STAG2 Regulates Homologous Recombination Repair and Sensitivity to ATM Inhibition.

Stromal antigen 2 (STAG2), a subunit of the cohesin complex, is recurrently mutated in various tumors. However, the role of STAG2 in DNA repair and its therapeutic implications are largely unknown. Here it is reported that knockout of STAG2 results in increased double-stranded breaks (DSBs) and chromosomal aberrations by reducing homologous recombination (HR) repair, and confers hypersensitivity to inhibitors of ataxia telangiectasia mutated (ATMi), Poly ADP Ribose Polymerase (PARPi), or the combination of both. Of note, the impaired HR by STAG2-deficiency is mainly attributed to the restored expression of KMT5A, which in turn methylates H4K20 (H4K20me0) to H4K20me1 and thereby decreases the recruitment of BRCA1-BARD1 to chromatin. Importantly, STAG2 expression correlates with poor prognosis of cancer patients. STAG2 is identified as an important regulator of HR and a potential therapeutic strategy for STAG2-mutant tumors is elucidated.

Association between Early Immune-Related Adverse Events and Survival in Patients Treated with PD-1/PD-L1 Inhibitors.

BACKGROUND: Immune-related adverse events (irAEs) are side effects that reflect the activation of patients' immune systems after treatment with immune checkpoint inhibitors (ICIs). However, there is no meta-analysis on the effect of early irAEs on patient survival. Thus, we assessed the association between early irAEs and the survival of patients treated with ICIs. METHODS: PubMed, Embase, and Web of Science were searched from May 2010 to May 2020 for all the retrospective and prospective comparative studies to evaluate the hazard ratios (HRs) for death. A random-effects model was used to calculate the pooled HR for death, and heterogeneity was assessed using I² statistics. The main outcomes were overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 11 reports with 2077 patients were included. A significant association was observed between early irAEs and a favorable clinical outcome. Patients with early irAEs had prolonged OS (HR: 0.62, 95% confidence interval (CI): 0.53-0.74, p < 0.001) and PFS (HR: 0.53, 95% CI: 0.41-0.66, p < 0.001) compared to those without; these results were confirmed using a sensitivity analysis. The irAE types, malignancy types, and sample size were correlated with patients' clinical outcomes. CONCLUSIONS: Early irAEs, especially cutaneous irAEs, correlated with a better clinical outcome in patients treated with ICIs.

PARP in colorectal cancer: Molecular mechanisms, immunity, clinical trials, and drug combinations.

The changes in cell homeostasis in the tumor microenvironment may affect the development of colorectal cancer (CRC). Genomic instability is an important factor. Persistent genomic instability leads to epigenetic changes, and mutations are a major factor in the progression of CRC. Based on these mechanisms, it is reasonable to link poly (ADP-ribose) polymerase (PARP) with the treatment of CRC. PARP is mainly involved in DNA repair, which has an essential role in the DNA damage response and prevention of DNA damage, and maintains oxidation and superoxide redox homeostasis in the intracellular environment of the tumor. This article reviews the latest research progress on PARP and PARP inhibitors (PARPi) in CRC. It mainly includes molecular mechanisms, immunity, clinical trials, and combination strategies of CRC. The research of PARPi in CRC has broad prospects, and the combinations with other drugs are the main research direction in the future.

Biological Functions of the DNA Glycosylase NEIL3 and Its Role in Disease Progression Including Cancer.

The accumulation of oxidative DNA base damage can severely disrupt the integrity of the genome and is strongly associated with the development of cancer. DNA glycosylase is the critical enzyme that initiates the base excision repair (BER) pathway, recognizing and excising damaged bases. The Nei endonuclease VIII-like 3 (NEIL3) is an emerging DNA glycosylase essential in maintaining genome stability. With an in-depth study of the structure and function of NEIL3, we found that it has properties related to the process of base damage repair. For example, it not only prefers the base damage of single-stranded DNA (ssDNA), G-quadruplex and DNA interstrand crosslinks (ICLs), but also participates in the maintenance of replication fork stability and telomere integrity. In addition, NEIL3 is strongly associated with the progression of cancers and cardiovascular and neurological diseases, is incredibly significantly overexpressed in cancers, and may become an independent prognostic marker for cancer patients. Interestingly, circNEIL3, a circular RNA of exon-encoded origin by NEIL3, also promotes the development of multiple cancers. In this review, we have summarized the structure and the characteristics of NEIL3 to repair base damage. We have focused on NEIL3 and circNEIL3 in cancer development, progression and prognosis.

Osteopontin and its downstream carcinogenic molecules: regulatory mechanisms and prognostic value in cancer progression.

Osteopontin (OPN) is a multifunctional phosphorylated glycoprotein that is expressed at significantly elevated levels in various cancers. OPN overexpression is closely associated with the development of cancer progression such as proliferation, metastasis, angiogenesis, apoptosis resistance, drug resistance, and immunosuppression, and may also be an independent prognostic biomarker for a variety of cancers. This review broadly summarizes the mechanisms that regulate the expression of downstream oncogenic molecules after OPN binds to integrin receptors or CD44 receptors, which involve a complex intracellular "signaling traffic network" (including key kinases, signaling pathways, and transcription factors). In addition, we review the prognostic value of OPN, OPN synergistic downstream oncogenic molecules in the female breast, non-small cell lung, prostate, colorectal, gastric, and hepatocellular carcinomas. The prognostic value of OPN in tissues or blood may vary due to differences in study subjects or detection methods, and this aspect of the study requires further systematization with a view to applying the detection of OPN to clinical applications. Importantly, based on the fact that the oncogenic effect of OPN correlates with the expression of the above-mentioned oncogenic molecules, this work may provide some help in the study of combination therapy targeting OPN and the above-mentioned oncogenic molecules.

Periostin: a predictable molecule to prognosis and chemotherapy responses of gastrointestinal and hepato-biliary-pancreatic malignant tumors?

With the continuous development of medical science and technology, the medical community's understanding of the disease is constantly updated, just as strategies for treating malignant tumors are constantly updated. New diagnoses, follow-up indicators, and treatment plan formulations need more evidence to be supported. To date, radical surgical resection is still the preferred treatment for advanced digestive system malignancies, and combination therapy including chemotherapy and targeted therapy before or after surgery is aimed at improving the prognosis and quality of life of patients. However, if tumor recurrence, metastasis, chemotherapy, and drug resistance to targeted agents after surgery prevent the achievement of the desired therapeutic effect, and if neoadjuvant chemotherapy and targeted therapy cannot reduce the staging of the tumor, surgery cannot be performed. These are huge problems that we face now and will continue to face for some time. Relevant scientific data and evidence have been produced to explain unsatisfactory efficacy, such as epithelial-mesenchymal transformation, the tumor microenvironment, extracellular matrix proteins, cancer-related fibroblasts, and other factors that may be related to tumor progression and poor therapeutic effects. An extracellular matrix protein, periostin (POSTN), influences the above factors and has received multidisciplinary attention. In this paper, periostin and digestive system-related tumors are reviewed, and the production, mechanism of action, drug resistance correlation analysis, and coping strategies of periostin are summarized to further understand its characteristics. This work provides evidence for potential therapeutic targets for digestive system tumors in the future.

Characteristics of lymph node (No.5 and No.6) metastasis and significance of lymph node dissection in Siewert type II esophagogastric junction adenocarcinoma (AEG): No.5 and No.6 lymph node metastases of AEG and clearance.

BACKGROUND: To analyze the characteristics, related risk factors, and prognosis of lymph node metastasis (Number [No.] 5 and No.6) in the group of adenocarcinoma of esophagogastric junction (AEG). METHODS: The patients with Siewert II AEG who underwent total gastrectomy and D2 lymph node dissection from September 2015 to December 2018 in Lanzhou University Second Hospital were enrolled in this study. The pathological features of the postoperative specimens were analyzed (sex, age, maximum diameter, location, depth of invasion, degree of differentiation, neurological and vascular invasion, etc), and the lymph node metastasis rate of No.5, No.6 groups were calculated. The analysis was performed by IBM SPSS statistical software. The risk factors associated with lymph node metastasis in No.5 and No.6 groups were analyzed. Survival analysis was performed by Kaplan-M method, and survival rate was estimated, Log-rank test was used for comparison, and the difference was statistically significant at P < .05. RESULTS: There were 142 cases of Siewert type II AEG with the positive rate of No.5 lymph nodes being 10.81% (8/74), and the positive rate of No.6 lymph nodes was 8.33% (11/132). No.5 and No.6 lymph nodes metastasis were not associated with gender, age, tumor maximum diameter, location (cardiac left/cardiac right) (P > .05), and were associated with invasion depth, differentiation degree, nerve and vascular invasion (P < .05). In the No.5 lymph node-positive group, the 3-year Overall Survival (OS) was 25.0%, and the No.5 lymph node-negative group had a 5-year OS of 57.8%, which was statistically different (P < .05). The 3-year OS was 18.2% in No.6 node-positive group and 53.8% in No.6 node-negative group, and the difference was statistically significant (P < .05). CONCLUSION: For Siewert type II AEG, the lymph node metastasis rate was higher in No.5 and No.6 groups when the tumor invaded all layers of gastric wall and was poorly differentiated complicated with vascular nerve invasion, and the lymph node metastasis rate was lower at 3 years, which may be more appropriate for total gastrectomy +D2 lymph node dissection.

In vitro and in silico studies of bis (indol-3-yl) methane derivatives as potential α-glucosidase and α-amylase inhibitors.

In this paper, bis (indol-3-yl) methanes (BIMs) were synthesised and evaluated for their inhibitory activity against α-glucosidase and α-amylase. All synthesised compounds showed potential α-glucosidase and α-amylase inhibitory activities. Compounds 5 g (IC50: 7.54 ± 1.10 µM), 5e (IC50: 9.00 ± 0.97 µM), and 5 h (IC50: 9.57 ± 0.62 µM) presented strongest inhibitory activities against α-glucosidase, that were ∼ 30 times stronger than acarbose. Compounds 5 g (IC50: 32.18 ± 1.66 µM), 5 h (IC50: 31.47 ± 1.42 µM), and 5 s (IC50: 30.91 ± 0.86 µM) showed strongest inhibitory activities towards α-amylase, ∼ 2.5 times stronger than acarbose. The mechanisms and docking simulation of the compounds were also studied. Compounds 5 g and 5 h exhibited bifunctional inhibitory activity against these two enzymes. Furthermore, compounds showed no toxicity against 3T3-L1 cells and HepG2 cells.HighlightsA series of bis (indol-3-yl) methanes (BIMs) were synthesised and evaluated inhibitory activities against α-glucosidase and α-amylase.Compound 5g exhibited promising activity (IC50 = 7.54 ± 1.10 µM) against α-glucosidase.Compound 5s exhibited promising activity (IC50 = 30.91 ± 0.86 µM) against α-amylase.In silico studies were performed to confirm the binding interactions of synthetic compounds with the enzyme active site.

Elective Splenectomy Combined with Modified Hassab's or Sugiura Procedure for Portal Hypertension in Decompensated Cirrhosis.

Objective: Portal hypertension is a major complication of decompensated cirrhosis. In China, modified Hassab's and Sugiura procedure are the two major methods of nonshunting surgery. This study aims to compare the efficacy and safety of the two procedures for portal hypertension. Method: Between January 1994 and December 2009, 172 elective patients diagnosed with decompensated cirrhosis with significant hypersplenism adopted elective splenectomy for hypersplenism, and also modified Hassab's (n = 91) or Sugiura (n = 81) procedure was additionally performed to reduce the risk of variceal bleeding. Postoperative mortality and morbidity data were collected, and a retrospectively comparative analysis was conducted. Results: All of the patients were treated successfully without death during operation, and no variceal bleeding occurred during hospitalization. There were 4 (4.4%) deaths in Hassab's group and 3 (3.7%) deaths in Sugiura group postoperatively (P > 0.05). During follow-up, the survival rate was 90.2%, 82.42%, and 71.43% in Hassab's group and 96.29%, 81.48%, and 75.31% in Sugiura group in 1, 3, and 5 years (P > 0.05). There were 22/71 and 12/63 patients in each groups who suffered no deadly variceal bleeding (P = 0.11). Bleeding related death and no bleeding related death occurred in 7/23 and 3/13 patients in each group (P = 0.26 and 0.14, respectively). Conclusion: Elective splenectomy combined with modified Sugiura procedure seemed to be associated with a reduced trend of no deadly variceal bleeding compared with Hassab's procedure. As statistical significance was not found, further large scale and prospective study was warranted.

Inhibitory effects of petasin on human colon carcinoma cells mediated by inactivation of Akt/mTOR pathway.

BACKGROUND: Colorectal cancer is the third most common cancer worldwide and still lack of effective therapy so far. Petasin, a natural product found in plants of the genus Petasites, has been reported to possess anticancer activity. The present study aimed to investigate the anticolon cancer activity of petasin both in vitro and in vivo. The molecular mechanism of petasin was also further explored. METHODS: Caco-2, LoVo, SW-620, and HT-29 cell lines were used to detect the inhibitory effect of petasin on colon cancer proliferation. Cell viability was determined using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Cell apoptosis was analyzed by flow cytometry. Hoechst 33258 staining was used to visualize morphological changes. Cell migration was assessed using a wound-healing migration assay, and cell invasion was investigated using Transwell chambers. Western blotting assays were employed to evaluate the expression levels of proteins in the protein kinase B/mammalian target of rapamycin (Akt/mTOR) signaling pathway. Finally, in vivo activity of petasin was evaluated using the SW-620 subcutaneous tumor model established in Balb/c nude mice. Twelve rats were randomly divided into control group and 10 mg/kg petasin group. The tumor volume was calculated every 7 days for 28 days. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay was performed to assess the apoptotic effect of petasin. Differences between two groups were assessed by analysis of independent-sample t tests. RESULTS: Petasin significantly inhibited the proliferation of human colon carcinoma cell lines, induced apoptosis, and suppressed migration and invasion in SW-620 cells. Western blotting results showed that petasin decreased the phosphorylation of Akt (1.01 ±â€Š0.16 vs. 0.74 ±â€Š0.06, P = 0.042), mTOR (0.71 ±â€Š0.12 vs. 0.32 ±â€Š0.11, P = 0.013), and P70S6K (1.23 ±â€Š0.21 vs. 0.85 ±â€Š0.14, P = 0.008), elevated the expression of caspase-3 (0.41 ±â€Š0.09 vs. 0.74 ±â€Š0.12, P = 0.018) and caspase-9 (1.10 ±â€Š0.27 vs. 1.98 ±â€Š0.22, P = 0.009), decreased the Bcl-2 protein (2.75 ±â€Š0.47 vs. 1.51 ±â€Š0.36, P = 0.008), downregulated the expression of matrix metalloproteinase (MMP)-3 (1.51 ±â€Š0.31 vs. 0.82 ±â€Š0.11, P = 0.021) and MMP-9 (1.56 ±â€Š0.32 vs. 0.94 ±â€Š0.15, P = 0.039) in SW-620 cell. In vivo, 10 mg/kg petasin inhibited tumor growth in Balb/c nude mice (924.18 ±â€Š101.23 vs. 577.67 ±â€Š75.12 mm at day 28, P = 0.001) and induced apoptosis (3.6 ±â€Š0.7% vs. 36.0 ±â€Š4.9%, P = 0.001) in tumor tissues. CONCLUSIONS: Petasin inhibits the proliferation of colon cancer SW-620 cells via inactivating the Akt/mTOR pathway. Our findings suggest petasin as a potential candidate for colon cancer therapy.

PRISMA-efficacy and safety of lixisenatide for type 2 diabetes mellitus: A meta-analysis of randomized controlled trials.

OBJECTIVE: We aimed to systematically evaluate the efficacy and safety of lixisenatide in patients with type 2 diabetes mellitus. METHODS: PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, Google, Web of Science and the Chinese Science Citation Database were searched up to March 2018. Randomized controlled trials determining the efficacy and safety of lixisenatide in patients with type 2 diabetes mellitus were eligible for inclusion. Two authors independently extracted the data in a prespecified Microsoft Excel spreadsheet. A meta-analysis was performed using Review Manager 5.3 software. Weighted mean difference (WMD) and relative risk (RR) together with their corresponding 95% confidence intervals (CIs) were estimated, and only the random effects model was used in order to achieve a more conservative estimate of the efficacy and safety. RESULTS: Fourteen multicenter randomized controlled trials involving 11,947 patients were eligible for inclusion. Compared to placebo, lixisenatide could more significantly reduce the level of HbA1c (WMD=-0.44; 95% confidence interval [CI] [-0.55,-0.33]), and a higher proportion of lixisenatide-treated patients achieved the HbA1c level of < 7.0% (RR = 1.89, 95% CI [1.75-2.03]) and < 6.5% (RR = 3.03, 95% CI [2.54-3.63]) than the placebo-treated patients. Lixisenatide was also associated with a significant reduction in fasting plasma glucose and 2-hour postprandial plasma glucose levels. The risks for any adverse events, gastrointestinal adverse events, and symptomatic hypoglycemia significantly increased in the lixisenatide-treatedment group compared to those in the placebo group. However, lixisenatideit did not increase the risks of serious adverse events, death, or severe hypoglycemia. CONCLUSIONS: Lixisenatide was more effective than placebo in patients with type 2 diabetes mellitus, and the mild-to-moderate adverse events were found to be tolerated during the follow-up.

Efficacy and Safety of Endoscopic Intralesional Triamcinolone Injection for Benign Esophageal Strictures.

OBJECTIVES: To evaluate the efficacy and safety of endoscopic intralesional triamcinolone injection (ITI) for benign esophageal strictures combined with endoscopic dilation (ED). METHODS: Online databases including MEDLINE, EMBASE, the Cochrane Library, and Web of Science were comprehensively searched for prospective randomized control trials (RCTs) between 1966 and March 2018. A meta-analysis was conducted according to the methods recommended by the Cochrane Collaboration. RESULTS: Six RCTs consisting of 176 patients were selected. Meta-analysis results showed that additional ITI had a significant advantage in terms of stricture rate and required ED sessions. Surgery-related and non-surgery-related strictures showed similar results. Additional ITI was not associated with significantly increased risk of complications. CONCLUSIONS: Our meta-analysis showed that additional ITI therapy was supposed to be effective and safe for benign esophageal strictures as it reduced the stricture rate and required ED sessions. However, more RCTs are necessary to support these findings.

Probiotics Reduce Postoperative Infections in Patients Undergoing Colorectal Surgery: A Systematic Review and Meta-Analysis.

Background. We performed this meta-analysis to investigate the efficacy of probiotics on prevention of infection-related complications following colorectal resection. Method. PubMed, EMBASE, Cochrane Library, and the Web of Science were searched up to January 2016. According to the results, only randomized controlled trials that compared the efficacy of probiotics on patients with colorectal resection were included for meta-analysis. Results. Nine studies including a total of 1146 patients met the criteria (556 received multistrain probiotic bacteria, 590 with non-multistrain probiotic bacteria). The combination of multistrain probiotics was beneficial in the reduction of total infections (OR = 0.30, 95%CI: 0.15-0.61, p = 0.0009), including surgical site infections (SSI) (OR = 0.48, 95%CI: 0.25-0.89, p = 0.02) and nonsurgical site infections (NSSI) (OR = 0.36, 95%CI: 0.23-0.56, p < 0.00001). However, there was no significant reduction in total infections (OR = 0.74, 95%CI: 0.50-1.09, p = 0.13) or SSI (OR = 0.77, 95%CI: 0.52-1.12, p = 0.17) with the application of non-multistrains of probiotics. Conclusion. Combinations of multistrain probiotic bacteria showed promise in preventing the incidence of infections following colorectal surgery. However, the efficacy of one or two strains of probiotics remains undetermined.

Effect of Acute and Chronic Exposure to High Altitude on the Aerobic and Anaerobic Metabolism in Rats.

In this study, we aimed to investigate the effect of acute and chronic exposure to HA on the aerobic and anaerobic metabolism in liver by determining the hepatic levels of ICDH and ATP. Lactate levels in liver and blood were also examined. Rats were exposed to an altitude of 4,300 m for 30 days, and those without HA exposure were used as controls. We observed an increased expression of liver ICDH following acute exposure (days 1, 3, and 7), whereas the liver ATP concentration was reduced on day 1. No changes in the hepatic expression of ICDH and ATP were found in rats chronically exposed to HA. Lactate concentrations of liver and blood did not show any significant changes following HA exposure. Thus, aerobic metabolism may be the major metabolic pathway in response to HA hypoxia in order to acclimatize themselves to the stressful environments.

Hemodynamics and vasoactive substance levels during renal congestion that occurs in the anhepatic phase of liver transplantation.

AIM: To explore hemodynamics and vasoactive substance levels during renal vein congestion that occurs in the anhepatic phase of liver transplantation. METHODS: New Zealand rabbits received ligation of the hepatic pedicle, supra-hepatic vena cava and infra-hepatic vena cava [anhepatic phase group (APH); n = 8], the renal veins (RVL; n = 8), renal veins and hepatic pedicle [with the inferior vena cava left open) (RVHP; n = 8)], or a sham operation (SOP; n = 8). Hemodynamic parameters (systolic, diastolic, and mean arterial blood pressures) and the levels of serum bradykinin (BK) and angiotensin II (ANGII) were measured at baseline (0 min), and 10 min, 20 min, 30 min, and 45 min after the surgery. Correlation analyses were performed to evaluate the associations between hemodynamic parameters and levels of vasoactive substances. RESULTS: All experimental groups (APH, RVL, and RVHP) showed significant decreases in hemodynamic parameters (systolic, diastolic, and mean arterial blood pressures) compared to baseline levels, as well as compared to the SOP controls (P < 0.05 for all). In contrast, BK levels were significantly increased compared to baseline in the APH, RVL, and RVHP groups at all time points measured (P < 0.05 for all), whereas no change was observed in the SOP controls. There were no significant differences among the experimental groups for any measure at any time point. Further analyses revealed that systolic, diastolic, and mean arterial blood pressures were all negatively correlated with BK levels, and positively correlated with ANGII levels in the APH, RVL, and RVHP groups (P < 0.05 for all). CONCLUSION: In the anhepatic phase of orthotopic liver transplantation, renal vein congestion significantly impacts hemodynamic parameters, which correlate with serum BK and ANGII levels.

Transabdominal Preperitoneal (TAPP) Versus Totally Extraperitoneal (TEP) for Laparoscopic Hernia Repair: A Meta-Analysis.

PURPOSE: To perform a meta-analysis of randomized controlled trials (RCTs) comparing transabdominal preperitoneal (TAPP) with totally extraperitoneal (TEP) in regards of hernia recurrence, pain scores, operation time, time to return to usual activities, length of hospital stay, and total complications. MATERIALS AND METHODS: Online databases including Pubmed, Embase and the Cochrane Library were searched with terms "hernia repair," "totally extraperitoneal (TEP) repair," and "transabdominal preperitoneal (TAPP) repair," as well as the medical subject headings. Relevant RCTs were further analyzed using the methods recommended by the Cochrane Collaboration. RESULTS: A total of 10 RCTs enrolling 1047 patients were included. There was no significant difference in terms of hernia recurrence, pain scores, operation time, time to return to usual activities, hospital stay, total complications, and cost between the 2 groups. Subgroup analysis revealed that pain scores would be affected by many clinical factors, operation time was mainly determined by state and surgeon's experience. CONCLUSIONS: On the basis of current evidence, TEP as a modified and more complex laparoscopic procedure than TAPP, did not lead to a significant difference in aspects of clinical outcomes and complications. Therefore, we firstly recommended TAPP for laparoscopic hernia repair, especially for nonexpert surgeons. Further choices would be made according to the specific clinical characteristics of patients and surgeons.

Efficacy of antiviral therapy with nucleotide/nucleoside analogs after curative treatment for patients with hepatitis B virus-related hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: A systematic review was conducted to evaluate whether or not antiviral therapy with nucleotide/nucleoside analogs (NA) have survival benefit for patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative treatment. METHODS: An electronic search of PubMed, EMBASE, and the Cochrane Library was performed to identify comparative studies in which the adjuvant effects of NA for patients with HBV-related HCC after curative treatment were evaluated. Primary outcome included survival rate, and secondary outcomes included tumor recurrence rate and side effects. Review Manager 5.1.6 software was used for meta-analysis. RESULTS: Twelve studies involving 6682 patients were included in our review. Meta-analysis results demonstrated that significant differences favoring the antiviral treatment groups were observed in 1-year survival rate (RR: 0.65, 95% CI: 0.53-0.79, P<0.0001), 3-year survival rate (RR: 0.58, 95% CI: 0.46-0.74, P<0.0001), and 5-year survival rate (RR: 0.56, 95% CI: 0.43-0.74, P<0.0001) compared with the control group. After NA was administered, recurrence was significantly reduced after one year (RR: 0.77, 95% CI: 0.64-0.93, P=0.006) and three years (RR: 0.81, 95% CI: 0.71-0.93, P=0.002) but not after five years (RR: 0.94, 95% CI: 0.76-1.16, P=0.55) compared with non-NA therapy. CONCLUSION: Current evidence showed that antiviral therapy with NA could improve survival and reduce early recurrence for patients with HBV-related HCC after curative treatment. More high-quality prospective trials are expected.

Laparoscopic Roux-en-Y gastric bypass versus sleeve gastrectomy for obese patients with Type 2 diabetes: a meta-analysis of randomized controlled trials.

We aimed to evaluate the efficacy and safety of laparoscopic Roux-en-Y gastric bypass versus sleeve gastrectomy for obese patients with Type 2 diabetes. We searched the Cochrane Library, PubMed, EMBASE, Google Scholar, and the Chinese Wan fang database up to October 2013. Randomized controlled trials regarding the efficacy and safety of laparoscopic gastric bypass versus sleeve gastrectomy for obese diabetic patients were included. Two review authors independently abstracted data and assessed the risk of bias. The mean difference and relative risk were estimated with 95 per cent confidence intervals. Four randomized controlled trials met inclusion criteria. There was no significant difference between gastric bypass and sleeve gastrectomy groups with regard to glycosylated hemoglobin (mean difference [MD], 0.41%; 95% confidence interval [CI], -0.09 to 0.91), fasting plasma glucose (standardized MD, 0.61 mg/mL; 95% CI, -0.10 to 1.32), the numbers of subjects using oral antihyperglycemic medications and insulin (relative rate [RR], 1.53; 95% CI, 0.45 to 5.24; RR, 1.44; 95% CI, 0.47 to 4.39, respectively), body weight (MD, 0.42 kg; 95% CI, -5.01 to 5.85), body mass index (MD, 0.85 kg/m(2); 95% CI, 0.13 to 1.58), or waist circumference (MD, 1.59 cm; 95% CI, -3.02 to 6.19). However, cardiovascular risk was more significantly lessened in the gastric bypass group. Our meta-analysis demonstrated that compared with laparoscopic sleeve gastrectomy, Roux-en-Y gastric bypass offers equal efficacy for treatment of diabetes in obese patients but is associated with a significantly decreased cardiovascular risk.

Study on the efficacies of splenic pedicle transection by using manual manipulation and Endo-GIA procedure for laparoscopic splenectomy.

Laparoscopy splenectomy (LS) was adopted in surgery from 1980s, it has become the main way of exploring for treating spleen diseases. Compared with conventional open surgery, LS has been gradually accepted by physicians and patients due to its advantages, including minimal surgical injury, less intraoperative blood loss, quick postoperative recovery, shorter hospital period, better cosmetic result, less risk of postoperative infections and improved postoperative quality of life Here, we try to investigate the splenic pedicle transection by using Endo-GIA (a linear stapling device) procedure and manual manipulation of secondary splenic pedicle for LS. A retrospective study was conducted on 60 patients who underwent LS. And patients were divided into two groups. 30 patients (group A) received splenic pedicle transection with Endo-GIA procedure and in the other 30 patients (group B) underwent secondary splenic pedicle transection for LS. Perioperative outcome measures of each group were recorded, including operation duration, intraoperative blood loss, postoperative flatus pass time, postoperative complications, drainage duration, hospital cost and length of hospital stay. Surgeries were successfully achieved in 60 patients. The operative duration of group A was significantly shorter than that of group B. However, group B was significantly superior over Endo-GIA group in terms of the intraoperative blood loss, postoperative flatus pass time, drainage duration, length of hospital stay and total cost of hospital stays. No significant differences were observed in postoperative fever, ascites and hyperamylasemia between two groups. Both of these two approaches for LS are safe and feasible. However, compared with Endo-GIA procedure, manual manipulation of secondary splenic pedicle for LS may leading to less intraoperative blood loss, results in less hospital expense, and hence can be widely adopted in clinical practice.

The role of death receptor 3 in the biological behavior of hepatocellular carcinoma cells.

Death receptor 3 (DR3) belongs to the tumor necrosis factor (TNF) receptor superfamily, primarily found in lymphoid tissues. Reports have determined that DR3 may also be distributed in numerous types of tumors. Therefore, it is thought that DR3 may have an important role in the process of tumorigenesis. The aim of the present study was to observe the effect of silencing DR3 expression on hepatocarcinoma cell growth, apoptosis and invasion in order to elucidate the role of DR3 in tumor development. The hepatocarcinoma cell lines (HepG2, Huh7, SMMC7721 and Bel­7402) and normal human liver cells (HL­7702) were transfected with three stealth RNA interference (RNAi) sequences that target the DR3 gene. Reverse transcription quantitative polymerase chain reaction was used to detect the expression levels of DR3 in hepatocarcinoma cell lines and normal liver HL­7702 cells. MTT assay and flow cytometry (FCM) were used to determine the rates of cell proliferation and apoptosis, respectively. Following silencing of the DR3 gene, western blot analysis was used to determine the protein expression of P53, Fas, Caspase8, nuclear factor kappa­light­chain­enhancer of activated B cells (NF­κB) and Caspase3. DR3 messenger RNA (mRNA) expression in hepatocarcinoma cell lines was significantly increased compared with that in the normal liver cell line. Three targeted DR3 gene small interfering RNAs significantly inhibited DR3 gene expression in Bel­7402 cells at the nucleic acid level. AF02670.1_stealth_883 and cocktail demonstrated the most efficient inhibition of DR3 gene expression at 48 and 72 h following transfection, with mRNA inhibition rates of 89.46 and 92.75%, and 90.53 and 94.25% (P<0.01), respectively. Cell viability was significantly reduced by AF02670.1_stealth_883 and RNAi cocktail at 24, 48 and 72 h following transfection. The inhibition rates of cell proliferation were 50.76 and 61.76% (P<0.05) at 72 h following transfection. FCM revealed that AF02670.1_stealth_883 and RNAi cocktail also induced apoptosis in Bel­7402 cells at 72 h following transfection. Reduction of NF­κB and P53 levels was observed (P<0.05) in Bel­7402 cells following DR3 silencing, whereas levels of Fas, Caspase3 and Caspase8 were markedly elevated (P<0.05). DR3 expression levels in hepatocellular carcinoma cells were significantly higher than those in normal cells. DR3 silencing effectively inhibited proliferation and invasion of hepatocellular carcinoma cells in vitro. However, silencing of the DR3 gene affect levels of apoptosis antigen­3 ligand in cells, therefore indicating that it may be involved with other pathways that regulate apoptosis in HCCs. In conclusion, the results of the present study indicated that DR3 may be a promising therapeutic target molecule for further study of hepatocellular carcinoma gene therapy.