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.

Liver fibrosis is a significant health burden,marked by the consistent deposition of collagen.Unfortunately,the currently available treatment approaches for this condition are far from optimal.Lysyl oxidase-like protein 2(LOXL2)secreted by hepatic stellate cells(HSCs)is a crucial player in the cross-linking of matrix collagen and is a significant target for treating liver fibrosis.Mesenchymal stem cell-derived small extracellular vesicles(MSC-sEVs)have been proposed as a potential treatment option for chronic liver disorders.Previous studies have found that MSC-sEV can be used for microRNA delivery into target cells or tissues.It is currently unclear whether microRNA-4465(miR-4465)can target LOXL2 and inhibit HSC activation.Additionally,it is uncertain whether MSC-sEV can be utilized as a gene therapy vector to carry miR-4465 and effectively inhibit the progression of liver fibrosis.This study explored the effect of miR-4465-modified MSC-sEV(MSC-sEVmiR-4465)on LOXL2 expression and liver fibrosis development.The results showed that miR-4465 can bind specifically to the promoter of the LOXL2 gene in HSC.Moreover,MSC-sEVmiR-4465 inhibited HSC activation and collagen expression by downregulating LOXL2 expression in vitro.MSC-sEVmiR-4465 injection could reduce HSC activation and collagen deposition in the CCl4-induced mouse model.MSC-sEVmiR-4465 mediating via LOXL2 also hindered the migration and invasion of HepG2 cells.In conclusion,we found that MSC-sEV can deliver miR-4465 into HSC to alleviate liver fibrosis via altering LOXL2,which might provide a promising therapeutic strategy for liver diseases.

Objective:To evaluate the effect of low-dose recombinant interleukin-2(rIL-2)therapy on immunocyte subsets and its side effects in children with solid tumor.Methods:A total of 22 children(11 males and 11 females)with solid tumor in our department from December 2012 to November 2017 were selected,with a median age of 9(3-16)years old when starting IL-2 therapy.ALL surgeries and chemotherapy of children had been completed before low-dose rIL-2 therapy,and 17 cases achieved complete remission(CR)and 5 cases achieved partial remission(PR).A low-dose rIL-2 therapy was given 1 month after chemotherapy for 1 year:4 × 105 IU/(m2·d),s.c.for every other day,3 times per week.The immunocyte subsets were detected every 3 months until the end of treatment,meanwhile,disease condition and therapy-related side effects were followed up.Results:After low-dose rIL-2 therapy in 22 children,the absolute values of CD3+T cells,CD3-CD56+natural killer cells,CD3+CD4+helper T cells(Th)and CD3+CD8+cytotoxic T cells were up-regulated remarkably,as well as Th/suppressor T cells(all P＜0.05).While,there were no significant differences in absolute value and proportion of CD4+CD25+CD127-Treg cells during therapy.Among the 17 children who achieved CR before rIL-2 therapy,14 cases continued to maintain CR after therapy,while 3 cases relapsed,and with 2 died after treatment abandonment.The 5 children who achieved PR before low-dose rIL-2 therapy were evaluated CR by PET/CT scan after treatment.In the early stage of low-dose rIL-2 therapy,1 child developed skin rashes at the injection sites,and 2 children ran a slight to mild transient fever.Their symptoms disappeared without any organ damage after symptomatic treatment.Conclusion:Low-dose rIL-2 therapy has good drug tolerance,and changes the distribution of anti-tumor immune-cell subgroup in peripheral blood of children with solid tumor remarkably without up-regulation of absolute value and ratio of Treg cells.

Objective To evaluate the clinical efficacy of navel application of Jianpi Hewei Adhesive Plaster combined with oral use of modified Sini Hewei Anshen Decoction in treating diabetic gastroparesis(DGP)accompanied by anxiety of liver-stomach disharmony type in type 2 diabetes patients.Methods One hundred patients with DGP accompanied by anxiety of liver-stomach disharmony type were randomly divided into a treatment group and a control group,with 50 patients in each group.The control group was given oral use of Mosapride Citrate Tablets orally,and the treatment group was given navel application of Jianpi Hewei Adhesive Plaster combined with oral use of modified Sini Hewei Anshen Decoction.The course of treatment for the two groups covered 4 weeks.The two groups were observed in the changes of the traditional Chinese medicine(TCM)syndrome scores,Gastroparesis Cardinal Symptom Index(GCSI)scores,Hamilton Anxiety Scale(HAMA)scores,gastric emptying time,and levels of fasting blood glucose(FBG),2-hour postprandial blood glucose(2hPG),glycated hemoglobin(HbA1c),plasma motilin(MOT),gastrin(GAS),and serum tumor necrosis factor alpha(TNF-α)and interleukin 6(IL-6)before and after the treatment.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)During the trial,4 patients in the treatment group and 3 patients in the control group fell off,and eventually a total of 93 patients were included for the efficacy statistics,including 46 patients in the treatment group and 47 patients in the control group.(2)After 4 weeks of treatment,the total effective rate of the treatment group was 95.65%(44/46)and that of the control group was 76.60%(36/47).The intergroup comparison(tested by chi-square test)showed that the therapeutic effect of the treatment group was significantly superior to that of the control group(P＜0.01).(3)After treatment,the TCM syndrome scores(including epigastric and abdominal congestion,depression or irritability,and poor appetite)and GCSI scores in the two groups were decreased compared with those before treatment(P＜0.05)and the gastric emptying time was shortened compared with that before treatment(P＜0.05),and the effect of the treatment group on decreasing TCM syndrome scores and GCSI scores and on shortening the gastric emptying time were significantly superior to that of the control group(P＜0.01).(4)After treatment,the plasma MOT and GAS levels of the two groups were increased compared with those before treatment(P＜0.05),and the increase in the treatment group was significantly superior to that in the control group(P＜0.01).(5)After treatment,the levels of glucose metabolism indicators of FBG,2hPG,and HbA1c in the two groups were decreased compared with those before treatment(P＜0.05),but the differences of all glucose metabolism indicators between the two groups after treatment were not statistically significant(P＞0.05).(6)After treatment,the serum TNF-α and IL-6 levels in the two groups were decreased compared with those before treatment(P＜0.05),and the decrease in the treatment group was significantly superior to that in the control group(P＜0.05).(7)After treatment,the total HAMA scores and the scores of mental anxiety factor and somatic anxiety factor of HAMA in the two groups were decreased compared with those before treatment(P＜0.05),and the effect on lowering the scores in the treatment group was significantly superior to that in the control group(P＜0.05).(8)During the treatment period,no significant adverse reactions occurred in the two groups of patients,which has high safety.Conclusion Navel application of Jianpi Hewei Adhesive Plaster combined with oral use of modified Sini Hewei Anshen Decoction exerts certain efficacy in treating DGP accompanied by anxiety of liver-stomach disharmony type.The therapy is effective on relieving clinical symptoms,enhancing gastric motility,inhibiting inflammatory response,and improving anxiety emotion and the quality of life of the patients.

Objective To observe the clinical efficacy of Yiqi Yangyin Jiangtang Prescription(mainly composed of Astragali Radix,Rehmanniae Radix,Imperatae Rhizoma,Ophiopogonis Radix,and Puerariae Lobatae Radix)combined with acupoint injection in the treatment of newly-diagnosed type 2 diabetes mellitus(T2DM).Methods One hundred patients with newly-diagnosed T2DM of qi-yin deficiency complicated with blood stasis type were randomly divided into a treatment group and a control group,with 50 patients in each group.The control group was given oral use of Metformin Hydrochloride Tablets,and the treatment group was given the granules of Yiqi Yangyin Jiangtang Prescription orally combined with acupoint injection at unilateral points of Zusanli(ST36),Shenshu(BL23)and Qihai(CV6)on the basis of treatment for the control group.The course of treatment lasted for 4 weeks.Before and after the treatment,the two groups were observed in the changes of traditional Chinese medicine(TCM)syndrome scores,fasting plasma glucose(FPG),2-hour postprandial blood glucose(2hPG),glycated hemoglobin(HbA1c),total cholesterol(TC),triglyceride(TG),and serum levels of inflammatory factors of interleukin 6(IL-6),C-reactive protein(CRP),tumor necrosis factor α(TNF-α),as well as the hemorheology indicators of whole blood low-shear viscosity and whole blood high-shear viscosity.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)During the trial,5 cases fell off from the treatment group and 4 cases fell off from the control group,and a total of 91 patients were eventually included in the efficacy statistics,of which 45 cases were in the treatment group and 46 cases were in the control group.(2)After 4 weeks of treatment,the total effective rate of the treatment group was 93.33%(42/45),and that of the control group was 71.74%(33/46).The intergroup comparison(tested by chi-square test)showed that the therapeutic effect of the treatment group was significantly superior to that of the control group(P＜0.01).(3)After treatment,the scores of TCM symptoms of dry mouth and throat,frequent nocturia,shortness of breath and fatigue,hot flushes and night sweating as well as the total TCM syndrome scores in the two groups were significantly lower than those before the treatment(P＜0.05),and the reduction of the scores in the treatment group was significantly superior to that of the control group(P＜0.01).(4)After treatment,the levels of blood glucose and lipid indicators of FPG,2hPG,HbA1c,TC and TG of patients in the two groups were decreased compared with those before treatment(P＜0.05),and the decrease in the treatment group was significantly superior to that in the control group(P＜0.05 or P＜0.01).(5)After treatment,the serum levels of inflammatory factors of IL-6,CRP,and TNF-α in the two groups were all lower than those before treatment(P＜0.01),and the reduction in the treatment group was significantly superior to that in the control group(P＜0.01).(6)After treatment,the levels of hemorheology indicators such as whole blood low-shear viscosity and high-shear viscosity in the two groups were all lower than those before treatment(P＜0.05),and the reduction in the treatment group was significantly superior to that in the control group(P＜0.05).(7)The incidence of adverse reactions in the treatment group was 8.89%(4/45),which was significantly lower than that of the control group(21.74%,10/46),and the difference was statistically significant(P＜0.01).Conclusion Yiqi Yangyin Jiangtang Prescription combined with acupoint injection exerts certain effect in treating patients with newly-diagnosed T2DM of qi-yin deficiency complicated with blood stasis syndrome type.The combined therapy can effectively alleviate the early clinical manifestations,decrease the levels of blood glucose,blood lipids,and inflammatory factors,and improve the hematological indicators and the quality of life of the patients.

Objective:To evaluate the reliability and validity of the Chinese version of HEMO-FISS-QoL(HF-QoL) questionnaire (HF-QoL-C) in the Chinese population with hemorrhoids.Methods:From November 2021 to November 2022, a self-constructed general information questionnaire, HF-QoL-C, and the 36-item short form health survey (SF-36), Goligher classification, and Giordano severity of hemorrhoid symptom questionnaire (GSQ) were used to conduct a questionnaire survey on 760 hemorrhoid patients in the anorectal department of six hospitals. The data was analyzed for reliability and validity using SPSS 21.0 and AMOS 26.0 software.Results:The Cronbach's α coefficient of HF-QoL-C and its dimension ranged from 0.831 to 0.960, and the split coefficient was 0.832-0.915. Four common factors were extracted through principal component exploratory factor analysis. Confirmatory factor analysis indicated acceptable structural validity( χ2/ df=8.152, RSMEA=0.097, CFI=0.881, IFI=0.881, NFI=0.867). HF-QoL-C was correlated with SF36 and GSQ( r=-0.694, 0.501, both P<0.01). There were differences in the total score and dimensional scores of HF-QoL-C between surgical and drug treated patients, different grades of Goligher classification for hemorrhoidal disease, and different ranges of hemorrhoid prolapse (all P<0.001). No ceiling effect was found in the total score and the scores of each dimension(0.3%-2.0%). There was a floor effect in both psychological function and sexual activity dimensions (16.7%, 35.1%). Conclusion:HF-QoL-C has good reliability and validity, which can be used to measure the quality of life of Chinese hemorrhoid patients.

Objective:To further improve the understanding of paroxysmal nocturnal hemoglobinuria (PNH), we retrospectively analyzed and summarized the clinical characteristics, treatment status, and survival status of patients with PNH in Zhejiang Province.Methods:This study included 289 patients with PNH who visited 20 hospitals in Zhejiang Province. Their clinical characteristics, comorbidity, laboratory test results, and medications were analyzed and summarized.Results:Among the 289 patients with PNH, 148 males and 141 females, with a median onset age of 45 (16-87) years and a peak onset age of 20-49 years (57.8% ). The median lactic dehydrogenase (LDH) level was 1 142 (604-1 925) U/L. Classified by type, 70.9% (166/234) were classical, 24.4% (57/234) were PNH/bone marrow failure (BMF), and 4.7% (11/234) were subclinical. The main clinical manifestations included fatigue or weakness (80.8%, 235/289), dizziness (73.4%, 212/289), darkened urine color (66.2%, 179/272), and jaundice (46.2%, 126/270). Common comorbidities were hemoglobinuria (58.7% ), renal dysfunction (17.6% ), and thrombosis (15.0% ). Moreover, 82.3% of the patients received glucocorticoid therapy, 70.9% required blood transfusion, 30.7% used immunosuppressive agents, 13.8% received anticoagulant therapy, and 6.3% received allogeneic hematopoietic stem cell transplantation. The 10-year overall survival (OS) rate was 84.4% (95% CI 78.0% -91.3% ) . Conclusion:Patients with PNH are more common in young and middle-aged people, with a similar incidence rate between men and women. Common clinical manifestations include fatigue, hemoglobinuria, jaundice, renal dysfunction, and recurrent thrombosis. The 10-year OS of this group is similar to reports from other centers in China.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective To investigate the distribution and antimicrobial resistance profiles of the common pathogens isolated from urine from 2015 to 2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods The bacterial strains were isolated from urine and identified routinely in 51 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Antimicrobial susceptibility was determined by Kirby-Bauer method,automatic microbiological analysis system and E-test according to the unified protocol.Results A total of 261 893 nonduplicate strains were isolated from urine specimen from 2015 to 2021,of which gram-positive bacteria accounted for 23.8％(62 219/261 893),and gram-negative bacteria 76.2％(199 674/261 893).The most common species were E.coli(46.7％),E.faecium(10.4％),K.pneumoniae(9.8％),E.faecalis(8.7％),P.mirabilis(3.5％),P.aeruginosa(3.4％),SS.agalactiae(2.6％),and E.cloacae(2.1％).The strains were more frequently isolated from inpatients versus outpatients and emergency patients,from females versus males,and from adults versus children.The prevalence of ESBLs-producing strains in E.coli,K.pneumoniae and P.mirabilis was 53.2％,52.8％and 37.0％,respectively.The prevalence of carbapenem-resistant strains in E.coli,K.pneumoniae,P.aeruginosa and A.baumannii was 1.7％,18.5％,16.4％,and 40.3％,respectively.Lower than 10％of the E.faecalis isolates were resistant to ampicillin,nitrofurantoin,linezolid,vancomycin,teicoplanin and fosfomycin.More than 90％of the E.faecium isolates were ressitant to ampicillin,levofloxacin and erythromycin.The percentage of strains resistant to vancomycin,linezolid or teicoplanin was＜2％.The E.coli,K.pneumoniae,P.aeruginosa and A.baumannii strains isolated from ICU inpatients showed significantly higher resistance rates than the corresponding strains isolated from outpatients and non-ICU inpatients.Conclusions E.coli,Enterococcus and K.pneumoniae are the most common pathogens in urinary tract infection.The bacterial species and antimicrobial resistance of urinary isolates vary with different populations.More attention should be paid to antimicrobial resistance surveillance and reduce the irrational use of antimicrobial agents.

Objective To understand the distribution and changing resistance profiles of clinical isolates of Enterococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Enterococcus according to the unified protocol of CHINET program by automated systems,Kirby-Bauer method,or E-test strip.The results were interpreted according to the Clinical & Laboratory Standards Institute(CLSI)breakpoints in 2021.WHONET 5.6 software was used for statistical analysis.Results A total of 124 565 strains of Enterococcus were isolated during the 7-year period,mainly including Enterococcus faecalis(50.7％)and Enterococcus faecalis(41.5％).The strains were mainly isolated from urinary tract specimens(46.9％±2.6％),and primarily from the patients in the department of internal medicine,surgery and ICU.E.faecium and E.faecalis strains showed low level resistance rate to vancomycin,teicoplanin and linezolid(≤3.6％).The prevalence of vancomycin-resistant E.faecalis and E.faecium was 0.1％and 1.3％,respectively.The prevalence of linezolid-resistant E.faecalis increased from 0.7％in 2015 to 3.4％in 2021,while the prevalence of linezolid-resistant E.faecium was 0.3％.Conclusions The clinical isolates of Enterococcus were still highly susceptible to vancomycin,teicoplanin,and linezolid,evidenced by a low resistance rate.However,the prevalence of linezolid-resistant E.faecalis was increasing during the 7-year period.It is necessary to strengthen antimicrobial resistance surveillance to effectively identify the emergence of antibiotic-resistant bacteria and curb the spread of resistant pathogens.