Establishment of a Risk Prediction Model for Metabolic Syndrome in High Altitude Areas in Qinghai Province, China: A Cross-Sectional Study.

Purpose: The prevalence of metabolic syndrome (MetS) is increasing worldwide, and early prediction of MetS risk is highly beneficial for health outcomes. This study aimed to develop and validate a nomogram to predict MetS risk in Qinghai Province, China, and it provides a methodological reference for MetS prevention and control in Qinghai Province, China. Patients and Methods: A total of 3073 participants living between 1900 and 3710 meters above sea level in Qinghai Province participated in this study between March 2014 and March 2016. We omitted 12 subjects who were missing diagnostic component data for MetS, ultimately resulting in 3061 research subjects, 70% of the subjects were assigned randomly to the training set, and the remaining subjects were assigned to the validation set. The least absolute shrinkage and selection operator (LASSO) regression analysis method was used for variable selection via running cyclic coordinate descent with 10-fold cross-validation. Multivariable logistic regression was then performed to develop a predictive model and nomogram. The receiver operating characteristic (ROC) curves was used for model evaluation, and calibration plot and decision curve analysis (DCA) were used for model validation. Results: Of 24 variables studied, 6 risk predictors were identified by LASSO regression analysis: hyperlipidaemia, hyperglycemia, abdominal obesity, systolic blood pressure (SBP), diastolic blood pressure (DBP), and body mass index (BMI). A prediction model including these 6 risk factors was constructed and displayed good predictability with an area under the ROC curve of 0.914 for the training set and 0.930 for the validation set. DCA revealed that if the threshold probability of MetS is less than 82%, the application of this nomogram is more beneficial than both the treat-all or treat-none strategies. Conclusion: The nomogram developed in our study demonstrated strong discriminative power and clinical applicability, making it a valuable reference for meets prevention and control in the plateau areas of Qinghai Province.

Efficacy of Sildenafil on healthy humans in high­altitude hypoxia at rest and during exercise: A meta­analysis.

The current meta-analysis aimed to fully evaluate the efficacy of Sildenafil in healthy humans at different altitudes, focusing on echocardiographic and hemodynamic parameters. Relevant studies were retrieved from the Cochrane, Embase and PubMed databases. Odds ratios (OR) were determined for dichotomous data and weighted mean differences with 95% confidence intervals (CIs) for continuous data. A total of 16 RCTs were included in the current meta-analysis. Short-term treatment with Sildenafil significantly elevated resting heart rate (P<0.01) at altitudes <4,000 meters. No significant differences in heart rate were observed between the Sildenafil and placebo groups at rest and during exercise at an altitude of >4,000 meters (P>0.05). Sildenafil improved resting cardiac output at an altitude of >5,000 meters (P<0.01) and exercising arterial oxygen saturation at <4,000 meters (P<0.01). Sildenafil reduced resting pulmonary artery systolic pressure (PASP) at altitudes >4,000 meters (P<0.01) and exercising PASP at altitudes >5,000 meters (P<0.01). Therefore, Sildenafil efficacy in healthy humans with high-altitude hypoxia is related to altitude and rest or exercise.

Ethnic differences in eating patterns and their associations with obesity among adults in West China.

Despite observed ethnic differences in eating patterns and obesity, evidence in China is limited. This study examined ethnic differences in eating patterns and their associations with weight outcomes among multi-ethnic adults in West China. A cross-sectional survey collected self-reported data on demographics, eating behaviours, weight and height in 2021. Principal component analysis and multivariate regression were conducted to identify eating patterns and examine their associations with weight outcomes. In total, 4407 subjects aged ≥ 18 years were recruited across seven provinces in West China. Four eating patterns were identified: 'meat-lover' - characterised by frequent consumption of meat and dairy products, 'indulgent' - by frequent intakes of added salt, sugar, alcohol and pickled food, 'diversified-eating' - by frequently consuming food with diversified cooking methods and eating out and 'nutri-health-concerned' - by good food hygiene behaviours and reading food labels. Ethnic differences in eating patterns were observed. Compared with Han, Hui were less likely to exhibit meat-lover or diversified-eating patterns; Tibetans were less likely to have meat-lover or nutri-health-concerned patterns; Mongolians were more likely to have indulgent pattern. BMI was positively associated with meat-lover pattern in both genders (exp(ß): 1·029; 95 % CI: 1·001, 1·058 for men; 1·018; 1·000, 1·036 for women) and negatively associated with nutri-health-concerned pattern in women (0·983; 0·966, 1·000). Mongolians were two times more likely to be overweight/obese than Han (OR: 3·126; 1·688, 5·790). Considerable ethnic differences existed in eating patterns in West China. Mongolians were more likely to be overweight/obese, which was associated with their indulgent eating patterns. Ethnic-specific healthy eating intervention programs are needed.

Sleep disturbance and quality of life among university freshmen in Qinghai-Tibet Plateau of China.

Purpose: University freshmen are particularly vulnerable as they are undergoing the transition from high school to university with a range of changes. Sleep problems among this group in the Qinghai-Tibet Plateau of China were barely studied. This study aimed to explore sleep disturbance, and its association with quality of life (QoL) and demographic and clinical characteristics among university freshmen in Qinghai-Tibet Plateau, China. Methods: A multistage stratified cluster random sampling method was performed to recruit student participants with a structured questionnaire to collect sociodemographic and clinical characteristics, and lifestyle behaviors. Sleep disturbance including three aspects of sleep disturbance (i.e., difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS), and early morning awakening (EMA)) was assessed using standardized measurement. Multiple logistic regression models were applied to analyze the data. Results: Among included 2,769 freshmen, the prevalence of sleep disturbance was 14.8% (95% CI: 14.2-15.5%), and corresponding prevalence of DIS, DMS, and EMA was 8.2% (95% CI: 7.7-8.7%), 8.3% (95% CI: 7.8-8.8%), and 4.2% (95% CI: 3.8-4.6%), respectively. Freshmen with sleeping disturbance had significantly lower QoL in physical [F (1, 2769) = 60.23, p < 0.001], psychological [F (1, 2769) = 46.18, p < 0.001], social [F (1, 2769) = 23.04, p < 0.001], and environment [F (1, 2769) = 6.07, p = 0.01] domains. Multiple logistic regression analyses revealed that having breakfast five times a week or less (less than three times, OR = 1.79, 95% CI: 1.34-2.40; 3-5 times, OR = 1.40, 95% CI: 1.09-1.79), self-perceived severe Internet dependence (OR = 1.71, 95% CI: 1.11-2.65), self-perceived poor health status (OR = 3.44, 95% CI: 2.06-5.74), high academic stress (OR = 1.42, 95% CI: 1.13-1.78), poor relationship with classmates (OR = 3.44, 95% CI: 1.53-7.71), and severe ADHD symptoms (OR = 1.08, 95% CI: 1.05-1.12) were positively associated with sleeping disturbance. Conclusion: Sleep disturbance was common among freshmen and is associated with poorer QoL. Prevention and intervention strategies should be developed and implemented, especially among the vulnerable university freshman groups.

Cognitive Impairment and Its Associated Factors in Older Adults Living in High and Low Altitude Areas: A Comparative Study.

Background: Cognitive impairment is a major health concern in older adults. Few studies have examined the association between environmental factors and cognitive impairment, especially in high altitude areas. In this study, the prevalence of cognitive impairment in older adults living in high altitude was compared with those living in low altitude areas. Methods: This was a comparative study conducted at Qinghai (high altitude group), and Guangzhou (low altitude group), China. Cognition, depressive symptoms and quality of life (QOL) were assessed using the Montreal Cognitive Assessment (MoCA), Patient Health Questionnaire (PHQ-9) and WHO Quality of Life brief version-WHOQOL-BREF, respectively. Results: Altogether, 644 older adults (207 in Qinghai and 437 in Guangzhou) completed the assessment. The prevalence rate of cognitive impairment was 94.7% (95% CI: 91.6-97.7%) in older adults living in the high altitude area, while the corresponding figure was 89.2% (95% CI: 86.3-92.1%) in the low altitude area. After controlling for covariates, the high altitude group appeared more likely to have cognitive impairment (OR = 2.92, 95% CI: 1.23-6.91, P = 0.015) compared with the low altitude group. Within the high altitude group sample, multinomial logistic regression analysis revealed that older age (aged 74 and above) was significantly associated with higher risk of severe cognitive impairment (OR = 3.58, 95%CI: 1.44-8.93, P = 0.006), while higher education level (secondary school and above) was associated with decreased risk of moderate cognitive impairment (OR = 0.43, 95%CI: 0.22-0.85, P = 0.006). Within the high altitude group, QOL did not differ significantly between normal/mild, moderate and severe cognitive impairment subgroups across physical [F (1, 207) = 1.83, P = 0.163], psychological [F (1, 207) = 1.50, P = 0.225], social [F (1,207) = 2.22, P = 0.111] and environmental domains [F (1,207) = 0.49, P = 0.614]. Conclusion: This study found that cognitive impairment was more common among older adults living in the high altitude area. Regular screening and appropriate interventions should be provided to older adults in need.

Novel insights into plasma biomarker candidates in patients with chronic mountain sickness based on proteomics.

Chronic mountain sickness (CMS) is a progressive incapacitating syndrome induced by lifelong exposure to hypoxia. In the present study, proteomic analysis was used to identify the differentially expressed proteins (DEPs) and then evaluate the potential plasma biomarkers between CMS and non-CMS groups. A total of 145 DEPs were detected in CMS Han Chinese people who live in the plateau (CMS-HPu), among which 89 were significantly up-regulated and 56 were significantly down-regulated. GO enrichment analysis showed that various biological processes were enriched, including the hydrogen peroxide metabolic/catabolic process, reactive oxygen species (ROS) metabolic, and acute inflammatory response. Protein-protein interaction analysis showed that antioxidant activity, the hydrogen peroxide catabolic process and peroxidase activity were primarily mapped in interaction proteins. Nine modules showed significantly clustering based on WGCNA analysis, with two being the most significant, and GO analysis showed that proteins of both modules were primarily enriched in oxidative stress-related biological processes. Four DEPs increased in CMS patients were evaluated as the candidate biomarkers, and three showed significant AUC: hemoglobin ß chain (HB-ß), thioredoxin-1 (TRX1), and phosphoglycerate kinase 1 (PGK1). The present study provides insights into the pathogenesis of CMS and further evaluates the potentially biomarkers for its prevention and treatment of it.

Hypoxic preconditioning ameliorated neuronal injury after middle cerebral artery occlusion by promoting neurogenesis.

OBJECTIVES: Sequelae of stroke were mainly caused by neuronal injury. Oxygen is a key factor affecting the microenvironment of neural stem cells (NSCs), and oxygen levels are used to promote NSC neurogenesis. In this study, effects of intermittent hypoxic preconditioning (HPC) on neurogenesis were investigated in a rat model of middle cerebral artery occlusion (MCAO). METHODS: SD rats were used to establish the MCAO model. Nissl staining and Golgi staining were used to confirm the neuronal injury status in the MCAO model. Immunofluorescence, transmission electron microscopy, Western blot, and qPCR were used to observe the effects of HPC on neurogenesis. At the same time, the hypothesis that HPC could affect proliferation, apoptosis, differentiation, and migration of NSC was verified in vitro. RESULTS: Hypoxic preconditioning significantly ameliorated the neuronal injury induced by MCAO. Compared with MCAO group, the dendrites, Edu+ /SOX2+ , Edu+ /DCX+ , Edu+ /NeuN+ , Edu+ /GFAP+ , and Edu+ /Tubulin+ positive cells in the HPC + MCAO group exhibited significantly difference. Similarly, axonal and other neuronal injuries in the HPC + MCAO group were also ameliorated. In the in vitro experiments, mild HPC significantly enhanced the viability of NSCs, promoted the migration of differentiated cells, and reduced apoptosis. CONCLUSIONS: Our results showed that HPC significantly promotes neurogenesis after MCAO and ameliorates neuronal injury.

Cognitive Protective Mechanism of Crocin Pretreatment in Rat Submitted to Acute High-Altitude Hypoxia Exposure.

Inadequate oxygen availability at high altitude leads to oxidative stress, resulting in hippocampal neurodegeneration and memory impairment. In our previous study, we found that the cognitive dysfunction occurred when male SD rat was rapidly exposed to 4200 m of high altitude for 3 days. And we also found that crocin showed a cognitive protective effect under hypoxia by regulating SIRT1/PGC-1α pathways in rat's hippocampus. In this article, focused on factors related to SIRT1/PGC-1α pathways, we proposed to further elucidate crocin's pharmacological mechanism. Adult male Sprague-Dawley rats were randomly divided into five groups: control group, hypoxia group (rats were rapidly transported to high altitude of 4200 m for 72 h), and crocins+hypoxia groups (pretreatment with crocin of 25, 50, and 100 mg/kg/d for 3 days). The learning and memory ability was tested by Morris water maze analysis. Hippocampal histopathological changes were observed by HE staining and Nissl staining. The expression of NRF1, TFAM, Bcl-2, Bax, and caspase-3 was detected by immunohistochemistry, RT-PCR, and western blotting test. The contents of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSHPx) were detected by the TBA, WST, and colorimetry method. Neuronal apoptosis was observed by TUNEL staining. After crocin pretreatment, the traveled distance was significantly reduced and the percentage of time in the target quadrant was significantly increased tested by Morris water maze. And neuronal damage in the hippocampus was also significantly ameliorated based on HE staining and Nissl staining. Furthermore, in hippocampus tissue, mitochondrial biosynthesis-related factors of NRF1, TFAM expression was increased; oxidative stress factors of SOD, GSH, and GSHPx expression level were increased, and MDA and glutathione disulfide (GSSG) level were decreased; antiapoptotic protein Bcl-2 expression was increased, and proapoptotic proteins Bax and caspase-3 expression were decreased, with a manner of crocin dose dependent. Therefore, the cognitive protective mechanism of crocin in rat under acute hypoxia was related to promoting mitochondrial biosynthesis, ameliorating oxidative stress injury, and decreasing neuronal apoptosis.

Tsantan Sumtang attenuated chronic hypoxia-induced right ventricular structure remodeling and fibrosis by equilibrating local ACE-AngII-AT1R/ACE2-Ang1-7-Mas axis in rat.

ETHNOPHARMACOLOGICAL RELEVANCE: Tsantan Sumtang, which consists of Choerospondias axillaris (Roxb.) Burtt et Hill, Myristica fragrans Houtt and Santalum album L, is a traditional and common prescription of Tibetan medicine. Tsantan Sumtang originates from Four Tantra with properties of nourishing heart and has been used as a folk medicine for cardiovascular diseases and heart failure in Qinghai, Tibet and Inner Mongolia. Our previous studies found that Tsantan Sumtang showed beneficial effects on right ventricular structure in hypoxia rats, while the underling mechanism remains unclear. AIM OF THE STUDY: To elucidate the underlying mechanisms of Tsantan Sumtang attenuated right ventricular (RV) remodeling and fibrosis of chronic hypoxia-induced pulmonary arterial hypertension (HPAH) rats. MATERIALS AND METHODS: Fifty male Sprague Dawley (SD) rats (170 ± 20 g) were randomly divided into control group, hypoxia group, and hypoxia + Tsantan Sumtang groups (1.0 g·â€¯kg-1·day-1, 1.25 g·â€¯kg-1·day-1, 1.5 g ·kg-1·day-1). Rats in the hypoxia group and hypoxia + Tsantan Sumtang groups were maintained in a hypobaric chamber by adjusting the inner pressure and oxygen content to simulate an altitude of 4500 m for 28 days. The mean pulmonary arterial pressure (mPAP), right ventricle hypertrophy index (RVHI), the ratio of RV weight to tibia length (TL) (RV/TL), heart rate (HR) and RV systolic pressure (RVSP) was determined. Histomorphological assay of RV structure was evaluated by hematoxylin and eosin (HE) staining. RV tissue fibrosis was assessed by collagen proportion area (CPA), collagen I, collagen III and hydroxyproline content. CPA was obtained by picro-sirius red staining (PSR). The expression of collagen I and collagen III were detected by immunohistochemistry and western blotting. The hydroxyproline content was detected by alkaline hydrolysis. In addition, the level of angiotensin II (AngII) and angiotensin 1-7 (Ang1-7) in RV tissue was tested by enzyme-linked immune sorbent assay (ELISA). Protein expression of angiotensin-converting enzyme (ACE), AngII, AngII type 1 receptor (AT1R), angiotensin-converting enzyme 2 (ACE2), Mas receptor (Mas) were determined by immunohistochemistry and western blotting. mRNA level of ACE, AT1R, ACE2, Mas were tested by qPCR. The chemical profile of Tsantan Sumtang was revealed by UHPLC-Q-Exactive hybrid quadrupole-orbitrap mass analysis. RESULTS: Our results showed that RVHI, RV/TL and RVSP were significantly increased in HPAH rat. Furthermore, levels of collagen I, collagen III and hydroxyproline were up-regulated in RV tissue under hypoxia. We found that RV hypertrophy and fibrosis were associated with increased expression of ACE, AngII, AT1R as well as decreased expression of ACE2, Ang1-7 and Mas. RV remodeling and fibrosis were attenuated after Tsantan Sumtang administration by up-regulating ACE2 and Mas level as well as down-regulating ACE, AngII and AT1R levels in RV tissue. 35 constituents in Tsantan Sumtang were identified. CONCLUSION: Tsantan Sumtang attenuated RV remodeling and fibrosis in rat exposed to chronic hypoxia. The pharmacological effect of Tsantan Sumtang was based on equilibrating ACE-AngII-AT1R and ACE2-Ang1-7-Mas axis of RV tissue in HPAH rat.

A meta-analysis of the safety and efficacy of bosentan therapy combined with prostacyclin analogues or phosphodiesterase type-5 inhibitors for pulmonary arterial hypertension.

Bosentan is an effective drug for the treatment of pulmonary arterial hypertension (PAH). The aim of the present meta-analysis was to examine the evidence concerning the efficacy and safety of bosentan therapy combined with prostacyclin analogues or phosphodiesterase type 5 (PDE-5) inhibitors for treating PAH. Eligible published studies were collected from Embase, PubMed, The Cochrane Library and the www.clinicaltrials.gov website. Heterogeneity was assessed using the Cochran Q-statistic test. Results were presented as risk ratios or mean differences with 95% confidence intervals (CI). A total of five studies, comprising 310 patients were included for analysis. No significant improvements in six-minute walk distance (6MWD; mean difference, 16.43 m), clinical worsening (risk ratio, 0.54) and the World Health Organization functional classification (class I: risk ratio, 1.17; class II: risk ratio, 1.18) were observed in patients treated with bosentan in combination with prostacyclin analogues or PDE-5 inhibitors. However, a significant reduction in the mean pulmonary artery pressure (mPAP; 95% CI: -17.06, -6.83; P<0.0001) following bosentan combination therapy was observed. Comparisons of adverse event rates in the bosentan combination therapy (55.6%) and monotherapy (51.8%) suggested that there is no reduction in adverse events (risk ratio, 1.10). The results indicated that bosentan combined with prostacyclin analogues or PDE-5 inhibitors may not improve 6MWD, cardiac function, clinical worsening and adverse events. However, bosentan combined with prostacyclin analogues or PDE-5 inhibitor therapy was able to significantly reduce mPAP compared with the effect of bosentan monotherapy.

Hypoxic preconditioning relieved ischemic cerebral injury by promoting immunomodulation and microglia polarization after middle cerebral artery occlusion in rats.

OBJECTIVES: This study was designed to investigate whether immunomodulation and Microglia polarization is involved in the anti-inflammatory and neuroprotective effect induced by hypoxic preconditioning (HPC) in the middle cerebral artery occlusion (MCAO) brain injury model. METHODS: Longa method, (neurological disability status scale) NDSS method and TTC staining were used to evaluate the degree of cerebral infarction injury under different treatments (Sham, HPC, MCAO and co-treatment with HPC and MCAO). Western blot was used to detect expression profiles of apoptosis and related factors of neurological function. Flow cytometry was performed to analyze changes in the ratio of helper T cells, toxic T cells and NK cells in peripheral immune cells. And immunohistochemistry was used to examine the changes in microglial morphology. ELISA was used to evaluate the levels of nerve growth factors and neurogenesis conditions. Finally, RT-PCR was determined to analyze the transformation of microglia phenotype after HPC and MCAO treatment. RESULTS: MCAO dramatically induced local formation of cerebral infarction. HPC relieved MCAO-induced cerebral infarction and increased rat cognition. HPC affected activation of microglia without significantly affecting in peripheral immune cell populations. After HPC co-treatment with MCAO, the M1 phenotype of microglia was changed and there was a transformation to M2. CONCLUSION: The treatment of HPC remarkably affected the polarization of microglia cells in MCAO rats, and reduced the cerebral nerve injury and played a protective role in MCAO model.

Uric acid lowering effect of Tibetan Medicine RuPeng15 powder in animal models of hyperuricemia.

OBJECTIVE: To evaluate the influence of the Tibetan medicine RuPeng15 powder (RPP15) on uric acid levels, and explore its possible mechanisms of action in hyperuricemic animal models. METHODS: Hyperuricemic mice were generated by orally administering yeast extract paste twice daily (30 g/kg) for 8 days, to mimic human hyperuricemia induced by high-protein diets. Hyperuricemic rats were generated by intraperitoneal injection of 250 mg/kg potassium oxonate to each animal 1 h before the last oral administration of test compounds, which raised the serum uric acid level by inhibiting the decomposition of uric acid. Levels of uric acid and creatinine in serum and urine were detected by the phosphotungstic acid and picric acid methods respectively, and the activity of xanthine oxidase (XOD) was assayed using a commercial test kit. RESULTS: RPP15 (0.4, 0.8, 1.2 g/kg) significantly decreased the level of serum uric acid in healthy rats (P < 0.05). Furthermore, hyperuricemic rats treated with RPP15 (0.4, 0.8, 1.2 g/kg) had lower serum uric acid levels (P < 0.05), accompanied by lower urine uric acid (P < 0.05). For the hyperuricemic mice, the levels of uric acid in the serum decreased significantly (P < 0.05) and the activity of XOD in the liver was restored to normal levels after treatment with RPP15 (P < 0.05). CONCLUSION: RPP15 (0.4, 0.8, 1.2 g/kg) demonstrated an anti-hyperuricemic effect on both healthy and hyperuricemic animals, and the mechanism is most likely associated with inhibiting the activity of XOD.