1.Dynamic immunological characteristics in acute rejection model of cervical heterotopic heart transplantation in mice
Xi CAO ; Tao HUANG ; Jiwei YANG ; Xiaowen WANG ; Wenfeng ZHU ; Haoqi CHEN ; Ning FAN ; Genshu WANG
Organ Transplantation 2025;16(2):256-263
Objective To establish an acute rejection model of cervical heart transplantation in mice and evaluate the survival and dynamic rejection process post-transplantation. Methods Mice were randomly divided into sham operation group (n=10), syngeneic transplantation group (n=21), and allogeneic transplantation group (n=65). Sham operation, syngeneic cervical heart transplantation, and allogeneic cervical heart transplantation were performed respectively. The survival of recipient mice and grafts, histopathological changes of graft tissues, subpopulations of splenic lymphocytes, and expression of inflammatory factors in serum and grafts were observed. Results The survival rate and graft survival rate of the sham operation group and syngeneic transplantation group were 100% at 7 days after surgery. In the allogeneic transplantation group, 5 cases failed and died on the first day after surgery. The survival rate at 7 days after surgery was 86%, and all surviving mice had grafts that stopped beating at 7 days after surgery. The allogeneic transplantation group showed significant rejection at 7 days after surgery, accompanied by tissue damage and CD8+ T cell infiltration. The proportion of CD8+ T cells in the spleen continued to rise post-operation, while the proportion of CD4+ T cells showed a downward trend. The expression of interferon-γ in serum and grafts peaked at 5 days after surgery, while the expression of tumor necrosis factor-α showed no statistical significance. Conclusions Acute rejection following heart transplantation in mice intensifies between 5 to 7 days after surgery, which may be a critical time window for immunological intervention.
2.Diagnosis and malignant analysis of mass versus pneumonia type of primary pulmonary mucinous adenocarcinoma
Yihui FENG ; Xiaolei ZHU ; Shaohan FANG ; Xiaowen ZHANG ; Ning LI ; Guojun GENG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(03):360-365
Objective To investigate the relationship between primary pulmonary mucinous adenocarcinoma (PPMA) mass type and pneumonia type and their difference in malignant degree, and to analyze the role of clinical manifestations and CT features in the diagnosis of this disease. Methods The clinical data of PPMA patients admitted in the First Affiliated Hospital of Xiamen University from May 2011 to March 2022 were retrospectively analyzed. According to CT features, they were divided into a mass type group and a pneumonia type group. The clinical manifestations, CT features and the degree of malignancy between the two groups were analyzed and compared. Results A total of 57 PPMA patients were enrolled. There were 17 males and 40 females, with an average age of (53.82±10.65) years, and 28 (49%) patients had reversed hato-like sign. There were 42 patients in the mass type group and 15 patients in the pneumonia type group. PPMA often occurs in both lower lungs, with clinical manifestations mainly of coughing and expectorating white mucoid sputum. There were statistical differences between the two groups in the maximum diameter of tumor (P<0.001), boundary condition (P<0.001) and pleural indentation sign (P=0.019). There was no statistical difference between the two groups in Ki-67 index (P>0.05). Conclusion There is no statistical difference in the degree of malignancy between the two types of PPMA. Considering their clinical manifestations and differences in imaging features, it is supported that the pneumonia type is just a progression of the mass type. CT can present various manifestations, among which the reversed hato-like sign is expected to become an important imaging feature. Combined with a high proportion of solid components, pleural indentation sign, and vacuole sign, reversed hato-like sign can play a significant role in the diagnosis of PPMA.
3.Hippo (YAP)-autophagy axis protects against hepatic ischemia-reperfusion injury through JNK signaling
Shuguang ZHU ; Xiaowen WANG ; Haoqi CHEN ; Wenfeng ZHU ; Xuejiao LI ; Ruiwen CUI ; Xiaomeng YI ; Xiaolong CHEN ; Hua LI ; Genshu WANG
Chinese Medical Journal 2024;137(6):657-668
Background::Hepatic ischemia-reperfusion injury (HIRI) remains a common complication during liver transplantation (LT) in patients. As a key downstream effector of the Hippo pathway, Yes-associated protein (YAP) has been reported to be involved in various physiological and pathological processes. However, it remains elusive whether and how YAP may control autophagy activation during ischemia-reperfusion.Methods::Human liver tissues from patients who had undergone LT were obtained to evaluate the correlation between YAP and autophagy activation. Both an in vitro hepatocyte cell line and in vivo liver-specific YAP knockdown mice were used to establish the hepatic ischemia-reperfusion models to determine the role of YAP in the activation of autophagy and the mechanism of regulation. Results::Autophagy was activated in the post-perfusion liver grafts during LT in patients, and the expression of YAP positively correlated with the autophagic level of hepatocytes. Liver-specific knockdown of YAP inhibited hepatocytes autophagy upon hypoxia-reoxygenation and HIRI ( P <0.05). YAP deficiency aggravated HIRI by promoting the apoptosis of hepatocytes both in the in vitro and in vivo models ( P <0.05). Attenuated HIRI by overexpression of YAP was diminished after the inhibition of autophagy with 3-methyladenine. In addition, inhibiting autophagy activation by YAP knockdown exacerbated mitochondrial damage through increasing reactive oxygen species ( P <0.05). Moreover, the regulation of autophagy by YAP during HIRI was mediated by AP1 (c-Jun) N-terminal kinase (JNK) signaling through binding to the transcriptional enhanced associate domain (TEAD). Conclusions::YAP protects against HIRI by inducing autophagy via JNK signaling that suppresses the apoptosis of hepatocytes. Targeting Hippo (YAP)-JNK-autophagy axis may provide a novel strategy for the prevention and treatment of HIRI.
4.Safety of high-carbohydrate fluid diet 2 h versus overnight fasting before non-emergency endoscopic retrograde cholangiopancreatography: A single-blind, multicenter, randomized controlled trial
Wenbo MENG ; W. Joseph LEUNG ; Zhenyu WANG ; Qiyong LI ; Leida ZHANG ; Kai ZHANG ; Xuefeng WANG ; Meng WANG ; Qi WANG ; Yingmei SHAO ; Jijun ZHANG ; Ping YUE ; Lei ZHANG ; Kexiang ZHU ; Xiaoliang ZHU ; Hui ZHANG ; Senlin HOU ; Kailin CAI ; Hao SUN ; Ping XUE ; Wei LIU ; Haiping WANG ; Li ZHANG ; Songming DING ; Zhiqing YANG ; Ming ZHANG ; Hao WENG ; Qingyuan WU ; Bendong CHEN ; Tiemin JIANG ; Yingkai WANG ; Lichao ZHANG ; Ke WU ; Xue YANG ; Zilong WEN ; Chun LIU ; Long MIAO ; Zhengfeng WANG ; Jiajia LI ; Xiaowen YAN ; Fangzhao WANG ; Lingen ZHANG ; Mingzhen BAI ; Ningning MI ; Xianzhuo ZHANG ; Wence ZHOU ; Jinqiu YUAN ; Azumi SUZUKI ; Kiyohito TANAKA ; Jiankang LIU ; Ula NUR ; Elisabete WEIDERPASS ; Xun LI
Chinese Medical Journal 2024;137(12):1437-1446
Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.
5.Diagnostic and therapeutic value of endoscopic irrigation for uncomplicated acute colonic diverticulitis(4 cases)
Chuantao SUN ; Xiaowen ZHU ; Baozhen SHAN ; Deping LI ; Fan YANG ; Xiaobo LIU
China Journal of Endoscopy 2024;30(6):37-42
Objective To study the diagnostic and therapeutic value of endoscopic irrigation for uncomplicated acute colonic diverticulitis.Methods From June 2021 to March 2022,4 patients suspected uncomplicated acute colonic diverticulitis who then underwent colonoscopy,and endoscopic irrigation treatment was performed after confirming.The endoscopic imaging of acute colonic diverticulitis was summarized.The changes of abdominal pain symptoms and prognosis of the patients were evaluated.The levels of white blood cell(WBC)and C-reactive protein(CRP)in serum before and after treatment were measured.Results 4 patients were diagnosed as uncomplicated acute colonic diverticulitis underwent colonoscopy.Two cases were located in the ascending colon and the other two in the cecum.Endoscopic imaging characteristics included mucosal hyperemia and swelling of diverticular orifice and nearby area,purulent secretions,purulent fur and fecalith at the diverticular orifice.After treatment,the symptom of abdominal pain was relieved,the levels of WBC and CRP in serum were lower than before treatment.Conclusion Endoscopic irrigation has a useful diagnostic and therapeutic value for uncomplicated acute diverticulitis of the colon.It is worthy of further clinical study.
6.Clinical effect of unilateral superior gluteal artery perforator propeller flap combined with contralateral centripetal advancement flap in repairing huge pressure ulcers in the sacrococcygeal region
Jun LI ; Mengdong LIU ; Liang ZHU ; Yuming LUO ; Qiying YANG ; Xiaowen GAO ; Juntao HAN
Chinese Journal of Burns 2024;40(6):551-556
Objective:To explore the feasibility and clinical effects of unilateral superior gluteal artery perforator propeller flap combined with contralateral centripetal advancement flap in repairing huge pressure ulcers in the sacrococcygeal region.Methods:The study was a retrospective observational study. From June 2020 to April 2023, 15 patients with stage Ⅳ pressure ulcers with sacrococcygeal defect area greater than 10.0 cm×10.0 cm who met the inclusion criteria were admitted to the First Affiliated Hospital of Air Force Medical University, including 8 males and 7 females, aged from 30 to 86 years. The pressure ulcers before debridement were all accompanied by different degree of infection and necrosis. Debridement and negative pressure sealing and irrigation treatment were performed in stage Ⅰ. After debridement, the skin and soft tissue defect area was 12.0 cm×10.5 cm to 20.0 cm×17.0 cm. After the wound bed infection was controlled, unilateral superior gluteal artery perforator propeller flap combined with contralateral centripetal advancement flap was used to repair the pressure ulcer wounds in stage Ⅱ. The perforator flap area was 12.0 cm×7.0 cm to 16.0 cm×10.5 cm. The donor area wound was sutured directly. After operation, the survival, complications, and wound healing of flap donor area were observed. During regular follow-up, the recurrence of pressure ulcers, the appearance and texture of the flap, and the scars in the donor site were observed.Results:After operation, 1 patient had fluid accumulation under the flap and survived after drainage and dressing change. The flaps of the other patients survived well without infection, local necrosis, and sinus formation under the flap. The wounds in the donor area healed well. All patients were followed up for more than 6 months, and there was no recurrence of pressure ulcers. The appearance of the flap was not bloated, the texture was soft, and the compression resistance and elasticity were good. The donor site wound healed well without obvious scar.Conclusions:The surgical method of repairing giant sacrococcygeal pressure ulcers with unilateral superior gluteal artery perforator propeller flap combined with contralateral centripetal advancement flap is simple and easy to operate. It can repair large defect area with the donor area being sutured directly, which is worthy of clinical promotion.
7.Analysis on the development strategy of clinical research in children's specialized hospital based on SWOT model
Yuhui LIN ; Xiaowen CHEN ; Yingyan ZHENG ; Yongkai ZHU ; Pin JIA ; Rui DONG
Modern Hospital 2024;24(6):965-969
Objective To provide strategies and suggestions for the development of clinical research in children's spe-cialized hospitals.Methods With a Class A tertiary children's specialty hospital in Shanghai as an example,the SWOT model is used to analyze the strengths,weaknesses,opportunities,and threats of clinical research development in the hospital,and to propose corresponding strategies and suggestions.Results The hospital has distinguished disciplinary advantages,tremendous strength in scientific research,a strong team of talents,and steady progress in the construction of clinical research center.The weaknesses include imperfect clinical research management system,imperfect informatization construction,and insufficient allo-cation of full-time management personnel.There are now opportunities of high policy support,increasing funding support,the shift in clinical demand,and good prospects for development of investigator-initiated trials(IIT).The hospital is also faced with the threat of difficulty in conducting pediatric clinical research and fierce competition among similar hospitals.Conclusion We could promote the development of pediatric clinical research by incentivizing the conduction of clinical research,strengthening the construction of clinical research system,improving the clinical research capabilities,and building a collaborative network for ped-iatric multicenter clinical research.
8.Efficacy and safety of chimeric antigen receptor T-cell therapy followed by allogeneic hematopoietic stem cell transplantation in 21 patients with Ph-like acute lymphoblastic leukemia
Haiping DAI ; Hongjie SHEN ; Zheng LI ; Wei CUI ; Qingya CUI ; Mengyun LI ; Sifan CHEN ; Mingqing ZHU ; Depei WU ; Xiaowen TANG
Chinese Journal of Hematology 2024;45(1):35-40
Objective:To evaluate the efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with Ph-like acute lymphoblastic leukemia (Ph-ALL) .Methods:Patients with Ph-ALL who underwent CAR-T therapy followed by allo-HSCT from March 2018 to August 2023 at the First Affiliated Hospital of Soochow University were included, and their clinical data were retrospectively analyzed.Results:Of the 21 patients, 14 were male and 7 were female. The median age at the time of CAR-T therapy was 22 (6-50) years. Seven patients had ABL1-like rearrangements, and 14 had JAK-STAT rearrangements. Prior to CAR-T therapy, 12 patients experienced hematologic relapse; 7 were multiparameter flow cytometry minimal residual disease (MFC-MRD) -positive and 2 were MFC-MRD-negative. CAR-T cells were derived from patients’ autologous lymphocytes. Nine patients were treated with CD19 CAR-T cells, and 12 were treated with CD19/CD22 CAR-T cells. After assessment on day 28 after CAR-T therapy, 95.2% of the patients achieved complete remission, with an MRD-negative remission rate of 75%. Nineteen patients developed grade 0–2 cytokine release syndrome (CRS) and 2 patients suffered grade 3 CRS, all cases of which resolved after treatment. All patients underwent allo-HSCT after CAR-T therapy. The median time from CAR-T therapy to allo-HSCT was 63 (38-114) days. Five patients experienced relapse after CAR-T therapy, including four with hematologic relapse and one with molecular relapse. The 3-year overall survival (OS) rates in the ABL1 and JAK-STAT groups were (83.3±15.2) % and (66.6±17.2) %, respectively ( P=0.68) . The 3-year relapse-free survival (RFS) rates were (50.0±20.4) % and (55.6±15.4) % in the ABL1 and JAK-STAT groups, respectively. There was no significant difference in 3-year OS or RFS between the two groups. Conclusions:CAR-T therapy followed by allo-HSCT leads to rapid remission in most patients with Ph-ALL and prolongs leukemia-free survival.
9.The efficacy and safety of protein A immunoadsorption combined with rituximab treatment for highly sensitized patients undergoing haplo-hematopoietic stem cell transplantation
Ling LI ; Wenjuan ZHU ; Qian ZHU ; Shiyuan ZHOU ; Chao MA ; Jun WANG ; Xiaohui HU ; Yue HAN ; Ying WANG ; Xiaowen TANG ; Xiao MA ; Suning CHEN ; Huiying QIU ; Luyao CHEN ; Jun HE ; Depei WU ; Xiaojin WU
Chinese Journal of Hematology 2024;45(5):468-474
Objective:To investigate the efficacy and safety of protein A immunoadsorption (PAIA) combined with rituximab (RTX) in highly sensitized patients who underwent haplo-hematopoietic stem cell transplantation (haplo-HSCT) .Methods:The clinical data of 56 highly sensitized patients treated with PAIA and RTX before haplo-HSCT at the First Affiliated Hospital of Soochow University and Soochow Hopes Hematonosis Hospital between March 2021 and June 2023 were retrospectively analyzed. The number of human leukocyte antigen (HLA) antibody types and the mean fluorescence intensity (MFI), humoral immunity, adverse reactions during adsorption, and survival within 100 days before and after adsorption were measured.Results:After receiving the PAIA treatment, the median MFI of patients containing only HLA Ⅰ antibodies decreased from 7 859 (3 209-12 444) to 3 719 (0-8 275) ( P<0.001), and the median MFI of HLA Ⅰ+Ⅱ antibodies decreased from 5 476 (1 977-12 382) to 3 714 (0-11 074) ( P=0.035). The median MFI of patients with positive anti-donor-specific antibodies decreased from 8 779 (2 697-18 659) to 4 524 (0–15 989) ( P<0.001). The number of HLA-A, B, C, DR, and DQ antibodies in all patients decreased after the PAIA treatment, and the differences were statistically significant (A, B, C, DR: P<0.001, DQ: P<0.01). The humoral immune monitoring before and after the PAIA treatment showed a significant decrease in the number of IgG and complement C3 ( P<0.001 and P=0.002, respectively). Forty-four patients underwent HLA antibody monitoring after transplantation, and the overall MFI and number of antibody types decreased. However, five patients developed new antibodies with low MFI, and nine patients continued to have high MFI. The overall survival, disease-free survival, non-recurrent mortality, and cumulative recurrence rates at 100 days post-transplantation were 83.8%, 80.2%, 16.1%, and 4.5%, respectively. Conclusions:The combination of PAIA and RTX has a certain therapeutic effect and good safety in the desensitization treatment of highly sensitive patients before haplo-HSCT.
10.Correlation analysis between AIP and vulnerable plaques of coronary CT
Xuankai ZHOU ; Xiaowen HAN ; Guan WANG ; Zhi ZHU ; Shuxin ZHAO ; Fan CUI ; Jiahang SHI ; Chenghao PIAO
China Medical Equipment 2024;21(10):46-50
Objective:To explore the relationship between atherosclerotic index of plasma(AIP)and vulnerable plaque of coronary under computed tomography(CT)based on coronary CT angiography(CCTA).Methods:Data were retrospectively collected on 213 patients with coronary heart disease(CHD)who underwent CCTA examination from January 2021 to February 2024 at the Second Affiliated Hospital of Shenyang Medical College,and they were divided into a vulnerable plaque group(123 cases)and a non-vulnerable plaque group(90 cases)according to whether existed vulnerable plaque of coronary artery.General clinical data such as age,gender,history of smoking,history of alcohol consumption,history of diabetes,and serum indicators such as AIP were collected.The differences in AIP and other factors between the two groups were compared.The independent influencing factors of vulnerable plaque of coronary artery were determined by multifactorial logistic regression analysis,and the predictive value of AIP for vulnerable plaque was assessed by drawing a receiver operating characteristic(ROC)curve.Results:AIP of vulnerable plaque group was 0.22±0.31,which was higher than that 0.05±0.27 of the vulnerable plaque group,and the difference of AIP between two groups was significant(t=4.223,P<0.001).Multifactorial logistic analysis showed there was independent correlation between AIP and vulnerable plaque under CT(OR=7.556,95%CI:2.442~23.385,P=0.002).The ROC curve showed that the best cut-off value of AIP was 0.20 in predicting vulnerable plaque under CT,and the value of area under curve(AUC)was 0.665,and the sensitivity was 55.56%and the specificity was 73.98%.Conclusion:AIP is an independent influencing factor for CHD patients who complicate vulnerable plaques,and it has a certain of predictive value for vulnerable plaques.

Result Analysis
Print
Save
E-mail