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Osteosarcoma is a quickly developing, malignant cancer of the bone, which is associated with a bad prognosis. In osteosarcoma, hypoxia promotes the malignant phenotype, which results in a cascade of immunosuppressive processes, poor prognosis, and a high risk of metastasis. Nonetheless, additional methodologies for the study of hyperoxia in the tumor microenvironment also need more analysis. We obtained 88 children patients with osteosarcoma from the Therapeutically Applicable Research to Generate Effective Treatment (TARGET) database and 53 children patients with RNA sequence and clinicopathological data from the Gene Expression Omnibus (GEO). We developed a four-gene signature related to hypoxia to reflect the immune microenvironment in osteosarcoma that predicts survival. A high-risk score indicated a poor prognosis and immunosuppressive microenvironment. The presence of the four-gene signature related to hypoxia was correlated with clinical and molecular features and was an important prognostic predictor for pediatric osteosarcoma patients. In summary, we established and validated a four-gene signature related to hypoxia to forecast recovery and presented an independent prognostic predictor representing overall immune response strength within the osteosarcoma microenvironment.

Background Diagnosis of malignant biliary obstruction is complicated and lacks accuracy. Exosomes may be secreted by malignant tumors; intact miRNAs from exosomes might serve as potential biomarkers for the disease. Aim To identify exosomal microRNAs in human bile among benign and malignant biliary obstructions. Methods Bile samples were collected from patients undergoing therapeutic endoscopic retrograde cholangiopancreatography for biliary obstruction. Exosome microRNAs were determined by RNA-sequencing in the discovery cohort, which comprising benign (n = 5) cases and malignant biliary obstruction (n = 5) cases. Then, the diagnostic performance of the two up-regulated microRNAs (mir-483-5p and mir-126-3p) of bile exosomes was verified by analysis of 82 patients with a diagnosis of malignant (n=37) or nonmalignant (n=45) biliary obstruction. Results In both cohorts, the expressions of mir-483-5p and mir-126-3p were significantly higher in bile exosomes samples from patients with malignant biliary obstructions than controls. In the verification cohort, the two miRNAs can distinguished the benign and malignant groups with high diagnostic accuracy and specificity; the diagnostic values of the two microRNAs were better than serum carbohydrate antigen 19-9 (CA19-9), area under the curve (AUC) were 0.81 and 0.74. Conclusion The expression of exosomal mir-483-5p and mir-126-3p in the bile samples discriminates between patients with malignant and nonmalignant biliary obstructions. Clinical Trial registration no NCT03102268

With the rapid advances in endoscopic technology, endoscopic therapy (ET) is increasingly applied to the treatment of small (≤ 20 mm) colorectal neuroendocrine tumors (NETs). However, long-term data comparing ET and surgery for management of T1N0M0 colorectal NETs are lacking. The purpose of this work was to compare overall survival (OS) and cancer-specific survival (CSS) of such patients with ET or surgery. Patients with T1N0M0 colorectal NETs were identified within the Surveillance Epidemiology and End Results (SEER) database (2004–2016). Demographics, tumor characteristics, therapeutic methods, and survival were compared. Propensity score matching (PSM) was used 1:3 and among this cohort, Cox proportional hazards regression models were performed to evaluate correlation between treatment and outcomes. Of 4487 patients with T1N0M0 colorectal NETs, 1125 were identified in the matched cohort, among whom 819 (72.8%) underwent ET and 306 (27.2%) underwent surgery. There was no difference in the 5-year and 10-year OS and CSS rates between the 2 treatment modalities. Likewise, analyses stratified by tumor size and site showed that patients did not benefit more from surgery compared with ET. Moreover, multivariate analyses found no significant differences in OS [Hazard Ratio (HR) = 0.857, 95% Confidence Interval (CI): 0.513–1.431, P = 0.555] and CSS (HR = 0.925, 95% CI: 0.282–3.040, P = 0.898) between the 2 groups. Similar results were observed when comparisons were limited to patients with different tumor size and site. In this population-based study, patients with lesions

Background. The functional characteristics of NLRP3 in the pathogenesis of coxsackievirus B3- (CVB3-) induced viral myocarditis (VMC) have not been fully elucidated, and the targeted therapeutic effect of NLRP3 or its related pathway in VMC has not been reported. Method. In this work, the change patterns of NLRP3- and Th17-related factors were detected during the pathological process of CVB3-induced VMC in Balb/c mice. The correlation between NLRP3 and Th17 cells during the VMC process was analyzed by Spearman test. The coculture system of spleen CD4+ T and bone marrow CD11c+ DC cells was set to explore the orchestration of NLRP3 and Th17 in the pathological development of VMC in vitro. Anti-IL-1β antibody or NLRP3-/- Balb/c were used to block the NLRP3 pathway indirectly and directly to analyze the NLRP3-targeting therapeutic value. Results. The change patterns of NLRP3- and Th17-related molecules in the whole pathological process of mouse CVB3-induced VMC were described. Through Spearman correlation analysis, it was confirmed that there was a close correlation between NLRP3 and Th17 cells in the whole pathological process of VMC. And the interaction mode between NLRP3 and Th17 was preliminarily explored in the cell experiment in vitro. Under the intervention of an anti-IL-1β antibody or NLRP3 knockout, the survival rate of the intervention group was significantly improved, the degree of myocardial inflammation and fibrosis was significantly alleviated, and the content of myocardial IL-17 and spleen Th17 was also significantly decreased. Conclusion. Our findings demonstrated a key role of the NLRP3 inflammasome and its close relationship with Th17 in the pathological progression of CVB3-induced VMC and suggested a possible positive feedback-like mutual regulation mechanism between the NLRP3 inflammasome and Th17 in vitro and in the early stage of CVB3 infection. Taking NLRP3 as a new starting point, it provides a new target and idea for the prevention and treatment of CVB3-induced VMC.

Aiming at the problem that the Aspect-based sentiment analysis in Chinese has low recognition rate due to many steps, this paper proposes an improved BiLSTM-CRF model based on combine the Chinese character vector and Chinese words position feature, which can extract attribute words and sentiment words jointly simultaneously, while extracting Polarity judges of sentiment words. Experiments show that the improved model improves the precision rate by 9.2% 13.32%, recall rate improves 0.48% 21.29%, F-measure improves 7.33% 15.74% compared with Conditional Random Fields (CRF) model and Long Short Term Memory (LSTM) model on the self-built 6357 mobile reviews dataset. The experimental results show that the model improves the accuracy of Aspect-based sentiment analysis and can effectively obtain the information required by users need in evaluation texts.

Objective. The aim of this research was to create a new genetic signature of immune checkpoint-associated genes as a prognostic method for pediatric acute myeloid leukemia (AML). Methods. Transcriptome profiles and clinical follow-up details were obtained in Therapeutically Applicable Research to Generate Effective Treatments (TARGET), a database of pediatric tumors. Secondary data was collected from the Gene Expression Omnibus (GEO) to test the observations. In univariate Cox regression and multivariate Cox regression studies, the expression of immune checkpoint-related genes was studied. A three-mRNA signature was developed for predicting pediatric AML patient survival. Furthermore, the GEO cohort was used to confirm the reliability. A bioinformatics method was utilized to identify the diagnostic and prognostic value. Results. A three-gene (STAT1, BATF, EML4) signature was developed to identify patients into two danger categories depending on their OS. A multivariate regression study showed that the immune checkpoint-related signature (STAT1, BATF, EML4) was an independent indicator of pediatric AML. By immune cell subtypes analyses, the signature was correlated with multiple subtypes of immune cells. Conclusion. In summary, our three-gene signature can be a useful tool to predict the OS in AML patients.

Biological evidence suggests that vitamin D has numerous anti-cancer functions, but the associations between vitamin D status and colorectal cancer (CRC) risk and survival remain inconclusive. Based on UK Biobank, we prospectively evaluated the associations of season-standardized 25-hydroxyvitamin D (25(OH)D) concentrations with CRC risk among 360,061 participants, and with survival among 2,509 CRC cases. We observed an inverse linear relationship between 25(OH)D concentrations and CRC risk (P for linearity = 0.01; HR per 1-standard deviation increment, 0.95; 95% CI, 0.91-0.99). Compared to the lowest quartile of 25(OH)D, the highest quartile was associated with a 13% (HR, 0.87; 95% CI, 0.77-0.98) lower risk of CRC. For CRC survival, compared to those in the lowest quartile of 25(OH)D, cases in the highest quartile had a 20% (HR, 0.80; 95% CI, 0.65-0.99) lower risk for overall death. Our findings indicate that higher concentrations of serum 25(OH)D are associated with lower incidence and improved survival of CRC, suggesting a role of vitamin D in the pathogenesis of CRC.

Background: Elderly patients with Intrahepatic Cholangiocarcinoma (ICC) are frequently under-represented in clinical trials, which leads to the unclear management of ICC in elderly patients. This study aimed to describe treatment patterns and establish a reliable nomogram in elderly ICC patients. Methods: Based on the Surveillance, Epidemiology, and End Results (SEER) database, we conducted a retrospective analysis of 1651 elderly patients (≥65 years) diagnosed with ICC between 2004 and 2016. Results: For the whole study population, 29.3% received only chemotherapy, 26.7% no tumor-directed therapy, 19.1% surgery alone, 17.5% radiotherapy, and 7.4% surgery plus chemotherapy. Compared with the age group of 65-74 years, patients aged ≥75 years were less likely to accept treatment. Among patients 66-74 years of age, surgery alone resulted in a median overall survival (OS) of 30 months, surgery combined with chemotherapy 26 months, radiotherapy 17 months, chemotherapy alone 10 months and no therapy 3 months; while among patients ≥75 years of age, the median OS was 21, 25, 14, 9 and 4, respectively. Moreover, independent prognostic indicators including age, gender, grade, tumor size, T stage, N stage, M stage, and treatment were incorporated to construct a nomogram. The C-indexes of the OS nomogram were 0.725 and 0.724 for the training and validation cohorts, respectively. Importantly, the predictive model harbored a better discriminative power than the American Joint Committee on Cancer TNM staging system. Conclusion: Active treatment should not be abandoned among all the elderly patients with ICC. The validated nomogram provided an effective and practical tool to accurately evaluate prognosis and to guide personalized treatment for elderly ICC patients.

Context Wei Chang An (WCA) is a commercial prescription developed for the coordination of gastrointestinal movement. Objective To investigate the role of WCA in the regulation of diarrhoea and constipation in rats. Material and methods The diarrhoea and constipation models were prepared by gavage of Folium senna and diphenoxylate hydrochloride. Rats were randomized equally (n = 6) into the normal group given saline daily, the positive group given Pinaverium Bromide (13.5 mg/kg) or Sennoside A (0.1 mg/kg) and three WCA-treated groups (22, 44, and 88 mg/kg) by gavage daily for 7 consecutive days. The effects of WCA were assessed by a series of faecal symptoms and histopathology. Gastrointestinal parameters were determined by ELISA. The effect of WCA on gastrointestinal tissues was evaluated by strip assay. Expression of ROCK-1 and MLCK was measured by RT-PCR and Western blotting. Results Data from Bristol stool form scale, diarrhoea index, visceral sensitivity, defaecation time, and intestinal propulsive rate showed that WCA protected rats against diarrhoea and constipation (p

In order to accurately analyze the safety management efficiency of China’s coal enterprises, based on the panel data of 14 coal listed enterprises in 2012–2018, this paper analyzes the overall technical efficiency (TE), pure technical efficiency (PTE) and scale efficiency (SE) of safety management of sample enterprises by the Data Envelopment Analysis (DEA) model, and builds Tobit model of random panel effect to evaluate the impact of business management and safety investment on safety management efficiency. The results show that: in 2012–2018, the average values of TE, PTE and SE of sample enterprises are respectively 0.674, 0.777 and 0.864; all have great room for improvement. The development of PTE and SE in most sample enterprises is unbalanced; TE of sample enterprises does not significantly improve, and shows a trend of rising-decreasing-rising; safety investment, enterprise scale and labor productivity are significantly positively related to safety management technical efficiency, while safety training person time and employees quality are negatively correlated. This paper identified the positive and negative effects of various influencing factors on the safety management efficiency of coal enterprises, and analyzed the main reasons that hinder the improvement of safety efficiency, and puts forward corresponding countermeasures and suggestions, which are helpful for coal enterprises to effectively improve their safety management efficiency and economic efficiency.

BACKGROUND Endoscopic retrograde cholangiopancreatography (ERCP) is a valuable therapeutic technique for pancreatobiliary diseases, and its application in the elderly is no longer limited. However, a higher incidence of procedure difficulty and periprocedural adverse events might be expected in elderly patients due to the presence of other medical disorders and the poor general condition of this population. AIM To evaluate the incidence, causes, and management of difficult biliary cannulation during ERCP in elderly patients and the role of difficult cannulation as a risk factor for adverse events. METHODS A total of 614 patients who underwent ERCP during the study period were prospectively studied and divided into two groups based on their age. One hundred and forty-six patients were aged 80 years or older and 468 patients were aged less than 80 years. The primary outcome measurements were cannulation difficulty, cannulation success rate, ERCP procedure time, and related adverse events. RESULTS There was no difference in the incidence of difficult cannulation among the two groups (32.9% vs 34.4%, P = 0.765), as well as in the cannulation success rate (96.6% vs 96.8%, P = 0.54). The cannulation techniques were shown to be safe and efficient in achieving successful cannulation. Logistic regression analysis showed that patients aged 80 years or older were not associated with increased adverse events; however, difficult cannulation cases [adjusted odds ratio (AOR) = 3.478; 95% confidence interval (CI): 1.877-6.442; P < 0.001] and patients with Charlson Comorbidity Index ≥ 2 (AOR = 1.824; 95%CI: 0.993-3.349; P = 0.045) were more likely to develop adverse events. In contrast, other factors including age ≤ 65 (AOR = 3.460; 95%CI: 1.511-7.922; P = 0.003), female gender (AOR = 2.362; 95%CI=1.089-5.124; P = 0.030), difficult cannulation (AOR = 4.527; 95%CI: 2.078-9.860; P < 0.001), and patients with cholangitis (AOR = 3.261; 95%CI: 1.204-8.832; P = 0.020) were strongly associated with a higher rate of post-ERCP pancreatitis. CONCLUSION Advanced age has not been proved to be a risk factor for difficult cannulation, and secondary cannulation techniques can be safely and efficaciously utilized in this group. Patients with a Charlson Comorbidity Index ≥ 2 and difficult cannulation are associated with an increased overall adverse events rate, while age ≥ 80 years is not.

Background It has been widely reported that the expression levels of SNHG20 are elevated in diverse types of cancers, indicating that SNHG20 may participate in cancer initiation and development. Besides, accumulating evidence reveals that SNHG20 overexpression is also connected with poor clinical outcomes among cancer patients. Herein, we carry out a systematic meta-analysis to further determine the prognostic and clinical significance of SNHG20 expression in various human cancers. Methods Qualifying publications were selected by searching for keywords in PubMed, Embase, Web of Science and Cochrane Library databases, up to September 1, 2019. Pooled hazard ratio (HR) or odds ratio (OR) with corresponding 95% confidence interval (CI) was computed to estimate the strength of association between SNHG20 and survival of cancer patients or clinicopathology using Stata 14.0 software. Results In total, 15 studies encompassing 1187 patients met the inclusion criteria were ultimately enrolled for analysis. According to the meta-analysis, patients with high SNHG20 expression were markedly linked to poorer overall survival (OS) (pooled HR = 2.47, 95% CI 2.05–2.98, P = 0.000) and disease-free survival/recurrence-free survival/progression-free survival (DFS/RFS/PFS) (pooled HR = 2.37, 95% CI 1.60–3.51, P = 0.000). Additionally, regarding clinicopathology of patients, enhanced SNHG20 was correlated with advanced tumour‐node‐metastasis (TNM) stage (OR = 2.80, 95% CI 2.00–3.93, P = 0.000), larger tumor size (OR = 3.08, 95% CI 2.11–4.51, P = 0.000), positive lymph nodes metastasis (OR = 2.99, 95% CI 2.08–4.31, P = 0.000), higher tumor stage (OR = 4.51, 95% CI 2.17–9.37, P = 0.000) and worse histological grade (OR = 1.95, 95% CI 1.44–2.63, P = 0.000), but not with gender, smoking status or distant metastasis. Conclusions Up-regulated SNHG20 expression is ubiquitous in different kinds of cancers. Moreover, up-regulated SNHG20 expression is capable of serving as an innovative predictive factor of inferior clinical outcomes in cancer patients. Nevertheless, higher-quality multicenter studies are required to corroborate our results.

Background Mounting epidemiologic studies have investigated the potential inverse association between Mediterranean diet (MD) adherence and colorectal cancer (CRC) incidence and mortality. Objectives This meta-analysis aimed to investigate the association between MD adherence and CRC incidence and mortality. Methods PubMed, Embase, and Web of Science were searched to identify eligible studies through September 2019. A random-effects model was used to estimate summary RRs and 95% CIs. Results This meta-analysis included 13 prospective cohort studies, of which 9 reported CRC incidence and 5 reported CRC mortality. The summary RR of CRC incidence was 0.90 (95% CI: 0.84, 0.96) for highest compared with lowest MD adherence and 0.96 (95% CI: 0.94, 0.99) per 2-score increase in MD adherence. The summary RRs for highest compared with lowest MD adherence were 0.82 for rectal cancer (95% CI: 0.71, 0.95), 0.94 for proximal colon cancer (95% CI: 0.87, 1.02), and 0.91 for distal colon cancer (95% CI: 0.79, 1.04). Neither the summary HR of overall mortality for highest compared with lowest pre- and postdiagnosis MD adherence, nor the summary HR of CRC-specific mortality for highest compared with lowest prediagnosis MD adherence achieved a value with statistical significance. Conclusions Our meta-analysis supports the inverse association of MD adherence with CRC incidence, but not with overall mortality or CRC-specific mortality among those diagnosed with CRC.

Studies published in recent years have demonstrated that abnormal long noncoding RNA (lncRNA) antisense RNA to TP73 gene (TP73-AS1) expression is markedly associated with tumorigenesis, cancer progression and the prognosis of cancer patients. We aimed to explore the prognostic value of TP73-AS1 in multiple cancers. We comprehensively searched PubMed, Embase, Web of Science and the Cochrane Library (up to February 21, 2019). Hazard ratios (HRs), odds ratios (ORs) and the corresponding 95% confidence intervals (95% CIs) were calculated to estimate the association of TP73-AS1 with survival and clinicopathological features. The potential targets and pathways of TP73-AS1 in multiple cancers were summarized. Nineteen studies that involved thirteen types of cancers and 1329 cancer patients were identified as eligible for this meta-analysis. The results showed that high TP73-AS1 expression was significantly correlated with shorter overall survival (OS) (HR = 1.962, 95% CI 1.630-2.362) and disease-free survival (DFS) (HR = 2.050, 95% CI 1.293-3.249). The summary HRs of OS were 2.101 (95% CI 1.516-2.911) for gastric cancer (GC) and 1.920 (95% CI 1.253-2.942) for osteosarcoma. Subgroup analysis of OS demonstrated that the differential expression of TP73-AS1 in cancer tissues was a potential source of heterogeneity. Furthermore, increased TP73-AS1 expression was markedly associated with larger tumor size (OR = 2.759, 95% CI 1.759-4.330), advanced histological grade (OR = 2.394, 95% CI 1.231-4.656), lymph node metastasis (OR = 2.687, 95% CI 1.211-5.962), distant metastasis (OR = 4.145, 95% CI 2.252-7.629) and advanced TNM stage (OR = 2.633, 95% CI 1.507-4.601). The results of Egger’s test and sensitivity analysis verified the robustness of the original results. High TP73-AS1 expression can predict poor survival and poor clinicopathological features in cancer patients and TP73-AS1 might be a potential biomarker and therapeutic target.

Colorectal cancer (CRC) is the second leading cause of cancer-associated mortality worldwide. Currently, available diagnostic biomarkers are neither sensitive nor specific. Thus, the present study aimed to identify novel circulating microRNAs (miRNAs) as biomarkers for the early diagnosis of CRC. All samples were provided by The Second Affiliated Hospital of Nanjing Medical University (Nanjing, China). Analysis of the GSE108153 and GSE55139 datasets, downloaded from the Gene Expression Omnibus (GEO) database was performed using the online tool, GEO2R. Reverse transcription-quantitative PCR was performed to determine miR-592 expression in CRC tissues, cells and serums of patients. Subsequently, the diagnostic value of serum miR-592 was assessed via receiver operating characteristic (ROC) curve analysis. Both the assessment of clinical samples and bioinformatics analysis demonstrated that miR-592 expression levels were significantly upregulated in the tissues and serum of patients with CRC, suggesting that elevated serum miR-592 may be tumor-derived. ROC analysis indicated that serum miR-592 levels may differentiate patients with early stage CRC and advanced adenoma from healthy individuals, with area under the curve values of 0.801 and 0.747, respectively. Taken together, the results of the present study suggest that serum miR-592 may be implicated as a potential biomarker for the early diagnosis of CRC.

Material composition changes of coal and gas under igneous intrusion have been one of the hot research fields in global geology. In this study, through in-depth discussion of a case from Huainan co...

The components of the tumor microenvironment (TME) in solid tumors, especially chemokines, are currently attracting much attention from scientists. C‐X‐C motif chemokine ligand 5 (CXCL5) is one of the important chemokines in TME. Overexpression of CXCL5 is closely related to the survival time, recurrence and metastasis of cancer patients. In TME, CXCL5 binds to its receptors, such as C‐X‐C motif chemokine receptor 2 (CXCR2), to participate in the recruitment of immune cells and promote angiogenesis, tumor growth, and metastasis. The CXCL5/CXCR2 axis can act as a bridge between tumor cells and host cells in TME. Blocking the transmission of CXCL5/CXCR2 signals can increase the sensitivity and effectiveness of immunotherapy and slow down tumor progression. CXCL5 and CXCR2 are also regarded as biomarkers for predicting prognosis and molecular targets for customizing the treatment. In this review, we summarized the current literature regarding the biological functions and clinical significance of CXCL5/CXCR2 axis in TME. The possibility to use CXCL5 and CXCR2 as potential prognostic biomarkers and therapeutic targets in cancer is also discussed

Background and aims: Xuanfei Baidu decoction (XFBD), a traditional Chinese medicine formulation, was designed and successfully applied for COVID-19 disease treatment in China, while the mechanism is still not clear.Methods: To evaluate the protective effect of XFBD on immunosuppression in cyclophosphamide (CY)-treated mice, XFBD was orally administrated, the body weight was measured, and the immune organ index was calculated. HE staining was performed to analyze the pathological structures of the liver, spleen, and thymus. The levels of cytokines and immunoglobulin in the serum and spleen were evaluated by ELISA and RT-PCR. Splenic lymphocytes were isolated, and LPS-stimulated cell proliferation and the number of CD4+ and CD8+ T lymphocytes were evaluated.Results: XFBD significantly suppressed body weight loss and increased the indices of spleen and thymus. The pathological alteration was much improved after XFBD administration. The reductions of TNF-α, IFN-γ, IgG, and IgM levels in serum and IL-2, IL-4, and IL-6 expressions in the spleen were all significantly alleviated by XFBD. Splenic lymphocyte proliferation in response to LPS was further enhanced after treatment with XFBD. The reduction of CD4+ and CD8+ T lymphocytes in CY-treated mice was also highly increased in XFBD groups.Conclusion: Our findings suggested that XFBD played a crucial role in protection against immunosuppression in CY-treated mice and could be a potential candidate for immune modification and therapy.

Triple-negative breast cancer (TNBC) is an aggressive disease with a high recurrence rate and poor outcomes in clinic. In this study, inspired by the enriched innate immune cell type tumor-associated macrophages (TAMs) in TNBC, we proposed a matrix metalloprotease 2 (MMP2) responsive integrated immunochemotherapeutic strategy to deliver paclitaxel (PTX) and anti-CD47 (aCD47) by detachable immune liposomes (ILips). In the TNBC microenvironment, the "two-in-one" ILips facilitated MMP2-responsive release of aCD47 to efficiently polarize M2 macrophages toward the M1 phenotype to enhance phagocytosis against tumor cells and activate the systemic T cell immune response. Together with the immune effect, the detached PTX-loaded liposomes were internalized in MDA-MB-231 cells to synergistically inhibit tumor cell proliferation and metastasis. In the TNBC-bearing mouse model, PTX-loaded ILips demonstrated superior antitumor efficacy against TNBC and inhibited tumor recurrence. Our integrated strategy represents a promising approach to synchronously enhance immune response and tumor-killing effects, improving the therapeutic efficacy against TNBC.

Traditional Chinese medicine (TCM) has been successfully applied worldwide in the treatment of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the pharmacological mechanisms underlying this success remain unclear. Hence, the aim of this review is to combine pharmacological assays based on the theory of TCM in order to elucidate the potential signaling pathways, targets, active compounds, and formulas of herbs that are involved in the TCM treatment of COVID-19, which exhibits combatting viral infections, immune regulation, and amelioration of lung injury and fibrosis. Extensive reports on target screening are elucidated using virtual prediction via docking analysis or network pharmacology based on existing data. The results of these reports indicate that an intricate regulatory mechanism is involved in the pathogenesis of COVID-19. Therefore, more pharmacological research on the natural herbs used in TCM should be conducted in order to determine the association between TCM and COVID-19 and account for the observed therapeutic effects of TCM against COVID-19.

Background: Substance P (SP) contributes to the pathogenesis of pain by acting on neurokinin‐1 receptor (NK-1R), specialized sensory neurons that detect noxious stimuli. Aprepitant, an antagonist of NK-1R widely used to treat chemotherapy-induced nausea and vomiting. In this study, we assessed aprepitant’s analgesic effect on inflammatory pain in mice and its mechanism of action in spinal cord.Methods: The excitability of DRG neurons treatment with aprepitant was measured using whole-cell patch-clamp recordings. The inflammatory pain model was induced in adult ICR mice by a single dose intraplantar injection of formalin and carrageenan. The mice were treated with aprepitant, and the behavioral tests were measured after the intraperitoneal injection of aprepitant. The morphological changes on inflamed paw tissues were determined by using hematoxylin eosin staining. The mRNA expressions of MCP-1, TNF-α, IL-6, IL-1β, and NF-κBp65 were measured by real-time quantitative PCR analysis. Changes in the protein expression levels were assayed using enzyme linked immunosorbent assay. Western blotting and immunohistochemistry were used to assay the cell signaling.Results: Aprepitant treatment showed a significantly higher AP threshold in vitro. In vivo, the aprepitant showed a significant anti-inflammatory and analgesia effect in the mice with inflammatory pain. After the administration of aprepitant, the paw tissues inflammatory damage was significantly relived. The mRNA levels of MCP-1, TNF-α, IL-6, IL-1β, and NF-κBp65 were down-regulate following aprepitant treatment. Meanwhile, aprepitant significantly suppressed over-expression of proinflammatory cytokines, as well as the phosphorylation of JNK and p38 MAPK in the spinal cord.Conclusions: The present study suggests that the extract of aprepitant attenuates inflammatory pain in mice via suppressing the phosphorylation of JNK and p38, and inhibiting the NF-κB signaling pathway.

Purpose MicroRNA-195 is dysregulated in different kinds of cancers and plays a pivotal role in tumorigenesis. It may function as a prognostic biomarker for cancers. However, the results from articles were not consistent. This study was designed to validate the prognostic value of microRNA-195 in human tumors. Methods We conducted a detailed search on PubMed until December 31, 2018. The quality of these publications was assessed on the basis of a list of key reviews presented by PRISMA statement. The pooled hazard ratios (HR) and pooled odds ratios (OR) of each 95% confidence interval (95% CI) were calculated to assess the effect. Results This meta-analysis included 12 studies involving 940 cancer patients to assess the prognostic value of miR-195 in different solid tumors. The results showed that patients with high expression of miR-195 had favorable tumor-node-metastasis (late vs early: pooled OR =0.16, 95% CI: 0.11-0.22, P

Background. Prothrombin time (PT) can predict survival in several types of malignancies. This study aims to investigate the predictive values of PT levels in patients with cholangiocarcinoma (CCA). Methods. We retrospectively analyzed the PT from 86 CCA patients who underwent curative resection in our hospital from December 2008 to August 2017. The relationship between PT and survival times was analyzed through univariate and multivariate analyses (Cox proportional hazards model). Kaplan–Meier curves and log-rank test were used to assess the effects of PT on overall survival (OS) and tumor recurrence-free survival (RFS). Results. Increased PT level was an effective predictor for OS (P = 0.021; hazard ratio (HR), 1.799) and RFS (P = 0.016; HR, 1.871) in CCA patients, independent of age, tumor differentiation, and TNM stage. In the low PT level group (PT < 12.3 s), patients showed a higher mean OS (23.03 m vs. 14.38 m, P = 0.0250) and RFS (17.78 m vs. 8.30 m, P = 0.0511) than those with high PT levels (PT ≥ 12.3 s). A highly significant association was observed between high PT level and shortened OS (P = 0.0373) and worse RFS (P = 0.0151). Conclusion. Preoperative increase in PT can serve as a simple but effective predictor of poor survival in CCA patients who undergo curative surgeries.

Background/aims Critically ill patients with cirrhosis with pneumonia are at an increased risk for mortality. Only a few accurate predictive models are existing specific to these patients. The aim of the present study was to compare the existing prognostic models and to develop an improved mortality risk model for patients with cirrhosis and pneumonia. Materials and methods A total of 231 patients were enrolled in our study (70% training and 30% validation cohorts). All participants were followed up for at least 21 days. Model for End-stage Liver Disease and Pneumonia (MELD-P) was derived by the Cox proportional hazards model. The performances of prognostic scoring systems were compared by calculation of the area under the receiver operating characteristic (AUROC) curve. Results MELD-P showed better discriminative capabilities than existing scoring systems. Four clinical variables, including loge bilirubin (hazard ratio (HR) 1.29, 95% confidence interval (CI) 1.01-1.73), loge international normalized ratio (HR 3.57, 95% CI 1.30-9.78), loge pulse oxygen saturation/fraction of inspired oxygen (HR 0.38, 95% CI 0.14-0.99), and vasopressors used (HR 3.72, 95% CI 1.85-7.49), were considered as independent prognostic values associated with 21-day mortality. MELD-P had AUROC curve values of 0.78 (95% CI 0.71-0.84) in predicting in-hospital mortality, 0.78 (95% CI 0.70-0.84) at 21-day, 0.88 (95% CI 0.82-0.93) at 14-day, and 0.87 (95% CI 0.81-0.92) at 7-day. A similar result was obtained in validation cohort. Conclusion MELD-P, as the first model specifically designed to evaluate the risk of mortality in critically ill patients with cirrhosis and pneumonia, performs well on the mortality assessment of short-term mortality.

Background: As reported by numerous research studies, the expression levels of SNHG1 (small nucleolar RNA host gene 1) are increased in different kinds of tumours, revealing that SNHG1 is likely to perform a crucial function in cancer prevalence and progression. Moreover, a mounting degree of evidence suggests that increased SNHG1 expression also has an association with poor medical outcomes among cancer patients. Materials and methods: Collection of qualifying research studies was performed through the retrieval of keywords in PubMed and Web of Science, up to March 20, 2018. This quantitative meta-analysis was carried out using Stata SE12.0 software and aimed at exploring the connection between the expression level of SNHG1 and clinicopathology. Results: Ten research studies, involving an aggregate of 715 patients, met the inclusion criteria. As suggested by the findings of the current meta-analysis, with regard to prognosis, the patients with high expression of SNHG1 had poorer overall survival (OS) (HR =3.36, 95% CI: 2.42, 4.67) and, with regard to their clinicopathology, increased SNHG1 was associated with advanced TNM stage (RR =1.88, 95% CI: 1.58, 2.24), poorly differentiated histological grade (RR =1.38, 95% CI:1.09, 1.76), and positive lymph node metastasis (RR =1.80, 95% CI: 1.42, 2.29). Conclusion: As revealed by this meta-analysis, elevated SNHG1 expression is typical in various types of cancer. In addition, elevated SNHG1 expression is likely to function as an advanced predictive element of poor prognosis and lymph node metastasis in various cancer types. Nonetheless, to date, it remains essential to carry out larger-size and better-designed research studies for the confirmation of our findings.

Cholangiocarcinoma (CCA) is the second most malignant tumor of the hepatobiliary system. Due to its cumbersome early diagnosis and rapid progression, chemotherapy has become the main treatment option. Primary drug resistance is a major cause of the poor efficacy of chemotherapeutic drugs. Therefore, it is considered urgent to explore new drugs to overcome primary drug resistance of CCA. Western blot and qRT-PCR assays were used to assess the expression of myotrophin (MTPN) and microRNA-885-5p (miR-885-5p) in CCA tissues and cells. The viability of CCA cells treated with arsenic trioxide (ATO), 5-fluorouracil (5-Fu) and cisplatin (CDDP) was analyzed using a CCK-8 assay. A luciferase reporter assay was used to assess the interaction between miR-885-5p and MTPN. Kaplan-Meier analyses were used for survival assessments. We found that ATO can reduce the resistance of CCA cells to 5-Fu and CDDP and promote the killing effect of 5-Fu and CDDP. Low-dose ATO showed an anti-drug-resistance effect through up-regulation of the expression of miR-885-5p. Combined with sequencing results and database predictions, we found that MTPN may serve as a direct target of miR-885-5p. After MTPN knockdown, the sensitivity of CCA cells to 5-FU and CDDP was increased. Finally, we found that ATO can reverse chemotherapy resistance induced by overexpression of MTPN. Our data indicate that the ATO/miR-885-5p/MTPN axis may serve as a target for improving the sensitivity of CCA cells to chemotherapy.

Local digital documentation platforms refer to the online platforms that cater to the people’s needs of browsing through, reading and obtaining knowledge. Libraries create the platforms by collecting local literature, classics and related research results, among others, and then convert and process them with digital humanities technology, as assisted by the Internet dispatch system. As Internet technologies develop rapidly and local literature data grows exponentially, digital documentation platforms based on cloud computing, wireless transmission, sensor networks and reading terminals have become an important option for readers to obtain reading services. Local libraries should take full advantage of Internet technologies and contribute to the promotion of local reading and cultural development. This paper analyzed the current local digital documentation platforms and their reading promotion models. In combination with digital humanities technologies such as information statistics, data mining and semantic analysis, and drawing on Lasswell’s communication model, the author then explored the construction of and possible innovations in the reading promotion models for local digital platforms.

BACKGROUND Artificial intelligence in colonoscopy is an emerging field, and its application may help colonoscopists improve inspection quality and reduce the rate of missed polyps and adenomas. Several deep learning-based computer-assisted detection (CADe) techniques were established from small single-center datasets, and unrepresentative learning materials might confine their application and generalization in wide practice. Although CADes have been reported to identify polyps in colonoscopic images and videos in real time, their diagnostic performance deserves to be further validated in clinical practice. AIM To train and test a CADe based on multicenter high-quality images of polyps and preliminarily validate it in clinical colonoscopies. METHODS With high-quality screening and labeling from 55 qualified colonoscopists, a dataset consisting of over 71000 images from 20 centers was used to train and test a deep learning-based CADe. In addition, the real-time diagnostic performance of CADe was tested frame by frame in 47 unaltered full-ranged videos that contained 86 histologically confirmed polyps. Finally, we conducted a self-controlled observational study to validate the diagnostic performance of CADe in real-world colonoscopy with the main outcome measure of polyps per colonoscopy in Changhai Hospital. RESULTS The CADe was able to identify polyps in the test dataset with 95.0% sensitivity and 99.1% specificity. For colonoscopy videos, all 86 polyps were detected with 92.2% sensitivity and 93.6% specificity in frame-by-frame analysis. In the prospective validation, the sensitivity of CAD in identifying polyps was 98.4% (185/188). Folds, reflections of light and fecal fluid were the main causes of false positives in both the test dataset and clinical colonoscopies. Colonoscopists can detect more polyps (0.90 vs 0.82, P < 0.001) and adenomas (0.32 vs 0.30, P = 0.045) with the aid of CADe, particularly polyps < 5 mm and flat polyps (0.65 vs 0.57, P < 0.001; 0.74 vs 0.67, P = 0.001, respectively). However, high efficacy is not realized in colonoscopies with inadequate bowel preparation and withdrawal time (P = 0.32; P = 0.16, respectively). CONCLUSION CADe is feasible in the clinical setting and might help endoscopists detect more polyps and adenomas, and further confirmation is warranted.

Aim: To evaluate the clinical value of plasma D-dimer/fibrinogen ratio (DFR) in patients hospitalized for heart failure (HF). Methods: Clinical data of 235 patients were retrospectively analyzed. Kaplan–Meier method and Cox regression analysis were used to identify significant prognosticators. Results: The Kaplan–Meier analysis showed that a higher DFR level was significantly associated with an increase in the end point outcomes, including HF readmission, thrombotic events and death (log-rank test: p

Background The differences in the clinical and functional outcomes of closed reduction and percutaneous pin fixation and open reduction with internal fixation (ORIF) using plate and screws have been systematically synthesized by one meta-analysis. With newer studies being published, an effort to update the earlier meta-analysis is necessary. Methods Comprehensive searches were done systematically through PubMed, Scopus, CENTRAL (Cochrane Central Register of Controlled Trials), and Google scholar databases. Randomized controlled trials, quasi-experimental studies, prospective comparative non-randomized studies, and even studies reporting findings from retrospective chart review were eligible to be included. Statistical analysis was done using STATA version 13.0. GRADE assessment was done to assess the quality of pooled evidence. Results A total of 9 studies were included. The pooled estimates did not suggest any significant differences in the disabilities of the arm, shoulder, and hand (DASH) score [WMD − 0.77; 95% CI, − 3.55, 2.00; I2 = 75.5%], range of movement (ROM) of the metacarpophalangeal joint (o) [WMD 4.44; 95% CI, − 4.19, 13.07; I2 = 86.0%], and grip strength [WMD − 4.63; 95% CI, − 14.52, 5.26; I2 = 86.9%] among the two intervention modalities. No difference was seen in the risk of complications between the two interventions (RR 0.93; 95% CI, 0.57, 1.53; I2 = 31.2%). For all the outcomes, the quality of pooled evidence was judged as low to very low. Conclusion No significant long-term differences were noted in the functional outcomes suggesting that both these techniques are comparable. The choice of modality should be made based on the skills and preference of the surgeon and availability of resources.

Benign esophageal strictures are a frequent complication after esophageal surgery or extensive endoscopic submucosal dissection. Endoscopic dilation is the preferred treatment in clinical practice. However, the allocation of time for each dilation is unclear. The aim of this study was to evaluate the appropriate duration of endoscopic dilation for benign esophageal strictures after esophageal surgery or endoscopic submucosal dissection. Patients with benign esophageal strictures after esophageal surgery or endoscopic submucosal dissection between July 2010 and July 2018 were retrospectively included in this study. According to the dilation time (1, 3, 5 min), patients were divided into three groups. The clinical effects and adverse events were compared among the three groups. Altogether, 57 patients, including 21 in the 1-min group, 18 in the 3-min group and 18 in the 5-min group, were included. All patients underwent endoscopic treatment successfully. The stricture recurrence rate was 76.19% in the 1-min group, 55.56% in the 3-min group and 61.11% in the 5-min group. The median overall dysphagia-free period was 2.60 (range, 0.80–12.00) months in the 1-min group, 6.60 (range, 1.80–12.00) months in the 3-min group and 6.25 (range, 2.40–12.00) months in the 5-min group (P

The aim of this study was to evaluate the prognostic value of a novel scoring system, based on D‑dimer, total cholesterol, high-sensitivity cardiac troponin T (hs-cTnT), and serum albumin levels, in patients with heart failure.A total of 221 patients diagnosed with heart failure between May 2016 to January 2020 were enrolled in this retrospective study. The prognostic significance of the biomarkers D‑dimer, total cholesterol, hs-cTnT, and serum albumin was determined with univariate and multivariate Cox proportional hazard models. A novel prognostic score based on these predictors was established. The Kaplan-Meier method and log-rank test were used to compare the adverse outcomes of patients in different risk groups.Results from univariate and multivariate analyses showed that high D‑dimer, low serum albumin, high hs-cTnT, and low total cholesterol levels were independent prognostic factors for adverse outcomes (D-dimer0.63 mg/l, HR = 1.84, 95% CI = 1.16-2.94, p = 0.010; serum albumin34 g/l, HR = 0.67, 95% CI = 0.45-0.99, p = 0.046; hs-cTnT24.06 pg/ml, HR = 1.65, 95% CI = 1.08-2.53, p = 0.020; total cholesterol3.68 mmol/l, HR = 0.63, 95% CI = 0.43-0.92, p = 0.017). Moreover, all the patients were stratified into low-risk or high-risk group according to a scoring system based on these four markers. Kaplan-Meier analyses demonstrated that patients in the high-risk group were more prone to having adverse outcomes compared with patients in the low-risk group.D‑dimer, total cholesterol, hs-cTnT, and serum albumin levels were independent prognostic factors in the setting of heart failure. A novel and comprehensive scoring system based on these biomarkers is an easily available and effective tool for predicting the adverse outcomes of patients with heart failure.ZIEL DER ARBEIT: Ziel der vorliegenden Studie war es, den prognostischen Wert eines neuen Score-Systems zu untersuchen, der auf den Werten für D‑Dimere, Gesamtcholesterin, hochsensitives kardiales Troponin (hs-cTnT) und Serumalbumin bei Patienten mit Herzinsuffizienz beruht.In diese retrospektive Studie wurden 221 Patienten mit Diagnosestellung einer Herzinsuffizienz zwischen Mai 2016 und Januar 2020 einbezogen. Die prognostische Bedeutung der Biomarker D‑Dimere, Gesamtcholesterin, hs-cTnT und Serumalbumin wurde anhand univariater und multivariater Cox-Proportional-Hazard-Modelle ermittelt. Es wurde ein neuer prognostischer Score auf der Grundlage dieser Prädiktoren etabliert. Um unerwünschte Ereignisse zwischen den Patienten in verschiedenen Risikogruppen zu vergleichen, wurden die Kaplan-Meier-Methode und der Log-Rank-Test eingesetzt.Die Ergebnisse der univariaten und multivariaten Analysen zeigten, dass hohe Werte für D‑Dimere und hs-cTnT sowie niedrige Werte für Gesamtcholesterin und Serumalbumin unabhängige prognostische Faktoren für ungünstige Outcomes waren (D-Dimere0,63 mg/l; Hazard Ratio, HR = 1,84; 95%-Konfidenzintervall, 95%-KI = 1,16–2,94; p = 0,010; Serumalbumin34 g/l; HR = 0,67; 95%-KI = 0,45–0,99; p = 0,046; hs-cTnT24,06 pg/ml; HR = 1,65; 95%-KI = 1,08–2,53; p = 0,020; Gesamtcholesterin3,68 mmol/l; HR = 0,63; 95%-KI = 0,43–0,92; p = 0,017). Darüber hinaus wurden alle Patienten gemäß einem Scoring-System auf Grundlage dieser 4 Parameter in eine Niedrigrisikogruppe oder Hochrisikogruppe eingeteilt. Die Kaplan-Meier-Analysen ergaben, dass bei den Patienten in der Hochrisikogruppe eine höhere Tendenz zu ungünstigen Outcomes als bei den Patienten in der Niedrigrisikogruppe bestand.Die Werte für D‑Dimere, Gesamtcholesterin, hs-cTnT sowie Serumalbumin stellten sich als unabhängige prognostische Faktoren bei Vorliegen einer Herzinsuffizienz heraus. Ein neues und umfassendes Scoring-System auf der Basis dieser Biomarker erwies sich als leicht verfügbares und effektives Instrument zur Vorhersage ungünstiger Outcomes bei Patienten mit Herzinsuffizienz.

Transpancreatic sphincterotomy (TPS) can be an alternative approach of difficult biliary access in endoscopic retrograde cholangiopancreatography (ERCP). We aimed to evaluate the efficacy and safety of TPS compared to needle-knife precut (NKP), considering the early and late outcomes of both techniques. The prospectively collected clinical data, ERCP procedure findings, and outcomes of patients who underwent ERCP with difficult biliary access in our hospital from July 2016 to January 2018 were retrospectively analyzed. The patients were divided into two groups according to the applied secondary cannulation techniques. The propensity score matching (PSM) was applied to reduce the potential selection bias and unify the preventive measures of post-ERCP pancreatitis (PEP) in both groups. A total of 125 patients were enrolled in this study, with 54.4% male and a mean age of 63.29 ± 16.33 years. NKP group included 82 patients, and 43 patients received TPS. Prophylactic pancreatic stents were placed in all patients with TPS and 58.5% of patients with NKP. After applying PSM, the cohort was comprised to 86 patients with 43 patients in each TPS and NKP groups. Successful selective cannulation was achieved by 95.3% using TPS and by 93% using NKP. The mean procedure time was shorter in the TPS group without significant difference. Compared to NKP, using TPS did not affect the rate of PEP. Moreover, TPS was associated with less frequent post-ERCP bleeding and perforation, but without significant differences (all p > 0.05). Patients who received TPS or NKP had no symptoms related to papillary stenosis or chronic pancreatitis during the follow-up period. In conclusion, using TPS in difficult cannulation cases was useful to achieve success cannulation with an acceptable PEP rate and less frequent post-ERCP bleeding and perforation compared to NKP. There were no symptoms related to papillary stenosis or chronic pancreatitis during the follow-up period.

Ethnopharmacological relevance Coptis chinensis Franch (CCF), also known as Huang Lian in China, is a traditional Chinese medicine that commonly used for more than 2000 years. Clinically, CCF often used as anti-inflammatory, immune regulation and other effects. It has been reported that the decoction containing CCF can be used for the treatment of benign prostatic hyperplasia (BPH) or lower urinary tract symptoms (LUTS). Aim of the study: This research aims to investigate the effect of CCF on inhibition of BPH development in vivo and in vitro, and further identify the active compound (s) and the possible mechanism involved in BPH-related bladder dysfunction. Materials and methods Oestrodial/testosterone-induced BPH rat model was established as the in vivo model. The prostate index (PI) was calculated, the pathogenesis was analyzed and the micturition parameters were determined in the shamed-operated, BPH model and BPH + CCF groups after 4-week administration. The tension in detrusor strips was then assessed upon KCl or ACh stimulation with or without incubation of CCF or active compounds. To further investigate the signaling involved, rat detrusor cells were cultured as the in vitro models, the instantaneous calcium influx was measured and the ROCK-1 expression was detected. Results Increased PI value and the aggravated prostatic pathology were observed with voiding dysfunction in BPH rats, which were significantly blocked by oral CCF taken. ACh or KCl-induced contractile responses in detrusor strips were significantly inhibited and the micturition parameters were improved when incubation with CCF or its active compounds such as berberine. Both CCF and berberine suppressed the cellular calcium influx and ROCK-1 expression upon ACh stimulation, demonstrating that berberine was one of the active compounds that contributed to CCF-improved micturition symptoms and function. Conclusions Taken together, our findings give evidence that CCF and its active compound berberine inhibited BPH and bladder dysfunction via Ca2+ and ROCK signaling, supporting their clinical use for BPH and BPH-related LUTS treatment.

Background/AimsTranspancreatic sphincterotomy (TPS) can be an alternative approach of biliary access in difficult cannulation cases. We aimed to prospectively evaluate the efficacy and safety of TPS compared to needle-knife precut (NKP), considering the late consequences of both techniques.MethodsA total of 122 enrolled patients have been divided into three groups based on the applied secondary cannulation techniques. Selective cannulation success, ERCP procedure findings, and immediate adverse events were compared between groups. We investigated the long-term outcomes during six-month after the procedure.ResultsSuccessful selective cannulation was achieved in 92.9% with TPS similarly to other groups. The mean procedure time was shorter in the TPS group without significant difference. Using TPS did not affect the rate of post-ERCP pancreatitis (PEP) with less frequent post-ERCP bleeding and perforation after TPS compared to NKP, without significant difference. Patients who received TPS, NKP, or both had no symptoms related to papillary stenosis or chronic pancreatitis during the follow-up period.ConclusionsUsing TPS was useful to achieve success cannulation in difficult cases with an acceptable PEP rate. Furthermore, it was associated with reducing bleeding and perforation rates comparing with NKP and no differences related to the long term consequences within the follow-up period.

Introduction Clinical guidelines suggest a glycated hemoglobin A1c (HbA1c) target of ≤ 6.5% for type 2 diabetes patients with short duration of disease, few comorbidities and/or long life expectancy—provided this goal can be achieved safely. We explored whether initial combination treatment with the dipeptidyl peptidase-4 inhibitor linagliptin and metformin could provide better glycemic control (HbA1c ≤ 6.5%) than metformin alone without increasing hypoglycemia. Methods We pooled and analyzed individual patient data from two randomized clinical trials of early combination therapy with linagliptin and metformin versus metformin monotherapy. The primary outcome in both trials was the change in HbA1c from baseline to week 24. We evaluated the percentage of patients who achieved HbA1c ≤ 6.5% at week 24 and the incidence of adverse events. Results Most (> 70%) of the 1160 patients analyzed were treatment naive, and more than half had had diabetes for ≤ 1 year; mean baseline HbA1c was approximately 8.7%. Combination therapy with linagliptin and metformin resulted in more patients achieving HbA1c ≤ 6.5% than metformin alone, both for a metformin dose of 500 mg (40.1 vs. 22.9%, respectively, odds ratio [OR] 2.84, 95% confidence interval [CI] 1.87–4.32) and 1000 mg (49.5 vs. 35.4%, respectively, OR 2.28, 95% CI 1.54–3.40). Hypoglycemia occurred in

Background and aim For localized disease, complete surgical resection is regarded as the "gold standard" therapeutic modality. With the rapid development of endoscopic techniques, endoscopic resection (ESR) has been confirmed as an efficient and safe alternative for the treatment of gastrointestinal stromal tumors (GISTs) in the stomach. Nevertheless, the management of gastric GISTs remains poorly defined. The purpose of this study is to evaluate the security and effectiveness of ESR with laparoscopic resection (LAR) for gastric GISTs. Methods A literature search of online databases was conducted to identify relevant comparative studies of ESR and LAR procedures for gastric GISTs published before April 10, 2020. The cumulative data analysis was also performed utilizing the software STATA. Results In total, 10 studies involving 1165 patients met the inclusion criteria for analysis (651 for ESR and 514 for LAR). From the results of meta-analysis, patients who underwent ESR experienced decreased operative time (P = 0.000), less intraoperative blood loss (P = 0.002), earlier time to diet (P = 0.000), shorter hospital stay (P = 0.000), and lower total charges (P = 0.000) compared with LAR. Moreover, there were no significant differences between these two approaches concerning tumor rupture, conversion rate to other procedure, complete resection rate, postoperative complication rate, recurrence rate, and disease-free survival. Conclusions Endoscopic resection, as an effective alternative treatment strategy with satisfactory outcomes, is acceptable for selective patients with gastric GISTs compared with LAR. Further well-designed randomized controlled trials with large samples are warranted to corroborate our observations.

Aim: This study aimed to investigate the association between periampullary diverticulum (PAD) and difficult biliary cannulation, as well as to evaluate the impact of different types of PAD on the cannulation success rate and adverse events. Methods: A total of 636 patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) during the study period were prospectively studied and divided into two groups based on the presence or absence of PAD. In group A, 126 patients had PAD compared with 510 patients in group B without PAD. The primary outcome measurements were ERCP procedures time, selective cannulation techniques, and cannulation difficulty in addition to cannulation success rate and ERCP-related adverse events. The difficult cannulation was analyzed using logistic regression considering age, co-morbidities, the presence of PAD types, and indications as independent factors. Results: The average cohort age was 65.30±16.67 years, and 52.7% were male. Significant higher rates of choledocholithiasis, cholangitis, and biliary pancreatitis were reported in the group of PAD (p0.05). The cannulation time was significantly longer in the presence of PAD (5.1 min, vs. 4.09 min, p

Objectives: This study aimed to investigate the association between periampullary diverticulum (PAD) and difficult biliary cannulation, as well as to evaluate the impact of different types of PAD on the cannulation success rate and adverse events. Methods: A total of 636 patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) during the study period were prospectively studied and divided into two groups based on the presence or absence of PAD. In group A, 126 patients had PAD compared with 510 patients in group B without PAD. The primary outcome measurements were ERCP procedures time, selective cannulation techniques, and cannulation difficulty in addition to cannulation success rate and ERCP-related adverse events. The difficult cannulation was analyzed using logistic regression considering age, co-morbidities, the presence of PAD types, and indications as independent factors. Results: The average cohort age was 65.30±16.67 years, and 52.7% were male. Significant higher rates of choledocholithiasis, cholangitis, and biliary pancreatitis were reported in the group of PAD (p0.05). The cannulation time was significantly longer in the presence of PAD (5.1 min, vs. 4.09 min, p

Quercetin is a kind of flavonoid compounds that comes from nature and is widely existed in the daily diet. Previous studies have found that quercetin has many effects such as anti-inflammatory, anti-oxidation and anti-cancer. Both in vivo and in vitro experiments have demonstrated that quercetin can exert anti-tumor effects by altering cell cycle progression, inhibiting cell proliferation, promoting apoptosis, inhibiting angiogenesis and metastasis progression, and affecting autophagy. This review summarizes the evidence for the pharmacological potential and inhibition of quercetin on cancers, supporting the viewpoint that quercetin should be adequately considered as a therapeutic agent against various cancers.

Facing the COVID-19 pandemic, governments have implemented a wide range of policies to contain the spread of the virus. During the pandemic, large amounts of COVID-19-related tweets emerge every day. Real-time processing of daily tweets may offer insights for monitoring public opinion about intervention measures implemented. In this work, lockdown policy in New York State has been set as a target of public opinion research. This task includes two stages, stance detection and opinion monitoring. For the stance detection stage, we explored several combinations of different text representations and classification algorithms, finding that the combination of Long Short-Term Memory (LSTM) with Global Vectors for Word Representation (GloVe) outperforms others. Due to the shortage of labeled data, we adopted the data distillation method for the training data augmentation. The augmentation of the training data allows to improve the performance of the model with a very small amount of manually-labeled data. After applying the distillation method, the accuracy of the model has been significantly improved. Utilizing the enhanced model, automatically classified tweets are analyzed over time to monitor the public opinion. By exploring the tweets in New York from January 22nd until September 30th, 2020, we show the correlation of public opinion with COVID-19 cases and mortality data, and the effect of government responses on the opinion shift. These results demonstrate the capability of the presented method to effectively and efficiently monitor public opinion during a pandemic.

// Xianxiu Ge 1, * , Youli Wang 2, * , Junjie Nie 1, * , Quanpeng Li 1, * , Lingyu Tang 1 , Xueting Deng 1 , Fei Wang 1 , Boming Xu 1 , Xiaochao Wu 1 , Xiuhua Zhang 1 , Qiang You 3 and Lin Miao 1 1 Institute of Digestive Endoscopy and Medical Center for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China 2 Department of Clinical Laboratory, Nanjing First Hospital, Nanjing, China 3 Department of Biotherapy, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China * These authors have contributed equally to this work Correspondence to: Lin Miao, email: miaolinxh@163.com Keywords: cholangiocarcinoma, exosome, long non-coding RNAs, RNA sequencing, functional analysis Received: January 21, 2017 Accepted: June 27, 2017 Published: July 25, 2017 ABSTRACT Cholangiocarcinoma (CCA) is an aggressive malignancy associated with unfavorable prognosis, and it’s difficult to diagnose and no effective treatments are available. Long non-coding RNAs (lncRNAs) play important roles in tumorigenesis and metastasis. Intact lncRNAs from exosomes have sparked much interest as potential biomarker for the non-invasive analysis of disease. Here, via exosome sequencing on lncRNAs, GO analysis, KEGG pathway and co-expression analysis, receiver operating characteristic curve and survival analyses, we found that, compared with control group, lncRNAs of ENST00000588480.1 and ENST00000517758.1 showed significantly increased expressions in CCA group. Moreover, area under the curve (AUC) was increased to 0.709 when combined the two lncRNAs, they had a sensitivity and specificity of 82.9% and 58.9% respectively. Further, the higher levels of the two lncRNAs showed a significantly increasing trend with the advancement of cancer TNM stages, and prognosticated a poor survival. In addition, KEGG pathway analysis showed that the most significant difference term was “p53 signaling pathway” (KEGG ID: hsa04115, p: 0.001). The altered lncRNAs and their target genes were included to reconstruct a co-expression network. These altered lncRNAs were mainly related to cellular processes, environmental information processing and organismal systems, etc. Collectively, our findings provided the potential roles of lncRNAs of ENST00000588480.1 and ENST00000517758.1 in CCA, and implicated these lncRNAs as potential diagnostic and therapeutic targets for CCA.

Background This study aims to investigate the effects of recombinant human brain natriuretic peptide (rhBNP) on serum enzyme data, cardiac function parameters and cardiovascular events in patients with acute anterior myocardial infarction (MI). Methods A total of 421 patients with acute anterior or extensive anterior MI were collected from 20 hospitals. These patients were randomly divided into two groups: rhBNP and control groups. Both groups of patients received primary percutaneous coronary intervention (PCI) within the effective time window. In the rhBNP group, rhBNP administration (0.01 µg/kg/min, 48-72 successive hours) was performed as early as possible after hospital admission. Prior to and one or seven days after PCI, serum concentrations of cardiac troponin (cTnT), creatine kinase-MB (CK-MB) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured. At seven days and 6 months after PCI, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd) and stroke volume (SV) were measured using 2D Doppler echocardiography. MACEs that occurred during hospitalization and within 6 months after PCI were recorded. Results At postoperative days one and seven, serum concentrations of cTnT were significantly lower in the rhBNP group than in the control group. At postoperative day one, serum concentrations of CK-MB were significantly lower in the rhBNP group than in the control group. At postoperative day seven, serum concentrations of NT-proBNP were significantly lower in the rhBNP group than in the control group, and LVEF was significantly greater in the rhBNP group than in the control group. At postoperative 6 months, LVEDd was significantly lower in the rhBNP group compared with the control group. In addition, SV and LVEF were significantly greater in the rhBNP group than in the control group. By postoperative month 6, the incidence of composite cardiovascular events (16.0% vs. 26.0%, P=0.012), cardiac death (7.0% vs.13.5%, P=0.030), and particularly cardiac death + re-hospitalization for congestive heart failure (13.1% vs. 25.5%, P=0.001) were significantly lower in the rhBNP group than in the control group. Conclusions Early intravenous rhBNP administration after PCI significantly lowered the serum concentrations of cTnT and NT-proBNP, increased LVEDd, SV and LVEF, and reduced MACEs, including cardiac death, in patients with acute anterior MI undergoing PCI.

For the treatment of stress urinary incontinence (SUI), various retropubic and transobturator techniques have demonstrated high cure rates. Single-incision tapes, such as Contasure-Needleless® (C-NDL), have demonstrated similar cure rates to the inside-out transobturator sling (TVT-O®). The aim of this study was to analyse if C-NDL® is equally as effective as an outside-in transobturator sling (Monarc®) for the treatment of SUI. We carried out a prospective, single-centre, randomised trial. The results were analysed for a non-inferiority test with a minimum postoperative follow-up of 12 months. The objective and subjective cure rates were evaluated by a stress test and a postoperative Sandvik Severity Index respectively. Patient satisfaction and operative complications were registered. The cure was defined by a negative stress test and SSI 0. A total of 187 patients were included, 89 and 98 undergoing C-NDL® and Monarc® respectively. Epidemiological and clinical data did not show and significant differences between both groups except a high prevalence of women who smoke (15.7% C-NDL® vs 6.1% Monarc®, p 0.03). The negative stress test was negative in 72 patients (80.9%) in C-NDL® compared with 85 (88.5%) in Monarc® (p 0.082). The SSI was 0 in 47 (66.2%) for C-NDL® and 61 (70.1%) for the Monarc® group (p 0.01). There were 14 (16.1%) and 8 (8.3%) dissatisfied patients for the C-NDL® and Monarc® groups respectively (p 0.068). The rate of complications was similar in both groups. According to the non-inferiority test, C-NDL® is not inferior to Monarc® (post-surgical SSI test), but it is inferior in the comparison of a negative stress test and patient satisfaction.

Topological insulators are bulk semiconductors that manifest in-gap massless Dirac surface states due to the topological bulk-boundary correspondence principle [1-3]. These surface states have been a subject of tremendous ongoing interest, due both to their intrinsic properties and to higher order emergence phenomena that can be achieved by manipulating the interface environment [4-11]. Here, angle resolved photoemission (ARPES) spectromicroscopy and supplementary scanning tunneling microscopy (STM) are performed on the model topological insulator Bi2Se3 to investigate the interplay of crystallographic inhomogeneity with the topologically ordered bulk and surface band structure. Quantitative analysis methods are developed to obtain key spectroscopic information in spite of a limited dwell time on each measured point. Band energies are found to vary on the scale of 50 meV across the sample surface, enabling single-sample measurements that are analogous to a multi-sample doping series (termed a "binning series"). Focusing separately on the surface and bulk electrons reveals a nontrivial hybridization-like interplay between fluctuations in the surface and bulk state energetics., 4 figures and 6 supplementary figures