Statistical analyses

Continuous variables were expressed as means with standard deviation (SD). Normality of distribution for continuous variables was assessed using the Shapiro-Wilk test. Categorical variables were expressed as counts and percentages. For the primary outcomes, the planned comparison of the incidence of AMS between groups was conducted using χ² test. The risk ratio with confidence intervals was reported. The AMS score between groups were investigated using one-way ANOVA or Kruskal-Wallis test. The comparisons of SpO₂ after hypoxic exposure were conducted using paired two-way ANOVA (different time point after hypoxia vs different intervention groups). For secondary outcomes, the systolic and diastolic blood pressure and heart rate after hypoxic exposure were investigated using paired two-way ANOVA. For exploratory outcomes, we pre-specified the comparisons of venous blood gas parameters after interventions using paired two-way ANOVA. We pre-specified the cytokine antibody research in each of Control, Rapid-Ripc, Acetazolamide, and Combined group before and after hypoxia. After identifying PDGF-AB, PDGF-AB levels were validated and investigated using paired two-way ANOVA, and means with SD and mean differences with their 2-sided 95% confidence interval (CI) were reported. We further divided the participants into subgroups based on AMS (+)/(-) and based on different intervention groups to analyze the change of PDGF-AB. Analyses were conducted with GraphPad Prism version 9.0 (GraphPad Software: San Diego, CA, USA). Turkey’s multiple comparisons were performed between each pair of groups.

Genetic data of PDGF were tested for Hardy–Weinberg equilibrium using χ²-test. Genotypes were analyzed in codominant, dominant, recessive, and log-additive model using SNPStats online software (http://bioinfo.iconcologia.net/SNPstats). Allele frequencies and genotype distribution were compared between AMS (+) and AMS (-) groups using the χ²-test. Binary logistic regression was used to analyze associations between genotypes and AMS, which were further adjusted for age, sex, and body mass index (BMI). We divided the participants into subgroups based on their genotype and interventions, and analyzed the PDGF-AB levels in different subgroups. The level of significance was set as a 2-sided P value less than 0.05.