[Treatment of ornithine transcarbamylase deficiency in a child with glyceryl phenylbutyrate]. / è‹¯ä¸é ¸ç”˜æ²¹é ¯æ²»ç–—å„¿ç«¥é¸Ÿæ°¨é ¸æ°¨ç”²é °åŸºè½¬ç§»é ¶ç¼ºä¹ç—‡1例.

Glyceryl phenylbutyrate (GPB) serves as a long-term management medication for Ornithine transcarbamylase deficiency (OTCD), effectively controlling hyperammonemia, but there is a lack of experience in using this medicine in China. This article retrospectively analyzes the case of a child diagnosed with OTCD at Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, including a review of related literature. After diagnosis, the patient was treated with GPB, followed by efficacy follow-up and pharmacological monitoring. The 6-year and 6-month-old male patient exhibited poor speech development, disobedience, temper tantrums, and aggressive behavior. Blood ammonia levels peaked at 327 µmol/L; urine organic acid analysis indicated elevated uracil levels; cranial MRI showed extensive abnormal signals in both cerebral hemispheres. Genetic testing revealed de novo mutation in the OTC gene (c.241T>C, p.S81P). Blood ammonia levels were approximately 43, 80, and 56 µmol/L at 1, 2, and 3 months after starting GPB treatment, respectively. During treatment, blood ammonia was well-controlled without drug-related adverse effects. The patient showed improvement in developmental delays, obedience, temperament, and absence of aggressive behavior.

A randomized double-blind clinical trial: Comparison of oclacitinib with a traditional Chinese herbal medicine product (Dihuang Guiqin capsule) in the treatment of canine atopic dermatitis.

Canine atopic dermatitis (cAD) is a common chronic inflammatory skin disease, which seriously affects the quality of life for both dogs and their owners. Currently, the common therapeutic drugs in the clinic have disadvantages such as obvious adverse effects and high prices. Traditional Chinese herbal medicine (TCHM) has great potential for the treatment of cAD. The aim of this study is to compare the effects of different doses of the TCHM product (Dihuang Guiqin capsule) and oclacitinib in the treatment of cAD through a randomized, double-blind trial. Sixty dogs diagnosed with AD were randomly and evenly divided into four groups (n = 15). The TCHM treatment group consisted of three subgroups that received three different oral doses (20, 40, and 60 mg/kg BW), while the control group received 0.5 mg/kg BW of oclacitinib. Each group was administered twice daily for 14 consecutive days. The results showed that both TCHM and oclacitinib significantly improved cAD-induced itching (evaluated by pVAS) and skin lesions (evaluated by CADESI-04), while interleukin 31 (IL-31) concentrations decreased significantly (P < 0.05) and serum biochemical indicators returned to normal. In particular, The therapeutic effects of TCHM medium- and high-dose groups were similar to those of oclacitinib (P > 0.05). The preliminary recommended dose of Dihuang Guiqin capsule for the treatment of cAD has been determined to be 40-60 mg/kg BW twice daily for 14 consecutive days, which can be reduced to once daily as appropriate. Dihuang Guiqin capsule was safe and well tolerated, which may be a new option for the treatment of cAD.

Ji-Chuan decoction ameliorates slow transit constipation via regulation of intestinal glial cell apoptosis.

BACKGROUND: Slow transit constipation (STC) is a common intestinal disease with increasing incidence. STC results from various factors, such as the enteric nervous system and metabolic changes. As a classical formula of traditional Chinese medicine, Ji-Chuan decoction (JCD) has been extensively and effectively used in STC treatment, yet its pharmacological mechanism remains unclear. AIM: To explore the integrated regulatory pattern of JCD against STC through hyphenated techniques from metabolism, network pharmacology and molecular methods. METHODS: STC model mice were generated by intragastric administration of compound diphenoxylate (10 mg/kg/d) for 14 d. The STC mice in the low dose of JCD (3.04 g/kg), middle dose of JCD (6.08 g/kg) and high dose of JCD (12.16 g/kg) groups were orally administered JCD solution once a day for 2 wk. The acetylcholine (ACH) level was examined by enzyme-linked immunosorbent assay. The pathological features of colon tissue were observed by hematoxylin and eosin staining. The differentially expressed metabolites and metabolic pathways were tested by nontargeted metabolomics. The main targets and core ingredients of JCD were identified by network pharmacology, and the expression of AKT was confirmed by immunohistochemistry. Finally, the pathways involved in JCD treatment were predicted using a combination of differentially expressed metabolites and targets, and intestinal glial cell apoptosis was demonstrated by immunofluorescence. RESULTS: JCD significantly promoted intestinal motility, increased the levels of the excitatory neurotransmitter ACH and reduced intestinal inflammation in STC mice. Untargeted metabolomics results showed that JCD significantly restored metabolic dysfunction and significantly affected taurine and hypotaurine metabolism. Network pharmacology and molecular experiments showed that JCD regulates AKT protein expression, and the core component is quercetin. Combined analysis demonstrated that apoptosis may be an important mechanism by which JCD relieves constipation. Further experiments showed that JCD reduced enteric glial cell (EGC) apoptosis. CONCLUSION: This work demonstrated that reducing EGC apoptosis may be the critical mechanism by which JCD treats STC. These findings call for further molecular research to facilitate the clinical application of JCD.

Kabuki syndrome: review of the clinical features, diagnosis and epigenetic mechanisms.

BACKGROUND: Kabuki syndrome (KS), is a infrequent inherited malformation syndrome caused by mutations in a H3 lysine 4 methylase (KMT2D) or an X-linked histone H3 lysine 27 demethylase (UTX/KDM6A). The characteristics in patients with KS have not yet been well recognized. DATA SOURCES: We used databases including PubMed and Google Scholar to search for publications about the clinical features and the etiology of Kabuki syndrome. The most relevant articles to the scope of this review were chosen for analysis. RESULTS: Clinical diagnosis of KS is challenging in initial period, because many clinical characteristics become apparent only in subsequent years. Recently, the genetic and functional interaction between KS-associated genes and their products have been elucidated. New clinical findings were reported including nervous system and intellectual performance, endocrine-related disorders and immune deficiency and autoimmune disease. Cancer risks of Kabuki syndrome was reviewed. Meanwhile, we discussed the Kabuki-like syndrome. Digital clinical genetic service, such as dysmorphology database can improve availability and provide high-quality diagnostic services. Given the significant clinical relevance of KS-associated genes and epigenetic modifications crosstalk, efforts in the research for new mechanisms are thus of maximum interest. CONCLUSIONS: Kabuki syndrome has a strong clinical and biological heterogeneity. The main pathogenesis of Kabuki syndrome is the imbalance between switch-on and -off of the chromatin. The direction of drug research may be to regulate the normal opening of chromatin. Small molecule inhibitors of histone deacetylases maybe helpful in treatment of mental retardation and reduce cancer risk in KS.

Two New Cytotoxic Compounds from a Deep-Sea Penicillum citreonigrum XT20-134.

Penicillum citreonigrum XT20-134 (MCCC 3A00956) is a fungus with cytotoxic activity, derived from deep-sea sediment. Five new compounds, adeninylpyrenocine (1), 2-hydroxyl-3-pyrenocine-thio propanoic acid (2), ozazino-cyclo-(2,3-dihydroxyl-trp-tyr) (3), 5,5-dichloro-1-(3,5-dimethoxyphenyl)-1,4-dihydroxypentan-2-one (4), and 2,3,4-trihydroxybutyl cinnamate (5), together with 19 known compounds (6-24), were isolated from an ethyl acetate (EtOAc) extract of its fermentation. The structures of the new compounds were comprehensively characterized by high-resolution electrospray ionization-mass spectrometry (HR-ESI-MS), 1D and 2D nuclear magnetic resonance (NMR). All isolates were evaluated for their cytotoxic activities. The heteroatom-containing new compounds 2 and 4 showed potent cytotoxicity to the human hepatoma tumor cell Bel7402 with IC50 values of 7.63 ± 1.46, 13.14 ± 1.41 µM and the human fibrosarcoma tumor cell HT1080 with IC50 values of 10.22 ± 1.32, 16.53 ± 1.67 µM, respectively.

Development of an on-line mixed-mode gel liquid chromatography×reversed phase liquid chromatography method for separation of water extract from Flos Carthami.

A novel on-line comprehensive two-dimensional liquid chromatography (2D-LC) method by coupling mixed-mode gel liquid chromatography (MMG-LC) with reversed phase liquid chromatography (RPLC) was developed. A mixture of 17 reference compounds was used to study the separation mechanism. A crude water extract of Flos Carthami was applied to evaluate the performance of the novel 2D-LC system. In the first dimension, the extract was eluted with a gradient of water/methanol over a cross-linked dextran gel Sephadex LH-20 column. Meanwhile, the advantages of size exclusion, reversed phase partition and adsorption separation mechanism were exploited before further on-line reversed phase purification on the second dimension. This novel on-line mixed-mode Sephadex LH-20×RPLC method provided higher peak resolution, sample processing ability (2.5mg) and better orthogonality (72.9%) versus RPLC×RPLC and hydrophilic interaction liquid chromatography (HILIC)×RPLC. To the best of our knowledge, this is the first report of a mixed-mode Sephadex LH-20×RPLC separation method with successful applications in on-line mode, which might be beneficial for harvesting targets from complicated medicinal plants.

[Endocrine and metabolic features of female children with Prader-Willi syndrome: an analysis of 4 cases].

This article reports the clinical features and endocrine and metabolic features of 4 children with Prader-Willi syndrome (PWS). All the patients were female and aged 6-12 years at diagnosis. All of them had clinical manifestations of obesity, unusual facies, developmental retardation, and intellectual disability. Genetic detection showed that 2 patients had paternal deletion of the 15q11.2-q13 region, one patient had maternal autodiploid in the 15q11.2-q13 region, and one patient had no abnormality in the 15q11.2-q13 region. All patients had varying degrees of endocrine and metabolic disorders: 2 patients had short stature, among whom one had delayed appearance of secondary sex characteristics and the other one had type 2 diabetes; one patient had insulin resistance and no mammary gland development; one patient had a body height of P3-P10 and precocious puberty. Patients with PWS have various endocrine disorders, so long-term endocrine follow-up and management is very important.

A novel nomogram based on LODDS to predict the prognosis of epithelial ovarian cancer.

BACKGROUND: To develop and validate a nomogram based on log of odds between the number of positive lymph node and the number of negative lymph node (LODDS) in predicting the overall survival (OS) and cancer specific survival (CSS) for epithelial ovarian cancer (EOC) patients. MATERIALS AND METHODS: A total of 10,692 post-operative EOC patients diagnosed between 2004 and 2013 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database and randomly divided into training (n = 7,021) and validation (n = 3,671) cohorts. Multiple clinical pathological parameters were assessed and compared with outcomes. Parameters significantly correlating with outcomes were used to build a nomogram. Bootstrap validation was subsequently used to assess the predictive value of the model. RESULTS: In the training set, age at diagnosis, race, marital status, tumor location, stage, grade and LODDS were correlated significantly with outcome in both the univariate and multivariate analyses and were used to develop a nomogram. The nomogram demonstrated good accuracy in predicting OS and CSS, with a bootstrap-corrected concordance index of 0.757 (95% CI, 0.746-0.768) for OS and 0.770 (95% CI, 0.759-0.782) for CSS. Notably, in this population our model performed favorably compared to the currently utilized Federation of Gynecology and Obstetrics (FIGO) model, with concordance indices of 0.699 (95% CI, 0.688-0.710, P < 0.05) and 0.719 (95% CI, 0.709- 0.730, P < 0.05) for OS and CSS, respectively. Using our nomogram in the validation cohort, the C-indices were 0.757 (95% CI, 0.741-0.773, P < 0.05, compared to FIGO) for OS and 0.762 (95% CI, 0.746-0.779, P < 0.05, compared to FIGO) for CSS. CONCLUSIONS: LODDS works as an independent prognostic factor for predicting survival in patients with EOC regardless of the tumor stage. By incorporating LODDS, our nomogram may be superior to the currently utilized FIGO staging system in predicting OS and CSS among post-operative EOC patients.

A high-fat high-energy diet influences hepatic CYP3A expression and activity in low-birth-weight developing female rats.

BACKGROUND: The objective of this study was to investigate the effects of a high-fat, high-energy (HFHE) diet on the hepatic expression of CYP3A in low-birthweight developing female rats. METHODS: Pregnant rats were divided into nourished and undernourished groups. The offspring of the nourished rats were defined as the normal-birth-weight (NBW) group, and those of undernourished rats were defined as the low-birth-weight (LBW) group. According to their birth weights and diets, the rats were subdivided into the following four groups: NBW-normal diet (NN) group; NBW-HFHE (NH) group; LBW-normal diet (LN) group; and LBW-HFHE (LH) group. Liver samples were isolated on days 3, 7, 14, 21, 28, 56 and 84 after birth. RESULTS: The CYP3A1 mRNA levels in the LH group on days 3, 56 and 84 were significantly higher than those of the NN group (P<0.05). CYP3A1 expression was significantly higher in the LH group than that in the NH group on days 21, 28 and 84 (P<0.05). CYP3A1 mRNA expression was higher in the LH group than that in the LN group on days 3 and 21 (P<0.05). No zonal CYP3A1 expression pattern was observed in the LH developmental group. The LH group had significantly higher mean activity than the LN group on days 7, 14, 28 and 56. CONCLUSION: Our results indicated that an HFHE diet can result in alterations of CYP3A expression in a developmental LBW rat model.

Cord blood C-peptide, insulin, HbA1c, and lipids levels in small- and large-for-gestational-age newborns.

BACKGROUND: Small- and large-for-gestational-age (SGA, LGA) newborns are associated with metabolic syndrome in their later life. Cord blood C-peptide, insulin, glycosylated hemoglobin (HbA1c), and lipids levels may be altered in SGA and LGA newborns; however, the results are conflicting. Therefore, this study aimed to determine the effect of cord blood markers on SGA and LGA newborns. MATERIAL AND METHODS: This was a prospective cohort study and included 2873 term newborns of non-diabetic women. Among these newborns, 83 (2.9%) were SGA, 2236 (77.8%) were appropriate-for-gestational-age (AGA), and 554 (19.3%) were LGA newborns. Cord blood C-peptide, insulin, HbA1c, triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were measured. The chi-square, Kruskal-Wallis, and Mann-Whitney tests were used to analyze categorical variables and continuous variables, respectively. Multinomial logistic regression analysis was used to determine the independent effect of these variables on SGA and LGA newborns. RESULTS: Cord serum TG level was significantly higher in the SGA group than in AGA and LGA groups (p<0.05). The LGA group had significantly higher cord serum insulin level than AGA and SGA groups (p<0.05). After adjustment for confounding variables, including maternal age, parity, pre-pregnancy body mass index (BMI), education, annual household income, pregnancy-induced hypertension (PIH), mode of delivery, and newborn sex, high TG and insulin levels remained significantly associated with SGA and LGA newborns, respectively (p<0.05). CONCLUSIONS: High cord serum TG and insulin levels are independently associated with SGA and LGA newborns, respectively.

Effect of maternal lipid profile, C-peptide, insulin, and HBA1c levels during late pregnancy on large-for-gestational age newborns.

BACKGROUND: Large-for-gestational age (LGA) newborns can increase the risk of metabolic syndrome. Previous studies have shown that the levels of maternal blood lipids, connecting peptide (C-peptide), insulin and glycosylated hemoglobin (HbA1c) were significantly different between LGA and appropriate-for-gestational age (AGA) newborns. This study aimed to determine the effect of the levels of maternal lipids, C-peptide, insulin, and HbA1c during late pregnancy on LGA newborns. METHODS: This study comprised 2790 non-diabetic women in late pregnancy. Among their newborns, 2236 (80.1%) newborns were AGA, and 554 (19.9%) newborns were LGA. Maternal and neonatal characteristics were obtained from questionnaires and their case records. The levels of maternal fasting serum apolipoprotein A1 (ApoA1), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), C-peptide, insulin and blood HbA1c were measured. The chi-square and Mann-Whitney U test were used to analyze categorical variables and continuous variables between the AGA and LGA groups, respectively. Binary logistic regression analysis was made to determine the independent risk factors for LGA newborns. RESULTS: Maternal TG, C-peptide, insulin and HbA1c levels were significantly higher in the LGA group than in the AGA group (P<0.05). The LGA group had significantly lower levels of maternal TC, HDL-C and LDL-C than the AGA group (P<0.05). After adjustment for confounding variables, including maternal age, pre-pregnancy body mass index, education, smoking, annual household income, amniotic fluid volume, gestational hypertension, newborn gender and gestational age at blood collection, high maternal TG levels remained significantly associated with LGA newborns (P<0.05). CONCLUSION: High maternal TG level during late pregnancy is significantly associated with LGA newborns.

Hepatic CYP3A expression and activity in low birth weight developing female rats.

BACKGROUND: We aimed to investigate the effects of low birth weight (LBW) on the hepatic expression of cytochrome P-450 3A (CYP3A) in developing female rats. METHODS: Pregnant rats were divided into two groups, a nourished group and an under-nourished group. The offspring of the nourished rats were defined as a normal weight, normal diet group (NN group). The offspring of the under-nourished rats were designated as a LBW, normal diet group (LN group). CYP3A mRNA expression, protein expression, protein localization and activity were determined. RESULTS: The CYP3A1 mRNA expression levels of the LN group on days 3, 21, and 56 were significantly higher than those of the same age in the NN group (P≤0.01). The mRNA expression of CYP3A2 in the LN group on day 21 was higher than in rats of the same age in the NN group (P<0.01). The staining intensity and frequency of CYP3A1-positive hepatocytes were significantly lower on days 7 and 21 in the LN group than those of rats of the same age in the NN group (P<0.05). The staining intensity and frequency of CYP3A2-positive hepatocytes on days 14 and 21 were higher in the LN group than those on the same days in the NN group (P<0.05). The mean CYP3A activity of the LN group on day 3 was significantly higher than that of the NN group (P<0.001). CONCLUSIONS: We found the effect of LBW on CYP3A activity was most prominent during the early days of life in rats. Investigators and clinicians should consider the effect of LBW on CYP3A in both pharmacokinetic study design and data interpretation, when prescribing drugs to LBW infants.

Early life programming and metabolic syndrome.

Metabolic syndrome (MS) has reached epidemic proportions worldwide among children. Early life "programming" is now thought to be important in the etiology of obesity, type 2 diabetes, cardiovascular disease and MS. Nutritional imbalance and exposures to endocrine disruptor chemicals during development can increase risk for MS later in life. Epigenetic marks may be reprogrammed in response to both stochastic and environmental stimuli, such as changes in diet and the in utero environment, therefore, determination of targets for early life effects on epigenetic gene regulation provides insight into the molecular mechanisms involved in the epigenetic transgenerational inheritance of a variety of adult onset disease phenotypes. The perinatal period is a crucial time of growth, development and physiological changes in mother and child, which provides a window of opportunity for early intervention that may induce beneficial physiological alternations.

Scalp acupuncture for acute ischemic stroke: a meta-analysis of randomized controlled trials.

Scalp acupuncture (SA) is a commonly used therapeutic approach for stroke throughout China and elsewhere in the world. The objective of this study was to assess clinical efficacy and safety of SA for acute ischemic stroke. A systematical literature search of 6 databases was conducted to identify randomized controlled trials (RCTs) of SA for acute ischemic stroke compared with western conventional medicines (WCMs). All statistical analyses were performed by the Rev Man Version 5.0. Eight studies with 538 participants were included in the studies. The studies were deemed to have an unclear risk of bias based on the Cochrane Back Review Group. Compared with the WCM, 6 RCTs showed significant effects of SA for improving neurological deficit scores (P < 0.01); 4 RCTs showed significant effects of SA for favoring the clinical effective rate (P < 0.01) However, the adverse events have not been documented. In conclusion, SA appears to be able to improve neurological deficit score and the clinical effective rate when compared with WCM, though the beneficial effect from SA is possibly overvalued because of generally low methodology of the included trials. No evidence is available for adverse effects. Rigorous well-designed clinical trials are needed.

Reversible cataract as the presenting sign of diabetes mellitus: report of two cases and literature review.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is the most common form of diabetes in young children. Serious optic complications, e.g. diabetic retinopathy and diabetic cataract involvement, are not usually detected in T1DM patients at the onset of the disease. CASE PRESENTATION: Two girls aged 11 years and 9 years were hospitalized in our unit in 2008 and 2009. They presented cataracts 1 and 6 months before the diagnosis of T1DM, respectively. After blood glucose level was controlled by insulin therapy, the cataract was resolved, totally in one and partly in the other girl. Meanwhile, visual acuity of both cases recovered, closely associated with fluctuation of plasma glucose level. In this study, we describe the symptoms, probable mechanism and treatment of diabetic cataract. CONCLUSION: Early antihyperglycemic therapy and maintenance of stable blood glucose level may reverse acute diabetic cataract or prevent it from getting worse.

[Detection of thyroid antibodies in children with type 1 diabetes mellitus].

OBJECTIVE: To investigate the prevalence of positive thyroid antibodies in children with type 1 diabetes mellitus (T1DM) and its influencing factors. METHODS: The clinical data of T1DM children who were treated in the Children's Hospital of Zhejiang University from May 2005 to April 2011 were retrospectively studied. The relationships of thyroid globulin antibody (TGAb) and thyroid peroxidase antibody (TPOAb) with cytokines IL-2, IL-4, IL-6, IL-10, TNF and IFN-γ were evaluated, and the percentages of CD3+, CD4+ and CD8+ T-lymphocytes in peripheral blood were examined. RESULTS: A total of 186 T1DM children with complete data of both TGAb and TPOAb were included in the study, among whom 143 with normal TGAb and TPOAb levels and 43 (23.1%) presented with positive thyroid antibody (including 21 cases with both positive TGAb and positive TPOAb). Eighteen cases (9.7%) were diagnosed as autoimmune polyglandular syndrome type 3 variant (APS3v). Significantly more patients in the positive thyroid antibody group had a family history of diabetes than in the negative thyroid antibody group (27.9% vs 14.7%; P<0.05). The average age of the positive thyroid antibody group was 10.1±3.2 years, which was significantly greater than that in the negative thyroid antibody group (8.1±4.0 years) (P<0.05). The IL-2 level (4.48 ±1.27 pg/mL vs 2.82 ±0.84 pg/mL, P<0.05) and the percentage of peripheral CD3+ T-lymphocyte[(61±11)% vs (66±11)%; P<0.05] were also different between the positive and negative thyroid antibody groups. CONCLUSIONS: Genetic background and abnormal function of T-lymphocytes (especially higher IL-2 level) may be involved in the elevated prevalence of positive thyroid antibody in T1DM children.

Metabolism of dl-praeruptorin A in rat liver microsomes using HPLC-electrospray ionization tandem mass spectrometry.

dl-Praeruptorin A (Pd-Ia) is the major active constituent of the traditional Chinese medicine Peucedanum praeruptorum Dunn. Recently it has been identified as a novel agent in the treatment and prevention of cardiovascular diseases. Accordingly, we investigated the metabolism of Pd-Ia in rat liver microsomes. The involvement of cytochrome P450 (CYP) and CYP isoforms were identified using a CYP-specific inhibitor (SKF-525A), CYP-selective inhibitors (α-naphthoflavone, metyrapone, fluvastatin, quinidine, disulfiram, ketoconazole and ticlopidine) and CYP-selective inducers (phenobarbital, dexamethasone and ß-naphthoflavone). Residual concentrations of the substrate and metabolites were determined by HPLC, and further identified by their mass spectra and chromatographic behavior. These experiments showed that CYP450 is involved in Pd-Ia metabolism, and that the major CYP isoform responsible is CYP3A1/2, which acts in a concentration-dependent manner. Four Pd-Ia metabolites (M1, M2, M3, and M4) were detected after incubation with rat liver microsomes. Hydroxylation was the primary metabolic pathway of Pd-Ia, and possible chemical structures of the metabolites were identified. Further research is now needed to link the metabolism of Pd-Ia to its drug-drug interactions.

[The prevalence of type 2 diabetes mellitus and prediabetes in children].

OBJECTIVE: To investigate the incident and prevalence of type 2 diabetes mellitus (T2DM) and prediabetes in obese children in the last ten years. METHODS: The clinical data of hospitalized children with newly diagnosed diabetes mellitus (DM) or obesity between October 2000 and September 2011 were retrospectively studied. RESULTS: A total of 503 newly onset cases were diagnosed as DM in the past ten years, of which 31 were diagnosed as T2DM. The prevalence of T2DM in the second five-year duration increased significantly compared with that in the first five-year duration (0.18‰ vs 0.05‰; P<0.01). The number of cases of type 1 diabetes mellitus (T1DM) and T2DM increased by 1.35 fold and 4.20 fold, respectively in the second five-year duration. A total of 1301 obese patients received oral glucose tolerance tests, and 29 cases were diagnosed with T2DM and 255 cases with prediabetes. Of the 255 cases of prediabetes, 133 had dyslipidemia, 138 had non-alcoholic fatty liver disease and 53 had hypertension. CONCLUSIONS: The prevalence rates of T1DM and T2DM increased significantly in the last 5 years. The prevalence of T2DM increased more significantly than T1DM. There was a higher prevalence of prediabetes in obese children. Childhood obesity predicts a higher risk of T2DM and cardiovascular disease in the future.

The levels of Pdx1/insulin, Cacna1c and Cacna1d, and ß-cell mass in a rat model of intrauterine undernutrition.

OBJECTIVE: To elucidate the underlying mechanisms responsible for ß-cell mass and function in response to intrauterine growth restriction (IUGR). METHODS: Offspring from undernourished mother rats with birth weight < -2 SD (IUGR group) and from standard-nourished rats with birth weight between mean +/- 1SD normal birth weight (NBW group) were examined. Levels of fasting glucose, serum insulin, and insulin-like growth factor-1 (IGF-1) were analyzed. Entire pancreas or islet-like cell clusters (ICCs) were collected to evaluate relative ß-cell mass and determine the genetic and protein profiles of pancreatic and duodenal homeobox 1 (Pdx1), Cacna1c and Cacna1d using real-time PCR, immunohistochemical staining, and western blotting at day (d) of birth and at d21 of age. RESULTS: Fasting serum insulin and IGF-1 concentrations were significantly lower in the IUGR group than in the NBW group at d0 and d21. The levels of Pdx1 and insulin mRNAs in IUGR pancreas were also decreased. At birth, the ratios of ß-cell mass to body weight were not significantly different between the two groups. However, by d21 the relative ß-cell mass in IUGR had not grown to compensate for the increase in body weight, as compared to the NBW group (p < 0.05). The Cacna1c and Cacna1d proteins were significantly higher in the NBW group than that in the IUGR group at birth, but there were no statistical differences at d21. CONCLUSION: Decreased Pdx1 levels and IGF-1 concentration restrain ß-cell mass and insulin expression in rat offspring from undernourished mothers. However, Cacna1c and Cacna1d expression were able to reach normal levels as the IUGR rats were aged, indicating that these factors were not responsible for the IUGR rat phenotype of insulin resistance and ß-cell dysfunction in later life.

Ginseng total saponins enhance neurogenesis after focal cerebral ischemia.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng, the root of Panax ginseng C.A. Meyer, is one of the most commonly used healing herbs for stroke and chronic debilitating conditions in China. Ginsenosides are the main active principles for ginseng's efficacy, but the mechanisms have not been fully clarified. AIM OF THE STUDY: To test the hypothesis whether or not the administration of Ginseng total saponins (GTS) can enhance neurogenesis after focal cerebral ischemia, and thereby improve neurological deficits. MATERIALS AND METHODS: Male Wistar rats received intraperitoneal injections of GTS dissolved at a dose of 25 mg kg(-1) d(-1) or normal saline (NS) of same volume 3 days before the permanent middle cerebral artery occlusion (MCAO) model establishment until the animals were killed at the time points of 1d, 3d, 7d and 14d. The neurological function was assessed blindly. BrdU immunostaining and double staining were performed by following the 3-steps method. RESULTS: (A) GTS-treated rats have better neurological scores compared with those in NS group at 14d time point (p<0.05); (B) the number of BrdU(+) cells and BrdU(+)/NeuN(+) cells in GTS group were significantly higher than those in NS group in the ipsilateral subventricular zone and in the ipsilateral infarct area after MCAO, respectively (p<0.05 or p<0.01); (C) the increase of the number of BrdU(+)/NeuN(+) cells highly correlated with the decrease of neurological scores. Coefficient correlation r=-0.828 (p<0.01). CONCLUSION: GTS can improve neurological deficits after focal cerebral ischemia by inducing endogenous neural stem cells activation and thereby enhance adult central nervous system regeneration.