Intermediate molecular phenotypes to identify genetic markers of anthracycline-induced cardiotoxicity risk.

Cardiotoxicity due to anthracyclines (CDA) affects cancer patients, but we cannot predict who may suffer from this complication. CDA is a complex disease whose polygenic component is mainly unidentified. We propose that levels of intermediate molecular phenotypes in the myocardium associated with histopathological damage could explain CDA susceptibility; so that variants of genes encoding these intermediate molecular phenotypes could identify patients susceptible to this complication. A genetically heterogeneous cohort of mice generated by backcrossing (N = 165) was treated with doxorubicin and docetaxel. Cardiac histopathological damage was measured by fibrosis and cardiomyocyte size by an Ariol slide scanner. We determine intramyocardial levels of intermediate molecular phenotypes of CDA associated with histopathological damage and quantitative trait loci (ipQTLs) linked to them. These ipQTLs seem to contribute to the missing heritability of CDA because they improve the heritability explained by QTL directly linked to CDA (cda-QTLs) through genetic models. Genes encoding these molecular subphenotypes were evaluated as genetic markers of CDA in three cancer patient cohorts (N = 517) whose cardiac damage was quantified by echocardiography or Cardiac Magnetic Resonance. Many SNPs associated with CDA were found using genetic models. LASSO multivariate regression identified two risk score models, one for pediatric cancer patients and the other for women with breast cancer. Molecular intermediate phenotypes associated with heart damage can identify genetic markers of CDA risk, thereby allowing a more personalized patient management. A similar strategy could be applied to identify genetic markers of other complex trait diseases.

He-Wei Granule enhances anti-tumor activity of cyclophosphamide by changing tumor microenvironment / 中草药·英文版

Objective: He-Wei Granule (HWKL) is a modern product derived from the modified formulation of traditional Chinese medicine Banxia Xiexin Decoction (BXD), which remarkedly enhanced the anti-proliferation activity of cyclophosphamide (CTX) on HepG2 and SGC-7901 cell lines in vitro in our previous research. The aim of the study was to investigate the synergistic effects of HWKL and CTX using a transplanted H22 hepatocellular carcinoma mouse model. Methods: The CTX-toxic-reducing efficacy of HWKL was evaluated by hematology indexes, organ indexes and marrow DNA detection. To investigate the underlying mechanisms, histopathology test, immunohistochemistry test and TUNEL staining were conducted. The efficacy of HWKL on the micro-vessel density (MVD) in tumor tissue was also evaluated by measuring CD34 level. Results: High dose HWKL (6.75 g/kg) markedly attenuated CTX-induced hepatotoxicity and myelosuppression while significantly enhanced CTX anticancer efficacy in vivo. Further mechanism investigation suggested that high dose HWKL significantly increased cleaved Caspase 3 level and promoted apoptosis in tumor tissue by up-regulating Bax expression and down-regulating Bcl-2 and FasL expressions. Compared with CTX alone group, the decrease in LC-3B and Beclin 1 levels suggested that the autophagy in H22 carcinoma was significantly inhibited with addition of high dose HWKL. ELISA assay results indicated that the autophagy inhibition was achieved by decreasing p53 expression, blocking PI3K/AKT/mTOR pathway and recovering Th1/Th2 cytokine balance. In addition, CD34 and EGFR immunohistochemistry assay suggest that high dose HWKL could significantly decrease micro-vessel density (MVD) and inhibit angiogenesis in H22 carcinoma. Conclusion: It can be concluded that high-dose HWKL enhanced CTX efficacy by promoting apoptosis, inhibiting autophagy and angiogenesis in tumor tissue while significantly alleviated CTX-induced toxicity, and could be applied along with CTX in clinical treatment as a supplement agent.

A simple method for the preparation of a nickel selenide and cobalt selenide mixed catalyst to enhance bifunctional oxygen activity for Zn-air batteries.

Developing a low-cost, simple, and efficient method to prepare excellent bifunctional electrocatalysts toward the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is critical in rechargeable zinc-air batteries. Non-stoichiometric M0.85Se (M = Ni or Co) nanoparticles are synthesized and modified on nitrogen-doped hollow carbon sphere (NHCS). The NHCS loaded Ni0.85Se (Ni0.85Se-NHCS) with rich Ni3+ presents higher OER activity, whereas the NHCS-loaded Co0.85Se (Co0.85Se-NHCS) with abundant Co2+ displays better ORR activity, respectively. When Co0.85Se-NHCS is mixed with Ni0.85Se-NHCS in a mass ratio of 1 : 1, the resulting mixture (Ni0.85Se/Co0.85Se-NHCS-2) shows better ORR and OER dual catalytic functions than a single selenide. Moreover, zinc-air batteries equipped with Ni0.85Se/Co0.85Se-NHCS-2 as the oxygen electrode catalyst exhibit excellent charge and discharge performance as well as improved stability over precious metals. This work has developed a simple and effective method to prepare excellent bifunctional electrocatalysts for ORR and OER, which is beneficial for the practical large-scale application of zinc-air batteries.

Development and validation of chest CT-based imaging biomarkers for early stage COVID-19 screening

Coronavirus Disease 2019 (COVID-19) is currently a global pandemic, and the early screening of COVID-19 is one of the key factors for COVID-19 control and treatment. Here, we developed and validated chest CT-based imaging biomarkers for COVID-19 patient screening. We identified the vasculature-like signals from CT images and found that, compared to healthy and community acquired pneumonia (CAP) patients, the COVID-19 patients revealed significantly higher abundance of these signals. Furthermore, unsupervised feature learning leads to the discovery of clinical-relevant imaging biomarkers from the vasculature-like signals for accurate and sensitive COVID-19 screening that has been double-blindly validated in an independent hospital (sensitivity: 0.941, specificity: 0.904, AUC: 0.952). Our findings could open a new avenue to assist screening of COVID-19 patients.

Epidemiological survey of lipid levels and factors in Kazakan people over 30-year old in Fukang of Xinjiang / 中华预防医学杂志

<p><b>OBJECTIVE</b>To study the lipids level in Kazakan individuals over 30-year-old in Fukang area of Xinjiang.</p><p><b>METHODS</b>Random cluster multistage sampling method were performed to select the subjects, and 991 individuals aged older than 30 from Fukang of Xinjiang were included. The plasma total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), plasma glucose and insulin were measured. Related adverse cardiovascular risk factors were discussed.</p><p><b>RESULTS</b>The mean plasma TC, TG, HDL-C and LDL-C of Kazakan residents over 30-year-old in Fukang of Xinjiang were (5.05 ± 1.07), (1.10 ± 0.66), (1.46 ± 0.38) and (3.06 ± 0.84) mmol/L, respectively. TC, TG and LDL-C levels in male subjects were higher than those in females (male vs female: TC: (5.19 ± 1.05) mmol/L vs (4.94 ± 1.07) mmol/L, t = 3.57, P < 0.01; TG: (1.32 ± 0.80) mmol/L vs (0.94 ± 0.46) mmol/L, t = 8.63, P < 0.01; LDL-C: (3.30 ± 0.85) mmol/L vs (2.88 ± 0.79) mmol/L, t = 8.06, P < 0.01). While the HDL-C level in male subjects was lower than that of female (male vs female: (1.32 ± 0.33) mmol/L vs (1.57 ± 0.38) mmol/L, t = 11.48, P < 0.01). The prevalence of dyslipidemia was 28.3% (280/991) in the overall populations. In the overall populations, the prevalence of hypercholesteremia, hypertriglyceridemia, high low-density lipoprotein cholesterolemia and low serum high density lipoprotein cholesterolemia were 12.6% (125/991), 6.6% (65/991), 11.0% (109/991) and 10.1% (100/991), respectively. The prevalence of individuals with borderline-high TC, TG and LDL-C were 27.0% (268/991), 7.6% (75/991) and 20.5% (203/991), respectively. The prevalence of dyslipidemia was 40.0% (172/430) in male populations. The prevalence of dyslipidemia in group aged 30 - 39, 40 - 49, 50 - 59, 60 and above were 26.2% (78/298), 26.0% (91/350), 31.2% (73/234) and 34.9% (38/109), respectively, the trend of prevalence was significant by trend test for groups comparison (χ(2) = 3.94, P < 0.05). Adjusting for age and gender, TG was positively correlated with waist circumference, abdominal circumference and BMI, the partial relation coefficients were 0.368 (P < 0.01), 0.336 (P < 0.01) and 0.331 (P < 0.01), respectively, and HDL-C was negatively correlated with waist circumference, abdominal circumference and BMI, the partial relation coefficients were -0.340 (P < 0.01), -0.339 (P < 0.01) and -0.321 (P < 0.01), respectively.</p><p><b>CONCLUSION</b>The lipid levels of Kazakan residents from Fukang area are high and are characterized by hypercholesteremia and high low-density lipoprotein cholesterolemia, and more attention of the prevention of dyslipidemia in this populations should be paid to males, border-line abnormal and those aged over 60-year old.</p>

Association of genetic variations of the prostasin gene with essential hypertension in the Xinjiang Kazakh population / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Transgenic overexpression of human prostasin in rats disturbs salt balance and causes hypertension. We investigated whether genetic variations in prostasin were implicated in hypertension or related phenotypes in the Xinjiang Kazakh population.</p><p><b>METHODS</b>We sequenced all exons and the promoter regions of the prostasin gene in 94 hypertensive individuals, and the genotype identification was performed by the TaqMan polymerase chain reaction method. Case-control studies were conducted in 938 Kazakh subjects.</p><p><b>RESULTS</b>E342K and 2827G > A, which are novel variants, were successfully genotyped in the general Xinjiang Kazakh population with a sample size of 938 individuals (406 men and 532 women). Only one hypertensive patient was identified with the E342K mutation. No significant association was observed between 2827G > A and hypertension. However, quantitative traits of hypertensive intermediate phenotypes were significantly associated with the A allele; P = 0.041 and 0.034 for body mass index (BMI) in the additive and recessive models, P = 0.042 and 0.018 for OGTT-2h glucose in the additive and recessive models, P = 0.031 for IRT-3h insulin in the recessive model, and P = 0.038 for serum potassium in the dominant model.</p><p><b>CONCLUSIONS</b>This study does not provide evidence of a major role of prostasin variation in blood pressure modulation. However, association of prostasin polymorphisms with hypertension and metabolic effects can be observed in our population. Further investigation is warranted to clarify the relevance of prostasin polymorphisms to blood pressure regulation.</p>

Relationship between rs3865418 polymorphism of neural precursor cell expressed developmentally downregulated 4-like gene and obesity in Kazakh general population / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the relationships between rs3865418 polymorphism of neural precursor cell expressed developmentally downregulated 4-like gene and obesity in Kazakh general population.</p><p><b>METHODS</b>Based on a cross-sectional epidemiological study in a Kazakh general population, a case-control study was conducted. The rs3865418 polymorphism in a Kazakh general population (856 subjects, including 364 males and 492 females; 478 in obesity group and 378 in normal control group) was genotyped by TaqMan polymerase chain reaction, and the relationship between rs3865418 polymorphism and obesity was analyzed.</p><p><b>RESULTS</b>The rs3865418 polymorphism was successfully genotyped in 851 Kazakh subjects. The distribution of the genotypes and alleles of rs3865418 polymorphism did not differ significantly between the obesity group and normal control group in terms of general populations, males, and females (all P > 0.05). The waist circumference showed a tendency of C/C > C/T > T/T in males and C/C < C/T < T/T in females, but without statistical significance (P > 0.05).</p><p><b>CONCLUSIONS</b>The rs3865418 polymorphism of neural precursor cell expressed developmentally downregulated 4-like gene may not be associated with obesity in Kazakh general population. In other words, it is not a predisposing factor for obesity in Kazakh.</p>

Association of the rs4149601 polymorphism of NEDD4L gene with obesity in Xinjiang Kazakh population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association of the rs4149601 polymorphisms of neural precursor cell expressed developmentally downregulated 4-like gene (NEDD4L) and obesity in Xinjiang Kazakh population.</p><p><b>METHODS</b>The rs4149601 polymorphism of the NEDD4L gene was genotyped in a Xinjiang Kazakh general population including 856 subjects (aged 30 to 60 years, 478 obese and 378 control individuals).</p><p><b>RESULTS</b>The polymorphism was successfully genotyped in 853 Xinjiang Kazakh subjects. The distribution of the additive model and dominant model (AG+ AA vs. GG) of the rs4149601 polymorphism differed significantly between the case and control in both total and females (all P< 0.05). After adjusting for confounding factors, logistic regression analysis showed that the rs4149601 polymorphism (in dominant model) was significantly associated with obesity (OR= 1.479, 95% CI: 1.103-1.983, P= 0.009) in Kazakh. Covariate variance analysis showed that compared with subjects with AA + AG genotypes, the waist circumference was significantly higher in subjects with GG genotype after adjusting for age, smoking and drinking (P= 0.028).</p><p><b>CONCLUSION</b>The genetic variations of the NEDD4L gene may be associated with obesity in Xinjiang Kazakh general population.</p>

Association between rs4149601 polymorphism and essential hypertension in Kazakh / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the association between a functional rs4149601 polymorphism of neural precursor cell expressed developmentally downregulated 4-like gene (NEDD4L) and essential hypertension in Kazakh.</p><p><b>METHODS</b>In this population-based association study, the genotypes of rs4149601 polymorphism were identified by TaqMan PCR in 883 subjects (male 375 383 hypertensives) and its distribution and relationship to hypertension were studied. The association between haplotype (rs4149601, 296921-296923delTTG, rs2288774 and rs2288775, the last three polymorphisms are representative variations identified from 94 Kazakh hypertensive individuals by screening the functional region of NEDD4L previously) and hypertension was also investigated.</p><p><b>RESULTS</b>The genotype distribution of rs4149601 polymorphism was in Hardy-Weinberg equilibrium. The genotype distribution of rs4149601 polymorphism was similar between the essential hypertension patients and the control individuals (all P > 0.05). In the haplotype-based case-control analysis, the distribution of the haplotypes was not significantly different between the case and the control individuals in total and in male subjects but the frequency of D-C-G-G (296921-3delTTG/rs2288774/rs2288775/rs4149601) haplotype was significantly higher in hypertensive than in control individuals in female (P = 0.026).</p><p><b>CONCLUSION</b>Our results suggested that D-C-G-G haplotype of NEDD4L but not rs4149601 polymorphism was linked with hypertension in Kazakh.</p>

Association of genetic variations of prostasin gene with the essential hypertension in Xinjiang Kazakhs / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the relationship between genetic variations of prostasin gene and essential hypertension (EH) in Xinjiang Kazakhs.</p><p><b>METHODS</b>Totally 938 Fukang City residents who were older than 30 years were enrolled in this study using cluster random sampling method. Standardized questionnaire and physical examination were performed. Among them there 451 EH patients (EH group) and 478 normotensive (NT) subjects (NT group) according to Guidelines of Prevention and Control for Hypertension in 2005. All the exons and promoter regions of prostasin gene were sequenced in 94 EH patients. Representative variations (297A>C, 2827C>T, and E342K) were genotyped using TaqMan polymerase chain reaction method in all 938 subjects. The frequencies of genotypes were compared between the EH and NT groups.</p><p><b>RESULTS</b>Ten variations were found as follows: -36G>C, -27C>T, 78G>A, 81G>C (rs8049043), 297A>C, 350C>T, 351A>C, 2827C>T, 3482G>A (E342K), and 3783A>G. E342K and 2827C>T were successfully genotyped. E342K mutation was identified in only one hypertensive patient. CC, CT, and TT genotypes existed in 2827C>T polymorphism. The frequencies of CC, CT, and TT were 81.0%, 17.3, and 1.7% in EH group and 80.3%, 18.9%, and 0.8% in NT group, respectively. The frequencies of C and T alleles were 89.6% and 10.4% in EH group and 89.8% and 10.2% in NT group, respectively. The distribution of genotypes and allele frequencies were not significantly different between these two groups (chi2=2.048, P=0.353 and chi2=0.001, P=0.973). Blood pressure was not significantly among subjects with these three genotypes (P>0.05).</p><p><b>CONCLUSIONS</b>The EH of Xinjiang Kazakhs is not associated with 2827C>T polymorphism in the prostasin gene. E342K mutation in the prostasin gene may contribute partly to the hypertensive phenotype in this population.</p>

[Molecular analysis on the S gene of three Crimean-Congo hemorrhagic fever virus strains in China].

OBJECTIVE: To compare the molecular characteristics of 3 Crimean-Congo hemorrhagic fever viruses(CCHFV) isolated in Xinjiang province. METHODS: YL05035, YT05099 and LT05146 were isolated in 2005 from Hyalomma ticks and viral RNA was extracted from suckling mouse brains infected with these three strains respectively. The polymerase chain reaction(PCR) products of S segments from the 3 strains of CCHFV were directly sequenced. RESULTS: The full-length'S RNA from the 3 strains of CCHFV all comprised 1673 nucleotides with ORF of them including 1449 nucleotides and encoding a protein which comprised 482 amino acids in a viral complementary sense. The sequences indicated that the three strains of CCHFV isolated from ticks in Xinjiang province were highly homologenic. Data from the phylogenetic analysis showed that the obtained sequences were identical. The homology between 3 strains of CCHFV was 99.5%. Their homologies compared with that of the other strains isolated from other region of Xinjiang were also high at nucleotide levels (92.7%-99.8%). The three strains which were clustered together with 7001 strain and 79121 strain (isolated from patient and rat in Xinjiang respectively) was only different by 2%-3%. The genetic difference from the prototype CCHFV Nigerian strain IBAR10200 was 13%. In comparison, the Nigerian CCHFV tick isolate was more divergent when compared with the reference China strains 66019 and with the three variants mentioned above. CONCLUSION: The CCHFV isolated from China comprised a group of genetically high conserved strains.

[In situ UV-visible absorption spectrum monitoring the electrochemical degradation of PAn films].

Kinetic degradation process of PAn films during aniline polymerization was in situ monitored by UV-Visible absorption spectrum. The effects of anodic potential, acidity and monomer concentration on the degradation process were also investigated. The experiment results displayed that the more positive the anodic potential, the higher the acidity of the solution, the higher the concentration of aniline, the faster the PAn films degradation speed. Which was similar to the results obtained when the kinetic degradation process of PAn films was studied in blank solutions by cyclic voltammetry.