Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

Rubi Fructus has a long history of medicinal and edible use in China. It contains chemical components such as terpenes, flavonoids, phenolic acids, fatty acids, and alkaloids, and possesses various pharmacological activities, including antioxidant, anti-inflammatory, hypoglycemic, anti-tumor, anti-osteoporosis, and liver-protective effects. Rubi Fructus is widely applied in medical, health, and food fields. The quality of Rubi Fructus can directly affect the safety and effectiveness of clinical medication. Therefore, this article reviews the research progress on the chemical constituents and pharmacological effects of Rubi Fructus. Based on the concept of traditional Chinese medicine(TCM) quality markers(Q-markers), the article explores the screening and determination of Q-markers for Rubi Fructus from various aspects, including plant kinship, traditional efficacy, medicinal properties, measurability of chemical composition, different processing methods, producing areas, harvesting periods, and planting conditions. The components ellagic acid, kaempferol, quercetin, kaempferol-3-O-rutinoside, rutin, astragalin, tiliroside, and hyperoside are preliminarily proposed as Q-markers for Rubi Fructus, providing a reference for the quality control of Rubi Fructus.
Drugs, Chinese Herbal/pharmacology* ; Humans ; Rubus/chemistry* ; Fruit/chemistry* ; Quality Control ; Animals

Through a systematic review of the literature on the treatment of eczema with Binghuang Fule Ointment, the "6+1" assessment model was used to comprehensively evaluate its clinical value, providing a basis for decisions on the allocation of medical resources, rational clinical medication use, and hospital procurement and supply of Chinese patent medicines in China. Based on the relevant standards in the Guidelines for the Management of Clinical Evidence and Value Evaluation of Drugs, diversified research methods were adopted, including evidence-based medical evidence, questionnaire surveys, and pharmacoeconomic evaluations. These methods were combined with both qualitative and quantitative research approaches, and the multi-criteria decision analysis(MCDA) model was applied to perform a comprehensive evaluation of Binghuang Fule Ointment in treating eczema. Safety was evaluated based on evidence adequacy assessments and known risk evaluations, and thus the safety was rated as grade A, indicating that its risk is controllable, its safety is good, and there is sufficient evidence to confirm its safety. The evidence of effectiveness came from the results of Meta-analysis, which showed that Binghuang Fule Ointment + conventional treatment/Binghuang Fule Ointment vs conventional treatment had better clinical effective effect, and the effectiveness was rated as grade A. The economic evaluation, integrating evidence value and evidence quality results, thus the economy was rated as grade B. Innovation was evaluated based on three primary indexes and 18 secondary indexes, with Binghuang Fule Ointment's innovation rated as grade B, indicating a good level of innovation. Suitability was assessed through a questionnaire survey and Chinese patent medicine information service data, and Binghuang Fule Ointment's suitability was rated as grade B, indicating good suitability. Accessibility was assessed based on the proportion of Binghuang Fule Ointment's daily cost relative to the median disposable income of urban and rural residents. The proportion was only 0.05% in urban residents' median disposable income, and 0.14% in rural residents' median disposable income. Accessibility was rated as grade B, reflecting good accessibility. Binghuang Fule Ointment was prescribed by a senior Tibetan doctor with many years of clinical experience at the People's Hospital of Tibet Autonomous Region. Its traditional Chinese medicine characteristics were rated as grade B. Based on the results from the "6+1" evaluation dimensions, the comprehensive value score of Binghuang Fule Ointment was calculated using CSC v2.0 software, yielding a score of 0.79, which corresponds to a class A, indicating good clinical value.
Humans ; Ointments ; Drugs, Chinese Herbal/therapeutic use* ; Eczema/economics*

Kidney-Yang deficiency syndrome is a common geriatric disease that underlies chronic conditions such as diabetic nephropathy, chronic kidney disease, and osteoporosis. As age progresses, the kidney-Yang deficiency syndrome showcases increasingly pronounced manifestations, emerging as a key factor in the comorbidities experienced by elderly patients and affecting their quality of life and overall health status. Traditional Chinese medicine(TCM) has been extensively utilized in the treatment of kidney-Yang deficiency syndrome, with Epimedii Folium, Cinnamomi Cortex, and Lycii Fructus widely used in clinical settings. Despite the complexity of the molecular mechanisms involved in treating kidney-Yang deficiency syndrome, the potential therapeutic value of TCM remains compelling. Delving into the mechanisms of TCM treatment of kidney-Yang deficiency syndrome by regulating the neuro-endocrine-immune system can provide a scientific basis for targeted treatments of this syndrome and lay a foundation for the modernization of TCM. The pathophysiology of kidney-Yang deficiency syndrome involves multiple systems, including the interaction of the neuro-endocrine-immune system, the decline in renal function, the intensification of oxidative stress responses, and energy metabolism disorders. Understanding these mechanisms and their interrelationships can help untangle the etiology of kidney-Yang deficiency syndrome, aiding clinicians in making more precise diagnoses and treatments. Furthermore, the research on the specific applications of TCM in research on these pathological mechanisms can enhance the international recognition and status of TCM, enabling it to exert a greater global influence.
Humans ; Yang Deficiency/physiopathology* ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Kidney Diseases/physiopathology* ; Neurosecretory Systems/physiopathology* ; Animals ; Kidney/physiopathology* ; Endocrine System/physiopathology* ; Immune System/physiopathology*

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

AIM To study the chemical constituents from Stelmatocrypton khasianum.(Benth.)Baill.and their in vitro anti-inflammatory activity and cytotoxic activity.METHODS Separation and purification were performed using thin layer chromatography,silica gel,semi-preparative HPLC and Sephadex LH-20,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The in vitro anti-inflammatory activity was evaluated by RAW264.7 model,and the cytotoxic activity was determined by CCK-8 method.RESULTS Fifteen compounds were isolated and identified as 2α,3β,19α,23-tetrahydroxy-urs-12-en-28-oic acid-3-O-β-D-glucopyranosyl-28-O-β-D-glucopyranosyl ester(1),dalzienoside(2),benzyl-(6-O-α-L-rhanmopyranosyl)O-β-D-glucopyranoside(3),corchorusoside C(4),cyclo(Ala-Tyr)(5),thymidine(6),(4S,5S)-5-hydroxy-4-hexanolide(7),2-methylpyridin-3-ol(8),butyl isobutyl phthalate(9),bis-(2-ethylhexyl)terephthalate(10),p-hydroxybenzaldehyde(11),vanilic acid(12),salicylic acid(13),isovanilic acid(14),3-hydroxy-p-anisaldehyde(15).The IC50 values of compounds 1,2 and 4 for NO were(27.69±5.51),(25.82±3.58)and(23.35±7.09)μmol/L,respectively.The IC50 value of compound 1 on MCF-7 cells was(18.15±6.45)μmol/L.The IC50 values of compound 4 on MCF-7 and HCCC-9810 cells were(19.43±2.66)and(21.76±5.81)μmol/L,respectively.CONCLUSION Compounds 2-11 are isolated from S.khasianum for the first time.Compounds 1,2 and 4 exhibit good in vitro anti-inflammatory activity,and 1,4 have cytotoxic activity.

Objective:To analyze the latent profile characteristics of self-management ability in patients with metabolic-associated fatty liver disease (MAFLD) and explore its influencing factors.Methods:This was a cross-sectional study. A total of 311 patients with metabolic-associated fatty liver disease (MAFLD) were selected from the First Affiliated Hospital of Sun Yat-sen University (including those receiving treatment and undergoing physical examinations) between August and October 2024. Data were collected using a general information questionnaire, the self-management Scale for Patients with Non-Alcoholic Fatty Liver Disease, and the Social Support Rating Scale. After excluding 51 patients due to incomplete questionnaire responses or logical inconsistencies, 260 patients were finally included in the analysis. Latent profile analysis was used to identify potential categories of patients′ self-management abilities. With the latent categories as the dependent variable and items with P<0.05 in univariate analysis as independent variables, a multivariate logistic regression analysis (with the "poor self-management group" as the reference group) was performed to explore the influencing factors. Results:Among the 260 participants included in the study, three potential categories of self-management behaviors were finally identified, namely the active self-management group with 106 cases (40.8%), the moderate self-management group with 118 cases (45.4%), and the passive self-management group with 36 cases (13.8%).Results of multivariate logistic regression analysis showed that, compared with the passive self-management group:Patients who resided in rural areas ( OR=0.130, 95% CI: 0.040-0.420), often stayed up late ( OR=0.200, 95% CI: 0.060-0.590), or had an average daily sleep duration of≤5 hours ( OR=0.160, 95% CI: 0.050-0.510) had a significantly lower probability of belonging to the "active self-management group";In contrast, patients with an education level of senior high school or above ( OR=7.530, 95% CI: 1.740-34.160) or a higher total score of social support ( OR=1.120, 95% CI: 1.030-1.210) had a significantly higher probability of being in the "active self-management group" (all P<0.05). Conclusion:There is heterogeneity in self-management ability among patients with metabolic associated fatty liver disease (MAFLD). Residential area, educational level, frequency of staying up late, average daily sleep duration, and social support are influencing factors of patients′ self-management ability.

To explore the application of sequential analysis in post-market safety dynamic surveillance of vaccines. Under the dynamic monitoring data of vaccines post-market approval, this research introduces the fundamental principles of maximizing sequential probability ratio test (MaxSPRT) and Bayesian sequential analysis, employing R software. Through an example of dynamic safety monitoring data of vaccines post-market approval, we analyze using the MaxSPRT and Bayesian sequential analysis. The MaxSPRT identified a safety signal in week 4 ( P<0.05), while Bayesian sequential analysis indicated that the 95% highest density interval for the RR value at week 4 is 1.13-3.27, suggesting the first appearance of a safety signal at week 4. The MaxSPRT and Bayesian sequential analysis effectively leverage continuously accumulating dynamic monitoring data, thereby serving as a valuable method for post-market safety surveillance of vaccines.

Eightly-four novel thioheterocyclic nucleoside derivatives were designed, synthesized, and evaluated for antitumor activity in vitro and in vivo. Most of the compounds inhibited the growth of HCT116 and HeLa cancer cells in vitro, among them 33a and 36b exhibited potent activity against HCT116 cells (IC₅₀ = 0.27 and 0.49 μmol/L, respectively). Both compounds 33a and 36b inhibited cell metastasis, arrested the cell cycle in the G₂/M phase, and induced apoptosis in vitro. Mechanistic studies revealed that 33a and 36b increased ROS levels, led to DNA damage, ER stress, and mitochondrial dysfunction, and inhibited autophagy in HCT116 cells. Biological information analysis, RNA-sequencing, Gene Set Enrichment Analysis (GSEA), drug affinity responsive target stability (DARTS) assay, cellular thermal shift assay (CETSA), and SPR experiments identified that compounds 33a and 36b showed antitumor activity by suppressing the c-MYC pathway. c-MYC silencing assays indicated that c-MYC proteins participated in 33a-mediated anticancer activities in HCT116 cells. More importantly, compound 33a presented favorable pharmacokinetic properties in mice (T _1/2 = 6.8 h) and showed significant antitumor efficacy in vivo without obvious toxicity, showing promising potential for further clinical development.