A Pt/CeO_(2)Hybrid Nanozyme with Stable Peroxidase Activity for the Detection of Acetylcholine

Acetylcholine(ACh)is a common neurotransmitterl)that is secreted by cholinergic neurons[2]and is found mainly in the peripheral and central nervous systems.[3]ACh transmits nerve signals from presynaptic to postsynaptic cells via synapses.

Expression of pituitary homeobox 1 gene in human gastric carcinogenesis and its clinicopathological significance

AIM: To investigate the effect of pituitary homeobox 1 (PITX1) expression in cases of human gastric cancer on cancer differentiation and progression, and carcinogenesis. METHODS: Using polyclonal PITX1 antibodies, we studied the expression of PITX1 in normal gastric mucosa, atypical hyperplasia, intestinal metaplasia, and cancer tissue samples from 83 gastric cancer patients by immunohistochemistry. Moreover, semi-reverse transcription polymerase chain reaction (semi-RT-PCR) was performed to detect the mRNA level of PITX1 in three gastric cancer cell lines and a normal gastric epithelial cell line. Subsequently, somatic mutations of the PITX1 gene in 71 gastric cancer patients were analyzed by a combination of denaturing high performance liquid chromatography (DHPLC) and DNA sequencing. RESULTS: Immunohistochemistry showed that PITX1 was strongly or moderately expressed in the parietal cells of normal gastric mucosa (100%), while 55 (66.3%) out of 83 samples of gastric cancers showed decreased PITX1 expression. Moreover, PITX1 expression was reduced in 20 out of 28 cases (71.5%) of intestinal metaplasia, but in only 1 out of 9 cases (11%) of atypical hyperplasia. More importantly, PITX1 expression was significantly associated with the differentiation, position and invasion depth of gastric cancers (r = -0.316, P < 0.01; r = 0.213, P < 0.05; r = -0.259, P < 0.05, respectively). Similarly, levels of PITX1 mRNA were significantly decreased in 2 gastric cancer cell lines, BGC-823 and SGC-7901, compared with the normal gastric epithelial cell line GES-1 (0.306 ± 0.060 vs 0.722 ± 0.102, P < 0.05; 0.356 ± 0.081 vs 0.722 ± 0.102, P < 0.05, respectively). Nevertheless, no somatic mutation of PITX1 gene was found in 71 samples of gastric cancer by DHPLC analysis followed by sequencing. CONCLUSION: Down-regulation of PITX1 may be a frequent molecular event in gastric carcinogenesis. Aberrant levels of PITX1 expression may be closely correlated with the progression and differentiation of gastric cancer.

Screening of Fabry disease in patients with end-stage renal disease of unknown etiology:the first Thailand study

We aimed to explore the prevalence of Fabry disease in Thai patients who were diagnosed with end-stage renal disease（ESRD） of an unknown origin.Venous blood samples were collected from ESRD patients for biochemical and molecular studies.Alpha-galactosidase A（a-GAL A） screening was performed from dried-blood spots using fluorometry.Molecular confirmation was performed using DNA sequencing of the GLA gene.A total of 142 male and female patients were included in this study.Ten patients（7.04%） exhibited a significant decrease in a-GAL A activity.There were no definitive pathogenic mutations observed in the molecular study.However,four patients revealed a novel nucleotide variant at c.l-10 C〉T,which was identified as a benign variant following screening in the normal population.In conclusion,the a-GAL A assay utilizing dried-blood spots revealed a significant false positive rate.There was no definitive Fabry disease confirmed in Thai patients diagnosed with ESRD of unknown etiology.

Influence of DAP1 Genotype and Psychosocial Factors on Posttraumatic Stress Disorder in Thai Tsunami Survivors: A GxE Approach

Background: Posttraumatic Stress Disorder (PTSD) is a psychiatric disorder found in individuals afflicted by a traumatic event including the natural disaster. “Tsunami” occurred in Andaman coast of Thailand on December 26, 2004, in which 33.6% of survivors were diagnosed as PTSD. This study aimed to explore the single nucleotide polymorphism (SNP). rs267943 genotype is located on chromosome 5 in the intron of the death-associated protein 1 (DAP1) gene and psychosocial factors for PTSD. Methods: Participants (N = 1970) were recruited from volunteers who have complete data both of DAP1 gene and psychosocial factor. Results: Using a binary logistic regression model, significant gene-environment interactions were found for the single nucleotide polymorphism (SNP) rs267943 and psychosocial factors including depression (adj. OR = 6.0, 95% CI = 4.29 - 8.39), neurotic personality (adj. OR = 2.73, 95% CI = 2.18 - 3.42), planning (adj. OR = 1.52, 95% CI = 1.20 - 1.93), use of emotional support (adj. OR = 1.32, 95% CI = 1.21 - 1.94) with statistical significant p Conclusion: This study demonstrated that GxE studies can be utilized to shed light on the origins of PTSD.

Implementing comprehensive genetic carrier screening in China―Harnessing the power of genomic medicine for the effective prevention/management of birth defects and rare genetic diseases in China

Carrier screening had been demonstrated as a powerful practice in preventing selected severe genetic disorders. This practice is expanding its scope and impact in the era of next-generation sequencing. Empirical and theoretical data support the utility of expanded carrier screening. The authors propose a comprehensive carrier screening program as a main component of the first-tier measure in preventing severe genetic disorders and birth defects in China. We discussed the key principles and important aspects to ensure the success of such a program. The authors believe this program will play a pivotal role in our endeavor for a healthier nation.

Variations in EXD3 caused congenital cataracts in three Chinese families

Congenital cataract is a clinically and genetically heterogeneous disease characterized by any opacity of the lens presenting at birth or in the first year of life,with an incidence of 1–6/10,000 live births in developed countries and 5–15/10,000 live births in developing countries.Congenital cataract accounts for 7.4%–15.5%of all childhood blindness,and it occurs as either a syndromic disease or an isolated(nonsyndromic)disease with or without other ocular malformations,such as microcornea.

Exome sequencing confirms molecular diagnoses in 38 Chinese families with hereditary spherocytosis

Hereditary spherocytosis(HS), the most common cause of congenital hemolytic anemia, is caused by deficiency of the erythrocyte membrane proteins. Five causative genes(ANK1, SPTB, SPTA1, SLC4 A1, and EPB42) have been identified. To date,molecular genetic studies have been performed in different populations, including the American, European, Brazilian, Japanese and Korean populations, whereas only a few studies have been described in the Chinese population. Here, by reanalysis of the exome data, we revealed causative mutations and established a definitive diagnosis of HS in all 38 Chinese families. We found 34 novel mutations and four reported mutations in three known HS-causing genes—17 in ANK1, 17 in SPTB and four in SLC4 A1,suggesting that ANK1 and SPTB are the major genes in Chinese patients with HS. All of the ANK1 or SPTB mutations, scattered throughout the entire genes, are non-recurrent; and most of them are null mutations, which might cause HS via a haploinsufficiency mechanism. De novo mutations in ANK1 or SPTB often occur with an unexpected high frequency(87.5% and64.2%, respectively). Our study updates our knowledge about the genetic profile of HS in Chinese and shows that family-based,especially parent-offspring trio, sequencing analysis can help to increase the diagnostic power and improve diagnostic efficiency.

Expression of survivin mRNA in peritoneal lavage fluid from patients with gastric carcinoma

Background Peritoneal dissemination is the most common pattern of metastasis in advanced gastric carcinoma with serosal invasion In the present study, we reported the clinical relevance of a new diagnostic method involving RT-PCR, using survivin as the target gene, for the detection of free cancer cells in peritoneal washes Methods Intraoperative peritoneal washes were obtained from 48 patients who underwent surgery for gastric cancer RT-PCR analysis with primers specific for survivin and conventional cytological examinations were both performed Results Survivin mRNA was not detected in any peritoneal wash samples from patients with benign disease, but was detected in 28 of 48 samples taken from patients with gastric cancer and in all metastastic nodules Survivin expression in the peritoneal cavity significantly correlated with depth of cancer invasion, lymph node metastasis, and TNM stage There were 92% of clinically evident peritoneal metastasis cases showed detectable survivin expression The combination of survivin RT-PCR and cytological examination yielded positive results in 66 7% (32/48) of patients with gastric cancer, much higher than the results produced by cytological method alone KH*2/5DConclusions Survivin mRNA detected in peritoneal lavage fluid might indicate the presence of free cancer cells in the peritoneal cavity The high sensitivity of the RT-PCR-based survivin assay suggests that survivin serves as a molecular marker for detecting peritoneal micrometastasis Its ubiquitous expression in peritoneal cancer cells and metastatic nodules also suggests a promising future therapeutic strategy based on survivin inhibition for cases of gastric cancer involving peritoneal metastasis.

A novel DLL4 missense mutation in a Chinese patient with Adams-Oliver syndrome

To the Editor:Adams-Oliver syndrome (AOS,including 6 types) was initially reported in a three-generation family by Adams and Oliver in 1945,[1] with an estimated incidence of 1 in 225,000 live births.[2] Approximately 84% of AOS patients have terminal transverse limb defects,including amputations,syndactyly,brachydactyly,or oligodactyly.

A 3.06-Mb interstitial deletion on 12p11.22-12.1 caused brachydactyly type E combined with pectus carinatum

Background:Brachydactyly,a developmental disorder,refers to shortening of hands/feet due to small or missing metacarpals/ metatarsals and/or phalanges.Isolated brachydactyly type E (BDE),characterized by shortened metacarpals and/or metatarsals,consists in a small proportion of patients with Homeobox D13 (HOXD13) or parathyroid-hormone-like hormone (PTHLH) mutations.BDE is often accompanied by other anomalies that are parts of many congenital syndromes.In this study,we investigated a Chinese family presented with BDE combined with pectus carinatum and short stature.Methods:A four-generation Chinese family was recruited in June 2016.After informed consent was obtained,venous blood was collected,and genomic DNA was extracted by standard procedures.Whole-exome sequencing was performed to screen pathogenic mutation,array comparative genomic hybridization (Array-CGH) analysis was used to analyze copy number variations,and quantitative real-time polymerase chain reaction (PCR),stride over breakpoint PCR (gap-PCR),and Sanger sequencing were performed to confirm the candidate variation.Results:A 3.06-Mb deletion (chr12:25473650-28536747) was identified and segregated with the phenotype in this family.The deletion region encompasses 23 annotated genes,one of which is PTHLH which has been reported to be causative to the BDE.PTHLH is an important regulator of endochondral bone development.The affected individuals showed bilateral,severe,and generalized brachydactyly with short stature,pectus carinatum,and prematurely fusion of epiphyses.The feature of pectus carinatum has not been described in the PTHLH-related BDE patients previously.Conclusions:The haploinsufficiency of PTHLH might be responsible for the disease in this family.This study has expanded the knowledge on the phenotypic presentation of PTHLH variation.