Extensive studies have identified potential adverse effects on semen quality of obesity, based on body mass index, but the association between body fat distribution, a more relevant indicator for obesity, and semen quality remains less clear. We conducted a longitudinal study of 4304 sperm donors from the Guangdong Provincial Human Sperm Bank (Guangzhou, China) during 2017-2021. A body composition analyzer was used to measure total and local body fat percentage for each participant. Generalized estimating equations were employed to assess the association between body fat percentage and sperm count, motility, and morphology. We estimated that each 10% increase in total body fat percentage (estimated change [95% confidence interval, 95% CI]) was significantly associated with a 0.18 × 10 6 (0.09 × 10 6 -0.27 × 10 6 ) ml and 12.21 × 10 6 (4.52 × 10 6 -19.91 × 10 6 ) reduction in semen volume and total sperm count, respectively. Categorical analyses and exposure-response curves showed that the association of body fat distribution with semen volume and total sperm count was stronger at higher body fat percentages. In addition, the association still held among normal weight and overweight participants. We observed similar associations for upper limb, trunk, and lower limb body fact distributions. In conclusion, we found that a higher body fat distribution was significantly associated with lower semen quality (especially semen volume) even in men with a normal weight. These findings provide useful clues in exploring body fat as a risk factor for semen quality decline and add to evidence for improving semen quality for those who are expected to conceive.
Humans ; Male ; Adult ; Semen Analysis ; China ; Body Fat Distribution ; Longitudinal Studies ; Sperm Count ; Sperm Motility ; Body Mass Index ; Tissue Donors ; Obesity/complications* ; Spermatozoa ; Young Adult ; Middle Aged ; East Asian People

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.

Long-term hypertension causes excessive vascular remodeling and leads to adverse cardiovascular events. Balance of ubiquitination and deubiquitination has been linked to several chronic conditions, including pathological vascular remodeling. In this study, we discovered that the expression of ubiquitin-specific protease 25 (USP25) is significantly up-regulated in angiotensin II (Ang II)-challenged mouse aorta. Knockout of Usp25 augments Ang II-induced vascular injury such as fibrosis and endothelial to mesenchymal transition (EndMT). Mechanistically, we found that USP25 interacts directly with Forkhead box O3 (FOXO3) and removes the K63-linked ubiquitin chain on the K258 site of FOXO3. We also showed that this USP25-mediated deubiquitination of FOXO3 increases its binding to light chain 3 beta isoform and autophagosomic-lysosomal degradation of FOXO3. In addition, we further validated the biological function of USP25 by overexpressing USP25 in the mouse aorta with AAV9 vectors. Our studies identified FOXO3 as a new substrate of USP25 and showed that USP25 may be a potential therapeutic target for excessive vascular remodeling-associated diseases.

Acetaminophen (APAP) is the primary cause of drug-induced acute liver failure. Ovarian tumor deubiquitinase 6A (OTUD6A), a recently discovered deubiquitinase of the OTU family, has been primarily studied in tumor contexts. However, its role in APAP-induced liver injury (AILI) remains unclear. Therefore, this study aimed to investigate the involvement of OTUD6A in the pathogenesis of AILI. Our findings demonstrated a substantial upregulation of OTUD6A in both the liver tissue and isolated hepatocytes of mice following APAP stimulation. OTUD6A knockout exacerbated APAP-induced inflammation, hepatocyte necrosis, and liver injury, whereas OTUD6A overexpression alleviated these pathologies. Mechanistically, OTUD6A directly interacted with the enhancer of zeste homolog 2 (EZH2) and selectively removed K48-linked polyubiquitin chains from EZH2, enhancing its stability. This resulted in increased protein levels of EZH2 and H3K27me3, as well as reduced endoplasmic reticulum (ER) stress and cell death in hepatocytes. Collectively, our research uncovers a novel role for OTUD6A in mitigating APAP-induced liver injury by promoting EZH2 stabilization.

Objective To study the medication law of TCM compounds for ischemic stroke using data mining methods;To provide reference for clinical medication.Methods Literature about TCM treatment for ischemic stroke was retrieved from CNKI,VIP,Wanfang Data and SinoMed from May 31,2014 to May 31,2024.Drug frequency analysis,dosage analysis,property and taste attribution analysis,association rule analysis,factor analysis and clustering analysis were performed using Excel 2019,SPSS Modeler 18,SPSS 25 software.Results A total of 180 prescriptions for the treatment of ischemic stroke were included,involving 208 kinds of Chinese materia medica,with a total frequency of 1 996 times,of which 20 were high-frequency medicines(≥24 times),with Chuanxiaong Rhizoma,Angelicae Sinensis Radix,Pheretima,Astragali Radix,Paeoniae Radix Rubra and Carthami Flos being the most frequent;the efficacy of the medicines included activating blood circulation and removing blood stasis,tonifying the deficiency,pacifying the liver,calming the wind and clearing away heat;the main properties were warm,cold and neutral;the main tastes were bitter,sweet and pungent;the main meridians were liver,spleen,heart and lung meridians;among the drug dosages of drugs with frequency≥24,the mean dosage of Chuanxiong Rhizoma,Angelicae Sinensis Radix,Pheretima,Astragali Radix and Paeoniae Radix Rubra were 12.24,12.91,10.52,40.00,12.13 g,respectively.In the systematic clustering and complex network analysis,it was suggested that the core TCM prescriptions were:Xuefu Zhuyu Decoction with modified Banxia Baizhu Tianma Decoction,modified Chaihu Shugan Powder,Buyang Huanwu Decoction with modified Huangqi Guizhi Wuwu Decoction and modified Liujunzi Decoction.Conclusion TCM treatment for ischemic stroke mostly uses the methods of activating blood circulation and expelling phlegm,nourishing blood to promote blood circulation,clearing heat and cooling blood,and benefiting qi and neutralizing qi,which provides ideas and methods for following research.

Objective To evaluate the efficacy of combining surgical treatment with biological agents for perianal fistulizing Crohn's disease(pfCD).Methods Sixty patients with perianal fistulizing Crohn's disease(pfCD)admitted to our hospital from May 2021 to December 2023 were randomly allocated into two groups:Treatment Group A(n=30)and Treatment Group B(n=30).Treatment Group A received pfCD surgery combined with inflix-imab(IFX)and azathioprine(AZA),while Treatment Group B underwent pfCD surgery along with ustekinumab(UST)and AZA.The CDAI score,PDAI score,and Assche score were monitored for both groups,and postoperative MRI examinations were conducted to evaluate the healing of pfCD.Results There were statistically significant differences in CDAI,PDAI,and Assche scores between pre-treatment and post-treatment comparisons within treat-ment groups A and B(P<0.05),as well as in the magnitude of change at each time point.Comparisons of CDAI,PDAI,and Assche scores at 8,16,24,and 32 weeks,and PDAI scores at 40 weeks between groups A and B using independent samples t-tests did not yield statistically significant results(P>0.05).However,significant differences were observed for CDAI and Assche scores at 40 weeks(P<0.05).Significant changes in CDAI,PDAI,and Assche scores were noted at 8,16,24,32,and 40 weeks post-treatment within both groups A and B(P<0.05).Multiple comparisons using the LSD method revealed that the changes in these scores at each time point were statistically significant(P<0.05).The data indicate a temporal trend in the changes of CDAI,PDAI,and Assche scores,with group B showing a more rapid decline compared to group A.In terms of fistula response rates,both groups A and B achieved 100%(30/30).However,the clinical healing rate of fistulas was higher in group B at 86.7%(26/30)compared to 76.7%(23/30)in group A.Conclusion The combination of surgical treatment with IFX/UST plus AZA is safe and effective for treating pfCD.However,the long-term efficacy of combining surgical treatment with UST appears to be superior.

In recent years,with the continuous advancement of deep space exploration missions,astronauts have been increasingly exposed to complex and extreme environmental factors in space,such as microgravity,space radiation,circadian rhythm disruption,and confined isolation.These conditions can easily induce brain dysfunction in astronauts,manifesting as cognitive decline,emotional disturbances,sleep disorders,and neuroinflammatory responses.Traditional Chinese Medicine(TCM),characterized by its holistic regulation and syndrome differentiation-based treatment principles,exhibits multi-target regulation and systemic coordination,and has attracted growing attention in the field of brain function protection.This study systematically reviews the protective applications and research progress of TCM and related techniques in both actual spaceflight missions and simulated space environment models against brain functional disorders.The underlying mechanisms and future prospects are discussed,with the aim of providing insights for safeguarding astronauts'brain health and laying a theoretical foundation for the precise intervention and systematic protection strategies of TCM in future deep space missions.

OBJECTIVE To observe the clinical efficacy of Yijinjing in the treatment of elderly sarcopenia and its effect on chro-nic inflammatory response in patients,and to explore the Yijinjing exercise prescription suitable for elderly patients with sarcopenia.METHODS A total of 120 elderly patients with sarcopenia admitted to the Department of Rehabilitation Medicine,Suzhou Hospital of Traditional Chinese Medicine from September 2022 to September 2024 were selected and randomly divided into a control group and a Yijinjing group,with 60 cases in each group.The control group received health education and dietary guidance,and the Yijinjing group received Yijinjing exercises on the basis of the intervention of the control group.The changes in skeletal muscle mass,upper and lower limb muscle strength,muscle thickness,muscle cross-sectional area,physical fitness and chronic inflammation level were observed in the two groups before and after the intervention.RESULTS After intervention,the skeletal muscle mass,grip strength,30 s sit-stand test times,rectus femoris thickness and cross-sectional area,vastus intermedius thickness,and physical fit-ness assessment of the patients in the Yijinjing group were significantly increased compared with those before treatment(P<0.05),and the indicators after intervention were higher than those in the control group(P<0.05);the serum TNF-α and IL-18 levels in the Yi-jinjing group were significantly decreased compared with those before treatment(P<0.05),and the indicators after intervention were lower than those in the control group(P<0.05);there was no statistically significant change in the biceps brachii thickness and serum IL-6 level in the Yijinjing group compared with those before treatment(P>0.05);there was no significant correlation between the bi-ceps brachii thickness and grip strength after Yijinjing intervention,r=0.139 8,P>0.05;there was a significant negative correlation between the TNF-α level and grip strength after Yijinjing intervention,r=-0.313 8,P<0.05.CONCLUSION Yijinjing exercises can improve muscle mass and strength in elderly patients with sarcopenia,and improve the physical fitness of patients,which may be related to improving the chronic inflammatory state of the body.

Objective To explore the factors influencing blood drug concentrations of first-line anti-tuberculosis drugs in fixed-dose combinations by analyzing therapeutic drug monitoring data from tuberculosis patients receiving these regimens.Methods This retrospective study enrolled 224 patients who received treatment at Guangzhou Chest Hospital between January 2020 and December 2024.All participants underwent standardized therapy during the intensive phase,with therapeutic drug monitoring of first-line anti-tuberculosis drugs(ANTDs),including isoniazid(INH)and rifampicin(RFP).Data collection was completed in January 2025,at which time clinical records and measured INH and RFP plasma concentrations were updated.Data analysis was conducted from January to February 2025.Eight baseline variables—gender,age,hypoproteinemia(serum albumin<35 g/L),glomerular filtration rate(GFR),and others—were collected.Univariate chi-square tests and multivariate logistic regression analyses were performed to identify independent risk factors associated with subtherapeutic INH and RFP plasma concentrations.Results Among the study participants,71.43%(160/224)exhibited blood drug concentrations below the reference range for INH,compared to 41.07%(92/224)for RFP.The mean blood concentrations(mg/L,±SD)were 2.532±1.371 for INH and 9.428±4.317 for RFP,respectively.One-way analysis indicated significant associations between male gender,positive etiological test results,and subtherapeutic RFP concentrations(P<0.05),suggesting statistically significant differences.Multivariate regression analysis further revealed that male gender(OR=1.992,95%CI:1.094～3.628)and positive etiological tests(OR=1.929,95%CI:1.058～3.517)were independent risk factors for low RFP levels.Conclusions This study demonstrates that therapeutic drug monitoring(TDM)frequently identifies subtherapeutic RFP concentrations in tuberculosis patients undergoing treatment.Multivariate analysis reveals that male sex and positive pathogen test results are independent risk factors associated with low RFP plasma levels.Consequently,clinicians should exercise heightened vigilance in patients exhibiting these characteristics,promptly implementing TDM to guide individualized dose adjustments.Such an approach is crucial for optimizing treatment efficacy and minimizing the risk of drug resistance development.