1.NAT10 inhibition alleviates astrocyte autophagy by impeding ac4C acetylation of Timp1 mRNA in ischemic stroke.
Li YANG ; Xiaotong LI ; Yaxuan ZHAO ; Hao CHEN ; Can WANG ; Angrong WU ; Xintong GUO ; Yue HUANG ; Qihui WANG ; Lingyun HAO ; Xiaowen LI ; Ying JI ; Jin BAN ; Guangtian WANG ; Junli CAO ; Zhiqiang PAN
Acta Pharmaceutica Sinica B 2025;15(5):2575-2592
Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.
2.Effect of degree of neuromuscular block on intraoperative surgical conditions and postoperative recovery quality in patients undergoing lumbar interbody fusion
Jie GUO ; Xiaoyi CHEN ; Junda CHEN ; Xinghe WANG ; Dong HUANG ; Dongmei YUE ; Linlin ZHAO ; Junli CAO ; Su LIU
Chinese Journal of Anesthesiology 2025;45(4):444-448
Objective:To evaluate the effect of the degree of neuromuscular blockade on the intraoperative surgical conditions and postoperative recovery quality in patients undergoing lumbar interbody fusion.Methods:In this randomized controlled trial, 100 patients of either sex, aged 18-79 yr, with a body mass index of 18.5-35.0 kg/m 2, of American Society of Anesthesiologists Physical Status classification < Ⅳ, scheduled for elective lumbar interbody fusion at the Affiliated Hospital of Xuzhou Medical University from August to October 2024, were allocated into 2 groups ( n=50 each) using stratified randomization based on the number of lumbar segments: deep neuromuscular blockade group (group D) and moderate neuromuscular blockade group (group M). The intraoperative post-tetanic count was maintained at 1 or 2 in group D, and the intraoperative train-of-four was maintained at 1 or 2 in group M. The scores for surgical conditions, duration of operation, blood loss, length of incision, occurrence of severe hypoxemia after extubation, requirement for rescue analgesia in post-anesthesia care unit, 15-item Quality of Recovery scale score and length of stay were recorded. Results:Compared with group M, the scores for surgical conditions were significantly increased, the rate of rescue analgesia in post-anesthesia care unit was decreased, 15-item Quality of Recovery scale scores were increased at 3 days after surgery ( P<0.05), and no significant changes were found in the duration of operation, blood loss, length of incision, incidence of severe hypoxemia after extubation and length of hospital stay in group D ( P>0.05). Conclusions:Compared with moderate neuromuscular blockade, deep neuromuscular blockade can provide better surgical conditions and improve the quality of early postoperative recovery for patients undergoing lumbar interbody fusion.
3.Effects of transcutaneous auricular vagus nerve stimulation on quality of early postoperative recovery in pa-tients undergoing thoracoscopic lung resection
Zhengxiu SUN ; Yuanyuan WANG ; Yong'ao LIN ; Tianxi MA ; Pinghao LI ; Mingkai ZHOU ; Junli CAO ; He LIU
The Journal of Practical Medicine 2025;41(17):2670-2675
Objective To investigate the effect of transcutaneous auricular vagus nerve stimulation(taVNS)on quality of early postoperative recovery in patients undergoing thoracoscopic lung resection.Methods A total of 168 patients scheduled for elective thoracoscopic lung resection(wedge resection,segmentectomy,lobectomy)under general anesthesia were enrolled and randomly assigned to active-taVNS group(group T)or sham-taVNS group(group S)(n=84).Participants received four consecutive 30-minute sessions of active stimulation or sham stimulation at four time points:(1)the afternoon prior to the surgery,(2)the morning of the surgery,(3)following extubation,and(4)the first afternoon post-surgery.The Quality of Recovery-15(QoR-15)scores of the patients,the Numerical Rating Scale(NRS)scores at rest and during cough at 24,48,and 72 hours after surgery were recorded;and the usage of opioids within 48 hours after surgery was recorded;the duration of chest tube indwelling,incidence of severe pulmonary complications,postoperative hospital stay and adverse reactions to the stimulation(such as nausea and vomiting,fever,constipation,dizziness and itching)were observed.Results Compared with group S,group T exhibited significantly higher QoR-15 scores at 24,48,and 72 h postoperatively,lower NRS pain scores during resting and coughing,and reduced opioid consumption within 48 hours postoperatively(P<0.05).There were no significant differences between the two groups in the duration of chest tube indwelling,incidence of severe pulmonary complications,hospital stay,and the incidence of adverse reactions to the stimula-tion(P>0.05).Conclusion TaVNS can significantly improve quality of early postoperative recovery in patients undergoing thoracoscopic lung resection,and provide more effective postoperative analgesia without increasing the risk of postoperative complications.
4.Effect of degree of neuromuscular block on intraoperative surgical conditions and postoperative recovery quality in patients undergoing lumbar interbody fusion
Jie GUO ; Xiaoyi CHEN ; Junda CHEN ; Xinghe WANG ; Dong HUANG ; Dongmei YUE ; Linlin ZHAO ; Junli CAO ; Su LIU
Chinese Journal of Anesthesiology 2025;45(4):444-448
Objective:To evaluate the effect of the degree of neuromuscular blockade on the intraoperative surgical conditions and postoperative recovery quality in patients undergoing lumbar interbody fusion.Methods:In this randomized controlled trial, 100 patients of either sex, aged 18-79 yr, with a body mass index of 18.5-35.0 kg/m 2, of American Society of Anesthesiologists Physical Status classification < Ⅳ, scheduled for elective lumbar interbody fusion at the Affiliated Hospital of Xuzhou Medical University from August to October 2024, were allocated into 2 groups ( n=50 each) using stratified randomization based on the number of lumbar segments: deep neuromuscular blockade group (group D) and moderate neuromuscular blockade group (group M). The intraoperative post-tetanic count was maintained at 1 or 2 in group D, and the intraoperative train-of-four was maintained at 1 or 2 in group M. The scores for surgical conditions, duration of operation, blood loss, length of incision, occurrence of severe hypoxemia after extubation, requirement for rescue analgesia in post-anesthesia care unit, 15-item Quality of Recovery scale score and length of stay were recorded. Results:Compared with group M, the scores for surgical conditions were significantly increased, the rate of rescue analgesia in post-anesthesia care unit was decreased, 15-item Quality of Recovery scale scores were increased at 3 days after surgery ( P<0.05), and no significant changes were found in the duration of operation, blood loss, length of incision, incidence of severe hypoxemia after extubation and length of hospital stay in group D ( P>0.05). Conclusions:Compared with moderate neuromuscular blockade, deep neuromuscular blockade can provide better surgical conditions and improve the quality of early postoperative recovery for patients undergoing lumbar interbody fusion.
5.Effects of transcutaneous auricular vagus nerve stimulation on quality of early postoperative recovery in pa-tients undergoing thoracoscopic lung resection
Zhengxiu SUN ; Yuanyuan WANG ; Yong'ao LIN ; Tianxi MA ; Pinghao LI ; Mingkai ZHOU ; Junli CAO ; He LIU
The Journal of Practical Medicine 2025;41(17):2670-2675
Objective To investigate the effect of transcutaneous auricular vagus nerve stimulation(taVNS)on quality of early postoperative recovery in patients undergoing thoracoscopic lung resection.Methods A total of 168 patients scheduled for elective thoracoscopic lung resection(wedge resection,segmentectomy,lobectomy)under general anesthesia were enrolled and randomly assigned to active-taVNS group(group T)or sham-taVNS group(group S)(n=84).Participants received four consecutive 30-minute sessions of active stimulation or sham stimulation at four time points:(1)the afternoon prior to the surgery,(2)the morning of the surgery,(3)following extubation,and(4)the first afternoon post-surgery.The Quality of Recovery-15(QoR-15)scores of the patients,the Numerical Rating Scale(NRS)scores at rest and during cough at 24,48,and 72 hours after surgery were recorded;and the usage of opioids within 48 hours after surgery was recorded;the duration of chest tube indwelling,incidence of severe pulmonary complications,postoperative hospital stay and adverse reactions to the stimulation(such as nausea and vomiting,fever,constipation,dizziness and itching)were observed.Results Compared with group S,group T exhibited significantly higher QoR-15 scores at 24,48,and 72 h postoperatively,lower NRS pain scores during resting and coughing,and reduced opioid consumption within 48 hours postoperatively(P<0.05).There were no significant differences between the two groups in the duration of chest tube indwelling,incidence of severe pulmonary complications,hospital stay,and the incidence of adverse reactions to the stimula-tion(P>0.05).Conclusion TaVNS can significantly improve quality of early postoperative recovery in patients undergoing thoracoscopic lung resection,and provide more effective postoperative analgesia without increasing the risk of postoperative complications.
6.COX-2 in lung cancer: Mechanisms, development, and targeted therapies
Xueqi LIU ; Junli ZHANG ; Wenwu SUN ; Jianping CAO ; Zhuang MA
Chronic Diseases and Translational Medicine 2024;10(4):281-292
Lung cancer (LC) is the leading cause of cancer-related death worldwide, with non-small cell lung cancer (NSCLC) comprising 85% of all cases. COX-2, an enzyme induced significantly under stress conditions, catalyzes the conversion of free arachidonic acid into prostaglandins. It exhibits high expression in various tumors and is closely linked to LC progression. COX-2 functions as a pivotal driver in cancer pathogenesis by promoting prostaglandin E2 synthesis and facilitating tumor cell occurrence and development. Furthermore, COX-2 holds potential as a predictive marker for early-stage NSCLC, guiding targeted therapy in patients with early COX-2 overexpression. Additionally, combining COX-2 inhibitors with diverse treatment modalities enhances tumor therapeutic efficacy, minimizes adverse effects on healthy tissues, and improves overall patient survival rates posttreatment. In conclusion, combined therapy targeting COX-2 presents a promising novel strategy for NSCLC treatment, offering avenues for improving prognosis and effective tumor treatment. This review provides novel insights and ideas for developing new treatment strategies to improve the prognosis of NSCLC.
7.COX-2 in lung cancer: Mechanisms, development, and targeted therapies
Xueqi LIU ; Junli ZHANG ; Wenwu SUN ; Jianping CAO ; Zhuang MA
Chronic Diseases and Translational Medicine 2024;10(4):281-292
Lung cancer (LC) is the leading cause of cancer-related death worldwide, with non-small cell lung cancer (NSCLC) comprising 85% of all cases. COX-2, an enzyme induced significantly under stress conditions, catalyzes the conversion of free arachidonic acid into prostaglandins. It exhibits high expression in various tumors and is closely linked to LC progression. COX-2 functions as a pivotal driver in cancer pathogenesis by promoting prostaglandin E2 synthesis and facilitating tumor cell occurrence and development. Furthermore, COX-2 holds potential as a predictive marker for early-stage NSCLC, guiding targeted therapy in patients with early COX-2 overexpression. Additionally, combining COX-2 inhibitors with diverse treatment modalities enhances tumor therapeutic efficacy, minimizes adverse effects on healthy tissues, and improves overall patient survival rates posttreatment. In conclusion, combined therapy targeting COX-2 presents a promising novel strategy for NSCLC treatment, offering avenues for improving prognosis and effective tumor treatment. This review provides novel insights and ideas for developing new treatment strategies to improve the prognosis of NSCLC.
8.Effect of individualized blood pressure management on postoperative delirium in elderly hypertensive patients undergoing radical resection for gastrointestinal tumor
Wensi LU ; Kedi GUO ; Shuting WANG ; Yuping YANG ; Junli CAO ; Su LIU
Chinese Journal of Anesthesiology 2023;43(5):551-554
Objective:To evaluate the effect of individualized blood pressure management on postoperative delirium in elderly hypertensive patients undergoing radical resection for gastrointestinal tumor.Methods:One hundred and sixty elderly hypertensive patients of both sexes, aged 60-80 yr, with body mass index of 19-28 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, scheduled for elective radical resection for gastrointestinal tumor under general anesthesia, were divided into 2 groups ( n=80 each) using a random number table method: standardized blood pressure management group (group S) and individualized blood pressure management group (group I). Combined intravenous-inhalational anesthesia was performed, and BIS values were maintained at 40-60 and heart rate at 50-100 times/min during surgery in both groups. In group S, intraoperative systolic blood pressure was maintained above 90 mmHg with a decrease of less than 30% of the baseline value, while intraoperative fluctuation of systolic blood pressure was maintained less than 10% of the baseline value in group I. The use of vasoactive agents, numerical rating scale scores within 3 days after operation, and length of hospital stay were recorded. Postoperative delirium was evaluated by Confusion Assessment Method within 5 days after surgery. Results:Compared with group S, the intraoperative usage rate of norepinephrine was significantly increased, the incidence of postoperative delirium was reduced( P<0.05), and no significant change was found in the numerical rating scale scores and length of hospital stay in group I ( P>0.05). Conclusions:Individualized blood pressure management can reduce the development of postoperative delirium in elderly hypertensive patients undergoing radical resection for gastrointestinal tumor.
9.Surgical treatment of duodenal fistula with intra-abdominal infection
Pengfei MA ; Sen LI ; Yanghui CAO ; Junli ZHANG ; Chenyu LIU ; Xijie ZHANG ; Zhenyu LI ; Changzheng LI ; Guangsen HAN ; Yuzhou ZHAO
Chinese Journal of General Surgery 2023;38(2):101-104
Object:To explore surgical treatments for duodenal fistula with intra-abdominal infection.Methods:The data of 19 patients with duodenal fistula treated at the Affiliated Tumor Hospital of Zhenzhou University between Jan 2015 and Dec 2021 were analyzed retrospectively. Surgery is performed with duodenostomy or modified duodenal shunt procedures.Result:All patients were accompanied by intra-abdominal infection, including 9 duodenal stump fistulas. All patients successfully completed the operation,11cases underwent duodenostomy, 8 case underwent modified duodenal shunt procedures. operating time was 110(60-140)min, postoperative hospitalization time was 29(9-103)d. Two patients died postoperatively. Fistula heals in other patients.Conclusion:Surgical intervention for duodenal fistula should focus on controlling the source of infection, strengthening intestinal and abdominal drainage, and reducing postoperative complications.
10.Application of OrVil TM in patients with recurrent or denovo esophagogastric junction cancer
Junli ZHANG ; Chenyu LIU ; Sen LI ; Yanghui CAO ; Pengfei MA ; Xijie ZHANG ; Zhenyu LI ; Changzheng LI ; Yuzhou ZHAO
Chinese Journal of General Surgery 2023;38(4):258-262
Objective:To investigate the effect of transorally inserted anvil (OrVil TM) in patients with relapsed or denovo carcinoma at the esophagogastric junction. Methods:The clinical data of 60 patients who underwent radical intent resection for locally relapsed or denovo esophagogastric junction adenocarcinoma at Zhengzhou University Cancer Hospital from Jan 2011 to Jun 2021 were retrospectively analyzed. The patients were divided into two groups according to whether transorally inserted anvil was used. Twenty-six patients who had used the system were assigned to the experimental group. Thirty-four patients without transorally inserted anvil were set to control group.Results:The incisor distance of the experimental group was shorter than that of the control group [36(34-40)cm vs. 39(36-41)cm, Z=-4.948, P<0.05]. Operation time in experimental group was 177 (145-260) min, compared to control group of 172 (140-225) min ( Z=-0.735, P=0.463). Intraoperative blood loss was 200 (100-900) ml in the experimental group and 300 (100-800) ml in the control group ( Z=-1.244, P=0.213). Postoperative upper margin distance of the experimental group was (3.6±1.7) cm compared to control group of (1.8±1.1) cm ( t=-0.735, P<0.01). The positive rate of margin in the experimental group was 4% vs. 15% in the control group ( χ2=1.931, P=0.165). The length of postoperative hospital stay in the experimental group was (18.6±5.2) d vs. (20.5±4.7) d ( t=-1.455, P=0.151). Surgery-related complications developed in 19% in the experimental group vs. 27% in the control group ( P>0.05). Conclusion:The application of the transorally inserted anvil in the operation of patients with locally relapsed or denovo esophagogastric junction cancer after initial operation reduces the difficulty of operation and decreases the positive rate of margin.

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