Approximately 60% of colorectal cancer (CRC) patients exhibit TP53 mutations, which are strongly associated with tumor progression, chemotherapy resistance, and an unfavorable prognosis. However, targeting p53 has historically been challenging, and currently, there are no approved p53-based therapeutics for clinical use worldwide. In this study, we discovered that ubiquitin carboxyl terminal hydrolase L3 (UCHL3) plays a crucial role in high-level glycolysis, enhanced stem-like properties, and 5-fluorouracil (5-FU) chemoresistance in TP53-mutant CRC by exerting its deubiquitinating enzyme activity to stabilize α-enolase (ENO1) protein. Notably, we identified a newly Food and Drug Administration (FDA)-approved drug, pacritinib, that potently suppresses UCHL3 expression by blocking the janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway in TP53-mutant CRC. Furthermore, Pacritinib was demonstrated to effectively inhibit glycolysis and improve the sensitivity to 5-FU chemotherapy in TP53-mutant CRC. Our findings suggest that targeting the JAK2-STAT3-UCHL3-ENO1 axis is a promising strategy to suppress glycolysis and enhance the efficacy of 5-FU chemotherapy in TP53-mutant CRC. Pacritinib shows potential for clinical application in the treatment of TP53-mutant CRC.

OBJECTIVETo explore the value of single nucleotide polymorphism array (SNP-array) for the analysis of pediatric patients with growth retardation.

METHODSOne hundred eighty one children with growth retardation were enrolled. DNA was extracted from peripheral samples from the patients, and whole genome copy number variations (CNVs) were detected using Illumina Human Cyto SNP-12. All identified CNVs were further analyzed with reference to databases including ClinGen, ClinVar, DECIPHER, OMIM and DGV as well as comprehensive review of literature from PubMed to determine their pathogenicity.

RESULTSForty seven patients (26%) with abnormal CNVs were detected, which included 12 known microdeletions/microduplications syndrome (26%), 10 pathogenic non-syndromic CNVs (21%), 3 numerical chromosome aberrations (6%), 3 unbalanced translocations (6%), 4 pathogenic mosaicisms (9%) and 15 cases with unknown clinical significance (32%). After excluding obvious numerical and/or structural chromosomal abnormalities, this study has detected 15 pathogenic microdeletions/microduplications sized 5 Mb or less, which may be missed by routine chromosomal karyotyping. In addition, there were 3 cases with loss of heterozygoisty (LOH) containing known or predicted imprinting genes as well as 2 cases with suspected parental consanguinity.

CONCLUSIONSNP-array technology is a powerful tool for the genetic diagnosis of children with growth disorders with advantages of high resolution and improved accuracy.

Adolescent ; Child ; Child, Preschool ; Chromosome Aberrations ; DNA Copy Number Variations ; Developmental Disabilities ; diagnosis ; genetics ; Female ; Humans ; Infant ; Karyotyping ; Male ; Oligonucleotide Array Sequence Analysis ; methods ; Polymorphism, Single Nucleotide

BACKGROUND:Anular repair after discectomy in intervertebral disc degeneration obtains good clinical outcomes and reduces the recurrent rate, but there is little report on the effective suturing method and reliable instrument. OBJECTIVE: To investigate the clinical effectiveness of annulus repair after discectomy under Mast Quadrant system for lumbar disc herniation. METHODS: Fifty patients with lumbar disc herniation admitted in the Hubei Provincial Hospital of TCM from August 2013 to August 2015 were selected, followed by divided into experimental and control groups (n=25 per group), and then received annulus repair after discectomy and simple discectomy, respectively. The length of incision, operation time and intraoperative blood loss were compared between two groups, and the Oswestry disability index and visual analogue scale scores for lumbago and lower limb pain before and after surgery were detected, as well as the incidence of complications and recurrence were recorded. RESULTS AND CONCLUSION:All patients in the experimental group completed the follow-up, while only 23 in the control group finished the follow-up. There were no significant differences in the baseline data between two groups (P > 0.05). The postoperative Oswestry disability index and visual analogue scale scores in both two groups were significantly lower than those before surgery (P < 0.05). There was a significant difference in the visual analog scale score at 1 month postoperatively between two groups (P < 0.05), while the scores at other time points showed insignificant difference between two groups (P > 0.05). There were two cases of recurrence in the control group, one of which received secondary treatment, and the recurrent rate was 9%. In the experimental group, there was only one case of recurrence receiving no treatment, and the recurrent rate was 4%. There were no cerebrospinal fluid leakage, infection, never root injury or other serious complications in both two groups. These results indicate that annulus repair after discectomy is minimally invasive, achieves the reconstruction of disc, and reduces the recurrence rate, which is available for lumbar disc herniation.

Objective To explore the incidence and significance of intra-and extraosseous edema accompanying benign tumors and tumor like diseases.Methods Imaging studies including MR,CT and plain radiograph were retrospectively reviewed in 245 cases of benign osseous tumors and tumor like diseases proved by pathology(borderline tumor,cases associated with pathological fractures,cases with lesions of skull were excluded from the study).The incidence of bone marrow and soft tissue edema were defined on T2WI with fat suppression on MRI in all the cases.x2 test was performed for the incidence rate of edema in the benign tumors and tumor like diseases.The pre-operative diagnoses were reviewed,and the influence of edema to the differential diagnosis between the benign and malignant was analyzed.Results The total incidence of bone marrow and soft tissue edema associated with benign tumors and tumor like diseases was 37.1％ (91/245),which included Langerhans cell histiocytosis 85.2％ (23/27),osteoblastoma85.0％ (17/20),osteoid osteoma93.6％ (29/31),ehondroblastoma 87.0％ (20/23).There was no statistically significant difference of edema incidence among the above-mentioned four diseases.(x2=6.35,P＞ 0.05).Both cases of endosteal capillary hemangioma had edema around.No edema was found around the lesions of other kinds of diseases.41 of 91 cases (45.1％) with edema were misdiagnosed as malignant tumor by MRI pre-operatively.Conclusion The marrow and soft tissue edema is a common sign in the benign bone tumor and tumor-like diseases,and it is frequently seen in Langerhans cell histiocytosis,osteoblastoma,osteoid osteoma,chondroblastoma.

OBJECTIVETo investigate the feasibility of constructing a capsular poly L-lactic acid (PLLA) ureteral stent seeded with autologous urothelial cells using tissue engineering methods.

METHODSThe capsular ureteral stent was constructed by subcutaneously embedding PLLA ureteral stent in the back of beagles for 3 weeks to induce the formation of connective tissue on the surfaces. After decellularization of the stent, the expanded autologous urothelial cells were seeded on the stent. The surface structure and cell adhesion of the stent were observed using HE staining, scanning electron microscope (SEM) and immunocytochemical staining. MTT assay was used to evaluate urothelial cell proliferation on the capsular PLLA ureteral stent and on circumferential small intestinal submucosa graft.

RESULTSHE staining and VIII factor immunohistochemistry revealed numerous capillaries in the connective tissue encapsulating the stent without obvious local inflammatory response. The results of SEM and immunocytochemical staining showed that the capsule contained rich collagenic fibers forming three-dimensional structures, and the seeded autologous urothelial cells could adhere and well aligned on the surface. MTT assay showed normal growth of the cells on the stent as compared with the cells grown on circumferential small intestinal submucosa graft.

CONCLUSIONThe capsular PLLA ureteral stent allows adhesion and proliferation of autologous urothelial cells and shows a potential in applications of constructing tissue-engineered ureter.

Animals ; Bacterial Adhesion ; Cell Proliferation ; Dogs ; Epithelial Cells ; cytology ; transplantation ; Female ; Lactic Acid ; Polyesters ; Polymers ; Stents ; Tissue Engineering ; methods ; Transplantation, Autologous ; Ureter ; surgery ; Urothelium ; cytology