给免疫治疗“减毒增效”的辅助药物（十二）--吸氢气或者补充辅酶Q10

《Hydrogen gas activates coenzyme Q10 to restore exhausted CD8+ T cells, especially PD-1+Tim3+terminal CD8+ T cells, leading to better nivolumab outcomes in patients with lung cancer》
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# y) k1 O+ O8 n0 b& I8 n: Z这是日本的一个O药联合或者不联合吸氢气治疗非小细胞肺癌的前瞻性随机对照试验。
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6 l5 g) p& \) G; v3 `制氢机出气量等情况是这样：“The Hycellvator ET 100 (Helix Japan, Co., Ltd.) generates 1.67 l/ min hydrogen gas (hydrogen purity, 99.99%) by electrolysis. As measured by gas chromatography at Kureha Special Laboratory, the gas generated 680,000 ppm hydrogen gas and 320,000 ppm oxygen gas. Recently, hydrogen gas inhalation was used in patients with post-cardiac arrest syndrome, and adverse events were not observed”
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患者每天吸三个小时氢气。
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60个月的随访，临床试验结果是：“Kaplan-Meyer analysis showed that the HGN-treated patients had a significantly longer OS than those treated with NO (Fig. 1A). Median survival time (MST) for the HGN-treated patients was 28 months, a length that is approximately 3-fold longer than that for NO-treated patients (MST 9 months) (Fig. 1A).”

5 ^9 x" @+ U; ?3 ^+ e, p联合吸氢组的中位生存期是28月，不联合吸氢组的中位生存期是9个月。

0 C& T* u  T; F; K# p& R研究者认为联合吸氢组疗效更好的原因是 “Hydrogen gas activates coenzyme Q10 to restore exhausted CD8+ T cells, especially PD-1+Tim3+terminal CD8+ T cells。”

0 B9 f7 W* U; b5 F; w# f% z研究者在临床试验基线和过程中检测了入组患者的血液辅酶Q10的含量极其变化。

“We measured the CoQ10 concentration in the 35 HGN-treated patients with stage IV lung cancer and investigated its association with OS. The cut-off value was found to be 0.985 µg/ml (ROC curve; AUC=0.803, Sensitivity=83.3%, Specificity=81.8%, (Fig. 2E). Further, the 35 HGN-treated patients were stratified as having high (>0.985 µg/ml) and low (<0.985 µg/ml) CoQ10 concentrations. There were no significant differences in the clinico-pathological factors between patients with high and low CoQ10 (Table III). Patients with high CoQ10 had a significantly longer OS than those with low CoQ10 (Fig. 2F). MST of patients with high CoQ10 was 25 months, while that of patients with low CoQ10 was 8 months (Fig. 2F).”

9 t) M! ~# ?: o2 ^6 d“Following hydrogen gas treatment, the concentration of CoQ10 was increased in 19 (46%) of 41 patients (Table IV). Hence, we proceeded to calculate the rate of change of CoQ10 by hydrogen gas treatment (CoQ10 ratio=CoQ10 concentration after treatment/CoQ10 concentration before treatment) and classified patients by high- and low-CoQ10 ratio using the cut-off value (1.175) (ROC curve; AUC=0.710, Sensitivity=75.0%, Specificity=66.7%) (Fig. 2G). Patients with a high-CoQ10 ratio survived significantly longer than those with a low-CoQ10 ratio, as shown in Fig. 2H. MST of patients with a high CoQ10 ratio was NR (not reached to 50% overall survival), while that of patients with low CoQ10 was 9 months (Fig. 2H).”

2 m9 c; }0 J3 a0 }# U7 [' b8 G$ _血液辅酶Q10浓度高的患者，用icb的OS更长。
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