Autophagy-related long non-coding RNAs act as prognostic biomarkers and associate with tumor microenvironment in prostate cancer.

Aberrant autophagy could promote cancer cells to survive and proliferate in prostate cancer (PCa). LncRNAs play key roles in autophagy regulatory network. We established a prognostic model, which autophagy-related lncRNAs (au-lncRNAs) were used as biomarkers to predict prognosis of individuals with PCa. Depending on au-lncRNAs from the Cancer Genome Atlas and the Human Autophagy Database, a risk score model was created. To evaluate the prediction accuracy, the calibration, Kaplan-Meier, and receiver operating characteristic curves were used. To clarify the biological function, gene set enrichment analyses (GSEA) were performed. Quantitative real-time PCR (qRT-PCR) was employed to determine the au-lncRNAs expression in PCa cell lines and healthy prostate cells for further confirmation. We identified five au-lncRNAs with prognostic significance (AC068580.6, AF131215.2, LINC00996, LINC01125 and LINC01547). The development of a risk scoring model required the utilization of multivariate Cox analysis. According to the model, we categorized PCa individuals into low- and high-risk cohorts. PCa subjects in the high-risk group had a worse disease-free survival rate than those in the low-risk group. The 1-, 3-, and 5-year periods had corresponding areas under curves (AUC) of 0.788, 0.794, and 0.818. The prognosis of individuals with PCa could be predicted by the model with accuracy. Further analysis with GSEA showed that the prognostic model was associated with the tumor microenvironment, including immunotherapy, cancer-related inflammation, and metabolic reprogramming. Four lncRNAs expression in PCa cell lines was greater than that in healthy prostate cells. The au-lncRNA prognostic model has significant clinical implications in prognosis of PCa patient.

Ten interleukins and risk of prostate cancer.

Background: Interleukins (ILs) have been reported to be related to prostate cancer. The aims of this study were to estimate the levels for several key interleukins in prostate cancer and the causal effects between them. Methods: We conducted a bi-directional two-sample Mendelian randomization (MR) study to assess the causal associations between ILs and prostate cancer. Genetic instruments and summary-level data for 10 ILs were obtained from three genome-wide association meta-analyses. Prostate cancer related data were obtained from the PRACTICAL (79,148 cases and 61,106 controls), UK Biobank (7,691 cases and 169,762 controls) and FinnGen consortium (10,414 cases and 124,994 controls), respectively. Results: The odds ratio of prostate cancer was 0.92 (95% confidence interval (CI), 0.89, 0.96; P=1.58×10-05) and 1.12 (95% CI, 1.07, 1.17; P=6.61×10-07) for one standard deviation increase in genetically predicted IL-1ra and IL-6 levels, respectively. Genetically predicted levels of IL-1ß, IL-2a, IL-6ra, IL-8, IL-16, IL-17, IL-18, and IL-27 were not associated with the risk of prostate cancer. Reverse MR analysis did not find the associations between genetic liability to prostate cancer and higher levels of IL-1ra (ß, -0.005; 95% CI, -0.010, 0.001; P=0.111) and IL-6 (ß, 0.002; 95% CI, -0.011, 0.014; P=0.755). Conclusion: This MR study suggests that long-term IL-6 may increase the risk of prostate cancer and IL-1ra may reduce it.

Identification of the MALAT1/miR-106a-5p/ZNF148 feedback loop in regulating HaCaT cell proliferation, migration and apoptosis.

Aims: This study aims to investigate the function of positive feedback loops involving noncoding RNA in diabetic wound healing. Methods: We developed a mouse diabetic wound model to confirm that hyperglycemia can impair wound healing. We also used an in vitro keratinocyte model in high-glucose conditions to investigate the mechanism of delayed wound healing. Results: MALAT1 was decreased in diabetic mouse wound tissue and can promote keratinocyte biological functions. MALAT1 could bind to miR-106a-5p to modulate the expression of ZNF148, a target gene of miR-106a-5p. Surprisingly, ZNF148 bound to a region in the MALAT1 promoter to stimulate gene expression. Conclusion: ZNF148-activated MALAT1 increases ZNF148 expression by competitively binding miR-106a-3p, generating a positive feedback loop that enhances keratinocyte function.

Delayed wound repair is a leading cause of diabetic foot ulcers. However, the molecular mechanism underlying impaired wound healing in diabetes is unclear. In our study we found that a positive feedback loop consisting of MALAT1, miR-106a-5p and ZNF148 could promote chronic wound repair. In diabetic skin tissues, MALAT1 levels were lower, causing impairments in skin cell function. On a molecular level, MALAT1 can bind miR-106a-5p to increase ZNF148 levels. Surprisingly, ZNF148 can bind the promoter of MALAT1 to reverse the decline of MALAT1 levels in diabetic wounds. Our findings advance our understanding of chronic diabetic wounds and, more crucially, open new therapeutic possibilities for this disease.

Coffee and caffeine consumption and risk of renal cell carcinoma: A Mendelian randomization study.

Background: The association between coffee and caffeine consumption and the risk of renal cell carcinoma was inconsistent among observational studies, and whether these observed associations were causal remained unclear. Therefore, we performed two-sample Mendelian randomization (MR) study to assess the causal nature of the association. Materials and methods: In this study, 12 and two independent single nucleotide polymorphisms (SNPs) related to coffee and caffeine consumption at a genome-wide significance level of p < 5 × 10-8 were used as instrumental variables (IVs), respectively. Summary-level data for renal cell carcinoma were taken from the FinnGen consortium with up to 174,977 individuals, and the International Agency for Research on Cancer (IARC) with 13,230 individuals. We used inverse-variance weighted (IVW) as the main method, followed by the weighted median method, the MR-Egger regression method, and the MR robust adjusted profile score method. Outlier and pleiotropic variants were assessed by the MR Pleiotropy RESidual Sum and Outlier test and MR-Egger regression. We used meta-analysis methods in fixed-effects to combine the estimates from the two sources. Results: The genetically predicted coffee consumption was not associated with the risk of renal cell carcinoma in the FinnGen consortium, and the relationship was consistent in the IARC consortium. The pooled odds ratio (OR) per 50% increase of coffee consumption was 0.752 [95% confidence interval (CI), 0.512-1.105; p = 0.147]. In addition, complementary analyses that separated the coffee-related SNPs according to their relationship with blood levels of caffeine metabolites (higher, lower, or unrelated) found no relationship with renal cell carcinoma. The results were consistent after excluding eight SNPs due to potential risk factors at genome-wide significance (p < 5 × 10-8). Moreover, genetically predicted per 80-mg increase in caffeine consumption was not associated with the risk of renal cell carcinoma (pooled OR = 0.872, 95% CI: 0.676-1.125, p = 0.292). Conclusion: Our MR study provided no convincing evidence for a causal effect between coffee and caffeine consumption and the risk of renal cell carcinoma. The associations for renal cell carcinoma need to be verified in well-powered studies.

The causal association between smoking, alcohol consumption and risk of bladder cancer: A univariable and multivariable Mendelian randomization study.

Smoking and alcohol consumption are associated with bladder cancer risk in observational studies. We conducted a two-sample univariable and multivariable Mendelian randomization (MR) analysis to determine whether those associations are causal. We used 21, 126, 360, 39 single nucleotide polymorphisms (SNPs) as instrumental variables for number of cigarettes per day, lifetime smoking index, smoking initiation, and drinks per week, respectively. A total of 1115 cases with bladder cancer and 174 006 noncases from FinnGen consortium and 2883 cases with bladder cancer and 417 955 noncases from UK Biobank study were obtained. Genetic predisposition to cigarettes per day, lifetime smoking index and smoking initiation were positively associated with an increased risk of bladder cancer in both the FinnGen and UK Biobank consortium. The summary odds ratio (OR) of bladder cancer was 1.79 (95% confidence interval [CI], 1.31-2.45; P = .0002), 2.38 (95% CI, 1.45-3.88; P = .0005) and 1.91 (95% CI, 1.46-2.50; P = 1.59 × 10-06 ) for one SD increase in the number of cigarettes per day, lifetime smoking index and smoking initiation, respectively. The genetically instrumented number of drinks per week was not associated with bladder cancer (OR = 0.69; 95% CI, 0.44-1.10; P = .1237). Estimates were consistent in multivariable MR analyses by the adjustments of body mass index and education. Our study suggests a causal potential of the association of smoking but not alcohol consumption with bladder cancer according to current evidence.

Using Haemocoagulase Agkistrodon in Patients Undergoing Transurethral Plasmakinetic Resection of the Prostate: A Pilot, Real-World, and Propensity Score-Matched Study.

Objectives: To compare the clinical outcomes of using different hemostatic agents after transurethral plasmakinetic resection of the prostate (TUPKP) in benign prostatic hyperplasia (BPH) patients. Methods: The patients were divided into 5 groups according to the hemostatic agents used after TUPKP, including the haemocoagulase agkistrodon for injection (HCA), hemocoagulase for injection (HC), hemocoagulase bothrops atrox for injection (HCB), ethylenediamine diaceturate injection (EDD), and tranexamic acid (TXA). Propensity score matching was performed based on age, body mass index, prostate volume, hypertension status, fasting blood glucose, smoking, and drinking history. The hospitalization time, bladder irrigation time, indwelling catheterization time, the patency of urine flow, and blood transfusion records were used as outcome indicators to compare the clinical effects of these five agents. Results: We finally matched 65 pairs receiving HCA or HC, 71 pairs receiving HCA or HCB, 38 pairs receiving HCA or TXA, and 29 pairs receiving HCA or EDD. Compared with HC, HCA given during the perioperative period significantly reduced the median hospitalization time [7.00 days (5.00, 8.00) vs. 9.00 days (8.00, 10.00); p < 0.001] and median catheterization time (109.00 hours [88.00, 129.00] vs. 164.00 hours [114.00, 189.00], p < 0.001). Compared with EDD, the median hospitalization time (7.00 days [6.00, 8.00] vs. 10.00 days [8.00, 11.00]; p < 0.001) and median catheterization time (113.00 hours [95.00, 143.00] vs. 160.00 hours [139.00, 168.00]; p < 0.001) were also significant shorter in HCA group. Compared with HCB, median bladder irrigation time (45.00 hours [27.00, 71.00] vs. 49.00 hours [45.00, 72.00]; p = 0.04) was shorter in the HCA group. However, there were no statistical differences in outcomes between HCA and TXA. Conclusions: HCA probably has an advantage over HC, HCB, and EDD in reducing the hospitalization time, catheterization time, and bladder irrigation time among BPH patients undergoing TUPKP.

Spatial and temporal patterns of prostate cancer burden and their association with Socio-Demographic Index in Asia, 1990-2019.

BACKGROUND: Prostate cancer is the second most frequently diagnosed cancer for males worldwide, but the spatial and temporal trends of prostate cancer burden remain unknown in Asia. This study aimed to investigate the changing spatial and temporal trends of incidence, prevalence, mortality, disability-adjusted life year (DALY), and mortality-to-incidence ratio (MIR) of prostate cancer, and their association with the Socio-Demographic Index (SDI) in 48 Asian countries from 1990 to 2019. METHODS: Data were extracted from the Global Health Data Exchange query tool, covering 48 Asian countries from 1990 to 2019. The average annual percent change was calculated to evaluate temporal trends. Spatial autocorrelation analysis was used to obtain spatial patterns, and the association between SDI and prostate cancer burden was estimated using a spatial panel model. RESULTS: In Asia, the age-standardized incidence and prevalence of prostate cancer increased in almost all countries, and its mortality and DALY also increased in over half of the countries. Significantly regional disparities were found in Asia, and the hot spots for incidence, prevalence, mortality, and DALY were all located in Western Asia, the hot spots of percent change also occurred in Western Asia for incidence and DALY. Furthermore, SDI had a positive association with mortality (coef = 2.51, 95% confidence interval [CI]: 2.13-2.90) and negative association with DALY (coef = -14.99, 95% CI: -20.37 to -9.60) and MIR (coef = -0.95, 95%CI: -0.99 to -0.92). CONCLUSIONS: Prostate cancer burden increased rapidly throughout Asia and substantial disparities had persisted between countries. Geographically targeted interventions are needed to reduce the prostate cancer burden throughout Asia and in specific countries.

Knowledge of and Compliance With Guidelines in the Management of Non-Muscle-Invasive Bladder Cancer: A Survey of Chinese Urologists.

BACKGROUND: Non-muscle-invasive bladder cancer (NMIBC) still poses a heavy load for resulting in many new cases which contribute significantly to medical costs. Although many NMIBC guidelines have been developed, their implementation remains deficient. OBJECTIVE: This study was conducted in order to analyze the knowledge of and compliance with the guidelines for NMIBC of Chinese urologists and to identify associated factors. METHODS: We conducted an online survey between August 2019 and January 2021. Respondents who were more than 65 years old or did not give informed consent were excluded. Linear/logistic regressions were performed to identify factors associated with the knowledge of and compliance with the guidelines of urologists, respectively. McNemar's tests were used to explore the divergence between knowledge and compliance. RESULTS: A total of 814 responses were received, and 98.77% of urologists acknowledged the positive effects of high-quality guidelines. The average knowledge score was 6.10 ± 1.28 (out of a full score of 9), and it was positively associated with educational level and the number of guidelines consulted. Only 1.61% and 39.36% of the respondents realized that the guidelines did not recommend further chemotherapy or BCG infusion for low-risk patients. There were 38.87% and 51.84% respondents "often" or more frequently utilizing BCG therapy for intermediate- and high-risk NMIBC patients, respectively. Divergence between knowledge and compliance in performing a second TURBT after incomplete initial resection reached statistical significance (p < 0.001). CONCLUSIONS: Although the vast majority of urologists acknowledged the positive effects of guidelines, knowledge of and compliance with some recommendations of NMIBC guidelines are still inadequate. Factors associated with guidelines, individual professionals, patients, organizations, and the environment jointly contributed to the non-compliance.

Effect of electrode temperature on measurements of transcutaneous carbon dioxide partial pressure and oxygen partial pressure in very low birth weight infants. / 电极温度对极低出生体重儿经皮二氧化碳分压和氧分压监测的影响.

OBJECTIVES: To evaluate the accuracy and safety of measurements of transcutaneous carbon dioxide partial pressure (TcPCO2) and transcutaneous oxygen partial pressure (TcPO2) at electrode temperatures lower than the value used in clinical practice in very low birth weight infants. METHODS: A total of 45 very low birth weight infants were enrolled. TcPCO2 and TcPO2 measurements were performed in these infants. Two transcutaneous monitors were placed simultaneously for each subject. One electrode was set and maintained at 42℃ used in clinical practice for neonates (control group), and the other was successively set at 38℃, 39℃, 40°C, and 41℃ (experimental group). The paired t-test was used to compare the measurement results between the groups. A Pearson correlation analysis was used to analyze the correlation between the measurement results of the experimental group and control group, and between the measurement results of experimental group and arterial blood gas parameters. RESULTS: There was no significant difference in TcPCO2 between each experimental subgroup (38-41℃) and the control group. TcPCO2 in each experimental subgroup (38-41℃) was strongly positively correlated with TcPCO2 in the control group (r>0.9, P<0.05) and arterial carbon dioxide partial pressure (r>0.8, P<0.05). There were significant differences in TcPO2 between each experimental subgroup (38-41℃) and the control group (P<0.05), but TcPO2 in each experimental subgroup (38-41℃) was positively correlated with TcPO2 in the control group (r=0.493-0.574, P<0.05) and arterial oxygen partial pressure (r=0.324-0.399, P<0.05). No skin injury occurred during transcutaneous measurements at all electrode temperatures. CONCLUSIONS: Lower electrode temperatures (38-41℃) can accurately measure blood carbon dioxide partial pressure in very low birth weight infants, and thus can be used to replace the electrode temperature of 42°C. Transcutaneous measurements at the lower electrode temperatures may be helpful for understanding the changing trend of blood oxygen partial pressure.

Oral microbiota in the oral-genitourinary axis: identifying periodontitis as a potential risk of genitourinary cancers.

Periodontitis has been proposed as a novel risk factor of genitourinary cancers: although periodontitis and genitourinary cancers are two totally distinct types of disorders, epidemiological and clinical studies, have established associations between them. Dysbiosis of oral microbiota has already been established as a major factor contributing to periodontitis. Recent emerging epidemiological evidence and the detection of oral microbiota in genitourinary organs indicate the presence of an oral-genitourinary axis and oral microbiota may be involved in the pathogenesis of genitourinary cancers. Therefore, oral microbiota provides the bridge between periodontitis and genitourinary cancers. We have carried out this narrative review which summarizes epidemiological studies exploring the association between periodontitis and genitourinary cancers. We have also highlighted the current evidence demonstrating the capacity of oral microbiota to regulate almost all hallmarks of cancer, and proposed the potential mechanisms of oral microbiota in the development of genitourinary cancers.

Ligand-Based and Docking-Based Virtual Screening of MDM2 Inhibitors as Potent Anticancer Agents.

A ligand-based and docking-based virtual screening was carried out to identify novel MDM2 inhibitors. A pharmacophore model with four features was used for virtual screening, followed by molecular docking. Seventeen compounds were selected for an in vitro MDM2 inhibition assay, and compounds AO-476/43250177, AG-690/37072075, AK-968/15254441, AO-022/43452814, and AF-399/25108021 showed promising MDM2 inhibition activities with K i values of 9.5, 8.5, 23.4, 3.2, and 23.1 µM, respectively. Four compounds also showed antiproliferative activity, and compound AO-022/43452814 was the most potent hit with IC50 values of 19.35, 26.73, 12.63, and 24.14 µM against MCF7 (p53 +/+), MCF7 (p53 -/-), HCT116 (p53 +/+), and HCT116 (p53 -/-) cell lines, respectively. Compound AO-022/43452814 could be used as a scaffold for the development of anticancer agents targeting MDM2.

Quality of and Recommendations for Relevant Clinical Practice Guidelines for COVID-19 Management: A Systematic Review and Critical Appraisal.

Background: The morbidity and mortality of coronavirus disease 2019 (COVID-19) are still increasing. This study aimed to assess the quality of relevant COVID-19 clinical practice guidelines (CPGs) and to compare the similarities and differences between recommendations. Methods: A comprehensive search was conducted using electronic databases (PubMed, Embase, and Web of Science) and representative guidelines repositories from December 1, 2019, to August 11, 2020 (updated to April 5, 2021), to obtain eligible CPGs. The Appraisal of Guidelines for Research and Evaluation (AGREE II) tool was used to evaluate the quality of CPGs. Four authors extracted relevant information and completed data extraction forms. All data were analyzed using R version 3.6.0 software. Results: In total, 39 CPGs were identified and the quality was not encouragingly high. The median score (interquartile range, IQR) of every domain from AGREE II for evidence-based CPGs (EB-CPGs) versus (vs.) consensus-based CPG (CB-CPGs) was 81.94% (75.00-84.72) vs. 58.33% (52.78-68.06) in scope and purpose, 59.72% (38.89-75.00) vs. 36.11% (33.33-36.11) in stakeholder involvement, 64.58% (32.29-71.88) vs. 22.92% (16.67-26.56) in rigor of development, 75.00% (52.78-86.81) vs. 52.78% (50.00-63.89) in clarity of presentation, 40.63% (22.40-62.50) vs. 20.83% (13.54-25.00) in applicability, and 58.33% (50.00-100.00) vs. 50.00% (50.00-77.08) in editorial independence, respectively. The methodological quality of EB-CPGs were significantly superior to the CB-CPGs in the majority of domains (P < 0.05). There was no agreement on diagnosis criteria of COVID-19. But a few guidelines show Remdesivir may be beneficial for the patients, hydroxychloroquine +/- azithromycin may not, and there were more consistent suggestions regarding discharge management. For instance, after discharge, isolation management and health status monitoring may be continued. Conclusions: In general, the methodological quality of EB-CPGs is greater than CB-CPGs. However, it is still required to be further improved. Besides, the consistency of COVID-19 recommendations on topics such as diagnosis criteria is different. Of them, hydroxychloroquine +/- azithromycin may be not beneficial to treat patients with COVID-19, but remdesivir may be a favorable risk-benefit in severe COVID-19 infection; isolation management and health status monitoring after discharge may be still necessary. Chemoprophylaxis, including SARS-CoV 2 vaccines and antiviral drugs of COVID-19, still require more trials to confirm this.

Circ-sirt1 inhibits growth and invasion of gastric cancer by sponging miR-132-3p/miR-212-3p and upregulating sirt1 expression.

circRNAs have been considered as a rising factor in cancers. However, the roles and mechanisms of circ-sirt1 in gastric cancer (GC) remain largely unknown. In this study, we found that the expressions of sirt1 and circ-sirt1 are decreased in tissues or serums of GC patients by real-time quantitative PCR (RT-qPCR). The expressions of miR-132-3p/miR-212-3p showed an opposite tendency in these samples. The co-transfection of miR-132-3p/miR-212-3p mimics counteracted the enhancement of sirt1 expression induced by circ-sirt1. The results of cell colony-formation assay and transwell assays demonstrated that the proliferation, migration, and invasion activities of BGC-823 cells were inhibited by circ-sirt1 overexpression or miR-132-3p/miR-212-3p knockdown, respectively. The xenograft tumor model result indicated that the circ-sirt1 overexpression suppressed the tumor growth of BGC-823 cells. The regulation of miR-132-3p/miR-212-3p between circ-sirt1 and sirt1 was verified in the mice tumor tissues. Thus, circ-sirt1 inhibited tumor growth and invasion probably by sponging miR-132-3p/miR-212-3p and upregulating sirt1 expression in GC. These findings may provide a theoretical basis for the classification of GC and a novel therapeutic target for GC patients.

LPS Enhances the Chemosensitivity of Oxaliplatin in HT29 Cells via GSDMD-Mediated Pyroptosis.

INTRODUCTION: Pyroptosis induced by lipopolysaccharide (LPS) is a dissolved form of cell death. The molecular marker gasdermin D, specifically GSDMD-N, is critically required for the induction of pyroptosis. Recently, there have been studies showing that LPS is closely related to tumor biology. METHODS: Specimens from 40 patients with colorectal cancer (CRC) were collected. Eight- to twelve-week-old C57BL6 male mice (n=30) were raised. Immunohistochemistry and Western blot were performed to test the expression of GSDMD. Moreover, cytotoxicity assay, IL-18 and IL-1ß ELISA, Annexin V and PI stain, and wound healing assay were also made. Gene Expression Profiling Interactive Analysis (GEPIA) was used to verify the expression of GSDMD and overall survival of CRC patients with a high/low expression of GSDMD. RESULTS: In the research, we showed that the poor prognosis in CRC patients was significantly related to the GSDMD expression and significantly down-regulated in human colorectal cancer (CRC) tissues. Treatment with LPS, but not TNF-α, induced pyroptosis via promoting the expression of GSDMD and GSDMD-N membrane translocation and enhanced chemosensitivity in response to L-OHP in HT29 cells. Furthermore, the enforced expression of GSDMD in HT29 cells reduced cell survival and induced cell death. DISCUSSION: These results of studies suggest that the low expression of GSDMD correlates with a poor CRC prognosis, and that pyroptosis induced by LPS may improve the anti-cancer effect of L-OHP, inhibiting the tumorigenesis of CRC by activating GSDMD. Our findings lay the foundation for further development of GSDMD serving as an important prognostic biomarker and a valid CRC therapeutic target.

Coronavirus Disease 2019 Related Clinical Studies: A Cross-Sectional Analysis.

OBJECTIVE: The quality and rationality of many recently registered clinical studies related to coronavirus disease 2019 (COVID-19) needs to be assessed. Hence, this study aims to evaluate the current status of COVID-19 related registered clinical trial. METHODS: We did an electronic search of COVID-19 related clinical studies registered between December 1, 2019 and February 21, 2020 (updated to May 28, 2020) from the ClinicalTrials.gov, and collected registration information, study details, recruitment status, characteristics of the subjects, and relevant information about the trial implementation process. RESULTS: A total of 1,706 studies were included 10.0% of which (n=171) were from France, 943 (55.3%) used an interventional design, and 600 (35.2%) used an observational design. Most of studies (73.6%) aimed to recruit fewer than 500 people. Interferon was the main prevention program, and antiviral drugs were the main treatment program. Hydroxychloroquine and chloroquine (230/943, 24.4%) were widely studied. Some registered clinical trials are incomplete in content, and 37.4% of the 1,706 studies may have had insufficient sample size. CONCLUSION: The quality of COVID-19 related studies needs to be improved by strengthening the registration process and improving the quality of clinical study protocols so that these clinical studies can provide high-quality clinical evidence related to COVID-19.

Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: An evidence-based clinical practice guideline (updated version).

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.

Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: an evidence-based clinical practice guideline (updated version)

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID19 patients

Bibliometric analysis of randomized controlled trials of colorectal cancer over the last decade.

BACKGROUND: Colorectal cancer is one of the most common cancers globally. In China, its prevalence ranks fourth and fifth among females and males, respectively. Presently, treatment of rectal cancer follows a multidisciplinary comprehensive treatment approach involving surgery, radiotherapy, chemotherapy, and targeted therapy. With deepening theoretical and molecular research on colorectal cancer, randomized controlled trials (RCTs) on colorectal cancer have made significant progress. However, many RCTs have shortfalls. AIM: To investigate the RCTs of global colorectal cancer spanning from 2008 to 2018. To provide suggestions for conducting Chinese RCTs of colorectal cancer. METHODS: PubMed and Web of Science databases were searched to obtain RCTs of colorectal cancer carried out between January 1, 2008, and January 1, 2018. The bibliometric method was used for statistical analysis of the publication years, countries/regions, authors, institutions, source journals, quoted times, key words, and authors. RESULTS: Colorectal cancer RCTs showed an upward trend between 2008 to 2018; the top 10 research institutions in the included literature were from the United States, the United Kingdom, and other countries with a high incidence of colorectal cancer. Most of the related research journals are sponsored by European and American countries. The 15 most cited studies involved international multicenter clinical research, having few participants from Chinese research institutions. Network visualization using key words showed that RCTs on colorectal cancer focus on screening, disease-free survival, drug treatment, surgical methods, clinical trials, quality of life, and prognosis. The result of the coauthorship network analysis showed that Chinese researchers are less involved in international exchanges compared to those from leading publication countries. CONCLUSION: High-quality RCTs are increasingly favored by leading international journals. However, there is still a large gap in clinical research between China and leading countries. Researchers should implement standardized and accurate clinical trials, strengthen international multicenter cooperation, and emphasize quality control.

Re-positive Cases of Nucleic Acid Tests in Discharged Patients With COVID-19: A Follow-Up Study.

Background: The frequent emergence of the re-positive patients with COVID-19 is a potential threat worldwide. This study aimed to describe data from admission to follow-up for patients with COVID-19 and analyze the possible causes for re-positive nucleic acid tests to provide more scientific basis for reducing the numbers of re-positive patients after discharge. Methods: We retrospectively recorded 15 patients with COVID-19 admitted to the Xianyang Central Hospital, China. The baseline, exposure histories, clinical syndromes, laboratory characteristics, nucleic acid, and follow-up tests were analyzed, and the radiological characteristics of re-positive patient at different periods were compared. Results: Eight (53.33%) patients had the history of travel to Wuhan, four (26.67%) patients had close contact with confirmed patients, and one (6.67%) patient had close contact with suspected patients. After treatment, all patients had two consecutively negative nucleic acid tests and were discharged from hospital. All patients were followed up for more than 14 days, and the average time from discharge to the first follow-up was 14.67 ± 3.31 days (from 9 to 22 days). Most patients showed no clinical symptoms and negative nucleic acid tests, while one patient had an itchy throat, her CT scan showed a light density shadow in the right lower lobe of the lung, and the nucleic acid was once again positive. The second follow-up of the other 14 patients (except the re-positive one) was conducted 20.80 ± 7.78 days (from 13 to 30 days) after discharge, and all of them had negative nucleic acid tests. The positive patient was immediately readmitted and received a new round of treatment. Her family members and colleagues remained healthy until now. Conclusions: The quality of nucleic acid testing reagents should be enhanced, and the training of nucleic acid sampling operators should be strengthened to reduce the false-negative results in the nucleic acid of SARS-CoV-2; the clinical specimens of throat and nasopharynx swabs can be collected at the same time; IgM- and IgG-specific antibodies of SARS-CoV-2 should be carried out for discharged patients; the radiological characteristics should be evaluated strictly; and the discharge standard can be specified according to the baseline and severity of disease of patients.

Hsa_circ_0002320: a novel clinical biomarker for colorectal cancer prognosis.

A great many circular RNAs (circRNAs) exist in different types of mammalian cells. Previous studies have verified that a low level of hsa_circ_0002320 is present in gastric cancer and that it might represent a good prognostic indicator. However, its value in colorectal cancer (CRC) is unclear. The aim of this research was to explore the value of hsa_circ_0002320 as a potential diagnostic biomarker for CRC prognosis.Plasma samples, CRC tissues, and adjacent normal tissues were obtained from 50 patients with CRC, before any treatment, and 100 plasma samples were acquired from healthy individuals. Hsa_circ_0002320 levels in these samples were analyzed by reverse transcription-quantitative polymerase chain reaction. Correlations between hsa_circ_0002320, clinicopathological characteristics, and overall survival (OS) of CRC patients were also investigated. Receiver-operating characteristic (ROC) curve analysis was used to assess the value of hsa_circ_0002320 for CRC diagnosis. Finally, a bioinformatics analysis was performed to verify the effect of hsa_circ_0002320 on CRC prognosis.Expression levels of hsa_circ_0002320 were significantly decreased in CRC plasma (P < .05). The expression level of hsa_circ_0002320 was significantly correlated with OS time (P < .05). Higher hsa_circ_0002320 reflected significantly greater OS; the HR of high hsa_circ_0002320 was 0.161 (95% CI, 0.066-0.393; P = .000). The area under the ROC curve of hsa_circ_0002320 in CRC was 0.823, which was higher than for the carcinoembryogenic antigen (area under the curve = 0.764). Kaplan-Meier analysis showed that CRC patients with low expression of hsa_circ_0002320 exhibited poorer OS times than those with high expression.Hsa_circ_0002320 could be a novel, noninvasive diagnostic blood biomarker for CRC prognosis.