[摘 要] 目的：探究钾钙激活通道亚家族N成员4（KCNN4）在胰腺癌组织中的表达及其对胰腺癌进展的影响，解析KCNN4在胰腺癌临床诊断及预后判断中的作用。方法：利用GEPIA2数据分析平台，结合TCGA和GTEx数据库的数据分析KCNN4在胰腺癌组织中的表达水平及其与患者预后的关系。收集24例海军军医大学长海医院手术切除的胰腺癌患者的癌及癌旁组织标本，通过qPCR、WB法和免疫组化染色技术验证KCNN4在胰腺癌组织中的表达水平。利用shRNA敲低人胰腺癌细胞中BXPC3和PANC-1中KCNN4的表达，通过CCK-8和克隆形成实验检测细胞增殖与生长情况。利用小鼠胰腺癌KPC细胞构建胰腺癌原位成瘤模型，观察敲低KCNN4对胰腺原位成瘤的影响，统计小鼠生存期（OS）。结果：整合TCGA和GTEx数据库数据分析结果发现，KCNN4在胰腺癌组织中高表达（P < 0.05），且与患者OS和DFS缩短相关（均P < 0.05）。胰腺癌组织中KCNN4 mRNA和蛋白表达量均显著高于癌旁组织（均P < 0.01）。KCNN4敲低后，胰腺癌细胞生长速率显著减慢、克隆形成数量显著减少（均P < 0.01）。小鼠胰腺原位荷瘤实验结果表明，KCNN4敲低可抑制肿瘤细胞在胰腺原位的生长并延长小鼠OS。结论：KCNN4在胰腺癌组织中高表达，其能促进胰腺癌细胞增殖和胰腺癌进展，与患者预后密切相关，有望作为胰腺癌临床诊断及预后评估的靶点。

Objective: To compare the biological characteristics of human induced pluripotent stem cell-derived platelet exosomes (hiPSC-Plt-Exos) with those of conventional apheresis platelet exosomes (Plt-Exos), specifically focusing on their differential abilities to enhance the proliferation and migration of human umbilical cord mesenchymal stem cells (hUC-MSCs). Methods: Exosomes were isolated from hiPSC-derived Plt and apheresis Plt concentrate using size exclusion chromatography. These exosomes were then characterized through nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and Western blotting. Co-culture experiments into hUC-MSCs were conducted with hiPSC-Plt-Exos and apheresis Plt-Exos, respectively. Their effects on the proliferation and migration of hUC-MSCs were assessed via cell proliferation assays and scratch tests. Results: hiPSC-Plt-Exos and apheresis Plt-Exos exhibited comparable particle sizes, morphological features (such as the characteristic cup-shaped structure), and surface markers (including CD9 and HSP70). Notably, hiPSC-Plt-Exos demonstrated a significantly greater ability to enhance the proliferation and migration of hUC-MSCs compared to apheresis Plt-Exos (P<0.05). These differences provide critical comparative data for their application in various clinical contexts. Conclusion: This study establishes a theoretical foundation for developing precise therapeutic strategies based on hiPSC-Plt-Exos. Furthermore, it underscores the necessity of selecting the appropriate type of exosomes according to the specific disease microenvironment to achieve optimal therapeutic outcomes.

ObjectiveTo investigate the high-risk detection rate and aggregation of cardiovascular diseases（CVD） in 8 districts of Shanghai and influencing factors， and to provide scientific references for prevention and control of CVD. MethodsBased on the Cardiovascular Disease Screening and Management Program in Shanghai from 2016 to 2021， 104 685 participants aged 35 to 75 in 8 districts of Shanghai were selected for analysis. χ² test and multivariate logistic regression were used for statistical analysis of the influencing factors of CVD and aggregation of CVD. ResultsThe proportion of high-risk CVD individuals in the population was 19.17%， including the high-risk individuals with hypertension （8.65%）， dyslipidemia （6.33%）， CVD history （5.58%）， and WHO assessed risk ≥20% types （2.69%）， respectively. Old age， overweight and obesity， central obesity， smoking， drinking， farmers， unmarried， and low family income were the risk factors of CVD， while high education level was the protective factor. In the participants， 16 323 people （81.34%） were classified as CVD high-risk groups； The number of aggregation of 1， 2 and ≥3 high risk types of CVD were 16 323（81.34%）， 3 236（16.13%）， 509（2.54%）， respectively. Old age， low education level， low annual family income， farmers， unmarried， smoking， drinking， overweight， obesity and central obesity were associated with the risk of aggregation of high risk types of CVD， and the correlation strength increased with the increase of aggregation types. ConclusionThe prevention and control of CVD in Shanghai should focus on the hypertension， elderly， overweight， obesity， central obesity， smoking， drinking， low educated， low family income， farmers and unmarried people， and targeted intervention measures should be taken to reduce the risk of CVD among residents.

ObjectiveTo investigate the effects of probiotics combined with bismuth quadruple therapy （BQT） on clinical efficacy、gastrointestinal adverse reactions and intestinal flora in Helicobacter pylori （HP） positive patients. MethodsThe patients who were positive for HP from May 2023 to July 2023 in the department of gastroenterology of Shanghai first people's hospital were randomly divided into2 groups with 40 people in each group. The probiotic group was given 2 weeks of quadruple therapy with probiotics and standard BQT， followed by 4 weeks of oral probiotics after quadruple discontinuation. The placebo group was given 2 weeks of probiotic placebo and standard BQT， followed by 4 weeks of oral probiotic placebo. ¹³C urea breath test was used to evaluate the clinical efficacy， gastrointestinal symptoms rating Scale was used to evaluate the gastrointestinal adverse reactions of patients before and after the intervention， and microbial diversity 16S rDNA sequencing technology was used to detect the level of intestinal flora of patients before and after the intervention. ResultsThere was no significant difference in the eradication rate between the two groups （P>0.05）. Before the intervention， there was no significant difference in the scores of the gastrointestinal symptom rating scale between the probiotic group and the placebo group. After the intervention， patients in the probiotic group had significantly lower pain scores on acid reflux （1.10±0.30 vs 1.35±0.53， P<0.05） and stomach or abdominal hunger than in the placebo group （1.07±0.26 vs 1.30±0.52， P<0.05）. Through the before-and-after comparison of the probiotic group， the scores of abdominal pain （1.24±0.44 vs 1.58±0.71， P<0.05）， stomach or abdominal hunger （1.07±0.26 vs 1.27±0.45， P<0.05） and dry and hard stool （1.24±0.49 vs 1.48±0.75，P<0.05） were significantly lower in the probiotic group than before the intervention in the probiotic group. ConclusionProbiotics combined with BQT can improve the gastrointestinal adverse reactions and intestinal flora disorders in the process of quadruple drug therapy， but it does not improve the eradication rate of HP.

ObjectiveTo investigate the pathogenic spectrum and molecular characteristics of infectious diarrhea among children in Putuo District of Shanghai from 2018 to 2023， and to provide scientific basis for the prevention and control of infectious diarrhea in children. MethodsFecal samples from the cases visited sentinel hospitals for children’s diarrheal disease in Putuo District， Shanghai， were collected from January 2018 to December 2023. A total of 11 species of bacteria were isolated and cultured， and 5 species of viruses were detected by real-time fluorescent polymerase chain reaction （PCR）. The molecular typing of some positive strains was analyzed by the standard pulsed-field gel electrophoresis （PFGE） method. The polymerase-capsid protein linkage region of some norovirus-positive samples was amplified by reverse transcription PCR， and was sequenced and analyzed by bioinformatics software. The Chi-square test and Fisher’s exact probability test were used to compare the pathogen-positive rates in 2018‒2019 and 2020‒2023. ResultsOf the 707 cases of children with infectious diarrhea， the total positive rate was 47.67%， with a single bacterial positivity rate of 16.27%， a single viral positivity rate of 22.63%， and a mixed positivity rate of 8.77%， respectively. The dominant pathogens were rotavirus （10.75%）， norovirus （10.33%）， enteropathogenic Escherichia coli （8.06%）， Salmonella （6.36%）， enteroaggregative Escherichia coli （5.52%）， and Campylobacter （5.23%）. Bacterial infections were predominant in summer and fall， and viral infections were predominant in winter and spring. The total positive rate decreased in 2020‒2023 compared with that of 2018‒2019 （χ²=5.753，P<0.05）. Thirty-seven strains of Salmonella， 81 strains of diarrheagenic Escherichia coli， and 19 strains of Campylobacter were completed for the molecular typing analysis by PFGE， which were classified into 28， 80 and 18 banding types， respectively， with a wide range of banding similarity. Nineteen copies of norovirus GⅡ group gene sequences were analyzed and classified into 5 genotypes， which were mainly GⅡ.Pe-GⅡ.4 and GⅡ.P16-GⅡ.2 types. ConclusionRotavirus， norovirus， diarrheagenic Escherichia coli， Salmonella， and Campylobacter are the dominant pathogens of infectious diarrhea in children in Putuo District of Shanghai. The pathogen spectrum shows a trend of seasonal epidemic characteristics， with a diversity of molecular characteristics of some pathogens. Surveillance and monitoring on molecular characteristics of the pathogens of infectious diarrhea in children should be strengthened in different seasons， so as to provide a laboratory basis for the prevention and control of infectious diarrhea.

Objective:To analyze the clinical application value of a novel magnetic navigation ultrasound (MNU) combined with digital subtraction angiography (DSA) dual-guided percutaneous transhepatic biliary drainage (PTCD) through the right hepatic duct for the treatment of malignant obstructive jaundice.Methods:Randomized controlled trial. The clinical data of 64 patients with malignant obstructive jaundice requiring PTCD through the right hepatic duct at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province People′s Hospital) from December 2018 to December 2021 were retrospectively analyzed. The MNU group ( n=32) underwent puncture guided by a novel domestic MNU combined with DSA, and the control group ( n=32) underwent puncture guided by traditional DSA. The operation time, number of punctures, X-ray dose after biliary stenting as shown by DSA, patients' tolerance of the operation, success rate of the operation, pre- and post-operative total bilirubin, and incidence of postoperative complications were compared between the two groups. Results:The operation time of the MNU group was significantly shorter than that of the control group [(17.8±7.3) vs. (31.6±9.9) min, t=-6.35, P=0.001]; the number of punctures in the MNU group was significantly lower [(1.7±0.6) vs. (6.3±3.9) times, t=-6.59, P=0.001]; and the X-ray dose after biliary stenting as shown by DSA in the MNU group was lower than that in the control group [(132±88) vs. (746±187) mGy, t=-16.81, P<0.001]; Five patients in the control group were unable to tolerate the operation, and two stopped the operation, however all patients in the MNU group could tolerate the operation, and all completed the operation, with a success rate of 100% (32/32) in the MNU group compared to 93.8%(30/32) in the control group; the common complications of PTCD were biliary bleeding and infection, and the incidence of biliary bleeding (25.0%, 8/32) and infection (18.8%, 6/32) in the MNU group was significantly lower than that in the control group, 53.1% (17/32) and 28.1% (9/32), respectively. Conclusion:Magnetic navigation ultrasound combined with DSA dual-guided PTCD through the right biliary system for the treatment of malignant obstructive jaundice is safe and feasible.

Objective:To explore the inhibitory mechanism of herb cake-partitioned moxibustion on tumor growth in colitis-associated colorectal cancer(CAC)based on histone lysine demethylase 4D(KDM4D). Methods:Inbred male Sprague-Dawley rats were randomly divided into a normal group,a CAC group,a herb cake-partitioned moxibustion group,and an inhibitor group.Except the normal group,rats in the other three groups were treated with azoxymethane(AOM)combined with dextran sulfate sodium(DSS)to make CAC rat models.Rats in the normal group and the CAC group did not receive interventions;rats in the herb cake-partitioned moxibustion group received moxibustion at Qihai(CV6)and bilateral Tianshu(ST25),2 cones for one point each time,once a day for 30 d with 1-day rest every week;rats in the inhibitor group received intraperitoneal injection of KDM4D inhibitor,5-chloro-8-hydroxyquinoline(5-c-8HQ),once a day for 30 d.After intervention,the general condition,colon length,tumor number and volume,and histopathological colon changes were observed.The expression of adenomatous polyposis coli(APC),axis inhibitor(Axin),cyclin D1,matrix metalloproteinase(MMP)-7 and MMP-9 mRNAs were detected by real-time quantitative polymerase chain reaction.The proliferating cell nuclear antigen(PCNA),cleaved caspase3,KDM4D,APC,and Axin proteins were detected by immunohistochemistry. Results:Compared with the normal group,the general condition was poor,the colon length was significantly shortened(P<0.01),the number and volume of colonic tumors were increased(P<0.01),the structure of glandular duct was obviously disordered with"back-to-back"and cowall phenomenon,and also high-grade adenocarcinoma formed;the protein expression levels of PCNA and KDM4D were significantly increased(P<0.01),while cleaved caspase3,APC,and Axin were significantly reduced(P<0.01);the mRNA expression levels of cyclin D1,MMP-7,and MMP-9 were significantly increased(P<0.01),while APC and Axin were significantly reduced(P<0.01)in the CAC group.Compared with the CAC group,the general condition was improved,the length of colon was significantly increased(P<0.01),the number and volume of the colonic tumors were reduced(P<0.05),and the colon tissues showed epithelial cell proliferation with enlarged and deep staining nuclei,dysplasia and inflammatory cell infiltration;the protein expression levels of PCNA and KDM4D were significantly reduced(P<0.01),while the cleaved caspase3,APC,and Axin were significantly increased(P<0.01);the mRNA expression levels of cyclin D1,MMP-7,and MMP-9 were reduced(P<0.05),while the APC and Axin were increased(P<0.05)in the colon tissues of rats in the herb cake-partitioned moxibustion group and the inhibitor group. Conclusion:Herb cake-partitioned moxibustion regulated abnormally expressed KDM4D in CAC rats,activated APC and Axin,the upstream molecules of Wnt/β-catenin pathway,inhibited abnormally activated downstream molecules of Wnt/β-catenin pathway.This may be a key mechanism of herb cake-partitioned moxibustion in inhibiting CAC tumor growth.

The problems caused by proximal contact loss(PCL)of dental implants have been a mainstream research topic in recent years,and scholars are unanimously committed to analyzing their causes and related factors,aiming to identify solutions to the problems related to PCL.The effects of the anterior component of force(ACF),the lifelong re-molding of the adult craniofacial jaw and alveolar socket,and the osseointegration characteristics of dental implants are the main causes of PCL.On the one hand,the closing movement of the mandible causes the ACF of the tooth to move through the posterior molar cusp.Moreover,drifting between the upper and lower posterior teeth and mandibular anteri-or teeth can cause the anterior teeth of the upper and lower jaws to be displaced labially.On the other hand,reconstruc-tion of the jaw,alveolar socket and tooth root,the forward horizontal force of the masticatory muscles,the dynamic com-ponent of the jaw and the forward force generated by the oblique plane of the tooth cusp can cause the natural tooth to experience near-middle drift.Additionally,natural teeth can shift horizontally and vertically and rotate to accommodate remodeling of the stomatognathic system and maintain oral function.Nevertheless,the lack of a natural periodontal mem-brane during implant osseointegration,the lack of a physiological basis for near-medium drift,the small average degree of vertical motion and the integrated silence of dental implants without the overall drift characteristics of natural teeth increases the probability of PCL.The high incidence of PCL is clearly associated with the duration of prosthesis delivery and the mesial position;but it is also affected by the magnitude of the bite force,occlusion,the adjacent teeth,restora-tion design,implant location,jaw,and patient age and sex.PCL has shown a significant correlation with food impaction,but not a one-to-one correspondence,and did not meet the necessary and sufficient conditions.PCL is also associated with peri-implant lesions as well as dental caries.PCL prevention included informed consent,regular examinations,se-lection of retention options,point of contact enhancement,occlusal splints,and the application of multipurpose digital crowns.Management of the PCL includes adjacent contact point additions,orthodontic traction,and occlusal adjust-ment.Existing methods can solve the problem of food impaction in the short term with comprehensive intervention to seek stable,long-term effects.Symmetric and balanced considerations will expand the treatment of issues caused by PCL.

Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.

Objective:To discuss the association between occupational acid fog exposure and accelerated biological aging of the workers,and to clarify its related risk factors.Methods:A total of 341 male workers exposed to occupational acid fog and 201 male workers without occupational exposure were selected as the study subjects,and they were divided into exposure group and control group,respectively.The general informations of the subjects in two groups were collected through questionnaires and physical examinations.The levels of red blood cell count(RBC),platelet count(PLT),albumin(ALB),urea(Urea),creatinine(CR),triglycerides(TG),total cholesterol(TC),glycated hemoglobin(HBA1c),and high-sensitivity C-reactive protein(Hs-CRP)in serum of the subjects in two groups were detected.The Klemera-Doubal method(KDM)was used to construct the composite aging measure,KDM-biological age(BA)(KDM-BA).The model parameters were trained using samples from the 2009 China Health and Nutrition Survey(CHNS)Database to calculate the BA acceleration of the subjects in two groups;stratified analysis based on the population characteristics was conducted to analyze the BA of the subjects in two groups with different population characteristics;generalized linear model was used to analyze the factors influencing BA acceleration due to acid fog exposure.Results:The model parameters were trained using samples from the 2009 CHNS Database,including 8 133 cases aged 20-79 years,of which 3 788 were male.The levels of Urea,CR,HBA1c,ALB,and TC,as well as systolic blood pressure(SBP),total working years,sleep duration,and body mass index(BMI)of the subjects between two groups had significant differences(P<0.05).Compared with control group,the BA acceleration of the subjects in exposure group was significantly increased(P<0.05).In entire population and exposure group,the BA acceleration in the smokers was significantly higher than that in the non-smokers(P<0.05).In entire population,control group,and exposure group,the BA accelerations of the subjects in different BMI groups were significantly decreased with the increase of BMI(P<0.05).Compared with control group,the BA acceleration of the subjects in exposure group was significantly increased(P<0.05),including those under 40 years old,with total working years of 4-7 years,Han nationality,unmarried,smokers,and sleep duration 6-7 h,and with overweight.Acid fog exposure,smoking,and BMI were associated with the BA acceleration(β=0.72,95%CI:0.24-1.21;β=0.59,95%CI:0.11-1.06;β=-0.29,95%CI:-0.35—-0.22).Conclusion:Occupational acid fog exposure may accelerate the biological aging in the workers,and acid fog is a risk factor to accelerate the biological aging of the body.