Acute respiratory distress syndrome (ARDS) is a common respiratory emergency, but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treatment measures. Our previous study confirmed that inhalation of hydrogen gas can reduce the acute lung injury of ARDS, but the application of hydrogen has flammable and explosive safety concerns. Drinking hydrogen-rich liquid or inhaling hydrogen gas has been shown to play an important role in scavenging reactive oxygen species and maintaining mitochondrial quality control balance, thus improving ARDS in patients and animal models. Coral calcium hydrogenation (CCH) is a new solid molecular hydrogen carrier prepared from coral calcium (CC). Whether and how CCH affects acute lung injury in ARDS remains unstudied. In this study, we observed the therapeutic effect of CCH on lipopolysaccharide (LPS) induced acute lung injury in ARDS mice. The survival rate of mice treated with CCH and hydrogen inhalation was found to be comparable, demonstrating a significant improvement compared to the untreated ARDS model group. CCH treatment significantly reduced pulmonary hemorrhage and edema, and improved pulmonary function and local microcirculation in ARDS mice. CCH promoted mitochondrial peripheral division in the early course of ARDS by activating mitochondrial thioredoxin 2(Trx2), improved lung mitochondrial dysfunction induced by LPS, and reduced oxidative stress damage. The results indicate that CCH is a highly efficient hydrogen-rich agent that can attenuate acute lung injury of ARDS by improving the mitochondrial function through Trx2 activation.

Acute respiratory distress syndrome (ARDS) is an acute and severe clinical complication lacking effective therapeutic interventions. The disruption of the lung epithelial barrier plays a crucial role in ARDS pathogenesis. Recent studies have proposed the involvement of abnormal mitochondrial dynamics mediated by dynamin-related protein 1 (Drp1) in the mechanism of impaired epithelial barrier in ARDS. Hydrogen is an anti-oxidative stress molecule that regulates mitochondrial function via multiple signaling pathways. Our previous study confirmed that hydrogen modulated oxidative stress and attenuated acute pulmonary edema in ARDS by upregulating thioredoxin 1 (Trx1) expression, but the exact mechanism remains unclear. This study aimed to investigate the effects of hydrogen on mitochondrial dynamics both in vivo and in vitro. Our study revealed that hydrogen inhibited lipopolysaccharide (LPS)-induced phosphorylation of Drp1 (at Ser616), suppressed Drp1-mediated mitochondrial fission, alleviated epithelial tight junction damage and cell apoptosis, and improved the integrity of the epithelial barrier. This process was associated with the upregulation of Trx1 in lung epithelial tissues of ARDS mice by hydrogen. In addition, hydrogen treatment reduced the production of reactive oxygen species in LPS-induced airway epithelial cells (AECs) and increased the mitochondrial membrane potential, indicating that the mitochondrial dysfunction was restored. Then, the expression of tight junction proteins occludin and zonula occludens 1 was upregulated, and apoptosis in AECs was alleviated. Remarkably, the protective effects of hydrogen on the mitochondrial and epithelial barrier were eliminated after applying the Trx1 inhibitor PX-12. The results showed that hydrogen significantly inhibited the cell apoptosis and the disruption of epithelial tight junctions, maintaining the integrity of the epithelial barrier in mice of ARDS. This might be related to the inhibition of Drp1-mediated mitochondrial fission through the Trx1 pathway. The findings of this study provided a new theoretical basis for the application of hydrogen in the clinical treatment of ARDS.

Septic lung injury is characterized by uncontrollable inflammatory infiltrations and acute onset bilateral hypoxemia. Evidence has emerged of the beneficial effect of hydrogen in acute lung injury (ALI), but the underlying mechanism is unclear. In this research, the recovery action of hydrogen on lipopolysaccharide (LPS)-induced ALI in mice and A549 cells was investigated. The 7-day survival rate and body weight of mice were measured after intraperitoneal injection of LPS. Lung function was determined by a whole body plethysmography (WBP) system using the indicators respiratory rate and enhanced pause. Hematoxylin and eosin (HE) staining confirmed the signs of pulmonary edema and inflammatory ooze. Reverse transcription-polymerase chain reaction (RT-PCR) quantification was used to detect the expression of inflammatory factors. Western blotting analysis evaluated the expression levels of involved proteins in the AMP-activated protein kinase (AMPK) pathway. The experimental results confirmed that hydrogen provided an essential solution to the dissipative effects of LPS on survival rate, weight loss and lung function. The LPS-stimulated inflammatory factors, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were also suppressed by hydrogen in A549 cells. Western blot analysis showed that hydrogen significantly upregulated the levels of phosphorylated AMPK (p-AMPK) and lowered the LPS-induced increased expression of dynamin-related protein 1 (Drp1) and Caspase3. These findings prove that hydrogen attenuated LPS-treated ALI by activating the AMPK pathway, supporting the feasibility of hydrogen treatment for sepsis.

Objective:To investigate the protective effect of hydrogen on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in septic mice and the effect on the expression of the NOD-like receptor thermal protein domain associated protein 3 (NLRP3)/tissue factor (TF) signaling pathway.Methods:A total of 64 male C57BL/6J mice were tested in two batches. According to the random number table method, mice in each batch were divided into four groups ( n=8): a control group (group C), a LPS group (group L), a LPS+ hydrogen group (group LH) and a hydrogen group (group H). Mice in groups C and H were intraperitoneally injected with normal saline at 10 ml/kg. Meanwhile, those in groups L and LH were intraperitoneally injected with 10 mg/kg LPS to establish an ALI model in septic mice. Groups C and L were conventionally housed for 12 h, while groups LH and H were inhaled with 4% hydrogen for 12 h. Then, 12 h after modeling, mice in batch 1 were used for lung histopathology, lung function tests and scattered Doppler flow imaging, while those in batch 2 were used for bronchoalveolar lavage and Western blot analysis. hematoxylin-eosin (H-E) staining was performed to observe lung histopathology and evaluate lung injury score. Whole-body plethysmography system was used to detect lung function indicators in mice: minute ventilation volume (MV), expiratory flow 50 (EF50), peak expiratory flow (PEF), and enhanced pause (Penh). Scattered Doppler flow imaging was conducted to detect blood flow in the right lung and the left hind foot of mice. The levels of NLRP3 inflammatory vesicles and TF in the lungs were measured by Western blot. The levels of inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 in bronchoalveolar lavage fluid (BALF) of mice were detected by enzyme-linked immunosorbent assay (ELISA). Results:According to H-E staining, the lung tissue structure of mice in group C and group H was normal. The lung tissue structure of mice in group L was disorganized, with a large number of neutrophils infiltrating. The lung tissue of mice in group LH showed reduced neutrophils infiltrating and relieved edema. Compared with group C, the lung tissue damage score was significantly elevated in groups L and LH ( P<0.05). MV, EF50 and PEF were significantly declined, and Penh was significantly elevated (all P<0.05). Blood flow in the right lung and the left hindfoot significantly decreased ( P<0.05). The relative content of NLRP3 and TF in lung tissue significantly increased ( P<0.05). The concentrations of TNF-α and IL-6 in BALF significantly increased ( P<0.05). Compared with group C, there was no statistical differences in all indicators in group H ( P>0.05). Compared with group L, the lung tissue injury score of mice in group LH was significantly reduced ( P<0.05). MV and PEF significantly increased, Penh was significantly elevated (all P<0.05). The difference in EF50 was not statistically significant ( P>0.05). Blood flow in the right lung and the left hindfoot was significantly higher ( P<0.05). The relative content of NLRP3 and TF in lung tissue was significantly lower ( P<0.05). The concentrations of TNF-α and IL-6 in BALF were significantly lower ( P<0.05). Conclusions:Hydrogen alleviates LPS-induced ALI in septic mice, which may be related to inhibition of the NLRP3/TF expression and reduction of secretion of inflammatory factors by hydrogen.

Background: The mortality rate of colorectal cancer (CRC) ranks second worldwide. Previous research had indicated that licochalcone A (LA) was a flavonoid in licorice with diverse anticancer effects. We explored the underlying mechanisms of LA-triggered anticancer activity in CRC. Methods: Thiazolyl Blue (MTT) experiment and EdU staining were utilized to evaluate cell proliferation. Meanwhile, cells were stained by Annexin V/PI to investigate apoptosis through flow cytometry assay. Moreover, expressions of proteins were detected by immunoblotting, and the level of related mRNA was investigated using real-time quantitative PCR. Results: LA selectively suppressed the proliferation and triggered apoptosis of CRC cells. Strikingly, LA induced cytoprotective autophagic activities since the suppression of autophagy significantly strengthened LA-induced cytotoxicity and FLICE inhibitory protein (c-FLIPL) degradation, meanwhile reversing LA-mediated heat shock protein 70 (Hsp70) upregulation. Moreover, autophagy-mediated Hsp70 upregulation resisted LA-induced anticancer effects since the suppression of Hsp70 strengthened LA-triggered cytotoxicity and c-FLIPL degradation. Furthermore, LA greatly activated extracellular signal-regulated protein kinases (ERK) and p38. However, blocking of ERK, but not p38, significantly boosted LA-triggered cell death and c-FLIPL downregulation. Suppression of ERK also reversed LA-mediated autophagic induction. Conclusions: LA increased Hsp70 expression depending on ERK-mediated autophagy, which protected CRC cells from LA-induced anticancer activities.

目的:探讨超声引导下高位髂筋膜阻滞对股骨头置换老年患者凝血功能的影响.方法:选择在静脉全身麻醉下行股骨头置换的老年患者80例.按随机数字表分为2组,每组40例:观察组在麻醉诱导前30 min行超声引导下高位髂筋膜阻滞然后再行静脉全身麻醉;对照组只行静脉全身麻醉.分别于入院检查时(基础值)、手术开始后1h、术后24h抽取肘静脉血进行血栓弹力图分析;离心分离血清,测定血清皮质醇、C-反应蛋白(C-reactive protein,CRP)、白介素(interleukin,IL)-6、肿瘤坏死因子(tumor necrosis factor,TNF)-α水平.记录患者术后6 h(T1)、24 h(T2)、48 h(T3)安静和运动时疼痛数字评分(numerical rating scale,NRS),记录术后不良反应和患者满意度评分.结果:与对照组比较,观察组术后24h的血栓弹力图反应时间(reac-tion time,R)延长,最大振幅(maximum amplitude,MA)、凝集块形成速率(α)、凝血综合指数(coagulation index,CI)降低(P＜0.05).与入院时比较,对照组患者术后24h的R值降低,且MA、α、CI升高(P＜0.05).与对照组相比,观察组手术开始后1h和术后24h皮质醇、CRP、IL-6和TNF-α的含量低(P＜0.05),术后T1～T3时点的静息和运动时NRS低(P＜0.05),满意度高(P＜0.05),苏醒期躁动和恶心呕吐的发生率低(P＜0.05).结论:超声引导下高位髂筋膜阻滞联合全身麻醉能降低老年患者股骨头置换术中和术后的应激反应和高凝状态,提供较好的术后镇痛效果.

We aimed to explore the mechanism for hydrogen in the treatment of neuropathic pain in diabetic rats.Eight-week-old male SD rats were randomly divided into control, model and hydrogen treatment groups.Th e hydrogen treatment group was intraperitoneally injected with hydrogen-rich saline daily in 7 th and 8 th weeks aft er modeling.Before and 2, 4, 6 and 8 weeks aft er modeling, the neurological function, behavioral changes and levels of infl ammatory factors TNF-α and IL-6 in the sciatic nerve were detected, and MCP1 and CCR2 protein expressions were measured by Western blotting.Compared with the model group, the hydrogen treatment group had significantly increased motor nerve conduction velocity, thermal withdrawal latency and mechanical withdrawal threshold (P<0.05).Th e significantly higher levels of TNF-α and IL-6 in the sciatic nerve of the model group than those of the control group decreased in the hydrogen treatment group (P<0.05).Th e protein expressions of MCP1 and CCR2 in the sciatic nerve of the model group significantly exceeded those of the control group.Such expressions of the hydrogen treatment group were lower than those of the model group.Hydrogen alleviated the inflammatory response of peripheral nerves in diabetic rats by inhibiting the MCP1-CCR2 signaling pathway, thus mitigating neuropathic pain.

目的 探讨腹腔镜肝切除术(LH)治疗原发性肝癌(PLC)患者应用氢吗啡酮联合纳布啡静脉自控镇痛(PCIA)控制疼痛的效果.方法 2018年1月～2021年1月我院收治的PLC患者104例,随机分为对照组52例和观察组52例,两组患者均接受LH手术,在对照组,给予舒芬太尼联合纳布啡用于术后PCIA,而在观察组给予氢吗啡酮联合纳布啡用于术后PICA.采用疼痛视觉模拟评分(VAS)评价术后疼痛程度,使用流式细胞仪检测外周血T细胞亚群CD3+细胞、CD4+细胞、CD8+细胞和NK细胞百分比.结果 在术后24 h,观察组静态VAS和动态VAS分别为(2.5±0.8)分和(3.7±1.2)分,显著低于对照组[分别为(4.3±1.2)分和(5.8±1.7),P<0.05],在术后72 h,静态VAS和动态VAS分别为(1.1±0.4)分和(3.2±0.9)分,显著低于对照组[分别为(2.6±0.7)分和(5.1±1.3),P<0.05];术后,两组肝功能指标变化无显著性差异(P>0.05);在术后7 d,观察组外周血CD3+细胞、CD4+细胞、CD8+细胞和NK细胞百分比分别为(76.3±7.5)％、(36.8±4.9)％、(32.5±3.2)％和(16.3±2.9)％,与对照组[分别为(75.2±7.4)％、(37.6±4.4)％、(31.2±3.4)％和(17.4±2.6)％]比,差异无统计学意义(P>0.05).结论 氢吗啡酮联合纳布啡用于LH后PCIA能够有效减轻患者疼痛程度.

We aimed to explore the mechanism for hydrogen in the treatment of neuropathic pain in diabetic rats. Eight-week-old male SD rats were randomly divided into control, model and hydrogen treatment groups. The hydrogen treatment group was intraperitoneally injected with hydrogen-rich saline daily in 7th and 8th weeks after modeling. Before and 2, 4, 6 and 8 weeks after modeling, the neurological function, behavioral changes and levels of inflammatory factors TNF-alpha and IL-6 in the sciatic nerve were detected, and MCP1 and CCR2 protein expressions were measured by Western blotting. Compared with the model group, the hydrogen treatment group had significantly increased motor nerve conduction velocity, thermal withdrawal latency and mechanical withdrawal threshold (P<0.05). The significantly higher levels of TNF-alpha and IL-6 in the sciatic nerve of the model group than those of the control group decreased in the hydrogen treatment group (P<0.05). The protein expressions of MCP1 and CCR2 in the sciatic nerve of the model group significantly exceeded those of the control group. Such expressions of the hydrogen treatment group were lower than those of the model group. Hydrogen alleviated the inflammatory response of peripheral nerves in diabetic rats by inhibiting the MCP1-CCR2 signaling pathway, thus mitigating neuropathic pain.

目的 术后谵妄脑缺血、缺氧损伤相关.文中探讨脑氧饱和度(rScO2)监测在预测骨科高龄患者术后谵妄的应用价值.方法 回顾性分析2020年4-12月在南京市江宁医院行骨科下肢手术的高龄患者154例,年龄70～85岁.患者均于术前行认知状态(MMSE量表)和抑郁状态(GDS量表)评估.手术均采用全身麻醉联合脑电双频指数(BIS)、无创脑氧饱和度(rScO2)监测,且术中均行动脉血气监测.以静息状态和吸氧状态下的脑氧和动脉平均压均值记为基线值rScO2和MAP,并计算rScO2曲线下面积(AUC-rScO2);以动脉血气值计算脑氧摄取(CMRO2),并记录患者发生并发症以及恶心、呕吐等术后不良反应情况.采用logistic多元回归法分析谵妄相关危险因素.结果 154例患者中发生谵妄25例,谵妄发生率16.23％.谵妄患者术中rScO2最高值与基线值比较下降幅度均>30％.与非谵妄组比较,谵妄组患者rScO2下降幅度差异有统计学意义(12.1％vs 6.1％,P<0.05),术前与手术结束即刻血气分析结果差值△Glu(5.12 mol/L vs 2.12 mol/L,P<0.05)、△CMRO2(7.98％vs 4.02％,P<0.05)显著升高,差异有统计学意义.logistic多元回归统计结果提示,术后谵妄的危险因素包括高龄(OR=0.711,95％CI=0.029～1.443)、rScO2变异度(OR=0.331,95％CI=0.051～1.941)、CMRO2变异度(OR=0.407,95％CI=0.049～1.713)、糖尿病(OR=0.491,95％CI=0.027～1.740).结论 rScO2术中监测可预测高龄骨科下肢手术患者术后谵妄的发生,提示调整术中脑灌注,对减少高龄骨科患者术后谵妄发生有指导意义.

Endotoxin-induced lung injury is one of the major causes of death induced by endotoxemia, however, few effective therapeutic options exist. Hydrogen inhalation has recently been shown to be an effective treatment for inflammatory lung injury, but the underlying mechanism is unknown. In the current study we aim to investigate how hydrogen attenuates endotoxin-induced lung injury and provide reference values for the clinical application of hydrogen. LPS was used to establish an endotoxin-induced lung injury mouse model. The survival rate and pulmonary pathologic changes were evaluated. THP-1 and HUVECC cells were cultured in vitro. The thioredoxin 1 (Trx1) inhibitor was used to evaluate the anti-inflammatory effects of hydrogen. Hydrogen significantly improved the survival rate of mice, reduced pulmonary edema and hemorrhage, infiltration of neutrophils, and IL-6 secretion. Inhalation of hydrogen decreased tissue factor (TF) expression and MMP-9 activity, while Trx1 expression was increased in the lungs and serum of endotoxemia mice. LPS-stimulated THP-1 and HUVEC-C cells in vitro and showed that hydrogen decreases TF expression and MMP-9 activity, which were abolished by the Trx1 inhibitor, PX12. Hydrogen attenuates endotoxin-induced lung injury by decreasing TF expression and MMP-9 activity via activating Trx1. Targeting Trx1 by hydrogen may be a potential treatment for endotoxin-induced lung injury.

肌松残余是指全麻术中使用肌松药物,术后出现肌松作用残留现象[1-2].目前以四个成串刺激(TOF)比值＜0.9为肌松残余的诊断标准.临床上常采用新斯的明拮抗肌松残余,然而新斯的明剂量使用不当可能会导致术后呼吸系统并发症增加[3].肝癌切除术患者由于术后肝实质减少,药物代谢减慢,术中常选择经霍夫曼消除的顺阿曲库铵维持肌松.本研究拟探讨新斯的明拮抗肝癌切除术患者麻醉恢复期残余肌松的适宜剂量.

麻醉科是外科手术患者在医院就诊时必须经历的一个重要科室,也是各外科进行手术的平台科室.麻醉科医务人员担负着患者“无影灯下的生命守护者”职责,做一名优秀的麻醉医生不仅需要过硬的业务素质,更需要充分考虑所有能影响患者围术期愈后的复杂因素,包括生理上的和心理上的综合诊治.因此,麻醉医生应积极拓展传统的工作范畴,将视线扩展到术前、术中和术后整个围术期的参与和管理,才能真正意义上满足广大人民群众的身心健康要求,使自身成长为不仅是合格,更是优秀的麻醉科医务人员.