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A meta-analysis was conducted to compare oxaliplatin-based with fluorouracil-based neoadjuvant chemoradiotherapy and adjuvant chemotherapy for locally advanced rectal cancer. MEDLINE, EMBASE and CENTRAL were systematically searched for relevant randomized controlled trials (RCTs) until January 31 2017. Review Manager (version 5.3) was used to analyze the data. Dichotomous data were calculated by odds ratio (OR) with 95% confidence intervals (CI). A total of 8 RCTs with 6103 stage II or III rectal cancer patients were analyzed, including 2887 patients with oxaliplatin+fluorouracil regimen and 3216 patients with fluorouracil alone regimen. Compared with fluorouracil-based regimen group, oxaliplatin-based regimen group attained higher pathologic complete response (OR = 1.29, 95% CI: 1.12−1.49, P = 0.0005) and 3-year disease-free survival (OR = 1.15, 95% CI: 0.93−1.42, P = 0.21), but suffered greater toxicity (OR = 2.07, 95% CI: 1.52−2.83, P < 0.00001). Also, there were no significant differences between two regimens in sphincter-sparing surgery rates (OR = 0.94, 95% CI: 0.83−1.06, P = 0.33), 5-year disease-free survival (OR = 1.15, 95% CI: 0.93−1.42, P = 0.21) and overall survival (3-year, OR = 1.14, 95% CI: 0.98−1.34, P = 0.09; 5-year, OR = 1.06, 95% CI: 0.78−1.44, P = 0.70). In conclusion, the benefits of adding oxaliplatin to fluorouracil-based neoadjuvant chemoradiotherapy and adjuvant chemotherapy for locally advanced rectal cancer remains controversial, and cannot be considered a standard approach.

Background Immunotherapy was widely used for the treatment of non‐small cell lung cancer (NSCLC). However, whether inhibition of immune checkpoints individually or simultaneously could improve the therapeutic efficacy of NSCLC remains to be investigated. Here, we explored the aberrant levels of several checkpoints and evaluated their potential diagnostic values for NSCLC. Methods Serum samples of 89 NSCLC patients and 57 healthy donors were collected from Nanjing Drum Tower Hospital between November 2019 and July 2020. Fourteen human immune checkpoints were quantified by Procarta‐Plex Human Immuno‐Oncology Checkpoint Panel. Results The expression levels of sTIM‐3, sCD137, sCD27, sLAG‐3, sIDO, sPD‐L2, sCD152, sCD80, and sPD‐1 were all significantly increased in serum of NSCLC patients. Especially, sLAG‐3 was significantly elevated in serum of NSCLC patients at early‐stage (stages I and II), TIM‐3, CD137, and CD27 were significantly higher in the advanced NSCLC patients (stages III and IV) than in the early‐stage groups. Receiver operating characteristics (ROC) results showed that except for PD‐1, all the other immune checkpoint proteins had potential diagnostic values for NSCLC. sTIM‐3 had the highest diagnostic accuracy, followed by sLAG‐3. Combining sTIM‐3, sLAG‐3, and sCD137 could increase the accuracy to a higher level. Moreover, sCD27 was correlated with NSCLC cancer type, age, sex, and disease stage, while sCD137 was correlated with age and disease stage. sTIM‐3 and sIDO were correlated with stage and age, respectively. Conclusions TIM‐3 and LAG‐3 were independent biomarkers for the early diagnosis of NSCLC. The combination of TIM‐3, LAG‐3, and CD137 could increase the diagnostic accuracy.

Background Nuclear receptor-binding SET domain protein 2 (NSD2) is a histone methyltransferase that has been demonstrated to regulate insulin secretion and glucose concentration. This study focused on the role of NSD2 in the renal impairment during diabetic nephropathy (DN). Methods Serum NSD2 level in patients with DN was examined, and its correlations with the renal impairment-related indicators were examined. A murine model of DN was established, and mouse mesangial cells (SV40-MES-13) were treated with high-glucose (HG) to mimic a DN-like condition in vitro. Overexpression of NSD2 was introduced into mice or cells for in vivo and in vitro studies. The m6A level in HG-treated SV40-MES-13 cells was analyzed. METTL3 expression and its correlation with NSD2 were determined. Results NSD2 was poorly expressed in the serum of patients with DN and was negatively correlated with the levels of fasting blood sugar (FBG), serum creatinine (SCr), serum cystatin C (S-Cys-C), the 24-h urine protein (24-h U-protein) and the urine cystatin C (U-Cys-C). NSD2 overexpression reduced the kidney weight and reduced renal impairment in mice. It also suppressed interstitial fibrosis in mouse kidney tissues and reduced fibrosis-related markers in HG-treated SV40-MES-13 cells. HG treatment reduced the m6A level in the cells. METTL3 promoted m6A modification of NDS2 mRNA and enhanced its stability by YTHDF1. METTL3 overexpression alleviated renal impairment and fibrosis in vivo and in vitro. But the protective role was blocked upon NSD2 silencing. Conclusion This study demonstrates that METTL3 promotes NSD2 mRNA stability by YTHDF1 to alleviate progression of DN.

Background: Various evidences showed that abnormally expressed long non-coding RNAs (lncRNAs) play important roles in the tumorigenesis and progression of malignancies. However, the exact role and regulatory mechanism of lncRNA TP73-AS1 in the pathogenesis and progression of lung adenocarcinoma remain to be further elucidated. Purpose: The aim of this study was to investigate the functional role and underlying mechanism of lncRNA TP73-AS1 in lung adenocarcinoma progression. Methods: RT-PCR assay was employed to detect TP73-AS1 expression in lung adenocarcinoma tissues and cells. The function of TP73-AS1 in lung adenocarcinoma progression was estimated by MTT assay, EdU assay, flow cytometry, Western blot, wound-healing assay and transwell assay. Results: LncRNA TP73-AS1 expression was significantly increased in lung adenocarcinoma tissues and cell lines. Moreover, functional assays revealed that silencing of lncRNA TP73-AS1 could attenuate cell proliferation, migration, invasion and epithelial-mesenchymal transition of lung adenocarcinoma, while enhanced expression of lncRNA TP73-AS1 led to the opposite results. Additionally, lncRNA TP73-AS1 knockdown could facilitate cell apoptosis and overexpression of lncRNA TP73-AS1 inhibited cell apoptosis. In addition, we further determined that lncRNA TP73-AS1 regulated cell metastasis through inducing the activation of Wnt/β-catenin signaling pathway in lung adenocarcinoma. Conclusion: Our results indicated that lncRNA TP73-AS1 may play an oncogenic role in lung adenocarcinoma progression, which provided a promising therapy strategy for the treatment of lung adenocarcinoma.