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     Global Translational Medicine                                               Hydrogen for acute lung injury
            (v)  Other:                                          Two evaluators (LYK and MY) independently extracted
               (a)  Experimental studies.                      the data and evaluated the quality scores of each study. Any
               (b)  Published between 2010 and 2021,           disagreements were resolved by the chief reviewer (GSZ).
               (c)  Published in any publication language,
               (d)  The cited literature sources should be retrievable.  2.5. Data synthesis and statistics analysis
                                                               The meta-analysis was performed using Stata software
            2.2.2. Exclusion criteria                          (version  14.0) and GraphPad Prism (version  9.4). The
            The exclusion criteria are as follows:             outcomes of W/D and PaO  were evaluated using the
                                                                                       2
            (i)  Types:                                        weighted mean difference (WMD) model to assess the
               (a)  Studies of non-animal experiments about ALI,  improvement in lung function. For MDA and SOD,
               (b)  Publications that did not comply with or   the same model was used to evaluate the antioxidant
                   adequately describe standard laboratory animal   effect of hydrogen, while TNF-α was assessed using the
                   rules.                                      standardized mean difference (SMD) model to analyze
            (ii)  Intervention: Did not use 2% H  or hydrogen saline   hydrogen’s anti-inflammatory effects. In cases where
                                          2
               but used other therapy to treat ALI animals.    studies reported standard error (SE) instead of standard
            (iii) Control: Group(s) given placebo or no treatment.  difference (SD), Equation I was used to convert the values:
            (iv)  Other:                                       SD = SE × √N                                (I)
               (a)  The same author published the same articles at
                   different times,                            2.6. Statistical heterogeneity test and exploration
               (b)  Unclear literature sources,                Study heterogeneity was assessed using the Q statistic and
               (c)  Data are only displayed in figures and unable to   I² statistic . Significant heterogeneity was considered
                                                                       [17]
                   contact the author to obtain original data.  present if the I² value exceeded 50% or if the  P-value
              After defining our strategy, each study was randomly   was less than the predefined significance level (α = 0.05).
            given to two independent authors (LYK and MY) and was   Conversely, non-significant heterogeneity was indicated
            selected  by  studies  of  title  and  abstract.  Disagreements   when the I² value was 50% or below, and P ≥ α = 0.05.
            between the two reviewers were solved by discussing with   Considering the possible high heterogeneity due to the
            the third author (GSZ).                            differences between interventions, we used subgroup
                                                                                              [18]
                                                               analysis  to explore the  heterogeneity .  Moreover, the
            2.3. Study selection and data extraction           diversity of species may affect the heterogeneity of the
            The  information  of the included studies,  including   meta-analysis results.  Therefore, meta-regression was
            authors, year of publication, species  of animal subjects,   used to explore the heterogeneity attributable to species.
            and language, were recorded and considered in the study   Meta-regression required a minimum of ten studies to
                                                                                     [19]
            selection based on the inclusion and exclusion criteria.   examine one characteristic . Consequently, the present
            In addition, we extracted data, including the number of   paper included studies using W/D and species as the
            animals in the experimental and control groups, types of   covariate to explore the sources of heterogeneity (n = 12
            ALI animal models, interventions, and outcomes. Data   > 10). Publication bias was assessed using Egger’s test,
            extraction followed predefined rules, with one author   and the stability of the results from the included studies
            (LYK) responsible for study data collection. In case of   was analyzed through the trim and fill funnel plot and
                                                                              [18]
            uncertainty, the chief author (GSZ) was consulted, and the   sensitivity analysis .
            final decision was reached collaboratively by all reviewers.
                                                               2.7. Grade evidence assessment
            2.4. Assessment of Methodological Quality          We followed the PRISMA checklists and used the GRADE
            In the present paper, we evaluated the research quality of   profiler (version  3.6) to evaluate the grade evidence of
            included studies using the CAMARADES checklist, which   included indicators. All the included studies were animal
            covered 10 items related to a series of animal experiment   experiments, and their grades were downgraded by 5 impact
            designs . Due to differences in the research, three   factors. The grade evidence for these included indicators
                  [16]
            evaluation indicators were modified as follows:    was divided into 4 levels: (i) High quality, indicating high
            (i)  Item no. 4: Blinded induction of model,       confidence in results; (ii) moderate quality, indicating
            (ii)  Item no. 6: Use of anesthetic agents without significant   general confidence in results; (iii) low quality, indicating
               intrinsic neuroprotective activity,             limited confidence in certain areas; and (iv) very low
            (iii) Item no. 7: Approval of animal ethics for creating the   quality, indicating the confidence could not be promised or
               ALI model.                                      predicted. The work was completed by GSZ, LYK, and MY.
            Volume 2 Issue 3 (2023)                         3                        https://doi.org/10.36922/gtm.0379
     	
