BACKGROUND:Development of neural crest cels, which is regulated by various genes, plays an important role in the formation of central nervous system, heart, craniofacial organs and other tissues. However, the relationship among these genes is unclear. OBJECTIVE:To investigate the molecular regulatory networks involved in the process of neural crest cel development based on a bioinformatic analysis. METHODS:Totaly 500 differentialy expressed genes during the process ofneural crest cel development were obtained from the GEO on-line database. Then the DAVID and STRING on-line databases were used to evaluate the relationship among these genes. RESULTS AND CONCLUSION:Totaly 500 differentialy expressed genes during theprocess of neural crest cel development could be enriched into different subgroups based on the analysis of DAVID database, including “transforming growth factor β signal pathway”, “WNT signal pathway”, “homeobox gene” , “neural crest cel differentiation” and “neural tube development”. Additionaly, 12 genes molecular networks were built based on the analysis of STRING database, such as DLX5, MSX2, SNAIL2, PAX7, SHH, SOX9, NOG, GSC, KAL1, bone morphogenetic protein 5, fibroblast growth factor 8 and WNT3a.These genes exhibited interactions by co-expression, activation and antagonism. Therefore, many genes involved in the process of neural crest cel development were interacted and formed the networks. These findings imply that we should understand these neural crest-related diseases from a holistic view of the signaling pathway and molecular regulatory networks.

BACKGROUND:Magnesium al oy as a fracture fixation material has mechanical properties similar to the bone, good biocompatibility and biodegradability, but its rapid degradation rate in body fluids becomes a clinical bottleneck. Therefore, the use of surface treatments to improve its corrosion resistance is important.
OBJECTIVE:To use magnetron sputtering technology and alkali heat treatment technology in the preparation of coating characterized as both corrosion resistance and biological activity.
METHODS:First, we prepared Mg-Zn-Mn al oy using the smelting technology, and prepared a dense coating on the al oy surface by the magnetron sputtering technique. Then, we processed the coating surface using an alkaline solution, and studied the corrosion behavior of the coating by use of simulated body fluid experiments. We speculated the biological activity of the coating by measuring the content of calcium and phosphorus from the surface products.
RESULTS AND CONCLUSION:We prepared the coating, which had both corrosion resistance and biological activity, on the surface of magnesium al oy by use of magnetron sputtering and alkali heat treatment technology. After soaking in the simulated body fluid for 24 hours and 168 hours, the deposition of the coating surface contained Ca, P products. Ca/P ratios were 1.54 and 2.11, respectively, closed to the bone-phosphate Ca/P ratio. The coating surface formed 5-10μm pitting after 24 hours of immersion, and the pitting grew up with the immersion time. The pitting was enlarged to 100-800μm after 168 hours.

Mycotic thoracic aortic aneurysm (MTAA) is a disease that is difficult to treat and often lethal. Open repair has high morbidity and mortality risks; additionally, thoracic endovascular aneurysm repair (TEVAR) often requires innovative techniques.We report the use of an innominate artery chimney endovascular aneurysm repair (ChEVAR) with carotid-carotid and carotid-left subclavian artery bypass for a time-sensitive Salmonella-related MTAA. A symptomatic type 1a endoleak was discovered and promptly and successfully treated. This report shows that the use of innominate artery ChEVAR to treat MTAA is feasible and safe, although the procedure is rarely performed, even in large series. We hypothesize that prophylactic gutter embolization is a feasible option in view of the high endoleak risks in such cases, although further evidence is required to support this.

Objective To explore the regulatory effects of HTLV-1 ( human T-cell leukemia virus type 1 ) Tax protein on the expression of HMGB 1 ( high mobility group box 1 ) gene in T cells .Methods Total RNA and protein were extracted from Tax +-T cells ( TaxP ) , Tax--T cells ( TaxN ) and Jurkat cells which were stably transfected with pCMV-Tax and pCMV-Neo, respectively.Then, the expression levels of HMGB1 mRNA and protein in different CD 4+T cells were analyzed by real-time PCR and Western blot (WB).By using liposome-mediated method, pGL3-HMGB1-luc reporter genes and pGL3-neo-luc were tran-siently transfected into TaxP and TaxN cells and the basal transcriptional activity was observed in different T cells.Additionally, pCMV-Tax and pGL3-HMGB1-luc reporter genes were also co-transfected into Jurkat cells and the regulatory effects of Tax protein on HMGB 1 gene was detected .The chromatin immunoprecipi-tation (ChIP) assay was used to identify HMGB1 genomic sites directly targeted by Tax .Results The ex-pression levels of HMGB1 mRNA and protein in Tax+-T cells ( TaxP) were higher than those in Tax--T cells (TaxN).The transcription regulation trends for HMGB1 gene in TaxN and TaxP cells were similar but not identical in diverse T cells.pHLuc3 (containing -504-+83 HMGB1) showed the highest transcriptional ac-tivity of HMGB1 gene in both TaxP and TaxN cells , but HMGB1 transcriptional activity of pHLuc 6 in TaxP cells was significantly stronger than that in TaxN cells .Luciferase assays also showed that Tax protein promo-ted the transcription of HMGB1 gene in a dose-dependent manner .The ChIP assay further confirmed that Tax protein enriched at the HMGB1 region of -1163--1043.Conclusion The region of nt -504--383 is essen-tial for the basal promoter activity of -1163-+83 HMGB1 gene originated from pHLuc 6 reporter plasmid , and Tax protein enriched probably at the HMGB 1 site of -1163--1043 enhances HMGB1 transcription.

Objective:To investigate the impact of geniposide(GE)on lung injury in rats with acute respiratory distress syn-drome(ARDS)by regulating AMP-activated protein kinase(AMPK)/silencing information regulator 1(SIRT1)/nuclear factor κB(NF-κB)signaling pathway.Methods:The ARDS rat model was established by tracheal instillation of lipopolysaccharide(LPS).Fifty rats after modeling were randomly group into ARDS group,GE low-dose(GE-L,12.5 mg/kg GE)group,GE medium-dose(GE-M,25 mg/kg GE)group,GE high-dose group(GE-H,50 mg/kg GE)group and GE-H+Compound C(AMPK inhibitor,50 mg/kg GE+250 μg/kg Compound C)group,another 10 normal rats were used as the control group.After the intervention,the bronchoalveolar la-vage fluid(BALF)and lung tissue of the rats in each group were taken out,respectively,and the ratio of lung wet to dry weight(W/D)was detected;ELISA was used to detect the levels of inflammatory factors IL-6,interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α)in BALF;the positive expressions of vascular cell adhesion factor(VCAM-1)and vascular endothelial cell growth factor(VEGF)in lung tissue were detected by immunohistochemistry;HE staining was used to observe the pathological changes of lung tissue;Western blot was used to detect the expression levels of AMPK/SIRT1/NF-κB pathway proteins in lung tissue.Results:The levels of W/D,IFN-γ,IL-6,TNF-α,p-NF-κB p65/NF-κB p65 and VCAM-1 in ARDS group were significantly higher than those in control group,the expressions of p-AMPK/AMPK,SIRT1 and VEGF were significantly decreased(P<0.05);after different doses of GE treatment,the levels of W/D,IFN-γ,IL-6,TNF-α,and the expressions of p-NF-κB p65/NF-κB p65 and VCAM-1 were gradually decreased compared with those in ARDS group;the expressions of p-AMPK/AMPK,SIRT1 and VEGF increased gradually(P<0.05);Compound C reversed the protective effect of GE-H on ARDS rats(P<0.05).Conclusion:GE can improve lung injury in ARDS rats and reduce levels of inflammatory factors,which may be related to activation of AMPK/SIRT1/NF-κB signaling pathway.

Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.

Cervical cancer is a prevalent gynecological malignancy worldwide,and despite established mea-sures for prevention,detection,and treatment at different stages,limited success has been achieved in effectively reducing its incidence.While treatments such as surgery for early-stage patients,adjuvant chemoradiotherapy based on postoperative pathology assessment of high-risk factors and intermediate risk factors,combined radiochemotherapy for patients at all stages,and systemic treatment for advanced cervical cancer have demonstrated effectiveness in numerous cases.Recent advancements in surgical pathology staging,selection of surgical approaches,options available for early-stage cases,utilization of neoadjuvant chemotherapy,novel approaches to radiotherapy adminis-tration,as well as clinical trials investigating new drugs targeting recurrent and metastatic cervical cancer have con-tributed to more precise and individualized treatment strategies while providing a wider range of choices.Therefore,this manuscript comprehensively discusses important developments concerning the diagnosis and treatment of cervi-cal cancer with the aim of offering an improved reference for clinical practice.

Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.

Objective:To determine the carrier frequency and hot-spot variants of a custom-designed expanded carrier screening (ECS) panel with 216 diseases (216-ECS panel) within a Chinese population of childbearing age.Methods:Whole-exome sequencing data from a cohort of 3 097 unrelated healthy individuals (including 1 424 couples) from Peking Union Medical College Hospital between January 2013 and December 2023 were analyzed. Totally 220 genes which inherited in a recessive manner of 216-ECS panel were included in the analysis. The analysis included variant carrier rate, gene carrier rate, cumulative carrier rate, at-risk couple rates, and variant spectrum.Results:(1) Pathogenic variants were identified in 1 472 (47.53%, 1 472/3 097) individuals, with an average of 0.65 pathogenic variants per individual. The rate of at-risk couples was 3.93% (56/1 424). (2) A total of 180 genes were identified, with 16 genes exhibiting a gene carrier rate of ≥1% and 33 genes having a rate of ≥0.5%, most of which were associated with inherited metabolic diseases. Noteworthy genes with higher gene carrier rates and high-frequency variants included GJB2: c.235del, PAH: c.728G>A, ATP7B: c.2333G>T, SLC26A4: c.919-2A>G, GALC: c.1901T>C, POLG: c.2890C>T, SLC22A5: c.1472C>G, USH2A: c.2802T>G, SLC25A13: c.852_855del, GAA: c.761C>T and c.752C>T. Conclusion:This study offers a focused analysis of carrier frequencies and hot-spot variants of 216 diseases of the ECS panel constructed by our laboratory among the Chinese population, laying a foundation for the development of ECS programs tailored to the Chinese population.

Objective: To investigate and analyze serological and hepatic morphological changes in aged rats with non-alcoholic fatty liver disease(NAFLD)by establishing NAFLD model with SD rats at different months of age. Methods: Male SD rats were randomly divided into four groups according to age: the aged model group(18-months-old), the aged control group(18-months-old), the young model group(2-months-old)and the young control group(2-months-old), with 12 rats in each group.Rats in the model groups and the control groups were fed a 45% high-fat diet and a normal diet, respectively, for eight weeks.Serum biochemical indexes and the insulin index were measured.Hepatic histological changes were evaluated under a light microscope following HE staining and Oil red staining. Results: The body and liver weights of the rats increased with age, and the average rate of weight growth and liver wet weight of the model groups were higher than those of their corresponding control groups(P<0.01). Levels of serum alanine aminotransferase(ALT), triglycerides(TG), cholesterol(CHOL), glucose(GLU), fasting insulin(FINS)and homeostatic model assessment of insulin resistance(HOMA-IR)in the aged model group were higher than those in the corresponding control group and of the young model group(P<0.05). Under the light microscope, hepatic cells stained with HE and Oil red showed diffuse swelling and were full of lipid vacuoles in the model groups.In the aged model group, hepatic cells were characterized by macrovesicular steatosis with focal necrosis. Conclusions Clear hyperlipemia, hyperglycemia and hyperinsulinemia can be seen in a NAFLD model induced by short-term high-fat feeding.Insulin resistance and decreased insulin sensitivity are more significant in aged rats with NAFLD.