Objective To study the pathological and immunohistochemical features of alimentary tract mesenchymal tumors and compare with computed tomographic virtue endoscopy (CTVE) imaging technology to evaluate the diagnostic value of CTVE in alimentary tract mesenchymal tumors. Methods Seventy-four pathological specimens of alimentary tract mesenchymal tumors were collected. The pathological features and the expression of CD117, CD34, SMA and S-100 were observed by immunohistochemical method with light microscope. The pathological types and characteristics were determined by pathologists and compared with CTVE imaging technology. Results In the 74 cases of alimentary tract mesenchymal tumors,40 cases were diagnosed as stromal tumor with pathological and immunohistochemical methods (54. 1%).Sixteen of them were malignant, accounting for 40% of the stromal tumor while 33 cases were diagnosed as leiomyoma(44. 6%)and 1 case as schwannoma(1.4%) . In the 74 GIMTs cases ,33 were jejunum GIMTs,21 were ileum GIMTs and 20 were large intestine GIMTs. Immunohistochemistry assay in the 74 GIMTs cases showed that 51.4% GIMTs were positive for CD117, approximately 36. 5% were positive for CD34 , 62.2% were positive for smooth-muscle actin (SMA) and 1. 4% were positive for S-100 protein. In the 74 GIMTs cases,69 cases were diagnosed right in the accuracy for location with CTVE(93. 2%) with 51 cases in small intestinal (94. 4%) and 18 cases in large intestinal (90. 0%). The sensitivity and the specificity of CTVE to distinguish benign from malignant stromal tumors by CTVE characteristics were 84. 2% and 85. 7%respectively. Conclusions GIST is common in GIMTs and is often originated from the small intestinal. The immunohistochemistry has great value in diagnosing alimentary tract mesenchymal tumors. The CTVE imaging technology also has great value in diagnosing alimentary tract mesenchymal tumors which can show the localization, shape size and artery of the tumor clearly. The diagnostic sensitivity and specificity of CTVE are high to distinguish benign from malignant alimentary tract GISTs. CTVE plays an important role in guiding the clinical management of GISTs.

Objective:To understand the epidemiological and etiological characteristics of hand-foot-mouth disease (HFMD) in the Nanshan District of Shenzhen City from 2019 to 2022 and to provide a scientific basis for HFMD prevention in the area.Methods:Epidemiological data on HFMD in Shenzhen Nanshan District from 2019 to 2022 in the China Information System for Disease Control and Prevention were analyzed using descriptive research methods.Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to analyze the etiology characteristics of clinical specimens from HFMD patients. The VP1 gene of the dominant pathogen coxsackievirus A6 (CV-A6) was amplified and sequenced. SepMan Pro of DNASTAR software was used for sequence assembly and MegAlign was used for nucleotide homology analysis.Results:A total of 13 195 HFMD cases were reported in Shenzhen Nanshan District from 2019 to 2022, with an average annual incidence rate of 186.18/100, 000. Summer and autumn are the main onset seasons and children under 7 years old were the main population, accounting for 93.1%. The male-to-female ratio is 1.44∶1. A total of 451 clinical HFMD specimens were detected in the laboratory, including 403 positive (87.36%) and 48 negative (10.64%). The main pathogens were CV-A6 (63.03%), coxsackievirus A16 (CV-A16) (27.79%), coxsackievirus A4 (CV-A4) (4.71%), coxsackievirus A10 (CV-A10) (1.99%), Echovirus 11 (Echo-11) (0.25%), and uncertain type accounted for 2.23%, with no detection for enterovirus71 (EV71) type. The nucleotide homology of the 13 CV-A6 strains ranged from 94.0%?99.6%, and the nucleotide homology with the prototype strain Gdula ranged 84.1%?85.8%. The results of phylogenetic tree showed that all 13 CV-A6 strains in Nanshan District were of the D3a genotype.Conclusions:FHFMD in Nanshan District of Shenzhen City in 2019-2022 shows obvious differences in population and time distribution. Therefore, it is necessary to strengthen publicity and education on HFMD prevention and control in the summer and fall seasons and among key populations. CV-A6 and CV-A16 are the dominant strains of HFMD in Nanshan District, Shenzhen in recent years, so the monitoring of the dominant strains should be improved.

Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.
Humans ; Apolipoprotein E4/genetics* ; Cytosine ; Mutation ; Blastocyst ; Heterozygote ; Gene Editing ; CRISPR-Cas Systems