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 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 re-mains 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 mitochon-drial 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.

Objective:To evaluate the analgesic effect of intercostal muscle plane block of external oblique muscle in patients undergoing endoscopic pancreaticoduodenectomy.Methods:A total of 48 patients undergoing endoscopic pancreaticoduodenectomy under elective general anesthesia in Nanjing First Hospital from February to July 2023 were prospectively selected and divided into two groups ( n=24) according to random number table method: abdominal external oblique intercostal muscle plane block combined with general anesthesia group (EG group) and general anesthesia group (G group). The EG group was blocked in the intercostal muscle plane of the external oblique muscle before general anesthesia induction, and 0.375% ropivacaine 20 ml was injected on both sides, respectively. Patient-controlled intravenous analgesia (PCIA) was performed in both groups after operation, and the pain Visual Analogue Scale (VAS) score was less than 4 points. When the VAS score was ≥4, 1 mg oxycodone was injected intravenously for relief and analgesia. VAS scores at 30 min (T 0), 6 h (T 1), 12 h(T 2), 24 h(T 3), 48 h(T 4) after extubation, intraoperative drug and fluid dosage, postoperative sleep quality, analgesic satisfaction score, remedial analgesia and the occurrence of adverse reactions were recorded. Results:The scores of rest and exercise VAS at T 0, T 1, T 2, T 3 and T 4 in the EG group were significantly lower than those in the G group (all P<0.05). The dosage of norepinephrine, propofol, remifentanil and total fluid infusion in the EG group were significantly lower than those in the G group (all P<0.05). The sleep quality and analgesic satisfaction of the EG group were better than those of the G group (all P<0.05), the first time of PCIA compression after surgery was longer than that of the G group ( P<0.05), the number of effective compressions, the amount of oxycodone relief and analgesia, the proportion of nausea and vomiting, and the stay time of anesthesia intensive care unit (AICU) were lower than those of the G group (all P<0.05). There was no significant difference in total hospital stay between the two groups ( P>0.05). Conclusions:Compared with general anesthesia alone, abdominal external oblique intercostal muscle plane block combined with general anesthesia in patients with endoscopic pancreaticoduodenectomy has significant postoperative analgesia effect, which can not only reduce postoperative VAS score and opioid consumption, but also improve sleep quality and increase postoperative analgesia satisfaction. Ultrasound-guided intercostal muscle plane block of external oblique muscle can be used as a better analgesic method in endoscopic pancreaticoduodenectomy.

Objective:To evaluate the analgesic effect of intercostal muscle plane block of external oblique muscle in patients undergoing endoscopic pancreaticoduodenectomy.Methods:A total of 48 patients undergoing endoscopic pancreaticoduodenectomy under elective general anesthesia in Nanjing First Hospital from February to July 2023 were prospectively selected and divided into two groups ( n=24) according to random number table method: abdominal external oblique intercostal muscle plane block combined with general anesthesia group (EG group) and general anesthesia group (G group). The EG group was blocked in the intercostal muscle plane of the external oblique muscle before general anesthesia induction, and 0.375% ropivacaine 20 ml was injected on both sides, respectively. Patient-controlled intravenous analgesia (PCIA) was performed in both groups after operation, and the pain Visual Analogue Scale (VAS) score was less than 4 points. When the VAS score was ≥4, 1 mg oxycodone was injected intravenously for relief and analgesia. VAS scores at 30 min (T 0), 6 h (T 1), 12 h(T 2), 24 h(T 3), 48 h(T 4) after extubation, intraoperative drug and fluid dosage, postoperative sleep quality, analgesic satisfaction score, remedial analgesia and the occurrence of adverse reactions were recorded. Results:The scores of rest and exercise VAS at T 0, T 1, T 2, T 3 and T 4 in the EG group were significantly lower than those in the G group (all P<0.05). The dosage of norepinephrine, propofol, remifentanil and total fluid infusion in the EG group were significantly lower than those in the G group (all P<0.05). The sleep quality and analgesic satisfaction of the EG group were better than those of the G group (all P<0.05), the first time of PCIA compression after surgery was longer than that of the G group ( P<0.05), the number of effective compressions, the amount of oxycodone relief and analgesia, the proportion of nausea and vomiting, and the stay time of anesthesia intensive care unit (AICU) were lower than those of the G group (all P<0.05). There was no significant difference in total hospital stay between the two groups ( P>0.05). Conclusions:Compared with general anesthesia alone, abdominal external oblique intercostal muscle plane block combined with general anesthesia in patients with endoscopic pancreaticoduodenectomy has significant postoperative analgesia effect, which can not only reduce postoperative VAS score and opioid consumption, but also improve sleep quality and increase postoperative analgesia satisfaction. Ultrasound-guided intercostal muscle plane block of external oblique muscle can be used as a better analgesic method in endoscopic pancreaticoduodenectomy.

OBJECTIVE: To investigate the effects of gene of phosphate and tension homology (PTEN)-induced putative kinase 1 (PINK1)/Parkin pathway on hippocampal mitophagy and cognitive function in mice with sepsis-associated encephalopathy (SAE) and its possible mechanism. METHODS: A total of 80 male C57BL/6J mice were randomly divided into Sham group, cecal ligation puncture (CLP) group, PINK1 plasmid transfection pretreatment groups (p-PINK1+Sham group, p-PINK1+CLP group), empty vector plasmid transfection control group (p-vector+CLP group), with 16 mice in each group. The mice in CLP groups were treated with CLP to reproduce SAE models. The mice in the Sham groups were performed laparotomy only. Animals in the p-PINK1+Sham and p-PINK1+CLP groups were transfected with PINK1 plasmid through the lateral ventricle at 24 hours before surgery, while mice in the p-vector+CLP group were transfected with the empty plasmid. Morris water maze experiment was performed 7 days after CLP. The hippocampal tissues were collected, the pathological changes were observed under a light microscope after hematoxylin-eosin (HE) staining, and the mitochondrial autophagy was observed under a transmission electron microscopy after uranyl acetate and lead citrate staining. The expressions of PINK1, Parkin, Beclin1, interleukins (IL-6, IL-1β) and microtubule-associated protein 1 light chain 3 (LC3) were detected by Western blotting. RESULTS: Compared with the Sham group, CLP group mice in Morris water maze experiment had longer escape latency, shorter target quadrant residence time, and fewer times of crossing the platform at 1-4 days. Under the light microscope, the hippocampal structure of the mouse was injured, the neuronal cells were arranged in disorder, and the nuclei were pyknotic. Under the electron microscope, the mitochondria appeared swollen, round, and wrapped by bilayer or multilayer membrane structures. Compared with the Sham group, CLP group had higher expressions of PINK1, Parkin, Beclin1, LC3II/LC3I ratio, IL-6 and IL-1β in hippocampus, indicating that sepsis induced by CLP could activated inflammatory response and caused PINK1/Parkin-mediated mitophagy. Compared with the CLP group, p-PINK1+CLP group had shorter escape latencies, spent more time in the target quadrant and had more number of crossings in the target quadrant at 1-4 days. Under the light microscope, the hippocampal structures of mice was destroyed, the neurons were arranged disorderly, and the nuclei were pyknotic. Under transmission electron microscope, swollen and rounded mitochondria and mitochondrial structure wrapped by double membrane or multilayer membrane structure were observed. Compared with the CLP group, the levels of PINK1, Parkin, Beclin1 and LC3II/LC3 ratio in the p-PINK1+CLP group were significantly increased [PINK1 protein (PINK1/β-actin): 1.95±0.17 vs. 1.74±0.15, Parkin protein (Parkin/β-actin): 2.06±0.11 vs. 1.78±0.12, Beclin1 protein (Beclin1/β-actin): 2.11±0.12 vs. 1.67±0.10, LC3II/LC3I ratio: 3.63±0.12 vs. 2.27±0.10, all P < 0.05], while the levels of IL-6 and IL-1β were significantly decreased [IL-6 protein (IL-6/β-actin): 1.69±0.09 vs. 2.00±0.11, IL-1β protein (IL-1β/β-actin): 1.11±0.12 vs. 1.65±0.12, both P < 0.05], suggesting that overexpression of PINK1 protein could further activate mitophagy and reduce the inflammatory response caused by sepsis. There was no statistically significant difference in the above pathological changes and related indicators between Sham group and p-PINK1+Sham group, CLP group and p-vector+CLP group. CONCLUSIONS PINK1 overexpression can further activate CLP-induced mitophagy by upregulating Parkin, thereby inhibiting inflammation response and alleviate cognitive function impairment in SAE mice.
Male ; Animals ; Mice ; Mice, Inbred C57BL ; Sepsis-Associated Encephalopathy ; Phosphates ; Actins ; Beclin-1 ; Interleukin-6 ; Autophagy ; Ubiquitin-Protein Ligases ; Cognitive Dysfunction ; Sepsis ; Mitochondria ; Protein Kinases

Objective:To evaluate the efficacy of subomohyoid anterior suprascapular nerve block (SSNB) in the patients undergoing arthroscopic shoulder surgery with general anesthesia.Methods:Sixty patients of either sex, aged 18-64 yr, with body mass index of 18-30 kg/m 2, of American Society of Anesthesiologists physical status Ⅰor Ⅱ, scheduled for elective arthroscopic shoulder surgery, were divided into 2 groups ( n=30 each) using a random number table method: SSNB group (S group) and interscalene brachial plexus block group (I group). Before induction, 0.375% ropivacaine hydrochloride 15 ml was injected between C 5-C 6 nerve roots in group I and around the anterior suprascapular nerve in group S under ultrasound guidance.Diaphragmatic excursion, occurrence and degree of diaphragmatic paralysis, decrease in SpO 2, dyspnea, Horner syndrome and sensory block in the C 5-T 1 dermatomes were assessed at 30 min after injection.The intraoperative consumption of remifentanil, extubation time, and length of post-anesthesia care unit stay were recorded.Quality of Recovery-15 score for patient′s satisfaction with analgesia, effective pressing frequency of analgesic pump, requirement for rescue analgesia, nausea and vomiting and nerve block-related complications within 24 h after surgery were recorded. Results:Compared with group I, the incidence of diaphragmatic paralysis was significantly decreased, the degree of diaphragmatic paralysis was reduced, diaphragmatic excursion was increased, the amplitude of decrease in SpO 2 was reduced, the incidence of dyspnea and Horner syndrome was decreased, extubation time was shortened ( P<0.05), and no significant change was found in the incidence of sensory block in the C 5-T 1 dermatomes, intraoperative consumption of remifentanil, effective pressing frequency of analgesic pump, requirement for rescue analgesia, score for patient′s satisfaction with analgesia, incidence of nausea and vomiting, length of post-anesthesia care unit stay, or Quality of Recovery-15 score in group S ( P>0.05). Conclusions:The subomohyoid anterior SSNB not only provides reliable perioperative analgesia, but also reduces the risk of diaphragmatic paralysis when used in the patients undergoing arthroscopic shoulder surgery with general anesthesia.

Objective:To evaluate the role of ten-eleven translocation methylcytosine dioxygenase 3 (TET3) in trigeminal ganglion in maxillofacial inflammatory pain in mice.Methods:Forty SPF healthy male C57BL/6J mice, aged 8-10 weeks, weighing 19-23 g, were divided into 5 groups ( n=8 each) using a random number table method: control group (group C), inflammatory pain group (group IP), control+ TET3-siRNA group (group C+ siTET3), inflammatory pain+ TET3-siRNA group (group IP+ siTET3) and inflammatory pain+ negative control Scrambled-siRNA group (group IP+ siNC). Normal saline or complete Freund′s adjuvant (CFA) 10 μl was injected into the temporomandibular joint of mice, respectively, and the mechanical paw withdrawal threshold (MWT) was measured at 1, 4, 8 and 12 days after injection (T 1-4). Before injection of normal saline or CFA, 0.75 μl siTET3 or siNC was injected into the trigeminal ganglion and the animals were then sacrificed and trigeminal ganglion was removed at T 2 for determination of the expression of TET3 by Western blot in C+ siTET3, IP+ siTET3 and IP+ siNC groups. Results:Compared with group C, MWT was significantly decreased at T 1-3 , the expression of TET3 in trigeminal ganglion was up-regulate in group IP ( P<0.05 or 0.01). Compared with IP and IP+ siNC groups, MWT was significantly increased at T 2, 3, and the expression of TET3 in trigeminal ganglion was down-regulate in group IP+ siTET3 ( P<0.05 or 0.01). Conclusion:TET3 in trigeminal ganglion is involved in the development of maxillofacial inflammatory pain in mice.

Objective: To analyze the clinical characteristics of cases of novel coronavirus pneumonia and a preliminary study to explore the relationship between different clinical classification and liver damage. Methods: Consecutively confirmed novel coronavirus infection cases admitted to seven designated hospitals during January 23, 2020 to February 8, 2020 were included. Clinical classification (mild, moderate, severe, and critical) was carried out according to the diagnosis and treatment program of novel coronavirus pneumonia (Trial Fifth Edition) issued by the National Health Commission. The research data were analyzed using SPSS19.0 statistical software. Quantitative data were expressed as median (interquartile range), and qualitative data were expressed as frequency and rate. Results: 32 confirmed cases that met the inclusion criteria were included. 28 cases were of mild or moderate type (87.50%), and four cases (12.50%) of severe or critical type. Four cases (12.5%) were combined with one underlying disease (bronchial asthma, coronary heart disease, malignant tumor, chronic kidney disease), and one case (3.13%) was simultaneously combined with high blood pressure and malignant tumor. The results of laboratory examination showed that the alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), and total bilirubin (TBil) for entire cohort were 26.98 (16.88 ~ 46.09) U/L and 24.75 (18.71 ~ 31.79) U/L, 39.00 (36.20 ~ 44.20) g/L and 16.40 (11.34- ~ 21.15) mmol/L, respectively. ALT, AST, ALB and TBil of the mild or moderate subgroups were 22.75 (16.31- ~ 37.25) U/L, 23.63 (18.71 ~ 26.50) U/L, 39.70 (36.50 ~ 46.10) g/L, and 15.95 (11.34 ~ 20.83) mmol/L, respectively. ALT, AST, ALB and TBil of the severe or critical subgroups were 60.25 (40.88 ~ 68.90) U/L, 37.00 (20.88 ~ 64.45) U/L, 35.75 (28.68 ~ 42.00) g/L, and 20.50 (11.28 ~ 25.00) mmol/L, respectively. Conclusion The results of this multicenter retrospective study suggests that novel coronavirus pneumonia combined with liver damage is more likely to be caused by adverse drug reactions and systemic inflammation in severe patients receiving medical treatment. Therefore, liver function monitoring and evaluation should be strengthened during the treatment of such patients.

Objective:To evaluate the role of hypoxia-inducible factor-1α (HIF-1α) in hydrogen-induced inhibition of lipopolysaccharide (LPS)-induced inflammatory responses in mouse macrophages.Methods:The mouse RAW264.7 macrophages cultured in vitro were divided into 4 groups ( n=24 each) according to the random number table method: control group (C group), LPS group (L group), hydrogen-rich solution plus LPS group (H+ L group), and hydrogen-rich solution plus LPS plus HIF-1α inhibitor 2-methoxyestradiol (2ME2) group (H+ L+ M group). LPS 1 μg/ml was added, and the cells were incubated for 6 h in group L. In group L+ H, LPS was added first, the medium was changed to 0.6 mmol/L hydrogen-rich solution, and cells were incubated for 6 h. In group H+ L+ M, 2ME2 10 μmol/L was given first, cells were then incubated for 30 min, LPS and hydrogen-rich solution were added, and cells were incubated for 6 h. Western blot was used to determine the expression of HIF-1α, Beclin-1, Bcl-2/E1B-19 kDa interacting protein 3 (BNIP3) and LC3.Enzyme-linked immunosorbent assay was used to detect the concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in the supernatant.The number of autophagosomes was observed using a transmission electron microscope. Results:Compared with group C, the concentrations of TNF-α, IL-6 and IL-1β in the supernatant were significantly increased, the expression of HIF-1α, Beclinl and BNIP3 in macrophages was up-regulated, the ratio of LC3Ⅱ/LC3Ⅰ was increased, and the number of autophagosomes was increased in group L ( P<0.05). Compared with group L, the concentrations of TNF-α, IL-6 and IL-1β were significantly decreased, the expression of HIF-1α, Beclin-1 and BNIP3 in macrophages was up-regulated, LC3Ⅱ/LC3Ⅰ ratio was increased, and the number of autophagosomes was increased in group H+ L ( P<0.05). Compared with group H+ L, the concentrations of TNF-α, IL-6 and IL-1β in the supernatant were significantly decreased, the expression of HIF-1α, Beclin-1, and BNIP3 in macrophages was down-regulated, and the ratio of LC3Ⅱ/LC3Ⅰ was decreased, and the number of autophagosomes was decreased in group H+ L+ M ( P<0.05). Conclusion:HIF-1α-mediated activation of autophagy is involved in the process of hydrogen-induced inhibition of LPS-induced inflammatory responses in mouse macrophages.