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Objective: To compare and predict the preventive effects of acetazolamide and other drugs on acute mountain sickness(AMS). Methods: Following the retrieval strategy of PRISMA statement of systematic review and meta-analysis, we searched the databases of PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, etc. from January 1, 1980 to November 30, 2020, and randomized controlled trials (RCT) consistent with drug prevention of AMS were conducted. Using R and other statistical software, Markov chain-Monte Carlo method was carried out for network meta-analysis under Bayesian framework, and node separation method was performed to check the consistency of closed-loop research. Results: Twenty-three literatures (25 studies) were included to compare the preventive effects of 4 drugs on AMS. Bayesian network meta-analysis showed that the incidence of AMS in acetazolamide group (ACE), dexamethasone group (DEX), ginkgo biloba extract group (GBE) and rhodiola group (RHO) was lower than that in placebo group (PLA). In the comparison of drug groups, the incidence of AMS in ACE, DEX and RHO was lower than that in GBE. There was no statistically significant difference in the incidence of AMS among ACE, DEX and RHO groups. Eight of these studies reported the effects of two drugs on pulse oxygen saturation (SpO 2 ) in people entering the target altitude. Bayesian network meta-analysis showed that SpO 2 in RHO was higher than that in ACE and PLA, but there was no statistically significant difference in SpO2 between ACE and PLA. The probability ranking of prevention AMS effect grade showed that the rank 5th probability of AMS in ACE, DEX, GBE, RHO and PLA was 45.72%, 48.80%, 0, 5.48% and 0, respectively. The probability ranking of improving the SpO 2 level of the target altitude population showed that the probability of the ACE, RHO and PLA ranking 1st in improving the SpO 2 effect at the target altitude was 2.27%, 97.66% and 0.07%, respectively; the results of direct comparison were in good agreement with those of Bayesian prediction model indirectly, and there was no statistical difference. Conclusions: Acetazolamide and dexamethasone can effectively prevent AMS, and should be the first choice for related supplementary research in the future. Rhodiola not only improves the SpO 2 of people entering high altitude, but also reduces the incidence of AMS, which needs more attention. Ginkgo biloba extract is not as effective as the above three drugs in preventing AMS and should be used depending on clinical situations.

Objective: To investigate the protective effects of betelnut polyphenols on the vital organs against high-altitude hypoxia in rats., Objective: We compared low-, medium-, and high- dose betelnut polyphenols (400, 800, and 1600 mg/kg, respectively) and rhodiola the effects of against high-altitude hypoxia in Wistar rats. The rats were kept in normal condition and given the drugs daily for 3 days before transfer to a facility at the altitude of 4010 m, where the rats were kept for 5 consecutive days for hypoxic exposure. The rats were then euthanized for measuring arterial blood gas and assessing liver, lung, brain and cardiac pathologies with HE staining. SOD activity, MDA content and GSH content in the organs were measured, and serum levels of inflammatory factors were detected using a protein microarray., Objective: Acute exposure to hypoxia significantly reduced blood oxygen saturation of the rats ( P < 0.05), caused damages in the liver, lung, brain and myocardium, lowered SOD activity and GSH content and increased MDA content in the vital organs, and increased serum levels of TIMP-1, MCP-1, ICAM-1, and L-selectin ( P < 0.05). Treatment with betelnut polyphenols significantly improved blood oxygen saturation, alleviated organ damages, decreased MDA content and increased SOD activity and GSH content in the tissues, and significantly lowered serum levels of inflammatory cytokines in rats with acute exposure to high-altitude hypoxia ( P < 0.05)., Objective: Betelnut polyphenols provides protection of the vital organs against acute high-altitude hypoxia in rats by enhancing the antioxidant capacity and reducing inflammatory response.

Objective: To investigate the interventive effects of Salvia przewalskii Maxim.(SPM)on high-altitude pulmonary hypertension(HAPH)in rats and possible mechanism., Methods: The male SD rats were randomly divided into the control group, the hypoxia group and SPM(0.5 g/kg,1 g/kg and 2 g/kg) group. There were 14 rats in each group. The rats in control group were feed in Xining(with an altitude about 2 260 m), and the other group rats were all feed in Maduo county people's hospital(with an altitude about 4 260 m). The rats in SPM groups were treated with SPM at the doses of 0.5 g/kg,1 g/kg and 2 g/kg by gavage respectively (100 g/ml). The rats in control and the hypoxia groups were received equal volume of distilled water, once a day. After 4 weeks, the mean pulmonary artery pressure (mPAP) of rats was measured and the same part of lung tissue of each rat was collected and stored in liquid nitrogen. Then the relative mRNA expression levels of the proliferation cell nuclear antigen(PCNA), the cell cycle dependent kinase 4(CDK4), CyclinD1, RhoA, ROCK1, ROCK2 in lung tissues of each group rats were all tested by RT-PCR., Results: Compared with the control group, the mPAP and the relative mRNA expression levels of PCNA, CDK4, CyclinD1, RhoA, ROCK1 and ROCK2 were increased significantly in the hypoxia group(P＜0.01). Compared with the hypoxia group, the mPAP and the relative mRNA expression levels of PCNA, CDK4, CyclinD1, RhoA, ROCK1 and ROCK2 in the lung tissues of the SPM group rats were all decreased significantly(P＜ 0.05 or P＜0.01)., Conclusion: SPM can prevent the HAPH in rats, and the mechanisms may be related to the inhibition of the excessive proliferation of smooth muscle cells in pulmonary artery and the excessive activation of the RhoA/Rho kinase(ROCK) signaling pathway.

Objective: To investigate the effect of ERK1 / 2 signaling pathway inhibitor PD98059 on Ras, Raf, MEK, ERK1, ERK2 expression in order to explore a new way for basic research and clinical treatment of the chronic mountain sickness(CMS)., Methods: Sixteen CMS patients were selected, the bone marrow was collected for isolation of monomuclear cells (MNC), the cells were sorted by using CD71 and CD235a antibody magnetic beads, then positive cells were diveded into 5 groups: blank control, DMSO and PD98059 5, 10 and 20 µmol/L, and were cultured in hypoxid condition for 72 hours. The Ras-GTP levels in supernatant was detected by ELISA, the RT-PCR was used to determine the expression of BRaf, MEK, ERK1, ERK2 mRNA in nucleated red blood cells, and the Western blot method was used to detect expression of BRaf, MEK, ERK1, ERK2 protein., Results: PD98059 had no effect on the level of Ras-GTP in each groups. Compared with the blank control group, the expression levels of BRaf, MEK mRNA in DMSO group were not statistically significant (P values were 0.826, 0.298). Compared with the PD98059 20 mol/L group, the expression level of ERK1/2 mRNA was statistically significant (P=0.001, 0.002). Compared with the blank control group, expression levels of p-BRaf, p-MEK protein in DMSO group were not statistically significant (P=0.370, 0.351). Compared with the PD98059 20 mol/L group, the difference of p-ERK1/2 protein level in other 4 groups were statistically significant (P values were <0.001, 0.007)., Conclusion: PD98059 can up-regulate the expressions of ERK1/2 miRNA and p-ERK1/2 protein in bone marrow nucleated red blood cells, the Ras / Raf / MEK / ERK 1/2 pathway is the main signal transduction pathway in regulating bone marrow nucleated red blood cells, suggesting that Ras/Raf /MEK /ERK 1/2 pathway may be involved in the pathogenesis of chronic mountain sickness process.

Objective: To observe the protective effect of salidroside against brain injury in rats exposed to hypobaric hypoxia, and investigate the molecular mechanism of salidroside in the prevention of hypobaric hypoxia-induced brain injury., Methods: Rats were placed in experiment module simulating 6000 m altitude to establish acute hypobaric hypoxia-induced brain injury models. Their respiratory frequency was observed and recorded. Cell apoptosis in the hippocampal dentate gyrus (DG) was detected by TUNEL assay; the expressions of Ras homolog family member A (RhoA), phosphorylated extracellular signal-regulated kinase (p-ERK) and phosphorylated c-Jun N-terminal kinase (p-JNK) were detected by Western blotting., Results: After acute exposure to 6000 m altitude, the respiratory frequency of the rats increased remarkably. The simulation of hypobaric hypoxia induced cell apoptosis in hippocampal DG region, and salidroside intervention inhibited the process of cell apoptosis. The expressions of RhoA, p-ERK, p-JNK decreased after hypobaric hypoxia exposure. Salidroside intervention reversed RhoA expression and raised the levels of p-ERK and p-JNK., Conclusion: Acute exposure to hypobaric hypoxia can induce cell apoptosis in rat hippocampal DG, and salidroside can protect the cells from the exposure-induced apoptosis.

Acute altitude reaction is a stress response of organism to special altitude environmental factors such as hypoxia, low pressure, cold, dry and strong ultraviolet. As it is the most incident disease in high altitude areas, its prevention remains a problem to be solved. In China, the traditional Chinese (Tibetan) medicines have been recognized as an effective means of preventing and treating acute altitude sicknesses. Some single-recipe or compound traditional Chinese (Tibetan) medicines have been proved to be effective for acute altitude sicknesses. In this article, we will describe traditional Chinese (Tibetan) medicines of different types with efficacy in prevention and treatment of altitude sicknesses.

Background: With the increase of troops entering the plateau for a variety of missions, the occurrence of de-adaptation increased significantly when the army returned to the plains, however, until now, there has been no effective treatment for de-adaptation to high altitude., Objective: To observe the interventional effects of compound Chinese herbal preparations (Sankang Capsule, Rhodiola Rosea Capsule and Shenqi Pollen Capsule) on de-adaptation to high altitude, and provide scientific evidence for appropriate treatment methods in the army health care for future missions., Design, Setting, Participants and Interventions: A randomized, single-blind, placebo-controlled trial design was used. Soldiers of a returning army unit who exhibited de-adaptation response symptoms were selected for observation after participating in earthquake relief at high altitude. A total of 543 soldiers were divided into a Sankang Capsule group, a Rhodiola Rosea Capsule group, a Shenqi Pollen Capsule group and a placebo group for drug intervention and administered with corresponding drugs. The course of treatment was 15 days. A self-evaluation scale for de-adaptation to high altitude was used to measure the signs and symptoms exhibited by the soldiers., Main Outcome Measures: Effective rate of signs and symptoms of de-adaptation to high altitude was analyzed after a 15-day treatment and the differences of improvement rate of symptoms between groups were compared to evaluate the efficacy of the drugs., Results: All three drugs improved the symptoms of de-adaptation to high altitude. Compared with the placebo group, symptoms of de-adaptation to high altitude in the drug-treated groups were remitted (P<0.05). Compared with placebo, Sankang Capsule mainly had well-marked effects on dizziness, fatigue, palpitations, cough, sputum and sore throat (P<0.05); Rhodiola Rosea Capsule significantly reduced the symptoms of fatigue, drowsiness, chest tightness, palpitations, vertigo, lack of attention and memory loss (P<0.05); Shenqi Pollen Capsule significantly reduced the symptoms of dizziness, fatigue, weakness, chest tightness, palpitations, cough, sputum, sore throat, memory loss, unresponsiveness and limb numbness (P<0.05). The symptom improvement rate of Shenqi Pollen Capsule was significantly higher than those of the other two drugs., Conclusion: All the three drugs played an evident role in ameliorating symptoms of de-adaptation, and the use of Shenqi Pollen Capsule was more effective than Rhodiola Rosea Capsule and Sankang Capsule.

Aim: To evaluate the hemodynamic effects of aminophylline and nifedipine in patients with HAPE., Methods: 10 patients with HAPE undergone Swan-Ganz catheter. The parameters of hemodynamics and arterial blood gases in HAPE were measured before and after administration of nifedipine 20 mg sublingually and aminophylline 0.25 g intravenously respectively., Results: After administering 0.25 g aminophylline the mPAP and PVR significantly decreased, the cardiac output and the level of PaO2, SaO2 increased obviously, the mSAP, HR did not change so much. After using 20 mg nifedipine, the mPAP, PVR and mSAP also decreased, while the cardiac output, HR and the level of PaO2, SaO2 did not show any changes., Conclusion: Both of aminophylline and nifedipine can attenuate pulmonary hypertension in patients with HAPE, but the effect of aminophylline was better than the effect of nifedipine.

Objective: To observe the preventive and therapeutic effects of gangliosides on acute altitude hypoxic brain damage., Method: Fifteen Wistar rats, weighed 180-220 g, were randomly divided into 3 groups, hypoxia group A, hypoxia group B and normoxia group. The rats in hypoxia group A were exposed to a simulated altitude of 7000 m for 5 hours and the rats in hypoxia group B were exposed to hypoxia after intraperitoneal administration of mixed gangliosides (100 mg/kg/d) for 3 days., Result: Gangliosides could ameliorate the severity of damage in neuronal bodies, cellular skeletons and synapses, especially in synapses., Conclusion: It is suggested that gangliosides are effective in preventing and treating hypoxic brain damages by decreasing the accumulation of intracellular Ca2+, and stabilizing CaM and CaM PKII activity during acute hypoxia.

Objective: To evaluate the clinical effects and mechanism of anticholinergics in treating high altitude pulmonary edema (HAPE)., Methods: 582 patients with HAPE (in 4700-5260 m) were divided into 2 groups: one group (393 patients) was treated with anticholinergic (Group A), and the other 189 cases were treated with a general therapy without anticholinergic (Grorp B)., Results: Compared with Group B, the average admitted days were reduced, the symptom, physical and X-ray signs disappeared more quickly (P < 0.001), the cure rate was raised clearly (P < 0.05) in Group A and the abnormal changes of hemodynamics had been adjusted (P < 0.05, P < 0.01)., Conclusions: Anticholinergic used for HAPE has a rapid and exact curative effect, a slight side effect, and a shorten course of treatment.

Objective: To investigate the therapeutic effect of low-concentration of nitroic oxide (NO) inhalation in high-altitude pulmonary edema., Method: Sixty-five male patients with high-altitude pulmonary edema were randomized into three groups. Patients in the conventional therapy group received oxygen, intravenous furosemide, aminophylline and dexamethasone; patients in the nifedipine group received oral nifedipine (10 mg, tid) in addition to conventional therapy; and patients in the NO group received NO (10 ppm) inhalation for 30 min, in addition to oral nifedipine. The time for which pulmonary rales on auscultation and shadows on chest radiograph lasted, and the course of disease, were compared., Result: In the NO group, pulmonary rales disappeared in 0.4 +/- 0.3 d, shadows on chest radiograph disappeared in 0.6 +/- 0.2 d, and the course of disease was 1.8 +/- 0.7 d, all of which were significantly different from those of the nifedipine group (2.4 +/- 1.4 d, 4.1 +/- 1.7 d, 6.8 +/- 1.8 d, respectively) and the conventional therapy group (3.7 +/- 1.2 d, 5.5 +/- 1.8 d, 9.6 +/- 3.1 d, respectively)., Conclusion: Low-concentration NO inhalation on the basis of conventional and nifedipine therapies was very effective in the treatment of high-altitude pulmonary edema, which deserves further and larger scale investigation.

Sodium nitroprusside (NP) alone Was given to the 39 cases with acute high-altitude pulmonary edema (AHPE). 33 of them (84.6%) fully recovered and 6 (15.38%) obviously improved in 72 hours. The total efficacy was 100%. There was obvious improvement in the cardiac pumping and contractile function as well as total peripheral resistance. The mean pulmonary artery pressure (MPAP) decreased from 52.22 +/- 7.51mmHg to 25.13 +/- 10.36mmHg in 3 to 5 hours after the first dose. Strophanthin K was given to another 11 cases with AHPE, But none fully recovered or obviously improved. During the 72 hours of treatment, 4 improved slightly, 4 showed no therapeutic effect and 3 became worse. The heart rate was reduced obviously and cardiac contractile function strengthened while the cardiac pumping function and total peripheral resistance had no change. Vasodilator therapy is a new method for AHPE treatment and this study shows that the NP is an ideal drug in treating AHPE and that dilation of the small pulmonary arteries by NP may explain its efficacy.