Female ; Humans ; Male ; Nervous System Neoplasms ; pathology ; Neuroglia ; pathology ; Neurons ; pathology

OBJECTIVETo explore the tumor growth inhibition of gamma secretase inhibitor MRK003 on human multiple myeloma xenograft mice by inhibition of AKT and Notch1 expression.

METHODSNOD/SCID mice were injected with human multiple myeloma cell lines RPMI8226 to establish a xenograft mouse model. Mice were randomized into two groups：the experimental group were injected with MRK003 at a dose of 5 mg× kg⁻¹×d⁻¹ for 14 days; the inhibitor was replaced by an equal saline in the control group. Mice were sacrificed by cervical dislocation on the next day after the last injection and tumor tissue was removed to detect the expression of Notch1 and AKT by immunohistochemistry.

RESULTSAfter subcutaneous injection with RPMI8226, mice had tumor formation in 5-7 days and the largest tumor block in 10-12 days. Before RPMI8226 injection, the mean sizes of tumor block in the experimental and the control groups were 509.2 mm³, 511.2 mm³(P>0.05). 9 days after injection, the mean sizes of tumor tissue in the experimental and the control groups were 636.6 mm³, 691.2 mm³(P<0.01). On the next day after the last injection, the tumor sizes of the experimental and the control groups were 683.5 mm³ and 1798.7 mm³(P<0.01). The size of tumor block in the experimental group was significantly smaller than that of the control group(P<0.01). Immunohistochemistry staining showed that the positive expression rates of Notch1(11.1%, P<0.01) and AKT(13.3%, P<0.01) in experimental group were significantly decreased compared with the control group(Notch1: 95.6%; AKT: 93.3%). Western blot results showed that Notch1 and AKT protein in experimental group were significantly lower than those in the control group.

CONCLUSIONMRK003 could inhibit the tumor growth of human multiple myeloma xenograft mice by downregulated expression of Notch1 signaling pathway.

Amyloid Precursor Protein Secretases ; antagonists & inhibitors ; Animals ; Cell Line, Tumor ; Cyclic S-Oxides ; pharmacology ; Humans ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Multiple Myeloma ; drug therapy ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Receptor, Notch1 ; metabolism ; Signal Transduction ; drug effects ; Thiadiazoles ; pharmacology ; Xenograft Model Antitumor Assays

OBJECTIVETo study the immunohistochemical expression of OCT4, CD117 and CD30 in germ cell tumors and to assess their diagnostic value.

METHODSImmunohistochemical study for OCT4 was performed on formalin-fixed, paraffin-embedded tissues of 63 cases of germ cell tumors, including seminoma (21), dysgerminoma (7), germinoma (8), embryonal carcinoma (8), yolk sac tumor (6), mature teratoma (10) and immature teratoma (3), as well as 25 cases of non-germ cell tumors, including granulosa cell tumor (8), clear cell adenocarcinoma (4), Leydig's cell tumor (5), diffuse large B-cell lymphoma (4) and malignant melanoma (4). Besides, the expression of CD117 and CD30 in all germ cell tumors was studied.

RESULTSAll cases of seminoma and germinoma, 6/7 cases of dysgerminoma and 7/8 cases of embryonal carcinoma were positive for OCT4, with strong nuclear staining. All other germ cell tumors and non-germ cell tumors were negative for OCT4, except for 1 case of yolk sac tumor and 1 case of clear cell adenocarcinoma which showed weak staining. Positive membranous expression of CD117 was demonstrated in 19/21(90.5%) seminoma, 5/7 dysgerminoma and 7/8 germinoma. Focal weak membranous staining was also noted in 1 case of yolk sac tumor. The melanocytes in teratoma were also positive for CD117. All cases of embryonal carcinoma were negative. On the other hand, positive membranous expression of CD30 were demonstrated in 6/8 embryonal carcinoma. One case of germinoma and 1 case of yolk sac tumor showed weak cytoplasmic positivity. All cases of seminoma and dysgerminoma, 7/8 germinoma and all cases of teratoma were negative for CD30.

CONCLUSIONSOCT4 is a sensitive and relatively specific marker for diagnosing seminoma, dysgerminoma, germinoma and embryonal carcinoma. CD117 and CD30 immunostains, when used in combination, represent valuable tools for distinguishing embryonal carcinoma and seminoma, dysgerminoma, germinoma.

Carcinoma, Embryonal ; metabolism ; pathology ; Diagnosis, Differential ; Dysgerminoma ; metabolism ; pathology ; Endodermal Sinus Tumor ; metabolism ; pathology ; Female ; Germinoma ; metabolism ; pathology ; Humans ; Ki-1 Antigen ; metabolism ; Male ; Neoplasms, Germ Cell and Embryonal ; metabolism ; pathology ; Octamer Transcription Factor-3 ; metabolism ; Ovarian Neoplasms ; metabolism ; pathology ; Proto-Oncogene Proteins c-kit ; metabolism ; Seminoma ; metabolism ; pathology ; Teratoma ; metabolism ; pathology ; Testicular Neoplasms ; metabolism ; pathology

Objectives: This study aims to determine the risk factors of new-onset atrial fibrillation (AF) in patients who underwent isolated coronary artery bypass grafting (CABG) to provide evidences for the prevention and treatment of new-onset AF after CABG. Methods: Between January 2015 and May 2016, a total of 602 patients who underwent CABG in our department were retrospectively analyzed. The patients were divided into the AF group and the non-AF group, according to the occurrence of post-operative AF. A comparative analysis was performed on the general characteristics and perioperative data of the patients. Univariate and multivariate logistic analysis was used to identify the predictors of new-onset AF after CABG. Results: 128 patients developed AF post CABG. Left ventricular ejection fraction was significantly lower in AF group than that in non-AF group (P<0.05), while the left ventricular end diastolic diameter (LVEDD) and left atrium diameter (LAD) were significantly larger in AF group than in non-AF group (all P<0.05). Moreover, mechanical ventilation time and ICU stay were significantly longer in AF group than in non-AF group (both P<0.05). Logistic univariate analyses showed that a history of hyperlipidemia (OR=1.738, P=0.019), higher left atrium diameter (OR=1.097, P=0.001), higher NYHA classes (OR=1.689, P=0.004), and use of nitrates (OR=2.196,P=0.030) were associated with new-onset AF after CABG. After adjusting for age and gender, multivariate analyses showed that higher NYHA classes (OR=1.597, P=0.007) and LAD enlargement (OR=1.113, P=0.0001) remained as independent risk factors for new-onset AF after CABG. Conclusions: Higher NYHA classes and LAD enlargement are independent risk factors for new-onset AF after CABG.

OBJECTIVETo investigate angiogenesis of collagen-chitosan porous scaffold, and to study survive of skin grafts on the scaffold after bilayer dermal equivalent (BDE) was transplanted on wounds with full thickness skin defects.

METHODSThe full thickness skin defects were made on 10 Bama miniature pigs and the BDE composed of collagen-chitosan porous scaffold and silicone membrane was transplanted on wound. Angiogenesis in dermal equivalent, wound healing, and healing and survive of skin grafts on dermal equivalent were observed in 1, 2, and 3 weeks after the BDE transplantation. At the same time, CD34 positive signals (neo-forming micro-vessels) were detected by immunohistochemical staining.

RESULTSInflammatory cells and fibroblasts infiltrated into dermal equivalent and a few new micro-vessels had been formed in 1 week after the BDE transplantation; neo-forming micro-vessels perpendicular to wound bed had increased significantly in 2 weeks after the BDE transplantation; neo-forming micro-vessels could be observed in almost all dermal equivalents in 3 weeks after the BDE transplantation. CD34 positive signals (neo-forming micro-vessels) in 3 weeks after the BDE transplantation was much more than those in 2 weeks after the BDE transplantation, and CD34 positive signals in 2 weeks after the BDE transplantation was much more than those in 1 week after the BDE transplantation. Survival rate of intermediate split thickness skin graft were 10%, 70% and 100% respectively after the skin grafts had been grafted for 2 weeks on surface of the scaffold which had been transplanted for 1, 2 and 3 weeks. Epidermis which had been grafted on surface of the scaffold for 1 or 2 weeks could perfectly survive after BDE had been transplanted for 1 or 2 weeks.

CONCLUSIONSCollagen-chitosan porous scaffold plays a very important role in wound healing of full thickness skin defect and can induce fibroblast infiltration and new micro-vessel formation. Epidermis grafted on surface of collagen-chitosan porous scaffold can perfectly repair wounds, and it has brilliant applied prospects in repairing skin defect.

Animals ; Chitosan ; Collagen ; Disease Models, Animal ; Female ; Graft Survival ; Neovascularization, Physiologic ; Silicones ; Skin ; injuries ; Skin Transplantation ; Swine ; Swine, Miniature ; Tissue Scaffolds ; Wound Healing

OBJECTIVETo evaluate the clinical efficacy of implanted biliary metallic stents in the management of malignant obstructive jaundice (MOJ).

METHODSPercutaneous transhepatic cholangiography and stent insertion were performed in 241 consecutive patients to treat malignant biliary obstruction between December 1998 and February 2009. The study end point was patient death. All patients were followed-up until death or until February 2010. The therapeutic efficacy was determined by statistical analysis of life span and pre- and post-operative laboratory indices.

RESULTSAll 241 patients were successfully stented. The level of bilirubin descended obviously within four weeks of implantation (P less than 0.05), and the early mortality rate was 4.56% (11/241). Two-hundred-and-two patients were followed-up (range: 8-193 weeks post-transplantation) and showed a median survival of 43.55 weeks. The survival rates at 13, 26, 39 and 52 weeks post-transplantation were 87%, 66%, 56%, and 41%, respectively. The stent patency rates at 13, 26, 39 and 52 weeks post-transplantation were 70%, 46%, 36% and 24%, respectively; the mean stent patency was 27.57 weeks. Cox regression analysis identified the strong predictors of improved survival as an initial bilirubin level of less than 221 mumol/L (P = 0.01) and a stent-induced bilirubin reduction of more than 50% (P = 0.002).

CONCLUSIONTranshepatic metallic biliary stenting is a safe and effective therapeutic intervention for malignant biliary obstruction. Significant periods of survival and palliation of jaundice can be achieved with this method. Hyperbilirubinemia and a stent-induced bilirubin reduction of less than 50% are independent predictive factors for the survival of MOJ patients.

Adult ; Aged ; Aged, 80 and over ; Biliary Tract Surgical Procedures ; Bilirubin ; metabolism ; Female ; Humans ; Jaundice, Obstructive ; surgery ; Male ; Metals ; Middle Aged ; Stents ; Survival Rate ; Treatment Outcome

OBJECTIVETo investigate the incidence of hot spot mutation of PDS gene by genetic screening testing method in Chifeng City, Inner Mongolia. The feasibility and effectiveness of genetic screening method in finding enlarged vestibular aqueduct syndrome were confirmed by temporal bone CT scan.

METHODSDNA were extracted from peripheral blood of 141 students of Chifeng Deaf and Dumb school. PDS IVS7-2 A-G mutation, the most common PDS mutation in Chinese population, was analyzed by direct sequencing for PDS exon 7, exon 8 with intron 7. The individuals found with homozygous or heterozygous PDS IVS7-2 A-G mutation were given further temporal CT scan, ultrasound scan of thyroid and thyroid hormone assays. The results of PDS genetic screening and temporal bone CT scan were compared with each other.

RESULTSThe sequencing results revealed twenty cases carrying PDS IVS7-2 A-G mutation, of whom nine cases were homozygous mutation and eleven cases were heterozygous mutation. Eighteen cases underwent temporal bone CT scan except two cases that left the school due to other health problem. Sixteen cases were confirmed to be enlarged vestibular aqueduct syndrome (EVAS) by CT scan and the shape and function of thyroid were clinically normal by ultrasound scan of thyroid and thyroid hormone assays, respectively.

CONCLUSIONSThe patients suffered from EVAS can be diagnosed by the screening for the PDS hot spot mutation which has unique advantage in epidemiologic study in large scale deaf population. The preliminary data of this study suggested relatively high incidence of EVAS in Chifeng area.

Adolescent ; Child ; Child, Preschool ; China ; Female ; Genetic Testing ; Hearing Loss ; genetics ; Humans ; Membrane Transport Proteins ; genetics ; Point Mutation ; Syndrome ; Vestibular Aqueduct ; pathology ; Vestibular Diseases ; genetics ; Young Adult

The Notch signaling pathway is a highly conserved cell signaling system that plays an essential role in many biological processes. Notch signaling regulates multiple aspects of hematopoiesis, especially during T cell develop-ment. Recent data suggest that Notch also regulates mature T cell differentiation and function. The latest data show that Notch also plays an essential role in alloreactive T cells mediating acute graft-versus-host disease (aGVHD), the most severe complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Notch inhibition in donor-derived T cells or blockade of individual Notch ligands and receptors after transplantation can reduce GVHD severity and mortality in mouse models of allo-HSCT, without causing global immunosuppression. These findings indicate Notch in T cells as an attractive therapeutic target to control aGVHD. In this article, the pathophysiology of aGVHD, the Notch signal pathway and aGVHD are reviewed.

Objective To study the correlation between serum prealbumin level before liver resection and prognosis of patients with primary hepatocellular carcinoma (HCC).Methods The clinical data of patients with HCC who underwent liver resection at the Affiliated Tumor Hospital of Guangxi Medical University from August 2007 to October 2016 were retrospectively analyzed.The previous albumin of 200 mg/L and the pre-albumin as predicted by the maximum selection rank statistic method were used as the bounding group,and reduced groups and the correlation between pre-operative serum pre-albumin levels and clinicopathological characteristics were analyzed.The Kaplan-Meier method was used to calculate the overall survival rate of patients with the different cutoff levels.The Cox proportional regression model was used to analyze,and cirrhosis,alpha-fetoprotein levels and Barcelona Clinic Liver Cancer staging were used to adjust the relationship between serum prealbumin and prognosis of liver resection for HCC patients.Analysis of stratified variables was performed and their interactions with serum prealbumin were analyzed.Results Of the 2 022 patients included in this study,there were 1 739 males and 283 females.Their age was 49.5 ± 11.2 years.The median follow-up was 37.4 months.The optimal cutoff value of prealbumin predicted by the maximum selection rank statistic method was 166 mg/L.Regardless of the cutoff values of previous albumin 200 mg/L or prealbumin 166 mg/L,multivariate analysis showed that preoperative serum prealbumin level was an independent prognostic risk factor for patients (P ＜0.05).The prognosis of patients with ＞200 mg/L (＞ 166 mg/L) serum prealbumin before surgery was significantly better than that of patients with ≤200 mg/L (≤166 mg/L) prealbumin,the differences were significant (all P ＜ 0.05).After adjusting for confounding factors,the prealbumin level correlated with prognosis of patients with HCC [cutoff value 200 mg/L:HR (95％ CI) was 1.59 (1.35-1.86),cutoff value 166 mg/L:HR (95％ CI) was 1.69 (1.44-1.98),all P ＜ 0.05].The results of stratified analysis showed that the relationship between prealbumin levels and the prognosis of HCC patients became more robust.Conclusions Preoperative serum prealbumin was an independent risk factor for prognosis of HCC patients,and it had predictive value on prognosis of HCC patients.

Rheumatoid arthritis (RA) is a chronic autoimmune disease with a high disability rate and unknown etiology.Early diagnosis and early treatment are essential to prevent the further development of the disease.In reeent years, metabolomics teeh- niques have been widely used in various fields of life sciences because of its wholism, dynamics, high sensitivity and high throughput.This artiele reviews the progress of metabolomics technology in various aspects of RA investigations sueh as early diagnosis, disease classification as well as drug efficacy prediction in order to provide new ideas for clinical diagnosis and treatment of RA from the metabolic perspective.