T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Objective To investigate the characteristics of epitope distribution on HLA class Ⅰ antigen in the regular platelet donors from Nanjing area and establish the HLA epitope database for regular platelet donors.Methods High-resolution HLA typing was per-formed using Sanger method for the blood samples from 649 regular platelet donors in Nanjing area.The polymorphism of HLA antigen epitopes corresponding to the high-resolution HLA typing results was analyzed using the HLA Eplet Registry website.The frequencies of allele frequencies,HLA haplotype,and HLA antigen epitope were calculated by using the direct counting method.Results Among the 649 regular platelet donors,38 HLA-A alleles were detected,corresponding to 36 HLA-A epitopes,and the higher frequencies were 79GT,144K and 138MI.Seventy-three HLA-B alleles were detected corresponding to 35 HLA-B epitopes,and the higher frequencies were 131S,69TNT,and 80N.Sixty-four HLA class Ⅰ antigen epitopes were detected,in which the higher frequencies were 79GT,131S,and 144K.Conclusions The distribution of HLA antigen epitopes in the regular platelet donors of Nanjing area exhibited u-nique polymorphic characteristics.The epitope matching strategies should be established based on the distribution characteristics of HLA antigen epitopes,which may expand the range of available donors and reduce the incidence of platelet transfusion refractoriness.

Objective To explore the specific mechanism by which circ_0084043/miR-31-5p regulates high mobility group AT-hook 1(HMGA1)and thus participates in atherosclerosis(AS).Methods Carotid plaque tissues,diseased vascular tissue,and corresponding normal tissue from areas adjacent to the plaques were collected from 49 AS patients between September 2020 and September 2023.Quantitative reverse transcription polymerase chain reaction(qRT-PCR)was used to determine circ_0084043 expression.The proliferation,migration,and invasion of vascular smooth muscle cells(VSMCs)induced by oxidized low-density lipoprotein(ox-LDL)were determined by CCK-8,clone formation,scratch,and Transwell assays.The targeted regulatory relationship among circ_0084043,miR-31-5p,and HMGA1 was verified by bioinformatics and dual luciferase reporter gene assay.An AS mouse model was established,and the pathological lesions in the aorta of AS model mice were observed by oil red O and HE stainings.Biochemical testing was performed to assess blood lipids in venous blood.qRT-PCR was used to determine the expression of miR-31-5p and HMGA1.Immunohistochemistry was performed to assess the expression of HMGA1 and α-smooth muscle actin(α-SMA)in the aorta of the AS model mice.Results In AS patients,the expression levels of circ_0084043 and HMGA1 in carotid plaque tissues and diseased vascular tissues were elevated(P＜0.05),while the expression level of miR-31-5p was decreased(P＜0.05).The expression of circ_0084043 was negatively correlated with the expression of miR-31-5p(r=-0.385 5,P=0.0062).HMGA1 expression was positively correlated with circ_0084043 expression(r=0.3317,P=0.0199),and negatively correlated with miR-31-5p(r=-0.3351,P=0.0186).MiR-31-5p had target binding sites for both circ_0084043 and HMGA1.Compared with the control group,the proliferation,clone formation,migration,and invasion abilities of the sh-NC group,the scramble group,the circ_0084043+miR-31-5p mimics group,the miR-31-5p inhibitor+sh-HMGA 1 group,and the circ_0084043+sh-HMGA1 group increased(P＜0.05).In contrast,the proliferation,clone formation,migration,and invasion abilities of the sh-0084043 group significant decreased compared to those of the sh-NC group(P＜0.05).The proliferation,clone formation,migration,and invasion abilities of the miR-31-5p mimics group and the sh-HMGA1 group decreased compared with those of the scramble group(P＜0.05).Compared with the sh-NC group,sh-0084043 group had decreased aortic lipid plaque and necrotic core areas(P＜0.05).Total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),and the expression levels of HMGA1 mRNA and protein and α-SMA decreased(P＜0.05),while high-density lipoprotein cholesterol(HDL-C)and miR-31-5p expression levels increased(P＜0.05).Conclusion circ_0084043 promotes the proliferation and migration of VSMCs and promotes the progress of AS by inhibiting miR-31-5p and increasing the expression of HMGA1.

Objective: To explore the growth characteristics of rat calvaria by detecting the calvaria of SD rats in different periods. Methods: The calvaria of SD rats at 1 , 4 , 7 , 10 , and 12 weeks from the same littermate were selected (3 rats per week) . Real⁃time PCR and Western blot techniques were used to detect the expression of focal adhesion kinase ( FAK) Ⅳ phosphatidylinositol 3 kinase/protein kinase B ( PI3K/AKT ) signal pathway in the calvaria , and the role of FAK⁃PI3K/AKT in the growth and development of the calvaria was analyzed by correlation. Results: The increase of brain volume and the thickness of calvaria increased synchronously , the expression of FAK was positively correlated with the changes of meridians , and the expression of FAK was positively correlated with the expression of PI3K/AKT. Conclusion The expression of FAK is related to the growth and development of rat skull. FAK plays a role in calvaria by activating PI3K/AKT signal pathway. FAK may be used as a marker of rapid skull growth and development , which provides a basic theoretical basis for the timing of clinical skull defect repair and treatment.

Objective To investigate the influence of limonin on the malignant biological behavior of non-small cell lung cancer (NSCLC) cells by regulating the protein tyrosine kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Methods CCK-8 method was applied to detect the survival rate of A549 cells treated with different concentrations of limonin (0, 5, 10, 25, 50, 75, 100 μmol/L). A549 cells were separated into normal culture (NC) group, low-dose limonin group (treatment with 10 μmol/L limonin for 24 h), medium-dose limonin group (treatment with 25 μmol/L limonin for 24 h), high-dose limonin group (treatment with 50 μmol/L limonin for 24 h), coumermycin A1 group (treatment with 10 μmol/L JAK2 activator coumermycin A1+50 μmol/L limonin for 24 h), and AG490 group (treatment with 10 μmol/L JAK2 inhibitor AG490+50 μmol/L limonin for 24 h). Clone formation assay was applied to detect the clones of each group of cells. Transwell assay was applied to detect cell migration and invasion, and flow cytometry was applied to detect apoptosis. Western blot analysis was applied to detect the protein expression levels of JAK2, p-JAK2, STAT3, p-STAT3, E-cadherin, N-cadherin, and vimentin in each group. Results The viability of A549 cells decreased significantly in a limonin concentration-dependent manner (P < 0.05), with IC₅₀ of 45.16±1.66 μmol/L. Concentrations of 10, 25, and 50 μmol/L were selected for subsequent experiments. The numbers of clones, migration, and invasion of A549 cells and the protein expression levels of IL-6, p-JAK2, p-STAT3, N-cadherin, and vimentin in the low-, medium-, and high-dose limonin groups significantly decreased, compared with those in the NC group, and the apoptosis rate and E-cadherin protein expression significantly increased (P < 0.05). The JAK2 activator coumermycin A1 attenuated the ability of limonin to inhibit the proliferation, migration, invasion, and other malignant biological behavior of A549 cells and attenuated the apoptosis ability. The JAK2 inhibitor AG490 enhanced the ability of limonin to inhibit the proliferation, migration, invasion, and other malignant biological behavior of A549 cells and enhanced the apoptosis ability. Conclusion Limonin can inhibit the malignant biological behavior of NSCLC cells, such as proliferation, migration, and invasion, by inhibiting the JAK2/STAT3 pathway.

Objective:To investigate the role and mechanisms of fibulin-1 in senescence-related calcification of rat vascular smooth muscle cells induced by high-concentrationphosphate treatment.Methods:From September 2020 to September 2021, rat primary vascular smooth muscle cells were extracted from the thoracic aorta and abdominal aorta of 10 male SD rats aged 6 to 8 weeks.Phosphate(2.5 mmol/L Pi)was used to stimulate the calcification of vascular smooth muscle cells(VSMCs)in a model of stress-induced senescence-related calcification.Cellular senescence was assessed by SA-β-gal staining.Cellular calcification was determined by alizarin red staining and quantification of calcium deposition.Phenotypic transformation indexes and the expression of fibulin-1 during the process of calcification were detected by Western blot.The expression of fibulin-1 in primary rat vascular smooth muscle cells was knocked down by siRNA, the expression of pSmad3 was detected by immunofluorescence, and the effects of fibulin-1 on phenotypic transformation indexes of smooth muscle cells were detected by Western blot.The cells were cultured with recombinant fibulin-1 while transforming growth factor beta(TGF-β)inhibitor A83-01 and pSmad3 inhibitor SIS3 were also added.The senescence and calcification indexes of smooth muscle cells were detected by Western blot.Results:In the stress-induced aging model with phosphate stimulation of calcification in rat VSMCs, the expression of fibulin-1 was up-regulated( t=11.20, P<0.01), the expressions of MHC and SM22α was down-regulated( t=7.97, P<0.01; t=10.27, P<0.01), and the expression of osteoblastic phenotype markers OPN and Bmp2 and senescence marker P53 was up-regulated( t=4.79, P<0.01; t=9.56, P<0.01; t=14.07, P<0.01). Knockdown of fibulin-1 attenuated the degree of senescence and calcium deposition in VSMCs( t=12.90, P<0.05)and decreased the expression of OPN, Bmp2 and P53( t=5.92, P<0.05; t=10.15, P<0.01; t=8.28, P<0.01), at the same time, and TGF-β and pSmad3 expression was inhibited( t=12.90, P<0.01; t=7.46, P<0.01). After the addition of TGF-β/ smad3 pathway inhibitors, the stimulatory effect of recombinant fibulin-1 on phenotypic transformation and senescence protein expression inVSMCs was significantly reduced( t=4.52, P<0.01; t=9.82, P<0.01; t=3.85, P<0.05). Conclusions:Fibulin-1 can promote aging-related calcification of vascular smooth muscle cells through the TGF-β/smad3 signaling pathway.

Esophagogastric variceal bleeding (EVB) is a common fatal complication secondary to cirrhotic portal hypertension. Terlipressin can shrink visceral blood vessels, reduce portal pressure, and increase renal perfusion and is mainly used in the treatment of EVB. This article summarizes the mechanism of action and clinical effect of terlipressin in the treatment of EVB in liver cirrhosis and points out that if conditions permit, terlipressin combined with endoscopic variceal ligation should be the preferred treatment method for EVB.

Objective To evaluate the effect of an emollient containing Prinsepia utilis Royle oil extracts and other extracts on clinical symptoms and disease recurrence in children aged 2-12 years with atopic dermatitis (AD) in the remission period.Methods A multicenter,randomized,parallel-group,controlled clinical trial was conducted from December 2017 to September 2018.A total of 297 children aged 2-12 years with moderate AD were enrolled from 5 hospitals in China,and randomly divided into the test group (148 cases) and control group (149 cases).In the acute stage,the two groups were both topically treated with mometasone furoate cream once a day on the skin lesions,and with an emollient containing Prinsepia utilis Royle oil extracts and other extracts twice a day throughout the whole body for 2-4 weeks.The children would be enrolled into the remission stage if their Investigator's Global Assessment (IGA) score was ≤ 1 at following visits.In the remission stage,the test group was only topically treated with the emollient twice a day throughout the whole body,while mometasone furoate cream and the emollient were both withdrawn in the control group.At weeks 4,8 and 12 in the remission stage,the recurrence of AD,eczema area and severity index (EASI),children's dermatology life quality index (CDQOL) and adverse events were evaluated.Statistical analysis was carried out with SAS 9.4 software by using t test for comparison of normally distributed continuous data between two groups,chi-square test for comparison of unordered categorical data,Kaplan-Meier method for analysis of survival rates,Cox regression analysis for evaluating the effect of different therapies on AD recurrence in children in the remission stage,and Logistic regression analysis for analysis of odds ratio (OR) of EASI or CDQOL at week 4 in the remission stage between the test group and control group.Results Of the 297 children with AD,31 breached the clinical trial protocol,and 266 were included in the per protocol set (PPS),including 132 in the test group and 134 in the control group.In the PPS,114 and 106 patients completed the follow-up in the test group and control group respectively,and the recurrence rate was significantly lower in the test group (47,41.23％) than in the control group (84,79.25％;x2 =32.96,P ＜ 0.001).The time to recurrence was significantly longer in the test group(61.99 d ± 2.80 d)than in the control group(39.17 d ± 2.54 d,t =6.03,P ＜ 0.001),and the recurrence risk was significantly lower in the test group than in the control group (Log rank test,x2 =32.02,P ＜ 0.001).After adjustment for age and gender,Cox regression analysis showed that the recurrence risk in the test group was 0.35 times that in the control group (HR =0.35,95％ CI:0.24-0.51,P ＜ 0.01).At week 4 in the remission stage,the EASI score at P50-P75 and P75-P100 in the test group were 0.42,0.25 times that in the control group respectively (95％ CI:0.20-0.86,0.12-0.54 respectively;P =0.02,＜ 0.01respectively).Moreover,the CDQOL score at P75-P100 in the test group was 0.33 times that in the control group (95％ CI:0.17-0.65,P ＜ 0.01).No significant difference in the incidence of adverse events was observed between the two groups (P ＞ 0.05).Conclusion Maintenance treatment with the emollient containing Prinsepia utilis Royle oil extracts and other extracts can markedly reduce the recurrence risk in AD children,improve clinical symptoms,and enhance the quality of life.

Midbrain periaqueductal gray ( PAG) is the midline structure of the brain and plays a crucial role in the regulation of a series of physiological functions, emotions and motivated behaviors. In recent years, with the developments of functional tracer technology, genetic technology and neuroimaging technology, the understandings of physiological and psychological functions of PAG have been expanded. The recent research progresses of PAG in the neural circuits in regulation of behaviors, emotions and the related mechanisms are reviewed.

Objective To analyze the CT and MR imaging characteristics of the subcutaneous and organ lesions of uvenile xanthogranuloma (JXG) in children.Methods The CT and MR images of the head,chest,abdomen and subcutaneous soft tissue of 11 patients (6 females and 5 males,aged 2 months-12 years old,median age 8 months old) with JXG from 2006 to 2018 were collected and retrospectively analyzed.Eight patients underwent CT scan and/or contrast-enhanced CT scan,and 7 patients underwent MRI and/or MRI and contrast-enhancement MRI.Results In 11 cases of JXG,5 cases were classified as simple skin type,involving the skin and deep soft tissue in the right posterior neck,the right frontal and parietal parts of the head,the nose root,and the fat layer and the deep muscle in the extremities.The lesions were the subcutaneous soft tissue nodules or mass showing isodensity on CT or high signal on T2WI.And the other 6 cases were classified as systemic type whose lesions involved one or more than one part except the skin.In the 6 cases,3 cases involved the central nervous system,including the pituitary gland,cerebral hemisphere,cerebellum,brain stem,basal ganglia,thalamus,optic chiasma and spinal cord.The lesions of the pituitary gland were manifested as pituitary enlargement,thickening of the pituitary stalk,and disappearance of high signal on T1WI in the neurohypophysis.The brain parenchyma,the spinal cord and the optic chiasma showed multiple flake or nodular masses,which were iso/low signal on T1WI,low / high signal on T2WI,diffusion restricted,and enhanced markedly.Two cases involved lung tissue,and their lesions showed diffuse or scattered multiple cloudy shadow,reticular opacity,strip and small nodule shadow on chest CT.There was pleural effusion in one case.Two cases involved the livers and 2 cases involved the kidneys,showing multiple nodules with low signal on T2,WI and slight enhancement.One case involving the pancreas showed a low density in the head of the pancreas and slight enhancement on CT.One case involving the greater omentum,chest wall and peritoneum showed thickening of the corresponding tissues on CT.Conclusions Subcutaneous and systemic lesions of JXG show some characteristics on CT and MRI images.The main manifestations are single or multiple nodulars,which are diffusely distributed and vary in size in subcutaneous soft tissue and various organs.The combination of imaging appearances,clinical manifestations and biopsy has important clinical significance for the correct diagnosis and evaluation of JXG.