Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.

OBJECTIVETo investigate the correlation between transformation growth factor (TGF- B) polymorphisms and IgA nephropathy and the therapeutic effect of dendrobium on IgA nephropathy.

METHODSPolymerase chain reaction- restriction fragment length polymorphism (PCR- RFLP) and direct sequencing were used for analysis of 118 patients with IgA nephropathy from core families in Guangxi Zhuang Autonomous Region. The imbalanced transfer of TGF iso1-509 C/T in the affected offsprings was observed by transfer imbalance test and HRR analysis. The TGF-B genotype of the patients and the core family members were detected. The therapeutic effects of Dendrobium candidum combined with hormone and ACEI/ARB treatments were evaluated by observing the patient's urine protein (24 hUpr), serum albumin (ALB), creatinine (Scr) and urea nitrogen (BUN) levels.

RESULTSIn the 118 patients with IgA nephropathy, we identified TGF-B 1 promoter -509C/T genotype CC in 32 (27.1%) cases, CT in 58 (49.2%) cases, and TT in 28 (23.7%) cases. In the core family of the patients, CC genotype was found in 33 (28.0%) cases, CT in 55 (46.6%) cases, and TT in 30 (28.0%) cases. The treatments significantly lowered 24 hUpr, Scr, and BUN levels ( > 0.05) in patients with CC genotype, significantly lowered 24 hUpr and BUN levels in patients with CT genotype ( < 0.05), and significantly lowered 24 hUpr and BUN level and increased ( < 0.05) ALB level ( < 0.01) in patients with TT genotype.

CONCLUSIONSThere is no significant correlation between TGF-B promoter - 509C/T polymorphism and IgA nephropathy. The patients with CC genotype are sensitive to the treatments with hormone and ACEI/ ARB and show a stronger response to combined treatments with dendrobium.

Burn medicine of China started in 1958. Great progress has been achieved in discipline construction, scientific research, clinical treatment level, and talent team construction in 60 years. A large number of severely burned patients have been successfully treated, and plans for treatment of burn patients with Chinese characteristics have been established with world-leading treatment level. At the same time, in the continuous improvement of clinical treatment level, extensive experimental researches for the key scientific problems in clinical treatment of burn patients have been conducted, and a large number of innovative research results have been achieved by Chinese burn medicine workers. The theoretical research of burn medicine in China has stepped into advanced ranks of the world. Burn medicine will confront development opportunity and tough challenge in the future. We can take advantage of wound repair of burn discipline to deal with the situation of decreasing incidence of burn and undiminished importance of burn medicine. To establish and improve the chain of burn treatment is an important direction for burn discipline development in the future.

Objective: To explore the short and mid-term efficacy of device closure of patent foramen ovale (PFO) for treating the patients with PFO combining cryptogenic stroke (CS) and transient ischemic attack (TIA). Methods: A total of 56 PFO patients with CS and TIA receiving device closure in our hospital from 2009-05 to 2015-12 were retrospectively studied. Transthoracic echocardiography (TTE), electrocardiogram (ECG), chest X-ray were examined at 24h, 1 month, 3 and 6 months after theoperation; telephone visit was conducted every 6 months thereafter. Results: There were 54/56 PFO patients combining CS and 2 combining TIA; 53 (94.6%)patients received PFO occluder from Starway medical technology. Aspirin was used for 6 months after the operation. The patients were followed-up for the average of (34.67±23.24) months. No body suffered from post-operative stroke and TIA; no residual shunt was observed. Conclusion: The short and mid-term efficacy of device closure has been satisfactory for treating the patients with PFO combining CS and TIA; its overall clinical value should be further investigated in large population and long-term study.

Objective To analyze the characteristics of contributions and the reasons why Chinese authors engaged in scientific research favor to contribute their papers to PLoS One by comparing the papers published in PLoS One and its series by authors from China and other countries.Methods Papers published in PLoS One by Chinese au-thors engaged in scientific research were retrieved from Web of Science by setting the retrieval parameters and ana-lyzed.Results The number of papers published in PLoS One series by authors from China increased rapidly.The number of papers published in PLoS One was significantly larger than that published in other PLoS One series. Conclusion The scientific research scale is unceasingly expanded.Why the Chinese authors engaged in scientific research favor to contribute their papers to PLoS One are due to its attractive power and the guidance of scientific and technological evaluation management in China.

Objective To investigate the role of ORAI1 in the balloon injury-induced rat carotid artery neointimal formation and the relationship between ORAI1 and sodium and calcium exchanger(NCX) 1.Methods According to condition of carotid artery balloon injury and observation time,Sprague Dawley rats were divided into 3 groups including sham group,7 days injury group,and 14 day injury group (n =3 each).According to virus of transfection,Sprague Dawley rats were divided into 2 groups including negative control group (negative lentiviruses particles transfection after establishment of carotid artery balloon injury model,n =3) and siORAI1 group(siORAI1 transfection after operation,n =3).Carotid artery neointimal formation was analyzed after HE staining.The ORAI mRNA expression level was detected using real-time PCR.The proliferating cell nuclear antigen (PCNA),ORAI and NCX1 protein expression level were measured by Western blot.Results (1) Carotid artery intima was significantly thicker in 7 days and 14 days injury group than in sham group((0.54 ±0.11) μm2 and (0.89 ±0.12) μm2 vs.(0.11 ±0.08) μm2,both P ＜0.05).Relative expression level of PCNA protein was significantly higher in 7 days and 14 days injury group than in sham group(1.43 ±0.16 and 1.95 ±0.16 vs.1,both P ＜0.05).Relative mRNA expression level of ORAI1 (1.39 ± 0.14 and 1.78 ± 0.21 vs.0.56 ± 0.09,both P ＜ 0.05) and protein expression level (1.42 ± 0.19 and 1.78 ±0.22 vs.1,both P ＜0.05) were significantly higher in 7 days and 14 days injury group than in sham group.(2) After 14 days,relative expression level of ORAI1 protein was significantly lower in siORAI1 group than in negative control group (0.21 ±0.16 比 1,P ＜0.05).Carotid artery intima thickness was significantly reduced in siORAI1 group compared to negative control group((0.19 ± 0.14)μm2 vs.(0.91 ±0.23) μm2,P＜0.05).Relative expression level of NCX1 protein was also significantly lower in siORAI1 group than in negative control group(0.53 ±0.13 比 1,P ＜0.05).Conclusions ORAI1 may play a key role in the balloon injury-induced neointimal formation and vascular smooth muscle cells proliferation in rat carotid artery.ORAI1 knockdown could down regulate the NCX1 expression and attenuate the balloon injury-induced neointimal formation and vascular smooth muscle cells proliferation in rat carotid artery.

Background and purpose:Colorectal cancer (CRC) is a malignancy which is the third incidence and the fourth mortality in the worldwide. The main reason for the development of CRC is that the changes of genetic and epigenetic causes the tumor suppressor gene methylation silencing. This study aimed to investigate the plasma and stool GATA5 gene promoter methylation was detected in clinical diagnosis of CRC. Methods: To collect the paired plasma and stool specimens of 34 cases of healthy and 43 cases of patients with CRC. Methylation speciifc PCR (MSP) was respectively detected the GATA5 gene methylation levels of GATA5 gene in plasma and stool. And then separately analyzed their correlations with clinical and pathological parameters in gastric carcinoma. Results: The result of MSP showed that GATA5 gene promoter methylation rates in plasma and stool of CRC patients were 60.74%, 76.60%, respectively, were higher than those of healthy persons (6.47%, 32.35%). And the differences were statistically signiifcant (P=0.006 7, P=0.000 2, respectively). GATA5 gene methylation rates in plasma of CRC patients were closely related to clinical stage (P=0.000 5) and lymph node metastasis(P=0.020), while GATA5 gene methylation rates in stool of CRC patients had no signiifcant with clinical and pathological parameters. Conclusion:Detection of faecal GATA5 gene methylation level and supplemented plasma GATA5 gene methylation level can become a simple, non-invasive, sensitive and speciifc method for clinical diagnosis of CRC.

Objective To explore the association of ATP-binding cassette (ABC) efflux pump gene Rv1217c-Rv1218c and the drug resistance of Mycobacterium tuberculosis.Methods A total of 34 Mycobacterium tuberculosis clinical isolates including 24 drug-resistance isolates which were resistant to riffampicin,isoniazid,streptomycin or ethambutol and resistant to at least one second-line antituberculosis drug,and 10 drug-sensitive isolates were involved in this study.The RNA of isolated strains was extracted and then reverse transcribed. Gene expression was performed by real-time polymerase chain reaction (PCR) and data was analyzed by t test and Logistic regression analysis.Results The expressions of Rv1217c in rifampicin-resistant group (2.13 ± 1.89,t =3.44,P＜0.01),isoniazid-resistant group ( 1.84 ± 1.86,t =3.16,P＜ 0.05),streptomycin-resistant group ( 1.86 ±1.96,t=2.78,P＜0.05) and ethambutol-resistant groups (3.36±2.35,t=3.04,P＜0.05) were all higher than sensitive isolates (0.42 ± 0.31).The expressions of Rv1218c in rifampicin-resistant group (2.54±1.84,t=3.82,P＜0.01),isoniazid-resistant group (2.34± 1.84,t=3.72,P＜0.01),streptomycin-resistant group (2.15±1.86,t=3.01,P＜0.01) and ethambutol-resistant groups (3.78± 1.78,t=4.22,P＜0.01 ) were all higher than sensitive isolates (0.65 ± 0.42).The expressions of Rv1217c and Rv1218c in multidrug resistant group were 2.74±2.07 and 3.33± 1.77,respectively,which were both higher than polydrug resistant group (0.79 ± 0.47 and 1.03 ± 0.79,respectively; t =2.91,P＜0.05 ; t =3.84,P＜0.01,respectively).Logistic regression analysis found that high Rv1217c expression was positively correlated with rifampicin resistance and negatively correlated with isoniazid resistance (both P＜ 0.01 ),while high Rv1218c expression was negatively correlated with rifampicin resistance and positively correlated with isoniazid resistance (both P＜0.01 ).High expressions of two genes were both positively correlated with ethambutol resistance and multidrug resistance (both P＜0.01 ) and not statistically correlated with streptomycin resistance (P＞0.05).Conclusions The expressions of ABC efflux pump gene,Rv1217c-Rv1218c,are correlated with multiple drug resistance.The overexpression may contribute to the multidrug resistance of Mycobacterium tuberculosis.

ObjectiveTo investigate the fusion sequence complexity of EML4-ALK in non-small cell lung cancer (NSCLC) patients,and the potential mutation in tyrosine kinase ( TK ) domain of ALK gene.MethodsIn routine practice,a novel echinoderm microtubule-associated protein-like4 and anaplastic lymphoma kinase (EML4-ALK) V3c variant was detected by rapid amplification of cDNA ends-polymerase chain reaction ( RACE-PCR )-sequencing technology in a patient with NSCLC.The further consecutive 39 cases( total of 40 cases)were screened by use of reverse transcription (RT)-PCR for EML4-ALK fusion.Positive PCR products were purified and cloned into T vectors,transformed into DH5a germ cells and colony picked up and sequenced for sequence complexity analysis.Tyrosine kinase domain of ALK was amplified by RT-PCR and sequenced.ResultsThree out of 40 cases had EML4-ALK fusion.One case had six novel variants of EML4-ALK co-existing,termed as V3c ( 64.6％ ),V3d ( 25.0％ ),V3e ( 2.1％ ),V3f (4.2％ ),V3g(2.1％ )and V3h(2.1％ ) variants,whereas without common V3a and V3b variants.In other two positive cases,one was V1 variant,another was concurrent V2,V3a and V3b variants.No mutations were detected in the TK domain of EML4-ALK in any case.ConclusionsSeveral EML-ALK variants could co-exist in a given lung cancer tissue,which suggest that the diversity and sequence complexity of EML4-ALK fusion are exist.Attentions should be paid to screen all the variants in clinic to improve the pick-up rate.

Objective To establish a HRM assay to screen for KRAS mutations in clinical colorectal cancer patients.Methods The sensitivity of HRM was analyzed by detecting somatic mutations in exon 2,notably codons 12 and 13 of the KRAS gene in the serial plasmid mixture samples which were mixed using the different proportions mutation plasmid and wide type plasmid of KRAS.HRM analysis was performed for KRAS on DNA insolated from a panel of 60 colorectal cancer samples derived from fresh tissues.The results were compared with the direct sequencing data.Results After the PCR amplification,the mutation results could be available by performing HRM analysis in the same tube on a real time PCR machine with HRM capability.HRM detection could identify KRAS mutation in a proportion of 10% of mutation plasmid DNA.All 60 samples identified the KRAS mutation by HRM and sequencing.17 samples were positive(28.3%) by HRM for KRAS exon 2 mutations,and 15 samples were confirmed the presence of codon 12 or 13 mutations(25.0%) and the other 2 samples were wild type by sequencing.The 60 samples detected by HRM were given 100% sensitivity with 96% specificity.Conclusions HRM is a sensitive intube methodology to screen for mutations in clinical samples.HRM will enable high-throughput screening to gene mutations to allow appropriate therapeutic choices for patients and accelerate research aimed at identifying novel mutations in human cancer.