To investigate the mechanism of peiminine (PEI) affects pain and cartilage injury in rats with knee osteoarthritis (KOA) by regulating the peroxisome proliferator-activated receptor gamma (PPARγ)/cellular sloan kettering institute(c-SKI) signaling pathway through a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5).

The KOA model was established in rats by intra-articular injection of sodium iodoacetate. The rats were divided into control group, model group, experimental group (intraperitoneal injection of 3.5 mg·kg^-1 PEI) and ADAMTS-5 overexpression group (tail vein injection of oe-ADAMTS-5 plasmid). The pain threshold of rats was measured using the mechanical stimulation method; the pathological injury of the rat knee joint was examined by hematoxylin-eosin (HE) staining; the protein levels of ADAMTS-5, matrix metalloproteinase (MMP)-3, MMP-13 and proteins in the PPARγ/c-SKI signaling pathway in rat knee joint tissues were detected by Western blot; the protein level of collagen type Ⅱ alpha 1 chain (Col2α1) in rat knee joint tissues was determined by immunohistochemistry; the levels of inflammatory factors in rat serum were measured using corresponding commercial kits.

The pain thresholds in control group, model group and experimental group were (19.15±2.87), (7.10±1.03) and (13.69±1.27) g, respectively; the relative expression levels of ADAMTS-5 were 1.00±0.16, 1.77±0.21 and 1.35±0.18, respectively; Col2α1 levels in control, model, experimental, and ADAMTS-5 overexpression groups were 1.00±0.10, 0.28±0.04, 0.76±0.13 and 0.58±0.06, respectively; the relative expression levels of MMP-3 were 1.00±0.15, 2.11±0.36, 1.62±0.22 and 1.83±0.25, respectively; the relative expression levels of MMP-13 were 1.00±0.18, 1.98±0.28, 1.27±0.16 and 1.45±0.19, respectively; the tumor necrosis factor-alpha (TNF-α) levels were (62.74±6.93), (159.37±26.40), (98.08±14.09) and (124.43±17.79) pg·mL^-1, respectively; the interleukin (IL)-4 levels were (75.62±11.54), (19.56±2.59), (53.28±6.34) and (41.67±5.31) pg·mL^-1, respectively; IL-6 levels were (42.65±9.77), (133.84±13.22), (84.19±11.71) and (105.24±18.19) pg·mL^-1, respectively; IL-10 levels were (98.06±24.50), (23.42±10.61), (64.72±20.96) and (38.09±12.86) pg·mL^-1, respectively; the relative expression levels of PPARγ were 1.00±0.13, 0.39±0.07, 0.73±0.09 and 0.51±0.08, respectively; the relative expression levels of c-SKI were 1.00±0.17, 0.32±0.05, 0.86±0.15 and 0.44±0.09, respectively. The above indicators in model group were statistically significantly different from those in control group, those in experimental group were statistically significantly different from those in model group, and those in ADAMTS5 overexpression group were statistically significantly different from those in experimental group (all P<0.05).

PEI inhibits inflammatory cytokine levels, alleviates bone fibrosis, and improves bone injury in KOA rats, thereby relieving joint pain, possibly by downregulating ADAMTS-5 expression to activate the PPARγ/c-SKI signaling pathway.

To evaluate the safety and bioequivalence of two formulations of agomelatine tablets in healthy Chinese subjects.

A randomized, open-label, two-treatment, four-period, two-sequence, fully replicated crossover bioequivalence study was conducted under both fasting and fed conditions. Each subject received a single 25 mg dose of the test (T) product or reference (R) product agomelatine tablet in both fasting and fed conditions. Plasma concentration of agomelatine was determined by the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The main pharmacokinetic parameters were derived using WinNonlin 8.3 software.

A total of 128 subjects were enrolled, 64 in the fasting group and 64 in the fed group. The primary pharmacokinetic(PK) parameters of the test and reference formulations under fasting condition were as follows: C_max were (25.55±29.65) and (26.59±28.04) ng·mL^-1, AUC_0-t were (28.59±26.66) and (29.33±26.98) ng·h·mL^-1, AUC_0-∞ were (29.13±26.96) and (29.62±27.17) ng·h·mL^-1. The primary pharmacokinetic parameters of the test and reference formulations under fed condition were as follows: C_max were (26.26±23.29) and (28.97±34.82) ng·mL^-1, AUC_0-t were (35.75±27.67) and (36.91±32.59) ng·h·mL^-1, AUC_0-∞ were (36.15±27.89) and (37.14±32.69) ng·h·mL^-1. Under both fasting and post-meal conditions, the 90% confidence interval of the geometric mean ratio (GMR) of the main PK parameters of the test formulation of agomelatine tablets compared to the reference formulation fell within the range of 80%-125%.

The test formulations and reference formulations of agomelatine are bioequivalent under both fasting and fed conditions.

To evaluate the bioequivalence and safety profile of ezetimibe and atorvastatin calcium tablets (10 mg/10 mg) in healthy subjects.

This study utilized a single-center, randomized, open-label, four-period replicate crossover design. A total of 36 participants were enrolled for both fasting and fed state evaluations. Subjects, following a randomization plan, were administered orally either a single tablet of the test (T) or reference (R) formulation on the designated dosing day of each period. An 8-day washout interval separated treatment periods. Quantification of plasma levels for free ezetimibe, total ezetimibe (sum of free ezetimibe and its glucuronide conjugates) and atorvastatin were performed employing validated high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters were analyzed using Phoenix WinNonlin 8.2 software, and the bioequivalence evaluation was conducted.

Fasting state was as following: pharmacokinetic metrics C_max of ezetimibe for T and R formulations were (6.35±3.22) and (7.04±3.20) ng·mL^-1; AUC_0-t were (107.10±46.61) and (109.67±50.23) ng·h·mL^-1; AUC_0-∞ were (114.88±49.96) and (117.14±50.74) ng·h·mL^-1. The 90% confidence intervals for the geometric mean ratio of C_max, AUC_0-t and AUC_0-∞ were 84.11%-98.34%, 94.60%-106.44% and 93.52%-105.82%, respectively, all in the range of 80.00%-125.00%. Pharmacokinetic metrics C_max of total ezetimibe for T and R formulations were (67.01±35.70) and (71.82±30.91) ng·mL^-1; AUC_0-t were (605.29±255.51) and (615.90±270.21) ng·h·mL^-1; AUC_0-∞ were (655.81±268.02) and (676.04±279.18) ng·h·mL^-1. The 90% confidence intervals for the geometric mean ratio of C_max, AUC_0-t and AUC_0-∞ were 85.32%-97.52%, 92.35%-103.46% and 91.43%-102.13%, all in the range of 80.00%-125.00%. Pharmacokinetic metrics C_max of atorvastatin for T and R formulations were (4.28±2.50) and (4.06±2.40) ng·mL^-1; AUC_0-t were (24.24±18.91) and (22.12±10.80) ng·h·mL^-1; AUC_0-∞were (23.86±12.05) and (23.44±10.98) ng·h·mL^-1. The individual coefficient of variation for C_max with the one-sided 95% upper confidence limit below the zero boundary value. The geometric mean ratio for C_max was 1.06, falling within the acceptance range 0.80-1.25. The 90% confidence intervals for the geometric mean ratios of AUC_0-t and AUC_0-∞ were 97.11%-109.14% and 97.24%-104.00%, all in the range of 80.00%-125.00%. The pharmacokinetic parameters of active ingredients in the fed group were as follows: for ezetimibe, the C_max values of the test and reference preparations were (12.50±8.43) and (12.10±10.20) ng·mL^-1, respectively; the AUC_0-t values were (115.66±61.86) and (114.91±61.10) ng·h·mL^-1, respectively; and the AUC_0-∞ values were (127.40±66.49) and (128.37±66.73) ng·h·mL^-1, respectively. The one-sided 95% upper confidence limit for ezetimibe C_max was <0, with a GMR of 1.09, within the range of 0.80-1.25. The 90% confidence intervals for the geometric mean ratios of AUC_0-t and AUC_0-∞ were 93.63%-107.27% and 91.07%-108.13%, respectively, both within 80.00%-125.00%. For total ezetimibe, the C_max values of the test and reference preparations were (102.02±50.21) and (95.10±48.31) ng·mL^-1, respectively; the AUC_0-t values were (660.62±342.67) and (645.43±290.84) ng·h·mL^-1, respectively; the AUC_0-∞ values were (728.80±356.15) and (711.88±301.04) ng·h·mL^-1, respectively. The one-sided 95% upper confidence limit for total ezetimibe C_max was <0, with a GMR of 1.08, within the range of 0.80-1.25. The 90% confidence intervals for the geometric mean ratios of AUC_0-t and AUC_0-∞ were 95.12%-106.95% and 95.27%-107.60%, respectively, both within 80.00%-125.00%. For atorvastatin, the C_max values of the test and reference preparations were (1.79±0.80) and (1.83±0.87) ng·mL^-1, respectively; the AUC_0-t values were (19.09±6.85) and (18.24±6.29) ng·h·mL^-1, respectively; and the AUC_0-∞ values were (21.25±6.97) and (20.34±6.84) ng·h·mL^-1, respectively. The 90% confidence intervals for the geometric mean ratios of C_max, AUC_0-t and AUC_0-∞ were 91.25%-106.96%, 99.81%-108.09% and 100.22%-108.73%, respectively, all falling within the range of 80.00%-125.00%.

The test formulation of ezetimibe and atorvastatin calcium tablets met bioequivalence criteria relative to the reference product in healthy subjects under both fasting and fed (high-fat meal) conditions.

To observe the clinical efficacy and safety of optimized clinical procedures combined with N-acetylcysteine (NAC) tablets in the diagnosis and treatment of testicular torsion.

Patients diagnosed with testicular torsion in our hospital from January 2020 to January 2022 were enrolled as control group and received routine diagnosis and treatment. Patients treated from January 2023 to January 2024 who underwent optimized clinical procedures combined with postoperative oral NAC tablets were enrolled as treatment group. The treatment group implemented optimized clinical procedures (including health education, fast track pathway, simplified evaluation and surgical preparation, etc.) and started oral NAC tablets on the second day after surgery (200 mg each time, 3 times daily, for 1 consecutive week). The two groups were compared in terms of time from symptom onset to hospital arrival (T1), time from hospital arrival to surgery start (T2), total ischemia time (T3), orchiectomy rate and testicular atrophy rate at 6 months postoperatively.

T1 in treatment group and control group were 8.00 (5.00, 12.00) and 62.00 (51.00, 72.00) min, respectively; T2 were 52.00 (48.00, 57.00) and 109.00 (85.00, 135.50) min, respectively; and T3 were 60.00 (56.00, 64.00) and 171.50 (149.00, 199.00) min, respectively. The differences in the above indicators between the two groups were statistically significant (all P<0.001). The orchiectomy rate was 65.00% in treatment group and 82.00% in control group, with a statistically significant difference (P<0.001, RR=0.78, 95%CI: 0.66-0.91). At 6 months postoperatively, among patients who underwent testicular salvage, the testicular atrophy rate was 11.43% in treatment group and 33.33% in control group, with a statistically significant difference (P<0.05, RR=0.30, 95%CI: 0.10-0.94). Multivariate logistic regression analysis showed that the combined intervention was an independent protective factor for reducing orchiectomy rate (P=0.001, OR=0.31, 95%CI: 0.15-0.64). In terms of safety, only 3 (3.00%) patients in treatment group reported mild nausea, with no serious adverse drug reactions; no related adverse reactions occurred in control group.

The application of optimized clinical procedures combined with N-acetylcysteine tablets shows significant clinical benefits in the treatment of testicular torsion, helping to shorten treatment time, reduce testicular injury, improve testicular survival rate, and exhibits a favorable safety profile.

To construct a clinical pharmacist intervention strategy for tislelizumab injection in the treatment of advanced non-small cell lung cancer (NSCLC) and evaluate its practical effects.

Patients with advanced NSCLC admitted to our hospital were divided into control group and treatment group. The control group received routine pharmaceutical care, while the treatment group received a clinical pharmacist intervention strategy. Therapeutic efficacy, incidence of immune-related adverse events (irAEs), incidence of grade ≥3 irAEs, treatment-related drug withdrawal rate, medication adherence, quality of life and satisfaction with pharmaceutical care were compared between the two groups.

A total of 106 patients were included, including 53 in control group and 53 in treatment group. After treatment, the objective response rates (ORR) of treatment group and control group were 47.17% and 28.30%, respectively; the disease control rates (DCR) were 60.38% and 39.62%, respectively. The above indicators in treatment group were statistically significantly higher than those in control group (all P<0.05). The incidences of irAEs in treatment group and control group were 39.62% and 60.38%, respectively; the incidences of irAEs≥grade 3 were 13.21% and 30.19%, respectively; the treatment-related discontinuation rates were 9.43% and 24.53%, respectively. The above indicators in treatment group were statistically significantly lower than those in control group (all P<0.05). After treatment, the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–lung cancer 13 (EORTC QLQ-LC13) scores for treatment group and control group were (50.15±9.06) and (53.94±7.19) points, respectively, with treatment group statistically significantly lower than control group (P<0.05). The satisfaction rate of pharmaceutical services in treatment group was 90.57%, statistically significantly higher than control group’s 75.47% (P<0.05).

The clinical pharmacist intervention strategy can improve medication adherence to tislelizumab injection, reduce immune-related adverse events and treatment interruption, improve quality of life, and enhance satisfaction with pharmaceutical care, thereby contributing to better clinical outcomes.

To explore the prescription rationality of compound dextromethorphan hydrobromide syrup and the review effectiveness of the rational drug use system in pediatric outpatient and emergency departments, clarify the key medication risk points and system shortcomings, and provide data support and practical evidence for optimizing the safety prevention and control process of pediatric medication.

A retrospective study was conducted to collect prescriptions of compound dextromethorphan hydrobromide syrup in the outpatient and emergency departments of our hospital from January to December 2024. The mode of system screening combined with manual review was adopted, and an age-weight dual-dimensional evaluation criteria was established with reference to drug instructions and relevant clinical guidelines. The irrational prescriptions were classified and analyzed, and statistical analysis was performed using Excel 2010 and SPSS 23.0 software.

A total of 74 905 prescriptions of this preparation were issued throughout the year. System screening identified 527 positive irrational prescriptions, among which 357 were confirmed as true positive irrational prescriptions after manual review, with a system precision rate of 67.74% (357 prescriptions /527 prescriptions) and a false positive rate of 32.26% (170 prescriptions /527 prescriptions), and the overall irrational prescription rate was 0.48% (357 prescriptions /74 905 prescriptions). The core issues of irrational prescriptions primarily include drug interactions, duplicate medication, inappropriate dosage and administration, and unsuitable indications, accounting for 29.41% (105 prescriptions/357 prescriptions), 26.05% (93 prescriptions /357 prescriptions), 29.41% (105 prescriptions /357 prescriptions) and 16.81% (60 prescriptions /357 prescriptions), respectively. 98.24% (167 prescriptions /170 prescriptions) of false positive prescriptions were from overweight patients, indicating defects in the single-dimensional judgment logic of the system; the true positive rate of nighttime prescriptions 75.56% (250 prescriptions /357 prescriptions) was higher than 65.05% (255 prescriptions/392 prescriptions) of daytime prescriptions.

The medication risks of compound dextromethorphan hydrobromide syrup in children are characterized by age concentration and vary among different age groups, and the rational drug use system has efficiency shortcomings. It is necessary to optimize the age-weight dual-dimensional judgment system, implement hierarchical prevention and control, source intervention and system upgrading, so as to effectively improve the level of pediatric medication safety, and provide reference for the clinical standardized management of this preparation and the optimization of rational drug use system.

To extract severe cutaneous adverse reactions (SCAR) associated with commonly used anti-influenza virus drugs from the US Food and Drug Administration (FDA) adverse event reporting system (FAERS) database, analyze the epidemiological characteristics of SCAR to provide a reference for safe clinical medication, and explore the underlying molecular mechanisms using network pharmacology.

Reports from January 2004 to December 2024 in FAERS database were collected, in which oseltamivir, peramivir, zanamivir and baloxavir marboxil were the primary suspected drugs and SCAR was the preferred term (PT). The reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) methods were used to mine and analyze adverse drug event (ADE) signals. Targets of commonly used anti-influenza virus drugs and SCAR were extracted, a protein-protein interaction network was constructed, and enrichment analysis was performed.

A total of 263 cases (1.90%) of SCAR related to commonly used anti-influenza virus drugs were collected. Females (55.13%) accounted for a higher proportion than males (35.36%). Positive signals were detected for all drugs except peramivir, with the association strength in descending order, baloxavir marboxil [n=42, ROR 1.75, information component(IC)0.8], zanamivir (n=53, ROR 1.61, IC 0.68) and oseltamivir (n=208, ROR 1.34, IC 0.42). The top 5 PT by frequency were blister, erythema multiforme, drug eruption, toxic epidermal necrolysis and acute generalized exanthematous pustulosis. Network pharmacology analysis showed that the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway may be a key pathway underlying SCAR induced by commonly used anti-influenza virus drugs.

Baloxavir marboxil, oseltamivir and zanamivir carry a risk of SCAR, with baloxavir marboxil and zanamivir showing higher signal intensity, while oseltamivir had the highest number of reports. Close monitoring of skin symptoms in female patients is recommended from 3 days after administration to guard against the occurrence of SCAR. Anti-influenza virus drugs may induce SCAR by regulating the JAK-STAT signaling pathway, which provides insights for further research.

To observe the clinical efficacy and safety of posaconazole injection and voriconazole injection in the treatment of patients with pulmonary tuberculosis complicated with invasive pulmonary aspergillosis (IPA).

Patients with pulmonary tuberculosis complicated with IPA were divided into control group and treatment group according to the treatment methods. Both groups maintained standardized anti-tuberculosis treatment. At the same time, the control group was given voriconazole for injection at a dose of 6 mg·kg^-1 ivgtt, q12 h on the first day; from the second day, 4 mg·kg^-1 ivgtt, q12 h. When the patient’s clinical condition was stable, switched to oral voriconazole tablets, 200 mg per dose, q12 h. Treatmen group was also given posaconazole injection, initially intravenously, with a dose of 300 mg ivgtt, q12 h on the first day; from the second day, 300 mg ivgtt, qd; when the patient’s clinical condition was stable, oral posaconazole oral suspension were switched to, 400 mg each time, bid. Both groups were treated for 12 weeks. The clinical efficacy, clinical symptom relief, galactomannan (GM) and 1-3-β-D glucan (BG) levels, lung function parameters, immune and inflammatory indicators were compared between the two groups of patients, and safety evaluation was carried out.

A total of 84 patients were enrolled, with 43 cases in control group and 41 cases in treatment group. The clinical effective rates in control group and treatment group were 79.07% (34 cases/43 cases) and 87.80% (36 cases/41 cases), respectively, with no statistically significant difference (P>0.05). The fever subsided time in control group and treatment group were (7.53±1.39) and (8.37±1.65) d, respectively; the recovery time of respiratory function were (5.26±1.66) and (4.44±1.70) months, respectively; the GM levels were (0.44±0.13) and (0.36±0.11) ng·mL^-1, respectively; BG levels were (25.62±5.86) and (22.77±5.34) pg·mL^-1, respectively; the arterial oxygen saturation (SaO₂) levels were (95.63±1.70)% and (96.56±1.70)%, respectively; the pulmonary dynamic compliance (Cdyn) levels were (32.25±4.65) and (34.72±4.49) mL·cm H₂O^-1, respectively; the levels of response frequency (Fres) were (11.39±1.78) and (10.46±1.75) Hz, respectively; the levels of maximum ventilation (MVV) were (78.12±8.87) and (83.68±8.19) L·min^-1, respectively; the carbon monoxide diffusing capacity (DLCO) levels were (62.93±4.37)% and (65.44±4.11)%, respectively; the levels of interleukin 5 (IL-5) were (1.31±0.38) and (1.11±0.32) ng·L^-1, respectively; the levels of interleukin 17 (IL-17) were (14.54±2.83) and (13.22±2.57) ng·L^-1, respectively; the levels of dendritic cell-associated C-type lectin-1 (Dectin-1) were (11.86±2.25) and (10.58±2.13) ng·L^-1, respectively; the immunoglobulinM (IgM) levels were (1.13±0.33) and (1.33±0.26) g·L^-1, respectively; the immunoglobulin E (IgE) levels were (1.09±0.27) and (0.90±0.25) g·L^-1, respectively. There were statistically significant differences in the above indexes between treatment group and control group (P<0.05, P<0.01). Regarding adverse drug reactions, control group primarily experienced nausea, elevated alanine aminotransferase, increased alkaline phosphatase and hallucinations, whereas the treatment group mainly reported nausea, vomiting, elevated alanine aminotransferase, elevated aspartate aminotransferase and hypokalemia. The total incidence of adverse drug reactions was 13.95% (6 cases/43 cases) in control group and 14.63% (6 cases/41 cases) in treatment group, with no statistically significant difference between two groups (P>0.05).

Both posaconazole injection and voriconazole injection can achieve good clinical responses in the treatment of patients with pulmonary tuberculosis complicated by IPA. Posaconazole has advantages in reducing fungal burden, improving lung function, and regulating immune inflammation. The safety of the two groups is equivalent. Posaconazole may have a slower onset of action, manifested by a longer time to resolve fever, but the long-term benefit in lung function is more significant.