OBJECTIVES: To investigate the targets and mechanisms of 7-hydroxyethyl chrysin (7-HEC) in prevention and treatment of high-altitude cerebral edema (HACE) in rats. METHODS: Fifty-four male Wistar rats were randomly divided into normal control group, HACE model group, and 7-HEC-treated group (18 rats in each group). Except for the normal control group, rats in the two other groups were exposed to a hypobaric hypoxic chamber simulating a 7000 m altitude for 72 h to establish the HACE model. The 7-HEC-treated group was intraperitoneally injected with 7-HEC (150 mg·kg^－¹·d^－¹) for 3 consecutive days before modeling, while the model group received equivalent isotonic sodium chloride solution. Tandem Mass Tag (TMT) proteomics technology was used to detect differentially expressed proteins (DEPs) with screening criteria set at a fold change >1.2 and P<0.05. Western blotting was used to verify the expression levels of target proteins. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) network analysis were performed. RESULTS: Compared with the normal control group, 256 DEPs were identified in the HACE model group. Compared with the HACE model group, 87 DEPs were identified in the 7-HEC-treated group. Among them, 19 DEPs that were dysregulated in the HACE model group were restored after 7-HEC intervention, of which seven (HSPA4, Arhgap20, SERT, HACL1, CCDC43, POLR3A, and PCBD1) were confirmed by Western blotting. GO enrichment analysis of the DEPs between the HACE model and 7-HEC-treated groups revealed their involvement in 13 biological processes, five cellular components, and two molecular functions. KEGG pathway analysis indicated associations with the mRNA surveillance pathway, Th17 cell differentiation, serotonergic synapse, RNA polymerase, protein processing in the endoplasmic reticulum, peroxisome, neuroactive ligand-receptor interaction, folate biosynthesis. PPI network analysis demonstrated that HSPA4, POLR3A, and HACL1, which were validated by Western blotting, interacted with multiple signaling pathways and ranked among the top 20 hub proteins by degree value, suggesting their potential role as core regulatory factors. Arhgap20, SERT and PCBD1 also exhibited interactions with several proteins, suggesting their potential as key regulatory proteins, whereas no interactions for CCDC43 were identified. CONCLUSIONS This study applied TMT proteomics to identify seven potential therapeutic targets of 7-HEC for the prevention and treatment of HACE. These targets may be involved in the pathogenesis of HACE through multiple pathways, including maintaining cellular homeostasis, ameliorating oxidative stress, regulating energy metabolism, and reducing vascular permeability.
Animals ; Male ; Proteomics/methods* ; Rats, Wistar ; Flavonoids/therapeutic use* ; Rats ; Brain Edema/etiology* ; Altitude Sickness/metabolism* ; Protein Interaction Maps

OBJECTIVE: To investigate the whole-genome differential methylation profile of patients with high-altitude polycythemia (HAPC). METHODS: In this study, a total of 20 adult male patients with HAPC were included, including 10 Tibetan and 10 Han patients. The control group consisted of 20 healthy adult males, including 10 Tibetan and 10 Han patients. Peripheral blood was collected from each group for DNA extraction and quality inspection, and DNA libraries were constructed. The differential methylation regions (DMRs) between groups were detected using reduced representation bisulfite sequencing, with enriched regions compared to those of the control group. The differential enrichment regions were selected, and the intersection of the enriched regions was associated with genes. The methylation enrichment regions that differed significantly between groups were filtered based on the number of enriched samples in the enriched regions between the groups. GO, KEGG functional, and pathway analysis were performed on the differentially associated gene sets to reveal significant differences between the patients and control groups at the functional and pathway levels. RESULTS: In comparison with the control group, 17 152 sites with more than 25% difference and 15 558 sites with less than -25% difference were identified in Tibetan patients. The top 5 genes with the largest methylation differences between the two groups were MCCC2, RP3-399L15.3, ZNF621, RP11-394A14.2 and SLC39A10. The top significantly different pathways annotated in the differentially expressed genes pathway was serotonergic synapse. In comparison with the control group, 2 687 CpG sites with a greater than 25% difference and 2 602 CpG sites with a less than -25% difference were identified in Han patients. The top 5 genes with the largest methylation differences between the two groups were NAA25, CORO2B, PDC, ZNF853, and MLLT10. The top significantly different pathways annotated in the differentially expressed genes pathway were glutamatergic synapse, retrograde endocannabinoid signaling, Rap1 signaling pathway and cholinergic synapse. In comparison with the control group, 3 895 CpG sites with a greater than 25% difference and 3 969 CpG sites with a less than -25% difference were identified in HAPC patients. The maximum methylation difference between the two groups could reach 78.1%, while the minimum was -42.6%. The top 5 genes with the largest methylation differences between the two groups were MCCC2, ARSJ, CTNNA3, SLC39A10, and SWAP70. The top significantly different pathways annotated in the differentially expressed genes pathway was signaling pathways regulating pluripotency of stem cells. CONCLUSION The occurrence of HAPC may be related to abnormal changes in DNA methylation, and methylation sites may be helpful for the early diagnosis of HAPC.
Humans ; DNA Methylation ; Altitude ; Polycythemia/genetics* ; Male ; Adult ; CpG Islands

OBJECTIVE: To analyze the effect of altitude on NIH-CPSI score in patients with chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS) Methods: Clinical data and the results of NIH-CPSI Questionnaire of the 321 patients with CP/CPPS at different altitudes were collected from March 2021 to March 2022. And the influence of altitudes on NIH-CPSI score of CP/CPPS was analyzed. RESULT: The NIH-CPSI score of patients living at an altitude of 4 300 m was significantly higher than that of patients living at an altitude of 1 500 m and 2 200 m. The CP/CPPS patients who lived in the higher altitude had more severe symptoms of pain and urination as well as lower scores of life quality (P<0.05). CONCLUSION NIH-CPSI score increased significantly with higher altitude, indicating more severe symptoms and decreased quality of life in CP/CPPS patients. These findings highlight the need for management strategies for specific heights in patients with CP/CPPS.
Humans ; Male ; Prostatitis ; Altitude ; Quality of Life ; Surveys and Questionnaires ; Pelvic Pain ; Adult ; Chronic Disease ; Middle Aged

OBJECTIVE: High-altitude hypoxia exposure often damages hippocampus-dependent learning and memory. Nogo-A is an important axonal growth inhibitory factor. However, its function in high-altitude hypoxia and its mechanism of action remain unclear. METHODS: In an in vivo study, a low-pressure oxygen chamber was used to simulate high-altitude hypoxia, and genetic or pharmacological intervention was used to block the Nogo-A/NgR1 signaling pathway. Contextual fear conditioning and Morris water maze behavioral tests were used to assess learning and memory in rats, and synaptic damage in the hippocampus and changes in oxidative stress levels were observed. In vitro, SH-SY5Y cells were used to assess oxidative stress and mitochondrial function with or without Nogo-A knockdown in Oxygen Glucose-Deprivation/Reperfusion (OGD/R) models. RESULTS: Exposure to acute high-altitude hypoxia for 3 or 7 days impaired learning and memory in rats, triggered oxidative stress in the hippocampal tissue, and reduced the dendritic spine density of hippocampal neurons. Blocking the Nogo-A/NgR1 pathway ameliorated oxidative stress, synaptic damage, and the learning and memory impairment induced by high-altitude exposure. CONCLUSION: Our results demonstrate the detrimental role of Nogo-A protein in mediating learning and memory impairment under high-altitude hypoxia and suggest the potential of the Nogo-A/NgR1 signaling pathway as a crucial therapeutic target for alleviating learning and memory dysfunction induced by high-altitude exposure. GRAPHICAL ABSTRACT available in www.besjournal.com.
Animals ; Oxidative Stress ; Hippocampus/metabolism* ; Rats ; Nogo Proteins/genetics* ; Male ; Rats, Sprague-Dawley ; Hypoxia/metabolism* ; Altitude ; Synapses ; Humans ; Altitude Sickness/metabolism*

Objective To evaluate the value of pre-ascent 6-minute walking test performed at a high altitude in predicting the incidence of acute mountain sickness(AMS)induced by rapid ascent to a very high altitude.Methods After baseline information was collected,participants completed the 6-minute walking test at a high altitude of 2 900 m.Then,they rapidly ascended to a very high altitude of 5 000 m.The Lake Louise score was recorded to assess AMS.Results The AMS group showed a shorter pre-ascent 6-minute walking distance(6MWD)at the high altitude than the non-AMS group[480.00(450.00,521.75)m vs.546.00(516.50,568.50)m,P=0.006].No difference was observed regarding the pre-ascent heart rate or peripheral oxygen saturation(both P>0.05).The pre-ascent 6MWD at the high altitude was negatively correlated with the Lake Louise score assessed after rapid ascent to the very high altitude(r=-0.497,P=0.012).Logistic regression analysis confirmed that the pre-ascent 6MWD at the high altitude was associated with the risk of AMS induced by rapid ascent to the very high altitude(OR=0.971,95% CI=0.947-0.996,P=0.022).The results indicated that the pre-ascent 6MWD demonstrated ideal prediction performance(area under receiver operating characteristic curve=0.846,P=0.006).Conclusion The pre-ascent 6MWD recorded at the high altitude is a convenient and reliable predictor of the AMS induced by rapid ascent to the very high altitude.
Humans ; Altitude Sickness/diagnosis* ; Male ; Adult ; Female ; Young Adult ; Middle Aged ; Acute Disease ; Walk Test ; Walking ; Altitude ; Exercise Test

The plateau environment is characterized by low oxygen, low air pressure, low temperature, and strong ultraviolet rays, etc. Chronic obstructive pulmonary disease (COPD) is a preventable and treatable chronic lung disease. High altitude environment increases COPD prevalence, clinical manifestation and mortality. The therapeutic window of theophylline drugs for COPD is narrow, and the high altitude environment has an influence on the pharmacokinetics of the drugs. This review summarizes the differences in the prevalence, mortality, clinical manifestation and clinical symptoms of COPD in the plateau and plain, providing a basis for identifying the risk factors of COPD in the plateau areas. The effects of plateau hypoxic environment on the pharmacokinetics of COPD drugs were also discussed. It can provide a rationale for more effective prevention and treatment of COPD at high altitude.
Humans ; Altitude ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Oxygen ; Hypoxia

Acute mountain sickness (AMS) is a clinical syndrome of multi-system physiological disorder after acute exposure to low pressure and low oxygen at high altitude. Quantitative proteomics can systematically quantify and describe protein composition and dynamic changes. In recent years, quantitative proteomics has been widely used in the prevention, diagnosis, treatment and pathogenesis of many diseases. This review summarizes the progress of quantitative proteomics techniques and its application in the prevention, diagnosis, treatment of AMS and mechanisms of rapidly acclimatizing to plateau, in order to provide a reference for the pathogenesis, early intervention, clinical treatment and proteomic research of AMS.
Humans ; Altitude Sickness/prevention & control* ; Proteomics ; Acute Disease ; Oxygen/metabolism*

OBJECTIVE: To investigate the risk factors of different types of Henoch-Schönlein purpura (HSP) in Tibetan patients at high altitude, as to provide reference for correctly identifying high-risk patients. METHODS: A retrospective study was used to analyze the 304 HSP patients admitted to Tibet Autonomous Region People's Hospital from April 2014 to March 2022. The gender, age, allergic history, family history, clinical type, laboratory indexes (hemoglobin, platelet count, eosinophil, C-reactive protein (CRP), albumin, immunoglobulin G, immunoglobulin A, complement C3 and C4) were analyzed retrospectively. Univariate and multivariate Logistic regression analysis to screen for risk factors affecting different types of HSP. RESULTS: Renal HSP patients showed higher IgA [(9.2±1.7) g/L vs. (6.4±2.4) g/L, P=0.015], lower complement C3 [(203.3±21.6) mg/dL vs. (301.1±19.5) mg/dL, P=0.043], and complement C4 [(33.5±2.3) mg/dL vs. (53.0±7.2) mg/dL, P=0.032]. The patients with abdominal HSP showed lower levels of hemoglobin [(119.6±19.6) g/L vs. (146.6±47.3) g/L, P=0.038] and plasma albumin [24.8 (22.1, 33.9) g/L vs. 32.6 (24.6, 35.1) g/L, P=0.045]. The patients with articular HSP exhibited higher CRP [13.5 (0.2, 20.6) g/L vs. 7.5 (0.1, 15.2) g/L, P=0.036] and erythrocyte sedimentation rate (ESR) [24 (5, 40) mm/h vs. 15 (4, 30) mm/h, P=0.049]. Elevated IgA and decreased complement C4 were risk factors for renal HSP, anemia and decreased plasma albumin were risk factors for abdominal HSP, and elevated CRP was a risk factor for articular HSP. CONCLUSION The clinical characteristics of different types of HSP in plateau areas were different. Patients with high IgA, low complement C4, anemia, hypoalbuminemia, and significantly elevated CRP should be highly vigilant. Early and effective intervention can improve the clinical efficacy, avoid severe development, and improve the prognosis.
Humans ; Retrospective Studies ; Tibet/epidemiology* ; Complement C3/analysis* ; IgA Vasculitis/complications* ; Altitude ; Complement C4 ; C-Reactive Protein/analysis* ; Immunoglobulin A ; Risk Factors ; Anemia ; Hemoglobins/analysis* ; Serum Albumin/analysis*

Objective: To explore the current situation of fetal heart defects in Yunnan Province and surrounding high altitude areas and the social factors affecting pregnancy outcome. Methods: This is a retrospective study. Pregnant woman who underwent fetal echocardiography and diagnosed as fetal cardiac defects in Yunnan Fuwai Cardiovascular Hospital from June 2017 to January 2021 were included. According to the clinical prognostic risk scoring system and grading criteria of fetal cardiac birth defects, the cases were divided into grade Ⅰ to Ⅳ. The disease distribution and proportion of each prognostic grade, pregnancy outcomes were analyzed and compared. The cases were divided into continued pregnancy group and terminated pregnancy group according to pregnancy outcome. The social factors that may affect the selection of pregnancy outcomes were analyzed by multivariate logistic regression analysis. Results: A total of 4 929 fetal echocardiography examination data were collected, and 4 464 cases (90.57%) were from Yunnan Province and surrounding high altitude areas. 2 166 cases of heart defects were finally analyzed, including 998 cases of congenital heart disease (CHD), 93 cases of cardiac tumors, cardiomyopathy and arrhythmia, 1 075 cases of foramen ovale, ductus arteriosus abnormalities and normal variations. The pregnant women were (29.2±5.0) years old with (25.6±3.8) gestational weeks. The number of cases with prognostic grade from Ⅰ to Ⅳ was 1 037 (47.88%), 620 (28.62%), 314 (14.50%), and 44 (2.03%), respectively. And 151 cases (6.97%) were not classified. The cases of normal variation and thin aortic arch development accounted for 42.66% (924/2 166), 5.22% (113/2 166), respectively. The top 3 diseases of grade Ⅱ were ventricular septal defect, coarctation of aorta and mild-moderate pulmonary stenosis, respectively, and their distribution was 11.63% (252/2 166), 3.92% (85/2 166) and 2.35% (51/2 166) respectively in all cases of heart defects, and 25.25% (252/998), 8.52% (85/998) and 5.11% (51/998) respectively in cases of CHD. Among the cases rated as grade Ⅲ and Ⅳ, most of them were complicated congenital heart disease, and the disease types are scattered. The more common cases in grade Ⅲ were complete transposition of great arteries (accounting for 2.40% (52/2 166) of all cases with heart defects, 5.21% (52/998) of all cases with CHD) and pulmonary artery occlusion (type Ⅰ to Ⅲ) with ventricular septal defect (accounting for 2.17% (47/2 166) of all cases with heart defects, and 4.71% (47/998) of all cases with CHD). In grade Ⅳ, single ventricle (0.74% (16/2 166) of all cases with heart defects, 1.60% (16/998) of all cases with CHD) and left ventricular dysplasia syndrome (0.65% (14/2 166) of all cases with heart defects, 1.40% (14/998) of all cases with CHD) are more common. A total of 1 084 cases were successfully followed up, and 675 cases were born, 392 cases were terminated, spontaneous abortion occurred in 17 cases. The proportion of terminated pregnancy cases was significantly increased from grade Ⅰ to Ⅳ, accounting for 5.24% (21/401), 27.78% (70/252), 89.54% (214/239) and 95.56% (43/45), respectively. Among the terminated pregnancy cases, those with grade Ⅲ accounted for the highest proportion (54.59% (214/392)). The distribution of terminated pregnancy cases was mainly complex congenital malformations or diseases with very poor prognosis (pregnancy outcome grade Ⅲ and Ⅳ), and proportion of terminated pregnancy with pregnancy outcome grade Ⅰ and Ⅱ cases (normal variation or good prognosis) accounted for 5.36% (21/392) and 17.86% (70/392), respectively. The results of multivariate logistic regression analysis showed that pregnant women with low education (high school and below: OR=2.73, 95%CI 1.26-5.93, P<0.001; illiteracy: OR=3.27, 95%CI 1.29-7.10, P<0.001) and low family income (Annual income<100 000 yuan: OR=2.47, 95%CI 1.69-5.12, P<0.001) were more likely to choose termination of pregnancy in case of fetal heart defect. Conclusion: In Yunnan province and the surrounding high altitude areas, the disease distribution of fetal heart defect is mainly simple or low-risk disease, but the complex malformation, especially the disease with poor pregnancy outcome, accounts for a relative high proportion. Pregnancy termination also occurs in some cases with good pregnancy outcome. The education level and family income of pregnant women may affect their choice of pregnancy outcome in case of fetal heart defect.
Pregnancy ; Female ; Humans ; Young Adult ; Adult ; Retrospective Studies ; Altitude ; China/epidemiology* ; Heart Defects, Congenital/diagnostic imaging* ; Heart Septal Defects, Ventricular ; Echocardiography ; Fetal Heart/diagnostic imaging*

Objective: To explore the associations of glycated hemoglobin (HbA1c) with FPG and oral glucose tolerance test 2-hour (OGTT-2 h) in areas at different altitude in China. Methods: Subjects who participated in 2018-2019 China Chronic Disease and Risk Factor Surveillance and had no prior type 2 diabetes diagnosis were included. Subsequently, they were categorized into three groups based on altitude of living area (<2 000, 2 000- and ≥3 000 m). With adjustment for intracluster correlation, multivariable linear regression analysis was performed to evaluate the associations of HbA1c with FPG and OGTT-2 h in the context of HbA1c was normal (<5.7%) or abnormal (≥5.7%). Furthermore, the shape of relationships between HbA1c and glucose indicators was examined using restricted cubic spline. Finally, receiver operating characteristic curve was used to evaluate the diagnostic performance of HbA1c for diabetes. Results: A total of 157 277 subjects were included in the analysis. While FPG and OGTT-2 h levels gradually decreased with increase of altitude, HbA1c level was similar among the three groups. When HbA1c was <5.7%, its association with FPG and OGTT-2 h was weak and no obvious difference was observed among the three groups. When HbA1c was ≥5.7%, the FPG and OGTT-2 h increased by 15.45% (95%CI:14.71%- 16.18%) and 24.54% (95%CI:23.18%-25.91%) respectively per one standard deviation increase in HbA1c in group in area at altitude <2 000 m. However, the FPG and OGTT-2 h increased by 13.08% (95%CI:10.46%-15.76%) and 21.72% (95%CI:16.39%-27.31%), respectively, in group in area at altitude 2 000- m, and increased by 11.41% (95%CI:9.32%-13.53%) and 20.03% (95%CI:15.38%- 24.86%), respectively, in group of altitude ≥3 000 m. The restricted cubic spline indicated that the curve showing the association of HbA1c with FPG and OGTT-2 h was flat when HbA1c was <5.7%, but showed a positive linear relationship when HbA1c was ≥5.7%. The area under curve for detecting diabetes was 0.808 (95%CI:0.803-0.812) in group of altitude <2 000 m and 0.728 (95%CI:0.660-0.796, P=0.022) in group of altitude ≥3 000 m. The relevant optimal cutoff value of HbA1c was 5.7%, with a sensitivity of 65.4% and a specificity of 83.0%, and 6.0%, with a sensitivity of 48.3% and a specificity of 93.7%, respectively. Conclusions: When HbA1c was ≥5.7%, the association between HbA1c and glucose indicators became weaker as the increase of altitude. In the area at altitude ≥3 000 m, it may not be appropriate to use HbA1c in the diagnosis of diabetes.
Adult ; Humans ; Glycated Hemoglobin ; Diabetes Mellitus, Type 2/diagnosis* ; Blood Glucose/analysis* ; Glucose ; Altitude ; Fasting ; China/epidemiology* ; Diabetes Mellitus/epidemiology*