Background Environmental metal exposure is closely associated with the onset and progression of mild cognitive impairment (MCI) in the elderly. Effectively identifying hazardous metal exposure and assessing their interaction effects have significant public health implications. Objective To explore the relationship between urinary single metal and metal mixture exposure and MCI in elderly compound residents. Methods This study included 391 elderly individuals aged 60 and above from residential compounds in Zhongshan City, Guangdong Province. Concentrations of iron (Fe), copper (Cu), selenium (Se), arsenic (As), cadmium (Cd), manganese (Mn), chromium (Cr), nickel (Ni), vanadium (V), cobalt (Co), antimony (Sb), thallium (Tl), zinc (Zn), calcium (Ca), and magnesium (Mg) in urine were measured using inductively coupled plasma mass spectrometry. Cognitive function in the elderly was assessed using the Chinese version of the Mini-Mental State Examination (MMSE). Logistic regression was used to explore the relationship between single metal exposure level and MCI. LASSO regression and multi-metal logistic regression models were used to identify key metal ions associated with MCI. Bayesian kernel machine regression (BKMR) was employed to analyze the relationship between key metal ion mixtures and MCI, as well as the interactions between metals. Age, gender, education level, occupation, and body mass index were adjusted as covariates. Results A total of 78 among the 391 elderly individuals surveyed (19.94%) were diagnosed with MCI (MCI group), and the other 313 individuals were controls. The levels of Se, Cd, Mn, and As in the urine of the MCI group were significantly higher than those in the control group (P < 0.05). In the single-metal model, after adjusting for covariates and using the first quartile (Q₁) of each metal concentration as the reference, the OR for MCI in the elderly in the Q₄ group of Se was 2.190 (95%CI: 1.017, 4.716); for Cd, the OR was 2.345 (95%CI: 1.041, 5.283) in the Q₃ group and 2.371 (95%CI: 1.043, 5.393) in the Q₄ group; for Mn, the OR was 2.355 (95%CI: 1.038, 5.344) in the Q₂ group; for As, the OR was 3.377 (95%CI: 1.442, 7.908) in the Q₃ group and 2.886 (95%CI: 1.227, 6.788) in the Q₄ group; for Sb, the OR was 2.779 (95%CI: 1.234, 6.257) in the Q₂ group. When urinary metal concentrations were ln-transformed and included as continuous variables in the single-metal model, Cd concentration was positively correlated with MCI (OR=1.377; 95%CI: 1.008, 1.882; P=0.044). Cd, Se, Mg, Ca, Mn, As, Cr, Co, Tl, and Sb were selected by the LASSO regression model and included in the multi-metal model. In the multi-metal model, compared with Q₁, the OR for MCI in the elderly was 0.395 (95%CI: 0.164, 0.953) in the Q₂ group of Co and 0.390(95%CI: 0.167，0.911) in the Q₃ group of Co; for Mn, the OR in the Q₂ group was 2.636 (95%CI: 1.053, 6.596); for Sb, the OR in the Q₂ group was 2.640 (95%CI: 1.047, 6.658). As continuous variables, Mg (OR=0.472; 95%CI: 0.248, 0.899; P=0.022) and Co (OR=0.857; 95%CI: 0.737, 0.996; P=0.044) concentrations were negatively correlated with MCI. The BKMR mixture analysis suggested that Mg and Co exhibited a synergistic negative correlation with MCI, while Mn and Sb exhibited a synergistic positive correlation with MCI. Mg and Co attenuated the positive correlation of Mn and Sb with MCI, whereas Mn weakened the protective effects of Mg and Co. Conclusion Elevated levels of Se, Cd, As, Mn, and Sb in urine may increase the risk of MCI in the elderly, while Mg and Co have protective effects. Potential synergistic or antagonistic interactions may be found among Mn, Sb, Mg, and Co, which should not be overlooked in terms of their impact on the cognitive function of the elderly.

BackgroundDementia seriously affects the quality of life and lifespan of elderly people， with Alzheimer's disease （AD） being the most common type of dementia. Previous studies have suggested that gout may reduce the risk of developing AD， but the causal relationship between the two still requires further research. ObjectiveTo investigate the potential causal relationship between gout and AD through a two-sample Mendelian randomization （MR） analysis， so as to provide references for the prevention and treatment of AD. MethodsData from Genome-Wide Association Studies （GWAS） extracted in 2024 were analyzed， using pooled data on gout （6 810 cases in the case group and 477 788 cases in the control group） published by UK Biobank in 2021 as the exposure variable， and data on AD （3 899 cases in the case group and 214 893 cases in the control group） published by FinnGen in the same year as the outcome variable. The inverse-variance weighted， MR-Egger regression， weighted median estimation， simple model and weighted model were used to analyze the potential causal relationship between gout and AD. Pleiotropic effects were assessed using MR-Egger regression. Heterogeneity assessment was conducted using Cochran's Q test. The leave-one-out analysis was carried out for sensitivity analysis. And a funnel plot was drawn to detect potential publication bias. ResultsThe inverse-variance weighted analysis demonstrated a negative causal relationship between gout and AD （OR=0.004， 95% CI： 0~0.700， P<0.05）. The plot resembled a symmetrical inversed funnel， indicating the absence of publication bias. No heterogeneity was detected by Cochran's Q test. The MR-Egger regression indicated no significant horizontal pleiotropy. Concerning the reverse directions， no significant associations between AD and gout were noted. ConclusionThere is a negative causal relationship between gout and AD， with gout potentially reducing the risk of developing AD. ［Funded by The Third Batch of Social Welfare and Basic Research Projects （Medical and Health） of Zhongshan City in 2022 （number， 2022B3017）］

Objective To investigate the effect of miR-206 on LPS-induced apoptosis and inflamma-tory response in H9c2 cardiomyocytes.Methods An inflammatory injury model was established in H9c2 cells with treatment of 10 μg/ml LPS.Then the cells were divided into control group,LPS group,LPS1 group(LPS+anti-negative control),LPS2 group(LPS+anti-miR-206),LPS3 group(LPS+miR-206 negative control),and LPS4 group(LPS+miR-206 mimic).The LPS1,LPS2,LPS3,and LPS4 groups(n=3)were transfected with anti-negative control,anti-miR-206 se-quence,miR-negative control,or miR-206 mimic sequence,using Lipofectamine 3000 reagent.CCK-8 and EdU assays were used to detect cell proliferation,Caspase-Glo 3/7 activity kit was em-ployed to measure Caspase-3/7 activity,and ELISA was utilized to test the secretion of inflamma-tory cytokines,TNF-α,IL-1β,and IL-6 in the cells.Results Compared with the control group,the LPS group had significantly reduced cell survival rate and EDU-positive cell rate,while elevated miR-206 expression,Bax/Bcl-2,activated Caspase-3,Caspase-3/7,TNF-α,IL-1β,IL-6,p-p38 and p-p65(P＜0.05,P＜0.01).The expression of miR-206,Bax/Bcl-2,activated Caspase-3,Caspase-3/7,TNF-α,IL-1β,IL-6,p-p38 and p-p65 were obviously reduced,while the cell survival rate and EDU-positive cell rate were notably increased in the LPS 2 group than the LPS group(P＜0.05).In the LPS 4 group,the activity of Caspase-3/7 was remarkably stronger than the LPS group(1586±58 vs 816±51,P＜0.05).Conclusion Suppression of miR-206 can effectively inhibit LPS-induced apoptosis and inflammatory response in H9c2 cardiomyocytes.

Objective:To evaluate the efficacy of bevacizumab in reducing dyspnea, avoiding tracheostomy, and assessing the overall safety and effectiveness of the treatment in patients with juvenile-onset recurrent respiratory papillomatosis (JORRP).Methods:This study included 19 patients with JORRP treated with Bevacizumab at the Department of Otolaryngology-Head and Neck Surgery, BenQ Medical Center, from March 2022 to June 2024. The age of patients ranged from 1.0 to 27.0 years (10.47±8.45 years), with age at onset ranging from 0.5 to 15.0 years (3.66±3.70 years). The cohort included 11 males and 8 females. Bevacizumab was administered intravenously at a dose of 10 mg/kg every three weeks for three sessions. Efficacy was evaluated by comparing the standardized lesion volume pre-and post-treatment, with statistical analysis performed using R software (4.3.1).Results:Among the 19 patients, 11 presented with dyspnea before treatment. All patients experienced varying degrees of dyspnea relief within 72 hours following the initial treatment, and only one patient had mild dyspnea by the second treatment session three weeks later. The average reduction rates at 24 and 48 hours post-initia treatment were 25.75% and 47.16%, respectively. Following three treatment cycles, the average cumulative reduction rate was 67.47%, significantly higher than after the first treatment ( Z=3.38, P=0.002). Throughout the treatment period, no adverse events that of grade 2 or higher were noted. Conclusions:Bevacizumab can rapidly alleviate dyspnea symptoms and significantly reduce lesion volume in JORRP patients, exhibiting satisfactory overall safety and effectiveness. However additional large-scale prospective studies are warranted to validate its long-term safety and efficacy.

This study aims to investigate the epidemic variation of porcine circovirus type2(PCV2)and its distribution in swine farms in Henan Province from 2022 to 2023.In this study,1 206 pig blood samples from 18 urban scale swine farms,and 318 pigs and environmental samples from 2 PCV2-positive swine farms in Henan Province were detected by fluorescence quantitative PCR.ORF2 gene sequencing and genetic evolution analysis were performed on the positive samples.The results showed that the positive rate of PCV2 was 7.05％(85/1 206)in Henan Province,11.15％in western Henan Province and 3.03％in southern Henan Province.The positive rate of PCV2 in spring was 11.60％(67/576).A total of 31 ORF2 gene sequences were obtained,of which 23 were PCV2d(74.19％),6 were PCV2a(19.35％),one was PCV2b(3.23％)and one was PCV2c(3.23％).The results of amino acid sequence comparison showed that the mutation sites mainly concentrated on amino acids at positions 40-68 and 180-209.The total positive rate of pig farm sam-ples was 37.42％(119/318),and the positive rate of pig samples from different types of pig houses was 60.71％(34/56),45.83％(11/24),35.09％(20/57),and 33.33(3/9)in order from high to low.The positive rate of environmental samples from high to low was 56.36％(31/55)in feeding system,46.67％(7/15)in feces system,12.50(1/8)in decontamination area,11.11％(2/18)in living area,and no PCV2 was detected in ventilation system.The highest positive rate was 45.00％(9/20)for the tools in the house,7.14％(1/14)for the surface and sole of the clothes after leaving the house,and no PCV2 was detected on the surface and sole of the clothes before entering the house.In this study,the epidemiological investigation of PCV2 in Henan Province and its distribu-tion in swine farms were carried out,and the main circulating strains,seasons,regions and gene mutations of PCV2 in H enan Province were identified.The distribution and transmission routes of PCV2 in positive pig farms were preliminarily analyzed and summarized,which provided data basis and reference for effective prevention and control of PCV and the establishment of accurate bio-safety prevention and control measures.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

This study aims to investigate the epidemic variation of porcine circovirus type2(PCV2)and its distribution in swine farms in Henan Province from 2022 to 2023.In this study,1 206 pig blood samples from 18 urban scale swine farms,and 318 pigs and environmental samples from 2 PCV2-positive swine farms in Henan Province were detected by fluorescence quantitative PCR.ORF2 gene sequencing and genetic evolution analysis were performed on the positive samples.The results showed that the positive rate of PCV2 was 7.05％(85/1 206)in Henan Province,11.15％in western Henan Province and 3.03％in southern Henan Province.The positive rate of PCV2 in spring was 11.60％(67/576).A total of 31 ORF2 gene sequences were obtained,of which 23 were PCV2d(74.19％),6 were PCV2a(19.35％),one was PCV2b(3.23％)and one was PCV2c(3.23％).The results of amino acid sequence comparison showed that the mutation sites mainly concentrated on amino acids at positions 40-68 and 180-209.The total positive rate of pig farm sam-ples was 37.42％(119/318),and the positive rate of pig samples from different types of pig houses was 60.71％(34/56),45.83％(11/24),35.09％(20/57),and 33.33(3/9)in order from high to low.The positive rate of environmental samples from high to low was 56.36％(31/55)in feeding system,46.67％(7/15)in feces system,12.50(1/8)in decontamination area,11.11％(2/18)in living area,and no PCV2 was detected in ventilation system.The highest positive rate was 45.00％(9/20)for the tools in the house,7.14％(1/14)for the surface and sole of the clothes after leaving the house,and no PCV2 was detected on the surface and sole of the clothes before entering the house.In this study,the epidemiological investigation of PCV2 in Henan Province and its distribu-tion in swine farms were carried out,and the main circulating strains,seasons,regions and gene mutations of PCV2 in H enan Province were identified.The distribution and transmission routes of PCV2 in positive pig farms were preliminarily analyzed and summarized,which provided data basis and reference for effective prevention and control of PCV and the establishment of accurate bio-safety prevention and control measures.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Objective To investigate the effect of miR-206 on LPS-induced apoptosis and inflamma-tory response in H9c2 cardiomyocytes.Methods An inflammatory injury model was established in H9c2 cells with treatment of 10 μg/ml LPS.Then the cells were divided into control group,LPS group,LPS1 group(LPS+anti-negative control),LPS2 group(LPS+anti-miR-206),LPS3 group(LPS+miR-206 negative control),and LPS4 group(LPS+miR-206 mimic).The LPS1,LPS2,LPS3,and LPS4 groups(n=3)were transfected with anti-negative control,anti-miR-206 se-quence,miR-negative control,or miR-206 mimic sequence,using Lipofectamine 3000 reagent.CCK-8 and EdU assays were used to detect cell proliferation,Caspase-Glo 3/7 activity kit was em-ployed to measure Caspase-3/7 activity,and ELISA was utilized to test the secretion of inflamma-tory cytokines,TNF-α,IL-1β,and IL-6 in the cells.Results Compared with the control group,the LPS group had significantly reduced cell survival rate and EDU-positive cell rate,while elevated miR-206 expression,Bax/Bcl-2,activated Caspase-3,Caspase-3/7,TNF-α,IL-1β,IL-6,p-p38 and p-p65(P＜0.05,P＜0.01).The expression of miR-206,Bax/Bcl-2,activated Caspase-3,Caspase-3/7,TNF-α,IL-1β,IL-6,p-p38 and p-p65 were obviously reduced,while the cell survival rate and EDU-positive cell rate were notably increased in the LPS 2 group than the LPS group(P＜0.05).In the LPS 4 group,the activity of Caspase-3/7 was remarkably stronger than the LPS group(1586±58 vs 816±51,P＜0.05).Conclusion Suppression of miR-206 can effectively inhibit LPS-induced apoptosis and inflammatory response in H9c2 cardiomyocytes.

Objective:To evaluate the efficacy of bevacizumab in reducing dyspnea, avoiding tracheostomy, and assessing the overall safety and effectiveness of the treatment in patients with juvenile-onset recurrent respiratory papillomatosis (JORRP).Methods:This study included 19 patients with JORRP treated with Bevacizumab at the Department of Otolaryngology-Head and Neck Surgery, BenQ Medical Center, from March 2022 to June 2024. The age of patients ranged from 1.0 to 27.0 years (10.47±8.45 years), with age at onset ranging from 0.5 to 15.0 years (3.66±3.70 years). The cohort included 11 males and 8 females. Bevacizumab was administered intravenously at a dose of 10 mg/kg every three weeks for three sessions. Efficacy was evaluated by comparing the standardized lesion volume pre-and post-treatment, with statistical analysis performed using R software (4.3.1).Results:Among the 19 patients, 11 presented with dyspnea before treatment. All patients experienced varying degrees of dyspnea relief within 72 hours following the initial treatment, and only one patient had mild dyspnea by the second treatment session three weeks later. The average reduction rates at 24 and 48 hours post-initia treatment were 25.75% and 47.16%, respectively. Following three treatment cycles, the average cumulative reduction rate was 67.47%, significantly higher than after the first treatment ( Z=3.38, P=0.002). Throughout the treatment period, no adverse events that of grade 2 or higher were noted. Conclusions:Bevacizumab can rapidly alleviate dyspnea symptoms and significantly reduce lesion volume in JORRP patients, exhibiting satisfactory overall safety and effectiveness. However additional large-scale prospective studies are warranted to validate its long-term safety and efficacy.