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.

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.

Objective:To investigate the correlation between hearing loss and microvascular complications in diabetes.Methods:This cross-sectional study conducted the data from 572 patients with diabetes hospitalized in the Endocrinology Department of the General Hospital of Southern Theater Command from September 2022 to July 2023. All participants underwent electrical audiometry and acoustic immittance in the ENY department. Based on the audiometric results, participants were categorized into normal hearing group and hearing loss group. Additionally, 572 non-diabetic patients from the outpatient department were enrolled as the non-diabetic group. The general information and laboratory results were collected and compared using t test, rank sum test or χ2 test. Binary logistic regression analysis was used to evaluate the association of diabetic hearing loss with diabetic kidney disease(DKD), diabetic retinopathy (DR), and diabetic peripheral neuropathy (DPN). Results:Among 572 patients with diabetes, 429 suffered from hearing loss and 143 were normal. χ2 test showed significant differences in combined DKD and DPN between two groups, but not in DR. Multivariate binary logistic regression analysis identified DKD and DPN as risk factors for hearing loss, but no correlation was found with DR. Conclusion:Diabetic patients with DKD or DPN should be monitored for potential hearing loss. Early screening and treatment are crucial to prevent severe hearing impairment.

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.

Objective To investigate the correlations of serum cyclic adenosine monophosphate-responsive element binding protein regulator of transcription coactivator 3 (CRTC3) and oxidative stress indicators with carotid atherosclerosis in patients with coronary heart disease (CHD). Methods A total of 154 CHD patients in the hospital from June 2021 to June 2023 were selected as study group and divided into mild, moderate, and severe atherosclerosis groups based on the degree of carotid atherosclerosis; another 154 healthy individuals with physical examinations in the same period were selected as control group. Pearson method was used to analyze the correlations of serum CRTC3 and oxidative stress indicators with carotid atherosclerosis indicators. Results Serum CRTC3 and malondialdehyde (MDA), carotid plaque area and intima-media thickness (IMT) in the study group were significantly higher than those in the control group, while the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were significantly lower than those in the control group (P < 0.05). In the mild, moderate and severe atherosclerosis groups, serum CRTC3 and MDA levels, carotid plaque area, and IMT significantly gradually increased, while SOD and GSH-Px levels significantly gradually decreased (P < 0.05). Pearson correlation analysis showed that serum CRTC3 and MDA levels were positively correlated with carotid plaque area and IMT (P < 0.05), while SOD and GSH-Px were negatively correlated with carotid plaque area and IMT (P < 0.05). The receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) for the combined diagnosis of severe carotid atherosclerosis by CRTC3, SOD, MDA and GSH-Px was 0.990 (95%CI, 0.982 to 0.998), with a sensitivity of 96.27% and a specificity of 76.28%. The diagnostic value of the combined application of these four indicators was significantly higher than that of each indicator alone (Z_{combined-CRTC3}=2.723, Z_combined-SOD=2.698, Z_combined-MDA=2.673, Z_{combined-GSH-Px}=2.803, P < 0.05). Conclusion The serum levels of CRTC3 and MDA are significantly increased while SOD and GSH-Px levels are significantly decreased in CHD patients. Both serum CRTC3 and oxidative stress levels are closely related to carotid atherosclerosis.

Objective:To establish a hyperuricemia rat model through the high temperature-humidity treatment, and monitor its vital signs and biochemical indicator characteristics, as well as observe the changes of renal histomorphology and ultrastructure.Methods:Male SD rats were randomly divided into control(CON) group, potassium oxonate(PO) group and high temperature-humidity(HTH) group, 6 rats each. The experiment lasted for 6 consecutive weeks. Rats from PO group was given 250 mg/kg PO by gavage every day. The rats from HTH group were treated with a special thermostatic incubator for one hour each day after gavaging 250 mg/kg PO. Serum uric acid, creatinine and other indicators were detected every 2 weeks. After 6 weeks, the kidney tissues were collected. The morphological changes and urate crystal deposition of kidney tissues were observed by hematoxylin-eosin staining, Masson′s trichrome staining and gomori staining, while the ultramicrostructural changes of kidney were observed by transmission electron microscope.Results:Two weeks after the experiment, the average serum uric acid values of PO group and HTH group increased significantly, HTH group was higher than PO and CON groups[(133.9±17.8), (107.6±12.4), and (85.7±4.1) μmol/L, P=0.001]. And after 6 weeks, the HTH group was still higher than the other two groups[(115.1±27.8), (82.7±13.9), and (72.9±17.8) μmol/L, P=0.008). The average serum creatinine in HTH group was slightly higher than that in PO group and CON group at 6 weeks[(46.2±4.7), (38.1±6.0), and (28.3±6.3) μmol/L, P=0.001]. Light microscope showed partial renal tubular dilatation in PO group, but renal tubular epithelial cells swelling and inflammatory cells infiltration were more significant in HTH group. The ultrastructural changes such as glomerular podocyte swelling were found in HTH group by transmission electron microscope. Conclusion:In this study, we had successfully established a hyperuricemia rat model by simulating the high temperature-humidity environment combined with potassium oxyzinate after 2 weeks of experiment. After 6 weeks of modeling, it was found that the high temperature-humidity induced rat models possessed a relatively higher and stabler serum uric acid level than that of the traditional chemical medicine induced rats. The method can be applied to the research of pathogenesis and pharmacotherapy of hyperuricemia caused by high temperature-humidity environment.

With the widespread use of mobile phones, laptops, and WIFI, the effects of radio frequency radiation (RFR) on human health are of increasing concern, and there are particular concerns about its reproductive toxicity. Studies have shown that the reproductive system is a sensitive target for RFR. In males, RFR is associated with decreased sperm quality and serum testosterone levels, but there are few studies on the biological effects of RFR by altering physical parameters on the male reproductive system. This paper introduced common sources of RFR, reviewed the toxic effects and mechanisms of RFR targeting male reproductive system from the aspects of spermatogenic cells, sperm structure, blood-testicular barrier, and testicular function, and analyzed male reproductive system related toxic effects of RFR by varying physical parameters including frequency, treatment duration, and specific absorption rate, so as to provide a theoretical basis and scientific basis for the safe and reasonable use of radio frequency electromagnetic field by humans and subsequent in-depth research.

Objective:To investigate the value of serum CD64, heparin binding protein (HBP) and procalcitonin (PCT) in early diagnosis of septic shock and its prognostic value.Methods:The clinical data of 40 children with sepsis (sepsis group) and 40 children with septic shock (septic shock group) in Children′s Hospital of Xuzhou Medical University from January 2018 to November 2021 were retrospectively analyzed. PCT was detected by chemiluminescence, HBP was detected by enzyme-linked immunosorbent assay, and CD 64 was detected by flow cytometry. All children were followed up within 1 month after discharge, and the occurrence of poor prognosis (including multiple organ failure and death) was recorded. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of serum CD 64, HBP and PCT for septic shock. Multivariate Logistic regression was used to analyze the independent risk factors for poor prognosis in children with septic shock. Results:The serum CD 64, HBP and PCT in septic shock group were significantly higher than those in sepsis group: 0.667 ± 0.120 vs. 0.501 ± 0.115, (116.46 ± 11.41) μg/L vs. (87.34 ± 23.49) μg/L and (11.41 ± 1.25) μg/L vs. (9.29 ± 1.31) μg/L respectively, and there were statistical differences ( P<0.05). ROC curve analysis result showed that the area under curve (AUC) of serum CD 64, HBP and PCT for predicting septic shock were 0.837, 0.894 and 0.880 respectively, and the optimal cut-off values were 0.586, 106.2 μg/L and 11.28 μg/L respectively; the AUC of serum CD 64, HBP and PCT combined detection for predicting septic shock was 0.914, with a sensitivity of 75.7%, specificity of 96.0%, and accuracy of 71.7%. According to the optimal cut-off values of serum CD 64, HBP and PCT, 40 children with septic shock were divided into high expression group and low expression group. The prognosis was good in 25 cases and bad in 15 cases. The incidence of poor prognosis in CD 64 high expression group, HBP high expression group and PCT high expression group was significantly higher than that in corresponding CD 64 low expression group, HBP low expression group and PCT low expression group: 56.52% (13/23) vs. 2/17, 10/17 vs. 21.74% (5/23) and 11/18 vs. 18.18% (4/22), and there was statistical difference ( P<0.01 or <0.05). Multivariate Logistics regression analysis result showed that serum CD64, HBP and PCT were independent risk factors for poor prognosis in children with septic shock ( OR = 0.818, 1.204 and 3.633; 95% CI 0.674 to 0.994, 1.022 to 1.419 and 1.090 to 12.108; P = 0.043, 0.026 and 0.036). Conclusions:The serum levels of CD 64, HBP and PCT in children with septic shock are significantly increased, which play an important role in the occurrence and development of septic shock, and which have predictive value for septic shock. The combined detection of the 3 indexes could be used to evaluate the prognosis, with a higher predictive value.

Objective:To explore the level of expression, clinical significance of receptor-interacting protein kinase-3(RIPK3) in the bronchoalveolar alveolar lavage fluid (BALF) of mycoplasma pneumoniae pneumonia(MPP) in children and the relationship between RIPK3 and various cytokines.Methods:Using a case-control study, 30 refractory mycoplasma pneumoniae pneumonia children treated in Children′s Hospital of Xuzhou Medical University from February 2019 to February 2021 were selected as the MRPP group, 35 mycoplasma pneumoniae pneumonia children as the RPP group.Meanwhile, 20 sex- and age-matched hospitalized children with bronchial foreign body were selected as the case-control group.In all subjects, protein levels of RIPK3 and mixed lineage kinase domain-like protein(MLKL) were determined by Western Blot.Meanwhile, levels of IL-6, IL-1β and TNF-α were determined by enzyme linked immuno sorbent assay(ELISA). Compare levels of different parameters between the three groups and analyze the correlation between levels of RIPK3 and MLKL, L-6, IL-1β, TNF-α in the BALF of MPP children using Spearman rank correlation analysis.Results:There were statistically significant differences in the levels of RIPK3, MLKL, IL-6, IL-1β and TNF-α in BALF between RMPP group, MPP group and control group (all P<0.001). Pairwise comparisons also showed statistical differences, and the RMPP group was the highest, followed by MPP group, and the control group was the lowest.The level of RIPK3 in BALF of MPP children was positively correlated with MLKL, IL-6, IL-1β and TNF-α ( r=0.711, 0.676, 0.725, 0.651, P<0.001). Linear regression analysis shows: MLKL=0.432×RIPK3. Conclusion:RIPK3 may be involved in the occurrence and development of MPP in children, and is closely related to cytokines such as IL-6, IL-1β and TNF-α.