Background and aims:Primary sclerosing cholangitis(PSC)is an autoimmune liver disease characterized by complex pathogenesis and limited available therapeutic options.The mechanisms underlying the development and progression of PSCs remain unclear.Liver X receptor beta(LXR-β)is recognized to modulate lipid metabolism and immune response,but its specific involvement in the PSC has not been elucidated.Here,we explored the role and mechanism of LXR-β in PSC induced by 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine(DDC).Methods:CRISPR-Cas9 technology was applied to generate Abcb4(coding MDR2,next named as Mdr2),Nr1h2(coding LXR-β,next named as Lxrβ),and Rag2(coding RAG2)knockout mice.DDC was used to induce PSC.Hematoxylin and eosin and Sirius red staining were used to assess the extent of hepatic injury and fibrosis.Flow cytometry was used to observe immune cell subsets.Results:We observed a declining trend in hepatic Lxrβ in the PSC model.Unexpectedly,Lxrβ knockout failed to modulate DDC-induced PSC pathogenesis.Concomitantly,assessment of the influence of Rag2 deficiency on PSC progression revealed the absence of aggravated or alleviated hepatic injury or fibrosis in the Rag2-/-DDC mice.However,Lxrβ depletion intensified DDC-induced PSC in the Rag2-/-mice,with more abundant infiltrative inflammatory cells and more severe liver fibrosis.Compared with Rag2-/-DDC mice,Lxrβ-/-Rag2-/-DDC mice had higher serum ALT and AST levels and mRNA expression of proinflammatory and profibrotic genes.Flow cytometry showed that LXR-β deficiency resulted in a diminished population of hepatic innate immune cells.Conclusion:This study indicated innate immune cell LXR-β deficiency can exacerbate hepatic injury and fibrosis in murine models of PSC suggesting that LXR-β may regulate the function of innate immunity in the fibrotic advancement of PSC.

Objective:To analyze the gene mutation spectrum of children with T-acute lymphoblastic leukemia (T-ALL) using next generation sequencing technology and to evaluate the value of gene mutations in prognosis stratification.Methods:A case series analysis was made.The clinical data of newly diagnosed pediatric T-ALL patients in the First Affiliated Hospital of Zhengzhou University from January 1, 2019 to February 29, 2024 were analyzed retrospectively.T-ALL gene mutations were analyzed.The relationships of gene mutations with clinical features and induction of responses to therapy were studied.The effects of gene mutations on overall survival (OS) and event-free survival (EFS) were examined by the Kaplan-Meier method and COX regression model.Results:A total of 80 newly diagnosed pediatric T-ALL patients were enrolled in the study, with a male-to-female ratio of 3.4∶1.0 and a median age of 8 (range, 2-17) years.A total of 57 mutations were detected in 74 patients, 46.2% (37/74) of whom showed 3 or more gene mutations.The coexistence of mutated genes was obvious. PTEN mutations were more prevalent in male patients ( P=0.018).Initial leukocyte counts were higher in patients with PTEN mutations ( P=0.038) and lower in patients with JAK3 mutations ( P=0.002).Patients with NOTCH1 mutations had a higher positive rate of fusion genes ( P=0.043).Patients with PTEN mutations had a higher rate of minimal residual disease(MRD) remission after 15/19 d of treatment with induction therapy, respectively ( P=0.013).The rate of MRD remission after 33/46 d of treatment with induction therapy was higher in patients with the FBXW7 mutation ( P=0.004) and lower in patients with JAK3 mutations ( P=0.003).Multifactorial COX regression analysis showed that IL7R mutation and three or more gene mutations were independent risk factors for OS and EFS in T-ALL patients(OS: HR=3.252, 7.357, 95% CI: 1.020-10.372, 1.646-32.882; EFS: HR=3.372, 3.009, 95% CI: 1.234-9.214, 1.174-7.708; all P<0.05). Conclusions:Gene mutations are prevalent in T-ALL children and correlate with clinical manifestations and prognosis.The coexistence of mutated genes is obvious.Pediatric T-ALL patients with IL7R mutations and three or more gene mutations have a poorer prognosis.

Objective:To analyze the gene mutation spectrum of children with T-acute lymphoblastic leukemia (T-ALL) using next generation sequencing technology and to evaluate the value of gene mutations in prognosis stratification.Methods:A case series analysis was made.The clinical data of newly diagnosed pediatric T-ALL patients in the First Affiliated Hospital of Zhengzhou University from January 1, 2019 to February 29, 2024 were analyzed retrospectively.T-ALL gene mutations were analyzed.The relationships of gene mutations with clinical features and induction of responses to therapy were studied.The effects of gene mutations on overall survival (OS) and event-free survival (EFS) were examined by the Kaplan-Meier method and COX regression model.Results:A total of 80 newly diagnosed pediatric T-ALL patients were enrolled in the study, with a male-to-female ratio of 3.4∶1.0 and a median age of 8 (range, 2-17) years.A total of 57 mutations were detected in 74 patients, 46.2% (37/74) of whom showed 3 or more gene mutations.The coexistence of mutated genes was obvious. PTEN mutations were more prevalent in male patients ( P=0.018).Initial leukocyte counts were higher in patients with PTEN mutations ( P=0.038) and lower in patients with JAK3 mutations ( P=0.002).Patients with NOTCH1 mutations had a higher positive rate of fusion genes ( P=0.043).Patients with PTEN mutations had a higher rate of minimal residual disease(MRD) remission after 15/19 d of treatment with induction therapy, respectively ( P=0.013).The rate of MRD remission after 33/46 d of treatment with induction therapy was higher in patients with the FBXW7 mutation ( P=0.004) and lower in patients with JAK3 mutations ( P=0.003).Multifactorial COX regression analysis showed that IL7R mutation and three or more gene mutations were independent risk factors for OS and EFS in T-ALL patients(OS: HR=3.252, 7.357, 95% CI: 1.020-10.372, 1.646-32.882; EFS: HR=3.372, 3.009, 95% CI: 1.234-9.214, 1.174-7.708; all P<0.05). Conclusions:Gene mutations are prevalent in T-ALL children and correlate with clinical manifestations and prognosis.The coexistence of mutated genes is obvious.Pediatric T-ALL patients with IL7R mutations and three or more gene mutations have a poorer prognosis.

Objective:To construct A novel scoring model of immune signatures for colon cancer based on machine learning,which improve the survival prediction and immune therapy.Methods:Screening immune signatures from 1 301 immune-related genes(IRG)by the combined strategy of Lasso+bootstrap+multi Cox to calculate IRG scores of colon cancer patients from TCGA databases,and comprehensive the differences on function,prognostic status and immune therapy between high IRG scores group and IRG scores group.Results:Groups based on IRG scores were significantly different on the prognostic status of colon cancer patients,which were validated by other independent datasets.The IRG scores also could assess the effect of immune therapy of colon cancer.Conclusion:This study provides ideas for immune therapy and researches of colon cancer based on immune genes,and IRG scores can be used to assess the prognosis of colon cancer patients.

Zhuang medicine believes that "toxin deficiency" is a key factor in the onset of primary dysmenorrhea, and the failure of the "three pathways and two pathways" is the direct cause of its onset. The treatment should follow the method of "restoring visceral function". The Zhuang medicine lotus needle cupping and dredging method has strong Zhuang characteristics, and is widely used in the treatment of neuropathic pain and has achieved good therapeutic effects. Based on the theory of "toxin deficiency" in Zhuang medicine, this article discussed the application of lotus needle cupping and dredging method in primary dysmenorrhea, and provided reference for its treatment.

As a newly discovered posttranslational modification (PTM), crotonylation has been identified in histone and nonhistone proteins and has important roles in the regulation of various diseases and biological processes. With the development of high-resolution mass spectrometry approaches, an increasing number of endogenous crotonylation has been detected and identified. The discovery of crotonylation regulatory enzymes paved the way for the study of crotonylation mechanism. In this review, we summarize the biological functions and regulatory mechanism of crotonylation in eukaryotes and introduce the recent progress on crotonylation in malignant tumor.

BACKGROUND: MicroRNA-20a (miR-20a) is dysregulated in many types of malignancies, including human hepatocellular carcinoma (HCC), but its expression level and functional significance in HCC are still disputed. We aimed to study the role of miR-20a-5p in HCC and its downstream molecular mechanisms. METHODS: We used real-time polymerase chain reaction to detect the expression of miR-20a-5p and runt-related transcription factor 3 ( RUNX3 ) in HCC and paraneoplastic tissue, transfected Huh7 and highly metastatic human hepatocellular carcinoma (MHCC97H) cells. A live cell workstation was used to observe the proliferation and migration of transfected cells. The invasiveness of transfected cells was verified by Transwell assay. Cell apoptosis was detected by flow cytometry. The expression levels of proteins after transfection were measured using simple western immunoblot measurements. Gene expression profiles between HCC and normal samples were obtained from The Cancer Genome Atlas. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment results were processed by the database for annotation, visualization and integrated discovery. Potential target genes of miR-20a-5p were predicted to further investigate how miR-20a-5p regulates epithelial-mesenchymal transition (EMT) in HCC. RESULTS: MiR-20a-5p was significantly highly expressed in HCC tissues, and overexpression of miR-20a-5p significantly promoted HCC cell proliferation, migration, and invasion and inhibited apoptosis in vitro. The protein expression of E-cadherin was decreased and that of vimentin was increased after overexpression of miR-20a-5p in HCC cells. We discovered the intersection of genes from miRDB, miR TarBase, and TargetScan, obtained 397 target genes and finally focused on RUNX3. RUNX3 was not only reduced in HCC specimens but also drastically reduced in HCC cells overexpressing miR-20a-5p. RUNX3 expression decreased with elevated miR-20a-5p, which activated downstream EMT signaling and promoted cell proliferation, migration, and invasion. CONCLUSIONS Since RUNX3 is involved in EMT in HCC, as proven by previous research, our findings provide further evidence for a novel regulatory pathway comprising the miR-20a/RUNX3/EMT axis that upregulates EMT signaling and enhances the migration of HCC cells.
Humans ; Carcinoma, Hepatocellular/pathology* ; Epithelial-Mesenchymal Transition/genetics* ; Liver Neoplasms/pathology* ; Gene Expression Regulation, Neoplastic/genetics* ; MicroRNAs/metabolism* ; Cell Movement/genetics* ; Cell Line, Tumor ; Cell Proliferation/genetics* ; Core Binding Factor Alpha 3 Subunit/metabolism*

In order to improve the management level of medicine list of medical institutions in China ，and help medical institutions build a medicine list of medical institutions with reasonable drug use structure ，standardized adjustment procedures ， convenient operation and application and scientific evaluation methods ，so as to meet the needs of clinical rational drug use to the greatest extent ，with the support of the Pharmaceutical Care Professional Committee of the Chinese Pharmaceutical Association ， China-Japan Friendship Hospital and the First Affiliated Hospital of University of Science and Technology of China （Anhui Provincial Hospital ）jointly initiate and complete Guideline for the Evaluation of Medicine List in Chinese Medical Institutions jointly with a number of medical institutions. In strict accordance with the methodological requirements of World Health Organization standard guidelines ，based on the Delphi method ，the guideline formulation working group has constructed the quality evaluation index system and quantitative scoring table of medicine list management in medical institutions from the 5 dimensions of organization and management ，structure，adjustment，application and e valuation of the list. It is used to help medical institutions evaluate the quality of their medicine list management ，so asto play a positive role in the fine management of medicine list in medical institutions.

Objective To analyze the expression of CXC chemokines in glioblastoma (GBM), and investigate their prognostic value and potential roles as therapeutic targets. Methods Differential expression and prognostic value of CXC chemokines in GBM were obtained in GEPIA. The String database was used to predict neighbor genes and construct the protein to protein interaction (PPI) network. GO analysis and KEGG pathway enrichment analysis were executed by DAVID tools. TRRUST and LinkedOmics were used to predict transcription factor and kinase targets for CXC chemokines. Finally, we discussed the correlation of immune cell infiltration and tumor purity with differential expression of CXC chemokines in GBM. Results CXC2/3/8/9/10/11/16 expression was significantly up-regulated in GBM, and CXC3/8 were significantly associated with the poor prognosis of GBM patients. Differentially expressed chemokines and their adjacent genes are mainly enriched in the immune regulatory and apoptosis functions and pathways. There was correlation between chemokines expression and infiltration of six immune cells. Conclusion CXCL3/8 could be the potential prognostic markers for GBM patients. CXC chemokines are related to GBM immunity.