Association of rs610604 in TNFAIP3 and rs17728338 in TNIP1 gene polymorphisms with psoriasis susceptibility: a meta-analysis of case-control studies.

BACKGROUND: To date, the fundamental pathophysiology underlying the occurrence and progression of psoriasis are still unanswered questions. Genome-wide association surveys have revealed that TNFAIP3 and TNIP1 were key biomarkers for psoriasis. Here, we intended to conduct a survey on the association between TNFAIP3 and TNIP1 gene polymorphisms and psoriasis risk. METHODS: A comprehensive search of four online databases-China National Knowledge Infrastructure (CNKI), PubMed, Embase, and Cochrane Library was undertaken up to August 25, 2019. We chose allele genetic model to deal with the original data. Newcastle-Ottawa scale (NOS) was used to evaluate the risk bias of each study. The RevMan 5.3 software was used to calculate the combined odds ratio and 95% confidence interval. RESULTS: In total, we included 13 case-control studies consist of 13,908 psoriasis patients and 20,051 controls in this work. Our results demonstrated that rs610604 in TNFAIP3 polymorphism was significantly associated with psoriasis risk using random-effect model (G vs. T, OR = 1.19, 95% CI: 1.09-1.31, P = 0.0002), and a significant association between rs17728338 in TNIP1 polymorphism and psoriasis vulnerability using fixed-effect model (A vs. G, OR = 1.69, 95% CI:1.58-1.80, P < 0.00001). CONCLUSIONS: Our findings indicated that rs610604 in TNFAIP3 and rs17728338 in TNIP1 gene polymorphisms were associated with psoriasis susceptibility.

Association of Helicobacter pylori infection with colorectal polyps and malignancy in China.

BACKGROUND: Gastric Helicobacter pylori (H. pylori) infection is related to chronic gastritis, gastroduodenal ulcer, and gastric malignancies; whether this infection is related to colorectal polyps and colorectal cancer (CRC), remains debatable. AIM: To investigate the relationship between gastric H. pylori infection and the risk of colorectal polyps and CRC. METHODS: We retrospectively analyzed 3872 patients with colorectal polyps who underwent colonoscopy and pathological diagnosis. We also analyzed 304 patients with primary CRC. The characteristics of these patients were compared with those of the control group, which included 2362 patients with the normal intestinal mucosa. All subjects completed a 14C-urea breath test, bidirectional gastrointestinal endoscopy, and a biopsy on the same day. Data on the number, size, location, and pathology of the polyps, the location, and pathology of the CRC, the detection of H. pylori, and the incidence of H. pylori-associated atrophic gastritis or intestinal metaplasia were obtained. A logistic regression model was used to analyze the relationship between gastric infection due to H. pylori, and the incidence of colorectal polyps and CRC. RESULTS: The prevalence of H. pylori infection was higher in the multiple polyps group than in the solitary polyp group and the control group [95% confidence interval (CI) = 1.02-1.31, P = 0.03; 95%CI: 2.12-2.74, P < 0.001]. The patients with adenomatous polyps had a higher incidence of H. pylori infection than patients with non-adenomatous polyps [59.95% vs 51.75%, adjusted odds ratio (OR) = 1.41, 95%CI: 1.24-1.60, P < 0.01]. Patients with H. pylori-associated atrophic gastritis or intestinal metaplasia were at high risk of CRC (adjusted OR = 3.46, 95%CI: 2.63-4.55, P < 0.01; adjusted OR = 4.86, 95%CI: 3.22-7.34, P < 0.01, respectively). The size and location of the polyps, the histopathological characteristics and the location of CRC were not related to H. pylori infection. CONCLUSION: Our study demonstrates that the incidence of gastric H. pylori infection and H. pylori-associated atrophic gastritis or intestinal metaplasia elevates the risk of colorectal polyps and CRC.

Association of Interleukin-23R Gene Polymorphisms with Behcet's Disease Susceptibility: A Meta-Analysis of Case-control Studies.

BACKGROUND: The pathological mechanisms associated with the occurrence and development of Behcet's disease (BD) are not yet known. Two large genome-wide association surveys revealed an association between interleukin (IL)-23R single nucleotide polymorphism and BD. This study aimed to investigate the association between IL-23R gene polymorphisms and BD susceptibility. METHODS: Comprehensive literature search was performed across four online databases - PubMed, Embase, Cochrane Library, and Web of science. The included studies had to be published before May 15, 2019. The Newcastle-Ottawa scale was used to assess the quality of every included study, and pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using the allele model of inheritance to evaluate the potential associations between IL-23R gene polymorphisms and BD risk. RESULTS: In all, 12 case-control studies comprising 6,926 BD patients and 10,211 controls were identified and included in this meta-analysis, in which 5 loci of IL-23R gene polymorphisms were investigated. Of these 5 loci, 2 were found to be significantly associated with BD susceptibility: rs17375018 (G vs. A, OR = 1.50, 95% CI: 1.34-1.68, P < .00001) and rs924080 (T vs. C, OR = 1.36, 95% CI: 1.29-1.43, P < .00001). Only a systematic review was conducted for rs12119179, rs11209032, and rs12141431, owing to the lack of sufficient data. CONCLUSION: This meta-analysis indicated that rs17375018 (G/A) and rs924080 (T/C) were associated with BD susceptibility. However, association of the other IL-23R polymorphisms could not be estimated owing to the lack of studies. ABBREVIATIONS: BD: Behcet's disease; SNP: single nucleotide polymorphism; HLA: human leukocyte antigen; IL: interleukin; OR: odds ratio; CI: confidence interval; HWE: Hardy-Weinberg equilibrium; UK: United Kingdom; NOS: Newcastle-Ottawa scale; GWAS: genome-wide association study; TNF-α: tumor necrosis factor-α.

Risk factors for infantile hemangioma: a meta-analysis.

BACKGROUND: Infantile hemangioma (IH) is one of the most common tumors in infants. Its pathogenesis is complex and poorly understood. The risk factors of IH have been extensively studied from clinical and epidemiological perspectives in recent years, but the conclusions in the literature reports are inconsistent. To provide a reference for the prevention of hemangioma, we conducted a meta-analysis of the published studies of potential risk factors for IH. METHODS: The Cochrane Library, Ovid, PubMed, and Web of Science databases were searched systematically. Log odds ratios (log ORs), logistic regression standard errors and 95% confidence intervals (CIs) were used to compare the correlation between IH and potential risk factors. Review Manager 5.3.3 was used for the statistical analysis. RESULTS: Six studies were included and 17 potential risk factors were eventually evaluated. P values < 0.05 were found for female gender (P < 0.01, OR 2.04, 95% CI 1.65-2.51), low birth weight (P < 0.01, OR 4.39, 95% CI 3.05-6.31), multiple gestation (P = 0.01, OR 2.39, 95% CI 1.21-4.71), preterm birth (P = 0.03, OR 2.37, 95% CI 1.07-5.23), progesterone therapy (P < 0.01, OR 2.73, 95% CI 2.12-3.51), and family history (P = 0.01, OR 1.98, 95% CI 1.16-3.38). CONCLUSIONS: This meta-analysis revealed that risk factors, including female gender, low birth weight, multiple gestation, preterm birth, progesterone therapy, and family history may affect the occurrence of IH.

Clinical characteristics of sentinel polyps and their correlation with proximal colon cancer: A retrospective observational study.

BACKGROUND: Colorectal cancer is a common malignant tumor of the digestive tract. The relationship between sentinel polyps (rectal polyps with proximal colon cancer) and proximal colon cancer has received extensive attention in recent years. However, there is still no clear conclusion regarding the relationship. AIM: To investigate the clinical characteristics of sentinel polyps and their correlation with proximal colon cancer. METHODS: A retrospective analysis of 2587 patients with rectal polyps from January 2006 to December 2017 was performed. According to whether or not proximal colon cancer was diagnosed, the patients were divided into either a sentinel polyp group (192 patients) or a pure rectal polyp group (2395 patients). The endoscopic features, clinicopathological features, therapeutic effects, and short-term prognosis were analyzed and compared between the two groups. RESULTS: The mean age of patients in the sentinel polyp group was generally higher than that of the pure rectal polyp group, and the positivity rates of anemia, stool occult blood, and tumor markers of the sentinel polyp group were also significantly higher than those in the rectal polyp group (χ 2 = 90.56, P < 0.01; χ 2 = 70.30, P < 0.01; χ 2 = 92.80, P < 0.01). The majority of the patients in the sentinel polyp group had multiple polyps, large polyps, adenomatous polyps, or sessile polyps (χ 2 = 195.96, P < 0.01; χ 2 = 460.46, P < 0.01; χ 2 = 94.69, P < 0.01; χ 2 = 48.01, P < 0.01). Most of the proximal colon cancers were Duke's A and B stages in the sentinel polyp group. In the pure rectal polyp group, 2203 patients underwent endoscopic treatment, and all of the patients were cured and discharged. In the sentinel polyp group, 65 patients underwent radical operation, and 61 patients received endoscopic submucosal dissection or endoscopic mucosal resection. Additionally, 21 patients were lost to follow-up after 6-12 mo, and the loss rate was 10.94%. A total of 63.16% of patients experienced remission without tumor recurrence or metastasis, 33.33% of patients experienced tumors regression or improved symptoms, and the other 3.51% of the patients died. CONCLUSION: If there are multiple, sessile, and adenomatous rectal polyps with a maximum diameter > 1 cm, the possibility of the carcinogenesis of the polyps or of the proximal colon should be monitored closely. These patients should be followed in the short-term and should undergo a whole-colon examination.

Bowen's disease on the palm: A case report.

BACKGROUND: Bowen's disease (BD) is a persistent, progressive intraepidermal carcinoma. BD usually occurs in areas exposed to sunlight. Involvement of the dorsum of the hand is not rare, but that of the palmar aspect is very unusual. Only a few cases have been reported in the literature. CASE SUMMARY: Here, we report the case of a 48-year-old male patient who presented with a history of persistent local erythema lasting for 2 years on the thenar eminence of the left palm. Initially diagnosed as hand eczema, the condition did not improve with intermittent treatment with anti-allergy medications or topical glucocorticoid ointments, among other approaches. Then, the area of erythema gradually enlarged and was accompanied by mild itching. For a definite diagnosis and treatment, the patient came to our hospital. Dermoscopic examination revealed BD, and histopathological examination confirmed the diagnosis. We performed partial resection of the skin lesion followed by photodynamic therapy. No recurrence was observed at the 6-mo follow-up. CONCLUSION: For all atypical palmar lesions, early dermoscopy and/or skin biopsy are needed to avoid missed diagnosis or misdiagnosis.

Bioinformatics analysis of key biomarkers and pathways in KSHV infected endothelial cells.

Kaposi sarcoma (KS) is an endothelial tumor etiologically related to Kaposi sarcoma herpesvirus (KSHV) infection. The aim of our study was to screen out candidate genes of KSHV infected endothelial cells and to elucidate the underlying molecular mechanisms by bioinformatics methods. Microarray datasets GSE16354 and GSE22522 were downloaded from Gene Expression Omnibus (GEO) database. the differentially expressed genes (DEGs) between endothelial cells and KSHV infected endothelial cells were identified. And then, functional enrichment analyses of gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were performed. After that, Search Tool for the Retrieval of Interacting Genes (STRING) was used to investigate the potential protein-protein interaction (PPI) network between DEGs, Cytoscape software was used to visualize the interaction network of DEGs and to screen out the hub genes. A total of 113 DEGs and 11 hub genes were identified from the 2 datasets. GO enrichment analysis revealed that most of the DEGs were enrichen in regulation of cell proliferation, extracellular region part and sequence-specific DNA binding; KEGG pathway enrichments analysis displayed that DEGs were mostly enrichen in cell cycle, Jak-STAT signaling pathway, pathways in cancer, and Insulin signaling pathway. In conclusion, the present study identified a host of DEGs and hub genes in KSHV infected endothelial cells which may serve as potential key biomarkers and therapeutic targets, helping us to have a better understanding of the molecular mechanism of KS.

MiR-497-5p, miR-195-5p and miR-455-3p function as tumor suppressors by targeting hTERT in melanoma A375 cells.

BACKGROUND: hTERT gene plays an important role in melanoma, although the specific mechanism involved is unclear. The aim of this study was to screen and identify the relative miRNAs with the regulation of hTERT in melanoma. MATERIALS AND METHODS: Quantitative real-time polymerase chain reaction (q-PCR) and immunohistochemistry were performed to detect hTERT mRNA and protein expression in 36 formalin-fixed paraffin-embedded melanoma tissues and 36 age- and sex-matched pigmented nevi cases, respectively. Bioinformatics analysis and custom miRNA polymerase chain reaction array were determined for predicting, screening and verifying miRNAs with the regulation of the hTERT gene. To investigate the biological functions, miRNAs mimics or inhibitors were transfected into melanoma A375 cells. The relative expression of miR-497-5p, miR-195-5p, miR-455-3p and hTERT mRNA was determined by q-PCR. The protein expression of hTERT was detected by Western blot. 3-(4,5-Dimethylthiazolyl-2-yl)-2,5-biphenyl tetrazolium bromide and flow cytometry were employed to detect cell proliferation ability, cell apoptosis and cell cycle. Transwell and wound healing assays were used to observe cell invasion and migration abilities. A direct target gene of miRNAs was analyzed by a dual luciferase reporter activity assay. RESULTS: MiR-497-5p, miR-195-5p, miR-455-3p were significantly downregulated, while hTERT was upregulated in melanoma tissues. hTERT expression level was inversely correlated with miR-497-5p, miR-195-5p and miR-455-3p. Overexpression of miR-497-5p, miR-195-5p and miR-455-3p inhibited A375 cell proliferation, migration and invasion, arrested the cell cycle, induced cell apoptosis and decreased hTERT expression at both mRNA and protein levels. Suppression of miR-497-5p, miR-195-5p and miR-455-3p partially reversed the inhibitory effects. Finally, hTERT was identified as a direct target of miR-497-5p, miR-195-5p and miR-455-3p. CONCLUSIONS: MiR-497-5p, miR-195-5p and miR-455-3p act as tumor suppressors by targeting hTERT in melanoma A375 cells. Therefore, miR-497-5p, miR-195-5p and miR-455-3p could be potential targeted therapeutic choice for melanoma.

Efficacy of alprostadil for preventing of contrast-induced nephropathy: A meta-analysis.

Contrast-induced nephropathy (CIN) has become the third-leading cause of hospital-acquired acute renal injury. Although alprostadil has been proposed as an effective preventative measure, this conclusion remains inconsistent. Thus, we performed a meta-analysis of the published studies on this topic to evaluate the preventative effect of alprostadil on CIN. Databases, including PubMed, the Web of Science, Cochrane Library, Wanfang, the China Biological Medicine Database (SinoMed) and the China National Knowledge Infrastructure (CNKI) were systematically searched. Nineteen clinical trials involving 2267 individuals were identified. We utilized a random or a fixed effect model to calculate the pooled odd ratios (ORs) and the standardized mean differences (SMD), respectively. Compared to the control group, the CIN risk decreased significantly in the alprostadil group (P < 0.00001, OR = 0.29, 95% CI = 0.21-0.39). In the subgroup of coronary angiography patients, the use of alprostadil also decreased the risk of CIN (P < 0.00001, OR = 0.27, 95% CI: 0.19-0.39). In conclusion, Alprostadil might be associated with a significant reduction in postcontrast Scr, BUN and CysC level and decrease the incidence of CIN.

Six generations of epidermolytic palmoplantar keratoderma, associated with a KRT9 R163W mutation.

Epidermolytic palmoplantar keratoderma (EPPK) is a rare autosomal dominant skin disorder characterized by diffuse hyperkeratosis on the palms and soles. Whole-exome sequencing (WES) has become a powerful tool for the detection of rare causal variants of Mendelian disorders. However, no causal gene for EPPK in the Uygur population has been identified until now, and no treatment exists than can address the underlying pathology.WES analysis was undertaken on two individuals from a large Uygur EPPK pedigree whose disease locus mapped to 17q21.2 (chr:38994621-39893408) following previous linkage analysis. KRT9 (NM_000226.3:c.487C>T, p.Arg163Trp), and KRT15 (XM_005257346.1:c.212G>T, XP_005257403.1:p.Gly71Val) located in this region, have been identified as two candidate causative genes for EPPK in the Uygur family. Sanger sequencing was conducted on this region in other affected individuals (n = 38) from this family, non-affected individuals (n = 56) from this family and 100 unrelated controls. The missense mutation KRT9 c.487C>T, identified in this large Uygur population, is a potential causative mutation. To date, EPPK has no effective therapy, and siRNA is a potential avenue for EPPK therapy. To investigate this, full-length wild-type Keratin9 (KRT9; pKRT9-WT) and p.Arg163Trp (pKRT9-R163W) were then transfected into HaCaT cells. The small interfering RNAs targeting the KRT9 R163W mutant and wildtype KRT9 were transfected into HaCaT cells, and total RNA isolated at 72 h post-transfection. Quantitative polymerase chain reaction and western blotting were used to analyse the effects of knock-down on KRT9 mRNA and protein levels, respectively. siRNA was shown to specifically inhibit mutant KRT9 mRNA and protein expression (p < 0.01, with 95% confidence limits). Our study suggests that KRT9 is a causal gene for EPPK. This information is helpful for understanding the pathogenesis of EPPK in the Uygur population and raises the possibility of designing a novel siRNA treatment strategy for this population of EPPK patients.

MicroRNA-126-3p suppresses cell proliferation by targeting PIK3R2 in Kaposi's sarcoma cells.

Kaposi's sarcoma is a highly vascular tumor of lymphatic endothelial origin. Many deregulated miRNAs, including miR-126-3p, have been identified in Kaposi's sarcoma tissues. miR-126-3p is the most highly endothelial-specific miRNA that regulates vascular integrity and angiogenesis. In this study, we aimed to determine the effect of miR-126-3p on Kaposi's sarcoma cells through transfection of a miRNA mimic and inhibitor. Moreover, we searched the target gene (PIK3R2) of miR-126-3p using bioinformatics software and further verified PIK3R2 using luciferase reporter assays, Real-time quantitative PCR (qRT-PCR) and western blot. The results demonstrated that miR-126-3p inhibited cell proliferation, arrested cell cycle progression, induced cell apoptosis, and inhibited cell invasion of SLK cells. The bioinformatics analysis and luciferase reporter assay revealed that PIK3R2 mRNA is a direct target of miR-126-3p. Moreover, the level of expression of the PIK3R2 gene was downregulated in SLK cells transfected with miR-126-3p siRNAs. Therefore, our data demonstrated that miR-126-3p is a tumor suppressor miRNA that acts by targeting PIK3R2 in Kaposi's sarcoma cells. These findings contribute to our understanding of the molecular mechanisms underlying Kaposi's sarcoma.

The expression profiles of microRNAs in Kaposi's sarcoma.

Kaposi's sarcoma (KS) is a multicentric angioproliferative tumor of mesenchymal origin. The molecular and biologic aspects of KS are not fully understood. MicroRNAs are non-protein-coding small RNAs in the size range 19-25 nucleotides (nt) that play important roles in biological processes, including cellular differentiation, proliferation, and death. We performed a miRNA microarray analysis by detecting six paired KS and matched adjacent healthy tissues using the 7th generation of miRCURY(TM) LNA Array (v.18.0) (Exiqon) containing 3100 capture probes. We selected 10 significant differentially expressed miRNAs, which were confirmed by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) in 18 paired KS and matched adjacent healthy tissue specimens. We also investigated the associations between clinical features and miRNA expression. Among the 3100 human miRNA probes in the microarrays, we identified 170 differentially expressed miRNAs (69 upregulated and 101 downregulated miRNAs) in KS versus adjacent healthy tissues. Among the most significantly upregulated miRNAs were miR-126-3p, miR-199a-3p, miR-16-5p, and the 13 KSHV-related miRNAs. The most significantly downregulated miRNAs included miR-125b-1-3p and miR-1183. Eight upregulated miRNAs, miR-181b-5p, miR-199a-3p, miR-15a-5p, miR-126-3p, miR-1297, kshv-miR-k12-12-3p, kshv-miR-k12-1-5p, and miR-16-5p, and two downregulated miRNAs, miR-125b-1-3p and miR-1183, were confirmed by qRT-PCR in 18 paired KS samples. The qRT-PCR results for 10 miRNAs were consistent with our microarray results. The miR-125b-1-3p and miR-16-5p had statistically significant associations with HHV-8 and HIV infections in KS. The results of miRNA profiling showed that KS appears to have unique expression patterns when compared with paired adjacent healthy tissues, suggesting that deregulation of miRNAs plays an important role in the progression of KS. These differentially expressed miRNAs may provide novel diagnostic and prognostic tools.

[A de nono I462S mutation in the KRT6A gene is associated with pachyonychia congenita type I].

OBJECTIVE: To analyze the KRT6A gene mutation and mutating patterns in a sporadic Chinese patient with Pachyonychia congenita (PC)-1 so as to provide a basis for gene diagnosis and genetic counseling of this disorder. METHODS: Genomic DNA was extracted from whole blood by standard methods from a female patient with PC-1 and her parents, and from 50 normal, unrelated individuals. Primers for specific amplification of the structural KRT6A gene without co amplification of homologous genes were designed and synthesized. All exons of the gene and their flanking intronic sequences were amplified using polymerase chain reaction (PCR) and subjected to automatic DNA sequencing. The mutation was confirmed by Mbo I restriction digestion of the KRT6A-specific PCR products. RESULTS: Direct sequencing of the PCR products revealed a novel heterozygous missense mutation, I462S in the KRT6A gene, which resulted from T to G transversion at nucleotide 1385 (1385T > G) in exon 7 was detected in the patient. This mutation would result in the substitution of Isoleucine by Serine at codon 462 (I462S) located in the end 2B domain of keratin 6A. No such mutation was found in the patient's parents by sequencing of PCR products and this mutation was confirmed in the patient and excluded from both parents and 50 normal, unrelated controls by restriction analysis of PCR fragments using Mbo I enzyme. CONCLUSIONS: A de novo missense mutation in the KRT6A gene, I462S, has been found in a sporadic PC-1 patient. The identification of this novel mutation in the KRT6A gene provides further evidence that mutation in the KRT6A gene causes PC-1 phenotype.