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. Here, we established a rat HAPC model and treated it with the HIF-2α inhibitor PT2385. We mainly evaluated the therapeutic effect of PT2385 on HAPC rats by observing the changes in rat phenotype, tissue and organ damage, red blood cell and hemoglobin content, angiogenesis, lipid peroxidation reaction, and inflammatory factors. The results showed that PT2385 treatment improved the congestion phenotype characteristics, inhibited increased erythrocytes and hemoglobin, reduced blood vessel formation, lipid peroxidation, and inflammation, and reduced tissue and organ damage in HAPC rats. This study preliminarly explains the physiological, pathological, and immunological effects of PT2385 treatment for HAPC. It provides a new idea, a reliable experimental basis, and theoretical support for the clinical prevention and treatment of HAPC.

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. OBJECTIVE: This study aimed to investigate whether the use of MPDS was associated with higher prehospital diagnosis accuracy and shorter prehospital delay for patients with ACS transferred by an emergency medical service (EMS), using a national database in China. METHODS: This retrospective analysis was based on an integrated database of China's MPDS and hospital registry. From January 1, 2016, to December 31, 2020, EMS-treated ACS cases were divided into before MPDS and after MPDS groups in accordance with the MPDS launch time at each EMS center. The primary outcomes included diagnosis consistency between hospital admission and discharge, and prehospital delay. Multivariable logistic regression and propensity score-matching analysis were performed to compare outcomes between the 2 groups for total ACS and subtypes. RESULTS: A total of 9806 ACS cases (3561 before MPDS and 6245 after MPDS) treated by 43 EMS centers were included. The overall diagnosis consistency of the after MPDS group (Cohen κ=0.918, P<.001) was higher than that of the before MPDS group (Cohen κ=0.889, P<.001). After the use of the MPDS, the call-to-EMS arrival time was shortened in the matched ACS cases (20.0 vs 16.0 min, P<.001; adjusted difference: -1.67, 95% CI -2.33 to -1.02; P<.001) and in the subtype of ST-elevation myocardial infarction (adjusted difference: -3.81, 95% CI -4.63 to -2.98, P<.001), while the EMS arrival-to-door time (20.0 vs 20.0 min, P=.31) was not significantly different in all ACS cases and subtypes. CONCLUSIONS: The optimized use of MPDS in China was associated with increased diagnosis consistency and a reduced call-to-EMS arrival time among EMS-treated patients with ACS. An emergency medical dispatch system should be designed specifically to fit into different prehospital modes in the EMS system on a regional basis.

Preliminary investigation of serum homocysteine level and its reference interval in apparent healthy population in Lhasa area / 中华检验医学杂志

Objective:To analyze the level of homocysteine (HCY) and its influencing factors in different ethnic groups in Lhasa, and to explore its reference interval.Methods:Reference interval study. The serum HCY (μmol/L) level of 820 healthy subjects was analyzed in Tibet autonomous region People′s hospital from January to December 2018. All the subjects were divided into groups according to ethnicity, gender, age and season. The general linear model was used to analyze the differences in serum HCY levels groups. According to the CLSI C28 document, the Nested ANOVA and Z test were used to analyze and determine whether or not different groups need to establish the reference interval. Results:Ethnicity, age and gender had significant effects on serum HCY. The level of HCY in Tibetan was higher than that in Han (P<0.001); the level of Hcy in male was higher than that in female ( P<0.001); the level of HCY in over-50 year old group was higher than that in under-50 year old group ( P=0.01). There was no significant difference in serum HCY level in seasonal distribution ( P=0.22). Nested ANOVA and Z tests confirmed that the HCY reference interval in Lhasa should be established according to ethnicity and gender in clinical application. The reference interval of HCY level in Lhasa area was established according to difference genders, including<22.41 μmol/L for Tibetan men,<18.41 μmol/L for Tibetan women. Conclusions:The serum HCY levels of the apparent healthy people in Lhasa area were slightly different among people of different ethnicities, genders and ages. We established the reference intervals of HCY of different ethnic groups and gender groups in Tibet and our results have practical significance for the prevention and treatment of cardiovascular and cerebrovascular diseases at high altitude.

Analysis of hospitalized cases with atrial fibrillation in high altitude areas in Tibet / 中国介入心脏病学杂志

Objective To analyze the etiological or associated factors and the treatment of patients with atrial fi brillation in high altitude areas in Tibet. Methods The clinical data of atrial fi brillation patients hospitalized in our hospital during January 2012 to Jane 2016 were analyzed retrospectively. Results (1) A total of 442 patients (male:female,1.2:1) were included in the study with ages of 30-96(65.9±12.3) years. The percentages of paroxysmal, persistent and permanent atrial fi brillation were 14.9%, 69.2%, and 15.8% respectively. The associated factors of atrial fi brillation included hypertension (53.4%), rheumatic heart disease (7.5%),chronic mountain sickness (10.6%), coronary heart disease(5.7%), hyperthyroidism (6.1%) and diabetes (9.0%).(2)Only 42 patients (9.5%) had evaluation with CHADS2score during hospitalization and actually 74.6% patients scored≥2. Twenty-one patients were restored to sinus rhythm during hospitalization and no patients had radiofrequency ablation.Conclusions The associated factors of atrial fi brillation in high altitude areas are similar to other areas. Thrombosis risk evaluation and anticoagulation therapy was not sufficient. Rhythm control rate was low and development of radio frequency ablation therapy should be considered.

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. In this study, we investigated the effect of NGF on human sperm motility, and the results showed that NGF could promote human sperm motility in vitro by increasing the movement distance and the number of A grade spermatozoa. Further analysis demonstrated that NGF promoted the sperm motility in a dose-dependent manner in vitro. These results may facilitate the further studies on human fertility and assisted reproduction techniques.

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. Primary outcome was defined as the change in BP levels measured from baseline to followed-up with an automated sphygmomanometer. Per protocol (PP) and intention to treat (ITT) analyses were conducted. RESULTS: After the three months' intervention period, the net reduction in SBP/DBP in the intervention group in comparison to the control group was -8.2/-3.4 mmHg (all p<0.05) in PP analysis, after adjusting for baseline BP and other variables. ITT analysis showed the net reduction in SBP/DBP at -7.6/-3.5 mmHg with multiple imputations (all p<0.05). Furthermore, the whole distribution of blood pressure showed an overall decline in SBP/DBP and the proportion of patients with BP under control (SBP/DBP<140 mmHg) was significantly higher in salt-substitute group in comparison to the regular salt group (19.2% vs. 8.8%, p = 0.027). CONCLUSION: Low sodium high potassium salt-substitute is effective in lowering both systolic and diastolic blood pressure and offers a simple, low-cost approach for hypertension control among Tibetans in China. TRIAL REGISTRATION: ClinicalTrials.gov NCT01429246.