Association of APP gene polymorphisms and promoter methylation with essential hypertension in Guizhou: a case-control study.

BACKGROUND: Single-nucleotide polymorphisms (SNPs) and DNA methylation are crucial regulators of essential hypertension (EH). Amyloid precursor protein (APP) mutations are implicated in hypertension development. Nonetheless, studies on the association of APP gene polymorphism and promoter methylation with hypertension are limited. Therefore, this case-control aims to evaluate the genetic association of APP gene polymorphism and promoter methylation with EH in Guizhou populations. OBJECTIVE AND METHODS: We conducted a case-control study on 343 EH patients and 335 healthy controls (including Miao, Buyi, and Han populations) in the Guizhou province of China to analyze 11 single-nucleotide polymorphisms (rs2040273, rs63750921, rs2211772, rs2830077, rs467021, rs368196, rs466433, rs364048, rs364051, rs438031, rs463946) in the APP gene via MassARRAY SNP. The MassARRAY EpiTYPER was employed to detect the methylation levels of the promoters. RESULTS: In the Han population, the rs2211772 genotype distribution was significantly different between disease and control groups (χ2 = 6.343, P = 0.039). The CC genotype reduced the risk of hypertension compared to the TT or TC genotype (OR 0.105, 95%CI 0.012-0.914, P = 0.041). For rs2040273 in the Miao population, AG or GG genotype reduced the hypertension risk compared with the AA genotype (OR 0.533, 95%CI 0.294-0.965, P = 0.038). Haplotype TCC (rs364051-rs438031-rs463946) increased the risk of EH in Guizhou (OR 1.427, 95%CI 1.020-1.996, P = 0.037). Each 1% increase in CpG_19 (- 613 bp) methylation level was associated with a 4.1% increase in hypertension risk (OR 1.041, 95%CI 1.002-1.081, P = 0.039). Each 1% increase in CpG_1 (- 296 bp) methylation level was associated with an 8% decrease in hypertension risk in women (OR 0.920, 95%CI 0.860-0.984, P = 0.015). CpG_19 significantly correlated with systolic blood pressure (r = 0.2, P = 0.03). The methylation levels of CpG_19 in hypertensive patients with rs466433, rs364048, and rs364051 minor alleles were lower than that with wild-type alleles (P < 0.05). Moreover, rs467021 and rs364051 showed strong synergistic interaction with EH (χ2 = 7.633, P = 0.006). CpG_11, CpG_19, and rs364051 showed weak synergistic interaction with EH (χ2 = 19.874, P < 0.001). CONCLUSION: In summary, rs2211772 polymorphism and promoter methylation level of APP gene may be linked to EH in Guizhou populations. Our findings will provide novel insights for genetic research of hypertension and Alzheimer's disease.

Polymorphism of NOS3 gene and its association with essential hypertension in Guizhou populations of China.

OBJECTIVE: A case-control study was conducted to evaluate the relationship between endothelial nitric oxide synthase (NOS3) gene polymorphism and essential hypertension in the Han, Miao, and Buyi populations in Guizhou China. METHODS: DNA was collected from the blood samples of 353 essential hypertension patients and 342 healthy controls from Guizhou province of China. Eight polymorphisms of the NOS3 gene were genotyped using the Sequenom MassARRAY platform. For genetic analysis, SPSS 26.0, Haploview, SNPStats, SHEsis, and MDR were utilized. RESULTS: All SNPs (rs11771443, rs1808593, rs753482, rs3918186, rs3918188, rs3918227, rs7830, and rs891512) satisfied the Hardy-Weinberg equilibrium test (P > 0.05). The allele and genotype frequencies of rs7830 and rs1808593 in case-control groups demonstrated significant differences (P < 0.05). Compared to the TT genotype of rs1808593, the TG or GG genotype reduced the risk of hypertension in the Miao population (OR = 0.410, 95% CI: 0.218-0.770, P = 0.006). Compared to the GG or GT genotype of rs7830, the TT genotype increased the risk of hypertension in the overall populations (OR = 1.716, 95%CI: 1.139-2.586, P = 0.010). The CATT (rs3918227-rs391818186-rs1808593-rs7830) haplotype was a risk factor for hypertension in the Miao and Han populations (OR = 1.471, 95%CI: 1.010-2.143, P = 0.044 and OR = 1.692, 95%CI: 1.124-2.545, P = 0.011). The CAGG haplotype in the Miao population was a protective factor against hypertension (OR = 0.555, 95%CI: 0.330-0.934, P = 0.025). The rs3918188, rs1808593, and rs7830 in the Miao population showed an interaction effect on hypertension (P < 0.001). The rs11771443, rs3918188, and rs7830 in the Buyi and Han populations showed an interaction effect on hypertension (P = 0.013 and P < 0.001). CONCLUSION: The single nucleotide polymorphisms rs1808593 and rs7830 of NOS3 gene are associated with essential hypertension in Guizhou ethnic populations.

Airway Management in Adult Intensive Care Units: A Survey of Two Regions in China.

The critical medicine residency training in China started in 2020, but no investigation on the practice of tracheal intubation in ICUs in China has been conducted. A survey was sent to the adult ICUs in public hospitals in Shenzhen (SZ) city and Xinjiang (XJ) province using a WeChat miniprogram to be completed by intensive care physicians. It included questions on training on intubation, intubation procedures, and changes in the use of personal protective equipment due to COVID-19. We analyzed 301 valid questionnaires which were from 72 hospitals. A total of 37% of respondents had completed training in RSI (SZ, 40% vs. XJ, 30%; p = 0.066), and 50% had participated in a course on the emergency front of the neck airway (SZ, 47% vs. XJ, 54%; p = 0.256). Video laryngoscopy was preferred by 75% of respondents. Manual ventilation (56%) and noninvasive positive pressure ventilation (34%) were the first-line options for preoxygenation. For patients with a high risk of aspiration, nasogastric decompression (47%) and cricoid pressure (37%) were administered. Propofol (82%) and midazolam (70%) were the most commonly used induction agents. Only 19% of respondents routinely used neuromuscular blocking agents. For patients with difficult airways, a flexible endoscope was the most commonly used device by 76% of respondents. Most participants (77%) believed that the COVID-19 pandemic had significantly increased their awareness of the need for personal protective equipment during tracheal intubation. Our survey demonstrated that the ICU doctors in these areas lack adequate training in airway management.

Water extract of Cayratia albifolia C.L.Li root relieves zymosan A-induced inflammation by restraining M1 macrophage polarization.

BACKGROUND: Cayratia albifolia C.L.Li (CAC) is a traditional Chinese herbal medicine used to treat inflammatory diseases. Our laboratory has firstly reported that the water extract from CAC relieved lipopolysaccharide (LPS)-induced inflammation, however stronger evidence is still needed to prove its anti-inflammatory effects and the mechanisms involved are also ambiguous. PURPOSE: This study sought to provide more evidence for the application of CAC in alleviating infectious inflammation and disclose novel pharmacological mechanisms. METHODS: Mice were injected with zymA into their paws or peritoneal cavities, and then treated with CAC. ELISA, immunofluorescence and flow cytometry were performed to detect the cytokines (IL-1ß, IL-6, TNF-α and IL-10) generation, the cell infiltration, and the CD86 or CD206 expression of macrophages. Then in vitro assays were performed on bone marrow-derived macrophages (BMDMs) and peritoneal macrophages (PMs) to detect their expression of iNOS, arg-1 and the cytokines above. On mechanisms, western blotting (WB), electrophoretic mobility shift assay (EMSA) and flow cytometry were carried out to measure NF-κB transcriptional activity, mitochondrial bioactivity and the mTORC1 activation when BMDMs were stimulated by zymA and treated with CAC. Finally, the chemical components consisted in the extract were analyzed by LC-MS. RESULTS: 200 mg/kg CAC clearly inhibited zymA induced mouse paw edema and reduced the contents of IL-1ß, IL-6 and TNF-α rather than IL-10 in local tissues. CAC also reduced CD86 but not CD206 in macrophages in situ. Through in vitro experiments, it was discovered that CAC reduced the protein and mRNA levels of IL-1ß, IL-6 and TNF-α, and also inhibited iNOS expression, but showed no influence on IL-10 and arg-1 in macrophages. We found CAC reduced NF-κB transcriptional activity, down-regulated mitochondrial membrane potential and ROS levels, and inhibited mTORC1 activity. Finally, we identified 15 major compounds in the extract, among which 4-guanidinobutyric acid and kynurenic acid were the most abundant. CONCLUSION: This study provides further evidence that CAC significantly reduces zymA induced infectious inflammation. In addition, this novel data revealed that CAC restrained M1 rather than promoting M2 macrophages polarization via multi-target inhibitory effects, based on its potentially active components.