To investigate the impact of preoperative serum follicle-stimulating hormone (FSH) levels on the probability of testicular sperm retrieval, we conducted a study of nonobstructive azoospermic (NOA) men with different testicular volumes (TVs) who underwent microdissection testicular sperm extraction (micro-TESE). A total of 177 NOA patients undergoing micro-TESE for the first time from April 2019 to November 2022 in Shenzhen Zhongshan Obstetrics and Gynecology Hospital (formerly Shenzhen Zhongshan Urology Hospital, Shenzhen, China) were retrospectively reviewed. The subjects were divided into four groups based on average TV quartiles. Serum hormone levels in each TV group were compared between positive and negative sperm retrieval subgroups. Overall sperm retrieval rate was 57.6%. FSH levels (median [interquartile range]) were higher in the positive sperm retrieval subgroup compared with the negative outcome subgroup when average TV was <5 ml (first quartile [Q1: TV <3 ml]: 43.32 [17.92] IU l -1 vs 32.95 [18.56] IU l -1 , P = 0.048; second quartile [Q2: 3 ml ≤ TV <5 ml]: 31.31 [15.37] IU l -1 vs 25.59 [18.40] IU l -1 , P = 0.042). Elevated serum FSH levels were associated with successful micro-TESE sperm retrieval in NOA men whose average TVs were <5 ml (adjusted odds ratio [OR]: 1.06 per unit increase; 95% confidence interval [CI]: 1.01-1.11; P = 0.011). In men with TVs ≥5 ml, larger TVs were associated with lower odds of sperm retrieval (adjusted OR: 0.84 per 1 ml increase; 95% CI: 0.71-0.98; P = 0.029). In conclusion, elevated serum FSH levels were associated with positive sperm retrieval in micro-TESE in NOA men with TVs <5 ml. In men with TV ≥5 ml, increases in average TVs were associated with lower odds of sperm retrieval.
Humans ; Male ; Azoospermia/surgery* ; Sperm Retrieval/statistics & numerical data* ; Adult ; Follicle Stimulating Hormone/blood* ; Retrospective Studies ; Testis/pathology* ; Microdissection ; Organ Size

BACKGROUND: Children's respiratory health demonstrates particular sensitivity to air pollution. Existing evidence investigating the association between short-term ozone (O₃) exposure and childhood pneumonia remains insufficient and inconsistent, especially in low- and middle-income countries (LMICs). METHOD: To provide more reliable and persuasive evidence, we implemented a multi-city, time-stratified case-crossover design with a large sample size, using data from seven representative children's hospitals across major geographical regions in China. To avoid the impact of the COVID-19 pandemic, individual-level medical records of inpatient children under 6 years of age diagnosed with pneumonia during 2016-2019 were collected. Conditional logistic regression models were fitted for each city, and city-specific estimates were pooled through a meta-analysis using a random-effects model. RESULTS: In total, the study included 137,470 pediatric pneumonia hospital admissions. The highest pooled estimate for O₃ occurred at lag0-1, with a 10 µg/m³ increase in O₃ associated with a 1.57% (95% CI: 0.67%-2.48%) higher risk of pediatric pneumonia hospital admissions. Stratified analyses indicated that the effects of O₃ were robust across different sexes, age groups, and admission seasons. We also observed a statistically significant increase in risk associated with O₃ concentrations exceeding the World Health Organization Air Quality Guidelines (WHO-AQGs). CONCLUSIONS This study revealed a significant positive association between O₃ and pediatric pneumonia hospital admissions. Our findings substantially strengthen the evidence base for the adverse health impacts of O₃, underscoring the importance of O₃ pollution control and management in reducing the public health burden of pediatric pneumonia.
Humans ; Ozone/analysis* ; China/epidemiology* ; Pneumonia/chemically induced* ; Child, Preschool ; Male ; Female ; Infant ; Cross-Over Studies ; Air Pollutants/analysis* ; Hospitalization/statistics & numerical data* ; Child ; Cities/epidemiology* ; Air Pollution/adverse effects* ; Infant, Newborn ; Environmental Exposure/adverse effects*

OBJECTIVE: To investigate the anti-inflammatory effect of rutaecarpine (RUT) on monosodium urate crystal (MSU)-induced murine peritonitis in mice and further explored the underlying mechanism of RUT in lipopolysaccharide (LPS)/MSU-induced gout model in vitro. METHODS: In MSU-induced mice, 36 male C57BL/6 mice were randomly divided into 6 groups of 8 mice each group, including the control group, model group, RUT low-, medium-, and high-doses groups, and prednisone acetate group. The mice in each group were orally administered the corresponding drugs or vehicle once a day for 7 consecutive days. The gout inflammation model was established by intraperitoneal injection of MSU to evaluate the anti-gout inflammatory effects of RUT. Then the proinflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA) and the proportions of infiltrating neutrophils cytokines were detected by flow cytometry. In LPS/MSU-treated or untreated THP-1 macrophages, cell viability was observed by cell counting kit 8 and proinflammatory cytokines were measured by ELISA. The percentage of pyroptotic cells were detected by flow cytometry. Respectively, the mRNA and protein levels were measured by real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot, the nuclear translocation of nuclear factor κB (NF-κB) p65 was observed by laser confocal imaging. Additionally, surface plasmon resonance (SPR) and molecular docking were applied to validate the binding ability of RUT components to tumor necrosis factor α (TNF-α) targets. RESULTS: RUT reduced the levels of infiltrating neutrophils and monocytes and decreased the levels of the proinflammatory cytokines interleukin 1β (IL-1β) and interleukin 6 (IL-6, all P<0.01). In vitro, RUT reduced the production of IL-1β, IL-6 and TNF-α. In addition, RT-PCR revealed the inhibitory effects of RUT on the mRNA levels of IL-1β, IL-6, cyclooxygenase-2 and TNF-α (P<0.05 or P<0.01). Mechanistically, RUT markedly reduced protein expressions of tumor necrosis factor receptor (TNFR), phospho-mitogen-activated protein kinase (p-MAPK), phospho-extracellular signal-regulated kinase, phospho-c-Jun N-terminal kinase, phospho-NF-κB, phospho-kinase α/β, NOD-like receptor thermal protein domain associated protein 3 (NLRPS), cleaved-cysteinyl aspartate specific proteinase-1 and cleaved-gasdermin D in macrophages (P<0.05 or P<0.01). Molecularly, SPR revealed that RUT bound to TNF-α with a calculated equilibrium dissociation constant of 31.7 µmol/L. Molecular docking further confirmed that RUT could interact directly with the TNF-α protein via hydrogen bonding, van der Waals interactions, and carbon-hydrogen bonding. CONCLUSION RUT alleviated MSU-induced peritonitis and inhibited the TNFR1-MAPK/NF-κB and NLRP3 inflammasome signaling pathway to attenuate gouty inflammation induced by LPS/MSU in THP-1 macrophages, suggesting that RUT could be a potential therapeutic candidate for gout.
Animals ; NF-kappa B/metabolism* ; Male ; Indole Alkaloids/therapeutic use* ; Signal Transduction/drug effects* ; Mice, Inbred C57BL ; Inflammation/complications* ; Uric Acid ; Quinazolines/therapeutic use* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Humans ; Gout/chemically induced* ; Inflammasomes/metabolism* ; Cytokines/metabolism* ; THP-1 Cells ; Mitogen-Activated Protein Kinases/metabolism* ; Mice ; Molecular Docking Simulation ; Lipopolysaccharides ; Quinazolinones

OBJECTIVES: Metabolic syndrome (MetS) is a major public health concern that poses a significant threat to human health. Investigating its underlying mechanisms and identifying potential intervention targets has important clinical implications. This study aims to explore the association between serum gastric biomarkers and MetS and its components. METHODS: A cross-sectional study was conducted among 24 635 individuals (aged 18 to 80 years) who underwent routine health examinations from May 2017 to June 2021 at the Health Management Medical Center, Third Xiangya Hospital, Central South University. Demographic data, medical and medication history, height, weight, blood pressure, fasting blood glucose, glycated hemoglobin (HbA1c), total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and creatinine levels were collected. Serum levels of pepsinogen (PG) I, PGII, and gastrin-17 (G-17) were measured using enzyme-linked immunosorbent assay kits. MetS was diagnosed based on the International Diabetes Federation criteria. Logistic regression was used to assess the association between gastric biomarkers and MetS. RESULTS: Among the 24 635 participants, the overall prevalence of MetS was 35.72%, with a higher rate in males than in females (42.41% vs 24.31%). Compared with the non-MetS group, MetS group were older and had higher metabolic-related diseases rate, Helicobacter pylori infection rate, body mass index (BMI), waist circumference, systolic and diastolic blood pressure, total cholesterol, triglycerides, fasting blood glucose, glycated hemoglobin, and creatinine levels (all P<0.05). Serum G-17 levels were significantly elevated in the MetS group, and PGI levels decreased (both P<0.05). Males had higher G-17, PGI, PGII, and PGI/PGII ratios than females (all P<0.05). Subgroup analysis revealed that G-17 was consistently elevated in MetS patients regardless of sex, whereas PGI was decreased. PGII levels exhibited sex-specific differences. After adjusting for confounders, Logistic regression analysis revealed that high G-17 level was independently associated with MetS, with a stronger correlation observed in males. Moreover, G-17 level progressively increased with higher MetS scores (all P<0.05). CONCLUSIONS Serum G-17 level is positively associated with both the presence and severity of MetS, with a more pronounced correlation in males, suggesting its potential involvement in MetS-related metabolic dysregulation.
Humans ; Metabolic Syndrome/epidemiology* ; Female ; Male ; Middle Aged ; Adult ; Cross-Sectional Studies ; Biomarkers/blood* ; Aged ; Young Adult ; Adolescent ; Gastrins/blood* ; Pepsinogen A/blood* ; Pepsinogen C/blood* ; Aged, 80 and over

Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

Under the trend of increasing aging， integrated elderly care and medical services is an important measure to optimize the supply of elderly care services and promote the good death of the elderly. Using the cooperative production theory and the classical grounded theory， a qualitative analysis was conducted on 38 cases of elderly palliative care and 25 cases of hospital-based palliative care under the integrated elderly care and medical services model from a hospital in Nanning City using Nvivo 20.0 software. This paper found that the integrated elderly care and medical services mode emphasized the deep integration of medical and elderly care services by integrating resources and improving service efficiency， to achieve the basic experience of comprehensive health care for the elderly. The promotion of these experiences has a positive significance for building a multi-agent cooperative production system， strengthening personnel training， perfecting the performance distribution mechanism， and further promoting the development of the national palliative care pilot.

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective To extract and summarize the clinical registration information of periodontitis registered in the US ClinicalTrials.gov and Chinese Clinical Trial Registry(ChiCTR),and further analyze the registration characteristics of periodontitis clinical trials.Methods The ClinicalTrials.gov and ChiCTR data-bases were searched and compiled for periodontitis clinical registration information from 2000 to December 26,2024,including registration number,country/region of registration,annual number of registered projects,sample size,study type and design,study phase,and trial progress status.Results As of December 26,2024,a total of 520 242 registered clinical trials were retrieved from the ClinicalTrials.gov registry platform,of which 1 542(0.30%)were related to periodontitis.There were 189(12.26%)studies on periodontitis-related pro-jects in Turkey,while a total of 37(2.4%)projects were initiated by researchers in China,which ranked ninth.The Chinese Clinical Trial Register(ChiCTR)had 92 954 registered projects,of which 165 were on pe-riodontitis,and most of them were conducted by well-known affiliated hospitals and stomatology hospitals.The number of registrations in the ClinicalTrials.gov database increased year by year and reached a peak in 2022(146 registrations).Trial designs were focused on interventional and observational studies.ClinicalTri-als.gov study phases were focused on phases 2 and 4,while ChiCTR was clustered at phase 0(pre-registra-tion).Conclusion The number of clinical registrations for periodontitis in China's database is relatively low,and despite a steady upward trend,there is still a gap compared with other countries internationally.Future re-search should focus on how to encourage more oral health related research institutions to register on the plat-form and how to increase the sample size.

Objective:To investigate the relationship between gestational weight gain (GWG) in twin pregnancies and adverse perinatal outcomes.Methods:This retrospective study included twin pregnant women with live births at≥25 weeks of gestation and their offspring, who delivered at Peking University People's Hospital from January 2012 to October 2022. Total GWG was standardized according to gestational age and categorized into three groups based on the 2009 Institute of Medicine (IOM) guidelines: insufficient GWG (GWG below IOM recommendations), appropriate GWG (GWG within IOM recommendations), and excessive GWG (GWG above IOM recommendations). Comparisons between data of the three groups used analysis of variance, Kruskal-Wallis test or Bonferroni correction or Chi-square partitions. Multivariable logistic regression models and generalized estimating equations with logistic regression models were used to analyze the independent effects of GWG on maternal and neonatal outcomes. Results:A total of 794 twin pregnant women and their 1 588 live-born neonates were included in the study. There were 360 women (45.3%) with appropriate GWG, 356 (44.8%) with insufficient GWG, and 78 (9.8%) with excessive GWG. Both insufficient and excessive GWG were associated with an increased risk of preterm birth [adjusted ORs of 1.39 (95% CI: 1.04-1.88) and 1.70 (95% CI: 1.05-2.78), respectively]. Insufficient GWG was associated with an increased risk of gestational diabetes mellitus (adjusted OR=1.42, 95% CI: 1.00-2.01) and low birth weight infants (adjusted OR=2.04, 95% CI: 1.57-2.66). Insufficient GWG was also associated with a reduced risk of eclampsia or preeclampsia (adjusted OR=0.50, 95% CI: 0.33-0.75), cesarean section (adjusted OR=0.48, 95% CI: 0.30-0.77), discordant twin growth (adjusted OR=0.56, 95% CI: 0.37-0.85), and large for gestational age infants (adjusted OR=0.46, 95% CI: 0.35-0.61). Excessive GWG was associated with an increased risk of eclampsia or preeclampsia (adjusted OR=2.85, 95% CI: 1.65-4.91), and large for gestational age infants (adjusted OR=2.49, 95% CI: 1.60-3.86), while with a decreased risk of low birth weight infants (adjusted OR=0.42, 95% CI: 0.27-0.65). Conclusions:More than half of the twin pregnancies have GWG outside the recommended range of the IOM guidelines. Both insufficient and excessive GWG are associated with adverse perinatal outcomes, particularly an increased risk of preterm birth.