) levels were (369.43±51.81) and (342.86±48.13) ng·mL-1, respectively; the advanced oxidation protein products (AOPP) levels were (66.19±12.36) and (58.97±11.74) μmol·L-1, respectively; the rescue analgesia rates at 0-11 h postoperatively were 33.33% (16 cases/48 cases) and 13.64% (6 cases /44 cases), respectively; and at 12-24 h were 22.92% (11 cases /48 cases) and 6.82% (3 cases /44 cases), respectively; the first ambulation time were (2.79±0.62) and (2.48±0.55) days, the first flatus time were (30.79±5.35) and (28.02±5.20) hours, the hospital stay were (7.38±1.44) and (6.66±1.29) days, respectively; and the quality of recovery-15 (QoR-15) score at postoperative day 3 were (116.69±7.42) and (121.66±8.72) points, respectively; statistically significant differences were observed in all the above indicators between the two groups (all P<0.05). The adverse drug reactions in treatment group included nausea and vomiting, fever and urinary retention, while those in control group included fever, nausea and vomiting, urinary retention and pruritus. The overall incidence of adverse drug reactions in treatment group and control group were 9.09% (4 cases/44 cases) and 14.58% (7 cases/48 cases), respectively; complications included poor wound healing, with incidence rates of 2.27% (1 case/44 cases) and 2.08% (1 case/48 cases), respectively, with no statistically significant differences between the groups (P>0.05, P>0.01).
In posterior lumbar interbody fusion, local infiltration of levobupivacaine injection combined with tranexamic acid injection around the incision provides more effective and sustained postoperative analgesia, significantly reduces systemic inflammation and stress response, promotes early postoperative rehabilitation, shortens hospital stay, and does not increase the risk of complications.
To investigate the clinical efficacy and safety of general anesthesia induced by benzenesulfonate remimazolam for injection combined with esketamine hydrochloride injection in elderly patients with severe knee osteoarthritis undergoing total knee arthroplasty.
The elderly patients with severe knee osteoarthritis undergoing total knee arthroplasty were divided into control group and treatment group according to the method of anesthesia induction. The treatment group received intravenous injection of 0.1 mg·kg-1 benzenesulfonate remimazolam for injection combined with 0.5 mg·kg-1 esketamine hydrochloride injection for anesthesia induction. The control group received 0.05 mg·kg-1 midazolam injection combined with 1 mg·kg-1 propofol emulsion injection for anesthesia induction. The other anesthesia methods were consistent between the two groups. The recovery time, hemodynamics, postoperative pain score (VAS), postoperative sedation score (Ramsay sedation scale), anxiety and depression score (HAD), mini-mental state examination score (MMSE), incidence of delirium (POD) and adverse anesthetic events were compared between the two groups.
A total of 232 patients were enrolled, with 115 cases in control group and 117 cases in treatment group. The recovery time of the control group and the treatment group were (26.30±4.84) and (24.52±4.66) min, respectively; heart rate after induction were (71.84±4.17) and (73.58±4.36) beats·min-1, respectively; heart rate at the end of operation were (74.59±4.46) and (76.13±4.32) beats·min-1, respectively; mean arterial pressure after induction were (81.90±5.69) and (84.11±5.72) mmHg, respectively; mean arterial pressure at the end of operation were (86.73±5.57) and (88.51±6.42) mmHg, respectively; VAS scores at 6 h after operation were (3.77±0.54) and (3.53±0.69) points, respectively; VAS scores at 12 h after operation were (3.21±0.64) and (3.00±0.66) points, respectively; the postoperative 1-hour Ramsay sedation scores were (3.82±0.66) and (3.21±0.57) points, respectively, and the postoperative 6-hour Ramsay scores were (2.65±0.48) and (2.31±0.46) points, respectively; at 3 d after operation, HAD-A scores were (10.53±1.86) and (9.94±1.73) points, respectively; HAD-D scores were (10.56±2.10) and (9.86±2.05) points, respectively; MMSE scores were (21.34±1.82) and (22.22±1.93) points, respectively; within 7 d after operation, the incidences of POD were 15.65% (18 cases/115 cases) and 6.84% (8 cases/117 cases), respectively; during anesthesia induction, the incidence of adverse drug reactions were 20.87% (24 cases/115 cases) and 9.40% (11 cases/117 cases), respectively. The differences of above indicators were all statistically significant comparing between the two group (P<0.05,P<0.01). The main adverse drug reactions during the anesthesia induction period in treatment group and control group included hypotension, hypertension, bradycardia and tachycardia.
Compared with the regimen of midazolam injection combined with propofol emulsion injection, the regimen of benzenesulfonate remimazolam for injection combined with esketamine hydrochloride injection for anesthesia induction can shorten recovery time, maintain stable hemodynamics, improve analgesic effect, relieve anxiety and depression, improve cognitive function, and have good safety.
To observe the clinical efficacy and safety of capecitabine tablets combined with oxaliplatin for injection (XELOX) in the treatment of gastric cancer.
Patients with stage Ⅱ gastric cancer who underwent D2 radical surgery in the hospital were divided into control group and treatment group by the random number table method. Starting at 4 weeks postoperatively, the control group was administered tegifur capsules with dosage adjusted based on body surface area of 40 or 60 mg, taken twice daily for 14 consecutive days, followed by a 1-week break, with each 21-day cycle repeated for 8 consecutive cycles. The treatment group received 130 mg·m-2 of intravenous oxaliplatin on the first postoperative day, followed by capecitabine tablets at 1 000 mg·m-2 per dose, twice daily from days 1 to 14, followed by a 1-week break, with each 21-day cycle repeated for 8 consecutive cycles. The carcinoembryonic antigen (CEA), carbohydrate antigen 72-4 (CA72-4), carbohydrate antigen 19-9 (CA19-9), microRNA-34a (miR-34a), disease-free survival (DFS) and overall survival (OS) were compared between the two groups, and the safety evaluation was performed.
A total of 150 patients were screened, and 130 cases were enrolled in the trial, including 65 cases in control group (with 5 dropouts) and 65 cases in treatment group (with 5 dropouts). Ultimately, 60 patients from each group were included in the statistical analysis. After 8 cycles of treatment, CEA levels in treatment group and control group were (4.83±1.22) and (6.33±1.14) ng·mL-1, CA19-9 levels were (24.33±3.58) and (28.86±4.18) U·mL-1, CA72-4 levels were (5.48±1.22) and (7.27±1.55) μg·L-1, the relative expression levels of miR-34a were 2.57±0.45 and 2.13±0.42, respectively. Compared with control group, the aforementioned indicators in treatment group showed statistically significant differences (all P<0.05). The median DFS values in treatment group and control group were 56 and 48 months, respectively, and the difference in DFS survival curve between the two groups was statistically significant (P<0.05); the median OS values were 62 and 60 months, respectively, and there was no statistically significant difference between the two groups (P>0.05). Adverse drug reactions in treatment group included leukopenia, thrombocytopenia and peripheral neurotoxicity, while those in control group included leukopenia and thrombocytopenia. The incidence rates of peripheral neurotoxicity in treatment group and control group were 6.67% (4 cases/60 cases) and 0% (0 cases /60 cases), the incidence rates of hand-foot syndrome were 21.67% (13 cases/60 cases) and 0% (0 cases/60 cases), the incidence rates of grade ≥ Ⅲ leukopenia were 16.67% (10 cases /60 cases) and 5.00% (3 cases /60 cases), the incidence rates of grade ≥ Ⅲ thrombocytopenia were 8.33% (5 cases /60 cases) and 0% (0 cases /60 cases), respectively. The incidence rates of the aforementioned adverse drug reactions in treatment group were statistically significantly different from those in control group (all P<0.05).
The application of XELOX regimen as postoperative adjuvant chemotherapy for stage Ⅱ gastric cancer can effectively improve the levels of tumor markers and prolong the DFS, and has more obvious advantages compared to tegafur capsule gimeracil oteracil potassium single-drug regimen, but the adverse drug reactions are also more obvious.
To observe clinical features of programmed cell death protein-1 (PD-1) inhibitor-induced liver injury in tumor patients and analyze its influencing factors.
Tumor patients treated with PD-1 inhibitors were enrolled. The clinical data were analyzed. The occurrence of liver injury during treatment was assessed according to CTCAE V5.0 criteria. Clinicopathological features of patients with liver injury were summarized. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for liver injury in tumor patients, and a nomogram prediction model was constructed receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were employed to evaluate validity of the model.
The incidence of PD-1 inhibitor-induced liver injury among the 310 patients enrolled was 11.94% (37 cases/310 cases). Grade 1, grade 2, grade 3 and grade 4 liver injuries were observed in 12 cases (32.43%), 15 cases (40.54%), 8 cases (21.62%) and 2 cases (5.41%), respectively. Clinical types included cholestatic type in 23 cases (62.16%), abnormal liver biochemistry type in 12 cases (32.43%), and hepatocellular injury type in 2 cases (5.41%). The median time to the occurrence of liver injury was 28.50 (5.00-217.00) d. After drug withdrawal or symptomatic treatment, liver function recovered, and the mean recovery time was (21.45±6.94) d. Multivariate logistic regression analysis found female gender [odds rotio (OR)=2.36, 95% confidence interval (CI)=1.11-4.99], history of comorbid liver disease (OR=2.62, 95%CI=1.10-6.24), and liver metastasis (OR=3.10, 95%CI=1.28-7.49) as independent risk factors influencing the occurrence of liver injury in tumor patients (all P<0.05). ROC analysis showed that the area under curve (AUC) (95%CI) of the nomogram prediction model for predicting liver injury was 0.86 (0.82-0.90), with sensitivity of 78.38% and specificity of 83.52%. Hosmer-Lemeshow test showed good goodness-of-fit (χ2=12.58, P>0.05). Validation with Bootstrap revealed good agreement between the calibration curve and the actual curve (Brier score=0.09). DCA demonstrated that the nomogram prediction model provided clinical benefit when the threshold was between 0.05 and 0.99.
PD-1 inhibitor-induced liver injury is relatively common in tumor patients. Female gender, history of liver disease and liver metastasis are associated with its occurrence. The nomogram prediction model constructed based on these factors exhibits good predictive performance and can provide reference for early identification of high-risk patients.
To investigate the effect and mechanism of liraglutide on cisplatin-induced acute kidney injury in renal tubular epithelial (HK-2) cells.
HK-2 cells were randomly divided into control group, model group and experimental group. The control group was cultured conventionally, the model group was treated with 20 μmol·L-1 cisplatin reagent for 48 hours, and the experimental group was treated with 100 nM liraglutide reagent in addition to the model group for 48 hours. Cell proliferation activity was detected by cell counting kit-8 (CCK-8) method. Western blot was used to detect cysteine-aspartic acid protease 3 (Caspase 3), cleaved cysteine-aspartic acid protease 3(C-Caspase3), B cell lymphoma-2 (Bcl-2) associated X protein (BAX), nuclear factor E2 related factor 2 (Nrf-2), superoxide dismutase 2 (SOD2), heme oxygenase-1 (HO-1) and reference β-actin protein relative expression levels; the relative expression levels of kidney injury molecule-1 (Kim-1), BAX and Bcl-2 related messenger ribonucleic acid (mRNA) were detected by real-time fluorescent quantitative polymerase chain reaction, and cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dutP nick end labeling (TUNEL). Reactive oxygen species (ROS) levels were measured by superoxide anion fluorescent probe (DHE).
CCK-8 assay showed that 100 nmol·L-1 was the optimal intervention concentration of liraglutide. After 48 hours of intervention, the relative expression levels of K1M-1 mRNA in control group, model group and experimental group were 0.98±0.25, 56.23±23.25 and 2.61±0.79, respectively; BAX /Bcl-2 mRNA relative expression levels were 1.01±0.08, 15.47±3.01 and 5.41±0.54, respectively; the apoptosis rates were (5.60±0.40)%, (40.00±4.79)% and (6.40±0.87)%, respectively; the fluores cence value of positive rates of DHE were 1.95±0.03, 3.01±0.28 and 1.51±0.13, respectively; the relative expression levels of Nrf-2 protein were 0.80±0.01, 0.47±0.01 and 0.68±0.02, respectively; the relative expression levels of SOD2 protein were 0.96±0.04, 0.57±0.28 and 0.91±0.04, respectively; the relative expression levels of HO-1 were 1.01±0.08, 0.47±0.05 and 1.56±0.18, respectively. There were statistically significant differences in the above indicators between model group and control group, and between experimental group and model group (P<0.05, P<0.01, P<0.001, P<0.000 1).
Liraglutide can reduce the apoptosis rate and oxidative stress level of renal tubular epithelial cells in cisplatin-induced acute kidney injury, and increase the level of superoxide.
To investigate the effects and mechanism of naringenin inhibiting the non-receptor tyrosine kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway on the proliferation and apoptosis of esophageal cancer cells.
The effects of different doses of naringenin on KYSE150 cell viability was screened using cell counting kit-8 (CCK-8), and naringenin concentration was selected. KYSE150 cells were sequentially divided into control group (conventional culture), low-dose experimental group (10 μmol·L-1 naringenin), high-dose experimental group (40 μmol·L-1 naringenin), JAK2/STAT3 pathway inhibitor group (20 μmol·L-1 AG490) and JAK2/STAT3 pathway activator group (40 μmol·L-1 naringenin and 10 μmol·L-1 coumermycin A1). The 5-bromo-2 ’- deoxyuridine (Brdu) positive cell rate was detected using the Brdu staining method, the number of cell clones formed was detected using the clone formation assay, the expression of proliferation and apoptosis related genes was detected using reverse transcription real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), the apoptosis rate was detected using flow cytometry, the terminal deoxynucleotide transferase mediated 2’-deoxyuridine-5’- triphosphate notch end labeling (TUNEL) positive rate was detected using the TUNEL staining method, the expression of JAK2/STAT3 pathway related proteins was detected using Western blot, and the effect of naringenin on the growth of KYSE150 xenograft tumors Ki-67 nuclear antigen (Ki67) and tumor tissues growth in nude mice was detected using immunohistochemistry.
The half maximal inhibitory concentration of naringenin on KYSE150 cell viability is close to 40 μmol·L-1. The Brdu positivity rates of KYSE150 cells in control group, low-dose experimental group, high-dose experimental group, JAK2/STAT3 pathway inhibitor group and JAK2/STAT3 pathway activator group were (58.64±5.23)%, (46.23±4.05)%, (21.05±3.04)%, (23.62±3.15)% and (35.98±3.21)%, respectively; the clone formation numbers were (102.36±10.25), (78.64±7.21), (50.05±4.32), (52.39±5.03) and (61.55±5.12) cells, respectively; the relative expression levels of CyclinB1 messenger ribonucleic aeid (mRNA) were 1.02±0.11, 0.74±0.05, 0.45±0.04, 0.48±0.05 and 0.62±0.06, respectively; the relative expression levels of cyclin dependent kinase 1 (CDK1) mRNA were 1.03±0.07, 0.62±0.05, 0.27±0.03, 0.30±0.04 and 0.51±0.04, respectively; the apoptosis rates were (4.15±0.42)%, (15.62±1.02)%, (29.65±2.03)%, (27.84±1.98)% and (19.66±1.20)%, respectively; the positive rates of TUNEL were (8.65±0.82)%, (20.64±2.03)%, (37.68±3.05)%, (35.62±2.16)% and (28.14±2.01)%, respectively; the relative expression levels of Bcl-xl mRNA were 1.02±0.07, 0.72±0.06, 0.41±0.04, 0.44±0.05 and 0.59±0.05, respectively; the relative expression levels of Bcl-2 mRNA were 1.01±0.05, 0.59±0.04, 0.36±0.03, 0.39±0.04 and 0.50±0.03, respectively. Compared control group with low-dose experimental group, high-dose experimental group and JAK2/STAT3 pathway inhibitor group, compared low-dose experimental group with high-dose experimental group and JAK2/STAT3 pathway inhibitor group, compared high-dose experimental group with JAK2/STAT3 pathway activator group, the above indicators all showed statistically significant differences (all P<0.05). In nude mouse experiments, the tumor volumes of animal control group, animal low-dose experimental group and animal high-dose experimental group were (1 287.65±98.54), (821.22±71.65) and (425.39±37.69) mm3, respectively; the tumor masses were (1.85±0.12), (1.20±0.09) and (0.73±0.05) g, respectively; the Ki67 positivity rates in tumor tissues were (69.52±5.36)%, (44.35±3.12)% and (20.06±2.85)%, respectively. The above indicators of the animal low and high-dose experimental groups were statistically significantly different from those of animal control group, and the above indicators of the animal high-dose experimental group were statistically significantly different from those of animal low-dose experimental group (all P<0.05).
Naringenin clearly inhibits the proliferation and promotes apoptosis of esophageal cancer KYSE150 cells by suppressing the JAK2/STAT3 signaling pathway.
To investigate the mechanism of esketamine (Esk) ameliorating postpartum depression (PPD)-like behaviors in mice by regulating the two pore domain potassium channel (TWIK)-related K+ channel 1(TREK-1) to activate the brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) pathway, and to provide experimental evidence for clarifying the pathogenesis of PPD and developing novel targeted therapeutic strategies.
A total of 50 C57BL/6J pregnant mice were randomly divided into five groups (n=10 per group): control group, model group, experimental group, oe-NC group and oe-TREK-1 group. A PPD model was established in pregnant mice using the chronic unpredictable mild stress (CUMS) method. The control group was given an equal volume of normal saline; the model group was given normal saline after CUMS modeling; the experimental group was intraperitoneally injected with Esk (5 mg·kg-1) once daily for 3 weeks after modeling; the oe-NC group was injected with lentivirus-encapsulated oe-NC by the tail vein before modeling and subsequent Esk administration; the oe-TREK-1 group was injected with lentivirus-encapsulated oe-TREK-1 by the tail vein before modeling and subsequent Esk administration. Depressive-like behaviors were evaluated using the sucrose preference test (SPT) and tail suspension test (TST). Hematoxylin-eosin (HE) staining and Nissl staining were used to observe the pathological morphology of hippocampal tissue; real-time fluorescent quantitative polymerase chain reaction and Western blotting were employed to detect the relative expression levels of TREK-1 in hippocampal tissue; enzyme-linked immunosorbent assay was utilized to measure the expression levels of serum sex hormones; immunohistochemistry was adopted to detect the expression of microglial marker proteins; Western blotting was used to determine the relative expression levels of endoplasmic reticulum stress-related proteins; immunofluorescence was applied to detect the relative expression levels of brain-derived neurotrophic factor (BDNF) and tyrosine protein kinase B (TrkB).
The sucrose preference rates in the control, model, experimental, oe-NC and oe-TREK-1 groups were (84.74±14.46)%, (19.08±2.86)%, (79.62±12.54)%, (80.15±11.38)% and (52.44±8.15)%, respectively; the immobility time ratios in the tail suspension test were (31.16±4.63)%, (75.38±14.62)%, (49.26±8.59)%, (48.97±7.82)% and (62.53±9.24)%, respectively; the relative expression levels of TREK-1 mRNA in the hippocampal tissues were 1.00±0.15, 2.87±0.45, 1.55±0.21, 1.56±0.19 and 2.18±0.36, respectively; the relative expression levels of TREK-1 protein were 1.00±0.16, 2.75±0.38, 1.86±0.27, 1.84±0.19 and 2.44±0.34, respectively; serum estradiol (E2) levels were (1 263.55±152.77), (638.16±78.32), (985.24±107.48), (981.67±106.34) and (752.33±116.45) pg·mL-1, respectively; progesterone (P) levels were (9.53±1.06), (3.48±0.59), (8.54±1.07), (8.47±1.04) and (5.62±1.02) ng·mL-1, respectively; prolactin (PRL) levels were (15.98±2.19), (29.31±4.62), (19.25±2.58), (19.88±2.67) and (23.47±3.46) ng·mL-1, respectively; the relative expression levels of Iba-1 protein in the hippocampus were 1.00±0.16, 0.35±0.05, 0.87±0.14, 0.85±0.13 and 0.61±0.11, respectively; the relative expression levels of GRP78 protein were 1.00±0.17, 1.58±0.16, 1.17±0.14, 1.09±0.18 and 1.35±0.17, respectively; the relative expression levels of CHOP protein were 1.00±0.14, 1.71±0.23, 1.13±0.16, 1.11±0.12 and 1.34±0.18, respectively; the relative expression levels of Cleaved caspase-12 protein were 1.00±0.16, 1.45±0.19, 1.19±0.13, 1.16±0.12 and 1.38±0.16, respectively; the relative fluorescence intensities of BDNF were 1.00±0.16, 0.38±0.06, 0.84±0.09, 0.83±0.11 and 0.64±0.08, respectively; the relative fluorescence intensities of TrkB were 1.00±0.17, 0.57±0.09, 0.92±0.14, 0.91±0.12 and 0.75±0.11, respectively. Statistically significant differences were observed in the above indicators between the model group and the control group, between the experimental group and the model group, and between the oe-TREK-1 group and the oe-NC group (P<0.05, P<0.01, P<0.001).
Esketamine can alleviate PPD-like behaviors in mice by inhibiting TREK-1 expression, regulating sex hormone balance, improving microglial function and endoplasmic reticulum stress, and thereby activating the BDNF/TrkB pathway.
To investigate the potential targets and pathways of eupalinolide B (EB) in doxorubicin (DOX)-induced dilated cardiomyopathy (DCM), and to verify EB inhibits cardiomyocyte apoptosis and inflammatory response by regulating the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway.
Database screening was used to identify the intersecting targets of EB and DCM, followed by functional and pathway enrichment analyses and molecular docking validation. A DCM mouse model was established. The successfully modeled mice were randomly divided into model group, experimental-L group (5 mg·kg-1 EB), experimental-H group (20 mg·kg-1 EB), positive control group (5 mg·kg-1 positive drug captopril), inhibitor group (1 mg·kg-1 p38 MAPK inhibitor SB203580) and activator group (20 mg·kg-1 EB+0.10 mg·kg-1 p38 MAPK activator anisomycin). In addition, normal and healthy mice were selected as the blank group. Each group had 10 mice. After the intervention, cardiac function was detected by echocardiography; serum and myocardial tissues were collected, serum inflammatory factors and myocardial injury markers were measured by enzyme-linked immunosorbent assay (ELISA); pathological damage, fibrosis and cell apoptosis of myocardial tissue were detected by hematoxylin and eosin (HE) staining, Masson staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining; the expression of apoptosis-related proteins, inflammatory factors, phosphorylation (p-)p38 MAPK and p38 MAPK in myocardial tissue was detected by immunohistochemistry and Western blot.
A total of 34 potential targets of EB and 1 018 DCM-specific targets were screened, and 5 potential targets of EB for DCM treatment were identified, involving the MAPK signaling pathway. The left ventricular fractional shortening (LVFS) values in blank group, model group, experimental-L group, experimental-H group, inhibitor group and activator group were (41.26±0.07)%, (26.60±0.72)%, (30.90±0.29)%, (44.26±1.73)%, (42.62±1.82)% and (33.66±2.74)%, respectively; the N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were (734.85±90.24), (1 509.28±163.17), (1 240.62±157.95), (841.57±88.06), (862.91±87.92) and (1 159.76±125.71) pg·mL-1, respectively; the B-cell lymphoma-2 (Bcl-2) positive rates were (16.81±1.82)%, (3.02±0.54)%, (6.97±0.86)%, (14.29±1.43)%, (13.51±1.46)% and (8.14±0.95)%, respectively; the Bcl-2-associated X protein (Bax) positive rates were (1.59±0.18)%, (18.37±2.51)%, (12.42±1.63)%, (3.84±0.45)%, (4.09±0.41)% and (11.53±1.28)%, respectively; the relative expression levels of p-p38 MAPK/p38 MAPK were 0.23±0.03, 0.86±0.09, 0.64±0.08, 0.35±0.04, 0.38±0.05 and 0.61±0.08, respectively. Comparisons between model group and blank group, between experimental-L/-H groups or inhibitor group and model group, and between activator groups and experimental-H group, the above indicators all showed statistically significant differences (all P<0.05).
EB may alleviate the myocardial inflammatory response and cardiomyocyte apoptosis in DOX-induced cardiomyopathy mice and improve myocardial damage by inhibiting the phosphorylation of p38 MAPK.
To discuss the effects of osthol (Ost) on melanocyte loss in vitiligo mice by regulating the Wnt/β-catenin signaling pathway.
A mouse model of vitiligo was established by applying hydroquinone cream. The successfully modeled mice were divided into model group (only modeling), low-dose experimental group (15 mg·kg-1 Ost), high-dose experimental group (45 mg·kg-1 Ost), positive control group (50.4 mg·mL-1 vitiligo capsules) and inhibitor group (45 mg·kg-1 Ost + 10 mg·kg-1 XAV939). The control group was given an equal volume of normal saline. Each group consisted of 10 mice. After the intervention, the degree of skin depigmentation in the treatment area was scored; orbital blood was collected, and the levels of malondialdehyde (MDA), α-melanocyte-stimulating hormone (α-MSH), tyrosinase (TYR) and tumor necrosis factor-α (TNF-α) in the serum were detected by enzyme-linked immunosorbent assay (ELISA); skin lesion tissues were collected, and the number of melanin-containing hair follicles and melanocytes in the basal layer were evaluated by hematoxylin-eosin (HE) and Masson staining; the positive expression levels of tyrosinase-related protein (TRP) 1 and TRP2 in the skin lesion tissues was detected by immunohistochemistry; the mRNA expression levels of tyrosinase (TYR) and microphthalmia-associated transcription factor (MITF) mRNA in the skin lesion tissues were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction (qRT-PCR); the protein expression levels of β-catenin and phosphorylated glycogen synthase kinase-3β (p-GSK-3β)/GSK-3β in the skin lesion tissues were detected by Western blotting.
The depigmentation scores of control group, model group, low-dose experimental group, high-dose experimental group, positive control group and inhibitor group were (0±0), (4.11±0.52), (2.41±0.28), (0.77±0.09), (0.55±0.07) and (2.55±0.28) score, respectively; the levels of α-MSH were (26.53±2.84), (7.56±0.84), (12.62±1.36), (22.91±2.44), (23.51±2.48) and (13.05±1.38) μg·L-1, respectively; the levels of MDA were (2.05±0.24), (7.94±0.85), (4.31±0.49), (2.27±0.25), (2.19±0.24) and (4.28±0.45) nmol·mg prot-1, respectively; the levels of TNF-α were (38.52±4.02), (105.65±10.94), (68.84±7.05), (42.84±4.45), (41.85±4.37) and (70.05±7.21) ng·mL-1, respectively; the levels of TYR were (105.62±11.14), (45.22±4.67), (65.41±6.77), (98.62±9.98), (97.65±9.89) and (66.08±6.81) μg·L-1, respectively; the numbers of melanocytes in the basal layer were (148.62±15.08), (52.11±5.34), (68.84±6.91), (108.64±11.14), (112.08±11.44) and (70.54±7.21) cells, respectively; the numbers of melanin-containing hair follicles were (98.64±9.98), (41.52±4.31), (62.05±6.37), (95.62±9.74), (96.05±9.78) and (61.08±6.29) cells, respectively; the positive expression levels of TRP1 were 17.05±1.94, 4.62±0.77, 8.05±0.85, 14.98±1.58, 15.22±1.64 and 8.11±0.88, respectively; the positive expressions levels of TRP2 were 14.32±1.55, 3.05±0.33, 5.74±0.66, 10.42±1.15, 11.05±1.17 and 6.05±0.62, respectively; the relative expression levels of TYR mRNA were 1.09±0.12, 0.19±0.02, 0.49±0.05, 0.79±0.08, 0.88±0.09 and 0.55±0.07, respectively; the relative expression levels of MITF mRNA were 0.98±0.11, 0.24±0.03, 0.44±0.05, 0.81±0.09, 0.85±0.10 and 0.51±0.06, respectively; the relative expression levels of β-catenin were 1.25±0.13, 0.34±0.05, 0.68±0.08, 1.07±0.11, 1.11±0.12 and 0.71±0.09, respectively; the relative expression levels of p-GSK-3β/GSK-3β were 0.85±0.09, 0.22±0.03, 0.44±0.06, 0.71±0.08, 0.79±0.09 and 0.42±0.05, respectively. There were statistically significant differences between model group and control group, between low, high dose experimental group and model group, and between inhibitor group and high-dose experimental group (all P<0.05).
Ost reduces melanocyte loss in vitiligo mice by activating the Wnt/β-catenin signaling pathway.
To investigate the effect and mechanism of dihydroartemisinin (DHA) on ferroptosis in cervical cancer by the microRNA (miRNA)-346/Kruppel-like factor 14 (KLF14) axis.
In cell experiment, human cervical cancer Hela cells were treated and divided into several groups including cell normal control group (only HcerEpic cell), cell negative control group (only Hela cell), cell experimental group (Hela cell treated with 246.90 μmol·L-1 DHA for 48 h), DHA+mimic NC group (transferred with mimic NC based on the cell experimental group), DHA+miR-346 mimic group (transfected with miRNA-346 mimic based on the cell experimental group), DHA+sh-NC group (transfected with sh-NC based on the cell experimental group) and DHA+sh-KLF14 group (transfected with sh-KLF14 based on the cell experimental group). In animal experiment, a xenograft tumor model was established by subcutaneous injection of Hela cells into 30 female BALB/c nude mice, which were then divided into the animal control group (gavaged with saline), animal experimental-L group (gavaged with 100 mg·kg-1 DHA) and animal experimental-H group (gavaged with 200 mg·kg-1 DHA), with 10 mice in each group. The relative expression level of miRNA-346 was detected by quantitative real-time polymerase chain reaction. The relative expression levels of KLF14 protein, glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) were measured by Western blot. Intracellular Fe2+ levels were detected using FerroOrange fluorescent probe. The apoptosis rate was determined by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay.
In cell experiment, the relative expression levels of miRNA-346 in the cell negative group and cell experimental group were 1.00±0.18 and 0.42±0.06, respectively; the relative expression levels of KLF14 mRNA were 1.00±0.17 and 2.22±0.32, respectively; the relative expression levels of KLF14 protein were 1.00±0.15 and 1.72±0.23, respectively; the relative fluorescence intensities of Fe2+ of cell negative control group, cell experimental group, DHA+mimic NC group, DHA+miRNA-346 mimic group, DHA+sh-NC group and DHA+sh-KLF14 group were 1.00±0.15, 4.86±0.81, 4.32±0.62, 3.12±0.57, 4.23±0.59 and 2.02±0.33, respectively; the relative expression levels of GPX4 protein were 1.00±0.17, 0.45±0.06, 0.48±0.07, 0.78±0.11, 0.44±0.06 and 0.59±0.08, respectively; the relative expression levels of SLC7A11 protein were 1.00±0.12, 0.37±0.05, 0.35±0.04, 0.86±0.12, 0.40±0.07 and 0.77±0.10, respectively; the cell proliferation rates were (100.00±3.65)%, (54.32±7.65)%, (56.32±8.02)%, (72.33±8.65)%, (52.32±9.23)% and (88.25±10.35)%, respectively; the apoptosis rates were (14.32±1.61)%, (61.33±8.25)%, (57.32±7.13)%, (32.44±5.37)%, (59.63±8.98)% and (23.88±3.49)%, respectively. Significant differences were observed in the aforementioned parameters when comparing the cell experimental group with the cell negative group, comparing the DHA + miRNA-346 mimic group with the DHA + mimic NC group, and comparing the DHA + sh-KLF14 group with the DHA + sh-NC group (P<0.01,P<0.001). In animal group, the tumor volumes in the animal control, experimental-L and experimental-H groups were (542.36±92.33), (402.85±92.28) and (295.52±60.56) mm3, respectively; the tumor masses were (1.55±0.33), (1.22±0.22) and(0.88±0.15)g, respectively; the relative positive levels of GPX4 were 1.00±0.18, 0.55±0.07 and 0.42±0.04, respectively; the relative positive levels of SLC7A11 were 1.00±0.16, 0.48±0.06 and 0.29±0.03, respectively. Significant differences were also detected between the animal experimenal-L, -H group and the animal control group (P<0.05, P<0.01, P<0.001).
DHA promotes ferroptosis in cervical cancer by the miRNA-346/KLF14 axis-mediated GPX4 signaling pathway.
To analyze the rationality of outpatient and emergency nebulization medication prescriptions in a tertiary pediatric specialty hospital based on the hospital’s rational drug use system, identify the main types, distribution characteristics, influencing factors of irrational prescriptions, and provide evidence for standardizing clinical medication use.
All outpatient and emergency prescriptions containing nebulized drugs from January to December 2024 were collected. Prescriptions were initially screened using the Puhua Hecheng rational drug use system, followed by manual review by pharmacists according to standards such as the "clinical practice guidelines for nebulized inhalation therapy in pediatric respiratory diseases (2024 edition)". A retrospective analysis was conducted on irrational prescriptions.
A total of 233 736 prescriptions were included. Initial screening identified 8 569 positive irrational prescriptions, and after review, 3 681 were confirmed as true positive irrational prescriptions, resulting in an overall irrationality rate of 1.57% (3 681 prescriptions/233 736 prescriptions). Irrational prescriptions were mainly from outpatient departments 70.33% (2 589 prescriptions/3 681 prescriptions), with emergency departments accounting for 29.67% (1 092 prescriptions/3 681 prescriptions). School-age children (36.00%, 1 325 prescriptions/3 681 prescriptions) and preschool children (35.51%, 1 307 prescriptions/3 681 prescriptions) were the high-risk groups. The departmental distribution showed a "long-tail distribution," with the top 10 departments accounting for 60.69% (2 234 prescriptions/3 681 prescriptions), primarily the respiratory center, gastroenterology department, and internal medicine teaching and research department. Among irrational prescription types, inappropriate indication was the most common (86.80%, 3 853 cases/4 439 cases), followed by inappropriate usage and dosage (9.89%,439 cases/4 439 cases), duplicate medication (1.85%, 82 cases/4 439 cases) and inappropriate route of administration (1.46%, 65 cases/4 439 cases). Among medication categories, inhaled corticosteroids (71.13%, 3 065 cases/4 309 cases) had the highest incidence of issues, with budesonide suspension for inhalation accounting for 60.43% (2 604 cases/4 309 cases), followed by bronchodilators, with ipratropium bromide solution for inhalation accounting for 23.25% (1 002 cases/4 309 cases).
The overall rationality of nebulized drug prescriptions in the outpatient and emergency departments of the hospital is favorable. Irrational medication issues are dominated by inappropriate indications, mainly concentrated in young children and departments with high-frequency use of nebulized drugs. To improve the rationality of clinical medication, a full-process management system of "prevention-control-optimization" should be established by strengthening guideline training, optimizing audit rules of the rational drug use system, and enhancing targeted management in key departments.
Heart failure (HF) refers to a clinical syndrome caused by structural or functional cardiac disorders that impair ventricular filling and/or ejection function, resulting in insufficient cardiac output to meet the metabolic demands of bodily tissues. Its clinical manifestations include congestion in the pulmonary and/or systemic circulation, as well as inadequate blood perfusion to organs and tissues. As the terminal stage of various cardiovascular diseases, HF ranks among the leading causes of death for urban and rural residents in China. microRNA (miRNA) is a class of endogenous non-coding single-stranded ribonucleic acids (RNAs) that regulate gene expression at the post-transcriptional level. They are involved in multiple pathological processes of HF, such as myocardial remodeling, cell death, energy metabolism and inflammatory immunity, thus exhibit potential as therapeutic targets for the disease. Traditional Chinese medicine (TCM), characterized by multi-targeted and multi-pathway actions, has shown unique advantages in the prevention and treatment of HF by modulating miRNAs. This article reviews the recent research status on miRNA-mediated regulation of HF and the mechanisms underlying TCM interventions, with the aim of providing insights for subsequent HF-related studies.
Diabetic kidney disease (DKD) is the most common and severe microvascular complication in clinical practice and one of the main causes for diabetic patients to develop chronic kidney disease and end-stage renal disease. The pathogenesis of this disease involves the combined effects of multiple factors, such as genetic factors, dysregulation of glucose and lipid metabolism, changes in renal hemodynamics, inflammatory responses and oxidative stress, among others. Among these, oxidative stress is the core process in the occurrence and development of DKD. The nuclear transcription factor E2-related factor (Nrf2) is an important regulatory factor for antioxidant stress transcription. Activating Nrf2 can stimulate the expression of downstream heme oxygenase-1 (HO-1), thereby widely participating in various biological processes such as regulating oxidative stress, reducing inflammatory responses and inhibiting cell apoptosis in the body. Recent studies have shown that the Nrf2/HO-1 signaling pathway is involved in the occurrence, development and drug intervention process of DKD. Traditional Chinese medicine (TCM) has the characteristics of multi-target, multi-pathway and multi-level, and the advantages of synergism and attenuation, showing unique advantages in making up for the shortcomings of modern medicine. However, there is still a lack of systematic summary of the mechanism of this pathway in the prevention and treatment of DKD and the research progress of traditional Chinese medicine. In this paper, the biological function and activation process of Nrf2/HO-1 pathway, the relationship between Nrf2/HO-1 pathway and DKD, the related research of traditional Chinese medicine to improve DKD by targeting the pathway in recent years, the treatment strategy of integrated traditional Chinese and western medicine, and the future research direction were systematically reviewed, in order to provide theoretical reference for the clinical treatment and drug development of DKD.
Cerebral ischemia-reperfusion injury (CIRI) refers to a secondary neurological injury that occurs after blood flow is restored in patients with ischemic stroke, and its pathological process involves inflammatory cascade imbalance, mitochondrial energy metabolism disorders, calcium ion overload and oxidative stress, which significantly affects the recovery of postoperative neurological function. In recent years, studies have shown that a variety of commonly used anesthetic drugs such as sevoflurane, propofol and dexmedetomidine can exert neuroprotective effects in the perioperative period through multi-target and pathway-specific mechanisms, thereby effectively alleviating CIRI. This paper summarizes the pathway and clinical application evidence of anesthetic drugs on neuroinflammation, energy metabolism, cell death and other pathways to alleviate CIRI, aiming to provide theoretical basis and research ideas for the optimization of clinical anesthesia regimens and the formulation of neuroprotective regimens.
To analyze the application effect of the intelligent management system for clinical trial drugs.
Based on the overall architecture established for the intelligent module and the management of experimental drugs, we compared the error rates of monthly prescriptions and recovery forms from 2024 to 2025, as well as the error rates of annual prescriptions and recovery forms from 2024 to 2025.
The prescription error rates for January 2024 and 2025 were 33.33% (4 prescriptions/12 prescriptions) and 0% (0 prescriptions/19 prescriptions), respectively; for May, they were 30.00% (6 prescriptions/20 prescriptions) and 5.56% (2 prescriptions/36 prescriptions), respectively; for June, they were 36.00% (9 prescriptions/25 prescriptions) and 3.21% (6 prescriptions/187 prescriptions), respectively; for July, they were 23.91% (11 prescriptions/46 prescriptions) and 5.14% (9 prescriptions/175 prescriptions), respectively; for August, they were 10.71% (6 prescriptions/56 prescriptions) and 1.82% (3 prescriptions/165 prescriptions), respectively; for September, they were 10.20% (10 prescriptions/98 prescriptions) and 2.84% (5 prescriptions/176 prescriptions), respectively; for October, they were 13.21% (7 prescriptions/53 prescriptions) and 2.70% (2 prescriptions/74 prescriptions), respectively; for December, they were 12.50% (6 prescriptions/48 prescriptions) and 3.02% (13 prescriptions/430 prescriptions), respectively. The above indicators were statistically significant differences between the two groups (P<0.05, P<0.01). The prescription error rates for the years 2024-2025 were 12.41% (82 prescriptions/661 prescriptions) and 3.38% (60 prescriptions/1 777 prescriptions), respectively, showing a downward trend, and there were statistically significant differences between the two groups(P<0.000 1). The overall error rate of the collected forms decreased, but differences were not statistically significant (P>0.05).
The intelligent management system can improve the efficiency and accuracy of drug management, and it is recommended to further optimize the recovery process.