OBJECTIVES: To investigate the clinical features of children with STAT gene mutations, and to explore corresponding immunotherapy strategies. METHODS: A retrospective analysis was performed for the clinical data of 10 children with STAT gene mutations who were admitted to the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University, from October 2015 to October 2024. Exploratory immunotherapy was implemented in some refractory cases, and the changes in symptoms, imaging manifestations, and cytokine levels were assessed after treatment. RESULTS: For the 10 children, the main clinical manifestations were recurrent rash since birth (7/10), cough (8/10), wheezing (5/10), expectoration (4/10), and purulent nasal discharge (4/10). Genotyping results showed that there was one child with heterozygous loss-of-function (LOF) mutation in the STAT1 gene, four children with heterozygous LOF mutation in the STAT3 gene, and five children with heterozygous gain-of-function (GOF) mutation in the STAT3 gene. Two children with LOF mutation in the STAT3 gene showed decreased interleukin-6 levels and improved clinical symptoms and imaging findings after omalizumab treatment. Three children with GOF mutation in the STAT3 gene achieved effective disease control after treatment with methylprednisolone (0.5 mg/kg per day). Two children with GOF mutation in the STAT3 gene received treatment with JAK inhibitor and then showed some improvement in symptoms. CONCLUSIONS STAT gene mutation screening should be considered for children with recurrent rash and purulent respiratory tract infections. Targeted immunotherapy may improve prognosis in patients with no response to conventional treatment.
Humans ; Male ; Immunotherapy ; Female ; Child, Preschool ; Child ; Gain of Function Mutation ; Retrospective Studies ; Infant ; Loss of Function Mutation ; STAT Transcription Factors/genetics*

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.

Human naïve pluripotent stem cells (PSCs) hold great promise for embryonic development studies. Existing induction and culture strategies for these cells, heavily dependent on MEK inhibitors, lead to widespread DNA hypomethylation, aberrant imprinting loss, and genomic instability during extended culture. Here, employing high-content analysis alongside a bifluorescence reporter system indicative of human naïve pluripotency, we screened over 1,600 chemicals and identified seven promising candidates. From these, we developed four optimized media-LAY, LADY, LUDY, and LKPY-that effectively induce and sustain PSCs in the naïve state. Notably, cells reset or cultured in these media, especially in the LAY system, demonstrate improved genome-wide DNA methylation status closely resembling that of pre-implantation counterparts, with partially restored imprinting and significantly enhanced genomic stability. Overall, our study contributes advancements to naïve pluripotency induction and long-term maintenance, providing insights for further applications of naïve PSCs.
Humans ; DNA Methylation/drug effects* ; Genomic Instability ; Pluripotent Stem Cells/metabolism* ; Cell Culture Techniques/methods* ; Cells, Cultured

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective:To investigate the feasibility, safety and reasonable operation of nasointestinal canal indwelling guided by miniature system in severe neurosurgery patients, and compare its advantages and disadvantages with traditional blind insertion.Methods:A prospective randomized controlled trial design was used to select 128 critically ill patients in need of enteral nutrition support at the Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University from March 2022 to October 2023 by convenient sampling method. They were divided into blind insertion group and visualization group by random number table method, with 64 cases in each group. Nasointestinal canal indwelling was performed in the blind insertion group by traditional blind insertion method, and in the visualization group, nasointestinal canal indwelling was performed by indentations guided by the miniature visualization system. The success rate of initial catheterization, the time of catheterization, complications, changes of vital signs during catheterization and changes of nutritional indexes after catheterization were evaluated in 2 groups.Results:In the blind insertion group, there were 35 males and 29 females, aged (59.44 ± 13.84) years old. In the visualization group, there were 41 males and 23 females, aged (58.28 ± 12.08) years old. The success rate of the first catheter placement in the visual group was 96.8% (62/64), higher than that in the blind group 82.8% (53/64), and the difference was statistically significant ( χ2=6.94, P<0.05). The catheter placement time of the visualization group was (20.08 ± 2.69) min, which was shorter than that of the blind insertion group (38.19 ± 3.79) min, and the difference between the two groups was statistically significant ( t=29.99, P<0.05). There was no significant difference in the incidence of complications, changes of vital signs during catheterization and the changes of nutritional indexes after catheterization between two groups (all P>0.05). Conclusions:Compared with traditional blind nasointestinal canal indwelling, nasointestinal canal indwelling guided by the miniature visualization system can improve the success rate of the first catheterization and shorten the catheterization time. Although there is no difference in the complication rate, changes in vital signs during catheterization and changes in nutritional indexes after catheterization, it is believed that with the continuous development and upgrading of this technology, it will further reflect the advantages of this technology, which is worthy of further clinical trials and application.

Objective To systematically evaluate the effect of virtual shopping on cognitive function of patients with mild cognitive impairment. Methods PubMed,EMBASE,Cochrane Library,Web of Science,and CNKI were searched for literatures on virtual shopping,mild cognitive impairment,and cognitive function published from database inception to Sep. 2023. The literatures were screened and the data were extracted in strict accordance with the inclusion criteria,and the Review Manager 5.3 was used for meta-analysis. Results A total of 12 randomized controlled trials involving 382 patients with mild cognitive impairment were included. Meta analysis showed that compared with traditional cognitive rehabilitation training,virtual shopping could improve the comprehensive cognitive function,executive function,attention and abilities of daily living of patients with mild cognitive impairment (all P<0.05),but had no significant effects on the memory,language,or visuospatial ability (all P>0.05). Conclusion Virtual shopping is beneficial for improving the comprehensive cognitive function,executive function,attention and abilities of daily living of patients with mild cognitive impairment.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To explore the feasibility of integrated imaging of portal vein and hepatic vein with"three low-contrast agents"combined with energy spectrum CT technology.Methods A total of 100 patients with enhanced abdominal CT scans were selected.The patients were randomly divided into two groups.The patients of experimental group(n=50)were injected with the isotonic con-trast agent iodixanol(320 mg I/mL)at a flow rate of 3 mL/s and a total volume of 1.2 mL/kg,and underwent energy spectrum CT scan in the portal venous phase.The patients of control group(n=50)were injected with the sub-hypertonic contrast agent iohexol(350 mg I/mL)at a flow rate of 5 mL/s and a total volume of 1.5 mL/kg,and underwent conventional multi-phase spiral CT enhancement scan.The image quality and radiation dose of portal vein and hepatic vein were compared between the two groups.Results The CT value of main portal vein in the experimental group was higher than that in the control group,and the difference was statistically sig-nificant(P＜0.05).There was no statistical significance in main portal vein contrast-to-noise ratio(CNR),main portal vein signal-to-noise ratio(SNR),hepatic vein CT value,and hepatic vein CNR between the two groups(P＞0.05).The SNR and image standard deviation(SD)of the hepatic vein in the control group were better than those in the experimental group(P＜0.05).There was no statistical significance in the subjective scores of portal vein and hepatic vein between the two groups(P＞0.05).The volume CT dose index(CTDIvol),dose length product(DLP),and effective dose(ED)of the portal venous phase spectrum CT scan in the experimental group were lower than those of the conventional single-phase spiral CT scan in the control group(P＜0.05).Conclusion"Three low-contrast agents"combined with energy spectrum CT technology can realize integrated imaging of portal vein and hepatic vein in late portal vein,and can reduce radiation dose.

AIM To study the chemical constituents from the leaves of Citrus reticulata Blanco and their anti-inflammatory activities.METHODS The 85%ethanol extract from the leaves of C.reticulata was isolated and purified by silica gel,D101 macroporous resin,MCI,ODS and Sephadex LH-20,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The Griess method was used to determine their inhibitory activities on lipopolysaccharide-induced NO production in macrophages RAW 264.7 cells.The mice foot swelling inflammation model induced by carrageenan was established,and the levels of IL-1β,TNF-α were detected.RESULTS Twelve compounds were isolated and identified as nobiletin(1),tangeretin(2),5-demethylinoblitin(3),5,4'-dihydroxy-6,7,8,3'-tetramethoxy flavone(4),5-hydroxy-7,8,3',4'-trimethoxyflavanone(5),3,5,6,7,8,3',4'-heptamethoxyflavanone(6),hesperetin(7),5-hydroxy-6,7,3',4'-tetramethoxyphenone(8),β-balsam alcohol(9),stigmaster-5-en-3β-alcohol(10),p-hydroxybenzaldehyde(11),vanillin(12).Compounds 1,4,6,7,10 and 12 had strong inhibitory activites on NO release in LPS-induced RAW 264.7 cells,and the IC50 values were(25.21±2.10),(37.77±0.50),(38.19±1.58),(21.89±1.73),(43.81±1.18),(47.98±2.55),(41.23±1.11),(43.80±1.43)μmol/mL,respectively.Compounds 2-3 reduced IL-1β and TNF-α levels(P＜0.05,P＜0.01).CONCLUSION Compounds 6-7,9 are isolated from this plant for the first time.Compounds 1-4,8 exhibit strong in vitro anti-inflammatory activities,and compounds 2-3 exhibit significant in vivo anti-inflammatory activities.