OBJECTIVETo investigate chondrocyte apoptosis and the expression of biochemical markers associated with apoptosis in Kashin-Beck disease (KBD) and in an established T-2 toxin- and selenium (Se) deficiency-induced rat model.

METHODSCartilages were collected from the hand phalanges of five patients with KBD and five healthy children. Sprague-Dawley rats were administered a selenium-deficient diet for 4 weeks prior to T-2 toxin exposure. The apoptotic chondrocytes were observed by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Caspase-3, p53, Bcl-2, and Bax proteins in the cartilages were visualized by immunohistochemistry, their protein levels were determined by Western blotting, and mRNA levels were determined by real-time reverse transcription polymerase chain reaction.

RESULTSIncreased chondrocyte apoptosis was observed in the cartilages of children with KBD. Increased apoptotic and caspase-3-stained cells were observed in the cartilages of rats fed with normal and Se-deficient diets plus T-2 toxin exposure compared to those in rats fed with normal and Se-deficient diets. Caspase-3, p53, and Bax proteins and mRNA levels were higher, whereas Bcl-2 levels were lower in rats fed with normal or Se-deficiency diets supplemented with T-2 toxin than the corresponding levels in rats fed with normal diet.

CONCLUSIONT-2 toxin under a selenium-deficient nutritional status induces chondrocyte death, which emphasizes the role of chondrocyte apoptosis in cartilage damage and progression of KBD.

Adolescent ; Animals ; Apoptosis ; drug effects ; Biomarkers ; Cartilage, Articular ; physiopathology ; Child ; Chondrocytes ; physiology ; Female ; Humans ; Kashin-Beck Disease ; etiology ; physiopathology ; Male ; Matrilin Proteins ; genetics ; metabolism ; Models, Animal ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Selenium ; deficiency ; T-2 Toxin ; pharmacology

OBJECTIVETo investigate the association of maternal body composition and dietary intake with the risk of gestational diabetes mellitus (GDM).

METHODSA total 154 GDM subjects and 981 controls were enrolled in a prospective cohort study in 11 hospitals from May 20, 2012 to December 31, 2013. Bioelectrical impedance analysis and dietary surveys were used to determine body composition and to evaluate the intake of nutrients in subjects at 21-24 weeks' gestation (WG). Logistic regression analysis was applied to explore the relationships of maternal body composition and dietary intake with the risk of GDM morbidity.

RESULTSAge, pre-pregnant body weight (BW), and body mass index (BMI) were associated with increased risk of GDM. Fat mass (FM), fat mass percentage (FMP), extracellular water (ECW), BMI, BW, energy, protein, fat, and carbohydrates at 21-24 WG were associated with an increased risk of GDM. In contrast, fat free mass (FFM), muscular mass (MM), and intracellular water (ICW) were associated with a decreased risk of GDM.

CONCLUSIONMaternal body composition and dietary intake during the second trimester of pregnancy were associated with the risk of GDM morbidity.

Adult ; Asian Continental Ancestry Group ; Body Composition ; Body Mass Index ; Cohort Studies ; Diabetes, Gestational ; epidemiology ; Diet ; Diet Surveys ; Feeding Behavior ; Female ; Humans ; Pregnancy ; Pregnancy Trimester, Second ; Risk Factors

BACKGROUNDVascular smooth muscle cell proliferation is an important process in the development of atherosclerosis and is associated with other cellular processes in atherogenesis. Telmisartan is reported to have partial peroxisome proliferator-activated receptor (PPAR)-γ activating properties and has been referred to as selective PPAR modulators, but valsartan just blocks angiotensin II (AngII) type 1 (AT1) receptors. This study aimed to compare the different effects of telmisartan and valsartan on human aortic smooth muscle cells (HASMCs) proliferation.

METHODSAbility of telmisartan and valsartan to inhibit proliferation of HASMCs was evaluated by the Cell Counting Kit-8 (CCK-8) in continuous cell culture. Whether the antiproliferative effects of telmisartan and valsartan depend on their effects on AngII receptors or activating the peroxisome PPAR-γ was also investigated in this study.

RESULTSTelmisartan inhibited proliferation of HASMCs by 52.4% (P < 0.01) at the concentration of 25 µmol/L and the effect depended on the dose of telmisartan, but valsartan had little effect on HASMCs proliferation (P > 0.05) and no dose response. When tested in cells stimulated with AngII, telmisartan had the same inhibition of HASMCs by 59.2% (P < 0.05) and valsartan also inhibited it by 41.6% (P < 0.05). Telmisartan and valsartan had the same effect on down-regulating AT1 receptor expression and telmisartan was superior to valsartan up-regulating AngII type 2 (AT2) receptor expression. Antiproliferative effects of telmisartan were observed when HASMCs were treated with the PPAR-γ antagonist GW9662 but antiproliferative effects of the PPAR-γ activator pioglitazone were not observed.

CONCLUSIONSTelmisartan, but not valsartan, inhibits HASMCs proliferation and has dose-dependent response without stimulation of AngII. AT2 receptor up-regulation of telmisartan contributes to its greater antiproliferative effects than valsartan. Its PPAR-γ activation does not play a critical role in inhibiting HASMCs proliferation.

Benzimidazoles ; pharmacology ; Benzoates ; pharmacology ; Cell Proliferation ; drug effects ; Humans ; Muscle, Smooth, Vascular ; cytology ; metabolism ; Myocytes, Smooth Muscle ; cytology ; drug effects ; PPAR gamma ; metabolism ; Receptor, Angiotensin, Type 1 ; metabolism ; Receptor, Angiotensin, Type 2 ; metabolism ; Tetrazoles ; pharmacology ; Valine ; analogs & derivatives ; pharmacology ; Valsartan

OBJECTIVETo investigate the usability of quick exposure check (Quick Exposure Check, QEC) for the field assessment of occupational musculoskeletal disorder risk factors.

METHODIn the shipyard and automobile manufacturing plants, QEC was used to observe the operations among workers with different jobs and to assess the work loads of workers. On the basis of results, the reliability of QEC was evaluated, and the correlation between QEC scores and morbidities of musculoskeletal disorders in workers was analyzed.

RESULTSThe inter-observer reliability (ICC) was in the range from 0.737 to 1.000, and intra-observer reliability (Spearman coefficient) was from 0.605 to 1.000. The order of exposure levels to risk factors of workers engaged in different jobs (QEC scores) in the shipyard factory was plumbers > assemblers > welders; The order of exposure levels to risk factors of workers engaged in different jobs (QEC scores) in the automobile factory was welders > punching workers > machinists > casters > assemblers. In different body parts, the exposure level at back and neck parts was the highest and the exposure level at the shoulder and wrist parts was the second. The regression analysis between QEC scores of body parts and the morbidities of musculoskeletal disorders showed that there was a good correlation between exposure levels and morbidities, the coefficients (r(2)) at the shoulder, wrist, and back (static work) were 0.670, 0.740 and 0.958, respectively (P < 0.05).

CONCLUSIONThe QEC method is suitable and reliable as demonstrated by the field assessment on the exposure to risk factors in shipyard and automobile workers, and its results is correlated closely to the disease prevalence.

Adult ; Cross-Sectional Studies ; Humans ; Musculoskeletal Diseases ; epidemiology ; Occupational Diseases ; epidemiology ; Occupational Exposure ; adverse effects ; Occupational Health ; Prevalence ; Risk Assessment ; Risk Factors ; Workload ; Workplace

OBJECTIVETo observe the effect of Tanshinone II A on the expression of epidermal growth facter (EGF) and epidermal growth facter recepter (EGFR) in human hepatocellular carcinoma cell line SMMC-7721.

METHODSThe human hepatocellular carcinoma SMMC-7721 cells cultured in vitro was treated with different concentrations of Tanshinone II A. The proliferation of the cells was measured by MTT assay, and the apoptosis of the cells was investigated by flow cytometry and cytochemical staining with Hoechst 33342. The expression of EGF and EGFR was detected by immunocytochemistry method. The levels of EGF in medium were measured by radioimmunoassay.

RESULTTanshinone II A inhibited the growth of SMMC-7721 cells remarkably in a dose-dependent manner. The inhibitory rate reached the peak (72.5%) after 0.5 microg/ml Tanshinone II A was used for 48 h, which was significantly higher than that in the controls (P<0.05). FCM analysis showed that when SMMC-7721 cells were treated with 0.5 microg/ml Tanshinone II A, the apoptosis rates for 24 h, 48 h and 72 h were (4.06+/-0.27)%, (7.58+/-0.56)% and (5.23+/-0.13)%, respectively which were markedly higher than those in the controls (all P<0.01). SMMC-7721 cell apoptosis with cell shrinkage, nuclear chromatin concentration and fragmentation as well as the formation of apoptotic bodies were observed by cytochemical staining when treated with Tanshinone II A. The immunocytochemistry showed that the expressions of EGF and EGFR were down regulated while the concentration of Tanshinone II A was increasing. The high expression rates for EGF and EGFR were 10%, 20%, respectively, and the gray scale was 181.52+/-1.63, 179.37+/-1.59, which were markedly higher than those in the controls (all P<0.05). The levels of EGF in medium measured by radioimmunoassay were decreased significantly after Tanshinone II A treatment.

CONCLUSIONTanshinone II A can inhibit cell proliferation and induce apoptosis in hepatocellular carcinoma cell line SMMC-7721, which may be related to the down-regulation of EGF and EGFR protein expression.

Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; Diterpenes, Abietane ; Down-Regulation ; drug effects ; Epidermal Growth Factor ; genetics ; metabolism ; Humans ; Liver Neoplasms ; metabolism ; pathology ; Phenanthrenes ; pharmacology ; Receptor, Epidermal Growth Factor ; genetics ; metabolism

OBJECTIVETo evaluate the clinical efficacy and safety of Chinese drugs for the treatment of children's infectious mononucleosis (CIM).

METHODSSixty CIM patients were assigned into the treated group and the control group, patients in the treated group were administered with Chinese herbal decoction, and those in the control group were treated with intravenous dripping of ganciclovir 10 mg/kg per day, for a treatment course of 14 days.

RESULTSThe total effective rate was 96.0% in the treated group and 97.1% in the control group, showing insignificant difference between groups. The efficacy in the treated group was superior to that in the control group on the fever clearance time (3.0+/-1.5 days vs 4.9+/-3.9 days ) and the disappearance time of cervical lymph node swelling (0.8+/-1.0 score vs 1.5+/-1.2 score), showing statistical significance (all P<0.05). T-cell subsets were markedly improved in both groups after treatment. Adverse reaction occurred in four cases of the control group.

CONCLUSIONUsing Chinese herbs for clearing heat, removing toxin, activating blood circulation, and dissolving stasis is effective and safe for the treatment of CIM. It can effectively improve the clinical symptoms and shows a certain effect on immune regulation.

Antigens, CD ; immunology ; Child ; Herpesvirus 4, Human ; genetics ; Humans ; Infectious Mononucleosis ; drug therapy ; immunology ; Medicine, Chinese Traditional ; Polymerase Chain Reaction

OBJECTIVEIn mid-July 2005, five patients presented with septic shock to a hospital in Ziyang city in Sichuan, China, to identify the etiology of the unknown reason disease, an epidemiological, clinical, and laboratory study were conducted.

METHODSAn enhanced surveillance program were established in Sichuan, the following activities were introduced: active case finding in Sichuan of (a) laboratory diagnosed Streptococcus suis infection and (b) clinically diagnosed probable cases with exposure history; supplemented by (c) monitoring reports on meningococcal meningitis. Streptococcus suis serotype 2 infection was confirmed by culture and biochemical reactions, followed by sequencing for specific genes for serotype and virulence factors.

RESULTSFrom June 10 to August 21, 2005, 68 laboratory confirmed cases of human Streptococcus suis infections were reported. All were villagers who gave a history of direct exposure to deceased or sick pigs in their backyards where slaughtering was performed. Twenty six (38%) presented with toxic shock syndrome of which 15 (58%) died. Other presentations were septicaemia or meningitis. All isolates were tested positive for genes for tuf, species-specific 16S rRNA, cps2J, mrp, ef and sly. There were 136 clinically diagnosed probable cases with similar exposure history but incomplete laboratory investigations.

CONCLUSIONAn outbreak of human Streptococcus suis serotype 2 infections occurred in villagers after direct exposure to deceased or sick pigs in Sichuan. Prohibition of slaughtering in backyards brought the outbreak to a halt. A virulent strain of the bacteria is speculated to be in circulation, and is responsible for the unusual presentation of toxic shock syndrome with high case fatality.

Animals ; Bacteremia ; epidemiology ; microbiology ; China ; epidemiology ; Disease Outbreaks ; Humans ; Meningitis, Bacterial ; epidemiology ; microbiology ; Shock, Septic ; epidemiology ; microbiology ; Streptococcal Infections ; epidemiology ; microbiology ; veterinary ; Streptococcus suis ; isolation & purification ; Swine ; Swine Diseases ; microbiology

BACKGROUNDRetroviral vectors have been widely used to introduce foreign into various target cells in vitro, thus showing relatively high systemic delivery efficiency of various transgene products. The authors investigated the stability and efficiency of skeletal muscle-specific hybrid retroviral vectors in expression of human factor IX (FIX) in vitro and iv vivo.

METHODSFIX cDNA in LIXSN vector was replaced with a FIX minigene containing splicing donor and splicing acceptor sequence of first intron of human FIX gene. Two copies of muscle creatine kinase enhancer (MCK, Me2) were inserted in forward or reverse orientation at NheI site of 3' long terminal repeat (LTR), resulting in two hybrid vectors, which were designated as LMe2IXm2SN(F) and LMe2IXm2SN(R), respectively. The vectors were tested in vitro and in vivo for stability and muscle-specificity of factor IX expression with SCID mice.

RESULTSMuscle cells carrying vector with Me2 expressed significantly higher levels of FIX (up to 1800 ng/106.24 h) than those without Me2, thus suggesting that Me2 could specifically increase expression level of FIX in muscle cells. Myoblasts transduced with LMe2IXm2SN(R) produced much less FIX in vivo in SCID mice than LMe2IXm2SN(F). One or two copies of Me2 sequence were deleted in myoblasts transduced with LMe2IXm2SN(R) without changing the orientation of Me2.

CONCLUSIONSLTR inserted with MCK enhancers can specifically increase human FIX expression in skeletal muscle cells in vitro and in vivo, and MCK enhancer should be positioned in the same orientation as that of LTR promoter.

Animals ; Creatine Kinase ; genetics ; Creatine Kinase, MM Form ; Enhancer Elements, Genetic ; Factor IX ; analysis ; genetics ; Gene Expression ; physiology ; Genetic Techniques ; Genetic Vectors ; Hybridization, Genetic ; Isoenzymes ; genetics ; Mice ; Mice, SCID ; Retroviridae ; genetics ; Terminal Repeat Sequences

OBJECTIVETo prepare the rAAV2/hFIX and evaluate the efficiency of the preparation on gene therapy of hemophilia B model mice.

METHODSThe rAAV-2/hFIX was prepared by "one helper virus-one vector cell line" strategy and transfected both BHK-21 and C2C12 cells in vitro. The hFIX antigen level in cell culture supernatant was assayed. The rAAV-2/hFIX was injected into muscles of hemophilia B model mice and assayed the serum hFIX levels, hFIX clotting activity, bleeding time, 5 min bleeding volume.

RESULTSThe hFIX antigen could be detected from 24 h till 120 h after BHK-21 and C2C12 cells were transfected with highest levels at 24 h reaching (51.0 +/- 6.5) ng/10(5) cells and (68.0 +/- 7.2) ng/10(5) cells, respectively. The rAAV2/hFIX injected mice could efficiently express hFIX and peaked at three weeks after injection, then slowly decreased but low level hFIX antigen was still detectable till 10 weeks after injection. There were significant differences between the high, middle and low dose groups of rAAV2/hFIX and the control group (P < 0.01), the plasma FIX clotting activities in the model mice were improved remarkably, bleeding time was greatly shortened and bleeding in 5 min was decreased. The hFIX expression level and FIX clotting activity of the high dose of rAAV2/hFIX group (1.6 x 10(13) v.g./kg) reached about (387.0 +/- 12.5) ng/ml plasma in contrast with the normal levels of (30.0 +/- 5.5)% at the third week after injection. No rAAV2 vector DNA was detected in the organs except for injected muscle tissue.

CONCLUSIONThe rAAV2/hFIX transfected BHK-21 and C2C12 cells could efficiently express hFIX antigen and was of therapeutic effects for the hemophilia B model mice by intramuscularly injection.The results provide the basis for clinical trial of rAAV2 gene therapy for hemophilia B.

Animals ; Cell Line ; Dependovirus ; genetics ; Disease Models, Animal ; Factor IX ; genetics ; metabolism ; Female ; Genetic Therapy ; methods ; Genetic Vectors ; Hemophilia B ; blood ; therapy ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Recombinant Fusion Proteins ; genetics ; metabolism ; Transfection

Animals ; Gene Expression ; Genetic Therapy ; Male ; Mice ; Spermatogenesis ; Stem Cell Transplantation ; Testis ; metabolism ; Transfection