1.Phosphatidylethanolamine promotes macrophage senescence and liver injury by activating endoplasmic reticulum stress
Longchuan HAN ; Yue LI ; Zhihui ZOU ; Jing LUO ; Ruoyi LI ; Yingting ZHANG ; Xinxin TANG ; Lihong TIAN ; Yuheng LU ; Ying HUANG ; Ming HE ; Yinkun FU
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(6):693-704
Objective·To investigate the effects and molecular mechanisms of phosphatidylethanolamine(PE)on macrophage senescence and its senescence-associated secretory phenotype(SASP),as well as its pathophysiological role in liver injury.Methods·A macrophage senescence model was established using doxorubicin(DOX),followed by PE treatment.A mouse liver injury model was generated via intraperitoneal co-administration of PE and lipopolysaccharide(LPS)to investigate the effects of PE on liver injury.Senescence markers and SASP factors,including senescence-associated β-galactosidase(SA-β-gal),cell cycle inhibitor p21,tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6),were evaluated using SA-β-gal staining,quantitative real-time PCR,and Western blotting.RNA sequencing(RNA-seq)was performed,followed by Gene Ontology(GO)cellular component enrichment analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,Gene Set Variation Analysis(GSVA),and Gene Set Enrichment Analysis(GSEA),to explore the molecular mechanisms and signaling pathways by which PE promotes macrophage senescence.The expression of endoplasmic reticulum(ER)stress-related proteins,including inositol-requiring enzyme 1 α(IRE1α),spliced X-box binding protein 1(XBP1s),activating transcription factor 6(ATF6),ATF4,and C/EBP homologous protein(CHOP),was analyzed through in vivo and in vitro experiments.Results·PE significantly promoted the expression of senescence markers SA-β-gal,p21,p16 and SASP factors.RNA-seq analysis revealed that ER stress was involved in PE-induced promotion of SASP.Further experiments demonstrated that PE activated the ER stress signaling pathway,promoting macrophage senescence and the expression of SASP factors.In vivo experiments further confirmed that PE exacerbated LPS-induced liver injury in mice through ER stress.Conclusion·PE promotes macrophage senescence and the expression of SASP factors by activating ER stress signaling pathway,thereby aggravating LPS-induced liver injury.
2.Construction of a competency evaluation index system for clinical teachers in teaching hospitals
Yuan ZHANG ; Zhihui ZOU ; Manjie ZHANG ; Zhiquan LIN ; Chuhong YU
Chinese Journal of Medical Education Research 2025;24(2):192-198
Objective:To construct a scientific and reliable clinical teacher competency evaluation index system, and provide a reference for strengthening the construction of clinical teachers in teaching hospitals.Methods:Based on literature research and group discussion, the initial expert consultation questionnaire was constructed. Two rounds of expert consultation were conducted using the Delphi method to form the competency evaluation index system for clinical teachers in teaching hospitals. A hierarchy analysis was conducted using Python to calculate the weights of indicators.Results:The positive coefficients of the two rounds of expert consultation were 100.00% and 95.24%, respectively, and the expert authority coefficients were 0.843 and 0.862, respectively. The Kendall's coefficients of concordance for the first-, second-, and third-level indicators in the first round of expert consultation were 0.207, 0.152, and 0.191 ( P<0.001), respectively, and these coefficients in the second round of expert consultation were 0.271, 0.176, and 0.252 ( P<0.001), respectively. The final evaluation index system included 7 first-level indicators, 15 second-level indicators, and 43 third-level indicators. The first-level indicators included professional quality, professional knowledge and skills, medical education knowledge, teaching ability, communication and cooperation, teaching motivation, and career development, and their weights were 0.147, 0.149, 0.142, 0.147, 0.146, 0.134, and 0.136, respectively. Conclusions:The evaluation index system is comprehensive, scientific, and reliable. It can provide a reference for clinical teacher selection, evaluation, and training in teaching hospitals.
3.Phosphatidylethanolamine promotes macrophage senescence and liver injury by activating endoplasmic reticulum stress
Longchuan HAN ; Yue LI ; Zhihui ZOU ; Jing LUO ; Ruoyi LI ; Yingting ZHANG ; Xinxin TANG ; Lihong TIAN ; Yuheng LU ; Ying HUANG ; Ming HE ; Yinkun FU
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(6):693-704
Objective·To investigate the effects and molecular mechanisms of phosphatidylethanolamine(PE)on macrophage senescence and its senescence-associated secretory phenotype(SASP),as well as its pathophysiological role in liver injury.Methods·A macrophage senescence model was established using doxorubicin(DOX),followed by PE treatment.A mouse liver injury model was generated via intraperitoneal co-administration of PE and lipopolysaccharide(LPS)to investigate the effects of PE on liver injury.Senescence markers and SASP factors,including senescence-associated β-galactosidase(SA-β-gal),cell cycle inhibitor p21,tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6),were evaluated using SA-β-gal staining,quantitative real-time PCR,and Western blotting.RNA sequencing(RNA-seq)was performed,followed by Gene Ontology(GO)cellular component enrichment analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,Gene Set Variation Analysis(GSVA),and Gene Set Enrichment Analysis(GSEA),to explore the molecular mechanisms and signaling pathways by which PE promotes macrophage senescence.The expression of endoplasmic reticulum(ER)stress-related proteins,including inositol-requiring enzyme 1 α(IRE1α),spliced X-box binding protein 1(XBP1s),activating transcription factor 6(ATF6),ATF4,and C/EBP homologous protein(CHOP),was analyzed through in vivo and in vitro experiments.Results·PE significantly promoted the expression of senescence markers SA-β-gal,p21,p16 and SASP factors.RNA-seq analysis revealed that ER stress was involved in PE-induced promotion of SASP.Further experiments demonstrated that PE activated the ER stress signaling pathway,promoting macrophage senescence and the expression of SASP factors.In vivo experiments further confirmed that PE exacerbated LPS-induced liver injury in mice through ER stress.Conclusion·PE promotes macrophage senescence and the expression of SASP factors by activating ER stress signaling pathway,thereby aggravating LPS-induced liver injury.
4.Construction of a competency evaluation index system for clinical teachers in teaching hospitals
Yuan ZHANG ; Zhihui ZOU ; Manjie ZHANG ; Zhiquan LIN ; Chuhong YU
Chinese Journal of Medical Education Research 2025;24(2):192-198
Objective:To construct a scientific and reliable clinical teacher competency evaluation index system, and provide a reference for strengthening the construction of clinical teachers in teaching hospitals.Methods:Based on literature research and group discussion, the initial expert consultation questionnaire was constructed. Two rounds of expert consultation were conducted using the Delphi method to form the competency evaluation index system for clinical teachers in teaching hospitals. A hierarchy analysis was conducted using Python to calculate the weights of indicators.Results:The positive coefficients of the two rounds of expert consultation were 100.00% and 95.24%, respectively, and the expert authority coefficients were 0.843 and 0.862, respectively. The Kendall's coefficients of concordance for the first-, second-, and third-level indicators in the first round of expert consultation were 0.207, 0.152, and 0.191 ( P<0.001), respectively, and these coefficients in the second round of expert consultation were 0.271, 0.176, and 0.252 ( P<0.001), respectively. The final evaluation index system included 7 first-level indicators, 15 second-level indicators, and 43 third-level indicators. The first-level indicators included professional quality, professional knowledge and skills, medical education knowledge, teaching ability, communication and cooperation, teaching motivation, and career development, and their weights were 0.147, 0.149, 0.142, 0.147, 0.146, 0.134, and 0.136, respectively. Conclusions:The evaluation index system is comprehensive, scientific, and reliable. It can provide a reference for clinical teacher selection, evaluation, and training in teaching hospitals.
5.Effects of Hewei Anshe Formula (和胃安神方) on the CLOCK and BMAL1 Gene Expression of Hypothalamic Biological Clock in Insomnia Rat Models
Shuo WANG ; Changzhen WANG ; Zhihui LI ; Tianke HUANG ; Liang WANG ; Chujiao TIAN ; Tao ZOU ; Zihan LIU ; Qi CHEN ; Shaodan LI
Journal of Traditional Chinese Medicine 2024;65(20):2145-2151
ObjectiveTo investigate the possible mechanism of Hewei Anshen Formula (和胃安神方) in the treatment of insomnia. MethodsSixty male SD rats were randomly divided into the normal group, the model group, the eszopiclone group and the low-, medium- and high-dose Hewei Anshen Formula groups. The insomnia model was constructed by intraperitoneal injection of p-chlorophenylalanine (PCPA) for 2 days in all groups except the normal group. After successful modelling, the eszopiclone group was given 0.33 mg/(kg·d) eszopiclone aqueous solution by gavage, the low-, medium- and high-dose Hewei Anshen Formula groups were given 10 ml/kg of Hewei Anshen Formula with a concentration of 1, 2 and 4 g/ml, respectively, and the rats in the normal group and the model group were given 10 ml/kg of saline by gavage, once a day for 7 consecutive days. The general condition of the rats was observed during the experiment, and the body mass of the rats was measured every day after medication administration. The following day after the last medication administration, pentobarbital sodium co-test was used to observe the sleep condition, and the sleep latency and sleep duration were recorded; immunohistochemistry and Western blot were used to detect the expression of hypothalamic clock rhythm regulating protein (CLOCK) and brain and muscle aromatic hydrocarbon receptor nuclear transporter-like protein 1 (BMAL1) in the rats. ResultsThe body mass of rats in the model group was lower than that of rats in the normal group at all time points (P<0.01); compared with the same time in the eszopiclone group, the body mass of rats in the low-dose Hewei Anshen Formula group was elevated on the 5th, 6th and 7th days of medication administration (P<0.05). Compared with the normal group, the sleep duration of rats in the model group was shortened (P<0.01); compared with the model group, the sleep duration of rats in each dosage group increased (P<0.01), and the difference between the high-dose Hewei Anshen Formula group and the eszopiclone group showed no statistically significant (P>0.05), while the sleep duration of the low- and medium-dose Hewei Anshen Formula groups were shorterned than the eszopiclone group (P<0.01). The difference in sleep latency showed no statistically significant among each group (P>0.05). The results of both immunohistochemistry and Western blotting showed that the expression of CLOCK and BMAL1 in the hypothalamus of rats in the model group was significantly reduced compared with that in the normal group (P<0.01); the expression of CLOCK and BMAL1 in the hypothalamus of rats in the low- and high-dose Hewei Anshen Formula groups increased than that in the model group (P<0.05 or P<0.01). ConclusionHewei Anshen Formula can improve insomnia in model rats, and its mechanism of action may be related to the up-regulation of the expression of the hypothalamic biological clock genes CLOCK and BMAL1 protein.
6.Surgical strategies and efficacy analysis for aortic dissection complicating intractable mesenteric artery ischemia
Lingwei ZOU ; Yifan LIU ; Hao LIU ; Bin CHEN ; Junhao JIANG ; Yun SHI ; Daqiao GUO ; Xin XU ; Zhihui DONG ; Weiguo FU
Chinese Journal of Surgery 2024;62(3):235-241
Objective:To explore the surgical strategies and clinical efficacy for aortic dissection combined with refractory superior mesenteric artery (SMA) ischemia.Methods:This is a retrospective case series study. Clinical data of 24 patients with aortic dissection and refractory SMA ischemia admitted to the Department of Vascular Surgery, Zhongshan Hospital, Fudan University from August 2010 to August 2020 were retrospectively collected. Of the 24 patients, 21 were males and 3 were females, with an age of (50.3±9.9) years (range: 44 to 72 years).Among them, 9 cases were Stanford type A aortic dissection, and 15 cases were type B. All patients underwent CT angiography upon admission, and based on imaging characteristics, they were classified into three types. Type Ⅰ: severe stenosis/occlusion of the SMA true lumen only; Type Ⅱ: stenosis of the true lumens in the descending aorta and SMA (isolated type); Type Ⅲ: stenosis of the true lumens in the thoracoabdominal aorta and SMA (continuation type). Surgical procedures, complications, mortality, and reintervention rates were recorded.Results:Among the 24 patients, 17 (70.8%) were classified as Type Ⅰ, 4 (16.7%) as Type Ⅱ, and 3 (12.5%) as Type Ⅲ. Fourteen cases of Type Ⅰ underwent thoracic endovascular aortic repair combined with SMA stent implantation. Additionally, 3 Type Ⅰ and 1 Type Ⅱ patients underwent only SMA reconstruction (with one case of chronic TAAD treated with iliac artery-SMA bypass surgery). Moreover, 3 Type Ⅱ and 3 Type Ⅲ patients underwent descending aorta combined with SMA stent implantation. There were 5 patients (20.8%) who underwent small bowel resection, either in the same sitting or in a staged procedure. During hospitalization, 4 patients died, resulting in a mortality rate of 16.7%. Among these cases, two patients succumbed to severe intestinal ischemia resulting in multiple organ dysfunction syndrome. The follow-up duration was (46±9) months (range: 13 to 72 months). During the follow-up, 2 patients died, unrelated to intestinal ischemia. The 5-year freedom from reintervention survival rate was 86.1%, and the 5-year cumulative survival rate was 82.6%.Conclusions:Patients with aortic dissection and refractory SMA ischemia have a high perioperative mortality. However, implementing appropriate surgical strategies according to different clinical scenarios can reduce mortality and alleviate intestinal ischemia.
7.Endovascular treatment for Stanford type B aortic dissection in Marfan syndrome patients: a series of 23 cases
Xiaolang JIANG ; Hao LIU ; Lingwei ZOU ; Bin CHEN ; Junhao JIANG ; Daqiao GUO ; Xin XU ; Zhihui DONG ; Weiguo FU
Chinese Journal of Surgery 2024;62(5):438-442
Objective:To evaluate the clinical outcomes of thoracic endovascular aortic repair (TEVAR) in the treatment of Stanford type B aortic dissection (TBAD) in Marfan syndrome patients who had no history of aortic arch replacement.Methods:This is a retrospective case-series study. From January 2009 to December 2019,the clinical data of Marfan syndrome patients who underwent TEVAR for TBAD at the Department of Vascular Surgery were collected. A total of 23 patients were enrolled,including 15 males and 8 females. The age was (38.0±11.0) years (range:24 to 56 years). Among them,12 patients had history of ascending aortic surgery. Details of TEVAR,perioperative complications and reintervention were recorded and survival rate was analyzed by Kaplan-Meier curve.Results:Technical success was 91.3% (21/23). Two patients with technical failure were as follows:one patient had type Ⅰa endoleak at the completion angiography,which healed spontaneously during the follow-up,and the other patient suffered aortic intimal intussusception after the deployment of the first stent-graft, and the second stent-graft was deployed. However, type Ⅲ endoleak was detected,which disappeared during the follow-up. One patient died during hospitalization. The median follow-up time ( M(IQR)) was 60 (48) months (range:12 to 132 months). Reintervention was performed on 7 patients,including 3 distal stent-graft-induced new entry,2 distal aortic dilation,1 Ⅰa endoleak and 1 retrograde type A aortic dissection,respectively. Five-year cumulative survival rate was 86.7% (95% CI:86.6% to 86.8%) and the 5-year freedom from reintervention rate was 81.8% (95% CI:61.8% to 92.8%). Conclusions:TEVAR is feasible in the treatment of TBAD in Marfan syndrome patients who has no history of aortic arch replacement. It has high technical success rate and low perioperative complication.
8.Effect of early postoperative activity on recovery of hepatocellular carcinoma patients with portal hypertension
Yali LIU ; Jieqiong ZHAO ; Xuxu HE ; Zhihui ZOU
Journal of Navy Medicine 2024;45(3):280-285
Objective To investigate the effect of early postoperative activities on rehabilitation and discharge in hepatocellular carcinoma patients with portal hypertension.Methods A total of 423 patients who underwent surgical treatment for hepatocellular carcinoma with portal hypertension in The Third Affiliated Hospital of Naval Medical University from June 2019 to June 2021 were collected as research objects.There were 348 patients without early postoperative activity and 75 patients with early postoperative activity.The impacts of preoperative factors(age,gender,smoking history,etc.)and intraoperative factors(intraoperative hepatic portal block,perioperative blood transfusion,and tumor size)on postoperative recovery of patients were analyzed.In order to reduce the selection bias,75 patients were chosen from 348 patients without early postoperative activity by propensity score matching and taken as non-early activity group.Early postoperative complications,gastrointestinal function recovery(including first ventilation time,abdominal distension,and diarrhea),postoperative hospital stay,and total hospital stay were compared between non-early activity group and early activity group before and after propensity score matching.Results There was no significant difference in the incidences of serious postoperative complications,postoperative diarrhea,or total length of hospital stay between non-early activity group and early activity group before and after propensity score matching(P>0.05).But there were significant differences in the incidences of first ventilation time,postoperative abdominal distension,and postoperative hospital stay between the two groups(P<0.05).Conclusion Early postoperative activities can accelerate the recovery of gastrointestinal function in portal hypertension patients undergoing hepatectomy,promote the intake and absorption of nutrients,facilitate the recovery of postoperative liver function,shorten the postoperative hospital stay,and promote the early recovery of patients.
9.Surgical strategies and efficacy analysis for aortic dissection complicating intractable mesenteric artery ischemia
Lingwei ZOU ; Yifan LIU ; Hao LIU ; Bin CHEN ; Junhao JIANG ; Yun SHI ; Daqiao GUO ; Xin XU ; Zhihui DONG ; Weiguo FU
Chinese Journal of Surgery 2024;62(3):235-241
Objective:To explore the surgical strategies and clinical efficacy for aortic dissection combined with refractory superior mesenteric artery (SMA) ischemia.Methods:This is a retrospective case series study. Clinical data of 24 patients with aortic dissection and refractory SMA ischemia admitted to the Department of Vascular Surgery, Zhongshan Hospital, Fudan University from August 2010 to August 2020 were retrospectively collected. Of the 24 patients, 21 were males and 3 were females, with an age of (50.3±9.9) years (range: 44 to 72 years).Among them, 9 cases were Stanford type A aortic dissection, and 15 cases were type B. All patients underwent CT angiography upon admission, and based on imaging characteristics, they were classified into three types. Type Ⅰ: severe stenosis/occlusion of the SMA true lumen only; Type Ⅱ: stenosis of the true lumens in the descending aorta and SMA (isolated type); Type Ⅲ: stenosis of the true lumens in the thoracoabdominal aorta and SMA (continuation type). Surgical procedures, complications, mortality, and reintervention rates were recorded.Results:Among the 24 patients, 17 (70.8%) were classified as Type Ⅰ, 4 (16.7%) as Type Ⅱ, and 3 (12.5%) as Type Ⅲ. Fourteen cases of Type Ⅰ underwent thoracic endovascular aortic repair combined with SMA stent implantation. Additionally, 3 Type Ⅰ and 1 Type Ⅱ patients underwent only SMA reconstruction (with one case of chronic TAAD treated with iliac artery-SMA bypass surgery). Moreover, 3 Type Ⅱ and 3 Type Ⅲ patients underwent descending aorta combined with SMA stent implantation. There were 5 patients (20.8%) who underwent small bowel resection, either in the same sitting or in a staged procedure. During hospitalization, 4 patients died, resulting in a mortality rate of 16.7%. Among these cases, two patients succumbed to severe intestinal ischemia resulting in multiple organ dysfunction syndrome. The follow-up duration was (46±9) months (range: 13 to 72 months). During the follow-up, 2 patients died, unrelated to intestinal ischemia. The 5-year freedom from reintervention survival rate was 86.1%, and the 5-year cumulative survival rate was 82.6%.Conclusions:Patients with aortic dissection and refractory SMA ischemia have a high perioperative mortality. However, implementing appropriate surgical strategies according to different clinical scenarios can reduce mortality and alleviate intestinal ischemia.
10.Endovascular treatment for Stanford type B aortic dissection in Marfan syndrome patients: a series of 23 cases
Xiaolang JIANG ; Hao LIU ; Lingwei ZOU ; Bin CHEN ; Junhao JIANG ; Daqiao GUO ; Xin XU ; Zhihui DONG ; Weiguo FU
Chinese Journal of Surgery 2024;62(5):438-442
Objective:To evaluate the clinical outcomes of thoracic endovascular aortic repair (TEVAR) in the treatment of Stanford type B aortic dissection (TBAD) in Marfan syndrome patients who had no history of aortic arch replacement.Methods:This is a retrospective case-series study. From January 2009 to December 2019,the clinical data of Marfan syndrome patients who underwent TEVAR for TBAD at the Department of Vascular Surgery were collected. A total of 23 patients were enrolled,including 15 males and 8 females. The age was (38.0±11.0) years (range:24 to 56 years). Among them,12 patients had history of ascending aortic surgery. Details of TEVAR,perioperative complications and reintervention were recorded and survival rate was analyzed by Kaplan-Meier curve.Results:Technical success was 91.3% (21/23). Two patients with technical failure were as follows:one patient had type Ⅰa endoleak at the completion angiography,which healed spontaneously during the follow-up,and the other patient suffered aortic intimal intussusception after the deployment of the first stent-graft, and the second stent-graft was deployed. However, type Ⅲ endoleak was detected,which disappeared during the follow-up. One patient died during hospitalization. The median follow-up time ( M(IQR)) was 60 (48) months (range:12 to 132 months). Reintervention was performed on 7 patients,including 3 distal stent-graft-induced new entry,2 distal aortic dilation,1 Ⅰa endoleak and 1 retrograde type A aortic dissection,respectively. Five-year cumulative survival rate was 86.7% (95% CI:86.6% to 86.8%) and the 5-year freedom from reintervention rate was 81.8% (95% CI:61.8% to 92.8%). Conclusions:TEVAR is feasible in the treatment of TBAD in Marfan syndrome patients who has no history of aortic arch replacement. It has high technical success rate and low perioperative complication.

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