OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective To explore the mechanism of Jiawei Jisheng Shenqi Decoction in improving the hypoxic microenvironment and antagonizing liver cirrhosis.Methods In vivo experiments were conducted using a rat model of carbon tetrachloride(CCL4)-induced liver cirrhosis.Rats were divided into normal,model,colchicine,JWJSSQ low-dose,JWJSSQ medium-dose,and JWJSSQ high-dose group.Pathological changes in liver tissues in each group were examined by hematoxylin and eosin(HE)and Masson staining,changes in serum liver function were detected using test kits,levels of hyaluronic acid(HA),laminin(LN),procollagen Ⅲ(PC Ⅲ),and collagen typeⅣ(COL4)were detected by enzyme-linked immunosorbent assay(ELISA),and protein expression levels of hypoxia-inducible factor-1α(HIF-1α),Notch1,Jagged1,and α-smooth muscle actin(α-SMA)were detected by Western blot.In vitro experiments were conducted in HSC-T6 cells,and the optimal concentration of CoCl2(100 μ mol/L,200μmol/L,400 μmol/L,600 μmol/L and 800 μmol/L)in the cultured cells and the optimal concentration of drug-containing serum(5％,10％,15％,20％)were determined by Cell Counting Kit-8(CCK-8)assay.The migration ability of cells in each group was detected by scratch testing,and changes in the apoptosis rates were determined by flow cytometry.Protein expression levels of HIF-1α,Notch1,Jagged1,α-SMA,matrix metallopeptidase 9(MMP9),and tissue inhibitor of metalloproteinases 1(TIMP-1)were detected by Western blot.Results In the in vivo experiments,liver swelling,inflammatory cell infiltration,collagen deposition,and the appearance of pseudolobules were significantly increased in the model group compared with those in the normal group.Serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),HA,LN,PCⅢ,and COL4 were significantly increased and albumin(ALB)was significantly decreased in the model group,while liver levels of HIF-1α,Notch1,Jagged1,and α-SMA proteins were significantly increased(P＜0.01).Liver swelling,inflammatory cell infiltration,and collagen deposition were significantly reduced in each treatment group compared with those in the model group,and the degree of fibrosis was reduced.Serum ALT,AST,HA,LN,PCⅢ,and COL4 were significantly decreased and ALB was significantly increased,while liver levels of HIF-1α,Notch1,Jagged1,and α-SMA proteins were also significantly decreased to varying degrees(P＜0.05).In the in vitro experiments,hypoxia promoted HSC-T6 migration and reduced apoptosis,increased the protein expression levels of HIF-1α,Notch1,Jagged1,α-SMA,and TIMP-1,and reduced the expression levels of MMP9(P＜0.01).Serum containing Jiawei Jisheng Shenqi Decoction inhibited HSC-T6 migration,promoted HSC-T6 apoptosis,lowered the expression of HIF-1α,Notch1,Jagged1,α-SMA,and TIMP-1 proteins,and enhanced the expression of MMP9 protein(P＜0.01).The inhibitory effect of Jiawei Jisheng Shenqi on HSC-T6 cell activation was reversed by the HIF-1α agonist dimethyloxalylglycine.Conclusions Jiawei Jisheng Shenqi Decoction can improve the hypoxic microenvironment via the HIF-1α/Notch pathway,thereby exerting an anti-liver cirrhosis effect.

Objective:To investigate the changes in the narrow band imaging (NBI) phenotypes of oropharyngeal, hypopharyngeal, and laryngeal squamous cell carcinoma after neoadjuvant immunochemotherapy, and to explore the clinical value of NBI endoscopy in re-evaluation and follow-up of pharyngeal and laryngeal squamous cell carcinoma after neoadjuvant immunochemotherapy.Methods:Twenty-nine patients diagnosed with locally advanced pharyngeal or laryngeal squamous cell carcinoma in the First Affiliated Hospital of Xiamen University from November 2021 to January 2024 and receiving 2 cycles of neoadjuvant immunochemotherapy were selected, including 26 males and 3 females, aged 43-80 years. Regular NBI and white light (WL) endoscopy examinations, as well as imaging examinations such as CT scans, were performed. After the neoadjuvant immunochemotherapy, 36 specimens from suspected lesions of the pharynx or the larynx were obtained through surgical resection. The NBI findings of the pharyngeal or laryngeal lesions and their relationships with corresponding pathological and imaging results were analyzed with kappa test, Pearson correlation analysis, McNemar test, and Wilcoxon Signed Rank Test.Results:After neoadjuvant immunochemotherapy, primary lesions showed pathological complete response (pCR) in 9 cases, partial response (PR) in 19 cases, and progressive disease (PD) in one case. The NBI phenotypes of pharyngeal and laryngeal malignant tumors after treatment showed high consistency (kappa=0.818, P<0.01) and significant correlations ( r=0.852, P<0.01) with their pathological results. WL endoscopic examinations showed inconsistency (kappa=0.239, P=0.12) with their pathological results. NBI endoscopy was more effective in identifying benign lesions after treatment than WL endoscopy ( P=0.031). In cases of both PR and pCR of the primary lesion, there were significant differences in NBI phenotypes before and after neoadjuvant immunochemotherapy (all P<0.05), with phenotypes transitioning to lower malignancy and benign lesions, respectively. Among 19 cases with PR, 16 showed concentric/eccentric regression, and 3 showed multipoint focal regression. NBI endoscopy was more accurate in diagnosing benign or malignant lesions, pCR or PR after treatment compared to CT (all P<0.05). Conclusions:The present NBI microvascular classification of the pharyngeal and laryngeal lesions is still applicable for the diagnosis and evaluation in pharyngeal and laryngeal squamous cell carcinoma after neoadjuvant immunochemotherapy. The changes in NBI phenotypes and ranges can indicate tumor regression, progression, and recurrence. NBI is more accurate in diagnosing pharyngeal and laryngeal squamous cell carcinoma after neoadjuvant immunochemotherapy compared to WL endoscopy and imaging examinations such as CT.

Objective:To evaluate the clinical efficacy of percutaneous balloon pulmonary valvuloplasty (PBPV) via antegrade venous-arterial loop in neonates with critical pulmonary stenosis with intact ventricular septum (CPS-IVS).Methods:A retrospective case review was conducted. Fifteen neonates with CPS-IVS who underwent PBPV via antegrade venous-arterial loop at the Women and Children′s Hospital, Qingdao University between September 2020 and September 2023 were included. Pre-and post-operative right ventricular functional parameters, surgical complications, and follow-up outcomes were analyzed. Paired-sample t-test was used to compare changes in right ventricular systolic pressure (RVSP), percutaneous oxygen saturation (SpO 2), and echocardiographic findings pre-and post-operatively, as well as during the follow-up period. Results:Among the 15 neonates (9 males and 6 females) with CPS-IVS, the surgical age was (3.6±0.5) d. All neonates underwent successful PBPV via antegrade venous-arterial loop under general anesthesia. The immediate post-operative trans-pulmonary valve pressure gradient was (35±6) mmHg (1 mmHg=0.133 kPa), with a significant reduction in RVSP from (96±16) mmHg to (59±14) mmHg ( t=6.70, P<0.001). SpO 2 (with an inspired oxygen concentration of 0.48) increased from 0.86±0.07 pre-operatively to 0.97±0.03 post-operatively ( t=4.81, P<0.001). One month postoperatively, SpO 2 (without oxygen supplementation) normalized in all patients, with a statistically significant difference compared to pre-operative values ( t=0.16, P<0.001). Immediately postoperative, mild to moderate diastolic pulmonary valve regurgitation was observed in 8 patients, with no cases of severe regurgitation. Additionally, the severity of tricuspid valve regurgitation decreased from severe to mild-to-moderate in 6 patients. Three months postoperatively, one patient underwent a second PBPV due to an increased trans-pulmonary valve pressure gradient of 74 mmHg, which decreased to 27 mmHg immediately after the procedure, with subsequent good recovery. Over a one-year follow-up period, all 15 patients demonstrated improvements in right ventricular indices. The Z-score of the tricuspid valve annulus significantly improved from -1.9±0.8 pre-operatively to -0.4±0.1 post-operatively ( t=6.88, P<0.001). At the last follow-up, mild to moderate pulmonary valve regurgitation was observed in 3 patients, and mild tricuspid regurgitation in 2 patients, with no cases of moderate or severe regurgitation. Conclusion:Intervention via antegrade venous-arterial loop for the treatment of CPS-IVS in neonates is safe and effective.

Objective:The aim of this study is to explore the clinical efficacy and safety of endocrinotherapy combined with Shenqi Pills on hormone-sensitive prostate cancer(HSPC).Methods:Eighty patients who were diagnosed with HSPC and renal-yang deficiency at the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine and the Hospital of Traditional Chi-nese Medicine of Mayang Miao Autonomous County from 1st April 2021 to 30th April 2024 were randomly divided into 2 groups.The patients in the control group were treated with androgen deprivation therapy(ADT).And the patients in treatment group were treated with Shenqi Pills orally on the basis of the control group.The baseline data of the two groups were analyzed.After 36 months of treat-ment,the differences between the two groups were compared in terms of overall survival(OS),prostate-specific antigen(PSA)level,PSA response rate,Functional Assessment Scale for Prostate Cancer Therapy(FACT-P),Chinese medicine evidence scores,testoster-one level and safety.Results:A total of 80 study subjects were included in this study,including 42 cases in the treatment group and 38 cases in the control group.There was no statistical difference in the baseline data between the two groups before treatment(P＞0.05).At the end of the observation period,a statistically significant difference in OS was found in the treatment group compared to the control group in the subgroup of patients with a disease duration ranged of 0-6 months(P＜0.05).There was no statistically signif-icant difference in PSA levels in the treatment group at 3 months(P＞0.05).And the differences in the proportion of PSA50(98.1％vs 91.4％),PSA90(92.9％ vs 84.6％)and the proportion of decrease in PSA(56.7％vs 33.8％)in the treatment group were found compared to those in the control group after 6 months of tre atment.After 12 months of treatment,the scores of FACT-4 and re-nal-yang deficiency in the treatment group were(95.28±7.93)and(15.73±5.70)respectively,compared to the scores in the con-trol group([85.46±10.12]and[18.20±4.27](P＜0.05).However,there was no significant difference in serum testosterone([0.60±0.24]nmol/L vs[1.09±2.10]nmol/L)between the two groups(P＞0.05).After 24 months of treatment,there were significant differences in in the FACT-4 total score([97.95±7.54]vs[80.33±8.58]),renal-yang deficiency syndrome score([14.64±5.15]vs[24.94±8.75])between the treatment group and the control group(P＜0.05).However,there was no signifi-cant difference in serum testosterone([0.73±1.01]nmol/L vs[0.59±0.25]nmol/L)between the two groups(P＞0.05).Bet-ter therapeutic results were showed in the treatment group in terms of total FACT-P score,physical situation score,social and family situation score,emotional state score,functional state score,additional score and renal-yang deficiency symptom score(P＜0.05).After treatment,there was no serious adverse reaction in the course of treatment,and no obvious abnormality was found in the liver and kidney function of the patients from two groups.Conclusion:Endocrinotherapy combined with Shenqi Pills is safe and effective in HSPC and can reduce the risk of death in HSPC patients,and the earlier the intervention,the longer the overall survival of the pa-tients.In addition,this treatment regimen can increase the PSA response rate,improve patients'quality of life,and reduce the renal-yang deficiency syndrome score without the risk of elevating serum testosterone levels.

AIM: To investigate the correlation of serum leucine-rich α-2 glycoprotein 1(LRG1)and fibroblast growth factor 21(FGF-21)levels with neovascular glaucoma(NVG).METHODS: A total of 110 cases(110 eyes)with NVG admitted to the ophthalmology department from September 2020 to September 2022 were selected as NVG group, with 23 cases of grade II, 44 cases of grade III, and 43 cases of grade IV, while 90 sex and age matched cataract patients(90 eyes)were selected as control group. The levels of LRG1, FGF-21, vascular endothelial growth factor(VEGF), pigment epithelium-derived factor(PEDF), and tumor necrosis factor-α(TNF-α)in serum were detected by ELISA; Pearson correlation analysis was used to analyze the correlation of serum LRG1 and FGF-21 levels with Teich grade, VEGF, PEDF and TNF-α levels.RESULTS: The levels of serum LRG1, FGF-21, VEGF, PEDF and TNF-α in the NVG group were significantly higher than those in the control group(all P<0.01). With the increase of Teich grading, the levels of serum LRG1, FGF-21, VEGF, PEDF and TNF-α in NVG patients significantly increased in turn(all P<0.05). Correlation analysis showed that the levels of LRG1 and FGF-21 in serum of NVG patients were positively correlated with the levels of VEGF, PEDF and TNF-α(all P<0.05).CONCLUSION: The levels of LRG1 and FGF-21 in serum of patients with NVG are obviously increased, which are positively correlated with the levels of VEGF, PEDF and TNF-α, both of which may be related to the development of NVG.

Objective To investigate the effect of Ching Shum Pills(CSP)for alleviating non-alcoholic fatty liver disease(NAFLD)and the underlying mechanism.Methods In a mouse model of NAFLD,the therapeutic effect of CSP was evaluated by measuring serum glucose,lipid profiles(TC,TG,LDL-C,HDL-C),and hepatic function markers.Network pharmacology was employed to identify active compounds in CSP and their targets using TCMSP,HERB,SwissTargetPrediction,GeneCards,OMIM,and DisGeNET.Protein-protein interaction(PPI)networks,Gene Ontology(GO),and KEGG pathway analyses were conducted.Molecular docking(AutoDock Vina)was used to assess the compound-target binding affinities.Quantitative real-time PCR(qRT-PCR)was used to validate the mRNA expressions of the core genes in the liver tissue of the mouse models.Results In the mouse model of NAFLD,treatment with CSP significantly reduced body weight gain and serum TG levels of the mice,and high-dose CSP treatment resulted in obvious reduction of ALT levels and hepatic fat accumulation.Network pharmacology analysis identified quercetin and 2-monolinolenin as the key bioactives in CSP,which target TNF,AKT1,IL6,TP53,and ALB.Docking simulations suggested strong binding between the two core compounds and their target proteins.The results of qRT-PCR showed that high-fat diet induced significant downregulation of Tp53,Cpt1,and Ppara expressions in mice,which was effectively reversed by CSP treatment.Conclusion CSP can improve lipid metabolism disorders in NAFLD mice through a regulatory mechanism involving multiple targets and pathways to reduce liver fat accumulation and protect liver function.The key components in CSP such as quercetin and linolenic acid monoacylglycerol may participate in the regulation of such metabolic processes as fatty acid oxidation by targeting TP53.

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

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.