Characteristics of phenotypic antibiotic resistance of Helicobacter pylori and its correlation with genotypic antibiotic resistance: A retrospective study in Ningxia.

BACKGROUND: Geographic differences exist in the antibiotic resistance patterns of Helicobacter pylori. Personalized treatment regimens based on local or individual resistance data are essential. We evaluated the current status of H. pylori resistance in Ningxia, analyzed resistance-related factors, and assessed the concordance of phenotypic and genotypic resistance. METHODS: Strains were isolated from the gastric mucosa of patients infected with H. pylori in Ningxia and relevant clinical information was collected. Phenotypic antibiotic susceptibility assays (Kirby-Bauer disk diffusion) and antibiotic resistance gene detection (Sanger sequencing) were performed. RESULTS: We isolated 1955 H. pylori strains. The resistance rates of H. pylori to amoxicillin, levofloxacin, clarithromycin, and metronidazole were 0.9%, 42.4%, 40.4%, and 94.2%, respectively. Only five tetracycline-resistant and one furazolidone-resistant strain were identified. Overall, 3.3% of the strains were sensitive to all six antibiotics. Multidrug-resistant strains accounted for 22.9%, of which less than 20% were from Wuzhong. Strains isolated from women and patients with nonulcerative disease had higher rates of resistance to levofloxacin and clarithromycin. Higher rates of resistance to metronidazole, levofloxacin, and clarithromycin were observed in the older age group than in the younger age group. The kappa coefficients of phenotypic resistance and genotypic resistance for levofloxacin and clarithromycin were 0.830 and 0.809, respectively, whereas the remaining antibiotics showed poor agreement. CONCLUSION: H. pylori antibiotic resistance is severe in Ningxia. Therefore, furazolidone, amoxicillin, and tetracycline are better choices for the empirical therapy of H. pylori infection in this region. Host sex, age, and the presence of ulcerative diseases may affect antibiotic resistance of the bacteria. Personalized therapy based on genetic testing for levofloxacin and clarithromycin resistance may be a future direction for the eradication therapy of H. pylori infection in Ningxia.

Predictors of psychological resilience trajectories in patients with knee arthroplasty: A longitudinal study.

AIMS: To identify the different classes of total knee arthroplasty patients according to the heterogenous trajectories of psychological resilience and investigate the predictors for different patterns of resilience. DESIGN: A prospective cohort study. METHODS: A total of 210 patients with total knee arthroplasty from March to December 2021 were included. Baseline assessment (T0) data were collected before surgery and included demographic, biological (clinical characteristics), psychological (psychological resilience, self-efficacy, psychological distress, hope, medical coping mode) and social (social support) factors. Resilience measurements were repeated at 3 days after surgery (T1), the date of discharge (T2), and 1 month (T3) and 3 months (T4) after discharge. Latent growth mixture modelling was employed to define different resilience trajectories. Predictors of class membership were identified using multinomial logistic regression. RESULTS: Data from 198 patients were analysed. Three latent classes were identified with similar patterns in different intercepts, showing a significant decrease in resilience from admission (T0) to 3 days after surgery (T1) followed by an increase from T1 to T4. The three trajectories of psychological resilience were named the stable-resilience class (65.66%), high-resilience class (17.68%), and low-resilience class (16.66%). Multinomial logistic regression showed that compared with the stable-resilience class, the high-resilience class was predicted by having a higher level of hope, having higher education, living in urban areas and having more children, while the low-resilience class was predicted by having lower levels of self-efficacy and hope, living in semirural areas, and having more children. CONCLUSIONS: The three trajectories indicated that surgery was the major stressor influencing patients' psychological resilience and that patients in the low-resilience class needed to be intervened. IMPACT: Predictors of patients in different classes provide evidence for the identification of vulnerable populations and lay a foundation for future research contributing to the development of targeted interventions for improving patients' psychological resilience. No patient or public contribution but the time points of investigation were decided based on our interviews with 12 total knee arthroplasty patients.

Light-dependent activation of HY5 promotes mycorrhizal symbiosis in tomato by systemically regulating strigolactone biosynthesis.

Light quality affects mutualisms between plant roots and arbuscular mycorrhizal fungi (AMFs), which modify nutrient acquisition in plants. However, the mechanisms by which light systemically modulates root colonization by AMFs and phosphate uptake in roots remain unclear. We used a range of approaches, including grafting techniques, protein immunoblot analysis, electrophoretic mobility shift assay, chromatin immunoprecipitation, and dual-luciferase assays, to unveil the molecular basis of light signal transmission from shoot to root that mediates arbuscule development and phosphate uptake in tomato. The results show that shoot phytochrome B (phyB) triggers shoot-derived mobile ELONGATED HYPOCOTYL5 (HY5) protein accumulation in roots, and HY5 further positively regulates transcription of strigolactone (SL) synthetic genes, thus forming a shoot phyB-dependent systemic signaling pathway that regulates the synthesis and accumulation of SLs in roots. Further experiments with carotenoid cleavage dioxygenase 7 mutants and supplementary red light confirm that SLs are indispensable in the red-light-regulated mycorrhizal symbiosis in roots. Our results reveal a phyB-HY5-SLs systemic signaling cascade that facilitates mycorrhizal symbiosis and phosphate utilization in plants. The findings provide new prospects for the potential application of AMFs and light manipulation to effectively improve nutrient utilization and minimize the use of chemical fertilizers and associated pollution.

Fucoxanthin treatment inhibits nasopharyngeal carcinoma cell proliferation through induction of autophagy mechanism.

Nasopharyngeal carcinoma (NPC) arises from the epithelium of the nasopharyngeal mucosa. Elderly people above the age of 65 years are more susceptible to NPC. Nasopharyngectomy is the renowned treatment procedure to NPC; however, it is too risky due to its complicated surgical procedure. Other treatment methods also reported with serious side effects such brain injury; hence, the alternative anticancer drug without any side effects was needed. Fucoxanthin is a carotenoid derived from marine algae with the numerous pharmacological functions. This study aims to examine the inhibitory potential in NPC cell proliferation via apoptosis and autophagy. The cytotoxicity of fucoxanthin on C666-1 cells was observed by the MTT assay. The expression of autophagy-linked proteins was assessed with immunoblotting analysis. The expression of autophagy protein LC3 was estimated using immunocytochemical analysis in C666-1 and GFP-LC3 transfected cells. Furthermore, the fucoxanthin-treated C666-1 cells were analyzed with TUNEL assay. The apoptotic level in the fucoxanthin-treated C666-1 cells was evaluated using acridine orange staining. Fucoxanthin significantly increased the expression of autophagy-linked proteins which is clearly depicted in the immunoblotting analysis and immunocytochemical analysis of GFP-tagged LC3 protein. The results of TUNEL assay of fucoxanthin-treated C666-1 in the presence autophagy inhibitors demonstrated the induction of autophagy by fucoxanthin. Acridine orange staining results of C666-1 confirmed fucoxanthin decreases the expression of autophagy-linked proteins during stressed condition thereby causes apoptosis. Our overall results authentically conclude that fucoxanthin induces autophagy and apoptosis in NPC cell line, and it can be ideal agent to treat nasopharyngeal cancer in future with further investigations.

A novel CO2 -responsive systemic signaling pathway controlling plant mycorrhizal symbiosis.

Elevated atmospheric carbon dioxide (eCO2 ) concentrations promote symbiosis between roots and arbuscular mycorrhizal fungi (AMF), modifying plant nutrient acquisition and cycling of carbon, nitrogen and phosphate. However, the biological mechanisms by which plants transmit aerial eCO2 cues to roots, to alter the symbiotic associations remain unknown. We used a range of interdisciplinary approaches, including gene silencing, grafting, transmission electron microscopy, liquid chromatography tandem mass spectrometry (LC-MS/MS), biochemical methodologies and gene transcript analysis to explore the complexities of environmental signal transmission from the point of perception in the leaves at the apex to the roots. Here we show that eCO2 triggers apoplastic hydrogen peroxide (H2 O2 )-dependent auxin production in tomato shoots followed by systemic signaling that results in strigolactone biosynthesis in the roots. This redox-auxin-strigolactone systemic signaling cascade facilitates eCO2 -induced AMF symbiosis and phosphate utilization. Our results challenge the current paradigm of eCO2 effects on AMF and provide new insights into potential targets for manipulation of AMF symbiosis for high nutrient utilization under future climate change scenarios.

Genome-Wide Association and Functional Studies Identify SCML4 and THSD7A as Novel Susceptibility Genes for Coronary Artery Disease.

OBJECTIVE: The genetic contribution to coronary artery disease (CAD) remains largely unclear. We combined genetic screening with functional characterizations to identify novel loci and candidate genes for CAD. APPROACH AND RESULTS: We performed genome-wide screening followed by multicenter validation in 8 cohorts consisting of 21 828 participants of Han ethnicity and identified 3 novel intragenic SNPs (single nucleotide polymorphisms), rs9486729 (SCML4 [Scm polycomb group protein-like 4]; odds ratio, 1.25; 95% CI, 1.17-1.34; P=3.51×10-11), rs17165136 (THSD7A [thrombospondin type 1 domain-containing 7A]; odds ratio 1.28; 95% CI, 1.21-1.35; P<1.00×10-25), and rs852787 (DAB1 [disabled-1]; odds ratio, 1.29; 95% CI, 1.21-1.38; P=2.02×10-14), associated with CAD with genome-wide significance. The risk allele of rs9486729 and protective allele of rs17165136 were associated with the decreased expression of their host genes, SCML4 and THSD7A, respectively, whereas rs852787 did not have transcriptional effects on any gene. Knockdown of SCML4 activated endothelial cells by increasing the expression of IL-6, E-selectin, and ICAM and weakened their antiapoptotic activity, whereas the knockdown of THSD7A had little effect on these endothelial cell functions but attenuated monocyte adhesion via decreasing the expression of ICAM, L-selectin, and ITGB2. We further showed that inhibiting the expression of SCML4 exacerbated endothelial dysfunction and vascular remodeling in a rat model with partial carotid ligation. CONCLUSIONS: We identify 3 novel loci associated with CAD and show that 2 genes, SCML4 and THSD7A, make functional contributions to atherosclerosis. How rs852787 and its host gene DAB1 are linked to CAD needs further studies.

The bZip transcription factor HY5 mediates CRY1a-induced anthocyanin biosynthesis in tomato.

The production of anthocyanin is regulated by light and corresponding photoreceptors. In this study, we found that exposure to blue light and overexpression of CRY1a are associated with increased accumulation of anthocyanin in tomato (Solanum lycopersicum L.). These responses are the result of changes in mRNA and the protein levels of SlHY5, which is a transcription factor. In vitro and in vivo experiments using electrophoretic mobility shift assay and ChIP-qPCR assays revealed that SlHY5 could directly recognize and bind to the G-box and ACGT-containing element in the promoters of anthocyanin biosynthesis genes, such as chalcone synthase 1, chalcone synthase 2, and dihydroflavonol 4-reductase. Silencing of SlHY5 in OE-CRY1a lines decreased the accumulation of anthocyanin. The findings presented here not only deepened our understanding of how light controls anthocyanin biosynthesis and associated photoprotection in tomato leaves, but also allowed us to explore potential targets for improving pigment production.

A novel block at chromosome 12q24.1 is associated with coronary artery disease in Han Chinese populations.

OBJECTIVE: The aim of this study was to refine the chromosomal region 12q24.1 associated with coronary artery disease in Han Chinese populations. METHODS AND RESULTS: Twenty tagging single nucleotide polymorphisms covering 1.2 Mb of chromosomal 12q24.1 were selected and genotyped in three geographically isolated case-control populations consisting of 7076 coronary artery disease (CAD) patients and non-CAD participants. In addition to replication of the previous block (block 1), we identified a novel block (block 2) associated with CAD. In a combined analysis, the odds ratio (95% confidence interval, permuted P value) were 0.79 (0.72-0.86, 8.358×10) and 1.24 (1.13-1.36, 2.576×10) for haplotypes ATGGG and GCACA in block 1 and 1.22 (1.14-1.30, 6.484×10) and 0.82 (0.77-0.88, 6.484×10) for haplotypes GA and AG in block 2, respectively. Protective alleles of two index single nucleotide polymorphisms decreased the expression of NAA25 (P=0.034), but did not alter the expression of other genes within block 2. CONCLUSION: We identified a novel block associated with CAD at chromosomal 12q24.

Adipose tissue reconstruction facilitated with low immunogenicity decellularized adipose tissue scaffolds.

There is currently an urgent need to develop engineered scaffolds to support new adipose tissue formation and facilitate long-term maintenance of function and defect repair to further generate prospective bioactive filler materials capable of fulfilling surgical needs. Herein, adipose regeneration methods were optimized and decellularized adipose tissue (DAT) scaffolds with good biocompatibility were fabricated. Adipose-like tissues were reconstructed using the DAT and 3T3-L1 preadipocytes, which have certain differentiation potential, and the regenerative effects of the engineered adipose tissuesin vitroandin vivowere explored. The method improved the efficiency of adipose removal from tissues, and significantly shortened the time for degreasing. Thus, the DAT not only provided a suitable space for cell growth but also promoted the proliferation, migration, and differentiation of preadipocytes within it. Following implantation of the constructed adipose tissuesin vivo, the DAT showed gradual degradation and integration with surrounding tissues, accompanied by the generation of new adipose tissue analogs. Overall, the combination of adipose-derived extracellular matrix and preadipocytes for adipose tissue reconstruction will be of benefit in the artificial construction of biomimetic implant structures for adipose tissue reconstruction, providing a practical guideline for the initial integration of adipose tissue engineering into clinical medicine.

Transition in metabolic health phenotypes across general adiposity categories and association with the risk of depression: a prospective analysis.

BACKGROUND: The association between obesity and depression may partly depend on the contextual metabolic health. The effect of change in metabolic health status over time on subsequent depression risk remains unclear. We aimed to assess the prospective association between metabolic health and its change over time and the risk of depression across body mass index (BMI) categories. METHODS: Based on a nationally representative cohort, we included participants enrolled at the wave 2 (2004-2005) of the English Longitudinal Study of Ageing and with follow-up for depression at wave 8 (2016-2017). Participants were cross-classified by BMI categories and metabolic health (defined by the absence of hypertension, diabetes, and hypercholesterolemia) at baseline or its change over time (during waves 3-6). Logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of depression at follow-up stratified by BMI category and metabolic health status with adjustment for potential confounders. RESULTS: The risk of depression was increased for participants with metabolically healthy obesity compared with healthy nonobese participants, and the risk was highest for those with metabolically unhealthy obesity (OR 1.62, 95% CI 1.18-2.20). Particularly hypertension and diabetes contribute most to the increased risk. The majority of metabolically healthy participants converted to unhealthy metabolic phenotype (50.1% of those with obesity over 8 years), which was associated with an increased risk of depression. Participants who maintained metabolically healthy obesity were still at higher risk (1.99, 1.33-2.72), with the highest risk observed for those with stable unhealthy metabolic phenotypes. CONCLUSIONS: Obesity remains a risk factor for depression, independent of whether other metabolic risk factors are present or whether participants convert to unhealthy metabolic phenotypes over time. Long-term maintenance of metabolic health and healthy body weight may be beneficial for the population mental well-being.

Construction of engineered 3D islet micro-tissue using porcine decellularized ECM for the treatment of diabetes.

Islet transplantation improves diabetes patients' long-term blood glucose control, but its success and utility are limited by cadaver availability, quality, and considerable islet loss after transplantation due to ischemia and inadequate angiogenesis. This study used adipose, pancreatic, and liver tissue decellularized extracellular matrix (dECM) hydrogels in an effort to recapitulate the islet sites inside the pancreas in vitro, and successfully generated viable and functional heterocellular islet micro-tissues using islet cells, human umbilical vein endothelial cells, and adipose-derived mesenchymal stem cells. The three-dimensional (3D) islet micro-tissues maintained prolonged viability and normal secretory function, and showed high drug sensitivity in drug testing. Meanwhile, the 3D islet micro-tissues significantly enhanced survival and graft function in a mouse model of diabetes. These supportive 3D physiomimetic dECM hydrogels can be used not only for islet micro-tissue culture in vitro, but also have great promise for islet transplantation for the treatment of diabetes.

Integrating CVOR-GWLR-Circuit model into construction of ecological security pattern in Yunnan Province, China.

In the traditional construction of ecological security pattern, the minimum cost path is extracted as the ecological corridor based on the minimum cumulative resistance model, and the ecological nodes are identified manually. This method lacks the consideration of the exchange process of energy flow and information flow in the ecological process, resulting in a certain lack of ecological security pattern in structure and function. Therefore, an ecological security pattern construction method integrating CVOR-GWLR-Circuit model is proposed to solve the above problems by transforming natural background data into localized correction variables and adding them to the ecological security pattern evaluation model. Taking Yunnan Province as an example, firstly, the ecological security evaluation system of "Contribution, Vigor, Organization, Resilience" (CVOR) is constructed based on the importance of ecosystem services and ecosystem health, and the ecological security of Yunnan Province in 2020 is evaluated, and the ecological source areas are identified combined with nature reserves. Then, the ecological resistance surface was constructed by considering land use data and topographic factors, and the landslide sensitivity evaluation model was constructed based on geographically weighted logistic regression model (GWLR) to correct the basic resistance surface. Finally, the circuit theory model is used to extract the ecological corridor and construct the ecological security pattern in Yunnan Province. The ecological pinch points and barriers in the ecological corridor are diagnosed by the current density, so as to identify the width of the ecological corridor and identify the key areas of ecological protection and restoration. The results showed that the ecological sources area of Yunnan Province was about 69,417.78 km2, accounting for 17.6% of the total area of the study area, mainly distributed in Dehong Prefecture, southwest Yunnan, Diqing Prefecture and Nujiang Prefecture in northwest Yunnan. A total of 780 ecological corridors were generated between the ecological sources, with a total length of about 197,598.2 km, an average length of 253.3 km, and the longest path length of 932.1 km. The ecological corridors are "spider web", linking southwest, northwest, northeast, central and southeast Yunnan Province. 36 ecological pinch points and 42 ecological barriers were identified. The research results verify that the ecological security pattern constructed by integrated CVOR-GWLR-Circuit model is more reasonable, which can provide scientific basis for regional ecological protection planning and ecological corridors design.

Study on the threshold relationship between landscape pattern and water quality considering spatial scale effect-a case study of Dianchi Lake Basin in China.

It is of great significance to analyze the threshold relationship between landscape pattern and water quality for watershed water environment treatment. However, previous studies did not consider the influence of spatial scale on threshold. Therefore, this study proposed the idea of the relationship between landscape pattern and water quality threshold considering the spatial scale effect to solve the above problems. Firstly, the percentage of landscape composition area under 9 spatial scales (riparian buffer zone and sub-basin) of 20 rivers entering the lake in Dianchi Lake Basin was extracted to identify the optimal spatial scale of landscape pattern and water quality by redundant analysis (RDA). Then, a variety of nonlinear regression models such as power regression, exponential regression, quadratic regression, and segmented regression are used to quantitatively detect the thresholds of landscape pattern and water quality. The results show that (1) the spatial scale has a significant influence on the threshold relationship between landscape pattern and water quality, and the total interpretation rate of landscape pattern on water quality is the largest at the buffer scale of 1100 m riparian zone, which is an effective buffer for river governance. (2) Different spatial scales have different effects on the threshold relationship between landscape pattern and water quality. In the nonlinear regression model of landscape pattern and water quality in the buffer zone of 1100 m riparian zone, the significance and R2 of the equation are better than those of the sub-basin. (3) From the nonlinear relationship between landscape pattern and water quality, it is found that the landscape threshold can be quantitatively identified when the water quality changes abruptly or reaches the I ~ V water quality standard. Among them, the type-1 landscape threshold at the water quality mutation point can be used as the long-term goal of water quality protection in Dianchi Lake Basin, and the type-2 landscape threshold can be used as the short-term goal of water quality adjustment. The research results can provide a scientific basis for the governance of water environment and the rational planning of landscape pattern in Dianchi Lake Basin, and have practical significance for guiding the sustainable development of cities.

Ultrasound-mediated microbubble destruction enhances the efficacy of bone marrow mesenchymal stem cell transplantation and cardiac function.

1. Application of ultrasound (US) to intravascular microbubble (MB) contrast agents causes small capillary ruptures. The purpose of the present study was to examine the effects of US-mediated MB destruction on bone marrow mesenchymal stem cell (BMSC) transplantation into the infarcted myocardium and to evaluate whether this approach could improve cardiac function. 2. Ultrasound was applied to the anterior chest of rabbits after intravenous injection of MB followed by infusion of BMSC. There were four groups investigated: (i) a control group, in which neither US nor MB were used prior to infusion of BMSC; (ii) one group subjected to US alone prior to infusion of BMSC; (iii) another group injected with MB prior to infusion of BMSC; and (iv) a group in which US was applied to MB prior to the infusion of BMSC. Cardiac function was evaluated by echocardiography 24 h and 4 weeks after cell transplantation. All rabbits were killed to enable histological and immunochemical examination. 3. Echocardiography 24 h after infusion of BMSC indicated no difference in cardiac function between any of the groups, as assessed by left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimensions (LVDD), left ventricular systolic diameter (LVSD) and fractional shortening (FS%; all P > 0.05). However, 4 weeks after BMSC transplantation, there was a significant improvement in LVEF in the group subjected to US plus MB compared with the control, US alone and MB alone groups (59.5 +/- 3.5, 52.5 +/- 5.5, 52.8 +/- 5.2 and 51.1 +/- 3.5%, respectively; all P < 0.05). In addition, treatment with US plus MB significantly reduced LVDD and LVSD and increased capillary density in the infarcted area. 4. In conslusion, the results of the present study indicate that using US-mediated MB destruction prior to BMSC transplantation into the infarcted myocardium improves the effectiveness of cardiac cell therapy and cardiac function in rabbits.

[Efficacy comparison with low and high dose nadroparin for patients with acute coronary syndrome underwent percutaneous coronary intervention].

OBJECTIVE: To evaluate the safety and optimal prior percutaneous coronary intervention (PCI) nadroparin dose in patients with acute coronary syndrome (ACS). METHODS: A total of 236 ACS patients were randomly treated with subcutaneously nadroparin 0.075 ml/10 kg (group I, n = 120) and 0.1 ml/10 kg (group II, n = 116) respectively (bid for 48 hours). PCI was the performed 1 h after final nadroparin injection. No additional nadroparin was applied during PCI. Plasmic anti-Xa level was assayed before and at 1, 2, 4 and 8 hours after final nadroparin administration. Adverse clinical events (death, myocardial infarction, need for revascularization) and bleeding events were recorded up to 30 days post PCI. RESULTS: Baseline clinical characteristics as well as the MACE and severe bleeding events between the two groups were similar (all P > 0.05). Plasmic anti-Xa level of group II was significantly higher than that of group I post nadroparin application (P < 0.01). CONCLUSION: Anticoagulation effects and MACE as well as severe bleeding events up to 30 days post PCI were similar with either 0.075 ml/10 kg or 0.1 ml/10 kg nadroparin dose in ACS patients.

Detection of posttrauma apoptosis and necrosis of hepatocytes and its significance.

OBJECTIVE: To study the role of apoptosis and necrosis of hepatocytes in the pathogenesis of acute liver dysfunction following severe trauma in rats. METHODS: Rat models of multiple fractures complicated by shock were established, in which apoptotic and necrotic hepatocytes were detected by flow cytometry (FCM) via double-staining technique of Annexin-V-flous and propidium iodide (PI). Observation of the pathological changes in the hepatocytes was also conducted by means of light and electron microscopy and electronphoresis respectively, and the correlation of these changes with liver function were evaluated. RESULTS: Hepatocytes underwent both apoptosis and necrosis in rat models of severe trauma. The quantities of necrotic hepatocytes increased progressively in positive correlation with the degree of hepatic injury, reaching the peak at 3 h post trauma. A proportion of the apoptotic cells underwent secondary necrosis, the number of the necrotic cells positively correlated with liver dysfunction deterioration. CONCLUSIONS: Both necrosis and apoptosis are important factors responsible for liver function damages following severe trauma. Necrosis of hepatic cells directly causes liver function damages that are further aggravated by secondary necrosis among apoptotic hepatocytes.

STK39 is an independent risk factor for male hypertension in Han Chinese.

BACKGROUND: STK39 interacts with OXSR1 and phosphorylates the sodium-chloride co-transporter (SLC12A3), which plays a critical role in regulating the salt/water balance and blood pressure. Here we tested whether STK39, OXSR1, and SLC12A3 genetically contribute to hypertension in the Han Chinese population and how the SNP to SNP or SNP to other risk factors interacts in the pathogenesis of hypertension. METHODS AND RESULTS: Eleven tagging SNPs from STK39, OXSR1, and SLC12A3 were selected and first genotyped in 1210 hypertensive and healthy individuals by sequencing. Two SNPs of STK39, rs6433027 and rs3754777, were found to be associated with hypertension in males (P=0.008-0.024). All other SNPs were not associated with hypertension in either gender. The association of rs6433027 and rs3754777 with male hypertension was validated by genotyping another 4598 hypertensive and healthy individuals. The odds ratios (95% confidence interval, P value) in males were 1.269 (1.13-1.43; P=0.0001) and 1.231 (1.078-1.41; P=0.004) of rs6433027 and rs3754777, respectively. The allele T of rs6433027 presented a strong epistatic effect on the allele A of rs3754777 in hypertensive trait. The minor allele frequencies of two SNPs were not stratified by age, BMI, or diabetes, the three major risk factors for hypertension. CONCLUSION: Our results suggest that STK39 is an independent risk factor for hypertension in men and that its intragenic SNPs can interact and function in the control of blood pressure.

Fine mapping of chromosome 3q22.3 identifies two haplotype blocks in ESYT3 associated with coronary artery disease in female Han Chinese.

OBJECTIVE: Genome-wide association study recently identified the chromosome 3q22.3 as a novel locus associated with coronary artery disease (CAD). This study was designed to identify the critical haplotype blocks within this region in Han Chinese populations. METHODS: We selected 1920 CAD patients and healthy participants from Han Chinese and genotyped 22 single nucleotide polymorphisms (SNPs) spanning 150 kilobases (kb) chromosomal region flanking rs9818870, a SNP associated with CAD at 3q22.3 in Caucasian. RESULTS: Seven SNPs were found to be strongly associated with CAD in females and clustered in two haplotype blocks of ESYT3 gene. This was validated in two geographically isolated case-control populations. The two blocks were 14 and 25kb long, respectively. In a combined haplotype analysis, the odds ratios (95% confidence interval, permuted P value) were 0.70 (0.58-0.83, 2×10(-5)) and 1.44 (1.20-1.72, 5×10(-5)) for haplotypes TTG and CCA in block 1 as well as 0.73 (0.61-0.87, 3×10(-4)) and 1.35 (1.13-1.62, 0.0013) for haplotypes TCG and CTT in block 2, respectively. ESYT3 was expressed in human lymphocyte, vascular endothelial cell, and smooth muscle cell. The risk factors including gender, obesity, hypertension, diabetes, and hyperlipidemia exhibited strong effects on the genetic contribution to CAD. CONCLUSION: We identified two haplotype blocks of ESYT3 gene in 3q22.3 region that likely harbor functional variants, which cooperate with other risk factors and play a role in the pathogenesis of coronary artery disease in females.

Apoptosis in organs of rats in early stage after polytrauma combined with shock.

OBJECTIVE: Apoptosis in organs of rats in early stage after polytrauma combined with shock was researched. METHODS: Sixty Sprague-Dawley rats were divided into six groups: normal control (A, n = 6), sham-operation (N, n = 6), single hemorrhagic shock (S, n = 6), two-site trauma/shock (B, n = 6), four-site trauma/shock (C, n = 6), and six-site trauma/shock (D, n = 30). Shock was kept 60 min by blood withdrawal. Polytrauma was performed by clamping different sites of limbs to make fractures according to different groups: B at both femurs; C at femurs and tibias; and D at femurs, tibias, and humeri. The animals of A were totally normal without any operation. The rats of N, S, B, and C were killed at 6 hours after resuscitation, and the rats of D were killed at 1, 3, 6, 12, and 24 hours, respectively. Then, DNA agarose gel electrophoresis, in situ end-labeling (ISEL), and light and electron microscopy were performed and the percentage of DNA fragmentation was detected to assess apoptosis. RESULTS: In B, C, and D, the special ladder patterns for apoptosis were seen in thymus, spleen, liver, lung, and intestine, but not in heart, kidney, and brain. However, positive responses were observed in all these eight organs by ISEL. At 6 hours after resuscitation, the percentages of DNA fragmentation in thymus, spleen, liver, lung, and intestine all increased together with the severity of trauma. In D, the percentages of DNA fragmentation in these five organs all increased significantly at 1 hour after resuscitation. At 3 hours, the percentages in spleen, liver, lung, and intestine reached peak, and declined gradually afterward, whereas those in thymus continued increasing after 3 hours and kept stable from 6 hours to 24 hours. It was shown by morphologic examination that the majority of apoptotic cells lay in cortex of thymus, in growth center of white pulp of spleen, in border area of hepatic lobule and portal area of liver, and at the base of crypts of intestine. In lung, multiple kinds of cells, including alveolar epithelial cells, vascular endothelial cells, and polymorphonuclear neutrophils, induced apoptosis. CONCLUSION: Apoptosis was induced in thymus, spleen, liver, lung, and intestine in early stage after polytrauma combined with shock, which may play partial roles in the development of multiple organ failure.