OBJECTIVE: To explore the genotype-phenotype correlation in a Chinese family with structural brain abnormalities due to variant of the TUBB gene. METHODS: A family undergoing prenatal diagnosis at Beijing Obstetrics and Gynecology Hospital in October 2024 was selected as the study subject. Clinical data were collected. Amniotic fluid sample was subjected to chromosomal copy number variation sequencing (CNV-seq). Trio whole-exome sequencing (Trio-WES) was carried out on the amniotic fluid and parental blood samples, and candidate variant was verified by Sanger sequencing. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2023-KY-076-01). RESULTS: Both prenatal ultrasound and fetal MRI showed deviation of brain midline, unilateral lateral ventriculomegaly, and bilateral gyral asymmetry. Trio-WES revealed that the fetus has harbored a maternally derived heterozygous missense variant of the TUBB gene [NM_178014.4: c.155A>G (p.N52S)]. Sanger sequencing confirmed that the woman and a previously terminated fetus both harbored the same variant. Both the proband and two fetuses exhibited similar neuroimaging abnormalities including midline deviation and asymmetrical gyri. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PM2_Supporting+PS2_Moderate+PS3). CONCLUSION The heterozygous c.155A>G (p.N52S) variant was the TUBB gene probably underlay the pathogenesis of the structural brain abnormalities in this family. Above findings have expanded the phenotypic spectrum associated with the variant and facilitated the prenatal diagnosis for this family.
Humans ; Female ; Pregnancy ; Prenatal Diagnosis ; Tubulin/genetics* ; Adult ; Brain/diagnostic imaging* ; Male ; Pedigree ; DNA Copy Number Variations/genetics* ; Exome Sequencing ; Genetic Association Studies ; Magnetic Resonance Imaging

Ulcerative colitis （UC）， a chronic relapsing inflammatory bowel disease， involves multifaceted pathological mechanisms such as intestinal barrier dysfunction， immune dysregulation， and oxidative stress. Current therapeutic strategies remain limited in efficacy and safety. In recent years， the adenosine monophosphate-activated protein kinase （AMPK） signaling pathway has emerged as a pivotal therapeutic target for UC due to its central role in energy metabolism， inflammatory regulation， and intestinal homeostasis. This article systematically reviewed the mechanisms by which traditional Chinese medicine （TCM） prevented and treated UC through the regulation of the AMPK signaling pathway， with a focus on elucidating AMPK's multidimensional regulatory network in inflammatory signaling crosstalk， alleviating oxidative stress， restoring intestinal immune balance， repairing the intestinal barrier， and modulating gut microbiota. Leveraging its unique advantages of multi-target engagement and low toxicity， TCM demonstrates promising potential in UC treatment and has become a focal area of research. By systematically summarizing and synthesizing the existing literature on TCM-mediated AMPK pathway modulation in UC， this review aims to provide a theoretical foundation for advancing mechanistic research and clinical interventions in UC.

ObjectiveTo investigate the effects of zinc finger protein 473 （ZNF473）， a member of the zinc finger protein family， on the proliferation and migration of liver hepatocellular carcinoma （LIHC） cells and to explore its potential underlying mechanism. MethodsThe expression levels of ZNF473 in pan-cancer and in HCC tissues versus normal tissues were analyzed using The Cancer Genome Atlas （TCGA） database. The prognostic significance of ZNF473 in patients with HCC was evaluated using the Kaplan-Meier Plotter database with the Log-rank test. Human HCC cell lines HepG2 and MHCC97-H were used as experimental models and divided into a negative control （NC） group and an experimental group （si-ZNF473）. ZNF473 interference vectors were transfected into HepG2 and MHCC97-H cells. CCK-8 assays， Transwell assays， and wound-healing assays were performed to assess the effects of ZNF473 on the proliferation and migration of HepG2 and MHCC97-H cells. Western blot was used to detect changes in the expression levels of phosphorylated protein kinase B （p-AKT）， c-Myc， AKT， and other related proteins in HCC cells after ZNF473 knockdown. All cell experiment data were analyzed using GraphPad Prism 9.0 software. ResultsTCGA database analysis showed that ZNF473 was highly expressed in 17 cancer types， including LIHC. Immunohistochemical （IHC） staining data from the Human Protein Atlas （HPA） database indicated that ZNF473 was highly expressed in LIHC tissues. Single-cell RNA sequencing analysis showed that ZNF473 expression was higher in the malignant cell subpopulation than in other cell subpopulations. Survival analysis of patients with LIHC using the Kaplan-Meier Plotter database demonstrated that the high-ZNF473-expression group had significantly shorter overall survival （OS）， disease-specific survival （DSS）， progression-free survival （PFS）， and recurrence-free survival （RFS） than the low-expression group. CCK-8 assays showed that knockdown of ZNF473 reduced the proliferative capacity of HepG2 and MHCC97-H cells. Wound-healing and Transwell assays demonstrated that ZNF473 knockdown suppressed the migratory ability of HepG2 and MHCC97-H cells. RT-qPCR results showed no statistically significant difference in phosphatase and tensin homolog （PTEN） relative expression in the si-ZNF473 group， whereas the expression levels of PIK3CA and PIK3R1 were significantly altered （P<0.05）. Western blot analysis showed that downregulation of ZNF473 significantly decreased the protein expression levels of p-AKT and c-Myc （P<0.05）. ConclusionZNF473 is highly expressed in LIHC cells and tissues. ZNF473 may promote the proliferation and migration of LIHC cells by regulating the PI3K/AKT/c-Myc signaling pathway.

The recombinant human thyroid-stimulating hormone (rhTSH) can be used for differentiated thyroid cancer (DTC) preparation before ¹³¹I therapy, and follow-up. Since its approval by the American Food and Drug Administration (FDA) in 1998, rhTSH has been clinically used in European countries, the United States, and other countries for nearly 30 years. In April 2024, China’s first independently developed rhTSH agent was approved. Based on clinical experience and evidence from domestic and international studies, an expert consensus on the application of rhTSH has been developed following thorough consultations among experts. The consensus offers evidence-based recommendations to guide the appropriate use of rhTSH in clinical practice.

Objective:To evaluate the outcomes of intensive conservative treatment compared to conventional conservative treatment in patients with acute aortic syndrome(AAS).Methods:The study prospectively enrolled consecutive patients with AAS who were admitted to Beijing Anzhen Hospital, affiliated with Capital Medical University, and Beijing Dawanglu Emergency Rescue Hospital from January 2024 to December 2024. These patients with surgical contraindications or refused surgery for various reasons opted for conservative treatment. A total of 282 patients were included, and 15 patients with missing data or those who died without any treatment were excluded. Finally, 267 patients were enrolled, of whom 94 received intensive conservative treatment, and 173 received conventional conservative treatment, the inverse probability of treatment weighting (IPTW) was used to reduce the influence of confoundings. After adjusting of baseline datas via IPTW, the survival outcomes of the two groups were compared at 14 days, 30 days, and at the end of follow-up.Results:The results showed significant differences in acute phase survival rates between the enhanced conservative treatment group and the conventional conservative treatment group at 14 days(82.40%vs.53.20%, P<0.0001). Significant survival differences were also observed at 30 days and at 276-day mid-term follow-up (96.29% vs.51.60%, P<0.0001; 78.50% vs.48.50%, P<0.0001). In the subgroup analysis, for type A aortic dissection, the enhanced conservative treatment group had higher survival rates compared to the conventional conservative treatment group at 14, 30 and 276 days (63.46% vs.41.35%, P<0.05; 52.17% vs.37.90%, P<0.05; 50.00% vs. 31.97%, P<0.05). However, for type B aortic dissection, although the enhanced conservative treatment group had higher survival rates than the conventional conservative treatment group, no statistically significant differences were observed (96.29% vs. 80.00%, P=0.054; 95.65% vs.78.37%, P=0.067; 94.12% vs.74.20%, P=0.088). Conclusion:For patients diagnosed with AAS are forced to choose conservative treatment if emergency surgery is not possible in the first place, intensive conservative treatment strategies can significantly reduce the mortality in the acute phase compared with conventional conservative treatment. Mid-term follow-up, intensive conservative treatment still has a significant survival advantage.

Objective To explore the expression pattern and molecular function of ubiquitin-like containing PHD and RING finger domains 1(UHRF1)gene in soft tissue sarcoma(STS),as well as its correlation with clinical characteristics and prognosis of STS.Methods RNA data and related clinical data of 263 STS tissues were obtained from Cancer Genome Atlas(TCGA).Wilcoxon rank-sum test was used to analyze correlation between two groups of data;Spearman correlation coefficient analyzed the top 35 co-expressed genes positively and negatively correlated with UHRF1 expression in STS database,ggplot2 statistical package displayed co-expressed gene heatmap,Pearson correlation coefficient showed correlation between UHRF1 expression and expression of the top 10 genes in the heatmap;different UHRF1 gene expression groups in STS were analyzed using DESeq2 package,ggplot2 package was used to draw volcano plots,gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyzed differentially expressed genes(DEGs)and protein functions,ggplot2 package for visualization,and cluster Profiler package for statistical analysis;STRING web was used to establish PPI network of DEGs,and the MCC algorithm in CytoHubba of Cytoscape was used to analyze hub genes.Results In STS,UHRF1 gene was significantly correlated with its histological type(liposarcoma 22.2％,synovial sarcoma 3.8％,leiomyosarcoma 40.7％,malignant peripheral nerve sheath tumor 3.8％,myxofibrosarcoma 9.6％,pleomorphic sarcoma 19.9％,P=0.001),tumor necrosis(none 38.8％,focal necrosis 20.8％,moderate necrosis 33.8％,extensive necrosis 6.6％,P=0.010),and tumor metastasis(no metastasis 67％,metastasis 33％,P＜0.001).In different clinical subgroups(age,gender,histological type,residual tumor,tumor necrosis,tumor depth,margin status,tumor multifocality,radiotherapy),high expression of UHRF1 led to poor prognosis of overall survival(OS),disease-specific survival(DSS),and progression-free interval(PFI);Three prognostic factors above were simultaneously shortened in the following five subgroups:namely residual tumor R0 and R1,tumor necrosis extensive,focal and moderate,tumor depth deep,positive margin status,tumor without multifocality.Analysis of the top 10 co-expressed genes associated with UHRF1 expression revealed that the associated positive genes were PAGE5,LINC01425,LCEP3,SERPINB7,AC074031.1,LCE3A,LCE2A,PAGE2B,MYF5,and AC037486.1(P＜0.05);the associated negative genes were CDH19,CSN1S1,TAC3,AC103563.7,SAA1,CHST8,PRLHR,MIR202HG,IGHV1-24,and ART4(P＜0.05).A total of 3 029 DEGs of UHRF1 in STS were obtained with a threshold of|log2 fold-change(FC)|＞1.0 and adjusted P value＜0.05,in which 1 228 genes were up-regulated and 1 801 genes were down-regulated;GO enrichment analyed primary biological processes(BP),original cellular components(CC),and original molecular functions(MF),and KEGG enrichment analyed signaling pathways.A total of 343 DEGs including 133 up-regulated genes and 210 down-regulated genes,were obtained with a threshold of|log2 fold-change(FC)|＞2.0 and adjusted P value＜0.05.The top 10 hub genes were analyzed.The top 3 hub genes were GCG,SST and SHH,respectively.Conclusion UHRF1 is significantly correlated with histological type,tumor necrosis,metastasis,OS,DSS,and PFI events in STS.In co expressed genes model and molecular functions of related positive and negative genes involved in multiple biological processes;The network of differentially expressed genes and protein product interactions involved in mechanisms of occurrence and development of the disease,and provided new ideas for in-depth researches on STS.

Objective To investigate the effect of drug-eluting bead DACE(DEB-TACE)combined with systemic treatment for hepatocellular carcinoma(HCC)in different locations.Methods A total of 204 HCC patients who underwent DEB-TACE combined with systemic therapy(targeted and immunotherapy)were retrospectively collected.According to the anatomical location of HCC,86 cases with lesions located at the main trunk of portal vein(PV)or within 1 cm of the first PV branch were classified into central type group,while 118 cases with lesions located at the other areas were classified as peripheral type group.Follow-up was regularly performed after DEB-TACE until August,2024.The objective response rate(ORR)and disease control rate(DCR)at 1,3,6 and 12 months after DEB-TACE,also patients'progression-free survival(PFS)and overall survival(OS)were compared between groups.Results All patients were followed up for a median of 32.6 months,during which 164 cases died.Significant differences of ORR at 1 and 3 months after DEB-TACE(77.91％[67/86]vs.89.83％[106/118],34.88％[30/86]vs.54.24％[64/118])and DCR at 3 and 6 months after DEB-TACE(51.16％[44/86]vs.66.95％[79/118],34.88％[30/86]vs.50.00％[59/118])were found between groups(all P＜0.05).Patients'PFS(30.18[9.12,48.54]months)and OS(37.36[17.79,56.68])in peripheral type group were better than those in central type group(20.11[11.35,28.87]months and 23.24[3.11,43.47]months,x2=3.971,4.162,P=0.048,0.041).Conclusion The effect of DEB-TACE combined with systemic treatment for peripheral type HCC was better than for central type HCC.

Objective:To evaluate the outcomes of intensive conservative treatment compared to conventional conservative treatment in patients with acute aortic syndrome(AAS).Methods:The study prospectively enrolled consecutive patients with AAS who were admitted to Beijing Anzhen Hospital, affiliated with Capital Medical University, and Beijing Dawanglu Emergency Rescue Hospital from January 2024 to December 2024. These patients with surgical contraindications or refused surgery for various reasons opted for conservative treatment. A total of 282 patients were included, and 15 patients with missing data or those who died without any treatment were excluded. Finally, 267 patients were enrolled, of whom 94 received intensive conservative treatment, and 173 received conventional conservative treatment, the inverse probability of treatment weighting (IPTW) was used to reduce the influence of confoundings. After adjusting of baseline datas via IPTW, the survival outcomes of the two groups were compared at 14 days, 30 days, and at the end of follow-up.Results:The results showed significant differences in acute phase survival rates between the enhanced conservative treatment group and the conventional conservative treatment group at 14 days(82.40%vs.53.20%, P<0.0001). Significant survival differences were also observed at 30 days and at 276-day mid-term follow-up (96.29% vs.51.60%, P<0.0001; 78.50% vs.48.50%, P<0.0001). In the subgroup analysis, for type A aortic dissection, the enhanced conservative treatment group had higher survival rates compared to the conventional conservative treatment group at 14, 30 and 276 days (63.46% vs.41.35%, P<0.05; 52.17% vs.37.90%, P<0.05; 50.00% vs. 31.97%, P<0.05). However, for type B aortic dissection, although the enhanced conservative treatment group had higher survival rates than the conventional conservative treatment group, no statistically significant differences were observed (96.29% vs. 80.00%, P=0.054; 95.65% vs.78.37%, P=0.067; 94.12% vs.74.20%, P=0.088). Conclusion:For patients diagnosed with AAS are forced to choose conservative treatment if emergency surgery is not possible in the first place, intensive conservative treatment strategies can significantly reduce the mortality in the acute phase compared with conventional conservative treatment. Mid-term follow-up, intensive conservative treatment still has a significant survival advantage.

Objective:To summarize the experience of diagnosis and treatment of unexplained neonatal intestinal perforation.Methods:A case summary was conducted.Intestinal perforation children who showed unclear etiology during surgical exploration in Fujian Children′s Hospital from October 2017 to October 2023 were retrospectively analyzed.The perforation characteristics, pathological characteristics, etiological analysis and surgical methods were analyzed, and the diagnosis and treatment experience was summarized.Results:There were 21 neonates with unexplained intestinal perforation, including 15 boys and 6 girls.There were more full-term infants (12 cases) than preterm ones (9 cases), and more neonates with normal birth weight (12 cases) than those with low birth weight (9 cases).Intraoperative perforation was detected in the ileum in 13 cases and colon in 8 cases.The perforation diameter ranged between 0.5-2.0 cm.Single perforation was detected in 20 cases, and 1 case had two perforations.All patients underwent full-layer multipoint biopsy and enterostomy.Pathological reports after surgery showed that Hirschsprung disease was confirmed in 10 cases, and Hirschsprung disease allied disorders were diagnosed in 8 cases.The remaining 3 cases had normal ganglion cells, and 2 cases of them had spontaneous intestinal perforation, and 1 case had meconium ileus.After operation, 3 cases gave up treatment, 1 case died, and 17 patients were discharged from hospital at the first stage.Nine cases with Hirschsprung disease received radical surgery at the age of 3-6 months.Six out of 8 patients with Hirschsprung disease allied disorders underwent fistula closure surgery after accurate evaluation.Among the 6 children who received fistula closure surgery, 1 case underwent Santulli enterostomy because of inability to defecate and abdominal distension after surgery.Two of the 6 children undergoing fistula closure surgery were still being followed up.Two cases of spontaneous intestinal perforation and 1 case of meconium ileus underwent fistula closure surgery at the age of 3 months, and postoperative defecation was normal.Conclusions:Intestinal neuronal dysplasia, meconium ileus combined with intestinal perforation and spontaneous intestinal perforation should be considered in unexplained neonatal intestinal perforation.It is recommended that enterostomy and multipoint biopsy should be performed to clarify the pathology before further treatment in children with unexplained intestinal perforation.Santulli enterostomy is a feasible staging operation.

BACKGROUND:Wolff's law points out that the lack of mechanical stress in the body will lead to the degradation of the microstructure of bone tissue,mass loss,and metabolic disorders,and eventually lead to osteoporosis,which suggests that mechanical stress plays an important role in the growth,reconstruction,and formation of bone tissue.At present,the relevant studies concerning mechanical stress on osteoblasts mainly focus on fluid shear force,but it is difficult to intervene in vivo.Meanwhile,some studies have found that compressive stress can also play a similar role in fluid shear force to a certain extent.Exploring the mode of action and influence of compressive stress on cells in vitro experiments can enrich the interaction relationship between mechanical stress and cells.It helps provide a theoretical basis for studies of metabolic bone diseases,including osteoporosis,and other diseases.OBJECTIVE:To review in vitro experiments,the application of compressive stress to cells,different biological behaviors caused by cells,the possible signaling pathways,and possible future applications.METHODS:We searched PubMed,Web of Science,CNKI,and WanFang databases from January 2000 to March 2024 to include all articles related to compressive stress on cells,including basic research and microscopic mechanism studies,using search terms"compressive stress,mechanical stress,hydrostatic pressure,cell"in Chinese and English.Finally,the 63 included articles were reviewed.RESULTS AND CONCLUSION:(1)There are various ways to apply compressive stress,and different experimental equipment has different ways of pressurizing cells,so it is necessary to further standardize the experimental equipment,standardize the pressurization unit,reduce the confounding factors,and make the reference and comparability between different experimental groups.(2)Compressive stress can cause changes in cell proliferation,differentiation,autophagy,apoptosis,migration,etc.,and the effect of compressive stress is time-or dose-dependent in most cases.(3)At present,most in vitro experimental studies have shown that compressive stress may mainly act on osteoblasts through MAPK signaling pathway and Wnt/β-catenin signaling pathway,causing osteoblasts to produce different responses.(4)The effect of compressive stress on different cells is not the same,and its possible biological effects need to be studied.(5)Further research on compressive stress is helpful to provide a theoretical basis for treatment in orthopedics,stomatology,tumors and other fields,and gentle disinfection using hydrostatic pressure is a promising disinfection method.