Kazakh Patients Research Articles

CLONAL HEMATOPOIESIS AND ITS ROLE IN THE DEVELOPMENT OF CARDIOVASCULAR DISEASES

Clonal hematopoiesis (CH) is the increase in somatic clones carrying mutations in hematopoietic stem cells. This biological condition can lead to cancer and is implicated in the development of atherosclerosis and cardiovascular diseases. CH of indeterminate potential (CHIP) refers to somatic mutations in genes that are associated with the development of Coronary heart disease (CHD) and leukemia. Now, with next-generation sequencing, we can detect mutations even if they are present in only a small number of cells in the tissue sample being studied. Consequently, numerous studies have shown that mutations in the DNMT3A, TET2, ASXL1, and JAK2 genes found in the blood are associated with coronary heart disease. The purpose of our study is to detect a genetic variant of genes in Kazakh patients with atherosclerosis, which will further allow us to study the role of CHIP in increasing the risk of developing coronary microvascular dysfunction and CHD. We perform high-throughput whole-exome sequencing in patients with atherosclerosis. The object of the study is samples delivered from the clinic “National Scientific Cardiac Surgery Center” in Astana. The study is carried out in accordance with the principles of the Declaration of Helsinki of the World Medical Association. Genomic DNA extraction was performed on 245 samples using the Illustra Blood Kit (Cytiva, USA). Qualitative and quantitative assessment of the extracted genomic DNA was conducted using the NanoDrop 2000 (Thermo Scientific) and Qubit 2.0 (Thermo Fisher Scientific). Subsequently, DNA library preparation was carried out using the Illumina DNA Prep with Exome 2.5 Enrichment kit. Quality control of the resulting DNA libraries was conducted on a 2100 Bioanalyzer system using the Agilent DNA 1000 Kit and High Sensitivity DNA kit (Agilent Technologies). Following assessment of the DNA library concentration on Qubit 2.0, they were loaded onto the high-performance sequencer NovaSeq 6000 (Illumina, USA) following the manufacturer’s protocol. We conducted human whole-exome sequencing on 245 samples to identify somatic clones in the peripheral blood of patients with atherosclerosis. Patients were divided into three groups – low risk, middle, and high risk of atherosclerotic complications. Bioinformatic analysis of sequence data were performed. We created list of genes associated with CH to deep analysis and to interpreter the data in patient groups. Subsequently, DNA extraction from the remaining samples is performed, followed by sequencing on the NovaSeq 6000 platform. Analysis of the resulting sequenced data is currently underway. Further research and monitoring of CHIP will enable us to understand the mechanisms underlying the development of cardiovascular diseases and to devise a comprehensive management plan for patients with this pathology. Supported by Committee of Science of the Ministry of Science and Higher Education of Republic of Kazakhstan (AP14869903), (BR21881970) and Nazarbayev University CRP (211123CRP1608).

The influence of polymorphism of genes associated with breast cancer on the effectiveness of drug antitumor therapy

Background. Increasing the survival rate of breast cancer patients is a problem all over the world and directly depends on the early detection of a malignant tumor. Genome-wide associative studies (GWAS) as a minimally invasive method may be used in determining risk of breast cancer or detection at an early stage. The increase in the number of patients with disseminated breast cancer in the Republic of Kazakhstan makes it necessary to search for molecular genetic markers of breast cancer for their use in the diagnosis and treatment of patients with this pathology.Aim. To retrospectively estimate the correlation of the effectiveness of drug antitumor therapy for breast cancer with gene polymorphism.Materials and methods. The study included the results of genotyping biomaterial samples on high-density DNA chips (venous blood of 1,277 Kazakh patients (in the third generation) with a verified diagnosis of breast cancer with locally advanced and disseminated breast cancer who received anticancer therapy), clinical data of patients, data on the clinical efficacy and toxicity of drug therapy. GWAS data (genotypes) associated with identified responses to chemotherapy drugs were compared with similar data recorded in international databases.Results. The family history study showed 16.52 % of women in the questionnaires had a family history of various types of ESR, and 86.25 % of them had a burden of breast cancer in women of the first degree of kinship. The average age of patients with breast cancer was 48.79 ± 11.44 years. According to the TNM classification, cancer in situ was detected in 4.78 % of patients, stage I of the disease was recorded in 15.27 %, stage II in 63.43 %, stage III in 12.60 %, stage IV in 3.92 % of patients. The vast majority of the patients (96.9 %) had a nodular form of breast cancer. The distribution of the patients by tumor phenotype: luminal type A was found in 20.4 % of patients, luminal type B in 38.3 %, luminal type B with HER2 overexpression in 14.3 %, HER2 positive form in 11.9 % of cases, 12.4 % of patients had an aggressive form – triple negative breast cancer. 18 main genotypes were identified in the Kazakh population as a result of the analysis of associations of the effectiveness of neoadjuvant chemotherapy (its individual components, according to chemotherapy regimens) and individual gene polymorphisms.Conclusion. An associative relationship between different types of gene polymorphism and the characteristics of response to various chemotherapeutic drugs used in the treatment of breast cancer has been confirmed. The obtained results formed the basis for the development of recommendations for making changes to the clinical practice of the Republic of Kazakhstan in order to use them in identifying a genetic predisposition to breast cancer and the effectiveness of drugs used in treatment.

Analysis on Chemical Composition of Urinary Calculi and Evaluation on Metabolic Disturbance in 1080 Uyghur, Kazakh and Han Nationality Patients of Xinjiang

Urinary stones pose a significant health concern globally. The incidence rates vary and are influenced by diverse factors. Despite advancements in the treatment modalities, increasing rate of urinary stones necessitates the development of stone prevention strategies and understanding of metabolic risk factors. Objective: To determine the relationship between chemical composition of urinary calculi and evaluation on metabolic disturbance in 1080 Uyghur, Kazakh and Han patients of Xinjiang. Methods: The stone composition of 1080 patients and analysis of 24-h urine and serum biochemistry results of 775 cases was evaluated by infrared spectroscopic analysis and automatic biochemical machine respectively. Results: Among 644 cases of urinary stones, calcium oxalate stones (409 cases) and mixed type stones (436 cases) were predominant. Metabolic disturbances were found in 643 cases (82.97%) out of 775 patients, showing various urinary abnormalities like hyperuricosuria, hyperoxaluria, hyper-phosphaturia, hyper-cystinuria, hypercalciuria, hypomagnesuria, hypocitraturia, and reduced urine volume (<2000ml in 407 cases). Conclusions: Urinary calculi have intimate connection with metabolic evaluation. Metabolic evaluation and composition of urinary calculi have great significance in treatment and prevention of urinary calculi.

Integrated analysis of microRNA expression in tears of Kazakh patients with climatic droplet keratopathy in Xinjiang, China

Climatic droplet keratopathy (CDK) is a corneal diseases, which is characterized by increased oil-like deposits on the anterior elastic lamina and anterior stromal layer. Severe CDK can even cause blindness, with no specific available treatment. Besides. CDK is poorly understood in terms of its pathogenic mechanisms. Thus, to determine potential biomarkers for CDK, we analyzed the microRNA expression profile in tear samples from CDK patients and investigated their putative roles in the pathogenesis of CDK. Herein, miRNA sequencing and following bioinformatics analysis was performed to explore the roles of their target genes in CDK. A total of 67 differentially expressed miRNAs were identified, of which 25 were upregulated and 42 were downregulated. qPCR verification showed that among the up- and down-regulated miRNAs, expression of five and six, respectively, was most significantly different.The target genes of the differentially expressed miRNAs are involved in the FoxO signaling pathway, tumor necrosis factor (TNF) signaling pathway, and steroid hormone biosynthesis. Protein–protein interaction network analyses identified 20 hub genes, including PTEN, GSK3B, and SMAD3. In conclusion, the panel of differentially expressed miRNAs identified may have potential utility as early diagnostic biomarkers for CDK. Moreover, the TNF signaling pathway is a new potential target in CDK for the development of treatments.

Bioinformatics analysis of lncRNA-related ceRNA networks in the peripheral blood lymphocytes of Kazakh patients with essential hypertension in Xinjiang.

Here, we aimed to investigate long non-coding RNA (lncRNA) expression characteristics in the peripheral blood lymphocytes of Xinjiang Kazakh people with essential hypertension and the underlying regulatory mechanisms of competing endogenous RNAs (ceRNA). From April 2016 to May 2019, six Kazakh patients with essential hypertension and six Kazakh healthy participants were randomly selected from the inpatient and outpatient cardiology departments of the First Affiliated Hospital of Shihezi University Medical College, Xinjiang. After detecting the expression levels of lncRNA and mRNA in the peripheral blood lymphocytes using gene chip technology, their levels in the hypertensive group were compared with those in the control group. Six differentially expressed lncRNAs were randomly selected for real-time PCR to verify the accuracy and reliability of the gene chip results. GO functional clustering and KEGG pathway analyses were performed for differentially expressed genes. The ceRNA regulatory network of lncRNA-miRNA-mRNA was constructed, followed by visualization of the results. The expressions of miR-139-5p and DCBLD2 after PVT1 overexpression in 293T cells were detected by qRT-PCR and Western blot. In the test group, 396 and 511 differentially expressed lncRNAs and mRNAs, respectively, were screened out. The trend of real-time PCR results was consistent with that of the microarray results. The differentially expressed mRNAs were found to be primarily involved in the adhesion spot, leukocyte migration via endothelial cells, gap junction, actin cytoskeleton regulation, and extracellular matrix-receptor interaction signaling pathways. By constructing the ceRNA regulatory network, we found that lncRNA PVT1-miR-139-5p-DCBLD2 has a potential ceRNA regulatory mechanism involved in the development of essential hypertension in Xinjiang Kazakh people. In 293T cells, lncRNA PVT1 overexpression inhibited miR-139-5p and DCBLD2 levels. Our findings indicate that differentially expressed lncRNAs may be involved in the development of essential hypertension. lncRNA PVT1-miR-139-5p-DCBLD2 was indicated to comprise a potential ceRNA regulatory mechanism involved in the development of essential hypertension in the Xinjiang Kazakh population. Thus, it may act as a novel screening marker or therapeutic target for essential hypertension in this population.

MRNA Expression Profiles and Molecular Biomarkers Involved in Inflammatory Response for Essential Hypertension in Kazakh Population From Xinjiang

Abstract Background To identify hypertensive inflammation-related mRNA in peripheral blood mononuclear cells (PBMCs) from patients with essential hypertension (EH) of Kazakh Chinese population in Xinjiang, and offer theoretical foundation for further understanding the immune mechanisms that contribute to EH in Kazakh and provide specific molecular biomarkers for clinical diagnosis and targeted-specific treatments of this disorder. Methods Thirty Kazakh patients with EH and 30 age-matched healthy Kazakh people were divided into EH group and control group. After performing blood pressure measurement and determination of serum lipids and blood glucose, total RNA was isolated from PBMCs of hypertensive Kazakh patients and healthy Kazakh subjects, and differentially expressed mRNA in 6 randomly selected samples from each group were identified with human lncRNA/mRNA V4.0 microarray. Gene set enrichment analysis (GSEA), disease process, the Gene Ontology (GO), and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis of differentially expressed mRNA were carried out using R language and ClusterProfiler software package. Reverse transcription quantitative real-time PCR (qRT-PCR) was used to validate the differential expression pattern of inflammation-related genes in the mRNA microarray data and results of bioinformatics analysis. Results The average blood pressure was significantly higher in the EH group than those in the control group (P < 0.01), while there was no statistical significance for the levels of serum lipids and blood glucose between the 2 groups. Compared with healthy Kazakh controls, a total of 522 mRNA were significantly differentially expressed from PBMCs of hypertensive Kazakh patients with fold change of ≥1.5 and P value <5% in expression. Among them, 411 were upregulated and 111 were downregulated. GO enrichment analysis of upregulated mRNA identified numerous inflammation-related biological processes and molecular functions. Many of these processes and molecular function were mainly involved in immune response-regulating signaling pathway, immune response-activating signal transduction, antigen binding, immunoglobulin receptor binding and peptide antigen binding, etc. GSEA and KEGG pathway analysis for the upregulated mRNA indicated several positively enriched gene sets and pathways related to inflammatory response, such as focal adhesion, cell adhesion molecules, chemokine signaling pathway, leukocyte transendothelial migration, cytokine–cytokine receptor interaction, and B-cell receptor signaling pathway. qRT-PCR validation results of 14 mRNA related to inflammatory response were consistent with the microarray data. Conclusions This is the first study to identify gene expression profile involved in hypertensive inflammation in Kazakh Chinese population in Xinjiang with EH, and not only provides specific molecular biomarkers for predicting and diagnosing progression of EH, but also will provide targeted-specific treatments of this disorder in Kazakh Chinese population in Xinjiang.

Effects of potassium channel knockdown on peripheral blood T lymphocytes and NFAT signaling pathway in Xinjiang Kazak patients with hypertension

ABSTRACT Backgroud and aim T lymphocytes are involved in the occurrence and development of essential hypertension, and potassium channels are thought to be critical for lymphocyte activation. This study is to examine the roles of the voltage-gated potassium channels (Kv1.3) and calcium-activated potassium channels (KCa3.1) in peripheral blood T lymphocytes in Kazakh hypertensive patients of Xinjiang, China, mainly focusing on the effects of these channels on nuclear factor of activated T cells (NFAT) and inflammatory cytokines of T lymphocytes. Method Kv1.3 and KCa3.1 gene silencing were performed in cultured T lymphocytes from Kazakh patients with severe hypertension. T cell proliferation after gene silencing was measured using CCK-8. The mRNA and protein expression levels were measured using RT-qPCR and Western blot analysis, respectively. Nuclear translocation of NFAT was observed using laser confocal fluorescence microscopy. Inflammatory cytokine levels were detected with ELISA. Results Compared with control group, gene silencing of Kv1.3 and KCa3.1 respectively inhibited the proliferation of T cells. Moreover, compared with the control group, the mRNA expression levels of NFAT, IL-6 and IFN-γ were significantly decreased after gene silencing. Furthermore, the NFAT protein expression level was significantly down-regulated. In addition, the levels of IFN-γ and IL-6 in the cell culture supernatant were significantly decreased. Conclusion Both Kv1.3 and KCa3.1 potassium channels activated T lymphocytes and enhanced the cytokine secretion possibly through CaN/NFAT signaling pathway, which may in turn induce micro-inflammatory responses and trigger the occurrence and progression of hypertension.

Predictors of health self-management behaviour in Kazakh patients with metabolic syndrome: A cross-sectional study in China.

Metabolic syndrome (MS) is common among Muslim patients living in China, most of whom are Kazakh adults. Continuous and effective health self-management plays a critical role in preventing negative health outcomes for individuals with MS. However, Muslim minority patients with MS face many difficulties in actively participating in health self-management, and the factors supporting their successful self-management of MS remain unclear. This study aimed to identify the factors predicting health self-management behaviour among Kazakh MS patients and provide empirical evidence for establishing recommendation guidelines or intervention programmes for health self-management among Muslim minorities. A cross-sectional study was conducted in Xinjiang Province, China, with the use of convenience sampling to explore the current health self-management behaviour of 454 Kazakh MS patients and its influencing factors. Univariate analysis and logistic regression were used to analyse the data. The total health self-management behaviour score of Kazakh MS patients was 85.84±11.75, and the weaknesses in self-management behaviour were mainly reflected in three dimensions: disease self-monitoring, emotion management and communication with physicians. The significant positive predictors of health self-management behaviour were sex, education, family monthly income per capita, weight, knowledge of MS, and self-efficacy, while the significant negative predictors were blood pressure, the number of MS components, chronic disease comorbidities, and social support (objective support and utilization of support). The health self-management behaviour of Kazakh MS patients is poor. Health care providers should aim to develop culturally specific and feasible health management intervention programmes based on the weaknesses and major modifiable influencing factors in Muslim minority MS patient health self-management, thus improving the health outcomes and quality of life of patients.

Risk Factors for the Development of Atrial Fibrillation in the Kazakh Patients

BACKGROUND: Atrial fibrillation (AF) is the most common persistent heart rhythm disorder. AIM: Assessment of clinical predictors of atrial fibrillation in the Kazakh population. METHODS: An analytical clinical and epidemiological study of 75 patients with AF of Kazakh nationality. Descriptive analysis of medical records was carried out and the results of laboratory and instrumental research methods. Statistical analysis was carried out using the Statistica 6.0 Software package from StatSoft Inc. (USA) and MS Excel. RESULTS: In the majority of the studied patients (86.7%), atrial fibrillation was associated with hypertension, in 49.3% of patients was diagnosed with coronary artery disease. A permanent form of atrial fibrillation was observed in 63%, in 20% AF manifested itself in the form of paroxysms, in 17% AF was persistent. AF, which arose against the background of CHF, was established in 41.3% of the patients studied by us, while a decrease in LVEF below 40% was observed in 21.3% of the examined patients. In our study, diabetes mellitus was diagnosed as a comorbid pathology in 24% of patients and diabetes mellitus correlated with permanent AF in 66.7%. Thyroid pathology was observed in 9.3% cases. CRHD as a concomitant disease occurred in 12% of cases. In 5.7% of cases, AF was registered as idiopathic (primary) without a history of cardiovascular and concomitant pathology. Smoking as a risk factor was observed in 16%, alcohol consumption, was noted by 8 patients (10.7%). In 40% of cases, patients with AF were obese, 45.3% of the patients were overweight (BMI ≥25).

Correlation between betatrophin/angiogenin-likeprotein3/lipoprotein lipase pathway and severity of coronary artery disease in Kazakh patients with coronary heart disease.

BACKGROUNDThe results of previous animal experiments and clinical studies have shown that there is a correlation between expression of betatrophin and blood lipid levels. However, there are still differences studies on the correlation and interaction mechanism between betatrophin, angiogenin-likeprotein3 (ANGPTL3) and lipoprotein lipase (LPL). In our previous studies, we found an increase in serum ANGPTL3 Levels in Chinese patients with coronary heart disease (CHD). Therefore, we retrospectively studied Kazakh CHD patients.AIMTo explore the correlation between the betatrophin/ANGPTL3/LPL pathway and severity of coronary artery disease (CAD) in patients with CHD.METHODSNondiabetic patients diagnosed with CHD were selected as the case group; 79 were of Kazakh descent and 72 were of Han descent. The control groups comprised of 61 Kazakh and 65 Han individuals. The serum levels of betatrophin and LPL were detected by enzyme-linked immunosorbent assay (ELISA), and the double antibody sandwich ELISA was used to detect serum level of ANGPTL3. The levels of triglycerides, total cholesterol, and fasting blood glucose in each group were determined by an automatic biochemical analyzer. At the same time, the clinical baseline data of patients in each group were included. RESULTSBetatrophin, ANGPTL3 and LPL levels of Kazakh patients were significantly higher than those of Han patients (P = 0.031, 0.038, 0.021 respectively). There was a positive correlation between the Gensini score and total cholesterol (TC), triglycerides (TG), low- density lipoprotein cholesterol (LDL-C), betatrophin, and LPL in Kazakh patients (r = 0.204, 0.453, 0.352, 0.471, and 0.382 respectively), (P = 0.043, 0.009, 0.048, 0.001, and P < 0.001 respectively). A positive correlation was found between the Gensini score and body mass index (BMI), TC, TG, LDL-C, LPL, betatrophin in Han patients (r = 0.438, 0.195, 0.296, 0.357, 0.328, and 0.446 respectively), (P = 0.044, 0.026, 0.003, 0.20, 0.004, and P < 0.001). TG and betatrophin were the risk factors of coronary artery disease in Kazakh patients, while BMI and betatrophin were the risk factors in Han patients.CONCLUSIONThere was a correlation between the betatrophin/ANGPTL3/LPL pathway and severity of CAD in patients with CHD.

Role and Mechanism of mir-5189-3p in Deep Vein Thrombosis of Lower Extremities

BackgroundThis study is to investigate the role and mechanism of mir-5189-3p in deep vein thrombosis (DVT) in lower extremity. MethodsThe blood samples were collected from Kazakh patients with DVT in lower extremity and were subjected to microRNA sequencing. Bioinformatics were used to identify mir-5189-3p and its target genes. Dual luciferase reporter assay was used to determine the regulatory effect of mir-5189-3p on JAG1. SD rats were randomly divided into normal control, DVT model, hsa-miR-5189-3p mimics and hsa-miR-5189-3p negative control groups. HE staining was used to observe the pathological changes. TUNEL method was used to observe apoptosis. Western blot was used to detect Bax and Bcl-2 protein expression. Real-time quantitative PCR was used to detect JAG1, Notch1 and Hes1 mRNA. ResultsThe target of Has-miR-5189-3p was JAG1. Co-transfection of miR-5189-3p mimics and pmirGLO/JAG1 wild-type plasmid induced significantly decreased luciferase activity. In hsa-miR-5189-3p mimics and hsa-miR-5189-3p negative control groups, there were more nucleated cells in the thrombus tissues, and the organization degree obviously increased. Signs of blood flow recanalization were observed. The apoptosis of hsa-miR-5189-3p mimics and hsa-miR-5189-3p negative control groups was lower than that in DVT model group. Furthermore, mir-5189-3p mimics significantly increased the mRNA levels of JAG1, Notch1 and Hes1. Additionally, mir-5189-3p mimics significantly increased Bcl-2 while decreased Bax protein. Conclusionsmir-5189-3p could inhibit apoptosis and promote thrombus organization in DVT possibly via Notch signaling pathway. Mir-5189-3p can be used as a potential target for DVT treatment.

The effect of high blood pressure-health literacy, self-management behavior, self-efficacy and social support on the health-related quality of life of Kazakh hypertension patients in a low-income rural area of China: a structural equation model

BackgroundHealth-Related Quality of Life (HRQoL) of hypertensive patients is not only affected by the disease itself but also by some subjective factors. Low health literacy is prevalent among ethnic minorities. Considering the Kazakh-Chinese people have the highest prevalence of hypertension in Xinjiang, and the High Blood Pressure-Health Literacy (HBP-HL) has not been included in the study of HRQoL. The synergistic effects and the potential mechanism HBP-HL, self-management behavior, therapeutic adherence, self-efficacy, social support on HRQoL remain unclear. This study aimed to introduce the HBP-HL, and develop a structural equation model (SEM) to identify the factors influencing of the HRQoL among Kazakh hypertensive patients.MethodsThe data was obtained by questionnaire survey and physical examination in 2015. Patients with hypertension were recruited through random cluster sampling in Kazakh settlements in Xinjiang. Firstly, the blood pressure was measured. Then the one-for-one household interviews were conducted by Kazakh investigators. The questionnaires regarding HBP-HL, HRQoL, self-management behavior, therapeutic adherence, self-efficacy, and social support were used to collect data. Finally, SEM was constructed, and p ≤ 0.05 was taken as significant.ResultsThe data was analysed by SPSS18.0 and AMOS18.0 software. 516 Kazakh hypertension patients were recruited, and 94.4% of them had a relatively low HBP-HL score. The mean standardized scores of HRQoL, self-management, therapeutic adherence were poor; they were 63.5, 66.2, and 64.4, respectively. But 96.1% and 98.3% of the participants had high levels of self-efficacy and social support. The SEM of the HRQoL had a good overall fit (χ2/df = 2.078, AGFI = 0.944, GFI = 0.968, CFI = 0.947, IFI = 0.949, RMSEA = 0.046). The model indicated that the HBP-HL has the highest correlation with HRQoL, following with self-management behavior, social support, and self-efficacy.ConclusionsLow HBP-HL is a major influenced factor of HRQoL among Kazakh hypertensive patients. Future programs should consider HBP-HL as the breakthrough point when designing targeting intervention strategies.

HPV16 infection promotes an M2 macrophage phenotype to promote the invasion and metastasis of esophageal squamous cell carcinoma.

High-risk human papillomavirus (HR-HPV) is an important risk factor for esophageal cancer. Macrophages constitute a crucial immune medium for regulating HPV-related tumors; however, the specific regulatory mechanisms remain unknown. Therefore, the purpose of our current study was to investigate the mechanism by which HPV16E6 regulates macrophages to promote the invasion and metastasis of esophageal cancer. HPV16E6 infection was detected by polymerase chain reaction. Immunohistochemistry was used to verify the distribution of tumor-associated macrophages (TAMs) and MMP-9 expression in esophageal squamous cell carcinoma tissues (ESCCs), and cancer adjacent normal tissues (CANs) from Kazakh patients. ESCC cells were transfected with a plasmid over-expressing HPV16E6 and non-contact cocultured with macrophages. The infection rate of HPV16E6 in Kazakh ESCCs was clearly higher than that in CANs (P < 0.05). The density of CD163-positive TAMs was significantly positively correlated with HPV16E6 infection in ESCCs (P < 0.05). After coculturing macrophages and EC9706 cells transfected with the HPV16E6 plasmid, the phenotype of macrophages transformed into M2 macrophages. The migration and invasion ability of ESCC cells were higher in the HPV16E6-transfected and coculture group than in the HPV16E6 empty vector-transfected and non-cocultured HPV16E6-transfected groups (all P < 0.05). The density of M2-like TAMs in ESCCs was positively correlated with the level of MMP-9 expression. MMP-9 expression in the HPV16E6-ESCC coculture macrophages group was substantially higher than that in controls (all P < 0.05). HPV16 infection mediates tumor-associated macrophages to promote ESCC invasion and migration.

SUMOylation of HSP27 regulates PKM2 to promote esophageal squamous cell carcinoma progression

A previous proteomic screening of differentially expressed biomarkers between Kazakh patients with esophageal squamous cell carcinoma (ESCC) and normal adjacent tissues demonstrated that heat shock protein 27 (HSP27) and pyruvate kinase isoenzyme M2 (PKM2) were both highly expressed in ESCC samples compared with normal controls. However, the regulatory association between HSP27 and PKM2 in ESCC remains elusive. In the present study, immunohistochemistry and immunoblotting were adopted to examine the expression of HSP27, PKM2 and other relevant biomarkers involved in epithelial-to-mesenchymal transition in clinical tissue samples. The interactions between proteins were detected by co-immunoprecipitation (Co-IP) assay and further confirmed by immunofluorescence assay. The growth and motility of ESCC cells were examined by MTT, Transwell and wound healing assays. Overexpression of HSP27 was found to be significantly associated with T-cell classification, lymph node metastasis and poor prognosis in ESCC. In addition, HSP27 expression was significantly correlated with PKM2 expression in ESCC specimens. Functionally, knockdown of HSP27 inhibited the growth and motility of ESCC cells. Moreover, HSP27 was found to directly interact with small ubiquitin-related modified protein 2/3 (SUMO2/3) in ESCC cell lines, as evidenced by Co-IP and laser confocal imaging. In addition, downregulation of HSP27 was shown to decrease PKM2 and E-cadherin expression. Knockdown of SUMO2/3 was observed to reduce the expression of HSP27, PKM2 and EMT-related biomarkers. The results of the present study indicated that the SUMOylation of HSP27 enhances the proliferation, invasion and migration of ESCC cells via PKM2.

Expression and filtering of TGF-β2 in aqueous humor and trabecular meshwork of Han and Kazakh patients with PACG

Expression and filtering of TGF-β2 in aqueous humor and trabecular meshwork of Han and Kazakh patients with PACG

Correlation between P-selectin rs1800807 and rs1800808 Gene polymorphisms and plasma soluble P-selectin concentrations in patients with atrial fibrillation complicated with thromboembolism in Xinjiang, China.

This study is to investigate the relationship of P-selectin (Ps) gene rs1800807 and rs1800808 polymorphisms with plasma soluble P-selectin (sPs) in Han, Uygur, and Kazakh people with atrial fibrillation (AF) and thromboembolism (TE) in Xinjiang, China.A total of 778 Han patients (including 131 patients with AF and TE, 229 patients with AF and 418 healthy individuals), 660 Uygur patients (including 118 patients with AF and TE, 232 patients with AF and 310 healthy individuals), and 505 Kazakh patients (including 42 patients with AF and TE, 156 patients with AF and 307 healthy individuals) were enrolled in this study. Polymerase chain reaction-restriction fragment length polymorphism and direct DNA sequence analysis were used to analyze the polymorphisms of rs1800807 and rs1800808 of Ps gene. ELISA was used to determine the plasma sPs level. The association between plasma sPs levels and Ps gene polymorphisms was further analyzed.The sPs concentrations of GG genotype at rs1800807 locus in the Han, Uygur and Kazakh ethnic groups in Xinjiang, China were significantly higher than those of the CC genotype and CG genotype (P < .05). In the rs1800808 locus, plasma sPs concentrations of the heterozygous mutant CT genotypes in Han and Uygur populations were significantly higher than those in the CC and TT genotypes, whereas the plasma sPs concentrations in Kazakh TT genotypes were significantly higher than those in the CC and CT genotypes (P < .05). Among different ethnic groups, there were significant differences in sPs levels of rs1800807 and rs1800808 genotypes (P < .05).Plasma sPs concentrations are associated with Ps genotypes and sPs concentration of the same genotype shows racial differences.

Overexpression of VEGF-C and MMP-9 predicts poor prognosis in Kazakh patients with esophageal squamous cell carcinoma.

Vascular endothelial growth factor (VEGF) and Matrix metalloproteinases (MMPs) are believed to participate in infiltration of tumors. High mortality of esophageal squamous cell carcinoma (ESCC) related to its primary infiltration; however, it is not clear whether the expression of VEGF and MMPs is involved in this process. Screening of The Cancer Genome Atlas (TCGA) database showed that among the VEGF family and MMP9, VEGF-A, VEGF-C, and MMP-9 mRNA were overexpression in ESCC. This result was verified using the Oncomine database and in Kazakh patients with ESCC. Overexpression of VEGF-C and MMP-9 and positive association with advanced esophageal cancer and invading ESCC cells (Gene Expression Omnibus (GEO): GSE21293). Immunohistochemical staining revealed that VEGF-C and MMP-9 were overexpressed in Kazakh ESCCs. VEGF-C expression was related to invasive depth, tumor-node-metastasis (TNM) staging, lymphatic, and lymph node metastasis of ESCC. The linear association between them was further confirmed in TCGA database and the specimens from Kazakh patients with ESCC. Patients with both proteins expression had tumors with greater aggressiveness, suffered from poor prognosis compared with patients who did not express either protein or expressed protein alone. Both proteins expression predicted high invasiveness of ESCC, which is related to worse prognosis of Kazakh ESCCs.

Effect of health literacy interventions with the stages of change on Kazakh-Chinese hypertension patients

Objective To evaluate the effect of the intervention combined the high blood pressure health literacy(HBP-HL) with the stages of change on waist circumference(WC), body mass index(BMI) and physiological-biochemical indexes among the Kazakh-Chinese hypertensive patients. Methods The interventional plan was built based on the Stages of Change of Transtheoretical Model . This randomized controlled trial study was carried out from July 2014 to January 2016, and Kazakh hypertension patients from qianjin and small canal pastoral areas were sampled using stratified cluster sampling method, with 74 patients from each place. The general health management combined with High Blood Pressure Health Education handbook was applied in the control group. The intervention group was given the 12-month intervention combined the HBP-HL with the stages of change based on the control group. Meanwhile, WC, BMI and other data were collected at the first, twelfth and eighteenth months. Results Repeated variance analysis showed interaction effects between time and group (F=14.396, 15.214, P<0.05), indicating that the effect of intervention factors on WC and BMI would increase over time when intervention existed. The total cholesterol ((5.69±0.93)mol/L), low density lipoprotein ((3.74±0.86)mol/L) and serum creatinine ((65.46±13.45)mol/L) of hypertension patients in intervention group were lower than those before intervention (t=3.998, 4.581, 2.574, P<0.05). After intervention, the scores of total health literacy (t=5.157) , understanding ability (t=6.504), the latest vital signs (t=11.583) and avoiding food allergy (t=3.778) of the intervention group were higher than those of the control group, and the differences were statistically significant (P<0.05). Conclusions The intervention strategy of health literacy-behavioral change stage is feasible and effective. It can significantly reduce WC, BMI, total cholesterol, low density lipoprotein and serum creatinine in Kazakh hypertension patients in pastoral areas, and the short-term maintenance effect of the intervention is acceptable. Key words: Kazakh; Hypertension; Health literacy; Stages of change; Waist circumference; Body mass index

Identifying the differentially expressed microRNAs in esophagus squamous cell carcinoma of Kazakh patients in Xinjiang.

Despite improvements in diagnosis and treatment, the survival of patients with advanced stages of esophageal squamous cell carcinoma (ESCC) remains poor. Therefore, novel biomarkers that can assist with early detection of ESCC are required. In the present study, three paired ESCC and normal esophageal tissue samples from Xinjiang Kazakh patients were obtained and microRNA (miRNA) microarray analysis was used to detect the differentially-expressed miRNAs. The target genes of the identified miRNAs were predicted using miRWalk software. A total of 23 miRNAs were differently expressed in Kazakh patients with ESCC. Gene Ontology enrichment analysis demonstrated that the upregulated miRNAs were predominantly associated with the ‘vesicle’ and ‘membrane-bounded vesicle’ terms, while the downregulated miRNAs were primarily associated with the term ‘negative regulation of integrin-mediated signaling pathway’. The most highly enriched Kyoto Encyclopedia of Genes and Genomes pathway for the differentially-expressed miRNAs was ‘Endocrine and other factor-regulated calcium reabsorption’. Protein-protein interaction network analysis revealed that IQ motif containing GTPase activating protein 1, RAB11A, lysine acetyltransferase 2B, catenin α 1 and tight junction protein 2 were hub genes of the network. In conclusion, a number of differentially-expressed miRNAs were identified in ESCC tissues samples from Xinjiang Kazakh patients, which may improve the understanding of the processes of tumorigenesis and development.

The effect of Glut1 and c-myc on prognosis in esophageal squamous cell carcinoma of Kazakh and Han patients.

Glucose transporter type 1 (Glut1) plays a crucial role in cancer-specific metabolism. We explored the expression of Glut1 and c-myc, the relationship between them and the effect of Glut1, c-myc on prognosis in esophageal squamous cell carcinoma. Immunohistochemistry was used to examine the expression of Glut1 and c-myc. χ2 test analyzes the relationship between c-myc, Glut1 and pathological parameters. Spearman correlation analyzes the relationship between c-myc and Glut1. Survival analysis was used to investigate the effect of Glut1 and c-myc on prognosis. Glut1 positivity was associated with tumor size (p < 0.01), depth of invasion (p = 0.021), Tumor, Node, Metastasis stage (IA+IB,II+IIB,IIIA+IIIB,IVA+IVB; p = 0.004), lymph node metastasis (p = 0.002) and nerve invasion (p = 0.050). C-myc positivity was associated with tumor location (p = 0.015), depth of invasion (p = 0.022) and lymph node metastasis (p = 0.035). There was a positive correlation between c-myc and Glut1 (r = 0.321). Patients with Glut1 c-myc co-expression had poorer prognosis. Inhibiting Glut1 c-myc co-expression may improve the prognosis of esophageal squamous cell carcinoma.