Background: Gut microbiota could modulate brain functions and consequent behavior through gut-brain axis. We evaluated the impact of intestinal flora using probiotics in patients with Crohn's disease (CD) on cognitive reactivity to sad mood. Method: Patients in Group 1 received multiple probiotics followed by Chamomile capsules. Patients in Group 2 received Chamomile capsules followed by multiple probiotics. Patients accomplished the Leiden Index of Depression Sensitivity (LEIDS-r), Beck Depression Inventory (BDI) questionnaires after each cycle of cross-over treatment. Results: The baseline LEIDS-r in two groups did not have significant difference. After 3 weeks of treatment, patients in Group 1 had better LEIDS-r scores compared with patients in Group 2 (36.6 vs. 40.9, P = 0.012). After crossover, patients in Group 1 had worse LEIDS-r scores compared with patients in Group 2 (39.2 vs. 35.2, P = 0. 0.016). Conclusion: Probiotics have the tendency to improve cognitive reactivity to sad mood in CD patients.

Purpose: Due to the lack of early-stage detection, pancreatic cancer (PC) remains a devastating disease worldwide. Lactate dehydrogenase (LDH) is associated with tumorigenesis and cancer progression. This study aims to analyze the diagnostic improvements in serum LDH levels combined with other common tumor biomarkers, including carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA), for monitoring PC. Patients and Methods: A retrospective analysis was performed on 73 patients with newly diagnosed PC, 90 patients with pancreatic benign diseases (PBD), and 92 people with healthy physical examination (HPE) at Zhongda Hospital, Southeast University from July 2013 to July 2020. The diagnostic efficiencies of serum levels of LDH, CA19-9, and CEA were analyzed through receiver operating characteristic (ROC) curves for PC. The sensitivity and specificity were evaluated at an optimal cutoff. The prognostic impacts of LDH on PC patients were also assessed. Results: The LDH level was elevated in 21 (28.77%) patients with PC, 3 (3.33%) PBD patients, and no HPE individuals (P<0.05). The sensitivities of LDH, CA19-9, and CEA for the diagnosis of PC were 63.0%, 78.1%, and 72.6%, respectively, but the combination of these three markers increased predictive sensitivity significantly to 87.6%. The specificities of LDH, CA19-9, and CEA for the diagnosis of PC were 93.4%, 84.1%, and 73.1%, respectively. The combined specificity reached up to 96.7%. The medium survival time of PC patients with low-level LDH was 21 +/- 5.1 months, whereas that of patients with highlevel LDH was only 7 +/- 0.92 months (P<0.05). Conclusion: The serum LDH level was higher in PC patients than in PBD patients and HPE individuals and was associated with a poor prognosis. The combined assessment of LDH, CEA, and CA19-9 showed higher sensitivity and specificity for the diagnosis of PC.

Background A higher vitamin D intake improves the prognosis of early stage breast cancer (BC) patients. We hypothesized that vitamin D intake should refer to vitamin D receptor (VDR) expression. In order to prove this hypothesis, we first intend to evaluate the correlation between VDR expression and prognosis of BC patients using meta-analysis. Methods Literatures from PubMed, Embase, and the Cochrane Library (last update by May 20, 2020) were retrieved to find studies assessing the prognostic role of VDR in BC. The hazard ratios (HRs) for patients’ survival were extracted for pooled analyses. Subgroup analysis, sensitivity analysis and meta-regression were performed to explore the sources of heterogeneity. Results Seven articles containing eight studies with 2503 patients were enrolled. The results from the pooled analyses showed that the VDR expression generally had no relationship with BC patients’ overall survival (OS), disease-free survival (DFS), cancer-specific survival (CSS), and progression-free survival (PFS) ( P > 0.05). Because only the number of studies exploring the relationship between VDR expression and OS is greater than five and there is heterogeneity, we explored the sources of heterogeneity of these studies. Subgroup analyses showed that the VDR expression in the nucleus had no relationship with OS, but high total VDR expression in the nucleus and cytoplasm was related to a better OS (pooled HR = 0.41; 95% CI = 0.18–0.95; P = 0.038). In addition, in subgroup of studies using cut-off values other than ‘immunoreactive score (IRS)>5’ and ‘IRS > 25′, high VDR expression was associated with a better OS (pooled HR = 0.47; 95% CI = 0.30–0.74; P = 0.001). Sensitivity analysis showed that the result pattern was not obviously affected by any single study. Meta-regression showed that the source of heterogeneity was not country ( P = 0.657), pathological type ( P = 0.614), molecular type ( P = 0.423), staining location ( P = 0.481), or cut-off value ( P = 0.509). Conclusions The protein expression level of VDR in entire BC cells evaluated by immunohistochemistry is related to the OS of BC patients. It is expected that a more individualized vitamin D intake and a more accurate prognosis assessment can be recommended for BC patients based on the VDR expression. Of course, more preclinical and clinical studies are needed.

Yao-Jie Pan Jian Wan Chun-Bin Wang 1Department of Oncology, The Affiliated Yancheng Hospital of Medicine School of Southeast University, The Third People’s Hospital of Yancheng, Yancheng 224001, People’s Republic of China; 2Department of General Surgery, Center for Difficult and Complicated Abdominal Surgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200092, People’s Republic of China Abstract: MicroRNAs (miRNAs) are small non-coding and highly conserved RNAs that act in biological processes including cell proliferation, invasion, apoptosis, metabolism, signal transduction, and tumorigenesis. The previously identified miRNA-326 (miR-326) has been reported to participate in cellular apoptosis, tumor growth, cell invasion, embryonic development, immunomodulation, chemotherapy resistance, and oncogenesis. This review presents a detailed overview of what is known about the effects of miR-326 on cell invasion, metastasis, drug resistance, proliferation, apoptosis, and its involvement in signaling pathways.

We attempted to analyze the effects of miR-1-3p and CCL2 on the proliferation, migration, and invasion of bladder cancer cells. A total of 18 pairs of bladder cancer tissues with corresponding adjacent tissues and the 6 cases of normal tissues were collected. The expressions of miR-1-3p and CCL2 in the cancer tissues were evaluated using quantitative real-time polymerase chain reaction and western blot. The relationship between miR-1-3p and CCL2 was assessed using luciferase reporter assay. The UM-UC-3 bladder cancer cells were transfected with CCL2 small interfering RNA and miR-1-3p mimics. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, colony formation assay, wound healing assay, Transwell assay, and the flow cytometry test were used to detect the proliferation, migration, invasion, and apoptosis of bladder cancer cells. Bladder cancer tissues had lower levels of miR-1-3p but higher levels of CCL2 than normal tissues (p<0.05). The transfection of miR-1-3p mimics and CCL2 small interfering RNA remarkably suppressed cell proliferation and invasion and promoted apoptosis of cells (p<0.05). Results of the luciferase reporter gene assay demonstrated that miR-1-3p targeted CCL2. MiR-1-3p suppresses the proliferation and invasion of urinary bladder cancer cells by targeting CCL2.

As a member of membrane-spanning 4A family, transmembrane protein 176A (TMEM176A) has been recently reported to be overexpressed in various cancers. However, the biological functions of TMEM176A in nonsmall cell lung cancer (NSCLC) remain unclear. In this study, we investigated the expression of TMEM176A in publicly available Oncomine database and found it was upregulated in lung cancer tissues compared with normal lung tissues. Similar results were also found in fresh primary NSCLC tumor tissues and corresponding normal tissues using Western blot analysis.Then the expression of TMEM176A was efficiently silenced in human NSCLC cell lines, A549 and 95D by RNA interference. Knockdown of TMEM176A obviously inhibited cell growth and colony formation, induced cell arrest at G0/G1 phase and promoted cell apoptosis in NSCLC cells, as determined by MTT, clonogenic assay and flow cytometry assays. Mechanistically, inhibition of TMEM176A significantly reduced the expression of CDK4 and Cyclin D1, but increased the expression of caspase-3, PARP cleavage and bad. In conclusion, these results firstly demonstrated that TMEM176A might serve as a potential oncogene that involved in the cell proliferation of NSCLC.

The prognostic effect of chemoradiotherapy in gastric cancer has been evaluated for decades while the results are still in debate and heterogeneous. We thus comprehensively updated the evidence through systematic review and meta-analysis to evaluate chemoradiotherapy in gastric cancer to determine its effect. Pubmed, EMBASE, and Cochrane Library from the earliest possible year to April 2017 were searched. Randomised controlled trials (RCTs) that assessed the effects of combined chemoradiotherapy for patients with gastric cancer compared with that of single chemotherapy were included. The main outcome measure was 5-year overall survival (OS) and the second was disease-free survival (DFS) or recurrence-free survival (RFS). Fifteen RCTs involving 3347 patients were included into this meta-analysis. Compared with single chemotherapy, the relative risk (RR) for 5-year OS for chemoradiotherapy was 1.05 (95% CI 0.88 to 1.25), with moderate heterogeneity across eligible trials (I2 = 55.7%, p = 0.016). Subgroup analyses and sensitivity analyses confirmed the consistent findings. We found that significant survival benefit for 5-year DFS/RFS for chemoradiotherapy over single chemotherapy (RR 0.89 95% CI 0.81 to 0.98) for patients with gastric cancer. This updated meta-analysis does not provide strong evidence for a 5-year survival benefit of chemoradiotherapy over chemotherapy alone in patients with gastric cancer. A clear advantage of chemoradiotherapy over chemotherapy has not been established. Further larger RCTs should be conducted to determine its true effect.

Background: Bladder cancer is of compelling morbidity and mortality due to its high recurrence rate. Little development has been made in the last decades in the therapy methods. Thus, the mechanism of its growth and invasiveness involving novel molecular targets are needed. Objective: Our research objective is to confirm the hypothesis that miR-1-3p suppresses the proliferation, invasion and migration of bladder cancer cells. Methods: The expression levels of miR-1-3p and SFRP1 were evaluated using RT-qPCR in bladder cancer tissues and cells as well as in normal tissues and cells. J82 cell lines were selected as experiment subjects due to their low expression levels of miR-1-3p. Plasmids carrying miR-1-3p mimics, miR-1-3p inhibitors and SFRP1 were transfected into the J82 cell lines. Subsequently, the protein expression of SFRP1 was detected using Western Blot analysis, and cell proliferation, apoptosis, invasion and migration ability was measured using MTT, the flow cytometry, the Transwell test and wound healing assays, respectively Results: Bladder cancer tissues and cells exhibited significant decrease in the expression of miR-1-3p and SFRP1 compared to normal tissues and cells, and human bladder cancer cell line J82 exhibited the most significant decrease in these expressions (P < 0.05). MiR-1-3p up-regulates SFRP1 expression in bladder cancer cells, and the over-expression of miR-1-3p can suppress the proliferation, invasion and migration ability of bladder cancer cells. This mechanism is similar to the effect of SFRP1 over-expression on bladder cancer cells. Conclusion: MiR-1-3p suppresses the proliferation, invasion and migration of bladder cancer cells by up-regulating SFRP1 expression.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. BCL2 apoptosis regulator (BCL2) and marker of proliferation Ki-67 (Ki-67) are established prognostic markers, which have traditionally been assessed separately in DLBCL. However, no studies have evaluated the prognostic value of the combination of BCL2 and Ki-67 index. Thus, the present study aimed to analyze the prognostic value of combination of these two markers. Immunohistochemical analysis was used to assess the expression of BCL2 and Ki-67 in 274 cases of DLBCL. The BCL2/Ki-67 index demonstrated a significant association with decreased overall and progression free survival of patients with DLBCL, particularly for the germinal center B-cell-like subtype of DLBCL. Following multivariate analysis, the BCL2/Ki-67 index retained prognostic significance. Patients with coexpression of BCL2 and Ki-67 constituted a unique group with poor survival, thus novel therapies targeting BCL2 protein and high proliferative activity may improve the outcome of these patients.