Type 2 diabetes is a hypermetabolic disease characterized with disorders of glucose/lipid metabolism, absolute or relative lack of insulin, and can induce skeletal muscle atrophy. Hyperglycemia, hyperlipidemia, insulin resistance, and abnormal release of inflammatory factors can lead to abnormal signal transduction in skeletal muscle, thus make protein synthesis and degradation imbalance and eventually causing muscle atrophy. Under normal conditions, insulin-like growth factor 1 (IGF-1)/insulin can activate phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT). AKT not only increases protein synthesis through mammalian target protein of rapamycin (mTOR), but also phosphorylates forkhead box O (FoxO) transcription factor and then inhibits the transcription of several ubiquitin ligases (such as MAFbx/atrogin-1 and MuRF1), or autophagy related genes. The weakened IGF-1/PI3K/AKT pathway in type 2 diabetes is an important factor leading to skeletal muscle atrophy. Studies have shown that the commonly used anti-type 2 diabetic drugs have different effects in regulating the synthesis and degradation of skeletal muscle protein. Studies reported that drugs with effect of anti-diabetic muscle atrophy include thiazolidinediones, glucagon-like peptide analogs, glucose-sodium cotransporter 2 inhibitors, etc.; drugs that are still in controversial or even promote skeletal muscle atrophy include metformin, and some sulfonylurea or non-sulfonylurea insulin secretagogues. This article overviewed and analyzed the currently commonly used drugs for type 2 diabetes and summarized the related mechanisms, with the aim to provide references for the rational applications of drugs for type 2 diabetes.

The status of marine bioresources and the marine eco-environment issues were summarized and discussed, and the strategies for the development of Chinese marine bioresources in the future were proposed. The degradation of marine eco-environment and unreasonable exploitation of the resources resulted in acute decline of Chinese marine bioresources. The feasible stratagies for the sustainable use of marine bioresources should be to intensify the basic research on marine bioresources science, to strengthen the protection of the marine environment and conservation of marine living resources, and to exploit and utilize marine bioresources scientifically and reasonably by using high-technology including marine biotechnology.

OBJECTIVETo study the impact of maternal weight gain during pregnancy on the risk of infant obesity within 1 year old.

METHODSA total of 785 infants who were born in Hefei and participated children medical care in one district health center and their mothers were chosen as the research subjects from September 2010 to September 2011. Three groups were classified by weight gain during pregnancy according to the percentiles: excessive pregnancy weight gain group of 126 pairs, adequate pregnancy weight gain group of 542 pairs and inadequate pregnancy weight gain group of 117 pairs. Mother's general demographic information was collected. The height and weight were measured when the infant was 42 days, 3, 6, 9, and 12 months of physical examination. Z score was calculated. The differences of Z score in different groups were compared and the RR values of different weight gain during pregnancy on infant obesity were computed.

RESULTSThe weight-for-age Z score (WAZ) of infant at 42 days 3, 6, 9 and 12 months in excessive pregnancy weight gain group were 0.23 ± 0.93, 0.25 ± 1.03, 0.23 ± 0.99, 0.28 ± 1.09, 0.26 ± 1.14, respectively, all higher than that of the corresponding age in adequate pregnancy weight gain group (-0.04 ± 1.02, -0.07 ± 0.99, -0.05 ± 0.98, -0.06 ± 0.97, -0.07 ± 0.95, respectively). The differences were statistically significant (all P values < 0.05). In excessive pregnancy weight gain group, infant body mass index (BMI) at 9 months ((18.01 ± 0.15) kg/m(2)) and 12 months ((17.66 ± 0.15) kg/m(2)) were higher than that of adequate pregnancy weight gain group ((17.63 ± 0.13) and (17.22 ± 0.15) kg/m(2), respectively). The differences were statistically significant (all P values < 0.05). Differences of infant Height-for-age Z score (HAZ) among three groups were not statistically significant (all P values > 0.05). Compared to adequate pregnancy weight gain group, RR (95%CI) value of infant obesity in excessive pregnancy weight gain group was 1.86 (1.14 - 3.03).

CONCLUSIONExcessive maternal weight gain during pregnancy increased the risk of infant obesity within 1 year old.

Female ; Humans ; Infant ; Infant, Newborn ; Obesity ; epidemiology ; Pregnancy ; Pregnancy Trimesters ; Weight Gain

The purpose of this study is to determine if paeonol can protect hippocampal neurons against injury due to oxygen-glucose deprivation (OGD) injury. The rat neurons were cultured in an OGD environment and the model of OGD injury was established. Paeonol and MK-801, a positive control drug, were added before deprivation. Neuron viability was measured by the reduction of MTT; glutamate was analyzed by amino acid analyzer; binding activity of NMDA receptor was evaluated by liquid scintillation counting and the expression of NMDA receptor NR1 subunit mRNA was semiquantitatively determined by RT-PCR. Compared with OGD injury group, paeonol treatment obviously increased cell survival rate and reduced the binding activity of NMDA receptors and the release of glutamate; and down-regulating the expression of NR1 subunit. These results suggest that paeonol may exhibit its protective effect against OGD injury by the action on NMDA receptor of rats.
Acetophenones ; isolation & purification ; pharmacology ; Animals ; Cell Hypoxia ; Cell Survival ; drug effects ; Cells, Cultured ; Dizocilpine Maleate ; pharmacology ; Glucose ; deficiency ; Glutamic Acid ; metabolism ; Hippocampus ; cytology ; Neurons ; cytology ; Neuroprotective Agents ; isolation & purification ; pharmacology ; Paeonia ; chemistry ; Plants, Medicinal ; chemistry ; Protein Binding ; RNA, Messenger ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate ; genetics ; metabolism

Objective To establish a liquid chromatography-mass spectrometry (LC-MS / MS) method for the determination of alprazo-lam and its two metabolites in human plasma. Methods Agilent Zorbax SB C_(18)s(2. 1 mm×30 mm, 3.5 μm) column was used at 40 ℃, with a mobile phase of 25 mmol ·L~(-1) formic acid-acetonitrile solution (58: 42) at a flow rate of 0. 2 mL · min~(-1). An injection volume of 50 μL was used. Quantitaion was performed using multiple reaction monitoring (MRM). Results The linear calibration curves were obtained in the range of 0. 5-50. 0 ng·mL~(-1) for alprazolam, and in the rage of 0. 05-2. 00 ng·mL~(-1) for α-hydroxyalprazolam and 4-hydroxyalprazolam. The extraction recovery for alprazolam and two metabolites were ranged from 75.0%-87.3%, respectively (RSD < 10%). Conclusion The analytical method appeared to be accurate, sensitive and convenient for the determination of alprazolam and its two metabolites. It is suitable for therapeutic drug monitoring and pharmacokinetic study of alprazolam and its two metabolites.

To investigate effects of rat bone marrow mesenchymal stem cells (rBMMSC) on hematopoiesis after allo-hematopoietic stem cell transplantation (HSCT), allogeneic BMT model from Fischer 344 rats (RT-1Al) to Wistar rats (RT-1Au) was established; effects of MSCs on hematopoietic reconstitution were studied by survival rate, peripheral blood counts, histological analysis and FACS at day 30 after transplantation. The results showed that (1) MSCs from donor Fisher344 could survive in recipient irradiated by lethal dose and could be found in the thymus, spleen and bone marrow of the recipient at 30 days after cotransplantation with BM by measuring EGFP gene. (2) Cotransplanation of MSCs and BM improved hematopoietic reconstitution. Lymphocyte and platelet counts of peripheral blood in cotransplantation group were higher than those in the control group. Active hematopoiesis and increase of bone marrow nucleated cells were observed in cotransplantation group. MSCs significantly enhanced hematopoiesis of B lymphocyte and megakaryocytopoietic lineages by FACS analysis. It is concluded that (1) MSCs of Fisher344 can be found in the thymus, spleen, bone marrow of the recipients at 30 days after cotransplantion by measuring EGFP gene. (2) hematopoietic reconstitution is significantly enhanced by MSCs cotransplanted with BM.
Animals ; Bone Marrow Transplantation ; methods ; Cell Differentiation ; physiology ; Flow Cytometry ; Hematopoiesis ; physiology ; Lymphocyte Count ; Male ; Mesenchymal Stem Cell Transplantation ; methods ; Mesenchymal Stromal Cells ; cytology ; physiology ; Models, Animal ; Platelet Count ; Rats ; Rats, Inbred F344 ; Rats, Wistar

OBJECTIVETo evaluate the significance of somatic mutations of VHL gene and hypoxia-inducible factor-1alpha (HIF-1alpha) expression in primary renal clear cell carcinoma (RCC).

METHODSMutation of VHL gene and HIF-1alpha expression were detected by means of PCR, denaturing high-performance liquid chromatography (DHPLC), direct sequencing and immunohistochemistry in 32 samples from primary renal clear cell carcinoma patients.

RESULTSIn 32 RCC samples, 17 samples (53.1%) had and 32 samples of adjacent nonmalignant renal tissue had not mutations of VHL gene expression. Twelve RCC samples (70.6%) which had mutations of VHL gene expressed HIF-1alpha, and it had significant difference to 4 RCC (26.7%) samples which didn't have mutations of VHL gene (P < 0.05).

CONCLUSIONMutations of VHL gene may play a significant role in the tumorigenesis of RCC, and HIF-1alpha expression correlates with it.

Adenocarcinoma, Clear Cell ; genetics ; pathology ; Adult ; Aged ; Carcinoma, Renal Cell ; genetics ; pathology ; Chromatography, Liquid ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; Immunohistochemistry ; Kidney ; chemistry ; metabolism ; pathology ; Kidney Neoplasms ; genetics ; pathology ; Male ; Middle Aged ; Mutation ; genetics ; Polymerase Chain Reaction ; Transcription Factors ; analysis ; genetics ; Tumor Suppressor Proteins ; analysis ; genetics ; Ubiquitin-Protein Ligases ; analysis ; genetics ; Von Hippel-Lindau Tumor Suppressor Protein

OBJECTIVETo describe and analyze epidemiological characteristics of babies with neural tube defects (NTD) by sex and birth outcome in a high-prevalence and a low-prevalence areas of China.

METHODSBirth defects surveillance data collected from 1992 through 1994, as a part of the Sino-American cooperative project on NTD prevention, were used to classify NTD as four categories, i.e., anencephaly, encephalocele, high-level and low-level spina bifida according to the sites of lesion (high vs. low level lesion were cervicothoracic and lumbosacral, respectively). Each category was sub-classified, according to single or compound defect, as isolated external defects (including those with NTD only) or multiple external defects (including those with NTD and another major external birth defects that is not the sequence of a defect such as cleft lip with or without cleft palate). The rates of anencephalus, encephalocele, high- and low-level spina bifida (SB) in males and females and their sex ratios were calculated, adjusted for urban and rural areas, season, category and birth outcome by sex and sites of lesions (high vs. low).

RESULTSTotally, 784 NTD cases were identified from 326 874 recorded births (including live births, stillbirths and fetal deaths with a gestation age of at least 20 weeks). The prevalence rates of anencephalus (1.30 per 1 000 female births) and high-level SB (3.99) in females were higher than those (0.66 and 1.66 per 1 000 male births) in males in the high-prevalence northern regions; with adjusted prevalence rates of females 1.8 - 2.1 times greater than those of males. In the low-prevalence southern regions, the prevalence of high- (0.32 per 1 000 female births) and low-level SB (0.21) in female were higher than those in males, with high- and low-level SB rate of 0.10 and 0.09 per 1 000 male births), with adjusted rates for females of 1.3 - 1.6 times higher than in males. Isolated NTD accounted for more than 80% of all NTD cases, and the prevalence of isolated NTD in females (2.57) was higher than that in males (1.40).

CONCLUSIONSThe sex differences in NTD existed between north and south, in accordance with the phenotype of NTD. It suggested that proportion of high level SB and anencephalus in females could increase as the prevalence of NTD going up, anencephaly, high- and low-level SB had the different genetic and environmental background.

China ; epidemiology ; Female ; Humans ; Infant, Newborn ; Male ; Neural Tube Defects ; epidemiology ; Prevalence ; Sex Distribution

Objective To investigate the nutritional status of children with Crohn's Disease (CD) at diagnosis and its association with clinical characteristics. Methods A retrospective analysis was performed for the clinical data and nutritional status of 118 children with CD who were admitted to Beijing Children's Hospital,Capital Medical University,from January 2016 to January 2024. A multivariate logistic regression analysis was used to investigate the risk factors for malnutrition. Results A total of 118 children with CD were included,among whom there were 68 boys (57.6％) and 50 girls (42.4％),with a mean age of (11±4) years. Clinical symptoms mainly included recurrent abdominal pain (73.7％,87/118),diarrhea (37.3％,44/118),and hematochezia (32.2％,38/118),and 63.6％ (75/118) of the children had weight loss at diagnosis. The incidence rate of malnutrition was 63.6％ (75/118),and the children with moderate or severe malnutrition accounted for 67％ (50/75). There were 50 children (42.4％) with emaciation,8 (6.8％) with growth retardation,and 9 (7.6％) with overweight or obesity. Measurement of nutritional indices showed a reduction in serum albumin in 83 children (70.3％),anemia in 74 children (62.7％),and a reduction in 25 hydroxyvitamin D in 15 children (60％,15/25). The children with malnutrition had significantly higher disease activity,proportion of children with intestinal stenosis,and erythrocyte sedimentation rate and a significant reduction in serum albumin (P<0.05). The multivariate logistic regression analysis showed that intestinal stenosis was an independent risk factor for malnutrition in children with CD (OR=4.416,P<0.05). Conclusions There is a high incidence rate of malnutrition in children with CD at diagnosis,which is associated with disease activity and disease behavior. The nutritional status of children with CD should be closely monitored.

OBJECTIVEHuman growth hormone (hGH) is an essential therapeutic drug for the treatment of growth hormone (GH) deficiency (GHD). However, the process of dissolving hGH of the powder form is complicated and potentially hazardous. In the present study, we evaluated the efficacy and safety of preparation in the replacement therapy for children with GH deficiency.

METHODSA 12-month randomized, open-label, multicenter trial was conducted in 31 previously untreated children with growth failure secondary to GH deficiency [20 boys and 11 girls, mean age (10.5 +/- 4.1) years]. An recombined human growth hormone (rhGH) solution (Iintropin AQ) was given via subcutaneous injection daily in every evening at a weekly dose of 0.25 mg/kg. The patients were followed up at 3, 6, 9, and 12 months of the treatment, and the course of treatment was 12 months. Body height was measured 3-monthly and height velocity (HV) and mean height standard deviation score (HT SDS) were calculated. Serum Insulin-like growth factor I (IGF-1), Insulin-like growth factor binding protein 3 (IGFBP-3), GH antibodies and safety parameters were assessed at the baseline and at 3-month intervals. Bone age (BA) was assessed at the baseline and the rate of skeletal maturation (DeltaBA/DeltaCA) was calculated after 6 and 12 months of rhGH treatment by a central bone age reader. Moreover, the safety of rhGH solution treatment was assessed.

RESULTSAfter 12 months of liquid rhGH therapy, growth parameters were significantly increased over baseline. (1) The mean (+/- SD) height increment DeltaHT (cm) was 4.0 +/- 1.3, 7.0 +/- 2.0, 10.3 +/- 2.6 and 12.9 +/- 3.3 after 3, 6, 9, and 12 months of treatment, respectively (P < 0.01), which indicated linear growth after treatment. The GV (cm/years) was 2.7 +/- 0.9 before treatment and increased to 16.0 +/- 5.1, 14.1 +/- 4.0, 13.7 +/- 3.5, and 12.9 +/- 3.3 after treatment, suggesting that catch-up growth was significant after treatment as compared to the pre-treatment status (P < 0.01). Accordingly, post-treatment catch-up growth was obvious, significant differences were observed in HT SDS, which was -4.62 +/- 1.46 at the onset of therapy and increased significantly after the treatment to -3.80 +/- 1.53, -3.28 +/- 1.60, -2.86 +/- 1.75 and -2.47 +/- 1.86, respectively (P < 0.01). The height difference between GH deficient children and unimpaired children of the same age and gender gradually decreased after treatment, which was significantly different from that seen before treatment (P < 0.01). (2) The levels of serum IGF-1 and IGFBP-3 were increased comparably for the treatment. IGF-1 level (microg/L) was 41 +/- 64 at baseline and increased to 179 +/- 155, 202 +/- 141, 156 +/- 155 and 159 +/- 167 after 3, 6, 9, 12 months of treatment. IGFBP-3 level (mg/L) was 1540 +/- 1325 at baseline, and increased to 3891 +/- 1815, 4051 +/- 1308, 3408 +/- 1435 and 3533 +/- 1413, respectively, suggesting that with the increases in height, IGF-1, and IGFBP-3 were significantly activated to relatively high levels by the medication and reached peak values between 3 and 6 months of treatment. The levels of IGF-1 and IGFBP-3 were significantly different before and after treatment (P < 0.01). The IGF-1/IGFBP-3 molar ratio significantly increased during GH therapy (0.143 +/- 0.013 pre-therapy up to 0.240 +/- 0.055 post-therapy, P < 0.01). The IGF-1/IGFBP-3 molar ratio tended to stabilize after 3-month GH therapy. (3) The bone age assessment carried out 6 and 12 months after treatment showed that the bone maturity (DeltaBA/DeltaCA) was 1.01 +/- 0.57 and 1.07 +/- 0.75, respectively, suggesting that there was no speed-up development in the bone age. No severe adverse events were observed during the trial and the most frequent accompanying event was mild hypothyroidism.

CONCLUSIONSrhGH solution (Iintropin AQ) is a safe and effective preparation in the replacement therapy for children with GH deficiency.

Child ; China ; Dwarfism, Pituitary ; blood ; drug therapy ; Female ; Growth Disorders ; blood ; drug therapy ; Human Growth Hormone ; deficiency ; therapeutic use ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; blood ; Insulin-Like Growth Factor I ; metabolism ; Male ; Prospective Studies ; Recombinant Proteins ; therapeutic use