Adjusted Global Antiphospholipid Syndrome Score (aGAPSS) and PLT, APTT: Predictive Value of Thrombotic Risk Assessment in SLE Patients.

BACKGROUND: Risk assessment of vascular thrombosis in SLE patients with the presence of antiphospholipid antibodies (aPL) remains a challenge. The adjusted global antiphospholipid syndrome score (aGAPSS) has been validated and used to predict aPL-related thrombosis in SLE patients in some countries. Relevant data of aGAPSS in thrombotic evaluation in SLE population from China has not been reported. We aim to validate aGAPSS in thrombosis assessment in Chinese patients with SLE and to explore the correlations of aGAPSS with routine laboratory parameters and their clinical significance as well. METHODS: A total of 166 consecutive SLE patients were retrospectively analyzed. Multivariate logistic regression analysis was performed to examine the impact of multiple cardiovascular risk factors and laboratory parameters in recurrent thrombosis risk in SLE. ROC was conducted to explore the discriminative ability of aGAPSS and platelet (PLT), activated partial thromboplastin time (APTT), alone or in combination. RESULTS: Significantly higher value of aGAPSS was seen in SLE patients with vascular thrombosis. ROC curve indicated that aGAPSS of 3.5 or more had the best diagnostic accuracy for the prediction of aPL-related thrombosis in SLE patients. PLT with cutoff of 187.5 x 109/L and APTT with 37.5 seconds were predictors of aPL-related thrombosis as well. The combination of aGAPSS with PLT and APTT improved AUC compared to aGAPSS alone. CONCLUSIONS: The aGAPSS could predict the risk of aPL-related vascular thrombosis in SLE patients from China. The combination of aGAPSS with PLT and APTT was first time proved to have better predictive performance in thrombosis risk assessment in SLE.

Score test for missing at random or not under logistic missingness models.

Missing data are frequently encountered in various disciplines and can be divided into three categories: missing completely at random (MCAR), missing at random (MAR), and missing not at random (MNAR). Valid statistical approaches to missing data depend crucially on correct identification of the underlying missingness mechanism. Although the problem of testing whether this mechanism is MCAR or MAR has been extensively studied, there has been very little research on testing MAR versus MNAR. A critical challenge that is faced when dealing with this problem is the issue of model identification under MNAR. In this paper, under a logistic model for the missing probability, we develop two score tests for the problem of whether the missingness mechanism is MAR or MNAR under a parametric model and a semiparametric location model on the regression function. The implementation of the score tests circumvents the identification issue as it requires only parameter estimation under the null MAR assumption. Our simulations and analysis of human immunodeficiency virus data show that the score tests have well-controlled type I errors and desirable powers.

Interfaces and Oxygen Vacancies-Enriched Catalysts Derived from Cu-Mn-Al Hydrotalcite towards High-Efficient Water-Gas Shift Reaction.

The water-gas shift (WGS) reaction is an important process in the hydrogen industry, and its catalysts are of vital importance for this process. However, it is still a great challenge to develop catalysts with both high activity and high stability. Herein, a series of high-purity Cu-Mn-Al hydrotalcites with high Cu content have been prepared, and the WGS performance of the Cu-Mn-Al catalysts derived from these hydrotalcites have been studied. The results show that the Cu-Mn-Al catalysts have both outstanding catalytic activity and excellent stability. The optimized Cu-Mn-Al catalyst has displayed a superior reaction rate of 42.6 µmolCO-1⋅gcat-1⋅s-1, while the CO conversion was as high as 96.1% simultaneously. The outstanding catalytic activities of the Cu-Mn-Al catalysts could be ascribed to the enriched interfaces between Cu-containing particles and manganese oxide particles, and/or abundant oxygen vacancies. The excellent catalytic stability of the Cu-Mn-Al catalysts may be benefitting from the low valence state of the manganese of manganese oxides, because the low valence manganese oxides have good anti-sintering properties and can stabilize oxygen vacancies. This study provides an example for the construction of high-performance catalysts by using two-dimensional hydrotalcite materials as precursors.

CRP gene polymorphism contributes genetic susceptibility to dyslipidemia in Han Chinese population.

C-reactive protein (CRP), an inflammatory marker that statistically predicts future cardiovascular risk, has been reported to be associated with plasma lipid level changes. Whether CRP genetic variants affect lipid metabolism is of importance to investigate. A community-based study population including 2,731 adult subjects aged 18-62 years was used to evaluate the association of CRP gene with dyslipidemia and five tagging SNPs (tagSNPs) were genotyped. Multiple logistic regression was applied to further evaluate relationships between the SNPs and lipid metabolism abnormality and general linear model was applied to compare plasma lipid levels between genotypes. Association analyses indicated that recessive model of SNPs rs876537 and rs4285692 had significant association with elevated HDL after adjustment for covariates. Odds ratio (OR) of rs876537 were 0.60 for HDL > 1.54 versus 1.04-1.54 mmol/L (P = 0.011), as well as, ORs were 0.617 for HDL > 1.83 versus ≤1.35 mmol/L (P = 0.002) and 0.724 for HDL = 1.59-1.83 versus ≤1.35 mmol/L (P = 0.028) respectively. OR of rs4285692 was 0.634 for HDL > 1.83 versus ≤1.35 mmol/L (P = 0.027). Further stratification analysis found significant associations of rs10737175 with elevated HDL (>1.54 vs. 1.04-1.54 mmol/L, OR 0.629 and P = 0.027) and elevated TG (≥1.70 vs. <1.70 mmol/L, ORs of additive and dominant models were 0.628, 0.545 and P values were 0.006, 0.003 respectively) in female. rs4285692 was significantly associated with elevated LDL (≥3.37 vs. <3.37 mmol/L), ORs equaled to 1.532, 2.281 for additive model and recessive model and P values were 0.028, 0.024 respectively in male. Furthermore, quantitative trait analysis indicated the variation T to C of rs876537 significantly affect decreased plasma HDL level (P = 0.014). Our findings suggest that CRP genetic polymorphisms independently had positive association with the risk of HDL, LDL and TG elevating and further replication in other large population and biological function research would be warranted.

Association study of common variations of FBN1 gene and essential hypertension in Han Chinese population.

Fibrillin-1 (FBN1) was reported to have impact on the physiological arterial stiffness and vascular remodeling with hypertension of recent years. In the previous study we reported the association of four functional single nucleotide polymorphisms (SNPs) of FBN1 gene and hypertension. Here, we further investigate the association of four tagging SNPs (tagSNPs) which covered remain genetic variation blocks of FBN1 gene with hypertension, blood pressure and efficacy of antihypertensive in a South Han Chinese population. A case-control study including 2,012 hypertension cases and 2,116 controls age- and sex-matched controls was conducted from a community-based population and four candidate tagSNPs of the FBN1 gene were genotyped. Association analysis by multiple logistic regression was conducted for allele, genotype and haplotype and hypertension, blood pressure trait and control status with antihypertensive. General linear model was applied to compare blood pressure levels between genotypes. The association of rs17361868 and hypertension was statistically significant and that was further observed in female, ≥55 years, non-smoking and non-drinking populations (P < 0.05). Significant association of rs668842, rs11635140 and hypertension were observed in <55 years population as well as the later in female and non-smoking populations respectively. Haplotype G-T constructed of rs668842 and rs11635140 was significantly associated with hypertension comparing to reference haplotype A-C (P = 0.022). Normally distributed square root of TGF-ß1 (pg/ml) of hypertension cases (148.56 ± 66.46) was significantly higher than that of control (128.52 ± 65.11), P = 0.008. Furthermore, TGF-ß1 was significantly correlated with SBP (r = 0.135, P = 0.018) and DBP (r = 0.154, P = 0.007) respectively whereas no statistical difference of blood pressure or TGF-ß1 was observed between genotypes. Remarkably, rs17361868 were significantly associated with the status of blood pressure in the patients taking three of the antihypertensive drugs, Zhen Ju Jiang Ya tablets, Jiang Ya tablet and compound reserpine (P < 0.05). The present study provides further association evidence of FBN1 gene polymorphisms and hypertension, antihypertensive efficacy. Further replication of these results via association or prospective studies conducted in other populations is warranted.

Learning to Sketch: A Neural Approach to Item Frequency Estimation in Streaming Data.

Recently, there has been a trend of designing neural data structures to go beyond handcrafted data structures by leveraging patterns of data distributions for better accuracy and adaptivity. Sketches are widely used data structures in real-time web analysis, network monitoring, and self-driving to estimate item frequencies of data streams within limited space. However, existing sketches have not fully exploited the patterns of the data stream distributions, making it challenging to tightly couple them with neural networks that excel at memorizing pattern information. Starting from the premise, we envision a pure neural data structure as a base sketch, which we term the meta-sketch, to reinvent the base structure of conventional sketches. The meta-sketch learns basic sketching abilities from meta-tasks constituted with synthetic datasets following Zipf distributions in the pre-training phase and can be quickly adapted to real (skewed) distributions in the adaption phase. The meta-sketch not only surpasses its competitors in sketching conventional data streams but also holds good potential in supporting more complex streaming data, such as multimedia and graph stream scenarios. Extensive experiments demonstrate the superiority of the meta-sketch and offer insights into its working mechanism.

Quantifying changes in soil organic carbon density from 1982 to 2020 in Chinese grasslands using a random forest model.

China has the second-largest grassland area in the world. Soil organic carbon storage (SOCS) in grasslands plays a critical role in maintaining carbon balance and mitigating climate change, both nationally and globally. Soil organic carbon density (SOCD) is an important indicator of SOCS. Exploring the spatiotemporal dynamics of SOCD enables policymakers to develop strategies to reduce carbon emissions, thus meeting the goals of "emission peak" in 2030 and "carbon neutrality" in 2060 proposed by the Chinese government. The objective of this study was to quantify the dynamics of SOCD (0-100 cm) in Chinese grasslands from 1982 to 2020 and identify the dominant drivers of SOCD change using a random forest model. The results showed that the mean SOCD in Chinese grasslands was 7.791 kg C m-2 in 1982 and 8.525 kg C m-2 in 2020, with a net increase of 0.734 kg C m-2 across China. The areas with increased SOCD were mainly distributed in the southern (0.411 kg C m-2), northwestern (1.439 kg C m-2), and Qinghai-Tibetan (0.915 kg C m-2) regions, while those with decreased SOCD were mainly found in the northern (0.172 kg C m-2) region. Temperature, normalized difference vegetation index, elevation, and wind speed were the dominant factors driving grassland SOCD change, explaining 73.23% of total variation in SOCD. During the study period, grassland SOCS increased in the northwestern region but decreased in the other three regions. Overall, SOCS of Chinese grasslands in 2020 was 22.623 Pg, with a net decrease of 1.158 Pg since 1982. Over the past few decades, the reduction in SOCS caused by grassland degradation may have contributed to soil organic carbon loss and created a negative impact on climate. The results highlight the urgency of strengthening soil carbon management in these grasslands and improving SOCS towards a positive climate impact.

[An association study between transforming growth factor-ß1 receptor 2 gene polymorphisms and essential hypertension].

OBJECTIVE: To evaluate the association between two single nucleotide polymorphisms located in the promoter of transforming growth factor-ß1 receptor 2 (TGFBR2) gene and hypertension in Han Chinese population. METHODS: The subjects were recruited from the population of cluster sampling survey for essential hypertension (EH) in two townships of Yixing city, Jiangsu province in 2009. Overall, 2012 patients with hypertension and 2116 age (± 2 years) and sex-matched unrelated controls were selected. Epidemiological data, physical measurements results and serum glucose and lipid biomarker were collected and detected. Linkage disequilibrium (LD) analysis were applied and two tagging single nucleotide polymorphisms (tagSNP) in 5' upstream of TGFBR2 gene (rs6785358, -3779A/G; rs764522, -1444C/G) were selected for genotyping and analyzing for the association with hypertension. RESULTS: The frequencies of AA, AG, GG in case and control of rs6785358 were 1455 (72.3%), 517 (25.7%), 40 (2.0%) and 1582 (74.8%), 490 (23.2%), 43 (2.0%) respectively, and CC, CG, GG of rs764522 were 1524 (75.7%), 464 (23.1%), 24 (1.2%) and 1654 (78.2%), 436 (20.6%), 26 (1.2%) respectively. SNP rs764522 was significantly associated with EH and OR (95%CI) were 1.17 (1.01 - 1.36) (P < 0.05) in dominant model after adjustment for confounding factors such as age, sex, glucose, lipids, smoking and alcohol drinking. Further stratification analysis by age, sex, smoking and alcohol drinking indicated that individuals carrying G allele (CG/GG genotype) of SNP rs764522 had higher susceptibility to EH than CC genotype (OR = 1.21, 95%CI: 1.01 - 1.45) (P < 0.05) in ≥ 55 years group. No statistical significance was detected in the distribution of genotypes and allele frequencies for SNP rs6785358 between cases and controls (P > 0.05). Haplotype analysis showed that no significant frequency difference of haplotype structured by rs6785358 and rs764522 was found between cases and controls (P > 0.05), and no significant blood pressure change was found between genotype variations of rs6785358 and rs764522 (P > 0.05). CONCLUSION: SNP rs764522 of TGFBR2 gene is associated with increased risk of EH in elderly Han Chinese population.

Drug susceptibility and molecular epidemiology of Escherichia coli in bloodstream infections in Shanxi, China.

OBJECTIVES: We carried out a retrospective study to investigate the drug susceptibility and genetic relationship of clinical Escherichia coli isolates from patients with BSIs in Shanxi, China. METHODS: E. coli isolates causing BSIs were consecutively collected from June 2019 to March 2020. Antimicrobial susceptibility testing was performed by broth microdilution method. PCR was used to detect antimicrobial resistance genes coding for extended-spectrum ß-lactamases (ESBLs), phylogenetic groups and seven housekeeping genes of E. coli. RESULTS: A total of 76 E. coli were collected. Antimicrobial susceptibility testing revealed that the top six E. coli resistant antibiotics were ampicillin (90.7%), ciprofloxacin (69.7%), cefazolin (65.7%), levofloxacin (63.1%), ceftriaxone and cefotaxime (56.5%). Among the 76 isolates, 43 produced ESBLs. Molecular analysis showed that CTX-M-14 was the most common ESBLs, followed by CTX-M-15 and CTX-M-55. Phylogenetic group D (42.2%) predominated, followed by group B2 (34.2%), group A (18.4%) and group B1 (5.2%). The most prevalent sequence types (STs) were ST131 (15/76), ST69 (12/76) and ST38 (6/76). CONCLUSIONS: This study is the first to report the phenotypic and molecular characteristics of E. coli isolated from BSIs in Shanxi, China. Our results indicated a high prevalence of MDR in E. coli strains isolated from BSIs and a serious spread of ESBL genes in Shanxi, especially the epidemiological bla CTX-M. Phylogenetic analysis indicated genetic diversity among E. coli BSIs isolates.

Correlation between multi-type human papillomavirus infections and viral loads and the cervical pathological grade.

OBJECTIVE: To investigate the relationship between single/multiple HPV infections and cervical lesions, and the correlation between viral load and the degree of cervical lesions. METHODS: A total of 27 284 patients who underwent testing for HPV were retrospectively screened and 3728 women were enrolled who tested positive for HPV when examined by liquid-based ThinPrep cervical smear cytology test and diagnosed by histopathology at the Shanxi Provincial People's Hospital between May 2017 and March 2019. The genotype and viral load of HPV were determined by fluorescence quantitative polymerase chain reaction. Based on the pathological grade, the cervical lesions were stratified into three groups: chronic cervicitis/cervical intraepithelial neoplasia (CIN) I; CIN II/CIN III; and cervical cancer. RESULTS: There were significant intergroup differences in the distribution of single and multiple HPV infections. There was a positive correlation between the viral load and cervical pathological grade when the infections were caused by HPV 16, 18, 31, 33, 51, 52, 53, and 58. CONCLUSION: Multi-type HPV infections are more likely to aggravate the degree of cervical lesions than single-type infections. The HPV type-dependent viral load is associated with the cervical pathological grade.

Drug Susceptibility and Molecular Epidemiology of Klebsiella pneumoniae Bloodstream Infection in ICU Patients in Shanghai, China.

Background: Bloodstream infections (BSIs) are recognized as important nosocomial infections. Klebsiella pneumoniae is one of the major causes of bacteremia. This retrospective study focused on drug susceptibility and molecular epidemiology of K. pneumoniae isolated from intensive care unit (ICU) patients with BSI in Shanghai, China. Methods: Consecutive K. pneumoniae isolates were collected from ICU patients. Antibiotic susceptibility testing was conducted by the broth microdilution method. PCR was performed to detect antimicrobial resistance genes. We also completed multilocus sequence typing (MLST) and GoeBURST was used to analyze the result of MLST. Results: A total of 78 K. pneumoniae isolates were enrolled. K. pneumoniae from ICU-BSIs were highly resistant to almost all common antibiotics. The most frequent resistance determinants responsible for extended-spectrum ß-lactamase (ESBL) producers were bla CTX-M-14, bla CTX-M-15, and bla CTX-M-55. KPC was the only enzyme, which was detected by the carbapenemase producers. The most principal sequence types (STs) were ST11, ST15, and ST23. Conclusion: This study presents for the first time the antibiotic resistance phenotype and molecular epidemiology of K. pneumoniae isolated from ICU patients with BSIs in Shanghai. ICU-BSI K. pneumoniae is characteristic of a high resistance rate. The occurrence of the KPC-2 enzyme may result from nosocomial clonal dissemination of ST11 K. pneumoniae.

Trifluoperazine Activates FOXO1-Related Signals to Inhibit Tumor Growth in Hepatocellular Carcinoma.

Schizophrenic patients tend to have reduced incidence of some cancers due to the treatment of antipsychotic drugs with antitumor effects, such as chlorpromazine and trifluoperazine (TFP). Forkhead Box O1 (FOXO1) as tumor suppressor in many malignancies is often inactivated by nuclear export, which could be inhibited by TFP. However, the antitumor efficiency of TFP and related role of FOXO1 in hepatocellular carcinoma (HCC) are unclear. Thus, two HCC cell lines SMMC-7721 and Bel-7402 were treated with different concentrations of TFP and the IC50 was determined. We found that TFP could inhibit the vitality of two cell lines and induce cell cycle arrest at G0/G1. Meanwhile, the apoptosis was also increased and the ability of migration or invasion was found to be impaired by TFP. Interestingly, TFP reversed the cytoplasmic localization of FOXO1 to nuclear and increased its expression in nuclear, and increased the ratio of Bax/Bcl-2. However, knockdown of FOXO1 significantly abrogated the TFP-induced apoptosis by decreasing the Bcl-2 expression [corrected]. Furthermore, we found that TFP in vivo could effectively restrict the angiogenesis and tumor growth with reduced expression of VEGF, Bcl-2, and PCNA, and increased the nuclear localization of FOXO1, which indicated its antitumor role in HCC.

[Malignant peripheral nerve sheath tumor in the maxillary sinus: a case report].

We report a case of 46-year-old xanthoderm woman who was diagnosed as malignant peripheral nerve sheath tumors of right maxillary sinus, and have a literature review. Histology confirmed a diagnosis of malignant peripheral nerve sheath tumor. The woman had the right total maxillectomy and postoperative adjuvant radiotherapy. There is no local recurrence or metastasis of one year following up. Literature review revealed MPNST in the nasal cavity and para-nasal sinuses were not common with poor prognosis. The main cause of death is local recurrence and metastasis. Surgical resection showed more advantage than adjuvant radiotherapy and chemotherapy.

Association between TGFBR2 gene polymorphisms and congenital heart defects in Han Chinese population.

BACKGROUND: Transforming growth factor-ß receptor II (TGFBR2) is a key component of TGF-ß signaling pathway. TGFBR2 can be detected in the generation of heart. The mouse embryos of TGFBR2 gene knockout exhibited congenital heart defects. METHODS: We conducted a case-control study to investigate the association between TGFBR2 gene polymorphisms and congenital heart defects in Han Chinese population. 125 patients with congenital heart defects and 615 unrelated controls were recruited. Two tagging single nucleotide polymorphisms (tagSNPs) in 5' upstream of TGFBR2 gene (rs6785358, -3779A/G; rs764522, -1444C/ G) were selected and genotyped by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) assay. RESULTS: A significant difference was seen in the distribution of genotypes between patients with congenital heart defects and controls for SNP rs6785358 (P=0.043). For SNP rs6785358 the carrier of the G allele (AG/GG genotype) showed a significantly higher risk of congenital heart defects compared with AA homozygotes (OR=1.545, 95% CI: 1.013-2.356). Further analysis by sex stratification indicated that individuals carrying G allele (AG/GG genotype) for SNP rs6785358 have a higher susceptibility to congenital heart defects (OR=2.088, 95%CI: 1.123-3.883, P=0.019) in males, but not females (OR=1.195, 95%CI: 0.666-2.146, P=0.55). No statistical significance was detected in the distribution of genotypes and allele frequencies for SNP rs764522 between patients and controls. CONCLUSION: Our result suggested that SNP rs6785358 of TGFBR2 gene was associated with increased risk of congenital heart defects in Han Chinese men and further research would be warranted.

Antecedentes: Factor de crecimiento transformante receptor II (TGFBR2) es un componente clave de la via de señalización de TGF - .TGFBR2 puede ser detectado en la generación de corazón. Los embriones de ratón de TGFBR2 gene knockout mostraron defectos congénitos del corazon. Métodos: Hemos realizado un estudio de casos y controles para investigar la asociación entre polimorfismos del gen TGFBR2 y defectos congénitos del corazón en la población china han. 125 pacientes con defectos congénitos del corazón y 615 unrelated controles fueron reclutados. Marcado de dos polimorfismos de nucleótido único (tagsnps) en 5 'aguas arriba del gen TGFBR2 (rs6785358, - 3779a / g; rs764522, - 1444c / g) fueron seleccionados y genotipados por reacción en cadena de la polimerasa (PCR) - polimorfismos de longitud de fragmentos de restricción (RFLP) de ensayo. Resultados: Se observó una diferencia significativa en la distribución de genotipos entre pacientes con defectos congénitos del corazón y controles para SNP rs6785358 (P = 0043). La SNP rs6785358 el porteador del alelo G (AG / GG genotipo) mostraron un importante crecimiento y mayor riesgo de defectos congénitos del corazón en comparación con AA homocigotos (OR = 1.545, IC del 95%: 1.013­2.356). Más análisis por sexo estratificación indicó que los individuos con alelo G (AG / GG genotipo) para SNP rs6785358 tienen una mayor susceptibilidad a defectos congénitos del corazón (OR = 2.088, IC del 95%: 1.123-3.883, p = 0.019) en machos, pero no en las mujeres (OR = 1.195, IC del 95%: 0.666-2.146, p = 0.55). No hay significación estadística fue detectado en la distribución de los genotipos y frecuencias de alelos de SNP rs764522 entre pacientes y controles. Conclusión: Nuestros resultados sugieren que el SNP rs6785358 de gen TGFBR2 se asoció con un mayor riesgo de defectos congénitos del corazón en los chinos han hombres y más investigación estaría justificada.

Common variants in TGFBR2 and miR-518 genes are associated with hypertension in the Chinese population.

BACKGROUND: An animal study reported that TGF-ß1 maturation was linked to the homeostasis of blood pressure and elastogenesis of essential hypertension (EH). Recent advances require further research of TGF-ß1 receptor in EH. METHODS: A case-control study comprised of 2,012 adult hypertension case patients and 2,210 adult control subjects was conducted, and the association with blood pressure was further tested in children. Logistic regression and calculated genetic risk score were used to evaluate the effects of one single nucleotide polymorphism (SNP) and multiple SNPs on EH, respectively. RESULTS: The genetic risk score of 10 SNPs showed a significant association with hypertension; the odds ratio of the upper quartile vs. the lower quartile was 1.282 (P = 4.67 × 10(-3)). rs7256241 in miR-518 was significantly associated with diastolic blood pressure (DBP) change in control subjects (P = 0.002), and this association was also observed in children (P = 0.04). The systolic blood pressure (SBP) and DBP of female patients taking reserpine were higher with the C and G alleles of rs3773661 (P = 0.004) and rs7256241 (P = 0.002), respectively. In patients taking Zhen Ju Jiang Ya tablets, SBP and DBP decreased linearly with rs749794 (P = 0.004 and P = 0.048, respectively). SBP decreased linearly with rs1155705 (P = 0.007) and rs11709624 (P = 0.04), but increased with rs1036096 (P = 0.03) in male patients. In male patients taking Jiang Ya tablets, SBP increased linearly with rs11709624 (P = 0.007), DBP increased linearly with rs1155705 (P = 0.03) whereas decreased with rs7256241 (P = 0.04). CONCLUSIONS: Our results suggest that TGFBR2 and miR-518 harbor variants that increase the risk of EH and affect blood pressure homeostasis as well as efficacy of antihypertensive agents.

Association study of CRP gene and ischemic stroke in a Chinese Han population.

High-sensitivity C-reactive protein (hsCRP) was reported as a strong, independent predictor of future myocardial infarction and stroke. It is of importance to illustrate the conformance of CRP genetic variation, increment of plasma hsCRP and cerebral events. A case-control study including 548 patients with acute ischemic stroke and 993 age-matched controls from community-based population was conducted and four tagging SNPs (tagSNPs) were genotyped. Multiple logistic regression was applied to evaluate the association of CRP gene and stroke hsCRP elevation with adjustment for covariates. The results indicated that rs3093059 and rs3091244 presented statistical associations with ischemic stroke. Odds ratios (ORs) (95 % confidence interval [CI]) of additive model, dominant model and minor allele at rs3093059 were 0.697 (0.528-0.921), 0.671 (0.487-0.923) and 0.811 (0.666-0.988), and ORs (95 % CI) of dominant model at rs3091244 was 0.728 (0.536-0.988), after adjusting for covariates. But there were no significant differences of genotype or allele frequencies of the four SNPs observed between hypertension (HT) and normal blood pressure (NBP) groups. Further analyses indicated the genetic variations of rs876537 and rs3093059 were positively associated with increased square root transformed hsCRP and hsCRP elevation (≥3 mg/l) in ischemic stroke patients, and rs876537 and rs3091244 were associated with hsCRP elevation in controls as well. Our finding suggests that the CRP genetic polymorphisms were associated with decreased risk of ischemic stroke and elevated plasma hsCRP and further replication study and functional research would be warranted.

Association study of CRP gene polymorphism and hypertension in Han Chinese population.

BACKGROUND: Serum C-reactive protein (CRP) and genetic variation of CRP gene have been reported as a strong, independent predictor of myocardial infarction and stroke. But there is rare association evidence of CRP genetic variation and hypertension (HT). METHODS: A community-based case-control study including 1331 cases with HT and 1400 controls was used to evaluate the association of tagSNPs covered CRP gene, CRPP1 gene and 40kb upstream with HT in a Chinese Han population. Haplotypes and stratification analysis were applied to further evaluate relationships between the screened SNPs and HT and general linear model (GLM) was applied to compare blood pressure levels between genotypes. RESULTS: In stage 1, five SNPs had positive association with HT (P<0.05) and entered stage 2 and two SNPs rs876537 and rs10737175 polymorphisms showed significant association with HT in joint sample. Haplotype analysis showed that comparing with common haplotype T-C which was constructed by rs6677719 and rs10737175, haplotype T-T significantly associated with HT after adjusted covariates. Stratification analysis found significant associations of HT for rs876537, rs2808630, rs6677719 and rs10737175 in ≥50years group, rs876537, rs10737175 in female, rs876537 and rs10737175 in non-smoking and non-drinking populations as well as rs2808630 in non-drinking population. Furthermore, quantitative trait analysis indicated significant differences of SBP and DBP between the genotypes of rs10737175, rs876537 and rs2808630 in non-treatment hypertensive cases and control population. CONCLUSIONS: The findings of this study support that CRP gene polymorphisms have significant association with genetic susceptibility of HT and quantitative traits of blood pressure.

Association study of AGER gene polymorphism and hypertension in Han Chinese population.

BACKGROUND: Advanced glycation end products (AGEs) are produced by non-enzymatic glycation or glycoxidation of proteins, lipids and nucleic acids. The bond of AGEs and the receptor of AGE (AGER) in a pro-oxidant environment could induce immune and inflammation reaction involved in progress of microvascular disease. Accumulated evidence warrant further study on AGE-AGER pathway and genetic susceptibility to hypertension (HT). METHODS: We designed a two-stage association study to evaluate the association of AGER polymorphism and HT. In stage 1, seven tagSNPs were tested in 524 cases and 531 controls and the significant SNPs (P<0.05) would enter into stage 2 including 807 cases and 869 controls. Furthermore, joint analysis was performed for all 2731 subjects including 1331 cases and 1400 controls, and meta-analysis was applied to evaluate combined estimations from the subgroups of stage 1 and stage 2. RESULTS: In stage 1, rs204994 had significant association with HT (P<0.05) and enter stage 2. Neither joint analysis nor meta-analysis found statistical association of rs204994 with HT after adjusted for the covariates in the whole population. However, further stratification analysis found that rs204994 was significantly associated with HT in <50years and ≥50years groups, ORs (95%CI) of dominant model were 1.623 (1.054-2.500) and 0.721 (0.546-0.952) respectively. No significant correlation was found between blood pressure and the polymorphisms of rs204994. CONCLUSIONS: Our data suggests that age might modulate the genetic effects of variation of rs204994 in AGER on HT and further replications in other populations and functional studies should be warranted.

Silencing STAT3 with short hairpin RNA enhances radiosensitivity of human laryngeal squamous cell carcinoma xenografts in vivo.

Short hairpin RNA (shRNA) targeting signal transducer and activator of transcription 3 (STAT3) potentiate the radiosensitivity of human laryngeal squamous carcinoma cells in vitro. In the present study, we investigated the inhibitory effect of STAT3 shRNA plus radiotherapy on nude mouse laryngeal squamous cell carcinoma xenografts. The xenotransplanted tumors were treated with STAT3 shRNA, with or without radiation, following a planned scheme. The inhibition rate for tumor growth was calculated and the tumor growth curve was plotted. In addition, the expression of p-STAT3, B cell lymphoma 2 (Bcl-2), p53, vascular endothelial growth factor (VEGF) protein and intratumoral microvessel density (MVD) was determined by immunohistochemistry. Flow cytometry was used to detect the rate of cell apoptosis. The results revealed that STAT3 shRNA transfection plus radiotherapy significantly minimized tumor volume and increased the rate of tumor inhibition. p-STAT3 protein expression and intratumoral MVD were observed to be down-regulated, whereas apoptosis was increased. There was a positive correlation between the expression of p-STAT3 and Bcl-2, and also between the expression of p53 and VEGF, and MVD. These findings indicate that STAT3 shRNA potentiate the radiosensitivity of laryngeal carcinoma xenografts in vivo by regulating downstream signaling proteins in the STAT3 pathway.

STAT3 blockade with shRNA enhances radiosensitivity in Hep-2 human laryngeal squamous carcinoma cells.

Signal transducer and activator of transcription 3 (STAT3) is an oncogene aberrantly activated in many human tumors. We studied whether radiation combined with STAT3 siRNA enhances radiosensitivity of Hep-2 human laryngeal squamous carcinoma cells (Hep-2 cells). Firstly, STAT3 targeting recombinant plasmid was constructed. Hep-2 cells were transfected with expression vector of STAT3 siRNA using Lipofectamine 2000. Semiquantitive RT-PCR detected effective STAT3 mRNA down-regulation by STAT3 siRNA. Secondly, Hep-2 cells were radiated with different doses of gamma-rays after transfection with STAT3 small interference RNA (siRNA). MTT assay showed cell proliferation decreased significantly (P<0.05) after STAT3 siRNA transfection combined with radiation. Thirdly, flow cytometry (FCM) demonstrated that cell apoptosis of combined treatment group increased significantly (P<0.05) and exhibited time dependency after 6 Gy irradiation (P<0.05). Simultaneously, STAT3, p-STAT3, Bcl-2, VEGF, p53 protein levels decreased in Hep-2 cells, with positive correlations between level of p-STAT3 and levels of Bcl-2, VEGF, p53, respectively (r=0.974, 0.988, 0.976, all P<0.01). Above all, specific siRNA targeting STAT3 gene is able to enhance the radiosensitivity in Hep-2 cells by regulating expression of Bcl-2, VEGF and p53 proteins.