Objective To investigate the association of hyponatremia with the degree of liver injury and complications in patients with decompensated liver cirrhosis.Methods A retrospective analysis was performed for the clinical data of 142 patients with decompensated liver cirrhosis complicated by hyponatremia who were admitted to Department of Gastroenterology,Xijing Hospital of Fourth Military Medical Uni versity from July 2015 to July 2016.The patients were divided into mild group,moderate group,and severe group according to serum sodium concentration on admission.The Child-Pugh score,Model for End-Stage Liver Disease (MELD) score,and major complications were compared between groups.All the patients were followed up for 3 months,and the complications such as ascites,spontaneous bacterial peritonitis,and hepatic encephalopathy were recorded.The association of hyponatremia with complications and mortality was investigated.The chi-square test was used for comparison of categorical data between groups,and the Spearman corretation analysis was also performed.Results The mild group had a high proportion of Child-Pugh class A patients (42.3％) and the severe group had a high proportion of Child -Pugh class C patients (72.4％).There was a significant difference in Child-Pugh score between the mild,moderate,and severe groups (x2 =50.175,P =0.000 2).The serum sodium level decreased with the increasing Child-Pugh score (r =-0.464,P =0.002 3).The mild group had a high proportion of patients with an MELD score of ≤9 (50.7％) and the severe group had a high proportion of patients with an MELD score of ≥30 (62.1％).There was a significant difference in the distribution of MELD scores between the mild,moderate,and severe groups (x2 =75.106,P =0.000 8).The serum sodium level decreased with the increasing MELD score (r =-0.644,P =0.004 5).The incidence rates of ascites,spontaneous bacterial peritonitis,and hepatic encephalopathy were 71.8 ％/92.9％/100.0％,14.1％/31.0％/65.5％,and 14.1％/35.7％/55.2％,respectively,in the mild,moderate,and severe groups.The mortality rate was 12.7％,33.3％,and 65.5％ in these three groups,respectively.There were significant differences in the incidence rate of complications and mortality rate between the three groups (x2 =14.127 and 24.467,both P ＜ 0.05).Conclusion Serum sodium level can be used as a predictor for the incidence rate of complications in patients with decompensated liver cirrhosis.

Objective To evaluate efficacy and safety of glucocorticoid (GC) with non-bioartificial liver support system (NBLS) in the treatment of severe drug-induced liver injury (DILI).Methods In the retrospective study,96 cases with severe DILI who had underwent the treatment of GC combined NBLS in our hospital from January 2008 to December 2015 were enrolled.Treatment,blood routine,liver functions,and so on,were recorded.The efficacy and complications of GC combined with NBLS in treating severe DIM were observed.Results Treatment of GC combined with NBLS was effective in 84 cases (87.5％).Levels of red blood cell (RBC) (4.22 ± 0.70) × 109/L and hemoglobin (Hb) (127.88 ±22.99) g/L were significantly higher at baseline than those after treatment (P＜0.05).Levels of alanine aminotransferase (ALT) (145.48± 158.94) U/L,aspartate amino transferase (AST)(98.06 ± 69.26) U/L,total bilirubin (TBil) (165.10 ± 124.21) μtmol/L bilirubin tra,direct bilirubin (DBil) (130.66 ± 89.46) μmol/L,indirect bilirubin (IBil) (35.43 ± 37.48) μmol/L,albumin (Alb) (41.12 ± 30.93) g/L and alkaline phosphatase (ALP) (178.64 ± 119.65) U/L were significantly improved compared to those before treatment (P＜0.05).However,levels of blood urea nitrogen (BUN) (5.61 ± 2.59)mmol/L and cre-recombinase (Cre) (61.00 ± 14.36) μmol/L in renal function were significantly higher after treatment (P＜0.05).No significant difference was observed in the level of prothrombin time (PT) and plasma thromboplastin antecedent (PTA) (P＞0.05).Conclusion The treatment of GC with NBLS showed satisfactory effectiveness and safety for severe DILI,which could ameliorate the disease progression,reduce total incidence of liver failure and improve the prognosis.

Objective To investigate the effect of surgical resection and ultrasound guided radiofrequency catheter ablation on the quality of life ( QOL) for the treatment of patients with early liver cancer. Methods The QOL scale was used to evaluate the patients’ QOL, which was investigated through the patients themselves and their main caregiver, nurse in charge and the doctor in charge. The recurrence rate and metastasis rate after the operation at 6 months and 1 year were compared. Results After the treatment of radiofrequency ablation, in addition to the main caregivers abroad, the QOL scores of the patient’ s own, director of doctor and nurse were better than those by the operation of liver cancer resection ( P<0 . 05 ) . There was no statistical difference in the recurrence rate and metastasis rate after the oper-ation at 6 months and 1 year between two groups ( P>0 . 05 ) . Conclusion Local radiofrequency ablation can improve the QOL of patients with early liver cancer, but there is no obvious difference in the long-term recurrence and metastasis between surgical resection and radiofrequency ablation.

ObjectiveTo summarize the clinical manifestations and pathological features of congenital hepatic fibrosis (CHF), and to improve the experience in the diagnosis and treatment of this disease. MethodsA total of 13 patients with a confirmed diagnosis of CHF based on histopathological examinations who were hospitalized and treated in Xijing Hospital, Fourth Military Medical University, from January 2011 to June 2015 were analyzed retrospectively. The clinical data including age, clinical manifestations, laboratory markers, and imaging findings were summarized and analyzed. ResultsOf all the patients, there were 8 cases of portal hypertension type, 1 case of cholangitis type, 1 case of mixed type, and 1 case of latent type. The imaging findings suggested that 8 patients had liver and kidney cysts, and 4 patients had cavernous transformation of the portal vein. ConclusionCHF patients often have portal hypertension and normal liver function as prominent manifestations, with concurrent liver and kidney cysts and Caroli disease. Liver biopsy should be performed for unexplained liver cirrhosis, especially for patients with inconsistency between reduction in liver function and portal hypertension.

1临床资料患者,男性,25岁,因纳差、乏力、腹胀20 d,皮肤巩膜黄染5 d,于2012年6月15日入院。病史:4个月前在当地医院体检确诊"慢性乙型肝炎",口服中成药治疗。20 d前出现纳差、乏力、腹部胀痛,5 d前发现全身皮肤巩膜黄染,遂来本院诊治。化验乙型肝炎5项提示HBsAg阳性,抗-HBs阴性,HBeAg阴性,抗-HBe阳性,HBcAg阳性;肝功能示:AST 872

>自身免疫性肝病是以肝脏为相对特异性免疫病理损伤器官的一类自身免疫性疾病,主要包括自身免疫性肝炎(AIH)、原发性胆汁性肝硬化(PBC)和原发性硬化性胆管炎(PSC),以及这三种疾病中任何两者之间的重叠综合征气随着认识及诊断水平的提高’国内外报道自身免疫性肝病特别是AIH和PBC患病率逐年升高’二#在发病机制上均存在自身免疫系统紊乱,表现为高免疫球蛋白血症和循环自身抗体,如抗

Objective: To establish the drug resistant cell model of gastric cancer and investigate the potential mechanisms of epirubicin drug resistance.Methods: Epirubicin-resistant cell line(SGC7901/EPI) was established by increasing dose of epirubicin.Drug sensitivity of the cell line was measured by in vitro MTT assay.Cell based assays for drug transportation and apoptosis were carried out.The expression levels of MRP1,Bcl-2,Bax were detected using western blot.Results: Significant difference was found in drug resistance between parent gastric cancer cell line SGC7901 and drug resistant subline 7901/EPI.Compared with SGC7901 cells,7901/EPI showed not only increased drug resistance,but also decreased drug sensitivity to other drugs.Increased drug transport was confirmed by the elevated expressions of MRP in 7901/EPI.Apoptosis rate of the SGC7901/EPI cell line was remarkably reduced due to increased expression of Bcl-2 and decreased Bax.Conclusion: Epirubicin resistant gastric cancer cell subline SGC7901/EPI was successfully established.The mechanisms of epirubicin may include elevated expression of MRP1 and increased Bcl-2/Bax ratio.

OBJECTIVE:  To investigate the cytotoxicity of silk fibroin/gelatin (SF/G) composite scaffolds in vitro as well as their biocompatibility and degradation in vivo. METHODS:  The proliferation and relative growth rate of human hepatic QZG cells grown on different blends of two-dimensional (2-D) SF/G scaffolds were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Flow cytometry was used to evaluate apoptotic rate of QZG cells on different blends of 2-D SF/G scaffolds. The effect of silk protein materials on cell growth was observed by scanning electron microscopy. Three-dimensional (3-D) SF/G scaffolds of three different ratios (diameter 10 mm, thickness 1 mm) were implanted into subcutaneous pockets on male Sprague–Dawley (SD) rats. On the 7th, 14th and 30th day post-implantation, the rats were sacrificed. The scaffold area including the surrounding tissues was retrieved. Hematoxylin and eosin staining was performed for observation under a light microscope. RESULTS:  Significant cell attachment and proliferation on the SF/G scaffolds were observed. As the increased gelatin concentration, SF/G scaffolds became more amenable to cell adhesion. After the subcutaneous implantation of the SF/G scaffolds in SD rats, immunological rejection tests showed only slight inflammation, measured by the presence of inflamed cells on day 7 and 14. By day 30, each scaffold had been completely infiltrated and organized by fibroblasts and inflamed cells. The greater the gelatin concentration in the scaffold, the faster the degradation rate. CONCLUSION:  Composite SF/G scaffolds are a promising candidate matrix for implantable bio-artificial livers.

Objective:To investigate the expression of Survivin in human gastric adenocarcinoma and analyze its relationship with clinicopathological parameters.Methods: The expression of Survivin expression was assessed using RT-PCR and western blot and immunohistochemistry(IHC) in 6 human gastric adenocarcinoma cell lines and 80 human gastric adenocarcinoma tissues and their corresponding normal tissues.The relationship between Survivin expression and the clinicopathological factors was analyzed.Results: Survivin was expressed in all 6 haman gastric carcinoma cell lines.The positive rates of Survivin protein expression was 60% in gastric adenocarcinoma tissue and not found in normal gastric mucosa respectively.Survivin protein was correlated with survival and lymph node metastasis(P0.05),but had no obvious relationship with differentiation status and stage(P0.05).Conclusion: The change of Survivin expression may be involved maily in gastric carcinogenesis and prognosis of gastric adenocarcinoma.Survivin would be a hopeful target of gastric carcinoma therapy.

OBJECTIVE: To investigate the cytotoxicity of silk fibroin/gelatin (SF/G) composite scaffolds in vitro as well as their biocompatibility and degradation in vivo.METHODS: The proliferation and relative growth rate of human hepatic QZG cells grown on different blends of two-dimensional (2-D) SF/G scaffolds were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide (MTT) assay. Flow cytometry was used to evaluate apoptotic rate of QZG cells on different blends of 2-D SF/G scaffolds. The effect of silk protein materials on cell growth was observed by scanning electron microscopy. Threedimensional (3-D) SF/G scaffolds of three different ratios (diameter 10 mm, thickness 1 mm) were implanted into subcutaneous pockets on male Sprague-Dawley (SD) rats. On the 7th, 14th and 30th day post-implantation, the rats were sacrificed. The scaffold area including the surrounding tissues was retrieved. Hematoxylin and eosin staining was performed for observation under a light microscope.RESULTS: Significant cell attachment and proliferation on the SF/G scaffolds were observed. As the increased gelatin concentration, SF/G scaffolds became more amenable to cell adhesion. After the subcutaneous implantation of the SF/G scaffolds in SD rats, immunological rejection tests showed only slight inflammation, measured by the presence of inflamed cells on day 7 and 14. By day 30, each scaffold had been completely infiltrated and organized by fibroblasts and inflamed cells. The greater the gelatin concentration in the scaffold, the faster the degradation rate.CONCLUSION: Composite SF/G scaffolds are a promising candidate matrix for implantable bioartificial livers.

Objective: To study the silk fibroin material's effect on proliferation of human normal hepatic cell line QZG,and to testify the cytocompatibility when blending of silk fibroin and gelatin into 3D scaffold.Methods:The activity of cell proliferation and relative growth rate(RGR) were assessed by MTT colorimetric assay and viable cell counting,The effect of silk protein materials on growth of cells was observed by scanning electron microscopy(SEM).Results: Human normal hepatic cell line QZG were cultivated in vitro directly on pure silk protein materials and silk fibroin/ gelatin materials.Cells solidly adhered to the materials.The activity of cell proliferation on silk fibroin/ gelatin materials was significantly more than that in the group of pure silk fibroin materials.The result of viable cell counting was compatible to MTT colorimetric assay.Conclusion:The silk fibroin materials together with gelatin has a good cytocompatibility with human normal hepatic cell line QZG.It will be useful in liver tissue engineering.

Objective To testify the immunological rejection of silk/gelatin composite scaffolds and its degradation in SD rats. Methods Male SD rats (200-250g) were anesthetized by intraperitoneal injections of sodium pentobarbital for subcutaneous pockets madding and 3D silk fibroin/gelatin scaffolds (10 mm diameter×1mm thickness) implantation. A total of 90 scaffolds were implanted in 45 rats (3 groups for 3 blends of scaffolds, 15 rats in each group). Five rats in each group were sacrificed at the 7th, 14th and 30th day. The scaffolds and the surrounding tissues were extracted, chemically fixed for 4 hours with 10% formalin, paraffin embedded, and cut into sections with 5μm thickness for HE staining. Results As the ratio of gelatin increased, the degradation of composite scaffolds became faster. On the 7th day, all the scaffold sections showed exudation of some monocytes and neutrophils. On the 14th day, exudation of some monocytes, neutrophils and fibroblasts were observed and the scaffold began to degrade. On the 30th day, most of the scaffolds were degraded and surrounded by the fibrous tissue. Conclusion The scaffold composed of silk protein materials and gelatin has good histocompatibility and degradation ability. It will be useful in liver tissue engineering.

Objective:To investigate the expression of ATM gene in six human gastric cancer cell lines and cellular responses to DNA damage.Methods:Western-blot analysis was performed on six human gastric cancer cell lines,and the apoptosis kinases and cellular responses were observed after two cell lines MKN28 and MGC803 were treated with the DNA damage reagent CDDP.Results:It was found that ATM was strongly expressed in MGC803,MKN28,MKN45,SGC7901 cell lines,but it weekly expressed in BGC823 and AGS cell lines.The level of ATM protein and apoptosis kinases in BGC823 were increased after treated with CDDP,while the G 2 phase checkpoint of MKN28 cells was deficient because the expressions of ATM,p-chk1 and p-chk2 were weak after treated with CDDP ( P 0.05).Conclusion:ATM deficiency may lead to apoptosis and sensitiveness to DNA damage.ATM may control multiple component elements in cell cycle and monitor cell cycle check point to restoration of cells after DNA damage.

Mitotic arrest-deficient 2 (MAD2) is one of the essential mitotic spindle checkpoint regulators, and it can protect cells from aberrant chromosome segregation. The Mad2 gene is very rarely mutated in many kinds of human cancer, but aberrantly reduced expression of MAD2 has been correlated with defective mitotic checkpoints in several human cancers. We have previously found that the MAD2 expression level is also shown to be associated with the multidrug resistance of tumour cells. In this study, we constructed a small interfering RNA (siRNA) eukaryotic expression vector of MAD2 and downregulated MAD2 expression in the gastric cancer cell line SGC7901 by transfection of MAD2-siRNA. SGC7901 cells stably transfected with the MAD2-siRNA exhibited significantly increased expression of phosphorylated survivin protein and enhanced drug resistance. Furthermore, MAD2-siRNA suppressed the proliferation of SGC7901 cells and inhibited tumour formation in athymic nude mice. This study clearly reveals that downregulation of MAD2 could regulate the cell cycle, increase proliferation, and improve the drug resistance of gastric cancer cells by regulating the activation of phosphorylated survivin. It also suggests both that MAD2 might play an important role in the development of human gastric cancer and that silencing the MAD2 gene may help to deal with the multidrug resistance of gastric cancer cells.

Objective:To investigate the expression of MAD2 in human normal tissues and gastric carcinoma.Methods:Immunohistochemistry was performed to test 23 human normal tissues and 102 gastrict cancer specimens.Results:MAD2 was localized in both the nucleus and cytoplasm in normal tissues.In normal stomach,MAD2 was expressed mainly in cytoplasm,but it showed additional staining in the nucleus in majority of gastric cancers.The positive rates of MAD2 protein expression were 70.59% in gastric cancer tissue and 38.24% in normal gastric mucosa respectively.Significant difference of MAD2 protein expression was found between cancer tissue and normal mucosa(P0.001).MAD2 protein was in versely correlated with histological grade and lymph node metastasis(P0.001).Conclusion:MAD2 inside cells may play a role in mitotic checkpoint control and the subcellular localizations of this protein undergo a shift in the subcellular localization during malignant transformation.The change of MAD2 expression may be involved maily in gastric carcinogenesis and prognosis of gastric cancer.

We studied the subcellular localization of MAD2 in normal human tissues and gastric cancers. MAD2 showed nuclear and cytoplasmic localization in normal tissues such as muscle, testis, thyroid gland, cerebrum, trachea, and skin: blood vessels in some organs were also MAD2+. In normal stomach, MAD2 was expressed mainly in cytoplasm but showed nuclear staining in the majority of gastric cancers. MAD2 was significantly overexpressed in gastric cancer compared with matched adjacent tissues (P < .001), and expression was related to differentiation and other clinical parameters of cancer (P < .001). The cancer/adjacent normal tissue (C/N) ratio of MAD2 expression was higher than 2 and more frequently observed in patients with lymph gland metastasis (P < .05) and related to cancer differentiation. Our findings suggest that the steady-state amount of MAD2 inside cells may serve as a molecular switch in mitotic checkpoint control and that the subcellular localizations of this spindle protein undergo a shift during malignant transformation. The change of MAD2 expression may be involved mainly in gastric carcinogenesis and associated with the prognosis of gastric cancer; a C/N of more than 2 may be associated with the worse prognosis for survival in gastric carcinoma.

Approximately 10-15% of the human prion disease is inherited and one of the important genetic mutations occurs in the octapeptide repeat region of prion protein gene. One of the variants, one octapeptide repeat deletion (1-OPRD), existed in several gastric cancer cell lines and its mutation frequency was higher in gastric cancer cases. However, the biological functions of it remain unknown. Wild-type and mutation forms of PrPC were cloned and transfected into gastric cancer cells. Cell apoptosis, adhesion, invasion, multidrug resistance (MDR) and proliferation were, respectively, investigated. Different expressed genes were screened by gene array and proved by PT-PCR. Further, luciferase report assay was used to explore the transcriptional activation of target genes. Forced overexpression PrPC (1-OPRD) could promote the gastric cancer cells SGC7901 growth through facilitating G1- to S-phase transition in the cell cycle. PrPC (1-OPRD) could also inhibit apoptosis, and promote adhesion, invasion and MDR in SGC7901. However, it exhibited no significant difference between wild-type PrPC (1-OPRD) and PrPC on apoptosis, invasion or MDR effects. Further experiments indicated that PrPC (1-OPRD) could trigger the transactivation of cyclinD3 besides cyclinD1 to promote cell transition and proliferation. Overexpression of PrPC (1-OPRD) might promote the proliferation of gastric cancer cells at least partially through transcriptional activation of cyclinD3 to accelerate the G1-/S-phase transition. The promoting proliferation effect of PrPC (1-OPRD) was more than that of wild-type PrPC. However, they showed no difference on apoptosis, adhesion, invasion or MDR effects of gastric cancer cells.