To explore the clinical efficacy and safety of tiotropium bromide powder for inhalation combined with salmeterol xinafoate powder for inhalation in patients with stable chronic obstructive pulmonary disease (COPD).

Patients with stable COPD in our hospital were divided into control group and experimental group by random number table method. The control group was given salmeterol fluticasone inhalation powder, 1 inhalations per time, twice a day; the treatment group was additionally treated with tiotropium bromide powder for inhalation, 1 tablet per time, once a day. Both groups were treated continuously for 8 weeks. The clinical efficacy, forced vital capacity, respiratory condition, serum elafin level, and adverse drug reactions were compared between the two groups.

A total of 102 patients were enrolled. There were 51 cases in each group. Throughout the treatment period, 2 participants in the control group were lost to follow-up, and 1 case in the treatment group withdrew due to withdrawal of informed consent. Ultimately, control group had 49 cases and treatment group had 50 cases. After treatment, the treatment group (92.00%, 46 cases/50 cases) exhibited a superior total clinical effective rate (75.51%, 37 cases/49 cases), respectively; and the difference was statistically significant (P<0.05). After treatment, the percentage of predicted value (FEV₁%) in the treatment group and the control group was (57.64±5.88)% and (54.78±5.61)%, respectively; FVC was (2.58±0.40) and (2.14±0.32) L, respectively; peak expiratory flow rate (PEF) was (1.43±0.31) and (1.31±0.21) L·s^-1, respectively; the treatment group showed significantly higher levels of the above indicators compared with the control group (all P<0.05). After treatment, the modified British Medical Research Council respiratory questionnaire (mMRC) scores of the treatment group and the control group were (1.05±0.11) and (1.15±0.18) points, respectively; The serum elafin levels of the treatment group and the control group were (10.28±1.95) and (9.34±1.20) pg·mL^-1, respectively; the secretory leukocyte protease inhibitor (SLPI) levels were (56.39±6.54) and (52.15±6.04) ng·mL^-1, respectively; the levels of growth differentiation factor-15 (GDF-15) were (867.44±108.50) and (930.16±121.39) ng·mL^-1, respectively; there were statistically significant differences in the above indicators between the two groups(all P<0.05). In the treatment group, adverse drug reactions such as arrhythmia, gastrointestinal reactions, and joint pain, while those in the control group included arrhythmia, gastrointestinal reactions, joint pain, and dry mouth. The total incidence rates of adverse drug reactions in the treatment group and the control group were 22.00% (11 cases/50 cases) and 26.53% (13 cases/49 cases), respectively; there was no statistically significant difference between the two groups (P>0.05).

Tiotropium bromide power for inhalation combined with salmeterol fluticasone power for inhalation has outstanding efficacy in the treatment of stable COPD, which can improve forced vital capacity, respiratory status and elafin level, and has a good safety profile.

To investigate the effects of intranasal dexmedetomidine hydrochloride nasal spray combined with lidocaine aerosol on anesthesia induction compliance, hemodynamics, stress response, and postoperative outcomes in children undergoing general anesthesia for adenoidectomy.

The pediatric patients who underwent adenoidectomy were divided into control group and treatment group based on their preoperative anesthesia protocol. Pediatric patients in the control group received intranasal dexmedetomidine hydrochloride nasal spray 2 μg·kg^-1 30 minutes before surgery. The control group received intranasal dexmedetomidine, while the treatment group received intranasal dexmedetomidine hydrochloride nasal spray 2 μg·kg^-1 combined with lidocaine aerosol 2 mg·kg^-1 30 minutes before surgery. A comparison was made between the two groups regarding preoperative anxiety, induction compliance, hemodynamic parameters, stress response markers, emergence agitation and pain, anesthesia recovery indices, and length of hospital stay, along with the incidence of adverse reactions.

A total of 82 pediatric patients were enrolled, with 39 cases in control group and 43 cases in treatment group. At anesthesia induction, the modified Yale Preoperative Anxiety Scale (m-YPAS) scores in the control and treatment groups were (26.56±5.13) and (23.14±4.91) points, respectively; the induction compliance checklist (ICC) scores were (0.81±0.26) and (0.69±0.12) points, respectively; the anesthesia induction time were (5.16±1.28) and (4.48±1.01) min, respectively. At T1, the heart rates (HR) in the control and experimental groups were (94.37±8.63) and (90.15±8.82) beats·min^-1, respectively, and the mean arterial pressures (MAP) were (72.63±5.81) and (69.58±5.75) mmHg, respectively; at T2, the HR values were (101.26±10.76) and (95.87±10.35) time·min^-1, respectively, and the MAP values were (78.94±7.44) and (74.23±6.72) mmHg, respectively; at T4, the HR values were (98.58±10.08) and (94.13±9.14) beats·min^-1, respectively, and the MAP values were (77.85±7.24) and (73.92±6.98) mmHg, respectively. Postoperative day 1, the serum cortisol (Cor) levels in the control and experimental groups were (331.67±48.47) and (309.42±45.87) ng·mL^-1, respectively; serotonin (5-HT) levels were (1.54±0.33) and (1.37±0.29) μmol·L^-1, respectively; norepinephrine (NE) levels were (195.73±20.35) and (184.67±21.42) ng·L^-1, respectively; glutamate (Glu) levels were (5.62±0.87) and (5.15±0.82) mmol·L^-1, respectively. At 30 minutes after extubation, the pediatric anesthesia emergence delirium scale (PAED) scores in the control and treatment groups were (4.06±1.37) and (3.28±1.13) points, respectively; the Face, Legs, Activity, Cry, Consolability Scale (FLACC) scores were (3.24±0.85) and (2.79±0.74) points, respectively; and the incidence of emergence agitation was 20.51% (8 cases/39 cases) and 4.65% (2 cases/43 cases), respectively. The comparisons of the above indicators showed statistically significant differences (all P<0.05). The adverse drug reactions in the control group and the experimental group mainly included cough, nausea and vomiting, laryngospasm, and bradycardia and the total incidence of adverse events was 12.82% (5 cases/39 cases) and 9.30% (4 cases/43 cases), respectively (P>0.05).

The intranasal administration of dexmedetomidine hydrochloride nasal spray combined with lidocaine aerosol for general anesthesia in pediatric adenoidectomy effectively alleviates preoperative anxiety, improves cooperation during induction, maintains hemodynamic stability, reduces surgical stress response, and decreases the incidence of emergence agitation and postoperative pain, with a good safety profile, demonstrating significant clinical promotion value.

To explore the clinical efficacy and safety of losartan potassium and hydrochlorothiazide tablets in the treatment of male patients with H-type hypertension complicated with osteoporosis.

Male patients with H-type hypertension complicated with osteoporosis were prospectively and randomly divided into control group and treatment group according to the random number table method. Both groups received conventional basic treatment. The control group was given amlodipine tablets on the basis of basic treatment, with an initial dose of 5 mg once a day (qd). If the blood pressure was not controlled after 2 to 4 weeks of treatment, the dose was adjusted to 10 mg qd. The treatment group was given losartan potassium and hydrochlorothiazide tablets on the basis of basic treatment, with an initial dose of 1 tablet qd. If the blood pressure was not controlled after 2 to 4 weeks of treatment, the dose was adjusted to 2 tablets qd. Both groups were treated for 12 weeks. The blood pressure efficacy, blood pressure monitoring, serum homocysteine (Hcy), cystatin C (CysC), folic acid, bone mineral density, bone metabolism indicators, and inflammatory indicators of the two groups were compared, and safety was evaluated.

A total of 88 patients were included, with 44 patients in the treatment group and 44 patients in the control group. The total effective rates of the treatment group and the control group were 90.91% (40 cases/44 cases) and 86.36% (38 cases/44 cases), respectively (P>0.05). After treatment, the Hcy levels of the treatment group and the control group were (9.28±2.13) and (10.94±2.40) μmol·L^-1, respectively; the CysC levels were (1.24±0.33) and (1.41±0.28) mg·L^-1, respectively; the folic acid levels in the treatment group and control group were (17.64±2.41) and (16.51±2.82) μg·L^-1, the type I collagen C-terminal telopeptide levels were (0.69±0.10) and (0.73±0.11) μg·L^-1, respectively; the osteocalcin levels were (20.81±3.67) and (19.11±2.64) μg·L^-1, respectively; the bone-specific alkaline phosphatase levels were (17.85±2.68) and (16.62±3.03) μg·L^-1, respectively; the alkaline phosphatase levels were (102.56±16.80) and (95.10±16.07) U·L^-1, respectively; the high-sensitivity C-reactive protein levels were (10.45±1.31) and (11.64±1.82) mg·L^-1, respectively; the matrix metalloproteinase-2 levels were (296.23±33.59) and (319.23±42.70) pg·mL^-1, respectively; and the interleukin-10 levels were (19.21±2.79) and (17.42±2.96) ng·mL^-1, respectively. Except folic acid, the differences of above indexes were all statistically significant (P<0.05, P<0.01). In the treatment group, adverse drug reactions included headache, dizziness, nausea and diarrhea; in the control group, adverse drug reactions included lower limb edema, headache, dizziness and gingival swelling. The total incidence of adverse drug reactions in the treatment group and the control group was 11.36% (5 cases/44 cases) and 13.64% (6 cases/44 cases), respectively (P>0.05).

Losartan potassium and hydrochlorothiazide tablets and amlodipine tablets have comparable efficacy and safety. The former showed positive effects on bone metabolism indicators during short-term treatment, and presented a certain positive trend in regulating Hcy, CysC, and inflammatory levels, which may provide a reference for the selection of combined medication regimens for such patients.

To investigate the clinical efficacy and safety of somatostatin injection combined with ulinastatin injection in patients with severe acute pancreatitis (SAP).

Patients with SAP were divided into control group and experimental group by random number table method. Both groups received routine basic treatment. On this basis, the control group was additionally given somatostatin injection (6 mg once daily). The experimental group was treated with ulinastatin injection by intravenous infusion at a dose of 100 000 units three times a day on the basis of the control group. Both groups continued to receive treatment for 7 days. Compare the clinical efficacy, inflammatory factor levels, symptom relief time, intestinal mucosal function [D-lactate, diamine oxidase (DAO), and Endotoxin] of the two groups, and conduct a safety evaluation.

A total of 160 patients were enrolled in this study, both the treatment group and the control group included 80 cases. The total effective rates in the treatment group and the control group were 91.25% (73 cases/80 cases) and 75.00% (60 cases/80 cases), respectively, with statistically significant difference (P<0.05). After treatment, the levels of tumor necrosis factor-α (TNF-α) in the treatment group and the control group were (22.46±5.90) and (28.85±6.37) pg·L^-1, respectively; the levels of interleukin-6 (IL-6) were (92.03±20.22) and (122.78±27.59) pg·L^-1, respectively; the levels of Presepsin were (1.25±0.54) and (1.55±0.58) μg·L^-1, respectively; the levels of D-lactate were (5.31±0.75) and (8.19±0.93) mg·L^-1, respectively; the levels of DAO were (4.29±0.88) and (9.84±1.05) U·L^-1, respectively; the levels of endotoxin were (0.63±0.18) and (1.21±0.25) EU·L^-1, respectively; the duration of abdominal pain relief was (3.14±0.42) and (4.98±0.51) d, respectively; the time for amylase to return to normal was (4.32±0.46) and (5.37±0.56) d, respectively. All these differences of the aforementioned indicators were statistically significant in both groups (P<0.05). The incidence of adverse drug reactions during treatment in the control group and the treatment group was 6.25% (5 cases/80 cases) and 6.25% (5 cases/80 cases), respectively, and the incidence of complications was 3.75% (3 cases/80 cases) and 2.50% (2 cases/80 cases), respectively. There were no statistical differences between the two groups (P>0.05).

Ulinastatin combined with somatostatin in the treatment of SAP patients can effectively reduce the levels of inflammatory factors, alleviate inflammatory response, promote the recovery of intestinal mucosal function, and has better curative effect, without increasing the occurrence of adverse reactions, with certain safety and effectiveness.

To observe the clinical efficacy and safety of low-dose mifepristone tablets combined with dienogest tablets in the treatment of ovarian chocolate cyst patients.

Patients with ovarian endometriomas were divided to control group, treated with dinoprost tablets at a dose of 2 mg once daily (qd), while the treatment group received additional low-dose mifepristone tablets at 5 mg qd in addition to the control regimen. Both groups were treated for 6 months. The clinical efficacy, dysmenorrhea symptom scores, hormone levels, carbohydrate antigen 125 (CA125) levels, endometrial thickness, uterine volume, inflammatory factor levels, and safety profiles before and after treatment were compared.

A total of 123 patients were enrolled, with 63 cases in the control group and 60 cases in the treatment group. The treatment group demonstrated a significantly higher overall response rate [91.67% (55 cases/60 cases) vs. 77.78% (49 cases/63 cases), P<0.05]. After treatment, the visual analog scale (VAS) scores of the control group and the treatment group were (2.13±0.67) and (1.78±0.55) points, respectively; the dysmenorrhea symptom scale (CMSS) scores were (21.78±4.19) and (19.86±4.54) points, respectively; the levels of FSH in the control group and the treatment group were (5.06±1.11) and (4.48±1.17) U·L^-1, respectively; the levels of estradiol (E₂) were (204.43±34.68) and (185.73±35.14) pmol·L^-1, respectively; the levels of progesterone (P) were (12.14±2.43) and (10.81±2.29) ng·mL^-1, respectively; the levels of CA125 were (37.31±4.34) and (33.12±4.49) U·mL^-1, respectively; endometrial thickness was (5.88±1.46) and (5.15±1.32) mm, respectively; the uterine volume was (106.15±13.62) and (98.89±11.57) cm³, respectively; the levels of interleukin-6 (IL-6) in the control group and treatment group were (14.38±2.19) and (13.44±2.05) ng·L^-1, respectively; the levels of IL-17 were (8.47±2.08) and (7.56±2.11) pg·mL^-1, respectively; the levels of amyloid A (SAA) were (18.62±2.17) and (17.59±2.13) mg·L^-1, respectively; the recurrence rate was 14.29% (9 cases/63 cases) and 5.00% (3 cases/60 cases), respectively; menstrual restoration time was (46.3±7.1) and (38.5±6.2) d, respectively; the differences of above indicators were all statistically significant compared betwwen two groups (P<0.05, P<0.01). The adverse drug reactions in the control group and the treatment group mainly included headache, breast discomfort, and mild irregular bleeding and the incidence was 9.52% (6 cases/63 cases) in the control group and 11.67% (7 cases/60 cases) in the treatment group (P>0.05).

For patients with ovarian chocolate cysts, low-dose mifepristone tablets combined with dienogest tablets represents a valuable therapeutic strategy, offering enhanced pain relief, hormonal control, and overall efficacy compared to dienogest monotherapy, alongside a comparable safety profile.

To discuss the effects of sauchinone on myocardial fibrosis and inflammatory injury in rats with acute myocardial infarction by adjusting the sonic hedgehog/glioma-associated oncogene homolog 1 (Shh/Gli1) signaling pathway.

A rat model of acute myocardial infarction was established by ligation of the left anterior descending coronary artery. A total of 72 rats were randomly divided into six groups: sham group (thoracotomy and suture without ligation), model group, experimental-L group (5 mg·kg^-1 sauchinone), experimental-M group (10 mg·kg^-1 sauchinone), experimental-H group (25 mg·kg^-1 sauchinone) and activator group [25 mg·kg^-1 sauchinone + 10 mg·kg^-1 purmorphamine (PUR)], with 12 rats in each group. Each group received the corresponding drug by gavage or intraperitoneal injection for 7 consecutive days. After the final administration, inflammatory cytokine levels were measured using enzyme-linked immunosorbent assay (ELISA); myocardial infarct size was assessed by 2,3,5-triphenyltetrazolium chloride (TTC) staining; myocardial tissue changes were observed using hematoxylin-eosin (HE) staining; apoptotic cells were detected by one-step terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining; superoxide anion levels were measured using dihydroethidium; collagen deposition was examined by Masson staining; and the protein expressions of Shh, Gli1 and α-smooth muscle actin (α-SMA) were detected by Western blot.

The serum levels of interleukin (IL)-6 in the sham group, model group, experimental-H group, and activator group were (56.31±9.21), (113.05±12.03), (59.67±9.67) and (103.71±11.68) pg·mL^-1, respectively; tumor necrosis factor (TNF)-α levels were (136.25±16.92), (220.16±22.14), (153.67±17.40) and (208.77±21.65) pg·mL^-1, respectively; IL-1β levels were (28.59±4.10), (52.07±5.38), (30.61±4.31) and (46.22±5.17) pg·mL^-1, respectively; myocardial infarct sizes were (0±0)%, (28.86±3.42)%, (10.24±1.28)% and (26.94±2.98)%, respectively; inflammation scores were (0±0), (2.88±0.32), (1.34±0.15) and (2.76±0.29), respectively; myocardial apoptosis rates were (2.46±0.25)%, (36.38±3.95)%, (12.23±1.45)% and (34.14±3.73)%, respectively; relative dihydroethidium fluorescence intensity in myocardial tissue was (4.58±0.68)%, (39.65±4.27)%, (15.36±1.73)% and (37.31±3.96)%, respectively; the percentage of myocardial fibrosis area was (11.34±1.32)%, (65.83±6.98)%, (18.48±2.24)% and (61.95±6.36)%, respectively; Shh protein relative expression levels were 1.04±0.11, 3.46±0.38, 1.29±0.16 and 3.28±0.35, respectively; Gli1 protein relative expression levels were 1.02±0.11, 2.73±0.31, 1.19±0.14 and 2.64±0.29, respectively; and α-SMA protein relative expression levels were (1.03±0.13), (2.33±0.27), (1.14±0.15), and (2.15±0.23), respectively. Comparisons between the sham group and the model group, between the model group and the experimental-H group, and between the experimental-H group and the activator group were statistically significant for all the above indicators (all P<0.05).

Sauchinone may alleviate myocardial fibrosis and inflammatory injury in rats with acute myocardial infarction by inhibiting the Shh/Gli1 signaling pathway.

To investigate the effects of pachymic acid (Pac) on cholesterol metabolism in a gallstone (GS) model and its underlying molecular mechanisms.

A mouse model of GS was established by feeding a high-fat diet. Fifty healthy SPF male mice were randomly divided into five groups: Control group (fed a normal diet), model group (gallstone model), experimental-L group (model + 25 mg·kg^-1 Pac), experimental-H group (model+50 mg·kg^-1 Pac), and inhibitor group (model + 50 mg·kg^-1 Pac + 1 mg·kg^-1 GW9662). Gallstone grades were determined based on macroscopic cholesterol crystals or stones observed in bile. The expression of proteins in the peroxisome proliferator-activated receptor γ (PPARγ)/liver X receptor α (LXRα) pathway was detected by Western blot.

The gallstone grades in the control, model, experimental-L, experimental-H, and inhibitor groups were (0±0), (4.70±0.46), (3.70±0.64), (1.10±0.70), and (3.20±0.60) grades, respectively; The relative expression levels of PPARγ protein were 1.41±0.13, 0.32±0.02, 0.48±0.05, 1.39±0.15, and 0.80±0.07, respectively; The relative expression levels of LXRα protein were 0.99±0.07, 0.33±0.03, 0.42±0.02, 1.00±0.09, and 0.73±0.05, respectively. Statistically significant differences were observed when comparing the model group with the control, experimental-L, and experimental-H groups, as well as when comparing the inhibitor group with the experimental-H group (all P<0.05).

Pachymic acid effectively prevents high-fat diet-induced cholesterol gallstone formation in mice. Its protective mechanism is associated with the activation of the PPARγ/LXRα signaling pathway, leading to the restoration of cholesterol metabolic homeostasis.

To explore the mechanisms of action of fructus broussonetiae regulating phosphoinositide 3-kinase/ protein kinase B (PI3K/Akt) in diabetic kidney disease (DKD).

The traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), the human gene database (GeneCards), online mendelian inheritance in man (OMIM) and therapeutic target database (TTD) were used to screen the active ingredients and targets. The protein-protein interaction (PPI) network and topology analysis were constructed and enriched using gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG), and molecular docking and molecular dynamics (MD) simulations were used to verify the interactions between the core ingredients and targets. Mouse podocyte cells 5 were divided into control group (without any treatment), model group (treated with 30 mmol·L^-1 glucose for 48 h), mannitol group (treated with 44.5 mmol·L^-1 mannitol for 48 h on the basis of the control group), experimental group (treated with 2.5, 5.0, 15.0, 30.0 and 45.0 μmol·L^-1 luteolin for 24 h, on the basis of the model group) and positive drug group (treated with 100 μmol·L^-1 captopril for 24 h on the basis of the model group). Cell viability were detected by cell counting kit-8 (CCK-8), apoptosis were detected by flow cytometry, levels of inflammatory factors interleukin-1β (IL-1β), IL-6 and tumour necrosis factor (TNF-a) were measured by enzyme-linked immunosorbent assay (ELISA), and B-cell lymphoma-2 gene (Bcl-2), Bcl-2-related X protein (Bax), cysteine aspartate specific proteinase-3 (Caspase-3), heat shock protein 90-α (HSP90AA1), phosphorylated protein kinase B (p-Akt) and Akt protein expression levels were detected by Weatern blot.

A total of 42 intersection targets of fructus broussonetiae and DKD were identified, and 13 core targets were screened out, including protein kinase B1 (Akt1), prostaglandin-endoperoxide synthase 2 (PTGS2), tumour protein 53 (TP53) and HSP90AA1, etc. The GO/KEGG enrichment analysis showed that the mechanism of action was involved in the regulation of PI3K/Akt signalling pathway as well as the oxidative stress, apoptosis, etc. The molecular docking and kinetic simulations confirmed that HSP90AA1 formed the most stable complex with luteolin (binding free energy -34.08 kcal·mol^-1), therefore, luteolin were selected for subsequent cellular experiments. CCK-8 showed that the effect of luteolin entered into a plateau phase when the concentration reached 30.0 μmol·L^-1, and this concentration was used for the subsequent experiments. The total apoptosis rates of the control group, model group, mannitol group, experimental group (30.0 μmol·L^-1) and positive drug group were (6.23±0.40)%, (35.47±3.08)%, (6.42±0.52)%, (11.20±1.46)% and (10.78±1.06)%, respectively; the IL-6 levels of the cells in the control, model and experimental groups (30.0 μmol·L^-1) were (29.52±2.21), (91.12±6.14) and (36.48±3.65) pg·mL^-1, respectively; IL-1β levels were (12.68±1.17), (47.42±3.49) and (18.08±1.42) pg·mL^-1, respectively; and TNF-α levels were (23.15±1.81), (79.35±7.01) and (29.62±2.17) pg·mL^-1, respectively; the relative expression levels of Bcl-2 protein were 1.02±0.11, 0.45±0.04 and 0.92±0.07, respectively; the relative expression levels of Bax protein were 1.01±0.09, 2.18±0.17 and 1.12±0.11, respectively; the relative expression levels of Caspase-3 protein relative expression levels were 1.03±0.08, 2.32±0.17 and 1.31±0.14, respectively. The relative expression levels of HSP90AA1 protein were 1.00±0.07, 1.96±0.12 and 1.08±0.10, respectively; the relative expression levels of p-Akt/Akt were 1.00±0.07, 2.25±0.07 and 1.11±0.06, respectively. The above indexes in the model group were statistically significant when compared with those in the control group, and when compared with those in the experimental and model groups (P<0.001).

The active component luteolin of fructus broussonetiae may reduce the expression of HSP90AA1, inhibit the activation of PI3K/Akt signaling pathway, and reduce the inflammatory response, thus achieving the purpose of treating DKD.

To discuss the effect of baicalin on renal injury in nephrotic syndrome (NS) rats by regulating the high mobility group protein B1 (HMGB1)/Toll like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) pathway.

SD rats were divided into control group, model group, experimental group, HMGB1 inhibitor group and HMGB1 activator group, with 12 rats in each group. Except for the control group, rats in all other groups were injected with adriamycin via the tail vein to establish the nephrotic syndrome (NS) model. Twenty-four hours after successful modeling, the rats in the experimental group were administered 100 mg·kg^-1 baicalin by gavage; rats in the HMGB1 inhibitor group were administered 0.03 g·kg^-1 HMGB1 inhibitor glycyrrhizic acid by gavage; rats in the HMGB1 activator group were administered 100 mg·kg^-1 baicalin by gavage combined with intraperitoneal injection of 8 μg·kg^-1 HMGB1 activator recombinant HMGB1 protein (rHMGB1); rats in the model group and control group were administered 10 mL·kg^-1 normal saline by gavage and intraperitoneal injection. All treatments were administered once daily for 30 consecutive days. Measure 24-hour urinary protein, serum creatinine, blood urea nitrogen levels, renal pathology, and renal levels of interleukin-1β (IL-1β), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α). TUNEL staining was used to detect the apoptosis rate of cells in renal tissue. Western blot was used to detect renal caspase-3, p53, HMGB1, TLR4, and p-NF-κB p65 proteins.

In the model group, the renal tissue showed thickening of the glomerular basement membrane, glomerular atrophy, and extensive inflammatory cell infiltration; the 24 h urinary protein levels in the control group, model group, experimental group, HMGB1 inhibitor group, and HMGB1 activator group were (65.56±4.73), (212.19±12.26), (87.76±5.15), (95.53±6.11) and (138.87±8.25) mg·24 h^-1, respectively; the serum creatinine levels were (51.57±3.18), (128.86±7.25), (63.69±4.12), (70.75±4.06) and (95.73±5.29) μmol·L^-1, respectively; the serum blood urea nitrogen levels were (4.23±0.25), (10.68±0.61), (5.44±0.32), (6.18±0.39) and (8.78±0.53) mmol·L^-1, respectively; the renal tissue IL-1β levels were (37.65±2.18), (83.39±5.07), (44.55±2.56), (50.52±2.89) and (69.89±4.17) pg·mL^-1, respectively; the renal tissue MCP-1 levels were (156.69±8.12), (314.45±17.36), (181.54±10.21), (201.16±11.54) and (264.45±14.58) pg·mL^-1, respectively; the renal tissue TNF-α levels were (34.99±2.15), (90.81±5.63), (43.78±2.52), (51.19±3.15) and (67.11±3.89) pg·mL^-1, respectively; the renal tissue apoptosis rates were (4.67±0.31)%, (28.81±1.76)%, (7.08±0.39)%, (8.26±0.51)% and (18.22±1.03)%, respectively; the renal tissue Caspase-3 protein expression levels were 0.86±0.10, 2.37±0.16, 0.98±0.09, 1.21±0.18 and 1.85±0.17, respectively; the renal tissue tumor protein p53 (p53) protein expression levels were 0.15±0.02, 0.68±0.07, 0.24±0.03, 0.36±0.04 and 0.51±0.05, respectively; the renal tissue HMGB1 protein expression levels were 0.65±0.08, 2.04±0.17, 0.87±0.09, 0.95±0.08 and 1.34±0.13, respectively; the renal tissue TLR4 protein expression levels were 0.41±0.05, 1.68±0.16, 0.63±0.07, 0.79±0.08 and 1.09±0.11, respectively; the renal tissue p-NF-κB p65 protein expression levels were 0.23±0.03, 0.81±0.09, 0.37±0.05, 0.45±0.04 and 0.68±0.07, respectively. All differences between the control group and the model group, between the model group and the experimental group/HMGB1 inhibitor group, and between the experimental group and the HMGB1 activator group were all statistically significant (all P<0.05).

Baicalin may inhibit the inflammatory response and cell apoptosis in NS rats, and alleviate renal injury by suppressing HMGB1/TLR4/NF-κB pathway.

To explore the mechanism of action of catechin (CAT) on mice with a model of high altitude polycythemia through mediating the intestinal hypoxia-inducible factor-2α (HIF2α) iron metabolism pathway.

SPF-grade male Balb/cmice were randomly divided into control group (reared in a normal atmospheric pressure environment: northeastern Qinghai province, China, at an altitude of 2 260 m, 36°73′ north latitude, 101°75′ east longitude, without any treatment), model group (reared in a high-altitude hypoxic environment: a certain place in southwestern Qinghai province, China, at an altitude of 4 208 m, 32°90′ north latitude, 95°25′ east longitude, without any treatment), the experimental group (based on model group, intragastrically administered with 100 mg·kg^-1 CAT once a day from the 29th to the 35th day) and the oe-HIF2α group (based on experimental group, intravenously injected with lentivirus-coated oe-HIF2α plasmids by the tail vein once a day from the 34th to the 35th day). Real-time fluorescence quantitative polymerase chain reaction was used to detect the relative expression level of HIF2α mRNA in intestinal tissues; Western blot assay was used to detect the relative expression levels of HIF2α, B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), cleaved-cysteine-aspartic acid protease 3 (Cleaved-Caspase3), ferroportin (FPN), transferrin receptor (TFRC) in intestinal tissues, as well as the relative expression levels of GATA binding factor 1 (GATA-1) and erythropoietin receptor (EpoR) in bone marrow red blood cells; automatic hematology analyzer was used to detect the levels of hemoglobin, red blood cell count and hematocrit in peripheral blood; the spectrophotometric method was used to detect the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and content of malondialdehyde (MDA) in intestinal tissues; the immunofluorescence staining assay was used to detect the positive expression of ferritin (Ferritin) in intestinal tissues.

The relative expression levels of HIF2α mRNA in control group, model group and experimental group were 1.00±0.18, 1.61±0.16 and 1.21±0.13, respectively; the hemoglobin levels in control group, model group, experimental group and oe-HIF2α group were (132.91±11.44), (221.37±26.92), (178.65±19.32) and (206.33±21.37) g·L^-1, respectively; the red blood cell count levels were (4.79±0.75), (9.26±1.11), (6.08±1.03) and (7.74±0.96)×10¹²·L^-1, respectively; the hematocrit levels were (44.17±4.06)%, (63.58±6.38)%, (51.79±4.45)% and (58.24±5.07)%, respectively; the relative expression levels of GATA-1 protein were 1.00±0.17, 2.03±0.33, 1.52±0.19 and 1.80±0.23, respectively; the relative expression levels of EpoR were 1.00±0.11, 1.83±0.31, 1.29±0.20 and 1.62±0.24, respectively; the relative fluorescence intensities of Ferritin were 1.00±0.12, 7.86±0.97, 2.97±0.49 and 4.75±0.51, respectively; the relative expression levels of FPN protein were 1.00±0.14, 1.69±0.25, 1.31±0.18 and 1.52±0.19, respectively; the relative expression levels of TFRC protein were 1.00±0.10, 2.18±0.23, 1.67±0.15 and 1.86±0.15, respectively. There were statistically significant differences in the above-mentioned indicators between model group and control group, between experimental group and model group, and between oe-HIF2α group and experimental group (all P<0.05).

CAT can inhibit cell apoptosis, oxidative stress and excessive iron metabolism in the intestines of mice with high altitude polycythemia by mediating the expression of intestinal HIF2α, and play a role in the prevention and treatment of high altitude polycythemia.

To analyze the bioequivalence and safety of the test and reference formulations of erlotinib hydrochloride tablets in healthy Chinese subjects under fasting conditions following a single oral dose.

The study was conducted as a randomized, open-label, two-period crossover trial. A total of 60 healthy subjects were assigned to two sequences by randomization. Under fasting conditions, subjects received a single 150 mg oral dose of either the test or reference formulation, with a 12-day washout period between doses. The plasma concentrations of erlotinib were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the pharmacokinetic parameters were calculated for bioequivalence evaluation using Phoenix WinNonlin software (version 8.3).

After a single oral administration of the test or reference formulation under fasting conditions, the main pharmacokinetic parameters of erlotinib hydrochloride were as follows: maximum concentration (C_max) was (1 649.48±567.44) and (1 548.15±529.59) ng·mL^-1, AUC_0-last were (28 830.12±11 507.57) and (29 396.47±11 121.61) h·ng·mL^-1, AUC_0-inf were (30 759.13±13 789.60) and (31 132.78±12 912.53) h·ng·mL^-1. The 90% confidence intervals for the geometric mean ratios of C_max, AUC_0-last, and AUC_0-inf for the two formulations were 92.44%-117.31%, 87.65%-103.90% and 87.66%-104.37%, respectively, all of which were within the bioequivalence acceptance range of 80.00%-125.00%. No serious adverse events, suspected unexpected serious adverse reactions, or adverse events leading to withdrawal occurred during the trial.

Under fasting conditions, the test erlotinib hydrochloride tablets were bioequivalent to the reference listed drug Tarceva^® in healthy Chinese subjects and the safety profile was favorable.

To develop and validate a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for determining the concentration of posaconazole in dried blood spot (DBS) samples, providing a feasible reference for the application of the dried blood spot method and the clinical practice of posaconazole therapeutic drug monitoring (TDM).

DBS samples were obtained by dropping whole blood samples containing posaconazole onto Whatman 903^® cards and drying them. The sample processing procedure involved cutting out a round hole with a diameter of 3 mm to obtain the analytical sample. The sample was extracted by adding 0.2% formic acid-50% acetonitrile (containing an internal standard of 0.50 μg·ml^-1), followed by sonication and centrifugation. The supernatant was directly injected for detection. LC-MS/MS was used for determination. The Phonomenex Kinetex XB-C₁₈ column was selected as the chromatographic column, and gradient elution was used for separation. The mass spectrometry detection mode was positive ion multiple reaction monitoring. The monitored ion pairs for the analyte posaconazole and the internal standard D₅-posaconazole were 701.3→614.4 and 705.3→618.4, respectively. Full method validation was conducted in accordance with ICH Guideline M10 (Bioanalytical Method Validation and Study Sample Analysis), covering selectivity, specificity, linearity, carryover, accuracy, precision, extraction recovery, matrix effect, analyte stability, together with DBS-specific validation parameters including hematocrit (Hct) impact, spotting volume effect and spot homogeneity. In addition, the developed DBS method was applied to the detection of clinical TDM samples of posaconazole and compared with the plasma method, and the consistency of the two methods was evaluated.

The LC-MS/MS method for the determination of posaconazole in DBS had good selectivity and linearity (0.10-10.00 μg·ml^-1), without the influence of cross-talk and carry-over. The recovery rate of the analyte during the sample processing was in the range of 70.67%-75.66%. The intra-batch accuracy and precision were in the ranges of -12.18%--0.86% and 3.05%-8.75%, respectively, and the inter-batch accuracy and precision were in the ranges of -4.21%-3.49% and 8.57%-12.21%, respectively. For the matrix effect tested with six blank whole blood samples from different sources, the accuracy was within ±15% and the precision was all <15%. The stability results showed that posaconazole was stable for at least 3, 3, 14, 30, and 90 days at room temperature (20-25 ℃), 37 ℃, 4 ℃ -20 ℃, and -70 ℃ in DBS samples, respectively. The results of Bland-Altman and Passing-Bablok analyses of 78 clinically verified samples showed that there was a good correlation between the determination results of posaconazole in dried blood spots (DBS) and plasma. However, there was a significant deviation (P<0.001). The determination results in DBS were lower than those in plasma (average difference=0.33 μg·ml^-1), and this was more significant in cases with low hematocrit (Hct).

A straightforward and practical LC-MS/MS method was successfully developed and fully validated for posaconazole quantitation in DBS samples. This method requires a minimal blood volume (minimum 10 μL whole blood), features a short analytical runtime (2.00 min per injection) and facilitates streamlined laboratory operation with robust practicability, which can serve as a convenient alternative analytical strategy for routine clinical TDM of posaconazole.

To establish a high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method for simultaneous determination of calcitonin salmon in human plasma.

Precipitate plasma samples using organic reagents, then centrifuge and collect the supernatant, proceed with concentration, reconstitution, and sample injection, and a phenomenex Jupiter^® C4-300A column (2.1 mm×50.0 mm, 5.0 μm) was used for chromatographic separation. The mobile phase was 0.1% formic acid water (phase A) -0.1% formic acid acetonitrile (phase B); gradient elution with a flow rate of 0.50 mL·min^-1, column temperature 50 ℃, injection volume 20 μL. A custom-labeled isotopic compound was used as the internal standard, scanning was carried out by means of multi reaction monitoring (MRM) in the positive ionization mode with an electric spray ionization source(ESI). Examine the specificity, standard curve, lower limit of quantification (LLOQ), precision, accuracy, recovery rate, matrix effect, and stability of the method.

The method showed a good specificity results of the method, and there is no interference between the analyte and the internal standard. The linear range of the standard curves for the tested substances was 2.00、4.00、10.00、50.00、100.00、200.00、360.00、400.00 pg·mL^-1, The standard curve was y=2.98×10^-2x+5.30×10^-3 (R²=0.997 4) and the lower limit of quantification(LLOQ) is 2.00 pg·mL^-1. The intra-day and inter day relative standard deviation (RSD) were both less than 15%, extraction recovery rates ranging from 60.13% to 75.39% (RSD<15%), and matrix effects ranging from 97.45% to 109.72% (RSD<10%). The stability of the matrix samples was verified by placing them at room temperature for 24 hours, repeatedly freezing and thawing at -20 ℃ and -70 ℃ for 5 times, freezing at -20 ℃ and -70 ℃ for 49 days, and placing the processed samples in an automatic sampler for 333 hours, with accuracy ranging from 97.03% to 108.64%, all stable.

The established HPLC-MS/MS method is simple, rapid, highly sensitive, and specific, and can be used for the detection of plasma samples in pharmacokinetic studies.

To analyze the adverse drug reactions (ADRs) of 0.01% atropine sulfate eye drops in myopia control among children and adolescents, providing safety evidence for its clinical application.

Retrospective analysis of ADR data from pediatric and adolescent patients using the 0.01% atropine sulfate eye drops (hospital-prepared formulation) in our institution from January 2022 to December 2024.

A total of 51 ADR cases were collected, with an incidence rate of 0.29%. Visual disorders were the most frequent (54.71%), primarily manifesting as eye pain, blurred vision, and photophobia; followed by skin and subcutaneous tissue disorders (11.76%), mainly presenting as rash; and nervous system disorders (9.80%), including dizzinessand headache. Newly reported ADRs accounted for 35 cases (68.63% of total reports). All ADRs were mild or moderate, with no severe cases observed.

0.01% atropine sulfate eye drops show favorable short-term safety and a low incidence of adverse drug reactions in myopia control among children and adolescents. As a real-world pharmacovigilance data report, this study provides certain cautions for the clinical use of 0.01% atropine sulfate eye drops; however, its long-term safety requires further investigation and validation.

To evaluate the effectiveness of the plan-do-check-act (PDCA) cycle combined with a drug use pathway in managing the rational use of proton pump inhibitors (PPIs) hospital-wide.

Based on evidence-based medicine, PPI treatment and prophylactic medication pathways were established and implemented through the PDCA cycle. The changes in PPI usage rationality, quarterly average sales amount and its proportion of total drug consumption, medication frequency (DDDs), usage intensity (AUD), medication structure and intravenous usage rate in hospitalized patients were compared before implementation (fourth quarter of 2023) and after implementation (first to third quarters of 2024).

After the implementation of medication pathways, the rationality of PPI use across the hospital significantly improved. The prescription compliance rate increased from 95.17% (571 prescription/600 prescription) to 98.50% (589 prescription /600 prescription), and the order compliance rate rose from 93.33% (140 prescription /150 prescription) to 97.33% (149 prescription /150 prescription). Costs also decreased, with quarterly consumption dropping from 37.82 to 25.98 million yuan, with a reduction of 31.31%, and the cost proportion declining from 0.97% to 0.80%, with a decrease of 17.53%. The reduction in usage intensity was greater than the total volume, with AUD decreasing from 208.48 to 126.28 (with a 39.43% reduction) and DDDs dropping from 153 071.29 to 103 490.17 (with a 32.39% reduction). The medication structure continued to optimize, with the proportion of high-cost PPIs decreasing from 52.35% to 38.28% (with a 26.88% reduction), while the proportion of centralized procurement/essential drugs increased from 40.99% to 42.42% (with a 3.45% rise). The intravenous usage rate declined from 15.51% to 14.67% (with a 5.41% reduction). The intervention effectively achieved the goals of cost control, quality improvement, and compliance.

The PDCA cycle can effectively promote the implementation of drug use pathways and enhance the level of rational drug use.

Sarcopenia-osteoporosis is an age-related syndrome caused by the coexistence of osteoporosis and sarcopenia, and it poses a serious threat to the health of the elderly population. The mitogen-activated protein kinases (MAPKs) signalling pathways, including extracellular signal-regulated kinase 1/2 (ERK1/2), p38 MAPK and c-Jun N-terminal kinase (JNK), regulate the proliferation, differentiation and apoptosis of skeletal muscle and bone tissue, and play a significant role in the development and progression of sarcopenia-osteoporosis. In recent years, various traditional Chinese medicine (TCM) constituents have demonstrated experimental value in modulating the MAPKs signalling pathway and influencing processes related to osteogenesis or muscle atrophy. This article reviews the regulatory effects of the MAPKs signalling pathway in osteogenesis and myogenesis, and summarises research progress on the use of various TCM monomers to intervene in sarcopenia-osteoporosis via this pathway, with the aim of providing new theoretical foundations and therapeutic strategies for the prevention and treatment of sarcopenia-osteoporosis.

Based on the previously established competency model for clinical investigators in drug clinical trials, this study aims to evaluate the effectiveness of a targeted training program, clarify the role of this model in improving investigators’ professional competence, operational skills, and ethical awareness, and provide evidence-based basis for the precise optimization of clinical trial training models.

Investigators from tertiary Grade A hospitals in Beijing who had participated in at least one clinical trial in the past three years were selected as the research subjects. The training content was designed based on the core elements of the competency model. A pre-training and post-training paired design was adopted to evaluate the improvement of knowledge and skills through standardized Good Clinical Practice (GCP) simulation tests; online questionnaire surveys were conducted to collect trainees’ satisfaction feedback on training content, teaching quality, organizational management and other dimensions. Wilcoxon signed-rank test was used to compare scores before and after training. Stratified by gender, the Mann-Whitney U test was used to compare the inter-group differences in post-training competency scores of investigators of different genders. Stratified by educational background, professional title and working years of clinical trial practice, the Kruskal-Wallis H test was adopted to analyze the inter-group differences in post-training scores among investigators with different educational levels, different professional titles, and different working years.

A total of 81 clinical investigators were included, with a median age of 34 (31.00, 44.00) years. The proportions of males and females were 27.16% and 72.84%, respectively. Among the participants, 62.96% held doctoral degrees, and 32.10% had senior professional titles. The median pre-training total score (Q1, Q3) was 35.00 (31.00, 39.00) scores, while the median post-training total score (Q1, Q3) was 43.00 (40.00, 46.00) scores, indicating a significant improvement in the trainees’ total scores (Z=-7.30, P<0.001). The scores for all competency sub-dimensions increased significantly compared to those before training. Among them, the differences in scores before and after training for ethical awareness and subject protection, GCP implementation capability, study design and protocol execution, and data quality control were all statistically significant (all P<0.001). Subgroup analysis showed that the total competency scores of investigators with different genders, professional titles, and years of experience in clinical trials significantly improved after training, with no statistically significant differences in the magnitude of improvement between groups. Participants with master’s or doctoral degrees showed significant improvements in post-training scores (all P<0.001), while those with bachelor’s degrees showed no significant difference between pre- and post-training scores (P>0.05). Furthermore, 85.19% of the trainees rated the overall performance of the training as very satisfied.

The training program designed based on the competency model could improve the GCP theoretical level and practical knowledge reserve of clinical investigators in clinical trials, and has good trainee acceptance and practicality. By accurately matching the core competency needs of clinical investigators, this training model provides a replicable practical path for the optimization of the clinical trial talent training system.