[Cognitive function analysis of chronic lead poisoning in adults].

Objective: To explore the changes of the auditory event-related potentials P300 and the Montreal Cognitive Assessment (MoCA) in the chronic mild lead poisoning in order to find out the impairment of cognitive function and intervene early. Methods: In February 2020, 50 patients with chronic mild lead poisoning in Wuhan Center for Prevention and Treatment of Occupational Diseases from June 2011 to June 2015 were selected as the case group, and 50 healthy people were selected as the control group. The changes of auditory event-related potential P300 and MOCA of the two groups were analyzed. Results: Compared with the control group, the latency of P300 of auditory event-related potential in the case group was prolonged and the amplitude was decreased (P<0.05) . Compared with the control group, the total score of MoCA in the case group was decreased, the mean score of language, abstract and delayed memory items decreased, and the differences were statistically significant (P<0.05) . Conclusion: The combination of auditory event-related potential P300 and MOCA is helpful to detect the early cognitive impairment in chronic lead poisoning population, and auditory event-related potential P300 is an objective and effective early detection method.

High hepatitis E virus antibody positive rates in dogs and humans exposed to dogs in the south-west of China.

Hepatitis E (HE) is a zoonotic viral disease caused by hepatitis E virus (HEV). The objective of this study was to investigate the prevalence of HEV infection among dogs and humans exposed to dogs in the south-west region of China. A total of 4,490 dog serum samples and 2,206 relative practitioner serum samples were collected from 18 pet hospitals and dog farms in Yunnan, Sichuan and Guizhou province, and the anti-HEV IgG antibodies were detected by ELISA. The results showed that the total positive rate of anti-HEV antibodies was 36.55% with the highest rate in city stray dogs, and the differences in distinct species and growth phases were significant. The positive rate of anti-HEV antibody in veterinarian and farm staff-related practitioners was significantly higher than the general population. The finding of the present survey suggested that high HEV seroprevalence in dogs and humans exposed to dogs in the south-west area of China poses a significant public health concern. It is urgent to improve integrated strategies to detect, prevent and control HEV infection in dogs and humans exposed to dogs in this area.

Effect of GJB2 235delC and 30-35delG genetic polymorphisms on risk of congenital deafness in a Chinese population.

Congenital deafness is a serious and irreversible condition in humans. The GJB2 gene is implicated in the pathogenesis of autosomal recessive nonsyndromic hearing loss. Its 235delC and 30-35delG polymorphisms are reported to be associated with risk of hereditary deafness. However, the effect of the interaction between GJB2 235delC and 30-35delG and environmental factors on congenital deafness has not been described. Therefore, we performed a case-control study to investigate the influence of these polymorphisms on congenital deafness risk, and their interaction with maternal and other environmental factors in the development of this disease. Between March 2014 and May 2015, 118 patients with congenital deafness and 242 healthy controls were enrolled into our study. Compared with the GG genotype, the adjusted odds ratios (ORs) [and 95% confidence intervals (CIs)] for the 235delC GC and CC genotypes were 4.66 (1.77-13.07) and 8.28 (2.06-47.52), respectively. Individuals harboring the GC+CC genotypes were at a greatly increased risk of congenital deafness compared to those with the GG genotype (OR = 5.65, 95%CI = 2.54-13.18). However, no significant relationship was established between the 30-35delG variant and this disease. The 235delC polymorphism exhibited an interaction with use of aminoglycoside antibiotics during pregnancy in conferring susceptibility to congenital deafness (chi-square = 8.76, P = 0.003). In conclusion, our study suggests that the GJB2 235delC polymorphism, but not the 30-35delG variant, contributes to congenital deafness susceptibility in the Chinese population examined, and demonstrates an interaction with consumption of aminoglycoside antibiotics during pregnancy in exerting this effect.

Lack of association between EPHX1 polymorphism and esophageal cancer risk: evidence from meta-analysis.

The microsomal epoxide hydrolase 1 (EPHX1) Tyr113His and His139Arg polymorphisms have been reported to be associated with esophageal cancer (EC) risk, yet the results of these previous results have been inconsistent or controversial. The objective of this study was to explore whether the EPHX1 Tyr113His and His139Arg polymorphisms confer risk to EC. The relevant studies were identified through a search of PubMed, Excerpta Medica Database (Embase), Elsevier Science Direct, and Chinese Biomedical Literature Database until May 2013. The association between the EPHX1 Tyr113His and His139Arg polymorphisms and EC risk was pooled by odds ratios (ORs) together with their 95% confidence intervals (95%CIs). A total of eight case-control studies with 1163 EC patients and 1868 controls (seven studies for both Tyr113His and His139Arg polymorphisms, one study only for Tyr113His polymorphism) were eventually identified. We found no association between EPHX1 Tyr113His and His139Arg polymorphisms and EC risk in overall population (For Tyr113His: His vs. Tyr: OR = 1.05, 95%CI = 0.95-1.15, P = 0.379; His/His vs. Tyr/Tyr: OR = 1.04, 95%CI = 0.88-1.22, P = 0.208; His/Tyr vs. Tyr/Tyr: OR = 0.96, 95%CI = 0.80-1.15, P = 0.577; His/His vs. His/Tyr + Tyr/Tyr: OR = 1.10, 95%CI = 0.96-1.26, P = 0.164; His/His + His/Tyr vs. Tyr/Tyr: OR = 1.01, 95%CI = 0.90-1.12, P = 0.543. For His139Arg: Arg vs. His: OR = 1.04, 95%CI = 0.94-1.14, P = 0.465; Arg/Arg vs. His/His: OR = 1.06, 95%CI = 0.91-1.24, P = 0.470; Arg/His vs. His/His: OR = 1.03, 95%CI = 0.91-1.16, P = 0.673; Arg/Arg vs. Arg/His + His/His: OR = 1.04, 95%CI = 0.85-1.27, P = 0.708; Arg/Arg + Arg/His vs. His/His: OR = 1.02, 95%CI = 0.93-1.13, P = 0.617). In subgroup analysis based on ethnicity, significant association has been found in neither EPHX1 Tyr113His nor His139Arg polymorphism. The current meta-analysis suggests no evidence of association between the EPHX1 polymorphism and EC risk.

Suppression of epithelial-mesenchymal transition and apoptotic pathways by miR-294/302 family synergistically blocks let-7-induced silencing of self-renewal in embryonic stem cells.

The embryonic stem cell (ESC)-enriched miR-294/302 family and the somatic cell-enriched let-7 family stabilizes the self-renewing and differentiated cell fates, respectively. The mechanisms underlying these processes remain unknown. Here we show that among many pathways regulated by miR-294/302, the combinatorial suppression of epithelial-mesenchymal transition (EMT) and apoptotic pathways is sufficient in maintaining the self-renewal of ESCs. The silencing of ESC self-renewal by let-7 was accompanied by the upregulation of several EMT regulators and the induction of apoptosis. The ectopic activation of either EMT or apoptotic program is sufficient in silencing ESC self-renewal. However, only combined but not separate suppression of the two programs inhibited the silencing of ESC self-renewal by let-7 and several other differentiation-inducing miRNAs. These findings demonstrate that combined repression of the EMT and apoptotic pathways by miR-294/302 imposes a synergistic barrier to the silencing of ESC self-renewal, supporting a model whereby miRNAs regulate complicated cellular processes through synergistic repression of multiple targets or pathways.

Protein-protein interaction network and significant gene analysis of osteoporosis.

This study used DNA microarray data to identify differentially expressed genes of osteoporosis and provide useful information for treatments of the disease. We downloaded gene expression data of Osteoporosis GSE35956 from the Gene Expression Omnibus database, which included five normal and five osteoporosis samples. We then identified the differentially expressed genes between normal and disease samples using the R language software, and constructed the protein interaction network. DAVID was used to perform the biological process enrichment and KEGG pathway cluster analyses. We used the Cytoscape plug-in unit, Cluster ONE, to perform cluster module analysis to find hub proteins of the network module and to analyze their Gene Ontology (GO) functions. A total of 294 genes were found to be differentially expressed between normal and disease samples, which were used to construct the differential gene-protein interaction network. GO function analysis revealed that the genes' functions were mainly involved in the intracellular signaling cascade. KEGG pathway analysis suggested that the main metabolic pathways of these genes were those of cancer: the neurotrophin/T cell/Fc epsilon RI/B cell/ ErbB/p53 signaling pathway, the cell cycle pathway, and the chronic myeloid leukemia pathway. Screening analysis of hub proteins revealed that KRT18 had the highest hub degree. In conclusion, we found differentially expressed genes related to osteoporosis. GO biological process enrichment and KEGG pathway enrichment analyses identified significant osteoporosis genes and their molecular functions. Finally, module analysis of hub proteins in interaction networks showed that cell death was one of the main biological processes of osteoporosis genes.

Efficacy and safety evaluation of intensive statin therapy in older patients with coronary heart disease: a systematic review and meta-analysis.

PURPOSE: To reveal and evaluate the efficacy and safety of intensive statin therapy in older patients (age ≥ 65 years) with coronary heart disease (CHD). METHODS: Electronic databases were searched for randomized controlled trials (RCTs) that involved intensive statin therapy use in older patients with CHD. Data was extracted and used to calculate risk ratios (RR) by software Revman 5.1. RESULTS: Five RCTs and 11,132 patients were included in. Compared with non-intensive statin therapy, intensive statin therapy had significant effect on reducing low density lipoprotein cholesterol (LDL-C) levels (55.4 %) and total cholesterol (TC) and triglyceride (Tg). Although the results showed that intensive statin therapy had no superior effect on reduction of mortality (both all-cause mortality [RR = 0.97, p = 0.65] and cardiac death [RR = 0.95, p = 0.57]) and cardiac arrest (RR = 1.09, p = 0.81), it possessed significant effects on prevention of nonfatal myocardial infarction (MI) (RR = 0.78, p = 0.008), stroke (RR = 0.72, p = 0.02) and coronary revascularization (RR = 0.69, p = 0.007). In terms of side effects, intensive statin therapy was associated with small absolute increase in incidence of drug discontinuation, due to adverse events (3.9 %) and liver enzymes abnormalities (1.7 %). And the occurrence rates of myopathy, rhabdomyolysis and creatine kinase (CK) elevation were very low. CONCLUSIONS: This results show that intensive statin therapy has excellent effects on reduction of serum lipid level including LDL-C, TC, Tg, and also on prevention of nonfatal MI, stroke and coronary revascularization with small absolute increased risk of side effects. Our analysis supports the use of intensive statin therapy in patients ≥ 65 years old with CHD.

Uneven evolutionary rates of bradykinin B1 and B2 receptors in vertebrate lineages.

Bradykinin acts through two receptor subtypes in mammals and generates a variety of responses including pain, inflammation and hypotension. The evolutionary history of the bradykinin system has been unclear due to shortage of information outside mammals. We describe here two receptor subtypes and the bradykinin precursor in three species of bony fish (the zebrafish Danio rerio, the Japanese pufferfish Takifugu rubripes, and the green spotted pufferfish Tetraodon nigroviridis) and chicken and analyze the relationships to mammals by a combination of phylogeny, conserved synteny and exon-intron organization. All of these species have two receptor genes located close to each other in a tandem formation, with the B2 gene 5' to the B1 gene, in chromosomal regions displaying conserved synteny between the species (albeit conservation of synteny in zebrafish is still unclear due to poor genome assembly). The evolutionary rate differs between the two genes as well as between lineages leading to differing pharmacological properties for both B1 and B2 across vertebrate classes. Also the bradykinin precursor gene was identified in all of these species in a chromosome region with conserved synteny. The tissue distribution of mRNA in T. rubripes is similar for B1 and B2, suggesting more similar regulation for the two genes than in mammals. In conclusion, the receptor tandem duplication predates the divergence of ray-finned fish and tetrapods and no additional duplicates of the receptors or bradykinin seem to have survived the ray-finned fish tetraploidization.

The amniotic sheet: a truly benign condition?

OBJECTIVE: Amniotic sheets are the result of uterine synechiae that have been encompassed by the expanding chorion and amnion. Radiologically they are seen as 'shelves' in the amniotic cavity. The benign nature of such amniotic sheets has been documented in many case series in the literature. The objective of this study was to determine the characteristics (if any) of amniotic sheets that predict fetal outcome. METHODS: Between January 2001 and December 2002, detailed scans were performed in 30 476 singleton pregnancies at 18-32 weeks' gestation. Of these, 44 cases of amniotic sheets were detected. The characteristics studied were site of amniotic sheet and whether the amniotic sheet was complete (i.e. no free edge seen on ultrasound) or incomplete (i.e. presence of free edge seen on ultrasound). The primary fetal outcome studied was stillbirth. RESULTS: The incidence of amniotic sheets was 0.14%. Two were complete and 42 were incomplete. Of the 38 cases with known outcomes there were two intrauterine deaths. There was no association between fetal outcome and the uterine location of the amniotic sheet (i.e. upper two-thirds vs. lower third, P = 0.5). There was, however, an association between the completeness of the amniotic sheets and intrauterine death (P = 0.002). Both instances of intrauterine death occurred in the two cases with complete amniotic sheets. Postmortem examination suggested that cord accidents were the cause of intrauterine death in both cases. CONCLUSIONS: This study supports the view that incomplete amniotic sheets are benign. It also suggests for the first time that complete amniotic sheets may be associated with intrauterine death.

Novel neuropeptide Y Y2-like receptor subtype in zebrafish and frogs supports early vertebrate chromosome duplications.

The Y receptors comprise a family of G-protein coupled receptors with neuropeptide Y-family peptides as endogenous ligands. The Y receptor family has five members in mammals and evolutionary data suggest that it diversified in the two genome duplications proposed to have occurred early in vertebrate evolution. If this theory holds true, it allows for additional family members to be present. We describe here the cloning, pharmacological characterization, tissue distribution, and chromosomal localization of a novel subtype of the Y-receptor family, named Y7, from the zebrafish. We also present Y7 sequences from rainbow trout and two amphibians. The new receptor is most similar to Y2, with 51-54% identity. As Y2 has also been cloned from some of these species, there clearly are two separate Y2-subfamily genes. Chromosomal mapping in zebrafish supports origin of Y7 as a duplicate of Y2 by chromosome duplication in an early vertebrate. Y7 has probably been lost in the lineage leading to mammals. The pharmacological profile of the zebrafish Y7 receptor is different from mammalian Y2, as it does not bind short fragments of NPY with a high affinity. The Y7 receptor supports the theory of early vertebrate genome duplications and suggests that the Y family of receptors is a result of these early genome duplications.

Foetal intralobar lung sequestration: antenatal diagnosis and management.

OBJECTIVES: The objectives of this study are to discuss the use of ultrasonography for the diagnosis of foetal intralobar sequestration (FILS) antenatally and the management options available for these pregnancies. METHODS: This is a retrospective review of six cases of FILS diagnosed antenatally by two dimensional (2D) and colour Doppler ultrasonography out of a total of 31,508 deliveries over a two-year period at the KK Women's and Children's Hospital. RESULTS: The incidence of FILS in this hospital was 1 in 5,251 deliveries. 2D ultrasonography showed an echogenic lung in all cases. FILS was confirmed by the demonstration of a systemic vessel leading to the affected lung on colour Doppler examination. After counselling, four terminated their pregnancies during mid-trimester, while two continued their pregnancies to term. Confirmation of the terminated cases was by post-mortem. In the two pregnancies that continued, regular growth scans were done to monitor the progression of the condition. Computed tomography confirmed the diagnosis post-delivery. Both were well but one had a resection of the sequestrated lung although he was asymptomatic. Histology also confirmed the diagnosis. CONCLUSION: FILS is a rare anomaly. 2D and colour Doppler ultrasonography are used to diagnose the condition antenatally. Termination of the pregnancy is not always indicated, as there are favourable outcomes from FILS.

In situ hybridization screen in zebrafish for the selection of genes encoding secreted proteins.

An in situ hybridization expression screen using a signal sequence trap system has been conducted in zebrafish to isolate cDNAs that encode secreted proteins. Random clones (secreted expressed sequence tags; sESTs) were sequenced from zebrafish embryonic (18-24 hr postfertilization) and adult kidney libraries. From the two RNA sources, 627 random sEST cDNAs were identified as being homologous or identical to known genes and 166 clones encode currently unidentified genes. The sESTs represent a broad range of enzymes and other regulatory molecules. Whole-mount in situ hybridization analysis was carried out by using antisense probes generated from 244 selected sESTs, and a range of expression patterns was obtained. Genetic mapping undertaken with sEST sequences demonstrated that assignment of map position was attainable by using 5' primers. The signal sequence trap system used in this work has yielded a range of cDNAs that encode secreted proteins and, together with analysis of patterns of expression and genetic mapping, has the potential to facilitate analysis of signaling pathways central to development and physiology.

Characterization of duplicated zebrafish cyp19 genes.

The zebrafish has recently been developed as a good genetic model system. We report here the use of zebrafish to study the regulation of estrogen biosynthesis. The CYP19 gene encodes cytochrome P450 aromatase, which catalyzes the synthesis of estrogens. Two cyp19 genes, termed cyp19a and cyp19b, have been isolated from zebrafish. Sequence comparison shows that Cyp19a and Cyp19b belong to two separate Cyp19 subfamilies. The cyp19a gene is expressed in the ovary, whereas cyp19b is expressed in the brain. The cyp19a and cyp19b genes are located on zebrafish chromosomes LG 18 and 25, respectively. Our data indicate that these gene loci arose through an ancient chromosomal duplication event. The expression of duplicated genes in distinct tissues may have evolutionary significance.

Synthesis and characterization of chiral N-O turns induced by alpha-aminoxy acids.

Chiral alpha-aminoxy acids of various side chains were synthesized with high optical purity starting from chiral alpha-amino acids. The conformations of diamides 13a-e, 15, and 16 were probed by using NMR, FT-IR, and CD spectroscopic methods as well as X-ray crystallography. The right-handed turns with eight-membered-ring intramolecular hydrogen bonds between adjacent residues (called the N-O turns) were found to be preferred for D-aminoxy acid residues, and they were independent of the side chains. The rigid chiral N-O turns should have great potential in molecular design.

Zebrafish smoothened functions in ventral neural tube specification and axon tract formation.

Sonic hedgehog (Shh) signaling patterns many vertebrate tissues. shh mutations dramatically affect mouse ventral forebrain and floor plate but produce minor defects in zebrafish. Zebrafish have two mammalian Shh orthologs, sonic hedgehog and tiggy-winkle hedgehog, and another gene, echidna hedgehog, that could have overlapping functions. To examine the role of Hedgehog signaling in zebrafish, we have characterized slow muscle omitted (smu) mutants. We show that smu encodes a zebrafish ortholog of Smoothened that transduces Hedgehog signals. Zebrafish smoothened is expressed maternally and zygotically and supports specification of motoneurons, pituitary cells and ventral forebrain. We propose that smoothened is required for induction of lateral floor plate and a subpopulation of hypothalamic cells and for maintenance of medial floor plate and hypothalamic cells.

The repertoire of Na,K-ATPase alpha and beta subunit genes expressed in the zebrafish, Danio rerio.

We have identified a cohort of zebrafish expressed sequence tags encoding eight Na,K-ATPase alpha subunits and five beta subunits. Sequence comparisons and phylogenetic analysis indicate that five of the zebrafish alpha subunit genes comprise an alpha1-like gene subfamily and two are orthologs of the mammalian alpha3 subunit gene. The remaining alpha subunit clone is most similar to the mammalian alpha2 subunit. Among the five beta subunit genes, two are orthologs of the mammalian beta1 isoform, one represents a beta2 ortholog, and two are orthologous to the mammalian beta3 subunit. Using zebrafish radiation hybrid and meiotic mapping panels, we determined linkage assignments for each alpha and beta subunit gene. Na,K-ATPase genes are dispersed in the zebrafish genome with the exception of four of the alpha1-like genes, which are tightly clustered on linkage group 1. Comparative mapping studies indicate that most of the zebrafish Na,K-ATPase genes localize to regions of conserved synteny between zebrafish and humans. The expression patterns of Na,K-ATPase alpha and beta subunit genes in zebrafish are quite distinctive. No two alpha or beta subunit genes exhibit the same expression profile. Together, our data imply a very high degree of Na,K-ATPase isoenzyme heterogeneity in zebrafish, with the potential for 40 structurally distinct alpha/beta subunit combinations. Differences in expression patterns of alpha and beta subunits suggest that many of the isoenzymes are also likely to exhibit differences in functional properties within specific cell and tissue types. Our studies form a framework for analyzing structure function relationships for sodium pump isoforms using reverse genetic approaches.

Two Cyp19 (P450 aromatase) genes on duplicated zebrafish chromosomes are expressed in ovary or brain.

Cytochrome P450 aromatase (Cyp19) is an enzyme catalyzing the synthesis of estrogens, thereby controlling various physiological functions of estrogens. We isolated two cyp19 cDNAs, termed cyp19a and cyp19b, respectively, from zebrafish. These genes are located in linkage groups 18 and 25, respectively. Detailed gene mapping indicated that zebrafish linkage groups 18 and 25 may have arisen from the same ancestral chromosome by a chromosome duplication event. Cyp19a is expressed mainly in the follicular cells lining the vitellogenic oocytes in the ovary during vitellogenesis. Cyp19b is expressed abundantly in the brain, at the hypothalamus and ventral telencephalon, extending to the olfactory bulbs. The expression of duplicated cyp19 genes at two different tissues highlights the evolutionary significance of maintaining two active genes on duplicated zebrafish chromosomes for specific functions in the ovary and the brain.