Kazakh Patients Research Articles

High MLL2 expression predicts poor prognosis and promotes tumor progression by inducing EMT in esophageal squamous cell carcinoma

BackgroundMLL2 has been identified as one of the most frequently mutated genes in a variety of cancers including esophageal squamous cell carcinoma (ESCC). However, its clinical significance and prognostic value in ESCC has not been elucidated. In the present study, we aimed to investigate the expression and role of MLL2 in ESCC.MethodsImmunohistochemistry (IHC) and qRT-PCR were used to examine the expression profile of MLL2. Kaplan–Meier survival analysis and univariate and multivariate Cox analyses were used to investigate the clinical and prognostic significance of MLL2 expression in Kazakh ESCC patients. Furthermore, to evaluate the biological function of MLL2 in ESCC, we applied the latest gene editing technique CRISPR/Cas9 to knockout MLL2 in ESCC cell line Eca109. MTT, colony formation, flow cytometry, scratch wound-healing and transwell migration assays were performed to investigate the effect of MLL2 on ESCC cell proliferation and migration. The correlation between MLL2 and epithelial–mesenchymal transition (EMT) was investigated by Western blot assay in vitro and IHC in ESCC tissue, respectively.ResultsBoth mRNA and protein expression levels of MLL2 were significantly overexpressed in ESCC patients. High expression of MLL2 was significantly correlated with TNM stage (P = 0.037), tumor differentiation (P = 0.032) and tumor size (P = 0.035). Kaplan–Meier survival analysis showed that patients with low MLL2 expression had a better overall survival than those with high MLL2 expression. Multivariate Cox analysis revealed that lymph node metastasis and tumor differentiation were independent prognostic factors. Knockout of MLL2 in Eca109 inhibited cell proliferation and migration ability, induced cell cycle arrest at G1 stage, but it had no significant effect on apoptosis. In addition, knockout of MLL2 could inhibit EMT by up-regulation of E-Cadherin and Smad7 as well as down-regulation of Vimentin and p-Smad2/3 in ESCC cells. In cancer tissues, the expression of E-Cadherin was negatively correlated with MLL2 expression while Vimentin expression was positively correlated with MLL2 expression.ConclusionOur results indicate that overexpression of MLL2 predicts poor clinical outcomes and facilitates ESCC tumor progression, and it may exert oncogenic role via activation of EMT. MLL2 may be used as a novel prognostic factor and therapeutic target for ESCC patients.

Inhibitory effects of candesartan on KCa3.1 potassium channel expression and cell culture and proliferation in peripheral blood CD4+T lymphocytes in Kazakh patients with hypertension from the Xinjiang region

ABSTRACTBackground and aim: Increasing evidence confirms that potassium channels are essential for lymphocyte activation, suggesting an involvement in the development of hypertension. Moreover, chronic inflammation is regarded as a direct or indirect manifestation of hypertension, highlighting the theoretical mechanisms. In this study, we investigated changes in KCa3.1 potassium channel expression in the blood of hypertensive and healthy Kazakh people in north-west China.Methods: Flow cytometry technology was used for T-lymphocyte subtype analysis. Changes in the messenger RNA and protein expression of the KCa3.1 potassium channel in CD4+ T lymphocytes were detected using real-time quantitative polymerase chain reaction and western blots, using CD4+ T-cell samples from hypertensive Kazakh patients divided into candesartan and TRAM-34 treatment groups, and healthy case controls. Peripheral blood CD4+ T lymphocytes were activated and proliferated in vitro and then incubated for 0, 24, and 48 h under various treatment conditions. Changes in CD4+ T-lymphocytic proliferation were determined using Cell Counting Kit-8 and electron microscope photography.Results: Expression of KCa3.1 was significantly higher in the hypertensive patients than in the controls (p < 0.05). Compared with the healthy group, Kazakh hypertensive patients had a reduced proportion of CD4+ T lymphocytes (p < 0.05).Candesartan and TRAM-34 intervention for 24 h and 48 h inhibited the expression of Kv1.3 and KCa3.1 at mRNA and protein level (p < 0.05).Conclusions: Increase in functional KCa3.1 channels expressed in CD4+ T lymphocytes of Kazakh patients with hypertension was blocked by candesartan, providing theoretical support for hypertension treatment at the cellular ion channel level. Candesartan may potentially regulate hypertensive inflammatory responses by inhibiting T-lymphocytic proliferation and KCa3.1 potassium channel expression in CD4 + T lymphocytes.

A Genetic Variant in miR-124 Decreased the Susceptibility to Esophageal Squamous Cell Carcinoma in a Chinese Kazakh Population.

Esophageal squamous cell carcinoma (ESCC) is characterized by high prevalence and mortality worldwide, and it is very highly prevalent in China. ESCC is caused by various factors, including microRNAs (miRNAs) whose expression have been shown to play a major role in tumor generation. Single nucleotide polymorphisms (SNPs) in miRNAs could affect susceptibility to numerous cancers. This study aimed to evaluate the relationship between SNPs in miR-124 and ESCC risk in the Chinese Kazakh population. A total of 239 Chinese Kazakh patients with ESCC and 227 healthy Chinese Kazakh individuals were recruited in this study. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was used to analyze the miR-124 rs531564 genotype. Allele G of the miR-124 rs531564 polymorphism significantly reduced the risk of ESCC in the Chinese Kazakh population [odds ratio (OR) = 0.711; 95% confidence interval (CI): 0.508-0.996; p = 0.047]. The dominant model indicated that the CG+GG genotypes were associated with significantly decreased ESCC risk compared to the CC genotype (adjusted OR = 0.586; 95% CI: 0.396-0.867; p = 0.007). Stratification analyses showed that compared with the CC genotype, the CG and CG+GG genotypes manifested reduced ESCC risks in the female group [CG vs. CC: OR = 0.472; 95% CI: 0.255-0.872; p = 0.016; (CG+GG) vs. CC: OR = 0.472; 95% CI: 0.255-0.872; p = 0.016] and the age group of <57 years old [CG vs. CC: OR = 0.456; 95% CI: 0.258-0.806; p = 0.006; (CG+GG) vs. CC: OR = 0.456; 95%CI: 0.258-0.806; p = 0.006]. The miR-124 rs531564 polymorphism showed no significant association with histological stage, lymph node metastasis, depth of invasion, or tumor/node/metastasis stage. Our findings are the first to be reported that the miR-124 rs531564 polymorphism decreased ESCC risk in the Chinese Kazakh population.

Genetic variability in LMP2 and LMP7 is associated with the risk of esophageal squamous cell carcinoma in the Kazakh population but is not associated with HPV infection.

The Kazakh population in Xinjiang Province in northwestern China exhibits a high incidence of esophageal squamous cell carcinoma (ESCC). Although the etiology of esophageal carcinoma (EC) has not been elucidated, there are reports of the involvement of an immunologic mechanism. In the current study, 268 Kazakh ESCC patients and 500 age- and sex-matched control subjects were recruited. DNA was extracted from paraffin-embedded tumor specimens from the patients and peripheral blood lymphocytes from the controls and used for LMP2/LMP7 genotyping. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was performed to detect LMP2/LMP7 gene single-nucleotide polymorphisms (SNPs). We found a clear increased risk of ESCC in the Kazakh population for the heterozygous LMP2 R/C genotype and the homozygous C/C genotype (OR = 1.470, 95%CI = 1.076–2.008, p = 0.015 forLMP2R/C; OR = 2.048, 95% CI = 1.168–3.591, p = 0.011 for LMP2 C/C). Conversely, the heterozygous LMP7 Q/K polymorphism was found to decrease the risk of ESCC in this population (OR = 0.421, 95% CI = 0.286–0.621, p = 8.83×10−6). Moreover, LMP2 R/C+C/C genotype was associated with increased tumor invasion depth (p = 0.041). Haplotype analysis showed that haplotype A, which includes wild-type homozygous LMP2/TAP1 and mutant LMP7, decreases susceptibility to ESCC in the Kazakh population; in contrast, haplotype E, which includes wild-type homozygous LMP2/LMP7/TAP1, acts as a risk factor for increased susceptibility to ESCC. This is the first study to report that the heterozygous LMP2 R/C and homozygous C/C genotypes increase susceptibility to ESCC in the Kazakh population and that the heterozygous LMP7 Q/K genotype decreases susceptibility to ESCC in this population. Nevertheless, neither LMP2 nor LMP7 was associated with human papillomavirus (HPV) infection. Understanding LMP2/LMP7 genetic variability will provide a new therapeutic perspective for Kazakh patients with ESCC.

Case-finding for alpha1-antitrypsin deficiency in Kazakh patients with COPD

Background Alpha-1-antitrypsin deficiency (AATD) is an under-diagnosed condition in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to screen for AATD in Kazakh patients with COPD using dried blood spot specimens.MethodsThe alpha1-antitrypsin (AAT) concentration was determined by nephelometry, PCR was used to detect PiS and PiZ alleles; and isoelectric focusing was used to confirm questionable genotype results and detect rare AAT variants.ResultsTo this aim, 187 Kazakh subjects with COPD were recruited. Blood samples were collected as dried blood spot. Genotyping of 187 samples revealed 3 (1.6%) PI*MZ and 1 (0.53%) PI*MS, Phenotyping identified also two sample (1.1%) with phenotype PiMI. Allelic frequencies of pathological mutations Z, S and I resulted 0.8%, 0.3%, 0.5%, respectively, in COPD Kazakh population.ConclusionThis study proved that AATD is present in the Kazakh population. These results support the general concept of targeted screening for AAT deficiency in countries like Kazakhstan, with a large population of COPD patients and low awareness among care-givers about this genetic condition.

Endoscopic analysis of early esophageal cancer and precancerous lesions in Kazakh patients

To explore the value of endoscopic narrow-band imaging in the diagnosis of early-stage esophageal cancer and precancerous lesions in Kazakh patients. A total of 106 Kazakh patients with esophageal mucosa lesions diagnosed by routine endoscopy in our hospital from January 2014 to July 2016 were enrolled in this analysis with 30 randomly selected patients with normal endoscopic findings of the esophageal mucosa as the control group. The morphological changes of papillary capillary loop (IPCL) of the esophageal epithelium in the two groups were observed by narrow-band imaging magnifying endoscopy. Pathological examinations were performed for all the patients with esophageal mucosa lesions. In patients with esophageal mucosa lesions, 10 were diagnosed to have early esophageal cancer, 16 had low-grade tumors, 11 had high-grade tumors and 69 had esophagitis. IPCL typing results showed IPCL type I in all the control subjects, predominantly type IV in patients with early esophageal carcinoma, type II and III in patients with low-grade tumor, type III in patients with high-grade tumor, and type II in patients with esophagitis. The location and size of the esophageal lesions can be observed clearly by narrow-band imaging magnifying endoscopy. The histopathology of the esophageal mucosa can be analyzed with IPCL classification for diagnosis of early esophageal cancer and precancerous lesions in Kazakhs.

Epigenetic silencing of miR-203 in Kazakh patients with esophageal squamous cell carcinoma by MassARRAY spectrometry

ABSTRACTDysregulation of miR-203 by promoter methylation is associated with the development of various cancers. We aimed to explore the underlying link between promoter methylation and miR-203 expression in Kazakh esophageal squamous cell carcinoma (ESCC). MassARRAY® System spectrometry was used to quantitatively analyze the DNA methylation of 32 CpG sites within miR-203 in 99 Kazakh ESCC and 46 normal esophageal tissues (NETs) with similar population characteristics. We conducted real-time PCR to detect miR-203 expression levels and evaluated their association with methylation. Eleven CpG units within miR-203 promoter were frequently hypermethylated in ESCC compared with NETs (P < 0.05). The hypermethylation of several CpG units positively correlated with age, lower esophagus, constrictive type of ESCC, and moderately differentiated ESCC. Given the involvement of human papillomavirus (HPV) in etiology of ESCC was confirmed from our previous reports, herein we found that CpG units within miR-203 in HPV16-positive ESCC are more heavily methylated. Furthermore, miR-203 expression showed a nearly 4.5-fold decrease in ESCC than NETs (0.206 ± 0.336 vs. 0.908 ± 1.424, P < 0.001) and was significantly associated with lymph node metastasis (P = 0.012). The expression of miR-203 with 11 completely hypermethylated CpG units was approximately 6.5-fold lower than that with at least 1 unmethylated CpG unit (P < 0.001) and especially the CpG_15.16 and CpG_31.32 with higher methylation levels in ESCC tissues exhibited lower expression levels of miR-203, which indicated a reverse association between miR-203 methylation and expression. Hypermethylated miR-203 is a potential biomarker and targeted delivery of miR-203 could therefore serve as a preventive or therapeutic strategy for Kazakh ESCC.

Case-finding for alpha1-antitrypsin deficiency in Kazakh patients with COPD

Background: Alpha-1-antitrypsin deficiency (AATD) is an under-diagnosed condition in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to screen for AATD in Kazakh patients with COPD using dried blood spot specimens.&#x0D; Methods: The alpha1-antitrypsin (AAT) concentration was determined by nephelometry, PCR was used to detect PiS and PiZ alleles; and isoelectric focusing was used to confirm questionable genotype results and detect rare AAT variants.&#x0D; Results: To this aim, 187 Kazakh subjects with COPD were recruited. Blood samples were collected as dried blood spot. Genotyping of 187 samples revealed 3 (1.6%) PI*MZ and 1 (0.53%) PI*MS, Phenotyping identified also two sample (1.1%) with phenotype PiMI. Allelic frequencies of pathological mutations Z, S and I resulted 0.8%, 0.3%, 0.5%, respectively, in COPD Kazakh population.&#x0D; Conclusions: This study proved that AATD is present in the Kazakh population. These results support the general concept of targeted screening for AAT deficiency in countries like Kazakhstan, with a large population of COPD patients and low awareness among care-givers about this genetic condition.

T-lymphocyte Kv1.3 channel activation triggers the NLRP3 inflammasome signaling pathway in hypertensive patients.

The aim of the current study was to investigate the correlation between voltage-gated potassium 1.3 (Kv1.3) channel of peripheral blood T-lymphocytes and the NLR family pyrin domain containing 3 (NLRP3) inflammasome pathway in hypertensive patients. Peripheral blood samples from the hypertensive Kazakh patients (n=30) and healthy Kazakh subjects (n=30) were collected. The T lymphocytes and serum were separated, and the state of Kv1.3 channels was detected using the patch-clamp technique. Reverse transcription-quantitative polymerase chain reaction and western blot analyses were used to detect the mRNA and protein expression levels of key molecules [NLRP3, caspase-1 and interleuking (IL)-β] in the lymphocyte NLRP3 inflammasome pathway, while serum IL-1β content was measured by ELISA assay. The results demonstrated no statistical difference in the subject baseline data between the two groups. While more significantly activated Kv1.3 channels were identified in the peripheral blood T-lymphocytes of the hypertension group compared to the normotension group, the mRNA and protein expression levels of NLRP3, caspase-1 and IL-1β were elevated and their peripheral serum interleukin-1β levels were significantly increased. After inhibiting the Kv1.3 channels using the classic potassium channel blocker, these indicators were all decreased significantly. The results indicate that the NLRP3 inflammasome pathway of peripheral blood T-lymphocytes in hypertensive Kazakh patients is activated, which may be correlated with the opening of the Kv1.3 channel.

Expression, prognosis and functional role of Thsd7a in esophageal squamous cell carcinoma of Kazakh patients, Xinjiang.

Thsd7a (Thrombospondin type 1 domain containing 7a) is a critical transmembrane protein. Studies have indicated that Thsd7a was associated with cytoskeletal organization, cell migration and filopodia formation. However, the involvement of Thsd7a remains elusive in human Esophageal Squamous Cell Carcinoma (ESCC). Consequently, immunohistochemistry and reverse transcription-polymerase chain reaction were utilized to study the correlation between the expression of Thsd7a and clinical-pathological characteristics. The influence of Thsd7a on apoptosis, cell proliferating activity, cell cycle, migratory and invasive capacity was determined in Eca 109 and EC 9706 cell lines in vitro. And the influence on proliferating activity was testified using naked mice model in vivo. In addition, the potential molecular mechanism was tested by microarray. It was discovered that there is a certain correlation between Thsd7a and the Kazakh ESCC. By knocking out Thsd7a, the invasion, migration and proliferation could be decreased. And it could also arrest the cell cycle at G1 phase and increase the apoptosis rate. It was further verified that Thsd7a had obvious effect on proliferation in naked mice with xenograft of Eca109 cells. Finally, it was uncovered by microarray analysis that a variety of tumor genes and pathways related to Thsd7a. Together, it was demonstrated that Thsd7a might have a certain degree of carcinogenesis in ESCC.

Ethnicity and the risk of ventricular arrhythmias due to stable ischemic heart disease

Objective: determination of the of life-threatening ventricular arrhythmias risk in native nationality patients with stable ischemic heart disease. Methods. The cohort study included 216 patients with stable ischemic heart disease with left ventricular ejection fraction not less than 40%. All participants initially underwent anthropometric measurements, laboratory routine tests, 6-minute walking test, ECG, 24-hours ECG monitoring, echocardiography. After 3, 6 and 12 months, participants were invited to repeat 24-hours ECG monitoring procedure for life-threatening ventricular arrhythmias episodes detection. Results. Participants cohort included 130 native nationality persons (Kazakhs) and 86 Caucasian patients. Characteristics of the sample: 181 men (84%), the average age of 62 [57; 66], the average follow-up period - 12,7 ± 1,2 months. Increased relative risk of ventricular arrhythmias in Kazakh patients was revealed: high grading ventricular premature beats RR 1.98 (95% CI 1,02-3,84), P = 0.010); non-sustained ventricular tachycardia RR 2.80 (95% CI 1,07-8,97), P <0.001). Signifcant independent influence on life-threatening ventricular arrhythmias development in patients Kazakh nationality had anemia, obesity, diabetes and limitation in 6-minute walking test performing. Conclusion. Arrhythmic events in native nationality patients with stable ischemic heart disease without severe left ventricle systolic dysfunction are different from those of Caucasians, that should be considered when predicting the individual risk of arrhythmic events and sudden cardiac death in native nationality patients.

The expression of cytokine and its significance for the intervertebral disks of Kazakhs.

BackgroundProinflammatory cytokine IL‐6 and anti‐inflammatory cytokine IL‐10 are expressed in herniated intervertebral disks of Kazakhs, but their significance is not yet understood.MethodsSpecimens of herniated lumbar disk were collected from 30 patients with single disk herniation during lumbar discectomy. As a control, 10 specimens were collected postmortem from the cadavers of individuals who did not die from spinal disease. The clinical symptoms in all cases were evaluated preoperation by the JOA index. The expressions of IL‐6 and IL‐10 in the degenerative disk cells of each specimen were detected using immunohistochemical staining. The amounts of IL‐6 and IL‐10 in each intervertebral disk were assessed by enzyme‐linked immunosorbent assay.ResultsThe expression levels of IL‐6 and IL‐10 were significantly higher in the patient group than in the control group. Statistical analysis showed differences between ethnic Kazakh and Han patients in both the expression of IL‐6 and JOA scores. Immunohistochemical staining showed that in the patient group, IL‐6 was found in 28 patients and IL‐10 was found in 27 patients.ConclusionThe high expression of cytokines, such as IL‐6 and IL‐10, has an important relationship with disk degeneration. Of course, age is another factor in cell apoptosis of degenerative disks. More research is necessary to discover how ethnicity and heredity impact the levels of expressed cytokines.

Inhibitory effects of telmisartan on culture and proliferation of and Kv1.3 potassium channel expression in peripheral blood CD4+ T lymphocytes from Xinjiang Kazakh patients with hypertension.

Introduction:Activation of T lymphocytes, for which potassium channels are essential, is involved in the development of hypertension. In this study, we explored the inhibitory effects of telmisartan on the culture and proliferation of and Kv1.3 potassium channel expression in peripheral blood CD4+ T lymphocytes derived from Xinjiang Kazakh patients with hypertension.Methods:CD4+ T-cell samples from hypertensive Kazakh patients and healthy Kazakh people were divided into healthy control, case control, telmisartan, and 4-aminopytidine groups. Changes in the expression levels of interleukin (IL)-6 and IL-17 in the blood of the healthy control and case control subjects were detected by enzyme-linked immunosorbent assay. Peripheral blood CD4+ T lymphocytes were first activated and proliferated in vitro and then incubated for 0, 24, and 48 h under various treatment conditions. Thereafter, changes in CD4+ T-lymphocytic proliferation were determined using Cell Counting Kit-8 and microscope photography. Changes in messenger RNA (mRNA) and protein expression of the Kv1.3 potassium channel in CD4+ T lymphocytes were detected using real-time quantitative polymerase chain reaction and Western blots, respectively.Results:The IL-6 and IL-17 expression levels were significantly higher in the blood of the hypertensive Kazakh patients than in the healthy Kazakh people. Telmisartan inhibited T-lymphocytic proliferation, as well as the mRNA and protein expression of the Kv1.3 potassium channel in CD4+ T lymphocytes, and the inhibitory effects were time-dependent, with the strongest inhibition observed after 48 h and significantly weaker inhibition observed after 24 h of treatment.Conclusions:Telmisartan may potentially regulate hypertensive inflammatory responses by inhibiting T-lymphocytic proliferation and Kv1.3 potassium channel expression in CD4+ T lymphocytes.

Cross-Cultural Validation of the High Blood Pressure Health Literacy Scale in a Chinese Community.

BackgroundConsidering the importance of health literacy (HL) for the maximum yield from the hypertension control programs, development of a reliable and valid instrument of hypertension-related HL is critical. This study aimed to translate and validate the High Blood Pressure-Health Literacy Scale (HBP-HLS) into Chinese (C-HBP-HLS) and evaluate its psychometric properties in Chinese context.MethodBetween June 2013 and January 2014, a cross-sectional study was conducted among recruited hypertensive patients belonging to the Han and Kazakh-Chinese communities in Urumqi, Xinjiang, China.ResultsA pilot sample (n = 242) was selected for the exploratory factor analysis of the translated and modified instrument. Another sample (n = 308) was recruited for the confirmatory factor analysis. C-HBP-HLS consisted of five dimensions (Print Health Literacy, Medication Label, Understanding Ability, Newest Vital Sign Test, and Avoiding Food Allergy) containing 15 items, accounting for 77.7% of the total variance. The 5-factor model demonstrated a good overall fit. The scale-level content validity index was 0.85. Cronbach’s alpha of the overall scale was 0.78 and test-retest reliability was 0.96. Education level had a strong positive correlation with the scores for items Q1, Q2, and Q3(r = 0.481, 0.492, 0.475, respectively). Health Literacy scores among Kazakh patients were significantly lower than Han (7.13±7.90 vs. 30.10±13.42, Z = -14.573, P<0.001).ConclusionC-HBP-HLS demonstrated suitable factor structure and robust psychometric properties for measuring health literacy level among hypertensive patients in China.

P53 expression but not p16(INK4A) correlates with human papillomavirus-associated esophageal squamous cell carcinoma in Kazakh population.

Backgroundp16INK4A expression has been used as a surrogate marker for human papillomavirus (HPV) infection in cervical cancer and head and neck cancer. p53 has also been reported as a feasible marker to identify HPV-positive oropharyngeal carcinoma and penile lesions. This study aimed to investigate p16INK4A and p53 expression levels and their correlation with HPV status and clinical parameters in Kazakh patients with esophageal squamous cell carcinoma.MethodsImmunohistochemical expression of p16INK4A and p53 were evaluated in 163 cases of esophageal squamous cell carcinoma in Kazakh patients. The presence of HPV DNA was detected by polymerase chain reaction.Resultsp16INK4A-positive expression was detected in 19.0 % of patients, and its expression was significantly correlated with a lower frequency of lymph node metastasis (p = 0.038). By contrast no significant association was found between p16INK4A-positive expression and HPV status (correlation coefficient = -0.062, p = 0.499). p16INK4A-positive expression did not affect the odds of tumors being HPV positive (odds ratio [OR] = 0.727 with 95 % confidence interval [CI] = 0.288–1.836). The sensitivity of p16INK4A-positive expression as an HPV marker was 0.164, with a specificity of 0.788 and a positive predictive value of 0.391. p53-positive expression was present in 88.3 % of all cases. Although no significant correlation with available clinical parameters was found, a significantly inverse correlation was observed between p53 expression and HPV status (correlation coefficient = -0.186, p = 0.039). Moreover, p53-positive expression decreased the odds of tumors being HPV positive (OR = 0.292 with 95 % CI = 0.086–0.990). The sensitivity of p53-negative expression as an HPV marker was 0.179, with a specificity of 0.940 and a positive predictive value of 0.714. The overall HPV prevalence was high (45.5 %) in Kazakh patients, with no significant association between HPV positivity and available clinical parameters or combined p16INK4A/p53 expression.Conclusionsp16INK4A-positive expression was associated with lymph node metastasis. Results indicate that p53-negative expression and not p16INK4A-positive expression may be used as a marker for HPV status in ESCC; however, this finding requires further studies for validation.

The effects of telmisartan on the nuclear factor of activated T lymphocytes signalling pathway in hypertensive patients.

Hypothesis:Previous studies provide links between the nuclear factor of activated T lymphocytes (NFAT) signalling pathway and the development of hypertension. Our preliminary studies indicate that telmisartan can block Kv1.3 potassium channels and effectively inhibit potassium current densities, along with Kv1.3 mRNA and protein expression levels. This paper aims to investigate whether telmisartan has an inhibitory effect on the NFAT signalling pathway after activation and proliferation of peripheral blood T lymphocytes in Kazakh patients with essential hypertension (EH) from Xinjiang, China.Materials and methods:T lymphocytes were isolated using the immunomagnetic cell sorting method (MACS). The mRNA expression of NFATc1, IL-6 and TNF-α was measured by quantitative polymerase chain reaction (qRT-PCR) and relative protein levels were evaluated by Western blot. T cell samples from 50 hypertensive Kazakh patients from Xinjiang were randomly divided into control, telmisartan, cyclosporin A (CsA), VIVIT, and 4-aminopytidine (4-AP) groups. Peripheral blood T lymphocytes were first activated and proliferated in vitro, then incubated for 48 h under different treatment conditions before determination of protein and mRNA expression of NFATc1, IL-6, and TNF-α by Western blot and qRT-PCR analyses, respectively.Results:There were no significant differences in cardiovascular risk factors among the patients with samples assigned to the five groups (p > 0.05). Expression of NFATc1, IL-6, and TNF-α mRNA and protein was significantly reduced in T lymphocytes in all treatment groups (telmisartan, CsA, VIVIT, and 4-AP) compared with controls.Conclusions:Antihypertensive function and inhibitory effects of telmisartan on the T lymphocyte NFAT signalling pathway are unlikely to affect the normal immune function of hypertensive patients. Telmisartan may exert anti-inflammatory effects by inhibition of the NFAT signalling pathway in the T lymphocytes of hypertensive patients.

Health-related quality of life in Kazakh heart failure patients evaluated by the Minnesota living with heart failure questionnaire and comparison with a published large international sample.

To assess health-related quality of life (HRQL) in Kazakh patients (n=285) treated in Cardiology Department of the Emergency Hospital of Semey during 2012 with acute myocardial infarction and to compare results with HRQL measured in 21 countries (n=3,847). Telephone interviews survey was conducted in February 2014 with the Russian translation of Minnesota Living with Heart Failure Questionnaire (MLHFQ). Descriptive statistics were used to characterize the sample according to each single item of MLHFQ and grouping them in three subset concerning physical, emotional, and social environment dimensions of patients' life. The distribution of scores was evaluated in terms of floor and ceiling effects; Cronbach's alpha coefficient was calculated for the different dimensions to assess internal consistency. Mean age of sample is 60.8 years, most of patients are male (71.6%) and retired (43.5%). The total MLHFQ score was generally low at a moderate degree (mean 34.7, range 0-105). Physical dimension score (mean 14.92) shows mild to moderate impairment in HRQL and a better perception than the average of the control countries (14.9 vs 16.6); emotional status (mean 4.8) is moderately adequate and better than the controls (4.8 vs 7.2); social environment (9.82) showed significant impairment of HRQL and a worse evaluation (9.82 vs 7.8). Kazakh patients reported better emotional and physical HRQL as consequence of the social structure where family environment promotes emotional support and improves self-care, social environment affects the total MLHFQ score that is low and related to the requested availability of free medicines.

Frequency of ABCG2 421C&gt;A Genetic Variant and The Efficiency of Treatment with Rosuvastatin in Kazakh Male Patients

Rosuvastatin is one of the most effective lipid-lowering drugs. Nevertheless its activity varies in different populations. Important role in this belongs to ABCG2. The objective of this study was to determine the impact of ABCG2 genotype on therapeutic effect of rosuvastatin in Kazakh population. This study included 82 Kazakh patients with metabolic disorder undergoing 10 -20 mg/day of rosuvastatin therapy for 12 weeks. Our findings indicated that people with 421AA genotype had higher response to the drug. The frequency of minor alleles in the studied group was 29.5%.

Antibiotic Resistance of Helicobacter Pylori Isolates from Kazakh Patients

Antibiotic Resistance of Helicobacter Pylori Isolates from Kazakh Patients

Potassium channel changes of peripheral blood T-lymphocytes from Kazakh hypertensive patients in Northwest China and the inhibition effect towards potassium channels by telmisartan.

Increasing evidence indicates that chronic inflammation is a direct or indirect manifestation of hypertension. Potassium channels are thought to be critical for lymphocyte activation, which suggests that hypertension may be an inflammatory disease initiated at the ion channel level. This study investigated changes in interleukin (IL)-6, IL-17, and transforming growth factor beta (TGF-b1) expression in the blood of Kazakh hypertensive patients in Northwest China using ELISA technology. Whole-cell patch clamp technology was used to evaluate current changes associated with Kv1.3 and KCa3.1 in peripheral blood T lymphocytes of hypertensive patients, and to investigate current changes induced by telmisartan. We also investigated the effects of telmisartan on expression of Kv1.3 and KCa3.1 at mRNA and protein levels in peripheral blood T lymphocytes using real-time polymerase chain reaction and Western blot analysis. Expression of IL-6, IL-17 and TGF-b1 in the blood of Kazakh hypertensive patients in Northwest China was significantly higher than in healthy controls (p < 0.05). The current mediated by Kv1.3 and KCa3.1 and the corresponding expression at mRNA and protein levels in T lymphocytes were also higher in these hypertensive patients than in controls (p < 0.05). Telmisartan intervention for 24 h and 48 h inhibited the current and expression of Kv1.3 and KCa3.1 at mRNA and protein levels (p < 0.05). These results indicated that the increase in functional Kv1.3 and KCa3.1 channels expressed in T lymphocytes of Kazakh patients with hypertension was blocked by telmisartan, resulting in a reduced inflammatory response. These results provide theoretical support for the treatment of hypertension at the cellular ion channel level.