Effectiveness of 13-valent pneumococcal conjugate vaccine against vaccine-serotype community acquired pneumococcal diseases among children in China: A test-negative case-control study.

BACKGROUND: In 2016, China licensed 13-valent pneumococcal conjugate vaccine (PCV13) based on a study that demonstrated its immunogenicity is non-inferior to PCV7. However, the real-world effectiveness of PCV13 against vaccine-serotype pneumococcal diseases in China has limited evidence. METHODS: A test-negative case-control study was conducted among children under 5 years old admitted to the Children's Hospital of Soochow University (SCH) with respiratory tract infections from January 2018 to December 2020. Cases were defined as children from whom the isolates were tested positive for Streptococcus pneumoniae (S. pneumoniae) with serotypes included in PCV13. Two control groups were included, one represented children with isolates positive for S. pneumoniae of non-PCV13 serotypes and the other comprised children who tested negative for S. pneumoniae. The S. pneumoniae-negative controls were selected by matching them to the cases based on gender, age and admission date in a 1:1 ratio. Vaccine effectiveness (VE) was calculated using a logistic regression model as (1- adjusted odds ratio) * 100 %. RESULTS: A total of 2371 pneumococcal isolates were included in the analysis, of which 75.0 % (1779/2371) were covered by PCV13 serotypes. Consequently, these 1779 children were classified as cases, and 592 children were designated as non-PCV13 serotype controls. Another 1779 children were correspondingly recruited as S. pneumoniae-negative controls. Overall, 40 cases (2.3 %) and 148 controls (6.2 %) had received vaccination. The overall VE in the PCV13/non-PCV13 serotypes case-control study was 50.0 % (95 % CI: 15.0, 70.7), which was lower than the VE of 74.4 % (95 % CI: 60.7, 83.3) in the matched PCV13/S. pneumoniae-negative case-control study. VE was higher for ≥ 2 or ≥ 3 doses of vaccination compared to ≥ 1 dose. VE against specific PCV13 serotypes (6B, 6A and 19F) was higher than for other serotypes. CONCLUSIONS: PCV13 vaccination demonstrates effectiveness against vaccine-serotype pneumococcal diseases in children, particularly for serotypes 6B, 6A and 19F.

Interaction between APOB gene polymorphism and risk factors in coronary heart disease patients without lipid-lowering treatment / 中华心血管病杂志

Objective@#To investigate the association between APOB gene R532W polymorphism and the risk of coronary heart disease (CHD) in patients without lipid-lowering treatment and to analyze the interactions between the variation of R532W and different risk factors of CHD.@*Methods@#CHD and non-CHD were diagnosed according to coronary artery angiography (CAG) and/or coronary computed tomography angiogram (CTA) results, as well as clinical features. Blood samples from 771 CHD patients and 772 age- and sex-matched non-CHD controls, who never accepted any lipid-lowering treatments, were collected. R532W was genotyped by HumanExome BeadChip at BGI and strict quality control was made. Firstly, the association between R532W polymorphism and the risk of CHD in 3 genetic models (GA+ AA vs.GG, AA vs. GG+ GA, AA vs. GA vs. GG) after adjusting confounding factors was explored. Then, the interactions between the variation of this loci and risk factors related to CHD were investigated.@*Results@#(1) Total cholesterol (TC) levels were significantly lower in AA genotype than in GA genotype in the total cohort and non-CHD controls, but was similar among the 3 genotypes in CHD patients. (2) R532W GG, GA and AA distribution was 80.7%, 18.2% and 1.2% in CHD patients, and 74.6%, 23.8% and 1.6% in non-CHD controls (P<0.05). (3) R532 polymorphism was related to the incidence of CHD in the dominant model, and A-allele carriers were related to about 35% reduced risk of CHD (OR=0.653, 95% CI 0.502-0.849, P=0.001) after adjusting for confounding factors. (4) R532W polymorphism had positive interactions with hypertension (1.452) and smoke (1.077), while negative interaction with diabetes (0.553) in the occurrence of CHD.@*Conclusions@#APOB gene R532W polymorphism is related to TC levels in Chinese north Han population. A-allele carries of R532W loci is linked with reduced risk of CHD in the absence of lipid-lowering treatment. R532W polymorphism has a positive additive interaction with hypertension and smoke, while a negative additive interaction with diabetes mellitus in the occurrence of CHD.

Distinct effects of different β-adrenoceptor stimulation patterns on car-diac AMP-activated protein kinase activity / 中国病理生理杂志

[ ABSTRACT] AIM:To investigate the cardiac AMP-activated protein kinase ( AMPK) activity and the effects of AMPK activator on cardiac structure and function in the mice with different β-adrenoceptor (β-AR) stimulation patterns . METHODS:Male BALB/c mice were subcutaneously injected with AMPK activator ( AICAR, 250 mg· kg -1 · d-1 ) or saline, and infused with β-AR agonist isoproterenol (ISO, 5 mg· kg-1· d-1) for 14 d.The cardiac functions were evalu-ated by echocardiography or hemodynamic method , and the hearts were harvested after infusion cessation immediately or 3 d later.Phosphorylated AMPK ( p-AMPK) was measured by Western blot .RESULTS:Sustained ISO infusion increased p-AMPK level.AICAR did not further increase p-AMPK but attenuated ISO-induced increase in heart weight .Sustained ISO infusion increased cardiac systolic function as indicated by left ventricular fractional shortening ( FS) and maximum rate of pressure rise (+dp/dtmax).The cardiac systolic function was not further increased by AICAR .The cardiac diastolic func-tion as indicated by left ventricular end-diastolic pressure (LVEDP) was not different in each group .In contrast, cardiac p-AMPK level was similar between the control mice and the mice with sustained ISO infusion and ceased infusion for 3 d. In this model, AICAR improved the cardiac systolic and diastolic functions , which were impaired by ISO.Moreover, the increased pattern of p-AMPK level was similar with that of heart rate upon ISO stimulation .CONCLUSION: Sustained ISO infusion increases p-AMPK.After ISO infusion cessation for 3 d, p-AMPK is decreased to the basal level .β-AR-in-duced inotropic effects should be avoided to investigate the cardioprotective role of AMPK activation in the β-AR stimulation models.

Isolation and culture of adult rat cardiomyocytes and characteristics of excitation-contraction coupling / 中国比较医学杂志

Objective To compare two separation medium of isolation of adult rat cardiomyocytes , and to observe the characteristics of excitation-contraction coupling of cardiomyocytes .Methods The isolated adult rat heart was hanged on to the Langendorff apparatus for aortic counter-current perfusion and collagenase digestion using two different separation medium.The single cardiomyocytes were cultured and infected with adenovirus . The morphological features of cardiomyocytes were observed with microscope and fluorescent microscope . The shortening-re-lengthening features of sarcomere and the intake-discharge features of calcium were simultaneously recorded by IonOptix equipment .Results 70%rod-shaped with clear-striation adult rat cardiomyocytes could be obtained with the stated two separation medium and cultured in serum-free medium for more than 7 days.GFP could express more than 7 days when the cardiomyocytes were infected with adenovirus .Cardiomyocytes obtained by the first separation medium could not contract with the electrical stimulation, while cardiomyoctyes obtained by the second separation medium could be used for the detection of excitation -contraction coupling .The shortening fraction of sarcomere was 11.61%±2.15% and the relaxing time was ( 0.177 ± 0.031) s.The amplitude of calcium transient was 30.79% ±9.74 % and the decaying time of calcium transient was (0.300 ±0.074) s.Conclusion With the stated two separation medium , adult rat cardiomyocytes can be well isolated , cultured and infected with adenovirus .The second separation medium can be used for the detection of excitation-contraction coupling characteristics .

Bioactivity of indolylpiperidine-piperazine derivatives on α1 -adrenoceptor-mediated inotropic response / 中国药理学与毒理学杂志

OBJECTIVE To investigate the blocking activities of a series of potential α1-adrenoceptor (α1-AR) antagonists (Compounds B1 -B9) on α1-AR.METHODS ① A series of potential α1-adrenoceptor (α1-AR) antagonists,indolylpiperidine derivative (IPD) and Compounds B1 -B9,with indolylpiperidine moiety and different substitutes were synthesized through the coupling of indolylpiperidine and piperazine derivatives.② Inotropic responses experiment was used to examine blocking effects of IPD and Compounds B1 - B9 in isolated rat atria by phenylephrine (PE) stimulation.③ Blocking effect of IPD and Compounds B1 - B9 on phosphorylation level of extracellular signal-regulated kinase (ERK) in PE treated HEK293 cells was tested by Western blotting.RESULTS ① Potential α1-adrenoceptor (α1-AR) antagonists with indolylpiperidine moiety and different substitutes were synthesized successfully.② PE caused a dose-dependent inotropic response which was inhibited by pre-incubation of phentolamine (Phen),a non-selective α1-AR antagonist,IPD and Compounds B1,B3,B4,B7,B8 and B9,respectively; IPD and Compounds B4 and B8 caused an obvious rightward shift of inotropic response-curve,the pA2 values for IPD and Compounds B4 and B8 were 6.72 ± 0.21,6.86 ± 0.29 and 6.67 ± 0.19,respectively.③ Phosphorylation level of ERK1/2 was inhibited by pre-incubation with Compounds B1,B2,B3,B5,B6,B7,B8 and B9 or IPD in PE treated α1A-AR stably expressed HEK293 cells; PE-stimulated phosphorylation level of ERK1/2 was inhibited by pre-incubation with Compounds B2,B4,B7 or B8 in α1B-AR stably expressed HEK293 cells.CONCLUSION Compound B4 has a selective blocking activity on α1B-AR,and Compounds B1,B3,B5,B6 and B9 or IPD have a selective blocking activity on the phosphorylation level of ERK1/2.

The features of adults' coronary artery anomalies shown by 64-multi-detector rows CT / 生物医学工程学杂志

To analyze the adults' coronary artery anomalies revealed by 64-MDCT, we retrospectively analyzed 34 cases of coronary artery anomalies (26 males and 8 females, averagely aged 53. 4 years with a range from 30 to 72 years). Multi-plannar reconstruction (MPR), maximum intensity projection (MIP), surface shadow display (SSD) and volume rendering (VR) were used to demonstrate the anomalous coronary artery. We found 4 cases of RCA from the left coronary sinus, 8 cases with secondary RCA, 1 case with high locations of left main (LM) segments from left sinus of valves, 1 case with LAD originated from main pulmonary artery, 3 cases with separate origin of LAD and LCX. Ten cases with myocardial bridge were shown (9 cases in LAD, 1 case in LCX); coronary fistula was seen in 2 cases (one was RCA-RA fistula, another was LAD-RV fistula), coronary aneurysm was found in 2 cases. Three cases in RCA were short and small. In conclusion, 64-MDCT is a good choice for diagnosing the anomalous coronary artery.

Construction of a genomic regulatory network based on gene expression profile of neonatal hypertrophic cardiomyocytes induced by phenylephrine / 中国病理生理杂志

AIM: To construct a genomic regulatory network based on gene expression profiling of hypertrophic cardiomyocytes induced by phenylephrine in neonatal rats. METHODS: Cultured neonatal hypertrophic cardiomyocytes were induced by phenylephedrine. The gene expression profiles of these cells were assessed by using a cDNA microarray, and the microarray data were further analyzed by Pathwaystudio and Agilent Literature Search software. RESULTS: A genes/proteins interaction network was constructed with 450 nodes and 592 edges by analyzing the gene expression in hypertrophic cardiomyocytes and literature mining. The network belongs to scale - free network by topological analysis, and 14 genes/proteins as key nodes, including PTPN11, TRAF6, HSPA8, VIM, RPS6KA3, PTHRP, GRB2 and PI3K, were predicted. Based on GO analysis, the genes/proteins associated with metabolism, signal transduction and cytoskeleton may play important roles in the process of cardiomyocytes hypertrophy induced by phenylephedrine in neonatal rat. CONCLUSION : The genomic regulatory network based on gene expression profiling and literature mining may provide integrated clue to elaborate hypotheses about the evolution of cardiomyocyte hypertrophy.

The preparation of HEK293 alpha1A or HEK293 alpha1B cell membrane stationary phase and the chromatographic affinity study of ligands of alpha1 adrenoceptor.

As a novel bioaffinity chromatographic technique, cell membrane chromatography (CMC) originated in 1996. The cell membrane stationary phase (CMSP) consists of porous silica coated with active cell membranes. By immersing silica into a suspension of cell membranes, the whole surface of silica was covered by the cell membranes. The present study repeatedly investigated the interaction between ligands and receptors by employing the system of CMC and especially evaluated the accuracy and feasibility of the CMC model in the study of subtype receptors. The cDNA encoding alpha1A or alpha1B adrenergic receptors (ARs) was transfected into human embryonic kidney 293 (HEK293) cell lines; cell lines stably overexpressing subtype receptors were obtained. HEK293 alpha1A or HEK293 alpha1B ARs CMSP were prepared by immobilizing relevant cell membranes on silica. In the described chromatography-based CMSP, the retention times of nine alpha1 adrenoceptor ligands and calculated capacity factors, as chromatographic parameters, were recorded carefully. These results showed a good correlation with the affinity of the same compounds for the corresponding cloned alpha1 adrenoceptor subtype. The rank order of capacity factors was consistent with the affinity rank order obtained from radioligand binding assays. The immobilized subtype-selective CMSP was stable and reproducible. The study demonstrates that the HEK293 alpha1A and HEK293 alpha1B CMSP can be utilized for initial screening of drug candidates.

Teaching Students How to Study / 中华医学教育探索杂志

This article chiefly defines the connotation of making students know how to study,from the aspects of both teachers and learners,discusses the requirements of qualities and techniques for modern teachers,and the ways to realize the students know how to study by 4 steps including education,instruction,assessment and encouragement.

alpha1A-adrenergic receptor mediated pressor response to phenylephrine in anesthetized rat.

To determine which subtype of alpha1-adrenergic receptors plays a role in the regulation of blood pressure, with alpha1A-adrenergic receptor-mediated vasoconstriction in perfused hindlimb as a control, we compared the inhibitory effects of various alpha1-adrenergic receptor selective antagonists on the vasopressure responses to phenylephrine between the mean arterial pressure and hindlimb perfusion pressure in anesthetized rats. In Normotensive Wistar rats, the results showed that the inhibitory effects (dose ratios of ED50, Dr) of alpha1-adrenoceptor selective antagonist (prazosin, Dr 13.5+/-3.6 vs.15.1+/-4.3, n = 11), alpha1A-adrenoceptor selective antagonist (5-methyl-urapidil, Dr 2.4+/-0.9 vs. 3.7+/-2.3, n = 12; RS-17053, Dr 3.2+/-1.6 vs. 4.4+/-3.3, n =12) and alpha1D-adrenoceptor selective antagonist (BMY7378, Dr 1.9+/-0.9 vs. 2.2+/-0.8, n=8) on phenylephrine- induced increases of perfusion pressure in the autoperfused femoral beds were the same as that in the mean arterial blood pressure in normotensive Wistar rats. The inhibitory effects of antagonists (RS-17053, Dr 3.4+/-0.6 vs. 4.3+/-0.9, n = 5; BMY7378, Dr 1.7+/-0.5 vs. 1.7+/-0.5, n = 8) in spontaneous hypertensive rats were similar with the Wistar rats. These results suggest that the mean arterial pressure induced by phenylephrine was mainly mediated by alpha1A-adrenergic receptor in both the anesthetized Wistar rats and spontaneous hypertensive rats.

Isoproterenol regulates lipopolysaccharide-induced tumor necrosis factor-alpha and interleukin-6 production in monocytes from essential hypertensive patients / 北京大学学报(医学版)

0.05). Conclusion: ?-adrenergic activation inhibits TNF-? (but not IL-6) production induced by LPS in monocytes. The inhibitory effects were not different between early staged hypertensive patients and healthy subjects.

Study on the relationship of an outbreak of Enterococcus facium sepsis between humans and pigs / 中华传染病杂志

Objective To assess the epidemiological relatedness on an outbreak of Enterococcus facium sepsis between humans and pigs based on genomic analysis. Methods Two bacterial isolates recovered randomly from the blood of one patient and one pig were analyzed for homogeneities by comparison with 16S rRNA gene sequences in the GeneBank. Moreover, The extracted genomic DNA was digested with the 20 U SamI enzyme respectively, then their interrelationship was performed according to the pulsed field gel electrophoresis. Results Sequences determined from both human and pig isolates were 100% identical and most closely related to E. facium , diverging from the prototype sequence by one nucleotide (99.9% similarity) and displayed indistinguishable pulsed field gel electrophoresis patterns. Conclusions These data demonstrate epidemiological relatedness of the bacterial isolates, and suggest spread of an E. facium -related sepsis outbreak from pigs to humans.

Effect of S100A8/A9 Protein Complex on F-actin Network in Human Cervical Carcinoma Cell Line,CasKi Cells / 中国微创外科杂志

Objective To investigate the effect of S100A8/A9 protein complex on the surface morphology and the F-actin network in human cervical carcinoma cell line,CasKi cells.Methods After being cultured with 20 ?g/ml S100A8/A9 protein complex,the cell skeleton of the CasKi cells were observed under a confocal scanning fluorescence microscope by staining the F-actin network.Atomic force microscopy(AFM) was employed to reveal the change of ultrastructure of the cell surface in vivo.ResultsAfter being cultured with the S100A8/A9 protein complex for 24 hours,the F-actin network disorder was revealed.Most of the F-actins distributed peripherally.The OD value of the F-actin decreased significantly from 92.42?5.16 to 57.67?3.70 after been treated with the S100A8/A9(t=5.268,P=0.000).The AFM showed a withdrawing morphology with reduced pseudopodia and destruction of stress fibers. Conclusion S100A8/A9 protein complex can change the ultrastructure of the surface of CasKi cells and its stress fibers by re-distributing of the F-actin in the cells.

DNA microarray profiling to identify norepinephrine-response genes in A7r5 aortic smooth muscle cells / 中国病理生理杂志

AIM: To define the gene expression changes of vascular smooth muscle cells (VSMCs) in response to norepinephrine (NE). METHODS: The expression adrenergic receptors (AR) were determined by radioligand binding assay in A7r5 cells. Gene expression profiles were identified by cDNA microarray after A7r5 cells were treated with NE for 24 h, and mRNA expressions of ? 1A -AR and ? 1B -AR were confirmed by real-time PCR. RESULTS: ? 1-AR and ?-AR existed in A7r5 cells. Seventy-five genes with changed expression in response to NE were screened out. These genes are involved in cell structure, cell/organism defense, metabolism, signal transduction and so on. ? 1A -, ? 1B -AR mRNA expression identified by microarray and realtime quantitive PCR displayed similar patterns. CONCLUSIONS: Gene expression profile in response to NE was analyzed comprehensively with the microarray technique. NE induces many kinds of different function genes in A7r5 cells, which may provide a novel insight into the particular role of NE that modulates multiple aspects of biological function in VSMCs. [

Impact of particulate matter in air pollution on cardi ovascular diseases / 中国病理生理杂志

Impact of air pollution on cardiovascular d is eases has been established. As the main source of city air pollution, particulat e matter has been demonstrated an independent correlation with incidence and mor tality of cardiovascular diseases. The mechanisms are not clear. Several plausib le mechanistic pathways have been described, including inflammation induced by o xidative stress, the followed enhanced coagulation/thrombosis resulted in instab ility of atherosclerosis, the promotion of ischemic heart diseases and imbalance of autonomic nerve tone resulted in the occurrence of arrhythmia. The article p rovides a review of the mechanisms on air pollution and cardiovascular diseases and suggestions for further research.

Expression of STAR protein QKI in norepinephrine-induced rat cardiac hypertrophy / 中国病理生理杂志

AIM: To study the expression profile of QKI m RNA and protein in rat heart during pathological cardiac hypertrophy. ME THODS: A rat cardiac hypertrophy model was established using continuous norepinephrine (NE) perfusion. Real-time PCR and Western blotting were applied t o examine QKI mRNA and protein expression respectively in rat heart. RES ULTS: Both mRNA and protein of three QKI isoforms were detected in adult rat heart. QKI-5 mRNA and total QKI protein were remarkably decreased in NE-ind uced hypertrophic heart compared with those in control group (P

Development and evaluation for volume overload-induced and pressure overload-induced cardiac hypertrophy in rats / 中国病理生理杂志

AIM: To compare the evaluations for the structure and function of the hypertrophic hearts induced by volume overload or pressure overload in rats. METHODS: Volume overload-induced cardiac hypertrophy was established by abdominal aortacaval fistula (ACF) and pressure overload-induced cardiac hypertrophy was developed by constriction of aorta (CA). The cardiac structure and function were analyzed by echocardiography, hemodynamic determination, heart weight measurement and histological examination. RESULTS: Heart weight of rats in all the operated groups was increased compared to the sham-operated groups. In 1-week ACF group, the internal diameter (0.67?0.03)cm vs (0.60?0.02)cm, P