Spinal sample showing p-JNK and P38 associated with the pain signaling transduction of glial cell in neuropathic pain.

OBJECTIVE: To investigate the signaling pathways after astrocytes were activated in neuropathic pain. METHODS: Thirty-six Sprague Dawley (s.d.) rats were randomly divided into two groups (each group with 18 s.d. rats) including chronic constriction injury (CCI) of the sciatic nerve model group and sham operation group. Operation was perform ed on the right leg in all rats. The lumbar spin al cord (L4 and L5) was taken to make paraffin slices on the 1st day before operation and the 1st, 3rd, 7th, 14th and 28th day after operation in each group. Paraffin slices were labeled with p38 mitogen-activated protein kinase (p38MAPK) and c-Jun N-terminal kinase (JNK) by immunofluorescence staining, and then were co-labeled with hexaribonucleotide binding protein-3 (NeuN), glial fibrillary acidic protein (GFAP) and anti-integrin αM (CD11b) antibody (OX-42) to explore the associations of p38MAPK and JNK with nerve cells or glial cell. RESULTS: Compared with sham group, the pain threshold was significantly decreased, and astrocyte-activated markers, GFAP and vimentin were significantly increased in CCI group. The mean fluorescence intensities of p38MAPK and JNK were increased in the right spinal dorsal horn of CCI group. The coexpression of JNK and GFAP was found in astrocytes of the spinal dorsal horn in CCI group. CONCLUSION: JNK signal transduction pathway is involved in the pain signaling transduction of astrocytes.

Functional analysis of differentially expressed genes associated with glaucoma from DNA microarray data.

Microarray data of astrocytes extracted from the optic nerves of donors with and without glaucoma were analyzed to screen for differentially expressed genes (DEGs). Functional exploration with bioinformatic tools was then used to understand the roles of the identified DEGs in glaucoma. Microarray data were downloaded from the Gene Expression Omnibus (GEO) database, which contains 13 astrocyte samples, 6 from healthy subjects and 7 from patients suffering from glaucoma. Data were pre-processed, and DEGs were screened out using R software packages. Interactions between DEGs were identified, and networks were built using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). GENECODIS was utilized for the functional analysis of the DEGs, and GOTM was used for module division, for which functional annotation was conducted with the Database for Annotation, Visualization, and Integrated Discovery (DAVID). A total of 371 DEGs were identified between glaucoma-associated samples and normal samples. Three modules included in the PPID database were generated with 11, 12, and 2 significant functional annotations, including immune system processes, inflammatory responses, and synaptic vesicle endocytosis, respectively. We found that the most significantly enriched functions for each module were associated with immune function. Several genes that play interesting roles in the development of glaucoma are described; these genes may be potential biomarkers for glaucoma diagnosis or treatment.

Renin-angiotensin system inhibitors for prevention of recurrent atrial fibrillation: a meta-analysis.

INTRODUCTION: Conflicting results exist now on the clinical utility of renin-angiotensin system (RAS) inhibitors in patients with atrial fibrillation (AF). This study aimed to elaborate the efficacy and safety of RAS blockade on preventing the relapse of AF by a meta-analysis based on randomised controlled trials (RCTs). METHODS: We searched Medline, ISI web of science and Cochrane databases through Jan 2012. We included RCTs comparing RAS inhibition treatment vs. placebo or alternative therapy after cardioversion of persistent AF or conventional medical therapy for paroxysmal AF and reporting outcome of recurrent AF. Odds ratios (OR) were calculated using a random effects model. RESULTS: Fifteen trials involving 3972 AF patients were included in the analysis. The pooling analysis showed that RAS inhibitors significantly reduced the recurrence of AF compared with non-RAS inhibitors (OR=0.50, 95% CI: 0.37-0.69, p<0.01), and the beneficial effect was shown consistently both in patients with paroxysmal and in those with persistent AF after cardoversion. However, administration of RAS inhibitors did not provide a greater survival advantage and a lower incidence of adverse effects than the control (OR=1.17, 95% CI, 0.65-2.10, p=0.59; OR=0.94, 95% CI: 0.65-1.35, p=0.73 respectively). In addition, clinical factors potentially affecting AF relapsing had no pronounced impacts on the above clinical outcomes. CONCLUSIONS: Based on the currently available data, inhibition of RAS is effective, safe and well tolerated for preventing the recurrence of AF.

Analysis of FOS, BTG2, and NR4A in the function of renal medullary hypertension.

The aim of this study was to identify differentially expressed genes (DEGs) in renal medullary hypertension and reveal their pathogenic mechanisms. We downloaded the gene expression profile of GSE28360 from the Gene Expression Omnibus database. The profile included 14 samples (5 normal and 9 hypertension). The DEGs in normal and disease samples were distinguished with a false-discovery rate threshold of <0.05 and a fold-change value of >2 or <-2. We put the selected genes into the online program String 8.3 to obtain the protein-protein interaction network and selected the hub proteins. These hub proteins were then placed in the PANTHER database to determine hub protein-related pathways and explain their functions. Finally, we cleared up the single-nucleotide polymorphisms (SNPs) of the hub genes via combing with the National Center for Biotechnology SNP database. A total of 13 genes were identified as DEGs between normal and disease samples. Five selected hub proteins, B-cell translocation gene 2 (BTG2), FBJ murine osteosarcoma viral oncogene homolog (FOS), nuclear receptor subfamily 4, group A, member 1 (NR4A1), NR4A member 2 (NR4A2), and NR4A member 3 (NR4A3), were mainly related to angiogenesis and B-cell activation. After SNP analysis, 103, 103, 595, 150, and 493 SNPs were found to correspond to BTG2, FOS, NR4A1, NR4A2, and NR4A3, respectively. Our results suggest that pathways of angiogenesis and B-cell activation may involve in the progression of renal medulla hypertension.

Gene expression profile and enrichment pathways in different stages of bladder cancer.

Bladder cancer is a highly heterogeneous neoplasm. We examined the gene expression profile in 3 bladder cancer stages (Ta, T1, T2) using expression microarray analysis of 40 bladder tumors. Differentially expressed genes were found by the t-test, with <0.005 as the significance threshold. KEGG pathway-enrichment analysis was used to study the signaling pathways of the genes. We found 36 genes that could be used as molecular markers for predicting the transition from Ta-T1 to T1-T2. Among these, 11 overlapped between Ta-T1 and T1-T2 stages. Six genes were down-regulated at the Ta-T1 stage, but were up-regulated at the T1-T2 stage (ANXA5, ATP6V1B2, CTGF, GEM, IL13RA1, and LCP1); 5 genes were up-regulated at the Ta-T1 stage, but down-regulated at the T1-T2 stage (ACPP, GNL1, RIPK1, RAPGEF3, and ZER1). Another 25 genes changed relative expression levels at the T1-T2 stage. These genes (including COL1A1, COL1A2, FN1, ITGA5, LGALS1, SPP1, VIM, POSTN, and COL18A1) may be involved in bladder cancer progression by affecting extracellular matrix-receptor interaction and focal adhesion. The cytokine-cytokine receptor interaction, neuroactive ligand-receptor interaction, and calcium-signaling pathway were associated with bladder cancer progression at both the Ta-T1 and T1-T2 stages.

[Application of single incision plus one port laparoscopic surgery in radical right hemicolon cancer surgery].

Objective: To investigate the feasibility and advantages of the SILS+1 technique in the radical right hemicolectomy, by comparing the short-term efficacy, postoperative recovery of intestinal function, and stress and inflammatory response of patients with right-sided colon cancer undergoing the conventional 5-hole laparoscopic technique or the single incision plus one port laparoscopic surgery (SILS+1). Methods: A retrospective cohort study was performed. Thirty-five patients with right-sided colon cancer undergoing SILS+1 surgery at Department of Gastrointestinal Surgery of Fujian Cancer Hospital from January 2018 to September 2020 were enrolled in the SILS+1 group. Then a total of 44 patients who underwent completely 5-hole laparoscopic right hemicolectomy at the same time were selected as the conventional laparoscopic surgery (CLS) group. The intraoperative observation indexes (operative time, intraoperative blood loss, and incision length) and postoperative observation indexes (time to ambulation after surgery, time to flatus, pain score in the first 3 days after surgery, hospitalization days, number of lymph node dissections, postoperative complication morbidity, and postoperative total protein, albumin and C-reaction protein) were compared between the two groups. Results: There was no conversion to laparotomy or laparoscopic-assisted surgery in both groups. All the patients successfully completed radical right hemicolectomy under total laparoscopy. There were no statistically significant differences in gender, age, body mass index or tumor stage between the two groups (all P>0.05). Compared with the CLS group, the SILS+1 group had shorter incision length [(5.1±0.6) cm vs. (8.5±4.1) cm, t=4.124, P=0.012], shorter time to the first ambulation (median: 27.6 h vs. 49.3 h, Z=4.386, P=0.026), and shorter time to the first flatus (median:42.8 h vs. 63.2 h, Z=13.086, P=0.012), lower postoperative pain score [postoperative 1-d: 2.0 ± 1.1 vs. 3.6 ± 0.9; postoperative 2-d: 1.4 ± 0.2 vs. 2.9±1.4; postoperative 3-d: 1.1 ± 0.1 vs. 2.3±0.3, F=49.128, P=0.003), shorter postoperative hospital stay [(9.1 ± 2.7) d vs. (11.2 ± 2.2) d, t=3.267,P=0.001], which were all statistically significant (all P<0.05). On the second day after surgery, as compared to CLS group, SILS+1 group had higher total protein level [(59.7±18.2) g/L vs. (43.0±12.3) g/L, t=2.214, P=0.003], higher albumin level [(33.6±7.3) g/L vs. (23.7±5.4) g/L, t=5.845, P<0.001], but lower C-reactive protein level [(16.3 ± 3.1) g/L vs. (63.3 ± 4.5) g/L, t=4.961, P<0.001], which were all statistically significant. There were no significant differences in the operative time, intraoperative blood loss, number of harvested lymph node, number of metastatic lymph node, and postoperative complication morbidity (all P>0.05). Conclusions: The SILS+1 technique has good operability and potential for popularization. Under the premise of radical resection, this technology not only reduces incision number and postoperative physical pain, but also speeds up postoperative recovery and shortens hospital stay.

[Effect of preservation of left colic artery on postoperative anastomotic leakage of patients with rectal cancer after neoadjuvant therapy].

Objective: To evaluate the effect of preservation of left colic artery (LCA) on postoperative anastomotic leakage in patients with rectal cancer after neoadjuvant therapy. Methods: A retrospective cohort study was conducted to collect data of rectal cancer patients at Department of Gastrointestinal Surgery of Fujian Cancer Hospital from September 2014 to August 2017. Inclusion criteria: (1) age of 18 to 79 years; (2) rectal adenocarcinoma confirmed by postoperative pathology; (3) patients without preoperative serious cardiovascular and cerebrovascular disease receiving preoperative neoadjuvant radiotherapy or chemoradiotherapy; (4) laparoscopic-assisted anterior rectal resection and distal ileostomy were performed simultaneously; (5) complete clinical data. Exclusion criteria: patients with extensive abdominal metastasis, or distant organ metastasis during operation, and combined organ resection. According to whether LCA was retained during operation, the patients were divided into two groups, then the intraoperative and postoperative clinical outcomes were compared. Moreover, univariate analysis and multivariate logistic regression were used to analyze risk factors of postoperative anastomotic leakage. Results: A total of 125 patients were included in this study, including 56 patients in the retained LCA group and 69 patients in the non-retained LCA group. Differences in baseline data, such as gender, age, diabetes mellitus, body mass index, hemoglobin, distance between tumor and anal margin, maximum diameter of tumor, preoperative neoadjuvant therapy, and ypTNM stage, between retained LCA group and non-retained LCA group were not statistically significant (all P>0.05), indicating that two groups were comparable. Meanwhile there were no significant differences in operation time, intraoperative blood loss, total number of lymph node harvested, number of harvested lymph node at the root of inferior mesenteric artery, circumferential margin, anastomotic bleeding, or postoperative hospital stay between two groups (all P>0.05). Thirteen patients in the non-retained LCA group (18.8%) developed postoperative anastomotic leakage, including 7 cases of grade A, 5 cases of grade B and 1 case of grade C, while in the retained LCA group, only 5.4% (3/56) of patients developed postoperative anastomotic leakage, including 1 case of grade A and 2 cases of grade B without case of grade C, whose difference was statistically significant (U=1674.500, P=0.028). Univariate analysis showed that preoperative hemoglobin <120 g/L and non-retained LCA were associated with postoperative anastomotic leakage (both P<0.05). Multivariate analysis cofirmed that preoperative hemoglobin < 120 g/L (OR=3.508, 95% CI: 1.158 to 10.628, P=0.017) and non-retained LCA (OR=4.065, 95%CI: 1.074 to 15.388, P=0.031) were independent risk factors for postoperative anastomotic leakage. Median follow-up time was 31 months (16 to 51 months), and no long-term complication was found. Local recurrence and distant metastasis were found in 1 case (1.8%) and 7 case (12.5%) in the retained LCA group, while those were found in 2 cases (2.9%) and 5 cases (7.2%) respectively, in the non-retained LCA group, whose differences were not statistically significant (P=1.000, P=0.321 respectively). Conclusion: Preservation of left colic artery not only can ensure radical lymph node dissection efficacy under the condition of similar operation time and blood loss, but also can effectively reduce the incidence of postoperative anastomotic leakage for rectal cancer patients after neoadjuvant therapy.