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

OBJECTIVE: To investigate the effect of 5-hydroxytryptamine (5-HT) on the proliferation, apoptosis and colony-forming unit-megakaryocyte (CFU-MK) of Meg-01 cells and its possible mechanisms. METHODS: The uptake and metabolism of 5-HT in Meg-01 cells were analysed by reverse-phase high-performance liquid chromatography (RP-HPLC) with electrochemical detection. The expression of 5-HT2B receptor (5-HT2BR) in megakaryocytes was detected by immunofluorescence staining. The cell proliferation and viability were measured by MTT and Trypan blue staining after Meg-01 cells were single-cultured or co-cultured with different concentrations of 5-HT/5-HT2BR inhibitor Ketanserin for 48 h. Meg-01 cells were incubated with 5-HT/ Ketanserin for 72 h, then the flow cytometry was used to detect early apoptosis of the cells and the activity of caspase-3. Using CFU-MK assay to investigate the effect of 5-HT on the differentiation of megakaryocytes. RESULTS: 5-HT could be uptaken by Meg-01 cells, and metabolized into 5-hydroxyindoleacetic acid (5-HIAA). The expression of 5-HT2BR on megakaryocytes could be detected after immunofluorescence staining. 5-HT could promote the proliferation of Meg-01 cells at a dose-dependent manner (r =0.82), with the most significant effect observed at a concentration of 200 nmol/L (P < 0.001). Trypan blue staining also indicated that 200 nmol/L 5-HT had the most significant effect on the viability of Meg-01 cells (P < 0.05). The proliferation of Meg-01 cells treated with 5-HT was increased compared with the untreated control (P < 0.001), while the combination of 5-HT with ketanserin downregulated this effect. 5-HT significantly reduced the early apoptosis rate (P < 0.001) and caspase-3 activity (P < 0.05) of Meg-01 cells, while addition of ketanserin significantly increased the early apoptosis rate of Meg-01 cells (P < 0.001) and caspase-3 activity also increased to some extent. 5-HT promoted the formation of CFU-MK in bone marrow cells in a dose-dependent manner (r =0.89). The addition of ketanserin reduced the promoting effect of 5-HT on CFU-MK formation (P < 0.01). CONCLUSION There may be monoamine oxidase present in megakaryocytes, which can metabolize and decompose 5-HT into 5-HIAA. 5-HT may promote the proliferation and differentiation of megakaryocytes through 5-HT2BR. Besides, 5-HT can also reduce the apoptosis of megakaryocytes, and its anti-apoptotic effect may be mediated by 5-HT2BR and caspase-3 pathways.
Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Megakaryocytes/metabolism* ; Serotonin/pharmacology* ; Humans ; Receptor, Serotonin, 5-HT2B/metabolism* ; Caspase 3/metabolism* ; Cell Differentiation

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*

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

ObjectiveTo investigate the analgesic effect and mechanism of dexmedetomidine （DEX） on dynamic allodynia （DA） in mice with trigeminal neuropathic pain. MethodsWe established the model of trigeminal neuropathic pain in male mice by a chronic constriction injury （CCI） of the infraorbital branch of the trigeminal nerve （ION）. Mice were randomly separated into the following groups： Sham， CCI-ION， CCI-ION+vehicle， CCI-ION+DEX， Sham+DEX （each group contained four to six mice）. For the measurement of DA， the ipsilateral and contralateral skin of the whisker pad within the infraorbital territory （V2） or the lower jaw within the mandibular nerve territory （V3） were stimulated by light-moving brush strokes. We used immunofluorescence staining to evaluate the possible mechanisms. ResultsCompare with the sham group， light-moving brush strokes induced obvious DA in ipsilateral and contralateral skin of V2 territory and V3 territory at 3 d or 7 d after CCI-ION surgery （P=0.004 8； P<0.000 1）， and the number of c-Fos （a marker for neuronal excitability） positive cells in bilateral mPFC increased significantly （P=0.044 1 ， P=0.044 4）. In addition， 15 μg/kg and 30 μg/kg DEX separately alleviated bilateral primary and secondary DA induced by light-moving mechanical facial stimuli in mice with trigeminal neuropathic pain （P<0.000 1）， and decreased the excitability of neurons in bilateral mPFC （P=0.012 5， P=0.048 8）. Furthermore， there was no significant difference in analgesic effect between the two concentrations of DEX （P>0.05）. ConclusionsDEX is a useful therapeutic approach for attenuating DA in trigeminal neuropathic pain disorders. This effect is associated with the inhibition of hyperexcitability of neurons in mPFC induced by light-moving mechanical facial stimuli after trigeminal neuropathic pain.

ObjectiveThe aspartate aminotransferase-to-platelet ratio index （APRI） and liver fibrosis-4 index （FIB-4） have been used for noninvasive prediction of liver fibrosis and cirrhosis and both indexes exhibit a high degree of accuracy in the the prediction of the prognosis of hepatocellular carcinoma（HCC）patients after hepatectomy.. This study aims to explore the predictive values of APRI and FIB-4 in the occurrence of posthepatectomy liver failure （PHLF） in HCC patients. MethodsThe clinical data of 426 patients with HCC who underwent hepatectomy in our hospital were retrospectively analyzed. Laboratory data were collected from patients within 2 weeks prior to hepatectomy. APRI， FIB-4 and Child-Pugh scores were calculated. Receiver operating characteristic （ROC） curves were used to determine the AUC values and optimal cut-off values of APRI， FIB-4 and Child-Pugh scores. Univariate and multivariate logistic regression analyses were employed to identify the independent risk factors for PHLF， and the predictive values of APRI and FIB-4 on PHLF were compared. ResultsA total of 48 patients （11.3%） developed PHLF. Multivariate analysis showed that major hepatectomy （≥3 segments resection）， blood loss >400 mL， total bilirubin （TBIL）， platelet （PLT）， fibrinogen （Fib）， APRI and FIB-4 were independent risk factors for PHLF. ROC curve analysis revealed that APRI （AUC = 0.816） and FIB-4 （AUC = 0.728） had better ability to predict PHLF than Child-Pugh score （AUC = 0.566； P<0.001）. ConclusionsPreoperative APRI and FIB-4 are independent predictors of PHLF in HCC patients after hepatectomy and have good predictive values.

ObjectiveThe aspartate aminotransferase-to-platelet ratio index （APRI） and liver fibrosis-4 index （FIB-4） have been used for noninvasive prediction of liver fibrosis and cirrhosis and both indexes exhibit a high degree of accuracy in the the prediction of the prognosis of hepatocellular carcinoma（HCC）patients after hepatectomy.. This study aims to explore the predictive values of APRI and FIB-4 in the occurrence of posthepatectomy liver failure （PHLF） in HCC patients. MethodsThe clinical data of 426 patients with HCC who underwent hepatectomy in our hospital were retrospectively analyzed. Laboratory data were collected from patients within 2 weeks prior to hepatectomy. APRI， FIB-4 and Child-Pugh scores were calculated. Receiver operating characteristic （ROC） curves were used to determine the AUC values and optimal cut-off values of APRI， FIB-4 and Child-Pugh scores. Univariate and multivariate logistic regression analyses were employed to identify the independent risk factors for PHLF， and the predictive values of APRI and FIB-4 on PHLF were compared. ResultsA total of 48 patients （11.3%） developed PHLF. Multivariate analysis showed that major hepatectomy （≥3 segments resection）， blood loss >400 mL， total bilirubin （TBIL）， platelet （PLT）， fibrinogen （Fib）， APRI and FIB-4 were independent risk factors for PHLF. ROC curve analysis revealed that APRI （AUC = 0.816） and FIB-4 （AUC = 0.728） had better ability to predict PHLF than Child-Pugh score （AUC = 0.566； P<0.001）. ConclusionsPreoperative APRI and FIB-4 are independent predictors of PHLF in HCC patients after hepatectomy and have good predictive values.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease, affecting about 0.6% of the Chinese population. Many patients are not well controlled by conventional treatments, thus there is need for new treatment regimens. In this study, we assessed the efficacy and safety of secukinumab in Chinese patients with moderate to severe plaque psoriasis. METHODS: This study was a 52-week, multicentre, randomized, double-blind, placebo-controlled, parallel-group, Phase 3 trial. A sub-population of study participants (≥18 years) of Chinese ethnicity were randomized to receive subcutaneous injections of 300 or 150 mg secukinumab, or placebo. The co-primary endpoints were psoriasis area severity index (PASI) 75 and Investigator's Global Assessment (IGA) 0/1 at Week 12. RESULTS: A total of 441 Chinese patients were enrolled in this study. Co-primary outcomes were achieved; 300 and 150 mg secukinumab were superior to placebo as shown in the proportion of patients that achieved PASI 75 (97.7% and 87.2% vs. 3.7%, respectively; P < 0.001), and IGA 0/1 (82.3% and 69.7% vs. 2.7%; P < 0.001) at Week 12. Treatment efficacy was maintained until Week 52. There was no increase in overall adverse events with secukinumab relative to placebo throughout the 52-week period. CONCLUSION: Secukinumab is highly effective and well tolerated in Chinese patients with moderate to severe plaque psoriasis. TRIAL REGISTRATION ClinicalTrials.gov, NCT03066609; https://clinicaltrials.gov/ct2/show/record/NCT03066609.
Antibodies, Monoclonal/therapeutic use* ; Antibodies, Monoclonal, Humanized ; China ; Double-Blind Method ; Humans ; Psoriasis/drug therapy* ; Severity of Illness Index ; Treatment Outcome

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

Multiple measurements of nocturnal penile tumescence and rigidity (NPTR) are widely accepted as a method to differentiate psychogenic erectile dysfunction (ED) from organic ED. However, direct evidence remains limited regarding the first-night effect on NPTR measurement using the RigiScan. Here, we evaluated the first-night effect on the results of NPTR measurement to validate the necessity of NPTR measurement for two consecutive nights, particularly when abnormal first-night measurements are recorded in a laboratory setting. We retrospectively reviewed 105 patients with a complaint of ED, who underwent NPTR measurement using the RigiScan in the Department of Infertility and Sexual Medicine, the Third Affiliated Hospital of Sun Yat-sen University (Guangzhou, China), for two consecutive nights, during the period from November 2015 to May 2016. NPTR parameters were collected and analyzed. We found that more effective nocturnal erections were detected during the second night than during the first night (P <0.001). Twenty percent of all patients had no effective erection during the first night, but exhibited at least one effective erection during the second night. The negative predictive value of NPTR measurement during the first night was 43.2%; this was significantly lower than that on the second night (84.2%; P = 0.003). Most NPTR parameters were better on the second night than on the first night. The first-night effect might be greater among patients younger than 40 years of age. In conclusion, two consecutive nightly measurements of NPTR can avoid a false-abnormal result caused by the first-night effect; moreover, these measurements more accurately reflect erectile capacity, especially when the first-night record is abnormal in a laboratory setting.
Adult ; Diagnosis, Differential ; Diagnostic Techniques, Urological ; Erectile Dysfunction/etiology* ; Humans ; Male ; Penile Erection ; Predictive Value of Tests ; Reproducibility of Results ; Retrospective Studies ; Sexual Dysfunction, Physiological/diagnosis* ; Sexual Dysfunctions, Psychological/diagnosis* ; Sleep ; Young Adult