[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.

[Risk factors for the development of liver cancer in patients with hepatitis B-related liver cirrhosis treated with long-term nucleos(t)ide analogues].

Objective: To retrospectively analyze the risk factors for the development of liver cancer in patients with hepatitis B-related liver cirrhosis (LC) treated and fully managed with long-term nucleos(t)ide analogues (NAs). Methods: The study subjects were derived from the follow-up cohort of chronic hepatitis B and liver cirrhosis who received antiviral therapy in the Department of Infectious Diseases of the First Affiliated Hospital of Guangxi Medical University from February 2004 to September 2019. LC patients who met the inclusion criteria were enrolled. The life-table method was used to calculate the incidence of liver cancer. Multivariable Cox regression model was used to analyze the risk factors that may affect the development of liver cancer in patients with LC. A subgroup analysis was conducted in liver cirrhotic patients who developed liver cancer to evaluate the effectiveness of antiviral treatment compliance. The (2) test was used for rate comparison. Results: The median follow-up time of 198 LC cases treated with NAs was 6.0 years (1.0-15.3 years). By the end of the visit: (1) 16.2% (32/198) of LC patients had developed liver cancer, and the cumulative incidence of liver cancer in 1, 3, 5, 7, and 9 years were 0, 8.9%, 14.3%, 18.6%, and 23.4%, respectively, with an average annual incidence of 3.1%. Among the 32 cases with liver cancer, 68.7% had developed small liver cancer (22/32). (2) Univariate Cox model analysis showed that the development of liver cancer was related to four factors, i.e., the presence or absence of LC nodules, whether the baseline was first-line medication, the family history of liver cancer, and patient compliance. The results of multivariate Cox model analysis showed that poor patient compliance and baseline non-first-line medication were risk factors for liver cancer. (3) The results of log-rank test subgroup analysis showed that the 5-year cumulative incidence of liver cancer in patients with hardened nodules was significantly higher than that of patients without hardened nodules (21.7% vs. 11.5%, P = 0.029). The 5-year cumulative incidence of liver cancer in patients with non-first-line drugs was significantly higher than that of patients with first-line drugs (22.0% vs.8.2%, P = 0.003). The 5-year cumulative incidence of liver cancer in patients with poor compliance was significantly higher than that of patients with good compliance (21.3% vs. 12.7%, P = 0.014). The 5-year cumulative incidence of liver cancer in patients with a family history of liver cancer was significantly higher than that of patients without a family history of liver cancer (22.3% vs. 8.1%, P = 0.006). (4) Compared with patients with poor compliance, patients with good compliance had higher HBV DNA negative serconversion rate (98.7% vs. 87.8%, P = 0.005), and a lower virological breakthrough rate (12.1% vs. 29.3%, P = 0.007). Conclusion: The long-term NAs antiviral therapy can reduce the risk of liver cancer, but it cannot completely prevent the development of liver cancer, especially in patients with a family history of liver cancer and baseline hardened nodules (high risk of liver cancer). Furthermore, the complete management can improve patient compliance, ensure the efficacy of antiviral therapy, and reduce the risk of liver cancer development, so to achieve secondary prevention of liver cancer, i.e., early detection, diagnosis and treatment.

Dendrobine attenuates isoniazid- and rifampicin-induced liver injury by inhibiting miR-295-5p.

The present study aims to investigate the protective effects of Dendrobine and its underlying mechanisms on liver injury induced by isoniazid (INH) and rifampicin (RIF). A mouse model of liver injury was induced by intragastrically administration of 100 mg/kg INH and 100 mg/kg RIF for 14 days. The mice were intragastrically administrated with Dendrobine (50, 100, and 200 mg/kg) before the administration of INH and RIF. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined. Oxidative stress markers including glutathione, superoxide dismutase, and malondialdehyde in the liver were measured and liver histopathological examinations were performed. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot were applied to determine the mRNA and protein expressions, respectively. Luciferase reporter assay was used to evaluate the interactions between miR-295-5p and CYP1A2. Dendrobine significantly decreased serum ALT and AST and inhibited the liver index and ameliorated the liver histological changes induced by INH and RIF. Besides, Dendrobine also regulated oxidative stress status in the liver by the regulation of CYP1A2. Moreover, mmu-miR-295-5p was identified to target CYP1A2 and to regulate the expression of CYP1A2. In summary, Dendrobine ameliorated INH and RIF induced mouse liver injury by miR-295-5p-mediated CYP1A2 expression.

[Liver histological status and clinic outcome in HBeAg-negative chronic hepatitis B with low viral load].

Objective: To retrospectively analyze the serological, virological, biochemical, liver histological status and clinical outcomes in HBeAg-negative chronic hepatitis B (CHB) patients with low HBV viral load, and to explore the necessity of antiviral therapy for these patients. Methods: A total of 99 HBeAg-negative CHB patients with HBV DNA level < 4 lg copies/ml who performed liver biopsy at the baseline were enrolled from the follow-up cohort. Among them, 23 cases received the second liver biopsy during follow-up. The relationships among the degree of inflammation and fibrosis of liver tissues, the status of HBsAg and HBcAg, age, gender, family history, HBV DNA load, serological markers and other indicators were analyzed. The pathological differences between two liver biopsy examinations were compared. The effect of nucleos(t)ide analogues (NAs) treatment on patient's clinical outcomes were analyzed. For multivariate analysis, a binary logistic regression model was performed. Log-rank test was used to compare the cumulative incidence of hepatocellular carcinoma (HCC) in NAs-treated and non-NA streated patients. Results: Baseline liver histology status showed that 58.6% (58/99) patients had obvious liver tissue damage in their baseline liver tissue pathology (G≥2 and /or S≥2). Univariate logistic regression analysis showed that a liver cirrhosis (LC) family history, a HBsAg-positive family history, baseline alanine aminotransferase and aspartate aminotransferase levels were positively correlated factors for liver tissue damage. Multivariate logistic regression analysis showed that a LC family history was the main risk factor for liver tissue damage. Twenty-three cases had received a second liver biopsy after an interval of 4.5 years. In 10 untreated cases, the second liver biopsy results showed the rate of obvious liver tissue damage (G≥2 and/ or S≥2) increased from 50.0% to 90.0%. In the other 13 cases who received NAs treatment, the second liver biopsy showed improvement in liver histology, and the rate of obvious liver tissue damage decreased from 61.5% to 46.2%. The 5-year HCC cumulative incidence in non-NAs-treated patients was significantly higher than that of in NAs-treated patients (17.7% vs. 3.8%, P = 0.046). Conclusion: For most HBeAg-negative CHB patients with low viral load, liver tissue pathology result suggests that it meets the indications for antiviral therapy, especially in patients with a LC familial history. Without antiviral therapy, liver tissue damage for these patients will progressively worse with the high incidence of HCC. Therefore, it is suggested that antiviral therapy should be started as soon as possible for the HBeAg-negative CHB patients with low viral load regardless of the alanine aminotransferase level, especially in patients over 30 years-old with a LC or HCC family history.

[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.

A comparative study of proximal femoral locking compress plate, proximal femoral nail antirotation and dynamic hip screw in intertrochanteric fractures.

OBJECTIVE: We aimed to compare the clinical efficacy of three different internal fixation methods, i.e. proximal femoral locking compress plate (PF-LCP), proximal femoral nail antirotation (PFNA) and dynamic hip screw (DHS) system in intertrochanteric femur fracture. PATIENTS AND METHODS: We selected a total of 150 patients with Intertrochanteric femur fracture who were admitted to this hospital between January 2015 and December 2016 for treatment, and those patients were divided into three groups according to the difference in treatment methods, i.e., Group A (n=50), Group B (n=50) and Group C (n=50). For patients in Group A, they received the PF-LCP treatment, patients in Group B received PFNA treatment while those in Group C received DHS treatment; ultimately, clinical efficacy was compared among three groups. RESULTS: In Group B, the efficacy was superior to those in Group A and C in terms of comparison of surgical duration, bleeding amount, time point of callus formation, healing time of fracture and length of stay (LOS) in hospital (p<0.05); after operation, the prevalence rate of complication in Group B was significantly lower than those in Group A and Group C (p<0.05); in comparison of preoperative Harris score among three groups, the different had no statistical significance (p>0.05). The Harris scores in Group B at the 1st, 3rd, and 6th month after operation were all significantly higher than those in Group A and C (p<0.05). CONCLUSIONS: Compared with PF-LCP and DHS, PFDA can better fix the intertrochanteric femur fracture with little effect on blood circulation at the fracture end and slight damage to sclerotin, thereby accelerating the recovery of hip joint function without any increase in prevalence of complications. Therefore, PFDA has a promising clinical efficacy and safety, which is worthy of being promoted in clinical practice.

[Effect of CD4(+) T cell surface CD1d molecules on progression of multiple sclerosis in mouse experimental autoimmune encephalomyelitis model].

Objective: To investigate the effect of CD1d molecules on the surface of CD4(+) T cells on the progression of experimental autoimmune encephalomyelitis (experimental, allergic, encephalomyelitis, EAE) mouse models. Methods: EAE model of C57BL/6 mice was established, Splenic cells were isolated at different stages of the progression of the disease.The proportion of CD1d(+) cells on the surface of activated and non activated CD4(+) T cells was detected by flow cytometry. Results: The proportion of CD1d(+) cells in the control group (normal group and complete Freund's adjuvant (CFA) group), in the peak and recovery period of disease in the EAE group were compared.The proportion of CD1d(+) cells in the control group was (8.98 ±0.36)%, and the proportion of CD1d(+) cells in the peak and recovery period of disease in the EAE group were respectively (2.14±0.15)% and (13.80±0.84)%.The differences were statistically significant difference (P<0.05). Conclusion: The trend of the proportion of CD4(+) T cells expressing CD1d molecules during the course of EAE pathogenesis is verified, which lays a foundation for further study on the interaction between CD4(+) T cells and NKT cells in the progression of EAE models.

Serotonin induces parathyroid hormone-related protein in goat mammary gland.

During lactation, large amounts of calcium are exported from the mammary gland into milk to ensure skeletal growth of the offspring. Recent studies revealed that serotonin (5-HT) is essential to stimulate skeletal calcium resorption for milk synthesis. Our objective was to explore the correlation between circulating 5-HT and serum calcium and parathyroid hormone-related protein (PTHrP) concentrations around parturition in dairy goats. We also investigated the effect of 5-HT on PTHrP expression in cultured primary goat mammary epithelial cells (GMEC). Blood samples of multiparous Guanzhong dairy goats were collected on day -5 to 3 postpartum for analysis of serum concentrations of calcium, 5-HT, and PTHrP. Results revealed that from day -3 to 0 postpartum serum calcium and 5-HT concentrations decreased progressively, but serum PTHrP concentration only had a sharp drop in the postpartum period sampled. Correlation analysis of circulating 5-HT and serum calcium and PTHrP concentrations on day 1 and 2 postpartum revealed that low serum 5-HT concentration was positively correlated with serum total calcium or PTHrP concentration. By knocking down tryptophan hydroxylase-1 (TPH1) or adding 5-hydroxytryptophan (5-HTP) to decrease or increase the levels of 5-HT in GMEC, we observed that 5-HTP increased PTHrP expression in a dose-dependent manner and siTPH1 decreased PTHrP protein expression. Furthermore, 5-HT increased mRNA abundance of calcium-sensing receptor (CaSR) in a dose-dependent manner and decreased the expression of plasma membrane Ca2+ ATPase-1 (PMCA1). Taken together, 5-HT seems to induce PTHrP expression in goat mammary cells during and after parturition. These findings suggest that increasing 5-HT biosynthesis could be a potential therapeutic target for prevention of hypocalcemia in dairy goats.

Autophagic dysfunction is improved by intermittent administration of osteocalcin in obese mice.

BACKGROUND: Osteoblast-specific secreted osteocalcin has been considered as an important regulator of energy and glucose metabolism, however, the causative role and clinical potential of osteocalcin implicated in insulin resistance remains not fully understood. METHODS: Osteocalcin was administered intermittently in vivo and in vitro, and metabolic parameters, autophagy and insulin signaling were assessed. RESULTS: The intermittent injections of osteocalcin in mice fed high-fat diet resulted in decreased body weight gain, fat-pad weight gain, serum triglycerides, serum-free fatty acid, blood glucose, insulin level and partial normalization of glucose tolerance relative to the mice fed high-fat diet and received vehicle injections. Meanwhile, the intermittent administration of osteocalcin not only led to the alleviation of autophagic dysfunction and endoplasmic reticulum (ER) stress, but also contributed to the restoration of the impaired insulin signaling in adipose tissue and skeleton muscle of mice consumed the high-fat diet. In accordance with these findings in vivo, osteocalcin treatment also displayed a protective impact on adipocytes and myocytes against tunicamycin- or palmitate-induced ER stress and autophagy dysfunction in an XBP-1-independent manner, with these effects of osteocalcin being reversed by inhibition of mammalian target of rapamycin (mTOR) or nuclear factor-κB (NF-κB). CONCLUSIONS: Intermittent administration of osteocalcin efficiently reversed the attenuated autophagy and ER stress, and restored the impaired insulin sensitivity in cellular and mice models of insulin resistance. Our findings provide new insights into the clinical potential of osteocalcin in metabolic homeostasis, and suggest an innovative strategy for the treatment against diabetes, obesity and metabolic syndrome.

Identifying differentially expressed genes under heat stress and developing molecular markers in orchardgrass (Dactylis glomerata L.) through transcriptome analysis.

Orchardgrass (Dactylis glomerata L.) is a long-lived, cool-season forage grass that is commonly used for hay production. Despite its economic importance, orchardgrass genome remains relatively unexplored. In this study, we used Illumina RNA sequencing to identify gene-associated molecular markers, including simple sequence repeats (SSRs) and single nucleotide polymorphisms (SNPs), as well as heat stress-induced differentially expressed genes (DEGs) in two orchardgrass genotypes, 'Baoxing' (heat resistant) and '01998' (heat susceptible). Approximately 163 million high-quality trimmed reads were generated from 207 million raw reads using the Illumina HiSeq 2000 platform. A total of 126,846 unigenes were obtained after de novo assembly of the trimmed reads, and 40,078 unigenes were identified as coding sequences (CDSs). Based on the assembled unigenes, 669,300 high-quality SNPs, including 416,099 transitions and 257,736 transversions, were contained in 75,875 unigenes. In addition, a total of 8475 microsatellites were detected in 7764 unigenes. When placed under heat stress, the total number of DEGs in 'Baoxing' (3527) was higher than in '01998' (2649), indicating that in comparison with heat-susceptible '01998', heat-resistant 'Baoxing' seems to have more unigenes that respond to heat stress. The high-throughput transcriptome sequencing of orchardgrass under heat stress provides useful information for gene identification and for the development of SNP and SSR molecular markers. The comparison of DEGs under different periods of heat stress allowed us to identify a wealth of candidate DEGs that can be further analysed in order to determine the genetic mechanisms underlying heat tolerance in orchardgrass.

Long noncoding RNA PEG10 regulates proliferation and invasion of esophageal cancer cells.

Long chain noncoding RNAs (LncRNAs), a class of noncoding RNA nucleotides longer than 200 bp, have important roles in a variety of biological processes. Accumulating evidence has confirmed the involvement of LncRNAs in cancer initiation, development and progression. We investigated the expression of LncRNA PEG10 in a cohort of esophageal carcinomas to assess its impact on esophageal cancer cell proliferation, apoptosis and invasion. Quantitaive reverse transcription polymerase chain reaction assays were used to quantify LncRNA PEG10 expression levels in 43 paired EC samples and adjacent non-neoplastic tissues. Cell growth, apoptosis and Transwell invasion assays were used to evaluate the effects of LncRNA PEG10 on esophageal cancer cells. LncRNA PEG10 was expressed at higher levels in esophageal cancer tissues than in adjacent non-neoplastic tissues (P<0.05). This relatively high expression was significantly associated with the occurrence of lymph node metastases (P<0.05). Apoptosis and migration rates were significantly decreased in two esophageal cancer cell lines (EC9706 and KYSE150) transfected with si-LncRNA PEG10 (P<0.05). Downregulation of LncRNA PEG10 decreased the expression of PEG10 (P<0.05). Our results indicated that LncRNA PEG10 is upregulated in esophageal cancer tissues, and its downregulation inhibits proliferation and invasion, and promotes apoptosis in esophageal cancer cells. LncRNA PEG10 may serve as a therapeutic agent in esophageal cancer.

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.

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.

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.

Bioinformatics analysis of two microarray gene-expression data sets to select lung adenocarcinoma marker genes.

BACKGROUND: Lung adenocarcinoma (LAC) is the most frequent histologic type of lung cancer and rates of adenocarcinoma are increasing in most countries. Recently, several molecular markers have been identified to predict LAC. However, more prognostic makers and the underlying role of those makers are still imperative. AIM: In this study, our objective was to identify a set of discriminating genes that can be used for characterization and prediction of response to LAC. MATERIALS AND METHODS: Using the bioinformatics analysis method, we merged two LAC datasets-GSE2514 and GSE7670 to find novel target genes and pathways to explain the pathogenicity. RESULTS: The results showed that EDNRB (endothelin receptor type B), ADRB2 (beta-adrenergic receptor), S1PR1 (sphingosine-1-phosphate receptor 1), P2RY14 (PsY purinoceptor 14), LEPR (leptin-receptor), GHR (growth hormone receptor), PPM1D (protein phosphatase-1D), and GADD45B (growth arrest and DNA-damage-inducible, beta) have high degrees in response to LAC. Additionally, EDNRB, ADRB2, S1PR1, P2RY14, LEPR, and GHR may be involved in LAC through Neuroactive ligand-receptor interaction, but PPM1D and GADD45B may be through p53 signaling pathway. Some of our prediction had been demonstrated by previous reports, such as ADRB2, S1PR1, GHR, PPM1D, and GADD45B. Therefore, we hope our study could lay a basis for further study of other target genes, such as EDNRB, P2RY14, and LEPR. CONCLUSIONS: It is effective to identify potential molecular marker for LAC and predict their underlying functions by bioinformatics analysis and graph clustering method. However, further experiments are still indispensable to confirm our conclusion.

Bioinformatics analysis reveals potential candidate drugs for psychological stress in ovarian cancer.

BACKGROUND: Women with ovarian cancer may be at increased risk for psychological distress around the time of diagnosis relative to patients diagnosed with other cancers, because of the seriousness of the disease. However, the molecular mechanism of this effect is far from clear. AIM: We sought to investigate the influence of psychological status in regulating gene expression among women with primary ovarian cancer and to identify the small molecules which exhibit similar effects with different psychological status. MATERIALS AND METHODS: DNA microarray analyses of 10 ovarian carcinomas (GSE9116, downloaded from GEO) identified 916 human transcripts that were differentially expressed in tumors from patients with high depression relative to grade-and stage-matched tumors from low depression patients, and pathways related to immune system were dysfunctional. RESULTS: Our results suggest that psychosocial stress is related to impaired immunity in ovarian cancer patients. Besides, we identified a group of small molecules which can be exploited as adjuvant drug to improve therapeutic effect for ovarian cancer, such as MS-275 and adiphenine. CONCLUSIONS: Our findings may be useful for the development of management strategies for psychological distress, and we suggest that there is a need for improvement in the quality of life of cancer outpatients being treated with chemotherapy.

[Risk of cerebrovascular disease incidence in the cohort of Mayak production association workers first employed during 1948-1958].

Incidence of cerebrovascular diseases (CVD) has been studied in a cohort of 12210 workers first employed at one of the main plants (reactors, radiochemical or plutonium) of the Mayak nuclear facility during 1948-1958 and followed up to the end of 2000. Information on external gamma doses is available for virtually all (99.9%) of these workers; the mean (+/- one standard deviation) total gamma dose was 0.91 +/- 0.95 Gy (99% percentile 3.9 Gy) for men and 0.65 +/- 0.75 Gy (99% percentile 2.99 Gy) for women. Plutonium body burden was measured only for 30.0% of workers. Amongst those monitored, the mean (+/- standard deviation) cumulative liver dose from plutonium alpha exposure was 0.40 +/- 1.15 Gy (99% percentile 5.88 Gy) for men and 0.81 +/- 4.60 Gy (99% percentile 15.95 Gy) for women 4418 cases (first diagnosis) of CVD were identified in the studied cohort. A statistically significant increasing trend in CVD incidence with total external gamma dose was revealed after adjustment for non-radiation factors and internal exposure from incorporated plutonium-239. Excess relative risk per Gy was 0.464 (95% confidence interval 0.360-0.567). Incidence of CVD was statistically significantly higher for the workers chronically exposed to external gamma rays at a dose above 1.0 Gy A statistically significant increasing trend in CVD incidence with internal liver dose from plutonium alpha exposure was observed after adjustment for non-radiation factors and external exposure. ERR per Gy was 0.155 (95% confidence interval 0.075-0.235). CVD incidence was statistically significantly higher among workers with a plutonium liver dose above 0.1 Gy, although the trend estimates differed between workers at different plants. The incidence risk estimates for external radiation are generally compatible with estimates from the study of Chernobyl clean-up workers, although the incidence data point to higher risk estimates compared to those from the Japanese A-bomb survivors.