Background and purpose:Brucine is one of the active components from Strychnos nux vomica,with signifi cant analgesic,anti-inflammatory and platelet-aggregating inhibitory properties.Due to its cytotoxic effect,the anti-tumor effect of brucine has increasingly been appreciated.In this study,we investigated the impact of brucine on A549 cells proliferation,apoptosis as well as the underlying mechanisms.Methods:MTT assay was used to examine the cell viability,flow cytometric analysis and fluorescent microscope were applied to examine cell apoptosis,ELISA method was used to examine the effect of brucine on PGE2 release from A549 cells and RT-PCR analysis was used to measure mRNA content,western blotting analysis was used to measure protein expression and luciferase activity was detected to examine the effect of brucine on COX-2 promoter activity.Results:Brucine was able to suppress the proliferation of A549 cells and induce cell apoptosis to time-dependent and dose-dependent manner.To understand the mechanisms,COX-2 was identifi ed to be an important target molecule involved in the apoptosis induced by brucine because brucine could suppress the COX-2 mRNA,protein expressions as well as PGE2 release in A549 cells in a timedependent manner.Furthermore,overexpression of COX-2 abrogated brucine-induced cell apoptosis,in contrast,when A549 cells were transfected with COX-2 siRNA,the apoptotic effect of brucine was dramatically enhanced.Further analysis revealed that brucine was able to suppress COX-2 transcriptional activation.Conclusion:Brucine was able to induce lung cancer apoptosis via downregulation of COX-2.

Aim To evaluate the effects of Brucine of restraining transplanted tumor growth,prolonging their survival time and its toxicity on haematopoietic and immune systems as well as hepatic and renal function in mice transplanted with Hepatocarcinoma Heps cells.Methods ICR male mice of Hepatocarcinoma Heps tumor model(Heps mice)was made through Heps cells inoculation.Anti-tumor activity of Brucine was evaluated in terms of tumor inhibitory ratio and life elongational ratio of mice transplanted with Heps tumor.The toxicity of Brucine was measured the mice weight,immune organ weight,blood cell index(leukocyte,erythrocyte,platelet,and hemachrome protein),and hepatic function index(ALT,AST)as well as renal function index(BUN) of Heps mice.Results Brucine had significant restraining effect on the growth of Heps tumor in mice.Its inhibitory rate was 30.34%(1.61 mg?kg~(-1)),46.21%(3.23 mg?kg~(-1))and 42.07%(6.46 mg?kg~(-1))respectively,and 3.23 mg?kg~(-1)(1/20 LD_(50)) was the best dosage of Brucine for treating Heps tumor in vivo,while Brucine had no distinct effect of prolonging the life of Heps mice.Moreover,it enhanced the weight of body and thymus index as well as spleen index,and had no distinct influence on blood cell index as well as ALT,AST and BUN in Heps mice.Conclusion Brucine can inhibit the growth of transplanted Heps tumor,enhance the weight of immune organ index significantly,and has no toxicity on haematopoietic and immune systems as well as hepatic and renal function of mice transplanted with Heps tumor.It may be developed into a promising anticancer drug through further study

Objective To evaluate the effect of neoadjuvant chemotherapy on advanced gastric cancer before laparoscopic radical gastrectomy.Methods 46 advanced gastric cancer cases in our hospital from January 2010 to January 2013 were included in experimental group who were given two courses of neoadjuvant chemotherapy with FOLFOX regimen prior to surgery,the responsives (38 cases) received two more courses of neoadjuvant chemotherapy before surgery,and those in whom the chemotherapy was judged as ineffective (8 cases),received radical gastrectomy 21 days later.As a control,36 diseasematched cases went on upfront surgery without neoadjuvant chemotherapy.All these 82 cases underwent successful laparoscopic gastrectomy.Results The overall effective rate of neoadjuvant chemotherapy was 59％.Before the operation,the differences of pathological staging between the two groups were significantly different; The difference in operation time,the intraoperative blood loss and harvested lymph node number between the experimental group and control group was not statistically different (P ＞ 0.05).The R0 resection rate in experimental group (63％) was higher than in the control group (36％),P ＜0.05.The recurrence rate and mortality rate in experimental group was lower than that in the control group,P ＜ 0.05.Conclusions In advanced gastric carcinoma preoperative neoadjuvant chemotherapy significantly improved the resection rate and reduced postoperative recurrence and mortality rate.

Objective:To investigate the safety of minimally invasive liver resection for resectable hepatocellular carcinoma (HCC) complicated with portal hypertension.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 807 patients with resectable HCC who underwent minimally invasive liver resection in 8 medical centers, including Sir Run Run Shaw Hospital, Affiliated with the Zhejiang University School of Medicine et al, from June 2011 to November 2022 were collected. There were 670 males and 137 females, aged 58(50,66)years. Of the 807 patients, 173 cases with portal hypertension were divided into the portal hypertension group, and 634 cases without portal hypertension were divided into the non-portal hypertension group. Observation indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) intraoperative and post-operative situations; (3) subgroup analysis. Propensity score matching was done by the 1:1 nearest neighbor matching method, with the caliper setting as 0.001. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was constructed using the non-parameter rank sun test. Results:(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of the 807 patients, 268 cases were successfully matched, including 134 cases in the portal hypertension group and 134 cases in the non-portal hypertension group. The elimination of the tumor diameter and robot-assisted surgery confounding bias ensured comparability between the two groups after propensity score matching. (2) Intraoperative and postoperative situations. The occlusion time of porta hepatis, cases with intraoperative blood transfusion, cases with postoperative complication, cases with complication >Ⅱ grade of Clavien-Dindo classification, cases of Clavien-Dindo classification as Ⅰ grade, Ⅱ grade, Ⅲ grade, Ⅳ grade, cases with liver related complication were 27.0(15.0,43.0)minutes, 33, 55, 15, 13, 29, 14, 1, 37 in the portal hypertension group, versus 35.0(22.0,60.0)minutes, 17, 25, 5, 14, 9, 4, 1, 13 in the non-portal hypertension group, showing significant differences in the above indicators between the two groups ( Z=-2.15, χ2=6.30, 16.39, 4.38, 20.72, 14.16, P<0.05). (3) Subgroup analysis. Results of subgroups analysis showed that in cases with major live resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 243.5(174.6,296.3)minutes, 200.0(150.0,600.0)mL, 7.5(6.0,13.0)days in the portal hypertension group, versus 270.0(180.0,314.5)minutes, 200.0 (75.0,450.0)mL, 7.0(5.5,10.0)days in the non-portal hypertension group, showing no significant difference in the above indicators between the two groups ( Z=-0.54, -1.73, -0.92, P>0.05). In cases with non-major live resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 170.0(120.0,227.5)minutes, 100.0(50.0,200.0)mL, 8.0(5.0,10.0)days in the portal hypertension group, versus 170.0(120.0,227.5)minutes, 100.0(50.0,200.0)mL, 7.0(5.5,9.0)days in the non-portal hypertension group, showing no significant difference in the above indicators between the two groups ( Z=-1.39, -0.10, 1.05, P>0.05). In cases with anatomical liver resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 210.0(150.0,285.0)minutes, 150.0(50.0,200.0)mL, 8.0(6.0,9.3)days in the portal hypertension group, versus 225.5(146.3,306.8)minutes, 100.0(50.0,250.0)mL, 7.0(6.0,9.0)days in the non-portal hypertension group, showing no significant difference in the above indica-tors between the two groups ( Z=-0.75, -0.26, -0.91, P>0.05). In cases with non-anatomical liver resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 173.5(120.0,231.5)minutes, 175.0(50.0,300.0)mL, 7.0(5.0,11.0)days in the portal hyper-tension group, versus 186.0(123.0,262.5)minutes, 100.0(50.0,200.0)mL, 7.0(5.0,9.5)days in the non-portal hypertension group, showing no significant difference in the above indicators between the two groups ( Z=-0.97, -1.12, -0.98, P>0.05). Conclusion:Minimally invasive liver resection or even major liver resection is safe and feasible for screened HCC patients complicated with portal hyper-tension, but attention should be paid to the prevention and treatment of postoperative complications.