As the number of patients with compromised immune function increases and fungal resistance develops, so does the risk of contracting deadly fungi in humans. Both fungi and humans are eukaryotes, so identifying unique targets for antifungal drug development is difficult. In addition, the existing antifungal drugs are limited by toxicity, drug interaction and drug resistance in practical application, which leads to the increasing incidence and fatal rate of fungal infections. Therefore, it is urgent to develop new antifungal drugs. The semi-synthetic technology using microbial fermentation products from natural sources as lead compounds has become the most used method in structural modification of antifungal drugs due to its advantages of few reaction steps and easy operation. This paper will introduce the current status of natural antifungal drugs in clinical use, as well as the latest progress in the research and development of new semi-synthetic antifungal drugs, and summarize their mechanism of action, structural modifications, advantages and disadvantages, so as to provide reference for the subsequent development of new antifungal drugs.

Objective To assess the situation and influencing factors of occupational burnout among the staff at the Center for Disease Control and Prevention (CDC) in Sichuan Province. Methods A total of 1 038 CDC staff members in Sichuan Province were selected as the study subjects using the stratified random sampling method. Occupational burnout of the staff was assessed using the Maslach Burnout Inventory General Survey via an online questionnaire. Results The detection rate of occupational burnout was 42.3% (439/1 038). Binary logistic regression analysis result showed that, after controlling for confounding factors such as education level and alcohol consumption, CDC staffs aged at 20-<31, 31-<41, and 41-<51 years were at higher risk of occupational burnout compared with those ≥51 years (all P<0.05). CDC staffs with 5-<10 or ≥10 years of service had higher occupational burnout risk compared with those with <5 years (both P<0.05). CDC staffs with poor or fair health status, irregular diet, and poor sleep quality had higher risk of occupational burnout compared with those healthy, have regular diet, and good sleep quality (all P<0.05). The risk of occupational burnout increased with higher overtime frequency (all P<0.05). Conclusion Occupational burnout among CDC staffs in Sichuan Province is relatively high. Age, years of service, health status, diet, sleep quality, and overtime frequency are key influencing factors.

Since the promulgation of the first Drug Administration Law of the People's Republic of China 40 years ago in 1984, China has undergone four main stages in the traditional Chinese medicine(TCM) regulation: the initial establishment of TCM regulation rules(1984-1997), the formation of a modern TCM regulatory system(1998-2014), the reform of the review and approval system for new TCM drugs(2015-2018), and the construction of a scientific regulation system for TCM(2019-2024). Over the past five years, a series of milestone achievements of TCM regulation in China have been achieved in the six aspects, including its strategic objectives and the establishment of a science-based regulatory system, the reform of the review and approval system for new TCM drugs, the optimization and improvement of the TCM standard system and its formation mechanism, comprehensive enhancement of regulatory capabilities for TCM safety, international harmonization of TCM regulation and its role in promoting innovation. Looking ahead, centered on advancing TCMRS to establish a sound regulatory framework tailored to the unique characteristics of TCM, TCM regulation will evolve into new reform patterns, advancing and extending across eight critical fronts, including the legal framework and policy architecture, the review and approval system for new TCM drugs, the quality standard and management system of TCM, the comprehensive quality & safety regulation and traceability system, the research and transformation system for TCMRS, AI-driven innovations in TCM regulation, the coordination between high-quality industrial development and high-level regulation, and the leadership in international cooperation and regulatory harmonization. In this way, a unique path for the development of modern TCM regulation with Chinese characteristics will be pioneered.
Humans ; China ; Drugs, Chinese Herbal/standards* ; History, 20th Century ; History, 21st Century ; Medicine, Chinese Traditional/trends*

OBJECTIVES: To evaluate the causal association between circulating levels of zinc, magnesium, and other minerals and autism spectrum disorder (ASD). METHODS: A two-sample Mendelian randomization (MR) analysis was performed using summary statistics from large-scale genome-wide association studies of European populations, including 18 382 ASD cases and 27 969 controls. Genetic data for iron, calcium, and magnesium were obtained from the UK Biobank, and data for zinc and selenium were sourced from an Australian-British cohort. A total of 351 genetic instrumental variables were selected. Causal inference was performed using inverse-variance weighting as the primary analysis method. Sensitivity analyses were performed by Cochran's Q test and MR-PRESSO global test to assess the robustness of the findings. RESULTS: No statistically significant causal effect was observed for circulating zinc, magnesium, calcium, selenium, or iron levels on ASD risk (all P>0.05). The odds ratios and 95% confidence intervals from the inverse-variance weighting analysis were 0.934 (0.869-1.003) for zinc, 1.315 (0.971-1.850) for magnesium, 1.055 (0.960-1.159) for calcium, 1.015 (0.953-1.080) for selenium, and 0.946 (0.687-1.303) for iron. Sensitivity analysis revealed significant heterogeneity in the causal association between circulating calcium and ASD (P=0.006), while the effect estimate remained stable after MR-PRESSO correction (P=0.487). The causal effect estimates for the remaining minerals demonstrated good robustness. CONCLUSIONS This study did not find significant evidence supporting a causal association between circulating zinc, magnesium, calcium, selenium, or iron levels and ASD risk, providing important clues for the etiology of ASD and precision nutritional interventions.
Humans ; Mendelian Randomization Analysis ; Autism Spectrum Disorder/genetics* ; Magnesium/blood* ; Zinc/blood* ; Minerals/blood* ; Genome-Wide Association Study ; Selenium/blood*

Objective： To analyze the symptoms, diagnosis and treatment of upper urinary tract calculi patients combined with mild and moderate benign prostatic hyperplasia (BPH) after ureteral stent implantation. Methods： One hundred and six BPH patients who were hospitalized for upper urinary tract calculi and had ureteral stents retained from January 2019 to December 2022 were selected and divided into 2 weeks group and 4 weeks group according to the time of removal of ureteral stents after surgery. Their general clinical data were analyzed and compared. International Prostatic Symptom Scale (IPSS), postoperative ureteral Stent Symptom Questionnaire (USSQ), and incidence of adverse events after ureteral stent removal were recorded before and after removal. Results： The scores of IPSS were significantly increased in all patients, and symptoms in urinary tract had improved significantly after discharge (P<0.05). Compared with the 2 weeks group, the USSQ score of the 4 weeks group was significantly increased (P<0.05). And no significant adverse event was observed in the 2 weeks group after the removal of ureteral sten. Conclusion： IPSS score and USSQ score increased significantly during stent implantation in BPH patients with lithiasis. And complications increased significantly over time. Following thorough clinical assessment, early ureteral stent removal demonstrates both safety and efficacy, representing an optimal therapeutic approach in selected cases.
Humans ; Male ; Prostatic Hyperplasia/surgery* ; Stents ; Ureter/surgery* ; Aged ; Middle Aged ; Urinary Calculi/surgery* ; Ureteral Calculi/surgery*

OBJECTIVE: To investigate the association between ABO blood types and gestational diabetes mellitus (GDM) risk. METHODS: A prospective birth cohort study was conducted. ABO blood types were determined using the slide method. GDM diagnosis was based on a 75-g, 2-h oral glucose tolerance test (OGTT) according to the criteria of the International Association of Diabetes and Pregnancy Study Groups. Logistic regression was applied to calculate the odds ratios ( ORs) and 95% confidence intervals ( CIs) between ABO blood types and GDM risk. RESULTS: A total of 30,740 pregnant women with a mean age of 31.81 years were enrolled in this study. The ABO blood types distribution was: type O (30.99%), type A (26.58%), type B (32.20%), and type AB (10.23%). GDM was identified in 14.44% of participants. Using blood type O as a reference, GDM risk was not significantly higher for types A ( OR = 1.05) or B ( OR = 1.04). However, women with type AB had a 19% increased risk of GDM ( OR = 1.19, 95% CI = 1.05-1.34; P < 0.05), even after adjusting for various factors. This increased risk for type AB was consistent across subgroup and sensitivity analyses. CONCLUSION The ABO blood types may influence GDM risk, with type AB associated with a higher risk. Incorporating it-either as a single risk factor or in combination with other known factors-could help identify individuals at risk for GDM before or during early pregnancy.
Humans ; Female ; Pregnancy ; Diabetes, Gestational/etiology* ; ABO Blood-Group System ; Adult ; Prospective Studies ; Risk Factors ; Young Adult

Objective: To investigate the effect and mechanism of methyltransferase-like3(METTL3),which functions as m6A modification methyltransferase,on the cellular proliferation,clone formation and migration of nonsmall cell lung cancer(NSCLC) cells. Methods: The METTL3 level and patient overall survival were analyzed by bioinformatics.In the transfected A549 cells,the expression of METTL3 was detected by RT-PCR and Western blot assays,the m6A level was detected by m6A RNA Methylation Assay kit,the cellular viability and growth were detected by CCK-8 assay,the apoptosis was detected by immunofluorescent assay,the colony growth was detected by clone formation assay,the cell migration growth was detected by scratch. Results : Bioinformatics showed that METTL3 was highly expressed in NSCLC and negatively correlated with patient overall survival.The RT-PCR and Western blot data showed that the METTL3 level was higher in NSCLC cells.Moreover,higher METTL3 significantly promoted m6A level,cell proliferation,colony formation,migration,inhibited cell apoptosis,increased the mRNA and protein expressions of EMT-related marker Vimentin but inhibited apoptosis and decreased the mRNA and protein expressions of EMT-related marker E-cadherin in the A549 cells.Furthermore,the contrasting results were obtained in the A549 cells with the knockdown of METTL3. Conclusion The over-expressed METTL3 increases the m6A levels in NSCLC cells and promotes cellular proliferation,colony formation,and migration growth,thereby laying a theoretical foundation for future research on early diagnosis and targeted drug development for NSCLC by targeting METTL3.

Objective:To evaluate the efficacy and safety of CD30 antibody-drug conjugates (ADC) brentuximab vedotin (BV) combined with chemotherapy in children with refractory or relapsed classic Hodgkin′s lymphoma (R/R cHL).Methods:Clinical data (including age, gender, B symptoms, clinical stage, previous treatment, etc.) of the 10 R/R cHL children diagnosed and treated at Beijing Children′s Hospital Affiliated to Capital Medical University from October 2021 to August 2023 were analyzed retrospectively. According to the different intensity of chemotherapy drugs, the dose of BV applied in the same course of treatment was 1.8 mg/kg for BV applied once every 3 weeks, and 1.2 mg/kg for BV applied once every 2 weeks. All 10 patients received at least 2 cycles of BV combined with chemotherapy and were evaluated every 2 cycles. The patients were followed up until May 31, 2024. The infusion reactions and adverse reactions after treatment were recorded.Results:In all 10 patients, there were 7 males and 3 females, the age ranged from 5.3-16.9 years, and there were 6 cases of refractory and 4 cases of relapsed. There were 6 cases of nodular sclerosis type, 2 cases of mixed cell type, 1 case of lymphocyte-rich type, and 1 case of lymphodepletion type. There were 5 cases of stage Ⅳ and 5 cases of stage Ⅲ. Previous treatment was mainly chemotherapy, 4 cases received radiotherapy and 1 case received programmed cell death protein 1 (PD-1) antibody therapy. The follow-up time ranged from 9 to 27 months. A total of 43 courses with 49 doses of BV alone or combined with chemotherapy were recorded, and the number of courses was 2 to 10 times. All 10 children responded to the treatment, and 9 achieved complete remission. BV infusion was successfully completed in all cases. A total of 28 cases of grade 3 or above adverse events were recorded, mainly myelosuppression, all of which were related to chemotherapy and did not affect sequential treatment.Conclusion:Brentuximab vedotin has demonstrated efficacy and a tolerable safety profile in the treatment of refractory and relapsed CD30-positive Hodgkin′s lymphoma in children.

Objective This study aimed to explore the heterogeneity and gene ontology of Wnt1-Cre-marked and Pax2-Cre-marked first branchial arch cranial neural crest cells(CNCs)in mice.Methods The embryos of Wnt1-Cre;R26RmTmG and Pax2-Cre;R26RmTmG at embryonic day(E)8.0-E9.25 were collected for histological observation.We per-formed immunostaining to compare green fluorescent pro-tein(GFP)-positive CNCs in Pax2-Cre;R26RAi9 and Wnt1-Cre;R26RAi9 mice at E15.5.Single-cell RNA sequencing(scRNA-seq)was used to analyze the first branchial arch GFP-positive CNCs from Wnt1-Cre;R26RmTmG and Pax2-cre;R26RmTmGmice at E10.5.Real time fluorescence quantitative polymerase chain reaction(q-PCR)was performed to val-idate the differential genes.Results Wnt1-Cre-marked and Pax2-Cre-marked CNCs migrated from the neural plateto first and second branchial arches and to the first branchial arch,respectively,at E8.0.Although Wnt1-Cre-marked and Pax2-Cre-marked CNCs were found mostly in cranial-facial tissues,the former had higher expression in palate and tongue.The results of scRNA-seq showed that Pax2-Cre-marked CNCs specifically contributed to osteoblast differentia-tion and ossification,while Wnt1-Cre-marked CNCs participated in limb development,cell migration,and ossification.The q-PCR data also confirmed the results of gene ontology analysis.Conclusion Pax2-Cre mice are perfect experimen-tal animal models for research on first branchial arch CNCs and derivatives in osteoblast differentiation and ossification.