Propranolol inhibits EMT and metastasis in breast cancer through miR-499-5p-mediated Sox6.

PURPOSE: This study will focus on 4T1 cells, a murine mammary adenocarcinoma cell line, as the primary research subject. We aim to investigate the inhibitory effects and mechanisms of propranolol on epithelial-mesenchymal transition (EMT) in breast cancer cells, aiming to elucidate this phenomenon at the miRNA level. METHODS: In this study, the EMT inhibitory effect of propranolol was observed through in vitro and animal experiments. For the screening of potential target miRNAs and downstream target genes, second-generation sequencing (SGS) and bioinformatics analysis were conducted. Following the screening process, the identified target miRNAs and their respective target genes were confirmed using various experimental methods. To confirm the target miRNAs and target genes, Western Blot (WB), reverse transcription polymerase chain reaction (RT-PCR), and immunofluorescence experiments were performed. RESULTS: In this study, we found that propranolol significantly reduced lung metastasis in 4T1 murine breast cancer cells (p < 0.05). In vitro and in vivo experiments demonstrated that propranolol inhibited the epithelial-mesenchymal transition (EMT) as evidenced by Western Blot analysis (p < 0.05). Through next-generation sequencing (SGS), subsequent bioinformatics analysis, and PCR validation, we identified a marked downregulation of miR-499-5p (p < 0.05), suggesting its potential involvement in mediating the suppressive effects of propranolol on EMT. Overexpression of miR-499-5p promoted EMT, migration, and invasion of 4T1 cells, and these effects were not reversed or attenuated by propranolol (Validated via Western Blot, wound healing assay, transwell migration, and invasion assays, p < 0.05). Sox6 was identified as a functional target of miR-499-5p, with its downregulation correlating with the observed EMT changes (p < 0.05). Silencing Sox6 or overexpressing miR-499-5p inhibited Sox6 expression, further promoting the processes of EMT, invasion, and migration in 4T1 cells. Notably, these effects were not alleviated by propranolol (validated via Western Blot, wound healing assay, transwell migration, and invasion assays, p < 0.05). The direct interaction between miR-499-5p and Sox6 mRNA was confirmed by dual-luciferase reporter gene assay. CONCLUSION: These results suggest that propranolol may have potential as a therapeutic agent for breast cancer treatment by targeting EMT and its regulatory mechanisms.

Integrative models of histopathological images and multi-omics data predict prognosis in endometrial carcinoma.

Objective: This study aimed to predict the molecular features of endometrial carcinoma (EC) and the overall survival (OS) of EC patients using histopathological imaging. Methods: The patients from The Cancer Genome Atlas (TCGA) were separated into the training set (n = 215) and test set (n = 214) in proportion of 1:1. By analyzing quantitative histological image features and setting up random forest model verified by cross-validation, we constructed prognostic models for OS. The model performance is evaluated with the time-dependent receiver operating characteristics (AUC) over the test set. Results: Prognostic models based on histopathological imaging features (HIF) predicted OS in the test set (5-year AUC = 0.803). The performance of combining histopathology and omics transcends that of genomics, transcriptomics, or proteomics alone. Additionally, multi-dimensional omics data, including HIF, genomics, transcriptomics, and proteomics, attained the largest AUCs of 0.866, 0.869, and 0.856 at years 1, 3, and 5, respectively, showcasing the highest discrepancy in survival (HR = 18.347, 95% CI [11.09-25.65], p < 0.001). Conclusions: The results of this experiment indicated that the complementary features of HIF could improve the prognostic performance of EC patients. Moreover, the integration of HIF and multi-dimensional omics data might ameliorate survival prediction and risk stratification in clinical practice.

The bared external anal sphincter (BEAS), a new technique for high horseshoe anal fistula: a hospital-based cohort study.

The aim of this study was to introduce a new technique, the bared external anal sphincter technique, and to evaluate its effectiveness and safety for primary or recurrent high horseshoe anal fistula (HHAF). We used data from a tertiary referral hospital's prospective database of a hospital-based cohort. All the patients underwent the bared external anal sphincter procedure. The main outcomes were short-term clinical outcomes including the 6-month cure rate, Visual Analog Scale pain score (VAS-PS) and Cleveland Clinic Florida incontinence score (CCF-IS). The secondary outcomes included the Quality of Life in Patients with Anal Fistula Questionnaire score (QoLAF-QS), Bristol stool chart and postoperative complications. A total of 48 HHAF patients (39 males) with a mean age of 34.2 years (SD 9.04; range, 21-54) were analyzed in this retrospective study. At the 6-month follow-up, the average VAS-PS and CCF-IS were 0.81 (SD 2.28; range, 0-10) and 1.29 (SD 2.87; range, 0-13), respectively. QoLAF-QS showed that the bared external anal sphincter procedure had no impact over their quality of life in 45 patients (93.75%), limited impact in 2 patients (4.16%), and moderate impact in one patient (2.08%). The Bristol stool scale showed that all patients had normal stool characteristics. The 6-month cure rate was 93.75%. Three patients (6.25%) experienced recurrent symptoms but recovered after surgical management. Urinary retention occurred in 1 case (2.78%). No other postoperative complications were reported. No patient had anal incontinence. The bared external anal sphincter procedure is a safe, effective and sphincter-sparing approach for patients with primary or recurrent HHAF in terms of short-term results.

Surgical laser therapy for cryptoglandular anal fistula: Protocol of a systematic review and meta-analysis.

INTRODUCTION: Anal fistula is the natural evolution of perianal abscess and one of the most common perianal diseases for adults. For complex fistula, it is still very challenging for anorectal surgeons to manage. With the introduction of laser technique in surgery, it is becoming more and more widely used for the treatment of cryptoglandular anal fistula. During the past decade, numerous studies have reported the clinical effectiveness and postoperative outcomes of different forms of laser treatment for anal fistula. However, as these studies were varied in terms of baseline characteristics, the evidence for the true clinical effectiveness of laser treatment for anal fistula need further critical appraisal. Therefore, the purpose of this study is to evaluate the outcomes of surgical laser therapy for cryptoglandular anal fistula stratified by laser type and Parks' classification through a synthesis of quantitative and qualitative evidence. METHODS AND ANALYSIS: This study will be carried out with adherence to the Cochrane Handbook. We will search PubMed, Cochrane Library, and Embase until June, 2022 to identify all relevant interventional and observational studies examining the effects of laser therapy on the clinical outcomes for cryptoglandular anal fistula. Data extraction from eligible studies will be performed independently by two unblinded authors using standardized extraction forms. Risk of bias assessment for each study will be conducted using Cochrane tool for randomized controlled trials (RCTs) and the Newcastle-Ottawa scale (NOS) tool for observational studies. The DerSimonian-Laird random-effects model will be used to calculate the pooled estimates. Heterogeneity will be examined by subgroup analysis stratified by laser type and Parks' classification and other study characteristics. Potential publication bias will be assessed by funnel plot symmetrical and Egger's regression tests. CONCLUSIONS: The synthesis of quantitative and qualitative evidence of this systemic review will yield updated and comprehensive evidence of laser treatment on specific outcomes, which can provide anorectal surgeons with high level evidence-based recommendations to improve patient care and clinical outcomes. OSF registration number: DOI 10.17605/OSF.IO/36ADW.

Sodium Tanshinone IIA Sulfonate as a Potent IDO1/TDO2 Dual Inhibitor Enhances Anti-PD1 Therapy for Colorectal Cancer in Mice.

Although the antitumor efficacy of immune checkpoint blockade (ICB) has been proved in colorectal cancer (CRC), the results are unsatisfactory, presumably owing to the presence of tryptophan metabolism enzymes indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase 2 (TDO2). However, only a few dual inhibitors for IDO1 and TDO2 have been reported. Here, we discovered that sodium tanshinone IIA sulfonate (STS), a sulfonate derived from tanshinone IIA (TSN), reduced the enzymatic activities of IDO1 and TDO2 with a half inhibitory concentration (IC50) of less than 10 µM using enzymatic assays for natural product screening. In IDO1- or TDO2- overexpressing cell lines, STS decreased kynurenine (kyn) synthesis. STS also reduced the percentage of forkhead box P3 (FOXP3) T cells in lymphocytes from the mouse spleen cocultured with CT26. In vivo, STS suppressed tumor growth and enhanced the antitumor effect of the programmed cell death 1 (PD1) antibody. Compared with anti-PD1 (α-PD1) monotherapy, combined with STS had lower level of plasma kynurenine. Immunofluorescence assay suggested that STS decreased the number of FOXP3+ T cells and increased the number of CD8+ T cells in tumors. Flow cytometry analysis of immune cells in tumor tissues demonstrated an increase in the percentage of tumor-infiltrating CD8+ T cells. According to our findings, STS acts as an immunotherapy agent in CRC by inhibiting both IDO1 and TDO2.

Microbiota and their metabolites potentiate cancer immunotherapy: Therapeutic target or resource for small molecule drug discovery?

Increasing evidence has proved that microbiota is not only the target of small molecule drugs but also an underexplored resource for developing small molecule drugs. Meanwhile, microbiota as a critical modulator of the immune system impacts the efficacy and toxicity of cancer immunotherapy. Harnessing microbiota or developing microbiota-derived medications provide novel therapeutic strategies to overcome resistance to cancer immunotherapy and immune-related adverse events (irAEs). In this review, we elucidate how microbiota and their metabolites impact anti-tumor immunity and immunotherapy efficacy and highlight the potential of microbiota and their metabolites as a resource for small molecule drug discovery. We further overview the current landscape of clinical trials evaluating the potential effect of microbiota and their metabolites on immunotherapy outcomes, presenting future trends in the field of microbiota-based therapies. Microbiota-based therapies are promising therapeutic options to promote therapeutic efficacy and diminish the toxicity of immunotherapy.

Risk factors for postoperative recurrence of anal fistula identified by an international, evidence-based Delphi consultation survey of surgical specialists.

BACKGROUND: Despite the emerging knowledge about postoperative anal fistula recurrence (AFR) and the increasing number of clinical studies, there is no better understanding or consensus regarding the risk factors for AFR. The aim of this study was to generate international consensus guidance statements focusing on AFR. METHODS: A two-round modified Delphi process was conducted among international surgical specialists via an online survey delivered by email with a secure link created with Google Forms. Surgeons were asked to use a 9-point Likert scale to rate the importance of patient-, fistula-, and surgery-related statements developed based on our previous systematic review. Consensus was reached when at least 70% of panel members rated a statement as being of critical importance (ratings of 7-9). RESULTS: Of a total of 60 experts invited, 38 experts representing 13 countries from four continents agreed to participate in the first round of the Delphi process and 31 in the second round. In total, consensus was reached on 14 statements on the risk factors for AFR in three domains: patient-related risk factors included comorbid colitis, inflammatory bowel disease and use of immunosuppressants; fistula-related factors included transsphincteric fistula, number of fistula, horseshoe extension, undetected internal opening, location of anal fistula, recurrent fistula, suprasphincteric fistula, and height of the internal opening; and surgery-related factors included type of surgery, previous fistula surgery and surgeon. CONCLUSION: This Delphi study provides an evidence-based profile of risk factors for AFR in the patient-, surgery- and fistula-related domains from a global perspective. Clinically, these indicators can be incorporated to develop risk calculation tools for the early detection of AFR in high-risk patients, allowing early prevention and intervention.

Surgical treatment for cryptoglandular and Crohn's perianal fistulas: Protocol of an umbrella review.

INTRODUCTION: A high prevalence of cryptoglandular and Crohn's perianal fistulas has been reported worldwide, and several surgical options are available for the management of anal fistula, with varying clinical efficacy. However, currently, the available evidence for the effectiveness of these surgical approaches are lacking and of concern in terms of the credibility and strength. The purpose of this study is to evaluate the credibility of the published systematic reviews and meta-analyses that assess the efficacy and safety of the surgical options for cryptoglandular and Crohn's perianal fistulas through an umbrella review. METHODS AND ANALYSIS: A systematic search in PubMed, Embase and Cochrane library will be performed from inception to December 2020 without any language restriction. We will include systematic reviews and meta-analyses that investigate the efficacy and safety of surgical approaches in the management of cryptoglandular and Crohn's perianal fistulas. Two reviewers will independently screen search results through reading the titles or abstracts. Relevant information will be extracted from each eligible systematic review or meta-analysis. Based on random effects model summary estimates along with their p values, 95% prediction intervals, between-study heterogeneity, small-study effects and excess significance, we will classify the evidence from convincing (class I) to weak (class IV). Findings will be summarized using quantitative synthesis combined with a narrative approach. Cryptoglandular and Crohn's perianal fistulas will be summarized separately. Two authors will independently perform the literature search, data extraction, and quality assessment of each included systematic review and meta-analysis. Any unresolved conflicts or doubts will be resolved by discussion or by consulting a senior author. The risk of bias of the systematic reviews will be assessed using a 16-item Assessment of Multiple Systematic Reviews 2 (AMSTAR2) checklist. The strength of evidence for the included systematic reviews will be classified as "high", "moderate", "low", or "critically low" quality. ETHICS AND DISSEMINATION: Ethics approval is not required as we will collect data from the published systematic reviews and meta-analyses without using individual patient data. The results of this umbrella review will be published in a peer-reviewed journal and will be presented at an anorectal disease conference. PROSPERO REGISTRATION NUMBER: CRD42020200754.

Highly regenerative and efficient adsorption of phosphate by restructuring natural palygorskite clay via alkaline activation and co-calcination.

Herein, we present a new strategy to create a highly regenerative and efficient phosphate adsorbent based on activating natural palygorskite structures. Both the regeneration via alkaline activation and synthesis via co-calcination restructured the palygorskite and created adsorptive metal oxides. The phosphate adsorbent exhibits excellent regeneration performance with high removal capacity.

Risk of Stroke in Cancer Survivors: A Meta-analysis of Population-Based Cohort Studies.

OBJECTIVE: Accumulating evidence suggests that cancer survivors may have a relatively higher risk of stroke. The aim of this meta-analysis was to determine whether cancer survivors have a relatively higher risk of stroke than cancer-free populations on the basis of published data from population-based cohort studies. METHODS: PubMed, Embase, and Cochrane Library were searched from inception to February 8, 2020, for population-based cohort studies. Effect estimates with 95% confidence intervals (CIs) were pooled using the random-effects model. We conducted subgroup analyses and meta-regression to explore sources of heterogeneity and the stability of the results. RESULTS: Twenty population-based cohort studies involving 10,479,530 participants were identified. Overall, the relative risk (RR) for stroke in cancer survivors was 1.66 (95% CI 1.35-2.04; p < 0.001) compared with that in cancer-free controls; survivors of head and neck, hematologic, lung, pancreas, and stomach cancer (all p < 0.05) showed consistently significant results, whereas no significant increased risk was observed for patients with other cancer types. The effects were more prominent in cancer survivors with female sex (RR 1.38, 95% CI 1.18-1.61; p < 0.001), younger age at cancer diagnosis (<45 years) (RR 2.57, 95% CI 1.27-5.19; p = 0.009), and shorter cancer survival duration (≥1-2 years) (RR 1.69, 95% CI 1.18-2.42; p = 0.004). Moreover, cancer survivors had a significantly increased risk of ischemic stroke (RR 1.53, 95% CI 1.28-1.84; p < 0.001) compared with hemorrhagic stroke. CONCLUSIONS: Cancer plays a critical role in the etiologic of stroke. Due to the existence of substantial heterogeneity among the included studies, the results should be interpreted with caution. However, early prevention and effective intervention of stroke in cancer survivors require attention from health policy makers.

Chronic stress promotes EMT-mediated metastasis through activation of STAT3 signaling pathway by miR-337-3p in breast cancer.

Chronic stress could induce cancer metastasis by constant activation of the sympathetic nervous system, while cellular mechanism remains obscure. The aim of this research is to explore the metastasis associated negative effect of chronic stress. The analysis of transcriptome sequencing implied that activation of STAT3 signaling pathway by downregulated miR-337-3p might be a potential mechanism to induce epithelial to mesenchymal transition (EMT) of cancer cell and promote metastasis under chronic stress. We also verified this biological process in further experiments. Downregulation of miR-337-3p could downregulate E-cadherin expression and upregulate vimentin expression in vitro and in vivo. STAT3, related signal pathways of which are involved in metastasis regulation, was directly targeted by miR-337-3p. In conclusion, the above results denoted that activation of miR-337-3p/STAT3 axis might be a potential pathway for the increasing metastasis of breast cancer under chronic stress.

Development of screening tools to predict the risk of recurrence and related complications following anal fistula surgery: protocol for a prospective cohort study.

INTRODUCTION: Postoperative recurrence and related complications are common and related to poor outcomes in patients with anal fistula (AF). Due to being associated with short-term and long-term cure rates, perioperative complications have received widespread attention following AF surgery. This study aims to identify a set of predictive factors to develop risk prediction models for recurrence and related complications following AF surgery. We plan to develop and validate risk prediction models, using information collected through a WeChat patient-reported questionnaire system combined with clinical, laboratory and imaging findings from the perioperative period until 3-6 months following AF surgery. METHODS AND ANALYSIS: This is a prospective hospital-based cohort study using a linked database of collected health data as well as the follow-up outcomes for all adult patients who suffered from AF at a tertiary referral hospital in Shanghai, China. We will perform logistic regression models to predict anal fistula recurrence (AFR) as well as related complications (eg, wound haemorrhage, faecal impaction, urinary retention, delayed wound healing and unplanned hospitalisation) during and after AF surgery, and machine learning approaches will also be applied to develop risk prediction models. This prospective study aims to develop the first risk prediction models for AFR and related complications using multidimensional variables. These tools can be used to warn, motivate and empower patients to avoid some modifiable risk factors to prevent postoperative complications early. This study will also provide alternative tools for the early screening of high-risk patients with AFR and related complications, helping surgeons better understand the aetiology and outcomes of AF in an earlier stage. ETHICS AND DISSEMINATION: The study was approved by the Institutional Review Board of Shuguang Hospital affiliated with Shanghai University of Traditional Chinese Medicine (approval number: 2019-699-54-01). The results of this study will be submitted to international scientific peer-reviewed journals or conferences in surgery, anorectal surgery or anorectal diseases. TRIAL REGISTRATION NUMBER: ChiCTR1900025069; Pre-results.

Effects of Layer-Charge Distribution of 2:1 Clay Minerals on Methane Hydrate Formation: A Molecular Dynamics Simulation Study.

Molecular dynamics simulations were used to investigate the effects of the external surface of a 2:1 clay mineral with different charge amounts and charge locations on CH4 hydrate formation. The results showed that 512, 51262, 51263, and 51264 were formed away from the clay mineral surface. The surface of the clay mineral with high- and low-charge layers was occupied by Na+ to form various distributions of outer- and inner-sphere hydration structures, respectively. The adsorbed Na+ on the high-charge layer surface reduced the H2O activity by disturbing the hydrogen bond network, resulting in low tetrahedral arrangement of H2O molecules near the layer surface, which inhibited CH4 hydrate formation. However, more CH4 molecules were adsorbed onto the vacancy in the Si-O rings of a neutral-charge layer to form semicage structures. Thus, the order parameter of H2O molecules near this surface indicated that the arrangement of H2O molecules resulted in a more optimal tetrahedral structure for CH4 hydrate formation than that near the negatively charged layer surface. Different nucleation mechanisms of the CH4 hydrate on external surfaces of clay mineral models were observed. For clay minerals with negatively charged layers (i.e., high and low charge), the homogeneous nucleation of the CH4 hydrate occurred away from the surface. For a clay mineral with a neutral-charge layer, the CH4 hydrate could nucleate either in the bulk-like solution homogeneously or at the clay mineral-H2O interface heterogeneously.

Risk Factors for Recurrence after anal fistula surgery: A meta-analysis.

BACKGROUND: Despite a burgeoning literature during the last two decades regarding perioperative risk management of anal fistula, little is known about its risk factors that influence postoperative recurrence. We performed a meta-analysis to summarize and assess the credibility of evidence of potential risk factors for anal fistula recurrence (AFR) after surgery. METHODS: Pubmed and EMBASE without language restriction were searched from inception to April 2018 that reported risk factors which predisposed recurrence after anal fistula surgery. We excluded studies that involved patients with anal fistula associated with Crohn's disease. MOOSE guidelines were followed when this meta-analysis was performed. We used random-effects models to pool relative risks (RRs) with 95% confidence intervals (CIs). Evidence from observational studies was graded into high-quality (Class I), moderate-quality (Class II/III) and low-quality (Class IV) based on Egger's P value, total sample size and between-study heterogeneity. RESULTS: Of 3514 citations screened, 20 unique observational studies comprising 6168 patients were involved in data synthesis. High-quality evidence showed that AFR was associated with high transsphincteric fistula (RR, 4.77; 95% CI, 3.83 to 5.95), internal opening unidentified (RR, 8.54; 95% CI, 5.29 to 13.80), and horseshoe extensions (RR, 1.92; 95% CI, 1.43 to 2.59). Moderate-quality evidence suggested an association with prior anal surgery (RR, 1.52; 95% CI, 1.04 to 2.23), seton placement surgery (RR, 2.97; 95% CI, 1.10 to 8.06), and multiple fistula tract (RR, 4.77; 95% CI, 1.46 to 15.51). High-quality evidence demonstrated no significant association with gender or smoking; moderate-quality evidence also suggested no association with age, tertiary referral, alcohol use, diabetes mellitus, obesity, preoperative seton drainage, high internal opening, postoperative drainage, mucosal advancement flap surgery, supralevator extensions, location or type of anal fistula. CONCLUSION: Several patient, surgery and fistula-related factors are significantly associated with postoperative AFR. These findings strengthen clinical awareness of early warning to identify patients with high-risk disease recurrence for AFR.

Activation of natural halloysite nanotubes by introducing lanthanum oxycarbonate nanoparticles via co-calcination for outstanding phosphate removal.

Halloysite nanotubes were activated via co-calcination of halloysite and the precursors of lanthanum oxycarbonate (LO), generating reactive alumina nanoparticles and uniformly anchoring LO nanoparticles to halloysite surfaces. The resulting LO-alumina combination exhibits record-high phosphate adsorption capacity as well as excellence in adsorption selectivity and sewage phosphate removal.

Effects of two translated phrases of distress thermometer on screening distress in Chinese cancer patients: A comparative study.

AIMS AND OBJECTIVES: To compare the screening effectiveness of two translated phrases of the Distress Thermometer (DT), namely the XinLiTongKu Thermometer (DT-X) and KunRao Thermometer (DT-K), in Chinese patients with cancer. BACKGROUND: The DT is one of the most commonly used tools to screen cancer patients' psychological states. However, translations of the DT are not uniform in China; this may affect the screening effectiveness of this tool. DESIGN: Cross-sectional survey with randomisation and self-control. METHODS: A sample of 172 cases was screened using the two DT translations, to check and compare the screening effectiveness of the two translations. The correlation between them was also investigated. The causes of the differences in screening effectiveness of the two translations were analysed, using 90 of the above 172 cases and an additional 68 cases. STROBE guidelines were used in reporting this study. RESULTS: For the DT-X (using a cut-off score of 4), the sensitivity value was 0.82 and the specificity value was 0.95, where for the DT-K (using a cut-off score of 3), the values were 0.78 and 0.79, respectively. The area under the receiver operating characteristic curve (AUC) was 0.914 and 0.797, respectively. Scores of the DT-X and the DT-K were positively correlated. In concepts of the participants, for both phrases, the sequences of the first three meanings were the same-worried, anxious and tired-while the fourth to sixth meanings were differed between phrases. CONCLUSION: The DT-X and DT-K were both effective screening tools. However, in this study, the DT-X had a larger AUC than the DT-K. RELEVANCE TO CLINICAL PRACTICE: This study may be useful for enabling better measurement of distress in Chinese patients and improving the indigenisation of the DT.

Activating 2D nano-kaolinite using hybrid nanoparticles for enhanced phosphate capture.

A synergistic host-guest coupling is exploited to disorder nano-kaolinite unit layers to form Al2O3 nanoparticles, which act as activated adsorptive sites; meanwhile, the coupling enables La-based nanoparticles to anchor homogenously on the nano-kaolinite surfaces, fully utilizing their adsorption ability. The activated hybrid nanostructures exhibit an excellent phosphate adsorption capacity.

The Multi-Purpose Tool of Tumor Immunotherapy: Gene-Engineered T Cells.

A detailed summary of the published clinical trials of chimeric antigen receptor T cells (CAR-T) and TCR-transduced T cells (TCR-T) was constructed to understand the development trend of adoptive T cell therapy (ACT). In contrast to TCR-T, the number of CAR-T clinical trials has increased dramatically in China in the last three years. The ACT seems to be very prosperous. But, the multidimensional interaction of tumor, tumor associated antigen (TAA) and normal tissue exacerbates the uncontrolled outcome of T cells gene therapy. It reminds us the importance that optimizing treatment security to prevent the fatal serious adverse events. How to balance the safety and effectiveness of the ACT? At least six measures can potentially optimize the safety of ACT. At the same time, with the application of gene editing techniques, more endogenous receptors are disrupted while more exogenous receptors are expressed on T cells. As a multi-purpose tool of tumor immunotherapy, gene-engineered T cells (GE-T) have been given different functional weapons. A network which is likely to link radiation therapy, tumor vaccines, CAR-T and TCR-T is being built. Moreover, more and more evidences indicated that the combination of the ACT and other therapies would further enhance the anti-tumor capacity of the GE-T.

Prognostic role of pretreatment blood neutrophil-to-lymphocyte ratio in advanced cancer survivors: A systematic review and meta-analysis of 66 cohort studies.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) is crucial for the incidence and mortality of various tumors. However, little is known on NLR and its association with prognosis in advanced tumors. Here we performed a meta-analysis to establish the prognostic significance of pretreatment blood NLR for advanced tumors. METHODS: A systematic literature search through April 2016 was performed to evaluate the association between pretreatment blood NLR and overall survival (OS) or progression-free survival (PFS) in patients with advanced tumors. Data were extracted from studies reporting hazard ratios (HRs) and 95% confidence interval (CI) and pooled using the Mantel-Haenszel random-effect model. RESULTS: Sixty-six studies with a total of 24536 individuals were included in the meta-analysis. Pooled analyses revealed that elevated pretreatment NLR was associated with worse OS (HR 1.70, 95% CI 1.57-1.84, P<0.001) and PFS (HR 1.61, 95% CI 1.42-1.82, P<0.001) in advanced tumors. Subgroup analysis stratified by tumor type demonstrated that pancreatic cancer patients with high pretreatment NLR had the worst OS (HR 1.94, 95% CI 1.55-2.54, P<0.001) and colorectal cancer with the worst PFS (HR 1.74, 95% CI 1.04-2.90, P<0.001). When stratified by cut-off value for NLR, we found that cut-off value being five indicated the worst PFS (HR 2.23, 95% CI 1.54-3.23, P=0.019). CONCLUSIONS: Overall, high pretreatment blood NLR could be an adverse prognostic indicator for advanced tumor. Large-scale prospective studies investigating its survival outcomes in specific cancer type are strongly advocated.

A multicenter study on the validation of the Burnout Battery: a new visual analog scale to screen job burnout in oncology professionals.

OBJECTIVES: The objective of the study is to develop a novel tool-the Burnout Battery-for briefly screening burnout among oncology professionals in China and assessing its validity. METHODS: A multicenter study was conducted in doctors and nurses of the oncology departments in China from November 2014 to May 2015. The Burnout Battery was administered with the Maslach Burnout Inventory-Human Services Survey (MBI-HSS) and the Doctors' Job Burnout Questionnaire. RESULTS: Of 538 oncology doctors and nurses who completed all the survey, using MBI-HSS as the standard tool for measuring burnout, 52% had emotional exhaustion, 39.4% had depersonalization, and 59.3% had a low sense of personal accomplishment. Receiver operating characteristic curve analyses showed that the best cut-off of the Burnout Battery was the battery with 3 bars, which yielded best sensitivity and specificity against all the 3 subscales of MBI-HSS. With this cut-off, nearly half of Chinese oncology professionals (46.8%) had burnout. The Burnout Battery correlated significantly with subscales of the MBI-HSS and the Doctors' Job Burnout Questionnaire. In multiple logistic regression analysis, those who worked more than 60 hours per week and who thought clinical work was the most stressful part of their job were more likely to experience burnout. CONCLUSION: Chinese oncology professionals exhibit high levels of burnout. The Burnout Battery appears to be a simple and useful tool for screening burnout. Working long hours and perceiving clinical work as the most stressful part of the job were the main factors associated with burnout.