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BACKGROUND: Enhanced recovery after surgery (ERAS), as a new concept in surgery, has dramatically changed the mode of perioperative treatment for children with acute appendicitis. METHODS: The retrieval strategy developed by the Cochrane Collaboration was conducted using the CNKI database, Wanfang Medical Network, PubMed, EBSCO, Medline, and Cochrane database by combining subject headings and free words. A review of the randomized controlled trials on the use of the ERAS concept in the perioperative treatment of acute appendicitis in children was conducted between the establishment of the database and May 15, 2021. Keywords included enhanced recovery after surgery, fast track surgery, ERAS, FTS, child, infant, and appendicitis. The quality of the literature was evaluated according to the RevMan 5.3 software provided by the Cochrane Collaboration. RESULTS: Five randomized controlled trials on ERAS in children with acute appendicitis were finally included. The heterogeneity of postoperative stay time was tested in 4 studies using continuous variables, with Chi-squared test (Chi(2)) =221.52, degree of freedom (df) =3, I(2)=99%>50%. An overall analysis using a random effects model showed that the ERAS group was significantly different compared to the control group [Z=5.26; mean difference (MD) =−1.65; 95% CI: −2.27 to −1.03; P

Investigation of the role of sedation during colonoscopy is meaningful as the advantages of colonoscopy performing with sedation are still controversial. Medical records of patients who underwent colonoscopy in our institution were retrospectively analyzed. The sedation rate, adenoma detection rate (ADR), polyp detection rate (PDR), cecal intubation rate (CIR), iatrogenic colonic perforation rate (ICP) were calculated. A total of 48,838 colonoscopies (24,498 in males) dated from July 2007 to February 2017 were analyzed. The median age was 50 years (range 16–85 years). An overall sedation rate was 80.38%. The PDR was 26.77%, and was not statistically different between colonoscopy with or without sedation (26.67% vs 27.22, p = 0.474). ADR was 12.9% regardless of applying sedation or not (13.0% vs 12.44%, p = 0.337). The CIR was 87.42% in all examinations with an adjusted CIR of 90.34%, and was higher when performed with sedation than without sedation (88.92% vs 80.64%, p

Objective: The purpose of this study was to investigate associations between the 14 reported loci (from a meta-analysis of genome-wide association studies [GWAS] in the Caucasian population) and vi...

This study was aimed to investigate whether NFKB1 participates in the pathogenesis of psoriasis by mediating Th1/Th17 cells. In this study, expression of NFKB1 was assessed in skin tissues from psoriasis patients and the healthy controls through Western blot and Immunohistochemistry. Enzyme-linked immunosorbent assay (ELISA) was used to analyze the serum levels of IFN-γ, IL-17 (IL-17A) and IL-17RA. The imiquimod-induced psoriasis mouse model was employed to examine the role of NFKB1 in psoriasis via the assessment of psoriasis area and severity index (PASI), including erythema, thickness and scales. The effects of NFKB1 on Th1/Th17 cells in were examined by flow cytometry. In vitro co-culture of Th1/Th17 cells isolated from different mice with HaCat cells was conducted to elucidate the effect of Th1/Th17 cells-mediated by NFKB1 on HaCat cells by MTT, wound healing and transwell invasion assay, respectively. The results showed that NF-κB p105/p50 expression in skin tissues was significantly increased in psoriasis (n = 21) compared to the healthy controls (n = 16), as well as levels of serum INF-γ and IL-17. Additionally, NF-κB p105/p50 expression in lesional skin tissues was much higher than that in non-lesional skin tissues of the same patients. In the psoriasis mouse model, NFKB1 overexpression significantly elevated the scores of erythema, thickness and scales. Besides, NFKB1 up-regulated the level of NF-κB p105/p50, INF-γ, T-bet, IL-17 and RORγt, as well as Th1/Th17 cells in skin tissues of psoriasis mice. Finally, in vitro assay confirmed that the activation of Th1 and Th17 mediated by NFKB1 in psoriasis promoted the proliferation, migration and invasion of keratinocytes. These findings suggest a critical role for NFKB1 in the regulation of Th1 and Th17 in psoriasis.

This study is the first attempt to comprehensively investigate deca-BDE and alternative flame retardants in a wastewater treatment plant in such a long term in China (2009-2016). Influent, effluent and sludge samples were collected. The mean concentration of deca-BDE, Σ19NBFRs and ΣDPs in influent were 311.5, 76.0 and 1.4ng/L, respectively, which were at the low end of the global range. The levels of deca-BDE, Σ19NBFRs and ΣDPs in effluent were range from 9.5-68.6, 4.1-38.5 and BLD-1.6ng/L, respectively. In sludge samples, the mean concentrations were 406.7, 510.5 and 6.9ng/g dw for deca-BDE, Σ19NBFRs and ΣDPs. The concentration of temporal trends in this study may reflected the release of those compounds. Compared to the beginning year of this study, the usage of deca-BDE was decreased but the usage of total NBFRs and DPs presented sustained increase over the sampling period. There were no significant variation of deca-BDE, NBFRs and DPs in the wastewater treatment plant in Harbin was observed in the four seasons except for NBFRs in influents, which the Σ19NBFRs mean concentration in influents in the summer was statistically significantly higher than that in winter indicating that NBFRs was easier impacted by temperature compared to deca-BDE and DPs. In addition, sorption and accumulation to sludge was the major removal mechanism for those compounds, accounting for 73.3% to 89.0%.

Objective This study was aimed to explore the effect of Bach2 on B cells in systemic lupus erythematosus (SLE), as well as the underlying mechanisms. Methods Expression of Bach2, phosphorylated-Bach2 (p-Bach2), Akt, p-Akt and BCR-ABL (p210) in B cells isolated from SLE patients and the healthy persons were assessed by Western blot. Immunofluorescence staining was performed to assess the localization of Bach2 in B cells. Enzyme-linked immunosorbent assay (ELISA) was employed to detect IgG produced by B cells. Cell counting kit-8 (CCK-8) and Annexin-V FITC/PI double staining assay were adopted to evaluate cell proliferation and apoptosis in B cells, respectively. Results Compared to the healthy controls, Bach2, p-Akt and p210 were significantly decreased, while nuclear translocation of Bach2, IgG, CD40 and CD86 obviously up-regulated in B cells from SLE patients. Bach2 significantly inhibited the proliferation, promoted apoptosis of B cells from SLE patients, whereas BCR-ABL dramatically reversed cell changes induced by Bach2. Besides, BCR-ABL also inhibited nuclear translocation of Bach2 in B cells from SLE patients. Further, LY294002 treatment had no effect on decreased expression of Bach2 induced by BCR-ABL, but significantly eliminated BCR-ABL-induced phosphorylation of Bach2 and restored reduced nuclear translocation of Bach2 induced by BCR-ABL in B cells from SLE. Conclusions Bach2 may play a suppressive role in B cells from SLE, and BCR-ABL may inhibit the nuclear translocation of Bach2 via serine phosphorylation through the PI3K pathway.

Synchronous colorectal cancers (syCRCs), which present two or more lesions at diagnosis, are rare and pose a great challenge for clinical management. Although some predisposing factors associated with syCRCs have been studied with limited accession, the full repertoire of genomic events among the lesions within an individual and the causes of syCRCs remain unclear. We performed whole-exome sequencing of 40 surgical tumour samples of paired lesions from 20 patients to characterize the genetic alterations. Lesions from same patient showed distinct landscapes of somatic aberrations and shared few mutations, which suggests that they originate and develop independently, although they shared the similar genetic background. Canonical genes, such as APC, KRAS, TP53 and PIK3CA, were frequently mutated in the syCRCs, and most of them show different mutation profile compared with solitary colorectal cancer. We identified a recurrent somatic alteration (K15fs) in RPL22 in 25% of the syCRCs. Functional analysis indicated that mutated RPL22 may suppress cell apoptosis and promote the epithelial–mesenchymal transition (EMT). Potential drug targets were identified in several signalling pathways, and they present great discrepancy between lesions from the same patient. Our data show that the syCRCs within the same patient present great genetic heterogeneity, and they may be driven by distinct molecular events and develop independently. The discrepancy of potential drug targets and mutation burden in lesions from one patient provides valuable information in clinical management for patients with syCRCs., The syCRCs within the same patient present great genetic heterogeneity and may be driven by distinct molecular events and develop independently. The discrepancy of potential drug targets in lesions from one patient provides valuable information in clinical management.

Vitiligo is an immune-related disease with patchy depigmentation of skin and hair caused by selective destruction of melanocytes. In recent decades, many studies have shown the association between vitiligo and HLA genes; however, the results of Han Chinese are scarce. In this study, we performed a fine-mapping analysis of the MHC region in 2818 Han Chinese subjects through a widely used HLA imputation method with a newly built large-scale Han-MHC reference panel. Three new four-digit HLA alleles (HLA-DQB1 ∗ 02:02, HLA-DQA1 ∗ 02:01 and HLA-DPB1 ∗ 17:01) were identified to be associated with the risk of vitiligo, and four previously reported alleles were confirmed. Further conditional analysis revealed that two important variants, HLA-DQβ1 amino acid position 135 (OR = 1.79, P = 1.87 × 10−11) and HLA-B amino acid positions 45–46 (OR = 1.44, P = 5.61 × 10−11), conferred most of the MHC associations. Three-dimension ribbon models showed that the former is located within the β2 domain of the HLA-DQβ1 molecule, and the latter lies in the α1 domain of the HLA-B molecule, while both are involved in specific antigen presenting process. Finally, we summarized all significant signals in the MHC region to clarify their complex relationships, and 8.60% of phenotypic variance could be explained based on all reported variants in Han Chinese so far. Our findings highlight the complex genetic architecture of the MHC region for vitiligo in Han Chinese population and expand our understanding of the roles of HLA coding variants in the etiology of vitiligo.

Importance Preventing anastomotic leakage (AL) is crucial for colorectal surgery. Some studies have suggested a positive role of transanal drainage tubes (TDTs) in AL prevention after low anterior resection, but this finding is controversial. Objective To assess the effect of TDTs in AL prevention after laparoscopic low anterior resection for rectal cancer. Design, setting, and participants This multicenter randomized clinical trial with parallel groups (TDT vs non-TDT) was performed from February 26, 2016, to September 30, 2020. Participants included patients from 7 different hospitals in China who were undergoing laparoscopic low anterior resection with the double-stapling technique for mid-low rectal cancer; 576 patients were initially enrolled in this study, and 16 were later excluded. Ultimately, 560 patients were randomly divided between the TDT and non-TDT groups. Interventions A silicone tube was inserted through the anus, and the tip of the tube was placed approximately 5 cm above the anastomosis under laparoscopy at the conclusion of surgery. The tube was fixed with a skin suture and connected to a drainage bag. The TDT was scheduled for removal 3 to 7 days after surgery. Main outcomes and measures The primary end point was the postoperative AL rate within 30 days. Results In total, 576 patients were initially enrolled in this study; 16 of these patients were excluded. Ultimately, 560 patients were randomly divided between the TDT group (n = 280; median age, 61.5 years [IQR, 54.0-68.8 years]; 177 men [63.2%]) and the non-TDT group (n = 280; median age, 62.0 years [IQR, 52.0-69.0 years]; 169 men [60.4%]). Intention-to-treat analysis showed no significant difference between the TDT and non-TDT groups in AL rates (18 [6.4%] vs 19 [6.8%]; relative risk, 0.947; 95% CI, 0.508-1.766; P = .87) or AL grades (grade B, 14 [5.0%] and grade C, 4 [1.4%] vs grade B, 11 [3.9%] and grade C, 8 [2.9%]; P = .43). In the stratified analysis based on diverting stomas, there was no significant difference in the AL rate between the groups, regardless of whether a diverting stoma was present (without stoma, 12 [5.8%] vs 15 [7.9%], P = .41; and with stoma, 6 [8.3%] vs 4 [4.5%], P = .50). Anal pain was the most common complaint from patients in the TDT group (130 of 280, 46.4%). Accidental early TDT removal occurred in 20 patients (7.1%), and no bleeding or iatrogenic colonic perforations were detected. Conclusions and relevance The results from this randomized clinical trial indicated that TDTs may not confer any benefit for AL prevention in patients who undergo laparoscopic low anterior resection for mid-low rectal cancer without preoperative radiotherapy. Trial registration ClinicalTrials.gov Identifier: NCT02686567.

Background Vitiligo is an autoimmune disease, characterized by progressive loss of skin pigmentation, which is caused by the interactions of multiple factors, such as heredity, immunity and environment. Recently, a single nucleotide polymorphism (SNP) rs638893 at 11q23.3 region was identified as a risk factor for vitiligo in genome-wide association studies and multiple SNPs in this region have been associated with other autoimmune diseases. Objective This study aims to identify additional susceptibility variants associated with vitiligo at 11q23.3 in the Chinese Han population. Methods We selected and genotyped 26 SNPs at 11q23.3 in an independent cohort including 2924 cases and 4048 controls using the Sequenom MassArray iPLEX® system. Bonferroni adjustment was used for multiple comparisons and P value

The human major histocompatibility complex (MHC) region has been shown to be associated with numerous diseases. However, it remains a challenge to pinpoint the causal variants for these associations because of the extreme complexity of the region. We thus sequenced the entire 5-Mb MHC region in 20,635 individuals of Han Chinese ancestry (10,689 controls and 9,946 patients with psoriasis) and constructed a Han-MHC database that includes both variants and HLA gene typing results of high accuracy. We further identified multiple independent new susceptibility loci in HLA-C, HLA-B, HLA-DPB1 and BTNL2 and an intergenic variant, rs118179173, associated with psoriasis and confirmed the well-established risk allele HLA-C*06:02. We anticipate that our Han-MHC reference panel built by deep sequencing of a large number of samples will serve as a useful tool for investigating the role of the MHC region in a variety of diseases and thus advance understanding of the pathogenesis of these disorders.

Objective To evaluate the efficacy and safety of lubiprostone in the treatment of chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C). Patients and Methods We performed a literature search of the MEDLINE, Cochrane, Google Scholar, and ClinicalTrials.gov databases (from January 1, 2005, through January 31, 2015). Relevant studies meeting the inclusion criteria were manually searched by 2 independent reviewers. Efficacy outcomes evaluated at 1 week, 1 month, and 3 months of intervention were weekly frequency of spontaneous bowel movements, severity of constipation, consistency of stools, degree of abdominal pain/discomfort, degree of straining, and abdominal bloating. Results Of 246 studies identified, data from 9 trials comprising 1468 patients (63.6%) in the lubiprostone group and 841 (36.4%) in the placebo group were analyzed. We found that lubiprostone treatment significantly improved the severity of constipation, stool consistency, abdominal pain, degree of straining, and abdominal bloating at 1 week ( P ≤.03) and 1 month ( P ≤.004), except for abdominal pain at 1 month, which was similar to that when treated with placebo ( P =.21). At 3 months, except for abdominal bloating ( P =.03), there was no difference between lubiprostone and placebo groups in all other outcomes ( P ≥.05). Adverse effects such as nausea, vomiting, and diarrhea were common (incidence rate, 2.4%-75%); however, the incidence of serious adverse effects was low ( Conclusion Lubiprostone is a safe and efficacious drug for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation, with limited adverse effects in 3 months of follow-up.

Generalized vitiligo is an autoimmune disease characterized by melanocyte loss, which results in patchy depigmentation of skin and hair, and is associated with an elevated risk of other immune-related diseases. However, there is no reported study on the associations between immune susceptibility polymorphisms and the risk of vitiligo with immune-related diseases. The aim of this study was to evaluate the potential influence of 10 single-nucleotide polymorphisms (SNPs) at 18q21.31 (rs10503019), 4p16.1 (rs11940117), 3q28 (rs1464510), 14q12 (rs2273844), 12q13.2 (rs2456973), 16q12.2 (rs3213758), 10q25.3 (rs4353229), 3q13.33 (rs59374417), and 10p15.1 (rs706779 and rs7090530) on vitiligo with immune-related diseases in the Chinese Han population. All SNPs were genotyped in 552 patients with vitiligo-associated immune-related diseases and 1656 controls using the Sequenom MassArray system. Data were analyzed with PLINK 1.07 software. The C allele of rs2456973 at 12q13.2 was observed to be significantly associated with vitiligo-associated immune-related diseases (autoimmune diseases and allergic diseases) (P = 0.0028, odds ratio (OR) = 1.27). In subphenotype analysis, the rs2456973 C allele was also significantly associated with early-onset vitiligo by comparing with controls (P = 0.0001) and in the case-only analysis (P = 0.0114). We confirmed that 12q13.2 was an important candidate locus for vitiligo with immune-related diseases (autoimmune diseases and allergic diseases) and affected disease phenotypes with early onset.

A cathartic colon is characteristic of slow transit constipation (STC), which can result following the long-term use of irritant laxatives. In the present study, the involvement of three opioid receptor subtypes (μ, MOR; δ, DOR; and κ, KOR), regulator of G protein signaling 4 (RGS-4) and β-arrestin-2 were investigated in the cathartic colon of rats. A rat model of a cathartic colon was established by feeding the animals with phenolphthalein, while normal rats were used as a control. The mRNA and protein expression levels of the opioid receptors, RGS-4 and β-arrestin-2 were detected in the rat colon using semi-quantitative reverse transcription polymerase chain reaction and western blot analysis, respectively. The rat model of a cathartic colon was successfully established using the phenolphthalein stimulus, and was shown to result in shrunken myenteric neurons and loose muscle fibers in the intestinal wall. The mRNA and protein expression levels of the three opioid receptor subtypes, RGS-4 and β-arrestin-2 were significantly higher in the cathartic colon group when compared with the levels in the normal control group (all P

The occurrence and fate of polycyclic aromatic hydrocarbons (PAHs) were investigated in wastewater, sludge and surrounding air from the wastewater treatment plant (WWTP) in Harbin, Northeast China. The concentration of total PAHs in the influent, effluent and sludge were 4080ng/L, 864ng/L and 8200ng/gdw, respectively. The total concentration of PAHs showed a trend of first rising, and then decreasing over years in the influent, effluent and sludge, which was in agreement with the usage of coal and oil in Harbin. The level of PAHs was 26-560ng/m3 in air from site 1 (the top of the A/O tank), 62-608ng/m3 in air from site 2 (the vicinity of the WWTP) and 61-686ng/m3 in air from site 3 (the urban district of Harbin). In the influent and effluent, the mean concentration of PAHs followed the sequence of summer>winter>autumn>spring, while the sequence was winter>summer>autumn>spring in sludge and air. Rainfall may be the main reason for higher contamination in summer. Coal fired central heating and indoor dust may be reasons for higher PAHs in winter. The mean removal efficiency of total PAHs was approximately 85% (20% of which was adsorbed onto sludge, and 65% volatilized into air or degraded by biodegradation), and 15% of PAHs were discharged through the effluent. There was approximately 6240kg of PAHs imported into the WWTP every year, 1005kg discharged into the Songhua River through the effluent, and 327kg absorbed onto sludge and the rest was degraded or volatilized into air. PCA was applied to identify the sources of PAHs for both heating and non-heating seasons. In general, coal combustion was the main source of PAHs during the heating season and vehicle exhaust was the main source of PAHs during the non-heating season.

ObjectivesSystemic lupus erythematosus (SLE) is a chronic autoimmune disease of considerable genetic predisposition. Genome-wide association studies have identified tens of common variants for SLE. However, the majority of them reside in non-coding sequences. The contributions of coding variants have not yet been systematically evaluated.MethodsWe performed a large-scale exome-wide study in 5004 SLE cases and 8179 healthy controls in a Han Chinese population using a custom exome array, and then genotyped 32 variants with suggestive evidence in an independent cohort of 13 246 samples. We further explored the regulatory effect of one novel non-coding single nucleotide polymorphism (SNP) in ex vivo experiments.ResultsWe discovered four novel SLE gene regions (LCT, TPCN2, AHNAK2 and TNFRSF13B) encompassing three novel missense variants (XP_016859577.1:p.Asn1639Ser, XP_016859577.1:p.Val219Phe and XP_005267356.1:p.Thr4664Ala) and two non-coding variants (rs10750836 and rs4792801) with genome-wide significance (pmeta −8). These variants are enriched in several chromatin states of primary B cells. The novel intergenic variant rs10750836 exhibited an expression quantitative trait locus effect on the TPCN2 gene in immune cells. Clones containing this novel SNP exhibited gene promoter activity for TPCN2 (P=1.38×10−3) whose expression level was reduced significantly in patients with SLE (P−2) and was suggested to be further modulated by rs10750836 in CD19+ B cells (P=7.57×10−5) in ex vivo experiments.ConclusionsThis study identified three novel coding variants and four new susceptibility gene regions for SLE. The results provide insights into the biological mechanism of SLE.

MicroRNA-107 (miR-107) has been demonstrated to regulate proliferation and apoptosis in many types of cancers. Nevertheless, its biological function in gastric cancer remains largely unexplored. Here, we found that the expression level of miR-107 was increased in gastric cancer in comparison with the adjacent normal tissues. The enforced expression of miR-107 was able to promote cell proliferation in NCI-N87 and AGS cells, while miR-107 antisense oligonucleotides (antisense miR-107) blocked cell proliferation. At the molecular level, our results further revealed that expression of FOXO1 was negatively regulated by miR-107. Therefore, the data reported here demonstrate that miR-107 is an important regulator in gastric cancer, which will contribute to a better understanding of the important mis-regulated miRNAs in gastric cancer.

To elucidate the relationship between dynamic variations of insular β cell mitochondria and type-2 diabetes by using a mouse model, the dynamic variation (fusion or fission) of insular β cell mitochondria present in two groups of Wistar mice with type-2 diabetes (high fat feeding and streptozotocin (STZ) adding with low dose and high frequency, high fat feeding and STZ adding with high dose and low frequency), and normal Wistar mouse were systematically compared. By analysing the insulin secretion level and other related indexes, the molecular mechanism of the fusion or fission phenomenon of insular β cell mitochondria in two different models (high fat feeding and STZ adding with low dose and high frequency, high fat feeding and STZ adding with high dose and low frequency) of mice with type-2 diabetes were initially elucidated. The phenomenon of mitochondrial fusion and fission was clearly seen. In initially determining the relationship between the change of insular β cell mitochondrial structure and its cell apoptosis generated by some factors such as treatment by glucose-oxidase (GO), the effect of GO on the mouse islet cells RIN-m5F including the effects on cell growth, reactive oxygen species (ROS), cell cycle, cell apoptosis of RIN-m5F were systematically examined. GO showed some influence on the mouse islet cells RIN-m5F cell activity, ROS and apoptosis, but its effect on the cell cycle was not significant.

There are many studies performed to assess the associations of CD95 A670G and G1377A polymorphisms with gastric cancer, and the association of CD95L T844C polymorphism with gastric cancer risk, but the data are remaining controversial. To get a comprehensive assessment of the association above, we performed a meta-analysis of published studies. PubMed, Embase, Web of Science, and Wanfang Medicine databases were searched for eligible studies. There were eight studies including 3,790 subjects on CD95 A670G polymorphism, eight studies including 4,563 subjects on CD95 G1377A polymorphism, and eight studies including 4,563 subjects on CD95L T844C polymorphism. Overall, CD95 G1377A polymorphism was associated with a significantly increased risk of gastric cancer (for AA versus GG: odds ratio (OR) = 1.24, 95 % confidence interval (95 % CI) = 1.02–1.52, P = 0.030; for AA versus GG + GA: OR = 1.27, 95 % CI = 1.05–1.53, P = 0.012). However, there were no associations of CD95 A670G and CD95L T844C polymorphisms with gastric cancer. Subgroup analysis by ethnicity found similar associations in Asians, but the associations in Caucasians were still unclear owing to the lack of relevant data. Therefore, the outcomes of this meta-analysis show that there is a significant association between CD95 G1377A polymorphism and risk of gastric cancer.

We extended our previous genome-wide association study for psoriasis with a multistage replication study including 8,312 individuals with psoriasis (cases) and 12,919 controls from China as well as 3,293 cases and 4,188 controls from Germany and the United States and 254 nuclear families from the United States. We identified six new susceptibility loci associated with psoriasis in the Chinese study containing the candidate genes ERAP1, PTTG1, CSMD1, GJB2, SERPINB8 and ZNF816A (combined P < 5 × 10⁻⁸) and replicated one locus, 5q33.1 (TNIP1-ANXA6), previously reported (combined P = 3.8 × 10⁻²¹) in the European studies. Two of these loci showed evidence for association in the German study at ZNF816A and GJB2 with P = 3.6 × 10⁻³ and P = 7.9 × 10⁻³, respectively. ERAP1 and ZNF816A were associated with type 1 (early onset) psoriasis in the Chinese Han population (test for heterogeneity P = 6.5 × 10⁻³ and P = 1.5 × 10⁻³, respectively). Comparisons with the results of previous GWAS of psoriasis highlight the heterogeneity of disease susceptibility between the Chinese and European populations. Our study identifies new genetic susceptibility factors and suggests new biological pathways in psoriasis.

Interaction of c-Kit and its ligand stem cell factor (SCF) is necessary for appropriate development and survival of interstitial cells of Cajal (ICC) in the intestine. Blockade of c-Kit will cause ICC loss in vivo. Stem cell leukemia (SCL) gene acts as a positive regulator of upstream transcription of c-Kit expression. This study aimed to explore whether the restoration of c-Kit expression promoted by SCL gene transfer could rescue ICC in vivo.A modified ICC-loss mouse model was created by continual administration of anti-c-Kit antibody (ACK2) to obtain a steady status of ICC loss, and a recombinant adenovirus vector containing SCL gene (Ad-SCL) was designed to rescue ICC in these mice. Western blot analysis and immunofluorescence labeling assays were performed to analyze the SCL and c-Kit expression in vitro and in vivo. The distribution and configuration of ICC were observed with immunohistochemistry and electromicroscope.Western blot analysis and immunofluorescence labeling assays showed that SCL gene was successfully delivered to cultured HeLa and ICC cells in vitro. Moreover, significantly increased c-Kit expression could be detected in the colon of Ad-SCL-infected ICC-loss mice. Furthermore, rescue of the ICC network and ICC with typical ultrastructural features could be detected in Ad-SCL-infected ICC-loss mice at day 37.Ad-SCL was able to enhance c-Kit expression, reactivate the c-Kit/SCF pathway, and rescue ICC in ICC-loss mice. Since loss and defects of ICC are associated with many human gut motility disorders, Ad-SCL may be of potential use in gene therapy of these patients.

We performed a genome-wide association study (GWAS) of systemic lupus erythematosus (SLE) in a Chinese Han population by genotyping 1,047 cases and 1,205 controls using Illumina Human610-Quad BeadChips and replicating 78 SNPs in two additional cohorts (3,152 cases and 7,050 controls). We identified nine new susceptibility loci (ETS1, IKZF1, RASGRP3, SLC15A4, TNIP1, 7q11.23, 10q11.22, 11q23.3 and 16p11.2; 1.77 x 10(-25) < or = P(combined) < or = 2.77 x 10(-8)) and confirmed seven previously reported loci (BLK, IRF5, STAT4, TNFAIP3, TNFSF4, 6q21 and 22q11.21; 5.17 x 10(-42) < or = P(combined) < or = 5.18 x 10(-12)). Comparison with previous GWAS findings highlighted the genetic heterogeneity of SLE susceptibility between Chinese Han and European populations. This study not only advances our understanding of the genetic basis of SLE but also highlights the value of performing GWAS in diverse ancestral populations.

The receptor tyrosine kinase EPHB2 has recently been identified as a TCF4 transcriptional target that controls the intestinal epithelial architecture through repulsive interactions with Ephrin-B ligands. Many reports have demonstrated that most human colorectal cancers lose EPHB2 expression despite constitutive Wnt activation. Therefore, we investigated the mechanisms that cause EPHB2 down-regulation in colorectal cancer. In this study, we demonstrate that DNA hypermethylation was not responsible for the frequent loss of EPHB2 expression in colorectal cancer. Cloning and functional characterization of the EPHB2 gene 5'-flanking region revealed a potential negative regulatory element in the distal regulatory region. In vitro electrophoretic gel mobility shift and in vivo chromatin immunoprecipitation assays demonstrated that c-Rel directly binds to the putative element. Inhibiting c-Rel activity or knocking down c-Rel expression by RNA interference in colon cancer cells was sufficient to induce EPHB2 expression. Furthermore, transient transfection assays demonstrated that c-Rel over-expression repressed endogenous EPHB2 expression in colon cancer cells. We demonstrate for the first time that c-Rel acts as a transcriptional repressor of EPHB2 and plays an active role in EPHB2 down-regulation in colorectal cancers.

Psoriasis is a common inflammatory skin disease with complex genetics and different degrees of prevalence across ethnic populations. Here we present the largest trans-ethnic genome-wide meta-analysis (GWMA) of psoriasis in 15,369 cases and 19,517 controls of Caucasian and Chinese ancestries. We identify four novel associations at LOC144817, COG6, RUNX1 and TP63, as well as three novel secondary associations within IFIH1 and IL12B. Fine-mapping analysis of MHC region demonstrates an important role for all three HLA class I genes and a complex and heterogeneous pattern of HLA associations between Caucasian and Chinese populations. Further, trans-ethnic comparison suggests population-specific effect or allelic heterogeneity for 11 loci. These population-specific effects contribute significantly to the ethnic diversity of psoriasis prevalence. This study not only provides novel biological insights into the involvement of immune and keratinocyte development mechanism, but also demonstrates a complex and heterogeneous genetic architecture of psoriasis susceptibility across ethnic populations., Psoriasis is a common inflammatory skin disease with complex genetics and different degrees of prevalence across ethnic populations. Here Yin et al. conduct a large trans-ethnic genome-wide meta-analysis and identify novel loci that contribute to population-specific susceptibility.

Background Vitiligo is an acquired depigmentary disorder of the skin and hair which results from selective destruction of melanocytes. Serological typing and genotyping of human leukocyte antigen (HLA) have shown discrepancies in HLA associations with vitiligo in different ethnic populations. Methods Polymerase chain reaction sequence-specific primer (PCR-SSP) method was used to analyze the distribution of HLA-DQA 1 and -DQB 1 alleles among 187 patients with vitiligo and 273 healthy controls through Epi Info version 6 package (Centers for Disease Control and Prevention, Atlanta, GA, USA). Results The frequencies of HLA-DQA1 *0302 (OR = 1.98, P c < 0.01), -DQB1 *0303 (OR = 3.14, P c < 0.001), and -DQB1*0503 (OR = 3.36, P c < 0.05) alleles were significantly increased in patients with vitiligo compared with controls, and HLA-DQA 1 *0501 (OR = 0.40, P c < 0.01) allele frequency was highly decreased. HLA-DQA1 *0302 (OR = 5.19, P c < 0.001), -DQA1*0601 (OR = 2.95, P c < 0.05), -DQB1 *0303 (OR = 4.50, P c < 0.001), and -DQB1 *0503 (OR = 6.69, P c < 0.001) alleles were positively associated, whereas HLA-DQA1*0501 (OR = 0.05, P c < 0.001) allele was negatively associated with childhood vitiligo patients, and HLA-DQB1*0303 (OR = 2.76, P c < 0.001) allele was positively associated with adult vitiligo patients compared with controls. The frequency of HLA-DQB1*0303 (OR = 3.72, P c < 0.001) allele was significantly increased in localized vitiligo patients vs. controls, whereas HLA-DQA1*0302 (OR = 2.47, P c < 0.01), -DQB1 *0303 (OR = 2.67, P c < 0.01), and -DQB1 *0503 (OR = 4.46, P c < 0.01) allele frequencies were significantly increased and -DQA1 *0501 (OR = 0.27, P c < 0.01) allele frequency was highly decreased in generalized vitiligo patients. Conclusions HLA-DQA1 *0302, -DQA1*0601, -DQB1 *0303, and -DQB1 *0503 alleles could be susceptible alleles of vitiligo, while HLA-DQA1*0501 allele could be a protective allele in Chinese Hans. There may be different genetic backgrounds between vitiligo patients of childhood and adult, localized and generalized.

Background Psoriasis vulgaris is a chronic skin disorder characterized by infiltration of inflammatory elements, keratinocyte hyperproliferation and altered differentiation. Although the pathogenesis of psoriasis is not fully understood, there is solid evidence of a susceptibility locus in the human leukocyte antigen (HLA) region. Objectives To investigate whether HLA-DQA1 and DQB1 alleles are associated with genetic susceptibility to psoriasis vulgaris in Chinese Han. Patients and methods The polymerase chain reaction–sequence-specific primer (PCR-SSP) method was used to analyse the distribution of HLA-DQA1 and DQB1 alleles in 189 patients with psoriasis and 273 healthy controls. Results The HLA-DQA1*0104 (OR = 2.33, P = 0.0001154, Pc = 2.0 × 10−3), DQA1*0201 (OR = 3.36, P 0.05) and DQB1*0303 (OR = 1.55, P = 0.0377, Pc > 0.05) alleles were more prevalent in patients with psoriasis vulgaris than in controls, and HLA-DQA1*0501 (OR = 0.30, P = 0.0000039, Pc

This study aims to investigate the influence of total colectomy with ileorectal anastomosis (IRA) and subtotal colectomy with cecorectal anastomosis (CRA) on curative effects, nutritional status, and health of patients with slow transit constipation (STC).The purpose of the present study is to compare the hemoglobin, the total protein level, the albumin, and the percentage of lymphocytes before and after operations. The 36-item short-form health survey questionnaire (SF-36), the mininutritional assessment (MNA), the postoperative general condition questionnaire, and the social activities questionnaire were used. The questionnaires were modified. The patients with higher scores were shown to recover better postoperatively.More than 87.5 % of patients in both groups were satisfied with the surgery. Increased stool frequency was improved 6 months after surgery. Antidiarrheal agent use, abdominal pain, and distention in the IRA group were more frequent than in the CRA group (p 0.05). Postoperative levels of hemoglobin, total protein level, albumin, and percentage of lymphocytes in the IRA group were higher than in the CRA group (p 0.05). There was no difference in MNA for both groups (p 0.05). There was no difference in the postoperative general condition questionnaire for both groups (p 0.05). But the scores for health condition, emotion, and feeling for life were low, only 68.8 to 82.4 % at their highest.Symptoms can be relieved by IRA and CRA surgeries. The postoperative nutritional conditions are fine. Health conditions and social life are affected. Both IRA and CRA surgeries are compliant for the treatment of STC.

Background Disseminated superficial actinic porokeratosis (DSAP) is a rare autosomal dominant genodermatosis characterised by annular lesions that has an atrophic centre and a prominent peripheral ridge distributed on sun exposed area. It exhibits high heterogeneity, and five linkage loci have been reported. The mevalonate kinase ( MVK ) gene located on 12q24 has been confirmed as one of the disease-causing genes. But, the pathogenesis of a large part of DSAP remains unclear so far. Methods The recruited with DSAP carried no MVK coding mutations. Exome sequencing was performed in two affected and one unaffected individual in Family 1. Cosegregation of the candidate variants was tested in other family members. Sanger sequencing in 33 individuals with familial DSAP and 19 sporadic DSAP individuals was performed for validating the causative gene. Results An average of 1.35×10 5 variants were generated from exome data and 133 novel NS/SS/indels were identified as being shared by two affected individuals but absent in the unaffected individual. After functional prediction, 25 possible deleterious variants were identified. In Family 1, a missense variant c.932G>A (p.Arg311Gln) in exon 10 of SLC17A9 was observed in cosegregation with the phenotype; this amino acid substitution was located in a highly conserved major facilitator superfamily (MFS) domain in multiple mammalian. One additional missense variant c.25C>T (p.Arg9Cys) in exon 2 of SLC17A9 was found in Family 2. Conclusions The result identified SLC17A9 as another pathogenic gene for DSAP, which suggests a correlation between the aberrant vesicular nucleotide transporter and the pathogenesis of DSAP.

The -1082A>G polymorphism is located in promoter region of interleukin-10 (IL-10) and it could affect the production of IL-10. Numerous studies have investigated the association between IL-10 -1082A>G and risk of digestive cancer. However, the conclusion is still inconsistent. Here, we have performed a meta-analysis and systematic review to determine the association between the IL-10 -1082A>G and susceptibility to digestive cancer. In this meta-analysis, we identified 40 eligible studies, involving 7195 patients of digestive cancer and 11755 controls. By pooling all eligible studies, we found the variant -1082G allele significantly increased risk of digestive cancer (G vs. A: OR = 1.181, 95% CI: 1.057–1.319). Further stratified analysis was performed to evaluate the influence of cancer types, ethnicities, study design, sample size and Hardy–Weinberg equilibrium. Stratified analysis suggested that, the -1082A>G polymorphism was only associated with increased risk for gastric cancer (G vs. A: OR = 1.281, 95% CI: 1.102–1.488) and in Asian population (G vs. A: OR = 1.399, 95% CI: 1.188–1.646). No significant publication bias was detected. Based on 40 studies and 18950 participants, we found the variant IL-10 -1082G allele significantly increased susceptibility to digestive cancer, especially for gastric cancer and in Asian population.

To explore the contribution of functional coding variants to psoriasis, we analyzed nonsynonymous single-nucleotide variants (SNVs) across the genome by exome sequencing in 781 psoriasis cases and 676 controls and through follow-up validation in 1,326 candidate genes by targeted sequencing in 9,946 psoriasis cases and 9,906 controls from the Chinese population. We discovered two independent missense SNVs in IL23R and GJB2 of low frequency and five common missense SNVs in LCE3D, ERAP1, CARD14 and ZNF816A associated with psoriasis at genome-wide significance. Rare missense SNVs in FUT2 and TARBP1 were also observed with suggestive evidence of association. Single-variant and gene-based association analyses of nonsynonymous SNVs did not identify newly associated genes for psoriasis in the regions subjected to targeted resequencing. This suggests that coding variants in the 1,326 targeted genes contribute only a limited fraction of the overall genetic risk for psoriasis.

Patients with cancer frequently develop autoantibodies. The identification of tumor autoantigens may have utility in early cancer diagnosis and immunotherapy. In this study, we used serological proteomics analysis (SERPA) to identify tumor proteins that elicit humoral response in colorectal cancer (CRC). The CRC cell line HCT116 was used as a source of proteins for 2-DE and subsequent Western blot analysis in which individual serum from patients with CRC was analyzed for autoantibodies. An autoantibody against HSP60 identified by MS was detected in 13 out of 25 patients with CRC and 1 out of 15 healthy subjects. In addition, the HSP60 expressions in tumor tissues collected from 40 patients with CRC were assessed by immunohistochemistry, and serum specimens from 100 patients with cancer and 30 healthy controls were screened for antibody titer to HSP60 by ELISA. The results showed that expressions of HSP60 in tumor tissue and serum antibody titer to HSP60 were significantly higher in patients with CRC than in healthy subjects. Thus, we conclude that the SERPA is an excellent assay for the identification of tumor-associated antigens and tumor markers. The detection of HSP60 may have clinical utility in CRC screening, diagnosis, and immunotherapy.

Summary Background Some studies have suggested that human HLA status might potentiate development of keloids phenotype, and exists ethnic differences. No report has been published about HLA-DQA1 and DQB1 alleles associated with keloids in Chinese Hans. Objectives To investigate whether HLA-DQA1 and DQB1 alleles are associated with genetic susceptibility to keloids in Chinese Hans. Methods Polymerase chain reaction-sequence-specific primer (PCR-SSP) method was used to analyze the distribution of HLA-DQA1 and DQB1 alleles among 192 patients with keloids and 273 healthy controls in Chinese Hans. Results (1) The frequencies of HLA-DQA1*0104, DQB1*0501 and DQB1*0503 (OR = 2.13, P c = 0.0063; OR = 14.42, P c −7 and OR = 6.09, P c −7 , respectively) were significantly higher, while the frequencies of DQA1*0501, DQB1*0201 and DQB1*0402 (OR = 0.46, P c = 0.0099; OR = 0.24, P c −4 and OR = 0.10, P c = 0.0054, respectively) were lower in patients than in controls. (2) In this study significant susceptibility haplotypes to keloids were DQA1*0104–DQB1*0501 and DQA1*0104–DQB1*0503. (3) HLA-DQB1*0501 and DQB1*0503 were positively associated with all subgroups of keloid patients. However, the DQA1*0104 (OR = 2.51, P c = 0.0009; OR = 2.22, P c = 0.0090 and OR = 2.20, P c = 0.0117, respectively) was only prevalent in keloid patients with single site, moderate severity and negative family history. (4) HLA-DQB1*0201 (OR = 0.27, P c = 0.0018 and OR = 0.27, P c = 0.0012, respectively) and DQB1*0402 (OR = 0.07, P c = 0.0270 and OR = 0.07, P c = 0.0306, respectively) were negatively associated with moderate severity and negative family history in keloids, moreover, HLA-DQB1*0201 (OR = 0.23, P c = 0.0003) and DQA1*0501 (OR = 0.43, P c = 0.0234) were less prevalent in patients with single site. Conclusion This study demonstrated the positive association of HLA-DQA1 and DQB1 alleles and haplotypes with keloids.

Summary Haplotype associations of the major histocompatibility complex (MHC) with psoriasis vulgaris (PV) have been demonstrated in different racial or ethnic populations. The objective of this study was to demonstrate the different haplotype associations of the MHC in Chinese patients with psoriasis according to the type of onset and their sex. One hundred and thirty-eight patients with PV and 149 normal control subjects without psoriasis were typed for HLA-A, -B, -C, -DQA1, -DQB1 and -DRB1 by using the PCR with sequence-specific primers. The results showed: (i) HLA-A*26 (26.1% vs. 12.1%, Pc < 1 x 10(-5)), -B*27 (17.03% vs. 1.01%, Pc < 1 x 10(-7)), -Cw*0602 (15.58% vs. 5.03%, Pc < 1 x 10(-2)), -DQA1*0104 (19.93% vs. 9.40%, Pc < 1 x 10(-3)), -DQA1*0201 (22.40% vs. 10.74%, Pc < 1 x 10(-3)), -DQB1*0303 (18.12% vs. 9.73%, Pc < 1 x 10(-7)), and -DRB1*0701/02 (26.09% vs. 9.73%, Pc < 1 x 10(-7)) were significantly increased in PV patients, while HLA-B*57, -DQB1*0201 were slightly increased in PV patients. HLA-Cw*0304 (5.07% vs. 14.43%, Pc < 1 x 10(-3)), -DQA1*0501 (5.79% vs. 14.09%, Pc < 0.05) were found to be negatively associated with PV, but HLA-A*2 (2.54% vs. 6.38%, Pc < 0.5) was decreased in PV patients without statistical significance. (ii) HLA-A*26-B*27 [P < 0.0001, odds ratio (OR) = 48.38], -A*26-Cw*0602 (P < 0.0001, OR = 11.84), -B*27-Cw*0602 (P < 0.0001, OR = undefined), -DRB1*0701/02-B*27 (P < 0.0001, OR = 22.62), -DRB1*0701/02-DQA1*0104 (P < 0.0002, OR = 3.59), -DRB1*0701/02-DQB1*0303 (P < 0.0001, OR = 5.63), -DQA1*0201-DQB1*0303 (P < 0.0002, OR = 7.77), -A*26-B*27-Cw*0602 (P < 0.0004, OR = undefined), -A*26-DRB1*0701/02-DQA1*0201-DQB1*0303 (P < 0.01, OR = undefined) were identified as risk haplotypes for patients with PV in China. (iii) HLA-A*26 -B*27 (P < 0.0001, OR = 58.47), -DQA1*0201-DQB1*0303 (P < 0.0001, OR = 8.62), -DRB1*0701/02 -DQA1*0104 (P < 0.0002, OR = 4.13), -DRB1*0701/02-DQB1*0303 (P < 0.0001, OR = 6.68) and -A*26-DRB1*0701-DQA1*0201 -DQB1*0303 (P < 0.006, OR = undefined) were only significantly associated with type I psoriasis compared with controls, while others showed no differences in either type I or type II psoriasis. (iv) These associated haplotypes with PV were not different by sex, except that the frequency of DRB1*0701/02-DQB1*0303 (P < 0.0001, OR = 10.14) was higher in male patients with psoriasis. To summarize, this study demonstrated a differential association of HLA and identified some special risk haplotypes in Chinese patients with PV compared with other ethnic or racial populations.

Background: Predisposing genetic factors in psoriasis include associations with human leukocyte antigen (HLA). Accumulative evidence has shown that certain HLA at class I locus, especially HLA-Cw6, are associated closely with psoriasis. Objective: To evaluate the association of HLA class I alleles with susceptibility to psoriasis in the southeastern Chinese Han population. Methods: We performed genotype for HLA-A, -B and -C loci in 166 patients with psoriasis vulgaris by means of polymerase chain reaction with sequence-specific primers technique. The distribution of HLA allelic frequencies was further analyzed according to age of onset, i.e. under 35-y and beyond 35-y groups. These data were compared with the healthy controls of 204 unrelated Hans. Results: The frequencies of HLA-A*26 (24.7% vs. 13.1%, OR=2.36, P c 0.01), -B*13 (27.2% vs. 14.8%, OR=2.34, P c 0.01), -B*27 (12.2% vs. 4.0%, OR=3.49, P c 0.01) and -Cw*0602 (17.9% vs. 5.3%, OR=4.20, P c 0.001) were significantly increased in psoriasis patients, whereas HLA-Cw*0304 frequency (4.9% vs. 13.4%, OR=0.32, P c 0.01) was highly decreased, when compared to the controls. HLA-A*26-B*27-Cw*0602 was identified as a high-risk haplotype of HLA class I in developing psoriasis in the test. HLA-Cw*0602 was found to be strongly associated with the early-onset psoriasis (age of onset Conclusion: This study demonstrated the positive associations of HLA class I markers with psoriasis vulgaris, of which HLA-Cw*0602 was the strongest susceptibility determinant for development of early-onset psoriasis, in the southeastern Chinese Han population.