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.

Comparative Study on Tuberculosis Drug Resistance and Molecular Detection Methods Among Different Mycobacterium Tuberculosis Lineages.

Purpose: This study aims to compare drug resistance and detection efficacy across different Mycobacterium tuberculosis lineages, offering insights for precise treatment and molecular diagnosis. Methods: 161 strains of Mycobacterium tuberculosis (M.tb) were tested for drug resistance using Phenotypic Drug Susceptibility Testing (pDST), High-Resolution Melting analysis (HRM), and Whole Genome Sequencing (WGS) methods. The main focus was on evaluating the accuracy of different methods for detecting resistance to rifampicin (RIF), isoniazid (INH), and streptomycin (SM). Results: Among the 161 strains of M.tb, 83.85% (135/161) were fully sensitive to RIF, INH, and SM according to pDST, and the rate of multidrug resistance was 4.35% (7/161). The drug resistance rates of lineage 2 M.tb to the three drugs (26/219, 11.87%) were significantly higher than those of non-lineage 2 M.tb (12/264, 4.45%) (P<0.05). Compared with pDST, WGS had a sensitivity of 100%, 94.12%, and 92.31% and a specificity of 100%, 99.31%, and 98.65% for RIF, INH, and SM, respectively, with no significant difference. The sensitivity of HRM for RIF, INH, and SM was 87.50%, 52.94%, and 76.92%, respectively, while the specificity was 96.08%, 99.31%, and 99.32%, respectively. The sensitivity of HRM for detecting INH resistance was significantly lower than that of pDST (P=0.039). Compared with HRM, WGS increased the sensitivity of RIF, INH, and SM by 12.50%, 41.18%, and 15.38%, respectively. Conclusion: There are significant differences in drug resistance rates among different lineages of M.tb, with lineage 2 having higher rates of RIF, INH, and SM resistance than lineages 3 and 4. The sensitivity of HRM is far lower than that of pDST, and currently, the accuracy of HRM is not sufficient to replace pDST. WGS has no significant difference in detecting drug resistance compared with pDST but can identify new anti-tuberculosis drug-resistant mutations, providing effective guidance for clinical decision-making.

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.

FAM172A affects cell proliferation and apoptosis not by targeting ß-tubulin in HepG2 cells.

BACKGROUND: Microtubules pull chromosomes apart during cell mitosis and take part in cell division, Inhibiting the formation of spindle microtubules during mitosis has become one of the current anti-tumor research strategies. Earlier studies have found that the family with sequence similarity 172, member A (FAM172A) can significantly inhibit the proliferation of human colorectal cancer cell line LOVO cells and promote apoptosis. The purpose of this study was to investigate the biological effects of FAM172A on liver cancer cells and the interaction mechanism with tubulin. METHODS: Use STRING software predicted the interactions between FAM172A and ß-tubulin, and verify by immunoprecipitation. Real-Time qPCR was used to determine the expression levels of ß-tubulin in liver cancer cell line HepG2, western blot was performed to detect protein expression levels. Immunofluorescence experiment to detect the distribution, shape and the dynamic behavior of depolymerization-aggregation of ß-tubulin in cells. MTT, wound healing and Transwell assay were employed to determine cell proliferation, migration and invasion respectively. Flow cytometry was conducted to determine cell cycle and apoptosis. RESULTS: There is no interactions between FAM172A and ß-tubulin. We determined that when FAM172A was up-regulated or down-regulated, the mRNA and protein levels of ß-tubulin did not change significantly (P>0.05). Furthermore, the distribution, shape of ß-tubulin in cells, and the dynamic behavior of depolymerization-aggregation was not affected. After FAM172A overexpression, the migration and invasion of HepG2 cells were significantly inhibited (P<0.05), the cell proliferation was also significantly inhibited (P<0.05) and was time-dependent. The HepG2 cells had apparent S phase arrest and apoptosis (P<0.05). After interfering with FAM172A, the opposite result will appear. CONCLUSIONS: The results show that FAM172A may be a new tumor suppressor gene, which has a specific role in cell cycle control and cell proliferation, but the specific mechanism of action has not been explained in this study and needs further exploration.