Objectives: Antibodies to gp210 and sp100 are specific and unique anti-nuclear autoantibodies (ANAs) associated with primary biliary cholangitis (PBC). Importantly the presence of anti-gp210 and anti-sp100 responses is indicative of poor clinical outcomes. However, the utility of measuring titers of these antibodies remains unclear. Materials and methods: Using the in-house purified gp210 (HSA108-C18) and sp100 (amino acid position 296-386), we quantitatively measured serum autoantibodies to gp210 and sp100 using chemiluminescence immunoassay (CLIA) in a very large cohort of 390 patients with PBC, including 259 cases with no prior ursodesoxycholic acid (UDCA) treatment and 131 cases with UDCA treatment. We also analyzed serial changes in anti-gp210 and anti-sp100 levels in 245 sequential samples from 88 patients. Results: In our cross-sectional analysis, we detected anti-gp210 immunoglobulin G (IgG) and anti-sp100 IgG autoantibodies in 129 out of 390 (33.1%) and 80 out of 390 (20.5%) PBC patients, respectively. Multivariate analysis revealed that serum IgG (st.8 = 0.35, P = 0.003) and gamma-glutamyltransferase (GGT) (st.8 = 0.23, P = 0.042) levels at baseline were independently associated with anti-gp210 concentrations. In serial testing, we observed significant fluctuations in anti-gp210 antibody levels. These fluctuations reflected responsiveness to UDCA therapy, particularly in anti-gp210-positive patients with initially lower concentrations in the stages of disease.

The biliary epithelial cells release CC chemokine receptor 6 (CCR6) ligand 20 (CCL20), leading to recruitment of CCR6+ T cells and subsequent infiltration into the biliary epithelium in primary biliary cholangitis patients. Previous genome-wide multi-national meta-analysis, including our Han Chinese cohort, showed significant association of CCR6 and CCL20 single nucleotide polymorphisms (SNP) with PBC. We report here that significantly associated SNPs, identified in the CCR6 locus based on our Han Chinese genome-wide association study, can be separated into “protective” and “risk” groups, but only “risk” SNPs were confirmed using a separate Han Chinese PBC cohort. Only weak association of CCL20 SNPs was observed in Han Chinese PBC cohorts. Fine-mapping and logistical analysis identified a previously defined functional variant that, leads to increased CCR6 expression, which contributed to increased genetic susceptibility to PBC in Han Chinese cohort.

>Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by the destruction of intrahepatic small bile ducts and progressive cholestasis,eventually leading to liver cirrhosis and hepatic failure without appropriate treatment (Terziroli BerettaPiccoli et al.,2019).Previous genome-wide association studies(GWAS) in European,Japanese,and Han Chinese populations have identified over 50 susceptibility loci for PBC,including IL6,IL12,IL12RB2,IL21R,IL21,STAT1,STAT4,and SOCS1,which encode genes upstream or downstream of the JAK-STAT signaling pathway (Hirschfield et al.,2009,2010;Liu et al.,2010;Mells et al.,2011;Nakamura et al.,2012;Cordell et al.,2015,2021;Kawashima et al.,2017;Qiu et al.,2017).

Gastric cancer peritoneal metastasis (GCPM) is an important cause of cancer-related deaths worldwide. Long non-coding RNAs (lncRNAs) play a key role in the regulation of GCPM, but the underlying mechanisms have not been elucidated. High-throughput RNA sequencing (RNA-seq) was performed on four groups of clinical specimens (non-metastatic gastric cancer primary tumor, adjacent normal gastric mucosal tissue, gastric cancer primary tumor with peritoneal metastasis and adjacent normal gastric mucosal tissue). After sequencing, many lncRNAs and mRNAs were screened for further Weighted Gene Co-expression Network Analysis (WGCNA). GCPM-related hub lncRNAs and genes were identified by cytoHubba and validated by Quantitative real-time PCR (qRT-PCR), Receiver operating characteristic curve (ROC) analysis and Kaplan-Meier survival analysis. GO, KEGG and GSEA showed GCPM-related pathways. Correlation analysis revealed the potential relationship between hub lncRNAs and genes. By analyzing lncRNA expression data by WGCNA, we found that blue module was highly correlated with GCPM (r = 0.44, p = 0.04) and six lncRNAs involved in this module (DNM3OS, lnc-MFAP2-53, lnc-PPIAL4C-4, lnc-RFNG-1, lnc-TRIM28-14 and lnc-YARS2-4) were identified. We then performed qRT-PCR validation of gastric cancer specimens and found that the expression of lnc-RFNG-1 and lnc-TRIM28-14 was significantly increased in gastric cancer tissues with peritoneal metastasis. Kaplan-Meier survival analysis showed shorter overall survival time (OS) for gastric cancer patients with high expression of lnc-TRIM28-14. Receiver operating characteristic curve (ROC) analysis showed that lnc-TRIM28-14 could improve the sensitivity and specificity of GCPM diagnosis. In addition, we identified three key mRNAs (CD93, COL3A1 and COL4A1) associated with gastric cancer peritoneal metastasis through WGCNA analysis and clinical specimen validation. Moreover, there was a positive correlation between lnc-TRIM28-14 and the expression of CD93 and COL4A1 in gastric cancer peritoneal metastasis, suggesting a regulatory relationship between them. Subsequent GO, KEGG and GSEA analysis suggested that ECM-receptor interaction and focal adhesion were the hub pathways of GCPM. In summary, lnc-RFNG-1, lnc-TRIM28-14, CD93, COL3A1 and COL4A1 could be novel tumor biomarkers and potential therapeutic targets for GCPM.

Purpose To find a useful disease marker for early diagnosis of gastric cancer, we tried to explore the expression of serum miR-181, miR-652, and carbohydrate antigen 72-4 (CA72-4). Patients and Methods According to clinical pathologic stages, 112 patients with gastric cancer were divided into early gastric cancer group (n = 60) and advanced gastric cancer group (n = 52), stage I-II (n = 65), and stage III-IV (n = 47). Another 50 cases of gastric benign lesions and 40 healthy controls were also selected. Real-time quantitative PCR together with chemiluminescence were applied to detect expression levels. ROC curve was applied to judge their diagnostic efficiency. Pearson's correlation analysis was put into use to investigate the relevance of three indicators. Results Compared with benign lesions group and control group, significantly higher expression levels were found in patients of gastric cancer (all p < 0.001). Similarly, compared with early gastric cancer group, significantly higher expression levels were found in advanced gastric cancer group (all p < 0.001). The same result was also found in stage III-IV (all p < 0.001). The best cutoff values were 0.93, 2.38, and 16.94 U/ml, respectively. The area under the curve (0.917, 95%CI: 0.856-0.975) of the three combined diagnosis of early gastric cancer was the largest, and its sensitivity and specificity were 92.5% and 86.8%. And miR-181 and miR-652 were positively correlated with CA72-4 (r = 0.772, p < 0.001, r = 0.853, p < 0.001). Conclusion Serum miR-181, miR-652, and CA72-4 are closely linked to the occurrence and development of gastric cancer. Combination of three indicators has diagnostic value for early gastric cancer.

Primary biliary cholangitis (PBC) is an autoimmune liver disease with a strong hereditary component. Here, we report a genome-wide association study that included 1,122 PBC cases and 4,036 controls of Han Chinese descent, with subsequent replication in a separate cohort of 907 PBC cases and 2,127 controls. Our results show genome-wide association of 14 PBC risk loci including previously identified 6p21 ( HLA-DRA and DPB1 ), 17q12 ( ORMDL3 ), 3q13.33 ( CD80 ), 2q32.3 ( STAT1 / STAT4 ), 3q25.33 ( IL12A ), 4q24 ( NF-κB ) and 22q13.1 ( RPL3 / SYNGR1 ). We also identified variants in IL21 , IL21R , CD28/CTLA4/ICOS , CD58 , ARID3A and IL16 as novel PBC risk loci. These new findings and histochemical studies showing enhanced expression of IL21 and IL21R in PBC livers (particularly in the hepatic portal tracks) support a disease mechanism in which the deregulation of the IL21 signalling pathway, in addition to CD4 T-cell activation and T-cell co-stimulation are critical components in the development of PBC.

Midkine (MK) is reported to be associated with the clinical stages and distant metastases in gastric cancer, and to positively regulate the proliferation of human gastric cancer cells. However, the possible mechanisms of MK in the development of gastric cancer are still not fully clarified. In this study, the therapeutic effect of MK inhibition in gastric cancer in vivo and in vitro was investigated, by knock-down of MK expression with a small interfering RNA (siRNA). MK was expressed in gastric carcinoma tissues and cancer cells. The cytotoxic effect of cisplatin on AGS cells in vitro was attenuated by recombinant human MK, but was promoted by suppressing MK expression via downregulating the Notch signaling pathway-related proteins (Notch 1, Notch 2, Delta-like 1 and Jagged 1). Suppression of MK expression also promoted the inhibitory effect of cisplatin on AGS cells in vivo. In concusion, suppression of midkine gene promoted the antitumoral effect of cisplatin on human gastric cell line AGS in vitro and in vivo via Notch signaling pathway.

Objective:To discuss and compare clinical outcomes between digital virtual surgical planning (VSP) and con-ventional experience method (CEM) for large segmental mandibular reconstruction using free fibula flap. Methods:A ret-rospective study was carried out on 15 patients who underwent fibula free flap surgery for mandibular reconstruction from January 2011 to December 2015. Patients were categorized by the type of reconstructive technique:CEM group ( n=9, be-tween 2011 and 2014) and VSP group (n=6, 2014 to 2015). Demographics, surgical factors, and clinical outcomes were compared. Results: Compared with cases in CEM group, those in VSP group needed less ischemia time and bony revi-sions, with better bony contact rate and appearance outcome. The difference between the angle of the mandible before and after operation was smaller in VSP group than in CEM group. There was not statistical significance in patients' mean age, operation time, stay length, and surgical success rate between two groups. Conclusion: Mandibular reconstruction using a VSP technique yielded significantly shorter ischemia time, higher reconstruction accuracy, and better aesthetic outcome.

The repair of bone defects poses a great challenge for reconstructive surgeons. Although the development of tißsue engineering has exhibited promise in replacing damaged bone, the fabrication of large constructs with functional blood veßsels remains an obstacle. From the orthopedic surgeon's point of view, the generation of axially vascularized bone, which can anastomose with the recipient vessel, might be a solution to this medical problem. In this study, we aimed to prefabricate an axially vascularized bone by combining a ß-TCP scaffold, arteriovenous loop (AVL), and cell sheet in a bioreactor in vivo. Twelve rabbits were randomly allocated into two groups: the experimental group (presence of AVL) and the control group (absence of AVL). The constructs were explanted at 8 weeks postoperatively. The histomorphometric results showed 42.8±5.9% of the bone area in the AVL group and 26.6±3.5% in the control group. Similarly, vessel analysis revealed the average vessel density in the AVL group (12.5±3.3) was significantly more than that in the control group (6.1±1.5, p<0.05). Our research indicated that the combination of a ß-TCP scaffold, AVL and cell sheet might engineer vascularized bone. This prefabrication strategy might facilitate clinical translation of bone tissue engineering in reconstructing large bone defects.

目的 探讨跨理论模型模式在提高高原基层部队官兵吸氧依从性中的应用效果.方法 选取597名西区部队官兵,应用跨理论模型进行干预,观察干预后各阶段行为改变情况.结果 干预前、干预1个月、3个月及6个月官兵吸氧时间和血氧饱和度比较,差异有统计学差异(P＜0.01).干预后期(3～6个月)较干预初期(1～3个月)效果更好,行动和维持阶段所占人数比例更高.结论 基于跨理论模型的教育模式能有效提高官兵吸氧的依从性,效果明显,适宜在基层部队推广.

目的:探讨牵张成骨技术在颞下颌关节强直伴小下颌畸形治疗中的应用效果.方法:对6例颞下颌关节强直伴严重小下颌畸形的患者采用一期下颌骨双向牵张成骨、二期颞下颌关节成形术进行治疗.结果:所有患者术后均顺利完成牵引计划,并在3个月后拆除牵张器,面容获得极大改善,张口度达到25 mm以上,睡眠呼吸暂停症状消失,营养状况改善,口内咬合关系基本恢复.结论:牵张成骨技术为临床上治疗颞下颌关节强直伴严重小下颌畸形提供了有效方法.

BLU is a candidate tumor suppressor gene, which is epigenetically inactivated in many human malignancies. However, the expression and biological functions of BLU in gastric cancer has not yet been reported. In the present study, we identified a functional BLU promoter which was regulated by the transcription activator Sp1. Bisulfite sequencing and qRT-PCR assays indicated that the silence of BLU expression in gastric cancer was significantly associated with DNA hypermethylation of BLU promoter including -39 CpG site located in the Sp1 transcription element. The expression of BLU was notably restored in AGS and SGC7901 cells following the demethylation-treatment with 5'-Aza-2'-deoxycytidine. Moreover, the results from ChIP, EMSA and luciferase reporter gene showed that -39 CpG methylation could prevent Sp1 from binding to the promoter of BLU and decreased transcription activity of the BLU gene by ~70%. In addition, knockdown of BLU significantly promoted cellular proliferation and colony formation in gastric cancer cells. In conclusion, we identified a novel functional BLU promoter and proved that BLU promoter activity was regulated by Sp1. Furthermore, we found that hypermethylated -39 CpG in BLU proximal promoter directly reduced its binding with Sp1, which may be one of the mechanisms accounting for the inactivation of BLU in gastric cancer.

Ras-association domain family 1A (RASSF1A), a candidate tumor suppressor gene, is frequently silenced and inactivated by hypermethylation of its promoter region in several human tumors. However, the association between RASSF1A promoter methylation and gastric cancer risk remains conflicting. The aim of this study was to assess the association of RASSF1A promoter methylation with gastric cancer risk by a comprehensive meta-analysis. Relevant studies were identified by searches of PubMed and Web of Science databases with no restrictions. Combined odds ratio (OR) and 95 % confidence interval (CI) were used to assess the strength of the association between RASSF1A promoter methylation and gastric cancer risk. A chi-square-based Q test and sensitivity analyses were performed to test the between-study heterogeneity and the contributions of single studies to the final results, respectively. Funnel plots were carried out to evaluate publication bias. Overall, a significant association was observed between RASSF1A promoter methylation and gastric cancer risk (OR, 12.67; 95 % CI, 8.12–19.78; p < 0.001) with no between-study heterogeneity. Subgroup analyses further revealed that gastric cancer risk was increased for individuals carrying the methylated RASSF1A compared with those with unmethylated RASSF1A. In addition, no publication bias was detected in the overall and subgroup analyses. This study identified a strong association between RASSF1A promoter methylation and risk of gastric cancer and highlighted a promising potential for RASSF1A promoter methylation in gastric cancer risk prediction.

Objective To investigate the risk factors for non-alcoholic fatty liver disease (NAFLD)and to provide a basis for the preven-tion of NAFLD.Methods A total of 190 patients with NAFLD who visited the First Affiliated Hospital of Soochow University from January 201 1 to January 2013 were included in the study.The investigated factors included sex,age,height,weight,dietary habit,smoking and al-cohol consumption,educational level,occupation,intensity and duration of physical exercise,bedtime,previous history,and family histo-ry.Univariate and multivariate analyses were performed using SPSS 18.0 to determine the risk factors for NAFLD.Results The univariate analysis showed that sex,age,dietary habit,occupation,body mass index (BMI),and educational level were associated with NAFLD (P<0.05).The logistic regression analysis showed that the risk factors for NAFLD were sex (OR=5.692,P=0.029),age (OR=0.423,P=0.041),occupation (OR=0.698,P=0.008),BMI (OR=3.939,P=0.003),educational level (OR=5.463,P=0.030),and dieta-ry habit (OR=9.235,P=0.039).Conclusion NAFLD may be related to many factors,and corresponding preventive measures may re-duce the development of NAFLD.

This study focused on the effects of micro-arc oxidation on the bond strength of the porcelain-titanium system. The phase, morphology, and oxide layer thickness of titanium were evaluated. In particular, the bond strength of porcelain fused to titanium was measured using a three-point bending test. Statistical analyses were performed using a one-way analysis of variance. Differences in the surface morphologies and the phase components were observed in three groups. For micro-arc oxidation specimens, the bonding of titanium and porcelain was compact with a thin oxide layer. The mean bond strength of the micro-arc oxidation group, pre-oxidation group and control group was 42.40 +/- 4.35 Mpa, 34.28 +/- 2.84 Mpa, and 28.58 +/- 2.74 Mpa, respectively. When titanium was subjected to micro-arc oxidation treatment, the bond strength was significantly increased compared with the pre-oxidation group and the control group (p < 0.05). These results suggest that the micro-arc oxidation treatment could be an effective but simple method for increasing the titanium-ceramic bonding strength.

目的:探讨牵张成骨技术在严重小下颌畸形矫治中应用的临床效果.方法:对5例严重小下颌畸形患者,术前评估正颌手术难以矫正者,采用牵张成骨技术治疗.结果:所有患者术后均顺利完成牵引计划,并在3个月后拆除牵引器,通过治疗,患者面容获得极大改善,睡眠呼吸暂停症状消失.结论:牵张成骨技术为临床上严重小下颌畸形的矫治提供了有效方法.

Objective: To compare the effects of bonding agent single Bond and Clearfil SE Bond at different blowing airflow conditions on permeability of human dentin hybrid layer to provide experimental basis for correct clinical selection and operation. Methods: Twenty-four extracted cariesfree molars for orthodontic treatment were used. The attachment of periodontal ligament and calculus was removed to expose dentin. 320 meshes,400 meshes and 600 meshes of watersandpaper were used to polish occlusal surfaces of molars for 60s in order to prepare an uniform adhesive surface. Bonding agent Single Bond or Clearfil SE Bond were randomly chosen. They were treated in light,heavy,3 seconds,and 10 seconds blowing group,followed by composite resin restorations. The specimens were cut in 1mm thickness,and then polished until translucent. Results: Resin process was shorter and mixed layer was relatively thinner in Clearfil SE Bond(SE) group. Thicker adhesive layer and shorter resin processes were observed in SBg3 and SEg3 groups. The adhesive layer was relatively uniform with suitable thickness in SEg10,SEs3,SBg10 and SBs3 groups. The adhesive layer was dispersed thinner and distribution was uneven in SBs10 and SEs10 groups. Conclusion: The penetration effect of Single Bond was better than that of Clearfil SE Bond by the laser confocal analysis. Regardless of Single Bond or Clearfil SE Bond,10 seconds gentle air or 3 seconds strong air is suggested after adhesive surface cured.

Background: To better understand gastric cancer occurrence and prognosis, we explored the expression of molecules in the CD40 pathway and their correlation with gastric cancer prognosis. Patients and Methods: We measured the expression of CD40, VEGF, AKT, PI3K, and S100 in gastric cancer tissues and adjacent normal tissues from 128 patients by immunohistochemistry. Results: The expression of CD40, VEGF, AKT, and PI3K were significantly higher in tumor tissue than in normal tissue, while S100 expression in dendritic cells (DC) was lower. Expression of CD40, VEGF, AKT, and PI3K significantly increased with T stage, while S100 expression decreased with T stage. Lymph node metastasis was associated with low or negative S100 expression. PI3K expression increased with clinical stage, while negative S100 expression was associated with higher clinical stages. Multivariate analysis did not indicate significant associations between any of these markers and recurrence or mortality. Conclusion: The correlation between T stage of gastric cancer and the higher expression of CD40, VEGF, AKT, and PI3K, along with lower S100 expression in DC, may provide insights into future targets for more effective immunotherapy for cancer.

<正>先天性唇腭裂是口腔颌面部最常见的先天性畸形,由于唇腭裂患儿口鼻腔相通,口腔不能形成一个完整的密闭结构而无法产生有效吸吮所需的负压,影响吸吮、吞咽,导致喂养困难,易发生上呼吸道感染、听力受损、吞咽、心理等功能障碍[1]。早期手术修复已成为唇腭裂序列治疗的重要环节,围手术期

This study is designed to screen the CD40 related signal transduction pathway in AGS cells and construction of gene silencing vector. Analysis results showed 414 differential genes expression, including upregulation of 209 genes and downregulation of 205 genes. Basing on the ratio of signal in experimental group to signal in control group, 45 genes (38 genes upregulation and seven genes downregulation) with significant (P < 0.01) change in expression levels were screened according to the screening standard (signal log ratio ≥1 or ≤−1). These genes involved into metabolism, cell cycle and apoptosis, signal transduction and stress response. Furthermore, PI3K mRNA expression level in PI3K siRNA transfected AGS cells was 0.2335 ± 0.0116 72 h after transfection. This value was significantly (P < 0.05) lower than that in blank and negative control groups. PI3K protein expression in PI3K siRNA transfected AGS cells was significantly (P < 0.05) lower than that in blank and PI3K siRNA/N transfected groups. Therefore, PI3K siRNA gene silencing vector can significantly inhibit PI3K mRNA and protein expression in AGS cells.