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 characterize the features of patent foramen ovale(PFO)-related cryptogenic stroke using diffusion-weighted imaging(DWI)and to investigate the correlation between infarct size and cardiac CT characteristics of PFO.Methods A retrospective,consecutive cohort study was conducted on acute ischemic stroke patients admitted to Neurology Department of Xuanwu Hospital,Capital Medical University from January 2022 to September 2024.Patients were categorized into PFO group,arterio-arterial embolism(AAE)group,and atrial fibrillation(AF)group based on etiological diagnosis.Baseline clinical data,including age,height,body mass index,admission National Institutes of Health stroke scale(NIHSS)score,history of old cerebral infarction,hypertension,diabetes mellitus,coronary heart disease,dyslipidemia,and smoking history were collected and compared.All patients underwent head MR within 24 h of admission.DWI was used to analyze and compare infarct characteristics across the three groups,including lesion number(single or multiple),location(cortical+subcortical,deep white matter,cortical+subcortical+deep white matter,cerebellum+thalamus+brainstem),size(≥15 mm or＜15 mm,based on maximum transverse diameter;for multiple lesions,if any lesion had a maximum diameter≥15 mm,it was categorized as≥15 mm),infarcted vascular territory(anterior,posterior,or both circulations),and specific arterial supply(anterior cerebral artery,middle cerebral artery,posterior cerebral artery,basilar artery,posterior inferior cerebellar artery,superior cerebellar artery,anterior choroidal artery,or multiple arteries).Patients in the PFO group additionally underwent cardiac CT to measure PFO-related parameters:tunnel length,width,height,septum secundum thickness,and fossa ovalis length.Spearman correlation analysis was performed to evaluate the relationship between infarct size and PFO cardiac CT features.Results A total of 232 acute ischemic stroke patients were included(mean age[57±17]years,ranged 19-86 years;141 males,91 females),comprising 116 in the PFO group,36 in the AAE group,and 80 in the AF group.(1)The proportion of males in the PFO group was higher than that in the AF group,it was lower than that in the AAE group.The age,body mass index and proportions of patients with hypertension,diabetes,hyperlipidemia,coronary heart disease were all lower than those in the other two groups(both P＜0.016 7),while other baseline characteristics showed no significant differences(all P＞0.05).(2)The PFO group exhibited a higher proportion of multiple infarcts compared to the AAE group(83.62％[97/116]vs.61.11％[22/36],P＜0.016 7),but a lower proportion than the AF group(83.62％[97/116]vs.98.75％[79/80],P＜0.016 7).The PFO group also showed a significantly higher proportion of cortical+subcortical infarcts(47.41％[55/116]vs.11.11％[4/36]and 6.25％[5/80],respectively,both P＜0.016 7)and infarcts with a maximum diameter＜15 mm compared to both AAE and AF groups(66.38％[77/116]vs.36.11％[13/36]and 11.25％[9/80],respectively,both P＜0.016 7).Furthermore,the PFO group had a lower proportion of anterior circulation infarcts(27.59％[32/116]vs.69.44％[25/36]in AAE group and 67.50％[54/80]in AF group,both P＜0.016 7),but a higher proportion of posterior circulation infarcts(62.07％[72/116]vs.16.67％[6/36]in AAE group and 8.75％[7/80]in AF group,both P＜0.016 7).Specifically,middle cerebral artery infarcts were less common in the PFO group(18.97％[22/116]vs.66.67％[24/36]in AAE group and 52.50％[42/80]in AF group,both P＜0.016 7),while posterior cerebral artery infarcts were more common(48.28％[56/116]vs.8.33％[3/36]in AAE group and 8.75％[7/80]in AF group,both P＜0.016 7).(3)Spearman correlation analysis revealed that infarct size was negatively correlated with PFO tunnel length(rs=-0.429,P=0.029),fossa ovalis length(rs=-0.408,P=0.038),and septum secundum thickness(rs=-0.525,P=0.006),but not correlated with PFO width or height(both P＞0.05).Conclusions PFO-related cryptogenic stroke is predominantly characterized by multiple small infarcts,primarily located in the cortical+subcortical regions and posterior circulation.Infarct size was found to be negatively correlated with PFO tunnel length,fossa ovalis length,and septum secundum thickness.Comprehensive assessment integrating DWI and cardiac CT features may facilitate the identification of PFO-related stroke.These findings warrant further validation through larger,prospective studies.

OBJECTIVES: To explore the mediating role of sleep duration in the relationship between depression symptoms and myopia among middle school students. METHODS: This study was a cross-sectional research conducted using a stratified cluster random sampling method. A total of 1 728 middle school students were selected from two junior high schools and two senior high schools in certain urban areas and farms of the Xinjiang Production and Construction Corps. Questionnaire surveys and vision tests were conducted among the students. Spearman analysis was used to analyze the correlation between depression symptoms, sleep duration, and myopia. The Bootstrap method was employed to investigate the mediating effect of sleep duration between depression symptoms and myopia. RESULTS: The prevalence of myopia in the overall population was 74.02% (1 279/1 728), with an average sleep duration of (7.6±1.0) hours. The rate of insufficient sleep was 83.62% (1 445/1 728), and the proportion of students exhibiting depression symptoms was 25.29% (437/1 728). Correlation analysis showed significant negative correlations between visual acuity in both eyes and sleep duration with depressive emotions as measured by the Center for Epidemiologic Studies Depression Scale (with correlation coefficients of -0.064, -0.084, and -0.199 respectively; P<0.01), as well as with somatic symptoms and activities (with correlation coefficients of -0.104, -0.124, and -0.233 respectively; P<0.01) and interpersonal relationships (with correlation coefficients of -0.052, -0.059, and -0.071 respectively; P<0.05). The correlation coefficients for left and right eye visual acuity and sleep duration were 0.206 and 0.211 respectively (P<0.001). Sleep duration exhibited a mediating effect between depression symptoms and myopia (indirect effect=0.056, 95%CI: 0.029-0.088), with the mediating effect value for females (indirect effect=0.066, 95%CI: 0.024-0.119) being higher than that for males (indirect effect=0.042, 95%CI: 0.011-0.081). CONCLUSIONS Sleep duration serves as a partial mediator between depression symptoms and myopia in middle school students.
Humans ; Myopia/etiology* ; Male ; Female ; Depression/physiopathology* ; Cross-Sectional Studies ; Sleep ; Adolescent ; Students ; Child ; Time Factors ; Sleep Duration

OBJECTIVES: To study the clinical and genetic characteristics of osteopetrosis (OPT) in children. METHODS: A retrospective analysis was performed on the clinical data of 14 children with OPT. Whole-exome sequencing was used to detect pathogenic genes, and clinical phenotypes and genotypic features were summarized. RESULTS: Among the 14 children (10 males and 4 females), the median age at diagnosis was 8 months. Clinical manifestations included systemic osteosclerosis (14 cases, 100%), anemia (12 cases, 86%), infections (10 cases, 71%), thrombocytopenia (9 cases, 64%), hepatosplenomegaly (8 cases, 57%), and developmental delay (5 cases, 36%). Malignant osteopetrosis (MOP) cases had lower platelet counts, creatine kinase isoenzyme, and serum calcium levels, but higher white blood cell counts, lactate dehydrogenase, and alkaline phosphatase levels compared to non-MOP cases (P<0.05). Genetic testing identified 15 variants in 12 patients, including 8 variants in the CLCN7 gene (53%), 6 in the TCIRG1 gene (40%), and 1 in the TNFRSF11A gene (7%). Three novel CLCN7 variants were identified: c.2351G>C, c.1215-43C>T, and c.1534G>A. All four patients with TCIRG1 variants exhibited MOP clinical phenotypes. Of the seven patients with CLCN7 variants, 4 presented with intermediate OPT, 2 with benign OPT, and 1 with MOP. CONCLUSIONS Clinical phenotypes of OPT in children are heterogeneous, predominantly involving CLCN7 and TCIRG1 gene variants, with a correlation between clinical phenotypes and genotypes.
Humans ; Osteopetrosis/genetics* ; Male ; Female ; Infant ; Child, Preschool ; Retrospective Studies ; Vacuolar Proton-Translocating ATPases/genetics* ; Child ; Chloride Channels/genetics* ; Mutation ; Receptor Activator of Nuclear Factor-kappa B

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 investigate the role of MK2 inhibitor MMI-0100 on inflammatory response after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and related mechanisms. METHODS: An allo-HSCT mouse model was established. Recipient rats were randomly divided into BMT+NaCl group and BMT+MMI-0100 group, and were injected with NaCl and MMI-0100 every day after transplantation, respectively. Samples of the two groups were collected on d 7 and 14, femur paraffin sections were stained with HE, and pathological changes in the bone marrow cavity were observed under the light microscope. The gene and protein expression levels of pro-inflammatory cytokines IL-1β and IL-18 were detected by qPCR and Western blot. Macrophage typing was detected by flow cytometry. The expression levels of NLRP3 and Caspase-1 were detected by Western blot. RESULTS: Inflammatory cell infiltration in the bone marrow cavity was significantly reduced in the BMT+MMI-0100 group. Western blot results showed that the protein expression levels of IL-1β and IL-18 in the BMT+MMI-0100 group were decreased compared to the BMT+NaCl group on day 7 and day 14 (all P <0.01). The qPCR results showed that compared to the BMT+NaCl group, the IL-18 gene expression levels in the BMT+MMI-0100 group were significantly reduced on day 7 and day 14 (both P <0.01). In the BMT+MMI-0100 group, the expression level of IL-1β gene decreased on day 7 (P <0.05), but increased and was higher than that in the BMT+NaCl group on day 14 (P <0.05). Flow cytometry results showed that the expression of M1 macrophages and M1/M2 ratio decreased in the BMT+MMI-0100 group compared to BMT+NaCl group (all P <0.05). Western blot results showed that the protein expression levels of NLRP3 and Caspase-1 in the BMT+MMI-0100 group were lower than those in the BMT+NaCl group (all P <0.05). CONCLUSION MMI-0100 can ameliorate bone marrow inflammatory injury after allo-HSCT and may act by reducing NLRP3 expression to promote M2 polarization.
Animals ; Interleukin-1beta/metabolism* ; Rats ; Interleukin-18/metabolism* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Mice ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Inflammation ; Bone Marrow/pathology* ; Protein Serine-Threonine Kinases/metabolism* ; Intracellular Signaling Peptides and Proteins/antagonists & inhibitors* ; Caspase 1/metabolism* ; Macrophages ; Transplantation, Homologous

Objective:To investigate the clinical effect of probiotic-assisted minocycline in the treatment of elderly patients with chronic periodontitis(CP).Methods:95 elderly patients with CP in our hospital from January 2021 to March 2023 were selected and divided into observation group(49 cases)and control group(46 cases)by random number table method.Both groups received oral health education,the control group received standard periodontal treatment,the observation group was given probiotic lozenges,and both groups were treated for 4 weeks.The therapeutic effect and occurrence of adverse reactions in the 2 groups were analyzed,and the periodontal index[loss of attachment(AL),probing depth(PD),bleeding index(BI)],oral flora(concentrations of Lac-tobacillus salivary and porphyromonas gingivalis)and oral health status[oral health assessment tool(OH AT)score]before and after treatment were compared.Results:No cases were excluded in 2 groups.After treatment,the total effective rate of observation group was 95.92％higher than that of control group 80.43％(P＜0.05).After treatment,the values of AL,PD and BI in the 2 groups were lower than before treatment(P＜0.05),and the values of AL,PD and BI in the observation group were lower than those in the control group(P＜0.05).After treatment,the concentration of porphyromonas gingivalis in saliva in 2 groups was lower than that be-fore treatment,and the concentration of lactobacillus in saliva was higher than that before treatment(P＜0.05).The concentration of porphyromonas gingivalis in saliva in observation group was lower than that in control group,and the concentration of lactobacillus in saliva was higher than that in control group(P＜0.05).After treatment,the OH AT score of the 2 groups was lower than that before treatment(P＜0.05),and the OHAT score of the observation group was lower than that of the control group(P＜0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion:Probiotics assisted mino-cycline in the treatment of elderly patients with CP can reduce periodontal index,regulate oral flora and improve oral health without increasing adverse reactions.

Objective:To investigate the characteristics of cell subsets in rheumatoid arthritis patients complicated with interstitial lung disease (RA-ILD).Methods:The clinical data of 344 patients with RA admitted to the Affiliated Hospital of Nantong University from June 2022 to November 2023 were analyzed. The patients were categorized into two groups based on the diagnostic criteria of ILD: 120 cases in the RA associated with ILD group (RA-ILD group) were included and 224 cases in the RA without ILD group (RA group), the clinical characteristics were compared between the RA-ILD group and the RA group. The influence factors of RA-ILD were analyzed by univariate and multivariate logistic regression.Results:Compared with RA patients, RA-ILD patients were more common in males, with older age, longer course of disease, and higher smoking rate ( P<0.05). The high titer anti-cyclic citrullinated peptide (CCP) antibody, white blood cells, neutrophil, neutrophil to lymphocyte count ratio, aspartate aminotr-ansferase(AST), creatinine (Cr) and lactate dehydrogenase (LDH) levels in RA-ILD patients were higher than those in RA patients. The triglyceride level was lower than that of RA patients ( P<0.05). The percentage of total T cells in peripheral blood lymphocyte subsets in RA-ILD patients [68.65%(62.22%, 76.78%)] was lower than that in RA patients [71.88%(65.83%, 78.39%)] ( Z=-2.26, P=0.024). The percentage of CD4 +T cells [40.2% (32.10%, 45.23%)] was lower than that of RA patients [46.5% (39.74%, 53.19%)] ( Z=-6.29, P<0.001). CD4 +T cell count [486.50 (324.25, 636.75)cells/μl] was lower than that of RA patients [564.50 (438.25, 752.00)cells/μl] ( Z=-4.50, P<0.001). CD4 +/CD8 + levels [1.86 (1.26, 2.18)] were lower than those of RA patients [2.03 (1.40, 2.94)] ( Z=-2.79, P=0.005). B cell count [127.00 (78.00, 207.25)cells/μl] was lower than that of RA patients [163.50 (91.25, 231.50)cells/μl] ( Z=-2.11, P=0.035), The percentage of NK cells in peripheral blood lymphocyte subsets in RA-ILD patients [19.72%(13.14%, 25.83%)] was higher than that in RA patients [12.55% (8.23%, 17.80%)] ( Z=6.13, P<0.001). NK cell count [182.50 (109.00, 293.75)cells/μl] was higher than that of RA patients [156.00 (89.00, 194.75)cells/μl] ( Z=3.17, P=0.002). The percentage of CD8 +T cells [25.10 %(18.74%, 29.86%)] was higher than that of RA patients [22.27% (17.32%, 29.21%)] ( Z=2.00, P=0.046). Imaging types of RA-ILD patients showed that usual interstitial pneumonia (UIP) was more common, followed by non-specific interstitial pneumonia (NSIP). CD8 + T cell count and percentage expression level in UIP were higher than NSIP, and CD4 +/CD8 + expression level was lower than NSIP ( P<0.05). Multivariate logistic regression analysis of indicators with statistical differences were male gender [ OR(95% CI)=2.888 (1.556, 5.360), P=0.001], age [ OR(95% CI)=1.065 (1.033, 1.098), P<0.001], disease duration [ OR(95% CI)=1.004 (1.001, 1.007), P=0.013], high titer anti-CCP antibody [ OR(95% CI)=2.764 (1.214, 6.292), P=0.015], LDH [ OR(95% CI)=1.006 (1.002, 1.009), P=0.001], CD4 +T cell percentage [ OR(95% CI)=0.964 (0.929, 1.000), P=0.049], CD4 +T cell count [ OR(95% CI)=0.998 (0.996, 1.000), P=0.011] and NK cell count [ OR(95% CI)=1.004 (1.001, 1.007), P=0.003]. These indicators were correlated factors for RA-ILD. Conclusion:Male patients with older age, history of smoking and a long disease course are more likely to develop ILD. Male gender with older, long disease course, high titer anti-CCP antibody, increased LDH and NK cell count, CD4 +T cell percentage and decreased CD4 +T cell count are correlation factors for RA-ILD, which may help RA patients to recognize ILD early.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To compare the effect of empirical cefazolin and vancomycin on the adverse outcomes in peritoneal dialysis (PD)-associated peritonitis patients.Methods:This was a retrospective analysis of a single-centre prospective cohort. Clinical data of consecutive PD-related peritonitis episodes occurring for the first time in patients (≥18 years) between January 1, 2008 and December 31, 2021 were reviewed. Patients were classified into a cefazolin group or a vancomycin group according to the empirical antibiotic regimen. The primary endpoint was peritonitis-related death within 1 month of onset and the secondary endpoint was transfer to haemodialysis for peritonitis-related reasons within the same period. Differences in both endpoints between the two regimens were analysed in the overall population and in the Gram-positive peritonitis subgroup. Univariable and multivariable logistic regression models were used to estimate the risk of adverse outcomes associated with antibiotic choice. Propensity-score matching was performed to control for confounding bias.Results:A total of 516 eligible PD patients developed peritonitis during the study period were included, among whom 138 received empirical cefazolin and 322 received vancomycin. Baseline characteristics were significantly different between the cefazolin and vancomycin groups, including annual income >50 000 yuan ( χ2=17.854, P<0.001), cardiovascular disease history ( χ2=3.909, P=0.048), prior peritonitis history ( χ2=18.327, P<0.001), serum albumin ( t=2.430, P=0.013), triglycerides ( Z=-3.108, P=0.002), total cholesterol ( t=3.752, P<0.001), phosphate ( t=3.362, P=0.002) and sodium ( t=3.021, P=0.004). Neither peritonitis-related mortality nor transfer to haemodialysis differed between the cefazolin and vancomycin groups in the overall cohort or in the Gram-positive peritonitis subgroup (all P>0.05). Logistic regression analysis (univariable and multivariable) showed that empirical vancomycin was not associated with a higher risk of adverse outcome when compared with cefazolin in the overall cohort or in the Gram-positive peritonitis subgroup (all P>0.05). After propensity-score matching, results remained consistent (all P>0.05). Conclusion:Empirical cefazolin and vancomycin yield similar rates of short-term adverse outcomes in patients with PD-associated peritonitis, including those caused by Gram-positive organisms.