This study explores whether the current external quality assessment (EQA) level and acceptable bias for basic semen analysis in China are clinically useful. We collected data of semen EQA from Andrology laboratories in the Hunan Province (China) in 2022 and searched for data in the published literature from January 2000 to December 2023 in China. On the basis of these data, we analyzed the coefficients of variation and acceptable biases of different quality control materials for basic semen analysis through robust statistics. We compared these findings with quality specifications based on biological variation from optimal, desirable, and minimum levels of bias to seek a unified and more suitable semen EQA bias evaluation standard for China's national conditions. Different sources of semen quality control material exhibited considerable variation in acceptable biases among laboratories, ranging from 8.2% to 56.9%. A total of 50.0% of the laboratories met the minimum quality specifications for progressive motility (PR), whereas 100.0% and 75.0% of laboratories met only the minimum quality specifications for sperm concentration and total motility (nonprogressive [NP] + PR), respectively. The Z value for sperm concentration and PR+NP was equivalent to the desirable performance specification, whereas the Z value for PR was equivalent only to the minimum performance specification. This study highlights the feasibility of operating external quality assessment schemes for basic semen analysis using quality specifications based on biological variation. These specifications should be unified among external quality control (EQC) centers based on biological variation.
Semen Analysis/standards* ; Humans ; China ; Male ; Quality Control ; Sperm Motility ; Sperm Count/standards*

OBJECTIVES: To investigate the effects of methylenetetrahydrofolate reductase (MTHFR) rs1801133 and γ-glutamyl hydrolase (GGH) rs11545078 gene polymorphisms on plasma concentrations and toxicity following high-dose methotrexate (MTX) therapy in children with acute lymphoblastic leukemia (ALL). METHODS: Children with ALL treated at the Xuzhou Children's Hospital of Xuzhou Medical University from January 2021 to April 2024 were selected for this study. Genotypes of MTHFR rs1801133 and GGH rs11545078 were determined using multiplex polymerase chain reaction. MTX plasma concentrations were measured by enzyme-multiplied immunoassay technique, and toxicity was graded according to the Common Terminology Criteria for Adverse Events version 5.0. The relationships between MTHFR rs1801133 and GGH rs11545078 genotypes and both MTX plasma concentrations and associated toxicities were analyzed. RESULTS: In the low-risk ALL group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 72 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05), and the GGH rs11545078 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with the occurrence of reduced hemoglobin (P<0.05), and the GGH rs11545078 genotype was associated with the occurrence of thrombocytopenia (P<0.05). CONCLUSIONS Detection of MTHFR rs1801133 and GGH rs11545078 genotypes can be used to predict increased MTX plasma concentrations and the occurrence of toxic reactions in high-dose MTX treatment of ALL, enabling timely interventions to enhance safety.
Humans ; Methotrexate/toxicity* ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood* ; Male ; Female ; Child ; Child, Preschool ; gamma-Glutamyl Hydrolase/genetics* ; Antimetabolites, Antineoplastic/adverse effects* ; Infant ; Polymorphism, Genetic ; Adolescent ; Genotype ; Polymorphism, Single Nucleotide

OBJECTIVE: To investigate the effect of miR-483-5p on hepatocellular carcinoma (HCC) cells proliferation and stemness, as well as the attenuating effect of Pien Tze Huang (PZH). METHODS: Differentially expressed miRNA between HepG2 cells and hepatic cancer stem-like cells (HCSCs) were identified by a miRNA microarray assay. miR-483-5p mimics were transfected into HepG2 cells to explore the effects of miR-483-5p on cell proliferation and stemness. HepG2 cells and HCSCs were treated with PZH (0, 0.25, 0.50 and 0.75 mg/mL) to explore the effects of PZH on the proliferation and stemness, both in non-induced state and the state induced by miR-483-5p mimics. RESULTS: miR-483-5p was significantly up-regulated in HCSCs and its overexpression increased cell proliferation and stemness in HepG2 cells (P<0.05). PZH not only significantly inhibited proliferation in HepG2 cells, but also significantly suppressed the cell proliferation and self-renewal of HCSCs (P<0.05). The effects of miR-483-5p mimics on proliferation and stemness of HepG2 cells were partially abolished by PZH. CONCLUSIONS miR-483-5p promotes proliferation and enhances stemness of HepG2 cells, which were attenuated by PZH, demonstrating that miR-483-5p is a potential molecular target for the treatment of HCC and provide experimental evidence to support clinical use of PZH for patients with HCC.
Humans ; MicroRNAs/metabolism* ; Cell Proliferation/drug effects* ; Liver Neoplasms/drug therapy* ; Carcinoma, Hepatocellular/drug therapy* ; Hep G2 Cells ; Neoplastic Stem Cells/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Gene Expression Regulation, Neoplastic/drug effects*

Objective To construct 5 machine-learning models and compare their performance in predicting the associations between pre-pregnancy socio-psycho-behavioral exposures of both spouses and preconception outcomes.Methods Based on Chongqing Preconception Reproductive Health and Birth Outcome Cohort of volunteers recruited from Chongqing Health Center for Women and Children during January 2019 and March 2022,5 447 couples were recruited and surveyed through interviewer-interview for the demographic and social-psychological-behavioral data of both spouses(221 variables).According to the inclusion and exclusion criteria,4 097 couples were finally included,and randomly assigned into a training set(n=2 867 spouses)and a validation set(n=1 230 spouses)at a ratio of 7∶3.Feature analysis and collinear screening were applied to select the potential exposure factors.In consideration of difficulty to carry out semen parameters analysis in primary healthcare institutions,feature Set 1 including sperm parameters and feature Set 2 excluding semen parameters were constructed by including or excluding sperm quality simultaneously in the training set and the validation set.Five algorithms,that is,Logistic Regression,Naive Bayes,Random Forest,Gradient Boosting Machine,and Support Vector Machine,were used to construct preconception outcome prediction models,and the parameters of each model were optimized using random search combined with grid search.The predictive performance of each model was compared using precision,recall,F1 score,area under the receiver operating characteristic curve(AUC),and calibration curve.The optimal model was then selected by comparing the changes in the predictive ability of the questionnaire data for fertility outcomes with or without semen parameters.Results There were 24 variables screened out in feature Set 1,and 16 variables in feature Set 2.In feature Set 1,the gradient boosting machine performed better,with a relatively higher AUC value(0.651)and better F1 score(0.61).The logistic regression model performed stably(AUC value=0.647)and was suitable as the reference model.The random forest(AUC value=0.641),Naive Bayes(AUC value=0.641),and support vector machine(AUC value=0.634)performed second-best.By utilizing the gradient boosting machine,comparable results were found between the predictions from feature sets with or without semen parameters,as in feature Set 1,the AUC value of its validation set was 0.651(95%CI:0.629～0.681),the prediction accuracy was 0.63,the recall rate was 0.65,and the average precision value F1 was 0.61;and in feature Set 2,the AUC value of its validation set was 0.649(95%CI:0.624～0.663),and both the calibration curves were close to the ideal curve.The prediction results indicated that in feature Set 1,the features highly negatively correlated with preconception outcomes were female age,male age,and no pregnancy within 1 year without contraception,while the features highly positively correlated with preconception outcomes were female pregnancy history,total sperm vitality,and use of contraceptive measures before enrollment.Conclusion Among the 5 machine-learning algorithms performed in this cohort data,the gradient boosting machine shows slightly better performance.There are 24 factors being associated with preconception outcomes in both spouses,and the performance of the simplified model excluding semen parameters is not significantly declined.It is feasible to use machine-learning methods to predict human preconception outcomes through social-psychological-behavioral questionnaires.

Inhalation therapy,as a drug delivery method directly targeting the respiratory tract and lungs,has been widely used in the treatment of respiratory diseases due to its characteristics of efficient drug delivery,rapid onset,and low systemic side effects.However,traditional inhalation particles still have some limitations in drug stability,release control,and pulmonary delivery efficiency.In recent years,with the continuous development of biochemical materials,the performance of new inhaled particles has been significantly improved,which can provide better drug-loading capacity,more precise release control,and more efficient pulmonary delivery,showing great potential in improving drug efficacy and reducing side effects.This review comprehensively summarizes the classification,preparation techniques,and applications of inhalable particles.It further explores their prospects in precise therapy,personalized medication,and the next-generation drug delivery systems,aiming to promote research and technological innovation in inhalation therapy,ultimately advancing therapeutic solutions for respiratory diseases.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective To investigate the effect of chronic psychological stress on testicular cell senescence in rats and the role of glucocorticoid receptor(GR)in the process.Methods Thirty-two male SD rats(4～6 weeks old,weighing 120～140 g)were randomly assigned into dimethyl sulfoxide(DMSO)group,mifepristone(RU486)group,chronic unpredictable mild stress(CUMS)group,and CUMS+RU486 group.DMSO of 0.5 ml/(kg·d)was injected subcutaneously into the rats of DMSO group.After the rats of the CUMS group were exposed to CUMS,mifepristone of 1 mg/(kg·d)was given to the rats of the RU486 group and CUMS+RU486 group.All the above 4 groups were inflicted for 42 consecutive days.After modeling,the psychological stress status of rats was evaluated with animal behavioral experiments.Computer-aided sperm analysis(CASA)system was used to detect sperm density.ELISA was employed to measure the serum levels of corticosterone(CORT),sex hormones and inflammation factors.The contents of malondialdehyde(MDA),H2O2,NAD+/NADH and ATP in the testicular tissues were tested with corresponding reagent kits.Western blotting was utilized to detect protein levels of[3-gal,p16,and GR in testicular tissue,and transmission electron microscopy was used to observe mitochondrial structure of spermatogenic cells.Results Compared with the DMSO group,the sperm density,serum levels of testosterone(T),luteinizing hormone(LH)and follicle stimulating hormone(FSH)were decreased while those of CORT and estradiol(E2)were increased in the CUMS group(all P＜0.001).Serum pro-inflammatory factors IL-6 and TNF-α concentrations were increased while anti-inflammatory factor IL-10 concentration was decreased in the CUMS group than the DMSO group(all P＜0.05).And,ATP content and NAD+/NADH ratio were decreased while MDA and H2O2 levels were elevated in testicular tissues in the CUMS group(all P＜0.05).Moreover,the protein levels of testicular cell aging markers β-gal,p16 and GR were significantly enhanced in the CUMS group(all P＜0.01),accompanied by swelling and vacuolization of mitochondrial structures in spermatogenic cells.RU486 treatment effectively improved sperm density and increased CORT level and down-regulated the testicularβ-gal,p16 and GR protein level(all P＜0.05).Conclusion Chronic psychological stress induces testicular damage in rats,presenting declines in sperm density and CORT level,which is possibly associated with GR-mediated cell senescence.

Bilastine,a new second-generation histamine H1 receptor antagonist,is used in the treatment of urticaria,in psoriasis,eczema,atopic dermatitis,prurigo,pruritus,eosinophilic dermatitis and many other skin diseases are also widely used.This article reviews the pharmacology,pharmacokinetics,safety and efficacy of bilastine,its application in skin diseases and adverse drug reactions for clinical reference.

Objective:To study the reproductive toxicity of lithium chloride (LiCl) in male mice and to explore the molecular mechanism of the protective effect of quercetin on testosterone production dysfunction.Methods:Twenty-five male C57BL/6 mice aged 4-5 weeks were randomly divided into five groups according to the random number table method: control group, LiCl infected group [38.4 mg/(kg·d) LiCl+corn oil, noted as LiCl group], quercetin control group [50 mg/(kg·d) quercetin, noted as High-Quer group], low-dose quercetin combined with LiCl infection group [38.4 mg/(kg·d) LiCl+10 mg/(kg·d) quercetin, noted as Low-Quer+LiCl group] and high dose quercetin combined with LiCl infected group [38.4 mg/(kg·d) LiCl+50 mg/(kg·d) quercetin, noted as High-Quer+LiCl group]. The structure of testicular tissue, semen parameters, and the ultrastructure of Leydig cells in mice were detected by HE staining, computer-aided sperm analysis system (CASA), and transmission electron microscopy, respectively. TM3 mouse Leydig cells were treated with 0 mmol/L, 5 mmol/L, 10 mmol/L, 20 mmol/L LiCl for 24 h. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), mitochondrial membrane potential (MMP), lipid peroxidation levels, and expression levels of testosterone-related protein were measured by SOD and GSH-Px kits, TMRE probe, Image-iT TM lipid peroxidation probe, and Western blotting, respectively. Intracellular Fe 2+ concentration was detected by Fe 2+ detection kit and FerroOrange probe. The levels of testosterone, progesterone, and estradiol were measured using enzyme-linked immunosorbent assay kits. Results:In the LiCl group, the total sperm count [(36.78±1.81)×10 6], sperm concentration [(18.39±0.90)×10 6/mL], sperm motility [(25.70±3.32)%] and serum testosterone level [(7.26±0.29) μg/L] were lower than those of control group [(51.60±4.96)×10 6, P=0.002; (25.80±2.48)×10 6/mL, P=0.002; (41.47±2.83)%, P=0.001; (7.87±0.29) μg/L, P=0.013], the expression levels of Cyp11a1, StAR and Cyp17a1, Leydig cell biomarkers (3β-HSD1, 17β-HSD3) and ferroptosis regulatory proteins (GPX4, SLC7A11 and Nrf2) in testis were significantly down-regulated compared with control group (all P<0.001). LiCl also induced mitochondrial vacuoles and swelling of Leydig cells. However, low-dose quercetin intervention could significantly ameliorate the above LiCl-induced damage (total sperm count: P<0.001, sperm concentration: P<0.001, sperm motility: P=0.015, serum testosterone level: P=0.026, Cyp11a1, StAR, Cyp17a1, 3β-HSD1, 17β-HSD3, GPX4, SLC7A11, and Nrf2: all P<0.001). In 20 mmol/L LiCl group, the testosterone level [(7.28±0.24) μg/L] in TM3 cells was lower than that of 0 mmol/L LiCl group [(12.50±0.38) μg/L, P<0.001], the protein levels of Cyp11a1, StAR and Cyp17a1 were significantly down-regulated compared with 0 mmol/L LiCl group (all P<0.001), the activities of SOD [(2.42±0.11) U/mg], GSH-Px [(1.29±0.03) mU/mg] and MMP [(57.24±1.69)%] were lower than those of 0 mmol/L LiCl group [(3.11±0.09) U/mg, (1.54±0.01) mU/mg, (100.00±0)%, all P<0.001], the level of lipid peroxidation [(211.18±3.60)%] and the concentration of Fe 2+ [(26.44±0.94) μmol/L] were higher than those of 0 mmol/L LiCl group [(100.00±0)%, (7.12±0.29) μmol/L, all P<0.001], and the expression of ferroptosis regulatory proteins was significantly down-regulated compared with 0 mmol/L LiCl group (all P<0.001). Compared with 20 mmol/L LiCl group cells [lipid peroxidation: (194.46±3.16)%, (194.70±3.93)%; MMP: (78.74±0.52)%, (75.32±1.29)%], ferroptosis inhibitors Fer-1 and quercetin significantly decreased the level of lipid peroxidation [(181.71±3.80)%, P=0.004; (166.88±3.22)%, P<0.001], increased the level of MMP [(86.26±0.79)%, P=0.040; (81.09±1.32)%, P=0.001], and significantly up-regulated the expression of key enzymes in testosterone synthesis and ferroptosis regulatory proteins (all P<0.05). Conclusion:Quercetin may protect LiCl-induced Leydig cells injury and testosterone production dysfunction by inhibiting cell ferroptosis.