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.

Objective: To determine the active components of Eupolyphaga sinensis Walker (Tu Bie Chong) and explore the mechanisms underlying its fracture-healing ability. Methods: A modified Einhorn method was used to develop a rat tibial fracture model. Progression of bone healing was assessed using radiological methods. Safranin O/fast green and CD31 immunohistochemical staining were performed to evaluate the growth of bone cells and angiogenesis at the fracture site. Methylthiazoletetrazolium blue and wound healing assays were used to analyze cell viability and migration. The Transwell assay was used to explore the invasion capacity of the cells. Tubule formation assays were used to assess the angiogenesis capacity of human vascular endothelial cells (HUVECs). qRT-PCR was used to evaluate the changes in gene transcription levels. Results: Tu Bie Chong fraction 3 (TF3) significantly shortened the fracture healing time in model rats. X-ray results showed that on day 14, fracture healing in the TF3 treatment group was significantly better than that in the control group (P = .0086). Tissue staining showed that cartilage growth and the number of H-shaped blood vessels at the fracture site of the TF3 treatment group were better than those of the control group. In vitro, TF3 significantly promoted the proliferation and wound healing of MC3T3-E1s and HUVECs (all P < .01). Transwell assays showed that TF3 promoted the migration of HUVECs, but inhibited the migration of MC3T3-E1 cells. Tubule formation experiments confirmed that TF3 markedly promoted the ability of vascular endothelial cells to form microtubules. Gene expression analysis revealed that TF3 significantly promoted the expression of VEGFA, SPOCD1, NGF, and NGFR in HUVECs. In MC3T3-E1 cells, the transcript levels of RUNX2 and COL2A1 were significantly elevated following TF3 treatment. Conclusion TF3 promotes fracture healing by promoting bone regeneration associated with the RUNX2 pathway and angiogenesis associated with the VEGFA pathway.

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.

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.

AIM To analyze the metabolites of nobiletin in rats in vivo based on characteristic ions.METHODS Ten rats were assigned into administration group and control group,and given intragastric administration of the 0.5％CMC-Na suspension of nobiletin(250 mg/kg)and 0.5％CMC-Na solution,respectively,after which plasma,urine and feces were collected,solid phase extraction method was adopted in pretreatment,UHPLC-HRMS analysis was performed.The candidate metabolites were systematically described according to diagnostic product ions,chromatographic retention time,accurate molecular weight and neutral loss fragments,after which accurate metabolites were obtained in the established metabolite data set with-CH3(m/z 15)characteristic ions as a baits.RESULTS A total of 64 metabolites were identified,whose main metabolic pathways were glucuronidation,sulfation,hydrogenation and their compound reactions.CONCLUSION This experiment elucidates the metabolites of nobiletin in rats in vivo,which provides a new reference for its further development.

Objective:To construct an evaluation index system of primary practice bases for standardized training of assistant general practitioners in Beijing.Methods:From September to December 2023, the evaluation index system was initially developed using the Context, Input, Process, and Product Evaluation Model (CIPP model), then 20 experts engaged in clinical teaching management and general practice standardized training base evaluation were invited for three rounds of Delphi expert consultation, and the weights of the indicators at all levels were determined using the Analytic Hierarchy Process.Results:The response rates of the three rounds of expert consultation were 100.0%, 95.0%, and 95.0% respectively. The degree of authority of the expert consultations was greater than 0.70. The index importance and feasibility coordination coefficients of three rounds of expert consultation were 0.123 and 0.100 ( P<0.001), 0.064 and 0.068 ( P>0.05), and 0.149 and 0.221 ( P<0.001), respectively, indicting the convergence of the experts′ opinions. The evaluation indexes of the primary practice bases for standardized training of assistant general practitioners in Beijing were finally constructed, including five first-level indexes, including qualification and conditions, teaching organization and system, teaching staff, operation management and quality control; 11 second-level indexes, including basic conditions, department setup, teaching facilities, teaching organization and teaching system; and 25 third-level indexes, including qualification, scale, essential departments, conditional departments and basic teaching facilities. The weights of the five first-level indexes were qualification and conditions (0.333), teaching organization and system (0.167), teaching staff (0.167), operation management (0.167), quality control (0.167). Among the 11 second-level indexes, the top five weights were basic conditions (0.163), department setup (0.104), teaching organization (0.084), teacher requirements (0.084), and basic practice rotation management (0.084). Among the 25 third-level indexes, the top five weights were qualification (0.083), quality control process (0.082), scale (0.081), essential departments (0.053), and conditional departments (0.051). Conclusion:The evaluation index system of primary practice bases for standardized training of assistant general practitioners in Beijing has been constructed in this study based on Delphi expert consultations.

Objective:To analyze the current status of utilization behavior of basic public health services among elderly migrants in China and to explore its association with social capital.Method:This was a cross-sectional study. The data were obtained from the 2017 National Dynamic Monitoring and Survey on the Health and Family Planning of Migrants (Volume A), and the study subjects were selected by stratified, multi-stage and probability proportional to size sampling methods, covering all 31 provinces (autonomous regions or municipalities), and Xinjiang Production and Construction Corps in China. Participants were migrants aged 60 and above who had resided in their current location for over 6 months without household registration. Demographic and sociological characteristics along with relevant information were collected. Utilization of basic public health services was indicated by the establishment of health records and receipt of health education. Social capital indicators encompassed social networks, family support, social participation, civic engagement, social trust, sense of social belonging, and social cohesion. Logistic regression models were applied to analyze the association between social capital and utilization of basic public health services among elderly migrants.Results:A total of 5 728 elderly migrants were included, with a mean age of (66.03±5.56) years, and 3 302 (57.6%) were males. Among them, 1 892 (33.0%) had established health records in their residence, and 2 372 (58.6%) had received health education. Logistic regression analysis revealed positive associations of social networks ( OR=1.287, 95% CI:1.130-1.466), social participation ( OR=1.426, 95% CI:1.238-1.644), and civic engagement ( OR=1.340, 95% CI:1.171-1.533), with the establishment of health records and receipt of health education among elderly migrants. Interestingly, lower levels of family support ( OR=0.741, 95% CI:0.642-0.855) were associated with higher rates of health record establishment and health education receipt. A sense of social belonging ( OR=1.355, 95% CI:1.150-1.596) showed a positive correlation with health record establishment, while social cohesion ( OR=1.264, 95% CI:1.080-1.478) positively correlated with the receipt of health education. Conclusions:Currently, the rates of health record establishment and health education receipt among elderly migrants in China are less satisfactory. Most dimensions of social capital demonstrate positive associations with the utilization of basic public health services among this population.

Objective:To explore the effect of patient engagement on medication safety for patients with chronic disease through a systematic review.Methods:Relevant randomized controlled trials of patient engagement on medication safety were searched from PubMed, EMBASE, The Cochrane Library, CNKI, Wanfang and VIP database. The literature was screened according to inclusion and exclusion criteria, and data extraction and literature quality evaluation was conducted on the selected literature.Results:A total of 15 eligible studies was included. Most of the studies occurred in outpatient and home settings, and the subjects were patients with chronic diseases. Patient engagement strategies can be divided into three categories: (1) patient engagement in medical decision-making; (2) patient engagement in medication adjustment; (3) patient engagement in medication management. The outcomes of medication safety included medication adherence, medication knowledge, medication beliefs, adverse events and medication errors. Intervention strategies for patients to actively engage in medication safety significantly improved patients′ medication knowledge and beliefs, but did not improve medication adherence of patients.Conclusion:Promoting patient active engagement is an effective intervention measure to improve patients ′ perception of medication safety. Due to the limited quality and quantity of the included studies, more high-quality studies are needed to verify the above conclusions.

OBJECTIVE: To compare and analyze the early clinical effect of direct superior approach(DSA) and posterior lateral approach (PLA) in hemiarthroplasty for elderly patients with femoral neck fracture. METHODS: The clinical data of 72 elderly patients with femoral neck fracture who underwent hemiarthroplasty from January 2020 to December 2021 were retrospectively analyzed. Among them, 36 patients were operated through minimally invasive DSA including 10 males and 26 females with an average age of (82.82±4.05) years old; the other 36 patients underwent traditional PLA including 14 males and 22 females with an average age of (82.79±3.21) years old. The perioperative related indexes and Harris scores during follow-up between two groups were compared. RESULTS: Comparison of operation time between two groups, (79.41±17.39) min of DSA group was shorter than(98.45±26.58) min of PLA group;incision length (8.33±2.69) cm was shorter than (11.18±1.33) cm of PLA group;intraoperative blood loss (138.46±71.58) ml was less than (173.51±87.17) ml of PLA group, initial landing time (3.04±0.95) d was earlier than (4.52±1.10) d of PLA group, hospitalization time (8.70±1.89) d was shorter than (10.67±2.35) d of PLA group(P<0.05). There was no statistical difference in Harris score between two groups before operation(P>0.05), but Harris score in DSA group was higher than that of PLA group at 1 month after operation(P<0.05), but at 12 months after operation, the difference was not statistically significant between two groups(P>0.05). CONCLUSION Compared with PLA, DSA is superior in clinical indexes such as operation time, intraoperative blood loss, incision length, first landing time, length of hospitalization and Harris score in the first month after operation in hemi hip replacement, and has comparative advantages in promoting early postoperative rehabilitation of elderly patients with femoral neck.
Male ; Female ; Humans ; Aged ; Aged, 80 and over ; Blood Loss, Surgical ; Hemiarthroplasty ; Retrospective Studies ; Arthroplasty, Replacement, Hip ; Femoral Neck Fractures/surgery* ; Treatment Outcome