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*

Alzheimer's disease (AD) is a neurodegenerative disease with clinical hallmarks of progressive cognitive impairment. Synergistic effects of the Aβ-Tau cascade reaction are tightly implicated in AD pathology, and microglial NLRP3 inflammasome activation drives neuronal tauopathy. However, the underlying mechanism of how Aβ mediates NLRP3 inflammasome remains unclear. Herein, we determined that oligomeric Aβ (o-Aβ) bound to microglial Kv2.1 and promoted Kv2.1-dependent potassium efflux to activate NLRP3 inflammasome resulting in neuronal tauopathy by using Kv2.1 inhibitor drofenine (Dfe) as a probe. The underlying mechanism has been intensively investigated by assays with Kv2.1 knockdown in vitro (si-Kv2.1) and in vivo (AAV-ePHP-si-Kv2.1). Dfe deprived o-Aβ of its capability to promote microglial NLRP3 inflammasome activation and neuronal Tau hyperphosphorylation by inhibiting the Kv2.1/JNK/NF-κB pathway while improving the cognitive impairment of 5×FAD-AD model mice. Our results have highly addressed that the Kv2.1 channel is required for o-Aβ-driven microglial NLRP3 inflammasome activation and neuronal tauopathy in AD model mice and highlighted that Dfe as a Kv2.1 inhibitor shows potential in the treatment of AD.

Objective:To investigate the efficacy of two types of micro-focused ultrasound devices combined with botulinum toxin type A (BoNT-A) injection for facial rejuvenation.Methods:A retrospective study was conducted, including 60 female patients aged 28-70 (41.3±7.9) years, who received facial rejuvenation treatment at the Department of Plastic and Reconstructive Surgery, Zhongnan Hospital of Wuhan University, from April 2023 to April 2024. Patients were divided into two groups based on the treatment method: the control group (received only micro-focused ultrasound treatment, n=30) and the combined group (received both micro-focused ultrasound and BoNT-A injection, n=30). Additionally, patients were further categorized into four subgroups based on the type of micro-focused ultrasound device used: Peninsula Microultra? (PM) device group ( n=15), Intelligent Ultrasound? (IU) device group ( n=15), PM device + BoNT-A injection group ( n=15), and IU device + BoNT-A injection group ( n=15). The severity of facial wrinkles was assessed using the wrinkle severity rating scale (WSRS), the Merz aesthetic scale (MAS), and the global aesthetic improvement scale (GAIS) at baseline and 6 months post-treatment. Adverse event rates were also recorded. Results:At 6 months post-treatment, the combined group showed significantly lower WSRS and MAS scores than the control group (both P<0.001). No significant differences were found between the PM and IU device groups, or between the PM + BoNT-A and IU + BoNT-A groups regarding WSRS and MAS scores (all P>0.05). Self-reported GAIS improvement was 56.7% (17/30) for the control group and 80.0% (24/30) for the combined group, with the combined group showing superior results ( P=0.015). The physician-assessed GAIS improvement was 70.0% (21/30) for the control group and 96.7% (29/30) for the combined group, again with the combined group showing superior results ( P=0.007). No significant differences were found in self-reported or physician-assessed GAIS improvement between the PM and IU device groups, or between the PM + BoNT-A and IU + BoNT-A groups (all P>0.05). No severe adverse reactions, such as blisters, scabbing, purpura, bruising, scarring, peripheral facial paralysis, allergies, muscle weakness, dysphagia, or dysphonia, were observed in any patient. Conclusion:The combination of micro-focused ultrasound and BoNT-A injection for facial rejuvenation is more effective than micro-focused ultrasound alone, while there are no significant differences in efficacy between the two micro-focused ultrasound devices.

Objective To investigate the research hotspot and development trend of noise-induced hearing loss(NIHL)in the past 30 years.Methods The CNKI(China national knowledge infrastructure)database,Wanfang Medical network and VIP database.NoteExpress were used for literature screening.CiteSpace 6.1.R6 software were used for bibliometric analysis and data visualization.Results A total of 3 823 articles were included for analy-sis.The top 3 keywords were:"noise","hearing loss",and"noise-induced deafness".A total of 358 literatures were published on the pathogenesis of NIHL.The pathogenesis included oxidative stress,genetic susceptibility,mechanical damage,microcirculation disturbance,calcium overload,etc.Conclusion The number of papers pub-lished in the field of NIHL has increased year by year,and the overall development can be divided into three stages:exploration of the influence of noise,research on etiology,and prevention and assessment of occupational noise-in-duced hearing loss.In terms of pathogenesis,the oxidative stress mechanism has been widely recognized by schol-ars,and genetic susceptibility has become a research hotspot.

Objective To investigate the research hotspot and development trend of noise-induced hearing loss(NIHL)in the past 30 years.Methods The CNKI(China national knowledge infrastructure)database,Wanfang Medical network and VIP database.NoteExpress were used for literature screening.CiteSpace 6.1.R6 software were used for bibliometric analysis and data visualization.Results A total of 3 823 articles were included for analy-sis.The top 3 keywords were:"noise","hearing loss",and"noise-induced deafness".A total of 358 literatures were published on the pathogenesis of NIHL.The pathogenesis included oxidative stress,genetic susceptibility,mechanical damage,microcirculation disturbance,calcium overload,etc.Conclusion The number of papers pub-lished in the field of NIHL has increased year by year,and the overall development can be divided into three stages:exploration of the influence of noise,research on etiology,and prevention and assessment of occupational noise-in-duced hearing loss.In terms of pathogenesis,the oxidative stress mechanism has been widely recognized by schol-ars,and genetic susceptibility has become a research hotspot.

Objective:To investigate the efficacy of two types of micro-focused ultrasound devices combined with botulinum toxin type A (BoNT-A) injection for facial rejuvenation.Methods:A retrospective study was conducted, including 60 female patients aged 28-70 (41.3±7.9) years, who received facial rejuvenation treatment at the Department of Plastic and Reconstructive Surgery, Zhongnan Hospital of Wuhan University, from April 2023 to April 2024. Patients were divided into two groups based on the treatment method: the control group (received only micro-focused ultrasound treatment, n=30) and the combined group (received both micro-focused ultrasound and BoNT-A injection, n=30). Additionally, patients were further categorized into four subgroups based on the type of micro-focused ultrasound device used: Peninsula Microultra? (PM) device group ( n=15), Intelligent Ultrasound? (IU) device group ( n=15), PM device + BoNT-A injection group ( n=15), and IU device + BoNT-A injection group ( n=15). The severity of facial wrinkles was assessed using the wrinkle severity rating scale (WSRS), the Merz aesthetic scale (MAS), and the global aesthetic improvement scale (GAIS) at baseline and 6 months post-treatment. Adverse event rates were also recorded. Results:At 6 months post-treatment, the combined group showed significantly lower WSRS and MAS scores than the control group (both P<0.001). No significant differences were found between the PM and IU device groups, or between the PM + BoNT-A and IU + BoNT-A groups regarding WSRS and MAS scores (all P>0.05). Self-reported GAIS improvement was 56.7% (17/30) for the control group and 80.0% (24/30) for the combined group, with the combined group showing superior results ( P=0.015). The physician-assessed GAIS improvement was 70.0% (21/30) for the control group and 96.7% (29/30) for the combined group, again with the combined group showing superior results ( P=0.007). No significant differences were found in self-reported or physician-assessed GAIS improvement between the PM and IU device groups, or between the PM + BoNT-A and IU + BoNT-A groups (all P>0.05). No severe adverse reactions, such as blisters, scabbing, purpura, bruising, scarring, peripheral facial paralysis, allergies, muscle weakness, dysphagia, or dysphonia, were observed in any patient. Conclusion:The combination of micro-focused ultrasound and BoNT-A injection for facial rejuvenation is more effective than micro-focused ultrasound alone, while there are no significant differences in efficacy between the two micro-focused ultrasound devices.

OBJECTIVE Alzheimer disease(AD)is a neurodegenerative disease with clinical hallmarks of pro-gressive cognitive impairment.Synergistic effects of Aβ-tau cascade reaction are tightly implicated in AD patholo-gy,and microglial NLRP3 inflammasome activation drives neuronal tauopathy through microglia and neurons cross-talk.However,the underlying mechanism of how Aβ medi-ates NLRP3 inflammasome remains unclear.Shab related potassium channel member 1(Kv2.1)as a voltage gated po-tassium channel widely distributed in the central nervous system and plays an important role in regulating the out-ward potassium flow in neurons and glial cells.In current work,we aimed to explore the underlying mechanism of Kv2.1 in regulating Aβ/NLRP3 inflammasome/tau axis by using a determined Kv2.1 inhibitor drofenine(Dfe).METHODS Cell-based assays including Western blot-ting and immunofluorescence staining against primary microglia or neurons were carried out to expound the role of Kv2.1 channel in NLRP3 inflammasome activa-tion and subsequent neuronal tau hyperphosphorylation.For animal studies,new object recognition,Y-maze and Morris water maze were performed to evaluate the ame-lioration of Kv2.1 inhibition through either Kv2.1 inhibitor Dfe treatment or adeno-associated virus AAV-ePHP-si-Kv2.1injectionon5×FADADmodel mice.Assays of histol-ogy and immunostaining of tissue sections and Western blotting of brain tissues were performed to verify the con-clusion of cellular assays.RESULTS We reported that oligomeric Aβ(o-Aβ)bound to microglial Kv2.1 and pro-moted Kv2.1-dependent potassium leakage to activate NLRP3 inflammasome through JNK/NF-κB pathway sub-sequently resulting in neuronal tauopathy.Treatment of either Kv2.1 inhibitor Dfe or AAV-ePHP-si-Kv2.1 for brain-specific Kv2.1 knockdown deprived o-A β of its capability in inducing microglial NLRP3 inflammasome activation and neuronal tau hyperphosphorylation,while improved the cognitive impairment of 5×FAD AD model mice.CONCLUSION Our results have highly addressed that Kv2.1 channel is required for o-Aβ driving NLRP3 inflammasome activation and neuronal tauopathy in AD model mice and highlighted that Kv2.1 inhibition is a prom-ising therapeutical strategy for AD and Dfe as a Kv2.1 inhibitor shows potential in the treatment of this disease.

Objectives : To investigate the expression and clinical significance of TRIM32 in Cutaneous Malignant Melanoma patients. Methods : Real⁃time PCR was used to detect the expression of TRIM32 in human melanoma cell lines (A375 , MV3) and human normal skin cell lines (HACAT) . Clinical characteristics of 31 CMM patients were collected. The expression of TRIM32 in the CMM tissues and para⁃cancerous tissues was detected by immunohistochemistry (IHC) . The correlation between TRIM32 expression and clinical characteristics was analyzed. Kaplan⁃Meier survival analysis and Cox univariate analysis model were used to analyze the prognostic factors. Results: The expression of TRIM32 mRNA in A375 melanoma cells was significantly higher than that in HACAT normal skin cells (P < 0. 001) ,while the expression in MV3 cells was comparable to that in HACAT cells. The expression of TRIM32 protein in the CMM tissues , detected by IHC , was significantly higher than that in the para⁃cancerous tissues (P < 0. 001) and positively correlated with Breslow thickness( r = 0. 771 , P < 0. 001) and Clark grade ( r =0. 635 ,P < 0. 001) , but not with sex , ulcer, age and primary location of tumor ( P > 0. 05) . Also , TRIM32 expression level was significantly correlated with prognosis of CMM. Conclusion TRIM32 is highly expressed in A375 melanoma cells and CMM tissues. TRIM32 may be helpful for the prognosis of CMM patients.

AIM: To examine the effects of three commonly used general anesthetics on the proliferation and activation of glial cells in neonatal rats. METHODS: Neonatal rats were exposed to either isoflurane, sevoflurane or desflurane for 2 h on postnatal day 2 (P2). The animals were euthanatihed and the brain were harvested on P7 and P14, respectively. The immunohistochemical localihation of glial markers (vimentin, GFAP, Iba1) were examined. RESULTS: Activation of astrocyte in granular layer and molecular layer of dentate gyrus of hippocampus was significantly enhanced on P7 and P14 after desflurane exposure, while that in isoflurane group the change was only significantly different on P14. The activation of microglia in the granular layer of dentate gyrus but not in the pyramidal cell layer of CA1 region was significantly enhanced in the desflurane group on P7 and P14, while the isoflurane group only showed significant difference on P14. CONCLUSION: Short time exposure of different inhalation anesthetics has different effects on the activation of glial cells in different subregions of hippocampus in neonatal rats on postnatal day 2, and sevoflurane may have the least effect on it.

Objective: To investigate the risk factors affecting the occurrence of complications in patients with vaginal bleeding after in vitro fertilization/intracytoplasmic sperm injection embryo transfer(IVF/ICSI-ET) and the construction of nomogram prediction model. Methods: A total of 272 patients with threatened abortion after IVF/ICSI-ET were retrospectively analyzed in this study. They were divided into the live birth group and abortion group according to the final outcome of pregnancy. Patient characteristics were evaluated using the chi-square test, independent-samples Student's t-test or Wilcoxon rank sum test. A nomogram was created to predict the pregnancy outcome of women with threatened abortion who received IVF/ICSI using multivariate logistic regression coefficients. Results: There was no significant difference in the basic data, percentage of frozen embryos, treatment method, number of embryos transferred, high-quality embryo rate, and embryo implantation rate of the live birth group and abortion group(P>0.05). There were significant differences in body mass index, the onset of vaginal bleeding time after transplantation, serum levels of hCG and progesterone on 14 th day after embryo-transfer, and the number of gestational sacs between the two groups(P<0.05). After multivariate logistic regression analysis, the onset of vaginal bleeding time after transplantation and serum hCG levels on 14 th day after transfer were statistically significant(P<0.05). The nomogram was established based on the above indicators, with an area under the curve of 0.710 for the nomogram. The area under the ROC curve of our nomogram was better than the area under the ROC curve of a single risk factor(AUC of bleeding time after embryo-transfer: 0.644, AUC of serum hCG14:0.625). Conclusion The nomogram model established based on the onset of vaginal bleeding time after embryo-transfer and serum hCG value on 14 th day after embryo-transfer can better predict pregnancy outcome of patients with threatened abortion after IVF/ICSI-ET.