Objective To investigate the effects of short-term continuous subcutaneous insulin infusion (CSII) in newly diag-nosed type 2 diabetes mellitus(T2DM ) and to evaluate the treatment regimen conversion after CSII therapy .Methods 72 patients with newly diagnosed T2DM were treated with CSII for 2 weeks .Then they were randomly divided into two groups :the basal insu-lin group(glargine) and the oral anti-diabetic drug(OAD) group .Both groups were followed up for 2 years .Blood glucose ,insulin and HbA1c were measured before and after CSII and during the 2-year follow-up .Results CSII significantly controlled the glucose levels ,reduced the TG ,TC ,LDL levels and the homeostasis model assessment of insulin resistance ( HOMA-IR) and increased the homeostasis model assessment of insulin secretion (HOMA-IS)(all P< 0 .05) .During 1-year follow-up ,HbA1c in the glargine group and the OAD group was (6 .13 ± 0 .47)% and(6 .21 ± 0 .38)% respectively .During 2-year follow-up ,the HbA1c values in the two groups were (6 .91 ± 0 .57)% and(6 .43 ± 0 .62)% respectively .T HOMA-IR and HOAM-IS obtained the long tern improve-ment without significant body weight increase .Conclusion Short-term intensive insulin therapy can effectively control the blood glucose ,improve the sensitivity of insulin and the β-cell function ;after CSII ,adopting basic insulin and oral antidiabetic drugs can a-chieve the ideal glycemic control .

Objective To explore the mechanism of protecting cells from hypoxia/ reoxygenation (H/R) injury by constructing specific small interference RNA (siRNA) to inhibit NALP3 expression in rat renal tubular epithelial cells (NRK-52E).Methods (1) To establish the H/R injury model of NRK-52E by regulating the pressure of N2 in incubator to hypoxia condition,the cells were cultured with hypoxia for 1 h and then with reoxygenation for 1 h,2 h,4 h,8 h,16 h and 24 h.The activity of lactae dehydrogenase (LDH) in the culture medium,cell count and cell viability,the expression of NALP3 were determined by biochemical method,trypan blue exclusion and Western blotting.(2) The siRNA was transfected into NRK-52E.The irrespective siRNA transfected group wasused as control.NALP3 expression was examined by Western blotting.(3) The cells were divided into 4 groups:control group,H/R group,irrespective siRNA transfected group and NALP3-siRNA transfected group.To establish the H/R injury model of NRK-52E by regulating the pressure of N2 in incubator to hypoxia condition,the cells were cultured with hypoxia for 1 h and then with reoxygenation for 4 h.And the expression of NALP3 was determined by Western blotting.(4)Cellular apoptosis was examined by Annexin V/PI staining and flow cytometry.NF-κB DNA binding activity,IκB-α,Bcl-2 and Bax expression were examined by EMSA and Western blotting.Results (1)Compared with the control group,the activity of LDH significantly increased,cell count and cell viability significantly decreased (all P＜0.05).The expression of NALP3 significantly increased and peaked at 4 h after H/R.(2)The specific siRNA could efficiently inhibit NALP3 expression in NRK-52E.Compared with the irrespective siRNA transfected group,the protein expression of NALP3 was significantly down-regulated in NALP3 siRNA transfected group (P＜0.05).(3)After hypoxia 1 h and reoxygenation 4 h,the activity of LDH and the expression of NALP3 increased.Compared with the irrespective siRNA transfected group,LDH concentration in media and the expression of NALP3 significantly decreased in NALP3-siRNA transfected group.(4)After hypoxia 1 h and reoxygenation 4 h,NF-κB DNA binding activity was increased,IκB-α phosphorylation and degradation,Bcl-2 and Bax were significantly up-regulated.However,compared with the irrespective siRNA transfected group,NF -κB DNA binding activity,IκB-α degradation and Bax/Bcl-2 were significantly decreased (P＜0.05) in NALP3-siRNA transfected group.At the same time,the ratio of apoptosis was significantly increased in three groups than that in control.Compared with the irrespective siRNA transfected group,the ratio of apoptosis in NALP3-siRNA transfected group was significantly decreased (P＜0.05).Conclusions H/R induces the expression of NALP3 in NRK-52E.The synthesized siRNA can inhibit the expression of NALP3 and protect NRK-52E from hypoxia/reoxygenation injury.The mechanism may be via inhibiting the activation of NF-κB,modulating expression of Bcl-2 and Bax,as well as decreasing cell apoptosis.

Aim To investigate the antioxidant capacity of crocetin and crocin in an in vivo system.Methods Column chromatography was applied to the seperation of crocetin and crocin-1 from gardenia.Crocetin(6.25,12.5 and 25.0 mg·kg~(-1)·d~(-1)) and crocin (18.7,37.5 and 75.0 mg·kg~(-1)·d~(-1)) were orally administered to kunming mice.Then,superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),total antioxidant capacity(TAOC)and malondialdehyde(MDA)in mice were determined for the comparison of antioxidant activity of crocetin and crocin-1.Results Oral administration of crocetin and crocin for six weeks could enhance SOD of liver and kidney,GSH-Px of liver and TAOC of heart and kidney.In addition,it could decrease MDA of serum in mice.Conclusions The comparison of results suggests the evidence supporting the comparable antioxidant activity of crocetin and crocin.The results of the research also indicate that liver and kidney are two organs targeted for protection concerning endogenous antioxidant among various tissues.

Previous studies have shown that ginsenoside Rb1 (Rb1), one of active components in ginseng, can activate insulin signaling pathway and promote translocation of glucose transporters (GLUTs) to increase glucose uptake in adipocytes. However, the effect of Rb1 on the expressions of GLUTs remains unknown. In this study, the effects of Rb1 on GLUT1 and GLUT4 were observed in 3T3-L1 adipocytes and epididymal adipose tissue of db/db obese diabetic mice. Male db/db mice were treated with Rb1 by intraperitoneal injection at the dosage of 20 mg x kg(-1) for 14 d. Rb1 reduced HOMA-IR significantly (P < 0.05, n = 5), and FBG and FINS sowed declining trend after treatment with Rb1. Rb1 recovered the expressions of GLUT1 and GLUT4 and phosphorylation of AKT in adipose tissue of db/db mice. In vitro, glucose consumption in 3T3-L1 adipocytes treated with 10 micromol x L(-1) Rb1 for 24 h was elevated (P < 0.05, n=3), and mRNA of GLUT1 and GLUT4 were up-regulated (P < 0.05, n=3) and proteins of GLUT1 and GLUT4 were also increased. AKT was activated in adipocytes treated with Rb1 for 3 h. It can be concluded that ginsenoside Rb1 can up-regulate the expression of GLUTs in adipose tissue, in addition to activate insulin signalling pathway, which may partially account for its insulin sensitizing activity and regulating effect of glucose metabolism.
3T3 Cells ; Adipocytes ; drug effects ; Animals ; Cell Line ; Diabetes Mellitus, Experimental ; metabolism ; Ginsenosides ; pharmacology ; Glucose ; metabolism ; Glucose Transport Proteins, Facilitative ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Up-Regulation ; drug effects

Objective:To evaluate the benefit of autologous stem cell transplantation (ASCT) as a consolidation therapy in the survival of multiple myeloma (MM) patients at different risks. Methods:A total of 67 MM patients who received ASCT as consolida-tion therapy between August 2006 and July 2011 were enrolled in the retrospective study. The cases were divided into three risk groups on the basis of the International Staging System and fluorescence in situ hybridization. Another 67 patients who accepted consolidation chemotherapy at the same period were selected as case-paired controls matched in terms of age, sex, optimal response after induction, and risk stratifications. All the patients received bortezomib-and/or thalidomide-based induction therapies. Results:No statistical differ-ences in non-complete remission (nCR)/complete remission (CR) rate were observed between the ASCT and chemotherapy groups (44.8%vs. 37.3%, P=0.380) after the induction therapy. The progression-free survival (PFS) was longer in the ASCT group than in the chemotherapy group (32.4 months vs. 15.1 months, P<0.001). The overall survival (OS) was longer in the ASCT group than in the che-motherapy group (58.8 months vs. 42.1 months, P=0.009). both the PFS (median:30.5 months vs. 11.2 months, P<0.001) and the OS (median:85.5 months vs. 34 months, P=0.015) rates were significantly prolonged in the high-risk subgroup after ASCT. In the interme-diate-risk subgroup, neither PFS nor OS showed any significance after ASCT (P>0.05). In the low-risk subgroup, only PFS was extend-ed (median: 34.8 months vs. 17.6 months, P=0.012) after ASCT, without significant improvements in the OS (P>0.05). Conclusion:The MM patients obtained cytogenetic high-risk benefits mostly from ASCT consolidation after inductions based on novel agents.

Weightlessness environment can lead to the muscle atrophy and body fluid distribution upward,which can cause the bone calcium metabolism disorder and always accompanied by the loss of bone microstructure and increased rate of bone fracture. Under microgravity,the astronauts are much easier to decrease the Ca2+ ion in bone, which can cause serious osteoporosis. However the bone lost is not equilibrium, it is especially serious in the mechanism loading bone and the recovery process is more difficult. These are very different from the osteoporosis in older people and postmenopausal osteoporosis. It is necessary to find an optimal method to due with it. In traditional Chinese medicine theory,the kidney stores "Jing" and dominates the bone, thus a lot of bone related diseases can be treated through the kidney. A lot of clinical practices have also proved that the Chinese herbs used under the guidance of basic Chinese medicine theory are always good at the treatment of common osteoporosis. In simulated weightlessness experiment, people found that the kidney nourishment drugs do can prevent the decrease of BMD. So in this article we want to review the causes of weightlessness and the potentials applications of tradition Chinese medicine in the treatment of weightlessness osteoporosis.
Humans ; Mechanical Phenomena ; Medicine, Chinese Traditional ; methods ; Osteoporosis ; etiology ; prevention & control ; therapy ; Weightlessness ; adverse effects

OBJECTIVETo investigate the relationship between the clinical features, pathogenesis, immunophenotype, different classification models and prognosis in Chinese patients with diffuse large B-cell lymphoma (DLBCL).

METHODSA total of 147 patients with DLBCL who were treated with CHOP-like or R-CHOP were subjected to analysis. Standard two-step Envision method of immunohistochemical staining was used to assess the expression of CD10, Bcl-6, MUM1, FOXP1, GCET1, CD5, Bcl-2, Ki-67, then according to Hans algorithm, Choi algorithm and Molecular markers, we compared the differences of their prognoses.

RESULTS(1) Kaplan-Meier univariate analysis of the clinical data of 147 DLBCL patients found that the 3-year overall survival (OS) rates were better in early stage (P=0.032), low IPI score (P=0.001), less than one extranodal involvement (P=0.014), and complete remission (P<0.01). The prognoses had no significant difference in terms of gender, age, LDH, B symptoms and treatment options (P value> 0.05). (2 )For Hans model, GCB group had 42 cases, the ABC group 85 cases; GCB were 47 cases, ABC 80 cases (according to Choi model). Choi model suggested GCB subtype showed much better prognosis than ABC subtype (P=0.047), while Hans model shed no statistically significant difference (P=0.285). (3) Ki-67 of 75% was found to significantly discriminate patients with good or bad prognosis. In R-CHOP group at the same time, low Ki-67 (P=0.017) and CD5-negative groups (P=0.012) were better. Cox proportional hazards regression model showed that IPI score (P=0.002) and Ki-67 (P=0.019) were independent adverse prognostic factors.

CONCLUSIONThe Ann Arbor stage, IPI score, extranodal involvement status and Ki-67 were significantly associated with prognosis .Compared to Hans algorithm, Choi had an advantage to predict the different prognosis between subtypes, and ABC group had poor outcome. Finally, both Ki-67 and IPI score were independent adverse prognostic factors.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Immunophenotyping ; Lymphoma, Large B-Cell, Diffuse ; diagnosis ; pathology ; therapy ; Male ; Middle Aged ; Prognosis ; Young Adult

BACKGROUNDOxymatrine has certain antiviral effects in the treatment of chronic hepatitis B (CHB), but its exact mechanism is unclear. The objective of the present study was to explore oxymatrine's antiviral mechanism by studying its effect on the hepatitis B virus (HBV) specific cytotoxic T lymphocyte (CTL) surface programmed death receptor-1 (PD-1) expression in CHB patients.

METHODSSixty-five CHB patients who had HBV DNA(3)10(4) copies/ml, positive HBeAg, positive human leukocyte antigen (HLA)-A2, alanine aminotransferase (ALT) > 2 x upper limit of normal value (ULN) were randomly divided into two groups: treatment group (n = 33), treated with an intravenous infusion of 600 mg oxymatrine in glucose solution once a day for a month, then with a 200 mg oxymatrine oral capsule three times a day, and a 200 mg silibin meglumine tablet three times a day; control group (n = 32) patients were treated only with silibin meglumine tablet, method and dosage were the same as those of treatment group. Three months later, peripheral blood HBV-specific CTL surface PD-1 expression, HBV-specific CTL level, HBV DNA, HBeAg, and results of liver function tests were analyzed and compared.

RESULTSThree months post-treatment, in the treatment group, peripheral blood HBV-specific CTL surface PD-1 expression ((19.42 ± 15.94)%) decreased significantly compared to the pretreatment level ((31.30 ± 24.06)%; P < 0.05), and decreased significantly compared to that of control group three months after treatment ((29.45 ± 21.62)%; P < 0.05). HBV-specific CTL level ((0.42 ± 0.07)%) significantly increased compared with the pretreatment ((0.29 ± 0.15)%; P < 0.01), and the control group posttreatment level was (0.31 ± 0.15)% (P < 0.05). HBV DNA level in 11 cases became negative (HBV DNA < 500 copies/ml, 33.33%), which was higher than that of the control group after treatment (two cases, 6.25%; χ(2) = 7.45, P < 0.01), HBeAg of nine cases turned negative (27.27%), which was higher than that of the control group after treatment (one case, 3.13%; χ(2) = 7.27, P < 0.01).

CONCLUSIONOxymatrine could downregulate peripheral blood HBV-specific CTL surface PD-1 expression in CHB patients, increase HBV-specific CTL level, which may be one of the possible mechanisms by which oxymatrine clears or inhibits HBV in CHB patients.

Adult ; Alkaloids ; therapeutic use ; Antiviral Agents ; therapeutic use ; DNA, Viral ; blood ; Female ; Hepatitis B virus ; immunology ; Hepatitis B, Chronic ; drug therapy ; immunology ; Humans ; Male ; Middle Aged ; Programmed Cell Death 1 Receptor ; analysis ; Quinolizines ; therapeutic use ; T-Lymphocytes, Cytotoxic ; chemistry

Objective To explore the anti-viral mechanism of kurarinol through studying its influence on cytotoxic T lymphocyte (CTL) surface program death receptor-1 (PD-1) expression of patients with chronic hepatitis B (CHB).Methods 69 cases of CHB,HBV DNA ≥ 104 copies/ml,HBeAg positive,human leukocyte antigen (HLA)-A2 positive,alanine aminotransferase (ALT) ＞ 2 × upper limit of normal value(ULN).69 cases were randomly divided into two groups:34 cases in treatment group,600 mg of kurarinol glucose injection was used for intravenous dripping,once a day,one month later,200 mg of kurarinol capsule was used orally,three times a day and.200 mg of silybin meglumine tablet was used orally,three times a day.35 cases in control group,only silibin meglumine tablet was used,method and dosage were the same as those of treatment group.Three months later,their peripheral blood HBV specific CTL surface PD-1 expression,non-specific CTL surface PD-1 expression and level of HBV specific CTL,HBV DNA and HBeAg negative rate and liver functions were analyzed and compared.Results 3 months after treatment,peripheral blood HBV specific CTL surface PD-1 expression of the treatment group decreased compared with that before treatment(t =2.39,P ＜ 0.05),it also decreased compared with that of the control group 3 months after treatment(t =2.26,P ＜ 0.05),HBV specific CTL increased compared with that before treatment(t =3.01,P ＜ 0.01),it also increased compared with that of the control group after treatment (t =2.65,P ＜0.05).There was no significant difference of non-specific CTL surface PD-1 expression compared with that before treatment(P ＞ 0.05),and there was no significant difference compared with that of the control group after treatment(P ＞ 0.05).HBV DNA of 11 cases (32.5％) turned negative (HBV DNA ＜ 500 copies/ml),higher than that of the control group after treatment(2 cases,5.71％)x2 =7.99,P ＜ 0.01,H BeAg of 9 cases(26.47％) turned negative,higher than that of the control group after treatment(1 case,2.86％),x2 =7.75,P ＜ 0.01.Conclusion Kurarinol can increase level of HBV specific CTL by down-regulating peripheral blood HBV specific CTL surface PD-1 expression of CHB patients,which may be one of the possible mechanisms that kurarinol can remove or inhibit HBV of CHB patients.

The objective of study was to investigate the origin and to classify the subtype of N-methyl-N-nitrosourea (MNU)-induced thymic lymphomas in mice. Histopathologic, immunohistochemical and ultrastructural studies were performed to analyze the pathological features of the neoplasms. The results showed that the thymus in all cases became totally replaced by sheets of cells of the lymphoid series. All the tumors coexpressed CD3 and TdT. Transmission electron microscopic study showed the plasma membranes of malignant lymphoma cells were smooth. The nuclear profiles were usually regular, with varying percentage of convoluted nuclei. Few cell organoids were observed in cytoplasm. In conclusion, all the MNU-induced tumor classified by histopathologic, immunohistochemical and ultrastructural studies as precursor lymphoblastic lymphoma that were unquestionably related to the thymus origin and T-cell lineage.
Animals ; Female ; Lymphoma ; chemically induced ; pathology ; ultrastructure ; Male ; Methylnitrosourea ; adverse effects ; Mice ; Mice, Inbred C57BL ; Thymus Gland ; pathology ; ultrastructure ; Thymus Neoplasms ; chemically induced ; pathology ; ultrastructure