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 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.

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 evaluate the effectiveness and safety of ultrasound-guided percutaneous polidocanol sclerotherapy of the thyroglossal duct cysts in children.Methods:A retrospective analysis of 26 children who were treated with ultrasound-guided percutaneous puncture sclerosis for thyroglossal duct cysts in Beijing Children′s Hospital, Capital Medical University from October 2019 to April 2022, the size of the cyst before treatment was recorded, and the cyst volume in accordance with V(ml) =1/6 πabc cyst volume was calculated. The follow-up time was the 1st, 3rd, 6th, and 12th months after sclerotherapy. And the cyst volume and volume reduction ratio at different time points was calculated. According to changes in the cystic volume, the treatment was considered effective if the cyst volume reduction rate was≥50%. Cosmetic grading scores (CGS) were performed pre-treatment and at the last follow-up after sclerotherapy using the WHO grading system. Complications were recorded during the follow-up period.Results:The cyst volume before treatment was 2.67 (3.78)ml, and the cyst volume at the 1st, 3rd, 6th and 12th month after treatment were 0.66(1.83), 0.45(0.87), 0.40(0.70), 0.38 (0.63)ml, respectively, there were significant differences between pre-treatment and each time point after-treatment (all P<0.001); the volume reduction rate at the last follow-up was (81.48±14.57)%. The reduction rate of cyst volume was more than 50% at the last follow-up in 22 children, the treatment efficiency was 84.62% (22/26). The cosmetic grading scores at the last follow-up after sclerotherapy was 1.74(1.50), and it decreased significantly compared with the pre-treatment score 3.85(0)( P<0.001). There was no skin pigmentation, pain in the injection area, local urticaria and blistering after sclerotherapy, no adverse reactions such as cyst bleeding and drunkenness-like reaction, and no serious complications occurred. There were 2 cases of cysts that presented infection with fever, and no serious complications occurred. Conclusions:Ultrasound-guided percutaneous sclerotherapy is a safe and effective minimally invasive treatment for thyroglossal duct cysts in children.

Objective:To construct an evaluation index system for the core competence of hospital specialist service operation assistants and provide reference for the evaluation of such competence.Methods:From January to March 2022, literature analysis and behavioral event interviews were used to initially establish a core competence evaluation index system of hospital specialist service operation assistants, based on the Donabedian model. Subsequently, the Delphi expert consultation method was applied to conduct correspondence consultation, inviting experts to evaluate the contents and importance of the index system, using analytic hierarchy process to determine the weights of the indexes at all levels.Results:Two rounds of expert consultation were carried out, and the valid recovery rate of the questionnaire was 100%. The familiarity coefficient of the second round of correspondence was 0.87, the basis of judgment coefficient was 0.90, and the authority coefficient was 0.89. The final evaluation index system for core competence of hospital specialist service operation assistant consisted of 3 first-level indexes, 13 second-level indexes and 81 third-level indexes. The weight of the first-level index structure index was 0.266, and the highest weight among the second-level indexes was the operational development ability (0.083), while the highest weight among the third-level indexes of operational development ability was the comprehensive coordination ability (0.193); The weight of the first-level index process index was 0.405, and the corresponding second-level and third-level indexes with the highest weight were department operation practice work (0.157) and reasonable resource allocation (0.303), respectively; The weight of the first-level index result index was 0.329, and the corresponding second-level and third-level indexes with the highest weight were the weight of medical quality and safety (0.103) and drug adverse reaction reporting rate (0.237), respectively.Conclusions:The evaluation index system constructed in this study proves scientific and reasonable in weight assignment, proving a reference for the management of the specialist service operation assistants.

Objective:To investigate the clinical manifestations and characteristics of tracheobronchial foreign bodies in children, and improve the diagnosis and treatment of foreign bodies.Methods:A retrospective analysis was performed on the clinical data of children with tracheobronchial foreign bodies confirmed by fiberoptic bronchoscopy between January 2010 to December 2019.The children with tracheobronchial foreign body who were treated in the Maternal and Child Health Hospital of Gansu Province.Results:A total of 967 cases were operated by soft electronic bronchoscope, and foreign bodies were removed by means of foreign body forceps or nets.Among them, 19 cases(3 cases with subglottic foreign bodies, one with row of pins, and the rest 15 cases with foreign bodies completely wrapped by granulation)were not removed, two cases were spontaneously coughed, and 946 cases (97.8%)were removed.Bronchial foreign bodies in children were more common in boys, with the ratio of male to female being 2.14∶1.The main age of onset was 1-3 years old(88.8%). The incidence was slightly higher in rural areas than that in urban areas(46.5% in urban areas, 53.5% in rural areas). Foreign bodies were inhaled most in March and least in June.From the perspective of season, winter and spring were more than summer and autumn.The foreign body types inhaled were mainly exogenous plant foreign body, accounting for 93.0%, among which peanut(31.7%)and melon seeds(19.2%)were the most common.The duration of foreign body inhalation was up to 347 cases(35.9%)in 1-3 days.There were 501 cases(51.8%)with endoscopic endobronchial inflammation, and 196 cases of children with varying degrees of granulomatous hyperplasia, accounting for 39.1% and 20.3% of the total.The foreign body in the right bronchus accounted for 50.0% and the left bronchus for 43.7%.There were 793 cases confirmed by imaging, with a positive rate of 81.9%, and 90.9% confirmed by CT.Conclusion:About 88.8% of tracheobronchial foreign bodies occurred in 1 to 3 years of age.The occurrence of foreign bodies had obvious gender, urban-rural and seasonal distribution characteristics, and more cases were male, in rural and winter as well as spring.

Objective:To analyze molecular genetic characteristics of standard strains for functional antibody detection of pneumococcal polysaccharide vaccine, and provide the foundation for clinical research of pneumococcal polysaccharide vaccine. Methods:The 24 strains for functional antibody detection of pneumococcal polysaccharide vaccine were detected by PCR amplification and sequencing using standard strain 16S rRNA gene fragment, and the molecular typing of the related strains was performed by multi locus sequence analysis (MLST) and pulsed field gel electrophoresis (PFGE). Results:The result of 16S rRNA gene sequence alignment showed that the similarity between the gene sequences of the 24 strains and that of NCTC 7465 (LN831051) ranged from 98.35% to 99.86%, and the base difference was 2-23 bp. Multi locus sequence analysis showed that the ST types of 24 standard strains were different. PFGE analysis showed that 24 standard strains had good isolation effect from DNA fragments of 100 kb-1 000 kb, and each serotype had its own characteristic bands (12-15 fragments).Conclusions:This study analyzed the molecular genetic characteristics of the standard strains for the detection of pneumococcal functional antibodies for the first time, and may provide a reference for the quality control method of the standard strains for the subsequent detection of pneumococcal functional antibodies.

Objective:To analyze the value and difference of the optic nerve sheath pulse dynamic deformation index (DI) in normal-tension glaucoma (NTG) and high-pressure primary open angle glaucoma (POAG).Methods:A cross-sectional study was conducted to collect clinical data at the Eye Center of Beijing Tongren Hospital from June 2016 to March 2017, 32 patients with NTG and 35 patients with high-pressure POAG were sampled.For all subjects, their basic information, body mass index (BMI), mean arterial blood pressure (MAP), 24 hours intraocular pressure, and ophthalmologic examinations required for diagnosis were recorded.All subjects underwent transorbital ultrasonography and for each 15 seconds of consecutive ultrasound images were taken.The dynamic post-processing technique was used to calculate the DI.The difference in DI between the two groups and the correlation of DI with other variables were analyzed.The study protocol was approved by the Ethics Committee of Beijing Tongren Hospital.Written informed consent was obtained from all subjects prior to their entering the study cohort and receiving the transorbital ultrasound examination.Results:The median level of DI in the NTG group was 0.51 (0.48, 0.54), which was higher than that in the high-pressure POAG group (0.23[0.20, 0.25]), exhibiting a significant difference ( Z=-7.01, P<0.01). The mean BMI in the NTG group was lower than that in the high-pressure POAG group([21.29±4.64]kg/m 2vs. [23.53±3.40]kg/m 2), the mean MAP in the NTG group was lower than that in the high-pressure POAG group([91.44±14.30]mmHg vs. [104.05±13.96] mmHg), the differences between the two groups were statistically significant ( t=-2.30, P<0.05; t=-3.65, P<0.01). There was no statistical association between the two groups of DI and age, MAP, BMI, mean intraocular pressure and maximum intraocular pressure (all at P>0.05). Conclusions:The DI of the NTG patient is higher than that of the POAG patient, which indicates that the optic nerve sheath subarachnoid pressure and optic nerve sheath stiffness in NTG patients are lower than those in POAG patients.Therefore, the DI is a potential indicator of non-invasive intracranial pressure and translaminar cribrosa pressure difference detection in ophthalmology.

Objective: To explore the safety of liver transplantation recipients with Rh blood group mismatchming. Methods: From May 2005 to December 2018, 1 546 cases of liver transplantation in our hospital were retrospectively analyzed. Among these cases, 5 cases of Rh blood group mismatched were Rh(-) recipients receiving Rh(+ ) donor liver. For each Rh blood group mismatched liver transplantation, 5 patients received the same Rh blood group liver allograft were matched according to a certain principle and were defined as Rh-mismatch group and Rh-match group respectively. The serum alanine aminotransferase (ALT), aspartate aminotransferase(AST)and creatinine(SCr)were compared between two groups at Days 7 & 14 post-operation. Serum total bilirubin(TB), gamma-glutamyl transpeptidase(GGT)were compared between two groups at Month 1, 6 & 12 post-operation. Hemoglobin (Hb)were compared between two groups Month 1, 3 & 6 post-operation. The rates of infection, vascular complications and acute rejection was also compared. Indirect antiglobulin test (IAT)was used for detecting the production of anti-RhD antibody in patients in Rh-mismatch group at Month 1, 6 & 12 post-operation. Results: At the mentioned time, no significant inter-group difference existed in serum ALT, AST, SCr, TB, GGT and blood Hb levels(all P>0.05); Also, no significant difference existed in the incidence of infection, vascular complications or acute rejection(all P>0.05). In Rhmismatch group, 4 recipients received Rh(+ )RBC transfusion during perioperative period and no hemolytic anemia occurred after operation. Rh(D) antibody was negative at all timepoints. Conclusions Taking into account the rarity of Rh-negative blood group in Chinese, it is safe and feasible to carry out Rh blood group mismatched liver transplantation when donor or recipient with the same Rh blood group is not available.

The biodiversity of the mycobiome, an important component of the oral microbial community, and the roles of fungal-bacterial and fungal-immune system interactions in the pathogenesis of oral lichen planus (OLP) remain largely uncharacterized. In this study, we sequenced the salivary mycobiome and bacteriome associated with OLP. First, we described the dysbiosis of the microbiome in OLP patients, which exhibits lower levels of fungi and higher levels of bacteria. Significantly higher abundances of the fungi Candida and Aspergillus in patients with reticular OLP and of Alternaria and Sclerotiniaceae_unidentified in patients with erosive OLP were observed compared to the healthy controls. Aspergillus was identified as an "OLP-associated" fungus because of its detection at a higher frequency than in the healthy controls. Second, the co-occurrence patterns of the salivary mycobiome-bacteriome demonstrated negative associations between specific fungal and bacterial taxa identified in the healthy controls, which diminished in the reticular OLP group and even became positive in the erosive OLP group. Moreover, the oral cavities of OLP patients were colonized by dysbiotic oral flora with lower ecological network complexity and decreased fungal-Firmicutes and increased fungal-Bacteroidetes sub-networks. Third, several keystone fungal genera (Bovista, Erysiphe, Psathyrella, etc.) demonstrated significant correlations with clinical scores and IL-17 levels. Thus, we established that fungal dysbiosis is associated with the aggravation of OLP. Fungal dysbiosis could alter the salivary bacteriome or may reflect a direct effect of host immunity, which participates in OLP pathogenesis.
Adult ; Bacteria ; isolation & purification ; Case-Control Studies ; Dysbiosis ; complications ; microbiology ; Female ; Humans ; Lichen Planus, Oral ; complications ; microbiology ; Male ; Microbiota ; Middle Aged ; Mouth Mucosa ; microbiology ; Mycobiome ; Saliva ; microbiology