Long Non-coding RNAs Regulating Macrophage Polarization in Liver Cancer.

Primary liver cancer is the second leading cause of cancer-related death worldwide. At present, liver cancer is often in an advanced stage once diagnosed, and treatment effects are generally poor. Therefore, there is an urgent need for other powerful treatments. Macrophages are an important component of the tumor microenvironment, and macrophage polarization is crucial to tumor proliferation and differentiation. Regulatory interactions between macrophage subtypes, such as M1 and M2, lead to a number of clinical outcomes, including tumor progression and metastasis. So, it is important to study the drivers of this process. Long non-coding RNA has been widely proven to be of great value in the early diagnosis and treatment of tumors. Many studies have shown that long non-coding RNA participates in macrophage polarization through its ability to drive M1 or M2 polarization, thereby participating in the occurrence and development of liver cancer. In this article, we systematically elaborated on the long non-coding RNAs involved in the polarization of liver cancer macrophages, hoping to provide a new idea for the early diagnosis and treatment of liver cancer. Liver cancer- related studies were retrieved from PubMed. Based on our identification of LncRNA and macrophage polarization as powerful therapies for liver cancer, we analyzed research articles in the PubMed system in the last ten years on the crosstalk between LncRNA and macrophage polarization. By targeting M1/M2 macrophage polarization, LncRNA may promote or suppress liver cancer, and the references are determined primarily by the article's impact factor. Consequently, the specific mechanism of action between LncRNA and M1/M2 macrophage polarization was explored, along with the role of their crosstalk in the occurrence, proliferation, and metastasis of liver cancer. lncRNA is bidirectionally expressed in liver cancer and can target macrophage polarization to regulate tumor behavior. lncRNA mainly functions as ceRNA and can participate in the crosstalk between liver cancer cells and macrophages through extracellular vesicles. lncRNA can potentially participate in the immunotherapy of liver cancer by targeting macrophages and becoming a new biomolecular marker of liver cancer.

LncRNA TINCR: an irreplaceable biological target in human malignancies.

BACKGROUND: Currently, malignant tumors of the digestive system tend to affect younger people, which has brought a catastrophic burden to people around the world. lncRNA has gained considerable attention because of its importance in the early diagnosis and treatment of tumors. In addition, since terminal differentiation-induced ncRNA ( abbreviated as TINCR )was reported in a Nature article, it has received focus on targeted therapy of tumors, especially in digestive system malignant tumors. This review aims to reveal and summarize its important molecular mechanisms in digestive system malignancies. METHOD: In this review, relevant research involving the relationship between TINCR and digestive system malignancies are collected through systematic retrieval of PubMed. RESULTS: TINCR is expressed bidirectionally in malignant tumors of the digestive system. TINCR functions primarily as a ceRNA in digestive system tumors, and TINCR also functions at the transcriptional level. CONCLUSION: lncRNA TINCR has the potential to become a novel biomolecular marker of the digestive system.

Genetic Diversity, Complicated Recombination, and Deteriorating Drug Resistance Among HIV-1-Infected Individuals in Wuhan, China.

To identify genotype distribution and drug resistance in people infected by HIV-1 in Wuhan, China, 105 infected people diagnosed with HIV-1 from January to December in 2019 were involved in this study. Ninety-eight gag genes, 101 PR genes, and 98 RT genes were successfully amplified. The phylogenetic analysis results showed that CRF01_AE (38.2%) and CRF07_BC (35.3%) were the two dominant genotypes, followed by CRF55_01B (6.9%), CRF59_01B (2.0%), B (2.0%), B' (2.0%), CRF08_BC (1.0%), CRF80_0107 (1.0%), and unique recombinant form (URF) (11.8%). Most URFs were the recombinants between CRF01_AE and CRF07_BC or CRF07_BC and CRF55_01B. Among the 93 subjects of antiretroviral therapy (ART)-naive, transmitted drug resistance against non-nucleoside reverse transcriptase inhibitors (NNRTIs) was 23.9%, of which V179D/E was the most frequent mutation, accounting for 18.2%. Among the 12 subjects of ART-experienced, drug resistance to first-line regimens developed severely.

Selective Esophagogastric Devascularization in the Modified Sugiura Procedure for Patients with Cirrhotic Hemorrhagic Portal Hypertension: A Randomized Controlled Trial.

Aim: Portal hypertension is a series of syndrome commonly seen with advanced cirrhosis, which seriously affects patient's quality of life and survival. This study was designed to access the efficacy and safety of selective esophagogastric devascularization in the modified Sugiura procedure for patients with cirrhotic hemorrhagic portal hypertension. Methods: Sixty patients with hepatitis B cirrhotic hemorrhagic portal hypertension and meeting the inclusion criteria were selected and randomly divided by using computer into the selective modified Sugiura group (sMSP group, n = 30) and the modified Sugiura group (MSP group, n = 30). The primary endpoint measurement is the postoperative rebleeding rate. Secondary endpoint measurements included free portal venous pressure, liver Child-Pugh score, liver volume, portal vein width and blood flow velocity, survival rate, quality of life, and dysphagia as well as other complications one year postoperatively. This trial is registered with ChiCTR, number ChiCTR2000033468. Results: There was no statistically significant difference in rebleeding rates within one year after surgery between patients in the sMSP and MSP groups (χ = 0.11, p=0.73). In comparison with the MSP group, the Child-Pugh score of liver function in the sMSP group significantly increased (χ = 6.4, p=0.04) and the incidence of dysphagia was significantly reduced (χ = 6.23, p=0.01) one year after surgery. There was a statistically significant difference in the quality of life between the two groups. However, there were no statistically significant differences in free portal venous pressure (MD = -3.44, 95% CI: -7.87 to 0.98, p=0.12), postoperative liver volume (3 months: MD = -258.81, 95% CI: -723.21 to 205.57, p=0.24; 1 year: MD = -320.12, 95% CI: -438.43 to 102.78, p=0.16), postoperative portal vein width (3 months: MD = -0.06, p=0.50; 1 year: MD = 0.17, p=0.21), portal vein flow velocity (3 months: MD = 1.64, p=0.21; 1 year: MD = -1.19, p=0.57), 1-year survival rate (χ = 1.01, p=0.31), and other complications between the two groups. Conclusions: Selective esophagogastric devascularization in the modified Sugiura procedure may not lower the incidence of rebleeding in the short term based on our findings. However, it may significantly improve quality of life of patients with cirrhotic hemorrhagic portal hypertension, improve liver function, and reduce postoperative dysphagia.

Ginsenoside Rh1 inhibits colorectal cancer cell migration and invasion in vitro and tumor growth in vivo.

Colorectal cancer (CRC) is the third leading cause of cancer-associated mortality worldwide. Ginsenoside Rh1 (Rh1) is a traditional medicine monomer with antitumor activity; however, the effects of Rh1 in CRC remain to be determined. In the present study, SW620 cells were treated with different concentrations of Rh1. Cell Counting Kit-8, wound healing and Transwell assays were performed to measure cell viability and proliferation, migration and invasion, respectively. Subsequently, the mRNA expression levels of matrix metallopeptidase (MMP)1, MMP3 and tissue inhibitor of metalloproteinases 3 (TIMP3) were detected by reverse transcription-quantitative PCR analysis. In addition, the protein expression levels of MMP1, MMP3, TIMP3, and total or phosphorylated (p-)ERK1/2, P38, JNK were detected by western blotting. Furthermore, tumor growth was examined in a nude mouse xenograft model. The results of the present study indicated that Rh1 was not toxic to CRC cells at various concentrations (0, 50 or 100 µM) and treatment durations (24 or 48 h). However, cell proliferation was suppressed by Rh1 in a dose-dependent manner. Rh1 (100 µM) significantly inhibited cell migration and invasion in vitro. Additionally, Rh1 suppressed the mRNA and protein expression of MMP1 and MMP3, and promoted TIMP3 expression. Rh1 decreased the ratios of p-P38/P38, p-ERK1/2/ERK1-2 and p-JNK/JNK in vitro and in vivo, which suggested that Rh1 inactivated the mitogen-activated protein kinase (MAPK) signaling pathway. Notably, Rh1 markedly decreased tumor volume and weight in vivo. In conclusion, the present study demonstrated that Rh1 inhibited the proliferation, migration and invasion of CRC cells in vitro and tumor growth in vivo. This inhibition was at least partially due to the inhibition of MMP1 and MMP3 expression, the increase in TIMP3 expression level and the MAPK signaling pathway inactivation. Therefore, Rh1 may effectively inhibit the development of CRC as an anticancer drug, and may have a supporting effect during CRC treatment.

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.

Profilin 1, negatively regulated by microRNA-19a-3p, serves as a tumor suppressor in human hepatocellular carcinoma.

Profilin 1 (PFN1) is a critical actin-regulatory protein; however, its functional role in hepatocellular carcinoma (HCC) progression remains to be further elucidated. In the present study, we observed that the expression levels of PFN1 were significantly decreased in HCC tissues and cell lines. Low PFN1 expression was significantly correlated with aggressive clinicopathological characteristics and poor prognosis of HCC patients. Further in vitro experiments demonstrated that overexpression of PFN1 remarkably inhibited the proliferation, migration, invasion and EMT of HCC cells. Moreover, we also found that PFN1 was a direct target gene of miR-19a-3p, and in HCC tissues, and there was a significantly inverse correlation between PFN1 mRNA and miR-19a-3p expression. Collectively, our results showed that PFN1 functions as a tumor suppressor in HCC, and might serve as a diagnostic and therapeutic target for HCC patients.

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.

Synergy with interferon-lambda 3 and sorafenib suppresses hepatocellular carcinoma proliferation.

Hepatocellular carcinoma (HCC) is a common and fatal malignancy of the liver. Sorafenib is a small molecule multikinase inhibitor that acts against different cancer cell lines and is used for the treatment of HCC. However, some advanced HCC patients fail to respond to sorafenib, and those who do lack a meaningful clinical benefit. Interferon-lambda 3 (IFN-λ3) is a type III interferon with antiviral, antiproliferative, and immunomodulatory functions. Here, we evaluated the use of IFN-λ3 as an adjuvant treatment with sorafenib in HCC. In the present study, CCK-8 and colony formation assay results showed that treatment with a combination of IFN-λ3 and sorafenib suppresses the viability of HepG2 and SMMC7721 liver cancer cell lines more than treatment with either alone. In addition, flow cytometry results confirmed that treatment with a combination of IFN-λ3 and sorafenib promotes the loss of mitochondrial membrane potential and induces the production of ROS more than treatment with either alone. Furthermore, using a subcutaneous SMMC7721 tumor model, treatment with a combination of IFN-λ3 and sorafenib significantly reduced the tumor growth/volume and induced apoptosis compared to treatment with sorafenib alone. These results show that combined treatment with IFN-λ3 and sorafenib facilitates a synergistic effect on suppressing HCC cancer growth and promoting cell apoptosis in vitro and in vivo. Thus, IFN-λ3 in combination with sorafenib might prove to be a useful adjunctive strategy for the clinical treatment of HCC.

Hepatocellular Carcinoma Growth Is Inhibited by Euphorbia helioscopia L. Extract in Nude Mice Xenografts.

Euphorbia helioscopia L. is a traditional Chinese medicine; recently research found that its ethyl acetate extract (EAE) plays an important role on tumor cell proliferation, apoptosis, invasion, and metastasis in vitro. But the effect of EAE for tumor cells in vivo has not been reported. To explore the inhibitory effect of EAE and molecular mechanism on hepatocellular carcinoma (HCC) SMMC-7721 cells in vivo, we utilized the nude mouse xenograft model of HCC. Treated with EAE (50, 100, and 200 µg/mL), the volume of xenograft was measured during the entire process of EAE treatment. In EAE treatment group, the volume of xenograft was significantly reduced compared with the control group (P < 0.05) and the protein expressions of CyclinD1, bcl-2, and MMP-9 were reduced, while those of bax, caspase-3, and nm23-H1 were increased. A significant change trend with increasing EAE concentrations has presented, compared with controls. Moreover, the ultrastructural morphology of xenografts showed significant changes, including nuclear pyknosis and chromatin condensation, We found that EAE could effectively inhibit tumor growth, induce apoptosis, and inhibit tumor invasion and metastasis in vivo; it is suggested that EAE is a potential candidate for as a new anticancer agent.

Effect of GP73 silencing on proliferation and apoptosis in hepatocellular cancer.

AIM: To investigate the roles of Golgi protein (GP) 73 in the regulation of cell proliferation and apoptosis. METHODS: Stealth RNAi targeting GP73 gene sequence was used to silence its expression in Hep G2 cells and Bel7402 cells. Stealth RNAi effects were assessed by reverse transcriptase polymerase chain reaction and ELISA. Cell proliferation assay and cell cycle analysis were assessed by MTT assay and flow cytometry. Apoptosis was assessed by flow cytometry and transmission electron microscopy. Apoptosis-related proteins were assessed by western immunoblot analysis. RESULTS: Stealth RNAi targeting GP73 gene sequence markedly reduced the expression of GP73 gene. The reduction of GP73 in Hep G2 cells and Bel7402 cells inhibited cell proliferation and induced apoptosis, however, terminal apoptosis occurred in Hep G2 cells, but early apoptosis occurred in Bel7402 cells. Reduced expression of GP73 gene might lead to a reduction in Bcl-2/Bax ratio, an increase in cytochrome c, but a reduction in capase-3. CONCLUSION: GP73 might play an important role in proliferation and apoptosis in hepatocellular carcinoma cells.

Chemotherapy for patients with gastric cancer after complete resection: a network meta-analysis.

AIM: To conduct a network meta-analysis to evaluate the effectiveness of different chemotherapy regimens for patients with gastric cancer. METHODS: PubMed (1966-2011.12), the Cochrane Library (2011 Issue 2) and EMBASE (1974-2011.12) were searched with the terms "gastric cancer" and "chemotherapy", as well as the medical subject headings. References from relevant articles and conferences were also included. Patients who had previous gastric surgery, radiation before or after surgery or chemotherapy before surgery were excluded. In this study, only randomized controlled trials (RCTs) were considered, and the end-point was the overall mortality. Direct comparisons were performed using traditional meta-analysis whereas indirect comparisons were performed using network meta-analysis. RESULTS: In total, 31 RCTs with 7120 patients were included. Five chemotherapy regimens, fluorouracil (FU) + BCNU, FU + methyl-CCNU (mCCNU), FU + cisplatin, FU + anthracyclines and FU + mitomycin c (MMC) + cytarabine (Ara-c), were found to be less beneficial in terms of overall mortality. In contrast, four chemotherapy regimens were effective for the patients after surgery, including FU + MMC + adriamycin (FMA), FU + MMC (FM), Tegafur and MMC, There was no significant difference in terms of overall mortality among these regimens. The evidence for the FM regimen and MMC regimen was poor. Additionally, the FMA regimen, which includes a variety of chemotherapy drugs and causes many side effects, was not better than the Tegafur regimen. CONCLUSION: Although the four chemotherapy regimens were effective in patients with gastric cancer after surgery and the overall mortality revealed no significant difference among them in the network meta-analysis, thorough analysis of the results recommends Tegafur as the first-line adjuvant chemotherapy regimen for patients after complete resection.

The effects of bariatric procedures versus medical therapy for obese patients with type 2 diabetes: meta-analysis of randomized controlled trials.

OBJECTIVE: To assess the effects of bariatric surgery versus medical therapy for type 2 diabetes mellitus. METHODS: The Cochrane library, PubMed, Embase, Chinese biomedical literature database, and Wanfang database up to February 2012 were searched. The literature searches strategies contained terms ("diabetes*", "surg*", and "medic*" were used), combined with the medical subject headings. Randomized controlled trails (RCTs) of frequently used bariatric surgery for obese patients with type 2 diabetes were included. Study selection, data extraction, quality assessment, and data analyses were performed according to the Cochrane standards. RESULTS: Three randomized controlled trials (RCTs) involving 170 patients in the bariatric surgery groups and 100 patients in the medical therapy group were selected. Compared with medical therapy, bariatric surgery for type 2 diabetes can significantly decrease the levels of HbA1c, FBG, weight, triglycerides, and the dose of hypoglycemic, antihypertensive, and lipid-lowering medicine, while increasing the rate of diabetes remission (RR = 9.74, 95%CI, (1.36, 69.66)) and the levels of high-density lipoprotein. However, there are no statistical differences in serious adverse events between the surgical and medical groups (RR = 1.23, 95%CI, (0.80, 1.87)). CONCLUSIONS: Surgical procedures were more likely to help patients achieve benefits than medical therapy alone. Further intensive RCTs of high-quality, multiple centers and long-term followup should be carried out to provide more reliable evidence.

Growth inhibition of insulin-like growth factor I receptor monoclonal antibody to human colorectal cancer cells.

AIM: Insulin-like growth factors (IGFs) and their receptors play a critical role in the growth and regulation of many type of malignant cells. The purpose of this study was to clarify the expression of Insulin-like growth factor I receptor (IGF-IR) in a human colorectal cancer cell line HT-29 and investigate the effects of 2 IGF-IR monoclonal antibodies (Mab) on the biological behavior of HT-29 cell line. METHODS: Immunohistochemistry was used to test the expression of IGF-IR in HT-29 cell line, MTT assay was used to determine the antiproliferation effects of 2 kinds of IGF-IR monoclonal antibody on HT-29 cells. The effects of apoptosis rate and cell cycle of HT-29 cells were estimated by flow cytometry (FCM). RESULTS: IGF-IR was expressed in the membranes of HT-29 cell line; MTT results show that each IGF-IR (alpha-Subunit)Ab-3 Mab group has remarkable difference (p < 0.01) as compared with control group, each IGF-IRalpha(1H7)L Mab group has no remarkable difference (p > 0.05) as compared with control group, each IGF-IRalpha(1H7)L Mab group has light antiproliferation effect on the HT-29 cells. IGF-IR(alpha-Subunit)Ab-3 has stronger antiproliferation effect on the HT-29 cells and dose-depended growth inhibition effects were observed when concentration is less than 1.5 ug/ml;The 2 kinds of IGF-IR monoclonal antibody can arrest the cell cycle at any phase of HT-29 cells and induce apoptosis. Under the incubating conditions of containing 5 percent fetal bovine serum (FCS) and no FCS, the apoptosis percentage of IGF-IR(alpha-Subunit)Ab-3 group and IGF-IRalpha(1H7)L group have obviously increased (p < 0.01). After the number of cells was increased 30 times, the apoptosis percentage of IGF-IR(alpha-Subunit)Ab-3 group and IGF-IRalpha(1H7)L group have no remarkable differences as compared with control group (p > 0.05). CONCLUSIONS: Blockade of the IGF-IR with IGF-IR Mab inhibiting proliferation, arresting cell cycle and inducing apoptosis of HT-29 cells may represent a valid approach to inhibit tumor growth.