Correlation between preoperative systemic immune-inflammatory indexes and the prognosis of gastric cancer patients.

OBJECTIVE: The aim of this study is to explore the potential value of high preoperative systemic immune-inflammation index (SII) expression in the prognosis of patients with gastric cancer (GC) by meta-analysis. MATERIALS AND METHODS: The major databases were searched to screen relevant clinical studies on the prognostic value of SII in gastric cancer (GC) patients, published from the establishment of the database to May 2022. RevMan 5.3 was utilized to perform a meta-analysis of relevant data. The differences in age, tumor size, differentiation degree, tumor-node-metastasis (TNM) stage, overall survival (OS), neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR) between the high SII expression group (H-SII) and the low SII expression group (L-SII) were compared. Heterogeneity was assessed by Cochran's Chi-square test. RESULTS: A total of 16 studies with 5,995 GC patients were included. Compared with the L-SII group, the proportion of patients older than 60 years in the H-SII group was markedly higher (OR=0.85, 95% CI: 0.75-0.97; Z=2.45, p=0.01); the proportion of patients with tumor size larger than 5 cm increased (OR=2.18, 95% CI: 1.69-2.81; Z=6.03, p<0.00001); the proportion of patients with TNM stage ≥T3 increased (OR=2.41, 95% CI: 1.89-3.08; Z=7.06, p<0.00001); overall survival (OS) decreased (OR=-23.92, 95% CI: -37.57 to -10.26; Z=3.43, p=0.0006); the 5-year survival rate (SR) decreased markedly (OR=0.39, 95% CI: 0.24-0.64; Z=3.81, p=0.0001); the proportion of patients with high NLR expression was increased (OR=22.19, 95% CI: 10.66-46.18; Z=8.29, p<0.00001); and the proportion of patients with high PLR expression was also markedly increased (OR=15.97, 95% CI: 8.57-29.75; Z=8.73, p<0.00001). CONCLUSIONS: A high preoperative SII was an independent risk factor for poor prognosis in GC patients.

Potential involvement of S1PR1/STAT3 signaling pathway in cardiac valve damage due to rheumatic heart disease.

Rheumatic heart disease (RHD) is a public health burden in developing countries. Th17 cell-associated cytokines might play a role in the pathogenesis and development of RHD, but the specific molecular mechanism is not completely understood. We investigated the potential role of sphingosine-1-phosphate receptor 1 (S1PR1)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in cardiac valve damage in a rat model of RHD. We used 20 Lewis rats divided randomly into control and RHD groups. The RHD model was constructed by injecting inactivated group A Streptococci and complete Freund's adjuvant (CFA). The rats in the control group were injected with normal saline and CFA. Th17 cell-related cytokines were measured by ELISA. Fibrosis was assessed by histological examination. RT-qPCR and western blot were used to detect the expression of S1PR1 and STAT3/phosphorylated STAT3 (p-STAT3). The S1PR1/STAT3 signaling pathway was activated in the RHD model. Compared to the control group, serum levels of IL-17 and IL-21 cytokines associated with Th17 cells were increased significantly in the RHD group; the collagen volume fraction also was substantially increased. The S1PR1/STAT3 signaling pathway might be involved in RHD induced cardiac valve damage by regulating Th17 cells.

LncRNA SNHG8 promotes the development and chemo-resistance of pancreatic adenocarcinoma.

OBJECTIVE: The aim of this study was to investigate the role of small nucleolar RNA host gene 8 (SNHG8) in the pathogenesis of pancreatic adenocarcinoma and to explore the possible underlying mechanism. PATIENTS AND METHODS: SNHG8 expression in 40 pairs of pancreatic adenocarcinoma tissues and para-cancerous tissues, as well as 10 normal pancreas tissues was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Survival analysis was conducted to explore the correlation between SNHG8 expression and the prognosis of pancreatic adenocarcinoma patients. After the transfection of SNHG8 siRNA into pancreatic adenocarcinoma cells, the proliferation and cell cycle were detected by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. Meanwhile, cell apoptosis was detected by flow cytometry and Western blot. The regulatory effect of SNHG8 on the chemo-sensitivity of pancreatic adenocarcinoma cells was assessed by CCK-8 assay. RESULTS: The expression of SNHG8 in pancreatic adenocarcinoma tissues was significantly higher than that of para-cancerous tissues and normal pancreatic tissues. Pancreatic adenocarcinoma patients with higher expression of SHNG8 presented shorter overall survival than those with lower expression. Meanwhile, SNHG8 expression was correlated with tumor stage and differentiation level, whereas not correlated with age, sex, tumor location and lymph node metastasis of pancreatic adenocarcinoma patients. In vitro results showed that SNHG8 knockdown significantly decreased the proliferative ability, prolonged G0/G1 phase and increased the apoptosis of Hs766T and PANC-1 cells. Western blot results elucidated that SNHG8 knockdown remarkably downregulated the protein expression levels of cleaved caspase-3 and cleaved PARP in Hs766T and PANC-1 cells. In addition, SNHG8 significantly decreased the chemo-sensitivity of pancreatic adenocarcinoma cells. CONCLUSIONS: SNHG8 is highly expressed in pancreatic adenocarcinoma tissues and is negatively correlated with its prognosis. Moreover, SNHG8 promotes cell proliferation and cell cycle, whereas inhibits cell apoptosis and reduces the chemo-sensitivity of pancreatic adenocarcinoma cells.

Cup-on-cup technique to manage severe protrusio acetabular defects.

Previous studies have demonstrated that revision of total hip arthroplasty consumes considerably more resources than the primary procedure. Worse, patients who need revision procedures are more likely to have radiographic evidence of acetabular and femoral bone loss than those undergone primary total hip arthroplasty. Many techniques have been introduced to manage different conditions of acetabular deficiencies. We describe a rare case of a 67-year-old man with severe acetabular bone loss, which was caused by a long-term loose acetabular component and was successfully managed by cup-on-cup technique. We also discuss the similarities and differences between cup-on-cup and cup-in-cup techniques in the management of protrusio acetabular defects, with a case-based approach.

MiR-377 suppresses cell proliferation and metastasis in gastric cancer via repressing the expression of VEGFA.

OBJECTIVE: In recent years, microRNAs have been identified to participate in tumor genesis and progression of different tumors including gastric cancer. However, the role of miR-377 played in gastric cancer (GC), and its mechanisms have not been demonstrated. PATIENTS AND METHODS: We detected miR-377 expression level in 86 GC and adjacent normal tissue samples by quantitative reverse transcription PCR (qRT-PCR) as well as in GC cell lines. The relationship between miR-377 and clinical pathological features was analyzed. Using miR-377 mimics and inhibitors, we interfered with miR-377 level and employed several functional experiments to study the miR-377 effects on cell proliferation, migration, and invasion. Western blot assay and dual-luciferase assay were used to verify the target of miR-377. RESULTS: miR-377 expressed significantly lower in GC tissues and cell lines compared to normal tissues and GES-1 cells. Overexpression of miR-377 inhibited cell growth, migration and invasion, while downregulation miR-377 obviously promoted cell growth and metastasis. Furthermore, vascular endothelial growth factor A (VEGFA) was confirmed as a direct target of miR-377 and reversed the influence of mir-377 over-expression. CONCLUSIONS: miR-377 expressed lower in GC and suppressed cell proliferation, migration and invasion partly via repressing the VEGFA expression, which could provide a potential target for GC diagnosis and therapy.

Meta-analysis comparing early versus delayed laparoscopic cholecystectomy for acute cholecystitis.

BACKGROUND: Previous studies comparing early laparoscopic cholecystectomy (ELC) with delayed laparoscopic cholecystectomy (DLC) for acute cholecystitis were incomplete. A meta-analysis was undertaken to compare the cost-effectiveness, quality of life, safety and effectiveness of ELC versus DLC. METHODS: PubMed, Embase, the Cochrane Library and Web of Science were searched for randomized clinical trials (RCTs) that compared ELC (performed within 7 days of symptom onset) with DLC (undertaken at least 1 week after symptoms had subsided) for acute cholecystitis. RESULTS: Sixteen studies reporting on 15 RCTs comprising 1625 patients were included. Compared with DLC, ELC was associated with lower hospital costs, fewer work days lost (mean difference (MD) -11·07 (95 per cent c.i. -16·21 to -5·94) days; P < 0·001), higher patient satisfaction and quality of life, lower risk of wound infection (relative risk 0·65, 95 per cent c.i. 0·47 to 0·91; P = 0·01) and shorter hospital stay (MD -3·38 (-4·23 to -2·52) days; P < 0·001), but a longer duration of operation (MD 11·12 (4·57 to 17·67) min; P < 0·001). There were no significant differences between the two groups in mortality, bile duct injury, bile leakage, conversion to open cholecystectomy or overall complications. CONCLUSION: For patients with acute cholecystitis, ELC appears as safe and effective as DLC. ELC might be associated with lower hospital costs, fewer work days lost, and greater patient satisfaction.

Integrated regulatory network involving differently expressed genes and protein-protein interaction on pancreatic cancer.

OBJECTIVE: Pancreatic cancer is a deadly disease with poor prognosis. However, comprehensive understanding about its pathogenesis remains insufficient. In this study, we aimed to find potential novel approaches for the treatment of pancreatic cancer and explore the regulatory mechanisms underlying pancreatic cancer progression. MATERIALS AND METHODS: The gene expression profile data GSE32688 were downloaded from Gene Expression Omnibus database followed by background correction and normalization through GCRMA (GC Robust Multi-array Average) method. Then DEGs (differentially expressed genes) were identified using t-test method and DEGs-related PPIs (protein-protein interaction) were extracted from STRING database. The PPI networks were constructed by calculating the pearson correlation coefficient under different conditions. Moreover, the network was divided into a number of unit modules, and KEGG pathway and GO analysis were performed for genes in module networks using clusterProfiler. RESULTS: In total, 199 DEGs (165 up-regulated genes and 34 down-regulated genes) were screened between tumor and normal samples. The integrated DEG. PPI network was established by comparing two different networks under tumor and normal conditions respectively. The top ten genes with high degrees such as ANLN, PSRC1 and ECT2 were identified in the integrated network, and they were mainly enriched in cell cycle pathway. CONCLUSIONS: ECT2 and PSRC1 might be used as two novel biomarkers for diagnosis and management of pancreatic cancer.

Effect of aerobic exercise on miRNA-TLR4 signaling in atherosclerosis.

Toll-like receptor 4 (TLR4)-tumor necrosis factor receptor 6 (TRAF6) signaling is activated in atherosclerosis (AS), inducing inflammatory mediators. Because miR-146a, a TLR4 microRNA (miRNA), can regulate TLR4 signaling during inflammatory responses, this study investigated the effects of aerobic exercise on TLR4-targeted miRNAs in AS. Apolipoprotein E-null mice fed a high-fat diet for 12 weeks were separated into 3 groups: (i) no treatment (AS), (ii) statin treatment (AD), or (iii) aerobic exercise (AE). Plaques and foam cells were observed in the untreated control and statin groups, respectively, but not in the AE group. Reduced angiotensin II (Ang II) and endothelin 1 (ET1) levels were observed in the AE group. Both treatment groups significantly altered the expression of inflammatory cytokine expression and reduced vascular TLR4 levels. Increased miR-146a and miR-126 and reduced miR-155 levels were observed in both treatment groups (all, P<0.001). miR-146a interacted with the 3' untranslated region of the TRAF6 gene, reducing its expression. Thus, aerobic exercise and statins may induce miR-146a expression, thereby reducing vascular TRAF and TLR4 signaling and vascular inflammatory injury in AS. Further analysis of this pathway may provide insight into the protective effects of aerobic exercise on vascular disease as well as new therapeutic targets.

Impact of a novel mutation in the 5'-flanking region of natriuretic peptide precursor B gene on the antihypertensive effects of sodium nitroprusside in patients with hypertension.

Our aim was to identify the possible mutations of the natriuretic peptide precursor B (NPPB) gene in a family with hereditary hypertension, and determine whether the mutations are associated with the antihypertensive effect of sodium nitroprusside. The subjects included one family with hereditary hypertension, 36 cases of sporadic hypertension and 120 healthy controls. The 5'-flanking sequence of NPPB was amplified with PCR, and the presence of mutations was analyzed by direct sequencing. Patients with hypertension were treated with sodium nitroprusside and blood pressure data and serum B-type natriuretic peptide (BNP) levels were measured. A novel complex mutation in 5'-flanking sequence of the NPPB gene was detected in three patients (II 2, III 2, and III 5) of the hypertension family, which included c.-1195_ -1176 insert 5'-CCTTCTTTCTTTCTTTCTTT-3', c.-1208 T>A, c.-1214 T>C, and c.-1216 T>A. Patients with this mutation were less sensitive to sodium nitroprusside treatment. Sporadic hypertension patients (without NPPB gene mutation) and patients with the c.-1181 T>A point mutation were sensitive to sodium nitroprusside treatment. BNP levels of patients with the complex mutation were significantly lower than that of sporadic hypertension patients and c.-1181 T>A mutation patients before and during the early stage of sodium nitroprusside treatment. The complex mutation of the NPPB gene might be an etiological factor of hereditary malignant hypertension, and it is associated with low sensitivity to the antihypertensive effect of sodium nitroprusside.

A rare-earth phosphor containing one-dimensional chains identified through combinatorial methods

An unusual luminescent inorganic oxide, Sr2CeO4, was identified by parallel screening techniques from within a combinatorial library of more than 25,000 members prepared by automated thin-film synthesis. A bulk sample of single-phase Sr2CeO4 was prepared, and its structure, determined from powder x-ray diffraction data, reveals one-dimensional chains of edge-sharing CeO6 octahedra, with two terminal oxygen atoms per cerium center, that are isolated from one another by Sr2+ cations. The emission maximum at 485 nanometers appears blue-white and has a quantum yield of 0.48 +/- 0.02. The excited-state lifetime, electron spin resonance, magnetic susceptibility, and structural data all suggest that luminescence originates from a ligand-to-metal Ce4+ charge transfer.