1.Establishment and consistency analysis of xenograft models for human tumors of primary liver cancer
Long YANG ; Pinsheng HAN ; Ze WANG ; Tao CUI ; Yamin ZHANG
Chinese Journal of Hepatobiliary Surgery 2025;31(11):846-850
Objective:To establish a patient-derived tumor xenograft (PDX) model of primary liver cancer (PLC), and to analyze the pathological features, proliferation and drug-related gene mutation characteristics of the primary tumor and the PDX model of primary liver cancer.Methods:A retrospective analysis was conducted on the tumor samples of 64 PLC patients who underwent hepatectomy in the Department of Hepatobiliary Surgery of Tianjin First Central Hospital from January 2019 to December 2020. Among them, there were 46 males and 18 females, with an average age of (60.7±9.4) years. The degree of tumor differentiation and whether there was vascular invasion were recorded. The pathology of the primary tumor and each generation of PDX models was observed. Immunohistochemical staining was used to detect the characteristic proteins and proliferation-related protein of PLC. The genes related to drug use in PLC PDX models were analyzed in the primary tumor.Results:Among the tumor tissues of 64 PLC patients, 31 cases (48.4%) were successfully transplanted into nude mice and passaged to subsequent generations. In the primary tumor tissues and PDX models of hepatocellular carcinoma (HCC), the cancer nodules were clearly distinguishable, the cancer cells were arranged disorderly, and distributed in nests or cords. The tumor cell nuclei were large and deeply stained. In the primary tumor tissues and each generation of PDX models of intrahepatic cholangiocarcinoma (ICC), there were ICC adenocarcinoma-like structures, with well-differentiated tumor glands and glandular structures composed of cuboidal or columnar tumor cells, presenting as small individual glands or interwoven glands. The degree of differentiation of the PDX models of HCC and ICC patients was basically consistent with that of the primary tumors. Immunohistochemistry showed that proliferating cell nuclear antigen staining of the primary tumors and PDX model transplanted tumors of HCC and ICC patients was strongly positive. The Ki-67 staining positive rate of the primary tumors and PDX model transplanted tumors of HCC was > 80%, and that of ICC was > 70%. Alpha-fetoprotein was strongly positive in the primary tumors and PDX model transplanted tumors of HCC and ICC. The common mutations of transplanted tumors and the primary tumors of P24 HCC patients were 90%, and those of P43 ICC patients were 89%, 94%, and 94%, respectively.Conclusion:The constructed PDX model is highly consistent with the biological characteristics of the primary tumor.
2.Establishment and consistency analysis of xenograft models for human tumors of primary liver cancer
Long YANG ; Pinsheng HAN ; Ze WANG ; Tao CUI ; Yamin ZHANG
Chinese Journal of Hepatobiliary Surgery 2025;31(11):846-850
Objective:To establish a patient-derived tumor xenograft (PDX) model of primary liver cancer (PLC), and to analyze the pathological features, proliferation and drug-related gene mutation characteristics of the primary tumor and the PDX model of primary liver cancer.Methods:A retrospective analysis was conducted on the tumor samples of 64 PLC patients who underwent hepatectomy in the Department of Hepatobiliary Surgery of Tianjin First Central Hospital from January 2019 to December 2020. Among them, there were 46 males and 18 females, with an average age of (60.7±9.4) years. The degree of tumor differentiation and whether there was vascular invasion were recorded. The pathology of the primary tumor and each generation of PDX models was observed. Immunohistochemical staining was used to detect the characteristic proteins and proliferation-related protein of PLC. The genes related to drug use in PLC PDX models were analyzed in the primary tumor.Results:Among the tumor tissues of 64 PLC patients, 31 cases (48.4%) were successfully transplanted into nude mice and passaged to subsequent generations. In the primary tumor tissues and PDX models of hepatocellular carcinoma (HCC), the cancer nodules were clearly distinguishable, the cancer cells were arranged disorderly, and distributed in nests or cords. The tumor cell nuclei were large and deeply stained. In the primary tumor tissues and each generation of PDX models of intrahepatic cholangiocarcinoma (ICC), there were ICC adenocarcinoma-like structures, with well-differentiated tumor glands and glandular structures composed of cuboidal or columnar tumor cells, presenting as small individual glands or interwoven glands. The degree of differentiation of the PDX models of HCC and ICC patients was basically consistent with that of the primary tumors. Immunohistochemistry showed that proliferating cell nuclear antigen staining of the primary tumors and PDX model transplanted tumors of HCC and ICC patients was strongly positive. The Ki-67 staining positive rate of the primary tumors and PDX model transplanted tumors of HCC was > 80%, and that of ICC was > 70%. Alpha-fetoprotein was strongly positive in the primary tumors and PDX model transplanted tumors of HCC and ICC. The common mutations of transplanted tumors and the primary tumors of P24 HCC patients were 90%, and those of P43 ICC patients were 89%, 94%, and 94%, respectively.Conclusion:The constructed PDX model is highly consistent with the biological characteristics of the primary tumor.
3.Differentiation and Treatment of Co-morbidity of Osteoporosis and Knee Osteoarthritis based on the Concept of "Wei (痿) and Bi (痹) Unity"
Yushi CUI ; Hongfei WU ; Yun GAO ; Runmin LAI ; Xingping ZHANG ; Shuai ZHANG ; Mingyuan WANG ; Yamin LI
Journal of Traditional Chinese Medicine 2024;65(15):1565-1570
Osteoporosis and knee osteoarthritis often co-occur and are closely related in terms of epidemiology, clinical symptoms, pathogenesis and other aspects. Therefore, it is necessary to manage the co-morbidity and treat the two as a whole. Based on the overall relationship between wei (痿) and bi (痹) in TCM, it is believed that osteoporosis and knee osteoarthritis have marrow loss and bone atrophy as the core pathogenesis of co-morbidity, and microfractures as the central pathological link. The overall treatment is rooted in boosting kidney, supplementing marrow and strengthening the bones. According to the pathological manifestations of microfractures in the process of co-morbidity, and the different deficiency and excess characteristics of wei and bi, it can be divided into three types, "wei emerging with mild bi", "wei and bi progressing simultaneously", and "emphasis on both wei and bi", for treatment. In terms of "wei emerging with mild bi", that is the early stage of osteoporosis, the traditional Daoyin (导引) is the main therapy. For "wei and bi progressing simultaneously", it can be divided into three stages further, including the onset stage, remission stage, and recovery stage of knee pain, treated with Taohong Siwu Decoction (桃红四物汤), Bushen Huoxue Formula (补肾活血方) and self-made Bushen Qianggu Formula (补肾强骨方) as the main formula respectively. For "emphasis on both wei and bi", the proven formula, Qianggu Zhitong Formula (强骨止痛方), is taken as the main prescription.
4.Analysis of the consistency between CTA and DSA in evaluating GLASS staging of chronic limb-threatening ischemia
Yaqing HAN ; Ningning DING ; Li ZHOU ; Yuling CUI ; Cuilin YIN ; Zhe LIU ; Jian YANG ; Yamin LIU ; Yan MENG
Journal of Interventional Radiology 2024;33(3):300-303
Objective To analyze the consistency between computer tomography angiography(CTA)and digital subtraction angiography(DSA)in evaluating the global limb anatomic staging system(GLASS)stage of patients with chronic limb-threatening ischemia(CLTI).Methods The clinical data of patients with CLTI,who were admitted to the First Affiliated Hospital of Xi'an Jiaotong University of China to receive treatment between January 2017 and December 2020,were retrospectively analyzed.Taking the DSA assessment as the gold standard,the consistency of CTA and DSA in evaluating the GLASS stage of patients with CLTI was analyzed.Results In the assessment of GLASS stage of CLTI,CTA showed strong agreement with DSA.The weighted Kappa coefficient of CTA and DSA for the staging of femoropopliteal segment was 0.798(95%CI=0.722-0.873,P<0.01),and the weighted Kappa coefficient of CTA and DSA for the staging of infrapopliteal artery segment was 0.785(95% CI=0.725-0.845,P<0.0l).For the overall staging of GLASS,the weighted Kappa coefficient of CTA and DSA was 0.832(95% CI=0.752-0.91 1,P<0.01).All the above results indicated that a very strong consistency existed between CTA and DSA in evaluating the GLASS stage of patients with CLTI.Conclusion CTA examination of lower limb can accurately evaluate GLASS score and stage of CLTI patient's target lesions,which is helpful in diagnosing lower extremity arteriosclerosis occlusion disease as well as in assessing the technical difficulty degree of its revascularization operation.(J Intervent Radiol,2024,33:300-303)
5.Research progress of organoids in liver regenerative medicine
Liuyang ZHU ; Sen LIU ; Tao CUI ; Long YANG ; Chuanliang CHENG ; Pinsheng HAN ; Yamin ZHANG
Chinese Journal of Hepatobiliary Surgery 2024;30(1):72-76
Liver regenerative medicine can use functional liver cells to repair or replace damaged liver tissue and it is expected to be rapidly developed as an alternative treatment to liver transplantation. However, regenerative medicine requires cells with stable proliferation ability and liver cell characteristics. Liver organoids are derived from adult stem cells or pluripotent stem cells. They can be proliferated in large quantities and cultured for a long time in vitro, meanwhile maintain genetic stability, and simulate the structural and functional characteristics of organs in the body, providing a new strategy for liver regeneration. This article reviews liver organoids and their research progress in liver regenerative medicine, and discusses their application potential and existing limitations.
6.Role of tumor-associated macrophages in cholangiocarcinoma
Pinsheng HAN ; Long YANG ; Tao CUI ; Yamin ZHANG
Journal of Clinical Hepatology 2023;39(2):469-473
Cholangiocarcinoma (CCA) is a highly malignant biliary tumor with strong invasion and poor prognosis and is insensitive to radiotherapy and chemotherapy. Tumor-associated macrophage (TAM) is an important component of the tumor microenvironment. CCA cells recruit TAM into tumor tissue by releasing cytokines and polarize them into M2 TAM, which promotes the progression of CCA through various mechanisms such as assisting immune escape, promoting tumor cell proliferation, regulating angiogenesis, promoting tumor metastasis, and mediating immune resistance. As an emerging target of tumor immunotherapy, TAM provides new ideas for targeted therapy for CCA. This article reviews the mechanisms of TAM in promoting the progression of CCA and immunotherapy targeting TAM in recent years.
7.Clinical application of robotic-assistant living donor left lateral segmentectomy
Yamin ZHANG ; Wei GAO ; Zilin CUI ; Chong DONG ; Rui FENG ; Chao SUN ; Yi BAI ; Zhongyang SHEN
Chinese Journal of Organ Transplantation 2023;44(6):339-345
Objective:To explore the feasibility and safety of robotic-assisted living donor left lateral segmentectomy (LDLLS) in a large pediatric liver transplant program.Methods:Retrospective analysis was performed for clinical data of 45 LDLLS donors and recipients from June 2021 to September 2022.Traditional open donor liver resection (n=30) and robotic-assisted segmentectomy (n=15) were performed.Two groups were compared with regards to operative duration, intraoperative hemorrhage, postoperative healing and postoperative complications.SPSS 21.0 was utilized for statistical analysis.Independent sample T, paired sample T, Wilcoxon rank sum and Chi-square tests were performed for examining the inter-group differences.Results:Operative duration of robot-assisted surgery group was substantially longer than that of traditional open surgery group ( P<0.001). Intraoperative blood loss was less in robot-assisted surgery group was less than that in traditional open surgery group[(106.0±39.8) vs.(251.0±144.8) ml, P=0.001]. Postoperative hospital stay of robot-assisted surgery group was shorter than that of traditional open surgery group[6.0(6.0, 6.0) vs.7.0(6.0, 9.0), P<0.05]. Two cases of postoperative biliary leakage were observed in donor of traditional open surgery group.Among 2 cases of abdominal infection, one was due to biliary leakage from liver section and secondary surgery was then performed.One case of incisional infection and another case of thrombosis occurred in donor of traditional open surgery group.In robot-assisted surgery group, only one donor had amylase elevation.In traditional open surgery group, there were one case of local thrombosis in middle hepatic vein and one case of bile duct stricture.No long-term complications occurred in robot-assisted surgery group during a follow-up period of over 6 months.Finally recipient data analysis indicated that no significant inter-group differences existed in operative duration, intraoperative blood loss, postoperative hospital stay or postoperative abdominal infection ( P=0.634, P=0.180, P=0.86 and P=0.153). Conclusions:Robotic-assisted LDLLS proves to be be a safe and reliable option for living donor segmentectomy.It is superior to conventional LDLLS in terms of shorter hospital stay, less intraoperative blood loss and fewer postoperative complications.
8.Preparation of HSV-IgM human-mouse chimeric antibody and development of stable recombinant cell line.
Yamin CUI ; Xiaoping TIAN ; Jingjing SUN ; Zhiqiang WANG ; Qiaohui ZHAO ; Guilin LI
Chinese Journal of Biotechnology 2023;39(9):3887-3898
In order to achieve large-scale production of HSV-IgM (HSV1, HSV2) human-mouse chimeric antibody in vitro, the gene sequence of the corresponding hybridoma cell was harvested by RNA ligase-mediated rapid amplification of cDNA ends (RLM-RACE) technique to clone the chimeric antibody into eukaryotic expression vectors, and express the target proteins in CHO-S cells. At the same time, the screening process of stable cell lines was optimized, and the pressure conditions of pool construction stage and monoclonal screening stage were explored. Finally, the target protein was purified by protein L affinity purification method and the biological activity was detected. The recombinant IgM antibodies, HSV1 and HSV2, weighted at 899 kDa and 909 kDa respectively, were prepared. The optimal screening pressure was 20P200M (the first phase of pressure) and 50P1000M (the second phase of pressure). The final titer for the monoclonal expression of HSV1-IgM and HSV2-IgM was 1 620 mg/L and 623 mg/L, respectively. This study may facilitate the development of quality control products of HSV1 and HSV2 IgM series recombinant antibodies as well as efficient expression of IgM subtype antibodies in vitro.
Cricetinae
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Humans
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Animals
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Mice
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Immunoglobulin M/genetics*
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Antibodies, Viral
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CHO Cells
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Cricetulus
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Hybridomas
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Recombinant Fusion Proteins
9.Research progress in the role of HMGB1-RAGE signaling axis in hepatic ischemia-reperfusion injury
Li ZHAO ; Zilin CUI ; Yamin ZHANG ; Jie LIU
International Journal of Biomedical Engineering 2022;45(2):166-170,185
Hepatic ischemia-reperfusion injury(HIRI) is a kind of liver injury caused by reperfusion after ischemic injury, which is clinically manifested by a series of deterioration phenomena such as liver function impairment, jaundice and even multi-organ failure after restoration of blood supply to the liver. HIRI seriously affects the patient's regression and prognosis. The essence of HIRI is a sterile inflammatory response. High mobility histone 1 (HMGB1) is an important intermediate mediator of HIRI and is a multiple cell type effector involved in HIRI. The receptor for glycosylated end products(RAGE) signaling axis of HMGB1 plays a key role in HIRI, but its mechanism is unclear. In this paper, the recent studies related to the pro-inflammatory mechanism of HMGB1-RAGE signaling axis in HIRI were summarized, and the relationship between HMGB1-RAGE signaling pathway and HIRI was discussed. The research progress of preventing and treating HIRI with surgical operation, ischemic preconditioning, drug and gene therapy using HMGB1-RAGE signaling axis as the target was reviewed.
10.Interpretation of acute abdomen in the immunocompromised patients: WSES/SIS-E/WSIS/AAST/GAIS guideline
Feibo ZHENG ; Chunyong YANG ; Yunfeng CUI ; Yamin ZHANG ; Federico COCCOLINI
Chinese Critical Care Medicine 2022;34(3):239-244
World Society of Emergency Surgery (WSES), in conjunction with Surgical Infection Society Europe (SIS-E), World Surgical Infection Society (WSIS), American Association for the Surgery of Trauma (AAST), and Global Alliance for Infection in Surgery (GAIS) developed guideline about the management of acute abdomen in immunocompromised patients, which was published in the World Journal of Emergency Surgery (WJES) on August 9, 2021. The guidelines elaborate on the definition, classification, diagnosis and treatment of immunocompromised patients. In addition, based on evidence-based medicine, it provides guidance and suggestion on the management of specific acute abdominal infections in immunocompromised patients, common acute abdominal infections in transplanted patients, patients with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS), as well as perioperative steroid management. An interpretation of the guideline was performed to accomplish a better understanding the current status and recommendations for the management of acute abdominal conditions in immunocompromised patients, and to make forward suggestions on its limitations.

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