Brucine suppresses proliferation and promotes apoptosis of human cholangiacarcinoma cells via the inhibition of COX2 expression.

Aims The aim of this study was to investigate the anti-tumor efficacy of brucine on intrahepatic cholangiocarcinoma (ICC). Methods ICC QBC939 cells were treated with brucine, cell viability, cell cycle and apoptosis were analyzed using CCK-8 and flow cytometry. The expression of COX-2 and apoptosis related proteins Casp3, Bax and Bcl-2 were detected by Western blot analysis. QBC939 cells were subcutaneously transplanted into nude mice and the mice were injected with brucine intraperitoneally. The expression of Ki67, COX-2 and apoptosis related proteins were detected by immunohistochemical staining and Western blot analysis. Results Brucine significantly inhibited the proliferation and cell cycle progression while promoted the apoptosis of QBC939 cells. The expression of the apoptotic proteins Casp3 and Bax was upregulated, while the expression of Bcl-2 and COX-2 was downregulated in QBC939 cells with brucine treatment. Moreover, the overexpression of COX-2 could antagonize the effects of brucine on QBC939 cells. In vivo, brucine inhibited subcutaneous tumor formation in nude mice, and the expression of Ki67, COX-2 and Bcl-2 decreased while the expression of Casp3 and Bax increased in tumor tissues from nude mice with brucine treatment. Conclusions Brucine can significantly inhibit the progression of cholangiocarcinoma in vitro and in vivo, and the mechanism may be related to the inhibition of COX-2 expression.

Secular trends of the prevalence of emaciation, overweight, and obesity among school-aged children in Yunnan province, 1985-2019: A serial cross-sectional surveillance study in China.

Objective: To understand the trends of nutrition in children and adolescents, which may further help to prevent and control chronic diseases in younger ages. Methods: The Chinese National Surveys on Students' Constitution and Health (CNSSCH) in Yunnan is a survey of growth conditions, physical fitness, and health status of students in Yunnan and uses a series of complex multistage stratified sampling of seven prefectures consisting of 16 counties. Sampling schools were held constant over 35 years. The participants were randomly selected among 7-18 aged students. We used data from 1985, 1991, 2000, 2005, 2010, 2014, and 2019 CNSSCH of Yunnan. According to body mass index (BMI) criteria of National Working Group for Obesity in China (WGOC-BMI criteria), a participant's nutrition (emaciation, overweight or obesity) was defined. This study is based on survey data from 129,520 participants in 1985 (n = 14,683), 1991 (n = 4,894), 1995 (n = 6,673), 2000 (n = 9,751), 2005 (n = 23,461), 2010 (n = 22,889), 2014 (n = 23,003) and 2019 (24,166). Results: Since 1985, the trends of emaciation over 35 years were decreasing. Regardless of gender, area, and age, the prevalence of obesity and overweight were increased. The average annual growth rate of overweight and obesity was quicker in rural areas and boys than in urban areas and girls. In Yunnan, emaciation, overweight, and obesity disparity in children were common phenomena, with differences in areas and gender. Conclusion: Children in Yunnan faced the triple burden of malnutrition (emaciation, overweight, and obesity). We should take comprehensive policies and effective intervention measures to decrease the rate of nutrition deficiencies in school-aged children.

Prevalence trends of hypertension and influence factors among children and adolescents aged 7-17 years in China, 2011-2015: A serial cross-sectional study.

Hypertension has rapidly increased in the last decades throughout the world. It is an emerging disease. However, limited information is available on secular trends and factors of childhood and adolescents' hypertension in China. In this study, 5-year successive data were derived from a cross-sectional study of the China Health and Nutrition Survey (CHNS) in 2011 and 2015. We used systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) at least 95th percentile on the basis of age, sex, and height percentiles to define hypertension (HBP). A total of 2,827 children and adolescents aged 7-17 years were included. The age-standardized prevalence of hypertension was increased significantly across 5 years: the standardized prevalence of hypertension was increased from 8.08% (2011) to 11.46% (2015) in China (P < 0.01). The mean SBP of boys increased from 101.21 to 102.79 mmHg, while the mean SBP of girls increased from 98.96 to 100.04 mmHg. The mean DBP of boys increased from 61.20 to 67.40 mmHg, while the mean DBP of girls increased from 64.34 to 65.76 mmHg. The prevalence of hypertension grew continuously in both sexes, but the pace of change for boys was more rapid than that for girls. This study confirmed that the association between rural (odds ratio [OR] = 1.394, 95%CI 1.032-1.883), overweight/obesity (OR = 2.621, 95%CI 1.506-4.562), and BP levels was highly correlated (P < 0.05). The possible protecting factors associated with hypertension were being a girl (OR = 0.788, 95%CI 0.595-1.043). There was no association between weekly physical activity, daily sleep duration, and hypertension (P > 0.05). Further in-depth analysis of influencing factors and comprehensive interventions should be urgently implemented to combat the hypertension epidemic among children and adolescents in China.

Elective Transjugular Intrahepatic Portosystemic Shunt Using Viatorr Stent-Grafts: A Single-Center Experience from China.

Background and Aims: Transjugular intrahepatic portosystemic shunt (TIPS) is a well-established approach for the management of variceal bleeding, refractory ascites, hepatic hydrothorax, and preoperative treatment of portal hypertension prior to major abdominal surgery in patients with compensated cirrhosis, and so on. This study aimed to investigate the safety and long-term efficacy of TIPS implantation using Viatorr TIPS stent-grafts. Material and Methods: A cohort of 59 patients undergoing TIPS placement using Viatorr TIPS stent-grafts were included, and the periprocedural events, and long-term mortality, shunt dysfunction, variceal rebleeding and incidence of hepatic encephalopathy (HE) were analyzed. Results: The technical success rate was 100%. The median portosystemic pressure gradient was reduced from 21 mmHg (interquatile range: 19-25) to 13 mmHg (interquatile range: 10-16) before and after TIPS, leading to a hemodynamic success rate of 72.9%. The cumulative rate of overall mortality was 34.2% at five years, and direct bilirubin (hazard ratio [HR] = 1.336, 95% confidence interval [CI]: 1.050-1.700, P = 0.018) and post-TIPS right atrial pressure (HR = 1.238, 95% CI: 1.015-1.510, P = 0.035) were independent predictors for mortality. The cumulative rates of shunt dysfunction and variceal rebleeding were 11.0% and 28.3% at five years, respectively, and portal venous pressure gradient (HR = 2.572, 95% CI: 1.094-6.047, P = 0.030) was the only independent predictor for shunt dysfunction. The cumulative four-year HE-free rate was 48.6%. No severe adverse event was noted during TIPS procedures. Conclusion: Elective TIPS implantation using Viatorr TIPS stent-grafts is generally safe, and the long-term efficacy is favorable for the treatment of cirrhotic patients with recurrent variceal bleeding or refractory ascites.

Clinical Outcomes of Transjugular Intrahepatic Portosystemic Shunt (Tips) Creation Using Fluency Versus Viatorr Stent-Grafts: A Single-Centre Retrospective Study.

PURPOSE: To investigate the effects of transjugular intrahepatic portosystemic shunt (TIPS) creation using Fluency versus Viatorr stent-grafts on the long-term clinical outcomes. MATERIALS AND METHODS: This was a single-center retrospective study from January 2010 to October 2021 in 213 patients receiving TIPS with Fluency (Fluency group, n = 154) versus Viatorr (Viatorr group, n = 59) stent-grafts. Inclusion criteria were: age > 18 years old and TIPS creation for variceal hemorrhage. Exclusion criteria were: age > 80 years old, concomitant chronic heart or lung disease, active tuberculosis or human immunodeficiency virus infection, extrahepatic malignancy, alcohol dependence, TIPS created outside of our hospital, without any follow-up data, or decline to participate. The primary outcome was primary patency rate and its associated risk factors. RESULTS: The 5-year cumulative primary patency rate was significantly higher in Viatorr group than in Fluency group (89.0% vs. 19.6%, p < 0.001), whereas the 5-year cumulative transplant-free survival rate (62.3% vs. 62.2%, p = 0.636) was comparable between two groups. Cox-regression models revealed that group (hazard ratio [HR]4.029, 95% confidence interval [CI] 1.486-10.927, p = 0.006), use of bare stents (HR 3.307, 95% CI 1.903-5.747, p < 0.001), and baseline portal vein thrombosis (HR 0.248, 95% CI 0.149-0.412, p < 0.001) were significantly associated with shunt patency. Incidences of adverse events were not significantly different between two groups (p > 0.05). CONCLUSIONS: TIPS creation using Viatorr stent-grafts is superior to using Fluency stent-grafts in terms of higher long-term primary patency rate but similar transplant-free survival rate.

Gold nano particles synthesized from Strychni semen and its anticancer activity in cholangiocarcinoma cell (KMCH-1).

Nanotechnology has been materialized as a proficient technology for the development of anticancer nanoparticles all the way through an environment-friendly approach. Conventionally, nanoparticles have been assembled by dissimilar methods, but regrettably rely on the negative impact on the natural environment. Amalgamation of nanoparticles by means of plant extract is alternate conservative methods. In the present study, we equipped gold nanoparticles (AuNPs) from Strychni semen; displayed as a less toxic and environment-friendly. Integration of AuNPs was famed by UV-absorbance which displays peak values. Moreover, high-resolution transmission electron microscopy (HR-TEM), energy dispersive X-ray analysis (EDX) and atomic force microscopy (AFM) substantiate the shape of the AuNPs in the combined materials. FTIR results exhibit the active molecules positioned in the flat surface of the AuNPs. Similarly, the anticancer effectiveness of AuNPs is considered in KMCH-1 cells. Also, AuNPs successfully aggravate cytotoxicity and apoptosis by conjugating apoptotic gene expressions in KMCH-1 cells. Eventually, our results confirm the synthesis of AuNPs from Strychni Semen shows anticancer effects with environment-friendly manner.

A meta-analysis of adoptive immunotherapy in postoperative hepatocellular carcinoma.

BACKGROUND: Adoptive immunotherapy (AIT) has been adopted as an adjuvant treatment for hepatocellular carcinoma (HCC) patients after curative therapy. However, the outcomes of AIT remain controversial. PURPOSE: The purpose of this study is to analyze the safety and efficacy of AIT with the recurrence rate and mortality. MATERIALS AND METHODS: We identified eight randomized controlled trials (RCTs) that adopted AIT to HCC after curative treatments. A meta-analysis was carried out to assess the recurrence rate and mortality. RESULTS: Eight RCTs with 964 patients were included in the study. The overall analysis showed that AIT treatment can not only decrease the 1-year (risk ratio [RR] =0.59, 95% confidence interval [95% CI] = 0.48-0.72, P < 0.00001), 2-year (RR = 0.69, 95% CI = 0.60-0.79, P < 0.00001), and 3-year (RR = 0.82, 95% CI = 0.74-091, P = 0.0001) recurrence, but also decrease the 1-year (RR = 0.43, 95% CI = 0.30-0.62, P = 0.00001), 2-year (RR = 0.56, 95% CI = 0.46-0.74, P < 0.00001), and 3-year (RR = 0.85, 95% CI = 0.73-0.99, P = 0.03) mortality. The results also indicate that the group of lymphokine-activated killer (LAK) cells showed lower pooled RR values compared to the group of cytokine-induced killer cells among every subgroups. However, the AIT treatment failed to affect the 5-year recurrence rate and mortality (P > 0.05). CONCLUSIONS: This review provides available evidences that AIT, especially the treatment of LAK, can be used to decrease the early recurrence and mortality of postoperative HCC but may not the long term.

Leptin promotes proliferation and metastasis of human gallbladder cancer through OB-Rb leptin receptor.

Emerging evidence has shown that leptin, an adipocyte-derived cytokine that is closely associated with obesity, play a significant role in carcinogenesis and tumorigenesis. However, its impact on gallbladder cancer (GBC) remains unclear. In this study, we firstly found that leptin and its functional receptor OB-Rb were significantly co-expressed in human GBC tissues and cell lines, the content of which were higher than those in normal human gallbladder tissues. Treatment with leptin promoted the proliferation, migration and invasion of GBC cells, which were attenuated by OB-Rb shRNA. Blocking in the G2/M period of cell cycle, increasing of MMP3 and MMP9, increasing of VEGF-C/D, activation of SOCS3/JAK2/p-STAT3 pathway was demonstrated after treatment with leptin. All of these positive responses were attenuated by OB-Rb receptor shRNA. Taken together, our findings suggest that leptin promoted the proliferation, migration and invasion of GBC cells by increasing OB-Rb expression through the SOCS3/JAK2/p-STAT3 signal pathway. Targeting the leptin/OB-Rb axis could be an attractive therapeutic strategy for treatment of GBC.