OBJECTIVETo analyze clinical features of 4 families with hereditary hemorrhagic telangiectasia (HHT) and potential mutations of ENG, ACVRL1 and SMAD4 genes.

METHODSFour unrelated HHT patients and their affected family members were analyzed. All exons and flanking regions of ENG, ACVRL1 and SMAD4 genes were analyzed with PCR and direct sequencing and multiplex ligation-dependent probe amplification (MLPA) methods.

RESULTSEleven patients from the 4 families were enrolled in this study. Two ENG and 1 ACVRL1 mutations were identified, among which an ENG mutation (c.207G>A; p.L69L) and an ACVRL1 mutation (c.817C>T; p.L273L) have been previously reported. In addition, a novel ENG mutation (c.1004A>T; p.Q335L) has been found in 3 different families. Similar mutations were not detected in 200 healthy individuals. No mutations of ENG, ACVRL1 and SMAD4 were found in the fourth family.

CONCLUSIONA novel mutation c.1004A>T (p. Q335L) of ENG has been identified in patients with HHT. And there is significant phenotypic variability and genetic heterogeneity with the disease.

Activin Receptors, Type II ; genetics ; Adolescent ; Adult ; Amino Acid Sequence ; Antigens, CD ; genetics ; Endoglin ; Female ; Genetic Testing ; Humans ; Male ; Molecular Sequence Data ; Mutation ; Receptors, Cell Surface ; genetics ; Smad4 Protein ; genetics ; Telangiectasia, Hereditary Hemorrhagic ; diagnosis ; genetics

Objective To investigate the distribution of ghitathione-S-transferase M1 (GSTM1) and T1 (GSTT1) genes polymorphisms in Chinese population and smear-positive pulmonary tuberculosis cases of Jilin province. Methods Articles about GSTM1 and GSTT1 genes polymorphisms published before 2009 in China were searched. The study population was obtained from fourteen counties (or districts) of Jilin province, which included all cases from November, 2007 to May, 2008, totally 1120. The genotypes of GSTM1 and GSTT1 were detected by multiplex PCR technique. Results The frequencies of GSTM1 and GSTT1 'null' genotypes and combination M1-T1 'null' genotype acquired from systematic review were 54.2%, 46.8% and 26.2%, respectively, in Chinese Hans they were 53.4%, 44.9% and 25.5%, and in our research they are 57.2%, 20.4% and 13.7%, respectively. No significant differences between the frequencies of males and females as well as among that of different age groups were observed(P>0.05). The frequency of GSTM1 'null' genotype in our research is slightly higher than that in systematic review (P=0.016) , and the frequencies of GSTT1 'null' genotype and combination M1-T1 'null' genotype and are significantly lower than those in systematic review (both P<0.001). Conclusion The frequencies of GSTM1 and GSTTI 'null' genotypes were different among ethnics. The statistical difference between systematic review and our research may due to our large sample size and mostly Soutbern people in previous studies.

Objective To understand the awareness status of diabetic nephropathy( DN)and its influence factors among diabetes patients. Methods A total of 1236 cases of diabetes were investigated on the awareness of DN and Logistic regression was used to analyze its influence factors. Results The awareness rate of DN was 77. 67% and its influence factors were age,education level,monthly household income and available diabetic health education( OR=1. 15,1. 80, 1. 41and 0. 98 respectively,all P< 0. 05). Moreover,the awareness status of DN prevention was at a low level. Among the 9 methods to prevent DN,only had 4 methods the awareness rate of which was over 80%. Conclusion Health education on DN control and prevention among diabetes patients should be emphasized.

Human calicivirus (HuCV) has been well known as an important pathogen of outbreak and sporadic acute nonbacterial gastroenteritis worldwide. To investigate epidemiological feature and genetic diversity of HuCV among children in China, fecal specimens were collected from children under 5 years of age with acute diarrhea at 13 hospitals in different provinces across China. The study was performed year-round from January 1999 to June 2005. Fecal specimens were tested for bacteria and rotavirus first and the negative specimens then were tested for HuCV using ELISA and RT-PCR. PCR amplicons were cloned and sequenced for strain characterization. A total of 4426 rotavirus- negative fecal samples were screened. From these, 840 (19%) were positive for HuCV by either or both ELISA (14%) and RT-PCR (9.6%). HuCV infection occurred year-round with an epidemic in each winter (October-January) and mainly in children at 6 -- 17 months of age. Of 151 HuCV strains characterized, 146 belong to norovirus (NV, 96.7%) and 5 were sapoviruses (SV). Among norovirus strains, genotype GG II/4 was most common (99/146), followed by GG II/3 (22/146), GG II/5 (8/146), and 2 strains of each of GG II/6, GG II/7, GG II/8, and GG I/2, the other 9 strains of NV GG II were unique, potentially belonging to new genotypes. These results plus the epidemiology data suggested that HuCVs are an important cause of severe diarrhea in Chinese children that were under reported due to a lack of a simple diagnostic assay. The finding of the potential new genotypes indicates that the current assays need to be improved for broader detection and besides, a continual surveillance for better understanding the epidemiology the disease burden and the searching for new strains of HuCVs is necessary.
Age Distribution ; Caliciviridae ; classification ; genetics ; isolation & purification ; Caliciviridae Infections ; epidemiology ; pathology ; virology ; Child, Preschool ; China ; epidemiology ; DNA-Directed RNA Polymerases ; genetics ; metabolism ; Diarrhea ; epidemiology ; virology ; Enzyme-Linked Immunosorbent Assay ; Feces ; virology ; Humans ; Infant ; Infant, Newborn ; Phylogeny ; Reverse Transcriptase Polymerase Chain Reaction ; Seasons ; Viral Proteins ; genetics ; metabolism

BACKGROUND:Clinical evaluation gives much attention to occlusion and improvement of soft tissue profile,while little is reported concerning the stress distribution on the temporomandibular joint in the treatment of Class Ⅱ division 1 malocclusion adult patients undergoing single maxillary extraction orthodontics.OBJECTIVE:To analyze the stress distribution on the temporomandibular joint in the treatment of Class Ⅱ division 1 malocclusion with single maxillary extraction orthodontics.METHODS:The three-dimensional finite element models of normal and Class Ⅱ division 1 malocclusion before and after single maxillary extraction orthodontics according to CT and MRI data.The stress distribution on the temporomandibular joint was analyzed after mechanical loading and boundary constraint.RESULTS AND CONCLUSION:Compared with Class Ⅱ division 1 malocclusion,the stress distribution on the temporomandibular joint after single maxillary extraction orthodontics had no significant stress concentration area,and the equivalent stress of the condyle was lower than that before treatment,and the equivalent stress of the articular disc and the glenoid fossa of temporal bone were larger than those before treatment.However,the stress was well-distributed,basically fulfilling the stress characteristics of normal occlusion.To conclude,single maxillary extraction orthodontics reduces the risk of temporomandibular joint disorder in the patients with Class Ⅱ division 1 malocclusion,which is balanced and stable in line with the goal of orthodontic treatment.

By RACE, 2 overlapping cDNA fragments (3'PCR and 5'PCR fragments) covering the full genome of swine vesicular disease virus strain HK'1/70 were amplified from total RNA extracted from experimentally infected suckling mice. These fragments were cloned into pGEM-T Easy vector, respectively. 5'PCR fragment was digested by enzymes of Aat II and BssH II, and the Aat II-BssH II-digested 5'PCR fragment was obtained and cloned into the recombinant pGEM-T Easy vector containing 3'PCR fragment,the recombinant plasmid encoding full-length cDNA of SVDV HK'I/70 strain was then obtained and sequenced. The results showed that the complete genome of HK'1/70 was 7401 nucleotides (nts) long (excluding the poly (A) tract) which encodes a single polyprotein of 2185 amino acids, a 5'u ntranslating region (UTR) of 743 nts, a 3'UTR of 102 nts and a poly (A) tail at least 74 adenines. T' promoter was added at the 5'e nd of the full-length cDNA and an additional Pspl406I restriction site was added at the 3'e nd of poly (A) tail. The nucleotide and amino acid sequences were compared and phylogenetic analysis was used to examine the evolutionary relationships. The results showed that HK'1 /70 belonged to the second antigenic group. SVD virus was antigenically closely related to Coxsackie B5 virus, and located on the branches of CB5 evolutionary tree. Successful construction of full-length cDNA clone of SVDV HK'1/70 strain lays foundation for rescuing SVDV effectively and enables further research of SVDV on molecular level.
Animals ; Cloning, Molecular ; DNA, Complementary ; chemistry ; genetics ; Enterovirus B, Human ; classification ; genetics ; Molecular Sequence Data ; Phylogeny ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, DNA ; Swine

Objectives: This study aimed to observe the change of arachidonic acid-induced platelet aggregation rate (AA-Ag) and short-term adverse reactions after taking 50 or 100 mg/d aspirin(enteric-coated sustained-release formulation) or 100 mg/d aspirin (enteric-coated aspirin tablet)in the elderly Chinese population (aged 60 years or older). Methods: A total of 1 194 participants aged 60 or older, who should be recommended to take aspirin therapy due to medical reasons, were recruited and randomly assigned into three groups to receive enteric-coated sustained-release aspirin tablet (50 mg, once daily, group A), or 100 mg, once daily (group B) or enteric-coated aspirin tablet 100 mg once daily (group C), respectively. AA-Ag was measured after (14±3)days of aspirin treatment. Adverse events and bleeding events were recorded during the (28±3)days of follow-up. Results: The AA-Ag in group A (n=347), B (n=338) and C (n=332) post 14-day aspirin therapy were 6.65 (4.03,10.84)%, 5.89(3.22,10.03) % and 6.00(3.68,10.09) %, respectively (P>0.05). During the 28 days follow-up, the adverse events rate of group A (n=388), B (n=387) and C (n=385) was 3.87%,3.36%, and 7.95%, and the mild bleeding events rate was 3.09%, 2.33%, and 6.23%, respectively. Adverse events rate and mild bleeding events rate were significantly higher in group C than in group A and B (P<0.05). Conclusions: Compared with 100 mg-dose aspirin, 50 mg-dose aspirin achieves similar anti-platelet aggregation effect in this elderly Chinese population. The short-term adverse events and mild bleeding risk of aspirin with enteric-coated sustained-release formulation were fewer than that of enteric-coated formulation.

Objective Focused cardiac ultrasound (FCU) and lung ultrasound (LU) are increasingly being used in critically ill patients. This study aimed to investigate the effect of FCU in combination with LU on these patients and to determine if the timing of ultrasound examination was associated with treatment change. Methods This is a multicenter cross-sectional observational study. Consecutive patients admitted to the intensive care unit (ICU) were screened for enrollment. FCU and LU were performed within the first 24 h, and treatment change was proposed by the performer based on the ultrasound results and other clinical conditions. Results Among the 992 patients included, 502 were examined within 6 h of ICU admission (early phase group), and 490 were examined after 6 h of admission (later phase group). The early phase group and the later phase group had similar proportions of treatment change (48.8%
Critical Illness ; Cross-Sectional Studies ; Echocardiography ; Humans ; Intensive Care Units ; Lung/diagnostic imaging* ; Retrospective Studies

Whether direct manipulation of Parkinson's disease (PD) risk genes in the adult monkey brain can elicit a Parkinsonian phenotype remains an unsolved issue. Here, we used an adeno-associated virus serotype 9 (AAV9)-delivered CRISPR/Cas9 system to directly co-edit PINK1 and DJ-1 genes in the substantia nigras (SNs) of two monkey groups: an old group and a middle-aged group. After the operation, the old group exhibited all the classic PD symptoms, including bradykinesia, tremor, and postural instability, accompanied by key pathological hallmarks of PD, such as severe nigral dopaminergic neuron loss (>64%) and evident α-synuclein pathology in the gene-edited SN. In contrast, the phenotype of their middle-aged counterparts, which also showed clear PD symptoms and pathological hallmarks, were less severe. In addition to the higher final total PD scores and more severe pathological changes, the old group were also more susceptible to gene editing by showing a faster process of PD progression. These results suggested that both genetic and aging factors played important roles in the development of PD in the monkeys. Taken together, this system can effectively develop a large number of genetically-edited PD monkeys in a short time (6-10 months), and thus provides a practical transgenic monkey model for future PD studies.
Animals ; Brain ; CRISPR-Cas Systems/genetics* ; Dependovirus/genetics* ; Haplorhini ; Phenotype ; Protein Kinases/genetics*

Whether direct manipulation of Parkinson’s disease (PD) risk genes in the adult monkey brain can elicit a Parkinsonian phenotype remains an unsolved issue. Here, we used an adeno-associated virus serotype 9 (AAV9)-delivered CRISPR/Cas9 system to directly co-edit PINK1 and DJ-1 genes in the substantia nigras (SNs) of two monkey groups: an old group and a middle-aged group. After the operation, the old group exhibited all the classic PD symptoms, including bradykinesia, tremor, and postural instability, accompanied by key pathological hallmarks of PD, such as severe nigral dopaminergic neuron loss (>64%) and evident α-synuclein pathology in the gene-edited SN. In contrast, the phenotype of their middle-aged counterparts, which also showed clear PD symptoms and pathological hallmarks, were less severe. In addition to the higher final total PD scores and more severe pathological changes, the old group were also more susceptible to gene editing by showing a faster process of PD progression. These results suggested that both genetic and aging factors played important roles in the development of PD in the monkeys. Taken together, this system can effectively develop a large number of genetically-edited PD monkeys in a short time (6–10 months), and thus provides a practical transgenic monkey model for future PD studies.