Machine learning identifies prominent factors associated with cardiovascular disease: findings from two million adults in the Kashgar Prospective Cohort Study (KPCS).

BACKGROUND: Identifying factors associated with cardiovascular disease (CVD) is critical for its prevention, but this topic is scarcely investigated in Kashgar prefecture, Xinjiang, northwestern China. We thus explored the CVD epidemiology and identified prominent factors associated with CVD in this region. METHODS: A total of 1,887,710 adults at baseline (in 2017) of the Kashgar Prospective Cohort Study were included in the analysis. Sixteen candidate factors, including seven demographic factors, 4 lifestyle factors, and 5 clinical factors, were collected from a questionnaire and health examination records. CVD was defined according to International Clinical Diagnosis (ICD-10) codes. We first used logistic regression models to investigate the association between each of the candidate factors and CVD. Then, we employed 3 machine learning methods-Random Forest, Random Ferns, and Extreme Gradient Boosting-to rank and identify prominent factors associated with CVD. Stratification analyses by sex, ethnicity, education level, economic status, and residential setting were also performed to test the consistency of the ranking. RESULTS: The prevalence of CVD in Kashgar prefecture was 8.1%. All the 16 candidate factors were confirmed to be significantly associated with CVD (odds ratios ranged from 1.03 to 2.99, all p values < 0.05) in logistic regression models. Further machine learning-based analysis suggested that age, occupation, hypertension, exercise frequency, and dietary pattern were the five most prominent factors associated with CVD. The ranking of relative importance for prominent factors in stratification analyses showed that the factor importance generally followed the same pattern as that in the overall sample. CONCLUSIONS: CVD is a major public health concern in Kashgar prefecture. Age, occupation, hypertension, exercise frequency, and dietary pattern might be the prominent factors associated with CVD in this region.In the future, these factors should be given priority in preventing CVD in future.

Short and long-term prognosis of admission hyperglycemia in patients with and without diabetes after acute myocardial infarction: a retrospective cohort study.

OBJECTIVE: Admission hyperglycemia is associated with poor prognosis in patients with acute myocardial infarction (AMI), but the effects of baseline diabetes status on this association remain elusive. We aim to investigate the impact of admission hyperglycemia on short and long-term outcomes in diabetic and non-diabetic AMI patients. METHODS: In this retrospective cohort study, 3330 patients with regard to first-time AMI between July 2012 and July 2020 were identified. Participants were divided into two groups according to diabetes status (1060 diabetic patients and 2270 non-diabetic patients). Thereafter, they were divided into four groups according to diabetes status-specific cutoff values of fasting blood glucose (FBG) identified by restricted cubic spline. Short-term outcomes included in-hospital death and cardiac complications. Long-term outcomes were all-cause mortality and major adverse cardiovascular events (MACE). Inverse probability of treatment weighting (IPTW) was conducted to adjust for baseline differences among the groups, followed by a weighted Cox proportional hazards regression analysis to calculate hazard ratios and 95% confidence intervals for all-cause mortality associated with each FBG category. Subgroup analysis and sensitivity analysis were performed to test the robustness of our findings. RESULTS: During a median follow-up of 3.2 years, 837 patients died. There was a significant interaction between diabetes status and FBG levels for all-cause mortality during long-term follow-up (p-interaction < 0.001). Moreover, restricted cubic spline curves for the association between FBG and all-cause mortality followed a J shape in patients with diabetes and a non-linear in patients without diabetes. Kaplan-Meier analysis demonstrated greater survival in non-hyperglycemia patients compared to hyperglycemia patients for both diabetic and non-diabetic patients groups. Survival of hyperglycemia patients without diabetes greater than in hyperglycemia patients with diabetes. In the weighted Multivariable cox analysis, admission hyperglycemia predicted higher short and long-term mortality. Subgroup analysis and sensitivity analysis showed the robustness of the results. CONCLUSIONS: The inflection points of FBG level for poor prognosis were 5.60 mmol/L for patients without diabetes and 10.60 mmol/L for patients with diabetes. Admission hyperglycemia was identified as an independent predictor of worse short and long-term outcomes in AMI patients, with or without diabetes. These findings should be explored further.

Distribution and identification of Mycobacterium tuberculosis lineage in Kashgar prefecture.

OBJECTIVES: Kashgar prefecture is an important transportation and trade hub with a high incidence of tuberculosis. The following study analyzed the composition and differences in Mycobacterium tuberculosis (M.tb) lineage and specific tags to distinguish the lineage of the M.tb in Kashgar prefecture, thus providing a basis for the classification and diagnosis of tuberculosis in this area. METHODS: Whole-genome sequencing (WGS) of 161 M.tb clinical strains was performed. The phylogenetic tree was constructed using Maximum Likelihood (ML) based on single nucleotide polymorphisms (SNPs) and verified through principal component analysis (PCA). The composition structure of M.tb in different regions was analyzed by combining geographic information. RESULTS: M.tb clinical strains were composed of lineage 2 (73/161, 45.34%), lineage 3 (52/161, 32.30%) and lineage 4 (36/161, 22.36%). Moreover, the 3 lineages were subdivided into 11 sublineages, among which lineage 2 included lineage 2.2.2/Asia Ancestral 1 (9/73, 12.33%), lineage 2.2.1-Asia Ancestral 2 (9/73, 12.33%), lineage 2.2.1-Asia Ancestral 3 (18/73, 24.66%), and lineage 2.2.1-Modern Beijing (39/73, 53.42%). Lineage 3 included lineage 3.2 (14/52, 26.92%) and lineage 3.3 (38/52, 73.08%), while lineage 4 included lineage 4.1 (3/36, 8.33%), lineage 4.2 (2/36, 5.66%), lineage 4.4.2 (1/36, 2.78%), lineage 4.5 (28/36, 77.78%) and lineage 4.8 (2/36, 5.66%), all of which were consistent with the PCA results. One hundred thirty-six markers were proposed for discriminating known circulating strains. Reconstruction of a phylogenetic tree using the 136 SNPs resulted in a tree with the same number of delineated clades. Based on geographical location analysis, the composition of Lineage 2 in Kashgar prefecture (45.34%) was lower compared to other regions in China (54.35%-90.27%), while the composition of Lineage 3 (32.30%) was much higher than in other regions of China (0.92%-2.01%), but lower compared to the bordering Pakistan (70.40%). CONCLUSION: Three lineages were identified in M.tb clinical strains from Kashgar prefecture, with 136 branch-specific SNP. Kashgar borders with countries that have a high incidence of tuberculosis, such as Pakistan and India, which results in a large difference between the M.tb lineage and sublineage distribution in this region and other provinces of China.

Green space and cardiovascular disease: A systematic review with meta-analysis.

Exposure to green space has been proposed to be beneficially associated with cardiovascular morbidity and mortality. Many studies have explored this topic, but the results remain conflicting. We aimed to evaluate the epidemiological evidence on this topic by performing a systematic review with meta-analysis. We searched PubMed, Web of Science and Embase for studies on the association between green space and cardiovascular disease (CVD) that were published till January 2022. Two authors independently performed study selection, data extraction, quality assessment, and risk of bias assessment. For studies providing detailed numeric data, we also conducted quantitative meta-analyses and calculated the pooled odd ratios (ORs) for associations between the most commonly used exposure estimate (normalized difference vegetative index [NDVI]) and five CVD events: CVD mortality, ischemic heart disease (IHD) mortality, cerebrovascular disease (CBVD) mortality, and stroke incidence/prevalence. Additional analyses were conducted to explore the geographical scale effects of NDVI. Publication bias tests were also conducted. Of the 6787 records identified, 53 studies were eligible for inclusion. These studies covered 18 countries and included data from more than 100 million persons. Meta-analyses showed that a 0.1 increase in NDVI was significantly associated with 2-3% lower odds of CVD mortality (OR: 0.97, 95% CI: 0.96-0.99), IHD mortality (OR: 0.98, 95% CI: 0.96-1.00), CBVD mortality (OR: 0.98, 95% CI: 0.97-1.00), and stroke incidence/prevalence (OR: 0.98, 95% CI: 0.96-0.99). There was no significant difference between the pooled estimates for different buffer sizes. No evidence of publication bias was detected. We provide strong and robust evidence for the beneficial effects of green space exposure on cardiovascular health. More prospective studies and mechanistic studies, especially that conducted in low- and middle-income countries, are merited to strengthen our conclusions.

Advances in Cardiac Computed Tomography Functional Imaging Technology.

Cardiovascular disease (CVD) is the leading cause of death among patients in China, and cardiac computed tomography (CT) is one of the most commonly used examination methods for CVD. Coronary artery CT angiography can be used for the morphologic evaluation of the coronary artery. At present, cardiac CT functional imaging has become an important direction of development of CT. At present, common CT functional imaging technologies include transluminal attenuation gradient, stress dynamic CT myocardial perfusion imaging, and CT-fractional flow reserve. These three imaging modes are introduced and analyzed in this review.

Cervical Screening by Pap Test and Visual Inspection Enabling Same-Day Biopsy in Low-Resource, High-Risk Communities.

OBJECTIVE: To develop an effective, low-cost, single-visit cervical screening strategy incorporating a modified Pap test and visual inspection with acetic acid and Lugol's iodine for low-income settings. METHODS: We conducted a prospective cohort trial. Two low-income Muslim Uyghur communities in China's far western Kashi Prefecture served as pilot and validation study sites, respectively, and 4,049 women (aged 30-59 years) were screened. The conventional Pap test was modified using a cotton swab to collect cervical cells without scraping the cervix using an Ayre spatula, allowing visual inspection with acetic acid (and visual inspection with Lugol's iodine if visual inspection with acetic acid was negative) to be performed in a single visit. Results from both tests were available within 1-2 hours. Women positive for either or both underwent same-day biopsy that was shipped by a courier service to a central pathology laboratory. RESULTS: Single-visit screening incorporating both a modified Pap test and visual inspection achieved a sensitivity of 96.0% (95% CI 91.6-100), which was superior to Pap testing (76%, 95% CI 66.3-85.7; P<.001) or visual inspection with acetic acid-visual inspection with Lugol's iodine (48%, 95% CI 36.7-59.3; P<.001) alone in detecting cervical intraepithelial neoplasia (CIN) 2 or worse lesions. Rapid interpretation of both diagnostic procedures facilitated efficient same-day biopsy that achieved a negative predictive value of 98.2% in detecting CIN 2 or worse lesions. The increased sensitivity and minimized loss of follow-up allowed this approach to identify an extremely high prevalence of CIN 1 (2,741/100,000, 95% CI 2,238-3,245/100,000), CIN 2 or 3 (1,457/100,000, 95% CI 1,088-1,826/100,000), and cervical cancer (395/100,000, 95% CI 202-589/100,000) among these underscreened, at-risk women. CONCLUSION: Single-visit cervical screening with both a modified Pap test and visual inspection has greater sensitivity to detect high-grade CINs, reduces loss of follow-up, and could be an efficient low-cost strategy for low-resource settings.

Associations of Polymorphism of rs9944155, rs1051052, and rs1243166 Locus Allele in Alpha-1-antitrypsin with Chronic Obstructive Pulmonary Disease in Uygur Population of Kashgar Region.

BACKGROUND: Previous studies conducted in various geographical and ethnical populations have shown that Alpha-1-antitrypsin (Alpha-1-AT) expression affects the occurrence and progression of chronic obstructive pulmonary disease (COPD). We aimed to explore the associations of rs9944155AG, rs1051052AG, and rs1243166AG polymorphisms in the Alpha-1-AT gene with the risk of COPD in Uygur population in the Kashgar region. METHODS: From March 2013 to December 2015, a total of 225 Uygur COPD patients and 198 healthy people were recruited as cases and controls, respectively, in Kashgar region. DNA was extracted according to the protocol of the DNA genome kit, and Sequenom MassARRAY single-nucleotide polymorphism technology was used for genotype determination. Serum concentration of Alpha-1-AT was detected by enzyme-linked immunosorbent assay. A logistic regression model was used to estimate the associations of polymorphisms with COPD. RESULTS: The rs1243166-G allele was associated with a higher risk of COPD (odds ratio [OR] = 2.039, 95% confidence interval [CI]: 1.116-3.725, P = 0.019). In cases, Alpha-1-AT levels were the highest among participants carrying rs1243166 AG genotype, followed by AA and GG genotype (χ2 = 11.89, P = 0.003). Similarly, the rs1051052-G allele was associated with a higher risk of COPD (OR = 19.433, 95% CI: 8.783-43.00, P < 0.001). The highest Alpha-1-AT levels were observed in cases carrying rs1051052 AA genotype, followed by cases with AG and GG genotypes (χ2 = 122.45, P < 0.001). However, individuals with rs9944155-G allele exhibited a lower risk of COPD than those carrying the rs9944155-A allele (OR = 0.121, 95% CI: 0.070-0.209, P < 0.001). In both cases and controls, no significant difference in Alpha-1-AT levels was observed among various rs9944115 genotypes. CONCLUSIONS: rs1243166, rs9944155, and rs1051052 sites of Alpha-1-AT may be associated with the COPD morbidity in Uygur population. While rs1243166-G allele and rs1051052-G allele are associated with an increased risk of developing COPD, rs9944155-G allele is a protect locus in Uygur population. Alpha-1-AT levels in Uygur COPD patients were lower than those in healthy people and differed among patients with different rs1051052 AG and rs1243166 AG genotypes.

Overweight and obesity among low-income Muslim Uyghur women in far western China: correlations of body mass index with blood lipids and implications in preventive public health.

BACKGROUND: The pandemic of obesity is a global public health concern. Most studies on obesity are skewed toward high-income and urban settings and few covers low-income populations. This study focused on the prevalence of overweight and obesity and their correlations with blood lipids/metabolites/enzymes (bio-indicators) in a rural community typical of low-income in remote western China. METHODS: This study was performed in a Muslim ethnic Uyghur rural community in Kashi Prefecture of Xinjiang, about 4,407 km (2,739 miles) away from Beijing. Body mass index (BMI) and major blood bio-indicators (25 total items) were measured and demographic information was collected from 1,733 eligible healthy women aged 21 to 71 yrs, of whom 1,452 had complete data for analysis. More than 92% of the women lived on US$1.00/day or less. According to the Chinese criteria, overweight and obesity were defined as BMI at 24 to <28 kg/m(2) and at ≥ 28 kg/m(2), respectively. RESULTS: The average BMI among these low-income women was 24.0 ± 4.0 (95% CI, 17.5-33.7) kg/m(2). The prevalence of obesity and overweight was high at 15.1% and 28.9%, respectively. Among 25 bio-indicators, BMI correlated positively with the levels of 11 bio-indicators including triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TCHOL), glucose (GLU), and uric acid (UA); but negatively with the levels of 5 bio-indicators including high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A/B (APO A/B). CONCLUSIONS: This is the first investigation reporting overweight and obesity being common in low-income Muslim Uyghur women, whose BMI correlates with several important blood bio-indicators which are risk factors for diabetes and cardiovascular diseases. These findings may help make preventive public health policies in Uyghur communities. To prevent diabetes and cardiovascular diseases in low-income settings, we therefore propose a cost-effective, two-step strategy first to screen for obesity and then to screen persons with obesity for diabetes and cardiovascular diseases.

Implementing a cervical cancer awareness program in low- income settings in Western China: a community-based locally affordable intervention for risk reduction.

BACKGROUND: Some 60 years after introduction of the Papanicolaou smear worldwide, cervical cancer remains a burden in developing countries where >85% of world new cases and deaths occur, suggesting a failure to establish comprehensive cervical-cancer control programs. Effective interventions are available to control cervical cancer but are not all affordable in low-income settings. Disease awareness saves lives by risk-reduction as witnessed in reducing mortality of HIV/AIDS and smoking-related cancers. SUBJECTS AND METHODS: We initiated a community-based awareness program on cervical cancer in two low-income Muslim Uyghur townships in Kashi (Kashgar) Prefecture, Xinjiang, China in 2008. The education involved more than 5,000 women from two rural townships and awareness was then evaluated in 2010 and 2011, respectively, using a questionnaire with 10 basic knowledge questions on cervical cancer. Demographic information was also collected and included in an EpiData database. A 10-point scoring system was used to score the awareness. RESULTS: The effectiveness and feasibility of the program were evaluated among 4,475 women aged 19-70 years, of whom >92% lived on/ below US$1.00/day. Women without prior education showed a poor average awareness rate of 6.4% (164/2,559). A onetime education intervention, however, sharply raised the awareness rate by 4-fold to 25.5% (493/1,916). Importantly, low income and illiteracy were two reliable factors affecting awareness before or after education intervention. CONCLUSIONS: Education intervention can significantly raise the awareness of cervical cancer in low-income women. Economic development and compulsory education are two important solutions in raising general disease awareness. We propose that implementing community-based awareness programs against cervical cancer is realistic, locally affordable and sustainable in low-income countries, which may save many lives over time and, importantly, will facilitate the integration of comprehensive programs when feasible. In this context, adopting this strategy may provide one good example of how to achieve "good health at low cost".

Stat6 activity-related Th2 cytokine profile and tumor growth advantage of human colorectal cancer cells in vitro and in vivo.

Signal transducer and activator of transcription 6 (Stat6) is critical in Th2 polarization of immune cells and active Stat6 activity has been suggested in anti-tumor immunity in animal models. The present study aims at investigating the impact of natural Stat6 activity on tumor microenvironment in human colorectal cancer cells in vitro and in vivo. Using colorectal cancer cell lines HT-29 and Caco-2 whose IL-4/Stat6 activities were known and nude mice as a model, we examined correlative relationships between Stat6 activities and gene expression profiles together with cellular behaviors in vitro and in vivo. HT-29 cells carrying active Stat6 signaling displayed spontaneous expression profiles favoring Th2 cytokines, cell cycle promotion, anti-apoptosis and pro-metastasis with increased mRNA levels of IL-4, IL-13, GATA-3, CDK4, CD44v6 and S100A4 using RT-PCR. In contrast, Caco-2 cells carrying defective Stat6 signaling exhibited spontaneous expression profiles favoring Th1 and Th17 cytokines, cell cycle inhibition, pro-apoptosis and anti-metastasis with elevated mRNA expression of IFNγ, TNFα, IL-12A, IL-17, IL-23, T-bet, CDKN1A, CDKNIB, CDKN2A and NM23-H1. Xenograft tumors of Stat6-active HT-29 cells showed a growth advantage over those of Stat6-defective Caco-2 cells. Furthermore, mice bearing HT-29 tumors expressed increased levels of Th2 cytokines IL-4 and IL-5 in the blood and pro-growth and/or pro-metastasis proteins CDK4 and CD44v6 in the tumor. To the contrary, mice bearing Caco-2 tumors expressed heightened levels of Th1 cytokines IFNγ and TNF in the blood and pro-apoptosis and anti-metastatic proteins p53 and p27(kip1) in the tumor. Colorectal cancer cells carrying active Stat6 signaling may create a microenvironment favoring Th2 cytokines and promoting expression of genes related to pro-growth, pro-metastasis and anti-apoptosis, which leads to a tumor growth advantage in vivo. These findings may imply why Stat6 pathway is constitutively activated in a number of human malignancies.

[Restoration of molar residual roots and crowns with multiple canals by unparalleled posts: an evaluation].

OBJECTIVE: To repair the residual roots and crowns of the molars with multi-canals using unparalleled posts and cores and ceramic crowns. METHODS: Unparalleled insertion of the posts and cores was adopted in the casting of the ceramic crown to repair the residual roots and crowns of the molars. RESULTS AND CONCLUSION: Unparalleled insertion of the posts increased the retention strength of the cores, which provided a solid foundation for the restoration of the molars with ceramic crowns, therefore yielding better clinical effect in repairing the molars.