Objective : To investigate the effects of branched-chain amino acid(BCAA) on the differentiation of 3T3-L1 preadipocytes and its potential mechanism. Methods : 3T3-L1 preadipocytes were divided into the Control, differentiation medium(DM), low-concentration BCAA, and high-concentration BCAA groups. A CCK-8 assay was utilized to evaluate pre-adipocyte survival under various BCAA concentrations. Oil-red O staining was used to observe the formation of lipid droplets in adipocytes. Intracellular triglyceride(TG) and total cholesterol(TC) were detected by enzymatic method. RT-qPCR and Western blot were used to detect the mRNA and protein expression of Stat3 and adipocyte differentiation-related genes. Results : CCK-8 results showed that the viability of 3T3-L1 cells was not affected when the BCAA concentration was ≤ 10 mmol/L. Compared with the DM group, the low-concentration BCAA groups(0.5 and 1.0 mmol/L) had significantly larger intracellular lipid droplets, increased number of lipid droplets, and elevated levels of the intracellular TC(0.88vs0.68 mmol/g; 0.83vs0.68 mmol/g,P<0.01) and TG(0.77vs0.40 mmol/g; 0.62vs0.40 mmol/g,P<0.01). Nevertheless, the cell differentiation in the high-concentration group(5.0 and 10.0 mmol/L) significantly decreased compared with that in the DM group. Further, levels of PPARγ, C/EBPα, Adiponectin, and FABP4 mRNA and protein expression significantly increased in the low-concentration group, but significantly decreased in the high-concentration group than that in the DM group(P<0.01). In addition, low concentrations of BCAA promoted stat3 phosphorylation, while high concentrations inhibited its phosphorylation(P<0.01). Conclusion BCAA have a dual role in regulating the differentiation of preadipocytes through Stat3, i.e. low concentrations of BCAA induce cell differentiation by promoting Stat3 phosphorylation; whereas high concentrations of BCAA inhibit Stat3 phosphorylation and cell differentiation.

Objective:To understand the current status of epidemiological investigation task force construction and the performance of infectious disease epidemic response in county (district) Centers for Disease Control and Prevention (CDCs) in China, analyze the influencing factors and provide scientific evidence to improve the construction of grassroot epidemiological investigation task force.Methods:A survey was conducted in epidemiological investigation staff in county (district) CDCs in 31 provinces (autonomous regions/municipalities) and Xinjiang Production and Construction Corps in China. A self-designed questionnaire was used to collect information based on the epidemiological dynamic data collection platform of China CDC. A descriptive epidemiological analysis was conducted, and multiple linear regression models were used to identify the factors associated with the performance of infectious disease epidemic response.Results:A total of 24 934 epidemiological investigation task force members from 2 897 county (district) CDCs were surveyed in the study. In the epidemiological investigation task force, women, those with bachelor's degree and public health workers accounted for 62.46%, 71.36%, and 49.05% respectively. Up to 91.72% of the task force members had participated in field epidemic response. The average score of awareness of epidemic investigation procedures was 60.00, while the average score of key skill proficiency in the investigation was 42.22. The epidemic response performance showed correlations with area, gender, age, education level, major, and field epidemiology training programs, those who had received longer training showed higher competency scores (all P<0.001). Conclusions:Progress has been made in the construction of epidemiological investigation task force in grass-root CDCs in China, but further improvements are needed, especially in the knowledge awareness and investigation skills of the task force. Field epidemiology training demonstrated substantial impact on the improvement of epidemic response performance, indicating that it is necessary to further strengthen the training in grassroot public health workers for the better response to infectious disease epidemics.

Objective To analysis the relationship between the lactate-to-albumin ratio(LAR)and the 28-day prognosis in patients with sepsis.Methods Based on the Medical Information Mart for Intensive Care-Ⅳ(MIMIC-Ⅳ)database,patients with sepsis aged≥18 years were selected.Patients were divided into survival and death groups according to their 28-day prognosis.The LAR was divided into quartiles:Q1(LAR<0.45),Q2(0.45≤LAR<0.70),Q3(0.70≤LAR<1.18),and Q4(LAR≥1.18);and into two groups based on the median LAR:low LAR group(LAR≤0.70)and high LAR group(LAR>0.70).Demographic characteristics,comorbidities,laboratory indicators,clinical treatments,and disease severity scores of patients were extracted.LAR was included as a continuous variable and a four-category variable in multiple Logistic regression models,with trend tests performed.Subgroup analyses were conducted based on gender,age,comorbidities,and sequential organ failure assessment(SOFA)score.Receiver operator characteristic curve(ROC curves)were plotted to analyze the predictive efficacy of lactate,albumin(Alb),LAR and SOFA score for the prognosis of sepsis patients.Kaplan-Meier survival curves were plotted to compare the difference of 28-day cumulative survival rates of sepsis patients in the high and low LAR groups.Results A total of 9 169 patients with sepsis were included,with 6 799 in the survival group and 2 370 in the death group.Compared with the survival group,the death group had older age[years:70.80(58.64,82.25)vs.65.07(53.56,76.92)],higher levels of potassium,creatinine,blood urea nitrogen(BUN),white blood cell count(WBC),lactate,LAR,SOFA score,simplified acute physiology scoreⅡ(SAPSⅡ),and higher proportions of chronic obstructive pulmonary disease(COPD),heart failure,use of vasopressors within 48 hours,and continuous renal replacement therapy(CRRT)[potassium(mmol/L):5.0(4.5,5.7)vs.4.8(4.4,5.4),creatinine(μmol/L):132.60(88.40,212.16)vs.97.24(70.72,159.12),BUN(mmol/L):11.42(7.14,18.56)vs.7.85(5.25,13.57),WBC(×109/L):13.1(8.7,19.1)vs.11.4(7.6,16.4),lactate(mmol/L):2.9(1.8,5.1)vs.2.0(1.4,3.1),LAR:1.03(0.63,1.88)vs.0.62(0.42,0.98),SOFA score:9(6,12)vs.6(4,8),SAPSⅡscore:52(42,64)vs.38(30,47),COPD:8.19%(194/2 370)vs.6.57%(447/6 799),heart failure:29.96%(710/2 370)vs.26.31%(1 789/6 799),use of vasopressors within 48 hours:62.19%(1 474/2 370)vs.37.56%(2 554/6 799),CRRT:19.45%(461/2 370)vs.9.56%(650/6 799),all P<0.05],while lower levels of body weight,chloride,calcium,hemoglobin(Hb),platelet count(PLT),Alb and lower proportions of hypertension were observed in the death group[body weight(kg):75.8(63.6,92.3)vs.78.7(66.5,95.0),chloride(mmol/L):104(98,109)vs.104(100,108),calcium(mmol/L):1.07(1.00,1.15)vs.1.09(1.03,1.15),Hb(g/L):103(87,120)vs.105(90,121),PLT(×109/L):173(104,246)vs.174(118,243),Alb(g/L):29(24,34)vs.33(28,37),hypertension:35.36%(838/2 370)vs.38.34%(2 607/6 799),all P<0.05].In the Logistic regression model adjusted for all confounding factors,the odds ratio(OR)and 95%confidence interval(95%CI)of LAR were 1.74(1.64-1.85),P<0.001;when LAR was treated as a four-category variable,the OR values of Q2,Q3,and Q4 increased progressively compared with Q1,being 1.49(1.22-1.82),2.27(1.88-2.75),and 5.05(4.20-6.08),respectively,P<0.001.Subgroup analyses showed that LAR was an independent risk factor for the 28-day prognosis of sepsis in different subgroups based on gender,age,comorbidities,and SOFA score(all P<0.001),with no interaction effects with the subgroup variables(all P>0.05).ROC curve analysis showed that the AUC of LAR predicted the 28-day prognosis of patients with sepsis was 0.688(0.675-0.700),higher than that of lactate[0.655(0.642-0.668)]and Alb[0.636(0.623-0.649)],both P<0.001,and not significantly lower than that of SOFA score[0.699(0.687-0.712),P=0.108].Kaplan-Meier survival analysis showed that the 28-day cumulative survival rate was significantly higher in the low LAR group than in the high LAR group(Log-Rank test:χ2=533.24,P<0.001).Conclusion LAR is an independent risk factor for the 28-day prognosis of sepsis patients.Higher LAR is associated with adverse outcomes,and its predictive efficacy is superior to that of lactate and albumin.

Objective:To understand the current status of epidemiological investigation task force construction and the performance of infectious disease epidemic response in county (district) Centers for Disease Control and Prevention (CDCs) in China, analyze the influencing factors and provide scientific evidence to improve the construction of grassroot epidemiological investigation task force.Methods:A survey was conducted in epidemiological investigation staff in county (district) CDCs in 31 provinces (autonomous regions/municipalities) and Xinjiang Production and Construction Corps in China. A self-designed questionnaire was used to collect information based on the epidemiological dynamic data collection platform of China CDC. A descriptive epidemiological analysis was conducted, and multiple linear regression models were used to identify the factors associated with the performance of infectious disease epidemic response.Results:A total of 24 934 epidemiological investigation task force members from 2 897 county (district) CDCs were surveyed in the study. In the epidemiological investigation task force, women, those with bachelor's degree and public health workers accounted for 62.46%, 71.36%, and 49.05% respectively. Up to 91.72% of the task force members had participated in field epidemic response. The average score of awareness of epidemic investigation procedures was 60.00, while the average score of key skill proficiency in the investigation was 42.22. The epidemic response performance showed correlations with area, gender, age, education level, major, and field epidemiology training programs, those who had received longer training showed higher competency scores (all P<0.001). Conclusions:Progress has been made in the construction of epidemiological investigation task force in grass-root CDCs in China, but further improvements are needed, especially in the knowledge awareness and investigation skills of the task force. Field epidemiology training demonstrated substantial impact on the improvement of epidemic response performance, indicating that it is necessary to further strengthen the training in grassroot public health workers for the better response to infectious disease epidemics.

Objective To analysis the relationship between the lactate-to-albumin ratio(LAR)and the 28-day prognosis in patients with sepsis.Methods Based on the Medical Information Mart for Intensive Care-Ⅳ(MIMIC-Ⅳ)database,patients with sepsis aged≥18 years were selected.Patients were divided into survival and death groups according to their 28-day prognosis.The LAR was divided into quartiles:Q1(LAR<0.45),Q2(0.45≤LAR<0.70),Q3(0.70≤LAR<1.18),and Q4(LAR≥1.18);and into two groups based on the median LAR:low LAR group(LAR≤0.70)and high LAR group(LAR>0.70).Demographic characteristics,comorbidities,laboratory indicators,clinical treatments,and disease severity scores of patients were extracted.LAR was included as a continuous variable and a four-category variable in multiple Logistic regression models,with trend tests performed.Subgroup analyses were conducted based on gender,age,comorbidities,and sequential organ failure assessment(SOFA)score.Receiver operator characteristic curve(ROC curves)were plotted to analyze the predictive efficacy of lactate,albumin(Alb),LAR and SOFA score for the prognosis of sepsis patients.Kaplan-Meier survival curves were plotted to compare the difference of 28-day cumulative survival rates of sepsis patients in the high and low LAR groups.Results A total of 9 169 patients with sepsis were included,with 6 799 in the survival group and 2 370 in the death group.Compared with the survival group,the death group had older age[years:70.80(58.64,82.25)vs.65.07(53.56,76.92)],higher levels of potassium,creatinine,blood urea nitrogen(BUN),white blood cell count(WBC),lactate,LAR,SOFA score,simplified acute physiology scoreⅡ(SAPSⅡ),and higher proportions of chronic obstructive pulmonary disease(COPD),heart failure,use of vasopressors within 48 hours,and continuous renal replacement therapy(CRRT)[potassium(mmol/L):5.0(4.5,5.7)vs.4.8(4.4,5.4),creatinine(μmol/L):132.60(88.40,212.16)vs.97.24(70.72,159.12),BUN(mmol/L):11.42(7.14,18.56)vs.7.85(5.25,13.57),WBC(×109/L):13.1(8.7,19.1)vs.11.4(7.6,16.4),lactate(mmol/L):2.9(1.8,5.1)vs.2.0(1.4,3.1),LAR:1.03(0.63,1.88)vs.0.62(0.42,0.98),SOFA score:9(6,12)vs.6(4,8),SAPSⅡscore:52(42,64)vs.38(30,47),COPD:8.19%(194/2 370)vs.6.57%(447/6 799),heart failure:29.96%(710/2 370)vs.26.31%(1 789/6 799),use of vasopressors within 48 hours:62.19%(1 474/2 370)vs.37.56%(2 554/6 799),CRRT:19.45%(461/2 370)vs.9.56%(650/6 799),all P<0.05],while lower levels of body weight,chloride,calcium,hemoglobin(Hb),platelet count(PLT),Alb and lower proportions of hypertension were observed in the death group[body weight(kg):75.8(63.6,92.3)vs.78.7(66.5,95.0),chloride(mmol/L):104(98,109)vs.104(100,108),calcium(mmol/L):1.07(1.00,1.15)vs.1.09(1.03,1.15),Hb(g/L):103(87,120)vs.105(90,121),PLT(×109/L):173(104,246)vs.174(118,243),Alb(g/L):29(24,34)vs.33(28,37),hypertension:35.36%(838/2 370)vs.38.34%(2 607/6 799),all P<0.05].In the Logistic regression model adjusted for all confounding factors,the odds ratio(OR)and 95%confidence interval(95%CI)of LAR were 1.74(1.64-1.85),P<0.001;when LAR was treated as a four-category variable,the OR values of Q2,Q3,and Q4 increased progressively compared with Q1,being 1.49(1.22-1.82),2.27(1.88-2.75),and 5.05(4.20-6.08),respectively,P<0.001.Subgroup analyses showed that LAR was an independent risk factor for the 28-day prognosis of sepsis in different subgroups based on gender,age,comorbidities,and SOFA score(all P<0.001),with no interaction effects with the subgroup variables(all P>0.05).ROC curve analysis showed that the AUC of LAR predicted the 28-day prognosis of patients with sepsis was 0.688(0.675-0.700),higher than that of lactate[0.655(0.642-0.668)]and Alb[0.636(0.623-0.649)],both P<0.001,and not significantly lower than that of SOFA score[0.699(0.687-0.712),P=0.108].Kaplan-Meier survival analysis showed that the 28-day cumulative survival rate was significantly higher in the low LAR group than in the high LAR group(Log-Rank test:χ2=533.24,P<0.001).Conclusion LAR is an independent risk factor for the 28-day prognosis of sepsis patients.Higher LAR is associated with adverse outcomes,and its predictive efficacy is superior to that of lactate and albumin.

Objective To investigate the related factor underlying the differential vulnerability of inner hair cell(IHC)ribbon synapses to noise exposure.Methods Twenty-eight C57BL/6J mice were randomly divided into the noise exposure group(NED1)and the control group(CTR)with 14 mice in each group.The noise exposure group was exposed to bandpass noise of 2～20 kHz at 103 dB SPL for two hours while the control group was bred in a quiet environment.Before and after noise exposure,auditory brainstem response was conducted to detect the audi-tory function,whole-mount immunofluorescence staining was used to observe the number of inner hair cell ribbon synapses in different turns.The calcium influx of inner hair cells in the apical and middle turn using whole-cell patch clamp recording was analyzed.Furthermore,the immunofluorescence intensity of calpain in inner hair cells from dif-ferent mouse cochlear turns using whole-mount immunofluorescence staining was compared.Western blotting was used to verify that CtBP2 was degraded by calpain.Results After noise exposure,the ABR threshold of 11.3,16.0,22.6,32.0 kHz increased significantly and the number of ribbon synapses of inner hair cells at the middle turn and basal turn of the cochlea decreased significantly.However,whole-cell patch clamp recordings showed that calcium ion channels were fewer but single-channel current was higher at the apical turn of the cochlea.The open probability of calcium ion channels in IHCs showed no significant difference between the apical turn and the middle turn of the cochlea.But the expression level of calpain of the inner hair cells at the middle and basal turn of the basi-lar membrane was significantly higher than that at the apical turn after noise exposure.The western blotting results also showed that CtBP2 was cleaved in a Ca2+-dependent manner by calpain.Conclusion Calpain may be the main related factor that accounts for the vulnerability of ribbon synapses in inner hair cells in the high frequency region of basal membrane.

Helicobacter pylori(Hp)infection is widely prevalent in the world and is a Group Ⅰ carcinogen announced by WHO.Colorectal polyps can be classified as non-adenomatous polyps and adenomatous polyps,and adenomatous polyps is recognized as precancerous lesion of colorectal cancer.More and more studies have found that Hp infection is associated with the formation of colorectal polyps.This article reviewed the progress of research on correlation between Hp infection and colorectal polyps,so as to provide reference for the formulation of clinical diagnosis and treatment strategies for gastrointestinal diseases.

Objective To screen and verify the genes that play key role in the occurrence and development of esophageal cancer by u-sing bioinformatics and real-time fluorescence quantitative PCR(qRT-PCR)methods to find new markers for diagnosis of esophageal cancer(ESCA).Methods Using the TCGA database and Wayne plot analysis,the cross genes between the differentially expressed genes of ESCA and the genes which have the most significant impacts on disease-free survival(DFS)rate in esophageal cancer patients were preliminarily identified.Following conducting protein-protein interaction(PPI)network analysis on the overlapping genes,GO and KEGG functional analysis was performed to screen the potential key genes as the diagnostic markers of esophageal cancer.qRT-PCR was used to quantitatively analyze the expression of mRNA of the key gene in peripheral blood.Statistical analysis was con-ducted based on the clinico-pathological characteristics of the patients to determine its potential value as a new diagnostic marker for e-sophageal cancer.Results After overlapping of differentially expressed genes of ESCA and disease-free survival genes in the TCGA database,39 upregulated genes and 20 downregulated genes were found to be differentially expressed,all of which affected disease-free survival rate.After conducting PPI network analysis,15 upregulated genes with core interactions were identified,and the downregulat-ed genes did not form any interaction network.Further enrichment analysis of these 15 core interacting genes through GO and KEGG,revealed that fibronectin 1(FN1)may be a potential biomarker for ESCA diagnosis.The qRT-PCR results showed that compared with the healthy control group,the mRNA expression level of FN1 in the peripheral blood of esophageal cancer patients was significantly ele-vated.After analyzing the clinical characteristics of patients,it was found that the patients with poor differentiation and high clinico-pathological staging had significantly increased peripheral blood FN1 mRNA levels.The model with FN1 mRNA expression levels can distinguish esophageal cancer patients from healthy individuals.Conclusion FN1 mRNA may be a potential non-invasive diagnostic biomarker for esophageal cancer.

Objective To investigate the correlation between blood glucose variability index(GLUCV)and postoperative delirium(POD)in elderly patients undergoing knee arthroplasty.Methods A total of 112 elderly patients undergoing elective knee arthroplasty were analyzed retrospectively,16 males and 96 females,aged 65-80 years,BMI 22.0-28.0 kg/m2,ASA physical status Ⅰ or Ⅱ.They were di-vided into two groups according to whether they had POD within 5 days after operation:POD group and non-POD group.The score of the last preoperative mini-mental state examination(MMSE),operation time,the duration of the intraoperative regional cerebral oxygen saturation(rScO2)value decreased by more than 13％of the rScO2 basic value(△rScO2＞13％),the preoperative hemoglobin(Hb)and C-reactive protein(CRP)concentration,the fingertip blood glucose concentration before entry,before anesthesia induction,5 minutes after anesthesia induction,1 minute after skin incision,and before leaving the chamber were col-lected,and the GLUCV was calculated.The risk factors of POD in elderly patients undergoing knee arthro-plasty were analyzed by univariate and multivariate logistic regression,and the odds ratio(OR)and 95％confidence interval(CI)were calculated.The receiver operating characteristic(ROC)curve was drawn to calculate the area under the curve(AUC)and analyze the predictive value of GLUCV.Results Thirty patients(26.8％)showed POD symptoms within 5 days after surgery.Compared with the non-POD group,the operation time and duration of intraoperative △rScO2＞13％in the POD group were significantly prolonged(P＜0.05),the CRP concentration and GLUCV were significantly increased(P＜0.05).Multi-variate logistic regression analysis showed that prolonged time of △rScO2＞13％(OR=3.542,95％CI 1.380-9.093,P=0.011),elevated CRP concentration(OR=1.984,95％CI 1.078-3.650.P=0.015),and elevated GLUCV(OR=5.257,95％CI 1.690-16.353,P=0.008)were risk factors of POD in elderly patients undergoing knee arthroplasty.ROC curve analysis showed that the area under the AUC of GLUCV in predicting POD in elderly patients undergoing knee arthroplasty was 0.747(95％CI 0.650-0.844,P＜0.001),while the optimal cutoff value was 23.4％,the sensitivity was 71.4％,and the specificity was 63.3％.Conclusion GLUCV is closely related to POD,and GLUCV level has a good pre-dictive effect on POD in elderly patients undergoing knee arthroplasty.

Objective·To investigate the pathological and physiological changes underlying noise-induced cochlear nucleus damage and the regulating function of astrocytes on the damage,using a combination of morphological analysis,and molecular biology techniques.Methods·Forty-eight male C57BL/6J mice were randomly divided into two groups and exposed to 110 dB SPL(sound pressure level)broadband noise for 2 hours.Auditory brainstem response(ABR)tests were performed on the mice on days 1,7,14,30,and 90 after the noise exposure.Immunofluorescence staining of cochlear nuclear tissue was conducted to observe cochlear nuclear neurons and auditory synapses,as well as astrocyte activation levels.In addition,the damage to the cochlear nuclear neurons and synapses caused by noise was verified through Western blotting.Results·A significant decrease in cochlear nuclear Bushy cells after noise exposure was observed.The Western blotting results showed that there was severe loss of nerve fibers in cochlear nuclear neurons,indicating that noise caused significant damage to cochlear nucleus neurons.Moreover,a significant loss of auditory synapses labeled with vesicular glutamate transporter 1(Vglutl)was observed,which was the severest on day 14 after noise exposure and slowly recovered on day 90.Interestingly,astrocytes in the cochlear nucleus displayed obvious clustering and activation after noise exposure.By staining with glial fibrillary acidic protein(GFAP),most astrocytes were distributed around the cochlear nucleus,granule cell area,and auditory nerve root before noise exposure,and they had a small size.However,on day 14 after noise exposure,a large number of activated astrocytes aggregated in the ventral cochlear nucleus,and they all showed a pattern of growth around the synapses.Conclusion·Noise exposure leads to significant damage in the cochlear nucleus,and it is possible that astrocytes are involved in its damage and repair processes.These findings will provide a crucial foundation for further understanding the mechanisms of sound signal analysis,integration,and neural plasticity in the cochlear nucleus.