Objective: To investigate the mechanism of Yishen Tongluo Formula in ameliorating renal pyroptosis in diabetic nephropathy mice by regulating the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway. Methods: Sixty C57BL/6 male mice were randomly divided into control (10 mice) and intervention groups (50 mice) using random number table method. The diabetes nephropathy model was established by intraperitoneally injecting streptozotocin(50 mg/kg). After modeling, the intervention group was further divided into model, semaglutide (40 μg/kg), and high-, medium-, and low-dose Yishen Tongluo Formula groups (15.6, 7.8, and 3.9 g/kg, respectively) using random number table method. The high-, medium-, and low-dose Yishen Tongluo Formula groups were administered corresponding doses of medication by gavage, the semaglutide group received a subcutaneous injection of semaglutide injection, and the control group and model groups were administered distilled water by gavage for 12 consecutive weeks. Random blood glucose levels of mice in each group were monitored, and the 24-h urinary protein content was measured using biochemical method every 4 weeks; after treatment, the serum creatinine and urea nitrogen levels were measured using biochemical method. The weight of the kidneys was measured, and the renal index was calculated. Hematoxylin and eosin, periodic acid-Schiff, periodic Schiff-methenamine, and Masson staining were used to observe the pathological changes in renal tissue. An enzyme-linked immunosorbent assay was used to detect urinary β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) levels. Western blotting and real-time fluorescence PCR were used to detect the relative protein and mRNA expression levels of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), Caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in renal tissue. Immunohistochemistry was used to detect the proportion of protein staining area of the TLR4, MyD88, and NF-κB in renal tissue. Results: Compared with the control group, the random blood glucose, 24-h urinary protein, serum creatinine, urea nitrogen, and renal index of the model group increased, and the urine β2-MG, NGAL, and KIM-1 levels increased. The relative protein and mRNA expression levels of NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18 in renal tissue increased, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas increased (P<0.05). Pathological changes such as glomerular hypertrophy were observed in the renal tissue of the model group. Compared with the model group, the Yishen Tongluo Formula high-dose group showed a decrease in random blood glucose after 12 weeks of treatment (P<0.05). The Yishen Tongluo Formula high- and medium-dose groups showed a decrease in 24-h urinary protein, creatinine, urea nitrogen, and renal index, as well as decreased β2-MG, NGAL, and KIM-1 levels. NLRP3, Caspase-1, GSDMD, IL-1 β, and IL-18 relative protein and mRNA expression levels were also reduced, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas was reduced (P<0.05). Pathological damage to renal tissue was ameliorated. Conclusion Yishen Tongluo Formula may exert protective renal effects by inhibiting renal pyroptosis and alleviating tubular interstitial injury in diabetic nephropathy mice by regulating the TLR4/MyD88/NF-κB signaling pathway.

ObjectiveTo investigate the effect and mechanism of Yishen Tongluo prescription in protecting mice from oxidative stress injury in diabetic kidney disease （DKD） via the nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/NAD（P）H quinone oxidoreductase 1 （NQO1） signaling pathway. MethodsSpecific pathogen-free （SPF） male C57BL/6 mice were assigned into a control group （n=10） and a modeling group （n=50）. The DKD model was established by intraperitoneal injection of streptozotocin. The mice in the modeling group were randomized into a model group， a semaglutide （40 μg·kg^-1） group， and high-， medium-， and low-dose （18.2， 9.1， 4.55 g·kg^-1， respectively） Yishen Tongluo prescription groups， with 10 mice in each group. The treatment lasted for 12 weeks. Blood glucose and 24-h urine protein levels were measured， and the kidney index （KI） was calculated. Serum levels of creatinine （SCr）， blood urea nitrogen （BUN）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） were assessed. The pathological changes in the renal tissue were evaluated by hematoxylin-eosin， periodic acid-Schiff， periodic acid-silver methenamine， and Masson’s trichrome staining. Enzyme-linked immunosorbent assay kits were used to measure the levels of β2-microglobulin （β2-MG）， neutrophil gelatinase-associated lipocalin （NGAL）， kidney injury molecule-1 （KIM-1）， liver fatty acid-binding protein （L-FABP）， nitric oxide synthase （NOS）， glutathione （GSH）， total antioxidant capacity （T-AOC）， and 8-hydroxy-2'-deoxyguanosine （8-OHdG）. Immunohistochemical staining was performed to examine the expression of Kelch-like ECH-associated protein 1 （Keap1） and malondialdehyde （MDA）. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR） and Western blot were employed to determine the mRNA and protein levels， respectively， of factors in the Nrf2/HO-1/NQO1 signaling pathway. ResultsCompared with the control group， the DKD model group showed rises in blood glucose， 24-h urine protein， KI， SCr， BUN， and ALT levels， along with glomerular hypertrophy， renal tubular dilation， thickened basement membrane， mesangial expansion， and collagen deposition. Additionally， the model group showed elevated levels of β2-MG， NGAL， KIM-1， L-FABP， NOS， and 8-OHdG， lowered levels of GSH and T-AOC， up-regulated expression of MDA and Keap1， and down-regulated expression of Nrf2， HO-1， NQO1， and glutamate-cysteine ligase catalytic subunit （GCLC） （P<0.05）. Compared with the model group， the semaglutide group and the medium- and high-dose Yishen Tongluo prescription groups showed reductions in blood glucose， 24-h urine protein， KI， SCr， BUN， and ALT levels， along with alleviated pathological injuries in the renal tissue. In addition， the three groups showed lowered levels of β2-MG， NGAL， KIM-1， L-FABP， NOS， and 8-OHdG， elevated levels of GSH and T-AOC， down-regulated expression of MDA and Keap1， and up-regulated expression of Nrf2， HO-1， NQO1， and GCLC （P<0.05）. ConclusionYishen Tongluo prescription exerts renoprotective effects in the mouse model of DKD by modulating the Nrf2/HO-1/NQO1 signaling pathway， mitigating oxidative stress， and reducing renal tubular injuries.

Objective:To investigate and analyze case reporting ethical review and patient informed consent reports published in the comprehensive journals of clinical medicine in China in 2022.Methods:According to the data from the 2022 Edition of the Chinese Science and Technology Journal of the Citation Reports(Extended Version),the case reports published in comprehensive journals of clinical medicine in 2022 were selected as the research objects.The information on ethics and patient informed consent was extracted from the case reports that met the selection criteria,and Microsoft Excel 2021 and SPSS 21.0 were used to sort out and analyze the data.Results:A total of 587 case reporting articles were published in the 42 included journals in 2022,of which 36(6.13%)reported on science and technology ethics and/or informed consent.Case reports reporting on science and technology ethics and/or informed consent mostly came from the key magazine of China technology(88.89%Vs.65.88%),and the proportion of manuscripts involving science and technology ethics on the official website of the journal was relatively high(86.11%Vs.63.88%),and the difference was statistically significant(P＜0.01).Conclusion:The proportion of case reports of science and technology ethics and/or informed consent in journals of comprehensive discipline classification of clinical medicine was relatively low.Currently,most international journals are required to obtain the informed consent of patients or legal guardians before publishing case reports.Compared with this,there are still certain gaps in China,which need to be paid great attention to.

Objective:To explore the mediating effect of unhealthy lifestyle and depressive symptom on the associations between life course factors and aging health.Methods:The study included 6 217 participants (aged ≥45 years) from the China Health and Retirement Longitudinal Study (CHARLS). We used principal component analysis (PCA) and hierarchical clustering analysis (HCA) to divide participants into six subgroups based on 70 life course factors. Five key life course factors were identified based on correlation analysis and their contribution to aging health. Physiological dysregulation (PD) was calculated by using eight biomarkers in the 2015 CHARLS biomarker dataset. Linear regression, logistic regression, and mediation models were used to explore the complex associations of life course subgroups, key factors, unhealthy lifestyle, depression symptom with PD.Results:Life course subgroups were significantly associated with PD after adjusting chronological age and gender ( β: 0.08-0.17, all P<0.05). Life-course subgroups and key factors, including adverse experiences in adulthood and lower education level, were significantly associated with unhealthy lifestyle ( β: 0.04-0.52, all P<0.05). Life-course subgroups and key factors, including childhood trauma, parental health in childhood, adverse experiences in adulthood, and lower education level, were significantly associated with depression symptom ( OR: 1.16-4.76, all P<0.05). Mediation analysis showed that unhealthy lifestyle had partial mediating effect on the association of life course subgroups and key factors, including adverse experiences in adulthood, and lower education levels, with PD (3.1%-3.6%). Depression symptom had partial mediating effect on the association of life course subgroups and key factors, including childhood trauma, adverse experience in adulthood, and lower education level, with PD (6.0%-16.2%). Conclusions:Unhealthy lifestyle and depression symptom has partial mediating effect on the impact of life course factors on aging health. It is important to pay attention to these two modifiable factors while targeting childhood trauma and adverse experience in adulthood.

Objective To investigate the potential active ingredients and the mechanism of Coreopsis tinctoria Nutt. in the prevention and treatment of hyperlipidemia. Methods Ultra-high performance liquid chromatography-Quadrupole-Exactive Orbitrap mass spectrometry (UPLC-Q-Exactive Orbitrap MS) was used to qualitatively analyze the fractions and blood components of flavones in Coreopsis tinctoria Nutt. The intersection targets of flavones in Coreopsis tinctoria Nutt. and hyperlipidemia were screened,and the protein-protein interaction network was constructed and analyzed by the STRING 12.0 database. Finally,the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used for enrichment analysis. Results A total of 25 compounds were detected from the flavones in Coreopsis tinctoria Nutt.,and their structures were identified,including ten chalcones,nine flavanones,four flavonols,one aurone,and one biflavone. The analysis of blood components showed that marein,flavanomarein,okanin,isookanin and 5,7,3',5'-tetrahydroxyflavanone-7-O-β-D-glucopyranoside were the main components of the flavones in Coreopsis tinctoria Nutt. in blood. Network pharmacological GO and KEGG enrichment analysis showed that the flavones in Coreopsis tinctoria Nutt. may regulate phosphatidylinositol 3-kinase/protein kinase B,tumor necrosis factor,hypoxia-inducible factor-1 signaling pathway and other signaling pathways in the regulation and prevention of hyperlipidemia. Conclusion Coreopsis tinctoria Nutt. can prevent and treat hyperlipidemia,and the mechanism may be related to the five blood components of the flavones in Coreopsis tinctoria Nutt.,including marein,flavanomarein,okanin,isookanin and 5,7,3',5'-tetrahydroxyflavanone-7-O-β-D-glucopyranoside.

Objective To analyze the clinical efficacy of transcatheter tricuspid valve replacement (TTVR) in cardiac implantable electronic lead-related tricuspid regurgitation (TR). Methods The patients with severe TR who underwent LuX-Valve TTVR in 9 Chinese medical centers from June 2020 to August 2021 were retrospectively enrolled. They were divided into a cardiac implantable electronic device (CIED) group and a non-CIED group based on whether they had pre-existing CIED implantation. Success of the procedure was defined as safe implantation of the LuX-Valve and complete withdrawal of the delivery system. Prognostic improvement was defined as a decrease of TR grade to≤2+ and an improvement of cardiac function by≥2 grades. Surgical success and postoperative prognosis were compared between the two groups. Results A total of 190 patients were collected, including 50 males and 140 females with a mean age of 66.2±7.8 years. There were 29 patients in the CIED group, and 161 patients in the non-CIED group. In the CIED group, 28 patients were implanted with a permanent pacemaker and 1 patient with a cardioverter-defibrillator. Preoperative New York Heart Association (NYHA) cardiac function class, TR degree, left ventricular ejection fraction, tricuspid annular plane systolic excusion, and cardiac risk scores were comparable between the two groups (P>0.05). Postoperative TR was reduced to≤2+ in all patients, and there was no statistical difference in the incidence of perivalvular leakage between the two groups (P=0.270). Postoperative CT of CIED patients showed the valve was in place, and the lead was not extruded, twisted, or deflected. The in-hospital mortality of the two groups were 10.3% and 1.9%, respectively, and the difference was statistically significant (P=0.047). In addition, there was no statistical difference between the two groups in terms of postoperative improvement of cardiac function and mortality in the 1- and 2-year follow-up. Conclusion TTVR is feasible, safe, and effective in patients with CIED implantation, and the pre-existing lead has no significant effect on the clinical efficacy.

Objective To investigate the anti-estrogenic activity of bisphenol A and its substitutes, and to analyze the relevant mechanisms. Methods Bisphenol A and its three most widely used substitutes (bisphenol S, bisphenol F and bisphenol AF) were selected as the docking ligand molecules, and estradiol was used as the control ligand molecule. The ligand molecules docking was simulated with estrogen receptor (ER) α and ERβ using AutoDock software. Results Bisphenol A forms a hydrogen bond with ERα at the His474 residue and with ERβ via three hydrogen bonds at Leu260, His428, and Asn431 residues. Similar to bisphenol A, bisphenol S, bisphenol F, bisphenol AF and estradiol primarily interact with ERα and ERβ through hydrophobic interactions and hydrogen bonds, but with varying optimal binding sites and affinities. The binding forces of the optimal binding sites for bisphenol A, bisphenol F, bisphenol AF, bisphenol S and estradiol with ERα were -4.15, -4.19, -2.73, -4.62 and -5.37 kcal/mol, respectively, and with ERβ were -3.76, -3.91, -2.86, -3.93, and -4.98 kcal/mol, respectively. The affinity ranking for two ERs with these five molecules from high to low was estradiol > bisphenol S> bisphenol F> bisphenol A > bisphenol AF. Conclusion The affinity between bisphenol compounds with ERα and ERβ is mainly based on the hydrophobic interaction with non-polar residues of the receptor and hydrogen bonding with key residues. Bisphenol S, bisphenol F and bisphenol AF showed similar or even stronger endocrine disrupting effects than bisphenol A.

Post-stroke urinary incontinence (PSUI) is a common complication in patients with stroke, affecting at least one-third of patients with stroke and seriously affecting their quality of life and rehabilitation process. This article reviews the pathogenesis, risk factors, and treatment of PSUI.

Background Perfluoroalkyl and polyfluoroalkyl substances (PFASs) exposure may affect male reproductive health. There are regional differences in PFASs exposure levels among men of childbearing age in China, and current research results on associated influencing factors are inconsistent. Objective To investigate the levels of PFASs in serum and their determinants among men of childbearing age. Methods The participants (n=113, 22-45 years old) were from a cross-sectional study of exposure to environmental pollutants and male reproductive health damage in Hubei Province conducted from April to June 2013 at the Reproductive Medicine Center of Tongji Hospital, Wuhan, Hubei Province. Eleven kinds of PFASs were measured in serum by isotopic dilution-high performance liquid chromatography-tandem mass spectrometry. The included PFASs were prefluorohexanoic acid (PFHxA), perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUdA), perfluorododecanoic acid (PFDoA), perfluorotridecanoic acid (PFTrDA), perfluorotetradecanoic acid (PFTeDA), perfluorohexane sulfonate (PFHxS), and perfluorooctane sulfonate (PFOS). Information about participants' demographic characteristics, lifestyle, and habits was collected by a set of self-designed questionnaires. The associations of demographic characteristics, lifestyle, and habits with exposure to PFASs were analyzed by linear regression. Results The major components of PFASs were PFOS and PFOA, and the concentrations expressed as M (P₂₅, P₇₅) were 8.31 (4.90, 17.79) ng·mL⁻¹ and 2.77 (2.18, 3.46) ng·mL⁻¹, respectively. The positive rates of six PFASs (PFOA, PFNA, PFDA, PFUdA, PFHxS, and PFOS) were 100%, followed by PFDoA and PFTrDA (87.61% and 88.59%, respectively). The linear regression results showed that age was positively associated with the levels of Σ₈PFASs (sum of the concentrations of the eight PFASs with a positive rate greater than 80%) (P < 0.05). The concentration of serum PFOA in men with monthly family income of 2000-4000 yuan was 53.73% (P < 0.01) higher than those in men with monthly family income of <2000 yuan. The serum concentrations of PFNA and PFTrDA were both 32.31% (P < 0.05) higher in men with monthly family income ≥4000 yuan than those in men with monthly family income <2000 yuan. The serum concentration of PFHxS in men who used plastic cups was 33.64% (P < 0.01) higher than that in men who did not report oral contact with plastic products (plastic tableware, plastic cups, and plastic bags for packing food). The serum concentrations of PFHxS, PFOS, and Σ₈PFASs were 33.64% (P < 0.01), 43.33% (P < 0.01), and 36.34% (P < 0.05) higher in men who bathed with laundry soap than those in men who did not use detergents. Men who bathed with toilet soap had a 34.99% (P < 0.05) higher serum concentration of PFHxS than those who bathed without detergents. Conclusion Men of childbearing age are exposed to PFASs extensively. Age, monthly household income, usage of laundry soap or toilet soap in bathing, and usage of plastic cups may influence the level of PFASs in serum. However, further investigation is needed to confirm these results.

The infection rate of Epstein-Barr virus(EBV)in the population is as high as 95%.It is the first carcinogenic virus found by human beings.Children infected with EBV often cause non-neoplastic diseases, including infectious mononucleosis, chronic active EBV infection and hemophagocytic lymphohistiocytosis.Most of the diseases related to non-neoplastic EBV infection in children are self-limited diseases, and a few of them are complicated with serious complications or develop into neoplastic diseases.The pathogenesis of this kind of disease is complex, the condition is varied, and some children with gene defects have a poor prognosis.Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is an effective treatment for refractory children.At the same time, the condition of some critically ill children is progressing rapidly, so it is very important to create the opportunity of allo-HSCT for such children.