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 explore the association between serum γ-aminobutyric acid ( GABA) levels and the risk of developing type 2 diabetes( T2DM) ． Methods : 187 cases of T2DM patients attending the hospital were selected as the T2DM group，and 187 cases of non-T2DM population attending the same period of time were selected as the control group according to age ( ± 3 years) and gender 1 ∶ 1．On-site questionnaires and physical examination were conducted for the study subjects，and serum levels of GABA，Malondialdehyde ( MDA) and activities of superoxide dismutase ( SOD) and Glutathione peroxidase ( GSH-Px) were detected by using ELISA kits．The differences in the levels of GABA and oxidative stress indicators ( SOD，GSH-Px，MDA) between the two groups were compared， and the correlation between GABA and oxidative stress indicators was analyzed by Spearman's method; GABA and oxidative stress indicators were divided into three groups according to their control quartiles，respectively ［low level group ( Q1: ＜P25) ，medium level group ( Q2: P25 －P75) ，high level group ( Q3: ＞P75) ］，and conditional logistic regression was applied to analyze the relationship between GABA，oxidative stress indicators and the risk of develo- ping T2DM; the dose-response relationship between GABA，oxidative stress indicators and the risk of developing T2DM was analyzed by using restricted cubic spline ( RCS) ． Results : T2DM group ( P＜0. 05) ．Spearman's correlation analysis showed that GABA level was positively correlated with SOD and GSH-Px activities and negatively correlated with MDA level ( P＜0. 001) ．Conditional logistic regression analysis showed that medium levels of SOD and GSH-Px as well as medium and high levels of GABA were protective factors for T2DM compared with low levels in each group ( P＜0. 05) ．RCS results showed that a negative dose-response relationship between GABA，GSH-Px and the risk of developing T2DM，and SOD showed a trend of decreasing and then increasing the risk of developing T2DM ( P＜0. 05) ． Conclusion Serum GABA levels have been associated with the risk of developing T2DM．As serum GABA levels increase，the risk of developing T2DM may decrease．

Objective To investigate the effect of Nutlin-3a,a mouse double minute 2 homolog(MDM2)inhibitor,on lipid metabolism of mouse adipose.Methods High-fat diet-induced obesity(DIO)C57BL/6J mice were randomly divided into a control group injected with DMSO and an experimental group injected with Nutlin-3a.Then we conducted glucose tolerance(GTT)and insulin tolerance(ITT)tests.The epididymal white adipose tissue(eWAT),inguinal white adipose tissue(iWAT)and brown adipose tissue(BAT)of animals were isolated and microscopy of WATs with hematoxylin-eosin(HE)staining was performed to observe the morphological changes of adipocytes.The expression of lipid metabolism related gene cell death-inducing DFF45-like effector C(CIDEC)in eWAT were detected by qPCR and Western blot.Results Compared with the control group,Nutlin-3a was found to promote the body weight(P＜0.001),but no effect on glucose tolerance and insulin sensitivity in DIO mice.Nutlin-3a treatment decreased the size of adipocytes and fat deposition in adipose tissue and downregulated the mRNA and protein levels of CIDEC in eWAT.Conclusions Nutlin-3a inhibits the formation of lipid droplets by downregulating expression of CIDEC in white adipose tissue.

Objective To study the effect of IL-22 on the colonic barrier and its relationship with Nrf2 pathway in liver fibrosis mice.Methods The mice were divided into four groups:the control group(CON group),the model group(MOD group),the interleukin-22 group(IL-22 group),and the IL-22+ML385 group(ML385,an inhibitor of Nrf2),with 10 mice in each group,and the modeling cycle was 8 weeks.Liquid feed containing alcohol and carbon tetrachloride olive oil were given intraperitoneally in all groups except the CON group;IL-22 was given on top of this in the IL-22 group;and ML385 was injected intraperitoneally in the IL-22+ML385 group one hour before IL-22 treatment.At the end of modeling,the livers were stained with HE and Masson staining to clarify whether fibrosis occurred in the mice;the feces were collected to detect the cocci to bacillus ratio and observe the growth of intestinal flora;the colons were stained with HE staining,immunofluorescence and immunohistochemistry,and analyzed for the expression of tight junction proteins ZO-1,Occludin,and the Nrf2 pathway proteins(Nrf2,HO-1,and NQO1).The expression of these proteins was analyzed by immunohistochemistry.Results Compared with the CON group,mice in the MOD group showed significant fibrosis in the liver tissue,inflammatory cell infiltration in the colon tissue,and decreased expression of tight junction proteins(P<0.05).No overgrowth of various pathogenic bacteria was seen in fecal media.And there was no significant difference in the bulb-to-bar ratio.Compared with the MOD group,both liver and colon histopathologic damage were reduced in the IL-22 group,and tight junction protein expression was elevated,in addition,the expression levels of Nrf2,NQO1,and HO-1 were also elevated(P<0.05),whereas there was no significant change in the IL-22+ML385 group.Conclusion IL-22 improved the colonic barrier function in liver fibrosis mice,and the mechanism was related to the activation of Nrf2 anti-oxidative stress pathway.

A 72-year-old female patient was admitted to the emergency department of Qintang District People′s Hospital of Guigang City in August 2023 due to chills and fever, abdominal distension and pain, diarrhea, cough and shortness of breath for 1 day. She had a history of chronic obstructive and pulmonary heart disease, stage Ⅲ hypertension, and ceftazidime allergy. Clinical diagnosis of acute bacterial infection of chronic obstructive pneumonia was made and levofloxacin combined with piperacillin/tazobactam were given as symptomatic treatment. The blood culture reported Campylobacter fetus after four days, and the patient was cured and discharged after seven days with negative blood culture. The morphology and mass spectrometry identification of the strain were consistent with the definition of Campylobacter fetus. Whole genome sequencing predicted the multi-site sequence type as Campylobacter fetus subsp. fetus( Cff) ST20, carrying the tetracycline resistance gene tet (O/M/O), 18 flagella genes (including rpoN gene from Campylobacter jejuni. these genes were not found in the other two Campylobacter fetus subspecies), and six virulence genes (including like-typhoidal toxin and typhoid toxin genes). The pathogen has the ecological characteristics of parasitic farmed animal colonization and the biological characteristics of high mobility and virulence. These attributes facilitated its entry into the bloodstream via the fecal-oral route, leading to invasive infections.

ObjectiveTo investigate the expression and role of response gene to complement 32 （RGC32） in liver regeneration after partial hepatectomy （PH）. MethodsA total of 42 male C57BL/6 mice， aged 10 weeks， were randomly divided into control group， postoperative day 1 group （1－d group）， postoperative day 2 group （2－d group）， postoperative day 4 group （4－d group）， postoperative day 6 group （6－d group）， postoperative day 8 group （8－d group）， and postoperative day 10 group （10－d group）， with 6 mice in each group. In the control group， the complete liver of the mice was resected for weighing and photography as the normal control group （sham group）； further， the left and middle lobes of the liver were resected for weighing and photography as the surgical control group （0－day group）； the sham group and the 0－day group shared the same group of mice. After successful modeling by PH， the mice were sacrificed on days 1， 2， 4， 6， 8， and 10 after surgery， and the liver was collected to measure the change in size. HE staining and oil red O staining were used to evaluate liver histomorphological changes； serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were measured to evaluate the changes in liver function； immunohistochemical staining was used to measure the expression of proliferating cell nuclear antigen （PCNA） and Ki67 and analyze the change in cell proliferation during liver regeneration； quantitatie real－time PCR and immunohistochemical staining were uused to measure the expression and subcellular distribution of RGC32 during liver regeneration； EdU cell proliferation assay was used to analyze the effect of RGC32 overexpression or knocknout on hepatocyte proliferation in L02 cells. For continuous data， comparison between multiple groups was made by analysis of variance， and further pairwise comparisons were conducted using the LSD－t test. The independent samples t－test was used for comparison of continuous data between two groups. A Pearson correlation analysis was performed. ResultsThe liver gradually enlarged after PH， and the liver/body weight ratio rose to the peak from days 0 to 6， with significant differences between different time points （all P<0.05）， while there was no significant change in liver size from days 6 to 10. The number of liver lipid droplets significantly increased after PH surgery and gradually decreased with liver regeneration， with a significant difference between the portal vein region and the central vein region （all P<0.05）. Compared with the sham group， the 1d group had significant increases in the serum levels of ALT and AST （all P<0.05）， which gradually returned to the levels of the sham group on day 6 and day 2 after surgery， respectively （P>0.05）. Immunohistochemical staining showed that there were rapid increases in the numbers of PCNA－ and Ki67－positive liver parenchymal cells after PH surgery， with the highest numbers of 86±5 and 89±5， respectively， on day 2， which then gradually decreased； however， there were gradual increases in the numbers of PCNA－ and Ki67－positive nonparenchymal cells， with the peak numbers of 34±5 and 25±3， respectively， on day 6， which then gradually decreased. The total expression of RGC32 increased to the highest level on day 2 after PH surgery and then gradually decreased， and the changing trend of RGC32 expression in cytoplasm was consistent with that of total RGC32 expression； however， the expression of RGC32 in nucleus decreased to the lowest level on day 2 after PH surgery and then increased gradually. The correlation analysis showed that the expression of RGC32 in nucleus was negatively correlated with the proliferation of liver parenchymal cells （R²=0.308 3， P=0.016 7）， and the expression of RGC32 in cytoplasm was positively correlated with the proliferation of liver parenchymal cells （R²=0.808 6， P<0.000 1）. Cell experiments showed that compared with the control group， the EdU－positive rate was reduced by 15.6% after RGC32 overexpression （P<0.01） and was increased by 19.2% after RGC32 knockdown （P<0.01）. ConclusionLiver parenchymal cells and nonparenchymal cells show asynchronous proliferation and participate in liver regeneration together. During liver regeneration after hepatectomy， there are differences in the expression of RGC32 between nucleus and cytoplasm， and RGC32 in nucleus may inhibit hepatocyte proliferation.

Objective To investigate the effects of the rhein on the mitochondria fission and epithelial-mesenchymal transition(EMT)of breast cancer cells MDA-MB-231.Methods Human breast cancer cells were intervened with rhein,and the cells were divided into control group(0 μmol·L-1),low dose rhein group(100 μmol·L-1),and high dose rhein group(200 μmol·L-1).The proliferation activity of the cells was detected by CCK-8,and migrations was detected by Scratch-healing migration assay.The morphology and distribution of mitochondria were detected by transmission electron microscope,and the expression levels of Dynamin-related protein 1(Drp1),mitofusin2(Mfn2),E-cadherin,Vimentin proteins were detected by Western blot.Results Compared with control group,Rhein significantly reduced the protein expression of Drp1、Vimentin(P<0.05),and increased E-cadherin and Mfn2,thus down-regulating mitochondria fission,inhibiting cell proliferation and migration.High dose Rhein was better than low dose.Conclusion Rhein can inhibit the proliferation and migration of breast cancer cells by reducing the expression of Drp1,Vimentin and up-regulating Mfn2,E-cadherin proteins.

Objective:To investigate the differences in understanding and diagnosis of polycystic ovary syn-drome(PCOS)among obstetricians and gynecologists with different clinical experiences,in order to promote com-munication and improve medical quality.Methods:This was a multi-center cross-sectional survey.Information on participants'basic information and their knowledge of PCOS comorbidities and treatment management was col-lected online.Physicians were divided into two groups according to their experience:experienced(>200 consulta-tions/year)and inexperienced(≤200 consultations/year).The differences in the diagnosis and treatment of PCOS among different groups were compared.Logistic regression analysis was used to explore other factors that might influence the diagnosis and treatment of PCOS.Results:1689 questionnaires were finally included,among which 95 were experienced and 1594 were inexperienced.①In the comparison of basic conditions,the proportion of experienced persons in tertiary hospitals and reproductive endocrinology specialties was higher than that of in-experienced persons(P<0.05);The percentage of experienced persons who predicted patients with comorbid insulin resistance(proportion>30%)and predicted comorbid overweight/obesity(proportion 30%-50%)was higher than that of less experienced persons(P<0.05).②There was no significant difference in the evaluation of PCOS and its complications among different groups(P>0.05).Logistic regression suggested that different expe-riencers did not significantly affect the assessment of androgens,OGTT and lipid testing(P>0.05).③There was no statistical significance in the choice of treatment for those with no fertility need(P>0.05).For those with fertili-ty needs,metformin and letrozole were more actively selected by experienced group than inexperience(P<0.05).In terms of weight loss,experienced participants were more active in using metformin(P<0.05)and were more likely to choose1.0 or1.5 g/d(P<0.05)than those with inexperience.Conclusions:There was no signifi-cant difference in PCOS assessment among participants with different experience,but in treatment,experienced participants were better able to take into account the multi-system abnormalities brought by PCOS,and at the same time,they give more comprehensive and accurate treatment opinions on patients with or without fertility needs.

Objective:To study the effect of different hemostasis methods on postoperative pain and sex hormone levels in patients undergoing laparoscopic ovarian cystectomy.Methods:A total of 118 patients with ovarian cysts admitted to our hospital from Jun. 2018.6 to Aug. 2020 were collected and grouped by digital table method into electrocoagulation hemostasis group (59 cases, electrocoagulation hemostasis) and suture hemostasis group (59 cases, suture hemostasis). Pain at time points, serum inflammatory factors and sex hormone levels in the two groups were measured, and the incidence of complications was counted 12 weeks after surgery.Results:The VAS scores of suture hemostasis group at 6, 12 and 24 h after operation (3.33±0.93, 3.63±1.02, 3.01±0.94) were significantly lower than those of the electrocoagulation hemostasis group (4.16±1.05, 4.61±1.17, 3.72±1.05) ; there was no significant difference in serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels between the preoperative suture hemostasis group and the electrocoagulation hemostasis group. The serum levels of IL-6 and TNF-α in the group (37.64±4.82ng/L, 39.67±4.71ng/L) were lower than those in the electrocoagulation hemostasis group (45.96±5.25ng/L, 48.96±5.14ng/L) ( P<0.05) .) ; there was no significant difference in serum follicle-stimulating hormone (FSH), estradiol (E 2) or luteinizing hormone (LH) levels between preoperative electrocoagulation hemostasis group and suture hemostasis group ( P>0.05) ; There was no significant difference in the three indexes in the suture hemostasis group 3 months after operation compared with those before treatment ( P>0.05). The serum FSH and LH [ (6.59±0.91) mIU/ml, (5.24±0.77) mIU/ml] in the suture hemostasis group were lower than those in the electrocoagulation hemostasis group [ (7.39±1.02) mIU/m, (5.97±0.89) mIU/m], E 2 in suture hemostasis group [ (51.08±6.09) pg/ml] was higher than that in electrocoagulation hemostasis group [ (46.88±5.59) pg/ml] ( P<0.05). In terms of the complication rate at 3 months after operation, the suture hemostasis group (32.20%) was significantly lower than electrocoagulation hemostasis (13.56%) ( P<0.05). After 1 year of follow-up, the pregnancy success rate of the suture hemostasis group (72.88%) was significantly higher than that of the electrocoagulation hemostasis group (52.54%) ( P<0.05). There was no significant difference in pregnancy outcomes ( P>0.05) . Conclusions:Suture hemostasis in patients undergoing laparoscopic ovarian cystectomy is beneficial to relieve postoperative pain, improve postoperative inflammatory response, protect their ovarian function, avoid complications such as abnormal ovulation and excessive menstrual flow, and improve the success rate of pregnancy. The overall application effect is better than electrocoagulation hemostasis.