Ameliorating effects of the HIF-2α inhibitor PT2385 on high-altitude polycythemia.

High-altitude polycythemia (HAPC) is a common chronic altitude disease caused by living in low-pressure and low-oxygen environment. At present, there is still no effective cure for HAPC. HIF-2α may play an important role in the development of HAPC in regulating the increased red blood cell excessively induced by HIF-EPO and the blood vessel formation induced by VEGF-VEGFR.

Hypermethylation of BMPR2 and TGF-β Promoter Regions in Tibetan Patients with High-Altitude Polycythemia at Extreme Altitude.

Although the expression of many genes is associated with adaptation to high-altitude hypoxic environments, the role of epigenetics in the response to this harsh environmental stress is currently unclear. We explored whether abnormal DNA promoter methylation levels of six genes, namely, ABCA1, SOD2, AKT1, VEGFR2, TGF-β, and BMPR2, affect the occurrence and development of high-altitude polycythemia (HAPC) in Tibetans. The methylation levels of HAPC and the control group of 130 Tibetans from very high altitudes (> 4500 m) were examined using quantitative methylation-specific real-time PCR (QMSP).

Predictive model for estimating the risk of high-altitude pulmonary edema: a single-centre retrospective outcome-reporting study.

Objective: To develop the first prediction model based on the common clinical symptoms of high-altitude pulmonary edema (HAPE), enabling early identification and an easy-to-execute self-risk prediction tool.

Methods: A total of 614 patients who consulted People's Hospital of Tibet Autonomous Region between January 2014 and April 2022 were enrolled. Out of those, 508 patients (416 males and 92 females) were diagnosed with HAPE and 106 were patients without HAPE (33 females and 72 males).

Optimizing an Emergency Medical Dispatch System to Improve Prehospital Diagnosis and Treatment of Acute Coronary Syndrome: Nationwide Retrospective Study in China.

Background: Acute coronary syndrome (ACS) is the most time-sensitive acute cardiac event that requires rapid dispatching and response. The medical priority dispatch system (MPDS), one of the most extensively used types of emergency dispatch systems, is hypothesized to provide better-quality prehospital emergency treatment. However, few studies have revealed the impact of MPDS use on the process of ACS care.

Neural network correlates of high-altitude adaptive genetic variants in Tibetans: A pilot, exploratory study.

Although substantial progress has been made in the identification of genetic substrates underlying physiology, neuropsychology, and brain organization, the genotype-phenotype associations remain largely unknown in the context of high-altitude (HA) adaptation. Here, we related HA adaptive genetic variants in three gene loci (EGLN1, EPAS1, and PPARA) to interindividual variance in a set of physiological characteristics, neuropsychological tests, and topological attributes of large-scale structural and functional brain networks in 135 indigenous Tibetan highlanders. Analyses of individual HA adaptive single-nucleotide polymorphisms (SNPs) revealed that specific SNPs selectively modulated physiological characteristics (erythrocyte level, ratio between forced expiratory volume in the first second to forced vital capacity, arterial oxygen saturation, and heart rate) and structural network centrality (the left anterior orbital gyrus) with no effects on neuropsychology or functional brain networks.

Whole-Genome Sequencing Identifies the Egl Nine Homologue 3 (egln3/phd3) and Protein Phosphatase 1 Regulatory Inhibitor Subunit 2 (PPP1R2P1) Associated with High-Altitude Polycythemia in Tibetans at High Altitude.

Background: The hypoxic conditions at high altitudes are great threats to survival, causing pressure for adaptation. More and more high-altitude denizens are not adapted with the condition known as high-altitude polycythemia (HAPC) that featured excessive erythrocytosis. As a high-altitude sickness, the etiology of HAPC is still unclear.

Mechanism of apoptosis involved in gastric mucosal lesions in Tibetans with high-altitude polycythemia.

The Tibetan high plateau is a low-oxygen environment, which may cause the pathogenesis of high-altitude polycythemia (HAPC). Gastric mucosal lesions (GML) are a common complication of HAPC. The molecular mechanisms involved in HAPC-induced GML have remained to be fully elucidated and were therefore investigated in the present study.

Transcriptome reveals the overexpression of a kallikrein gene cluster (KLK1/3/7/8/12) in the Tibetans with high altitude-associated polycythemia.

High altitude-associated polycythemia (HAPC) is a very common disease. However, it the disease is still unmanageable and the related molecular mechanisms remain largely unclear. In the present study, we aimed to explore the molecular mechanisms responsible for the development of HAPC using transcriptome analysis.

Reversible Brain Abnormalities in People Without Signs of Mountain Sickness During High-Altitude Exposure.

A large proportion of lowlanders ascending to high-altitude (HA) show no signs of mountain sickness. Whether their brains have indeed suffered from HA environment and the persistent sequelae after return to lowland remain unknown. Thirty-one sea-level college students, who had a 30-day teaching on Qinghai-Tibet plateau underwent MRI scans before, during, and two months after HA exposure.

Genome-Wide Transcriptional Analysis Reveals the Protection against Hypoxia-Induced Oxidative Injury in the Intestine of Tibetans via the Inhibition of GRB2/EGFR/PTPN11 Pathways.

The molecular mechanisms for hypoxic environment causing the injury of intestinal mucosal barrier (IMB) are widely unknown. To address the issue, Han Chinese from 100 m altitude and Tibetans from high altitude (more than 3650 m) were recruited. Histological and transcriptome analyses were performed.

Comparative Analysis of Gut Microbiota of Native Tibetan and Han Populations Living at Different Altitudes.

The factors driving the composition of gut microbiota are still only partly understood but appear to include environmental, cultural, and genetic factors. In order to obtain more insight into the relative importance of these factors, we analyzed the microbiome composition in subjects of Tibetan or Han descent living at different altitudes. DNA was isolated from stool samples.

Transcriptome Reveals 1400-Fold Upregulation of APOA4-APOC3 and 1100-Fold Downregulation of GIF in the Patients with Polycythemia-Induced Gastric Injury.

High-altitude polycythemia (HAPC) inducing gastric mucosal lesion (GML) is still out of control and molecular mechanisms remain widely unknown. To address the issues, endoscopy and histopathological analyses were performed. Meanwhile, microarray-based transcriptome profiling was conducted in the gastric mucosa from 3 pairs of healthy subjects and HAPC-induced GML patients.

CD14 knockdown reduces lipopolysaccharide-induced cell viability and expression of inflammation-associated genes in gastric cancer cells in vitro and in nude mouse xenografts.

The present study examined the role of CD14 in the regulation of lipopolysaccharide (LPS)-induced effects on gastric cancer cells. MGC‑803 cells were stably transfected with CD14 short hairpin (sh)RNA and treated with LPS, followed by assessment of cell proliferation, apoptosis and gene expression using a cell counting kit‑8 assay, flow cytometry, reverse transcription‑polymerase chain reaction and western blot analysis, respectively. The cells subjected to CD14 knockdown were treated with 10 g/ml LPS and injected into nude mice to form tumor xenografts.

Nerve growth factor promotes human sperm motility in vitro by increasing the movement distance and the number of A grade spermatozoa.

Nerve growth factor (NGF) was first found in the central nervous system and is now well known for its multiple pivotal roles in the nervous system and immune system. However, more and more evidences showed that NGF and its receptors TrkA and p75 were also found in the head and tail of spermatozoa, which indicate the possible effect of NGF on the sperm motility. Nevertheless, the exact role of NGF in the human sperm motility remains unclear until now.

Using a low-sodium, high-potassium salt substitute to reduce blood pressure among Tibetans with high blood pressure: a patient-blinded randomized controlled trial.

Objectives: To evaluate the effects of a low-sodium and high-potassium salt-substitute on lowering blood pressure (BP) among Tibetans living at high altitude (4300 meters).

Method: The study was a patient-blinded randomized controlled trial conducted between February and May 2009 in Dangxiong County, Tibetan Autonomous Region, China. A total of 282 Tibetans aged 40 or older with known hypertension (systolic BP≥140 mmHg) were recruited and randomized to intervention (salt-substitute, 65% sodium chloride, 25% potassium chloride and 10% magnesium sulfate) or control (100% sodium chloride) in a 1: 1 allocation ratio with three months' supply.

Association of CD14/-260 polymorphism with gastric cancer risk in Highland Tibetans.

Aim: To investigate the relationship between CD14-260 and -651 polymorphisms and the risk of developing gastric cancer.

Methods: DNA was extracted from peripheral blood samples obtained from 225 Tibetans with gastric cancer and 237 healthy Tibetans, and analyzed using the polymerase chain reaction/ligase detection (PCR/LDR) method to determine the genotypes at -260 and -651 loci of the CD14 promoter. The allele frequencies, genotype frequencies, and haplotypes were analyzed for their association with gastric cancer risk using online SHEsis software.

CD14 regulates gastric cancer cell epithelial‑mesenchymal transition and invasion in vitro.

Cluster of differentiation 14 (CD14) protein functions as a co-receptor with either the Toll-like receptor TLR4 or MD-2 in the detection of bacterial lipopolysaccharide (LPS) and plays a role in the innate immune system. Recently, it was shown to have effects on the regulation of epithelial-mesenchymal transition (EMT). Thus, the present study investigated the effects of CD14 knockdown on the regulation of gastric cancer cell EMT and invasive capacity following treatment with or without LPS.

A1166C polymorphism of the angiotensin II type 1 receptor gene and essential hypertension in Han, Tibetan and Yi populations.

Our aim was to clarify whether substitution of cytosine for adenine at position 1166 (A1166C) polymorphism of the angiotensin II type 1 receptor (AT1R) gene is associated with susceptibility to essential hypertension in Han, Tibetan and Yi populations in China. This study involved 302 normotensive and 446 hypertensive subjects. The polymorphism was detected by polymelase chain reaction of genomic DNA and restriction fragment length polymorphism (PCR-RFLP) in genomic DNA.

Angiotensin-converting enzyme gene polymorphism and its association with essential hypertension in a Tibetan population.

There is strong evidence to support the idea that the renin-angiotensin system (RAS) plays an important role in the pathogenesis of essential hypertension (EH) and its complications. However, existing data about the association of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with blood pressure is conflicting, mainly due to racial differences and environmental exposure status. We therefore conducted a case control study to observe the relationship between ACE I/D polymorphism and EH in a Tibetan population who live in relatively isolated areas and are genetically homogeneous.