Congenital Hyperinsulinism ; diagnosis ; Humans ; Infant, Newborn ; Male

Aim To study the pharmacokinetics characteristics of galanthamine hydrohromide sustained release tablets and conventional tablets in healthy volunteers after a single and multiple oral doses. MethodsA single and multiple oral doses of galanthamine hydrohromide sustained release tablets and conventional tablets were given to 20 healthy male volunteers in a randomized cross-over study. We developed an LC-MS assay using naloxone as the internal standard to determine the plasma concentrations of galanthamine, calculate the pharmacokinetic parameters and evaluate the relative bioavailability and sustained release characteristics of galanthamine hydrohromide sustained release tablet. Results The pharmacokinetic parameters of the sustained release tablet and conventional tablet obtained from the single-dose study were as follows: the HVD_12 C_max(time span during which the plasma concentration is at least half of the C_max value)were (15.4?1.7) h and (5.4?2.5) h, the retard quotients (R△,the HVD_12 C_max ratio of sustained release tablets to conventional tablets) of sustained release tablet was 3.4?1.4, the T_max were (4.4?1.5) h and (1.3?1.2) h, the C_max were (27.5?2.9) ?g?L-1 and (53.7?12.7) ?g?L-1.Results showed significant sustained release characteristics of the sustained release tablet. The relative bioavailability of the sustained release tablet was (95.9?14.2) %。The pharmacokinetic parameters of the sustained release tablet and conventional tablet obtained from the multi-dose study were as follows: the T_max were (3.0?1.6) h and (0.9?0.3) h,the CSS_max were (58.8?9.4) ?g?L-1 and (52.0?6.9) ?g?L-1,the CSS_min were (16.2?4.0) ?g?L-1 and (22.5?5.0) ?g?L-1,the C_av were (39.0?3.9) ?g?L-1 and (37.1?5.0) ?g?L-1,the DF were 1.1 ?0.3 and 0.8?0.1, respectively. Results of two one-side t test showed that AUC_SS、CSS_max、C_av of two tablets were bioeqivalent. Conclusion Results showed that the sustained release tablet and the regular tablet were bioequivalent in absorbed extent, and the sustained release tablet exhibited a good retarding effect in release.

Objective To observe the distribution of blood vessels in tibial metaphysis in ovariectomized and control mice by micro-CT(?CT),and investigate the relationship between bone regional blood supply and osteoporosis. MethodsForty mice were randomly divided into ovariectomy group(n=20) and control group(n=20).Four weeks after operation,?CT analysis was conducted to observe the bone blood vessel distribution after silicone rubber perfusion,and bone mineral density measurement,?CT bone microarchitecture analysis and biomechanical test were performed. Results Bone mineral density,bone microarchitecture in ?CT analysis,biomechanical properties and bone blood vessel distribution in ?CT analysis of ovariectomy group were significantly lower than those of control group(P

Dietary surveyis a method to evaluate whether dietary intake meets body requirements by recording food consumed during a certain period.Widely-used dietary survey methods include:24 h dietary recall,dietary record,food frequency questionnaire and dietary history questionnaire.Since each method has its own advantages and limitations,researchers need to choose appropriate methods according to research purposes,accuracy requirements,availability of resources,etc.Obese children who are the focus and the major difficulty in dietary survey,it is important to choose an appropriate survey method.This article reviews widely-used dietary survey methods and evaluates them in the study of obese children related dietary surveys.

Objective To investigate the prevalence of endemic fluorosis in Guide county of Qinghai province, in order to provide appropriate measures to monitor and control the disease. Methods Damo, Wenquan, Baoning villages(water source has been changed) and Taiping village(water source has not been changed) in Guide county were involved in the study in 2008. One tap water sample was collected in dry and rainy seasons, respectively. Water fluoride was tested in accordance with the "Standard Test Methods for Drinking Water" (GB/T 5750.5-2006); of all the children aged 8 to 12, dental fluorosis was diagnosed using Dean criteria; 6 copies of urine samples were collected in each age group, urinary fluoride was measured using fluoride ion-selective electrode (WS/T 89-1996). According to the "Clinical Diagnostic Criteria of Endemic Skeletal Fluorosis "(WS 192-2008), clinical skeletal fluorosis was determined in adults over the age of 16 by X-ray examination for 10 people in each selected village. Results The mean water fluoride was 0.58,0.38,2.28,0.37 mg/L in Damo, Wenquan, Taiping, and Baoning villages, respectively, and that of Taiping village exceeded the national standard(1.0 mg/L). One hundred and ninety-three children aged 8-12 were checked, the detection rate of dental fluorosis was 49.74% (96/193); urine samples of 116 children were tested, median urinary fluoride was 1.49 mg/L A total of 1503 adults over the age of 16 were examined, the clinical detection of skeletal fluorosis was 51.63%(776/1503); a total of 82 people were X-rayed, X-ray detection of skeletal fluorosis was 20.73%(17/82). The characteristic of X-rays were degeneration and ossification of interosseous membrane. Conclusions Prevalence of dental fluorosis of children and adult clinical skeletal fluorosis are higher. The endemic fluorosis is still comparatively serious. Prevention efforts need to be further strengthened.

Isoliquiritigenin (ISL) is an active chalcone compound isolated from licorice. It possesses anti-inflammatory and anti-oxidative activities. In our previous study, we uncovered a great potential of ISL in treatment of type 2 diabetes mellitus (T2DM). Therefore, this study aims to reveal the mechanism underlying the alleviatory effects of ISL on T2DM-induced glycolipid metabolism disorder. High-fat-high-sugar diet (HFD) combined with intraperitoneal injection of streptozotocin (STZ) were used to establish T2DM mice model. All animal experiments were carried out with approval of the Committee of Ethics at Beijing University of Chinese Medicine. HepG2 cells were used in in vitro experiments, and sodium palmitate (SP) was applied to establish insulin resistance (IR) model cells. The effects of ISL on body weight, fasting blood glucose levels, and pathological changes in the livers of mice were examined. Enzyme-linked immune sorbent assay (ELISA) and real-time quantitative PCR (RT-qPCR) were applied to detect the regulatory effects of ISL on key targets involved in glucolipid metabolism. Additionally, molecular docking and analytical dynamics simulation methods were used to analyze the interaction between ISL and key target protein. The results indicate that ISL significantly downregulates the transcriptional levels and inhibits the activities of key enzymes involved in gluconeogenesis, including pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), and fructose-1, 6-bisphosphatase (FBP). It also downregulates the transcriptional and protein levels of hepatocyte nuclear factor 4α (HNF4α) and cAMP response element binding protein (CREB), the two transcriptional factors involved in gluconeogenesis. Thus, ISL inhibits hepatic gluconeogenesis in T2DM mice. In addition, ISL reduces total cholesterol (TC) and triglyceride (TG) levels in the livers of T2DM mice. Moreover, ISL downregulates the mRNA levels of lipogenesis genes and upregulates those of genes involved in fatty acid oxidation, lipid uptake, and lipid export. In conclusion, ISL suppresses hepatic gluconeogenesis, promotes lipolysis, and restrains lipogenesis in T2DM mice, thereby improving the abnormal glycolipid metabolism caused by T2DM.

Isoliquiritigenin (ISL) is a flavonoid compound isolated from licorice. It possesses excellent antioxidant and anti-diabetic activities. This study aims to investigate the molecular mechanism underlying the alleviatory effect of ISL on energy metabolism imbalance caused by type 2 diabetes mellitus (T2DM). 8-week-old male C57BL/6J mice were used in in vivo experiments. The high-fat-high-glucose diet combined with intraperitoneal injection of streptozotocin was applied to establish T2DM animal model. All animal experiments were performed in accordance with the Institutional Guidelines of Laboratory Animal Administration issued by the Committee of Ethics at Beijing University of Chinese Medicine. HepG2 cells were used in in vitro experiments. Enzyme-linked immunosorbent assay (ELISA) and real-time quantitative polymerase chain reaction (RT-qPCR) were used to examine the protein and mRNA levels of mitochondrial function-related targets. The levels of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) in HepG2 cells were measured by the flow cytometry. Additionally, the molecular docking of ISL and key target proteins was analyzed. It was found that ISL significantly inhibited the activity of mitochondrial respiratory chain complex I and increased the protein levels of uncoupling protein 2 (UCP2) in the livers of mice and HepG2 cells. It also obviously decreased the ROS levels and increased the MMP levels in cultured HepG2 cells. In addition, ISL promoted mitochondrial biogenesis by activating proliferator-activated receptor gamma co-activator 1α (PGC-1α) and enhanced mitophagy by upregulating Parkin. It also improved mitochondrial fusion by increasing the mRNA and protein levels of mitofusin 2 (MFN2). In conclusion, ISL alleviates energy metabolism imbalance caused by T2DM through suppression of excessive mitochondrial oxidative phosphorylation and promotion of mitochondrial biogenesis, mitophagy, and fusion.

ObjectiveTo investigate the relationship between Dicer expression and clinicopathological characteristics and prognosis by detecting the expression of Dicer in hilar cholangiocarcinoma tissues and cells.MethodsThe expression of Dicer in tissues was detected using immunohistochemistry.Western blotting and RT-PCR were used to investigate Dicer expression in QBC939 and HIBEpic cells.The relationship between Dicer expression and clinicopathological characteristics was analyzed.A Kaplan-Maier analysis was performed to analyze the disease-free survival (DFS) and overall survival (OS) after radical surgical resection of hilar cholangiocarcinoma.ResultsWhen compared to control,Dicer was significantly down-regulated in hilar cholangiocarcinoma tissues (P＜0.05) and in QBC939 (P＜0.05).The expression of Dicer was higher in well differentiated adenocarcinoma than poorly and moderately differentiated tumours. Univariate analysis showed low expression of Dicer protein was significantly correlated with short disease-free survival and overall survival of patients with hilar cholangiocarcinoma after radical surgical resection (P＜0.01). Multivariate analysis revealed that the expression of Dicer was the most important factor for predicting prognosis after radical surgical resection of hilar cholangiocarcinoma (P＜0.05).ConclusionsDicer could be used as a prognostic marker for hilar cholangiocarcinoma.

Objective To compare the normal anatomy of the anterior cruciate ligament (ACL) of fresh frozen cadaveric knee specimen in oblique coronal thin-slice section with oblique coronal magnetic resonance imaging. Methods One fresh cadaveric knee specimen was scanned with MR T1-weighted spinecho sequence.then the specimen was frozen and sliced with a band saw along the oblique coronal plane into 1.0-mm-thick sections that corresponded to the MR images,MR images including oblique coronal T1-weighted and T2-weighted images of 50 normal the knee joints were retrospectively reviewed to observe the MR imaging features of the cruciate ligament. Results Anteromedial and posterolateral bundles of ACL were clearly depicted on both anatomic slices and MR images.The anteromedial bundles originated from the posteromedial aspect of the lateral femoral condyle,coursing through the lateral intercondylar notch in an anterior,inferior,and medial direction,and inserted on the anteromedial aspect of the intercondylar eminence. The posterolateral bundles originated from the anteromedial aspect of the lateral femoral condyle,passing laterally and inferiorly through the lateral intercondylar notch,and inserted on the posterolateral side of the intercondylar eminence.The full length of ACL of all 50 individuals was showed on MR images.MRI clearly differenitated the anteromedial and posterolateral bundles of ACL and depicted the full length of the bundles.similar to the findings on sectional anatomy.Conclusion Oblique coronal MR imaging is the best way to demonstrate ACL and should be used for clinically suspected injury of ACL.

OBJECTIVETo investigate the protective effects of cistanche total glycosides (CTG) on dopaminergic neuron in substantia nigra (SN) of model mice of Parkinson's disease (PD).

METHODSExperimental mice were randomly divided into 5 groups, the normal control group, the model group, the high (400 mg/kg), moderate (200 mg/kg) and low (100 mg/kg) dose CTG groups. Mouse model of chronic PD was induced by peritoneal injection of MPTP (1-methyl-4-phenyl-1,2,3,6-ttrahydropyridine) 30 mg/kg for 5 successive days. Climbing test was used to estimate the neurobehavior of mice on the 7th and 14th day (D7 and D14) after initiating MPTP injection; meantime, quantitative immunohistochemistry was conducted to detect the number of dopaminergic neuron in SN and expression of tyrosine hydroxylase (TH) in striatum.

RESULTSThe average time of climbing in the high dose CTG group on D7 and D14 was significantly shorter than that in the model group (P < 0.01). The mean optic density (OD) of TH in striatum was higher in the three CTG groups than that in the model group on D7 (P < 0.01); but on D14, significance only showed in the high and moderate dose CTG groups (P < 0.01). Moreover, the MPTP induced decrease of TH positive neuron could be antagonized by CTG, but significant difference only showed between the high dose CTG group and the model group at the two time points of observation (P < 0.05).

CONCLUSIONCTG could improve the neurobehavior of PD model mice significantly, and inhibit the decrease of nigral dopaminergic neurons and TH expression in striatum.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Animals ; Behavior, Animal ; drug effects ; Cistanche ; chemistry ; Dopamine ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Glycosides ; pharmacology ; Immunohistochemistry ; Male ; Mice ; Mice, Inbred C57BL ; Neurons ; drug effects ; metabolism ; pathology ; Neuroprotective Agents ; pharmacology ; Parkinson Disease, Secondary ; chemically induced ; physiopathology ; Random Allocation ; Substantia Nigra ; drug effects ; metabolism ; pathology ; Tyrosine 3-Monooxygenase ; metabolism