Identification of species-specific RNA N6-methyladinosine modification sites from RNA sequences.

N6-methyladinosine (m6A) modification is the most abundant co-transcriptional modification in eukaryotic RNA and plays important roles in cellular regulation. Traditional high-throughput sequencing experiments used to explore functional mechanisms are time-consuming and labor-intensive, and most of the proposed methods focused on limited species types. To further understand the relevant biological mechanisms among different species with the same RNA modification, it is necessary to develop a computational scheme that can be applied to different species. To achieve this, we proposed an attention-based deep learning method, adaptive-m6A, which consists of convolutional neural network, bi-directional long short-term memory and an attention mechanism, to identify m6A sites in multiple species. In addition, three conventional machine learning (ML) methods, including support vector machine, random forest and logistic regression classifiers, were considered in this work. In addition to the performance of ML methods for multi-species prediction, the optimal performance of adaptive-m6A yielded an accuracy of 0.9832 and the area under the receiver operating characteristic curve of 0.98. Moreover, the motif analysis and cross-validation among different species were conducted to test the robustness of one model towards multiple species, which helped improve our understanding about the sequence characteristics and biological functions of RNA modifications in different species.

dbPTM in 2022: an updated database for exploring regulatory networks and functional associations of protein post-translational modifications.

Protein post-translational modifications (PTMs) play an important role in different cellular processes. In view of the importance of PTMs in cellular functions and the massive data accumulated by the rapid development of mass spectrometry (MS)-based proteomics, this paper presents an update of dbPTM with over 2 777 000 PTM substrate sites obtained from existing databases and manual curation of literature, of which more than 2 235 000 entries are experimentally verified. This update has manually curated over 42 new modification types that were not included in the previous version. Due to the increasing number of studies on the mechanism of PTMs in the past few years, a great deal of upstream regulatory proteins of PTM substrate sites have been revealed. The updated dbPTM thus collates regulatory information from databases and literature, and merges them into a protein-protein interaction network. To enhance the understanding of the association between PTMs and molecular functions/cellular processes, the functional annotations of PTMs are curated and integrated into the database. In addition, the existing PTM-related resources, including annotation databases and prediction tools are also renewed. Overall, in this update, we would like to provide users with the most abundant data and comprehensive annotations on PTMs of proteins. The updated dbPTM is now freely accessible at https://awi.cuhk.edu.cn/dbPTM/.

dbAMP 2.0: updated resource for antimicrobial peptides with an enhanced scanning method for genomic and proteomic data.

The last 18 months, or more, have seen a profound shift in our global experience, with many of us navigating a once-in-100-year pandemic. To date, COVID-19 remains a life-threatening pandemic with little to no targeted therapeutic recourse. The discovery of novel antiviral agents, such as vaccines and drugs, can provide therapeutic solutions to save human beings from severe infections; however, there is no specifically effective antiviral treatment confirmed for now. Thus, great attention has been paid to the use of natural or artificial antimicrobial peptides (AMPs) as these compounds are widely regarded as promising solutions for the treatment of harmful microorganisms. Given the biological significance of AMPs, it was obvious that there was a significant need for a single platform for identifying and engaging with AMP data. This led to the creation of the dbAMP platform that provides comprehensive information about AMPs and facilitates their investigation and analysis. To date, the dbAMP has accumulated 26 447 AMPs and 2262 antimicrobial proteins from 3044 organisms using both database integration and manual curation of >4579 articles. In addition, dbAMP facilitates the evaluation of AMP structures using I-TASSER for automated protein structure prediction and structure-based functional annotation, providing predictive structure information for clinical drug development. Next-generation sequencing (NGS) and third-generation sequencing have been applied to generate large-scale sequencing reads from various environments, enabling greatly improved analysis of genome structure. In this update, we launch an efficient online tool that can effectively identify AMPs from genome/metagenome and proteome data of all species in a short period. In conclusion, these improvements promote the dbAMP as one of the most abundant and comprehensively annotated resources for AMPs. The updated dbAMP is now freely accessible at http://awi.cuhk.edu.cn/dbAMP.

Interpretable Multi-Scale Deep Learning for RNA Methylation Analysis across Multiple Species.

RNA modification plays a crucial role in cellular regulation. However, traditional high-throughput sequencing methods for elucidating their functional mechanisms are time-consuming and labor-intensive, despite extensive research. Moreover, existing methods often limit their focus to specific species, neglecting the simultaneous exploration of RNA modifications across diverse species. Therefore, a versatile computational approach is necessary for interpretable analysis of RNA modifications across species. A multi-scale biological language-based deep learning model is proposed for interpretable, sequential-level prediction of diverse RNA modifications. Benchmark comparisons across species demonstrate the model's superiority in predicting various RNA methylation types over current state-of-the-art methods. The cross-species validation and attention weight visualization also highlight the model's capability to capture sequential and functional semantics from genomic backgrounds. Our analysis of RNA modifications helps us find the potential existence of "biological grammars" in each modification type, which could be effective for mapping methylation-related sequential patterns and understanding the underlying biological mechanisms of RNA modifications.

Lobe-Specific Lymph Node Dissection for Clinical Early-Stage (cIA) Peripheral Non-small Cell Lung Cancer Patients: What and How?

OBJECTIVE: We investigated the possible lobe-specific lymph node (LN) metastasis pattern of early-stage peripheral non-small cell lung cancers (NSCLC) and define the extent of lobe-specific LN dissection for them. METHODS: We retrospectively collected clinical data of patients undergoing lobectomy or segmentectomy with systematic lymphadenectomy for clinical T1N0M0 peripheral NSCLC from January 2015 to December 2018. The LN metastasis pattern was analyzed by tumor lobe location. RESULTS: A total of 590 patients were included for analysis. The mean number of total dissected LNs was 12.3 ± 5.8 and 8.2 ± 4.1 for total dissected mediastinal LNs. The rate of mediastinal LN metastasis was 9.5%. For cases of upper lobe tumor and lower lobe tumor, 8.8% and 6.0% of them respectively metastasized to the upper LN zone (P = 0.274). However, upper lobe tumors hardly metastasized to the subcarinal (0.3%) and lower (0.3%) LN zones while for lower lobe tumors, the rate of LN metastasis was 10.2% and 5.4% respectively (both P < 0.001). However, all cases (100%) metastasizing from lower lobes to the upper LN zone had a tumor size of 2-3 cm, whereas cases with a tumor size ≤ 2 cm had no metastasis (0%). None of the tumors in the right middle lobe metastasized to the lower LN zone (0%). CONCLUSIONS: A lobe-specific LN metastasis pattern was observed in clinical stage IA peripheral NSCLC. For tumors in upper lobes (≤ 3 cm), there may be no need to dissect lower mediastinal LNs and for tumors in lower lobes (≤ 2 cm), dissecting upper mediastinal LNs may not be required.

Surgical Consideration Based on Lymph Nodes Spread Patterns in Patients with Peripheral Right Middle Non-small Cell Lung Cancer 3 cm or Less.

BACKGROUND: The optimal extent of lung resection and lymph nodes dissection for peripheral early-stage right middle non-small cell lung cancer (NSCLC) still remains controversial. In this study, we analyzed the patterns of lymph nodes metastasis (LNM) of patients with peripheral right middle NSCLC ≤ 3 cm, aiming to provide evidences for surgical choice for early-stage peripheral right middle lobe NSCLC. METHODS: We retrospectively investigated the clinical and pathological data of patients diagnosed with peripheral right middle lobe NSCLC ≤ 3 cm between January 2015 and December 2019. The LNM patterns were analyzed by tumor size. RESULTS: A total of 60 patients were included for analysis. The tumor size was preoperatively divided as follows: ≤ 1 cm (13 patients); > 1 cm but ≤ 2 cm (36 patients); > 2 cm but ≤ 3 cm (11 patients). Fifty-four patients were categorized as N0 group, 1 patient as N1 group, and 5 patients as N2 group. In the upper zone, 3 patients were found to have LNM. In the subcarinal zone, another 3 patients had LNM. But the lymph nodes of all these patients were negative in the lower zone. In station 10, 1 patient (1.67%) was found to have LNM, while in station 11-13, 2 patients (3.33%) were found to have LNM. CONCLUSION: For the right middle lobe peripheral NSCLC ≤ 1 cm, sublobar resection with lymph node sampling may be a feasible treatment. For cancers > 1 cm but ≤ 2 cm, lobectomy with lobe-specific lymph node dissection (especially station 2R and 4R) may be a preferred choice. For tumors > 2 cm but ≤ 3 cm, lobectomy with systematic lymph node dissection may still be the standard of care.

Diabetes mellitus and survival of esophageal cancer patients after esophagectomy: a systematic review and meta-analysis.

Diabetes mellitus (DM) is one of the most common comorbidities in esophageal cancer patients who undergo esophagectomy. It is well established that DM has an unfavorable impact on short-term outcomes of patients with surgically treated esophageal cancer; however, whether DM has any impact on long-term survival of these patients remains unclear. We performed the first meta-analysis to investigate the impact of DM on survival of surgically treated esophageal cancer patients. We searched the following databases systematically to retrieve relevant studies on January 2, 2019: PubMed, Embase, and Web of Science. The main outcome data consisting of 3- and 5-year overall survival (OS) rates and hazard ratios (HRs) of OS were extracted to compare survival between patients with and without DM. We finally included for meta-analysis a total of eight cohort studies involving 5,044 esophageal cancer patients who underwent esophagectomy. We found no significant difference between 3-year (risk ratio [RR] = 0.94, 95% CI: 0.73-1.21; P = 0.65) and 5-year (RR = 0.92, 95% CI: 0.80-1.08; P = 0.31) OS rates between patients with and without DM after esophagectomy. Moreover, DM was not found to be an independent predictor of OS for these patients (HR = 1.10, 95% CI: 0.65-1.84; P = 0.72). Our study suggests that DM appears to have no significant impact on long-term survival of esophageal cancer patients who undergo esophagectomy. To improve the prognosis of these patients, it may be more important to control glycemic level in patients with DM who undergo esophagectomy. However, further high-quality studies with appropriate adjustment for confounding factors are needed to verify this conclusion.

Joint DNA-RNA-based NGS for diagnosis and treatment of a rare CD47-MET fusion lung adenocarcinoma which was immunoresistant and savoltinib-sensitive: a case report.

Targeted therapy and immunotherapy are both important in the treatment of non-small-cell lung cancer (NSCLC). Accurate diagnose and precise treatment are key in achieving long survival of patients. MET fusion is a rare oncogenic factor, whose optimal detection and treatment are not well established. Here, we report on a 32-year-old female lung adenocarcinoma patient with positive PD-L1 and negative driver gene detected by DNA-based next-generation sequencing (NGS). A radical resection of the primary lesion after chemotherapy combined with PD-1 checkpoint inhibitor administration indicated primary immuno-resistance according to her pathological response and rapid relapse. A rare CD47-MET was detected by RNA-based NGS, which was confirmed by fluorescence in situ hybridization. Multiplex immunofluorescence revealed a PD-L1 related heterogeneous immunosuppressive microenvironment with little distribution of CD4+ T cells and CD8+ T cells. Savolitinib therapy resulted in a progression-free survival (PFS) of >12 months, until a new secondary resistance mutation in MET p.D1228H was detected by re-biopsy and joint DNA-RNA-based NGS after disease progression. In this case, CD47-MET fusion NSCLC was primarily resistant to immunotherapy, sensitive to savolitinib, and developed secondary MET p.D1228H mutation after targeted treatment. DNA-RNA-based NGS is useful in the detection of such molecular events and tracking of secondary mutations in drug resistance. To this end, DNA-RNA-based NGS may be of better value in guiding precise diagnosis and individualized treatment in this patient population.

Landscape of adenosine pathway and immune checkpoint dual blockade in NSCLC: progress in basic research and clinical application.

Lung cancer poses a global threat to human health, while common cancer treatments (chemotherapy and targeted therapies) have limited efficacy. Immunotherapy offers hope of sustained remission for many patients with lung cancer, but a significant proportion of patients fail to respond to treatment owing to immune resistance. There is extensive evidence to suggest the immunosuppressive microenvironment as the cause of this treatment failure. Numerous studies have suggested that the adenosine (ADO) pathway plays an important role in the formation of an immunosuppressive microenvironment and may be a key factor in the development of immune resistance in EGFR-mutant cell lung cancer. Inhibition of this pathway may therefore be a potential target to achieve effective reversal of ADO pathway-mediated immune resistance. Recently, an increasing number of clinical trials have begun to address the broad prospects of using the ADO pathway as an immunotherapeutic strategy. However, few researchers have summarized the theoretical basis and clinical rationale of the ADO pathway and immune checkpoint dual blockade in a systematic and detailed manner, particularly in lung cancer. As such, a timely review of the potential value of the ADO pathway in combination with immunotherapy strategies for lung cancer is warranted. This comprehensive review first describes the role of ADO in the formation of a lung tumor-induced immunosuppressive microenvironment, discusses the key mechanisms of ADO inhibitors in reversing lung immunosuppression, and highlights recent evidence from preclinical and clinical studies of ADO inhibitors combined with immune checkpoint blockers to improve the lung cancer immunosuppressive microenvironment.

Gas6/AXL pathway: immunological landscape and therapeutic potential.

Cancer is a disease with ecological and evolutionary unity, which seriously affects the survival and quality of human beings. Currently, many reports have suggested Gas6 plays an important role in cancer. Binding of gas6 to TAM receptors is associated with the carcinogenetic mechanisms of multiple malignancies, such as in breast cancer, chronic lymphocytic leukemia, non-small cell lung cancer, melanoma, prostate cancer, etc., and shortened overall survival. It is accepted that the Gas6/TAM pathway can promote the malignant transformation of various types of cancer cells. Gas6 has the highest affinity for Axl, an important member of the TAM receptor family. Knockdown of the TAM receptors Axl significantly affects cell cycle progression in tumor cells. Interestingly, Gas6 also has an essential function in the tumor microenvironment. The Gas6/AXL pathway regulates angiogenesis, immune-related molecular markers and the secretion of certain cytokines in the tumor microenvironment, and also modulates the functions of a variety of immune cells. In addition, evidence suggests that the Gas6/AXL pathway is involved in tumor therapy resistance. Recently, multiple studies have begun to explore in depth the importance of the Gas6/AXL pathway as a potential tumor therapeutic target as well as its broad promise in immunotherapy; therefore, a timely review of the characteristics of the Gas6/AXL pathway and its value in tumor treatment strategies is warranted. This comprehensive review assessed the roles of Gas6 and AXL receptors and their associated pathways in carcinogenesis and cancer progression, summarized the impact of Gas6/AXL on the tumor microenvironment, and highlighted the recent research progress on the relationship between Gas6/AXL and cancer drug resistance.

Parotid metastases from primary lung cancer: Case series and systematic review of the features.

Most parotid metastases have been reported to come from the head and neck; however, cases metastasized from the lung are extremely rare. Missed diagnoses and misdiagnoses occurred quite a few times. Thus, accurately identifying the clinical features of parotid metastasis of lung cancer is important. However, current studies about this issue are mostly case reports, and little is known about the detailed and systematic aspects. We reported three cases of parotid metastases from lung cancer and then systematically searched similar cases through "Pub-Med" and "Web of Science". Finally, twenty-three patients were included in the study. Eighty-three percent of which were males, and 19 patients were over 50 years old. In all cases with smoking history mentioned, 93% were smokers. The predominant pathological type was small cell lung cancer (SCLC, 13 patients, 56%). Seventeen combined with other site metastasis, while more than half of which were brain metastases. The survival time ranged from 3months-17years, and as for SCLCs, it was only 3months-40months. It can be concluded that clinical features, such as sex, age, smoking history, pathological types, and metastasis patterns, could provide valuable evidence for diagnosis. The lung seems to be the most common primary site of parotid metastases except for head and neck tumors. The two circumstances, SCLC coexisting with Warthin's tumor and parotid small cell carcinoma with lung metastasis, should be differentiated from parotid metastasis of lung cancer with caution For cases presented as SCLC, more aggressive strategies, such as chemotherapy with immunotherapy and maintenance therapy, may be more suitable. Due to the greater tendency of brain metastasis in such diseases, whole-brain radiation therapy, stereotactic radiosurgery or prophylactic cranial irradiation should be applied to corresponding patients in time. Additionally, lung cancer parotid metastases may be a marker of poor prognosis.

Residue-Residue Contact Can Be a Potential Feature for the Prediction of Lysine Crotonylation Sites.

Lysine crotonylation (Kcr) is involved in plenty of activities in the human body. Various technologies have been developed for Kcr prediction. Sequence-based features are typically adopted in existing methods, in which only linearly neighboring amino acid composition was considered. However, modified Kcr sites are neighbored by not only the linear-neighboring amino acid but also those spatially surrounding residues around the target site. In this paper, we have used residue-residue contact as a new feature for Kcr prediction, in which features encoded with not only linearly surrounding residues but also those spatially nearby the target site. Then, the spatial-surrounding residue was used as a new scheme for feature encoding for the first time, named residue-residue composition (RRC) and residue-residue pair composition (RRPC), which were used in supervised learning classification for Kcr prediction. As the result suggests, RRC and RRPC have achieved the best performance of RRC at an accuracy of 0.77 and an area under curve (AUC) value of 0.78, RRPC at an accuracy of 0.74, and an AUC value of 0.80. In order to show that the spatial feature is of a competitively high significance as other sequence-based features, feature selection was carried on those sequence-based features together with feature RRPC. In addition, different ranges of the surrounding amino acid compositions' radii were used for comparison of the performance. After result assessment, RRC and RRPC features have shown competitively outstanding performance as others or in some cases even around 0.20 higher in accuracy or 0.3 higher in AUC values compared with sequence-based features.

High pretreatment D-dimer level is an independent unfavorable prognostic factor of small cell lung cancer: A systematic review and meta-analysis.

BACKGROUND: High pretreatment level of D-dimer in small cell lung cancer (SCLC) is commonly encountered, but the impact of high pretreatment D-dimer level on the prognosis of SCLC patients remains undetermined. Therefore, we conducted this meta-analysis focusing specifically on the prognostic value of high pretreatment D-dimer level in SCLC patients comprehensively. METHODS: We searched systematically in PubMed, Embase, and Web of Science for relevant studies published before January 28, 2019. Outcomes including 1-year overall survival (OS), progression-free survival (PFS) rates, and hazard ratios (HRs) of OS and PFS from multivariate analysis were extracted and analyzed. RESULTS: A total of 5 cohort studies consisting of 813 SCLC patients (473 patients with high pretreatment level of D-dimer and 340 with normal level of D-dimer) were finally included for meta-analysis. We found that patients with high pretreatment level of D-dimer had significantly shorter 1-year OS (47.6% vs 79.9%; fixed effects: risk ratio [RR] = 2.506; 95% confidence interval [CI] = [1.948, 3.224]; P < .001) and PFS (15.8% vs 34.0%; random effects: RR = 1.294; 95% CI = [1.060, 1.579]; P = .011) rates than those with normal level of D-dimer. Moreover, high pretreatment D-dimer level was further proved to remain as an unfavorable predictor of OS (fixed effects: HR = 1.865; 95% CI = [1.469, 2.367]; P < .001; I2 = 7.6%) and PFS (fixed effects: HR = 1.513; 95% CI = [1.183, 1.936]; P = .001; I2 = 0.0%) in patients with SCLC. CONCLUSION: High pretreatment level of D-dimer was found to be an independent unfavorable prognostic factor in SCLC patients. However, more studies with sufficient adjustment for confounding factors are encouraged to confirm our conclusions.

Characterization and identification of lysine crotonylation sites based on machine learning method on both plant and mammalian.

Lysine crotonylation (Kcr) is a type of protein post-translational modification (PTM), which plays important roles in a variety of cellular regulation and processes. Several methods have been proposed for the identification of crotonylation. However, most of these methods can predict efficiently only on histone or non-histone protein. Therefore, this work aims to give a more balanced performance in different species, here plant (non-histone) and mammalian (histone) are involved. SVM (support vector machine) and RF (random forest) were employed in this study. According to the results of cross-validations, the RF classifier based on EGAAC attribute achieved the best predictive performance which performs competitively good as existed methods, meanwhile more robust when dealing with imbalanced datasets. Moreover, an independent test was carried out, which compared the performance of this study and existed methods based on the same features or the same classifier. The classifiers of SVM and RF could achieve best performances with 92% sensitivity, 88% specificity, 90% accuracy, and an MCC of 0.80 in the mammalian dataset, and 77% sensitivity, 83% specificity, 70% accuracy and 0.54 MCC in a relatively small dataset of mammalian and a large-scaled plant dataset respectively. Moreover, a cross-species independent testing was also carried out in this study, which has proved the species diversity in plant and mammalian.

Surgical Choice for Clinical Stage IA Non-Small Cell Lung Cancer: View From Regional Lymph Node Metastasis.

BACKGROUND: We aimed to investigate the pattern of regional lymph node (LN) metastasis of early-stage non-small cell lung cancer (NSCLC) to provide novel rationale for surgical choice (lobectomy, segmentectomy, or wedge resection) for these patients. METHODS: We retrospectively collected clinical data of patients undergoing lobectomy with systematic mediastinal LN dissection or sampling for cT1N0M0 peripheral NSCLC from January 2015 to December 2018. The regional LN metastasis pattern was analyzed based on tumor size. RESULTS: We included a total of 354 patients for analysis. The rate of hilar or intrapulmonary LN metastasis was 13.6%. When stratified by tumor size, NSCLC less than or equal to 1 cm had no hilar or intrapulmonary LN metastasis (0%) while NSCLC greater than 2 cm but less than or equal to 3 cm had a significantly high rate of hilar or intrapulmonary LN metastasis (18.4%) and the rates of hilar, interlobar, and peripheral LN metastasis were also relatively high (5.4%, 5.4%, and 12.2%, respectively). NSCLC greater than 1.5 cm but less than or equal to 2 cm also had relatively high rates of hilar (6.5%) and peripheral (18.3%) LN metastasis, while NSCLC greater than 1 cm but less than or equal to 1.5 cm had significantly low rates of hilar or intrapulmonary (2.5%) and peripheral (2.5%) LN metastasis. Radiographic feature and histology were found to be independent predictors of regional LN metastasis. CONCLUSIONS: The pattern of regional LN metastasis in clinical stage IA peripheral NSCLC was significantly influenced by tumor size, which may provide evidence on surgical choice (lobectomy, segmentectomy, or wedge resection) for these early-stage NSCLC patients based on tumor size.

Age-different extent of resection for clinical IA non-small cell lung cancer: analysis of nodal metastasis.

Whether age has any impact on the risk of lymph node (LN) metastasis in patients with early-stage non-small cell lung cancer (NSCLC) remains controversial. Therefore, we aimed to objectively compare the risk of LN metastasis between elderly and young patients so as to justify for age-different extent of surgical resection for treating these patients. We retrospectively collected clinical data of patients undergoing lobectomy or segmentectomy with systematic hilar and mediastinal LN dissection for clinical stage IA peripheral NSCLC from January 2015 to December 2018. Both multivariate logistic regression analysis and propensity score-matched (PSM) analysis were applied to compare the risk of LN metastasis between elderly (>65 years old) and young (≤65 years old) patients. We finally included a total of 590 patients for analysis (142 elderly patients and 448 young patients). In the analysis of unmatched cohorts, young patients tended to have higher rates of hilar/intrapulmonary LN (13.4% VS 9.2%) and mediastinal LN metastasis (10.5% VS 6.3%) than elderly patients. In the multivariate analysis, age was found to be an independent predictor of both hilar/intrapulmonary (Odds ratio(OR) = 2.065, 95%confidence interval(CI): 1.049-4.064, P = 0.036) and mediastinal (OR = 2.400, 95%CI: 1.083-5.316, P = 0.031) LN metastasis. Moreover, in the analysis of well-matched cohorts generated by PSM analysis, young patients had significantly higher rates of hilar/intrapulmonary (18.8% VS 9.4%, P = 0.039) and mediastinal LN metastasis (17.1% VS 6.0%, P = 0.008) than elderly patients. Therefore, age remains to be an independent predictor of LN metastasis in early-stage NSCLC and age-different extent of surgical resection may be justified for these patients.

[A Meta-Analysis of Efficacy and Adverse Effects of Lobaplatin and Cisplatin in the Treatment of Malignant Pleural Effusion].

BACKGROUND: The aim of this study is to systematically evaluate the efficacy and adverse effects of Lobaplatin and Cisplatin in the treatment of malignant pleural effusion. METHODS: The databases of Medline (PubMed), Embase, Web of Science, Cochrane, Wanfang, CNKI and VIP were retrieved so as to search the studies about the randomized controlled clinical trials (RCT) that compared the Lobaplatin and Cisplatin for malignant pleural effusion. The main outcome indicators include objective response rate, complete response, partial response, nephrotoxicity, chest pain, gastrointestinal reaction, myelosuppression, fever response and hepatotoxicity. Relative risk was used as the effect size, which was expressed as 95% confidence interval. The meta-analysis was performed using Stata 14.0 statistical software. RESULTS: A total of 12 RCTs and 720 MPE patients were included. The results showed that the ORR (RR=1.27, 95%CI: 1.15-1.40, P<0.001), CR (RR=1.39, 95%CI: 1.09-1.78, P=0.007), PR (RR=1.21, 95%CI: 1.02-1.42, P=0.026) in LBP thoracic perfusion chemotherapy were significantly higher than those in DDP thoracic perfusion chemotherapy. The incidence of nephrotoxicity (RR=0.31, 95%CI: 0.13-0.71, P=0.005) and gastrointestinal reactions (RR=0.44, 95%CI: 0.31-0.62, P<0.001) in the LBP group were significantly lower than those in DDP group. CONCLUSIONS: Compared with DDP pleural perfusion chemotherapy, the ORR, CR and PR of LBP pleural perfusion chemotherapy for MPE are significantly better than DDP, and its nephrotoxicity and gastrointestinal reactions are remarkably lower than DDP.

The association between statin use and survival of esophageal cancer patients: A systematic review and meta-analysis.

Whether statin use has any impact on survival of esophageal cancer patients remains controversial. Therefore, we conducted a meta-analysis focusing on current topic for the first time.We systematically searched the following databases for relevant studies comparing survival between statin users and non-users among esophageal cancer patients up to March 16, 2019: Pubmed, Embase, and Web of Science. We extracted data of hazard ratio (HR) with 95%confidence interval (CI) of all-cause and cancer-specific mortality for analysis. We used the STATA 12.0 software to perform this meta-analysis.We finally included a total of 4 cohort studies involving a total of 20,435 esophageal cancer patients (5319 statin users and 15116 non-users). Our meta-analysis found that statin use after diagnosis of esophageal cancer was significantly correlated to decreased all-cause (random effects: HR = 0.81, 95%CI: 0.75-0.89, P < .001; I = 68.1%) and cancer-specific mortality (fixed effects: HR = 0.84, 95%CI: 0.78-0.89, P < .001; I = 46.6%) in esophageal cancer patients. When stratified by pathological subtypes, the protective effect of statin use after diagnosis of esophageal cancer was observed in both esophageal adenocarcinoma patients and esophageal squamous cell carcinoma patients. Moreover, statin use before diagnosis of esophageal cancer was also confirmed to have favorable survival benefit for esophageal cancer patients.Statin use was significantly correlated to lower mortality risk of esophageal cancer patients regardless of the time when statins were taken and pathological subtypes of esophageal cancer. Statins may serve as promising adjunctive anticancer agents for treating esophageal cancer.