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Background: The association between body shape and depressive symptoms has been reported in adults. The present study aimed to investigate the association between body shape-specific abdominal obesity and depressive symptoms among multi-regional Asian adults., Methods: The 2011-2012 China Health and Retirement Longitudinal Study and 2022-2023 Hangzhou study were used as the discovery and validation datasets, respectively. Body shape was assessed by body mass index categories. Abdominal obesity was defined as a body shape index (ABSI) ≥ 75th centile. Depression was measured using 10-item Centre for Epidemiological Studies Depression Scale and Geriatric Depression Scale short 15-item version, respectively. General linear and multinomial logistic models were used to explore the association of ABSI, abdominal obesity with depressive scores and presence, respectively., Results: A total of 12,229 and 1210 participants were included in the discovery and validation datasets, respectively. A non-linear reverse L-shaped association was found between ABSI and depressive scores. Participants with abdominal obesity had higher depressive scores (β = 0.05, 95%CI = 0.01-0.09; and β = 0.13, 95%CI = 0.01-0.24; respectively). Stratified analyses showed that abdominal obesity was associated with higher depressive scores (β = 0.09, 95%CI = 0.00-0.17; and β = 0.25, 95%CI = 0.05-0.46; respectively) and presence (OR = 1.46, 95%CI = 1.02-2.10; and OR = 3.95, 95%CI = 1.58-9.84; respectively) in overweight adults. Furthermore, abdominal obesity was associated with depressive symptoms among overweight females, but not among males., Limitation: Causal links weren't addressed because of the observational study design., Conclusion: Abdominal obesity exhibited a positive association with depressive symptoms among Asian overweight adults, particularly in females. Prevention and early diagnosis of depressive symptoms should focus on overweight females., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The ability to teach, as a core competency, has always suffered from a lack of systematic cultivation., Objective: This study aimed to explore the difference in teaching quality before and after the application of the UTOP (UTeach observation protocol)-based multiple source feedback (MSF) formative assessment of the quality improvement of medical education classrooms., Methods: This study retrospectively analyzed the teaching quality of the Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine and the Third Affiliated Hospital of Chongqing Medical University. The participants were divided into control and UTOP groups according to the actual training they took in the teaching. All the participants, including teachers and trainee teachers, who were under conventional teaching methods were in the control group, and those who were under MSF training were in the UTOP group. UTOP and New Teacher Assessment Scores (NTAS) were evaluated, and the differences between the two courses were analyzed. The UTOP group was divided into a teacher group and a practice group according to differences in the participants' teaching experience. The UTOP-MSF evaluation data were extracted and analyzed, and the differences in teaching quality were compared before and after the implementation of MSF training., Results: The study was conducted for 10 months, with 43 participants completing 120 web-based lectures. In the control group, 32 participants were included, including 22 teachers with 27 courses and 10 trainee teachers who had no teaching experience with 13 courses. Eleven participants in the UTOP group received 9 rounds of MSF feedback training and completed 80 online lectures, including 3 teachers with 19 courses and 8 trainee teachers with 61 courses. A total of 324 evaluations from researchers were extracted and analyzed, including 162 UTOP scores and 162 NTAS; 575 MSF assessments were analyzed, including 438 from the teachers and 137 from the trainee teachers. The participants in the UTOP group had significantly higher UTOP and NTAS scores than did those in the control group did (59.84 ± 14.64 vs. 40.74 ± 6.80, p = 0.000; 73.00 (62.25, 80.00) vs. 53.00 (50.75, 57.00), p = 0.000, respectively). Among the participants who performed UTOP training, the UTOP-MSF scores increased for both teachers and trainee teachers (51.50 (37.75, 68.25) vs. 73.00 (68.00, 76.50), p = 0.022; 41.00 (36.00, 51.75) vs. 68.00 (59.75, 77.00), p = 0.000, respectively). The mean UTOP MSF scores were strongly positively correlated with the mean NTAS (r = 0.640, p = 0.000)., Conclusion: UTOP-based MSF training significantly improved teaching quality in medical education, and it can be an effective tool for evaluating teaching quality., Competing Interests: Declarations Ethics approval and consent to participate This study was approved by the Ethics Committee of the Third Affiliated Hospital of Chongqing Medical University (2024–37), and consent to participate was waived because the retrospective data analysis did not harm participants. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background and Objective: Mitiperstat (AZD4831) is a novel irreversible oral myeloperoxidase inhibitor in clinical development for heart failure with preserved ejection fraction, metabolic dysfunction-associated steatohepatitis and chronic obstructive pulmonary disease. This study evaluated the pharmacokinetics, safety and tolerability of multiple ascending doses of mitiperstat in healthy male Japanese and Chinese volunteers., Methods: Three cohorts of eight Japanese participants were randomized to receive once-daily oral doses of mitiperstat 2.5, 5 or 10 mg or matching placebo for 10 days (six receiving mitiperstat and two receiving placebo, per cohort). One cohort of eight Chinese participants was randomized to receive mitiperstat 5 mg or matching placebo for 10 days (six receiving mitiperstat and two receiving placebo)., Results: Mitiperstat was rapidly absorbed, with a time to maximum plasma concentration of 1-2 h. Exposure was dose proportional over the investigated dose range, as assessed by area under the concentration-time curve and maximum and trough plasma concentrations. Steady state was reached within 10 days, and accumulation was observed, consistent with the observed long elimination half-life of mitiperstat (50.2-57.8 h). Except for a few events of maculopapular rash, mitiperstat up to 5 mg was well tolerated in participants of Japanese or Chinese origin., Conclusions: The pharmacokinetics of mitiperstat were similar among Japanese and Chinese participants. These characteristics were similar to those in a previous multiple ascending-dose study in healthy primarily white and Black/African American volunteers. Therefore, the pharmacokinetics of mitiperstat do not affect dosing regimens in these different populations., Trial Registration: NCT04232345 (03/01/2020)., Competing Interests: Declarations Funding This study was funded by AstraZeneca. Conflicts of interest MS, CB, KN, MA, MH, AC, MT and HE are employees and stockholders of AstraZeneca. PG and JH were employees and stockholders of AstraZeneca when the study was conducted. DH is an employee of PAREXEL, which received funding from AstraZeneca for the conduct of this study. Ethics approval The study was performed in accordance with ethical principles that had their origins in the Declaration of Helsinki and were consistent with the International Conference on Harmonisation Good Clinical Practice and the AstraZeneca policy on Bioethics and Human Biological Samples. The study was approved by Aspire IRB, LLC, 11491 Woodside Avenue, Santee, CA 92071, USA (ASPIRE® Protocol #2019336727, 27 December 2019). Consent to participate All participants provided written informed consent before entering the study. Consent for publication All participants provided written informed consent for their anonymised data to be published. Data availability Data underlying the findings described in this manuscript may be obtained in accordance with AstraZeneca's data-sharing policy described at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Code availability Not applicable. Author contributions Substantial contributions to study conception and design: HE, PG, KN. Substantial contributions to analysis and interpretation of the data: MS, JH, MT, DH, PG, CB, HE. Drafting the article or revising it critically for important intellectual content: all authors. Final approval of the article to be published: all authors., (© 2024. The Author(s).)

Aim: This study aims to explore the association between declining lung function and depression in middle-aged and older adults, with a special focus on the mediating role of cognitive function., Methods: This study utilizes self-reported and physical examination data from 5345 individuals participating in the 2015 cycle of the China Health and Retirement Longitudinal Study (CHARLS) to explore the role of cognitive function changes in mediating the effects of diminished lung function on depression among middle-aged and older adults., Results: Multivariate linear regression analysis revealed a positive correlation between pulmonary and cognitive functions (β = 0.003, 95% CI: 0.002∼0.003, P < 0.01) and a negative correlation between cognitive function and depression (β = -0.279, 95% CI: -0.330-0.228, P < 0.01). Cognitive function plays a mediating role in linking pulmonary function with depression, exhibiting a mediation effect of -0.0007 and a total effect of -0.0046, wherein the mediation effect contributes to 15.22% of the total effect. For females, the mediating effect of cognitive function was stronger (β = -0.0013, 95% CI: -0.0018∼-0.0008, P < 0.01) than it was for males (β = -0.0006, 95% CI: -0.0009∼-0.0003, P < 0.01)., Conclusions: The study underscores the importance of monitoring lung and cognitive functions as interconnected factors contributing to the mental health of middle-aged and older adults. It suggests that interventions aimed at improving pulmonary health and cognitive function may help mitigate depressive symptoms among middle-aged and older adults. Further research is warranted to validate these findings across diverse cultural and demographic settings. Geriatr Gerontol Int 2024; 24: 1210-1217., (© 2024 Japan Geriatrics Society.)

Objective: Increasing antimicrobial resistance has led to the revival of the polymyxins as a last-resort therapeutic option for multidrug-resistant Gram-negative bacterial infections. A parenteral formulation of colistin sulfate is available solely in China. While the onset of action of IV colistin may occur faster than with its prodrug CMS, its pharmacokinetic (PK) profile remains unclear., Methods: This single-centre, open-label, single- and multi-dose, phase 1 trial examined the PKs and safety of colistin sulfate in healthy Chinese adults. Participants received a single 10,000 units/kg (equivalent to 0.452 mg/kg) dose of colistin sulfate (single-dose group, n = 12) or the same dose q12h for 7 days (multi-dose group, n = 12) via a 2-h IV infusion. Colistin concentrations in plasma and urine were determined using LC-MS/MS, and the PK parameters calculated using non-compartmental analysis., Results: After a single dose the peak concentration (C max ), area under the curve from 0 to 12 h (AUC 0-12h ), terminal half-life (T 1/2 ), volume of distribution (V d ), and total body clearance (CL) of colistin were 1.08 ± 0.18 mg/L, 4.73 ± 0.89 h·mg/L, 3.65 ± 0.55 h, 16.82 ± 2.70 L, and 3.24 ± 0.51 L/h, respectively. No accumulation of colistin was observed after multiple doses. The cumulative urinary recovery of colistin was 0.9 ± 0.7% within 24 h after multi-dose administration. No nephrotoxicity was reported., Conclusions: This study is the first to report colistin PKs in healthy Chinese subjects after single and multiple doses of colistin sulfate. The PK and safety data are required for optimal dose selection in clinical practice., (Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Purpose: This study aims to assess the predictive performance of published valproic acid (VPA) population pharmacokinetic (PPK) models using an external data set in Chinese adults with epilepsy or after neurosurgery., Methods: A total of 384 concentrations from 290 Chinese adults with epilepsy or after neurosurgery were used for external validation. Data on published VPA PPK models were extracted from the literature. Prediction-based diagnostics (such as F20 and F30), simulation-based diagnostics, and Bayesian forecasting were used to evaluate the predictability of models., Results: The results of prediction-based diagnostics of all models were unsatisfactory. Models B, F, and H showed the best prediction performance in simulation-based diagnostics and Bayesian forecasting, demonstrating superior precision and accuracy. Bayesian forecasting demonstrated significant improvements in the model predictability., Conclusion: The published PPK models showed extensive variation in predictive performance for extrapolation among Chinese adults with epilepsy or after neurosurgery patients. Fixed parameters of Vd and Ka in the PPK modeling of VPA might be the reason for the unsatisfied predictive performance. Bayesian forecasting significantly improved model predictability and may help to individualize VPA dosing., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study aimed to evaluate the pharmacokinetics (PKs) and safety of a generic drug, linezolid, compared to those of a reference drug in healthy Chinese subjects under both fasting and fed conditions. This was a randomized, open-label, 2-period, 2-sequence crossover study. The subjects received a single dose of the test or reference drug, linezolid (600 mg), in each period. The PK parameters were calculated using a non-compartmental method and compared between the 2 drugs. Bioequivalence was analyzed using geometric mean ratios (GMRs) of the 2 formulations and their corresponding 90% confidence intervals (CIs). The safety of the 2 formulations was assessed under both fasting and fed conditions. Forty-eight subjects completed the study, 24 each in the fasting and feeding groups. The average plasma concentration-time patterns of linezolid were similar for both medications under both conditions. The GMR and 90% CIs of the maximum plasma concentration and the area under the plasma concentration-time curve of linezolid were ranged from 0.80 to 1.25. Both drugs were well tolerated with a similar incidence of adverse drug reactions. In conclusion, the PK and safety profiles of the 2 formulations were comparable. Food intake did not influence the PK profiles of linezolid. These results suggest that the test drug can be used as an alternative to reference drugs., (© 2024, The American College of Clinical Pharmacology.)

Aims: Programmed cell death receptor (ligand)-1 inhibitors (PD-(L)1), as the preferred immunotherapy, have been widely used in the Chinese mainland and drug-induced liver injury (DILI) has been reported. The study aimed to investigate the clinical features or risk factors for immunotherapy-related DILI., Methods: Patients who received PD-(L)1 inhibitors from January 2020 to July 2021 were retrospectively reviewed. The likelihood of DILI was adjudicated by the Roussel-Uclaf causality assessment., Results: A total of 1175 patients were included in the study and 89 patients (7.6%) developed DILI, of which 12 (13.5%) progressed to acute liver failure (ALF) and three (3.4%) died. Among the DILI population, 56 (62.9%) had a cholestatic pattern and exhibited a prolonged treatment course and duration for resolution compared to the hepatocellular and mixed patterns. Hepatocellular carcinoma (HCC), hepatitis B virus (HBV) and abnormal baseline of alkaline phosphatase (ALP) had increased risks of DILI by 2.1-fold (95% confidence interval [CI], 1.231-3.621), 1.9-fold [95% CI, 1.123-3.325] and 2.1-fold [95% CI, 1.317-3.508], respectively. The model for end-stage liver disease (MELD) score had a c-statistic of 0.894 (95% CI, 0.778-1.000) with a sensitivity of 67% and a specificity of 95% for poor outcomes. COX analysis showed that the MELD ≥ 18 was predictive of immunotherapy-related ALF or death., Conclusions: PD-(L)1 inhibitor-related liver injury manifests primarily as a cholestatic pattern, on which corticosteroid treatment has minimal effect compared to hepatocellular and mixed patterns. MELD score ≥ 18 at the time of liver injury performed best in the prediction of ALF or death in immune checkpoint inhibitor (ICI)-related DILI., (© 2024 British Pharmacological Society.)

Different antibiotics are used to treat mastitis in dairy cows that is caused by Escherichia coli (E. coli). Antimicrobial resistance in food-producing animals in China has been monitored since 2000. Surveillance data have shown that the prevalence of multiresistant E. coli in animals has increased significantly. This study aimed to investigate the occurrence and molecular characteristics of resistance determinants in E. coli strains ( n  = 105) obtained from lactating cows with clinical bovine mastitis (CBM) in China. A total of 220 cows with clinical mastitis, which has swollen mammary udder with reduced and red or gangrenous milk, were selected from 5000 cows. The results showed 94.3% of the isolates were recognized as multidrug resistant. The isolates (30.5%) were positive for the class I integrase gene along with seven gene cassettes that were accountable for resistance to trimethoprim resistance ( dfrA17, dfr2d and dfrA1 ), aminoglycosides resistance ( aadA1 and aadA5 ) and chloramphenicol resistance ( catB3 and catB2 ), respectively. The bla TEM gene was present in all the isolates, and these carried the bla CTX gene. A double mutation in gyrA (i.e., Ser83Leu and Asp87Asn) was observed in all fluoroquinolone-resistant isolates. In total, nine fluoroquinolone-resistant E. coli isolates were identified with five different types of mutations in parC . In four (44.4%) isolates, Ser458Ala was present in parE, and in all nine (9/9) fluoroquinolone-resistant isolates, Pro385Ala was present in gyrB. Meanwhile, fluoroquinolone was observed as highly resistant, especially in isolates with gyrA and parC mutations. In summary, the findings of this research recognize the fluoroquinolone resistance mechanism and disclose integron prevalence and ESBLs in E. coli isolates from lactating cattle with CBM.

Objectives: This study addresses the growing importance of health economics and pharmacoeconomics in preparing healthcare professionals for economic decision-making, particularly in China's evolving healthcare system. Despite their significance, these subjects are inconsistently included in health education in Southwest China, making it crucial to assess students' proficiency and educational needs., Methods: A cross-sectional study was conducted from July to October 2023, involving medical and pharmaceutical programs across universities in Sichuan, Chongqing, Guizhou, and Yunnan. Data on students' knowledge, attitudes, and proficiency were captured using a structured questionnaire. Advanced statistical methods, including descriptive analysis, ANOVA, regression analysis, PCA, and Spearman correlation heatmaps, were employed for data analysis using IBM SPSS and Python. The sample consisted of 781 students, with the survey facilitated via the Questionnaire Star platform., Results: The survey revealed moderate comprehension of health economics and pharmacoeconomics among 781 health-related students, with an average knowledge score of 2.9. The majority were pharmacy students (45.58%) and aged 21-24 years (65.81%) with a significant female majority (64.92%). Academic year significantly influenced understanding, while gender differences were minimal. Spearman correlation indicated a strong linkage (0.78) between Supply and Demand and Cost Effectiveness, with minimal correlations between knowledge and attitudes towards the educational importance of health economics. Multiple regression analysis highlighted the impact of gender and academic progression on students' comprehension of Supply and Demand concepts, as well as the influence of knowledge levels on their attitudes towards the importance of health economics education. PCA indicated the complex structure of knowledge and attitudes., Conclusions: The study found moderate knowledge levels in health economics among health professions students in Southwest China, with academic year affecting comprehension and minimal gender differences. Pharmacy students had higher proficiency in pharmaceutical-related areas, but gaps in complex topics like 'Economic Evaluation' highlight the need for targeted educational improvements to better prepare students for healthcare economic decision-making., (© 2024. The Author(s).)

A significant Omicron wave emerged in China in December 2022. To explore the duration of humoral and cellular response postinfection and the efficacy of hybrid immunity in preventing Omicron reinfection in patients with lung cancer, a total of 447 patients were included in the longitudinal study after the Omicron wave from March 2023 to August 2023. Humoral responses were measured at pre-Omicron wave, 3 months and 7 months postinfection. The detected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific antibodies including total antibodies, anti-receptor binding domain (RBD) specific IgG, and neutralizing antibodies against SARS-CoV-2 wild type (WT) and BA.4/5 variant. T cell responses against SARS-CoV-2 WT and Omicron variant were evaluated in 101 patients by ELISpot at 3 months postinfection. The results showed that Omicron-infected symptoms were mild, while fatigue (30.2%), shortness of breath (34.0%) and persistent cough (23.6%) were long-lasting, and vaccines showed efficacy against fever in lung cancer patients. Humoral responses were higher in full or booster vaccinated patients than those unvaccinated (p < .05 for all four antibodies), and the enhanced response persisted for at least 7 months. T cell response to Omicron was higher than WT peptides (21.3 vs. 16.0 SFUs/10 6 PBMCs, p = .0093). Moreover, 38 (9.74%) patients were reinfected, which had lower antibody responses than non-reinfected patients (all p < .05), and those patients of unvaccinated at late stage receiving anti-cancer immunotherapy alone were at high risk of reinfection. Collectively, these data demonstrate the Omicron infection induces a high and durable immune response in vaccinated patients with lung cancer, which protects vaccinated patients from reinfection., (© 2024 UICC.)

Organ transplant recipients with hepatitis E virus (HEV) infection bears high risk to develop chronic hepatitis, which is generally associated with immunosuppressive therapies. This study aimed to identify the incidence and predictors of de novo HEV infection in patients after receiving transplantation. We performed a large retrospective study to investigate the prevalence of anti-HEV at baseline, incidence of de novo HEV infection after transplantation, and the risk factors of HEV infection among patients with liver transplant in China. A total of 407 liver transplant recipients were examined for the presence of anti-HEV immunoglobulin G, IgM antibodies, and HEV RNA in serum. Basal indexes in individuals with evidence of post-transplant HEV infection were compared with those without evidence of that, and risk factors associated with HEV infection were assessed. The prevalence of anti-HEV at pretransplant in liver transplant recipients was 25.8% (105/407). Serum-negative conversion occurred in 34 (32.38%) of 105 liver transplant patients. Sixty-five out of 302 patients had de novo HEV infection after transplantation, with a cumulative incidence of 42.74% during follow-up. After transplantation, HEV infection was associated with liver failure (p = 0.012), hypoproteinemia (p = 0.030) and higher level of r-glutamyl transferase (GGT) (p = 0.022) before transplantation. Graft rejection (OR = 0.075; p = 0.045) was negatively associated with serum-negative conversion in patients who had positive anti-HEV antibody before transplantation. The incidence of de novo HEV infection after transplantation were higher in China. Liver failure, hypoproteinemia, and GGT elevation may be associated with HEV infection after liver transplantation. This study suggests that prevention and control of HEV infection after liver transplantation should be paid attention in patients bearing these risk factors., (© 2024 Wiley Periodicals LLC.)

The objective of this phase 1 single-dose study was to evaluate the safety, tolerability, and pharmacokinetics of mirikizumab in Chinese healthy adults. Sixty participants were randomized within 5 planned dose cohorts: intravenous (IV) 300 mg, IV 600 mg, IV 1200 mg, subcutaneous (SC) 200 mg, and SC 400 mg to receive mirikizumab (10 participants in each cohort) or placebo (2 participants in each cohort). No death or serious adverse events occurred. Twenty-eight (56.0%) participants who received mirikizumab reported 49 treatment-emergent adverse events (TEAEs) and 8 (80.0%) participants who received placebo reported 18 TEAEs. The majority of TEAEs were mild in severity. Following IV 300-1200 mg mirikizumab, the arithmetic mean of both area under the concentration versus time curve from time 0 to infinity (AUC 0-∞ ) and maximum observed drug concentration (C max ) increased by approximately 3.5-fold, and the arithmetic mean half-life (t 1/2 ) ranged from 9.64 to 12.0 days. Following SC 200 and 400 mg mirikizumab, the arithmetic mean of both AUC 0-∞ and C max increased by approximately 1.6-fold, the median time to C max  (t max ) was 2.98 days for both, and the arithmetic mean t 1/2 was 10.6 and 10.5 days, respectively. Absolute bioavailability based on pooled SC and IV dose data was 38.2%. In this study, the safety and pharmacokinetic profile of mirikizumab were consistent with what has been reported in other studies., (© 2024, The American College of Clinical Pharmacology.)

The study aimed to evaluate the impact of compensating retinal nerve fiber layer (RNFL) thickness for demographic and anatomical factors on glaucoma detection in Chinese and Indian adults. A population-based study included 1995 healthy participants (1076 Chinese and 919 Indians) to construct a multivariable linear regression compensation model. This model was applied to 357 Chinese glaucoma patients, 357 healthy Chinese, and 357 healthy Indians using Cirrus spectral-domain optical coherence tomography (OCT). The compensated RNFL thickness considered age, refractive error, optic disc parameters, and retinal vessel density. Results showed that although the average RNFL thickness was significantly higher in Chinese participants compared to Indians, the compensation model reduced this difference to nonsignificance. Moreover, the compensation model significantly improved the area under the receiver operating characteristic curve (0.90 vs. 0.78; p<0.001), sensitivity (75% vs. 51%), and specificity (67% vs. 32%) in distinguishing Chinese glaucoma patients from healthy Indian individuals. The compensation model significantly enhanced the diagnostic accuracy of RNFL thickness in distinguishing glaucoma in the Chinese ethnic group compared to the OCT instrument's default values. These results suggest that modifying RNFL measurements based on individual characteristics can yield substantial benefits for glaucoma detection across ethnicities., (© 2024 The Author(s). Annals of the New York Academy of Sciences published by Wiley Periodicals LLC on behalf of The New York Academy of Sciences.)

Background: Lamotrigine is a new antiepileptic drug with substantial interindividual variability in its pharmacokinetics and therapeutic responses. This study aimed to develop population pharmacokinetic (PPK) models of lamotrigine and its N2-glucuronide metabolites for model-informed individualized therapy., Methods: A total of 353 plasma concentrations from Chinese patients with epilepsy receiving oral lamotrigine were used to develop a population PPK model using a nonlinear mixed effects modeling method. One- and two-compartment models were applied to the nonmetabolite and metabolite model, respectively. Forward addition and backward elimination were used to establish the final model. Model validation was performed using standard goodness-of-fit, bootstrap, visual predictive checks, and normalized prediction distribution errors. Finally, simulations were performed to propose lamotrigine dosages in different situations to achieve trough concentrations within the reference interval (2.5-15 mg/L)., Results: For both final population PPK models, coadministration with valproic acid (VPA) or enzyme inducer, and body weight significantly affected lamotrigine clearance. The final models for lamotrigine clearance were and for nonmetabolite and metabolite models, respectively. The precision of the PPK parameters was acceptable, and the models exhibited good predictability. Monte Carlo simulations revealed that the lamotrigine dosage administered to patients combined with an enzyme inducer must be tripled that administered with VPA to reach the target trough concentration., Conclusions: Variability in the pharmacokinetics of lamotrigine is large. Coadministration of VPA or an enzyme inducer and body weight are the most important factors in lamotrigine clearance in Chinese patients with epilepsy. The developed population PPK models might support further optimization of lamotrigine dosing regimens., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Type 2 diabetes (T2D) is a heterogeneous metabolic disease with large variations in the relative contributions of insulin resistance and β-cell dysfunction across different glucose tolerance subgroups and ethnicities. A more precise yet feasible approach to categorize risk preceding T2D onset is urgently needed. This study aimed to identify potential metabolic biomarkers that could contribute to the development of T2D and investigate whether their impact on T2D is mediated through insulin resistance and β-cell dysfunction., Methods: A non-targeted metabolomic analysis was performed in plasma samples of 196 incident T2D cases and 196 age- and sex-matched non-T2D controls recruited from a long-term prospective Chinese community-based cohort with a follow-up period of ∼ 16 years., Results: Metabolic profiles revealed profound perturbation of metabolomes before T2D onset. Overall metabolic shifts were strongly associated with insulin resistance rather than β-cell dysfunction. In addition, 188 out of the 578 annotated metabolites were associated with insulin resistance. Bi-directional mediation analysis revealed putative causal relationships among the metabolites, insulin resistance and T2D risk. We built a machine-learning based prediction model, integrating the conventional clinical risk factors (age, BMI, TyG index and 2hG) and 10 metabolites (acetyl-tryptophan, kynurenine, γ-glutamyl-phenylalanine, DG(18:2/22:6), DG(38:7), LPI(18:2), LPC(P-16:0), LPC(P-18:1), LPC(P-20:0) and LPE(P-20:0)) (AUROC = 0.894, 5.6% improvement comparing to the conventional clinical risk model), that successfully predicts the development of T2D., Conclusions: Our findings support the notion that the metabolic changes resulting from insulin resistance, rather than β-cell dysfunction, are the primary drivers of T2D in Chinese adults. Metabolomes as a valuable phenotype hold potential clinical utility in the prediction of T2D., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Production and hosting by Elsevier B.V.)

Background: This phase I clinical study aimed to assess the safety, tolerability, and population pharmacokinetic-pharmacodynamics (PK-PD) target attainment analysis of etimicin sulfate in healthy participants, and to provide scientific reference for further development of clinical breakpoints., Methods: A total of 24 healthy Chinese subjects were enrolled in this study and received an etimicin sulfate infusion. A population PK model was constructed for the estimation of the PK profiles of etimicin sulfate. The area under the concentration-time curve divided by the minimum inhibitory concentration (AUC 0-24h /MIC) and the peak concentration divided by the MIC (C max /MIC) were selected as the PK/PD indices. The probability of target attainment (PTA) was calculated for each designed dosing regimen using Monte Carlo simulations. The minimum MIC value with a PTA ≥ 90% for each regimen was considered as the PK/PD cutoff values., Results: Etimicin sulfate demonstrated safety, tolerability, and predictable PK characteristics. No deaths or serious adverse events were reported. Seven treatment-emergent adverse events (TEAEs) were reported by five participants; all TEAEs were minor and were rapidly relieved. A two-compartment model was developed and validated for describing the PK features of etimicin sulfate among Chinese healthy participants. The diagnostic goodness-of-fit plots and visual predictive check plots showed that this developed model could describe these data well., Conclusions: The PTA results showed that etimicin sulfate provided clinical improvement against strains with an MIC of 0.5-1 mg/L and below, and antibacterial effect against strains with an MIC of 0.25 mg/L and below. However, etimicin sulfate had limited clinical efficacy for clinical isolates with MIC values > 1 mg/L., (Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Capecitabine (CAP) is one of the fluoropyrimidine deoxynucleoside carbamates, which can be converted to 5-fluorouracil (5-FU) by thymine deoxynucleoside phosphorylase (dThdPase) to exert antitumor effects. The purpose of this study is to compare the pharmacokinetics (PK), bioequivalence (BE), and safety of two CAP tablets in Chinese patients with solid tumor cancer. The results showed that the geometric mean ratios (GMRs) of C max , AUC 0-t and AUC 0-∞ of CAP T/R reagent were 90.26%, 95.27%, and 95.07, respectively. The values and 90% confidence intervals (CI) of AUC 0-t , AUC 0-∞ , and C max all fall within the range of 80.00-125.00%. In addition, a total of 22 subjects in this study had 30 adverse events, with an incidence of 45.83%, and there were no serious adverse events and adverse events that led to withdrawal from the trial., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Maternal lipid metabolism has been implicated in elevating the risk of adverse pregnancy outcomes, which is a particularly significant concern in twin pregnancies. However, the precise relationship between early pregnancy dyslipidemia and the risk of preterm birth (PTB) in twin pregnancies remains unclear., Methods: This retrospective cohort study included women with twin pregnancies between January 2018 and December 2023. Early pregnancy blood lipid profiles, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C), were examined. Dyslipidemia was diagnosed based on the diagnostic criteria outlined in the 2016 guidelines for the prevention and treatment of dyslipidemia in Chinese adults. PTB was defined as birth occurring before 37 weeks of pregnancy. Logistic regression models were used to evaluate the association of early pregnancy dyslipidemia with PTB in twin pregnancies., Results: A total of 613 women with twin pregnancies were included, and 141 women were complicated with dyslipidemia. The incidence of PTB < 37 weeks was significantly higher in the dyslipidemia group compared to the group without dyslipidemia (64.5% vs. 50.4%, P = 0.003). After adjusting for confounding factors, dyslipidemia was positively associated with PTB < 37 weeks (adjusted odds ratio: 1.71; 95% confidence interval: 1.13-2.58). However, these associations varied depending on the chorionicity and mode of conception of the twins. The positive associations between early pregnancy dyslipidemia and PTB < 37 weeks remained significant only in spontaneously conceived (SC) or dichorionic diamniotic (DCDA) twin pregnancies. No statistically significant associations were observed between dyslipidemia and the other secondary outcomes., Conclusion: Early pregnancy dyslipidemia was positively associated with PTB < 37 weeks in twin pregnancies, and this association remained significant in SC or DCDA twin pregnancies. Comprehensive lipid profile assessment in the first trimester may be beneficial for patients' monitoring and implementing interventions to mitigate adverse pregnancy outcomes., (© 2024. The Author(s).)

Objective: To evaluate the efficacy and safety of discriminative application of Chinese patent medicines in female patients after percutaneous coronary intervention (PCI) due to acute coronary syndrome (ACS). Methods: The study population was from the Chinese Patent Medicine (CPM) trial. CPM trial was a multicenter prospective cohort study, which enrolled patients from 40 centers in mainland China between February 2012 and December 2015, with the discriminative use of Chinese patent medicines as the exposure factor. Female patients with ACS after PCI who completed 36-month follow-up were included in this analysis, and were divided into a conventional treatment group (using conventional western medicine recommended by the guidelines) and a group with the discriminative use of proprietary Chinese medicines (on the basis of conventional western medicine treatment, discriminative use of Qishen Yiqi dropping pills for Qi deficiency and blood stasis syndrome, Guanxin Danshen dropping pills for blood stasis syndrome, and Danlou tablets for phlegm and blood stasis syndrome combined with the conventional western medicine). The primary endpoint event was a composite endpoint event including cardiovascular death, nonfatal myocardial infarction, and emergency revascularization surgery. Secondary endpoint events were composite endpoint events including readmission for ACS, heart failure, stroke, and other thrombotic events. Adverse events were collected. Cox proportional risk model was used to assess the effect of discriminatory application of Chinese patent medicine on endpoint events, and sensitivity analysis was performed by comparing the results with propensity score matching analysis. Results: A total of 748 female ACS post-PCI patients were included in the analysis, aged (63.2±8.3) years. There were 370 patients in the group of discriminative application of Chinese patent medicines and 378 patients in the conventional treatment group. There were 37 cases (10.0%) and 58 cases (15.3%) of primary endpoint events in the discriminatory application of Chinese patent medicines group and the conventional treatment group, respectively. Cox analysis showed that the risk of primary endpoint in the discriminatory application of Chinese patent medicines group was lower than that in the conventional treatment group after adjusting for confounding factors (adjusted HR =0.62, 95% CI 0.40-0.96, P =0.031). There were 38 (10.3%) and 57 (15.1%) cases of secondary endpoint events in the two groups, respectively. Cox regression analysis showed that the risk of secondary endpoint events in the discriminatory application of Chinese patent medicine group was lower than that in the conventional treatment group after adjusting for confounders (adjusted HR =0.56, 95% CI 0.37-0.87, P =0.001). The results of propensity score matching analysis also showed that Chinese patent medicines based on discriminatory application could reduce the risk of primary endpoint ( HR= 0.62,95% CI 0.40-0.97 ,P =0.033) and second endpoint ( HR =0.56, 95% CI 0.37-0.87, P =0.009) significantly. There was no significant difference in adverse events between the two groups (12.4% (46/370) vs. 10.3% (39/378), P =0.362). Conclusion: On the basis of conventional western medicine treatment, discriminatory application of Chinese patent medicines can reduce the risk of endpoints in female patients after PCI due to ACS without significant adverse effects.

Objectives: To establish the epidemiology cut-off (ECOFF) values of eravacycline against Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Acinetobacter baumannii and Staphylococcus aureus, from a multi-centre study in China., Methods: We collected 2500 clinical isolates from five hospitals in China from 2017 to 2020. The MICs of eravacycline were determined using broth microdilution. The ECOFF values of eravacycline against the five species commonly causing cIAIs were calculated using visual estimation and ECOFFinder following the EUCAST guideline., Results: The MICs of eravacycline against all the strains were in the range of 0.004-16 mg/L. The ECOFF values of eravacycline were 0.5 mg/L for E. coli, 2 mg/L for K. pneumonia and E. cloacae, and 0.25 mg/L for A. baumannii and S. aureus, consistent with the newest EUCAST publication of eravacycline ECOFF values for the populations. No discrepancy was found between the visually estimated and 99.00% ECOFF values calculated using ECOFFinder., Conclusions: The determined ECOFF values of eravacycline against the five species can assist in distinguishing wild-type from non-wild-type strains. Given its promising activity, eravacycline may represent a member of the tetracycline class in treating cIAIs caused by commonly encountered Gram-negative and Gram-positive pathogens., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Introduction: Generalized pustular psoriasis (GPP) is a rare and potentially life-threatening inflammatory skin disease. Interleukin (IL)-36 signalling may play a central role in GPP pathogenesis. Spesolimab is a humanized anti-IL-36 monoclonal antibody inhibiting the IL-36 signalling pathway. Here, we investigated the pharmacokinetics and safety of spesolimab in healthy Chinese subjects., Methods: In this Phase 1, single-dose, parallel-group, open-label study, healthy Chinese subjects aged 18-45 years received a single spesolimab dose by intravenous infusion (IV; 450 mg, 900 mg, or 1200 mg) or subcutaneous (SC) administration (300 mg or 600 mg). Primary endpoints were spesolimab exposure (area under the plasma concentration-time curve and maximum plasma concentration); secondary endpoints were treatment-emergent adverse events (TEAEs) and drug-related adverse events (AEs)., Results: Fifty subjects received IV (n = 30) or SC (n = 20) spesolimab (n = 10 per dose group); 60.0% were male, mean ± standard deviation age was 31.5 ± 6.6 and 31.0 ± 6.5 years in the IV and SC groups, respectively. Spesolimab exposure increased in a dose-proportional manner in both groups. TEAEs were reported in 83.3% and 80.0% of subjects in the IV and SC groups, the most common TEAE was upper respiratory tract infection (20.0% and 25.0%, respectively). One serious AE of hand fracture was reported in the 900 mg IV group that was not considered drug-related. Drug-related AEs were reported in 53.3% and 55.0% of subjects in the IV and SC groups. All laboratory-related AEs were mild and resolved., Conclusion: Spesolimab exposure increased in a dose-proportional manner after a single dose by IV and SC administration. Spesolimab was well tolerated in healthy Chinese subjects., Clinical Trial Registration: Clinicaltrials.gov registration: NCT04390568., (© 2024. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

X-linked microhaplotypes (X-MHs) have the potential to be a valuable supplementary tool in complex kinship identification or the resolution of DNA mixtures, because they bring together the distinctive genetic pattern of X chromosomal markers and the benefits of microhaplotypes (MHs). In this study, we used the 1000 Genome database to screen and select 63 X-MHs; 18 MHs were filtered out though a batch sequencing assessment of the DNA samples collected from 112 unrelated Chinese Han individuals. The resulting 45-plex panel performed well in comprehensive assessments including repeatability, sensitivity, species specificity, resistance to PCR inhibitors or degradation, mutation rate, and accuracy in detecting DNA mixture samples. The minimum amount of DNA template that can be tested with this panel is 0.5 ng. Additionally, the alleles of the minor contributor can be accurately detected when the mixture rate is larger than 1:9 in female-male mixture or 1:19 in male-male mixture. Then, we calculated population parameters on each MH based on the allele frequency data obtained from the sequence results of the aforementioned 112 unrelated samples. Combining these parameters on each MH, it can be calculated that TDP m , TDP f , CPET, CPED FM , CPED FF and CNCEP 3 of the 45-plex system were 1-8.99×10 -13 , 1-1.62×10 -19 , 0.9999999995, 0.9999981, 0.9955, 0.9999971 and 0.99940, respectively, indicating that the panel is capable in personal identification and parentage testing. To reveal the unique advantage of X-MHs in the analyses of complex kinship and male DNA mixture, further assessments were made. For complex kinship identification, 22 types of individual pairs with different second-degree kinship were simulated and different types of likelihood ratios (LR) were calculated for each. The results revealed that the panel can achieve accuracy of approximately 70 %∼80 % when dividing each of the three types of second-degree kinships into three or four groups. Theoretically, such sub-division cannot be done by using independent autosomal markers. For male DNA mixture analysis without suspects, the maximum likelihood ratio strategy was derived and employed in the estimation of the number of male contributors (NOMC). Simulations were conducted to verify the efficacy of the 45-plex panel in the field and to compare it with autosomal markers by assuming the 45 MHs as autosomal ones. The results showed that X-MHs can achieve higher accuracy in the estimation of NOMC than autosomal ones when the mixed males were unrelated. The results highlighted the unique value of X-linked MHs in complex kinship and male mixture analyses., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Two new ent-labdane diterpenoids, hypoestesins A-B (1-2) and five new labdane diterpenoids, hypopurolides H-L (3-7), were isolated from the aerial parts of Hypoestes purpurea. All of the structures were fully determined based on extensive analysis of 1 H, 13 C, 2D NMR, and HRESIMS data. The absolute configurations of 1-3 was established through comparing the experimental and calculated ECD curves and the structure of 5 was confirmed by single crystal X-ray diffraction experiment. Compounds 5-7 were unusual C23 labdane diterpenoids having a γ-acetonyl-α, β-unsaturated γ-lactone unit and each assigned as C-15 epimeric mixture. Furthermore, cytotoxic and anti-inflammatory activities of 3-7 were evaluated. The results showed that 3 had remarkable cytotoxic activity against HL-60, A549, SMMC-7721, MDA-MB-231, and SW480 cancer cell lines with IC 50 values ranging from 2.35 to 17.06 μM. Compound 4 showed moderate cytotoxic activity against HL-60 and SMMC-7721 cancer cell lines with IC 50 values of 15.12 ± 0.53 and 12.92 ± 0.60 μM, respectively. Furthermore, compound 4 was also found to exhibit inhibitory activity against NO production in RAW 264.7 macrophages with IC 50 values of 23.56 ± 0.99 μM, compared to the positive control L-NMMA with an IC 50 value of 41.11 ± 1.34 μM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Aim: To develop 10-year cardiovascular disease (CVD) risk prediction models in Chinese patients with type 2 diabetes mellitus (T2DM) managed in primary care using machine learning (ML) methods., Methods: In this 10-year population-based retrospective cohort study, 141 516 Chinese T2DM patients aged 18 years or above, without history of CVD or end-stage renal disease and managed in public primary care clinics in 2008, were included and followed up until December 2017. Two-thirds of the patients were randomly selected to develop sex-specific CVD risk prediction models. The remaining one-third of patients were used as the validation sample to evaluate the discrimination and calibration of the models. ML-based methods were applied to missing data imputation, predictor selection, risk prediction modelling, model interpretation, and model evaluation. Cox regression was used to develop the statistical models in parallel for comparison., Results: During a median follow-up of 9.75 years, 32 445 patients (22.9%) developed CVD. Age, T2DM duration, urine albumin-to-creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), systolic blood pressure variability and glycated haemoglobin (HbA1c) variability were the most important predictors. ML models also identified nonlinear effects of several predictors, particularly the U-shaped effects of eGFR and body mass index. The ML models showed a Harrell's C statistic of >0.80 and good calibration. The ML models performed significantly better than the Cox regression models in CVD risk prediction and achieved better risk stratification for individual patients., Conclusion: Using routinely available predictors and ML-based algorithms, this study established 10-year CVD risk prediction models for Chinese T2DM patients in primary care. The findings highlight the importance of renal function indicators, and variability in both blood pressure and HbA1c as CVD predictors, which deserve more clinical attention. The derived risk prediction tools have the potential to support clinical decision making and encourage patients towards self-care, subject to further research confirming the models' feasibility, acceptability and applicability at the point of care., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Previous studies exploring the relationship between dietary potassium and magnesium intake and the risk of type 2 diabetes mellitus (T2DM) have yielded inconsistent results and the lack evidence from rural China. Therefore, we aimed to investigate the association between dietary potassium and magnesium intake and the risk of T2DM in rural China. Data was collected from the Henan Rural Cohort Study in 2017. A validated semi-quantitative food frequency questionnaire assessed dietary potassium and magnesium intake. Logistic regression models were used to calculate odds ratio (ORs) and 95% confidence intervals (CIs) to evaluate the effect of dietary potassium, magnesium and the potassium-magnesium ratio on the risk of T2DM. A total of 38384 individuals were included in the study, and 3616 participants developed T2DM. Logistic regression analysis revealed that the OR (95% CI) of the highest versus dietary potassium and magnesium and potassium-magnesium ratio intakes were 0.67 (0.59, 0.75), 0.76 (0.67, 0.88), and 0.57 (0.50, 0.66), respectively, compared to the subjects with the lowest quartile of intakes. In addition, gender partially influences the relationship between dietary magnesium and T2DM prevalence (P- interaction = 0.042). The group with the highest dietary potassium and dietary magnesium intake had the lowest risk of T2DM, with an OR (95% CI) of 0.63 (0.51-0.77). Dietary potassium and magnesium intake are important modifiable risk factors for T2DM in rural China. Dietary potassium intake > 1.8g/day, dietary magnesium intake > 358.6mg/day and < 414.7mg/day and potassium-magnesium ratio >5.1 should be encouraged to prevent better and manage T2DM., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Daphne genkwa, as a traditional medicine, is widely distributed in China, Korea and Vietnam. In China, the dried flower buds of this plant are named "Yuanhua". It has the ability to effectively promote urination, eliminate phlegm and alleviate cough, eliminate parasites and cure of scabies, with a broad spectrum of pharmacological effects and considerable clinical efficacy. This paper provides a summary and classification of the main chemical constituents of D. genkwa based on a review of relevant domestic and foreign literature. It also outlines the current research status of traditional clinical usage, pharmacological effects, and toxicity of D. genkwa. The aim is to provide a theoretical basis for further study of D. genkwa and its potential new clinical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Emerging studies have suggested the association of ambient air pollution with worse cognitive function; however, causal evidence remains scarce. We aimed to estimate the effect of particulate matter (PM) exposure on overall and domain-specific cognitive function. A total of 14,205 participants aged 45 years and above were drawn from the 2015 wave of the China Health and Retirement Longitudinal Study (CHARLS). Cognitive function was assessed using a standardized questionnaire consisting of two domains: episodic memory and mental status. Participants' exposure to city-level PM (PM 1 , PM 2.5 , and PM 10 ) was evaluated using satellite-based spatiotemporal models. To avoid potential endogenous biases, an instrumental variable method with two-stage least squares estimation was employed to examine the effect of air pollution on overall and domain-specific cognitive function. Stratified analysis was further performed based on sociodemographic characteristics. We found PM exposure exertedsignificant adverse effects on overall and domain-specific cognitive function, with mental status being more adversely affected as compared to episodic memory. The effect of PM exposure was more pronounced with smaller particle sizes, with PM 1 exhibiting the largest effect size. Moreover, participants with lower education attainment were more adversely affected by PM exposure. Our findings add additional evidence of the potential causal role of PM exposure in worsening overall and domain-specific cognitive function. Efforts to further reduce PM are needed to protect the cognitive health of the aging Chinese population., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Six new prenylated flavonoids, named visconaeas A-F (1-6), and eleven known isopentenyl flavonoids (7-17) were isolated from Dodonaea viscosa (L.) Jacq. The structures of the separated compounds were determined through comprehensive spectral analysis and quantum chemical calculations. These compounds were tested for their anti-Zika virus and cytotoxicity activities. The results indicated that compound 4 showed low cytotoxicity and strong anti-Zika virus potential with EC 50 16.34 μM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Delphinium belongs to Ranunculaceae, which is widely distributed in Northwest China. In folk, this genus of plants has analgesic, anti-inflammatory, and insecticidal effects. By studying non-alkaloid components in the whole herbs of Delphinium forrestii, we obtained a total of 11 compounds (1-11), including five new (1-5) and six known polyphenols (6-11). On the basis of chemical evidences and spectral data analysis (UV, Optical rotation data, 1D/2D-NMR and HR-ESI-MS), the structures of new compounds were elucidated. The inhibitory effect of compounds 1-11 on lipopolysaccharide (LPS) induced NO production in RAW 264.7 cells was detected. Compounds 4 and 11 showed significant inhibitory effects. This study indicated the presence of compounds with good anti-inflammatory activity among non-alkaloid components in the whole herbs of Delphinium forrestii., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Livestock farms are major reservoirs of antibiotic resistance genes (ARGs) that are discharged into the environment. However, the abundance, diversity, and transmission of ARGs in duck farms and its impact on surrounding environments remain to be further explored. Therefore, the characteristics of ARGs and their bacterial hosts from duck farms and surrounding environment were investigated by using metagenomic sequencing. Eighteen ARG types which consist of 823 subtypes were identified and the majority conferred resistance to multidrug, tetracyclines, aminoglycosides, chloramphenicols, MLS, and sulfonamides. The floR gene was the most abundant subtype, followed by sul1, tetM, sul2, and tetL. ARG abundance in fecal sample was significantly higher than soil and water sample. Our results also lead to a hypothesis that Shandong province have been the most contaminated by ARGs from duck farm compared with other four provinces. PcoA results showed that the composition of ARG subtypes in water and soil samples was similar, but there were significant differences between water and feces samples. However, the composition of ARG subtypes were similar between samples from five provinces. Bacterial hosts of ARG subtypes were taxonomically assigned to eight phyla that were dominated by the Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria. In addition, some human bacterial pathogens could be enriched in duck feces, including Enterococcus faecium, Acinetobacter baumannii, and Staphylococcus aureus, and even serve as the carrier of ARGs. The combined results indicate that a comprehensive overview of the diversity and abundance of ARGs, and strong association between ARGs and bacterial community shift proposed, and benefit effective measures to improve safety of antibiotics use in livestock and poultry farming. KEY POINTS: • ARG distribution was widespread in the duck farms and surroundings environment • ARG abundance on the duck farms was significantly higher than in soil and water • Human bacterial pathogens may serve as the vectors for ARGs., (© 2024. The Author(s).)

Background: Cardiovascular disease (CVD) is the leading cause of mortality in type 2 diabetes mellitus (T2DM) patients. Shrunken pore syndrome (SPS) is defined as eGFR cystatin C /eGFR creatinine ratio <0.70 and predicts high CVD mortality. The Framingham Risk Score (FRS) is used to estimate an individual's 10-year CVD risk. This study investigated the association between FRS and eGFR cystatin C /eGFR creatinine ratio in T2DM patients., Methods: Patients aged 18-80 years who were newly diagnosed with T2DM were included in this retrospective study. Ordinal logistic regression analysis was used to investigate the association between risk factors of T2DM and FRS. A Generalized Linear Model was used to calculate odds ratios (OR) and 95% confidence intervals (CI)., Results: There were 270 patients included in the study. Only 27 patients (10%) met the diagnostic criteria of SPS. Ordinal logistic regression analysis showed that SPS was not correlated with FRS risk (OR = 1.99, 95%CI = 0.94-4.23, p  = 0.07), whereas eGFR cystatin C /eGFR creatinine (OR = 0.86, 95%CI = 0.77-0.97, p  = 0.01) showed a significant negative association with FRS risk. Compared with eGFR cystatin C /eGFR creatinine >0.85, eGFR cystatin C /eGFR creatinine ≤0.85 increased FRS risk (OR = 1.95, 95%CI = 1.18-3.21, p  < 0.01). After adjustment for confounding factors, increased eGFR cystatin C /eGFR creatinine ratio was associated with decreased FRS risk when considered as a continuous variable (OR = 0.87, 95%CI = 0.77-0.99, p  = 0.03). The FRS risk in patients with eGFR cystatin C /eGFR creatinine ≤0.85 is 1.86 times higher than that in patients with eGFR cystatin C /eGFR creatinine >0.85 (OR = 1.86, 95%CI = 1.08-3.21, p  = 0.03)., Conclusions: In the current study, no significant association between SPS and FRS was identified. However, lower eGFR cystatin C /eGFR creatinine and eGFR cystatin C /eGFR creatinine ≤0.85 were associated with a significantly increased CVD risk in T2DM.

Objective: To analyze the genetic test results of 378 patients suspected of thalassemia., Methods: 378 suspected thalassemia patients in Shaoxing People's Hospital from 2014 to 2020 were selected and venous blood was tested using Gap-PCR and PCR-reversed dot blottin. The distribution of genotypes and other information of gene-positive patients was observed., Results: Thalassemia genes were detected in 222 cases, with an overall detection rate of 58.7%, of which 41.4% were α deletion type, 1.35% were α dot, 52.7% were α thalassemia, and 4.5% were αβ complex type. Among the 86 people with provincial household registration, the α-thalassemia gene accounted for 65.1% and the β-thalassemia gene accounted for 25.6%. Follow-up found that Shaoxing nationality accounted for 53.1% of positive patients, of which β-thalassemia gene accounted for 72.9% and α-thalassemia gene accounted for 25.4%; other cities in the province accounted for 8.1% of the total. Other provinces and cities accounted for 38.7%, most of which were from Guangxi and Guizhou. Among all positive patients, the most common α-thalassemia genotypes were --sea / αα, --α / αα,--α 3.7 4.2 / αα , --α3.7 / --sea. The most common mutations in β-thalassemia were IVS-II-654, CD41-42, CD17 and CD14-15., Conclusion: The thalassemia gene carrier status was sporadically distributed outside the traditional thalassemia high prevalence areas. The local population in Shaoxing has a high detection rate of thalassemia genes, and the genetic composition is different from the traditional high prevalence area of thalassemia in the south.

Purpose: Secukinumab, a monoclonal antibody targeting interleukin (IL)-17A, is approved for the treatment of psoriasis, psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, enthesitis-related arthritis, and hidradenitis suppurativa. This study compared the pharmacokinetics (PK), safety, and immunogenicity of CMAB015, a candidate secukinumab biosimilar, with the reference product secukinumab (Cosentyx ® ) in healthy Chinese male subjects., Patients and Methods: This double-blind, parallel-group study randomized healthy Chinese male subjects (N=130) to receive either a single dose of 150 mg CMAB015 or secukinumab subcutaneously. Primary study endpoints were PK parameters such as the maximum concentration (C max ) and area under the curve from zero to infinity (AUC 0-inf ), while safety and immunogenicity were secondary endpoints., Results: The 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) of C max and AUC 0-inf for CMAB015 to secukinumab were all within the bioequivalence limits (80.00-125.00%). Other PK parameters were comparable between the groups. The safety profile of CMAB015 was similar to that of secukinumab, with no serious adverse events related to treatment. The incidence of TEAEs was slightly higher in the CMAB015 group, but these events were mild to moderate in severity and did not lead to any withdrawals from the study. Immunogenicity analysis revealed low rates of anti-drug antibody (ADA) positivity, with similar rates between CMAB015 and secukinumab., Conclusion: This study demonstrated equivalent PK, comparable safety, and immunogenicity of CMAB015 to secukinumab in healthy Chinese male subjects. These findings support further clinical evaluation of CMAB015 as a secukinumab biosimilar., Trial Registration: The trial was registered on Clinicaltrials.gov (Identifier No. NCT05734482) and Chinadrugtrials.org.cn (Identifier No. CTR20230105)., Competing Interests: Chenguang Wang, Tianshu Yang, Xunmin Zhang, Yong Shan, Sheng Hou, and Hao Wang are affiliated with Taizhou Mabtech Pharmaceutical Co. Ltd. The authors report no other conflicts of interest in this work., (© 2024 Yao et al.)

Background: The management of multidrug-resistant tuberculosis (MDR-TB) remains challenging. Treatment outcome is influenced by multiple factors; the specific roles of diabetes and glycemic control remain uncertain. This study aims to assess the impact of glycemic control on drug exposure, to investigate the association between drug exposure and treatment outcomes, and to identify clinically significant thresholds predictive of treatment outcome, among patients with diabetes., Methods: This multicenter prospective cohort study involved patients with confirmed MDR-TB and diabetes. Drug exposure level was estimated by noncompartmental analysis. The minimum inhibitory concentrations (MICs) were determined for the individual Mycobacterium tuberculosis isolates. The influence of poor glycemic control (glycated hemoglobin ≥7%) on drug exposure and the associations between drug exposure and treatment outcome were evaluated by univariate and multivariate analysis. Classification and regression tree analysis was used to identify the drug exposure/susceptibility thresholds., Results: Among the 131 diabetic participants, 43 (32.8%) exhibited poor glycemic control. Poor glycemic control was independently associated with decreased exposure to moxifloxacin, linezolid, bedaquiline, and cycloserine, but not clofazimine. Additionally, a higher ratio of drug exposure to susceptibility was found to be associated with a favorable MDR-TB treatment outcome. Thresholds predictive of 6-month culture conversion and favorable outcome were bedaquiline area under the concentration-time curve (AUC)/MIC ≥245 and moxifloxacin AUC/MIC ≥67, demonstrating predictive accuracy in patients, regardless of their glycemic control status., Conclusions: Glycemic control and optimal TB drug exposure are associated with improved treatment outcomes. This dual management strategy should be further validated in randomized controlled trials of patients with MDR-TB and diabetes., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Mycoplasma ovipneumoniae is associated with respiratory disease in wild and domestic Caprinae globally, with wide variation in disease outcomes within and between host species. To gain insight into phylogenetic structure and mechanisms of pathogenicity for this bacterial species, we compared M. ovipneumoniae genomes for 99 samples from 6 countries (Australia, Bosnia and Herzegovina, Brazil, China, France and USA) and 4 host species (domestic sheep, domestic goats, bighorn sheep and caribou). Core genome sequences of M. ovipneumoniae assemblies from domestic sheep and goats fell into two well-supported phylogenetic clades that are divergent enough to be considered different bacterial species, consistent with each of these two clades having an evolutionary origin in separate host species. Genome assemblies from bighorn sheep and caribou also fell within these two clades, indicating multiple spillover events, most commonly from domestic sheep. Pangenome analysis indicated a high percentage (91.4 %) of accessory genes (i.e. genes found only in a subset of assemblies) compared to core genes (i.e. genes found in all assemblies), potentially indicating a propensity for this pathogen to adapt to within-host conditions. In addition, many genes related to carbon metabolism, which is a virulence factor for Mycoplasmas, showed evidence for homologous recombination, a potential signature of adaptation. The presence or absence of annotated genes was very similar between sheep and goat clades, with only two annotated genes significantly clade-associated. However, three M. ovipneumoniae genome assemblies from asymptomatic caribou in Alaska formed a highly divergent subclade within the sheep clade that lacked 23 annotated genes compared to other assemblies, and many of these genes had functions related to carbon metabolism. Overall, our results suggest that adaptation of M. ovipneumoniae has involved evolution of carbon metabolism pathways and virulence mechanisms related to those pathways. The genes involved in these pathways, along with other genes identified as potentially involved in virulence in this study, are potential targets for future investigation into a possible genomic basis for the high variation observed in disease outcomes within and between wild and domestic host species.

Objectives: Both age and CYP2C19 genotypes affect voriconazole plasma concentration; the interaction of age and CYP2C19 genotypes on voriconazole plasma concentration remains unknown. This study aims to investigate the combined effects of age and CYP2C19 genotypes on voriconazole plasma concentration in Chinese patients., Methods: A total of 480 patients who received voriconazole treatment were recruited. CYP2C19*2 (rs4244285) and CYP2C19*3 (rs4986893) polymorphisms were genotyped. Patients were divided into the young and the elderly groups by age of 60 years old. Influence of CYP2C19 genotype on steady-state trough concentration (C ss-min ) in overall patients and in age subgroups was analyzed., Results: Voriconazole C ss-min correlated positively with age, and mean voriconazole C ss-min was significantly higher in the elderly group ( P  < 0.001). CYP2C19 poor metabolizers showed significantly increased mean voriconazole C ss-min in the young but not the elderly group. The percentage of patients with subtherapeutic voriconazole C ss-min (<1.0 mg/l) was higher in the young group and that of supratherapeutic voriconazole C ss-min (>5.5 mg/l) was higher in the elderly patients. When the average C ss-min in the CYP2C19 normal metabolizer genotype was regarded as a reference, CYP2C19 genotypes showed greater impact on voriconazole C ss-min in the young group, while the influence of age on voriconazole C ss-min exceeded CYP2C19 genotypes in the elderly., Conclusion: CYP2C19 genotypes affects voriconazole exposure is age dependent. Influence of CYP2C19 poor metabolizer genotype on increased voriconazoleexposure is prominent in the young, while age is a more important determinant factor for increased voriconazole exposure in the elderly patients., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Limited studies have investigated the association between statin therapy and poor glycemic control, especially in the Chinese diabetic population., Methods: Two prospective diabetes cohorts were drawn from the Kailuan Cohort. In Cohort 1, linear regression models were used to evaluate the association between statin therapy and glycated hemoglobin (HbA1c) level change. In Cohort 2, new user design and conditional logistic models were used to assess associations between statin initiation and poor glycemic control which was a composite outcome comprised of hypoglycemic agent escalation and new-onset hyperglycemia., Results: Among 11,755 diabetic patients with medication information, 1400 statin users and 1767 statin nonusers with repeated HbA1c measurements were included in Cohort 1 (mean age: 64.6 ± 10.0 years). After a median follow-up of 3.02 (1.44, 5.00) years, statin therapy was associated with higher HbA1c levels (β: 0.20%; 95%CI: 0.05% to 0.34%). In Cohort 2, 1319 pairs of matched cases/controls were included (mean age: 61.6 ± 9.75 years). After a median follow-up of 4.87 (2.51, 8.42) years, poor glycemic control occurred in 43.0% of statin new users and 31.8% of statin nonusers (OR: 1.69; 95% CI: 1.32 to 2.17; P < 0.001). The statin-associated poor glycemic control risk was significantly higher among patients with lower body mass index (P int  = 0.089). Furthermore, a nonlinear association was observed between statin therapy duration and poor glycemic control (P = 0.003)., Conclusions: Among Chinese diabetic adults, statin therapy was associated with a higher level of HbA1c, and a higher risk of hypoglycemic agent escalation and new-onset hyperglycemia, especially among those who had lower body mass index levels and longer statin therapy duration., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Purpose: To investigate the clinical features of endogenous Klebsiella pneumoniae endophthalmitis (EKPE) and the molecular characteristics of pathogenic K. pneumoniae ., Methods: A retrospective study was conducted between January 2014 and January 2021. Clinical data were extracted. K. pneumoniae isolates cultured from EKPE patients' specimens were characterized by antimicrobial susceptibility testing, multilocus sequence typing, capsular serotyping, and virulence gene profiles. Virulence phenotypes were confirmed by mouse lethality assay., Results: Thirty-nine patients (47 eyes) were diagnosed with EKPE. Administration of systemic antibiotics and eye treatment within 24 hours of ocular symptom onset was statistically associated with better visual outcomes ( p = .007). Sixteen K. pneumoniae isolates were collected, three of which were carbapenem-resistant and avirulent. Only salmochelin encoding gene was harbored by all isolates., Conclusions: Systemic and eye treatment administered within 24 hours from the onset improves visual prognosis. Besides hypervirulent strains, avirulent carbapenem-resistant K. pneumoniae can cause EKPE.

Four new γ-lactam alkaloids, suberitolactams A-D (1-4), two new pyridine alkaloids, suberitopyridines A-B (7-8), and two known compounds (5-6) were isolated from the South China Sea sponge Pseudospongosorites suberitoides. The structures were elucidated by detailed 1D and 2D NMR experiments along with HRESIMS analysis and single crystal X-ray diffraction. Compounds 1 and 8 showed moderate to weak antiviral activity against H1 N1 virus with IC 50 values of 27.6 and 13.3 μM, respectively., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

This study examined the associations of long-term exposure to ambient fine particulate matter (PM 2.5 ) compositions/ozone with methylation of peripheral brain-derived neurotrophic factor (BDNF) promoters. A total of 101 participants were recruited from a cohort in Shijiazhuang, Hebei province, China. They underwent baseline and follow-up surveys in 2011 and 2015. DNA methylation levels were detected by bisulfite-PCR amplification and pyrosequencing. Participants' three-year average levels of PM 2.5 compositions and ozone were estimated. Bayesian kernel machine regression (BKMR) models were used to examine the joint effects of pollutants on methylation levels. Exposure to PM 2.5 compositions and ozone mixtures at the 75th percentile was associated with increased methylation levels at CpG2 of BDNF promoter (203%, 95% CI: 89, 316) than the lowest level of exposure, and sulfate dominated the effect in the BKMR models.Our findings provide clues to the epigenetic mechanisms for the associations of PM 2.5 compositions and ozone with BDNF.

In addition to topography and climate, biogeographic dispersal has been considered to influence plant diversity in the Himalaya-Hengduan Mountains (HHM), yet, the mode and tempo of sky island dispersal and its influence on species richness has been little explored. Through phylogenetic analysis of Gaultheria ser. Trichophyllae, a sky island alpine clade within the HHM, we test the hypothesis that dispersal has affected current local species richness. We inferred the dynamics of biogeographic dispersal with correlation tests on direction, distance, occurrence time, and regional species richness. We found that G. ser. Trichophyllae originated at the end of the Miocene and mostly dispersed toward higher longitudes (eastward). In particular, shorter intra-regional eastward dispersals and longer inter-regional westward dispersals were most frequently observed. We detected a prevalence of eastward intra-region dispersals in both glacial periods and interglacials. These dispersals may have been facilitated by the reorganization of paleo-drainages and monsoon intensification through time. We suggest that the timing of dispersal corresponding to glacial periods and the prevalence of intra-region dispersal, rather than dispersal frequency, most influenced the pattern of species richness of G. ser. Trichophyllae. This study facilitates a more comprehensive understanding of biodiversity in the sky islands within the HHM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Birth defects are the leading cause of mortality in newborn babies and children under five years old. In response, the Chinese government has implemented a three-tiered prevention strategy, which has brought ethical concerns about fetuses with birth defects. This study aims to explore the attitudes toward fetuses with birth defects among health professionals engaged in maternal and child health services., Methods: A qualitative study was conducted among 13 health professionals engaged in maternal and child health services in Hunan Province, China. The questions were designed to elicit the participants' work experience and attitudes toward fetuses with birth defects. The data were collected through in-depth semi-structured interviews, and NVivo 12 was used for data coding and analysis. A thematic analysis approach was employed following the SRQR checklist., Results: Five themes and 13 attributes were generated regarding health professionals' perspectives on fetuses with birth defects. The five themes included: (1) severity and curability of diseases (two attributes), (2) family relations (four attributes), (3) medical assessments (two attributes), (4) social situations (three attributes), (5) self-value orientations (three attributes). The findings showed that the majority of health professionals held the view that a fetus with a curable disease could be born, whereas a fetus with severe disability and teratogenesis should be terminated. Twelve out of the 13 health professionals believed that parents should be the decision-makers, while only one thought that the family should make a decision together., Conclusions: Attitudes toward birth defects were influenced by various factors, indicating the complexity of real-world cases identified in this study. The findings highlight the dilemmas faced by both families and health professionals regarding birth defects. Adequate medical knowledge and support from society are crucial to inform decision-making among family members. Additionally, standardized norms and policies for birth defects are needed. Establishing an ethics committee for prenatal diagnosis is necessary to address current ethical issues in this field., (© 2024. The Author(s).)

Background: Health care workers (HCWs) frequently face multiple stressors at work, particularly those working night shifts. HCWs who have experienced distress may find it difficult to adopt stress management approaches, even if they are aware of the effects of stress and coping processes. Therefore, an individualized intervention may be required to assist distressed HCWs in bridging the "knowledge-practice" gap in stress management and effectively alleviating stress symptoms., Objective: The main objective of this research was to compare the effects of a complex interactive multimodal intervention (CIMI) to self-guided stress management interventions on stress symptoms of distressed HCWs, as measured by physiological (heart rate variability), psychological (perceived stress, mental distress, and subjective happiness), and sleep disorder (fatigue and sleepiness) indicators., Methods: We conducted a nonrandomized, controlled study in 2 Chinese general hospitals. The participants in this study were 245 HCWs who fulfilled at least 1 of the 3 dimensions on the Depression, Anxiety, and Stress Scale. All eligible individuals were required to complete a questionnaire and wear a 24-hour Holter device to determine the physiological signs of stress as indexed by heart rate variability at both baseline and after the intervention. The CIMI group received a 12-week online intervention with 4 components-mobile stress management instruction, a web-based WeChat social network, personalized feedback, and a nurse coach, whereas the control group simply received a self-guided intervention., Results: After a 12-week intervention, the Perceived Stress Scale (PSS) scores reduced significantly in the CIMI group (mean difference [MD] -5.31, 95% CI -6.26 to -4.37; P<.001) compared to the baseline levels. The changes in PSS scores before and after the intervention exhibited a significant difference between the CIMI and control groups (d=-0.64; MD -4.03, 95% CI -5.91 to -2.14; P<.001), and the effect was medium. In terms of physiological measures, both the control group (MD -9.56, 95% CI -16.9 to -2.2; P=.01) and the CIMI group (MD -8.45, 95% CI -12.68 to -4.22; P<.001) demonstrated a significant decrease in the standard deviation of normal-to-normal intervals (SDNN) within the normal clinical range; however, there were no significant differences between the 2 groups (d=0.03; MD 1.11, 95% CI -7.38 to 9.59; P=.80)., Conclusions: The CIMI was an effective intervention for improving sleep disorders, as well as parts of the psychological stress measures in distressed HCWs. The findings provide objective evidence for developing a mobile stress management intervention that is adaptable and accessible to distressed HCWs, but its long-term effects should be investigated in future research., Trial Registration: ClinicalTrials.gov NCT05239065; https://clinicaltrials.gov/ct2/show/NCT05239065., (©Wenhua Liu, Quan Wang, Danli Zheng, Junhua Mei, Jiajia Lu, Guohua Chen, Wei Wang, Fengfei Ding. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 12.07.2024.)

Objective: We explored whether the Clustered regularly interspaced short palindromic repeat (CRISPR)-Cas and restriction-modification (R-M) systems are compatible and act together to resist plasmid attacks., Methods: 932 global whole-genome sequences from GenBank, and 459 K. pneumoniae isolates from six provinces of China, were collected to investigate the co-distribution of CRISPR-Cas, R-M systems, and bla KPC plasmid. Conjugation and transformation assays were applied to explore the anti-plasmid function of CRISPR and R-M systems., Results: We found a significant inverse correlation between the presence of CRISPR and R-M systems and bla KPC plasmids in K. pneumoniae, especially when both systems cohabited in one host. The multiple matched recognition sequences of both systems in bla KPC -IncF plasmids (97%) revealed that they were good targets for both systems. Furthermore, the results of conjugation assay demonstrated that CRISPR-Cas and R-M systems in K. pneumoniae could effectively hinder bla KPC plasmid invasion. Notably, CRISPR-Cas and R-M worked together to confer a 4-log reduction in the acquisition of bla KPC plasmid in conjugative events, exhibiting robust synergistic anti-plasmid immunity., Conclusions: Our results indicate the synergistic role of CRISPR and R-M in regulating horizontal gene transfer in K. pneumoniae and rationalize the development of antimicrobial strategies that capitalize on the immunocompromised status of KPC-KP., (© 2024. The Author(s).)

Background: Oliceridine is a novel G protein-biased ligand μ-opioid receptor agonist. This study aimed to assess the pharmacokinetics and safety profile of single-ascending doses of oliceridine fumarate injection in Chinese patients with chronic non-cancer pain., Methods: Conducted as a single-center, open-label trial, this study administered single doses of 0.75, 1.5, and 3.0 mg to 32 adult participants. The trial was conducted in two parts. First, we conducted a preliminary test comprising the administration of a single dose of 0.75mg to 2 participants. Then, we conducted the main trial involving intravenous administration of escalating doses of oliceridine fumarate (0.75 to 3 mg) to 30 participants. Pharmacokinetic (PK) parameters were derived using non-compartmental analysis. Additionally, the safety evaluation encompassed the monitoring of adverse events (AEs)., Results: 32 participants were included in the PK and safety analyses. Following a 2-min intravenous infusion of oliceridine fumarate injection (0.75, 1.5, or 3 mg), Cmax and Tmax ranged from 51.293 to 81.914 ng/mL and 0.034 to 0.083 h, respectively. AUC 0-t and half-life (t 1/2 ) increased more than proportionally with dosage (1.85-2.084 h). Treatment emergent adverse events (TEAEs) were found to be consistent with the commonly reported adverse effects of opioids, both post-administration and as documented in the original trials conducted in the United States. Critically, no serious adverse events were observed., Conclusion: Oliceridine demonstrated comparable PK parameters and a consistent PK profile in the Chinese population, in line with the PK results observed in the original trials conducted in the United States. Oliceridine was safe and well tolerated in Chinese patients with chronic non-cancer pain at doses ranging from 0.75 mg to 3.0 mg., Trial Registration: The trial is registered at chictr.org.cn (ChiCTR2100047180)., Competing Interests: The authors declare no conflicts of interest in this work., (© 2024 Ni et al.)

Purpose: Programmed death-1 antibody plus chemotherapy has gained approval for the treatment for (human epidermal growth factor receptor 2 negative locally advanced or metastatic gastric or gastroesophageal junction cancer. This study aims to analyze the efficacy and safety of anti-programmed death-1 antibody combined with chemo- or anti-angiogenesis therapy in Chinese patients with advanced or metastatic gastric or gastroesophageal junction cancer in a real-world setting., Methods: In total, 122 patients treated with anti-programmed death-1 antibody-based combination therapy between April 2019 and December 2021 were encompassed. Clinical outcomes and safety profile were measured and analyzed., Results: In the whole cohort, median overall survival was 17.2 months, median progression-free survival was 10.9 months, and median duration of response was 9.4 months. Notably, in the first-line patients, the median overall survival was not reached, median progression-free survival was 14.8 months, objective response rate was 68.4%. In the second-line group, median overall survival, median progression-free survival, median duration of response, and objective response rate were 10.9 months, 5.9 months, 4.5 months, and 41.5%, respectively. Treatment-related adverse events of any grade were observed in 28.2% of the overall cohort, primarily affecting the hematological and liver function. Grade 3 or 4 adverse events were mainly characterized by increased levels of aspartate aminotransferase, alanine aminotransferase, along with decreased lymphocyte and white blood cells, as well as anemia., Conclusions: Patients in our cohort experienced a clinical benefit from anti-programmed death-1 antibody-combined treatment in first-line treatment settings, with acceptable treatment-related adverse events. The benefit of anti-programmed death-1 antibody combined with chemo- or anti-angiogenesis treatment to the second-line patients should be further confirmed by large multi-center randomized, controlled clinical trials., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Tiragolumab is an immunoglobulin G1 monoclonal antibody targeting the immune checkpoint T cell immunoreceptor with immunoglobulin and immunoreceptor ITIM domains. Targeting multiple immune pathways may improve anti-tumor responses. The phase I YP42514 study assessed the pharmacokinetics (PK), safety, and preliminary efficacy of tiragolumab plus atezolizumab in Chinese patients with advanced solid tumors., Methods: Adult patients from mainland China with Eastern Cooperative Oncology Group performance score 0/1, life expectancy of ≥ 12 weeks, and adequate hematologic/end organ function were eligible. Patients received tiragolumab 600 mg and atezolizumab 1200 mg intravenous every 3 weeks. Key endpoints were PK (serum concentrations of tiragolumab and atezolizumab) and safety. Results from this study were compared with the global phase I study, GO30103 (NCT02794571)., Results: In this study, 20 patients received a median of five doses of tiragolumab plus atezolizumab. Median age was 57.5 years, 85.0% of patients were male and the most common tumor type was non-small cell lung cancer. Exposures in Chinese patients were comparable to the global GO30103 population: geometric mean ratio was 1.07 for Cycle 1 tiragolumab area under the concentration-time curve 0-21 and 0.92 and 0.93 for Cycle 1 peak and trough atezolizumab exposure, respectively. Treatment-related adverse events were consistent across the Chinese and global populations. Two patients (10.0%) in this study achieved a partial response., Conclusion: In this study, tiragolumab plus atezolizumab was tolerable and demonstrated preliminary anti-tumor activity. There were no meaningful differences in the PK or safety of tiragolumab plus atezolizumab between the Chinese and global populations., Clinical Trial Registration Number: China Clinical Trial Registry Identifier CTR20210219/YP42514. Date of registration 16 March 2021., (© 2024. The Author(s).)

Background and Objectives: The 1 + X certificate system, introduced in China in 2019, integrates academic credentials with vocational skill certificates to meet the heightened demand for skilled talents in the growing economy. This study aims to innovate and evaluate the vocational pharmaceutical education system under the 1 + X certificate framework, specifically addressing the gap between theoretical education and workplace requirements., Materials and Methods: A retrospective observational approach analyzed 490 pharmacy students over two academic years. The 2021 cohort underwent 1 + X integrated education, while the 2020 cohort followed conventional education. We collaborated closely with industry partners to identify and compile typical job competencies, formulating work projects aligned with industry demands. Combining the skill level standards and assessment content of "1+X Pharmaceutical Purchasing and Sales" and "1+X Pharmaceutical Preparation", we revised the course standards, incorporating typical work projects into the 2021 pharmacy professional teaching curriculum. This constituted the fundamental content of the 1 + X education reform. Statistical analysis compared course scores and 1 + X certificate examination performance., Results: The 2021 cohort, under the 1 + X educational model, demonstrated higher average scores in pharmacy courses, with significant improvements in pharmacology (1 + X vs. Traditional education: 58.40 ± 14.20 vs. 53.44 ± 14.67), clinical pharmacotherapy (72.74 ± 10.28 vs. 63.15 ± 11.03), and pharmaceutical distribution and marketing (79.34 ± 10.96 vs. 67.50 ± 15.82). 1 + X certificate pass rates and satisfaction with the model were also higher than the 2020 cohort., Conclusion: The 1 + X certificate system is useful for developing talent in Chinese vocational education, effectively integrating assessments with industry standards. Future research should aim at evaluating long-term outcomes and improving quantitative skills assessments for enhanced effectiveness., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)