OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Based on standard sampling for Bufonis Venenum, this study analyzed the effect of the origin, and body weight and gender of Bufo bufo gargarizans on the quality of Bufonis Venenum. To be specific, mass spectrometry(MS) and the content determination methods in Chinese Pharmacopoeia(2020) were adopted. First, MS was performed on 76 Bufonis Venenum samples collected from 40 cities/counties in 17 provinces/autonomous regions which were derived from B. bufo gargarizans and B. melanostictus. Based on content determination, the body weight and gender of B. bufo gargarizans, which influenced the quality of Bufonis Venenum, were evaluated. Multivariate statistical analysis suggested huge difference in the material basis of the medicinal material derived from B. bufo gargarizans and B. melanostictus, and 9 differential compounds were identified. The content of components specified in Chinese Pharmacopoeia was higher in the medicinal material derived from B. bufo gargarizans than in the medicinal material derived from B. melanostictus. The content of the components specified in Chinese Pharmacopoeia was low in Bufonis Venenum derived from heavy B. bufo gargarizans, and higher in the Bufonis Venenum produced by male B. bufo gargarizans than in that produced by female B. bufo gargarizans irrespective of time and geographic location. In summary, this study provide new ideas and reference for the quality control of Bufonis Venenum, collection and processing of Bufonis Venenum, artificial breeding of B. bufo gargarizans, and biosynthesis mechanism of Bufonis Venenum.
Animals ; Male ; Female ; Bufanolides/analysis* ; Bufonidae ; Mass Spectrometry ; Quality Control ; Body Weight

Many therapies are effective in treating varicoceles, including dilation of the pampiniform plexus in males. The most common method of treatment is varicocelectomy. We aimed to assess an alternative technique (microsurgical spermatic [distal end]-superficial or inferior epigastric vein anastomosis) that preserves the normal blood flow pattern for varicocele treatment. We retrospectively analyzed 27 men with varicocele between October 2019 and July 2020. All patients underwent microsurgical spermatic (distal end)-superficial or inferior epigastric vein anastomosis. The prognosis was reviewed retrospectively with an additional survey conducted 3 months after surgery. The mean ± standard deviation of the age was 26.1 ± 7.3 years in patients with microsurgical spermatic (distal end)-superficial or inferior epigastric vein anastomosis. The maximum diameter of the varicocele vein, perineal pain score, sperm density, and forward movement of sperm improved over 3 months after surgery. Microsurgical spermatic (distal end)-superficial or inferior epigastric vein anastomosis is a safe and efficient surgical treatment for varicoceles.
Humans ; Male ; Adolescent ; Young Adult ; Adult ; Varicocele/surgery* ; Retrospective Studies ; Microsurgery/methods* ; Semen ; Anastomosis, Surgical/methods* ; Spermatozoa ; Pain/surgery*

Objective: Interferon-induced transmembrane protein 3 (IFITM3) is an important member of the IFITM family. However, the molecular mechanisms underlying its antiviral action have not been completely elucidated. Recent studies on IFITM3, particularly those focused on innate antiviral defense mechanisms, have shown that IFITM3 affects the body's adaptive immune response. The aim of this study was to determine the contribution of IFITM3 proteins to immune control of influenza infection . Methods: We performed proteomics, flow cytometry, and immunohistochemistry analysis and used bioinformatics tools to systematically compare and analyze the differences in natural killer (NK) cell numbers, their activation, and their immune function in the lungs of -/- and wild-type mice. Results: -/- mice developed more severe inflammation and apoptotic responses compared to wild-type mice. Moreover, the NK cell activation was higher in the lungs of -/- mice during acute influenza infection. Conclusions Based on our results, we speculate that the NK cells are more readily activated in the absence of IFITM3, increasing mortality in -/- mice.
Acute Disease ; Animals ; Disease Models, Animal ; Female ; Humans ; Influenza, Human ; virology ; Male ; Membrane Proteins ; genetics ; metabolism ; Mice ; Mice, Inbred C57BL ; Orthomyxoviridae Infections ; veterinary ; virology ; Rodent Diseases ; virology

There has been increasing interest in the psycho-socio-relational and sexual disorders of infertility, as the risk of psychological burden among infertile men with sexual dysfunctions is significant. The purpose of this study was to develop and to validate a predictive model to estimate individual psychological burden among infertile men with sexual dysfunction and study the association between them. Comprehensive data were collected for infertile men (n = 480) who sought treatment for infertility in a reproductive medicine center between June 2012 and December 2013. Using independent predictors of psychological burden from the least absolute shrinkage and selection operator, univariable and multivariable analyses were developed into two models. Predictive accuracy was compared between the models. We explored the association between sexual dysfunction and psychological burden. A total of 480 patients were analyzed using 10-fold cross-validation. Independent predictors of psychological burden were incorporated into a model to measure anxiety (corrected-area under curve (AUC): 77.3%) and a model to measure depression (corrected-AUC: 70.2%). Anxiety and depression were both associated with erectile dysfunction (P < 0.05), with anxiety demonstrating the strongest association. Only anxiety was associated with premature ejaculation (P < 0.05). Premature ejaculation was not found to be associated with depression (P > 0.05). Predictive models for psychological burden among infertile men with sexual dysfunction are presented, and we found that there is an association between psychological burden and sexual dysfunction. According to the models, proper counseling and treatment of sexual dysfunction in infertile men may reduce the psychological burden, help attain natural pregnancy, and improve the quality of life.
Adolescent ; Adult ; Anxiety/psychology* ; Cross-Sectional Studies ; Depression/psychology* ; Erectile Dysfunction/psychology* ; Humans ; Infertility, Male/psychology* ; Male ; Quality of Life/psychology* ; Surveys and Questionnaires ; Young Adult

Objective:The mechanism of action of cardiac toxicity of Radix Aconiti Agrestis was explored by establishing the active components-targets network of Radix Aconiti Agrestis, protein interaction network, the biological function and pathway network of targets, and using molecular docking technology. Methods:The Traditional Chinese Medicine Systems Pharmacology(TCMSP) database and the Comparative Toxicogenomics Database(CTD) were used to filtrate the toxic candidates of Radix Aconiti Agrestis. Predicting the functional targets of toxic candidates of Radix Aconiti Agrestis by PharmMapper and compared with the cardiac related gene proteins found in the human gene database (GeneCards), and the overlapping proteins were selected as potential cardiac toxicity targets of Radix Aconiti Agrestis. The Cytoscape software was used to construct the network between toxic candidate components and targets. The protein interaction network was mapped by the String database combined with Cytoscape software. The biological functions of the targets and the involved pathways were analyzed with the DAVID platform.The binding of the key proteins with certain toxic candidate components of Radix Aconiti Agrestis was verified by Discover Studio software finally. Results:There were six candidates for toxic ingredients, which involving 27 cardiac toxicity targets. Network analysis results show that the targets were mainly by participating in the heart of phosphorus metabolism, regulation and other related phosphorus metabolism and regulation of phosphorylation and FKBP1A,TGF4-β₂, INSR targets to have an important impact on the metabolism,development and form of the heart,and further to have cardiac toxicity. Conclusion:Based on the characteristics of the multi-component, multi-target and multi-pathway of traditional Chinese medicine, the mechanism of cardiac toxicity of Radix Aconiti Agrestis was explored and its possible toxicity was predicted, which provided a new idea and method for further research on the mechanism of cardiac toxicity of Radix Aconiti Agrestis.

Objective: To explore the mechanism of renal toxicity of Tripterygii Radix et Rhizoma by establishing the active component-target, protein interaction, biological function and pathway network corresponding to the target, and using molecular docking technology. Method: The traditional Chinese medicine(TCM) systems pharmacology database(TCMSP) and the comparative toxicogenomics database (CTD) were used to screen The toxic candidate compounds.In PubChem database, convert all candidate compounds into standard Canonical SMILES format, SMILES format file import SwissTargetPrediction platform, target prediction, will be the target of the corresponding compounds in TCMSP supplement with uniprot converts protein antipodal gene name, and from the human genome database (GeneCards) seek to compare the renal related gene protein,overlapping proteins were screened as potential renal toxicity targets of Tripterygii Radix et Rhizoma.Cytoscape software was used to construct the candidate components-target network of Tripterygii Radix et Rhizoma.Cytoscape software was combined with String database to draw the protein interaction network, DAVID platform was used to analyze the biological function of the target and the pathways involved, and Glide software was used to verify the combination of the key protein and the candidate components of tripterygiumwildiitoxicity. Result: The screening of 30 kinds of candidates for toxic ingredients of Tripterygii Radix et Rhizoma, involving 209 renal toxicity targets, network analysis results showed that Tripterygii Radix et Rhizoma by amino acid metabolism,phospholipid metabolism, catecholamine metabolism, inhibiting renal organic anion transporter Oatl, Oat2, Oat3 function, and inducing apoptosis, and participate in the mitogen-activated protein kinase(MAPK) signaling pathways, JAK-STAT signaling pathway,vascular endothelial growth factor(VEGF)signaling pathways,Toll-like receptor signaling pathway,ERBB signaling pathway, FcεRI signaling pathway, peroxisome proliferators-activated receptors(PPAR) signaling pathway such as toxic to the kidneys. Conclusion: The mechanism of kidney toxicity of Tripterygii Radix et Rhizoma was explored by using the characteristics of multi-component, multi-target and multi-pathway of TCM, which provided new ideas and methods for further research on the mechanism of kidney toxicity of Tripterygii Radix et Rhizoma.

OBJECTIVE: To observe the dynamic changes of hematopoietic reconstitution and multiple lineages differentiation at early phase after transplantation. METHODS: Whole bone marrow mononuclear cells (wBMMNC, 5×10) and enriched c-Kit hematopoietic stem/progenitor cells (HSPC, 3×10) from the BM of B6-Ly5.1 mice were transplanted into lethally irradiated B6-Ly5.2 mice, the frequencies and absolute numbers of donor-derived cells (including LKS and LKS) were detected by flow cytometry. The multiple lineages differentiation of donor-derived cells was also monitored by flow cytometry. The homing and early phase proliferations of donor-derived cells were observed by two-photon microscope. RESULTS: The donor-derived cells started to proliferation from 5-7 days after transplantation and reached the peak value at 2-3 weeks after wBMMNC transplantation. The donor-derived cells proliferated from 1-2 weeks and maintained until 4 weeks after c-kitHSPC transplantation. At 1 week after transplantation, the donor-derived cells mainly differentiated into myeloid cells with a few lymphoid cells production (B cells) but the production of T cells was not observed at most in wBMMNC transplanted group, while myeloid cells occupied the majority of donor-derived cells at 2-4 weeks; donor-derived cells almost totally differentiated into myeloid cells at 1-3 weeks after transplantation in c-Kit transplanted group and donor-derived B cells appeared at 4 weeks. The absolute number of donor-derived LKS and LKS cells in the BM of c-Kit transplanted group were much higher than that of wBMMNC group (P＜0.001) at 2 weeks respectively. The clustering proliferation of cKit cells at 4-5 days after transplantation was observed by two photon microscope. CONCLUSION The dynamical rate of proliferation and reconstitution of donor-derived cells are much earlier and quicker in c-Kit group than those of wBMMNC group. c-Kit cells mainly differentiate into myeloid cells within 1-3 weeks and the lymphoid cell differentiation starts at 4 weeks after transplantation. The immediate proliferation and differentiation of c-Kit cells within 1 week maybe due to the urgent needs of hematopoietic regeneration under the myeloablated hosts.
Animals ; Bone Marrow Transplantation ; Cell Differentiation ; Cell Proliferation ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Mice ; Mice, Inbred C57BL

The present study analyzed the predictive value of combined analysis of collapsin response mediator protein 4 (CRMP4) methylation levels and the Cancer of the Prostate Risk Assessment (CAPRA-S) Postsurgical score of patients who required adjuvant hormone therapy (AHT) after radical prostatectomy (RP). We retrospectively analyzed 305 patients with prostate cancer (PCa) who received RP and subsequent androgen deprivation therapy (ADT). Two hundred and thirty patients with clinically high-risk PCa underwent immediate ADT, and 75 patients with intermediate risk PCa underwent deferred ADT. CRMP4 methylation levels in biopsies were determined, and CAPRA-S scores were calculated. In the deferred ADT group, the values of the hazard ratios for tumor progression and cancer-specific mortality (CSM) in patients with ≥15% CRMP4 methylation were 6.81 (95% CI: 2.34-19.80) and 12.83 (95% CI: 2.16-26.10), respectively. Receiver-operating characteristic curve analysis indicated that CRMP4 methylation levels ≥15% served as a significant prognostic marker of tumor progression and CSM. In the immediate ADT group, CAPRA-S scores ≥6 and CRMP4 methylation levels ≥15% were independent predictors of these outcomes (uni- and multi-variable Cox regression analyses). The differences in the 5-year progression-free survival between each combination were statistically significant. Combining CAPRA-S score and CRMP4 methylation levels improved the area under the curve compared with the CRMP4 or CAPRA-S model. Therefore, CRMP4 methylation levels ≥15% were significantly associated with a poor prognosis and their combination with CAPRA-S score accurately predicted tumor progression and metastasis for patients requiring AHT after RP.
Aged ; Androgen Antagonists/therapeutic use* ; Biomarkers, Tumor/blood* ; Female ; Hormone Replacement Therapy ; Humans ; Male ; Methylation ; Middle Aged ; Muscle Proteins/metabolism* ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Progression-Free Survival ; Prostatectomy ; Prostatic Neoplasms/metabolism* ; Retrospective Studies ; Risk Assessment ; Treatment Outcome

OBJECTIVETo investigate the dynamic quantitative changes in expression of hepatitis B virus (HBV) surface antigen (HBsAg) that occurs during the natural recovery course and the short-term antivirus treatment period of patients suffering from flares in chronic hepatitis B (CHB).

METHODSCHB patients presenting for treatment of flare-ups were randomly assigned to receive treatment with Entecavir antiviral (group A, n = 39) or to naturally resolve the acute condition (group B, n = 22). All patients MELD scores were calculated and HBsAg levels and HBV DNA loads were measured upon admission (baseline), at worst-condition stage, and end of treatment/flare-up (discharge). Pairwise comparisons of intergroup differences were made to evaluate the change in the three disease parameters over time in response to the management approach.

RESULTSThe levels of HBsAg were not significantly different between the two groups at baseline, worst-condition stage and discharge (group A: (3.68+/-0.45), (3.84+/-0.19) and (3.69+/-0.58) log10 cut-off index (COI) respectively; group B: (3.59+/-0.54), (3.47+/-0.76) and (3.43+/-0.68) log10 COI respectively; all P more than 0.05). However, the HBV DNA loads were significantly lower in group A than in group B at the worst-condition stage and at discharge (all P less than 0.05). In group A, the MELD scores were significantly higher at baseline and at worst-condition stage than at discharge (all P = 0.000), but the difference between baseline and worst-condition stage was not significant. Also in group A, the HBV DNA load showed a gradually decreasing trend over time (baseline more than worst-condition stage more than discharge, all P less than 0.05). No significant differences were observed over time in the HBsAg levels of group A. In group B, the MELD scores were significantly higher at baseline and at worst-condition stage than at discharge (all P = 0.000), but the difference between baseline and worst-condition stage was not significant (P = 0.619). Also in group B, the HBV DNA loads were significantly higher at baseline and worst-condition stage than at discharge (P = 0.000 and P = 0.003 respectively), but the difference between baseline and worst-condition stage was not significant. Finally, no significant differences were observed over time in the HBsAg levels of group B.

CONCLUSIONNatural recovery from an acute flare-up of CHB is not accompanied by a change in HBsAg levels. In addition, short-term antiviral treatment to resolve the flare-up has no influence on HBsAg level.

Adult ; Antiviral Agents ; therapeutic use ; Female ; Guanine ; analogs & derivatives ; therapeutic use ; Hepatitis B Surface Antigens ; blood ; Hepatitis B virus ; drug effects ; physiology ; Hepatitis B, Chronic ; blood ; drug therapy ; Humans ; Male ; Middle Aged ; Viral Load