Background: Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly. Choroidal neovascularization (CNV) is the major pathologic feature of neovascular AMD. Oxidative damages and the ensuing chronic inflammation are representative of trigger events. Hydrogen gas (H2) has been demonstrated as an antioxidant and plays a role in the regulation of oxidative stress and inflammation. This experiment aimed to investigate the influence of H2 inhalation on a mouse model of CNV. Methods: Laser was used to induce CNV formation. C57BL/6J mice were divided into five groups: the control group; the laser-only group; and the 2 h, 5 h, and 2.5 h/2.5 h groups that received laser and H2 inhalation (21% oxygen, 42% hydrogen, and 37% nitrogen mixture) for 2 h, 5 h, and 2.5 h twice every day, respectively. Results: The severity of CNV leakage on fluorescence angiography showed a significant decrease in the H2 inhalation groups. The mRNA expression of hypoxia-inducible factor 1 alpha and its immediate downstream target vascular endothelial growth factor (VEGF) showed significant elevation after laser, and this elevation was suppressed in the H2 inhalation groups in an inhalation period length-related manner. The mRNA expression of cytokines, including tumor necrosis factor alpha and interlukin-6, also represented similar results. Conclusion: H2 inhalation could alleviate CNV leakage in a laser-induced mouse CNV model, and the potential mechanism might be related to the suppression of the inflammatory process and VEGF-driven CNV formation.

Diabetes is an independent risk factor for stroke and amplifies inflammation. Diabetic stroke is associated with a higher risk of death and worse neural function. The identification of effective anti-inflammatory molecules with translational advantages is particularly important to promote perioperative neurorestorative effects. Applying molecular hydrogen, we measured blood glucose levels before and after middle cerebral artery occlusion (MCAO), 48-h cerebral oedema and infarct volumes, as well as 28-day weight, survival and neurological function. We also measured the levels of TLR4, NF-κB p65, phosphorylated NF-κB p65, catecholamines, acetylcholine and inflammatory factors. All measurements comprehensively showed the positive effect and translational advantage of molecular hydrogen on diabetic stroke. Molecular hydrogen improved the weight, survival and long-term neurological function of rats with diabetic stroke and alleviated changes in blood glucose levels before and after middle cerebral artery occlusion (MCAO), but no difference in circadian rhythm was observed. Molecular hydrogen inhibited the phosphorylation of NF-κB and significantly reduced inflammation. Molecular hydrogen mediates neurorestorative effects after stroke in diabetic rats. The effect is independent of circadian rhythms, indicating translational advantages. The molecular mechanism is related to the TLR4/NF-κB pathway and inflammation. Graphical abstract Molecular hydrogen (H2) affects outcomes of ischemic stroke with diabetes mellitus (DM).

Recent development regarding mixture of H 2 (concentration of ~66%) with O 2 (concentration of ~34%) for medical purpose, such as treatment of coronavirus disease-19 (COVID-19) patients, is introduced. Furthermore, the design principles of a hydrogen inhaler which generates mixture of hydrogen (~66%) with oxygen (~34%) for medical purpose are proposed. With the installation of the liquid blocking module and flame arresters, the air pathway of the hydrogen inhaler is divided by multiple isolation zones to prevent any unexpected explosion propagating from one zone to the other. An integrated filtering/cycling module is utilized to purify the impurity, and cool down the temperature of the electrolytic module to reduce the risk of the explosion. Moreover, a nebulizer is provided to selectively atomize the water into vapor which is then mixed with the filtered hydrogen-oxygen mix gas, such that the static electricity of a substance hardly occurs to reduce the risk of the explosion. Furthermore, hydrogen concentration detector is installed to reduce the risk of hydrogen leakage. Result shows that the hydrogen inhaler implementing the aforesaid design rules could effectively inhibit the explosion, even ignition at the outset of the hydrogen inhaler which outputs hydrogen-oxygen gas (approximately 66% hydrogen: 34% oxygen).

Purpose: To investigate whether hydrogen-oxygen (67%–33%) therapy could improve the postoperative pulmonary function, recovery, complications, inflammatory reactions, and oxidative stress in patients undergoing lung surgery.Methods: We performed a prospective, randomized, single-blind, controlled clinical trial between December 2020 and December 2021. Eligible patients received either a lobectomy or sublobar resection. Postoperatively, they had 2-hour hydrogen-oxygen therapy (group H) or oxygen therapy (group C) daily, for three consecutive days. The pulmonary functions, recovery, pain intensity, oxygen saturation, inflammatory cytokines, and anti-oxidative markers were documented.Results: A total of 66 patients were analyzed, with 33 patients in each group. Both groups had decreased postoperative pulmonary functions, but group H had significantly better postoperative pulmonary functions than group C (forced vital capacities were 1.4±0.5 and 1.0±0.4 L and forced expiratory volumes in the first second were 1.1±0.3 and 0.9±0.3 L in group H and C, respectively (both P<0.01)). Compared to group C, group H had significantly decreased drainage volume, reduced catheter indwelling duration, shortened length of hospital stay, and lower pain intensity. Group H had statistically significantly decreased postoperative serum cytokine TNF-α and IL-6 levels and increased anti-oxidative markers compared to group C. The incidences of postoperative complications were comparable between the two groups. Conclusion: Hydrogen-oxygen therapy could improve postoperative pulmonary functions, decrease pain intensity, accelerate recovery, and shorten the length of the hospital stay in patients who have undergone lung resection, which may be related to its anti-inflammatory and anti-oxidative effects. Trial registration: The Chinese Clinical Trial Registry (registration number ChiCTR2100042101)，the date of registration was January,13,2021.