Objective: To explore the effect of transcatheter embolization combined with radiofrequency ablation (RFA) in treatment of VX2 liver tumors of rabbits. Methods: Sixty rabbit VX2 liver tumor models were randomly divided into 4 groups (each n=15). Fifteen minutes after TACE or transcatheter arterial embolization (TAE), RFA was performed in both TACE+RFA group and TAE+RFA group, respectively.And RFA group was only treated with RFA, TACE group underwent only TACE. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured 1 day before and 3 and 7 days after operation. Tumor growth rate, tumor necrosis rate and Suzuki score were measured 7 days after operation. The expression of heat shock protein 70 (HSP70) in liver lesions surrounding ablation zone or embolized zone was detected with immunohistochemistry 1, 3 and 7 days after operation, and hepatocyte apoptosis index and proliferation index were calculated. Results: The levels of ALT and AST in TACE+RFA group were higher than those in other groups 3 and 7 days after operation (all P<0.05). Seven days after operation, the Suzuki score in TACE+RFA group was higher than that in other groups, and tumor growth rates in TACE+RFA and TAE+RFA groups significantly decreased, while the necrosis rates in TACE+RFA and TAE+RFA groups increased compared with RFA and TACE groups (all P<0.05). The expression of HSP70 in hepatic lesions surrounding the ablation zone or embolized zone increased gradually 1, 3 and 7 days after operation, and in TACE+RFA group were higher than in other groups, in TAE+RFA group were higher than in TACE group and RFA group 3 days after operation (all P<0.05). The hepatocyte apoptosis index in hepatic lesions surrounding the ablation zone or embolized zone decreased gradually in all 4 groups 1, 3 and 7 days after operation, while in TACE+RFA group were higher than the other 3 groups, in TACE group 1 and 3 days after operation were higher than in TAE+RFA group and RFA group (all P<0.05). The hepatocyte proliferation index in 4 groups were higher 3 days after operation than that 1 and 7 days after operation, and compared with other groups, in TAE+RFA group were higher 1, 3 and 7 days after operation, in RFA group was higher 1 and 3 days after operation than in TACE+RFA group and TACE group (all P<0.05). Conclusion: The effects of TACE+RFA and TAE+RFA on inhibiting tumor growth are better than TACE and RFA alone for treatment of VX2 liver tumors of rabbits. Compared with TACE+RFA, TAE+RFA can promote hepatocyte proliferation and inhibit hepatocyte apoptosis more effectively with less liver damage.

ObjectiveTo investigate the efficacy of laparoscopic hepatectomy for regional hepatolithiasis.MethodsThe clinical data of 81 patients with regional hepatolithiasis who received laparoscopic hepatectomy at the Southwest Hospital from March 2007 to March 2011 were retrospectively analyzed.Based on the classification of the Guideline for the diagnosis and treatment of hepatolithiasis 2007 version and indications for open surgery,hepatic lobes with calculi,biliary stricture or dilated bile ducts were resected laparoscopically after preoperative examination.Bile ducts of the remnant hepatic lobes were explored using fiber choledochoscope or electronic choledochoscope for the prevention of residual stones. Results Laparoscopic hepatectomy was successfully performed on 72 patients,and the other 9 patients were converted to open surgery. Left lateral lobectomy ( segments Ⅱ,Ⅲ ) was performed on 20 patients,left hemihepatectomy ( segments Ⅱ,Ⅲ,Ⅳ ) on 30 patients,right posterior lobectomy ( segments Ⅵ,Ⅶ ) on 11 patients,right anterior lobectomy ( segments Ⅴ,Ⅷ ) on 6patients,right hemihepateetomy (segments Ⅴ,Ⅵ,Ⅶ,Ⅷ ) on 9 patients,hepatic Ⅲ segmentectomy on 2 patients and hepatic Ⅵ segmentectomy on 3 patients.Gallbladders were resected,and intermittent portal triad clamping was performed on 15 patients.Hepateetomy combined with biliary exploration and stone removal was performed on 57 patients.The mean operation time and operative blood loss were (328 ± 80)minutes and (451 ±288) ml,respectively.No operative mortality was observed.Sixteen patients had postoperative complications,including pulmonary infection in 2 patients,pleural effusion in 4 patients,encapsulated effusion in the resection margin in 6 patients,abdominal infection and abscess in 2 patients and wound infection in 2 patients.Of the 16patients with complications,9 were cured by medicine,6 by pleural or abdominal drainage and 1 by wound debridement.The mean duration of hospital stay was ( 13 + 6)days.The intraoperative stone clearance rate was 96％ (69/72),and the residual stone in 3 patients were removed by choledochoscopy.Sixty-nine patients were followed up for 7-55 months,7 patients had symptoms of cholangitis and 2 patients had common bile duct stone recurrence.ConclusionsLaparoscopie hepatectomy is sate and effective for regional hepatolithiasis.Accurate positioning of the stones and lesions pre- and intra-operatively,reasonable designing of the parenchymal transection plane,and anatomical liver resection are the key points for achiving good therapeutic effects.

ObjectiveTo investigate the effect of arsenic trioxide-loaded CalliSpheres beads (CBATO) in transarterial chemoembolization (TACE) in the treatment of rabbits with VX2 liver tumor. MethodsA total of 120 tumor-bearing rabbits were divided into control group, CalliSpheres beads (CB) group (blank beads for TACE), CBATO group, and conventional TACE (cTACE) group (arsenic trioxide lipiodol for TACE) using a random number table, with 30 rabbits in each group. Five rabbits in each group were sacrificed at 12 hours and on days 3, 7, and 14 after TACE, and immunohistochemistry was used to measure the proliferation index and apoptosis percentage of tumor cells in the residual tumor area. The tumor necrotic volume was measure on day 7 after TACE, and the growth rate and necrosis rate of tumor cells were calculated. Ten rabbits were randomly selected from each group for the observation of survival time. An analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups; the Kaplan-Meier survival analysis was used to evaluate survival time, and the log-rank test was used for comparison. ResultsOn day 7 after TACE, the CBATO group had a significantly lower growth rate and a significantly higher necrosis rate of tumor cells than the cTACE group, the CB group, and the control group (all P＜0.05). At each time point after TACE, there were significant differences in the proliferation index and apoptosis percentage of tumor cells between the CBATO group and the other three groups (all P＜0.05). The median survival time was 26 days in the CBATO group, 18.5 days in the CB group, 22 days in the cTACE group, and 15.5 days in the control group, and the CBATO group had a significantly longer survival time than the other three groups (χ2=3.95, 8.99, and 13.47, P=0.049, P=0.003, and P＜0.01). ConclusionCBATO has a better effect than cTACE and CB in the treatment of rabbits with VX2 liver tumor and can significantly improve tumor necrosis rate, promote the apoptosis of tumor cells, and prolong the survival time of experimental animals.

Objective:To investigate the morphological feature and clinical significance of MRI around tumor after drug-eluting bead transcatheter arterial chemoembolization (DEB-TACE) of primary hepatocellular carcinoma.Methods:We reviewed and analyzed the data of hepatocellular carcinoma patients admitted from January 2017 to December 2018 in the Department of Radiological Intervention of the First Affiliated Hospital of Zhengzhou University. A total of 42 patients were enrolled, including 35 males and 7 females, aged (57.0±11.9) years. For the first time after operation, MRI enhancement showed peri-tumor margin enhancement as the starting point of follow-up. Follow-up and measure enhanced edge thickness, delayed enhancement, progression or remission data.Results:A total of 49 tumors and 84 peritumoral enhancement margins were included in 42 patients, with 30 sharp type , 40 rough type and 14 nodular type. The thickness of sharp type is less than that of rough type and nsodular type, and the differences were statistically significant (all P<0.05). The sharp type is the majority of the tumors with maximum diameter <5 cm, rough type and nodule type are the majority of tumors with maximum diameter ≥5 cm. Most of the sharp type are continuously enhanced, while the rough type and nodular type are not. Most sharp type relief (93.3%, 28/30), while rough type (80.0%, 32/40) and nodular type ( n=12) are mostly of deterioration, the differences are statistically significant (all P<0.05). Conclusion:Compared with the rough type and nodular type, the sharp type usually occurs in smaller tumors and more prone to local mitigation in the enhanced morphology around MRI after DEB-TACE in primary hepatocellular carcinoma.

Objective:To evaluate whether underdilated stent could reduce the occurrence of hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS) creation.Methods:A total of 197 patients with decompensated liver cirrhosis, who had underwent TIPS creation at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, were analyzed retrospectively, including 110 males and 87 females with age 25-79 (54±11) years old. Uncovered and covered stents with 8 mm diameter were implanted in all subjects, and then dilated by balloon catheters with 6 mm or 8 mm diameter. The patients were divided into two groups, including underdilated group (6 mm, n=105) and control group (8 mm, n=92).Kaplan-Meier curves were used to illustrate cumulative rate of HE, and the differences were assessed with the log-rank test. Multivariate analyses with a Cox regression model were conducted to explore the risk factors for HE. Results:During a median follow-up period of 29 (12-54) months, 16 (15.2%) patients developed HE in the underdilated group and 27 (29.3%) patients in the control group. There was a significant difference in the cumulative rate of HE ( P=0.014), but no statistical differences were found in terms of variceal rebleeding, shunt dysfunction and survival between the two groups ( P=0.608, P=0.659, P=0.968). In multivariated analysis, group assignment (underdilated vs. control, HR=0.291, 95% CI 0.125-0.674, P=0.004) was identified as an independent risk factor for HE after TIPS creation. Conclusion:Underdilated TIPS could reduced the risk of HE compared with completely dilated TIPS, with comparable risk of variceal rebleeding, shunt dysfunction and mortality. And it is worthy of applying this technique to a large sample of patients in clinical practice.

Objective To investigate the cost-effect of transarterial chemoembolization (TACE) with CalliSpheres beads loaded with arsenic trioxide (ATO) (CBATO) versus ATO iodized oil emulsion (conventional TACE, cTACE) in the treatment of unresectable liver cancer. Methods A total of 100 patients with advanced liver cancer who attended The First Affiliated Hospital of Zhengzhou University from May 2017 to December 2018 were enrolled and divided into CBATO group( n =45) and cTACE group( n =55) according to the treatment regimen. Progression-free survival (PFS) was used to evaluate the efficacy of quality-adjusted life year (QALY), and European Quality of Life-5 Dimensions (EQ-5D) index was used to evaluate quality of life. The t -test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups; the number of surgeries, length of hospital stay, treatment cost, and incremental cost-effectiveness ratio (ICER) were calculated for the two groups, and then a cost-effect analysis was performed. Results Within the PFS time, the per capita hospital cost was 96 446 yuan in the CBATO group and 91 230.43 yuan in the cTACE group. There were significant differences between the two groups in the mean number of surgeries (2.5±0.7 vs 3.4±0.8, t =16.911, P < 0.01) and mean hospital stay (5.8±1.2 days vs 7.5±1.8 days, t =12.459, P < 0.01). The CBATO group had a significantly higher QALY than the cTACE group (0.804 vs 0.512). Compared with the cTACE group, the CBATO group had an ICER of 17 861.53 yuan/QALY for unresectable liver cancer. Conclusion Although CBATO has a higher surgery cost than cTACE, CBATO has a better clinical effect than cTACE and can reduce the number of surgeries and length of hospital stay, with a better postoperative quality of life than cTACE, suggesting that CBATO has marked cost-effect advantages.

Objective To investigate the effect of Yipi Yanggan prescription on the malignant transformation of liver stem cells in liver precancerous lesion induced by diethylnitrosamine (DEN) and its possible molecular mechanism. Methods A total of 35 male Sprague-Dawley rats were randomly divided into normal control group (blank group), DEN model group (model group), DEN+Yipi Yanggan prescription group (Yipi Yanggan prescription group), and DEN+Hugan tablet group (Hugan tablet group), with 5 rats in the blank group and 10 rats in the other three groups. Intraperitoneal injection of DEN was performed to establish a model of liver precancerous lesion, the rats were sacrificed after 16 weeks of administration. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin (Alb) were measured; liver tissue was collected to observe the changes in size and appearance and calculate liver weight ratio (liver index); HE staining and Sirius Red staining were used to observe the pathological and morphological changes of rat liver tissue; immunohistochemistry was used to measure the expression of OV6 and glutathione S-transferase-Pi (GST-Pi); RT-PCR was used to measure the mRNA expression of EpCAM, CD133, and CD90, and Western blot was used to measure the protein expression of PI3K, Akt, and mTOR and their phosphorylation level. A one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Compared with the model group, the Yipi Yanggan prescription group and the Hugan tablet group had significant improvements in liver pathology and morphology, significant reductions in liver index and the levels of ALT and AST, and a significant increase in the level of Alb (all P < 0.05), as well as significant reductions in the protein expression levels of GST-Pi, OV6, p-PI3K, p-Akt, and p-mTOR and the mRNA expression levels of EpCAM, CD133, and CD90 (all P < 0.05). Compared with the Hugan tablet group, the Yipi Yanggan prescription group showed a more significant protective effect on the liver, with significant reductions in liver index and the levels of ALT and AST, and a significant increase in the level of Alb (all P < 0.05), as well as significant reductions in the protein expression levels of GST-Pi, OV6, p-PI3K, p-Akt, and p-mTOR and the mRNA expression levels of EpCAM, CD133, and CD90 (all P < 0.05). Conclusion Yipi Yanggan prescription can improve liver precancerous lesion induced by DEN in rats by inhibiting the malignant transformation of liver stem cells, and its mechanism of action may be associated with the PI3K/Akt/mTOR signaling pathway.

OBJECTIVE: To study the effect of electroacupuncture (EA) on oxaliplatin-induced peripheral neuropathy (OIPN) in rats. METHODS: Male Sprague-Dawley rats were equally divided into 3 groups using a random number table: the control group, the OIPN group, and the EA (OIPN + EA) group, with 10 rats in each. The time courses of mechanical, cold sensitivity, and microcirculation blood flow intensity were determined. The morphology of the dorsal root ganglion (DRG) was observed by electron microscopic examination. The protein levels of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and the transient receptor potential (TRP) protein family in DRGs were assayed by Western blot. RESULTS: EA treatment significantly reduced mechanical allodynia and cold allodynia in OIPN rats (P<0.01). Notably, oxaliplatin treatment resulted in impaired microcirculatory blood flow and pathomorphological defects in DRGs (P<0.01). EA treatment increased the microcirculation blood flow and attenuated the pathological changes induced by oxaliplatin (P<0.01). In addition, the expression levels of Nrf2 and HO-1 were down-regulated, and the TRP protein family was over-expressed in the DRGs of OIPN rats (P<0.01). EA increased the expression levels of Nrf2 and HO-1 and decreased the level of TRP protein family in DRG (P<0.05 or P<0.01). CONCLUSION EA may be a potential alternative therapy for OIPN, and its mechanism may be mainly mediated by restoring the Nrf2/HO-1 signaling pathway.
Animals ; Electroacupuncture/methods* ; Hyperalgesia/therapy* ; Male ; Microcirculation ; NF-E2-Related Factor 2 ; Oxaliplatin/adverse effects* ; Peripheral Nervous System Diseases/chemically induced* ; Rats ; Rats, Sprague-Dawley

At present, the issues regarding multi-center clinical trials of new drugs of traditional Chinese medicine(TCM) remain: the lack of agreement on the content and scope of the ethical review among the ethics committee members of the center and the participating units results in repeated review, which leads to a time-consuming ethical review process. Moreover, the review capabilities of the ethics committees of various research centers are uneven, which is not necessarily beneficial to the protection of subjects' rights and safety. In view of the existing problems, to improve the efficiency of ethical review of multi-center clinical trials of new drugs of TCM and avoid repeated reviews, the TCM Clinical Evaluation Professional Committee of Chinese Pharmaceutical Association organized experts to formulate the "Consensus on collaborative ethical review of multi-center clinical trials of new drugs of TCM(version 1.0)"(hereinafter referred to as "Consensus"). The "Consensus" is formulated in accordance with the requirements of relevant documents such as but not limited to "the opinions on deepening the reform of the evaluation and approval system to encourage the innovation of pharmaceutical medical devices", "the regulations of ethical review of biomedical research involving human subjects". The "Consensus" covers the scope of application, formulation principles, conditions for the ethics committee of the center, sharing of ethical review resources, scope and procedure of collaborative review, rights and obligations, etc. The aims of the "Consensus" is to preliminarily explore and establish a scientific and operable ethical review procedure. Additionally, on the basis of fully protecting the rights and interests of the subjects, a collaborative ethical review agreement needs to be signed to clarify the ethical review responsibilities of all parties, to avoid repeated review, and to improve the efficiency and quality of ethical review in multi-center clinical trials of new drugs of TCM.
Biomedical Research ; Clinical Trials as Topic ; Consensus ; Drugs, Chinese Herbal ; Ethical Review ; Humans ; Medicine, Chinese Traditional ; Multicenter Studies as Topic ; Pharmaceutical Preparations

Since the 18th National Congress of the Communist Party of China(CPC), the CPC and the government have highligh-ted the development of traditional Chinese Medicine(TCM) and issued a series of policies, such as the Plan for Protection and Deve-lopment of Chinese Medicinal Materials(2015-2020) forwarded by the General Office of the State Council in 2015, the Plan for Healthy Development of Traditional Chinese Medicine(2015-2020) released by the General Office of the State Council in the same year, the Healthy China 2030 Plan published by the CPC Central Committee and the State Council in 2016, the Law of the People's Republic of China on Traditional Chinese Medicine which took effect on July 2017, On the Preservation and Innovative Development of Traditional Chinese Medicine promulgated by CPC Central Committee and the State Council in 2019, and Plan for the Development of Traditional Chinese Medicine during the 14th Five-Year Plan Period of China released by the General Office of the State Council in March 2022, to promote the development of the TCM industry, which have brought historical opportunities to the TCM industry. However, TCM industry faces various challenges in the development. In terms of drug development in TCM, the current studies mainly focused on the chemical research and technical requests, which neglected TCM characteristics and cased in conformity between new drug transformation of TCM and clinical practice. Therefore, a more considerable and profound authoritative guideline is needed, and innovative thought and research are necessary for academics and the industry. Through the investigation of the development TCM industry in recent years, this study summarized the policies on and trends of Chinese medicinal materials, new drug development in TCM, catalogue of national basic drugs, and national basic health insurance, and proposed suggestions for further development of TCM industry.
China ; Drugs, Chinese Herbal ; Humans ; Industry ; Medicine, Chinese Traditional ; Policy