1.SLC38A1 drives malignant progression of hepatocellular carcinoma by activating PI3K/AKT signaling via enhanced glutamine uptake
Yuanyuan YANG ; Ping ZHANG ; Peng HU ; Maonian LIU ; Yanjiao OU
Journal of Army Medical University 2025;47(23):2922-2932
Objective To investigate the mechanism by which SLC38A1 promotes hepatocellular carcinoma(HCC)progression through glutamine transport-mediated activation of the PI3K/AKT signaling pathway.Methods Bioinformatics analysis was employed to assess the correlation between SLC38A1 expression and clinicopathological features/prognosis in HCC patients,with functional enrichment analysis of SLC38A1 conducted.SLC38A1 was silenced or over expressed via transfection in Huh-7 cells,with glutamine inhibited using DRP-104 and the PI3K/AKT pathway suppressed using LY294002.Cell viability,proliferation,migration,invasion,and glutamine concentration were evaluated using CCK-8,EdU staining,scratch wound healing assay,Transwell chamber assay,and glutamine assay kits,respectively.PI3K/AKT pathway activity was assessed by Western blotting.Results SLC38A1 mRNA and protein levels were significantly higher in HCC tumor tissues than in adjacent normal tissues(P<0.05).HCC patients with high SLC38A1 expression exhibited significantly lower overall survival than those with low expression(P<0.05).SLC38A1 expression correlated significantly with pathologic T-stage(pT),N-stage(pN),M-stage(pM),survival status,and immune infiltration in HCC patients(P<0.05).SLC38A1 silencing markedly reduced glutamine uptake in HCC cells(P<0.001),suppressing cell viability,proliferation,migration,invasion,and PI3K/AKT pathway activity(P<0.001).Conversely,SLC38A1 overexpression promoted proliferation,migration,invasion,and PI3K/AKT activation(P<0.001).DRP-104-mediated glutamine inhibition suppressed HCC cell malignancy and PI3K/AKT signaling while abolishing the oncogenic effects of SLC38A1 overexpression(P<0.001).PI3K/AKT pathway inhibition blocked the pro-tumorigenic effects of SLC38A1 overexpression(P<0.001).Conclusion SLC38A1 promotes proliferation,migration,and invasion in HCC by activating the PI3K/AKT pathway through enhanced glutamine transport.
2.Diagnosis and treatment of graft-versus-host disease after liver transplantation: a single-center 25-year experience and literature review
Jiayun JIANG ; Hong WANG ; Rui LIAO ; Jiejuan LAI ; Fenghao LIU ; Chengcheng ZHANG ; Wei LIU ; Yanjiao OU ; Leida ZHANG
Chinese Journal of Organ Transplantation 2025;46(7):504-515
Objective:To explore the diagnostic key points, treatment strategies, and prognosis of graft-versus-host disease (GVHD) after liver transplantation.Methods:The clinical data of 5 recipients diagnosed with GVHD after liver transplantation at the Liver Transplantation Center of the First Affiliated Hospital of Army Medical University from May 1999 to October 2024 were retrospectively analyzed. The causes, onset, diagnosis, treatment, and prognosis of GVHD after liver transplantation were summarized and analyzed. Literature was searched in CNKI, Wanfang, VIP, Chinese Medical Journal Full-text Database, PubMed, Web of Science, and Google Scholar using the Chinese keywords "移植物抗宿主病+肝移植", and the English keywords "graft versus host disease + liver transplantation". The search time ranged from January 1988 to January 2025. Inclusion criteria for the literature: (1) meeting the clinical or pathological diagnostic criteria of GVHD after liver transplantation; (2) recipient age >18 years; (3) case number ≥2. Exclusion criteria: incomplete clinical data such as incidence, mortality, and clinical manifestations of GVHD after liver transplantation. The retrieved literature was reviewed.Results:All 5 recipients were male. Among them, 4 cases underwent liver transplantation at this center. The incidence of GVHD after liver transplantation in this center was 0.46% (4/872). All 5 cases developed symptoms such as fever, rash, diarrhea, oral ulcers, and pancytopenia on the 19th (5-21) day after liver transplantation. One case had gastrointestinal bleeding. Two cases were diagnosed by skin pathological biopsy, and three cases were diagnosed based on clinical manifestations such as fever, rash, diarrhea, and bone marrow suppression. One case discontinued immunosuppressants, and four cases reduced the dosage of immunosuppressants. Four cases were treated with high-dose glucocorticoids, four with intravenous immunoglobulin (IVIG), three with ruxolitinib, and three with hematopoietic factors. All five cases received protective isolation, anti-infection, and symptomatic supportive treatment. Among the three recipients treated with ruxolitinib, body temperature returned to normal, rash gradually faded, oral ulcers gradually healed, blood cells returned to normal, and they were eventually discharged after recovery. The remaining two cases showed no symptom improvement and died of severe lung infection and multiple organ failure. Literature review A total of 34 articles were included. The incidence of GVHD after liver transplantation was 1.03% (279/27 018), and the onset time ranged from 7 to 1,865 days post-transplantation; 272 cases (97.49%) occurred within 1-8 weeks. The main clinical manifestations included fever (195 cases, 69.89%), rash (267 cases, 95.70%), diarrhea (173 cases, 62.01%), and bone marrow suppression (214 cases, 76.70%). Treatment mainly involved adjustment of immunosuppressants (201 cases, 72.04%), high-dose corticosteroids (215 cases, 77.06%), and IVIG pulse therapy (146 cases, 52.33%). In the end, 83 cases (29.75%) recovered and were discharged, while the mortality rate was 70.25% (196/279), with causes of death including infection, gastrointestinal bleeding, and multiple organ failure.Conclusions:GVHD after liver transplantation has a low incidence, high mortality, and poor prognosis. Diagnosis mainly relies on typical clinical manifestations and pathological results of tissue biopsy. Early administration of high-dose corticosteroids combined with IVIG pulse therapy, timely reduction or discontinuation of immunosuppressants, use of ruxolitinib, active infection management, and enhanced symptomatic and supportive care are effective strategies for treating GVHD after liver transplantation.
3.Diagnosis and treatment of graft-versus-host disease after liver transplantation: a single-center 25-year experience and literature review
Jiayun JIANG ; Hong WANG ; Rui LIAO ; Jiejuan LAI ; Fenghao LIU ; Chengcheng ZHANG ; Wei LIU ; Yanjiao OU ; Leida ZHANG
Chinese Journal of Organ Transplantation 2025;46(7):504-515
Objective:To explore the diagnostic key points, treatment strategies, and prognosis of graft-versus-host disease (GVHD) after liver transplantation.Methods:The clinical data of 5 recipients diagnosed with GVHD after liver transplantation at the Liver Transplantation Center of the First Affiliated Hospital of Army Medical University from May 1999 to October 2024 were retrospectively analyzed. The causes, onset, diagnosis, treatment, and prognosis of GVHD after liver transplantation were summarized and analyzed. Literature was searched in CNKI, Wanfang, VIP, Chinese Medical Journal Full-text Database, PubMed, Web of Science, and Google Scholar using the Chinese keywords "移植物抗宿主病+肝移植", and the English keywords "graft versus host disease + liver transplantation". The search time ranged from January 1988 to January 2025. Inclusion criteria for the literature: (1) meeting the clinical or pathological diagnostic criteria of GVHD after liver transplantation; (2) recipient age >18 years; (3) case number ≥2. Exclusion criteria: incomplete clinical data such as incidence, mortality, and clinical manifestations of GVHD after liver transplantation. The retrieved literature was reviewed.Results:All 5 recipients were male. Among them, 4 cases underwent liver transplantation at this center. The incidence of GVHD after liver transplantation in this center was 0.46% (4/872). All 5 cases developed symptoms such as fever, rash, diarrhea, oral ulcers, and pancytopenia on the 19th (5-21) day after liver transplantation. One case had gastrointestinal bleeding. Two cases were diagnosed by skin pathological biopsy, and three cases were diagnosed based on clinical manifestations such as fever, rash, diarrhea, and bone marrow suppression. One case discontinued immunosuppressants, and four cases reduced the dosage of immunosuppressants. Four cases were treated with high-dose glucocorticoids, four with intravenous immunoglobulin (IVIG), three with ruxolitinib, and three with hematopoietic factors. All five cases received protective isolation, anti-infection, and symptomatic supportive treatment. Among the three recipients treated with ruxolitinib, body temperature returned to normal, rash gradually faded, oral ulcers gradually healed, blood cells returned to normal, and they were eventually discharged after recovery. The remaining two cases showed no symptom improvement and died of severe lung infection and multiple organ failure. Literature review A total of 34 articles were included. The incidence of GVHD after liver transplantation was 1.03% (279/27 018), and the onset time ranged from 7 to 1,865 days post-transplantation; 272 cases (97.49%) occurred within 1-8 weeks. The main clinical manifestations included fever (195 cases, 69.89%), rash (267 cases, 95.70%), diarrhea (173 cases, 62.01%), and bone marrow suppression (214 cases, 76.70%). Treatment mainly involved adjustment of immunosuppressants (201 cases, 72.04%), high-dose corticosteroids (215 cases, 77.06%), and IVIG pulse therapy (146 cases, 52.33%). In the end, 83 cases (29.75%) recovered and were discharged, while the mortality rate was 70.25% (196/279), with causes of death including infection, gastrointestinal bleeding, and multiple organ failure.Conclusions:GVHD after liver transplantation has a low incidence, high mortality, and poor prognosis. Diagnosis mainly relies on typical clinical manifestations and pathological results of tissue biopsy. Early administration of high-dose corticosteroids combined with IVIG pulse therapy, timely reduction or discontinuation of immunosuppressants, use of ruxolitinib, active infection management, and enhanced symptomatic and supportive care are effective strategies for treating GVHD after liver transplantation.
4.Clinical efficacy and safety of TACE combined with lenvatinib and PD-1 antibody in treatment of intermediate-advanced hepatocellular carcinoma
Jiayun JIANG ; Hui ZHANG ; Shiyu ZHANG ; Jiejuan LAI ; Yanjiao OU ; Leida ZHANG
Journal of Army Medical University 2024;46(22):2529-2538
Objective To analyze the clinical efficacy and safety of transcatheter arterial chemoembolization(TACE)combined with lenvatinib and PD-1 antibody in the treatment of intermediate-advanced hepatocellular carcinoma(HCC).Methods A retrospective cohort trial was conducted on 105 patients with intermediate-advanced HCC(BCLC B or C stage)treated with TACE combined with lenvatinib and PD-1 antibody in our institute from January 2021 to June 2023.The blood biochemical indicators and imaging characteristics of the patients were collected before and after TACE.Objective response rate(ORR),disease control rate(DCR),conversion resection rate,overall survival(OS)and progression-free survival(PFS)were analyzed to evaluate the clinical efficacy of the triple therapy,and the frequency and severity of all adverse reactions during treatment were recorded to evaluate the safety of the therapy.Results Among the 105 patients with intermediate-advanced HCC who received triple therapy,33 died and 72 survived.The ORR was 62.8%and the DCR was 72.3%.The conversion resection rate was 11.4%.The median OS(mOS)was not reached.The median PFS(mPFS)was(10.3±0.8)months.The incidence of adverse reactions of all grades was 97.1%,and the incidence of those of grade 3~4 was 33.3%.No treatment-related death occurred.Conclusion The triple therapy of TACE combined with lenvatinib and PD-1 antibody is a safe and effective comprehensive treatment regimen,which provides a new treatment strategy for improving the prognosis of intermediate-advanced HCC.
5.Preliminary clinical experiences of hepatic sinusoidal obstruction syndrome after orthotopic liver transplantation
Jiayun JIANG ; Yu FU ; Feng WU ; Chengcheng ZHANG ; Wei LIU ; Yanjiao OU ; Leida ZHANG
Chinese Journal of Organ Transplantation 2022;43(11):675-682
Objective:To explore the etiology, pathogenesis, clinical features, diagnosis and treatment of hepatic sinus obstruction syndrome(HSOS)after orthotopic liver transplantation(OLT).Methods:Clinical data were reviewed for 3 HSOS patients after OLT.Baseline profiles, primary disease, onset, clinical manifestations, abdominal imaging and pathological changes were recorded for summarizing the key points of diagnosis, treatment and outcomes of HSOS after OLT.Results:HSOS was an extremely rare complication after OLT with an incidence of 2%(2/117)and a median onset of 15(13-50)days.The major clinical manifestations were hepatic pain, abdominal distension, poor appetite, fatigue, jaundice, oliguria, peritoneal effusion and pleural effusion.Some of them were complicated with acute renal insufficiency.Abdominal ultrasonography revealed that blood stream of hepatic and portal veins was smooth but rather slow and hepatic parenchyma showed uneven echo changes.Abdominal enhanced computed tomography(CT)demonstrated " mosaic" and " map-like" uneven enhancement in portal vein and balance phases.The pathological manifestations of liver biopsy included obvious dilation and congestion of hepatic sinuses, swelling and necrosis of hepatic cells, thickening of hepatic venules and luminal stenosis or occlusion.All of them received immunosuppressants.Tacrolimus was switched to sirolimus, low molecular weight heparin or plus rivaroxaban anticoagulant thrombolytic therapy, methylprednisolone regulatory immunotherapy, albumin supplementation, diuresis, hepatic protection and fluid replacement.Afterward clinical symptoms of 2 patients improved, became cured and discharged.One case died from gastrointestinal hemorrhage and acute renal failure secondary to multiple organ failure.Conclusions:HSOS is an extremely rare but severe complication after OLT.Early diagnosis and fine-tuning of treatment protocols can avoid poor prognosis such as liver and kidney failure and significantly improve patient survival.
6.Application value of artificial neural network in laparoscopic surgery training
Yitai GUO ; Zeyu LIU ; Yanjiao OU ; Yong DENG ; Hong WANG ; Peng HU ; Leida ZHANG
Chinese Journal of Digestive Surgery 2020;19(6):660-665
Objective:To investigate the application value of artificial neural network in laparoscopic surgery training.Methods:The prospective cohort study was conducted. A total of 158 trainees from the First Hospital Affiliated to Army Medical University between Semptember and November, 2019 who had no experience in laparoscopic technology were selected for laparoscopic surgery training, including 52 graduate students of surgery from grade 2019, 2018 and 2017, 58 surgeons receiving standardized residency training, 12 interns and 36 refresher physicians. The 158 trainees were divided into two groups using the random number table. Trainees trained by artificial neural network laparoscopic simulator were allocated into artificial neural network group, and trainees trained by box laparoscopic simulator were allocated into general laparoscopic simulator group. Trainees in both groups were trained using the laparoscopic simulator for 10 hours (5-day continuous training, 2 hours per day) on fundamentals of laparoscopic surgery. Observation indicators: (1) comparison of operation grades on laparoscopic simulator before and after training in the two groups; (2) comparison of improvement of the operation grades on laparoscopic simulator after training between the two groups. Measurement data with normal distribution were represented as Mean± SD, comparison within groups was analyzed using the paired t test and comparison between groups was analyzed using the independent sample t test. Measurement data with skewed distribution were represented as M (range). Results:A total of 158 trainees were selected for eligibility, including 140 males and 18 females, aged from 23 to 34 years, with a median age of 27 years. Of the 158 trainees, 79 were in the artificial neural network group and 79 were in the general laparoscopic simulator group. (1) Comparison of operation grades on laparoscopic simulator before and after training in the two groups: operation grades of the nails transferring, pattern cutting, ligation, sewing knots in vivo and sewing knots in vitro for the artificial neural network group before training were 51.2±4.9, 45.6±3.7, 43.0±3.6, 42.1±3.1, and 39.6±3.1, respectively. The above indicators for the artificial neural network group after training were 78.6±3.0, 76.4±3.9, 79.9±2.5, 78.3±3.5, and 84.1±3.8, respectively. There were significant differences in the above indicators for the artificial neural network group before and after training ( t=-42.490, -56.256, -80.373, -70.802, -79.742, P<0.05). The above indicators for the general laparoscopic simulator group before training were 50.1±2.9, 45.4±3.9, 42.7±3.0, 42.3±3.4, and 39.2±4.7, respectively. The above indicators for the general laparoscopic simulator group after training were 70.4±5.0, 69.8±4.0, 72.3±3.3, 72.3±3.5, and 72.8±3.2, respectively. There were significant differences in the above indicators for the general laparoscopic simulator group before and after training ( t=-28.942, -42.436, -58.357, -52.322, -53.098, P<0.05). (2) Comparison of improvement of the operation grades on laparoscopic simulator after training between the two groups: improvement of the operation grades in the nails transferring, pattern cutting, ligation, sewing knots in vivo and sewing knots in vitro for the artificial neural network group after training were 27.4±5.7, 30.8±5.0, 36.9±4.1, 36.2±4.5 and 39.5±5.4, respectively. The above indicators for the general laparoscopic simulator group after training were 20.3±6.2, 24.4±5.1, 29.6±4.5, 29.9±5.1 and 33.5±5.6, respectively. There were significant differences in the above indicators between the two groups ( t=7.597, 7.946, 10.638, 8.200, 6.969, P<0.05). Conclusion:The introduction of artificial neural network in laparoscopic surgery training can improve the training effects.
7. Application effect of mixed reality in the teaching of hepatobiliary surgery
Hong WANG ; Yanjiao OU ; Peng HU ; Yong DENG ; Liqin ZOU ; Qiangting DENG ; Zhengrong SHI ; Leida ZHANG
Chinese Journal of Medical Education Research 2019;18(12):1230-1234
Objective:
To explore the application effect of mixed reality technology in the teaching of hepatobiliary surgery.
Methods:
A total of 120 professional postgraduates majored in surgery who had received the four-month standardized training of residents in hepatobiliary surgery department of the First Affiliated Hospital of Army Military Medical University and the First Affiliated Hospital of Chongqing Medical University during 2016-2018 were selected and were equally allocated into the control group and the research group via random number table method. Students in the control group were trained with traditional surgical teaching mode and in the research group were trained with three-dimensional visualization model which was constructed by mixed reality. Students in both groups received assessment and questionnaires at the end of training.
Results:
Scores of theoretical examination and surgical operation assessment of students in the research group were higher than those in the control group (
8.Attaching importance to endoscopic therapy for biliary stricture after liver transplantation
Chinese Journal of Digestive Surgery 2018;17(12):1152-1155
At present,liver transplantation has become an important therapy for patients with end-stage liver and gallbladder diseases.However,biliary stricture after liver transplantation occurs commonly and greatly,which hampers the clinical efficacy.Endoscopic retrograde cholangiopancreatography has become the first choice for diagnosis and treatment of biliary stricture after liver transplantation,though its operation is difficult and complicated.In recent years,a large number of studies on the pathogenesis and prevention of biliary stricture after liver transplantation have been investigated.Endoscopic diagnosis and treatment also have made great theoretical and technological advances.In this review the author aims to analyze the current literature and make a detailed discussion on the above issues,in order to provide reference for domestic counterparts.

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