TFIIB-related factor 1 (BRF1) is an important transcription factor. It specifically regulates the transcription of RNA polymerase III-dependent genes (RNA Pol III genes). The products of these genes are some small non-coding RNAs, including transfer RNAs (tRNAs) and 5S ribosomal RNAs (5S rRNA). The transcription levels of tRNAs and 5S rRNA vary with changes in intracellular BRF1 amounts. tRNAs and 5S rRNA play a crucial role in determining protein synthesis. Studies have demonstrated that dysregulation of tRNAs and 5S rRNA is closely related to cell growth, proliferation, transformation, and even tumorigenesis. BRF1 is a key factor determining the generation of tRNAs and 5S rRNA. Increasing BRF1 expression enhances cell proliferation and transformation, promoting tumor development. In contrast, repressing BRF1 activity decreases the rates of cell proliferation and transformation, and inhibits tumor growth. High levels of BRF1 are found in the samples of patients suffering from hepatocellular carcinoma, breast cancer, gastric carcinoma, lung cancer, prostate carcinoma, and other cancers. It indicates that high levels of BRF1 are closely related to the occurrence of human cancer and may be a common landmark of tumors. But there is discrepancy in the regulatory mechanisms and signaling pathways of BRF1 overexpression in different cancers. In general, high levels of BRF1 in patients suffering from cancer show short survival period and poor prognosis. However, there is one exception, namely breast cancer. Approximate 80% of cases of breast cancer are estrogen receptor-positive (ER+) and 20% are ER-. The cases with high levels of BRF1 reveal longer survival period and better prognosis after they accepted the hormone treatment by Tamoxifen (Tam), compared to the cases with low level BRF1. It seems like a contradiction. Most of the cases with high levels of BRF1 belong to ER+ status. Tam has been used to treat ER+ cases of breast cancer after diagnosis and surgery. Thus, hormone therapy, such as Tam, is more effective on these patients. This is because, on one hand, that Tam competes with E2 (17β-estradiol) to bind to estrogen receptor α (ERα), but does not dissociate to occupy the receptors, blocking E2 binding to this receptor and inhibiting its biological effects. On other hand, Tam can inhibit the expression of BRF1, leading to a decline of intracellular BRF1 levels. Therefore, the actual levels of BRF1 are lower in the patients with ER+ breast cancer. It appears the prognosis of the high BRF1 expression cases better than that of the low BRF1 expression cases. Myocardial hypertrophy manifests magnification of cardiomyocyte volume rather than number increasing in the postnatal heart. Myocardial hypertrophy is a critical risk factor underlying cardiovascular diseases. No matter how myocardial hypertrophy occur, it will ultimately lead to myocardial dysfunction and heart failure. Hypertrophic growth of cardiomyocytes requires a large amount of protein synthesis to meet its needs of cardiomyocyte growth. Animal models and cell experiments have shown that myocardial hypertrophy stimulates a significant increase in BRF1 expression and transcription of tRNAs and 5S rRNA. Interestingly, elevated levels of BRF1 are found in the myocardium tissues of patients with myocardial hypertrophy. These studies demonstrate that BRF1 indeed plays a critical role in myocardial hypertrophy. In summary, high levels of BRF1 are found in patients suffering from different cancers and myocardial hypertrophy. It implies that BRF1 is a promising biological target of cancer and cardiomyopathy. BRF1 is expected to become a common biomarker for early diagnosis and prognostic observation of different human cancers. It is also an important biomarker for the diagnosis and treatment of cardiomyopathy. BRF1 not only holds an important position in the field of basic medical research but also has great prospects for translational medicine. In the present article, we summarize the progress on studies of BRF1 expressions in cancer and cardiomyopathy, proposes future research directions. It is a new research area. Here, we emphasize the significancy of BRF overexpression in the two huge diseases of human, cancer and cardiomyopathy to raise people's attention to this field.

OBJECTIVES: To evaluate the effectiveness of single-balloon and double-balloon enteroscopy in diagnosing pediatric small bowel diseases and assess the diagnostic efficacy of computed tomography enterography (CTE) for small bowel diseases using enteroscopy as the reference standard. METHODS: Clinical data from 576 children who underwent enteroscopy at Hunan Children's Hospital between January 2017 and December 2023 were retrospectively collected. The children were categorized based on enteroscopy type into the single-balloon enteroscopy (SBE) group (n=457) and double-balloon enteroscopy (DBE) group (n=119), and the clinical data were compared between the two groups. The sensitivity and specificity of CTE for diagnosing small bowel diseases were evaluated using enteroscopy results as the standard. RESULTS: Among the 576 children, small bowel lesions were detected by enteroscopy in 274 children (47.6%).There was no significant difference in lesion detection rates or complication rates between the SBE and DBE groups (P>0.05), but the DBE group had deeper insertion, longer procedure time, and higher complete small bowel examination rate (P<0.05). The complication rate during enteroscopy was 4.3% (25/576), with 18 cases (3.1%) of mild complications and 7 cases (1.2%) of severe complications, which improved with symptomatic treatment, surgical, or endoscopic intervention. Among the 412 children who underwent CTE, the sensitivity and specificity for diagnosing small bowel diseases were 44.4% and 71.3%, respectively. CONCLUSIONS SBE and DBE have similar diagnostic efficacy for pediatric small bowel diseases, but DBE is preferred for suspected deep small bowel lesions and comprehensive small bowel examination. Enteroscopy in children demonstrates relatively good overall safety. CTE demonstrates relatively low sensitivity but comparatively high specificity for diagnosing small bowel diseases.
Retrospective Studies ; Treatment Outcome ; Double-Balloon Enteroscopy/statistics & numerical data* ; Single-Balloon Enteroscopy/statistics & numerical data* ; Humans ; Male ; Female ; Child ; Operative Time ; Tomography, X-Ray Computed/statistics & numerical data* ; Sensitivity and Specificity ; Intestine, Small/surgery* ; Intestinal Diseases/surgery*

Congenital lower urinary tract obstruction (CLUTO) is a spectrum of fetal malformations caused by anatomical abnormalities of the urethra, characterized by high rates of perinatal complications and mortality. The 2024 joint guideline from the European Association of Urology (EAU) and the European Society for Paediatric Urology (ESPU) introduced systematic revisions to the comprehensive management of CLUTO. Key updates encompass advancements in prenatal and postnatal screening and precise diagnosis, refined fetal prognosis assessment, clearer indications and modality selection for prenatal intervention, optimization of postnatal treatment strategies, and the establishment of a lifelong follow-up framework within an integrated care pathway. This article elucidates these key updates by comparing the 2024 EAU/ESPU guideline with the 2022 European Rare Kidney Disease Reference Network (ERKNet) consensus. It also discusses ongoing controversies and future research directions. The aim is to provide clinicians with the latest evidence-based insights to inform practice, ultimately improving outcomes and quality of life for children with CLUTO.
Humans ; Urology ; Female ; Urethral Obstruction/therapy* ; Pregnancy ; Child ; Europe ; Prenatal Diagnosis ; Infant, Newborn ; Urethra/abnormalities*

Objective To analyze the changing trends of the burden of non-alcoholic fatty liver disease(NAFLD)in China from 1990 to 2021 and provide a basis for formulating prevention and treatment strategies.Methods The standardized incidence rate,prevalence,mortality,and disability-adjusted life year(DALY)rate of NAFLD in China from 1990 to 2021 were extracted from the Global Burden of Disease Study 2021.The average annual percentage change of rate data was calculated by Joinpoint 4.2 and the age,period,and birth cohort effects of the prevalence and DALY rate were analyzed by the age-period-cohort model.Results Compared to 1990,the incidence rate and prevalence of NAFLD have been on the rise,while the mortality and DALY rate have been declining.The age effect curves of prevalence and DALY rate showed an upward trend followed by a downward trend for both males and females.With the period from 1992 to 1996 as the reference group,the period effect curve of prevalence showed a downward trend followed by an upward trend,being the lowest in the period from 2002 to 2006(RR=0.93).The period effect curve of DALY rate showed a downward trend from 1992 to 2011 and then tended to flatten out.With the period from 1972 to 1981 as the reference group,the birth cohort effect curve of prevalence showed a steady upward trend in the general population and both male and female populations.The birth cohort effect curve of DALY rate showed an overall upward trend followed by a downward trend,with the peak occurring in the birth cohort group between 1922 and 1931.The DALY rate of NAFLD caused by smoking and high fasting blood glucose has shown a downward trend since 2014,and fasting blood glucose gradually became the dominant factor as age increased.Conclusions From 1990 to 2021,NAFLD in China has shown a rising prevalence but a significantly declining DALY rate.This suggests that current prevention and control strategies are effective,and further efforts should be made to raise residents' health awareness in controlling the occurrence and development of NAFLD.
Humans ; Non-alcoholic Fatty Liver Disease/epidemiology* ; China/epidemiology* ; Prevalence ; Female ; Male ; Incidence ; Disability-Adjusted Life Years ; Middle Aged ; Adult

Following the principles of evidence-based medicine,in accordance with the structure and drafting rules of standardized documents,based on literature research,according to the characteristics of chronic cough in children and issues that need to form a consensus,the TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children was formulated based on the Delphi method,expert discussion meetings,and public solicitation of opinions.The guideline includes scope of application,terms and definitions,eti-ology and diagnosis,auxiliary examination,treatment,prevention and care.The aim is to clarify the optimal treatment plan of Chinese medicine in the diagnosis and treatment of this disease,and to provide guidance for improving the clinical diagnosis and treatment of chronic cough in children with Chinese medicine.

Objective:To observe the clinical and imaging features of patients with retinal vein occlusion (RVO) complicated with retinal artery occlusion (RAO).Methods:A retrospective clinical study. Fifteen patients with 15 eyes with RVO combined with RAO and macular edema diagnosed by ophthalmology examination in the Department of Ophthalmology, First People's Hospital of Xianyang City during 2 years from February 1, 2022 to January 31, 2024 were included in the study. Branch retinal vein occlusion (BRVO) combined with branch retinal artery occlusion (BRAO) occurred in 3 cases and 3 eyes. Central retinal vein occlusion (CRVO) complicated with central retinal artery occlusion (CRAO) in 12 eyes. Best corrected visual acuity (BCVA), intraocular pressure, scanning laser ophthalmoscope, optical coherence tomography (OCT), fluorescein fundus angiography (FFA) and serum homocysteine were all performed. OCT angiography (OCTA) was performed in 6 eyes. All eyes were treated with intravitreal injection of anti-vascular endothelial growth factor drugs. After the initial 1 treatment, dosage was assessed as needed. Follow-up was performed every month for 12 months after treatment. FFA inspection was performed at 3 months. During follow-up, it was found that there were no perfusion areas of capillaries, and retinal laser photocoagulation therapy was given in time. Fundus manifestations, FFA, OCT, OCTA characteristics and causes of disease were analyzed retrospectively.Results:There were 15 eyes in 15 cases, 9 eyes in 9 males; 6 women with 6 eyes. Age was (61.0±9.7) years. All complained of painless vision loss in one eye. All eyes were positive for relative afferent pupillary disorder. Contralateral congenital optic disc defect was in 1 case; hypertension was in 6 cases; hyperhomocysteinemia was in 2 cases; cerebral infarction was in 3 cases; coronary heart disease was in 1 case. CRVO combined with CRAO was in 12 eyes BCVA light sensitivity-0.25. The BCVA of BRVO combined with BRAO were 0.1, 0.4 and 0.25, respectively. All the patients had retinal edema in the posterior pole of the eye, venous sinuous, dilated, thin arteries and stiff shape. The retina presents with flaky or flame-like bleeding. Posterior polar retinal lint patch was in 13 eyes. In 12 eyes with CRVO combined with CRAO, optic disc edema was observed and the boundary was not clear. In 3 eyes with BRVO combined with BRAO, no obvious abnormality was found in the optic disc, and the boundary was clear. FFA examination showed no or prolonged arterial filling, delayed retinal vein laminar flow, relatively slow or even no capillary filling, macular arteriole atretosis to varying degrees, arch ring structure destruction, optic disc telangiectasia and fluorescein leakage. OCT examination showed that the middle and inner layers of the retina were thickened to varying degrees, the diffuse reflex was enhanced, the interlayer structure was unclear, and the reflex of the lower retinal tissue was weakened. The blood flow density of superficial capillary plexus and deep capillary plexus (DCP) decreased in 6 eyes undergoing OCTA examination. Decreased or interrupted blood flow in the vascular bed of DCP. During the follow-up period, there were 13 eyes with no perfusion area of retinal capillary. The time of occurrence was (1.14±0.95) (0-2) months, and the area was 10-75 disc area. Optic nerve atrophy occurred in 5 eyes. At the last follow-up, visual acuity increased, unchanged and decreased in 12, 2 and 1 eyes, respectively.Conclusions:The pathogenesis of RVO-RAO is complicated. Most RVO and RAO occurred simultaneously, and a few RVO occurred several days after RAO. Although the RAO manifestations are not typical, the radiographic features are both RVO and RAO. Compared with BVRO combined with BRAO, the prognosis of visual acuity in CRAO patients with CRVO is worse.

Aim To investigate the synergistic sensiti-zation effect of saikosaponin D(SSD)combined with temozolomide(TMZ)on glioblastoma cells(GBM)and its molecular mechanism.Methods The sensitiv-ity of RG-2,U251 and LN-428 GBM cell lines to SSD and TMZ was analyzed by CCK-8 method combined with HE staining,and the optimal compatible concen-tration was screened.The effect of HE staining com-bined with Hoechst fluorescence staining on the prolif-eration of GBM cell line was detected by clonal forma-tion experiment.The autophagosome formation of GBM cells was observed by monodansylcadaverine(MDC)staining.The expression and distribution of endoplas-mic reticulum stress-related factors and apoptosis and autophagy proteins were detected by Western blot and ICC.Results The sensitivity order of GBM cells to TMZ was RG-2＞U251＞LN-428.The results of com-bined administration showed the synergistic inhibitory effect of SSD combined with TMZ on proliferation of GBM cell lines,which was confirmed by cell cloning formation experiment.Compared with the TMZ group,Hoechst fluorescence staining showed a significant in-crease in the number of nuclear bright staining in the combined administration group.MDC fluorescence staining showed that there were more dense green parti-cles in the cytoplasm of SSD/TMZ plus group than that of TMZ group.Western blot results showed that com-pared with TMZ group,the expression of ER stress markers GRP78,CHOP,p-PERK and ATF6 signifi-cantly increased in SSD/TMZ group(P＜0.05).The expressions of apoptosis proteins caspase-12,caspase-9,caspase-3,cleaved caspase-3,Bax and autophagy proteins LC3 and Beclin-1 significantly increased(P＜0.05),which were verified by ICC test.Conclusions SSD can cooperate with TMZ to inhibit the prolifera-tion of GBM cells and induce apoptosis and autophagy,and enhance the sensitivity of GBM cells to TMZ by ac-tivating endoplasmic reticulum stress pathway.

Objective:To analyze and summarize the clinical characteristics of mpox patients, thereby to rise clinicians′ awareness of severe mpox and provide a foundation for clinical diagnosis and treatment.Methods:The clinical data were retrospectively analyzed in 41 mpox patients treated at the Beijing You′an Hospital, Capital Medical University, from June to November 2023. Patients were categorized into mild and severe cases based on clinical manifestations, and laboratory results of the two groups were compared. Statistical analysis was performed using the Mann-Whitney U test. Results:The clinical manifestations of 41 mpox patients mainly included fever, rash and lymphadenopathy. Five patients with severe mpox might develop serious complications, including bacterial pneumonia, type Ⅰ respiratory failure, fungal infections, penile or perianal dry gangrene, penile soft tissue edema, intestinal obstruction, septic shock, perianal abscess, and necrotizing fasciitis. Patients with severe mpox had significantly higher white blood cell count (WBC), neutrophil count and C-reactive protein (CRP) level compare to those with mild cases (14.60(9.92, 24.08)×10 9/L vs 6.41(5.64, 8.37)×10 9/L, 12.43(7.02, 21.15)×10 9/L vs 3.35(2.46, 5.03)×10 9/L, 108.20(56.20, 124.10) mg/L vs 16.6(6.25, 49.98) mg/L), while the albumin level and CD4 + T lymphocyte count in the severe group were significantly lower compared to the mild cases (31.80(22.90, 35.15) g/L vs 44.70(42.90, 47.40) g/L, 24.00(12.00, 81.50)/μL vs 606.00(414.50, 767.50)/μL)). All these differences were statistically significant ( U=2.81, 3.02, 2.98, 3.56 and 3.26, respectively, all P<0.01). Conclusions:In clinical practice, clinicians should be vigilant for the possibility of severe mpox if patients exhibit a significant increase of WBC and CRP, a significant decrease in CD4 + T lymphocyte count, or if they develop severe complications.

Objective:To explore the relevancy between the uridine diphosphate-glucuronylgly-cosyltransferase 1A1 (UGT1A1) gene mutation and the phenotype of indirect hyperbilirubinemia in children.Methods:Sixteen cases with indirect hyperbilirubinemia who visited the Department of Gastroenterology, Children's Hospital of Nanjing Medical University from July 2013 to November 2019 were retrospectively analyzed and were divided into Gilbert syndrome (GS), Crigler-Najjar syndrome type II (CNS-II), and indirect hyperbilirubinemia groups unexplained by UGT1A1 gene mutations. The differences in gene mutation site information and general clinical data were compared. The association between gene mutation spectrum and bilirubin level was explored by t-test analysis.Results:Ten of the sixteen cases with indirect hyperbilirubinemia had GS, three had CNS-II, and three had indirect hyperbilirubinemia unexplained by UGT1A1 gene mutations. A total of six mutation types were detected, of which c.211G?>?A accounted for 37.5% (6/16), c.1456T?>?G accounted for 62.5% (10/16), and TATA accounted for 37.5% (6/16), respectively. Compared with the GS group, the CNS group had early disease onset incidence, high serum total bilirubin ( t ?=?5.539, P ??0.05) and age of onset ( t ?=?0.3611, P ?>?0.05) between the two groups. There was no significant correlation between the number of UGT1A1 gene mutations and serum bilirubin levels. Children with c.1456T?>?G homozygous mutations had the highest serum bilirubin levels. Conclusion:The common pathogenic variants of the UGT1A1 gene sequence are c.1456T?>?G, c.211G?>?A, and TATA, indicating that these site mutations are related to the occurrence of indirect hyperbilirubinemia and have important guiding significance for the etiological analysis of indirect hyperbilirubinemia in children.

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.