1.Anti-PD-L1 antibody enhances curative effect of cryoablation via antibody-dependent cell-mediated cytotoxicity mediating PD-L1highCD11b+ cells elimination in hepatocellular carcinoma.
Jizhou TAN ; Ting LIU ; Wenzhe FAN ; Jialiang WEI ; Bowen ZHU ; Yafang LIU ; Lingwei LIU ; Xiaokai ZHANG ; Songling CHEN ; Haibiao LIN ; Yuanqing ZHANG ; Jiaping LI
Acta Pharmaceutica Sinica B 2023;13(2):632-647
Cryoablation (CRA) and microwave ablation (MWA) are two main local treatments for hepatocellular carcinoma (HCC). However, which one is more curative and suitable for combining with immunotherapy is still controversial. Herein, CRA induced higher tumoral PD-L1 expression and more T cells infiltration, but less PD-L1highCD11b+ myeloid cells infiltration than MWA in HCC. Furthermore, CRA had better curative effect than MWA for anti-PD-L1 combination therapy in mouse models. Mechanistically, anti-PD-L1 antibody facilitated infiltration of CD8+ T cells by enhancing the secretion of CXCL9 from cDC1 cells after CRA therapy. On the other hand, anti-PD-L1 antibody promoted the infiltration of NK cells to eliminate PD-L1highCD11b+ myeloid cells by antibody-dependent cell-mediated cytotoxicity (ADCC) effect after CRA therapy. Both aspects relieved the immunosuppressive microenvironment after CRA therapy. Notably, the wild-type PD-L1 Avelumab (Bavencio), compared to the mutant PD-L1 atezolizumab (Tecentriq), was better at inducing the ADCC effect to target PD-L1highCD11b+ myeloid cells. Collectively, our study uncovered the novel insights that CRA showed superior curative effect than MWA in combining with anti-PD-L1 antibody by strengthening CTL/NK cell immune responses, which provided a strong rationale for combining CRA and PD-L1 blockade in the clinical treatment for HCC.
2.Application value of donor liver autologous portal venous blood rinse in orthotopic liver trans-plantation
Yafei GUO ; Zebin ZHU ; Hao ZHENG ; Ning WANG ; Zhijun XU ; Xuefeng LI ; Wei CAI ; Ruipeng SONG ; Jizhou WANG ; Dalong YIN ; Lianxin LIU ; Shugeng ZHANG
Chinese Journal of Digestive Surgery 2023;22(2):244-250
Objective:To investigate the application value of donor liver autologous portal venous blood rinse in orthotopic liver transplantation (OLT).Methods:The retrospective cohort study was conducted. The clinicopathological data of 35 pairs of donors and recipients who underwent OLT in the First Affiliated Hospital of University of Science and Technology of China from May 2018 to June 2019 were collected. Of the 35 donors, there were 31 males and 4 females, aged (48±9)years. Of the 35 recipients, there were 25 males and 10 females, aged (47±9)years. Of the 35 recipients, 16 recipients undergoing donor liver autologous portal venous blood rinse were allocated into the portal vein group, and 19 recipients undergoing donor liver albumin water rinse were allocated into the albumin group. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and compari-son between groups was analyzed using the t test. Measurement data of skewed distribution were represented as M(range). Count data were descried as absolute numbers, and comparison between groups was analyzed using the Fisher exact probability. Results:(1) Surgical situations. The anhepatic phase time and arterial blood Ca 2+ concentration within 5 minutes after reperfusion of the recipients were (52±12)minutes and (0.99±0.10)mmol/L in the portal vein group, versus (64±12)minutes and (1.05±0.07)mmol/L in the albumin group, showing significant differences in the above indicators between the two groups ( t=2.94, 2.22, P<0.05). The mean arterial pressure, arterial blood K +concentration and arterial blood pH within 5 minutes after reperfusion of the recipients were (70±24)mmHg (1 mmHg=0.133 kPa), (4.7±1.3)mmol/L and 7.27±0.06 in the portal vein group, versus (71±28)mmHg, (4.6±1.1)mmol/L and 7.30±0.07 in the albumin group, showing no significant difference in the above indicators between the two groups ( t=0.14, 0.30, 1.22, P>0.05). (2) Post-operative situations. Cases with post-reperfusion syndrome (PRS), cases with severe PRS of cardiac arrest, cases with primary graft nonfunction of the recipients were 6, 0, 2 in the portal vein group, versus 8, 1, 1 in the albumin group, showing no significant difference in the above indicators between the two groups ( P>0.05). Total bilirubin on postoperative day 7 of the recipients was (90±52)μmol/L in the portal vein group, versus (166±112)μmol/L in the albumin group, showing a significant difference between the two groups ( t=2.66, P<0.05). International normalized ratio on postoperative day 7, the highest alanine aminotransferase and aspartate aminotransferase within 7 days after operation of the recipients were 2.1±2.0, (1 952±2 813)IU/L and (3 944±6 673)IU/L in the portal vein group, versus 1.8±0.6, (1 023±1 014) IU/L and (2 005±2 910)IU/L in the albumin group, showing no significant difference in the above indicators between the two groups ( t=0.66, 1.23, 1.08, P>0.05). Recipients with hepatic artery complication and biliary complication were 1 and 2 in the portal vein group, versus 0 and 4 in the albumin group, showing no significant difference in the above indicators between the two groups ( P>0.05). There were 3 cases and 2 cases died during the perioperative period in the portal vein group and the albumin group, respectively. (3) Follow-up. Of the 35 recipients, 30 recipients were followed up for 534(range, 28?776)days after operation. During the follow-up, there were 3 patients with postoperative complications in the portal vein group including 2 cases died and 1 case recovered after sympto-matic treatment. There were 5 patients with postoperative complications in the albumin group including 1 case died and 4 cases recovered after symptomatic treatment. Up to the follow-up date, 11 patients in the portal vein group and 16 patients in the albumin group were in good condition. Conclusion:Rinse of the donor liver with autologous portal venous blood during liver transplantation can shorten the time of anhepatic phase, without increasing the occurrence of post-reperfusion syndrome, ischemia re-perfusion injury and biliary tract complications.
3.Current status of surgery for portal hypertension in China: a national multi-center survey analysis
Lei ZHENG ; Haiyang LI ; Jizhou WANG ; Xiao LIANG ; Jian DOU ; Jitao WANG ; Qiang FAN ; Xiong DING ; Wenlong ZHAI ; Yun JIN ; Bo LI ; Songqing HE ; Tao LI ; Jun LIU ; Kui WANG ; Zhiwei LI ; Yongyi ZENG ; Yingmei SHAO ; Yang BU ; Dong SHANG ; Yong MA ; Cheng LOU ; Xinmin YIN ; Jiefeng HE ; Haihong ZHU ; Jincai WU ; Zhidan XU ; Dunzhu BASANG ; Jianguo LU ; Liting ZHANG ; Jianguo ZHAO ; Ling LYU ; Guoyue LYU ; Nim CHOI ; To Tan CHEUNG ; Meng LUO ; Wanguang ZHANG ; Xiaolong QI ; Xiaoping CHEN
Chinese Journal of Organ Transplantation 2023;44(3):152-159
Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.
4.Epidemiological investigation on a cluster epidemic of COVID-19 in a school in Longchuan County, Yunnan Province
Jizhou HAN ; Zhiqun HE ; Suoju XU ; Youdong GAO ; Yuecheng YANG ; Chaoliang DONG ; Yanling LI ; Lin LI ; Shitang YAO
Shanghai Journal of Preventive Medicine 2022;34(9):884-887
ObjectiveTo investigate a cluster epidemic of coronavirus disease 2019 (COVID-19) infections in a school in Longchuan County, Yunnan Province, and further guide the prevention and control of COVID-19 in the border area. MethodsAccording to the Protocol on Prevention and Control of Novel Coronavirus Pneumonia (8th Edition), an epidemiological investigation was performed on all COVID-19 cases to collect the information on demographics, onset, diagnosis and treatment, prognosis, and epidemiological history. Close contacts were also tracked to determine the transmission chains. ResultsIn this cluster epidemic, a total of 37 COVID-19 cases were identified, including 32 females and 5 males aged from 13 to 25 years, who were 35 students and 2 teachers. The student cases were found in four classes of two grades. Furthermore, gene sequencing showed that all cases had been infected with delta variants, belonging to the same transmission chain that was not related to the previous epidemics in Dehong Prefecture. In additionally, a total of 2 127 close contacts were found. After 21 days of centralized quarantine for medical observation, all close contacts tested negative for SARS-CoV-2. In the COVID-19 cases, only one case remained positive for SARS-CoV-2, while the other 36 cases were successfully treated and became negative. ConclusionThis school cluster is caused by the border villagers who contacted the water polluted with SARS-CoV-2. It warrants more strict management of students from border villages and their belongings to prevent similar epidemics in school settings.
5.Clinical efficacy of avatrombopag combined with recombinant human thrombopoietin versus avatrombopag in the treatment of severe thrombocytopenia associated with chronic liver disease
Yongshuai WANG ; Sai ZHANG ; Lei LI ; Wei WANG ; Wei WANG ; Shenyu ZHANG ; Huachuan SONG ; Huanzhang YAO ; Ruipeng SONG ; Lianxin LIU ; Jizhou WANG
Chinese Journal of Digestive Surgery 2022;21(2):281-286
Objective:To investigate the clinical efficacy of avatrombopag combined with recombinant human thrombopoietin (rhTPO) versus avatrombopag in the treatment of severe thrombocytopenia associated with chronic liver disease.Methods:The retrospective cohort study was conducted. The clinical data of 56 patients with severe thrombocytopenia associated with chronic liver disease who were admitted to the First Affiliated Hospital of University of Science and Technology of China from May 2020 to October 2021 were collected. There were 36 males and 20 females, aged from 33 to 74 years, with a median age of 54 years. Of 56 patients, 21 cases undergoing treatment of avatrombopag combined with rhTPO were allocated into the combined treatment group and 35 cases undergoing treatment of avatrombopag were allocated into the monotherapy group. Observation indicators: (1) changes of platelet after treatment; (2) adverse drug reaction. Follow-up was conducted using outpatient examination and telephone interview to detect changes of platelet and effects of treatment within 2 weeks after treatment. The follow-up was up to October 2021. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and compari-son between groups was analyzed using the chi-square test or Fisher exact probability. Repeated measurement data were analyzed using the repeated ANOVA. Results:(1) Changes of platelet after treatment. The platelet level within 1 to 5 days and 6 to 10 days after treatment in the combined treatment group were (35±19)×10 9/L and (73±41)×10 9/L, respectively. The above indicators of the monotherapy group were (40±30)×10 9/L and (70±51)×10 9/L, respectively. There was no significant difference in change trends of platelet before and after treatment between the two groups ( Fgroup=0.30, P>0.05). There was a significant difference in platelet count before and after treatment between the two groups ( Ftime=59.96, P<0.05). There was no interaction effect in change trends of platelet between the two groups ( Finteraction=0.40, P>0.05). The effective rates were 66.67%(14/21) in the combination therapy group and 54.29%(19/35) in the monotherapy group. There was no significant difference in the effective rate between the two groups ( χ2=0.83, P>0.05). (2) Adverse drug reaction. Cases with headache, dizziness, blood transfusion reaction, hematuria, proteinuria, fever, abdominal pain, diarrhea, dyspepsia, fatigue, nausea or peripheral tissue edema were 2, 4, 1, 2, 2, 7, 10, 6, 8, 14, 12, 5 in the combined treatment group, versus 5, 8, 1, 3, 5, 7, 19, 11,20, 19, 14, 5 in the monotherapy group, respectively. There was no significant difference in cases with headache, dizziness, blood transfusion reaction, hematuria, proteinuria between the two groups ( P>0.05), and there was no significant difference in cases with fever, abdominal pain, diarrhea, dyspepsia, fatigue, nausea, peripheral tissue edema between the two groups ( χ2=1.24, 0.23, 0.05, 1.91, 0.83, 2.04, 0.81, P>0.05). Conclusion:Both of avatrombopag combined with rhTPO and monotherapy of avatrom-bopag can be used to promote the platelet level in patients with severe thrombocytopenia associated with chronic liver disease, and avatrombopag combined with rhTPO does not provide better clinical benefits compared with monotherapy avatrombopag.
6.Classification and evolution of the surgical approach of laparoscopic hepatectomy
Decai YU ; Xiao LIANG ; Jizhou WANG ; Jianwei LI ; Hongguang WANG ; Qifan ZHANG
Chinese Journal of Digestive Surgery 2022;21(7):966-970
In the past 30 years, laparoscopic hepatectomy has developed rapidly, which multi-dimensionally promoted the innovation of hepatectomy technology and strategy. This is mainly attributed to the key factors such as the improvement of domestic and foreign scholars′ under-standing of liver anatomy, the conversion and application of laparotomy technology, the expansion of laparoscopic vision and the feedback in surgery related fields. The authors summarize the enlighten-ment, development, promotion and sublimation of laparoscopic hepatectomy, and discuss the classi-fication and evolution of the surgical approach of laparoscopic hepatectomy.
7.Processing and identification of delicate fat particles for clinical application
Chen CHENG ; Jizhou HE ; Qingfeng LI ; Yun XIE
Chinese Journal of Medical Aesthetics and Cosmetology 2022;28(3):177-181
Objective:In the process of fat grafting, there is no good solution to achieve delicate filling while retaining the viability of fat particle. There was still no research on the composition and activity of delicate fat particle. In this study, two different methods for delicate fat process were established to explore the feasibility and clinical efficacy.Methods:From December 2015 to June 2016, 5 patients (22-31 years old, with average 26.2 years) with abdominal liposuction in Shanghai Ninth People's Hospital were inclueded. The fat particles were obtained by floating method and filtration method respectively, and compared with emulsified fat/nanofat and traditional fat grafts. The cell viability and composition of adipose tissue were compared in each group through cell viability test, flow analysis and tissue staining.Results:The fat particles obtained by floating and filtration methods, emulsified fat could pass through OT needle. Cell viability test revealed the presence of living cells in the fat obtained by both methods, but not in the emulsified fat. Flow analysis showed that the expression of CD90 in floating group was higher than that in control group ( P=0.048). Conclusions:The delicate fat particle can be obtained by floating or filtration method, which can preserves the tissue integrity and cell viability; meanwhile it can achieve fine needle injection and clinical application.
8.A comparative study of time series models in predicting COVID-19 cases
Zhongqi LI ; Bilin TAO ; Mengyao ZHAN ; Zhuchao WU ; Jizhou WU ; Jianming WANG
Chinese Journal of Epidemiology 2021;42(3):421-426
Objective:To compare the performances of different time series models in predicting COVID-19 in different countries.Methods:We collected the daily confirmed case numbers of COVID-19 in the USA, India, and Brazil from April 1 to September 30, 2020, and then constructed an autoregressive integrated moving average (ARIMA) model and a recurrent neural network (RNN) model, respectively. We applied the mean absolute percentage error (MAPE) and root mean square error (RMSE) to compare the performances of the two models in predicting the case numbers from September 21 to September 30, 2020.Results:For the ARIMA models applied in the USA, India, and Brazil, the MAPEs were 13.18%, 9.18%, and 17.30%, respectively, and the RMSEs were 6 542.32, 8 069.50, and 3 954.59, respectively. For the RNN models applied in the USA, India, and Brazil, the MAPEs were 15.27%, 7.23% and 26.02%, respectively, and the RMSEs were 6 877.71, 6 457.07, and 5 950.88, respectively.Conclusions:The performance of the prediction models varied with country. The ARIMA model had a better prediction performance for COVID-19 in the USA and Brazil, while the RNN model was more suitable in India.
9.Identification and Molecular Analysis of Ixodid Ticks (Acari: Ixodidae) Infesting Domestic Animals and Tick-Borne Pathogens at the Tarim Basin of Southern Xinjiang, China
Li ZHAO ; Jizhou LV ; Fei LI ; Kairui LI ; Bo HE ; Luyao ZHANG ; Xueqing HAN ; Huiyu WANG ; Nicholas JOHNSON ; Xiangmei LIN ; Shaoqiang WU ; Yonghong LIU
The Korean Journal of Parasitology 2020;58(1):37-46
Livestock husbandry is vital to economy of the Tarim Basin, Xinjiang Autonomous Region, China. However, there have been few surveys of the distribution of ixodid ticks (Acari: Ixodidae) and tick-borne pathogens affecting domestic animals at these locations. In this study, 3,916 adult ixodid ticks infesting domestic animals were collected from 23 sampling sites during 2012-2016. Ticks were identified to species based on morphology, and the identification was confirmed based on mitochondrial 16S and 12S rRNA sequences. Ten tick species belonging to 4 genera were identified, including Rhipicephalus turanicus, Hyalomma anatolicum, Rh. bursa, H. asiaticum asiaticum, and Rh. sanguineus. DNA sequences of Rickettsia spp. (spotted fever group) and Anaplasma spp. were detected in these ticks. Phylogenetic analyses revealed possible existence of undescribed Babesia spp. and Borrelia spp. This study illustrates potential threat to domestic animals and humans from tick-borne pathogens.
10.Prognostic Value of TP53 Mutation for Transcatheter Arterial Chemoembolization Failure/Refractoriness in HBV-Related Advanced Hepatocellular Carcinoma
Miao XUE ; Yanqin WU ; Wenzhe FAN ; Jian GUO ; Jialiang WEI ; Hongyu WANG ; Jizhou TAN ; Yu WANG ; Wang YAO ; Yue ZHAO ; Jiaping LI
Cancer Research and Treatment 2020;52(3):925-937
Purpose:
This study aimed to investigate the clinicopathologic features and mutational landscape of patients with hepatitis B virus (HBV)–related advanced hepatocellular carcinomas (HCC) undergoing transcatheter arterial chemoembolization (TACE).
Materials and Methods:
From January 2017 to December 2018, 38 patients newly diagnosed with HBV-related advanced HCC were enrolled in the final analysis. Their pathological tissues and corresponding blood samples before TACE treatment were collected for whole-exome sequencing. Response to TACE was evaluated at 1-3 months after two consecutive use of TACE. Predictive factors were analyzed by univariate and multivariate analyses in a bivariate Logistic regression model. Enrichment of related pathways of all driver genes were acquired using the gene set enrichment analysis (GSEA).
Results:
Among 38 patients, 23 (60.5%) exhibited TACE failure/refractoriness. Patients with TACE failure/refractoriness showed higher frequency of TP53 mutation than their counterparts (p=0.020). Univariate and multivariate analyses showed that only vascular invasion and TP53 mutation were significantly correlated with TACE failure/refractoriness in HBV-related advanced HCC. Of the 16 patients without vascular invasion, eight (50.0%) had TP53 mutations, and TP53 mutation was associated with TACE failure/refractoriness (p=0.041). Moreover, GSEA showed that mitogen-activated protein kinase and apoptosis pathways induced by TP53 mutation were possibly associated with TACE failure/refractoriness.
Conclusion
Our study suggested that TP53 mutation was independently related with TACE efficacy, which may work via mitogen-activated protein kinase and apoptosis pathways. These findings may provide evidence to help distinguish patients who will particularly benefit from TACE from those who require more personalized therapeutic regimens and rigorous surveillance in HBV-related advanced HCC.

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