Objective To investigate the assciation between hypertriglyceridemia and insulin resistance in type 2 diabetes (T2DM).Methods One hundred and forty-nine T2DM patients were divided into hypertriglyceridemia (n =88) and normal-triglyceridemia (n =61) groups according to triglyceridemia levels,waist circumference (WC),waist to height ratio (WHtR),fasting blood-glucose (FPG),glycosylated hemoglobin (HbA1 c),uric acid (UA),total cholesterol (TC),fasting insulin (FINS) and homeostatic model assessment for insulin resistance (HOMA-IR) levels were measured and compared between the two groups.Results Compared with the normal-triglyceridemia group,The levels of WC,WHtR,UA,TC,FINS and HOMA-IR of patients in the thypertri-glyceridemia group were significantly higher (Hypertriglyceridemia group:WC(89.51 ±10.31) cm,WHtR 0.55 ±0.06,UA(316.95 ±88.50) μmol/L,TC(5.74 ± 1.72) mmol/L,FINS (8.63 ± 4.91) μU/L,HOMA-IR 4.48 ± 3.14 ; Normal-triglyceridemia group:WC (86.31 ± 7.98) cm,WHtR 0.53 ± 0.05,Uric(275.48 ± 88.36) μmol/L,TC (5.15 ± 1.13) mmol/L,FINS (6.20 ± 3.89) μU/L,HOMA-IR 3.38 ± 2.76; t value were 2.133,2.315,2.815,2.349,2.364,2.221 ; P ＜ 0.05) ; HOMA-IR correlated positively with WC (r =0.233,P ＜ 0.01),WHtR(r =0.268,P ＜ 0.01),BMI (r =0.161,P ＜ 0.05),FPG(r=0.442,P ＜0.01),AST(r=0.169,P ＜0.0S),UA (r =0.907,P ＜0.01),TG(r =0.220,P ＜0.01)and FINS(r =0.907,P ＜0.01).Conclusion T2DM with hypertriglyceridemia increased insulin resistance.

OBJECTIVETo explore causes of shoulder pain and propose prevention measures in treating acromioclavicular joint dislocation.

METHODSFrom January 2005 to January 2013, 86 patients with acromioclavicular joint dislocation (Tossy III) were treated with hook plate fixation, and were divided into two groups. Bsaed on recovery of shoulder function mostly, the patients who suffered from rest pain, motion pain were named as shoulder pain group, while the patients without pain were named as painless group. In shoulder pain group, there were 21 cases including 15 males and and 6 females ranging the age from 22 to 62 years old with an average of (40.6±11.2) years old. There were 8 cases were on the left side and 13 cases were on the right side. In painless group, there were 65 cases including 36 males and and 29 females ranging the age from 19 to 65 years old with an average of (40.0±11.3) years old. There were 33 cases were on the left side and 32 cases were on the right side. The time from injury to operation ranged from 3 h to 8 d with an average of 34.6 h. Shoulder function of all patients were normal before injuried. Postoperative pain, activity of daily living (ADL), range of motion, deltoid muscle strength were compared. Anteflexion,rear protraction, abduction and upthrow of shoulder joint were also compared. Postoperative complications between two groups were observed and compared.

RESULTSAll patients were followed up from 12 to 48 months with an average of 18.5 months. Constant-Murley score were used to evaluate clinical efficacy at the least following up, and 13 cases got an excellent results, 5 moderate, 2 good and 1 poor in shoulder pain group ; while 61 cases were obtained excellent results, 3 moderate and 1 good in painless group. There were significantly differences between two groups in Constant-Murley score and activity of shoulder joint (P<0.05). In shoulder pain group, 3 cases were disconnected, 1 case occurred stress fracture, 9 cases were subacromial impingement syndrome, 5 cases occurred subluxation, 1 case occurred plate breakage and 11 cases were acromioclavicular arthritis.

CONCLUSIONChosing individual clavicular hook plate, fulfilling anatomic reset, paying attention to the repair of articular capsule ligament, and reducing hook and bone antagonism between stress is the key point of preventing and decreasing postoperative shoulder pain.

Acromioclavicular Joint ; injuries ; physiopathology ; surgery ; Adult ; Bone Plates ; adverse effects ; Case-Control Studies ; Female ; Fracture Fixation, Internal ; instrumentation ; methods ; Humans ; Male ; Middle Aged ; Postoperative Complications ; etiology ; Range of Motion, Articular ; Shoulder Dislocation ; complications ; physiopathology ; surgery ; Shoulder Pain ; etiology ; Treatment Outcome ; Young Adult

This study examined the effect of nicotine on the expression of mutant p53 (mt-p53) in bladder cancer rats. The rat models of bladder cancer were established by infusing N-methyl-nitroso-urea (MNU, 10 mg/kg every 2 weeks for 8 weeks) into the bladder. Pathological examination on the bladder was conducted to confirm the establishment of the model. All the bladder cancer rats were randomly divided into an MNU group and 3 nicotine groups. In the nicotine groups, the rats were intragastrically administered nicotine at different concentrations (25, 15, 5 mg/kg respectively) 3 times per week for 8 weeks. The mt-p53 expression was detected by the immunohistochemical method. The results showed that rat bladder cancer models developed histopathological changes of bladder transitional cell carcinoma. The positive rate of mt-p53 expression in the 3 nicotine groups (25, 15, 5 mg/kg) was 75.00%, 58.33% and 41.67% by the 14th week, respectively, significantly higher than that in the MNU group (33.33%) (all P<0.05). The mt-p53 expression rate was positively correlated with the medication dose and time (P<0.05). It is concluded that nicotine may play an important role in the development of bladder cancer partially by increasing the expression of mt-p53.

This study is aimed at investigating the potentials of ex vivo expansion and pluri-differentiation of cryopreservation of adult human bone marrow mesenchymal stem cells (hMSCs) into chondrocytes, adipocytes and neurocytes. Cryopreserved hMSCs were resuscitated and cultured for 15 passages, and then induced into chondrocytes, adipocytes and neurocytes with corresponding induction medium. The induced cells were observed for morphological properties and detected for expressions of type II collagen, triglyceride or neuron-specific enolase and nestin. The result showed that the resuscitated cells could differentiate into chondrocytes after exposure to transforming growth factor beta(1) (TGF-beta(1)), insulin-like growth factor I (IGF-I) and vitamin C (V(C)), and uniformly changed morphologically from a spindle-like fibroblastic appearance to a polygonal shape in three weeks. The induced cells were heterochromatic to safranin O and expressed cartilage matrix-procollagenal (II) mRNA. The resuscitated cells cultured in induction medium consisting of dexamethasone, 3-isobutyl-1-methylxanthine, indomethacin and IGF-I showed adipogenesis, and lipid vacuoles accumulation was detectable after 21 d. The resuscitated hMSCs were also induced into neurocytes and expressed nestin and neuron specific endolase (NSE) that were special surface markers associated with neural cells at different stage. This study suggested that the resuscitated hMSCs should be still a population of pluripotential cells and that it could be used for establishing an abundant hMSC reservoir for further experiment and treatment of various clinical diseases.
Bone Marrow Cells ; cytology ; Cell Culture Techniques ; methods ; Cell Differentiation ; Cells, Cultured ; Cryopreservation ; methods ; Humans ; Mesenchymal Stromal Cells ; cytology ; Pluripotent Stem Cells ; cytology ; Tissue Engineering ; methods

OBJECTIVETo establish strategies for preventing graft versus host disease (GVHD) and reducing treatment associated morbidity while preserving graft versus leukemia (GVL) effect in nonmyeloablative allogeneic bone marrow transplantation (allo-BMT), with or without donor lymphocyte infusion (DLI) after BMT.

METHODS3 x 10(7) bone marrow cells mixed with 1 x 10(7) spleen cells from the same BALB/c mouse were transplanted into the nonablative irradiated inbred 615 mouse which received a single subcutaneous injection of 1 x 10(6) L615 leukemia cells three days before. The experiments were designed as follows (ten mice in each group): myeloablative BMT control group (group A), nonmyeloablative conditioning without BMT group (group B), nonmyeloablative BMT group (group C), and nonmyeloablative BMT + DLI group (group D). GVL effects were assessed by survival time, white blood cell count and L615 cells in peripheral blood and histologic changes. GVHD was assessed by signs of weight loss, ruffled fur, diarrhea and histologic changes of skin, liver and small intestines. Chimerism was detected by cytogenetic analysis and PCR technique.

RESULTSThe survival time of group A, B, C and D was (20.3 +/- 13.4), (15.9 +/- 1.1), (21.6 +/- 1.7) and (37.8 +/- 2.0) days, respectively, being no significant difference between group A and group C (P > 0.05). The survival time of group C was longer than that of group B (P < 0.01). And among group B, C and D, group D had the longest survival time (P < 0.01). GVHD signs and histologic changes were observed in 60% of control group mice at + 14 day, but none of group C and group D. 40% of mice in group A died of treatment associated morbidity within two weeks, but none in group C and group D. Allogeneic chimerism was kept in group A, but excluded gradually in group C.

CONCLUSIONGVL effect seems preserved in nonmyeloablative BMT mice, but weaker than that in myeloablative BMT mice. GVL effect seems to be enhanced by DLI after nonmyeloablative BMT. GVHD and transplantation associated morbidity seems to be reduced in nonmyeloablative BMT.

Animals ; Bone Marrow Transplantation ; immunology ; methods ; Combined Modality Therapy ; Female ; Graft vs Host Disease ; prevention & control ; Graft vs Leukemia Effect ; Leukemia, Experimental ; therapy ; Leukemia, Lymphoid ; therapy ; Lymphocyte Transfusion ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Transplantation Conditioning ; methods ; Transplantation, Heterologous

OBJECTIVETo investigate the effect of rosiglitazone on the expression of nuclear factor-kappaB (NF-kappaB) and coupling factor 6 (CF6) induced by tumor necrosis factor-alpha (TNF-alpha) in cultured human umbilical vein endothelial cells (HUVEC).

METHODSCultured HUVEC of passage 3-5 were stimulated with TNF-alpha and then cultured in the presence of rosiglitazone. The expression of CF6 and NF-kappaB subunit p65 were evaluated by immunocytochemistical method.

RESULTSPretreatment of HUVECs with rosiglitazone inhibited TNF-alpha-induced expression of CF6 in a dose-dependent manner. The activation of CF6 stimulated by TNF-alpha was suppressed by ROS in a dose-dependent manner.

CONCLUSIONTNF-alpha-induced enhancement of the gene expression and release of CF6 is mediated by activation of NF-kappaB signaling pathway. ROS can inhibit the activation of IKK, block NF-kappaB signaling pathway and inhibit the expression of CF6, which may be the mechanism underlying the action of TZDs on hypertension.

Cells, Cultured ; Endothelial Cells ; cytology ; drug effects ; metabolism ; Humans ; Hypoglycemic Agents ; pharmacology ; Immunohistochemistry ; Mitochondrial Proton-Translocating ATPases ; biosynthesis ; NF-kappa B ; biosynthesis ; Oxidative Phosphorylation Coupling Factors ; biosynthesis ; Thiazolidinediones ; pharmacology ; Tumor Necrosis Factor-alpha ; pharmacology ; Umbilical Veins ; cytology

Accidents, Occupational ; statistics & numerical data ; China ; epidemiology ; Humans

OBJECTIVETo explore the prophylaxis effect of pretreatment of allograft with methoxypolyethylene glycol-succinimidyl-propionic acid ester (mPEG-SPA) and anti-OX40L monoclonal antibody (McAb) on acute graft-versus-host disease (aGVHD) after allogeneic bone marrow transplantation (allo-BMT) in mice.

METHODSResponder splenocytes from C57BL/6 donor mice (H-2(b)) were co-cultured with stimulator splenocytes from BALB/c recipient mice (H-2(d)) for 7 days in the presence or absence of anti-OX40L McAb followed by mPEG-SPA chemical modification. Donor bone marrow cells plus the mixed culture of T-cells were then transplanted into lethally irradiated BALB/c mice. The BALB/c recipient mice were divided into four groups: group A (allo-BMT control group), group B(mPEG-SPA modification group), group C (anti-OX40L McAb pretreated group) and group D (mPEG-SPA and anti-OX40L McAb dual-treated group). Survival time and survival rate of the recipients were observed after allo-BMT. GVHD was assessed by clinical signs and histological changes of skin, liver and small intestines. Enzyme-linked immunosorbent assay (ELISA) was used to detect cytokines (IL-4, IL-10 and INF-gamma) production. Flow cytometry (FCM) analysis was used to detect allogeneic chimerism.

RESULTS(1) The mice in group A developed typical clinical signs of aGVHD and all mice died within 17 days after BMT with an average survival time (AST) of (12.1 +/- 5.5) days. The signs of aGVHD were less evident in mice of groups B, C and D, and their AST (36.2 +/- 24.9, 32.0 +/- 24.8 and 44.3 +/- 23.2 days, respectively) were all longer than that in group A (P < 0.05). AST of group D being the longest (P < 0.05). The survival rates at day 60 post-BMT in groups B, C and D were 50%, 41.7% and 66.7%, respectively. (2) Serum IFN-gamma level was increased after BMT in group A, and peaked in day 10 to day 15 post-BMT, while the level was decreased in groups B, C and D, reached the nadir on the day 10 post-BMT, with the lowest in group D (P < 0.01). After BMT, IL-4 and IL-10 levels were slightly decreased in group A, their levels were elevated in groups B and C (P < 0.05) and even more significantly increased in group D (P < 0.01). IL-4 and IL-10 levels peaked between day 10 and 15 post-BMT. (3) The average proportion of H-2(b) positive cells in recipient mice was 95% - 100% on day 60 post-BMT, with complete donor-type implantation.

CONCLUSIONCombination of mPEG-SPA and anti-OX40L McAb can block T-cell activated antigens and co-stimulatory pathway, regulate the T cells differentiation and induce the immune shift of Th0 cells toward Th2 cells. The immune tolerance induced by this method can significantly relieve aGVHD after allo-BMT.

Animals ; Bone Marrow Transplantation ; Graft vs Host Disease ; prevention & control ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Transplantation, Homologous

BACKGROUNDNonmyeloablative allogeneic bone marrow transplantation has been used since the 1990s as a new hematological stem cell transplantation strategy for treating hematological diseases. The purpose of this study was to explore the graft-versus-leukemia (GVL) effects of donor lymphocyte infusions (DLIs) after nonmyeloablative allogeneic bone marrow transplantations, while assessing the declines in treatment-associated morbidity, mortality, and graft-versus-host disease (GVHD).

METHODSA total of 615 (H-2k) mice were injected with L615 tumor cells and received 500 cGy (60Co gamma-ray) irradiation three days later, followed by an allogeneic bone marrow transplantation (allo-BMT). The allo-grafts consisted of 3 x 10(7) bone marrow cells and 1 x 10(7) spleen cells from BALB/C (H-2d) donor mice. Two days after the allo-BMT, the recipient mice were given 200 mg/kg of cyclophosphamide. Subsequently, recipient mice were infused with either donor spleen cells (2 x 10(7)) on day 14 or 21, or donor spleen cells (5 x 10(7)) pretreated with hydrocortisone and cyclosporin A (CsA) in vitro on day 14 post-BMT.

RESULTSThe median survival time of mice that received DLI on day 21 and pretreated DLI on day 14 post-BMT was longer than that of controls and the day 14 DLI group (P < 0.01). No evidence of severe GVHD was observed in the day 21 DLI group nor in the day 14 treated DLI group. Mixed chimerism was confirmed in the day 14 DLI group, the day 14 treated DLI group, and the day 21 DLI group on the thirteenth day post-transplantation; full donor chimerism was observed two weeks after DLI.

CONCLUSIONDonor lymphocyte infusion after nonmyeloablative bone marrow transplantation may reduce transplantation-associated morbidity and mortality while strengthening graft-versus-leukemia effects.

Animals ; Bone Marrow Transplantation ; immunology ; Cyclosporine ; pharmacology ; Female ; Graft vs Host Disease ; etiology ; Graft vs Leukemia Effect ; immunology ; Hydrocortisone ; pharmacology ; Lymphocyte Activation ; Lymphocyte Transfusion ; Male ; Mice ; Mice, Inbred BALB C ; Transplantation Chimera ; Transplantation, Homologous

OBJECTIVETo study the effect of delayed sequential bone marrow transplantation on acute graft-versus-host disease (aGVHD) in major H-2 incompatible mouse transplantation.

METHODSC57BL/6 (H-2b) mice were used as donors and BALB/c (H-2d) mice as recipients. BALB/c mice were given 8.0 Gys total body irradiation (TBI) on day 0 and infused with a blend of bone marrow cells and spleen cells in different time. Transplantation was carried out as follows: group I TBI on day 0 and transplantation at 4 h after TBI; groups of II TBI on day 0 and transplantation at 4 h, d1, d2, d3 after TBI; groups III TBI on day 0 and transplantation at day 4 after TBI; groups IV TBI on day 0 and transplantation at day 4 through day 7 after TBI. Recipient's spleen H-2b cells were detected by flow cytometry and the level of serum cytokines (IL-2, IL4, IL-6, IL-10 and IFN-gamma) by ELISA. The survival, aGVHD and hematopoietic recovery were observed.

RESULTSaGVHD occurred in group I and the mice all died within 3 weeks after transplantation. The 60 day survival rates of groups of II and III were 30% and 50% respectively. The degree of aGVHD in group III was modest and the survival rate was higher than that in other groups (P <0.05). The peak time of IL-2, IFN-gamma, IL-4 and IL-10 in groups III and IV were later than that in group I. The levels of IL-4 and IL-10 in groups III and IV were higher than that in group I and for the levels of IL-2 and IFN-gamma were on the contrary (P < 0.05). The level of IL-6 in all groups peaked on day 5 to day 10 after TBI and was higher in group I than in others (P <0.05). In group IV the mean value of donor H-2b cells was (98.1 +/- 1.1)% on day 60 and WBC counts recovered normal on day 20.

CONCLUSIONSDelayed sequential transplantation can reduce the morbidity of aGVHD ,improve the survival rate and not affect the engraftment and reconstitution of hematopoiesis in mouse allo-BMT. The mechanism of aGVHD prevention may be related to the reducing of type 1 cytokines of T lymphocyte and the increasing of type 2 cytokines.

Animals ; Bone Marrow Transplantation ; immunology ; methods ; Disease Models, Animal ; Female ; Graft vs Host Disease ; immunology ; prevention & control ; Interleukin-2 ; blood ; Interleukin-4 ; blood ; Interleukin-6 ; blood ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL