目的:探索新冠疫情下线上教学期间医学生的自我调节学习(self-regulated learning,SRL)能力以及其与学业成就的关系,为开展线上学习、提高医学生SRL能力和学业成就提供依据.方法:应用SRL量表对中国医科大学临床医学生进行网络问卷调查,分析SRL能力与学习成绩间的关系.结果:每天自学时间越长、父亲受教育程度越高以及对线上教学满意度越高的学生SRL得分越高;学习成绩与SRL及各维度得分存在显著相关性,SRL能力越强,学习成绩越好,SRL各维度能力之间亦存在显著正相关.结论:SRL能力对医学生学习成绩具有正向预测作用,教育者可通过提升教师教学水平、改善学习环境、提供更多优质教学资源等方法提高医学生SRL能力及学业成就.

The purpose of this meta-analysis was to evaluate the efficacy and safety of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, in addition to standard anticancer therapy. Randomized controlled trials (RCTs) that evaluated the efficacy and safety of celecoxib-combined cancer therapy were systematically searched in PubMed and Embase databases. The endpoints were overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), objective response rate (ORR), disease control rate (DCR), pathological complete response (pCR), and adverse events (AEs). The results of 30 RCTs containing 9655 patients showed limited benefits in celecoxib-combined cancer therapy. However, celecoxib-combined palliative therapy prolonged PFS in epidermal growth factor receptor (EGFR) wild-type patients (HR = 0.57, 95%CI = 0.35–0.94). Moreover, despite a slight increase in thrombocytopenia (RR = 1.35, 95%CI = 1.08–1.69), there was no increase in other toxicities. Celecoxib combined with adjuvant therapy indicated a better OS (HR = 0.850, 95%CI = 0.725–0.996). Furthermore, celecoxib plus neoadjuvant therapy improved the ORR in standard cancer therapy, especially neoadjuvant therapy (overall: RR = 1.13, 95%CI = 1.03–1.23; neoadjuvant therapy: RR = 1.25, 95%CI = 1.09–1.44), but not pCR. Our study indicated that adding celecoxib to palliative therapy prolongs the PFS of EGFR wild-type patients, with good safety profiles. Celecoxib combined with adjuvant therapy prolongs OS, and celecoxib plus neoadjuvant therapy improves the ORR. Thus, celecoxib-combined cancer therapy may be a promising therapy strategy.

Gastric cancer (GC) is known as a top malignant type of tumors worldwide. Despite the recent decrease in mortality rates, the prognosis remains poor. Therefore, it is necessary to find novel biomarkers with early diagnostic value for GC. In this study, we present a large-scale proteomic analysis of 30 GC tissues and 30 matched healthy tissues using label-free global proteome profiling. Our results identified 537 differentially expressed proteins, including 280 upregulated and 257 downregulated proteins. The ingenuity pathway analysis (IPA) results indicated that the sirtuin signaling pathway was the most activated pathway in GC tissues whereas oxidative phosphorylation was the most inhibited. Moreover, the most activated molecular function was cellular movement, including tissue invasion by tumor cell lines. Based on IPA results, 15 hub proteins were screened. Using the receiver operating characteristic curve, most of hub proteins showed a high diagnostic power in distinguishing between tumors and healthy controls. A four-protein (ATP5B-ATP5O-NDUFB4-NDUFB8) diagnostic signature was built using a random forest model. The area under the curve (AUC) values of this model were 0.996 and 0.886 for the training and testing sets, respectively, suggesting that the four-protein signature has a high diagnostic power. This signature was further tested with independent datasets using plasma enzyme-linked immune sorbent assays, resulting in an AUC value of 0.778 for distinguishing GC tissues from healthy controls, and using immunohistochemical tissue microarray analysis, resulting in an AUC value of 0.805. In conclusion, this study identifies potential biomarkers and improves our understanding of the pathogenesis, providing novel therapeutic targets for GC.

tRNA-derived fragments (tRFs) are a new classification of small non-coding RNAs (sncRNAs) derived from the specific cleavage of precursors and mature tRNAs. Accumulating recent evidence has shown that tRFs are frequently abnormal in several cancers. Nevertheless, the role of tRFs in gastric cancer and its mechanism remain unclear. In this study, we found abnormal expression of tRF-3017A (derived from tRNA-Val-TAC) in gastric cancer tissues and cell lines and confirmed its effect on promoting the invasion and migration of gastric cancer cells through functional experiments in vitro . Analysis of clinicopathologic data showed patients with higher tRF-3017A were associated with significantly higher lymph node metastasis. Mechanistic investigation implies that tRF-3017A regulates the tumor suppressor gene NELL2 through forming the RNA-induced silencing complex (RISC) with Argonaute (AGO) proteins. In this study, we found that higher tRF-3017A were associated with significantly higher lymph node metastasis in gastric cancer patients and the tRF-3017A may play a role in promoting the migration and invasion of gastric cancer cells by silencing tumor suppressor NELL2.

BACKGROUND:Neoadjuvant (chemo) radiotherapy is used as a standard treatment for locally advanced rectal cancer (LARC), but there is no general consensus on either the efficacy of postoperative adjuvant chemotherapy in patients with LARC after neoadjuvant treatment and surgery, or whether the addition of oxaliplatin to adjuvant chemotherapy provides survival benefits. METHODS:We performed a meta-analysis of data from the PubMed and Embase databases. We included patients with LARC who received neoadjuvant (chemo) radiotherapy and curative surgery. Overall survival (OS), disease-free survival (DFS), toxicity, and compliance were analyzed in the oxaliplatin/fluorouracil- (OX/FU-) based group compared with the FU-based group, and in the chemotherapy group compared with the observation group. RESULTS:Twenty studies were included in the analysis. Our results indicated that adjuvant chemotherapy prolonged OS (hazard ratio [HR] = 0.78, 95%CI = 0.67-0.91) in patients with LARC treated with neoadjuvant (chemo) radiotherapy and surgery compared with those in the observation group. Subgroup analysis showed the same results in both the ypStage II and ypStage III groups. Compared with those in the observation group, patients in the chemotherapy group also showed an increase in DFS (HR = 0.75, 95%CI = 0.60-0.93). No significant increase was observed in OS (HR = 1.04, 95%CI = 0.87-1.24) or DFS (HR = 0.98, 95%CI = 0.76-1.27) when oxaliplatin was added to FU-based adjuvant chemotherapy, as compared with the FU-based treatment, and subgroup analysis also indicated no survival benefits in the clinical stage II, clinical stage III, ypStage II, and ypStage III groups. CONCLUSIONS:For patients with LARC who have already received neoadjuvant (chemo) radiotherapy and curative surgery, adjuvant chemotherapy improves OS over that in the observation group. Adding oxaliplatin to FU-based adjuvant chemotherapy does not confer survival benefits beyond those from FU-based adjuvant chemotherapy.

Abstract Background tRNA-derived fragments (tRFs) are 14–40-nucleotide-long, small non-coding RNAs derived from specific tRNA cleavage events with key regulatory functions in many biological processes. Many studies have shown that tRFs are associated with Argonaute (AGO) complexes and inhibit gene expression in the same manner as miRNAs. However, there are currently no tools for accurately predicting tRF target genes. Methods We used tRF-mRNA pairs identified by crosslinking, ligation, and sequencing of hybrids (CLASH) and covalent ligation of endogenous AGO-bound RNAs (CLEAR)-CLIP to assess features that may participate in tRF targeting, including the sequence context of each site and tRF-mRNA interactions. We applied genetic algorithm (GA) to select key features and support vector machine (SVM) to construct tRF prediction models. Results We first identified features that globally influenced tRF targeting. Among these features, the most significant were the minimum free folding energy (MFE), position 8 match, number of bases paired in the tRF-mRNA duplex, and length of the tRF, which were consistent with previous findings. Our constructed model yielded an area under the receiver operating characteristic (ROC) curve (AUC) = 0.980 (0.977–0.983) in the training process and an AUC = 0.847 (0.83–0.861) in the test process. The model was applied to all the sites with perfect Watson–Crick complementarity to the seed in the 3′ untranslated region (3′-UTR) of the human genome. Seven of nine target/nontarget genes of tRFs confirmed by reporter assay were predicted. We also validated the predictions via quantitative real-time PCR (qRT-PCR). Thirteen potential target genes from the top of the predictions were significantly down-regulated at the mRNA levels by overexpression of the tRFs (tRF-3001a, tRF-3003a or tRF-3009a). Conclusions Predictions can be obtained online, tRFTars, freely available at http://trftars.cmuzhenninglab.org:3838/tar/ , which is the first tool to predict targets of tRFs in humans with a user-friendly interface.

Background The effects of adjuvant chemotherapy in patients with stage II colorectal cancer (CRC) has been in controversy for a long time. Our study aimed to find an effective inflammatory marker to predict the effects of chemotherapy. Methods Seven hundred eight stage II CRC patients in our institution were included. The subpopulation treatment effect pattern plot (STEPP) analysis was used to determine the optimal inflammatory marker and cut-off value. Propensity score matching (PSM) was performed to balance discrepancy between the chemotherapy and non-chemotherapy group. Survival analyses based on overall survival (OS) and cancer-specific survival (CSS) were performed with Kaplan-Meier methods with log-rank test and Cox proportional hazards regression. The restricted mean survival time (RMST) was used to measure treatment effect. Results The platelet to lymphocyte ratio (PLR) was chosen as the optimal marker with a cut-off value of 130 according to STEPP. In OS analysis, PLR was significantly associated with the effects of chemotherapy (interaction p = 0.027). In the low-PLR subgroup, the chemotherapy patients did not have a longer OS than the non-chemotherapy patients (HR: 0.983, 95% CI: 0.528–1.829). In the high-PLR subgroup, the chemotherapy patients had a significantly longer OS than the non-chemotherapy patients (HR: 0.371, 95% CI: 0.212–0.649). After PSM, PLR was still associated with the effects of chemotherapy. In CSS analysis, PLR was not significantly associated with the effects of chemotherapy (interaction p = 0.116). In the low-PLR subgroup, the chemotherapy patients did not have a longer CSS than the non-chemotherapy patients (HR: 1.016, 95% CI: 0.494–2.087). In the high-PLR subgroup, the chemotherapy patients had a longer CSS than the non-chemotherapy patients (HR: 0.371, 95% CI: 0.212–0.649). After PSM, PLR was not associated with the effects of chemotherapy. Conclusions PLR is an effective marker to predict the effects of chemotherapy in patients with stage II CRC.

Abstract Background Neoadjuvant therapy can lead to different tumor regression grades (TRG) in rectal cancer after neoadjuvant therapy. The purposes of this study are to investigate the relationships among TRG, pathologic complete response (pCR) and long-term survival, on the basis of reconstructed individual patient data (IPD). Methods The PubMed, Embase, Ovid and Cochrane CENTRAL databases were searched. The primary endpoint was to evaluate the survival landscape of different TRGs after neoadjuvant therapy and the secondary endpoint was to evaluate the associations between pCR and survival. IPD were reconstructed with Kaplan–Meier curves. Results The 10-year overall survival (OS) and 5-year disease-free survival (DFS) were clearly higher in the pCR group than in the non-pCR (npCR) group (80.5% vs. 48.3, 90.1% vs. 69.8%). Furthermore, the OS and DFS increased with improvement in tumor regression after neoadjuvant therapy. According to the IPD, the pCR group had longer OS (HR = 0.240, 95% CI = 0.177–0.325, p < 0.001) and DFS (HR = 0.274, 95% CI = 0.205–0.367, p < 0.001) than the npCR group. Better tumor regression was associated with better survival outcomes (p < 0.005). Direct calculation of published HR values yielded similar results. Conclusions Our results indicate a positive relationship between better tumor regressions and improved survival benefits among the npCR group and patients with rectal cancer achieving pCR had much longer OS and DFS than patients achieving npCR, presenting a survival landscape of different TRGs and pCR in rectal cancer after neoadjuvant therapy.

[This corrects the article DOI: 10.3892/ol.2017.5886.].

Postoperative pain management is an essential module for perioperative care, especially for enhanced recovery after surgery programs. Continuous wound infiltration (CWI) with local anesthetic may be a promising postoperative analgesic strategy. However, its analgesic efficacy and safety remain debatable. Embase and PubMed databases were systematically searched for relevant randomized controlled trials (RCTs). RCTs assessing the analgesic efficacy and safety of CWI with local anesthetic for postoperative analgesia were selected. The outcomes contained pain scores during rest and mobilization, total opioid consumption, time to the first request of rescue analgesia, length of hospital stay, satisfaction with analgesia, time to return of bowel function, postoperative nausea and vomiting, total complication, wound infection, hypotension, and pruritus. The weighted mean difference and risk ratio were used to pool continuous and dichotomous variables, respectively. A total of 121 RCTs were included. CWI with local anesthetic reduced postoperative pain during rest and mobilization at different time points, increased satisfaction with analgesia, shortened recovery of bowel function, and reduced postoperative nausea and vomiting compared with the placebo group, especially for laparotomy surgery. There were no significant differences in these clinical outcomes compared to epidural and intravenous analgesia. CWI with local anesthetic reduced the total opioid consumption and hypotension risk and did not increase total complications, wound infection, or pruritus. CWI with local anesthetic had a better analgesic efficacy without increased side effects for sternotomy surgery. However, CWI with local anesthetic did not translate into favorable analgesic benefits in laparoscopic surgery. CWI with local anesthetic is an effective postoperative analgesic strategy with good safety profiles in laparotomy and sternotomy surgery, and thus CWI with local anesthetic may be a promising analgesic option enhancing recovery after surgery programs for these surgeries. Continuous wound infiltration (CWI) with local anesthetic may be a promising postoperative analgesic strategy, but its effect remains debatable. We performed this meta-analysis based on 121 high-quality articles (RCTs) to evaluate the analgesic efficacy and safety of CWI with local anesthetic. We found that CWI with local anesthetic could reduce postoperative pain, increase satisfaction with analgesia, shorten recovery of bowel function, and reduce postoperative nausea and vomiting, especially for laparotomy surgery. However, CWI with local anesthetic did not show favorable analgesic benefits in laparoscopic surgery.

ABSTRACT It is critical to identify patients with stage II and III colorectal cancer (CRC) who will benefit from adjuvant chemotherapy (ACT) after curative surgery, while the only use of clinical factors is insufficient to predict this beneficial effect. In this study, we performed genetic algorithm (GA) to select ACT candidate genes, and built a predictive model of support vector machine (SVM) using gene expression profiles from the Gene Expression Omnibus database. The model contained four ACT candidate genes (EDEM1, MVD, SEMA5B, and WWP2) and TNM stage (stage II or III). After using Subpopulation Treatment Effect Pattern Plot to determine the optimal cutoff value of predictive scores, the validated patients from The Cancer Genome Atlas database can be divided into the predictive ACT‐benefit/‐futile groups. Patients in the predictive ACT‐benefit group with 5‐fluorouracil (5‐Fu)–based ACT had significantly longer relapse‐free survival (RFS) compared to those without ACT (P = .015); However, the difference in RFS in the predictive ACT‐futile group was insignificant (P = .596). The multivariable analysis found that the predictive groups were significantly associated with the effect of ACT (Pinteraction = .011). Consequently, we developed a predictive model based on the SVM and GA algorithm which was further validated to define patients who benefit from ACT on recurrence.

蛋白激酶的异常功能与肿瘤密切相关,通过研发相应的蛋白激酶抑制剂调控对应的信号转导通路是现今抗肿瘤药物开发的重点与热点.自从第一种蛋白激酶抑制剂在2001年被美国食品药品监督管理局(FDA)批准上市以来,已有50余种激酶抑制剂获得批准用于治疗乳腺癌和肺癌等恶性肿瘤,在肿瘤患者的治疗中起到重要的作用.小分子蛋白激酶抑制剂同样存在许多亟待解决的问题,为此,研究者不断地开发新的激酶靶向药物来克服发现的问题,许多新的小分子激酶抑制剂已处于临床试验阶段.本综述就抗肿瘤小分子蛋白激酶抑制剂的分类、作用底物以及作用机理进行分析和总结,并系统阐述抗肿瘤小分子激酶抑制剂的研发现状、研究进展和发展趋势.

Aim: To evaluate the impact of age on the efficacy of immune checkpoint inhibitors (ICI) in cancer patients. Materials & methods: The primary outcomes included overall survival (OS) and progression-free survival (PFS). Subgroup, meta-regression analysis and within-trial interaction HR were conducted. Results: A total of 34 studies containing 20,511 cancer patients were included. ICI could improve the OS and PFS in patient aged <65 and ≥65 years. Patients aged <75 years treated with ICI also had favorable OS and PFS compared with the control groups. Conclusion: ICI has comparable efficacy in cancer patients aged <65 and ≥65 years. Cancer patients aged ≥75 years need more attention in the future clinical trials.

Background : The tRNA-derived fragments (tRFs) are 14–40 nucleotides, small non-coding RNAs from specific tRNA cleavages, and they have key regulatory functions in many biological processes. Many studies showed that tRFs are associated with Argonaute complexes and inhibit gene expression in the same manner as miRNAs. However, there are currently no tools to accurately predict tRF target genes. Methods : We used tRF-mRNA pairs identified by crosslinking, ligation, and sequencing of hybrids (CLASH) and covalent ligation of endogenous Argonaute-bound RNAs (CLEAR)-CLIP to assess features that may participate in tRF targeting, including sequence context of each individual site and tRF-mRNA interactions. We applied genetic algorithm (GA) to select key features and support vector machine (SVM) to construct tRF predicting models. Results : We first identified features that globally influenced tRF targeting. Among them, the most significant ones were minimum free folding energy (MFE), position 8 match, number of bases paired in tRF-mRNA duplex, and length of tRF, which were consistent with previous findings. We built the model with the area under the receiver operating characteristic (ROC) curve (AUC) = 0.980 (0.977-0.983) in the training process and AUC = 0.847 (0.83-0.861) in the test process. The model was applied to all the sites with perfect Watson-Crick complementarity to the seed in the 3'-UTR of human genome. Seven of nine target / non-target genes of tRFs confirmed by reporter assay were predicted. Conclusions : Predictions can be obtained online, tRFTar, freely available at http://trftar.cmuzhenninglab.org:3838/tar/, which is the first tool to predict targets of tRFs in human with a user-friendly interface.

The gut microbiota plays a critical role in the anti-tumor immune response. There is increasing data showing that antibiotics (ATBs) change the composition of the gut microbiota and affect the efficacy of immune checkpoint inhibitors (ICIs). However, this is the first meta-analysis to evaluate the association between ATB use and ICI efficacy in cancer patients to provide a better understanding of the strength of this association. We performed a literature search for relevant studies that evaluated the relationship between ATB use and ICI efficacy using the PubMed, Embase, and conference databases. The primary outcomes consisted of overall survival (OS) and progression-free survival (PFS) measured by hazard ratios (HR) and corresponding 95% confidence intervals (CI). Subgroup and sensitivity analyses were also performed. A total of 19 eligible studies comprising 2,740 cancer patients treated with ICIs were included in the analysis. Our results indicated that ATB use was negatively associated with OS in cancer patients (HR = 2.37; 95% CI = 2.05-2.75; P < .001), without heterogeneity (I-2 = 0.0%; P = .851). Moreover, ATB use significantly reduced PFS in patients treated with ICIs (HR = 1.84; 95% CI = 1.49-2.26; P < .001; I-2 = 56.2%). Similar results were obtained in the subgroup analyses stratified by the time of ATB use and cancer type. Sensitivity analyses confirmed the stability of our results. Therefore, the findings of our meta-analysis indicated that ATB use is negatively associated with OS and PFS in cancer patients treated with ICI immunotherapy.

Bowel obstruction (BO) is a complication that commonly affects patients with colorectal cancer (CRC). BO causes severe outcomes, and its treatment leads to a dilemma for many surgeons. Moreover, the factors correlated to BO in preoperative CRC patients remain unclear. The objectives of this study were to investigate the clinical characteristics of BO to identify risk predictors and to construct a BO prediction model with preoperative CRC patients. A large-scale, retrospective cohort, population-based study analyzed the data of 11,814 patients obtained from the Surveillance, Epidemiology, and End Results and Medicare claims-linked databases (SEER-M database). Patients aged ≥ 66 years and primarily diagnosed with CRC from 1992 to 2009 were divided into BO and non-BO groups. Cox proportional hazards regression models were used to determine predictors, and then, a nomogram was constructed by those predictors. A total of 11,814 patients (5293 men and 6251 women) were identified. In multivariate analysis, 14 factors were found to be associated with BO including age, race, marital status, residence location, T category, M category, primary tumor site, histologic type, histologic grade, tumor size, history of alcoholism, chemotherapy, radiotherapy, abdominal pain, and anemia. A nomogram predicting the 90- and 180-day rates of BO was built for the preoperative CRC patients with a C-index of 0.795. This study identified 14 BO-related factors, and a statistical model was constructed to predict the onset of BO in preoperative CRC patients. The obtained data may guide decision-making for the intervention of patients at risk for BO.

BACKGROUND:Chronic sinusitis (CRS) is a high incidence disease and seriously affects the patients' quality of life, causes tremendous economic burden as well. Endoscopic sinus surgery (ESS) is one of the most common therapies for chronic sinusitis. While whether there is a need for nasal packing and which is the best one is still unclear. METHOD AND ANALYSIS:A systematic search will be performed using PubMed, EMBASE.com, the Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, China National Knowledge Infrastructure and Wanfang database to include randomized controlled trials (RCTs), comparing the efficacy and comfort in patients with nasal packings after ESS who is diagnosed as CRS. The risk of bias of the included RCTs will be assessed by the Cochrane Handbook version 5.1.0. A Bayesian network meta-analysis will be conducted using R-3.3.2 software. RESULTS:This study is ongoing and the results will be published in a peer-reviewed journal. CONCLUSION:The results of this study will be sent to clinicians and healthcare providers in the National Health Service, which is expected to help clinicians make more informed choices on nasal packings. ETHICS AND DISSEMINATION:Ethical approval is not applicable since this study is a network meta-analysis based on published trials. PROTOCOL REGISTRATION NUMBER:CRD42019119233.

Mitochondrial DNA mutations play an important role in hereditary hearing loss. The present study aimed at identifying more novel genetic variants of mitochondrial DNA. Complete Mitochondrial genomes were detected in 97 Northwestern Chinese probands with non-syndromic hearing loss and 376 control subjects. The variants were evaluated for the pathogenicity using the following criteria: (1) present in <1% of the controls, (2) evolutional conservation, (3) potential structural and functional alterations. Mutational analysis in probands identified 706 variants, including 180 variants in the D loop region, 27 variants in the 12S rRNA gene, 29 variants in the 16S rRNA gene, 122 missense variants and 312 silent variants in the protein coding gene, 29 variants in the tRNA genes and 7 variants in the non-coding region. After further analysis assessed for the potential structural and functional significance, we identified 5 new candidate variants for hearing loss: 12S rRNA1473C>T, tRNAPhe 614A>C, tRNALys 8339A>G, ND1 3866T>C and non-coding 5656A>G. Our findings may provide the role of these genes in hearing loss development in China and valuable information for the further understanding of pathogenic mechanism of hearing loss.

Background: Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths, and squamous cell carcinoma (SCC) is a rare histological type. Due to the lack of cases, there is no standard treatment for colorectal SCC. Methods: In our study, we compiled data from the Surveillance, Epidemiology, and End Results Program (SEER) database between 1988 and 2014 and analyzed overall survival (OS) between groups stratified by histological type, primary tumor site or treatment regimens. The SEER-Medicare database was also used to analyze the treatment regimens in the groups stratified by tumor-node-metastasis (TNM) stage. Results: Our results show that the colorectal SCC was commonly seen in females, and tends to have higher pT category and TNM stage. The 5-year survival rate for colorectal SCC was much lower than adenocarcinoma or mucinous adenocarcinoma and higher than signet ring cell carcinoma. Patients with rectal SCC also showed better prognosis compared with colon SCC. The colorectal patients received surgery with chemoradiotherapy or chemoradiotherapy alone have a significantly better prognosis than receiving surgery alone in SEER database. For stage I–III colorectal SCC patients who underwent an operation, chemotherapy and radiotherapy could improve the prognosis but failed to reach statistical significance, and chemotherapy is also an independent prognosis factor which could significantly improve the prognosis of stage IV colorectal SCC in SEER-Medicare database. Conclusions: The OS rate for colorectal SCC is much lower than for adenocarcinoma and mucinous adenocarcinoma. Rectal SCC patients had better prognosis than colonic SCC.