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:This study aims to construct an evaluation index system suitable for the core competency of Clinical Research Coordinators (CRCs) in Investigator-Initiated Trials (IITs) in China.Methods:This study developed a system framework through the Onion Model, literature research, and expert interviews, utilized the Delphi method to build the index system. and analyzed the weight of each indicator through the Analytic Hierarchy Process (AHP).Results:Four first-level indicators were basic knowledge (0.143), job skills (0.300 8), professional quality (0.483 9), and personality traits (0.072 3). Besides, 18 second-level indicators and 49 third-level indicators were developed through the Delphi method. According to the third round expert′s consultation, the average scores of all indexes were >3.50, the authoritative coefficient was 0.86, the coefficient of variation of each index was <0.30, and Kendall coefficients of concordance were 0.183~0.366 ( P<0.001). The consistency ratios of single-sort were<0.1, and the overall sort of all indexes was 0.043 7, which showed good logical reliability. Conclusions:This evaluation index system for Clinical Research Coordinators is of great scientific sense. It provides IIT-conducting investigators in institutions with a proficient assessment tool to help them find qualified and reliable CRCs.

Although thyroid nodules are less common in children than in adults，some benign nodules enlarge with age，causing symptoms or aesthetic concerns. Preserving thyroid function is crucial due to its role in children's growth and development. Thermal ablation，a safe and minimally invasive technique，offers a new option for treating benign thyroid nodules in children. This article reviewed the indications，methods，outcomes，and complication management of thermal ablation，in order to provide a reference for clinical practice.

Objective To explore the potential causal relationship between opioids and chronic renal failure(CRF)using Mendelian randomization analysis.Methods Screening for single nucleotide polymorphisms(SNPs)strongly associated with opioids and CRF firstly,causality was analyzed by using two-sample Mendelian randomization methods,heterogeneity,horizontal pleiotropy and sensitivity analyses were then performed.Results A total of 41 opioid-related SNPs were screened in this study,inverse variance weighting analysis suggested that opioid use is a risk factor for CRF(OR=1.15,95％CI:1.04-1.27,P＜0.01).The heterogeneity test showed that there was no heterogeneity in the SNPs,and the horizontal multivariate analysis and sensitivity analysis confirmed the robustness of the results.Conclusion Genetically,the study suggests a positive causal association between opioids and CRF,opioid use is a risk factor for CRF.

Objective To explore the potential causal relationship between opioids and chronic renal failure(CRF)using Mendelian randomization analysis.Methods Screening for single nucleotide polymorphisms(SNPs)strongly associated with opioids and CRF firstly,causality was analyzed by using two-sample Mendelian randomization methods,heterogeneity,horizontal pleiotropy and sensitivity analyses were then performed.Results A total of 41 opioid-related SNPs were screened in this study,inverse variance weighting analysis suggested that opioid use is a risk factor for CRF(OR=1.15,95％CI:1.04-1.27,P＜0.01).The heterogeneity test showed that there was no heterogeneity in the SNPs,and the horizontal multivariate analysis and sensitivity analysis confirmed the robustness of the results.Conclusion Genetically,the study suggests a positive causal association between opioids and CRF,opioid use is a risk factor for CRF.

Objective:This study aims to construct an evaluation index system suitable for the core competency of Clinical Research Coordinators (CRCs) in Investigator-Initiated Trials (IITs) in China.Methods:This study developed a system framework through the Onion Model, literature research, and expert interviews, utilized the Delphi method to build the index system. and analyzed the weight of each indicator through the Analytic Hierarchy Process (AHP).Results:Four first-level indicators were basic knowledge (0.143), job skills (0.300 8), professional quality (0.483 9), and personality traits (0.072 3). Besides, 18 second-level indicators and 49 third-level indicators were developed through the Delphi method. According to the third round expert′s consultation, the average scores of all indexes were >3.50, the authoritative coefficient was 0.86, the coefficient of variation of each index was <0.30, and Kendall coefficients of concordance were 0.183~0.366 ( P<0.001). The consistency ratios of single-sort were<0.1, and the overall sort of all indexes was 0.043 7, which showed good logical reliability. Conclusions:This evaluation index system for Clinical Research Coordinators is of great scientific sense. It provides IIT-conducting investigators in institutions with a proficient assessment tool to help them find qualified and reliable CRCs.

Although thyroid nodules are less common in children than in adults，some benign nodules enlarge with age，causing symptoms or aesthetic concerns. Preserving thyroid function is crucial due to its role in children's growth and development. Thermal ablation，a safe and minimally invasive technique，offers a new option for treating benign thyroid nodules in children. This article reviewed the indications，methods，outcomes，and complication management of thermal ablation，in order to provide a reference for clinical practice.

The second edition of the Chinese guideline for the prevention and treatment of anxiety disorders was published in August 2023, 13 years after the first edition. The revision principles for the second edition were maintaining the first edition's framework, and based on that framework, making necessary revisions by incorporating research progress and supplementing the latest research findings from the domestic studies and the overseas literature. Referring to the DSM-5 and ICD-11 classifications of mental disorders and the actual clinical situation in China, the anxiety disorders in the second edition were panic disorder, generalized anxiety disorder, social anxiety disorder, separation anxiety disorder, and anxiety disorder due to another medical condition. The latest epidemiological data on anxiety disorders in China were added. Following the international guidelines, medications not included in the first edition have been added. Chinese traditional medicines, physical therapy, and internet web-based psychotherapy were also supplemented to fit Chinese clinical settings. Based on a literature review, the latest information on the risks of using antidepressants during pregnancy has been added.A whole course of treatment across the acute phase, consolidation phase, and maintenance phase was further addressed as the treatment principle. First-line and second-line recommendations are provided for medication selections.

Objective To investigate the clinical distribution,antimicrobial resistance,carbapenemase resistance genes,virulence genes,capsular serotypes and ST subtypes of carbapenem-resistant Klebsiella pneumoniae(CRKP)strains in intensive care unit of a tertiary hospital in Hunan Province for better management of CRKP infections.Methods CRKP strains were isolated from 8 intensive care units of the First People's Hospital of Chenzhou City from January 2020 to December 2021.The isolates were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and tested by VITEK Compact 2 for antimicrobial susceptibility.Carbapenemase phenotype was detected by modified carbapenem inactivation method(mCIM).The capsular serotypes were determined by wzi sequencing.Carbapenem resistance genes and virulence genes were identified by PCR and Sanger sequencing.The strains were also analyzed by multilocus sequence typing(MLST)in terms of ST subtypes.Results The 75 CRKP strains were mainly isolated from geriatric ICU(28.0％)and neurosurgery ICU(20.0％).Overall,6.7％(5/75)and 16.0％(12/75)of the CRKP strains were resistant to tigecycline and ceftazidime-avibactam,respectively.The CRKP strains(＞96.0％resistant)were highly resistant to carbapenems,cephalosporins,β-lactam/β-lactamase inhibitor combinations,and levofloxacin.PCR and sequencing analysis found blaKPC-2 gene in 61 strains(81.3％),blaNDM-1 gene in 11 strains(14.7％),blaNDM-5 gene in 1 strain(1.3％),and blaOXA-48 gene in 2 strains(2.7％).MLST revealed that ST11(54.7％,41/75),ST1883(13.3％,10/75),and ST307(6.7％,5/75)were the top three ST subtypes.All ST11 and ST1883 CRKP strains harbored blaKPC-2.KL64(38.7％,29/75)and KL47(25.3％,19/75)were the most prevalent capsular serotypes among the 75 CRKP strains.The most common virulence genes among these CRKP strains were rmpA2(48.0％,36/75),iroN(38.7％,23/75)and iucA(37.3％,15/75).Conclusions The CRKP strains isolated from the intensive care units were mainly ST11-KL64 and ST11-KL47 types.Most of the strains harbor blaKPC-2 and virulence gene,and associated with high level antimicrobial resistance.It is urgent to strengthen the monitoring of molecular epidemiological characteristics of CRKP in order to inform individualized and precision treatment of CRKP infections.

Objective To investigate the changes in serum levels of claudin-5 and Apelin-13 in patients with depression and their relationship with disease progression and sleep disorders.Methods A total of 128 patients with depression admitted to our hospital from June 2021 to July 2023 were selected as the study group,and another 128 patients who underwent physical examinations during the same period were selected as the control group.The correlation between the expression levels of serum claudin-5 and Apelin-13 in patients with depression and the Hamilton Depression Rating Scale(HAMD)score,as well as the diagnostic value of serum claudin-5 and Apelin-13 for the severity of depression in patients were analyzed.Results The expression level of claudin-5 in the serum of patients in study group was higher than that of the control group,which increased with the severity of the disease(P<0.05)and was positively correlated with the HAMD score(r=0.713,P<0.05).In addition,the expression level of claudin-5 in the serum of patients with sleep disorders was higher than that of those without sleep disorders(P<0.05),and the trend of changes in the expression level of Apelin-13 was opposite;Age,age at onset of depression,and claudin-5 were factors for sleep disorders in patients with depression,while Apelin-13 was a protec-tive factor(P<0.05);The combined detection of serum claudin-5 and Apelin-13 is superior to their individual detection(Z combined detection-claudin-5=2.393,Z combined detection-Apelin-13=1.964,P=0.016,0.044).Conclusion The expression levels of claudin-5 and Apelin-13 in serum of patients with depression were related to the progression of disease and the sleep disorders and the combined detection has high diagnostic value for severe depression.