AFF4 Predicts the Prognosis of Colorectal Cancer Patients and Suppresses Colorectal Cancer Metastasis via Promoting CDH1 Expression.

INTRODUCTION: AF4/FMR2 family member 4 (AFF4) is a core component of super elongation complex (SEC) and regulates the transcription elongation of many genes. AFF4 depletion or amplification is associated with multiple cancers, but its role in colorectal cancer (CRC) has not been investigated so far. METHODS: qRT-PCR and Western blot analyzed AFF4 expression in the paired clinical CRC tissues. The patients' overall survival curve was determined using the Kaplan-Meier plotter. In vitro experiments, such as cell proliferation, migration, and invasion, were used to preliminarily ascertain the role of AFF4 in CRC. A CRC cell liver metastasis animal model was well established. Livers were harvested and examined histologically by a series of indicators, such as tumor nodules, liver weight, ALT/AST activity, and tumor cell identification by hematoxylin-eosin (HE) staining. RESULTS: We firstly examined the expression of AFF4 in colorectal cancer and normal tissues by collecting paired CRC tissues and adjacent normal tissues, revealing that AFF4 was significantly downregulated in CRC patients and lower expression of AFF4 was correlated with poor prognosis. Next, we observed that presence or absence of AFF4 in CRC cells had no effect on cancer cell proliferation, while AFF4 depletion significantly promoted the migration or invasion of CRC cells in vitro. Furthermore, we confirmed that AFF4 deficiency enhanced the metastatic capacity of CRC cells in vivo. Mechanistically, we found that AFF4 upregulated the transcription of CDH1 gene, which encodes E-cadherin and suppresses the epithelial-mesenchymal transition (EMT). Knockdown of AFF4 interfered with CDH1 transcription, resulting in downregulation of E-cadherin expression and the progression of CRC. Moreover, restored CDH1 expression could rescue the phenotype of CRC cells without AFF4. CONCLUSIONS: Collectively, our data demonstrated that AFF4 served as a significant novel regulator of CRC via CDH1 transcriptional regulation and a potential effective therapy target for patients with CRC.

[Lingze Tablets for BPH with kidney-deficiency, blood stasis and dampness resistance: A phase-â £ open-label single-arm multicenter clinical study and safety evaluation].

OBJECTIVE: To evaluate the efficacy and safety of Lingze Tablets in the treatment of BPH with kidney deficiency, blood stasis and dampness resistance. METHODS: Totally 235 eligible BPH patients, aged 50－80 years and meeting the inclusion criteria, were enrolled and treated with Lingze Tablets orally, 4 tablets per time, tid. Before and after an 8-week course of medication, IPSS, quality of life (QOL) and TCM syndromes scores were obtained from the patients. RESULTS: Of the total number of patients, 211 completed the whole course of treatment. Compared with the baseline, the IPSS was dramatically reduced after 4 and 8 weeks of medication (18.28 ± 5.29 vs 12.82 ± 4.66 and 9.23 ± 4.21, P < 0.01), and so were the QOL scores (6.44 ± 1.99 vs 4.95 ± 1.64 and 3.16 ± 1.53, P < 0.01) and TCM syndromes scores (17.49 ± 5.30 vs 12.45 ± 3.74 and 9.17 ± 3.24, P < 0.01). The incidence rates of adverse events and drug-related adverse reactions were 15.2% and 1.9%, respectively, and no organ function impairment was observed. CONCLUSIONS: Lingze Tablets are definitely effective and safe for the treatment of BPH with kidney deficiency, blood stasis and dampness resistance.

Exploration of differentially-expressed exosomal mRNAs, lncRNAs and circRNAs from serum samples of gallbladder cancer and xantho-granulomatous cholecystitis patients.

Gallbladder cancer (GBC) is the most common biliary tract malignancy worldwide. Although a growing number of studies have explored the mechanism of GBC, thus far, few molecules have been discovered that can be utilized as specific biomarkers for the early diagnosis and therapeutic treatment of GBC. Recent studies have shown that exosomes not only participate in the progression of tumors, but also carry specific information that can define multiple cancer types. The present study investigated the expression profiles of coding (or messenger) ribonucleic acids (mRNAs) and non-coding RNAs (ncRNAs, including long non-coding RNAs [lncRNAs] and circular RNAs [circRNAs]) in plasma-derived exosomes from GBC patients. Using high-throughput RNA sequencing and subsequent bioinformatic analysis, a number of differentially expressed (DE) mRNAs, lncRNAs, and circRNAs were identified in GBC exosomes, compared to their expressions in xantho-granulomatous cholecystitis (XGC) exosomes. Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) analyses were then conducted to investigate the potential functions of these DE RNAs. Furthermore, the interaction networks and competing endogenous RNA networks of these DE RNAs and their target genes were investigated, revealing a complex regulatory network among mRNAs and ncRNAs. In summary, this study demonstrates the diagnostic value of plasma-derived exosomes in GBC and provides a new perspective on the mechanism of GBC.

Comparative Efficacy of Oral Chinese Patent Medicine for Chronic Prostatitis/Chronic Pelvic Pain Syndrome With Sexual Dysfunction: A Bayesian Network Meta-Analysis of Randomized Controlled Trials.

Background: Oral Chinese patent medicine (OCPM) combined with western medicine (WM) are believed to be effective for the therapy of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) with sexual dysfunction (SD). These western medicines mainly involve antibiotics, phosphodiesterase type-5 inhibitor (PDE-5i), α-blockers. But there is no randomized controlled trial (RCT) that directly compares the efficacy of different OCPM. Hence, we operated a network meta-analysis (NMA) to contrast the efficacy of different OCPM for CP/CPPS with SD. Methods: Relevant studies were searched in PubMed, Cochrane Library, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), and Wanfang database. All of the RCTs concentrated on the use of OCPM to cure CP/CPPS with SD from the inception of the databases to November 2020. We appraised the risk of bias under the Cochrane Handbook and CONSORT statement. The data were statistically analyzed via STATA 13.0 and WinBUGS 1.4.3 instrument. Results: Altogether, 30 pieces of literature with 2,996 participants containing 11 oral Chinese patent medicine and 11 interventions were included in the NMA. In terms of The National Institutes of Health chronic prostatitis symptom index (NIH-CPSI), Qianlie Shutong Capsules (QLSTC) + WM had the most possible of being the optimal treatment. In the light of the International Index of Erectile Function (IIEF-5), Congrong Yishen Granules (CRYSG) + WM had the most possible of being the optimal treatment. Shugan Yiyang Capsules (SGYYC) + WM performed the highest likelihood efficacy under cluster rank graph combined NIH-CPSI and IIEF-5. Liuwei Dihuang Pills/Yougui capsules (LWDHP/YGC) + WM had highly possible to be the optimal treatment not only for the clinical effective rate of CP/CPPS but also for the clinical effective rate of SD. Considering four outcomes, QLSTC, CRYSG, SGYYC, LWDHP/YGC, Qianlie Beixi Capsules (QLBXC) plus WM were the best therapy approach for CP/CPPS with SD, especially LWDHP/YGC + WM and QLBXC + WM. Conclusion: Based on the NMA, QLSTC, CRYSG, SGYYC, LWDHP/YGC, QLBXC plus WM demonstrated the maximum probability of being the optimal therapies. Owing to the limitations of this research, these results should be confirmed by elaborate RCTs. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021224060].

Development and validation of risk score for predicting spontaneous rupture of hepatocellular carcinoma.

PURPOSE: Spontaneous rupture is a potentially serious complication of liver cancer. A risk score was developed and validated for predicting spontaneous rupture based on a retrospective study. METHODS: Multiple logistic regression analysis was used to study the relationship between clinical variables and spontaneous rupture. The independent rupture predictors were converted into a score based on the odds ratio. Predicted attributes of the developed scores were then verified using a dataset in 2019. RESULTS: The incidence of spontaneous rupture was 5.5% from 2002 to 2019. A 10-point score (α-FP of ≥400 µg/L, 1; protrusion from liver surface, 2; ascites, 3; tumor size of >5 cm, 4) was derived for prediction of rupture and area under the receiver-operating characteristic curve was 0.9 (95% confidence interval, 0.87-0.92). When applying a cutoff value of 5 points or more, the specificity was 0.87 and the sensitivity was 0.84. A validation cohort consisting of 202 hepatocellular carcinoma patients reproduces the predictive, identification, and calibration characteristics. The observed rate of spontaneous rupture according to risk stratification of the score was 0.6% for those with a score of 0-4, 21.6% for a score of 5-7, and 36.4% for a score of 8-10 in the validation cohort. CONCLUSION: Here, based on routine clinical data, we determine the factors that affect prognosis and propose an effective tool for predicting spontaneous rupture, which may be useful in guiding priority treatment of high-risk patients or clinical routine preventive treatment.

Five lncRNAs Associated With Prostate Cancer Prognosis Identified by Coexpression Network Analysis.

Prostate cancer (PCa) is a highly malignant tumor, with increasing incidence and mortality rates worldwide. The aim of this study was to identify the prognostic lncRNAs and construct an lncRNA signature for PCa diagnosis by the interaction network between lncRNAs and protein-coding genes (PCGs). The differentially expressed lncRNAs (DElncRNAs) and PCGs (DEPCGs) between PCa and normal prostate tissues were screened from The Cancer Genome Atlas (TCGA) database. The DEPCGs were functionally annotated in terms of the enriched pathways. Weighted gene co-expression network analysis (WGCNA) of 104 PCa samples identified 15 co-expression modules, of which the Turquoise module was negatively correlated with cancer and included 5 key lncRNAs and 47 PCGs. KEGG pathway analyses of the core 47 PCGs showed significant enrichment in classic PCa-related pathways, and overlapped with the enriched pathways of the DEPCGs. LINC00857, LINC00900, LINC00908, LINC00900, SNHG3 and FENDRR were significantly associated with the survival of PCa and have not been reported previously. Finally, Multivariable Cox regression analysis was used to establish a prognostic risk formula, and the patients were accordingly stratified into the low- and high-risk groups. The latter had significantly worse OS compared to the low-risk group (P < 0.01), and the area under the receiver operating characteristic curve (ROC) of 14-year OS was 0.829. The accuracy of our prediction model was determined by calculating the corresponding concordance index (C-index) and risk curves. In conclusion, we established a 5-lncRNA prognostic signature that provides insights into the biological and clinical relevance of lncRNAs in PCa.

Assessment of the efficacy of Chinese patent medicine on treating pain caused by prostate cancer: A protocol for systematic review and meta analysis.

INTRODUCTION: With the development of economy and the acceleration of population aging, Prostate cancer (PCa) has presented a situation of high morbidity and mortality worldwide. The recent studies have shown that Chinese patent medicine combined with endocrine therapy in the treatment of prostate cancer not only plays a synergistic role in enhancing the efficacy. This review hopes to adopt meta-analysis to evaluate the efficacy and safety of Chinese patent medicine in the treatment of pain caused by prostate cancer and provides evidence for its application in clinical practice. METHODS AND ANALYSIS: We will search for PubMed, Cochrane Library, AMED, EMbase, WorldSciNet; Nature, Science online and China Journal Full-text Database (CNKI), China Biomedical Literature CD-ROM Database (CBM), and related randomized controlled trials included in the China Resources Database. The time is limited from the construction of the library to June 2019. We will use the criteria provided by Cochrane 5.1.0 for quality assessment and risk assessment of the included studies, and use the Revman 5.3 and Stata13.0 software for meta-analysis of the effectiveness, recurrence rate, and symptom scores of pain caused by prostate cancer. ETHICS AND DISSEMINATION: This systematic review will evaluate the efficacy and safety of Chinese patent medicine for pain caused by prostate cancer. Because all of the data used in this systematic review and meta-analysis has been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process Trial. TRIAL REGISTRATION NUMBER: PROSPERO CRD42019131544.

Traditional Chinese medicine on treating chronic prostatitis/chronic pelvic pain syndrome: A systematic review and meta-analysis.

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common urinary system disease in the male population. Recent studies have shown that traditional Chinese medicine (TCM) can alleviate the pain caused by CP/CPPS to a certain extent and improve the quality of life of patients. In this systematic review, we aim to evaluate the effectiveness and safety of TCM for chronic prostatitis/chronic pelvic pain syndrome. METHODS AND ANALYSIS: We will search for PubMed, Cochrane Library, AMED, EMbase, WorldSciNet; Nature, Science online and China Journal Full-text Database (CNKI), China Biomedical Literature CD-ROM Database (CBM), and related randomized controlled trials included in the China Resources Database. The time is limited from the construction of the library to May 2019. The quality of the included randomized controlled trials (RCTs) will be evaluated with the risk of bias (ROB) tool and evidence will be evaluated by Grading of Recommendations Assessment Development and Evaluation (GRADE). STATA 13.0 and Revman 5.3 will be used to perform a systematic review and meta-analysis to synthesize direct and indirect evidence. ETHICS AND DISSEMINATION: This systematic review will evaluate the efficacy and safety of TCM for treating chronic prostatitis/chronic pelvic pain syndrome. Because all of the data used in this systematic review and meta-analysis has been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process trial. TRIAL REGISTRATION NUMBER: PROSPERO CRD42019131527.

Traditional Chinese medicine on treating premature ejaculation: A systematic review and meta-analysis.

BACKGROUND: Premature ejaculation is a form of male sexual dysfunction. As people's lifestyle changes and the population ages, the incidence of premature ejaculation continues to increase. Many clinical trials have proven that Chinese medicine has a significant effect in the treatment of premature ejaculation. In this systematic review, we aim to evaluate the effectiveness and safety of Traditional Chinese medicine for premature ejaculation. METHODS: We will search for PubMed, Cochrane Library, AMED, EMbase, WorldSciNet; Nature, Science online and China Journal Full-text Database (CNKI), China Biomedical Literature CD-ROM Database (CBM), and related randomized controlled trials included in the China Resources Database. The time is limited from the construction of the library to April 2019. We will use the criteria provided by Cochrane 5.1.0 for quality assessment and risk assessment of the included studies, and use the Revman 5.3 and Stata13.0 software for meta-analysis of the effectiveness, recurrence rate, and symptom scores of premature ejaculation. ETHICS AND DISSEMINATION: This systematic review will evaluate the efficacy and safety of Traditional Chinese medicine for treating premature ejaculation. Because all of the data used in this systematic review and meta-analysis has been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process Trial. TRIAL REGISTRATION NUMBER: PROSPERO CRD42017065316.

Effectiveness comparison of a Chinese dicitraditionalmene formula Wuzi Yanzong Pill and its analogous prescriptions for the treatment of oligoasthenozoospermia: A systematic review and meta-analysis protocol.

BACKGROUND: Among male sterility factors, oligoasthenozoospermia is the most common. As people's lifestyle changes and the population ages, the incidence of oligoasthenozoospermia continues to increase. The studies have shown that about 15% of married couples in the world are affected by infertility, among which infertility caused by male factors alone accounts for about 50%. Many clinical trials have proven that Wuzi Yanzong Pill has a significant effect in the treatment of oligoasthenozoospermia. In this systematic review, we aim to evaluate the effectiveness and safety of Wuzi Yanzong Pill for oligoasthenozoospermia. METHODS: We will search for PubMed, Cochrane Library, AMED, EMbase, WorldSciNet; Nature, Science online, and China Journal Full-text Database (CNKI), China Biomedical Literature CD-ROM Database (CBM), and related randomized controlled trials included in the China Resources Database. The time is limited from the construction of the library to April 2019. We will use the criteria provided by Cochrane 5.1.0 for quality assessment and risk assessment of the included studies, and use the Revman 5.3 and Stata13.0 software for meta-analysis of the effectiveness, recurrence rate, and symptom scores of oligoasthenozoospermia. ETHICS AND DISSEMINATION: This systematic review will evaluate the efficacy and safety of Wuzi Yanzong Pill for treating oligoasthenozoospermia. Because all of the data used in this systematic review and meta-analysis has been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process Trial. TRIAL REGISTRATION NUMBER: PROSPERO CRD42019119170.

Effectiveness comparisons of acupuncture for chronic prostatitis/chronic pelvic pain syndrome: A Bayesian network meta-analysis protocol.

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common urinary system disease in the male population. Recent studies have shown that acupuncture can alleviate the pain caused by CP/CPPS to a certain extent and improve the quality of life of patients. This study used a network meta-analysis (NMA) to compare the effectiveness and safety of different forms of acupuncture on CP/CPPS. METHODS AND ANALYSIS: We will search for PubMed, Cochrane Library, AMED, EMbase, WorldSciNet; Nature, Science online and China Journal Full-text Database, China Biomedical Literature CD-ROM Database, and related randomized controlled trials (RCTs) included in the China Resources Database. The time is limited from the construction of the library to December 2018. The quality of the included RCTs will be evaluated with the risk of bias tool and evidence will be evaluated by grading of recommendations assessment, development, and evaluation. STATA 13.0 and WinBUGS 1.4.3 through the GeMTC package will be used to perform a NMA to synthesize direct and indirect evidence. RESULTS: The results of this NMA will be submitted to a peer-reviewed journal for publication. TRIAL REGISTRATION NUMBER: PROSPERO CRD42018111408.

Clinical efficacy of robot-assisted versus laparoscopic liver resection: a meta analysis.

To compare the clinical efficacy and safety of robotic-assisted liver resection (RLR) and laparoscopic liver resection (LLR) by the means of meta-analytical techniques. We searched PubMed, Cochrane library, Embase and Web of Science databases, collecting randomized or non-randomized studies about robotic-assisted and laparoscopic liver resections. The searching cutoff date was 2017/6/30, all the data obtained were statistically analyzed using RevMan5.3 software recommended by Cochrane Collaboration. A total of thirteen articles, involving 938 patients were enrolled in meta-analysis. Among them, 435 cases underwent RLR, and 503 cases underwent LLR. Compared with LLR, the RLR had longer operative time [MD=65.49, 95%CI (42.00, 88.98) P＜0.00001＝more intraoperative blood loss [MD=69.88, 95%CI (27.11, 112.65) P=0.001] and a higher cost [MD=4.24, 95%CI (3.08, 5.39) P＜0.00001＝. There were no significant differences between the two groups in transfusion rate, complication rate, conversion rate, the R1 resection rate and hospital stay. In the subgroup analysis of surgery after 2010, a lower conversion rate was observed in RLR, other clinical outcomes are comparable between RLR and LLR. In the subgroup analysis of minor hepatectomy, RLR is still associated with longer operative time, but there is no difference in other outcomes. In the subgroup analysis of left hemihepatectomy or left lateral hepatectomy, RLR is associated with more blood loss. Although RLR associated with Longer operative time and more intraoperative blood loss, it displays the same safety and effectiveness as LLR for hepatectomies. And the high cost is still a major hindrance for the widely application of robotic surgery.

Transarterial chemoembolization prior to liver transplantation for patients with hepatocellular carcinoma: A meta-analysis.

BACKGROUND AND AIM: A debate exists over whether using preoperative transarterial chemoembolization for patients with hepatocellular carcinoma before liver transplantation. Numerous studies have been investigating on this, but there is still no unanimous conclusion about the effect of preoperative transarterial chemoembolization. We conducted the meta-analysis of all available studies to systematically evaluate the influence of preoperative transarterial chemoembolization on liver transplant. METHODS: A systematic search was performed by two authors (Si TF. and Guan RY.) through PubMed, Embase, Cochrane, and Science Citation Index Expanded, combined with Manual Retrieval and Cited Reference Search. The searching cut-off date was 2016/07/31, and all the data obtained were statistically analyzed using Review Manager version 5.1 software (Copenhagen, The Nordic Cochrane Center, The Cochrane Collaboration, 2011) recommended by Cochrane Collaboration. RESULTS: The study showed that there was no difference between the experimental group and the control group on perioperative mortality (RR = 1.10, 95% confidence interval (CI) = [0.49-2.48], P = 0.82) or biliary complications (RR = 0.96, 95%CI = [0.66-1.39], P = 0.83). Preoperative transarterial chemoembolization had no obvious effect on improving overall survival (HR = 1.05, 95%CI = [0.65-1.72], P = 0. 83) but would result in a higher rate of vascular complications (RR = 2.01, 95%CI = [1.23-3.27], P = 0.005) and a reduction of disease free survival (HR = 1.66, 95%CI = [1.02-2.70], P = 0.04). Subgroup analysis also revealed that patients from transarterial chemoembolization group in Asia had a much lower overall survival rate (HR = 2.65, 95%CI = [1.49-4.71], P = 0.0009) compared with the control group. CONCLUSIONS: Considering the possible adverse impacts on liver transplantation and the variation in sensitivity to transarterial chemoembolization, clinicians should be more cautious when considering transarterial chemoembolization as the bridging therapy for patients in the waiting list.

Preoperative transarterial chemoembolization for resectable hepatocellular carcinoma in Asia area: a meta-analysis of random controlled trials.

OBJECTIVE: We aimed to systematically evaluate the influence of preoperative transarterial chemoembolization (TACE) for resectable hepatocellular carcinoma (HCC) on long-term prognosis and perioperative safety. MATERIALS AND METHODS: Databases including PubMed, Embase, Cochrane, Wanfang, CNKI, VIP data were searched, combined with Manual Retrieval and Cited Reference Search to collect the published randomized controlled trial (RCT) about the influence of pre-TACE for curative resection of HCC. The searching cutoff date was 2016/02/25, all the data obtained were statistically analyzed using RevMan5.2 software recommended by Cochrane Collaboration. RESULTS: A total of 5 RCT including 430 (pre-TACE group: 212, surgery alone group: 218) patients were included. The results of meta-analysis showed that: there was no difference between the 2 groups on overall survival (OS) rate [HR 1.25, 95%CI (0.92-1.68)], disease free survival (DFS) rate [HR 0.95 (0.76-1.19)], perioperative mortality rate [OR 0.70 (0.22-2.30)], or blood loss [SMD 0.07 (-0.14-0.29)], whereas the subgroup analysis revealed that pre-TACE would result in longer operation time [SMD 0.31 (0.06-0.57)], higher postoperative morbidity rate [OR 1.90 (1.02-3.53)] and combined resection rate of perihepatic organs [OR 5.46 (2.73-11.78)] in subgroup with mean tumor diameter >5cm. CONCLUSIONS: According to our study, pre-TACE treatment cannot improve the long-term prognosis of resectable HCC. With the growth of the tumor diameter, especially when it is over 5cm, it might add difficulties to surgery and affect the perioperative safety.

Treatment of nutcracker syndrome with spermatic vein ligation and iliac vein anastomosis: case report of three cases.

Three patients with nutcracker syndrome (NCS) were enrolled in the study. Their clinical symptoms mainly included proteinuria and serious varicocele. Color Doppler ultrasound and computed tomography showed that the patients had constricted abdominal aortas, reduced superior mesenteric artery angles, and thinned left renal veins. Patients then underwent left spermatic vein ligation and iliac vein anastomosis. They were checked three months after their operation, and results showed that their sperms were improved and their proteinuria disappeared. The color Doppler ultrasound showed new cycle pathways. NCS clinical manifestations are complicated, and need combination diagnosis of symptoms and auxiliary examination to determine surgical indications. Ligation of spermatic vein and vein anastomosis can be used to treat NCS.