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.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.
3.Coating with flexible DNA network enhanced T-cell activation and tumor killing for adoptive cell therapy.
Ziyan ZHANG ; Qiaojuan LIU ; Jizhou TAN ; Xiaoxia ZHAN ; Ting LIU ; Yuting WANG ; Gen LU ; Minhao WU ; Yuanqing ZHANG
Acta Pharmaceutica Sinica B 2021;11(7):1965-1977
Adoptive cell therapy (ACT) is an emerging powerful cancer immunotherapy, which includes a complex process of genetic modification, stimulation and expansion. During these
4.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.
5.Thoughts and strategies on ethical issues in clinical research of surgery
Lijie TAN ; Ziyu LI ; Yan ZHANG ; Jizhou WANG ; Lianxin LIU ; Jianming WANG ; Yun LU ; Chaoqun MA ; Surong HUA ; Wenming WU ; Yupei ZHAO ; Hongwei YAO ; Jingjing HE ; Yuanyuan KONG ; Zhongtao ZHANG ; Ziwen LIU
Chinese Journal of Digestive Surgery 2019;18(1):57-64
Medical ethics has a long history and rich connotations.It has developed from the simple "medical morality" of ancient times to the modem medical ethics.The basic principles of medical ethics include autonomy,non-maleficence,beneficence,justice,and so on.Researchers often conduct clinical researches in the balance between achievements and ethical norms.Clinical researchers of surgery should have a deep understanding of medical ethical principles and strictly abide by medical ethics.Ethics committee should strictly perform their duties and play the role of inspection and supervision.Modem medical knowledges should be popularized throughout the society to make clinical research correctly understood.Adhering principles of ethics first,people orientation and cooperation practice,with patients' benefit as evaluation criteria,balance of surgical "Dao" and "Shu" can be achieved.
6.Effect of zinc ion on the expression of osteoblastic proteins in MC3T3-E1 cells in inflammatory environment
Jizhou TAN ; Ermin NIE ; Chunyuan ZHANG ; Rui JIANG
Chinese Journal of Stomatology 2016;51(8):486-490
Objective To investigate the effect of zinc ion on the expression of osteoblastic proteins.Methods Mice osteoblasts MC3T3-E1 cells were subcultured.Inflammatory environment model was established by tumor necrosis factor α(TNF-αt) at a concentration of 10 mg/L.According to different concentration of Zn2+,the cells were divided into TNF-α group,control group,group A(TNF-α+ 10-4 mol/L Zn2+),group B(TNF-α+ 10-5 mol/L Zn2+),group C(TNF-α+10-6 mol/L Zn2+).After 24,48,and 72 h of culture,cell counting kit-8(CCK-8) assay was used to analyze the proliferation of the cells.ALP activity was examined.Bone morphogenetic protein-2(BMP-2),Runt-related transcription factor 2(RUNX2),Osterix and receptor activator of NF-κB ligand(RANKL) protein levels were determined by Western blotting after 72 h of culture.Results The cells grew by adherence after 24 h.After 72 h,the cells grew dense,and the cells showed long spindle shape or irregular shape.The proliferation of osteoblasts in TNF-α group,group B and group C became lower than that in the control group(P<0.05),and was not significantly different between group A and the control group(P > 0.05).ALP activity examination demonstrated that the groups cultured for 72 h revealed the highest ALP activity and the most prominent differentation compared with 24 h and 48 h groups.ALP activity was significantly decreased in TNF-α group,group B and group C compared with control group(P<0.05),but was not significantly different between group A and control group(P>0.05).The protein levels of BMP-2,RUNX2 and Osterix were significantly decreased in TNF-α group,group B and group C compared with control group(P<0.05),while showed no significant difference between group A and the control group.Protein level of RANKL was significantly increased in TNF-α group,grope B and group C compared with control group(P<0.05),while showed no significant difference between group A and control group.Conclusions The concentration of 10-4 mol/L Zn2+ can significantly increase the expression of osteoblastic proteins such as ALP,BMP-2,RUNX2,Osterix and decrease the expression of RANKL in mice osteoblasts in TNF-α inflammatory environment.
7.Biocompatibility of Fe-Cr-Mo soft magnetic alloy with chromium plating
Yinhua XIA ; Ermin NIE ; Rui JIANG ; Chunyuan ZHANG ; Jindi ZENG ; Jizhou TAN
Chinese Journal of Tissue Engineering Research 2015;(47):7660-7664
BACKGROUND:Studies have demonstrated that Fe-Cr-Mo soft magnetic aloy has desired magnetic properties and machining properties. Surface Cr6+ plating treatment can significantly enhance the corrosion resistance in oral environment, but its biosecurity needs further testing. OBJECTIVE: To evaluate the biocompatibility of Fe-Cr-Mo soft magnetic aloy with chromium plating. METHODS:Logarithmic growth phase L929 cel suspension was obtained and seeded in 96-wel plates at a cel concentration of 6×107/L. Pure titanium extract, Fe-Cr-Mo soft magnetic aloy original extract, Cr6+-plated Fe-Cr-Mo soft magnetic aloy and PVC extract were added respectively. After 5 days of culture, cel morphology and adherent circumstances were observed. The absorbance value was detected using cel counting kit-8 assay. The relative growth rate of cels in each group was calculated. The cytotoxicity grades of materials were evaluated. RESULTS AND CONCLUSION:In the pure titanium extracts group, the cels with normal morphology showed good adherent growth and no cytotoxicity. In the Fe-Cr-Mo soft magnetic aloy original extract group, the cel morphology and growth status were both good, with occasionaly individual cel lysis. Scattered reddish brown particles were visible in the culture solution, showing no or very mild cytotoxicity. In Cr6+-plated Fe-Cr-Mo soft magnetic aloy extract group, the cels grew wel and showed no or very mild cytotoxicity. In PVC extract group, more than 70% of cels were vacuole-shaped and presented with pyknosis or dissolution, there was a large number of cel debris, and cel growth was inhibited in over 50% cels, showing moderate cytotoxicity or above. The cytotoxicity of Cr6+-plated Fe-Cr-Mo soft magnetic aloy extract was grade 0-1. These results demonstrate that Fe-Cr-Mo soft magnetic aloywith chromium plating has good biocompatibility.
8.Clinical application of temporary crown and cement materials: physical properties and biological safety
Ermin NIE ; Rui JIANG ; Chunyuan ZHANG ; Jindi ZENG ; Jizhou TAN
Chinese Journal of Tissue Engineering Research 2015;19(21):3392-3397
BACKGROUND:Temporary crown has been used widely in clinic. The physical properties and biological safety of temporary crown and cement materials are more superior along with the development of material science. OBJECTIVE:To summarize clinical application, physical properties and biological safety of the temporary crown and cement materials. METHODS:PubMed database was searched by the key words of temporary crown, provisional crown, temporary restoration, provisional restoration, interim restoration in English to retrieve relevant articles published from January 2004 to December 2014. Literatures addressing the temporary crown and cement materials were included, and the repetitive researches were excluded. RESULTS AND CONCLUSION:Through the clinical evaluation and experimental study, the physical properties (polymerization shrinkage, polymerization heat production, polymerization monomer release) and biological safety (cytotoxicity, irritation to the soft tissue) of the temporary crown and cement materials are the key problems needed to overcome. With the appearance of new materials and new fabrication methods, the temporary crown and adhesive materials have great application prospect and higher clinical value, but in the exploration process of the laboratory research and clinical application, there are many problems to be solved.
9.Long-term effects of five kinds of pulp capping agents: a comparative study
Ermin NIE ; Rui JIANG ; Chunyuan ZHANG ; Jindi ZENG ; Jizhou TAN
Chinese Journal of Tissue Engineering Research 2015;19(16):2557-2561
BACKGROUND:In the deep caries treatment, the pulp capping agent used in indirect pulp can induce the formation of dentin bridge (the complex of dental pulp and dentin), to protect the pulp tissue from stimulus and save the pulp vitality, completely avoid the occurrence of complications, with a higher clinical success rate. OBJECTIVE:To evaluate the differences in clinical efficacy of five kinds of calcium hydroxide preparations. METHODS:Totaly 236 patients with deep caries were selected and randomized to undergo indirect pulp with the double-component calcium hydroxide powder (n=46), Metapex with one-component injection dosage form and the chemical curing calcium hydroxide preparation (n=47), Dycal with the chemical curing calcium hydroxide preparation (n=45), Ionosit-Baseliner (n=49) and Calcimol LC (n=49) with one-component and the light curing calcium hydroxide preparation. The status of the dental pulp, the restoration and the root tip were observed at 1, 6, 12 and 24 months after operation. RESULTS AND CONCLUSION: There was no significant difference between the five groups in the success rate of indirect pulp capping at 1, 6 and 12 months (P> 0.05). At 24 months, the success rate of indirect pulp capping in the double-component calcium hydroxide powder group was lower than that in the other four groups (P < 0.05), but there was no significant difference between the latter four groups (P > 0.05). Metapex, Dycal, Ionosit-Baseliner and Calcimol LC al have a good effect on indirect pulp capping to deep caries, which can be used as agents for long-term pulp protection.
10.Temporary protection of cracked teeth using orthodontic band and resin temporary crown
Ermin NIE ; Rui JIANG ; Chunyuan ZHANG ; Jindi ZENG ; Jizhou TAN
Chinese Journal of Tissue Engineering Research 2015;19(30):4805-4809
BACKGROUND:In the comprehensive treatment of cracked teeth, the temporary protection using the orthodontic band and resin temporary crown can effectively prevent tooth fracture and protect the cracked teeth with a higher clinical success rate. OBJECTIVE:To evaluate the differences in clinical efficacy of orthodontic band and resin temporary crown on the temporary protection of cracked teeth. METHODS: Totaly 189 patients (97 males and 92 females, aged 19-65 years) with cracked teeth were selected, randomly divided into two groups and respectively underwent the temporary protection to cracked teeth with the orthodontic band (n=93) and resin temporary crown (n=96) in the comprehensive treatment. Retention effect, periodontal status and patient satisfaction were observed. RESULTS AND CONCLUSION:There were three cases with loose band and one case with faling band in the group of orthodontic band; there were two cases with faling band in the group of resin temporary crown. No significant difference between two groups in the retention effect was found. There were 11 cases of gingivitis or exploring hemorrhage in the group of orthodontic band and 2 cases in the group of resin temporary crown, indicating the periodontal status in the group of resin temporary crown was better than that in the group of orthodontic band (P< 0.05). There were 18 cases of lower satisfaction for poor color, expand feeling caused by the rubber band and discomfort caused by the band protruding from tooth surface in the group of orthodontic band; there were 3 cases of lower satisfaction in the group of resin temporary crown, and the patient satisfaction in the group of resin temporary crown were higher than that in the group of orthodontic band (P < 0.05). There is a better clinical effect in the temporary protection to cracked teeth by using the resin temporary crown, especialy in the terms of retention effect, periodontal status and patient satisfaction.

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