ObjectiveTo observe the expression of syntaxin-1 in hippocampus of adult rats with hypothyroidism and the role of different doses of thyroid hormone replacement therapy,further to explore the molecular mechanism of brain damage.MethodsAll 44 male adult SD rats were randomly divided into 4 groups according to their body mass(250 - 300 g):hypothyroidism group,routine dosage thyroxine treatment group,high dosage thyroxine treatment group and control group (11 in each group).Hypothyroidism group,routine dosage thyroxine treatment group and high dosage thyroxine treatment group received daily intraperitoneal injection of propylthiouracil (PTU) 10 mg/kg.Hypothyroidism group was given PTU by intraperitoneal injection for two weeks after the previous four week treatment,the routine dosage thyroxine treatment group and the high dosage thyroxine treatment group were given 50,200 μg/kg L-thyroxine daily intraperitoneally for two weeks; the control group received daily intraperitoneal injection of saline.The levels of serum T3,T4 were assayed by radioimmunoassay method,and the level of syntaxin-1 in hippocampus was analyzed by immunohistochemistry.ResultsIn the hypothyroidism group,the levels of serum T3,T4[(0.34 ± 0.04),(43.01 ± 2.95)nmol/L] were significantly lower than those in the control group[(0.65 ± 0.05),(55.20 ± 3.56)nmol/L,all P ＜ 0.05].In the routine dosage of thyroxine treatment group,the levels of serum T3,T4[(0.63 ± 0.05),(55.04 ± 3.77)nmol/L] were not significantly different compared to the control group (all P ＞ 0.05 ).In the high dosage thyroxine thyroid hormone treatment group,the levels of serum T3,T4[(1.11 ± 0.10),(96.68 ± 6.42)nmol/L] were significantly higher than those in the control group(all P ＜ 0.05).The levels of syntaxin-1 protein in the CA1,CA3 and dentate gyrus(DG) of all layer regions of hippocampus (0.059 ± 0.016,0.064 ± 0.014,0.068 ± 0.016,0.069 ± 0.017,0.072 ± 0.016,0.070 ± 0.011,0.051 ± 0.012,0.072 ± 0.017) were significantly higher compared to the control group(0.037 ± 0.008,0.045 ± 0.010,0.042 ±0.009,0.040 ± 0.010,0.053 ± 0.009,0.042 ± 0.009,0.032 ± 0.007,0.047 ± 0.010,all P ＜ 0.05).In the routine dosage and the high dosage thyroxine thyroid hormone treatment group,the level of syntaxin-1 in CA1,CA3and DG regions(0.041 ± 0.011,0.046 ± 0.017,0.044 ± 0.014,0.037 ± 0.008,0.051 ± 0.010,0.043 ± 0.010,0.033 ± 0.011,0.045 ± 0.014 and 0.040 ± 0.010,0.045 ± 0.011,0.043 ± 0.010,0.033 ± 0.009,0.050 ± 0.010,0.041 ± 0.009,0.032 ± 0.009,0.046 ± 0.009)were not significantly different compare to the control group(all P＞0.05).ConclusionThe expression of syntaxin-1 in hippocampus of adult-onset hypothyroidism is increased,which can be reversed by routine dosage treatment of thyroxine.

OBJECTIVETo explore the effects of ICAM-1 gene transfection on the differentiation of MSCs to adipocytes.

METHODSThe recombinant retroviral expression plasmid MIGR1-ICAM-1 containing full length of mouse ICAM-1 gene was constructed. The constructed plasmid MIGR1-ICAM-1, empty plasmid MIGR1 and packaging plasmid ECOS were transfected into T293 cell lines and then the supernatant generated from T293 cells were used to infect mouse MSCs cell line C3H10T 1/2. The transfective efficiency was determined by inverted fluorescence microscope, real-time PCR and flow cytometry. Furthermore, ICAM-1 overexpressing MSCs (C3H10T 1/2-ICAM-1) and empty vector transfection MSCs (C3H10T 1/2-MIGR1) were cultured in medium with or without induction reagents, Oil-red-O staining was used to detect the lipid accumulation, and the expression of transcriptional factors C/EBPα and PPARγ, which were key factors in the differentiation of MSCs to adipocytes, were tested by real-time-PCR.

RESULTSThe recombinant retrovirus vector containing mouse ICAM-1 gene was successful constructed. After transfection into MSCs cell line C3H10T 1/2, the overexpression ICAM-1 MSCs cell line (C3H10T 1/2-ICAM-1) and control cell line (C3H10T 1/2-MIGR1) were obtained. Furthermore, these two cell lines were treated without or with adipocytic induction reagents, C3H10T 1/2-ICAM-1 showed significantly lower mRNA expression level for C/EBPα [(1.2 ± 0.7), (2.9 ± 0.9)] and PPARγ [(1557.6 ± 70.2), (7547.0 ± 442.2)] when compared with C3H10T 1/2-MIGR1 [(5.8 ± 0.5), (23.0 ± 2.3) and (2453.0 ± 215.6), (9856.3 ± 542.2)](P < 0.05). Moreover, little lipid droplet and decreased quantity of adipocytes were detected in C3H10T 1/2-ICAM-1 [(3.2 ± 0.5)/well, (12.2 ± 3.8)/well] than that in C3H10T 1/2-MIGR1 [(11.2 ± 0.4)/well, (51.3 ± 2.8)/well] (P < 0.05).

CONCLUSIONOverexpression of ICAM-1 in MSCs can inhibit its adipocytic differentiation.

Adipocytes ; cytology ; Animals ; Cell Differentiation ; Cell Line ; Intercellular Adhesion Molecule-1 ; genetics ; Mesenchymal Stromal Cells ; cytology ; Mice ; Transfection

Through cluster multistage sampling,a resident group of 6 412 subjects with hypertension in the rural area of Liaoning province were recruited.According to IDF and NCEP-ATPm criteria the age-standardized prevalences of metabolic syndrome were 36.2%and 25.9%respectively.The prevalence of metabolic syndrome decreased with advancing age,but increased with rising of blood pressure.

OBJECTIVETo study the effects of cadmium chloride in anterior pituitary and the relation between apoptosis and expression of procaspase-9 mRNA.

METHODSIn vivo studies:40 SD male rats were randomly distributed into four groups which were administered with CdCl2 at different doses by gavage for 6 weeks;

IN VITRO STUDIESthe rats' anterior pituitary cells were primarily cultured for 120 hours, then treated with CdCl2 at the dose of 0, 1.56, 3.12, 6.25, 12.50, 25.00, 50.00, 100.00 micromol/L for 6 hours; The indices included: expression of procaspase-9 mRNA, detection of apoptosis with TUNEL assay.

RESULTSThe results showed the excretion of ACTH, LH seemed to be decreased dramatically and the apoptosis inclined to enhance remarkably, and further more, the expression of procaspase-9 mRNA appeared to be increased significantly as compared with those of the control. It was show that a dose-effect relationship between the CdCl2 dosing and indices above with the regression analysis and a linear correlation between the mean gray value of apoptosis cell and the relative gray value of procaspase-9 mRNA positive cell. The results indicated that damnification, for example, apoptosis could be caused by certain dose of CdCl2 in anterior pituitary cells with dose dependent manner. Caspase-9 might play a role in the occurrence of apoptosis.

CONCLUSIONIt was suggested that cadmium could induce apoptosis of anterior pituitary both in vivo and in vitro in the manner of dose-dependent, and caspase-9 might play a role during above processes.

Animals ; Apoptosis ; drug effects ; Cadmium Chloride ; administration & dosage ; toxicity ; Caspase 9 ; genetics ; Cells, Cultured ; Dose-Response Relationship, Drug ; Male ; Pituitary Gland, Anterior ; cytology ; drug effects ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; drug effects

Abstract: Objective　To analyze the association between drug resistance and the risk of latent tuberculosis infection and disease among household contacts of patients with pulmonary tuberculosis, and to explore whether the compensatory mutation of drug-resistant Mycobacterium tuberculosis will enhance its pathogenicity or transmission ability. Methods　The English and Chinese databases, including PubMed, web of science, EMBASE, Cochrane library database, CNKI and Wanfang database, were searched by computer from the time of establishment of the database to January 2022. Cohort studies on the risk of infection and disease among household contacts of patients with drug-resistant and sensitive pulmonary tuberculosis were searched and screened according to the inclusion and exclusion criteria. The data were extracted and evaluated by NOS scale, using stata16.0 software meta-analysis to calculate the combined effect of tuberculosis infection and disease risk of family contacts, and carry out heterogeneity test, subgroup analysis and sensitivity analysis. Results　A total of 7 cohort studies involving 9653 TB index cases and 29, 734 house contacts were included. The results of meta-analysis showed that compared with drug-sensitive pulmonary tuberculosis patients, the risk of tuberculosis infection in house contacts of drug-resistant pulmonary tuberculosis patients was increased (OR=1.56, 95%CI=1.25-1.96, P<0.001), but there was no difference in the risk of incidence (RR=1.06, 95%CI=0.80-1.41, P=0.67>0.05). Subgroup analysis showed that the risk of latent tuberculosis infection in house contacts was affected by the study area, and the size of family contacts had an impact on the risk of TB . Sensitivity analysis showed that the results of meta-analysis were robust. Conclusion　Compared with drug sensitive TB patients, household contacts with drug-resistant TB patients had a higher risk of tuberculosis, but there was no difference in the risk of TB among the two groups.

The payment methods,such as Diagnosis Related Group(DRG)for hospitalization and capitation for outpatient treat-ment,have achieved positive results in protecting the rights and interests of insured persons and improving the efficiency of the use of medical insurance funds.However,for patients with chronic diseases and rehabilitation nursing,the hospitalization period is long and the conditions complicated,and the payment method of DRGs is not reasonable.It analyzes the experiences of paying for long-term hospital cases in the US.and Germany from the aspect of reform process,payment method and regulatory measures.In order to pro-vide references for the reform of per-diem payment in rehabilitation nursing and other long-term hospitalized cases,it puts forward suggestions from aspects of realizing value care,reflecting individual differences,exploring complex payment methods,improving data quality and establishing constraint mechanism.

BACKGROUNDSurrogate markers may be used to assess the response to neoadjuvant treatment. The association between HER2 overexpression and favorable response to specific therapy in breast cancer is controversial, and the mechanism unclear. The purpose of the study was to evaluate HER2 and topoisomerase IIalpha (Topo IIalpha) as candidates for predicting the response to neoadjuvant chemotherapy in breast cancer patients.

METHODSBetween 1999 and 2006, seventy-six breast cancer patients who had received neoadjuvant chemotherapy were studied. Regimens including either CEF (cyclophosphamide, epirubicin, 5-fluorouracil) or CMF (cyclophosphamide, methotrexate, 5-fluorouracil) were given in more than three cycles to this group of patients. Protein expression of HER2 and Topo IIalpha were determined by immunohistochemistry. The primary endpoint was pathological and clinical response.

RESULTSOf 76 primary breast cancer samples, 27 (35.5%) showed overexpression of either HER2 (25%) or Topo IIalpha protein (10.5%), whereas in 7 tumors (9.2%) both proteins were found to be overexpressed. Ten patients (13.2%) had a clinical complete response and 21 (27.6%) had a clinical partial response. Five women (6.6%) had a pathological complete response, 5 (6.6%) had microscopic residual disease, and 46 (60.5%) had macroscopic residual disease. HER2 and Topo IIalpha overexpression was significantly associated with a favorable response (P < 0.001 and P = 0.005 respectively).

CONCLUSIONOur study suggests that HER2 and Topo IIalpha overexpression could be predictors of the response to neoadjuvant chemotherapy in both the CEF and CMF arms.

Adult ; Aged ; Antigens, Neoplasm ; analysis ; genetics ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; chemistry ; drug therapy ; DNA Topoisomerases, Type II ; analysis ; genetics ; DNA-Binding Proteins ; analysis ; genetics ; Female ; Humans ; Middle Aged ; Neoadjuvant Therapy ; Receptor, ErbB-2 ; analysis ; genetics ; Retrospective Studies

OBJECTIVENeurally adjusted ventilatory assist (NAVA) is a new mode of mechanical ventilation that delivers ventilatory assist in proportion to neural effort. This study aimed to compare the hemodynamic safety, oxygenation and gas exchange effects ventilated with NAVA and with pressure support ventilation (PSV) in infants who underwent open-heart surgery.

METHODSTwenty-one infants who underwent open-heart surgery for congenital heart disease (mean age 2.9+/- 2.1 months and mean weight 4.2+/- 1.4 kg) were enrolled. They were ventilated with PSV and NAVA for 60 minutes respectively in a randomized order. The hemodynamic, oxygenation and gas exchange effects produced by the two ventilation modes were compared.

RESULTSThree cases failed to shift to NAVA because of the bilateral diaphragmatic paralysis after operation. In the other 18 cases, there were no significant differences in the heart rate (HR), systolic blood pressure (BPs) and central venous pressure (CVP) in the two ventilation modes. The PaO2/FiO2 (P/F) ratio in NAVA was slightly higher than in PSV, but there was no statistical difference. PaCO2 did not show significant differences in the two modes. The peak inspiratory pressure (PIP) and electrical activity of the diaphragm (EAdi) in NAVA were significantly lower than in PSV. The EAdi signal after extubation was higher in infants who needed reintubation or intervention of noninvasive mechanical ventilation than in those who were extubated successfully (30.0+/- 8.4 microV vs 11.1+/- 3.6 microV; P<0.01).

CONCLUSIONSAs the first study of application of NAVA in infants in China, this study shows that NAVA has the same homodynamic effects as PSV. However the PIP for maintaining the same level of PaCO2 in NAVA is significantly lower than that in the traditional PSV. Monitoring the EAdi signal after extubation may show the risks of reintubation or intervention of noninvasive mechanical ventilation.

Female ; Heart Defects, Congenital ; physiopathology ; surgery ; Hemodynamics ; Humans ; Infant ; Male ; Respiration, Artificial ; methods

OBJECTIVEThe incidences of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) are very high in obese children, and insulin resistance may be the key point linking them together. Debates still remain as to whether NAFLD could be a component of MS. Some researchers reported that NAFLD was a composition of MS, while the others stated that NAFLD was an independent predicting factor of MS. Here we analyzed the prevalence of NAFLD and MS in 308 obese children who came to our endocrinology department from June 2003 to September 2006, and we also evaluated the relationship between NAFLD and MS in this group of obese children.

METHODTotally 308 obese children aged from 9 to 14 years with mean age of (10.7 +/- 2.6) years were enrolled. Two hundred and thirty one were males, and 77 were females. Body mass index (BMI), waist circumference (WC), biochemical indicators, liver B-mode ultrasound examination, oral glucose tolerance test (OGTT) and insulin releasing test were performed for all of the cases. The incidences of NAFLD including simple nonalcoholic fatty liver (SNAFL) and nonalcoholic steatohepatitis (NASH) as well as MS were calculated. Three subgroups were selected according to the diagnostic criteria: Group 1: OCWLD (obese children without liver disorder), Group 2: SNAFL and Group 3: NASH. The prevalence of MS, components of MS, free insulin, whole body insulin sensitivity index (WBISI), homeostasis model of insulin resistance (HOMA(IR)) were compared among these three subgroups.

RESULT(1) Among all the obese children, the prevalence of NAFLD, SNAFL, NASH and MS was 65.9% (203), 45.5% (140), 20.5% (63) and 24.7% (76) respectively. Among all the MS children, the prevalence of NAFLD was 84.2% (64/76). The prevalence of MS was 29.3% (41/140) in SNAFL group and 36.5% (23/63) in NASH group, which was significantly higher than that of OCWLD group 11.4% (12/105) (P < 0.05), but no significant difference was found between SNAFL group and NASH group (P > 0.05). Moreover, there were significantly higher incidences in NASH group concerning every component of MS (hypertension, hyperlipidemia, hyperglycemia) compared with that of OCWLD group. The incidence of hypertension in SNAFL was significantly higher than that of OCWLD group. And the incidence of hyperlipidemia was markedly increased in NASH group compared with SNAFL group. NAFLD group had higher free insulin and more severe IR compared with that of OCWLD group. When OCWLD developed to SNAFL and NASH, free insulin and IR deteriorated calculated by HOMA-IR and WBISI. However there was no significant difference between NAFLD and MS children concerning free insulin and IR.

CONCLUSIONThe prevalence of NAFLD and MS hits high in obese children. The prevalence of NAFLD was very high among children with MS and NAFLD and MS shared the common mechanism of IR. The higher prevalence of MS and higher frequencies of MS components were tightly associated with the development of NAFLD and severity of IR.

Adolescent ; Child ; Fatty Liver ; diagnosis ; epidemiology ; etiology ; metabolism ; Female ; Humans ; Male ; Metabolic Syndrome ; diagnosis ; epidemiology ; Obesity ; complications ; epidemiology ; Prevalence

OBJECTIVETo investigate the relationship of serum dehydroepiandrosterone (DHEA) levels and female precocious puberty.

METHODSThe serum levels of DHEA and dehydroepiandrosterone sulfate (DHEAS) were measured by ELISA in 60 idiopathic central precocious puberty (ICPP) girls, 62 premature thelarche (PT) girls and 31 age-matched health prepuberty girls. Bone age,volume of uterus and ovary, DHEA and DHEAS were re-measured in 3, 12 months after treatment with Diphereline in ICPP girls.

RESULT(1) The Log(DHEA) and Log(DHEAS) were (0.81 +/-0.36)microg/L and (2.31 +/-0.31)microg/L in ICPP group, (0.72 +/-0.30)microg/L and (2.31 +/-0.28)mg/L in PT group, and (0.32 +/-0.26)microg/L and (2.16+/-0.27)microg/L in controls (P <0.05). However, no significant differences were found between ICPP and PT group (P >0.05). Moreover, the serum levels of DHEA and DHEAS in precocious puberty girls with Tanner III stage were significant higher than those with Tanner II stage (P <0.05). (2) With bivariate correlation analysis, Log(DHEA) was positively correlated with height, bone age, volume of uterus and ovary (r=0.429, 0.339, 0.217, 0.282; all P<0.05), while no significant correlation with Log(LH peak), Log(FSH peak) and BMI (r=0.135, -0.165, 0.059). Log(DHEAS) was positively correlated with height,bone age and volume of ovary (r=0.319, 0.210, 0.181; P <0.05), while no correlated with Log(LH peak), Log(FSH peak), volume of uterus and BMI (r=0.012, -0.173, 0.146 and 0.081 respectively). (3) Serum Log (DHEA) and Log(DHEAS) of 32 ICPP were decreased from (0.83 +/-0.35) microg/L and (2.27 +/-0.30)microg/L to (0.68 +/-0.44)microg/L and (2.11 +/-0.43)microg/L (P<0.05) 3 months after treatment. The serum Log(DHEA) and Log(DHEAS) in 12 months after treatment were (0.78 +/-0.30)microg/L and (2.40+/-0.34)microg/L, which was not significantly different with that before treatment (P>0.05). However, the volume of uterus and ovary, bone age/age in 12 months after treatment were significantly different with those before treatment (2.82 +/-1.52 compared with 1.09 +/-0.50 ml, 3.15 +/-1.13 compared with 1.18 +/-0.42 ml, 1.43 +/-0.23 compared with 1.25 +/-0.12, all P<0.05).

CONCLUSION(1) The serum levels of DHEA and DHEAS are increased in precocious puberty girls with the development of Tanner stage. (2) Serum levels of DHEA and DHEAS are declined transiently when the hypothalamic-pituitary-gonadal axis is inhibited. (3) Serum DHEA is associated with the acceleration of growth and bone age in precocious puberty girls.

Child ; Dehydroepiandrosterone ; blood ; Dehydroepiandrosterone Sulfate ; blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Puberty, Precocious ; blood