Background:Clinical outcomes of undifferentiated arthritis (UA) are diverse,and only 40 ％ of patients with UA develop rheumatoid arthritis (RA) after 3 years.Discovering predictive markers at disease onset for further intervention is critical.Therefore,our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development.Methods:We performed a prospective,multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals.Clinical and serological parameters were obtained at recruitment.Follow-up was undertaken in all patients every 12 weeks for 2 years.Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression.Results:A total of 234 patients were recruited in this study,and 17 (7.3％) patients failed to follow up during the study.Among the 217 patients who completed the study,83 (38.2％) patients went into remission.UA patients who developed RA had a higher rheumatoid factor (RF)-positivity (42.9％ vs.16.8％,x2=8.228,P=0.008),anti-cyclic citrullinated peptide (CCP) antibodypositivity (66.7％ vs.10.7％,x2 =43.897,P ＜ 0.001),and double-positivity rate of RF and anti-CCP antibody (38.1％ vs.4.1％,x2 =32.131,P ＜ 0.001) than those who did not.Anti-CCP antibody but not RF was an independent predictor for RA development (hazard ratio 18.017,95％ confidence interval:5.803-55.938;P ＜ 0.001).Conclusion:As an independent predictor of RA,anti-CCP antibody should be tested at disease onset in all patients with UA.

Objective To assess the value of salivary gland scintigraphy in diagnosis of Sj(o)gren's syndrome (SS).Methods A total of 44 patients with clinically suspicious SS were included.The data of salivary gland scintigraphy were retrospectively analyzed and the time-radioactivity curve (TAC) was obtained by outlining ROI in bilateral parotid glands and submaxillary glands.Uptake index (UI) and excretion fraction (EF) were defined.Both UI and EF were compared with the visual assessment and final diagnosis respectively.Results UI and EF of bilateral parotid glands and submaxillary glands in SS patients were significantly lower than those in non-SS patients (all P＜0.05).The impaired salivary gland function was classified as 0-3 grades by visual assessment.The UI of bilateral parotid glands and submaxillary glands were negatively correlated with the qualitative classification.While there were no significant correlations between EF and qualitative classification (all P＞0.05),except for that of right submaxillary gland (r=-0.312,P=0.039).The comprehensive diagnostic efficacy of UI on SS patients was higher than those of visual assessment,but their area under curves of ROC were not significantly different (all P＞0.05).Conclusion UI and EF can effectively evaluate salivary gland function and serve as objective tools to distinguish patients with SS.

Objective:Vacuolar ATPase (V-ATPase) was found within the membranes and internal organelles of a vast array of eukaryotic cells,and was related to various kinds of highly metastatic tumors.LASS2/TMSG1 gene was a novel tumor metastasis suppressor gene cloned from human prostate cancer cell line PC-3M in 1999 by our laboratory.It was found out that protein encoded by LASS2/TMSG1 could interact with the c subunit of V-ATPase (ATP6V0C).In this study,To use RNA interference to suppress the expression of ATP6V0C and try to further investigate the molecular mechanism of ATP6V0C in tumor metastasis and its relationship with LASS2/TMSG1 gene.Methods and Results:The expression level of ATP6V0C mRNA and protein in high metastatic potential prostate cancer cell lines (PC-3M-1E8 and PC-3M) was significantly higher than that in low metastatic potential prostate cancer cell lines (PC-3M-2B4 and PC-3),the expression level in PC-3M-1E8 being the highest.Follow-up tests selected PC-3M-1E8 cells for gene silencing.The expression and secretion of MMP-2 and the expression of MMP-9 in ATP6V0C siRNA transfected PC-3M-1E8 cells displayed no obvious change,but the activity of secreted MMP-9 was abated noticeably compared with the controls (P ＜ 0.05).Extracellular hydrogen ion concentration and V-ATPase activity in interference group were both reduced significantly compared with the controls (P ＜ 0.05).The migration and invasion capacity of ATP6V0C siRNA interfered cells in vitro were diminished significantly compared with the controls (P ＜ 0.05).Furthermore,a dramatic reduction of LASS2/TMSG1 mRNA and protein level after transfection of siRNA in PC-3M-1 E8 cells was discovered (P ＜ 0.05).Confocal immunofluorescence showed a vast co-localization of ATP6V0C protein and LASS2/TMSG1 protein in plasma and membrane.The co-localization signals of control group were much stronger than those of interference group.Conclusion:Specific siRNA silencing of ATP6V0C gene inhibits the invasion of human prostate cancer cells in vitro by mechanism of inhibiting V-ATPase activity and then reducing the extracellular hydrogen ion concentration,inhibiting MMP-9 activation and affecting ECM degradation and reconstruction.Meanwhile,ATP6V0C and LASS2/TMSG1 have interaction and it is likely that ATP6V0C functions as a feedback regulator of LASS2/TMSG1.

Objective To observe the effects of bone marrow?derived mesenchymal stem cells (BMSC) on glomerular podocyte injured by lipopolysaccharide (LPS) and the expression of related protein. Methods Podocytes are divided into control group, BMSC group, LPS group and LPS plus BMSC group. After 24 hours of intervention, observing each experimental group podocyte form under inverted phase contrast microscope;detecting the expressions of mRNA and protein of nephrin, CD2AP, synaptopodin, and TRPC6 by RT?PCR and Western?blot. Results Compared with control group, expressions of nephrin, CD2AP, and synaptopodin in LPS group decreased (P<0.05) while that of TRPC6 increased (P<0.05); compared with LPS group, expressions of nephrin, CD2AP, and synaptopodin in LPS+MSC group increased (P<0.05) while that of TRPC6 decreased (P<0.05). Conclusion BMSC may relieve LPS?induced podocyte injury.

AIM:We investigated how AT 1-R stimulated by mechanical stresses induces cardiac fibrosis .METHODS:We produced in vivo cardiac pressure overload model in angiotensinogen knockout ( ATG-/-) mice and in vitro mechanically-stretched cell model in cultured neonatal cardiac cells of ATG-/-mice both lack the participation of Ang II .RESULTS: Pressure overload for 4 weeks in ATG-/-mice induced myocardial hypertrophy accompanied by the significant interstitial fibrosis , however , the TGF-β, a key regulatory factor of fibrosis, was not significantly increased in these ATG-/-mice.Meanwhile, the inhibitor for AT1-R significantly inhibited mechani-cal stress-induced cardiac fibrosis in these ATG-/-models whereas inhibition of TGF-βdid not.CONCLUSION:The results showed that mechanical stress-induced fibrotic responses through AT 1-R required the phosphorylation of Smad 2 but not the involvement of TGF-β.

This study was aimed to investigate the effect of exogenous VEGF on hematopoietic stem cell mobilization and immune system. The C57BL/6J mice were randomly divided into the normal control group, VEGF short-term group (5 d) and VEGF long-term group (27 d). Mice in the experimental group were injected ip with VEGF (100 ng/d); mice in control group were injected ip with PBS. The white blood cell (WBC) count and the ratio of lymphocyte in the peripheral blood at different time point were assayed by hemacytometer. The percentage of hematopoietic stem cell (HSC), lymphocyte subgroup, regulatory T cell (Treg), myeloid-derived suppressor cells (MDSC) in the peripheral blood and spleen of different groups were detected by flow cytometry. The morphological changes of spleen and spleen index of mice in the control and long-term group were observed by microscopy. The results showed that the absolute number of WBC in the peripheral blood of mice significantly increased after injection of VEGF, and the peak value was at day 3. The percentage of Lin(-)Sca-1(+)CD117(+) cells in the peripheral blood and spleen of the long-term group were significantly higher than that in the normal control group (P < 0.05). The spleen of the mice in VEGF long-term group was larger than that of the control group, the spleen index also increased (P < 0.05), and remarkable extramedullary hematopoietic signs were found in the HE stained sections. There was no significant change in the total ratio of lymphocytes in the peripheral blood after injection, but the percentage of CD3(+) cells and the CD3(+)/B220(+) ratio in the long-term group deceased; the percentages of Treg and Gr-1(+)CD11b(+) MDSC in the experimental groups increased (P < 0.05), which more significantly increased in the long-term group than that in the short-term group (P < 0.05). It is concluded that the exogenous VEGF promotes hematopoietic stem cell mobilization, and at same time up-regulates the many kinds of suppressive immune cell levels which leads to changes of immuno-function.
Animals ; Hematopoietic Stem Cell Mobilization ; methods ; Male ; Mice ; Mice, Inbred C57BL ; Spleen ; cytology ; T-Lymphocytes, Regulatory ; Vascular Endothelial Growth Factor A ; pharmacology

A female patient diagnosed with acute myelocytic leukemia M5a (AML-M5a) relapsed 986 days after her allogeneic peripheral blood stem cell transplantation (allo-PBSCT) from an unrelated male donor with matched human leukocyte antigen (HLA). Three re-induction chemotherapies were administered, and partial remission was achieved. The patient was given repetitive infusion of cytokine-induced killer (CIK) cells expanded from recipient peripheral mononuclear cells of full donor chimerism due to loss of contact of quondam donor for donor lymphocyte infusion (DLI) and rejection of second transplantation. The patient achieved complete cytogenetical remission. This strategy might overcome the obstacle of donor unavailability and present an appealing new therapeutic alternative to donor-recruited adoptive immunotherapy for relapsed disease at post-transplantation.
Adult ; Cytokine-Induced Killer Cells ; transplantation ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia ; therapy

OBJECTIVETo assess the characteristics and daily treatment compliance of non-alcoholic fatty liver disease (NAFLD) patients in China.

METHODSNAFLD adult patients from 21 clinics of 12 cities in China were enrolled in this registry. Physical examination such as demographic characteristics (height, weight, waist circumference measurement), blood pressure and clinical laboratory and ultrasonographic examination of liver were undertaken. Daily practice including life style and medication were recorded and assessed in accordance with 2006 Chinese NAFLD treatment guidelines.

RESULTSA total of 1656 patients were enrolled (1146 male and 510 female), mean of 45.8 ± 12.6 years old, mean duration of NAFLD history was (47.2 ± 47.7) months. 44.9% of NAFLD were suffering from metabolic syndromes. Patients with central obesity have higher incidence of hypertension and lower level of high-density lipoprotein cholesterol (HDL-C) than those without central obesity, P < 0.05. Body mass index (BMI), waist circumference, triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) in ALT abnormal group were higher than those in ALT normal group (P < 0.05), HDL-C was lower in ALT abnormal group (P < 0.05). Significant differences existed between the BMI, female waist circumference, TG, fast insulin, HOMA index, ALT, AST and HDL-C among subgroups with mild, moderate and severe steatosis. Majority of the patients did not follow recommendations of NAFLD treatment guidelines. Among targeted population only 15.3% of patients used insulin sensitizers and 23.8% took lipid lowering medicine according to the guideline.

CONCLUSIONData indicated that nearly half of NAFLD patients co-morbid with metabolic disorders. Therapy compliance was unsatisfactory and the gap between current practice and Chinese NAFLD treatment guidelines was not optimal.

Adult ; Asian Continental Ancestry Group ; China ; epidemiology ; Fatty Liver ; diagnosis ; epidemiology ; therapy ; Female ; Humans ; Male ; Metabolic Syndrome ; epidemiology ; Middle Aged ; Non-alcoholic Fatty Liver Disease ; Risk Factors ; Waist Circumference

Objective To evaluate the outcome of combination of intensive preconditioning regimen allo-HSCT with imatinib for treatment of Ph chromosome positive acute lymphocyte leukemia (ALL). Methods Between 2009 and 2010, 8 patients diagnosed as Ph+ ALL received allo-HSCT from HLA identical sibling during complete remission. Imatinib was added into the therapies of 5 patients.Seven patients received the intensive preconditioning regimen based on BuCy2, one patient received the regimen of TBI-Cy. A median of 6. 02 × 108/kg mononuclear cells and 3. 14 × 106/kg CD34+ cells were transfused. GVHD prophylaxis included cyclosporine A and methotrexate. Results All patients were well tolerant to the regimen without serious regimen-related toxicity. The median time of ANC≥0. 5 × 109/L was 15. 5 days, and that of PLT≥20 × 109/L was 19 days. Thirty days after allo-HSCT, all patients got donor engraftment successfully. Among 8 cases, 4 cases presented acute GVHD, 2 developed degree Ⅰ , one developed degree Ⅱ , and one developed degree Ⅳ. Seven patients were alive 100 days after allo-HSCT, 3 of whom presented chronic GVHD. At the end of following-up period, 6 patients were alive, among them, 3 patients were alive without relapse; 3 patients relapsed; Two patients died, one from acute GVHD, and one from leukemia relapse. Conclusion Combined intensive preconditioning regimen allo-HSCT with Imatinib was an effective treatment for Ph+ ALL, but the effect of anti-chronic GVHD of imatinib should arouse certain attention.

Adolescent ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Male ; Tongue, Hairy ; etiology ; Transplantation, Homologous ; adverse effects