Predicting Acute Mountain Sickness Using Regional Sea-Level Cerebral Blood Flow

Objective To investigate the role of sea-level cerebral blood flow(CBF)in predicting acute mountain sickness(AMS)using three-dimensional pseudo-continuous arterial spin labeling(3D-pCASL).Methods Forty-eight healthy volunteers reached an altitude of 3,650 m by air after undergoing a head magnetic resonance imaging(MRI)including 3D-pCASL at sea level.The CBF values of the bilateral anterior cerebral artery(ACA),middle cerebral artery(MCA),posterior cerebral artery(PCA),and posterior inferior cerebellar artery(PICA)territories and the laterality index(LI)of CBF were compared between the AMS and non-AMS groups.Statistical analyses were performed to determine the relationship between CBF and AMS,and the predictive performance was assessed using receiver operating characteristic(ROC)curves.Results The mean cortical CBF in women(81.65±2.69 mL/100 g/min)was higher than that in men(74.35±2.12 mL/100 g/min)(P<0.05).In men,the cortical CBF values in the bilateral ACA,PCA,PICA,and right MCA were higher in patients with AMS than in those without.Cortical CBF in the right PCA best predicted AMS(AUC=0.818).In women,the LI of CBF in the ACA was different between the AMS and non-AMS groups and predicted AMS with an AUC of 0.753.Conclusion Although the mechanism and prediction of AMS are quite complicated,higher cortical CBF at sea level,especially the CBF of the posterior circulatory system,may be used for prediction in male volunteers using non-invasive 3D-pCASL.

Traditional Chinese medicine for acute mountain sickness prevention: A systematic review and meta-analysis of randomized controlled trials

Objective: To evaluate the efficacy of traditional Chinese medicine(TCM) for preventing acute mountain sickness(AMS).Methods: We included randomized controlled trials(RCTs) which evalueded the effect of TCM for preventing AMS, compared with a placebo, no treatment or acetazolamide. The literature was searched in 6major databases. RevMan 5.4 software was used for the meta-analysis. The relative risk for discrete variables and the mean difference for continuous variables with 95% confidence intervals(CIs) were applied to express the effect size. The risk of bias in the included studies was evaluated using the Cochrane risk assessment tool 2.0(RoB 2.0), and the evidence certainty was assessed using the Grading of Recommendations Assessment and the Development and Evaluation(GRADE) approach.Results: Twenty RCTs involving 3015 participants and 16 TCM patent drugs were included. The overall risk of bias in the majority of studies(15/20) was of some concerns. In terms of the AMS incidence,Rhodiola rosea(R. rosea, Hong Jing Tian) and Ginkgo biloba(G. biloba, Yin Xing Ye) were equivalent to the placebo/no treatment [RR(95% CI): 0.66(0.43-1.01), 0.82(0.63-1.06), respectively]. The AMS incidence in the G. biloba group was higher than that in the acetazolamide group [RR(95% CI): 2.92(1.69-5.06)]. In terms of improving the AMS symptom score on days 1 and 3 in the plateau, R. rosea and G. biloba were superior to the placebo or no treatment [MD(95% CI):-0.98(-1.71,-0.25),-2.05(-3.14,-0.95), respectively]. The other 14 Chinese patent medicines were evaluated in a single trial, and the majority of the results were negative. The subgroup analysis showed that the effect of R. rosea was related to the intervention time, way of ascending, and altitude.Conclusion: R. rosea and G. biloba were effective in improving AMS symptoms but had no effect in reducing the AMS incidence. There was insufficient evidence to support the use of other TCM patent drugs to prevent AMS. More randomized double-blind placebo-controlled trials are warranted to evaluate and screen effective Chinese patent medicines for AMS prevention.

Physiological Variables Associated with the Development of Acute Mountain Sickness

Objective To identify the physiological variables associated with the development of acute mountain sickness(AMS).Methods Eighty four young Chinese men residing at low altitude were taken to an altitude of 4000 m within 40 hours.At sea level and at high altitude,we measured the heart rate,blood pressure,and peripheral oxygen saturation(SpO2)respectively.We also collect blood samples from each participants before and after the altitude elevation.The blood routine and biochemical examinations were performed for all blood samples.The revised Lake Louise Criteria was adopted to diagnose AMS after the subjects arrived at the target high altitude.The association between the presence of AMS and subjects’physiological variables were analysed statistically.Results Of 84 participants,34(40.5%)developed AMS.Compared with non AMS group,in the AMS group,the percentage of neutrophils was significantly higher(64.5%±11.2%vs.58.1%±8.8%,P=0.014),while the level of SpO2 was significantly lower(79.4%±5.4%vs.82.7%±5.6,P=0.008).Binary logistic regression analyses emphasized the association of neutrophils(OR:1.06,95%CI:1.01-1.12,P=0.034)and SpO2 level(OR:0.87,95%CI:0.79-0.95,P=0.004)with the development of AMS.Conclusion The ability to sustain SpO2 after altitude elevation and the increase of neutrophils were associated with the development of AMS in young males.

Early Warning of Acute Altitude Sickness by Physiological Variables and Noninvasive Cardiovascular Indicators

Objective To examine if the variations at sea level would be able to predict subsequent susceptibility to acute altitude sickness in subjects upon a rapid ascent to high altitude.Methods One hundred and six Han nationality male individuals were recruited to this research.Dynamic electrocardiogram,treadmill exercise test,echocardiography,routine blood examination and biochemical analysis were performed when subjects at sea level and entering the plateau respectively.Then multiple regression analysis was performed to construct a multiple linear regression equation using the Lake Louise Score as dependent variable to predict the risk factors at sea level related to acute mountain sickness(AMS).Results Approximately 49.05%of the individuals developed AMS.The tricuspid annular plane systolic excursion(22.0+2.66 vs.23.2+3.19 mm,t=l.998,P=0.048)was significantly lower in the AMS group at sea level,while count of eosinophil[(0.264+0.393)×109/L vs.(0.126+0.084)×109/L,t=-2.040,P—0.045],percentage of diflerences exceeding 50 ms between adjacent normal number of intervals(PNN50,9.66%±5.40%vs.6.98%±5.66%,t=-2.229,P=0.028)and heart rate variability triangle index(57.1+16.1 vs.50.6+12.7,t=-2.271,P=0.025)were significantly higher.After acute exposure to high altitude,C-reactive protein(0.098+0.103 vs.0.062+0.045 g/L,t=-2.132,P=0.037),aspartate aminotransferase(19.7+6.7275.17,3±3.95 U/L,t=-2.231,P=0.028)and creatinine(85.1±12.9 vs.77.7±11.2 mmol/L,t=3.162,P=0.002)were significantly higher in the AMS group,while alkaline phosphatase(71.7+18.2 vs.80.6+20.2 U/L,t=2.389,P=0.019),standard deviation of normal-to-normal RR intervals(126.5+35.9 vs.143.3+36.4 ms,t—2.320,P—0.022),ejection time(276.9+50.8 vs.313.8+48.9 ms,t—3.641,P—0.001)and heart rate variability triangle index(37.1+12.9 vs.41.9+11.1,t=2.O2O,P=0.047)were significantly lower.Using the Lake Louise Score as the dependent variable,prediction equation were established to estimate AMS:Lake Louise Score=3.783+0.281Xeosinophil-0.219Xalkaline phosphatase+O.O32XPNN50.Conclusions We elucidated the differences of pl^siological variables as well as noninvasive cardiovascular indicators for subjects after high altitude exposure compared with those at sea level.We also created an acute high altitude reaction early warning equation based on the physiological variables and noninvasive cardiovascular indicators at sea level.

A specific objective supplemental factor in evaluating acute mountain sickness: ΔHR in combination with SaO_2

Background: So far, there have been no measurements confirmed useful in diagnosing acute mountain sickness(AMS). The aim of this study was to determine the role of heart rate(HR) difference(ΔHR) and oxygen saturation(Sa O2) as objective risk factors in aiding the diagnosis of AMS.Methods: A total of 1,019 participants were assigned to either the acute exposure group(AEG): from 500 m to 3,700 m by flight within 2.5 hours(n=752); or the pre-acclimatization group(PAG): ascended to 4,400 m from 3,650 m within three hours by car after adapting 33 days at 3,650m(n=267). The questionnaires or measurements of resting Sa O2 and HR were completed between 18 and 24 hours before departure and after arrival.Results: Incidence of AMS was 61.3%(461) in AEG, with 46.1%(347) mild cases and 15.2%(114) severe cases. In PAG, the incidence was 38.9%(104), with 30.7%(82) mild cases and 8.2%(22) severe cases. The AMS subjects showed a significant increase in HR and a decrease in Sa O2 levels compared with the non-AMS subjects in both groups. ΔHR and post-exposure Sa O2 were significantly correlated with the Lake Louise Score(LLS) in both groups. Stepwise logistic regression analysis revealed the ΔHR >25 and Sa O2 <88% in AEG as well as ΔHR >15 and Sa O2 <86% in PAG to be independent risk factors of AMS. Combining these two measurements could specifically indicate participants with AMS, which showed a positive predictive value of 89% and specificity of 97% in AEG as well as 85% and 98% in PAG.Conclusion:ΔHR or Sa O2, as objective measurements, correlate with AMS. Combination of these two measurements may be useful as an additional specific and objective factor to further confirm the diagnosis of AMS.

Association between acute mountain sickness(AMS) and age: a meta-analysis

Background: Acute mountain sickness(AMS) is a potentially lethal condition caused by acute hypoxia after ascending to altitudes higher than 2500 m in a short time. The main symptom of AMS is headache. Numerous risk factors of AMS have been examined, including gender, obesity, ascent rate, age and individual susceptibility. In previous studies, age was considered a predisposing factor for AMS. However, different opinions have been raised in recent years. To clarify the association between AMS and age, we conducted this meta-analysis.Methods: We obtained observational studies that explored risk factors for AMS by searching PubMed, Embase, China National Knowledge Internet(CNKI), the Wanfang database and CQVIP for articles published before March 2017.The studies included were required to provide the mean age and its standard deviation for subjects with and without AMS, the maximum altitude attained and the mode of ascent. The Lake Louse Score(LLS) or the Chinese AMS score(CAS) was used to judge the severity of AMS symptoms and incidence. Studies were pooled for the analysis by using a random effects model in RevMan 5.0. Meta-regression and subgroup analyses were conducted to identify sources of heterogeneity using Stata 14.2 and RevMan 5.0.Results: In total, 17 studies were included, and the overall number of subjects with and without AMS was 1810 and3014, respectively. The age ranged from 10 to 76 years. Analysis of the 17 included studies showed that age was not associated with AMS(mean difference(MD)=0.10; 95%CI: —0.38-0.58; P=0.69).Conclusions: This meta-analysis suggests that there is no association between age and the risk of AMS. Race, age,and ascent mode are common sources of heterogeneity, which may provide an analytical orientation for future heterogeneity analyses.

Relationship between excessive erythrocytosis and acute mountain sickness: A field study

Background: Alterations in hematology, especially erythroid changes, may be involved in acute mountain sickness(AMS) at high altitude. This study aimed to identify the relationship between excessive erythrocytosis and AMS following different durations of high-altitude exposure.Methods: A total of 692 healthy young Chinese men were recruited for the study in June and July of 2012 and were divided into the following five groups: I) the 24-h group(24 hours after arrival at Lhasa, 3,700 m, n=261); II) the 7-d group(exposed at Lhasa, 3,700 m for seven days, n=99); III) the re-exposure group(re-exposed at Yang Bajing, 4,400 m for seven days after 】1 year of acclimation at 3,700 m, n=94); IV) the acclimated group(】1 year of acclimation at 3,700 m, Lhasa, n=42); and V) the sea-level control(control group, Chengdu, n=196). Case report forms were used to record the subjects’ demographic information and AMS-related symptoms. All of the subjects underwent routine blood tests.Results: The red blood cell(RBC) count fell slightly but was not significant upon acute exposure to high altitude, whereas the hemoglobin concentration([Hb]) increased significantly. After high-altitude re-exposure, both of the [Hb] and RBC count showed significant increases. The incidence of AMS was 65.1%, 26.3% and 51.1%, respectively in the 24-h, 7-d and re-exposure groups. The [Hb](P=0.024) and hematocrit(P=0.017) were greater in the AMS+ individuals than in the AMS– individuals in 7-d group. A correlation analysis revealed that the [Hb] and hematocrit were closely related with AMS score in 7-d and re-exposure groups, while the RBC showed a correlation with AMS score only in the re-exposure group. The AMS incidence was lowest when the [Hb] was between 140 and 160 g/L in the 24-h and 7-d groups.Conclusions: AMS is associated with both [Hb] and excessive erythrocytosis. Additionally, our findings indicate the existence of an optimal [Hb] for preventing AMS.

Relationship between autonomic nervous system function and acute mountain sickness

Objective: To elucidate the role of the autonomic nervous system (ANS) in acute mountain sickness (AMS) during the initial phase at acute high-altitude exposure. Methods: Ninety-nine healthy sea-level residents rapidly ascended to Tibet plateau (3 675 m altitude) by airplane from Chengdu plain (560 m altitude). ANS function was tested in plain and day 2–4 in Tibet by heart rate variability (HRV), cold pressor test (CPT). AMS was evaluated by clinic symptomatic scores. All subjects were divided into non-AMS group (57, scores≤4) and AMS group (42, scores>4). Results: Compared with non-AMS group, AMS group had higher standard deviation of normal to normal intervals (SDNN), root mean square of delta RR (rMSSD), low-frequency (LF) power, and normalized low-frequency (LFnu) power in plain (P<0.05). After arrival at 3 675 m altitude, AMS group had greater reduction in percentage of delta RR>50 ms(PNN50), rMSSD (P<0.01) and SDNN, LF, total power (TP) (P<0.05). Although no significant differences in the increase of SP and DP during CPT were found between 2 groups in plain, the SP increase during CPT of AMS group was less than non-AMS group (P<0.05) at 3 675 m altitude. AMS symptomatic scores was not only positively correlated with SDNN, rMSSD, LF/HF in plain (P<0.05), but also negatively correlated with HFnu in plain (P<0.05). Conclusion: During the initial high altitude exposure, ANS modulation is generally blunted, but the relatively predominant sympathetic control is enhanced, and this characteristic change of ANS function is positively correlated with the development of AMS.

Association between physiological responses after exercise at low altitude and acute mountain sickness upon ascent is sex-dependent

Background:Acute mountain sickness(AMS)is the mildest form of acute altitude illnesses,and consists of nonspecific symptoms when unacclimatized persons ascend to elevation of≥2500 m.Risk factors of AMS include:the altitude,individual susceptibility,ascending rate and degree of pre-acclimatization.In the current study,we examined whether physiological response at low altitude could predict the development of AMS.Methods:A total of 111 healthy adult healthy volunteers participated in this trial;and 99(67 men and 32 women)completed the entire study protocol.Subjects were asked to complete a 9-min exercise program using a mechanically braked bicycle ergometer at low altitude(500 m).Heart rate,blood pressure(BP)and pulse oxygen saturation(SpO2)were recorded prior to and during the last minute of exercise.The ascent from 500 m to 4100 m was completed in 2 days.AMS was defined as≥3 points in a 4-item Lake Louise Score,with at least one point from headache wat 6–8 h after the ascent.Results:Among the 99 assessable subjects,47(23 men and 24 women)developed AMS at 4100 m.In comparison to the subjects without AMS,those who developed AMS had lower proportion of men(48.9%vs.84.6%,P<0.001),height(168.4±5.9 cm vs.171.3±6.1 cm,P=0.019),weight(62.0±10.0 kg vs.66.7±8.6 kg,P=0.014)and proportion of smokers(23.4%vs.51.9%,P=0.004).Multivariate regression analysis revealed the following independent risks for AMS:female sex(odds ratio(OR)=6.32,P<0.001),SpO2 change upon exercise at low altitude(OR=0.63,P=0.002)and systolic BP change after the ascent(OR=0.96,P=0.029).Women had larger reduction in SpO2 after the ascent,higher AMS percentage and absolute AMS score.Larger reduction of SpO2 after exercise was associated with both AMS incidence(P=0.001)and AMS score(P<0.001)in men but not in women.Conclusions:Larger SpO2 reduction after exercise at low altitude was an independent risk for AMS upon ascent.Such an association was more robust in men than in women.Trial registration:Chinese Clinical Trial Registration,ChiCTR1900025728.Registered 6 September 2019.

Association between smoking and the risk of acute mountain sickness： a meta-analysis of observational studies

Background: People rapidly ascending to high altitudes(>2500m) may suffer from acute mountain sickness(AMS). The association between smoking and AMS risk remains unclear. Therefore, we performed a meta-analysis to evaluate the association between smoking and AMS risk.Methods: The association between smoking and AMS risk was determined according to predefined criteria established by our team. Meta-analysis was conducted according to the PRISMA guidelines. We included all relevant studies listed in the Pub Med and Embase databases as of September 2015 in this meta-analysis and performed systemic searches using the terms "smoking", "acute mountain sickness" and "risk factor". The included studies were required to provide clear explanations regarding their definitions of smoking, the final altitudes reached by their participants and the diagnostic criteria used to diagnose AMS. Odds ratios(ORs) were used to evaluate the association between smoking and AMS risk across the studies, and the Q statistic was used to test OR heterogeneity, which was considered significant when P<0.05. We also computed 95% confidence intervals(CIs). Data extracted from the articles were analyzed with Review Manager 5.3(Cochrane Collaboration, Oxford, UK).Results: We used seven case-control studies including 694 smoking patients and 1986 non-smoking controls to analyze the association between smoking and AMS risk. We observed a significant association between AMS and smoking(OR=0.71, 95% CI 0.52–0.96, P=0.03).Conclusion: We determined that smoking may protect against AMS development. However, we do not advise smoking to prevent AMS. More studies are necessary to confirm the role of smoking in AMS risk.

Sex-based differences in the prevalence of acute mountain sickness: a meta-analysis

Background:When lowlanders rapidly ascend to altitudes>2500 m,they may develop acute mountain sickness(AMS).The individual susceptibility,ascending velocity,time spent at altitude,activity levels and altitude reached are considered risk factors for AMS.However,it is not clear whether sex is a risk factor.The results have been inconclusive.We conducted a meta-analysis to test whether there were sex-based differences in the prevalence of AMS using Lake Louise Scoring System.Methods:Systematic searches were performed in August 2019 in EMBASE,PubMed,and Web of Science for prospective studies with AMS data for men and women.The titles and abstracts were independently checked in the primary screening step,and the selected full-text articles were independently assessed in the secondary screening step by the two authors(YPH and JLW)based on pre-defined inclusion criteria.The meta-analysis was performed using by the STATA 14.1 software program.A random-effects model was employed.Results:Eighteen eligible prospective studies were included.A total of 7669 participants(2639[34.4%]women)were tested.The results showed that there was a statistically significant higher prevalence rate of AMS in women than in men(RR=1.24,95%CI 1.09–1.41),regardless of age or race.However,the heterogeneity was significant in the analysis(Tau2=0.0403,Chi2=50.15,df=17;I2=66.1%,P=0.000),it was main caused by different numbers of subjects among the studies(coefficient=–2.17,P=0.049).Besides,the results showed that there was no evidence of significant publication bias in the combined studies on the basis of Egger’s test(bias coefficient=1.48,P=0.052)and Begg’s test(P=0.130).Conclusions:According to this study,the statistically significant finding emerging from this study was that women have a higher prevalence of AMS.However,the authors could not exclude studies where patients were on acetazolamide.Our analysis provided a direction for future studies of the relationship of sex and the risk of AMS,such as the pathological mechanism and prevention research.

Prior transfusion of umbilical cord mesenchymal stem cells can effectively alleviate symptoms of motion sickness in mice through interleukin 10 secretion

BACKGROUND Motion sickness(MS)is a disease that occurs during unbalanced movement,characterized by gastrointestinal symptoms and autonomic nervous system activation.Current clinical treatments for MS are limited.Recent evidence indicates that the levels of pro-inflammatory cytokines increase during MS and are associated with an inner ear immune imbalance.In the present study,mesenchymal stem cells(MSCs)have been shown to exert strong immunosuppressive effects.AIM To explore whether umbilical cord-derived mesenchymal stem cells(UC-MSCs)can prevent the occurrence of MS,and the underlying mechanism regulated by MSCs in a mouse model of MS.METHODS A total of 144(equal numbers of males and females)5wkold BALB/c mice were randomly divided into five groups:Normal group(n=16),MS group(n=32),MSCs group(n=32),MS+MSCs group(n=32),and MS+AS101/MSCs group(n=32).The MSCs group(n=32),MS+MSCs group(n=32),and MS+AS101/MSCs group(n=32)were preventively transplanted with UC-MSCs or AS101-treated UC-MSCs(1×106 cells/mouse).Mice in the MS(n=32),MS+MSCs,and MS+AS101/MSCs groups were subjected to rotation on a centrifuge for 10 min at 8×g/min for MS model establishment on days 3,5,8,and 10 after UC-MSCs injection.The Morris water maze(MWM)test was used to observe the symptom of dizziness.Enzyme-linked immunosorbent assay(ELISA)and reverse transcription-quantitative polymerase chain reaction(RT-qPCR)were used to detect the levels of inflammatory cytokines in mice peripheral blood and the petrous part of the temporal bone samples.Western blot analysis was performed to analyze the JAK2/STAT3 signaling pathway in the cochlear tissues.Histological examination was performed by hematoxylin and eosin(HE)staining for conventional morphological evaluation in the petrous part of temporal bone samples.RESULTS The MWM test demonstrated that UC-MSCs improved the symptoms of MS.The MS+MSCs group was faster than the MS group on days 3 and 5(P=0.036 and P=0.002,respectively).ELISA and RT-qPCR showed that the serum and mRNA levels of interleukin-10(IL-10)in the cochlear tissues were increased after transplantation with UC-MSCs(MS+MSCs group vs MS group at 3 and 5 d,P=0.002 and cP<0.001,respectively).RT-qPCR results confirmed a significant increase in IL-10 levels at four time points(MS+MSCs group vs MS group,P=0.009,P=0.009,P=0.048,and P=0.049,respectively).This suggested that UCMSCs reduced the sensitivity of the vestibular microenvironment by secreting IL-10.Moreover,Western blot analysis showed that the MSCs activated the JAK2/STAT3 signaling pathway in the cochlear tissues.The levels of IL-10,IL-10RA,JAK2,STAT3,and phosphorylated JAK2 and STAT3 in the MS+MSCs group were increased compared to those of the MS group(P<0.05).The morphological changes in the four groups showed no significant differences.The role of IL-10 secretion on the ability of UC-MSCs to successfully improve the symptoms of MS was confirmed by the diminished therapeutic effects associated with treatment with the IL-10 inhibitor ammonium trichloro(dioxoethylene-o,o′)tellurate(AS101).CONCLUSION Prophylactic transplantation of UC-MSCs can alleviate the clinical symptoms of MS in mice,particularly at 3-5 d after preventive transplantation.The mechanism for UC-MSCs to reduce the sensitivity of vestibular cortex imbalance may be the secretion of IL-10.The next step is to demonstrate the possibility of curing MS in the vestibular environment by intermittent transplantation of MSCs.Above all,MSCs are expected to become a new method for the clinical prevention and treatment of MS.

Ataxia,acute mountain sickness,and high altitude cerebral edema

Previous investigations suggest that ataxia is common and often one of the most reliable warning signs of high altitude cerebral edema(HACE). The aim of this study was to investigate the diagnostic role of ataxia in acute mountain sickness(AMS)and HACE among mountain rescuers on the quake areas,and in approaching the relation between AMS and HACE. After the earthquake on April 14,2010,approximately 24 080 lowland rescuers were rapidly transported from sea level or lowlands to the mountainous rescue sites at 3 750 ~ 4 568 m,and extremely hardly worked for an emergency treatment after arrival. Assessments of acute altitude illness on the quake areas were using the Lake Louise Scoring System. 73 % of the rescuers were found to be developed AMS. The incidence of high altitude pulmonary edema(HAPE)and HACE was 0.73 % and 0.26 %,respectively,on the second to third day at altitude. Ataxia sign was measured by simple tests of coordination including a modified Romberg test. The clinical features of 62 patients with HACE were analyzed. It was found that the most frequent,serious neurological symptoms and signs were altered mental status(50/62,80.6 %)and truncal ataxia(47/62,75.8 %). Mental status change was rated slightly higher than ataxia,but ataxia occurred earlier than mental status change and other symptoms. The earliest sign of ataxia was a vague unsteadiness of gait,which may be present alone in association with or without AMS. Advanced ataxia was correlated with the AMS scores,but mild ataxia did not correlate with AMS scores at altitudes of 3 750~4 568 m. Of them,14 patients were further examined by computerized tomographic scanning of the brain and cerebral magnetic resonance imagines were examined in another 15 cases. These imaging studies indicated that the presence of the cerebral edema was in 97 % of cases who were clinically diagnosed as HACE(28/29). Ataxia seems to be a reliable sign of advanced AMS or HACE,so does altered mental status.

EPAS1 and VEGFA gene variants are related to the symptoms of acute mountain sickness in Chinese Han population: a cross-sectional study

Background: More people ascend to high altitude(HA) for various activities, and some individuals are susceptible to HA illness after rapidly ascending from plains. Acute mountain sickness(AMS) is a general complaint that affects activities of daily living at HA. Although genomic association analyses suggest that single nucleotide polymorphisms(SNPs) are involved in the genesis of AMS, no major gene variants associated with AMS-related symptoms have been identified.Methods: In this cross-sectional study, 604 young, healthy Chinese Han men were recruited in June and July of 2012 in Chengdu, and rapidly taken to above 3700 m by plane. Basic demographic parameters were collected at sea level, and heart rate, pulse oxygen saturation(Sp O2), systolic and diastolic blood pressure and AMS-related symptoms were determined within 18–24 h after arriving in Lhasa. AMS patients were identified according to the latest Lake Louise scoring system(LLSS). Potential associations between variant genotypes and AMS/AMS-related symptoms were identified by logistic regression after adjusting for potential confounders(age, body mass index and smoking status).Results: In total, 320 subjects(53.0%) were diagnosed with AMS, with no cases of high-altitude pulmonary edema or high-altitude cerebral edema. Sp O2 was significantly lower in the AMS group than that in the non-AMS group(P=0.003). Four SNPs in hypoxia-inducible factor-related genes were found to be associated with AMS before multiple hypothesis testing correction. The rs6756667(EPAS1) was associated with mild gastrointestinal symptoms(P=0.013), while rs3025039(VEGFA) was related to mild headache(P=0.0007). The combination of rs6756667 GG and rs3025039 CT/TT further increased the risk of developing AMS(OR=2.70, P<0.001).Conclusions: Under the latest LLSS, we find that EPAS1 and VEGFA gene variants are related to AMS susceptibility through different AMS-related symptoms in the Chinese Han population;this tool might be useful for screening susceptible populations and predicting clinical symptoms leading to AMS before an individual reaches HA.Trial registration: Chinese Clinical Trial Registration, Chi CTR-RCS-12002232. Registered 31 May 2012.

Rong Shuan Jiao Nang in the treatment of acute mountain sickness and high altitude myocardial ischemic syndrome in Yushu

To evaluate the therapeutic effects of Rong Shuan Jiao Nang （RSJN） on treatment of acute mountain sickness （AMS） and high altitude myocardial ischemic syndrome in workers in Yushu, three groups were studied： group A （60 patients with AMS, given RSJN）, group B （15 patients with altitude myocardial ischemic syndrome, given RSJN）, and group C （control, without drugs）. All studied subjects were lowland workers who were first time entry to Yushu for work at an altitude of 4 250 m. During the course of treatment, a routing physical examina- tion was performed, AMS Lake Louise Scores were estimated, arterial oxygen saturation （SaO2）, electrocardiography and hemoglobin concentration were measured before and after using RSJN for 10 days. In group A, the effective rate was 68 %, symptomatic improvement in 54 cases （90 %） within 5 days. In group B, the effective rate was 93 %, episodes of angina pectoris stopped in 12 patients within 3 - 7 days, one lasted 8 days. After treatment, the level of SaO2 increased 15.5 %, 21.8 % and 5.6 % in group A, group B and group C, respectively. RSJN tak- en at the start of the arrival at Yushu can decrease AMS scores and facilitate cure. If taken after the illness has begun, RSJN may help lessen symptoms, especially effectively improved angina pectoris of the high altitude myocardial ischemic syndrome. Symptoms usually subside after 3 - 8 days. RSJN should be continually used lbr at least 7 days after ascent.

Identifying changes in punitive transcriptional factor binding sites from regulatory single nucleotide polymorphisms that are significantly associated with disease or sickness

AIM To identify punitive transcriptional factor binding sites(TFBS) from regulatory single nucleotide polymorphisms(rS NPs) that are significantly associated with disease.METHODS The genome-wide association studies have provided us with nearly 6500 disease or trait-predisposing SNPs where 93% are located within non-coding regions such as gene regulatory or intergenic areas of the genome. In the regulatory region of a gene, a SNP can change the DNA sequence of a transcriptional factor(TF) motif and in turn may affect the process of gene regulation. SNP changes that affect gene expression and impact gene regulatory sequences such as promoters, enhancers, and silencers are known as rS NPs. Computational tools can be used to identify unique punitive TFBS created by rS NPs that are associated with disease or sickness. Computational analysis was used to identify punitive TFBS generated by the alleles of these rS NPs.RESULTS r SNPs within nine genes that have been significantly associated with disease or sickness were used to illustrate the tremendous diversity of punitive unique TFBS that can be generated by their alleles. The genes studied are the adrenergic, beta, receptor kinase 1, the v-akt murine thymoma viral oncogene homolog 3, the activating transcription factor 3, the type 2 demodkinase gene, the endothetal Per-Arnt-Sim domain protein 1, the lysosomal acid lipase A, the signal Transducer and Activator of Transcription 4, the thromboxane A2 receptor and the vascular endothelial growth factor A. From this sampling of SNPs among the nine genes, there are 73 potential unique TFBS generated by the common alleles comparedto 124 generated by the minor alleles indicating the tremendous diversity of potential TFs that are capable of regulating these genes.CONCLUSION From the diversity of unique punitive binding sites for TFs, it was found that some TFs play a role in the disease or sickness being studied.

Establishment of an animal model of acute mountain sickness

Aim To simulate the condition when people travel to the plateau. To make a primary investigation about the mice models, which are respectively provoked by exhaustive exercise, cold and fatigue, and epinephrine. Methods Divide the Kunming mice into 8 groups in random, with 10 in a single group, control group in plain; exhaustive exercise group in plain; fatigue ＆ cold group in plain; epinephrine stimulating group in plain; control group in plateau; exhaustive exercise group in plateau; fatigue ＆ cold group in plateau; epinephrine stimulating group in plateau. To simulate the condition when people travel to Lhasa whose altitude reaches 3700m, those mice were carried there during a five-day period. Day 1： Weight the mice after fasting for 12hrs, then treated different with corresponding methods. Day 2： Collect the data of mortality in each group and sacrifice the alive. Weight the cardiac, pulmonary and cerebral tissues and calculate for the Viscera Index. Results After the journey to the plat- eau, the weight of mice decreases significantly, in exhaustive exercise group and fatigue ＆ cold group also with the increase of pulmonary and cerebral index and decrease of cardiac index compared with groups in plain. As for those who are stimulated with epinephrine, the ones in plateau suffer more from pneumonedema but have a longer life span. The sensitivity to epinephrine can decrease in female mice in plateau, which can be reversed in plain. Con- clusions After the journey to plateau, acute plateau pneumonedema and cerebral edema can be provoked by ex- haustive exercise, fatigue and cold, and starvation; The severity of pneumonedema caused by epinephrine are relat- ed to the environment, strength and gender.

Oxidative stress is not involved in motion sickness of mice

Aim Some indirect evidences indicate a possible correlation between oxidative stress and motion sick- ness. The aim of this research was to investigate whether oxidative stress contributing to motion sickness in mice or not. Methods We examined the mRNA levels of peroxiredoxin 6 （PRDX6） , catalase and enzyme superoxide dis- mutase 1 （SOD1）; reactive oxygen species （ROS）; total antioxidant capacity and SOD activity in different brain regions after rotary stimulation. Mice motion sickness index was recorded after rotation when pretreated with pa- raquat, vitamin C or vitamin E. Results The R0S level and antioxidant capacity were both increased in cerebel- lum plus brainstem （CB） after rotation, a critical region determines motion sickness. However, manipulation of ox- idants or antioxidants using pharmacological method in vivo had no influence on motion sickness index in mice. Conclusion Oxidative stress is not involved in the development of motion sickness in mice.

Role of Histamine H1 Receptors in Vestibular Nucleus in Motion Sickness

Objectives To investigate the expression of histamine H1 receptors （H1R） in the vestibular nucleus of brainstem in rats and the role of H1R in motion sickness （MS）. Methods A total of 24 healthy Sprague-Dawley rats were divided randomly into four groups （n=6 each） which determined if the animals would receive induction of MS or drug （promethazine） treatment： MS （ - ）/Drug （ - ）; MS（＋）/Drug （ - ）; MS （ - ）/Drug （ ＋ at 0.25 mg）; and MS （ ＋ ）/ Drug（＋）. MS was induced by complex motion stimulation and the conditioned taste aversion was used as a behavioral indicator of MS. The volume of 0.15% sodium saccharin solution （SS） intake within 45 minutes after motion stimulation was measured. H1R in the vestibular nucleus was examined by immunofluorescence staining. The expression of H 1R protein in brainstem tissue at vestibular nucleus level was detected by western blot. Results The mean SS intake volume in the MS （ ＋ ）/Drug （ - ） group （8.8 ml） was significantly less than that of the MS （ - ）/Drug （ - ） group （15.1 ml） （P 〈 0.01）. The mean SS intake volume of the MS （-）/Drug （＋） group （14.8 ml） was similar to that of the MS（-）/Drug（-） group. The mean SS intake volume （9.6 ml） of the MS（＋）/Drug（＋） group was more than that of the MS（＋）/Drug（-）group （P〈0.01）, but less than that of the MS（-）/Drug（-） group or MS（-）/Drug（＋） group （P 〈 0.01）. Immunofluorescence staining showed positive expression of H1R in the vestibular nucleus of brainstem and the expression was enhanced by motion stimulation. Western blot analysis showed that H1R protein expressed in the brainstem tissue at vestibular nucleus level and the expression also increased significantly after motion stimulation. The MS-induced increase of H1R was not affected significantly by promethazine. Conclusions H1Rs exist in the vestibular nucleus in rats and H 1R expression is up-regulated by motion stimulation, but not affected by promethazine. The findings indicate that the histaminergic system is involved in MS. Promethazine, as an H1R blocker, may play its anti-MS role by competing the binding site on H1Rs with histamine rather than inhibiting H1R expression.

The dynamic distribution of nitric oxide synthase in the small intestine of mice with intestinal radiation sickness

in order to understand the dynamic change of nitric oxide (NO) and its pathological significance during intestinal radiation sickness, we gave mice 60Co γ-ray irradiation and sacrificed them after different periods of survival.The dynamic distribution of nitric oxide synthase (NOS) in the small intestines (duodenum, jejunum and ileum) was studied by using NADPH-diaphorase histochemistry. The results showed that in the animal groups that survived 48 h and 72 h after irradiation (the 48 h and 72 h groups), the number of NOS-positive neuronal bodies and the density of NOS-positive fibers increased obviously in the myenteric plexus and deep muscular plexus as compared with the control group. The neuronal bodies and fibers were stained intensely. The NOS-positive reaction product in the glandular cavities of the intestines and on the mucosa also increased. The results suggest that the activation of NOS or increase of NO production might be one of the main causes of intestinal and vascular dilatation during intestinal radiation sickness.