1.Epirubicin-loaded chitosan microspheres combined with microwave coagulation for treating hepatocellular carcinoma in mice
Jing YANG ; Senming WANG ; Manruing CAO ; Weimin DING ; Xigang HU ; Hui MEN ; Zexin WANG
Chinese Journal of Tissue Engineering Research 2010;14(8):1382-1385
BACKGROUND: The surgical resection rate of pdmary hepatic carcinoma is low, thus, the local treatment arose more attention. Microwave coagulation therapy can inactivate rather than kill the hepatic carcinoma ceils. Slow-release chemotherapy has been used in treating primary hepatic carcinoma because it can form local high concentrations and last for a long time. OBJECTIVE: To observe the therapeutic effect of epirubicin-loaded chitosan microspheres combined with microwave coagulation on treating hepatocellular carcinoma in mica. METHODS: Epirubicin-loaded chitosan microspheres were prepared by using emulsion-chemical cross linking technique. The surface morphology and particles size of chitosan microspheres were observed by scanning electron microscope. Ultraviolet speotrophotometer was used to analyze the entrapment efficiency, entrapment efficiency and cumulative release rates of epirubicin-loaded chitosan microspheres. Totally 24 mice with transplanted subcutaneous H22 HCC were divided into 4 groups, which were respectively treated by microwave coagulation therapy, intratumoral injected with physiological saline after microwave coagulation therapy, intratumoral injected with epirubicin after microwave coagulation therapy, intratumoral injected with epirubicin-ioaded chitosan microspheres after microwave coagulation therapy. The tumor inhibitory rate was calculated. RESULTS AND CONCLUSION: The average diameter of chitosan microsphere was 105 μm, with uniformed particle diameter. The ratio of drug loading was 11% and the entrapment was 80%. The in vitro drug cumulative release rate was 84% after 2 weeks. The tumor inhibitory rates of the microwave coagulation combined with physiological saline, epirubicin, and drug carried microspheres groups were 8%, 20%, and 47%. It suggested that chitosan microsphere is a safe and effective slow-release dosage form, which exhibits strong anti-tumor effect when combined with microwave treatment.
2.Regularity and mechanism of traditional Chinese medicine compound prescriptions in the treatment of primary osteoporosis
Jingtao ZHANG ; Minhua HU ; Shitao LIU ; Shuyuan LI ; Zexin JIANG ; Wenxing ZENG ; Luyao MA ; Qishi ZHOU
Chinese Journal of Tissue Engineering Research 2024;28(16):2555-2560
BACKGROUND:Traditional Chinese medicine compound prescription has a long history in the treatment of primary osteoporosis,and the curative effect is definite,but the medication rule and mechanism are not clear. OBJECTIVE:Using the methodology of data mining and network pharmacology,to explore and verify the law of drug use and molecular mechanism of modern traditional Chinese medicine in the treatment of primary osteoporosis. METHODS:The relevant documents included in CNKI,WanFang,VIP and PubMed were used as data sources,and the relevant data were statistically counted and extracted by Microsoft EXCEL2019,IBMSPSS25.0 and other software.The high-frequency drugs obtained from the data statistics were analyzed by association rules analysis and cluster analysis,and the core drug combination of traditional Chinese medicine compound prescription in the treatment of primary osteoporosis was obtained by combining the two results.The therapeutic mechanism of this combination was explained by network pharmacology and verified by molecular docking. RESULTS AND CONCLUSION:Finally,151 articles were included and 207 prescriptions were selected,involving 285 flavors of Chinese herbs.(1)Ten groups of important drug combinations were obtained through the above two analyses,among which the core drug combination with the highest confidence and improvement was"Drynaria-Eucommia-Angelica."The key components of the combination in the treatment of primary osteoporosis were quercetin,kaempferol,naringenin and so on.The core targets were SRC proto-oncogene,phosphoinositide-3-Kinase regulatory subunit 1 and RELA proto-oncogene.The main pathways were cancer signaling pathway,JAK-STAT signaling pathway,VEGF signaling pathway,and NF-κB signaling pathway.(2)The key active components were docked with the core targets,and the two showed a good combination.To conclude,Chinese herbal compound therapy in the treatment of primary osteoporosis can use a variety of active components to exert its efficacy through multiple signal pathways and acting on multiple targets,which can provide a theoretical basis for the research and development of new drugs for the follow-up treatment of primary osteoporosis.
3.HPLC method for the simultaneous determination of hydroxyphenyl esters and quaternary ammonium bacteriostatic agents in eye drops
Jin GAO ; Dan HU ; Yi BAO ; Xiaocui YU ; Zexin WANG ; Jing LIU ; Guiying ZHANG ; Yingying ZHAO ; Zhenyu CAO ; Chunpu LI ; Xiaoxu HONG
Drug Standards of China 2024;25(3):234-243
Objective:To establish a general method for the simultaneous determination of hydroxyphenyl esters and quaternary ammonium bacteriostatic agents in eye drops.Methods:The chromatographic analysis was per-formed on an Agilent C18 column(4.6 mm ×250 mm,5 μm)with 1%triethylamine solution(pH adjusted to 5.0 with phosphoric acid)as mobile phase A and methanol as mobile phase B.Gradient elution was performed at col-umn temperature of 40 ℃.The detection wavelength was 214 nm,the flow rate was 1 mL·min-1,and the injec-tion volume was 20 μL.Results:Methylparaben,ethylparaben,propylparaben,butylparaben,benzalkonium chlo-ride and benzalkonium bromide were 0.11-559.0,0.10-513.0,0.10-258.8,0.11-270.5,1.07-537.0 and 1.03-512.8 μg·mL-1,respectively.The linear range was good(r>0.999).The average recoveries of meth-ylparaben,benzalkonium bromide and benzalkonium chloride were 104.7%(RSD=1.3%),102.6%(RSD=1.1%)and 100.9%(RSD=1.1%),respectively.The contents of bacteriostatic agent in 100 batches of eye drops from 36 varieties of 12 enterprises were determined,and the accurate results were obtained.Conclusion:This meth-od provides a reference for the content quality control and safety evaluation of bacteriostatic agents in eye drops.
4.Current status and prospects of transarterial chemoembolization and its combined regimens in the treatment of hepatocellular carcinoma
Zexin HU ; Jintao HUANG ; Binyan ZHONG ; Jian SHEN ; Xiaoli ZHU
Journal of Clinical Hepatology 2024;40(1):175-180
Transarterial chemoembolization (TACE) is currently the primary treatment method for advanced liver cancer. This article elaborates on the current status of application of TACE in hepatocellular carcinoma from the aspects of existing techniques, patient selection, and efficacy assessment and summarizes the research advances and prospects of TACE combined with local treatment and systemic therapy, so as to provide new ideas for clinical practice and experimental studies.
5.Efficacy and safety of transcatheter arterial chemoembolization combined with targeted therapy and immunotherapy in treatment of patients with stage Ⅱb/Ⅲa hepatocellular carcinoma based on China Liver Cancer Staging
Zexin HU ; Jiaqing LI ; Wanci LI ; Binyan ZHONG ; Shuai ZHANG ; Jian SHEN ; Xiaoli ZHU
Journal of Clinical Hepatology 2024;40(3):550-555
ObjectiveTo evaluate the efficacy and safety of first-line transcatheter arterial chemoembolization (TACE) combined with targeted therapy and immunotherapy in the treatment of patients with stage Ⅱb/Ⅲa hepatocellular carcinoma (HCC) based on China Liver Cancer Staging (CNLC). MethodsA total of 198 patients who received first-line TACE combined with targeted therapy and immunotherapy or received TACE alone from January 2015 to December 2022 in the First Affiliated Hospital of Soochow University were enrolled in this study, and after propensity score matching, there were 50 patients in combination group and 50 patients in TACE group. The Kaplan-Meier method was used to calculate median overall survival (mOS) and median progression-free survival (mPFS). Modified Response Evaluation Criteria in Solid Tumors was used to evaluate objective response rate (ORR) and disease control rate (DCR), and Common Terminology Criteria for Adverse Events v5.0 was used to evaluate adverse events. The chi-square test was used for comparison of categorical data between two groups; the t-test was used for comparison of normally distributed continuous data between two groups, and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups. The Kaplan-Meier method was used to estimate survival time and calculate 95% confidence interval (CI), and the Log-rank test was used for comparison of mOS and mPFS between two groups. ResultsThe combination group had an mOS of 30.1 months (95%CI: 21.9 — 38.3), and the TACE group had an mOS of 14.5 months (95%CI: 11.0 — 18.0), with a significant difference between the two groups (χ2=17.8, P<0.001); the combination group had an mPFS of 10.3 months (95%CI: 8.8 — 11.8), and the TACE group had an mPFS of 7.1 months (95%CI: 5.8 — 8.4), with a significant difference between the two groups (χ2=10.4, P<0.001). There were significant differences between the combination group and the TACE group in ORR (84% vs 58%, P<0.05) and DCR (94% vs 80%, P<0.05). There was no significant difference between the combination group and the TACE group in the incidence rate of adverse events (24% vs 16%, P=0.317), and no adverse event-related deaths were observed in either group. ConclusionCompared with TACE alone, TACE combined with targeted therapy and immunotherapy has a better efficacy in the treatment of patients with CNLC stage Ⅱb/Ⅲa HCC, without increasing the incidence rate of severe adverse events.
6.Value of modified albumin-bilirubin grade in predicting the prognosis of patients with Child-Pugh class A unresectable hepatocellular carcinoma after transcatheter arterial chemoembolization combined with immunotherapy and anti-angiogenic drugs
Jiaqing LI ; Xiaoyang XU ; Zexin HU ; Shen ZHANG ; Binyan ZHONG ; Xiaoli ZHU
Journal of Clinical Hepatology 2024;40(12):2450-2456
ObjectiveTo investigate the ability of the modified albumin-bilirubin (mALBI) grade in predicting the prognosis of patients with Child-Pugh A unresectable hepatocellular carcinoma (uHCC) after transcatheter arterial chemoembolization (TACE) combined with immunotherapy and anti-angiogenic drugs (hereafter referred to as targeted immunotherapy). MethodsA retrospective analysis was performed for the data of 76 patients with Child-Pugh A uHCC who met the inclusion criteria and underwent TACE combined with targeted immunotherapy in The First Affiliated Hospital of Soochow University from January 2020 to January 2023, and according to the mALBI grade, they were divided into mALBI 1/2a group with 38 patients and mALBI 2b group with 38 patients. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Evaluation criteria included complete remission, partial remission, stable disease, and progressive disease. The independent-samples t test was used for comparison of normally distributed continuous data between groups, and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical variables between two groups. The Kaplan-Meier method was used to plot survival curves, and the Log-rank test was used for comparison of median OS (mOS) and median PFS (mPFS) between groups. The univariate and multivariate Cox proportional hazards models were used to analyze the influencing factors for prognosis. ResultsThere were significant differences in albumin and tumor burden between the two groups (both P<0.05). The 76 patients had an mOS of 25.2 months (95% confidence interval [CI]: 18.4 — 32.0), an mPFS of 9.4 months (95%CI: 7.1 — 11.7), an ORR of 63.2%, and a DCR of 82.9%. The mOS was 30.1 months (95%CI: 19.8 — 40.4) in the mALBI 1/2a group and 19.5 months (95%CI: 7.1 — 31.9) in the mALBI 2b group, and there was a significant difference in mOS between the two groups (χ2=4.490, P=0.034). The mALBI 1/2a group had an mPFS of 10.2 months (95%CI: 8.4 — 12.0), an ORR of 71.1%, and a DCR of 86.8%, while the mALBI 2b group had an mPFS of 7.6 months (95%CI: 4.6 — 10.6), an ORR of 55.3%, and a DCR of 78.9%; there were no significant differences in mPFS, ORR, and DCR between the two groups (all P>0.05). ECOG status, tumor burden, mALBI grade, portal vein invasion, and extrahepatic metastasis were independent risk factors for mOS in patients undergoing TACE combined with targeted immunotherapy (all P<0.05). There were no treatment-related deaths. ConclusionThe mALBI grade has a good value in predicting the survival of patients with Child-Pugh A uHCC undergoing TACE combined with targeted immunotherapy.
7.Status of HVPG clinical application in China in 2021
Wen ZHANG ; Fuquan LIU ; Linpeng ZHANG ; Huiguo DING ; Yuzheng ZHUGE ; Jitao WANG ; Lei LI ; Guangchuan WANG ; Hao WU ; Hui LI ; Guohong CAO ; Xuefeng LU ; Derun KONG ; Lin SUN ; Wei WU ; Junhui SUN ; Jiangtao LIU ; He ZHU ; Dongliang LI ; Wuhua GUO ; Hui XUE ; Yu WANG ; Jiancuo GENGZANG ; Tian ZHAO ; Min YUAN ; Shirong LIU ; Hui HUAN ; Meng NIU ; Xin LI ; Jun MA ; Qingliang ZHU ; Wenbo GUO ; Kunpeng ZHANG ; Xiaoliang ZHU ; Birun HUANG ; Jianan LI ; Weidong WANG ; Hongfeng YI ; Qi ZHANG ; Long GAO ; Guo ZHANG ; Zhongwei ZHAO ; Kai XIONG ; Zexin WANG ; Hong SHAN ; Mingsheng LI ; Xueqiang ZHANG ; Haibin SHI ; Xiaogang HU ; Kangshun ZHU ; Zhanguo ZHANG ; Hong JIANG ; Jianbo ZHAO ; Mingsheng HUANG ; Wenyong SHEN ; Lin ZHANG ; Feng XIE ; Zhiwei LI ; Changlong HOU ; Shengjuan HU ; Jianwei LU ; Xudong CUI ; Ting LU ; Shaoqi YANG ; Wei LIU ; Junping SHI ; Yanming LEI ; Jinlun BAO ; Tao WANG ; Weixin REN ; Xiaoli ZHU ; Yong WANG ; Lei YU ; Qiang YU ; Huiling XIANG ; Wenqiang LUO ; Xiaolong QI
Chinese Journal of Hepatology 2022;30(6):637-643
Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.