Aim To study the protection and possible mechanism of 5-hydroxy-1 H-indazole against 1-methyl-4-phenylpyridinium iodide ( MPP+)-induced SH-SY5 Y cell apoptosis. Methods An apoptotic model was es-tablished in human neuroblastoma SH-SY5 Y by MPP+in vitro. MTT analysis was used to evaluate the protec-tive effect of 5-hydroxy-1H-indazole. Immunochemistry and Hoechst33258 nuclear staining were used to ob-serve the neuroprotection and anti-apoptosis of 5-hy-droxy-1H-indazole. Western blot was used to detect the levels of P-tau ( Ser396 ) closely related to neuronal apoptosis and its upstream kinases:P-GSK-3β and CDK5 . Results MPP+ induced activation of GSK-3β, increase of activity of CDK5 , tau hyperphosphory-lation and neuronal cell apoptosis. However,5-hydrox-y-1 H-indazole reduced the activities of GSK-3β and CDK5,then decreased the level of tau hyperphosphory-lation and inhibited MPP+-induced SH-SY5 Y cells ap-optosis. Conclusions 5-hydroxy-1H-indazole could attenuate MPP+-induced SH-SY5 Y neuronal cell apop-tosis. Possible mechanism is that 5-hydroxy-1H-in-dazole inhibits GSK-3βand CDK5 two signal transduc-tion pathways to lower the level of tau phosphorylation, then plays a role of neuroprotection.

Aim To study the effect of chromomycin on MPP~+-induced dopaminergic neuronal apoptosis.Methods An apoptosis model induced by 1-methyl-4-phenylpridnium ion(MPP~+)was established in cultured fetal mesencephalic neurons in vitro.Dopaminergic neuronal apoptosis was detected by Hoechst 33258 staining and phospho-Tau levels were detected by immunofluorescence.Results 10 μmol·L~(-1) MPP~+ hyperphosphorylated Tau at Ser396 and induced dopaminergic neuronal apoptosis.Chromomycin increased the number of TH-positive cells via inhibiting Tau phosphorylation.Conclusion These results indicate thatchromomycin inhibits Tau phosphorylation at Ser396 and therefore protects dopaminergic mesencephalic neurons from apoptosis induced by MPP+,which suggests that Chromomycin may be used to cure neurodegenerative disorders such as Parkinson's disease in clinic.

Aim To study the protective effect of 6-Hydroxy-1 H-indazole via inhibition of Tau phosphoryla-tion on MPP +-induced SH-SY5Y cells apoptotsis. Methods An apoptotic model induced by 1 -methy-4-phenylpridnium ion (MPP +)was established in cul-tured human neuroblastoma SH-SY5Y in vitro.MTT a-nalysis was used to evaluate the protective effect of pre-treatment of cells with 6-Hydroxy-1 H-indazole for 2 h. Hoechst33258 staining was used to observe apoptotic situation.Immunohistochemistry was used to detect the p-Tau (Ser396)expression.Results The viability of cells exposed to 200 μmol · L -1 MPP + for 48h was (47.80 ±0.84)% (P <0.01 ),MPP + induced phos-phorylation of Tau at Ser396 and neuronal apoptosis, while 6-Hydroxy-1 H-indazole inhibited MPP +-induced cellular apoptosis,increased the number of TH-positive cells via inhibiting Tau phosphorylation.Conclusion These results indicate that Tau may be a new target used to cure neurodegenerative disorders such as PD.

Objective To investigate the effect and recurrence of the esomeprazole combined with trimebutine on treatment for non-erosive reflux disease(NERD).Methods One hundred and twenty-five cases of patients with NERD were randomly divided into the treatment group (n =62) and the control group (n =63).Patients in treatment group were received the esomeprazole 20 mg,twice a day and trimebutine 0.2 g,3 times a day,in control group were received the esomeprazole 20 mg,twice a day and mosapride 5 mg,3 times a day.After 8 weeks treatment,6 months follow-up was conducted and the effects and recurrence were evaluated.Results The clinical curative rates at 4th and 8th weeks treatment in treatment group were 75.8％ (47/62) and 95.2％ (59/62),higher than that of control group (57.1％ (36/63),x2 =4.879,P =0.027 ; 84.1％ (53/63),x2 =4.083,P =0.043).The GERDQ curative rates at 4th and 8th weeks treatment in treatment group were 72.6％ (45/62),93.5％ (58/62) respectively,significantly higher than that of the control group (52.4％ (33/ 63),x2 =5.434,P =0.020 ; 79.4％ (50/63),x2 =5.350,P =0.021).The recurrence rates of 6 months followup were 77.4％ (48/62) in the treatment group and 81.0％ (51/63) in the control group,there was no significant difference between the two groups (P =0.627).Conclusion Esomeprazole combined with trimebutine is safe and effective treatment on non-erosive reflux disease,and the recurrence rates was lower than that in the control group.

Objective To assess the relationship between fruit intake and gastric cancer.Methods Articles published during January 2001 and October 2012 that assessed the relationship between fruit intake and gastric cancer were searched on PubMed,Ovid and Willey database.Adjusted relative risk (RR) and 95％ confidence intervals (CI) were calculated by using fixed-effect or random-effect model.Variants of subgroup analysis included living regions,followup duration,and adjusted factors.Results A total of 3679 gastric cancer patients and 1 173 859 subjects from 7 prospective cohorts were included in this metaanalysis,and the pooled RR was 0.89 (95％ CI:0.78-1.01).In the subgroup analysis,the pooled RR in the 10-year followup group was 0.94 (95％ CI:0.85-0.99) before age,cigarette smoking and alcohol drinking were adjusted (RR =0.81,95％ CI:0.54-0.99).Conclusion Fruit intake may prevent the development of gastric cancer.

Objective To develop a new treament strategy for Kasabach-Merritt syndrome.Methods Three infants who were diagnosed with Kasabach-Merritt syndrome and suffered from thrombocytopenia as well as bleeding and clotting disorders were treated with percutaneous selective digital subtraction angiography combined with transarterial hardened embolization under general anesthesia.Sclerosing agents included bleomycin A5 (4.0 mg),iodized oil (1.5 ml),dexamethasone (2.5 mg) and iopamidol (3 ml).Polyvinyl alcohol mixed with iopamidol (at a volume fraction of 0.5) served as the embolic material.Results All the three patients were successfully treated by the minimally invasive surgery.The amount of blood platelet returned to normal within 24 hours after the operation.On the fourth day,all the patients were discharged from hospital with the restoration of coagulation function.Revisits at one month and three months after the operation showed that hemangiomas markedly shrank and even subsided,and blood platelet count was maintained within normal range.Conclusions Percutaneous selective digital subtraction angiography combined with transarterial hardened embolization can result in a recovery of blood platelet count and shrinkage of hemangioma,and may serve as a minimally invasive treatment option for Kasabach-Merritt syndrome.

Objective To survey the satisfaction degree of the postgraduates in professional degree with The Joining Together of Double-Track education model in the current stage of professional degree graduate education and standardized training of residents in China. Methods According to various factors, such as the current situation of postgraduates in medical universities, we sought the opinions of relevant experts to design questionnaire. Meanwhile, to enhance the reliability of the questionnaire and the survey, we chose the postgraduates of Shengjing Hospital of China Medical University first to do the pre-survey, and according to the feedback, we adjusted part of the aspects, thus formed a formal questionnaire, which included the satisfaction with training of clinical practice ability, training of research ability, and tutors' assessment etc. Finally, the Chinese New Youth Forum online released the questionnaires, selecting the postgraduates in professional degree who were participating in, or had participated in the completion of the standardized training as the participants, which took place between March 2016 and May 2016. SPSS 16.0 was used for statistical analysis. The evaluation results of different majors were tested by Kruskal-Wallis rank sum test. Results According to the results of the survey, the aspects in the clinical resident standard-ized training that the 1000 postgraduates were more satisfied with were as follows: training time [42.8%(n=428)], training center [41.8% (n=418)], training of clinical practice ability [41.6% (n=416)], tutors [40.2%(n=402)], economic income [38.8%(n=388)], department arrangements [38.4% (n=384)], training of research ability [37.5%(n=375)]. There is a significant difference in the satisfaction degree of different pro-fessional graduate students in theJoining Together of Double-Trackeducation model (P<0.05). ConclusionThe Joining Together of Double-Track education model should be compatible with the training objectives of postgraduates in professional degree. Much more attention should be paid to the post-graduates, satisfac-tion degree with the clinical resident standardized training, as well as the requirements during the training period, improve the evaluation of graduate students' ability of scientific research, econo-mic income and so on, so as to improve the training system for the postgraduates.

OBJECTIVETo provide a scientific basis for the drug-combination and aim to examine whether astragaloside IV has the impact on the cytochrome P450 enzymes.

METHODTolbutamide, chlorzoxazone, coumarin, nifedipine, and phenacetin were as probe substrates of rat CYP2C9, CYP2E1, CYP2A6, CYP3A4, and CYP1A2, and were incubated in rat liver microsomes with astragaloside IV. Triplicate samples were run to generate IC50 value by incubating P450 probe substrates in the presence of five concentrations of astragaloside IV in the incubation mixture. The K(i) values were determined by fitting the probe substrate at various inhibitor concentrations to the equations for competitive inhibition, noncompetitive inhibition, noncompetitive inhibition, and mixed-type inhibition.

RESULTIC50 and K(i) values were estimated, and the types of inhibition were determined. Among the five probe substrates, astragaloside IV might not significantly affect CYP2E1, CYP2A6 and CYP1A2-mediated metabolism in rats, but was a competitive inhibitor of CYP2C9 (IC50 35.40 micromol x L(-1), K(i) 42.88 micromol x L(-1)), and was a uncompetitive inhibitor of CYP3A4 (IC50 88.24 micromol x L(-1), K(i) 33.31 micromol x L(-1)).

CONCLUSIONThese results suggested that astragaloside IV inhibited CYP2C9 and CYP3A4, which provided useful information for safe and effective use of astragaloside IV.

Animals ; Cytochrome P-450 Enzyme Inhibitors ; Cytochrome P-450 Enzyme System ; chemistry ; metabolism ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Enzyme Inhibitors ; chemistry ; pharmacology ; Kinetics ; Male ; Microsomes, Liver ; chemistry ; drug effects ; enzymology ; Rats ; Rats, Sprague-Dawley ; Saponins ; pharmacology ; Triterpenes ; pharmacology

Objective: To investigate the effect of intestinal flora in children with functional constipation (FC) on expression of acid-sensitive Ion channel 3(ASIC3) in rats and their regulation in intestinal motility. Methods: Faeces of FC children identified according to RomeⅣ criteria and healthy children from the First Affiliated Hospital of Anhui Medical University from December 2017 to June 2018 were collected, and then made into fecal microbiota solution.A pseudo - sterile rat model was established, according to the random number table method, and the rats were randomly divided into the treatment group and the control group, with 12 rats in each group, then the treatment group was given fecal microbiota solution of the children with FC and the control group was given fecal microbiota solution of the healthy children.The visceral sensitivity and intestinal propulsion rate of rats were determined by means of abdominal withdrawal reflex (AWR), while the intestinal microorganism of rats and children with FC were determined by 16SrDNA high-throughput sequencing, and the expressions of ASIC3 of intestinal in mRNA and protein were determined by adopting fluorescence quantitative PCR and Western blot. Results: The species and quantity of intestinal flora of the children with FC and rats implanted with FC faecal bacteria were reduced(all P<0.05), and firmicutes and bacteroidetes were the main bacteria; compared to the control group, the small intestine propulsion rate(52% vs.74%) and visceral sensitivity(78 mmHg vs.63 mmHg) of the treated group were significantly decreased compared with those in the control group (all P<0.05); the mRNA (0.003 1±0.000 8 vs.0.012 4±0.002 5) and protein levels of ASIC3 (0.013 2±0.001 9 vs.0.072 1±0.008 7) in the small intestine were down-regulated significantly(all P<0.05); and the mRNA (0.002 8±0.000 7 vs.0.009 4±0.001 1) and protein levels of ASIC3(0.038 2±0.004 5 vs.0.089 7±0.009 4) in the colon were down-regulated significantly(all P<0.05). Conclusions Children with FC have intestinal flora disorder, and intestinal flora of FC children may affect intestinal motility by down-regulating the expression of intestinal ASIC3 in rats.

OBJECTIVE: To explore the clinical and genetic characteristics of a patient with hypertrophic cardiomyopathy as the initial manifestation of Mucopolysaccharidosis type Ⅲ A (MPS Ⅲ A). METHODS: A female patient with MPS Ⅲ A who was admitted to the Affiliated Hospital of Jining Medical University in January 2022 and her family members (seven individuals from three generations) were selected as the study subjects. Clinical data of the proband were collected. Peripheral blood samples of the proband was collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing. Heparan-N-sulfatase activity was determined for the disease associated with the variant site. RESULTS: The proband was a 49-year-old woman, for whom cardiac MRI has revealed significant thickening (up to 20 mm) of left ventricular wall and delayed gadolinium enhancement at the apical myocardium. Genetic testing revealed that she has harbored compound heterozygous variants in exon 17 of the SGSH gene, namely c.545G>A (p.Arg182His) and c.703G>A (p.Asp235Asn). Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PM2_Supporting +PM3+PP1Strong+PP3+PP4; PS3+PM1+PM2_Supporting +PM3+PP3+PP4). Sanger sequencing confirmed that her mother was heterozygous for the c.545G>A (p.Arg182His) variant, whilst her father, sisters and her son were heterozygous for the c.703G>A (p.Asp235Asn) variant. Determination of blood leukocyte heparan-N-sulfatase activity suggested that the patient had a low level of 1.6 nmol/(g·h), whilst that of her father, elder and younger sisters and son were all in the normal range. CONCLUSION The compound heterozygous variants of the SGSH gene probably underlay the MPS ⅢA in this patient, for which hypertrophic cardiomyopathy is an associated phenotype.
Female ; Humans ; Cardiomyopathy, Hypertrophic ; Contrast Media ; East Asian People ; Gadolinium ; Mucopolysaccharidosis III ; Mutation ; Pedigree ; Male ; Middle Aged