BackgroundNumerous studies have delved into the relationship between magnesium (Mg) and metabolic diseases, however, the impact of Mg on novel glycolipid metabolic indicators remains largely unexplored. This study aims to conduct a comprehensive evaluation of the relationship between plasma Mg levels and glycolipid metabolism among a general population in Shenzhen, China.MethodsA cross-sectional study was performed in 1,429 adults who underwent medical check-ups at a hospital in Shenzhen, China. Plasma Mg levels were measured using inductively coupled plasma mass spectrometry (ICP-MS). To investigate the association between plasma Mg levels and glycolipid metabolism indicators, the multivariate linear and logistic regression models, along with the restricted cubic spline (RCS) model were employed.ResultsRegarding to the glucose indicators, plasma Mg showed a negative linear association with the triglyceride-glucose index adjusted for Body Mass Index (TyG-BMI) and a positive linear association with the single point insulin sensitivity estimator (SPISE), while demonstrating a negative non-linear association with fasting blood glucose (FBG) and the metabolic score for insulin resistance (METS-IR). For lipid indicators, Mg exhibited a negative linear association with the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol ratio (HDL-c), while the LDL-c/HDL-c ratio showed a V-shaped non-linear relationship with Mg. Furthermore, the level of Mg exhibited a negative linear association with diabetes and a V-shaped non-linear association with hyperlipidemia.ConclusionsMg plays a critical role in the glucose and lipid metabolism, particularly highlighting its association with the novel indicators for glycolipid metabolism. The results of our study need to be confirmed in large-scale prospective research in the future.

Background The current treatment strategies for myocardial infarction (MI) mainly focus on recanalization of infarct-related arteries to alleviate myocardial damage. In contrast, the role of promoting microangiogenesis has not received sufficient attention. Lysine crotonylation (Kcr), a novel posttranslational protein modification, has an unclear role in revascularization following MI. Purpose This study investigated the role of TOM70 crotonylation in angiogenesis following MI and elucidated its potential mechanisms. Study design We first established a mouse model of MI and an in vitro model of hypoxia in hypoxic human umbilical vein endothelial cells (HUVECs). Using crotonylation-based sequencing, we identified the key gene TOM70 and its modification sites. Subsequently, we generated a specific antibody against TOM70 K199 crotonylation to validate this modification. To explore the underlying mechanism, we constructed an adeno-associated virus (AAV) vector carrying a mutation at the TOM70 locus. Finally, we performed high-throughput drug screening to identify compounds that potentially bind to the TOM70 K199 crotonylated protein. Results In this study, we found that the crotonylation of TOM70 was significantly increased in MI mice and hypoxic HUVECs. Quantitative analysis of crotonylation further identified K199 as the critical modification site. In vivo studies have shown that the TOM70 K199R mutant virus can improve cardiac function in mice with MI and promote angiogenesis. In vitro, transfection with the TOM70 K199R plasmid mitigated the hypoxia-induced reduction in tube-forming ability of HUVECs, whereas the K199Q plasmids exacerbated the damage. Mechanistically, acyl-coA synthetase short-chain family member 2 (ACSS2) serves as an upstream regulatory factor, upregulating TOM70 K199cr, leading to mitochondrial morphological abnormalities and dysfunction by inhibiting the mitochondrial import of MIC19. This inhibition ultimately worsens myocardial remodeling and impedes the revascularization process. Based on this mechanism, we identified parishin as specific inhibitor of TOM70 K199cr, which demonstrated efficacy in improving cardiac function and promoting revascularization. Conclusion We found that ACSS2 upregulates TOM70 K199cr, inhibits mitochondrial import of MIC19 protein, causes mitochondrial structural and functional damage, and suppresses angiogenesis, thereby aggravating the progression of myocardial infarction. Administration of parishin can inhibit this process, improve angiogenesis, and enhance cardiac function.

OBJECTIVES:This study aimed to elucidate the global origins, evolutionary trajectory, and adaptive strategies of the MT28-ptxP3 macrolide-resistant Bordetella pertussis lineage driving the recent resurgence. METHODS:We integrated long-term epidemiologic surveillance data from Shenzhen (2013-2024) with comparative genomic analysis of 632 isolates (2018-2024), including early international MT28 strains from the United States, Japan, Austria, and Vietnam. Multilocus variable-number tandem-repeat analysis and single-nucleotide polymorphism-based phylogenetics were used to define population structure and evolutionary dynamics. RESULTS:The study revealed a dramatic clonal replacement: the MT28 lineage surged from 6.5% in 2018 to 89.4% in 2024 (P <0.001), establishing dominance. Phylogenetic analysis traced the global seeding of the MT28 backbone to the USA in 2018 and Japan/Austria in 2019. These early strains lacked the 23S ribosomal RNA (rRNA) A2047G mutation, suggesting that the recent resurgence may be due to the localized fixation of resistance within this lineage. This genotype-phenotype convergence provided a decisive fitness advantage in an antibiotic-rich environment. Epidemiologically, this expansion coincided with a significant shift in infection burden toward adolescents (age 7-15 years), indicating effective transmission in populations with waning vaccine-induced immunity. CONCLUSIONS:The 2024 resurgence in China is linked to the localized fixation of macrolide resistance within the globally dispersed MT28 lineage. Its evolution, combining resistance, hyper-virulence, and vaccine escape (prn deficiency), highlights the urgent need for revisions in global antibiotic stewardship and vaccination strategies.

Cadmium (Cd) exposure is an emerging environmental risk factor for atherosclerotic cardiovascular diseases (ASCVDs), particularly ischemic stroke (IS). MicroRNAs are potential mediators linking environmental exposure to health hazards. However, the role of miRNAs in the development of IS triggered by Cd exposure remains largely unknown. In this study, we first demonstrate that Cd exposure, even at a relatively low dosage (4 mg/L), significantly facilitates the progression of atherosclerosis in apolipoprotein E-deficient mice fed a high-fat diet. This pro-atherogenic effect was accompanied by comprehensive disturbances in systemic and vascular cholesterol homeostasis, evidenced by altered plasma lipid profiles, hepatic lipid accumulation, and dysregulated expression of key genes governing cholesterol uptake (CD36), efflux (ABCA1), and hydrolysis (NCEH1) within the aortic wall. Integrated transcriptomic and metabolomic analyses further corroborated the profound disruption of the lipid metabolism pathways. Through miRNA microarray, bioinformatics analysis, and qRT-PCR validation, we identified miR-30d-5p and miR-504-3p as novel epigenetic regulators mediating Cd-induced foam cell formation. Specifically, Cd treatment upregulated miR-30d-5p and downregulated miR-504-3p, which directly targeted NCEH1 and CD36, respectively, thereby promoting intracellular lipid accumulation. In a case-control population (494 IS patients and 494 controls), plasma miR-30d-5p levels were positively associated with Cd exposure and partially mediated the Cd-stroke association, accounting for 16.4% of the total effect. Moreover, miR-30d-5p significantly improved the discrimination and reclassification of IS patients beyond the traditional risk factors. In summary, our findings reveal that Cd induces atherosclerosis by disrupting cholesterol homeostasis and modulating miRNA-regulated pathways with plasma miR-30d-5p serving as a potential biomarker and mediator for Cd-related ischemic stroke. Further perspective investigations are warranted to validate our findings.

Metals disequilibrium is crucial in the progress of metabolic syndrome (MetS), whereas the underlying mechanism remains largely unclear. Aging is closely related with the major diseases, and recent studies show environmental exposure also accelerate aging. Therefore, we aimed at investigating the mediation impact of biological age (BA) on relationships of metals exposure with MetS risk. A cross-sectional study with 1,504 participants was conducted. BA predictors were established by Klemera and Doubal method (KDM) and Mahalanobis distance, based on clinical measures. KDM-accel [the residual difference of regressing KDM-BA to chronological age] and physiological dysregulation (PD) were further calculated and recorded as biological aging indexes (BAIs). Seven plasma metals (calcium, cobalt, copper, magnesium, molybdenum, selenium, and zinc), reported to be linked with MetS in our preceding study, were involved. Multivariate linear and logistic regression models were performed to evaluate the relationships of BAIs with metals exposure or MetS risk, respectively. The mediation effect of BA linking metals to MetS was also explored. Quantiles of magnesium, molybdenum, and cobalt showed significant negative relationships with MetS risk and two BAIs (all p-trend<0.05). Significant positive associations were observed for two BAIs and MetS risk (P<.001). Mediation analysis showed that BAIs mediated 19.15% and 13.23% of the negative associations between plasma molybdenum, magnesium and MetS risk, respectively. Our findings suggested that essential metals might reduce MetS risk via decelerating biological aging, emphasizing the significance of essential metals in prevention of aging and MetS.

Equilibration of metal metabolism is critical for normal liver function. Most epidemiological studies have only concentrated on the influence of limited metals. However, the single and synergistic impact of multiple-metal exposures on abnormal liver function (ALF) are still unknown. A cross-sectional study involving 1493 Chinese adults residing in Shenzhen was conducted. Plasma concentrations of 13 metals, including essential metals (calcium, copper, cobalt, iron, magnesium, manganese, molybdenum, zinc, and selenium) and toxic metals (aluminum, cadmium, arsenic, and thallium) were detected by the inductively coupled plasma spectrometry (ICP-MS). ALF was ascertained as any observed abnormality from albumin, alanine transaminase, aspartate transaminase, γ-glutamyl transpeptidase, and direct bilirubin. Diverse statistical methods were used to evaluate the single and mixture effect of metals, as well as the dose-response relationships with ALF risk, respectively. Mediation analysis was conducted to evaluate the role of blood lipids in the relation of metal exposure with ALF. The average age of subjects was 59.7 years, and 56.7 % were females. Logistic regression and the least absolute shrinkage and selection operator (LASSO) penalized regression model consistently suggested that increased levels of arsenic, aluminum, manganese, and cadmium were related to elevated risk of ALF; while magnesium and zinc showed protective effects on ALF (all p-trend < 0.05). The grouped weighted quantile sum (GWQS) regression revealed that the WQS index of essential metals and toxic metals showed significantly negative or positive relationship with ALF, respectively. Aluminum, arsenic, cadmium, and manganese showed linear whilst magnesium and zinc showed non-linear dose-response relationships with ALF risk. Mediation analysis showed that LDL-c mediated 4.41 % and 14.74 % of the relationship of plasma cadmium and manganese with ALF, respectively. In summary, plasma aluminum, arsenic, manganese, cadmium, magnesium, and zinc related with ALF, and LDL-c might underlie the pathogenesis of ALF associated with cadmium and manganese exposure. This study may provide critical public health significances in liver injury prevention and scientific evidence for the establishment of environmental standard.

Background: Metal exposure were assumed to be closely related with declined renal function, but the conclusions were controversial. We employed diverse statistical models and assessed the association between metal mixture exposure and mild renal impairment. Methods: A total of 13 plasma metals were measured in 896 general population from Southern China. Subjects with estimated glomerular filtration rate within 60-89 ml/min/1.73 m2 and urinary albumin-creatinine ratio <30 mg/g creatinine were defined as mild renal impairment (MRI). Results: About 31.47 % participants showed MRI. In the multivariate logistic regression models, compared with the first quartile, high levels of arsenic and molybdenum (the fourth quartile) were both associated with MRI, and the ORs (95 % CI) were 1.68 (1.05, 2.68) and 2.21 (1.40, 3.48), respectively. Their predominant roles were identified by the weighted quantile regression (WQS). Besides, restricted cubic spline analysis verified the relationship between molybdenum level and increased MRI risk in a linear and dose-response manner. Conclusion: High levels of arsenic and molybdenum might be independent risk factors of MRI, and they showed combined effect. Our findings might provide vigorous evidence in preventing mild decline in renal function.

目的 分析2015-2019年深圳市疫苗单独接种和同时接种过敏反应的发生情况,明确同时接种的安全性.方法 利用2015-2019年深圳市在国家疑似预防接种异常反应(adverse event following immunization,AEFI)监测系统上报的异常反应中过敏反应数据,对单独接种和同时接种疫苗发生过敏反应的情况进行对比分析.结果 2015-2019年深圳市共报告过敏反应3 718例,其中单独接种组为2 537例,同时接种组为1 181例,两组间性别、接种时年龄、接种前过敏史及患病史、接种途径等方面比较,差异均无统计学意义(x2=0.889、1.520、2.757、2.064、1.835,均P＞0.05).在接种后接种部位红肿、硬结及异常反应分型方面,两组间差异均无统计学意义(x2=2.674、1.926、5.621,均P＞0.05);在间隔时间、发热症状及转归状态方面,两组间差异均有统计学意义(x2=40.582、20.701、9.764,均P＜0.01),同时接种过敏反应发生在24h内的占比和出现发热症状的占比均高于单独接种.结论 2015-2019年深圳市两种及以上疫苗同时接种不会增加接种部位局部红肿、局部硬结等症状的发生机率,过敏反应的临床分型也与单独接种没有明显差异,但接种24 h内发生过敏反应和伴发热的占比高于单独接种.提示两种或以上疫苗同时接种的安全性较好,但需关注接种24 h内的过敏反应和发热症状.

[背景]金属暴露可能与动脉粥样硬化(AS)发生有关,关于多金属暴露与AS风险关系的研究结论存在争议.[目的]探讨深圳市中老年体检人群中血浆多种金属水平与AS风险之间的关联.[方法] 664名研究对象均来自2012-2017年于中山大学附属第八人民医院接受常规健康体格检查的中老年人群.通过问卷调查、体格检查等收集研究对象的人口学特征、生活方式及生理生化指标;采集研究对象的血浆,采用电感耦合等离子体质谱仪检测13种金属的质量浓度(后称浓度);采用颈动脉彩色超声测量颈总动脉内膜中层厚度,确定是否有AS.采用Iogistic回归模型和限制性立方样条图分析血浆金属浓度与AS风险的关联以及剂量-反应关系.[结果]研究对象的平均年龄为(64.41±7.23)岁,男性占比52.26％ (347/664),AS检出率为45.33％.校正混杂因素后,单金属logistic回归模型结果显示:与第一分位组相比,血浆铁、硒、镉的第四分位组AS风险下降,OR (95％ CI)分别为0.50 (0.29～0.88)、0.59 (0.36～0.96)和0.54 (0.33～0.90);而血浆铊的第三分位组AS风险上升[OR (95％ CI):1.75 (1.08～2.83)].进一步采用多金属logistic逐步回归后发现,与第一分位组相比:血浆铁的第四分位组AS风险下降[OR (95％ CI):0.47 (0.28～0.79)],而血浆铊的第三分位组AS风险上升[OR (95％ CI):1.81(1.11～2.99)];且随着铊浓度的升高,AS风险亦逐渐增加(P趋势=0.046).限制性立方样条分析结果表明,血浆铁浓度增加与AS风险下降有关,两者之间呈现非线性剂量-反应关系(非线性关联P=0.043,剂量-反应关系P=0.022).[结论]血浆铁浓度的增加可能与AS风险下降有关,而血浆铊浓度增加可能与AS风险增加有关.

BackgroundAlthough the global epidemic of pertussis has been controlled through the expanded Programme on Immunization (EPI), the incidence of pertussis has increased significantly in recent years, with a "resurgence" of pertussis occurring in developed countries with high immunization coverage. The incidence of pertussis in Shenzhen, was about 2.02/100,000, far exceeding that of the whole province and the whole country (both < 1/100,000). At the same time, more and more studies have shown that there is antigenic drift in Bortella pertussis , which may be associated with the increased incidence. 50 strains of Bordetella pertussis isolated from 387 suspected cases were collected in Shenzhen in 2018 for genotype distributions and molecular epidemiological characteristics analysis. MethodsThere were 387 suspected cases of pertussis enrolled at surveillance sites in Shenzhen from June to August 2018. Nasopharyngeal swabs of suspicious cases were collected for separation and culture, and the positive strains were identified by real-time PCR. The immunization histories of patients were analyzed to investigate the relationship between pertussis vaccination and infection. The major antigen genes of the isolated positive strains, including ptxA, ptxC, ptxP, prn, fim2, and fim3, were analyzed by second-generation sequencing. The homology and phylogenetic analysis of these genes was performed using the public genome sequence downloaded from GenBank. Results50 strains of Bordetella pertussis were successfully isolated from nasopharyngeal swabs of 387 suspected cases, with a positive rate of 12.9%, including 28 males and 22 females, accounting for 56.0% and 44.0% respectively. It is worth noting that 38 were under one-year-old among the positive patients, accounting for 76.0%. Among the cases with a history of vaccination, 71.4% of positive patients did not complete the basic vaccination process of the DTaP at the time of onset. Three major antigen genotypes different from CS and Tohama I vaccine strains were identified, and they had distant genetic relationships and 62.0% of which was prn2/ptxC2/ptxP3/ptxA1/fim3-1/fim2-1 . ConclusionsThe positive rate of cases under one-year-old was significantly higher than that of other age groups and should be monitored. The major antigenic genes of the Bordetella pertussis strains isolated in Shenzhen were different from those of common vaccine strains. This study explained the resurgence of whooping cough from certain angles, including immunization strategy, vaccination time and genome variation of strains, which is beneficial to prevent pertussis infections.

目的 探讨木酮糖激酶rs17118多态性与冠心病发病风险的关联性.方法 纳入2016年6月至2018年2月在深圳市中山大学附属第八医院诊治的、资料完整并成功完成基因分型的患者.按照1:1的比例,选择年龄、性别匹配的冠心病患者(病例组)和健康体检者(对照组)各597例,采用Taqman探针荧光定量PCR技术检测rs17118 C/A基因型分布情况,应用多因素logistic回归分析各位点多态性与冠心病的关联性.结果 病例组CA基因型(44.6％比38.5％,χ2=4.536,P=0.038)以及CA+AA基因型(51.6％比45.7％,χ2=4.008,P=0.045)分布频率均高于对照组.多变量logistic回归分析显示,校正传统危险因素后,CA基因型携带者冠心病发病风险是CC基因型携带者的1.41倍(95％CI:1.03～1.94,P=0.034).病例组中,AA基因型携带者低密度脂蛋白胆固醇[(2.31±0.82)mmol/L]和总胆固醇[(3.93±1.22)mmol/L]水平明显低于CC基因型[(2.61±0.86)mmol/L、(4.40±1.19)mmol/L,P=0.050、0.035]和CA基因型[(2.68±0.82)mmol/L、(4.49±1.22)mmol/L,P=0.016、0.012],CA+AA基因型携带者高密度脂蛋白胆固醇水平也明显低于CC基因型携带者[(1.05±0.26)mmol/L比(1.10±0.31)mmol/L,P=0.035].结论 木酮糖激酶基因可能通过调整脂质代谢,影响冠状动脉粥样硬化的形成和发展,进而改变个体的疾病遗传易感性,rs17118多态性与中国汉族人群冠心病发病风险有关.

BACKGROUND:Metal exposures are suspected to associate with the risk of hyperuricemia (HUA), but the current results are still conflicting. OBJECTIVE:To investigate the associations between multiple plasma metal exposures and HUA risk. METHODS:A cross-sectional study was conducted in 1406 Chinese Han adults who underwent routine physical examination in the Eighth Affiliated Hospital of Sun Yat-Sen University in Shenzhen. The plasma levels of 13 metals were measured by the inductively coupled plasma mass spectrometry (ICP-MS). Multivariable logistic, linear regression models, least absolute shrinkage and selection operator (LASSO) penalized regression analysis, and restricted cubic spline (RCS) models were applied to assess the associations. RESULTS:The median plasma uric acid concentration in HUA group (434 μmol/L) was significantly higher than that in non-HUA group (305 μmol/L). The multivariate-adjusted odds ratios (95% confidence intervals) of HUA were 1.62(1.08-2.43) for magnesium, 1.61(1.05-2.47) for copper, 1.62(1.06-2.49) for zinc, 1.87(1.26-2.81) for arsenic, 1.50(1.01-2.23) for selenium, and 1.70(1.16-2.49) for thallium based on the single-metal logistic regression models, comparing the highest versus the lowest quartile of metal levels. Further multi-metal logistic, linear regression models and the LASSO analysis all indicated positive associations of zinc, arsenic with HUA risk or uric acid levels. RCS model indicated an inverted V-shaped positive association between zinc levels and HUA risk (p for non-linearity = 0.048, p for overall association = 0.022), while arsenic levels showed a positive and linear dose-response relationship with HUA risk (p for non-linearity = 0.892, p for overall association<0.001). CONCLUSIONS:Higher plasma levels of zinc and arsenic might increase HUA risk and showed positive dose-response relationships. Further cohort studies in larger population are required to testify our findings.

目的 建立季节性差分自回归移动平均(seasonal autoregressive integrated moving aver-age,SARIMA)-广义回归神经网络(generalized regression neural network,GRNN)组合模型,为伤寒与副伤寒发病数的预测提供方法学上的新思路.方法 利用2011年1月-2019年12月中国伤寒与副伤寒逐月发病数资料,分别构建SARIMA模型和SARIMA-GRNN组合模型,比较两种模型的拟合和预测效果.结果 最优的SARIMA模型为SARIMA(2,1,1)(0,1,1) 12,SARIMA-GRNN组合模型的最优光滑因子(spread)为0.21.评价SARIMA-GRNN组合模型拟合效果的参数均方根误差(root mean squared error,RMSE)、平均绝对误差(mean absolute error,MAE)和平均绝对百分比误差(mean absolute percentage error,MAPE)为90.08、71.44和7.07％,分别小于SARIMA模型的99.44、79.15和7.86％;评价预测效果的RMSE、MAE和MAPE为100.86、75.94和9.57％,均小于SARIMA模型的125.44、97.33和10.89％.结论 SARIMA-GRNN组合模型比传统SARIMA模型更能拟合中国伤寒与副伤寒逐月的发病数,而且预测精度更高,可应用于伤寒与副伤寒逐月发病数的预测.

Background Although pertussis cases globally have been controlled through the Expanded Programme on Immunization (EPI), the incidence of pertussis has increased significantly in recent years, with a “resurgence” of pertussis occurring in developed countries with high immunization coverage. Attracted by its fast-developing economy, the population of Shenzhen has reached 14 million and has become one of the top five largest cities by population size in China. The incidence of pertussis here was about 2.02/100,000, far exceeding that of the whole province and the whole country (both < 1/100,000). There are increasing numbers of reports demonstrating variation in Bordetella pertussis antigens and genes, which may be associated with the increased incidence. Fifty strains of Bordetella pertussis isolated from 387 suspected cases were collected in Shenzhen in 2018 for genotypic and molecular epidemiological analysis. Methods There were 387 suspected cases of pertussis enrolled at surveillance sites in Shenzhen from June to August 2018. Nasopharyngeal swabs from suspected pertussis cases were collected for bacterial culture and the identity of putative Bordetella pertussis isolates was confirmed by real-time PCR. The immunization history of each patient was taken. The acellular pertussis vaccine (APV) antigen genes for pertussis toxin ( ptxA, ptxC ), pertactin ( prn ) and fimbriae ( fim2 and fim3) together with the pertussis toxin promoter region ( ptxP ) were analyzed by second-generation sequencing. Genetic and phylogenetic analysis was performed using sequences publicly available from GenBank, National Institutes of Health, Bethesda, MD, USA ( https://www.ncbi.nlm.nih.gov/genbank/ ). The antimicrobial susceptibility was test by Kirby-Bauer disk diffusion. Results Fifty strains of Bordetella pertussis were successfully isolated from nasopharyngeal swabs of 387 suspected cases, with a positivity rate of 16.79%, including 28 males and 22 females, accounting for 56.0% and 44.0% respectively. Thirty-eight of the 50 (76%) patients were found to be positive for B. pertussis by culture. Among the positive cases with a history of vaccination, 30 of 42 (71.4%) cases had an incomplete pertussis vaccination history according to the national recommendation. Three phylogenetic groups (PG1-PG3) were identified each containing a predominant genotype. The two vaccines strains, CS and Tohama I, were distantly related to these three groups. Thirty-one out of fifty (62%) isolates belonged to genotype PG1, with the allelic profile prn2/ptxC2/ptxP3/ptxA1/fim3-1/fim2-1 . Eighteen out of fifty (36%) isolates contained the A2047G mutation and were highly resistant to erythromycin, and all belonged to genotype PG3 ( prn1/ptxA1/ptxP1/ptxC1/fim3-1/fim2-1 ), which is closely related to the recent epidemic strains found in northern China. Conclusions The positive rate of cases under one-year-old was significantly higher than that of other age groups and should be monitored. The dominant antigen genotypes of 50 Shenzhen isolates are closely related to the epidemic strains in the United States, Australia and many countries in Europe. Despite high rates of immunization with APV, epidemics of pertussis have recently occurred in these countries. Therefore, genomic analysis of circulating isolates of B. pertussis should be continued, for it will benefit the control of whooping cough and development of improved vaccines and therapeutic strategies.

目的 探讨微小RNAs(miRNAs)对肺癌细胞系侵袭、迁移及凋亡的影响.方法 通过hsa-mir-933、hsa-mir-4700-3p、hsa-mir-3144-3p、hsa-mir-3972和hsa-mir-548a-5p感染目的细胞,流式细胞术检测5种miRNAs对肺癌细胞系的细胞凋亡的影响;Transwell分析5种miRNAs对肺癌细胞系的细胞侵袭效果;划线分析5种miRNAs对肺癌细胞系的细胞迁移的影响;Real-time PCR检测miRNA表达情况.结果 与感染空载体组和无感染的对照组相比,感染了hsa-mir-933、hsa-mir-4700-3p、hsa-mir-3144-3p、hsa-mir-3972和hsa-mir-548a-5p的细胞凋亡明显增加,其中NCI-H460和A549均以转染hsa-mir-4700-3p凋亡率最高;5种miRNAs对肺癌细胞的侵袭数目明显减小;5种miRNAs对肺癌细胞的细胞的迁移效果减弱;Real-time PCR检测hsa-mir-933、hsa-mir-4700-3p、hsa-mir-3144-3p、hsa-mir-3972和hsa-mir-548a-5p处理后相应miRNA的水平表达均相应增加.结论 5种miRNAs能够促进肺癌细胞系的凋亡,降低肺癌细胞系的高侵袭性,抑制肺癌细胞系的迁移,增加对应miRNA的表达.

目的:探讨不同免疫状态和年龄对百日咳发病的影响。方法:回顾性分析2018年深圳市儿童医院468例百日咳患儿的临床资料。比较不同免疫状态和年龄患儿的临床特征。率的比较采用 χ2检验，计量资料组间比较采用 t检验和方差分析。 结果:按年龄分为≤3月龄患儿221例，4～6月龄患儿119例，7～11月龄患儿53例，1～3岁患儿53例，>3～10岁患儿22例；按接种疫苗情况，将患儿分为未接种组216例，接种1剂组76例，接种2剂组37例，接种3剂组63例，全程接种组24例和接种情况不详组52例。468例百日咳患儿中，有密切接触咳嗽病史者105例，多为父母和兄弟姐妹。全程接种组患儿的病程为(20.00±9.21) d，未接种组为(13.82±10.52) d，接种1剂组为(15.28±9.46) d，接种2剂组为(12.41±7.78) d，接种3剂组为(14.60±9.34) d，组间差异有统计学意义( F＝3.551, P＝0.007)；接种1剂组患儿的白细胞计数为(22.32±12.82)×10 9/L，未接种组为(20.18±11.76)×10 9/L，接种2剂组为(16.69±8.87)×10 9/L，接种3剂组为(17.55±14.79)×10 9/L，全程接种组为(15.16±9.59)×10 9/L，组间差异有统计学意义( F＝2.724， P＝0.029)；淋巴细胞比例由未接种组患儿的0.665 8±0.152 7到全程接种组患儿的0.490 0±0.179 5，呈下降趋势( F＝8.740, P<0.01)。此外，淋巴细胞比例从年龄≤3月龄组患儿的0.675 6±0.146 1到年龄>3～10岁组患儿的0.438 1±0.165 0，呈下降趋势( F＝13.889, P<0.01)。 结论:不同免疫状态和年龄对百日咳病程、临床表现、实验室检查结果均有明显的影响，家庭内与咳嗽患者密切接触是婴幼儿发病的主要原因。

Aim: We aimed to investigate the relationship of trimethylamine N-oxide (TMAO) concentrations with ischemic stroke in a large-scale case-control study conducted among the hospital-based general population. Methods: We recruited 953 case-control sex- and age-matched pairs, and cases were confined to first acute ischemic stroke in this study. Fasting plasma TMAO was measured using high-performance liquid chromatography-tandem mass spectroscopy. Conditional logistic regression analysis was conducted to calculate odds ratios (OR) for the association of plasma TMAO with ischemic stroke. Results: We found that plasma TMAO concentrations in patients with ischemic stroke were significantly higher than that in the control group (median: 2.85 mu mol/L vs. 2.33 mu mol/L, P< 0.001). In multivariable conditional logistic regression models, higher plasma TMAO concentrations were associated with increased odds of ischemic stroke [fully adjusted OR for highest vs. lowest TMAO quartile: 1.81; 95% confidence interval (CI): 1.27, 2.59; P for trend <0.001]. The multivariable-adjusted OR for ischemic stroke per 1 mu mol/L increment of plasma TMAO was 1.05 (95% CI: 1.02, 1.08). Additionally, the positive association also persisted in subgroups stratified by age, sex, body mass index, smoking status, alcohol habits, history of diabetes, and history of hypertension. Conclusions: This study suggested a positive association between plasma TMAO and ischemic stroke. Further studies are required to explore the role of plasma TMAO concentrations in predicting stroke risk.

目的 探讨血浆长链非编码RNA (lncRNA) RNF5P1表达水平与缺血性脑卒中(ischemic stroke,IS)发病风险的关联,评估血浆RNF5P1作为IS生物标记物的可行性.方法 采用1∶1匹配的病例对照研究,在深圳地区选取302对性别年龄匹配的IS新发病例和正常体检对照,采用微滴式数字PCR检测血浆lncRNA RNF5P1的表达水平,采用条件Logistic回归分析模型分析RNF5P1表达水平与IS发病风险之间的关联,采用受试者工作特征曲线及重新分类的方法评估RNF5P1是否可作为IS的分子标记物.结果 IS病例组血浆lncRNA RNF5P1的表达水平高于对照组,差异有统计学意义(P＜0.001).高表达水平的RNF5P1与IS发病风险增加有关,校正其他危险因素后,OR值为2.52(95％ CI:1.12～5.64).与传统危险因素模型相比,加入lncRNA RNF5P1后,模型的曲线下面积增加(P＜0.001),净重分类改善度为0.42(95％ CI:0.26-0.57),综合区分改善度为0.24(95％ CI:0.14～0.34).结论 血浆lncRNA RNF5P1表达水平升高与IS发病风险增加有关,lncRNA RNF5P1有望作为IS的生物标记物.

目的 探索血浆长链非编码RNA(LncRNA)PITPNA-AS1表达水平与缺血性脑卒中(IS)发病风险的关联,分析PITPNA-AS1是否可作为IS的生物标记物.方法 采用病例对照研究,收集深圳地区IS新发病例及正常对照各302例,按同性别、年龄(±3)岁进行1∶1匹配,通过微滴式数字PCR检测血浆PITPNA-AS1的表达水平,采用条件logistic回归分析PITPNA-AS1表达水平与IS发病风险之间的关联,采用受试者工作特征曲线及重新分类的方法分析PITPNA-AS1作为IS生物标记物的可行性.结果 与对照组相比,IS病例组血浆PITPNA-AS1的表达水平较高,差异有统计学意义(P＜0.001),校正其他危险因素后,OR为2.87(95％CI:1.84～4.46).与只纳入其他危险因素的模型相比,加入PITPNA-AS1能增加模型的曲线下面积(P=0.013),净重分类改善度为0.35(95％ CI:0.19～0.51),综合区分改善度为0.10(95％ CI:0.03～ 0.17).结论 血浆lncRNA PITPNA-AS1表达水平与IS发病风险有关,PITPNA-AS1具有成为IS生物标记物的潜能.

Background and Purpose- Circulating metals synchronously reflect multiple metal exposures from both natural and anthropogenic sources, which may be linked with the risk of stroke. However, there is a lack of prospective studies investigating the associations of multiple metal exposures with incident stroke. Methods- We performed a nested case-control study within the ongoing Dongfeng-Tongji cohort launched in 2008. A total of 1304 incident stroke cases (1035 ischemic strokes and 269 hemorrhagic strokes) were prospectively identified by December 31, 2016, and matched to incident identity sampled controls according to age (within 1 year), sex, and blood sampling date (within 1 month). We determined the concentrations of 24 plasma metals and assessed the associations of plasma multiple metal concentrations with incident stroke using conditional logistic regression and elastic net model. Results- The average follow-up was 6.1 years. After adjusting for established risk confounders, copper, molybdenum, and titanium were significantly associated with higher risk of ischemic stroke (odds ratios according to per interquartile range increase, 1.29 [95% CI, 1.13-1.46], 1.19 [95% CI, 1.05-1.35], and 1.30 [95% CI, 1.07-1.59]), whereas rubidium and selenium were associated with lower risk of hemorrhagic stroke (odds ratios according to per interquartile range increase, 0.66 [95% CI, 0.50-0.87] and 0.68 [95% CI, 0.51-0.91]). The predictive plasma metal scores based on multiple metal exposures were significantly associated with higher risk of ischemic and hemorrhagic stroke (adjusted odds ratios according to per interquartile range increase, 1.37 [95% CI, 1.20-1.56] and 1.53 [95% CI, 1.16-2.01]). Conclusions- Plasma copper, molybdenum, and titanium were associated with higher risk of ischemic stroke, whereas plasma rubidium and selenium were associated with lower risk of hemorrhagic stroke. These findings may have important public health implications given the ever-increasing burden of stroke worldwide.