OBJECTIVE: To explore the genetic etiology for a Chinese pedigree affected with Alazami syndrome. METHODS: Genomic DNA was extracted for 2 patients and 2 unaffected members from the pedigree. Whole exome sequencing was carried out to detect potential variant in the proband, and the result was verified by Sanger sequencing. RESULTS: The proband and her sister were both found to harbor compound heterozygous variants of LARP7 gene, namely c.94A>T (p.Lys32*) and c.1141A>G (p.Lys381Glu), which were inherited from their father and mother, respectively. Both variants were predicted to be pathogenic based on bioinformatic analysis. CONCLUSION The two variants of the LARP7 gene, both were unreported previously, probably underlay the Alazami syndrome in this pedigree. Above finding has expanded the mutational spectrum of the LARP7 gene.
China ; Dwarfism ; Female ; Humans ; Intellectual Disability/genetics* ; Mutation ; Pedigree ; Ribonucleoproteins/genetics* ; Exome Sequencing

Objective To predict the potential mechanism of Yifei Sanjie prescription in the treatment of lung adenocarcinoma based on network pharmacology,and to verify one of the key signal pathways,Janus protein tyrosine kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3),by cell experiments in vitro.Methods To screen the main active components and potential action targets of Yifei Sanjie prescription,with traditional Chinese medicine system pharmacological database(TCMSP).To search and retrieve the main targets of lung adenocarcinoma,with human genetic database(GeneCards)and online human Mendelian genetic database(OMIM).To obtain the intersection targets by screening and apply Wayne diagram,then analysis the topology and establish the traditional Chinese medicine-active compound-target network diagram by using of Cytoscape 3.7.2 software.To construct the protein-protein interaction(PPI)network,with the protein-protein interaction platform(STRING)and Cytoscape3.7.2 software.To analyze the functional enrichment of gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG),with the Metascape database.To carry out the molecular docking verification by using of Vina1.2.3 software.Using CCK-8 method to detect the effect of Yifei Sanjie prescription on cell activity.Using the cell scratch test to observe the effect on cell migration.And using Western blot method to test the expression of p-STAT3,STAT3,p-JAK2,JAK2 and VEGF-A.Results 94 active components,329 related drug targets and 1358 lung adenocarcinoma targets were obtained from Yifei Sanjie prescription,among which,150 of them intersected.PPI network visualization analysis shows that the potential key targets of Yifei Sanjie prescription in the treatment of lung adenocarcinoma are protein kinase B1(AKT1),β-actin(ACTB),tumor suppressor gene p53(TP53),serum albumin(ALB),caspase-3(CASP3)and vascular endothelial growth factor A(VEGFA).KEGG enrichment analysis screened 138 related signal pathways,indicating that JAK/STAT signaling pathway may play a key role in the treatment of lung adenocarcinoma with Yifei Sanjie prescription.Molecular docking results showed that quercetin,luteolin,and ursolic acid had good binding activities with JAK2 and STAT3.The cell experiment showed that compared with the blank group,Yifei Sanjie prescription could significantly inhibit the activity of A549 cells,inhibit the migration of A549 cells,and decrease the expression of p-JAK2/JAK2,p-STAT3/STAT3 and VEGF-A protein.In addition,Colivelin,an activator of JAK2/STAT3 pathway,could reverse the effect of Yifei Sanjie prescription on the expression of A549 related proteins.Conclusion Yifei Sanjie prescription has the characteristics of multi-component,multi target and multi pathway in the treatment of lung adenocarcinoma,and its mechanism may be related to the down-regulation of p-JAK2,p-STAT3 and VEGF-A protein expression,thereby inhibiting cell proliferation and migration.

Objective To investigate the effect of PDCA cycle management combing with ECG guidance in improving the rate of catheter tip in right place when is conducting the PICC catheterization. Methods A total of 36 intravenous treatment specialist nurses from Jiangsu Tumor Hospital were trained with PDCA cycle management method from 1st June to 31st September,2016. The training knowledge and skills included catheter tip positioning under intracardiac electrocardiogram. The knowledge and skills were analyzed and compared before and after training finally. Results The training not only could help to improve the score of knowledge and skill of PICC specialist nurses with knowledge before (88.28±3.10) and after (96.10±1.25) (P< 0.05) and skill before (83.55±5.11) and after (98.81±2.50) (P< 0.05); but also increased the rate of catheter tip in right place in the process of PICC catheterization (χ2=12.35,P <0.05). Meanwhile, the results showed that patient satisfaction with nurses could also be improved from 88.7% to 96.8% (χ2=10.79,P <0.05) and the operating time could be shorted [before (40.23±3.56)min,after (28.76±4.34)min](P< 0.05). Conclusions The use of PDCA circulatory method to train nurses can improve the ability to deal with puzzling questions of nurses in the process of PICC catheterization,and increase the rate of PICC catheter tip in right place.

ObjectiveTo explore the possible mechanisms of Tongfengning （痛风宁， TFN） in treating hyperuricemia （HUA） of spleen deficiency with exuberance of dampness syndrome. MethodsTen of 60 mice were randomly selected， and were fed with regular diet as the control group， while the remaining 50 mice were fed with high-fat and high-sugar diet combined with excessive exercise and potassium oxonate-allopurinol suspension to establish an HUA animal model of syndrome of spleen deficiency with exuberance of dampness. After the successful modeling， in order to better observe the effects of TFN on the intestinal microbiota of the model mice， a mixed antibiotic suspension was administered by gavage to induce further dysbiosis of the intestinal microbiota in the model mice. Fifty sucessfully modeled mice were randomly divided into model group， TFN group， allopurinol group， probiotics group， and an allopurinol + probiotics group， 10 in each group. The TFN group was administered TFN liquid at a dosage of 19.11 g/（kg·d） by gavage. The allopurinol group was administered allopurinol suspension at a dosage of 78 mg/（kg·d） by gavage. The probiotics group was administered live combined Bifidobacterium and Lactobacillus tablets suspension at a dosage of 3 g/（kg·d） by gavage. The allopurinol + probiotics group was administered allopurinol at a dosage of 78 mg/（kg·d） and live combined Bifidobacterium and Lactobacillus tablets suspension at a dosage of 3 g/（kg·d） by gavage. The control group and model group were administered normal saline at a dosage of 19.11 ml/（kg·d） by gavage. The interventions were continued for 21 days. In order to maintain a stable high blood uric acid state， all groups but the control group continued modeling while receiving drug intervention. The changes in spleen deficiency syndrome scores， blood uric acid levels， microbial community structure， acetic acid and butyric acid content in intestinal lavage fluid， adenosine deaminase （ADA） and xanthine oxidase （XOD） content in small intestine tissue， as well as ATP-binding cassette transporter G2 （ABCG2）， glucose transporter 9 （GLUT9） protein and mRNA expression in the small intestine tissue were compared among the groups of mice. ResultsCompared with the control group， the model group showed increased spleen deficiency syndrome scores， blood uric acid levels， relative abundance of phylum Firmicutes， Firmicutes/Bacteroidetes ratio， abundance of Bacteroides genus， Klebsiella genus， and Enterococcus genus， acetic acid content in intestinal lavage fluid， ADA and XOD content in small intestine tissue， as well as GLUT9 protein and mRNA expression （P<0.05）. The number of operational taxonomic units （OTUs） of intestinal microbiota， relative abundance of Bacteroidetes phylum， abundance of Lactobacillus genus and uncultured Bacteroides genus， butyric acid content in intestinal lavage fluid， and ABCG2 protein and mRNA expression in small intestine tissue were significantly decreased （P＜0.05）. Compared with the model group， in the group treated with TFN， probiotics， and allopurinol + probiotics， the spleen deficiency syndrome score， blood uric acid level， relative abundance of Firmicutes， acetic acid content in intestinal lavage fluid， ADA and XOD content in small intestine tissue， GLUT9 protein and mRNA expression significantly decreased. The number of gut microbiota OTUs， relative abundance of proteobacteria， butyric acid content in intestinal lavage fluid， ABCG2 protein and mRNA expression in small intestine tissue significantly increased （P＜0.05）. In the probiotics group， the ratio of Firmicutes to Bacteroidetes decreased. In the TFN group， the abundance of Lactobacillus and uncultured Bacteroidetes significantly increased， while the abundance of Parabacteroides， Klebsiella， and Enterococcus significantly decreased （P＜0.05）. Compared with the TFN group， allopurinol group and the probiotics group showed elevated blood uric acid levels， abundance of Bacteroidetes， ADA and XOD levels in intestinal tissue， and GLUT9 mRNA expression. The relative abundance of Firmicutes， abundance of lactobacilli， and ABCG2 mRNA expression significantly decreased. The probiotics group showed elevated GLUT9 protein expression in intestinal tissue. The probiotics group and the allopurinol plus probiotics group showed significantly higher scores for spleen deficiency syndrome in mice， and lower levels of butyric acid in mouse intestinal lavage fluid. The allopurinol group showed decreased numbers of OTUs in mouse intestinal flora， decreased abundance of proteobacteria， and butyric acid levels in intestinal lavage fluid. The allopurinol group also showed decreased ABCG2 protein expression in intestinal tissue， increased acetic acid levels in intestinal lavage fluid， increased abundance of Klebsiella， and significantly elevated GLUT9 protein expression （P＜0.05）. ConclusionsThe treatment of HUA with TFN may be associated with the regulation of intestinal probiotics （such as lactobacilli） and pathogenic bacteria （such as Klebsiella）， as well as the production of bacterial metabolites such as acetic acid and butyric acid. It may also involve reducing the expression of ADA and XOD in the intestines， decreasing intestinal uric acid production， upregulating the expression of intestinal epithelial urate transporter ABCG2， downregulating GLUT9 expression， and promoting intestinal uric acid excretion. These factors are related to the syndrome of spleen deficiency with exuberance of dampness.