Association between metabolic syndrome and the risk of colorectal cancer: a prospective study in China.

OBJECTIVE: To evaluate the correlation between metabolic syndrome (MetS) and its components on the incidence of colorectal cancer (CRC) based on data from Jinchang Cohort. METHODS: This is a large prospective cohort study. Between 2011 and 2020, a total of 43 516 individuals from Jinchang Cohort were included for this study. Hazard ratios (HRs) with 95% confidence intervals (CIs) for CRC according to MetS were calculated with the Cox proportional hazard models. The restricted cubic spine models with four knots were conducted to fit the dose-response relationships. RESULTS: MetS was associated with increased risk of CRC (n = 141; HR: 1.64, 95% CI: 1.15-2.33) after adjusting for confounding factors (age, sex, education level, family history of CRC, smoking index and alcohol index). Participants with hyperglycemia had a significantly higher risk of developing incident CRC (HR: 1.70; 95% CI: 1.19-2.43). The positive association between MetS and CRC was observed in males (HR: 1.76; 95% CI: 1.17-2.63), but not in females (HR: 1.24; 95% CI: 0.59-2.64). Furthermore, linear dose-response relationship was found between fasting plasma glucose (FPG) and CRC risk in males ( Poverall < 0.05, Pnon-linear = 0.35). When stratified by smoke and drink, MetS was found to increase the incidence of CRC only in the smoke (HR: 2.07, 95% CI: 1.35-3.18) and drink (HR: 2.93, 95% CI: 1.51-5.69) groups. CONCLUSION: MetS was associated with a higher risk of CRC incidence. Hyperglycemia lended strong support to the role of MetS in new-onset CRC, especially in males. Other components of MetS were not found to be associated with increased risk of CRC.

Value of GPR, APPRI and FIB-4 in the early diagnosis of hepatocellular carcinoma: a prospective cohort study.

OBJECTIVE: There is an urgent need for novel biomarkers that are inexpensive, effective and easily accessible to complement the early diagnosis of hepatocellular carcinoma. This study aimed to analyze the relationship between serum gamma-glutamate-transpeptidase to platelet ratio, alkaline phosphatase-to-platelet ratio index, fibrosis index based on four factors and the risk of hepatocellular carcinoma, and to determine the optimal cut-offs for predicting hepatocellular carcinoma. METHODS: Based on a prospective cohort study, 44 215 participants who were cancer-free at baseline (2011-13) were included in the study. Cox proportional hazard models and receiver operating characteristics curves were used to analyze the diagnostic value and optimal cut-off value of gamma-glutamyl-transpeptidase to platelet ratio, alkaline phosphatase-to-platelet ratio index and fibrosis index based on four factors in predicting hepatocellular carcinoma patients. RESULTS: Gamma-glutamyl-transpeptidase to platelet ratio, alkaline phosphatase-to-platelet ratio index and fibrosis index based on four factors can be used as early independent predictors of hepatocellular carcinoma risk. The risk of hepatocellular carcinoma in the fourth quantile of gamma-glutamyl-transpeptidase to platelet ratio and alkaline phosphatase-to-platelet ratio index was 4.04 times (hazard ratio = 4.04, 95% confidence interval: 2.09, 7.80) and 2.59 times (hazard ratio = 2.59, 95% confidence interval: 1.45, 4.61), respectively, compared with the first quantile. With fibrosis index based on four factors first quantile as a reference, fibrosis index based on four factors fourth quantile had the highest risk (hazard ratio = 18.58, 95% confidence interval: 7.55, 45.72). Receiver operating characteristic results showed that fibrosis index based on four factors had a stronger ability to predict the risk of hepatocellular carcinoma (area under curve = 0.81, 95% confidence interval: 0.80, 0.81), and similar results were shown for gender stratification. In the total population, the optimal cut-off values of gamma-glutamyl-transpeptidase to platelet ratio, alkaline phosphatase-to-platelet ratio index and fibrosis index based on four factors were 0.208, 0.629 and 1.942, respectively. CONCLUSIONS: Gamma-glutamyl-transpeptidase to platelet ratio, alkaline phosphatase-to-platelet ratio index and fibrosis index based on four factors were independent predictors of hepatocellular carcinoma risk. Amongst them, fibrosis index based on four factors shows a stronger predictive ability for hepatocellular carcinoma risk, and gamma-glutamyl-transpeptidase to platelet ratio and alkaline phosphatase-to-platelet ratio index can be used as complementary indicators.

Progression from different blood glucose states to cardiovascular diseases: a prospective study based on multi-state model.

AIMS: To quantify the trajectories from normoglycaemia to pre-diabetes, subsequently to type 2 diabetes mellitus (T2DM), cardiovascular diseases (CVD), and cardiovascular death, and the effects of risk factors on the rates of transition. METHODS AND RESULTS: We used data from the Jinchang Cohort of 42 585 adults aged 20-88 free of coronary heart disease (CHD) and stroke at baseline. A multistate model was applied for analysing the progression of CVD and its relation to various risk factors. During a median follow-up of 7 years, 7498 participants developed pre-diabetes, 2307 developed T2DM, 2499 developed CVD, and 324 died from CVD. Among 15 postulated transitions, transition from comorbid CHD and stroke to cardiovascular death had the highest rate (157.21/1000 person-years), followed by transition from stroke alone to cardiovascular death (69.31/1000 person-years) and transition from pre-diabetes to normoglycaemia (46.51/1000 person-years). Pre-diabetes had a sojourn time of 6.77 years, and controlling weight, blood lipids, blood pressure, and uric acid within normal limits may promote reversion to normoglycaemia. Among transitions to CHD alone and stroke alone, transition from T2DM had the highest rate (12.21/1000 and 12.16/1000 person-years), followed by transition from pre-diabetes (6.81/1000 and 4.93/1000 person-years) and normoglycaemia (3.28/1000 and 2.39/1000 person-years). Age and hypertension were associated with an accelerated rate for most transitions. Overweight/obesity, smoking, dyslipidaemia, and hyperuricaemia played crucial but different roles in transitions. CONCLUSION: Pre-diabetes was the optimal intervention stage in the disease trajectory. The derived transition rates, sojourn time, and influence factors could provide scientific support for the primary prevention of both T2DM and CVD.

Former single-outcome studies on the relationship between glycaemia and cardiovascular disease (CVD) may ignore the complexity and multi-transformations across the multiple stages from normoglycaemia to CVD in real-world setting. We aimed to quantify the trajectories from normoglycaemia to pre-diabetes, subsequently to type 2 diabetes, CVD, and cardiovascular death. Pre-diabetes was the optimal intervention stage in the disease trajectory. Transitions from CVD to death had much higher rates than other transitions. Age and hypertension were associated with an accelerated rate for most transitions. Overweight/obesity, smoking, dyslipidaemia, and hyperuricaemia played crucial but different roles in transitions.

Fasting plasma glucose and alanine aminotransferase on the risk of hepatocellular carcinoma: A nested case-control study.

BACKGROUND: The risk of hepatocellular carcinoma (HCC) is associated with a variety of factors. However, the possible association between the abnormal metabolism of fasting plasma glucose (FPG) and alanine aminotransferase (ALT) and the risk of HCC has not been widely studied. We examined this relationship based on a prospective cohort study. METHODS: 162 first-attack HCC cases during three follow-up periods (2014-2020) were selected as the case group. A control group of 648 participants was obtained by 1:4 matching of age (± 2 years) and sex with noncancer participants in the same period. Conditional logistic regression models, restricted cubic spline models, additive interaction models, and generalized additive models were used to explore the effects of FPG and ALT on the risk of HCC. RESULTS: After correction for confounding factors, we found that abnormal FPG and elevated ALT increased the risk of HCC, respectively. Compared with the normal FPG group, the risk of HCC was significantly increased in the impaired fasting glucose (IFG) (OR = 1.91, 95 %CI: 1.04, 3.50) and diabetes groups (OR = 2.12, 95 %CI: 1.24, 3.63). Compared with the lowest quartile of ALT, subjects in the fourth quartile had an 84 % increased risk of HCC (OR = 1.84, 95 %CI: 1.05-3.21). Moreover, there was an interaction between FPG and ALT on the risk of HCC, and 74 % of the HCC risk could be attributed to their synergistic effect (AP = 0.74, 95 %CI: 0.56-0.92). CONCLUSION: Abnormal FPG and elevated ALT are independent risk factors for HCC, and they have a synergistic effect on the risk of HCC. Therefore, serum FPG and ALT levels should be monitored to prevent the development of HCC.

Coronary Atherosclerotic Disease and Cancer: Risk Factors and Interrelation.

Background: In our clinical work, we found that cancer patients were susceptible to coronary atherosclerotic heart disease (CAD). However, less is known about the relationship between CAD and cancer. The present study aimed to identify the risk factors for CAD and cancer, as well as the relationship between CAD and cancer. Methods: In this retrospective study, 1600 patients between January 2012 and June 2019 were enrolled and divided into groups according to whether they had CAD or cancer. Single-factor and multivariate analysis methods were applied to examine the risk factors for CAD and cancer. Results: (1) Cancer prevalence was significantly higher in patients with CAD than in patients without CAD (47.2 vs. 20.9%). The prevalence of CAD in cancer and non-cancer patients was 78.9 and 52.4%, respectively. (2) Multivariable logistic regression showed that patients with cancer had a higher risk of developing CAD than non-cancer patients (OR: 2.024, 95% CI: 1.475 to 2.778, p < 0.001). Respiratory (OR: 1.981, 95% CI: 1.236-3.175, p = 0.005), digestive (OR: 1.899, 95% CI: 1.177-3.064, p = 0.009) and urogenital (OR: 3.595, 95% CI: 1.696-7.620, p = 0.001) cancers were significantly associated with a higher risk of CAD compared with no cancer. (3) Patients with CAD also had a higher risk of developing cancer than non-CAD patients (OR = 2.157, 95% CI: 1.603 to 2.902, p < 0.001). Patients in the Alanine aminotransferase (ALT) level ≥ 40 U/L group had a lower risk of cancer than patients in the ALT level < 20 U/L group (OR: 0.490, 95% CI: 0.333-0.722, p < 0.001). (4) An integrated variable (Y = 0.205 × 10-1 age - 0.595 × 10-2 HGB - 0.116 × 10-1 ALT + 0.135 FIB) was identified for monitoring the occurrence of cancer among CAD patients, with an AUC of 0.720 and clinical sensitivity/specificity of 0.617/0.711. Conclusion: (1) We discovered that CAD was an independent risk factor for cancer and vice versa. (2) Digestive, respiratory and urogenital cancers were independent risk factors for CAD. (3) We created a formula for the prediction of cancer among CAD patients. (4) ALT, usually considered a risk factor, was proven to be a protective factor for cancer in this study.

The accuracy and influencing factors for preference of self-sampling in group B streptococcus screening: a cross-sectional study.

OBJECTIVE: Self-sampling with proper instruction in 35-37 weeks' gestation is an option to clinician sampling to prevent early-onset invasive group B streptococcal disease of infants. We aimed to assess the accuracy of self-sampling and influencing factors of preference for collection method in Chinese women. METHODS: We compared the screening results of self-sampling with clinician collection in a sample of 520 women in late pregnancy. We collected their demographics, clinical information and preference for collection method. A multi-nominal logistic regression model was used to measure the association between the influencing factors and these participants' preference. RESULTS: A good agreement between the two collection methods was found with a Cohen's Kappa coefficient 0.83 (95%CI = 0.71-0.95). The prevalence of GBS infection in the two methods is statistically different in this low-risk group when self-sampling presented a better outcome in terms of detecting positive cases. Self-sampling is preferable by 20.9% of the participants. No less pain during self-sampling and age older than 35 years old was statistically related to preference for clinician collection. CONCLUSION: The accuracy of self-sampling is no worse than clinician collection. It could be an option for those younger than 35 years old, especially for those who report low pain threshold. Pregnant women are able to collect rectovaginal samples prior to their antenatal visit. Self-sampling followed by appropriate transportation of the sample to an advanced laboratory could eliminate the effects of local laboratory capacity. There are implications in increasing GBS screening participation in resource-limited settings.

Pericardial tamponade after chronic total occlusion revascularization: a case report and literature review.

Pericardial tamponade is a complication of percutaneous coronary intervention (PCI) with extremely high mortality. The rupture of coronary artery causes hypotension and shock, eventually resulting in death due to pericardial tamponade. Because of the complex operation in revascularization of chronic total occlusion (CTO-PCI) lesion, the incidence of pericardial tamponade increases. Usually, we use coronary angiogram to identify the rupture of coronary artery after PCI by the contrast agent. We presented a 67-year-old woman with pericardial tamponade after CTO revascularization. She had chest pain and out of breath for nearly two years. The coronary angiogram showed three branch lesion and CTO lesion of the right coronary artery (RCA). After revascularization of the RCA CTO lesion, the pericardial effusion and low blood pressure occurred, but we didn't find the leak of contrast agents during the final angiography. Then the patient was transferred to cardiac surgery department for emergency thoracotomy. They found the hematoma on the surface of the RCA and finally discharged without any symptoms. Our case approved: (I) there was still the possibility of coronary artery rupture even the coronary angiogram showed no contrast agent leakage from the coronary artery after PCI; (II) the combined use of IVUS and coronary angiogram may improve the accuracy and safety of CTO revascularization procedure.

Genetic risk of clozapine-induced leukopenia and neutropenia: a genome-wide association study.

BACKGROUND: Clozapine is considered to be the most effective antipsychotic medication for schizophrenia. However, it is associated with several adverse effects such as leukopenia, and the underlying mechanism has not yet been fully elucidated. The authors performed a genome-wide association study (GWAS) in a Chinese population to identify genetic markers for clozapine-induced leukopenia (CIL) and clozapine-induced neutropenia (CIN). METHODS: A total of 1879 patients (225 CIL cases, including 43 CIN cases, and 1,654 controls) of Chinese descent were included. Data from common and rare single nucleotide polymorphisms (SNPs) were tested for association. The authors also performed a trans-ancestry meta-analysis with GWAS results of European individuals from the Clozapine-Induced Agranulocytosis Consortium (CIAC). RESULTS: The authors identified several novel loci reaching the threshold of genome-wide significance level (P < 5 × 10-8). Three novel loci were associated with CIL while six were associated with CIN, and two T cell related genes (TRAC and TRAT1) were implicated. The authors also observed that one locus with evidence close to genome-wide significance (P = 5.08 × 10-8) was near the HLA-B gene in the major histocompatibility complex region in the trans-ancestry meta-analysis. CONCLUSIONS: The associations provide novel and valuable understanding of the genetic and immune causes of CIL and CIN, which is useful for improving clinical management of clozapine related treatment for schizophrenia. Causal variants and related underlying molecular mechanisms need to be understood in future developments.

Cigarette smoking and schizophrenia: Mendelian randomisation study.

BACKGROUND: The link between schizophrenia and cigarette smoking has been well established through observational studies. However, the cause-effect relationship remains unclear. AIMS: We conducted Mendelian randomisation analyses to assess any causal relationship between genetic variants related to four smoking-related traits and the risk of schizophrenia. METHOD: We performed a two-sample Mendelian randomisation using summary statistics from genome-wide association studies (GWAS) of smoking-related traits and schizophrenia (7711 cases, 18 327 controls) in East Asian populations. Single nucleotide polymorphisms (SNPs) correlated with smoking behaviours (smoking initiation, smoking cessation, age at smoking initiation and quantity of smoking) were investigated in relation to schizophrenia using the inverse-variance weighted (IVW) method. Further sensitivity analyses, including Mendelian randomisation-Egger (MR-Egger), weighted median estimates and leave-one-out analysis, were used to test the consistency of the results. RESULTS: The associated SNPs for the four smoking behaviours were not significantly associated with schizophrenia status. Pleiotropy did not inappropriately affect the results. CONCLUSIONS: Cigarette smoking is a complex behaviour in people with schizophrenia. Understanding factors underlying the observed association remains important; however, our findings do not support a causal role of smoking in influencing risk of schizophrenia.

Body Mass Index and Polycystic Ovary Syndrome: A 2-Sample Bidirectional Mendelian Randomization Study.

BACKGROUND: Observational studies have shown a link between elevated body mass index (BMI) and the risk of polycystic ovary syndrome (PCOS). While Mendelian randomization (MR) studies in Europeans have suggested a causal role of increased BMI in PCOS, whether the same role is suggested in Asians has yet to be investigated. We used MR studies to infer causal effects using genetic data from East Asian populations. METHODS AND FINDINGS: We performed a 2-sample bidirectional MR analysis using summary statistics from genome-wide association studies (GWAS) of BMI (with up to 173 430 individuals) and PCOS (4386 cases and 8017 controls) in East Asian populations. Seventy-eight single nucleotide polymorphisms (SNPs) correlated with BMI were selected as genetic instrumental variables to estimate the causal effect of BMI on PCOS using the inverse-variance weighted (IVW) method. To test the reliability of the results, further sensitivity analyses included MR-Egger regression, weighted median estimates, and leave-one-out analysis. The IVW analysis indicated a significant association between high BMI and the risk of PCOS (odds ratio per standard deviation higher BMI, 2.208; 95% confidence interval 1.537 to 3.168, P = 1.77 × 10-5). In contrast, the genetic risk of PCOS had no significant effect on BMI. CONCLUSIONS: The results of our bidirectional MR study showed that an increase in BMI causes PCOS, while PCOS does not cause an increased BMI. This study provides further genetic support for a link between BMI and PCOS. Further research is needed to interpret the potential mechanisms of this association.

Toward universal human papillomavirus vaccination for adolescent girls in Hong Kong: a policy analysis.

Studies have assessed early population-level impact of human papillomavirus (HPV) vaccination programs for preventing cervical cancer. Through a case study in Hong Kong we examined stakeholder engagement and interactions to promote a universal HPV vaccination program using the Health Policy Triangle framework for structured health policy analysis. Using data from a document review and semi-structured in-depth interviews, we used thematic and stakeholder analyses to describe the process of policy formation. Given Hong Kong's political and health system, and a mix of Chinese and Western values, stakeholders judged legitimacy of the process differently. We discuss their varied ethical stances and the role of research evidence for informing policy-making. For effective HPV vaccination policy and promotion of universal free HPV vaccination among adolescent girls, new strategies are needed to broaden acceptance of the process, to frame policies in terms of facts and values, and to connect research to policy-making and improve coalition-building.

Taurine protects against cardiac dysfunction induced by pressure overload through SIRT1-p53 activation.

BACKGROUND: Heart failure (HF) is an epidemic disease with increased incidence annually. It has been reported that taurine can improve cardiac function. This study investigated the cardioprotective effects of taurine in pressure-loaded HF mice and elucidated the possible mechanism. METHODS: HF models were established by transverse aortic constriction (TAC). Animals were treated with either taurine for 9 weeks and/or the SIRT1 inhibitor EX527 (5 mg/kg/day, every 2days) after TAC operation. Cardiac function and geometry were revealed by echocardiography. Myocardial hypertrophy and fibrosis were assessed using Fluorescent wheat germ agglutinin (WGA) staining and Masson's trichrome staining. Western blot and RT-PCR were performed to elucidate the expression of target proteins and genes respectively. Apoptosis in cardiomyocytes was detected by TUNEL staining. Myocardial oxidative stress was assessed by detecting the concentration of myocardial super oxidative dismutase (SOD) and malonyldialdehyde (MDA) and reactive oxygen species (ROS). Taurine concentrations and NAD+/NADH ratio were determined by taurine and NAD+/NADH assay kit. RESULTS: Taurine notably relieved cardiac dysfunction after TAC. The mechanisms were attributed to reduced myocyte hypertrophy and fibrosis, and alleviated apoptosis and oxidative stress. Meanwhile, taurine increased NAD+/NADH ratio，promoted the expression of SIRT1 and suppressed p53 acetylation. However, EX-527(inhibitor of SIRT1) decreased NAD+/NADH ratio and increased acetyl-p53 levels, and abolished the cardioprotective effects of taurine on mice subjected to TAC and increased apoptosis and oxidative stress. CONCLUSION: The mechanism responsible for cardiac-protective effects of taurine in HF induced by pressure overload is associated with the activation of the SIRT1-p53 pathway.

The feasibility of universal HPV vaccination program in Shenzhen of China: a health policy analysis.

BACKGROUND: HPV vaccination for the prioritized adolescent girls is well accepted and implemented in developed countries as an effective measure for cervical cancer prevention and control with increasing population-level effectiveness evidence accumulated. This study is to assess the feasibility of universal HPV vaccination among adolescent girls to inform strategies to manage political dimensions of policy-making process in Shenzhen, China, offering insights for other low- and middle-income countries undergoing HPV vaccine introduction. METHODS: Document review and in-depth interviews with identified stakeholders were conducted. The framework of Health Policy Triangle was adapted to guide data collection and analysis in terms of context, actors, process and content. Stakeholder analysis examining actors' position, power, role and interest and thematic analysis focusing on data coding and theme development were used. RESULTS: Shenzhen's contextual factors include legislative authority under a unitary political system, economic developments and cultural values on immunization and sexuality. Stakeholders' position and power could be explained by their role and interest in the Top-down health administration. Mothers could be potential bystanders if having little knowledge on HPV vaccination. Themes in policy-making process were problem definition, advocacy activities to promote HPV vaccination, HPV vaccine demand and access, the role of media and political attention on evidence-informed policy-making in Shenzhen. These stakeholders also discussed different aspects of program planning prospectively. CONCLUSIONS: Shenzhen witnesses a possibility of demonstration projects for local government's horizontal accountability but no potential advocates were identified at local level for fragmented organization of public health facilities and health professionals' lacking mobilization skills. A cervical cancer prevention expert could be a policy entrepreneur. Despite of these challenges, the recommendations to enhance the feasibility include multi-participation to engage non-governmental organizations, pharmaceuticals, target girls and their mothers, power enforcement along governing system, as well as better use of the media.

Effect of biochar origin and soil type on the greenhouse gas emission and the bacterial community structure in N fertilised acidic sandy and alkaline clay soil.

Soil amendment with biochar has received increased attention because of its potential to i) sequester carbon and ii) reduce N2O emission when applied to N fertilised soils. To study the effect of biochar origin on greenhouse gas emission in two contrasting soil types, we used a robotized continuous flow incubation system and δ13C stable isotope approach to compare four biochar types (feed stock: olive mill, corn cob, pistachio shell, cotton stalk) in an alkaline clay soil and two selected biochar types (feed stock: olive mill and corn cob) in an acidic sandy soil. Furthermore, high-throughput sequencing of 16S rRNA genes was performed at the end of the incubation to investigate the effect of different biochars on bacterial community structure in the two different soils. In the alkaline clay soil, all biochar types in conjunction with N fertiliser decreased CO2 emissions up to 12% compared to the N added control treatment causing negative priming, whereas no significant effect of biochar addition on N2O emissions was observed. In contrast, application of olive mill biochar to the acidic sandy soil significantly increased soil pH, CO2, and N2O fluxes, whereas no significant effect of corn cob biochar addition was observed. There was a significant linear relationship between the biochar induced increase in soil pH and the biochar induced increase in soil born N2O emission. Additionally, we detected a clear variation in bacterial community structure in the acidic sandy soil (phyla Acidobacteria, Nitrospirare, and Arthrobacter) with the olive mill biochar addition. Overall, the amendment of different biochars failed to mitigate N2O emissions in both soil types when mineral fertiliser was added. Furthermore, amendment of olive mill biochar stimulated both N2O and CO2 emissions in the low pH sandy soil and altered the bacterial community structure, which was possibly related to its liming effect.

Sphingosine 1-phosphate promotes mesenchymal stem cell-mediated cardioprotection against myocardial infarction via ERK1/2-MMP-9 and Akt signaling axis.

AIMS: The sphingolipid metabolite sphingosine 1­phosphate (S1P) has emerged as a potential cardioprotective molecule against ischemic heart disease. Moreover, S1P triggers mobilization and homing of bone marrow-derived stem/progenitor cells into the damaged heart. However, it remains elusive whether S1P promotes mesenchymal stem cells (MSCs)-mediated cardioprotection against ischemic heart diseases. MAIN METHODS: Adipose tissue-derived MSCs (AT-MSCs) were obtained from GFP transgenic mice or C57BL/6J. Myocardial infarction (MI) was induced in C57BL/6J mice by ligation of the left anterior descending coronary artery (LAD). Subsequently, S1P-treated AT-MSCs or vehicle-treated AT-MSCs were intravenously administered for 24 h after induction of MI or sham procedure. KEY FINDINGS: Pre-conditioning with S1P significantly enhanced the migratory and anti-apoptotic efficacies of AT-MSCs. In MI-induced mice, intravenous administration of S1P-treated AT-MSCs significantly augmented their homing and engraftment in ischemic area. Besides, AT-MSCs with S1P pre-treatment exhibited enhanced potencies to inhibit cardiomyocyte apoptosis and fibrosis, and stimulate angiogenesis and preserve cardiac function. Mechanistic studies revealed that S1P promoted AT-MSCs migration through activation of ERK1/2-MMP-9, and protected AT-MSCs against apoptosis via Akt activation. Further, S1P activated the ERK1/2 and Akt via S1P receptor 2 (S1PR2), but not through S1PR1. S1PR2 knockdown by siRNA, however, significantly attenuated S1P-mediated AT-MSCs migration and anti-apoptosis. SIGNIFICANCE: The findings of the present study revealed the protective efficacies of S1P pretreatment on the survival/retention and cardioprotection of engrafted MSCs. Pre-conditioning of donor MSCs with S1P is an effective strategy to promote the therapeutic potential of MSCs for ischemic heart diseases.

Lysinibacillus alkaliphilus sp. nov., an extremely alkaliphilic bacterium, and emended description of genus Lysinibacillus.

A novel aerobic, alkaliphilic, Gram-staining-positive, endospore-forming bacterium, strain OMN17T, was isolated from a typical sandy loam soil under long-term OMN fertilization (half organic manure N plus half mineral N fertilizer) in northern China and was subjected to a polyphasic taxonomic study. The best growth was achieved at 30 °C and pH 8-10 in medium containing 0.5% (w/v) NaCl. The cell-wall peptidoglycan of strain OMN17T was type A4α; (l-Lys-Gly-d-Asp) and the cell-wall sugars were ribose, traces of galactose and arabinose. The only respiratory quinone found in strain OMN17T was menaquinone 7 (MK-7). The major cellular fatty acids were iso-C15 : 0 and anteiso-C15 : 0. The major polar lipids were found to be phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. Phylogenetic analysis of strain OMN17T based on the 16S rRNA gene sequence showed that the strain was most closely related to Lysinibacillus halotolerans (97.8%), Lysinibacillus sinduriensis (97.5%), Lysinibacillus chungkukjangi (97.4%) and Lysinibacillus xylanilyticus (97.0%). The DNA-DNA hybridization results indicated that this strain was distinct from other species of the genus Lysinibacillus, the degree of relatedness being 21.8 ± 0.2% with L. halotolerans, 45.6 ± 1.8% with L. sinduriensis, 33.7 ± 1.2% with L. chungkukjangi and 23.7 ± 0.7% with L. xylanilyticus. The DNA G+C content of strain OMN17T was 38.1 mol%. The phenotypic, chemotaxonomic and genetic analyses identified strain OMN17T as a novel species of the genus Lysinibacillus, for which the name Lysinibacillus alkaliphilus sp. nov. is proposed. The type strain is OMN17T ( = DSM 28019T = CCTCC AB 2014073T). An emended description of the genus Lysinibacillus is also provided.

Bacillus fengqiuensis sp. nov., isolated from a typical sandy loam soil under long-term fertilization.

A Gram-staining-positive, endospore-forming, moderately alkaliphilic bacterium, strain NPK15(T), was isolated from a typical sandy loam soil under long-term NPK fertilization in northern China and was subjected to a polyphasic taxonomic study. The diamino acid of the cell-wall peptidoglycan of strain NPK15(T) was found to be meso-diaminopimelic acid and the cell-wall sugars were xylose, glucose and traces of mannose. The only respiratory quinone found in strain NPK15(T) was menaquinone 7 (MK-7). The major cellular fatty acids were iso-C(15 : 0), anteiso-C(15 : 0), C(16 : 0) and C(16 : 1)ω6c/C(16 : 1)ω7c. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol. Phylogenetic analysis of the strain based on its 16S rRNA gene sequence showed that it was related most closely to 'Bacillus thaonhiensis' KACC 17216 (99.59%), B. songklensis KCTC 13881(T) (99.52%) and B. abyssalis CCTCC AB 2012074(T) (99.00%). DNA-DNA hybridization results indicated that the strain was distinct from other species of the genus Bacillus, the degree of relatedness being 35.4% with B. abyssalis CCTCC AB 2012074(T), 39.7% with B. songklensis KCTC 13881(T) and 51.2% with 'B. thaonhiensis' KACC 17216. The DNA G+C content of strain NPK15(T) was 45.5 mol%. Phenotypic, chemotaxonomic and molecular analyses identified strain NPK15(T) as a member of a novel species of the genus Bacillus, for which the name Bacillus fengqiuensis sp. nov. is proposed. The type strain is NPK15(T) ( = DSM 26745(T) = CCTCC AB 2013156(T)).

Meta-analysis: the relationship between TNF-alpha polymorphisms and susceptibility to primary biliary cirrhosis.

BACKGROUND/AIMS: To investigate the possible influence of TNF-α gene promoter polymorphisms in conferring a predisposition to PBC patients. METHODOLOGY: We performed a meta-analysis of nine articles searched from PubMed up to July 2010 that investigated the association between two TNF-α polymorphisms (-308 and -238) and PBC. RESULTS: The data showed no significant association between TNF-α-308, -238 gene polymorphisms and the susceptibility to PBC in the global group (OR=0.95, 95%CI=0.80-1.13, p=0.55; OR=1.00, 95%CI=0.65-1.55, p=0.99, respectively). Stratified by sub-groups (European, American, Asian), TNF -308 minor allele, but not -238, was found to be a protective factor in the European population (OR= 0.81, 95%CI=0.67-0.99, p=0.04; OR=0.99, 95%CI=0.55-1.77, p=0.97, respectively). Moreover, no significant difference was observed between TNF-α-308 alleles and PBC when stratified by histological stages (stages I-II, OR=0.68, 95%CI=0.32-1.48, p=0.33; stages III-IV, OR=0.69, 95%CI=0.41-1.15, p=0.15). CONCLUSIONS: TNF-α promoter polymorphisms might not be associated with PBC risk. However, studies with larger population of varying ethnicity and stratified by clinical and laboratory characteristics are needed to validate our findings.