ObjectiveTo explore the clinical safety of Feilike Mixture （FLK） in the real world. MethodsThe safety of all children who received FLK from 29 institutions in 12 provinces between January 21，2021 and December 25，2021 was evaluated through prospective centralized surveillance and a nested case control study. ResultsA total of 3 035 juveniles were included. There were 29 research centers involved，which are distributed across 12 provinces，including one traditional Chinese medicine （TCM） hospital and 28 general hospitals. The average age among the juveniles was （4.77±3.56） years old，and the average weight was （21.81±12.97） kg. Among them，119 cases （3.92%） of juveniles had a history of allergies. Acute bronchitis was the main diagnosis for juveniles，with 1 656 cases （54.46%）. FLK was first used in 2 016 cases （66.43%），and 142 juvenile patients had special dosages，accounting for 4.68%. Among them，92 adverse drug reactions （ADRs） occurred，including 73 cases of gastrointestinal system disorders，10 cases of metabolic and nutritional disorders，eight cases of skin and subcutaneous tissue diseases，two cases of vascular and lymphatic disorders，and one case of systemic diseases and various reactions at the administration site. The manifestations of ADRs were mainly diarrhea，stool discoloration，and vomiting，and no serious ADRs occurred. The results of multi-factor analysis indicated that special dosages （the use of FLK）［odds ratio （OR） of 2.642， 95% confidence interval （CI） of 1.105-6.323］，combined administration： spleen aminopeptide （OR of 4.978， 95%CI of 1.200-20.655），and reason for combined administration： anti-infection （OR of 1.814， 95%CI of 1.071-3.075） were the risk factors for ADRs caused by FLK. Conclusion92 ADRs occurred among 3 035 juveniles using FLK. The incidence of ADRs caused by FLK was 3.03%，and the severity was mainly mild or moderate. Generally，the prognosis was favorable after symptomatic treatment such as drug withdrawal or dosage reduction，suggesting that FLK has good clinical safety.

Transcranial temporal interference stimulation (tTIS) is a novel non-invasive transcranial electrical stimulation technique that achieves deep brain stimulation through multiple electrodes applying electric fields of different frequencies. Current studies on the mechanism of tTIS effects are primarily based on rodents, but experimental outcomes are often significantly influenced by electrode configurations. To enhance the performance of tTIS within the limited cranial space of rodents, we proposed various electrode configurations for tTIS and conducted finite element simulations using a realistic mouse model. Results demonstrated that ventral-dorsal, four-channel bipolar, and two-channel configurations performed best in terms of focality, diffusion of activated brain regions, and scalp impact, respectively. Compared to traditional transcranial direct current stimulation (tDCS), these configurations improved by 94.83%, 50.59%, and 3 514.58% in the respective evaluation metrics. This study provides a reference for selecting electrode configurations in future tTIS research on rodents.
Animals ; Transcranial Direct Current Stimulation/instrumentation* ; Electrodes ; Mice ; Computer Simulation ; Finite Element Analysis ; Brain/physiology*

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.

OBJECTIVES: To explore the correlation of ELFN1 expression level with prognosis of colorectal cancer and its regulatory role in colorectal cancer cell proliferation and metastasis. METHODS: We analyzed the expression levels of ELFN1 across 33 cancer types using publicly available databases and identified differential genes related to ELFN1 in colorectal cancer. Gene function annotation and enrichment analysis were used to identify the involved signaling pathways. Logistic analysis, Kaplan-Meier analysis and Cox regression analysis were performed to evaluate the correlation between ELFN1 expression and clinicopathological parameters and survival of colorectal cancer patients. qPCR and Western blotting were used to validate the expression levels of ELFN1 in different colorectal cancer cell lines and tissues, and Transwell and EDU experiments were carried out to assess the effect of ELFN1 knockdown on biological behaviors of SW480 cells. RESULTS: ELFN1 was highly expressed in 14 cancers, and its expression was significantly higher in colon cancer tissues than in adjacent tissues. A high expression of ELFN1 mRNA was associated with a poorer overall survival of colorectal cancer patients. Cox regression analysis indicated that ELFN1 expression was an independent prognostic factor for overall survival of the patients. ELFN1 was significantly enriched in tumor metastasis and proliferation and participated in several tumor signaling pathways. The colon cancer cell lines showed significantly higher expression levels of ELFN1 than normal cells, ELFN1 knockdown obviously inhibited proliferation and migration of SW480 cells in vitro. CONCLUSIONS ELFN1 is overexpressed in colorectal cancer and is associated with poor clinical prognosis of the patients. A high ELFN1 expression is associated with malignant phenotypes of colorectal cancer and promotes cancer cell proliferation and metastasis, suggesting its potential as a prognostic biomarker for colorectal cancer.
Humans ; Colorectal Neoplasms/diagnosis* ; Cell Proliferation ; Prognosis ; Cell Line, Tumor ; Biomarkers, Tumor/metabolism* ; Neoplasm Metastasis ; Gene Expression Regulation, Neoplastic ; Nerve Tissue Proteins/metabolism* ; Female ; Male

Objective To systematically identify the key genes regulating the exit from na?ve pluripotency in embryonic stem cells(ESCs)in order to provide novel targets and theoretical insights into the mechanisms for pluripotency transition and early cell fate determination.Methods Nanog-green fluorescent protein(Nanog-GFP)reporter-labeled ESCs were infected with a genome-wide Brie knockout library,and further cultured under leukemia inhibitory factor/serum(LIF/S)conditions for 14 d.Flow cytometry was used to sort Nanog-GFP?(na?ve-state)and Nanog-GFP-(primed state)cell populations,followed by genomic DNA extraction and high-throughput sequencing.Model-based Analysis of Genome-wide CRISPR/Cas9 Knockout(MAGeCK)was applied to identify differential genes between GFP?/Input,GFP?/Input,and GFP?/GFP? groups.Metascape and Gene Set Enrichment Analysis(GSEA)were conducted for functional enrichment analysis.Then the obtained candidate genes were employed to construct knockout models,and their roles were assessed through cell morphology observation,Nanog-positive rate detection,colony formation assays,and pluripotency gene expression analysis.Results The GFP?/Input screening revealed 2 921 negatively regulated genes(mainly enriched in basic life processes,such as RNA metabolism and cell cycle)and 1 393 positively regulated genes(enriched in the processes of nervous system development,carbohydrate metabolism,and vascular system development).In the GFP?/Input screening,2 765 negatively regulated genes(enriched in RNA metabolism,cell cycle,and other fundamental processes)and 1 303 positively regulated genes(enriched in neural development,cell survival,and endothelial migration)were identified.The GFP?/GFP? comparison identified 1 001 negatively regulated genes[involved in stress response and inhibition of mitogen-activated protein kinase(MAPK)signaling]and 983 positively regulated genes[related to fibroblast growth factor/extracellular signal-regulated kinase(FGF/ERK)signaling pathway and glucose metabolism).These genes,were not only known pluripotency regulators(e.g.,Nanog,Nr5a2,Klf2,Klf4)and exit-associated genes(e.g.,Gata6,Grb2,Zeb1,Fgfr1),but also some novel candidates(e.g.,Dmrt1,Rxra,Zbtb14 and Tmem41b).Functional validation showed that transient knockout of Dmrt1,Tmem41b,and Hic2 significantly increased the proportion of Nanog? cells(P<0.01),suggesting their role in suppressing ground-state exit.ESCs with stable Dmrt1 knockout exhibited a more na?ve-state phenotype,presenting compact,dome-shaped colonies,with increased ratio of undifferentiated colonies(P<0.01),up-regulation of ground-state markers(Nanog,Nr5a2,Dppa3,P<0.01),and down-regulation of primed-state markers(Fgf5,Lefty1,Dnmt3b,P<0.01).Rescue experiments for Dmrt1 expression reversed these above phenotypes.Conclusion A candidate gene set regulating exit from na?ve pluripotency in ESC is screened out and identified with genome-wide CRISPR.Our findings implicate Dmrt1 plays a critical role in promoting the exit.

Objective To analyze the main epidemiological characteristics of fungal infection in this hospital in the past 7 years,and to provide reference for clinical treatment and prevention and control strategies of fun-gal infection.Methods The fungal data and clinical data of related patients isolated from clinical samples in Peking Union Medical College Hospital from early January 2018 to the end of May 2024 were selected,and the main epidemiological characteristics of fungal infection in this hospital were identified and described through multi-angle statistical analysis.Results A total of 4 479 patients with filamentous fungal infection were en-rolled.The proportion of male patients[57.5％(2 576/4 479)]was higher than that of female patients[42.5％(1 903/4 143)],mainly distributed in internal medicine,Intensive Care Unit(ICU)and emergency de-partment,among which internal medicine accounted for the highest proportion[50.0％(2 241/4 479)].About 90.0％of the specimens were from the lower respiratory tract,in addition to specimens from skin and soft tis-sue,tissue,ear and blood culture.In terms of seasonal distribution,there are more patients in winter.The fun-gi were mainly composed of Aspergillus,Mucor,Cerdosporium,Fusarium and Penicillium,among which As-pergillus was the most abundant,accounting for 74.6％of the total.Aspergillus fumigatus was the most a-bundant Aspergillus,accounting for 42.5％of the total Aspergillus(1 418/3 340).Among the related infec-tions caused by mold,Aspergillus was the most common in the lower respiratory tract,accounting for 76.8％.Among them,Aspergillus fumigatus accounted for the highest proportion(33.6％).98.6％of the molds infected the ear were Aspergillus,of which Aspergillus niger and Aspergillus terreus were the most common.Skin infections are mainly caused by Sporothrix schenckii,Trichophyton rubrum,Microsporum ca-nis.The results of in vitro drug sensitivity test showed that the four common Aspergillus isolated in this hos-pital were sensitive to voriconazole,and amphotericin B had better antifungal activity against Mucorales in vitro.Conclusion Based on the main epidemiological characteristics of fungal infections in this hospital,it is recommended that special attention be paid to the admission of patients in the respiratory department during the peak infection period in autumn and winter.In the treatment of fungal infections in different regions and on different body parts,attention should be paid to the differences in the distribution of bacterial species.

This article aims to initially establish a traditional Chinese medicine(TCM)syndrome scale for pediatric bronchial asthma based on syndrome element differentiation through literature research and expert consultation and by referencing multiple editions of textbooks,clinical guidelines,and expert consensus.The TCM syndrome scale for pediatric bronchial asthma covers 17 relevant syndrome elements,namely lung,exterior,kidney,spleen,heart,phlegm,cold,yin deficiency,yang deficiency,fluid retention,qi deficiency,wind,heat,qi stagnation,blood stasis,qi failing in astringing,and blood deficiency.It corresponds to 5 major TCM syndrome items(i.e.,wheezing or shortness of breath,cough,chest tightness,wheezing sound in the throat or sputum expectation,and lung signs),over 30 secondary TCM syndrome items,and items related to TCM tongue signs,pulse signs,infantile finger signs(conditions of radial superficial vein of infantile index finger),and facial complexion.The Cronbach's alpha coefficients for the total scale and all syndrome element dimensions were greater than 0.7,indicating good structural validity.The process of establishing this scale,i.e,setting syndrome items,determining syndrome elements,and forming a scale,is consistent with the process of syndrome element differentiation(analyzing the syndromes,defining syndrome elements,forming a syndrome pattern).The establishment of the scale has taken into consideration of both the characteristics of pediatric bronchial asthma and the features of syndrome element differentiation,harnessing the advantage of the disease-syndrome combination pattern.The constructed scale holds certain reference significance for clinical practice in TCM pediatrics.

Objective:To explore the role of conducting a"thematic morning report"based on post-competency in the standardized residents training in hospital in the Intensive Care Unit(ICU).Methods:A total of 60 resident training physicians who participated in the standardized residents training in hospital in the ICU of this hospital from January 2020 to December 2022 were included,and randomly divided into an observation group and a control group,with 30 in each group.The observation group adopted an interactive teaching method of themed morning report based on post-competency,while the control group adopted the traditional teaching method.The assessment results of clinical theoretical knowledge and operational skills of the two groups of resident training physicians under different teaching methods were compared.The 360°assessment method was used to record the multi-directional evaluation of patients or their families,nurses,colleagues,and teaching teachers on the post-competence of resident training physicians(self-learning ability,team collaboration ability,effective communication ability,and learning interest).Results:The assessment scores of clinical theoretical knowledge and practical skills in the observation group after teaching were higher than those in the control group,with statistically significant differences(theoretical assessment:t=2.101,P＜0.05;practical assessment:t=9.647,P＜0.05).The post-competence scores of nurses,colleagues,and teaching teachers on resident training physicians in the observation group were higher than those in the control group after one-month regular training,and the differences were statistically significant(nurses'evaluation of self-learning ability:t=3.182,P=0.002,team collaboration ability:t=3.978,P＜0.05,effective communication ability:t=2.180,P=0.0335,learning interest:t=3.884,P＜0.05;colleagues'evaluation of self-learning ability:t=2.888,P=0.005,team cooperation ability:t=6.816,P＜0.05,effective communication ability:t=3.833,P＜0.05,learning interest:t=4.086,P＜ 0.05;teaching teacher's evaluation of self-learning ability:t=3.429,P=0.001,team cooperation ability:t=3.086,P=0.003,effective communication ability:t=3.493,P=0.001,learning interest:t=3.126,P=0.003).There was a statistically significant difference in the satisfaction scores of patients or their familymembers towards the two groups of resident training physicians(t=3.126,P=0.003).Conclusion:The use of the interactive teaching method of thematic morning report based on post-competency in the standardized residents training in hospital in the ICU can not only improve the theoretical practice and case analysis test scores of resident training physicians,but also improve the post-competence and the satisfaction of patients and their families.

Objective To evaluate 99mTc-HYNIC-TOC somatostatin receptor and 131 I-MIBG imaging in clinical diag-nostic of pheochromocytoma and paraganglioma(PPGL).Methods This was a retrospective study.359 PPGL pa-tients diagnosed by pathology microscopy were included.The diagnostic sensitivity and influencing factors on 99mTc-HYNIC-TOC somatostatin receptor and 131 I-MIBG imaging were analyzed.Results The positive rate of 99mTc-HYN-IC-TOC somatostatin receptor scintigraphy was 57.7%(184/319)and 131I-MIBG imaging was 83.2%(232/279).The positive rates of 99m Tc-HYNIC-TOC somatostatin receptor imaging in the adrenal glands,retroperitoneum,head and neck,heart and mediastinum,pelvis and bladder were 53.3%,62.5%,95.0%,66.7%,50.0%and 11.0%respec-tively and the positive rates of 131I-MIBG imaging were 86.7%,88.5%,45.4%,50.0%,75.0%and 33.3%respec-tively.The positive rate of the two imaging did not showed difference among patients with different genetic back-grounds(SDH,VHL,RET mutations).The median maximum diameter of tumors was 4.4(3.0,6.1)cm.and the diag-nostic sensitivity of somatostatin receptor imaging and 131 I-MIBG imaging for larger tumors(≥4.4 cm)was signifi-cantly higher than those for the smaller tumor group(＜4.4 cm)(64.0%vs.51.3%;92.3%vs.74.1%)(P＜0.01).Tumors in 19 patients(5.3%)failed to uptake neither imaging method.Conclusions This is the largest PPGL cohort in China concerning 99m Tc-HYNIC-TOC somatostatin receptor imaging and 131 I-MIBG imaging.The sensitivity of 131 I-MIBG imaging is higher than that of 99m Tc-HYNIC-TOC somatostatin receptor imaging,but for some tumors,such as head and neck paraganglioma,the latter has obvious advantages.These two imagings technol-ogies are complementary and the choice of them should depend the individual situation of patients.