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Supplementary Methods

Supplementary Table 8. Sequence of primers for real-time PCR. Supplementary Table 9. Sequence of primers for CHIP real-time PCR.

Supplementary Table 5. Proteins in the two distict bands specific to GClnc1 identified by Liquid Chromatography-Mass Spectrometry.

Supplementary Table 4. RNA-seq analysis in BGC823 cells after GClnc1 shRNA and control shRNA transfection.

Supplementary Table 6. A, ChIP-Seq Library Statistics. B, ChIP-Seq Library Peak Calls. C, WDR5 and KAT2A peaks within 2kb of RefSeq gene promoters where read coverage were significant decreased in BGC823 GC cells after transduction of GClnc1 shRNA virus,compared with transduction of control shRNA virus. D, the differentiated expression genes in BGC823 cells after downregulation of GClnc1. E, Intersection of ChIP-Seq and RNA seq data. Supplementary Table 7. The association between GClnc1 with target genes in the coexpression network analysis.

Supplementary Figure 1, related to Figure 1. Clinical relevance of lncRNA candidate BC041951 in gastric cancer. Supplementary Figure 2, related to Figure 2. Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA) in gastric cancer cells and gastric cancer patients with high and low GClnc1 expression. Supplementary Figure 3, related to Figure 3. GClnc1 is an oncogenic lncRNA in gastric cancer. Supplementary Figure 4, related to Figure 4. GClnc1 interacts with WDR5 and KAT2A epigenetic modification complex. Supplementary Figure 5, related to Figure 5. GClnc1 coordinates the localization of WDR5 and KAT2A genome-wide. Supplementary Figure 6, related to Figure 6. GClnc1 promotes gastric cancer progression via SOD2. Supplementary Figure 7, related to Figure 7. GClnc1 is a molecular link among WDR5/KAT2A and SOD2.

Fig. S1. RNF6 genomic amplification is prevalent in colorectal cancer and correlated with shortened patient survival. Fig. S2. RNF6 is clinically relevant in colorectal cancer. Fig. S3. Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA) in RNF6-higher/lower expression CRC cells and patients, and RNF6 is an oncogenic gene. FigureS4. RNF6 upregulates pSTAT3 via downregulating SHP-1 expression. Figure S5. RNF6 Interacts with SHP-1 and enhances ubiquitylation and degradation of SHP-1. Figure S6. Effectiveness of pSTAT3 inhibitors in treating RNF6-amplified tumors.

Supplementary Material and Methods clean

Fig. S1. RNF6 genomic amplification is prevalent in colorectal cancer and correlated with shortened patient survival. Fig. S2. RNF6 is clinically relevant in colorectal cancer. Fig. S3. Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA) in RNF6-higher/lower expression CRC cells and patients, and RNF6 is an oncogenic gene. FigureS4. RNF6 upregulates pSTAT3 via downregulating SHP-1 expression. Figure S5. RNF6 Interacts with SHP-1 and enhances ubiquitylation and degradation of SHP-1. Figure S6. Effectiveness of pSTAT3 inhibitors in treating RNF6-amplified tumors.

Table S1.Expression of human ubiquitin ligase genes in 246 CRC patients of TCGAdatabase.TableS2.Clinial information of 62 cases CRC patients (fresh tissues).Table S3.Clinial information of 78 cases CRC patients (paraffin tissues).Table S4.Clinial information of 97 cases CRC patients (paraffin tissues).Table S5.RNA sequence data. TableS 6. Primer sequences

Objective: The E3 ubiquitin ligase RNF6 (RING-finger protein 6) plays a crucial role in carcinogenesis. However, the copy number and expression of RNF6 were rarely reported in colorectal cancer. We aimed to explore the mechanical, biological, and clinical role of RNF6 in colorectal cancer initiation and progression.Design: The copy number and expression of RNF6 were analyzed from Tumorscape and The Cancer Genome Atlas (TCGA) datasets. Gene expressions were examined by real-time PCR, Western blot, and immunohistochemical staining. Gene expression profiling studies were performed to identify pivotal genes regulated by RNF6. Biological function of RNF6 on tumor growth and metastasis was detected in vivo and in vitro. Role of RNF6 in modulating SHP-1 expression was examined by coimmunoprecipitation and confocal microscopy, respectively.Results: The copy number of RNF6 was significantly amplified in colorectal cancer, and the amplification was associated with RNF6 expression level. Amplification and overexpression of RNF6 positively correlated with patients with colorectal cancer with poor prognosis. The gene set enrichment analysis (GSEA) revealed cell proliferation, and invasion-related genes were enriched in RNF6 high-expressed colorectal cancer cells as well as in patients from TCGA dataset. Downregulation of RNF6 impaired the colorectal cancer cell proliferation and invasion in vitro and in vivo. RNF6 may activate the JAK/STAT3 pathway and increase pSTAT3 levels by inducing the ubiquitination and degradation of SHP-1.Conclusions: Genomic amplification drives RNF6 overexpression in colorectal cancer. RNF6 may be a novel biomarker in colorectal carcinogenesis, and RNF6 may increase pSTAT3 level via promoting SHP-1 ubiquitylation and degradation. Targeting the RNF6/SHP-1/STAT3 axis provides a potential therapeutic option for RNF6-amplified tumors. Clin Cancer Res; 24(6); 1473–85. ©2017 AACR.

Objectives: To investigate whether cytomegalovirus (CMV) infection plays a role in the pathogenesis and prognosis of idiopathic inflammatory myopathy (IIM), particularly in anti-MDA5 antibody-positive (anti-MDA5+) dermatomyositis (DM).Methods: A prospective cohort of 204 newly diagnosed IIM patients and 50 healthy individuals were enrolled in the study. CMV-IgM and CMV-IgG antibody concentrations and lymphocyte counts were analyzed. Differences in categorical data were compared using Fisher's exact test and the chi-square test. One-year survival rates were analyzed in MDA5+ DM patients with and without CMV infection.Results: In IIM patients, the median CMV-IgM level was significantly higher than in healthy controls (6 U/mL vs. 0 U/mL, p < 0.05) as was the median CMV-IgG level (114 U/mL vs. 105 U/mL, p < 0.05). The percentage of recent CMV infections in the MDA5+ DM group was much higher than it was in the MDA5− IIM group (19.1% vs. 7.0%, p = 0.009). MDA5+ DM patients with CMV DNA-emia had poorer 1 year survival than the CMV-DNA− group (33.3% vs. 86.3%, p = 0.010). CMV-IgM-positive (CMV-IgM+) MDA5+ DM patients had lower CD4+ T cell counts (245.7 cells/μL vs. 420.5 cells/μL, p < 0.05) and CD19+ B cell counts (97.3 cells/μL vs. 240.6 cells/μL, p < 0.05).Conclusion: The number of CMV infections was significantly higher in IIM patients, particularly in MDA5+ DM patients. Lower CD4+ T cells and CD19+ B cells were observed in CMV-IgM+ MDA5+ DM patients. CMV infection may have an important role in the pathogenesis and prognosis of MDA5+ DM by disrupting immunity.

Background Idiopathic inflammatory myopathies (IIM) are associated with a significantly higher risk of opportunistic infections including Pneumocystis jirovecii pneumonia (PJP), a potentially fatal opportunistic infection. However, no prior studies have evaluated PJP infection in subtypes of IIM. Objectives To investigate the prevalence and mortality rate of PJP infection in subgroups of IIM patients stratified according to myopathy-specific antibodies. Methods In the first part of the study, 463 consecutive patients with IIM were prospectively followed for a period of at least 1 year to analyze the incidence of PJP. In the second part of the study, we enrolled 30 consecutive PJP patients with any rheumatic disease in order to identify the mortality rate and risk factors by Cox regression analysis. The Kaplan-Meier method with log-rank testing was used to assess differences in survival. Results The prevalence of PJP in IIM patients was found to be 3.0/100 person-years, while in MDA5+ DM patients it was 7.5/100 person-years and in MDA5− IIM patients 0.7/100 person-years (P < 0.05). PJP typically occurred in the first 2 months in the case of MDA5+ DM patients who had a significant decrease in their CD4+ T cell counts and lymphocyte counts (P < 0.05). In PJP patients, 3-month mortality was higher for MDA5+ DM patients than in those with other rheumatic diseases (83.3% vs 38.9%, P < 0.05). Alarmingly, MDA5+ DM patients seemed not to benefit from prompt anti-PJP treatment, unlike patients with other rheumatic diseases whose survival improved when anti-PJP treatment was started within 6 days (P < 0.05). Conclusion PJP has an alarming high incidence and mortality in MDA5+ DM patients. Timely treatment for PJP seems not to improve the prognosis of patients with this particular subtype. Hence, there remains a crucial unmet need to develop PJP prophylaxis for MDA5+ DM patients.

Neurolisteriosis is a foodborne infection of the central nervous system that is easily misdiagnosed, especially in healthy adults with atypical symptoms. A 50-year-old man presented with a 3-day history of distortion of the oral commissure. Facial neuritis was diagnosed and treated with intravenous dexamethasone. His condition deteriorated rapidly, and he presented with a slow pharyngeal reflex, stiff neck, and signs of peripheral facial paralysis. Brain magnetic resonance imaging revealed multiple ring-enhanced foci in the brainstem. Routine and biochemical cerebrospinal fluid (CSF) analyses showed increased white blood cells and microproteins. Blood culture and high-throughput genome sequencing revealed Listeria monocytogenes DNA in the CSF. Ampicillin, amikacin, and meropenem were administered, and the patient was transferred from the intensive care unit to a standard medical ward after 2 months. The patient could walk and eat normally; however, he required intermittent mechanical ventilation at 11 months after discharge. Although L. monocytogenes meningitis is rare in healthy immunocompetent adults, it must be considered as a differential diagnosis, especially in adults whose conditions do not improve with cephalosporin antibiotic administration. L. monocytogenes rhombencephalitis mimics facial neuritis and develops quickly. Prompt diagnosis is essential for rapid initiation of antibiotic therapy to achieve the best outcome.

Objective To evaluate the efficacy and safety of SHR4640, a highly selective urate transporter 1 inhibitor, in Chinese subjects with hyperuricaemia. Methods This was a randomized double-blind dose-ranging phase II study. Subjects whose serum uric acid (sUA) levels were ≥480 µmol/l with gout, ≥480 µmol/l without gout but with comorbidities, or ≥540 µmol/l were enrolled. Subjects were randomly assigned (1:1:1:1:1) to receive once daily 2.5 mg, 5 mg, 10 mg of SHR4640, 50 mg of benzbromarone or placebo, respectively. The primary end point was the proportion of subjects who achieved target sUA level of ≤360 µmol/l at week 5. Results 99.5% of subjects (n = 197) were male and 95.9% of subjects had gout history. The proportions of subjects who achieved target sUA at week 5 were 32.5%, 72.5% and 61.5% in the 5 mg, 10 mg SHR4640 and benzbromarone groups, respectively, significantly higher than the placebo group (0%; P Conclusions The present study indicated a superior sUA-lowering effect and well tolerated safety profile after 5-week treatment with once-daily 5 mg/10 mg of SHR4640 as compared with placebo in Chinese subjects with hyperuricaemia. Trial registration ClinicalTrials.gov number, NCT03185793

Objective: By comparing the psychometric properties of the Short Form 36 (version 1, SF-36) and the Short Form 12 (version 1, SF-12), we supply evidence for the selection of instruments measuring the quality of life (QOL) and decision-making processes of adolescents in China. Methods: Stratified cluster random sampling was adopted, and the SF-36 was administered to assess QOL. The Pearson correlation coefficient was used to show correlation. Cronbach’s alpha and construct reliability (CR) were used to evaluate the reliability of SF-36 and SF-12, while criterion validity and average variance extracted (AVE, convergence validity) were used to evaluate validity. Confirmatory factor analysis was used to calculate the load factor for each item, then to obtain the CR and AVE. The Semejima grade response model (logistic two-parameter module) in item response theory was used to estimate item discrimination, item difficulty, and item average information for each item. Results: 19,428 samples were included in the study. The mean age of respondents was 14.78 years (SD = 1.77). High correlations between the corresponding domains and components of both scales were found. Reliability of each domain of the SF-36 was better than for the corresponding domain of SF-12. The domains of PF, RP, BP, and GH in SF-36 had good construct reliability (CR > 0.6). The criterion validities of SF-36 were a little higher in some corresponding dimensions, except for PCS. The convergence validities of SF-12 were higher than SF-36 in PF, RP, BP, and PCS. The items of BP, SF, RP, and VT in SF-12 had acceptable discrimination of items that were higher than in SF-36. The items’ average amounts of information of BP, VT, SF, RE, and MH in SF-36 and SF-12 were poor. Conclusion: Two component measurements of the SF-12 (PCS and MCS) appeared to perform at least as well as the SF-36 in cross-sectional settings in adolescence, but the reliability and validity of 8 domains of the SF-36 were better than those of SF-12. Some domains, for instance SF and BP, were not suitable for adolescents or need no further study.

Objective: By comparing psychometric properties of the SF-36 and the SF-12, supplied evidence for the election of instruments of the quality of life (QOL) and decision-making processes to promote the Quality of Life of adolescent. Methods: Stratified cluster random sampling was adopted. The Short-Form 36 (SF-36) was used to assess QOL. Pearson Correlation Coefficient was used to show correlation. Cronbach’s Alpha and Construct Reliability (CR) were used to evaluate reliability of SF-36 and the Short-Form 12 (SF-12), Criterion Validity and Average Variance Extracted (AVE, Convergence Validity) for validity. Confirmatory factor analysis was used to calculate load factor for each item, then obtained CR and AVE. The Semejima grade response model (Logistic two-parameter module) in the item response theory was used to estimate the Item Discrimination, Item Difficulty and Item Average Information of each item. Results: 19,428 samples were included in the study. The mean age was 14.78 years (SD=1.77). High correlations between corresponding domains and components of both scales were found. Reliability of sf-36 each domain was better than that corresponding domain of sf-12. Domains of PF, RP, BP, and GH in SF-36 had good construct reliability (CR,>0.6). The Criterion Validities of SF-36 were little higher in some corresponding dimensions except PCS. Convergence validities of SF-12 were higher than SF-36 in PF, RP, BP and PCS. The items of BP, SF, RP and VT in SF-12 had acceptable discriminations of items and higher than in SF-36. The items Average Amounts of Information of BP, VT, SF, RE and MH in SF-36 and SF-12 were poor. Conclusion: Two components (PCS and MCS) measurements of SF-12 appeared to perform at least as well as the SF-36 in cross-sectional settings in adolescence. Some domains, for instance SF and BP, were suitable for adolescents or not need study further.

Although several prognostic signatures have been developed for gastric cancer (GC), the utility of these tools is limited in clinical practice due to lack of validation with large and multiple independent cohorts, or lack of a statistical test to determine the robustness of the predictive models. Here, a prognostic signature was constructed using a least absolute shrinkage and selection operator (LASSO) Cox regression model and a training dataset with 300 GC patients. The signature was verified in three independent datasets with a total of 658 tumors across multiplatforms. A nomogram based on the signature was built to predict disease-free survival (DFS). Based on the LASSO model, we created a GeneExpressScore signature (GESGC ) classifier comprised of eight mRNA. With this classifier patients could be divided into two subgroups with distinctive prognoses [hazard ratio (HR) = 4.00, 95% confidence interval (CI) = 2.41-6.66, P

Objective: The E3 ubiquitin ligase RNF6 (RING-finger protein 6) plays a crucial role in carcinogenesis. However, the copy number and expression of RNF6 were rarely reported in colorectal cancer. We aimed to explore the mechanical, biological, and clinical role of RNF6 in colorectal cancer initiation and progression. Design: The copy number and expression of RNF6 were analyzed from Tumorscape and The Cancer Genome Atlas (TCGA) datasets. Gene expressions were examined by real-time PCR, Western blot, and immunohistochemical staining. Gene expression profiling studies were performed to identify pivotal genes regulated by RNF6. Biological function of RNF6 on tumor growth and metastasis was detected in vivo and in vitro. Role of RNF6 in modulating SHP-1 expression was examined by coimmunoprecipitation and confocal microscopy, respectively. Results: The copy number of RNF6 was significantly amplified in colorectal cancer, and the amplification was associated with RNF6 expression level. Amplification and overexpression of RNF6 positively correlated with patients with colorectal cancer with poor prognosis. The gene set enrichment analysis (GSEA) revealed cell proliferation, and invasion-related genes were enriched in RNF6 high-expressed colorectal cancer cells as well as in patients from TCGA dataset. Downregulation of RNF6 impaired the colorectal cancer cell proliferation and invasion in vitro and in vivo. RNF6 may activate the JAK/STAT3 pathway and increase pSTAT3 levels by inducing the ubiquitination and degradation of SHP-1. Conclusions: Genomic amplification drives RNF6 overexpression in colorectal cancer. RNF6 may be a novel biomarker in colorectal carcinogenesis, and RNF6 may increase pSTAT3 level via promoting SHP-1 ubiquitylation and degradation. Targeting the RNF6/SHP-1/STAT3 axis provides a potential therapeutic option for RNF6-amplified tumors. Clin Cancer Res; 24(6); 1473–85. ©2017 AACR.

Objective: To explore the influencing factors of the utilization of primary health care from the perspective of social contact among internal elderly migrants in China to provide further insights that might promote their utilization of primary health care. Methods: 1544 internal elderly migrants in eight cities participated in the survey. Whether to participate in the free health checkup organized by community health service institutions in the past year was adopted as an indicator of the utilization of primary health care, number of local friends and exercise time per day were measured for social contact. Multivariate binary logistic regression was used to understand the association of the variables with the likelihood of using community health services. Results: Internal elderly migrants who had more social contact were more inclined to use primary health care. Conclusion: The role of the community should be expanded, such as creating community-based promotions targeting internal elderly migrants or designing social or sports activities tailored to increase the opportunity for contact between local elders and internal elderly migrants.

// Ji-Lin Wang 1, * , Wen-Yu Su 1, * , Yan-Wei Lin 2 , Hua Xiong 1 , Ying-Xuan Chen 1 , Jie Xu 1 , Jing-Yuan Fang 1 1 Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai 200001, China 2 Department of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, China * These authors have contributed equally to this work Correspondence to: Ji-Lin Wang, email: wangjilin811123@163.com Jie Xu, email: xujieletter@163.com Jing-Yuan Fang, email: jingyuanfang@sjtu.edu.cn Keywords: CD44v6, prognosis, colorectal cancer, meta-analysis Received: October 04, 2016 Accepted: November 24, 2016 Published: December 24, 2016 ABSTRACT CD44v6 has recently been reported as a biomarker for colorectal cancer. However, the clinical and prognostic significance of CD44v6 in colorectal cancer remains controversial. Therefore, we performed a meta-analysis to clarify this issue. A comprehensive literature search was performed using Medline, Embase and Web of Science, and the statistical analysis was conducted using Stata software. A total of twenty-one studies including 3918 colorectal cancer cases were included. The pooled analysis showed that CD44v6 overexpression in colorectal cancer was an independent prognostic marker correlating with lower 5-year overall survival rate (OR=0.78, 95%CI =0.67-0.91, p=0.001). CD44v6 overexpression was also associated with more lymph node invasion (OR=1.48, 95%CI= 1.02-2.15, p=0.04), and advanced Dukes stage (OR=2.47, 95%CI= 1.29-4.73, p=0.01). In addition, while excluding Zolbec’s study, CD44v6 overexpression was associated with distance metastasis (OR=1.65, 95%CI =1.13-2.40, p=0.01). Taken together, this meta-analysis suggested that CD44v6 is an efficient prognostic factor in colorectal cancer.

Background Microstructural changes of lupus nephritis (LN) kidney such as inflammatory cell infiltration or fibrosis could influence water molecular movement or diffusion, which indicates that diffusion-weighted imaging (DWI) may become a valuable tool in evaluation of this disease. Purpose To explore whether multiparameter diffusion-weighted imaging (mDWI) could contribute to characterize pathological patterns in LN patients. Study type Retrospective. Population Twenty-two patients with LN. Field strength/sequence Multi-b value DWI was performed with a 3.0 T scanner. Assessment Apparent diffusion coefficient (ADC)m , perfusion-related diffusion coefficient (Df ), molecular diffusion coefficient (Ds ), perfusion fraction (f), ADCs , α, ADCk , and mean kurtosis (MK) were calculated by monoexponential, biexponential, stretched-exponential, and kurtosis models fits, respectively. Statistical tests Independent sample t-test, Pearson analysis and receiver operating characteristic (ROC). Results In the whole group, the activity index (AI) correlated significantly with alpha values in the medulla (rho = -0.54, P = 0.03). The chronicity index (CI) correlated significantly with Ds values in the medulla (rho = -0.61, P = 0.02). No significant association was found between any other diffusion parameter and histologic grade with all P > 0.05. For differentiating proliferative LN (Class III or IV) from Class V, the area under the ROC curve (AUC) of alpha in the medulla was 0.833 (P = 0.023). DATA CONCLUSION: mDWI might be used for the characterization of pathological patterns in LN patients. Level of evidence 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:1075-1084.

Objective To assess the association between acculturation and body weight status among internal migrant children in China. Design, setting and participants A cross-sectional study was conducted among 1154 pairs of migrant children aged 11–17 years and their primary caregivers in Guangzhou, China, from April to May 2016. Measures Migrant children’s body weight status was measured by body mass index. Acculturation was measured by a questionnaire, developed and validated by the research team. The questionnaire had three dimensions with five factors, namely language, social interaction, custom, dressing and diet. Social anxiety was measured by Social Anxiety Scale for Children. Food intake was measured by the food frequency table that was developed from a previous study. Logistic regression was performed to examine the association between acculturation and overweight/obesity while controlling for migrant children’s and their caregivers’ demographic characteristics, children’s social anxiety and food intake. Results Seventy-six out of 1154 (6.6%) migrant children were overweight, and 36 (3.1%) were obese. The overall prevalence of overweight/obesity was 12.5% in boys, and 6.1% in girls (p

Interleukin (IL)-22, a member of the IL-10 family, is a cytokine secreted by several types of immune cells including IL-22(+)CD4(+) T cells (Th22) and IL-22 expressing innate leukocytes (ILC22). Recent studies have demonstrated that IL-22 is a key component in mucosal barrier defense, tissue repair, epithelial cell survival, and proliferation. Furthermore, accumulating evidence has defined both protective and pathogenic properties of IL-22 in a number of conditions including autoimmune disease, infection, and malignancy. In this review, we summarize the expression and signaling pathway and functional characteristics of the IL-22 and IL-22 receptor axis in physiological and pathological scenarios and discuss the potential to target IL-22 signaling to treat human diseases.

Volume 200, no. 2, e00447-17, 2018, [https://doi.org/10.1128/JB.00447-17][1]. Page 1, footnote box, line 4: “2018” should read “2017.” [1]: /lookup/doi/10.1128/JB.00447-17

Lincomycin A is a clinically important antimicrobial agent produced by Streptomyces lincolnensis In this study, a new regulator designated LmbU (GenBank accession no. ABX00623.1) was identified and characterized to regulate lincomycin biosynthesis in S. lincolnensis wild-type strain NRRL 2936. Both inactivation and overexpression of lmbU resulted in significant influences on lincomycin production. Transcriptional analysis and in vivo neomycin resistance (Neor) reporter assays demonstrated that LmbU activates expression of the lmbA, lmbC, lmbJ, and lmbW genes and represses expression of the lmbK and lmbU genes. Electrophoretic mobility shift assays (EMSAs) demonstrated that LmbU can bind to the regions upstream of the lmbA and lmbW genes through the consensus and palindromic sequence 5'-CGCCGGCG-3'. However, LmbU cannot bind to the regions upstream of the lmbC, lmbJ, lmbK, and lmbU genes as they lack this motif. These data indicate a complex transcriptional regulatory mechanism of LmbU. LmbU homologues are present in the biosynthetic gene clusters of secondary metabolites of many other actinomycetes. Furthermore, the LmbU homologue from Saccharopolyspora erythraea (GenBank accession no. WP_009944629.1) also binds to the regions upstream of lmbA and lmbW, which suggests widespread activity for this regulator. LmbU homologues have no significant structural similarities to other known cluster-situated regulators (CSRs), which indicates that they belong to a new family of regulatory proteins. In conclusion, the present report identifies LmbU as a novel transcriptional regulator and provides new insights into regulation of lincomycin biosynthesis in S. lincolnensisIMPORTANCE Although lincomycin biosynthesis has been extensively studied, its regulatory mechanism remains elusive. Here, a novel regulator, LmbU, which regulates transcription of its target genes in the lincomycin biosynthetic gene cluster (lmb gene cluster) and therefore promotes lincomycin biosynthesis, was identified in S. lincolnensis strain NRRL 2936. Importantly, we show that this new regulatory element is relatively widespread across diverse actinomycetes species. In addition, our findings provide a new strategy for improvement of yield of lincomycin through manipulation of LmbU, and this approach could also be evaluated in other secondary metabolite gene clusters containing this regulatory protein.

Objectives To assess the health service utilisation of internal migrant children in Guangdong, China, and to explore the association between children’s health service utilisation and their parents’ acculturation. Design Cross-sectional survey between April and May 2016. Setting Six society-run schools of Tianhe and Baiyun districts in Guangzhou City of China. Participants We recruited all students at grade 7 or 8 and one of their parents who resided in Guangzhou over 6 months without permanent registered residence (hukou) in Guangzhou (1161 pairs completed this survey). 258 children were ill within the past 2 weeks or during the last year. Main outcome measures The main outcome was self-reported health service utilisation. Logistic regression analysis was conducted to explore the association between children’s unmet needs for outpatient or inpatient service and their parents’ acculturation (categorised into high, middle and low groups). Results In total, 216 children, or 18.6% of the total subjects, were ill within the past 2 weeks and were in need of outpatient service; 94 children, or 8.1% of the total subjects, were in need of inpatient service. Among them, 17.6% and 46.8% of the migrant children had unmet needs for outpatient and inpatient services, respectively. After controlling for enabling resources and predisposing characteristics, migrant children with parents in the middle-acculturation group (adjusted OR=3.17, 95% CIs 1.2 to 8.3, P

microRNAs (miRNA) are promising predictors in colorectal cancer (CRC). We investigated whether miRNAs could predict adenoma recurrence in patients with advanced colorectal adenoma (ACRA) after polypectomy. miRNA expression profiling was performed by miRNA microarray to identify recurrence-related miRNAs. Candidate miRNAs extracted from formalin-fixed paraffin-embedded blocks of patients with ACRA were measured using real-time PCR. Logistic regression analysis was conducted to investigate whether validated miRNA expression profiles were independent from other known adenoma recurrence risk factors. The prognostic values of six miRNAs and three independent risk factors were assessed by the area under the receiver operating characteristic (ROC) curve analysis. The expressions of six candidate miRNAs were significantly decreased from levels in normal colorectal tissue compared with ARCA with adenoma recurrence (RACRA) in this retrospective cohort. However, only miRNA (miR)-194 emerged as a practical predictor. The sensitivity and specificity of miR-194 as a predictor were 71.0% and 78.0%, respectively, at a cutoff value of 0.1311 in the retrospective cohort. Sensitivity and specificity were 76.1% and 77.2%, respectively, in the prospective cohort using the same cutoff value. Low expression levels of miR-194, adenoma size ≥2 cm, and ≥3 adenomas were independent risk factors for adenoma recurrence. Moreover, low expression of miR-194 was a better predictor of adenoma recurrence than the adenoma size and numbers according to ROC curve analysis. miR-194 may be an independent predictor for adenoma recurrence in patients with ACRA after polypectomy. Cancer Prev Res; 7(6); 607–16. ©2014 AACR.

SummaryLittle is known about how the immune system impacts human colorectal cancer invasiveness and stemness. Here we detected interleukin-22 (IL-22) in patient colorectal cancer tissues that was produced predominantly by CD4+ T cells. In a mouse model, migration of these cells into the colon cancer microenvironment required the chemokine receptor CCR6 and its ligand CCL20. IL-22 acted on cancer cells to promote activation of the transcription factor STAT3 and expression of the histone 3 lysine 79 (H3K79) methytransferase DOT1L. The DOT1L complex induced the core stem cell genes NANOG, SOX2, and Pou5F1, resulting in increased cancer stemness and tumorigenic potential. Furthermore, high DOT1L expression and H3K79me2 in colorectal cancer tissues was a predictor of poor patient survival. Thus, IL-22+ cells promote colon cancer stemness via regulation of stemness genes that negatively affects patient outcome. Efforts to target this network might be a strategy in treating colorectal cancer patients.

Background: To investigate and analyze the hospitalization costs of inpatients with primary acute angle closure glaucoma (PACG), and to explores the influencing factors of hospitalization cost and to provide reference for specialized hospitals to carry out clinical pathways. Methods: The first page diagnostic data of PACG patients’ medical records were collected, and an Excel database was established according to the International Classification of Diseases (ICD-10) code. Statistical analysis of hospitalization data was performed using SPSS 17.0 software. Results: Hospitalization days and clinical pathway which affect the change of the hospitalization cost (P Conclusions: Hospitalization day is an important factor affecting the hospitalization cost, reducing unnecessary hospitalization time can control the increase of hospitalization cost.

ObjectivesThe aim of this study was to examine the pathway and associations among acculturation (ie, language, social interaction and lifestyle), psychological adjustment and mental health of internal migrant adolescents in China.DesignCross-sectional questionnaire study.SettingSix private migrant junior high schools located in Tianhe and Baiyun districts in Guangzhou were chosen as the study sites.ParticipantsA total of 1122 migrant adolescents aged 11–17 years old completed the study.Main outcome measuresMental health was measured by using the Social Anxiety Scale for Children (SASC) and major depression disorder (MDD) in a Brief Child and Family Phone Interview. Acculturation and psychological adjustment were measured by a self-designed and verified questionnaire. Multiple regression models and structural equation models were performed to analyse the association among acculturation, psychological adjustment and mental health while controlling for participant demographic characteristics.ResultsThe average MDD score for boys was 8.78 (SD=2.17) and for girls was 8.56 (SD=2.22), while the average SASC score for boys was 14.67 (SD=3.72) and for girls was 13.41 (SD=4.01). Psychological adjustment had a direct positive effect on MDD (pConclusionsThe association between acculturation and the mental health of internal migrant adolescents was complex and could be mediated by psychological adjustment. Interventions such as promoting local language and social interaction are needed to enhance psychological adjustment and further improve the mental health of migrant adolescents.

Persistent infection with Helicobacter pylori (H. pylori) contributes to gastric diseases including chronic gastritis and gastric cancer. However, the pathogenesis of this carcinogenic bacterium has not been completely elucidated. Here, we report that H. pylori rapidly triggers STAT3 signaling and induces STAT3-dependent COX-2 expression both in vitro and in vivo. STAT3 upregulates COX-2 by binding to and increasing the activity of COX-2 promoter. COX-2 in turn regulates IL-6/STAT3 signaling under basal conditions and during H. pylori infection. These findings suggest that a positive feedback loop between STAT3 and COX-2 exists in the basal condition and H. pylori infectious condition. Immunohistochemical staining revealed that H. pylori-positive gastritis tissues exhibited markedly higher levels of pSTAT3(Tyr705) than H. pylori-negative ones. High pSTAT3(Tyr705) levels are correlated with intestinal metaplasia and dysplasia, suggesting pSTAT3(Tyr705) may be useful in the early detection of gastric tumorigenesis. Additionally, a strong positive correlation between STAT3/pSTAT3(Tyr705) levels and COX-2 expression was identified in gastritis and gastric cancer tissues. Together, these findings provide new evidence for a positive feedback loop between STAT3 signaling and COX-2 in H. pylori pathogenesis and may lead to new approaches for early detection and effective therapy of gastric cancer

Cancer not only is associated with inherited genetic sequences but also results from epigenetic changes. Thus, understanding the mechanisms underlying epigenetic modifications is important for cancer prevention, diagnosis, and therapy. There is much evidence showing that some Polycomb group (PcG) proteins are abnormally expressed in certain tumors. This review addresses biological functions and biochemical behaviors of the Polycomb repression complex proteins, including their enzymatic activities. Additionally, the potential mechanisms of PcG gene silencing by PcG and its link to cancers are summarized that will shed light on this novel area of study in cancer.

Internal migrants are the individuals who migrate between regions in one country. The number of internal migrants were estimated at 245 million in China in 2013. Results were inconsistent in the literature about the relationship between their health statuses and social integration. The main difference exists on how to measure the social integration and whether health statuses of internal migrants improve with years of residence. To complement the existing literature, this study measured social integration more comprehensively and estimated the internal migrants' health statuses with varying years of residence, and explored the associations between the migrants' social integration and health. We used the data from 2014 Internal Migrant Dynamic Monitoring Survey of Health and Family Planning in ZhongShan, China. Health status was measured from four aspects: self-reported health, subjective well-being, perception of stress, mental health. We measured social integration through four dimensions: economy, social communication, acculturation, and self-identity. The analyses used multiple linear regressions to examine the associations between self-reported health, subjective well-being, and perception of stress, mental health and social integration. The analytical sample included 1,999 households of the internal migrants and 1,997 local registered households, who were permanent residents in ZhongShan. Among the internal migrants, Adults in the labor force, who were aged 25 to 44 years old, accounted for 91.2% of the internal migrant population, while 74.6% of the registered population were in that age group. Median residential time among migrants was 2.8 (1.3-6.2) years, and 20.2% of them were migrating in the same Guangdong province. Except for mental health, other health statuses among migrants had significant differences compared with local registered population, e.g. self-reported health was better, but subjective well-being was worse. However, these health measurements were improved with more years of residence. Moreover, our results show that two aspects of social integration, economic integration and self-identity, were significantly associated with health status. Subjective feeling of relative social status levels were more associated with health, which prompted the attention to social fairness and the creation of a fair and respectful culture. More interventions could be experimented, such as encouraging internal migrants to participate in community activities more actively, educating local registered residents to treat internal migrants more equally, and developing self-identity among internal migrants. Better social, economic, and cultural environment can benefit internal migrants' health statuses.