Objective:To investigate the pathways involved in bisphenol S(BPS)and bisphenol F(BPF)induced male reproductive injury by bioinformatics methods and experimental verification.Methods:Bioinformatics analysis was conducted to screen the genes related to male reproductive system diseases associated with BPF and BPS from the Comparative Toxicogenomics Database(CTD).Functional enrichment using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed to predict potential signaling pathways and key genes.Cell counting kit-8(CCK-8)method was used to assess the cell viability in various groups treated with different concentrations of BPS and BPF(1×10-3,1×10-2,1×10-1,1×100,1×101,and 1×102 μmol·L-1).TM3 cells were divided into control group(0.1％DMSO),different doses of BPS groups,and different doses of BPF groups.The cells were treated with 20,40,and 80 μmol·L-1 of BPS and BPF for 72 h,respectively.Real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting method were used to detect the expression levels of key genes mRNA and proteins in various groups.Results:The bioinformatics analysis results revealed that 507 and 447 male systemic disease genes related to BPS and BPF were screened by CTD,respectively.The GO enrichment analysis results showed that the selected genes were primarily enriched in biological processes(BP)such as reproductive system development and reproductive structure development.The KEGG pathway analysis results indicated that these genes were significantly enriched in signaling pathways such as phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT),hypoxia-inducible factor-1(HIF-1),and cellular senescence(P＜0.001).The CCK-8 method results showed that compared with control group,the cell viabilities in 1× 102 μmol·L-1 BPF and BPS groups were significantly decreased(P＜0.05),while the viabilities of TM3 cells in other groups had no significant changes(P＞0.05).After BPS treatment,compared with control group,the expression levels of PI3K,AKT,hypoxia-inducible factor-1α(HIF-1α),and CREB-binding protein(CBP)mRNA in low,medium,and high doses of BPS groups were decreased(P＜0.05),the expression levels of PI3K protein were decreased(P＜0.05),the expression levels of B-cell lymphoma-2-associated X protein(Bax)protein were increased(P＜0.05),and the expression levels of serine protease inhibitor clade B,member 10(SERPINB10)mRNA were increased(P＜0.01);the expression levels of Bax and intraflagellar transport 80 homolog(IFT80)mRNA in the cells in medium and high doses of BPS groups were increased(P＜0.05);the expression levels of B-cell lymphoma-2(Bcl-2)mRNA and protein in low and high doses of BPS groups were decreased(P＜0.05);the expression levels of additional sex combs like 2(ASXL2)mRNA in low and medium doses of BPS groups were decreased(P＜0.01).After BPF treatment,compared with control group,the expression levels of Bcl-2,HIF-1α,and structural maintenance of chromosomes protein 1B(SMC1B)mRNA in low,medium,and high doses of BPF groups were decreased(P＜0.05),and the expression levels of IFT80 mRNA(P＜0.01)and Bax protein(P＜0.01)were increased;the expression levels of PI3K,AKT,and ring finger protein 130(RNF130)mRNA in low and high doses of BPF groups were decreased(P＜0.05);the expression level of CBP mRNA in medium dose of BPF group was decreased(P＜0.05),while the expression level of RNF130 mRNA was increased(P＜0.05);the expression levels of PI3K and Bcl-2 proteins in high dose of BPF group were decreased(P＜0.05).Conclusion:BPF and BPS may cause cell cytotoxicity and impair male reproductive health through PI3K/AKT and HIF-1 signaling pathways.RNF130 and SMC1B may be important targets for their induction of male reproductive toxicity.

Objective:To investigate the relationship between serum interacting protein kinase (RIPK)-3 levels and mycoplasma pneumoniae pneumonia (MPP) correlation between disease severity and lung function in children.Methods:A case-control study was conducted. A total of 147 children with MPP admitted to the Children's Hospital Affiliated to Xuzhou Medical University from April 2023 to March 2024 were selected, including 76 cases of mild MPP (mild MPP group) and 71 cases of severe MPP (severe MPP group). Additionally, 36 healthy children who underwent physical examinations during the same period were selected as the healthy control group. The levels of serum RIPK3, C-reactive protein (CRP), lactate dehydrogenase (LDH), and D-dimer of each group were compared, and the correlations between each index and the severity of MPP in children were analyzed. The lung function indicators, including the percentage of peak expiratory flow (PEF% pred) and the percentage of forced expiratory volume in one second (FEV1% pred), were compared between groups, and the correlations between these indicators and the serum RIPK3 levels in children with MPP were analyzed. Measurement data with normal distribution was expressed as " xˉ±s", one-way ANOVA was used on comparison between groups, LSD-t test was used on pairwise comparison.Measurement data with skewed distribution were expressed as M( Q1, Q3). The Kruskal-Wallis H test was used for comparisons among multiple groups, and the Dunn test was used for pairwise comparisons. Counting data was expressed as case(%), χ2 test was used on comparison between groups. The relationships between serum RIPK3, CRP, LDH, D-dimer and the severity of MPP in children were analyzed by Spearman correlation analysis. The relationships between serum RIPK3 levels and PEF% pred, FEV1% pred were analyzed by Pearson correlation analysis. Results:The levels of serum RIPK3, CRP, LDH and D-dimer in children with mild MPP and severe MPP were all higher than those in the healthy control group [(329.67±59.69), (406.77±47.47) ng/L vs. (103.16±15.93) ng/L, (13.49±4.76), (37.76±18.94) mg/L vs. (1.59±0.81) mg/L, (253.12±50.96), (501.96±167.55) U/L vs. (186.06±45.49) U/L, (0.90±0.19), (3.01±1.46) mg/L vs. (0.29±0.12) mg/L], and the levels in the severe MPP group were all higher than those in the mild MPP group (all P < 0.05). The levels of serum RIPK3, CRP, LDH and D-dimer in children with MPP were positively correlated with the severity of the disease (r values were 0.59, 0.76, 0.83, 0.67, all P < 0.001). The levels of PEF% pred and FEV1% pred in children with mild MPP and severe MPP were all lower than those in the healthy control group [(72.65±7.67)%, (59.93±10.17)% vs. (98.54±4.81)%, (73.79±6.56)%, (60.56±10.54)% vs. (98.08±4.65)%], and the levels in the severe MPP group were all lower than those in the mild MPP group (all P < 0.05). The level of serum RIPK3 in children with MPP was negatively correlated with the lung function indicators PEF% pred and FEV1% pred (r values were -0.78, -0.77, all P < 0.001). Conclusions:The serum RIPK3 level in children with MPP is positively correlated with the severity of their condition and negatively correlated with the lung function indicators PEF% pred and FEV1% pred.

Objective:To investigate the relationship between serum interacting protein kinase (RIPK)-3 levels and mycoplasma pneumoniae pneumonia (MPP) correlation between disease severity and lung function in children.Methods:A case-control study was conducted. A total of 147 children with MPP admitted to the Children's Hospital Affiliated to Xuzhou Medical University from April 2023 to March 2024 were selected, including 76 cases of mild MPP (mild MPP group) and 71 cases of severe MPP (severe MPP group). Additionally, 36 healthy children who underwent physical examinations during the same period were selected as the healthy control group. The levels of serum RIPK3, C-reactive protein (CRP), lactate dehydrogenase (LDH), and D-dimer of each group were compared, and the correlations between each index and the severity of MPP in children were analyzed. The lung function indicators, including the percentage of peak expiratory flow (PEF% pred) and the percentage of forced expiratory volume in one second (FEV1% pred), were compared between groups, and the correlations between these indicators and the serum RIPK3 levels in children with MPP were analyzed. Measurement data with normal distribution was expressed as " xˉ±s", one-way ANOVA was used on comparison between groups, LSD-t test was used on pairwise comparison.Measurement data with skewed distribution were expressed as M( Q1, Q3). The Kruskal-Wallis H test was used for comparisons among multiple groups, and the Dunn test was used for pairwise comparisons. Counting data was expressed as case(%), χ2 test was used on comparison between groups. The relationships between serum RIPK3, CRP, LDH, D-dimer and the severity of MPP in children were analyzed by Spearman correlation analysis. The relationships between serum RIPK3 levels and PEF% pred, FEV1% pred were analyzed by Pearson correlation analysis. Results:The levels of serum RIPK3, CRP, LDH and D-dimer in children with mild MPP and severe MPP were all higher than those in the healthy control group [(329.67±59.69), (406.77±47.47) ng/L vs. (103.16±15.93) ng/L, (13.49±4.76), (37.76±18.94) mg/L vs. (1.59±0.81) mg/L, (253.12±50.96), (501.96±167.55) U/L vs. (186.06±45.49) U/L, (0.90±0.19), (3.01±1.46) mg/L vs. (0.29±0.12) mg/L], and the levels in the severe MPP group were all higher than those in the mild MPP group (all P < 0.05). The levels of serum RIPK3, CRP, LDH and D-dimer in children with MPP were positively correlated with the severity of the disease (r values were 0.59, 0.76, 0.83, 0.67, all P < 0.001). The levels of PEF% pred and FEV1% pred in children with mild MPP and severe MPP were all lower than those in the healthy control group [(72.65±7.67)%, (59.93±10.17)% vs. (98.54±4.81)%, (73.79±6.56)%, (60.56±10.54)% vs. (98.08±4.65)%], and the levels in the severe MPP group were all lower than those in the mild MPP group (all P < 0.05). The level of serum RIPK3 in children with MPP was negatively correlated with the lung function indicators PEF% pred and FEV1% pred (r values were -0.78, -0.77, all P < 0.001). Conclusions:The serum RIPK3 level in children with MPP is positively correlated with the severity of their condition and negatively correlated with the lung function indicators PEF% pred and FEV1% pred.

Objective To explore the hearing characteristics and early screening methods of hearing loss in diabetes mellitus(DM)patients.Methods From September 2022 to November 2023,800 DM patients in the Department of Endocrinology in People's Liberation Army General Hospital of Southern Theater Command were enrolled.According to the results of electrical audiometry,they were divided into a normal hearing DM group(n=214)and a hearing loss group(n=586).Binary logistic regression was used to analyze the influencing factors of hearing loss in DM patients.Results Age,homeostasis model assessment of insulin resistance(HOMA-IR),serum creatinine(Scr),urinary albumin/creatinine ratio(UACR)DM duration,hearing loss value,and proportion of DPN,DR,DKD,hypertension,coronary heart disease,perceived hearing loss,DPOAE abnormality and ABR abnormality in hearing loss group was higher than that in normal hearing group(P<0.05).DBP,homeostasis model insulin sensitivity index and estimated glomerular filtration rate(eGFR)were lower than those in normal hearing group(P<0.05).Logistic regression analysis showed that DM duration(OR 0.987,95%CI 0.987～1.002,P=0.001),eGFR(OR 0.974,95%CI 0.964～0.983,P=0.000),and hypertension(OR 0.659,95%CI 0.443～0.980,P=0.040)and coronary heart disease(OR 0.488,95%CI 0.246～0.968,P=0.040)were the influencing factors of hearing loss in DM patients.Conclusions Hearing loss is the complications of DM and is related to factors such as the DM duration.Given the insidious onset of hearing loss,DM patients should undergo a combined hearing screening using multiple methods in the early stage.

Objective To establish two osteoarthritis models of destabilization of the medial meniscus(DMM)and chronic ankle instability(CAI)in mice,and compare the effects of knee osteoarthritis with varus deformity on ipsilateral ankle cartilage degeneration.Methods Thirty 6-week-old C57BL/6J male mice were randomly divided into a control group and two surgical groups(DMM group and CAI group),respectively.The progression of ankle joint degeneration was quantitatively evaluated through behavioral observation,imaging techniques and histopathology analysis in each group of mice over a 12-week period.Results A decline in gait stability and balance was observed in two surgical groups.Compared to the control group,the time required to cross the balance beam was increased by 23.20％,and the number of slips was increased by 43.26％at 12th week postoperatively in the DMM group.The bone volume fraction and bone mineral density of ankle joints also increased.Meanwhile,wear and tear of the ankle cartilage were found,with the formation of osteophytes,and OARSI score was increased by 88.89％.These changes in ankle joint were more pronounced in the CAI group.Conclusions This mouse model-based study revealed a coupling relationship between the knee and ankle motion.Knee osteoarthritis with varus deformity could lead to a significant ankle joint degeneration,while the damage was less severe than that observed in CAI.

Objective To establish two osteoarthritis models of destabilization of the medial meniscus(DMM)and chronic ankle instability(CAI)in mice,and compare the effects of knee osteoarthritis with varus deformity on ipsilateral ankle cartilage degeneration.Methods Thirty 6-week-old C57BL/6J male mice were randomly divided into a control group and two surgical groups(DMM group and CAI group),respectively.The progression of ankle joint degeneration was quantitatively evaluated through behavioral observation,imaging techniques and histopathology analysis in each group of mice over a 12-week period.Results A decline in gait stability and balance was observed in two surgical groups.Compared to the control group,the time required to cross the balance beam was increased by 23.20％,and the number of slips was increased by 43.26％at 12th week postoperatively in the DMM group.The bone volume fraction and bone mineral density of ankle joints also increased.Meanwhile,wear and tear of the ankle cartilage were found,with the formation of osteophytes,and OARSI score was increased by 88.89％.These changes in ankle joint were more pronounced in the CAI group.Conclusions This mouse model-based study revealed a coupling relationship between the knee and ankle motion.Knee osteoarthritis with varus deformity could lead to a significant ankle joint degeneration,while the damage was less severe than that observed in CAI.

Objective To explore the hearing characteristics and early screening methods of hearing loss in diabetes mellitus(DM)patients.Methods From September 2022 to November 2023,800 DM patients in the Department of Endocrinology in People's Liberation Army General Hospital of Southern Theater Command were enrolled.According to the results of electrical audiometry,they were divided into a normal hearing DM group(n=214)and a hearing loss group(n=586).Binary logistic regression was used to analyze the influencing factors of hearing loss in DM patients.Results Age,homeostasis model assessment of insulin resistance(HOMA-IR),serum creatinine(Scr),urinary albumin/creatinine ratio(UACR)DM duration,hearing loss value,and proportion of DPN,DR,DKD,hypertension,coronary heart disease,perceived hearing loss,DPOAE abnormality and ABR abnormality in hearing loss group was higher than that in normal hearing group(P<0.05).DBP,homeostasis model insulin sensitivity index and estimated glomerular filtration rate(eGFR)were lower than those in normal hearing group(P<0.05).Logistic regression analysis showed that DM duration(OR 0.987,95%CI 0.987～1.002,P=0.001),eGFR(OR 0.974,95%CI 0.964～0.983,P=0.000),and hypertension(OR 0.659,95%CI 0.443～0.980,P=0.040)and coronary heart disease(OR 0.488,95%CI 0.246～0.968,P=0.040)were the influencing factors of hearing loss in DM patients.Conclusions Hearing loss is the complications of DM and is related to factors such as the DM duration.Given the insidious onset of hearing loss,DM patients should undergo a combined hearing screening using multiple methods in the early stage.

Long-term burden of illness and associated medication usage make osteoporosis(OP) a common complication of respiratory diseases. The pathogenic risk factors and treatment strategies for respiratory diseases related OP are similar to primary OP. However, due to differences in the pathogenesis of each disease, there are distinctions in the characteristics of bone loss and treatment approaches. Therefore, targeted diagnostic and therapeutic plans need to be formulated. This article provides a comprehensive review of secondary OP caused by common respiratory diseases in terms of epidemiological characteristics, related risk factors or possible mechanisms, changes in bone metabolic indexes or characteristics of bone damage, and progress in diagnosis and treatment. The aim of this review is to offer insights into the prevention and treatment of secondary OP related to respiratory diseases and promote the development of a multidisciplinary collaborative approach.

Gene-knockout technology is increasingly used as a powerful tool for establishing animal models of hyperuricemia(HUA).HUA gene-knockout animal models are not only helpful in revealing the molecular mechanisms of uric acid metabolism but are also of great value for evaluating potential therapeutic strategies.In this paper,the application of gene-knockout technology in HUA animal models is discussed in detail by reviewing the domestic and foreign literature,focusing on the knockout of urate oxidase,glucose transporter 9,and ATP-binding cassette transporter G2.The review provides a reference and guidance for the further establishment of HUA animal models by gene knockout technology.

Abstract: Objective To explore the risk factors for macrolide unresponsive mycoplasma pneumoniae pneumonia (MUMPP) in children and to develop a model for predicting the risk of MUMPP. Methods Children with mycoplasma pneumoniae pneumonia admitted to the Pediatric Department of Leshan People's Hospital who met the inclusion criteria from March 1, 2023, to December 1, 2023, were retrospectively selected and divided into the responsive group and unresponsive group according to their reactions to macrolides. General patient data, laboratory tests, and imaging findings were collected and compared. Logistic regression analysis was used to analyze the risk factors of the Macrolide unresponsive mycoplasma pneumoniae pneumonia, and R language (R4.2.3) to establish the nomogram model. The goodness of fit, discriminative ability, calibration, and clinical utility of the model were assessed using the Hosmer-Lemeshow goodness of fit test, receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis, respectively. Results A total of 224 patients were included in the analysis of children. Among them, 156 (70%) were randomly selected as the training set, and the remaining 68 cases (30%) were used as the validation set. Logistic regression analysis revealed that pleural effusion (OR=6.986, 95%CI 1.362-35.847), highest temperature before admission (OR=3.095, 95%CI 1.487-6.439), neutrophil count (OR=1.294, 95%CI:1.103-1.519), C-reactive protein (OR=1.030, 95%CI 1.002-1.058), and procalcitonin (OR=2.899, 95%CI:1.353-6.214) were independent risk factors for MUMPP in children (all P<0.05). A nomogram was established using R software. The Hosmer-Lemeshow goodness of fit tests for the training set and the validation set were χ2=4.018 and χ2=4.657 (all P>0.05), indicating a good fit of the model. The AUC values for the training set and validation were 0.825 (95%CI: 0.755-0.894) and 0.828 (95%CI 0.729-0.928), respectively, suggesting good discriminative ability of the model. Calibration curve analysis suggested that the model had good predictive performance, while decision curve analysis indicated a high clinical application value of the predictive model. Conclusions Pleural effusion, highest body temperature before admission, neutrophil count, C-reactive protein, and procalcitonin are independent risk factors for MUMPP in children. The prediction model constructed based on the above variables has high predictive efficacy and clinical application value.