1.Research advances in hepatocellular carcinoma-related imbalance of bile acid metabolism and related regulatory mechanism
Zherui LIU ; Xiaodong JIA ; Yinying LU
Journal of Clinical Hepatology 2021;37(3):690-694
Bile acid metabolism, gut microbiota, and bile acid receptors are involved in the development and progression of hepatocellular carcinoma (HCC). There are substantial increases in the levels of some bile acids, such as glycocholic acid, taurocholic acid, and taurochenodeoxycholic acid, in the liver tissue of HCC mice and the serum and feces of HCC patients. Bile acid metabolism due to the imbalance of the abundance of bacteria producing bile salt hydrolases and Clostridium in the intestine and the change in immune microenvironment may also promote the development of HCC. Moreover, some bile acid receptors, such as farnesoid X receptor, G protein-coupled bile acid receptor 1, pregnane X receptor, constitutive androstane receptor, and sphingosine-1-phosphate receptor 2, have been shown to participate in the development and progression of HCC through various pathways. Each link of bile acid metabolism plays a different role in the progression of HCC, and a systematic elaboration of the interaction between these links may help to deepen the understanding of the pathogenesis of HCC and develop the biological targets for early diagnosis, prognosis prediction, and precise treatment.
2.Treatment of open abdomen combined with entero-atmospheric fistula: A retrospective study
Jinpeng ZHANG ; Yitan TENG ; Ye LIU ; Ruixia TIAN ; Zherui ZHANG ; Lei WU ; Zhiwu HONG ; Huajian REN ; Gefei WANG ; Jian'an REN
Chinese Journal of Gastrointestinal Surgery 2023;26(9):853-858
Objective:The purpose of this study was to analyze the course and outcome of patients with combined entero-atmospheric fistulas in open abdomen treatment.Methods:In this retrospective observational study, we collected data on 214 patients with open abdomen complicated by entero-atmospheric fistulas admitted to Research Institute of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School from January 2012 to January 2021. We collected their basic characteristics, aetiology, treatment plan, and prognosis, including the durations of hospitalization and open treatment, time to resumption of enteral nutrition, duration and prognosis of definitive surgery, and overall prognosis.Results:Of the 214 patients with open abdomen complicated with entero–enteral fistulas, 23 (10.7%) died (11 of multiple organ failure caused by abdominal infection, five of abdominal cavity bleeding, four of pulmonary infection, one of airway bleeding, one of necrotizing fasciitis, and one of traumatic brain injury). The remaining 191 underwent definitive surgery at our hospital. The patients who underwent definitive surgery were predominantly male (156 patients, 81.7%); their age was (46.5±2.5) years. Trauma and gastrointestinal tumors (120 cases, 62.8%) predominated among the primary causes. The reasons for abdominal opening were, in order, severe abdominal infection (137 cases, 71.7%, damage control surgery (29 cases, 15.2%), and abdominal hypertension (25 cases, 13.1%). Temporary abdominal closure measures were used to classify the participants into a skin-only suture group (104 cases) and a skin-implant group (87 cases). Compared with the skin-implant group, in the skin-suture-only group the proportion of male patients was lower (74.7% [65/87] vs. 87.5% [91/104], χ 2=5.176, P=0.023), the mean age was older ([48.3±2.0] years vs. [45.0±1.9] years, t=-11.671, P<0.001), there were fewer patients with trauma (32.2% [28 /87] vs. 58.7% [61/104), χ 2=13.337, P<0.001), intensive care stays were shorter ([8.9±1.0] days vs. [12.7±1.6] days, t=19.281, P<0.001), total length of stay was shorter ([29.3±2.0] days vs. [31.9±2.0] days, t=9.021, P<0.001), there was a higher percentage of colonic fistulas (18.4% [16/87] vs. 8.7% [9/104], χ 2=3.948, P=0.047), but fewer multiple fistulas (11.5% [10/87] vs. 34.6% [36/104], χ 2=14.440, P<0.001). As to fistula management, a higher percentage of fistula sealing methods using 3D-printed intestinal stents were implemented in the skin-only suture group (60.9% [53/87] versus 43.3% [45/104], χ 2=5.907, P=0.015). Compared with the implant group, the skin-only suture group had a shorter mean time to performing provisional closure ( [9.5±0.8] days vs. [16.0±0.6] days, t=66.023, P<0.001), shorter intervals to definitive surgery ( [165.0±10.7] days vs. [198.9±8.3] days, t=26.644, P<0.001), and less use of biopatches (56.3% [49/87) vs. 71.2% [74/104], χ 2=4.545, P=0.033). Conclusions:Open abdomen complicated with entero-enteral fistulas is more common in male, and is often caused by trauma and gastrointestinal tumor. Severe intra-abdominal infection is the major cause of open abdomen, and most fistulae involves the small intestine. Collection and retraction of intestinal fluid and 3D-printed entero-enteral fistula stent sealing followed by implantation and skin-only suturing is an effective means of managing entero-enteral fistulas complicating open abdominal cavity. Earlier closure of the abdominal cavity with skin-only sutures can shorten the time to definitive surgery and reduce the rate of utilization of biopatches.
3.Treatment of open abdomen combined with entero-atmospheric fistula: A retrospective study
Jinpeng ZHANG ; Yitan TENG ; Ye LIU ; Ruixia TIAN ; Zherui ZHANG ; Lei WU ; Zhiwu HONG ; Huajian REN ; Gefei WANG ; Jian'an REN
Chinese Journal of Gastrointestinal Surgery 2023;26(9):853-858
Objective:The purpose of this study was to analyze the course and outcome of patients with combined entero-atmospheric fistulas in open abdomen treatment.Methods:In this retrospective observational study, we collected data on 214 patients with open abdomen complicated by entero-atmospheric fistulas admitted to Research Institute of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School from January 2012 to January 2021. We collected their basic characteristics, aetiology, treatment plan, and prognosis, including the durations of hospitalization and open treatment, time to resumption of enteral nutrition, duration and prognosis of definitive surgery, and overall prognosis.Results:Of the 214 patients with open abdomen complicated with entero–enteral fistulas, 23 (10.7%) died (11 of multiple organ failure caused by abdominal infection, five of abdominal cavity bleeding, four of pulmonary infection, one of airway bleeding, one of necrotizing fasciitis, and one of traumatic brain injury). The remaining 191 underwent definitive surgery at our hospital. The patients who underwent definitive surgery were predominantly male (156 patients, 81.7%); their age was (46.5±2.5) years. Trauma and gastrointestinal tumors (120 cases, 62.8%) predominated among the primary causes. The reasons for abdominal opening were, in order, severe abdominal infection (137 cases, 71.7%, damage control surgery (29 cases, 15.2%), and abdominal hypertension (25 cases, 13.1%). Temporary abdominal closure measures were used to classify the participants into a skin-only suture group (104 cases) and a skin-implant group (87 cases). Compared with the skin-implant group, in the skin-suture-only group the proportion of male patients was lower (74.7% [65/87] vs. 87.5% [91/104], χ 2=5.176, P=0.023), the mean age was older ([48.3±2.0] years vs. [45.0±1.9] years, t=-11.671, P<0.001), there were fewer patients with trauma (32.2% [28 /87] vs. 58.7% [61/104), χ 2=13.337, P<0.001), intensive care stays were shorter ([8.9±1.0] days vs. [12.7±1.6] days, t=19.281, P<0.001), total length of stay was shorter ([29.3±2.0] days vs. [31.9±2.0] days, t=9.021, P<0.001), there was a higher percentage of colonic fistulas (18.4% [16/87] vs. 8.7% [9/104], χ 2=3.948, P=0.047), but fewer multiple fistulas (11.5% [10/87] vs. 34.6% [36/104], χ 2=14.440, P<0.001). As to fistula management, a higher percentage of fistula sealing methods using 3D-printed intestinal stents were implemented in the skin-only suture group (60.9% [53/87] versus 43.3% [45/104], χ 2=5.907, P=0.015). Compared with the implant group, the skin-only suture group had a shorter mean time to performing provisional closure ( [9.5±0.8] days vs. [16.0±0.6] days, t=66.023, P<0.001), shorter intervals to definitive surgery ( [165.0±10.7] days vs. [198.9±8.3] days, t=26.644, P<0.001), and less use of biopatches (56.3% [49/87) vs. 71.2% [74/104], χ 2=4.545, P=0.033). Conclusions:Open abdomen complicated with entero-enteral fistulas is more common in male, and is often caused by trauma and gastrointestinal tumor. Severe intra-abdominal infection is the major cause of open abdomen, and most fistulae involves the small intestine. Collection and retraction of intestinal fluid and 3D-printed entero-enteral fistula stent sealing followed by implantation and skin-only suturing is an effective means of managing entero-enteral fistulas complicating open abdominal cavity. Earlier closure of the abdominal cavity with skin-only sutures can shorten the time to definitive surgery and reduce the rate of utilization of biopatches.
4.CiteSpace bibliometric analysis of safety and risk studies of antibody drugs in China
Yue PENG ; Lingling LIU ; Yuanxuan CAI ; Yuhang ZHAO ; Xiaofang SHANGGUAN ; Kangling LI ; Zherui CHEN ; Ke LI ; Rui HUANG ; Yuanyuan LU
China Pharmacist 2024;27(6):1019-1027
Objective To analyze the domestic antibody drug safety and risk research status,the latest research hotspots and frontiers in the current ten years.Methods CiteSpace 6.2.R2 software was used to analyze all literature related to the safety and risk of antibody drugs in CNKI,WanFang data and Vip database from 2012 to 2022.Results A total of 2 773 pieces of literature were obtained from the three databases,which were imported into CiteSpace after deduplication,and finally,1 870 pieces were included in the analysis.In the past decade,the number of articles published in the field of antibody drugs safety and risk research has remained at about 100 articles per year from 2012 to 2019,since 2020,the number of articles published has started to increase,and the annual number of articles published has increased to around 300 articles from 2021 to 2022.The network graph of domestic institutional cooperation showed that there was a lack of cooperation among the research institutions of antibody drug safety and risk research,mainly due to the fact that hospitals were conducting research in this field,and the types of research subjects were relatively single.The author collaboration network graph showed that the core teams in this research field,such as Li Bo,Yang Yanwei,and Lin Zhi,had the closest collaboration,while there was less collaboration among high-yield authors,additionally,some experts and scholars conducted research on their own as individuals or small groups,the research focused on adverse reactions,safety,bevacizumab,Rituximab,Meta-analysis,etc.Conclusion In the past decade,domestic research has mainly focused on the clinical efficacy and safety of antibody drugs,with few scholars exploring the risk of antibody drugs,therefore,in the future,it is necessary to pay attention to the research on the risks of antibody drugs.
5.Clinical research advances in chimeric antigen receptor T-cell therapy for primary liver cancer
Shuang LI ; Zherui LIU ; Qi ZHAO ; Yinying LU
Journal of Clinical Hepatology 2023;39(5):1019-1029
Primary liver cancer (PLC) has the features of insidious onset and difficulties in early diagnosis, with limited and ineffective therapeutic options. Chimeric antigen receptor (CAR) T-cell therapy is a genetically modified T-cell therapy that recognizes tumor-specific antigens and activates T cells to exert a tumor-killing effect. CAR T-cell therapy has made great progress in the treatment of hematological tumors and has achieved a good clinical effect in the field of solid tumors in recent years, and although CAR T-cell therapy has developed from the first to the fifth generation, there are still many challenges in the field of solid tumors. This article comprehensively reviews the mechanisms of CAR T-cell therapy for PLC and related research advances, including the main targets such as GPC3, AFP, MUC1, and NKG2D in CAR T-cell therapy for PLC, CAR T-cell therapy for PLC and oncolytic virus, and combined treatment with immune checkpoint inhibitors, as well as the advances in the biological, preclinical, and clinical studies on these targets and treatment modalities and the challenges and solutions for CAR T-cell therapy in the treatment of PLC, so as to provide a reference for the future clinical development of CAR T-cell therapy in liver cancer.