1.Effects and Mechanism of Chaperone-Mediated Autophagy on Severe Acute Pancreatitis-Associated Liver Injury
Zhongbiao LI ; Min DU ; Jiang WANG
Journal of Medical Research 2025;54(4):39-44
Objective Acute liver injury(ALI)exacerbates the condition of patients with severe acute pancreatitis(SAP)and neg-atively affects their prognosis.Recent studies have highlighted the crucial role of chaperone-mediated autophagy(CMA)in regulating liver injury.This study aims to explore the effects of CMA on the pathophysiologic mechanisms of SAP-induced acute liver injury(SAP-ALI).Methods A SAP rat model was established via retrograde injection of 5%sodium taurocholate into the biliary-pancreat-ic duct.Rats were randomly divided into the sham operation(Sham)group,SAP group,CMA activator(AR7)control group,and AR7+SAP treatment group.After 24hours,serum amylase(AMY),liver function,and oxidative stress-specific markers were meas-ured.HE staining was used to evaluate the pathological injury in the pancreatic and liver tissues.The expression levels of lysosomal-as-sociated membrane protein 2 A(LAMP2A),GAPDH,keleh-like ECH-associated protein 1(Keap1),and nuclear factor E2-related factor 2(Nrf2)proteins and LAMP2A,Nrf2mRNA were analyzed by Western blot,immunofluorescence staining,and qRT-PCR.Results AR7 pretreatment significantly improved liver function(P<0.05),alleviated the pathological damage to the pancreas and liver and enhanced the antioxidant stress capacity(P<0.05)of SAP-ALI rats.The downregulation of LAMP2A(P<0.05)and accumula-tion of the CMA substrate GAPDH(P<0.05)indicated CMA dysfunction in SAP-ALI.Furthermore,AR7-induced upregulation of CMA promoted the activation of the Keap1/Nrf2 pathway in liver(P<0.05),contributing to its antioxidative effect.Conclusion Our study demonstrates that CMA dysfunction is involved in the pathological process of SAP-induced acute liver injury.AR7-induced CMA reactivation regulates the Keap1/Nrf2 antioxidant pathway,providing protection against SAP-induced acute liver injury in rats.
2.Effects and Mechanism of Chaperone-Mediated Autophagy on Severe Acute Pancreatitis-Associated Liver Injury
Zhongbiao LI ; Min DU ; Jiang WANG
Journal of Medical Research 2025;54(4):39-44
Objective Acute liver injury(ALI)exacerbates the condition of patients with severe acute pancreatitis(SAP)and neg-atively affects their prognosis.Recent studies have highlighted the crucial role of chaperone-mediated autophagy(CMA)in regulating liver injury.This study aims to explore the effects of CMA on the pathophysiologic mechanisms of SAP-induced acute liver injury(SAP-ALI).Methods A SAP rat model was established via retrograde injection of 5%sodium taurocholate into the biliary-pancreat-ic duct.Rats were randomly divided into the sham operation(Sham)group,SAP group,CMA activator(AR7)control group,and AR7+SAP treatment group.After 24hours,serum amylase(AMY),liver function,and oxidative stress-specific markers were meas-ured.HE staining was used to evaluate the pathological injury in the pancreatic and liver tissues.The expression levels of lysosomal-as-sociated membrane protein 2 A(LAMP2A),GAPDH,keleh-like ECH-associated protein 1(Keap1),and nuclear factor E2-related factor 2(Nrf2)proteins and LAMP2A,Nrf2mRNA were analyzed by Western blot,immunofluorescence staining,and qRT-PCR.Results AR7 pretreatment significantly improved liver function(P<0.05),alleviated the pathological damage to the pancreas and liver and enhanced the antioxidant stress capacity(P<0.05)of SAP-ALI rats.The downregulation of LAMP2A(P<0.05)and accumula-tion of the CMA substrate GAPDH(P<0.05)indicated CMA dysfunction in SAP-ALI.Furthermore,AR7-induced upregulation of CMA promoted the activation of the Keap1/Nrf2 pathway in liver(P<0.05),contributing to its antioxidative effect.Conclusion Our study demonstrates that CMA dysfunction is involved in the pathological process of SAP-induced acute liver injury.AR7-induced CMA reactivation regulates the Keap1/Nrf2 antioxidant pathway,providing protection against SAP-induced acute liver injury in rats.
3.Exploration of the clinical application of combined endoscopic and laparoscopic surgery in early gastric cancer: 15 cases
Zhongbiao CHEN ; Dazhou LI ; Zaizhong ZHANG ; Pan ZHAO ; Long YI ; Ruifeng YE ; Qin GAO ; Wen WANG ; Lie WANG
Chinese Journal of Gastrointestinal Surgery 2023;26(8):757-762
Objective:To investigate the application of combined gastroscopy and laparoscopy (dual scope) in the treatment of early gastric cancer.Methods:In this descriptive case series study, we retrospectively collected data on 15 patients with cT1b stage gastric cancer who had undergone combined laparoscopic and endoscopic surgery in the 900th Hospital of the People's Liberation Army of China from May 2020 to October 2022. The study cohort comprised nine men and six women of median age 59 (range: 47–76) years and median body mass index 20.9 (range: 18.3–26.2) kg/m 2. Seven of the lesions were located on the lesser curvature of the gastric antrum and eight in the gastric angle. All lesions were biopsied for pathological examination and evaluated by endoscopic ultrasonography, followed by endoscopic submucosal dissection (ESD) and laparoscopic regional lymph node dissection. Studied variables included surgical and pathological features, postoperative factors, and outcomes. Results:In this group of patients, the median (range) operative time for ESD was 45 (30–82) minutes, the duration of laparoscopic lymph node dissection (45.1±8.6) minutes, and the median (range) intraoperative blood loss during lymph node dissection 30 (10–80) mL. Of the 13 patients with negative postoperative horizontal margins, four were stage SM1 and had no lymph node metastases (Stage SM1) and nine were Stage SM2, of which had one positive regional lymph node and two received additional standard distal gastrectomy with D2 lymphadenectomy concurrently because of positive ESD specimens (lymph node negative). No lymph node metastases were found in the surgical specimens of these patients. The remaining two patients had positive vertical margins; both had undergone concurrent standard distal gastrectomy with D2 lymphadenectomy. One of them was found to be lymph node positive (No. 3, one node). Four patients had impaired gastric emptying after dual-scope treatment, all of whom recovered well with symptomatic management; one patient with a suspected lymphatic leak was also managed conservatively. There were no cases of postoperative bleeding, abdominal infection, or incisional infection. At a median follow-up of 14 (6–26) months, no tumor recurrence or metastasis had been identified in any of the patients. Three patients had a grade B nutrition score 3 to 6 months after surgery, all of whom had undergone major gastrectomy, and two patients who had undergone dual-scope surgery reported an increase in acid reflux and belching after surgery compared with the preoperative period.Conclusion:A combined technique is safe and feasible for the treatment of early gastric cancer and is worthy of further exploration.
4.Exploration of the clinical application of combined endoscopic and laparoscopic surgery in early gastric cancer: 15 cases
Zhongbiao CHEN ; Dazhou LI ; Zaizhong ZHANG ; Pan ZHAO ; Long YI ; Ruifeng YE ; Qin GAO ; Wen WANG ; Lie WANG
Chinese Journal of Gastrointestinal Surgery 2023;26(8):757-762
Objective:To investigate the application of combined gastroscopy and laparoscopy (dual scope) in the treatment of early gastric cancer.Methods:In this descriptive case series study, we retrospectively collected data on 15 patients with cT1b stage gastric cancer who had undergone combined laparoscopic and endoscopic surgery in the 900th Hospital of the People's Liberation Army of China from May 2020 to October 2022. The study cohort comprised nine men and six women of median age 59 (range: 47–76) years and median body mass index 20.9 (range: 18.3–26.2) kg/m 2. Seven of the lesions were located on the lesser curvature of the gastric antrum and eight in the gastric angle. All lesions were biopsied for pathological examination and evaluated by endoscopic ultrasonography, followed by endoscopic submucosal dissection (ESD) and laparoscopic regional lymph node dissection. Studied variables included surgical and pathological features, postoperative factors, and outcomes. Results:In this group of patients, the median (range) operative time for ESD was 45 (30–82) minutes, the duration of laparoscopic lymph node dissection (45.1±8.6) minutes, and the median (range) intraoperative blood loss during lymph node dissection 30 (10–80) mL. Of the 13 patients with negative postoperative horizontal margins, four were stage SM1 and had no lymph node metastases (Stage SM1) and nine were Stage SM2, of which had one positive regional lymph node and two received additional standard distal gastrectomy with D2 lymphadenectomy concurrently because of positive ESD specimens (lymph node negative). No lymph node metastases were found in the surgical specimens of these patients. The remaining two patients had positive vertical margins; both had undergone concurrent standard distal gastrectomy with D2 lymphadenectomy. One of them was found to be lymph node positive (No. 3, one node). Four patients had impaired gastric emptying after dual-scope treatment, all of whom recovered well with symptomatic management; one patient with a suspected lymphatic leak was also managed conservatively. There were no cases of postoperative bleeding, abdominal infection, or incisional infection. At a median follow-up of 14 (6–26) months, no tumor recurrence or metastasis had been identified in any of the patients. Three patients had a grade B nutrition score 3 to 6 months after surgery, all of whom had undergone major gastrectomy, and two patients who had undergone dual-scope surgery reported an increase in acid reflux and belching after surgery compared with the preoperative period.Conclusion:A combined technique is safe and feasible for the treatment of early gastric cancer and is worthy of further exploration.
5.Analysis the model for end-stage liver disease of hepatic encephalopathy in patients with cirrhosis
Changjiang LIU ; Li WANG ; Liyuan ZHANG ; Hailan RUAN ; Zhongbiao FU ; Huizhong XIE
Chinese Journal of Postgraduates of Medicine 2014;37(22):45-47
Objective To evaluate the relationship between the incidence rate of hepatic encephalopathy in patients with cirrhosis and the model for end-stage liver disease (MELD).Methods The total of 120 patients with decompensated cirrhosis were enrolled and followed-up.MELD score was obtained to observe the incidence of hepatic encephalopathy.Results The incidence of hepatic encephalopathy was 44.17%(53/120).MELD score in hepatic encephalopathy patients was significantly higher than that in none hepatic encephalopathy patients[(21.69 ± 9.22) scores vs.(9.32 ± 4.63) scores],and there was significant difference (P < 0.05).With the increase of MELD score,the incidence of hepatic encephalopathy increased (P < 0.01).The best critical value of MELD score was 14.13 scores (the sensitivity of 86.05% and the specificity of 88.37%),when MELD ≥14.13 scores,the incidence of hepatic encephalopathy within 3 months was significantly higher [63.16%(48/76) vs.11.36%(5/44)] (x2 =30.32,P< 0.01).Conclusion MELD can help predicting the incidence of hepatic encephalopathy in decompensated cirrhosis patients.

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