Objective To investigate the expression profile, prognostic value, gene co-expression network, and immunomodulatory role of BRF1 in a pan-cancer context, and to explore its biological functions and molecular regulatory mechanisms in esophageal squamous cell carcinoma (ESCC). Methods The pan-cancer dataset from The Cancer Genome Atlas (TCGA) was utilized to analyze the differential expression of BRF1 in tumor versus normal tissues, its association with patient survival, pathway enrichment for co-expressed genes, and immune features (including immune checkpoints, cytokines, and immune cell infiltration). The expression profile of BRF1 in ESCC was validated using the Gene Expression Omnibus (GEO) database. In vitro, BRF1 was knocked down in ESCC cells using siRNA. Cell proliferation and migration were assessed by MTT and Transwell assays, respectively. The expression levels of proliferation- and migration-related proteins were detected by Western blotting. The correlation between BRF1 and ferroptosis was analyzed using TCGA data. Results BRF1 was significantly upregulated in over 20 types of cancer, and its high expression was associated with poor prognosis in patients with adrenocortical carcinoma and prostate adenocarcinoma. BRF1 was found to positively regulate the T-cell-mediated cell death pathway in esophageal adenocarcinoma and was associated with the circadian rhythm regulation pathway in pancreatic adenocarcinoma. The correlation of BRF1 with immune checkpoints, cytokine networks, and immune cell infiltration was found to be cancer type-specific. In vitro experiments demonstrated that knocking down BRF1 significantly inhibited the proliferation of ESCC cells, accompanied by the downregulation of the proliferation marker PCNA. Cell migration was also significantly impaired, with decreased expression of Vimentin and MMPs and increased expression of E-cadherin. Furthermore, the expression of BRF1 was positively correlated with that of ferroptosis-antagonizing genes, such as GPX4, HSPA5, and SLC7A11. Conclusion BRF1 plays complex roles in pan-cancer, participating in the regulation of tumorigenesis, progression, and immune infiltration. BRF1 promotes the proliferation and migration of ESCC cells, a mechanism potentially associated with the regulation of ferroptosis resistance. These findings suggest that BRF1 could be a potential therapeutic target for ESCC.

Background and purpose:Gastric cancer,as one of the most common malignant tumors,requires early diagnosis and treatment to improve patient prognosis.This study,based on serum quantitative proteomics research of early-stage gastric cancer patients and non-gastric cancer patients,aims to identify potential diagnostic biomarkers for early gastric cancer.Methods:Serum samples from primary gastric cancer patients and healthy control individuals were collected from Lanzhou University Second Hospital between June and December 2023,following inclusion and exclusion criteria.A protein spectral library was established using Data-Dependent Acquisition(DDA)mode,and each sample was analyzed using Data-Independent Acquisition(DIA)mode.The STRING database was used to analyze protein-protein interactions of upregulated proteins in gastric cancer serum.Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)were used to analyze the pathways and functional annotations of the corresponding genes.Gene expression levels in gastric cancer and non-gastric cancer tissues were analyzed using GEPIA 2,and overall survival of each gene in gastric cancer was analyzed using Kaplan-Meier Plotter.Differential gene expression in clinical gastric cancer and adjacent tissues was validated by quantitative reverse transcription polymerase chain reaction(qRT-PCR)This study was approved by the Ethics Committee of Lanzhou University Second Hospital(Ethical No.:2023A-459)and was exempt from the informed consent.Results:Finally,serum samples from 30 primary gastric cancer patients,29 healthy control individuals,along with the para-cancerous tissues from 8 patients were collected.A total of 666 intersecting proteins were identified through serum quantitative proteomics.Among them,16 proteins showed upregulated expression and 22 proteins showed downregulated expression in the gastric cancer group(P＜0.05,|FC|≥1.5).STRING database analysis showed that 10 upregulated proteins were involved in interaction networks.KEGG and GO analysis indicated that these genes were closely related to the biological processes of cancer occurrence and development.GEPIA 2 and Kaplan-Meier Plotter analysis showed that 6 genes,B2M,TAGLN2,CTSD,HSP90AB1,SH3BGRL3,and CFL1,which were highly expressed in the gastric cancer group(P＜0.05)and associated with poor prognosis.Clinical verification by qRT-PCR confirmed that TAGLN2,CTSD,SH3BGRL3,CFL1 and HSP90AB1 were highly expressed in gastric cancer tissues(P＜0.05).Conclusion:TAGLN2,CTSD,SH3BGRL3,CFL1,and HSP90AB1 have the potential to serve as clinical early gastric cancer diagnostic serum biomarkers,which may facilitate early diagnosis and treatment of gastric cancer.

Objective:To investigate the relationship between lipid levels and cognitive impairment in the elderly Chinese population using prospective cohort data.Methods:Based on the China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) cohort, this study included 24 380 individuals aged ≥60 years who participated in the cognitive function follow-up survey from 2018 to 2019. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), with cognitive impairment defined according to different educational levels: MMSE ≤17 for illiterate individuals, MMSE ≤20 for those with primary education and MMSE ≤24 for those with secondary education or above. Multivariable linear regression and logistic regression models were employed to examine the associations between six baseline lipid indicators and cognitive scores, as well as cognitive impairment. Additionally, restricted cubic splines were used to explore the exposure-dose relationship between lipid levels and cognitive function.Results:The study population had a median follow-up time of 11.6 years, with a baseline age of (59.7±6.8) years. Among the participants, 9 510 (39.0%) were males, and the mean MMSE score was 24.7±6.8. A total of 3 887 individuals (15.9%) were identified as cognitively impaired. The results of multivariable linear regression and logistic regression indicated that total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) levels were not only significantly positively associated with cognitive scores but also significantly associated with a lower risk of cognitive impairment. Each 1 mmol/L increase in these lipid levels corresponded to β values (95% CI) of 0.267 (0.173-0.361), 0.385(0.271-0.499) and 0.331(0.231-0.431), respectively. Each 1 mmol/L increase in these lipid levels corresponded to odds ratio ( OR) (95% CI) values of 0.915 (0.876-0.956), 0.875 (0.830-0.923) and 0.886 (0.848-0.927), respectively. The dose-response curve demonstrated that the negative association was primarily observed within the guideline-recommended optimal lipid level range. Specifically, when LDL-C was less than 3.4 mmol/L and non-HDL-C was less than 4.1 mmol/L, the corresponding OR (95% CI) values were 0.859 (0.796-0.926) and 0.876 (0.818-0.939). Conclusion:Lipid levels exhibit a certain linear negative association with cognitive impairment in elderly Chinese adults, with LDL-C and non-HDL-C demonstrating a stronger effect, particularly within the guideline-recommended optimal range.

Objective:To explore the neuropathological characteristics of brain tissues from autopsy of patients with schizophrenia.Methods:Forty-two autopsy cases from National Human Brain Bank for Health and Disease, School of Medicine, Zhejiang University from January 2013 to December 2024 were selected as research subjects, among which, 21 were schizophrenia patients(schizophrenia group) and 21 were non-schizophrenia patients (non-schizophrenia group). Clinical data of patients from the two groups were compared. HE staining was used to detect the pathological changes such as infarction, hemorrhage and arteriosclerosis in the brain tissues, silver-nitrate staining was used to detect the amyloid plaques in the brain tissues, Congo red staining was used to detect the pathological changes related to cerebral amyloid angiopathy (CAA) in the brain tissues, modified Gallyas silver staining was used to detect the neurofibrillary tangles in the brain tissues, and immunohistochemical staining was used to detect the expressions of phosphorylated tau protein, β-amyloid protein (Aβ), TAR DNA binding protein 43 (TDP-43), and α-synuclein in the brain tissues. Alzheimer's disease neuropathologic change (ADNC), primary age-related tauopathy (PART), limbic-predominant age-related TDP-43 encephalopathy (LATE), aging-related tau astrogliopathy (ARTAG), Lewy body disease (LBD), and cerebrovascular disease (CVD)-related pathological changes in the brain tissues were evaluated, and differences in positive rates of the above pathological changes were compared.Results:No significant difference in gender, age of death, brain weight, or apolipoprotein E genotype was noted between the schizophrenia group and non-schizophrenia group ( P>0.05). Six schizophrenia patients exhibited low-to-intermediate ADNC, including 4 with low ADNC and 2 with intermediate ADNC. Compared with the non-schizophrenia group, the positive rates of ADNC- and CVD-related pathological changes in the schizophrenia group were significantly higher (0 vs. 28.6%; 9.5% vs. 47.6%, P<0.05). No significant differences in positive rates of PART-, LATE-, ARTAG-, and LBD-related pathological changes were noted between the schizophrenia group and non-schizophrenia group ( P>0.05). Conclusion:Schizophrenia patients show high proportions of ADNC- and CVD-related pathological changes, but relatively low ADNC severity.

Geminiviruses cause substantial crop yield losses worldwide. The replication initiator protein (Rep) encoded by geminiviruses is indispensable for geminiviral replication. The Rep protein encoded by beet severe curly top virus (BSCTV, genus Curtovirus, family Geminiviridae) induces VARIANT IN METHYLATION 5 (VIM5) expression in Arabidopsis leaves upon BSCTV infection. VIM5 functions as a ubiquitination-related E3 ligase to promote the proteasomal degradation of methyltransferases, resulting in reduction of methylation levels in the BSCTV C2-3 promoter. However, the specific domains of Rep responsible for VIM5 induction remain poorly characterized. Although Rep proteins from several geminiviruses act as viral suppressors of RNA silencing (VSRs), whether BSCTV Rep also possesses VSR activity remains to be illustrated. In this study, we employed a transient expression system in the 16c-GFP transgenic and the wild-type Nicotiana benthamiana plants to analyze the VSR and the VIM5-inducing activities of different truncated Rep proteins haboring distinct domains. We found that the N-terminal domain (amino acids 1-180) of Rep suppressed GFP silencing in 16c-GFP transgenic N. benthamiana leaves. The minimal N-terminal fragment (amino acids 1-104) induced VIM5 expression upon co-infiltration, while C-terminal truncations lacked VIM5-inducing activity. Our results indicate that the N-terminal domain of Rep encoded by BSCTV mediates the suppression of RNA silencing and induces VIM5 expression. Thus, our findings contribute to a better understanding of interactions between geminiviral Rep and plant hosts.
Geminiviridae/genetics* ; Nicotiana/metabolism* ; Arabidopsis/metabolism* ; RNA Interference ; Viral Proteins/metabolism* ; Arabidopsis Proteins/metabolism* ; Plants, Genetically Modified/metabolism* ; Protein Domains ; Plant Diseases/virology* ; Methyltransferases/metabolism* ; Ubiquitin-Protein Ligases/metabolism* ; DNA Helicases/genetics*

Objective To explore the diagnostic and therapeutic strategies for primary small round cell malignant tumor of the seminal vesicle,so as to provide reference for the early prevention and treatment of this disease.Methods The clinical features,diagnostic approaches and treatment strategies of this case were reported based on literature review.Results A 26-year-old male patient was admitted due to"progressive dysuria complicated with painful urination and difficult defecating for two weeks."Pelvic MRI revealed a large,round,heterogeneous signal mass in the pelvic cavity(rectovesical pouch,posterior-superior to the prostate).Needle biopsy indicated a small round cell malignant tumor.Based on ancillary tests and clinical features,the case was diagnosed as advanced-stage malignancy with no opportunity for surgical intervention,and conservative treatment was initiated.The patient ultimately died two months after pathological diagnosis.A review of literature on seminal vesicle small round cell tumors over the past 20 years indicated that Ewing's sarcoma and rhabdomyosarcoma were the predominant subtypes.Conclusion Primary small round cell malignant tumor of the seminal vesicle is exceptionally rare,and clinically atypical with poor outcomes.While it is diagnostically and therapeutically challenging,early surgical intervention may significantly improve the prognosis and quality of life.

Objective To analyze cases of Langerhans cell histiocytosis(LCH)initially presenting with hemophagocytic lymphohistiocytosis(HLH)in order to enhance clinicians'awareness and avoid misdiagnosis or missed diagnosis.Methods Clinical characteristics of two cases of LCH with HLH as the initial symptom cases were retrospectively collected and analyzed.Results Both patients were male and admitted with"fever and bicytopenia".The physical examination revealed scattered rashes and hepatosplenomegaly.Based on the laboratory results,HLH was initially considered in both children.In case 1,the underlying disease was not immediately identified,but a skin biopsy later confirmed LCH.The patient's symptoms improved with LCH-directed therapy;however,a secondary pulmonary infection triggered progressive hemophagocytosis,which was successfully controlled after adding HLH treatment.In Case 2,HLH treatment initially stabilized the fever.After a skin biopsy confirmed LCH,combined LCH therapy was administered,and the symptoms improved.Both patients received regular chemotherapy according to the CCHG-LCH-2019 protocol.During follow-up,Case 1 developed a BRAF gene mutation and was treated with oral trametinib in addition to chemotherapy.As of the latest follow-up,both patients remained in stable condition.Conclusion Children with HLH and accompanied by a rash should actively search for the underlying cause.A skin biopsy should be performed promptly to clarify the diagnosis.Once the diagnosis is confirmed,active treatment is necessary,a single treatment approach should be avoided,and timely assessment of the condition should be conducted to achieve personalized treatment.

Objectives:This study aims to investigate the association between Chinese visceral adiposity index(CVAI)and the risk of cardiovascular disease(CVD),and explore the sex differences.Methods:Participants were screened from the three sub-cohorts of Prediction for Atherosclerotic Cardiovascular Disease Risk in China(China-PAR)project,baseline information on body measure and biochemistry examinations were collected from 1998,2000-2001,and 2007-2008,separately.Participants were followed up to 2015.Cohort-stratified Cox proportional risk models were used to analyze the relationship between CVAI,both in continuous(per standard deviation increase)and categorical(quartiles,with Q1 as reference)scales,and CVD risk in the total population,men and women.The multiplicative interaction between sex and CVAI on CVD risk were calculated.Restricted cubic spline regression was employed to investigate the dose-response relationship.Results:A total of 98 464 participants without CVD at baseline were included.During the 723 508 person-years of follow-up,3 605 CVD events were recorded.After multivariate adjustment,the HRs(95％CIs)of CVD were 1.25(1.20-1.29),1.09(1.04-1.15),and 1.54(1.46-1.64)for per standard deviation increment in CVAI in the general population,men and women,respectively.Besides,compared with Q1 group,the HRs(95％CIs)in Q4 group were 1.87(1.67-2.10),1.33(1.14-1.54)and 3.84(3.09-4.78),correspondingly,and the effect of CVAI on the risk of CVD was significantly higher in women than in men(Pinteraction<0.05).Additionally,there was a positive dose-response relationship between CVAI and the risk of CVD.Conclusions:Elevated CVAI is an independent risk factor for CVD,especially in women.

Objective:To integrate the best evidence of non drug intervention for blood lipid management of breast cancer survivors used the evidence-based method, and provide evidence-based evidence for clinical medical staff to carry out dynamic monitoring and management of blood lipid abnormalities.Methods:According to the 6S model, the evidence summary, clinical decision, recommended practice, guidelines, systematic review, expert consensus, scientific position statement and other non-drug interventions on lipid management of breast cancer survivors were systematically searched from the evidence-based guidelines website and related databases from database establishment until June 10, 2024. The quality of the included literature was evaluated, and the evidence was extracted, summarized and formed.Results:A total of 14 literatures were included, including 7 guidelines, 5 expert consensus and 2 systematic reviews. Totally 21 best evidences were collected from the necessity of lipid management, lipid management objectives, individualized lipid monitoring and lipid management strategies.Conclusions:The quality and level of the best evidence collected in this study are generally high, which has reference significance for clinical medical staff to carry out scientific and effective non drug intervention in lipid management of breast cancer survivors. In the evidence transformation stage, it is necessary to fully consider the individual differences of patients, in order to improve the intervention effect and the quality of life of patients.

Objective To explore the diagnostic and therapeutic strategies for primary small round cell malignant tumor of the seminal vesicle,so as to provide reference for the early prevention and treatment of this disease.Methods The clinical features,diagnostic approaches and treatment strategies of this case were reported based on literature review.Results A 26-year-old male patient was admitted due to"progressive dysuria complicated with painful urination and difficult defecating for two weeks."Pelvic MRI revealed a large,round,heterogeneous signal mass in the pelvic cavity(rectovesical pouch,posterior-superior to the prostate).Needle biopsy indicated a small round cell malignant tumor.Based on ancillary tests and clinical features,the case was diagnosed as advanced-stage malignancy with no opportunity for surgical intervention,and conservative treatment was initiated.The patient ultimately died two months after pathological diagnosis.A review of literature on seminal vesicle small round cell tumors over the past 20 years indicated that Ewing's sarcoma and rhabdomyosarcoma were the predominant subtypes.Conclusion Primary small round cell malignant tumor of the seminal vesicle is exceptionally rare,and clinically atypical with poor outcomes.While it is diagnostically and therapeutically challenging,early surgical intervention may significantly improve the prognosis and quality of life.