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     Global Translational Medicine                                               Hydrogen for acute lung injury
            Table 1. (Continued)
            Author         Species    Type & modeling process          Treatment           Indicator
            Liu et al., 2013    SD rats   SI Process: Smoke inhalation  Hydrogen saline    Artery blood: TNF-α↓ Lung
                      [40]
            [Chinese]      (Male, 6/6)                                 (10 ml/kg, ip)      tissue: MDA↓
            Notes: Author: First author or corresponding author; Language: The language used for the publication; Species: Including sex, numbers of experiment group,
            and control group; Type and modeling process: The types of acute lung injury and modeling process in animal models; Treatment: The use of intervention and
            lasting times; Indicator: Indicators of included study that can be used for this meta-analysis.
            Abbreviations: BI: Burn injury; CLP: Cecal ligation and puncture; ip: Intraperitoneal; IH: Intraperitoneal hydration; I/R: Ischemia/reperfusion; LPS:
            Lipopolysaccharide; MDA: Malondialdehyde; OA: Oleic acid; PaO : Arterial oxygen partial pressure; PQ: Paraquat; SI: Smoke inhalation; SOD: Superoxide
                                                     2
            dismutase; TNF-α: Tumor necrosis factor-alpha; W/D: Wet-to-dry ratio.
            Table 2. Risk of bias assessment for included studies  group. All studies provided complete data and reported
                                                               positive results. This indicator also revealed that hydrogen
            Study          1  2  3  4  5  6  7  8  9  10  Score  therapy could significantly improve the situation of hypoxia
            Fang et al., 2011 [26]  √  √  √  -  -  √  √  -  √  -  6  in ALI animals to a certain degree (effect size: WMD = 14.19,
            Tian et al., 2012 [27]  √  -  -  -  -  √  √  -  √  -  4  95% CI = 6.08 – 22.30, P < 0.001; heterogeneity: I  = 95.7%,
                                                                                                     2
            Chen et al., 2012 [20]  √  -  -  -  -  -  √  -  √  -  3  P < 0.001; random-effects model; Figure 3).
            Li et al., 2014 [23]  √  √  √  -  -  -  √  -  √  -  5
            Zhang et al., 2016 [21]  √  √  √  -  -  -  √  -  √  -  5  3.4.3. MDA
            Xie et al., 2010 [22]  √  √  √  -  -  √  √  -  √  -  6  Nine  studies  provided  complete  data  for  both  the
            Bu et al., 2015 [28]  √  -  √  -  -  √  √  -  √  -  5  experimental group and the control group. The results
            Shi et al., 2013 [29]  √  √  √  -  -  √  √  -  √  -  6  demonstrated a significant difference in MDA levels
            Zhou et al., 2018 [37]  √  √  √  -  -  -  √  -  √  √  6  when hydrogen therapy was used to treat ALI animal
            Liu et al., 2013 [38]  √  √  √  -  -  -  √  -  √  √  6  models compared to control groups. It revealed that
            Mao et al., 2015 [25]  √  -  √  -  -  -  √  -  √  -  4  hydrogen therapy could repress lipid peroxidation (effect
            Xu et al., 2019 [30]  √  √  √  -  -  -  √  -  √  -  5  size: WMD  = −1.59, 95% CI = −2.12 – −1.06, P < 0.001;
                                                                            2
            Liang et al., 2012 [31]  √  -  √  -  -  -  √  -  √  -  4  heterogeneity: I   =  97.3%,  P  < 0.001; random-effects
            Song et al., 2016 [32]  √  -  √  -  -  -  √  -  √  -  4  model; Figure 4).
            Ying et al., 2017 [33]  √  √  √  -  -  √  √  -  √  √  7  3.4.4. SOD
            Ying and He, 2011 [34]  √  -  √  -  -  -  √  -  √  -  4
            Fang et al., 2012 [26]  √  -  √  -  -  -  √  -  -  -  3  Six studies reported that both 2% H  and hydrogen saline
                                                                                            2
            Liu et al., 2015 [24]  √  √  √  -  -  -  √  -  -  -  4  improved SOD levels in lung tissues. The findings suggested
                                                               that hydrogen may scavenge superoxide free radicals in the
            Zhang et al., 2011 [35]  √  -  √  -  -  -  √  -  -  √  4  lung by promoting the expression of SOD in ALI animal
            Liu et al., 2013 [36]  √  -  √  -  -  -  √  -  √  -  4  models (effect size: WMD = 20.09, 95% CI = 10.12 – 30.07,
            Notes: 1. Peer-review publication; 2. Control of temperature; 3. Random   P < 0.001; heterogeneity: I  = 98.7%, P < 0.001; random-
                                                                                    2
            allocation to treatment or control; 4. Blinded induction of model (group   effects model; Figure 5).
            randomly after modeling); 5. Blinded assessment of outcome (s); 6.
            Use of anesthetic without significant intrinsic neuroprotective activity;   3.4.5. TNF-α
            7. Appropriate animal model (s) (conform to the types of participants);
            8. Sample size calculation; 9. Compliance with animal welfare   Eight studies were included in the analysis, and the results
            regulations; 10. Statement of potential conflict of interests.  demonstrated that the experimental groups showed
                                                               significantly lower TNF-α levels compared to the control
                                                               group. The findings confirmed that hydrogen has an
            that hydrogen therapy has a significant treatment   inhibitory effect on inflammatory factors (effect size:
            effect in ALI-induced pulmonary edema (effect size:   SMD  =  −3.62, 95% CI  = −5.52 –  −1.72; heterogeneity:
            WMD =  −0.91, 95%  CI = −0.98 – −0.85,  P  < 0.001;   I  = 93.8%, P < 0.001; random-effects model; Figure 6).
                                                                2
            heterogeneity: I  = 98.5%,  P  < 0.001, tau =0.9132;
                          2
                                                   2
            random-effects model; Figure 2).                   3.6. Subgroup analysis
                                                               According to the heterogeneity values of W/D, PaO ,
            3.4.2. PaO                                                                                      2
                     2                                         MDA, SOD, and TNF-α, we performed a subgroup
            Nine studies demonstrated the influence of hydrogen   analysis, dividing the treatments into 2% H  and hydrogen
                                                                                                 2
            therapy on improving PaO  when compared to the control   saline. The analysis aimed to explore whether different
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            Volume 2 Issue 3 (2023)                         6                        https://doi.org/10.36922/gtm.0379
     	
