Objective:To analyze the changes of DNA methylation in peripheral blood mononuclear cells (PBMC) of patients with hepatocellular carcinoma (HCC) and to evaluate the clinical value of a combined model based on FSIP1 gene methylation on the early diagnosis of HCC.Methods:This is a case-control study. From May 2023 to September 2024, 183 HCC patients and 155 healthy controls were collected in Qilu Hospital of Shandong University. The selected study subjects were divided into three cohorts: 14 HCC patients and 39 healthy controls formed the discovery cohort, a screening cohort consisted of 36 HCC patients and 39 healthy controls, 133 HCC patients and 77 healthy controls were included in the model construction cohort. 935k methylation chip analysis was used to identify specific differentially methylated sites in peripheral blood PBMC of the discovery cohort. The absolute value of the average methylation level difference between HCC group and healthy control group (|Δβ|) and P value were calculated. Then targeted bisulfite sequencing was used to verify the differentially methylated sites in the screening cohort. Finally, based on MethylTarget methylation sequencing technology, differential methylation sites were further verified in model construction cohort (divided into training set and validation set, training set consisted of 99 HCC patients and 57 healthy controls; validation set consisted of 34 HCC patients and 20 healthy controls). HCC early diagnosis model was constructed by random forest algorithm combined with clinical parameters and the diagnostic performance of the model was evaluated by receiver operating characteristic (ROC) curve in the validation set. Results:The total of 7 249 differentially methylated sites between HCC patients and healthy controls in discovery cohort were selected under the rule of |Δβ|≥0.06 and P<0.01. Among them, the cg02155073 site located on FSIP1 was hypermethylated in PBMC of HCC patients in the screening cohort and model cohort ( P<0.001). The AUC of HCC early diagnosis model (FmAP) based on FSIPI in the validation set was 0.967 (95% CI 0.924-1.000); sensitivity was 88%, specificity was 95%. The model had good diagnostic efficacy for patients with early HCC, stage Ⅰ-Ⅱ HCC AUC was 0.958 (95% CI 0.898-1.000). The FmAP model also had diagnostic value for tumor size <2 cm HCC and AFP negative HCC, with AUC of 0.955 (95% CI 0.898-1.000) and 0.964 (95% CI 0.934-0.994).The sensitivity were 92% and 93% and specificity both were 84%. Conclusion:The FmAP model based on FSIP1 gene methylation has good clinical value for the early diagnosis of hepatocellular carcinoma.

Objective To analyze the epidemiological characteristics of acute respiratory infections(ARIs)during the autumn-winter season in Beijing,providing evidence for the prevention,control,diagnosis,and treatment of ARIs.Methods A convenience sampling method was employed,enrolling patients who visited Peking Union Medical College Hospital(PUMCH)between September 2023 and February 2024 due to ARIs.Na-sopharyngeal swabs were collected,and real-time fluorescence quantitative PCR was used to detect six common respiratory pathogens[influenza A virus(FluA),influenza B virus(FluB),human rhinovirus(HRV),Myco-plasma pneumoniae(MP),respiratory syncytial virus(RSV),and adenovirus(ADV)],as well as SARS-CoV-2 infection.The distribution patterns of pathogen infections were analyzed.Results A total of 5556 eligible patients were included.The overall positivity rate for the six common respiratory pathogens was 63.7％,with sin-gle-pathogen positivity at 54.0％,dual-pathogen positivity at 8.9％,and triple or more pathogen positivity at 0.7％.The predominant pathogens detected were FluA(16.1％)and RSV(15.7％),followed by ADV(11.1％),MP(11.1％),HRV(10.0％),and FluB(10.0％).No significant difference in overall pathogen positivity was observed between genders.However,significant differences were found between autumn and winter(x2=34.617,P＜0.001)and among pediatric,young/middle-aged,and elderly patients(x2=422.38,P＜0.001).Specifically,MP(x2=8.647,P=0.003),FluA(x2=131.932,P＜0.001),and HRV(x2=174.199,P＜0.001)exhibited significantly higher positivity rates in autumn than in winter,whereas FluB was more prevalent in winter(x2=287.894,P＜0.001).In pediatric patients,MP,RSV,HRV,and ADV positivity rates were significantly higher than in young/middle-aged and elderly patients(all P＜0.001),whereas FluB was more common in young/middle-aged patients(both P＜0.001).The positivity rates of the six common respiratory pathogens significantly declined during the SARS-CoV-2 epidemic period,exhibiting an asynchronous seasonal pattern.Conclusions The prevalence of respiratory pathogens in Beijing is associated with age and season.Tar-geted preventive measures should be implemented in different seasons and for key populations.

The objective of this study was to evaluate the protective effect and possible related mechanisms of Sophora subprostrate polysaccharide(SSP)on intestinal epithelial cell injury in-duced by Tert-Butyl hydroperoxide(TBHP).The optimal dose of TBHP and the safe concentra-tion range of SSP were determined using the MTT method.In this study,IPEC-J2 cells were divid-ed into five groups:the control group,the model group,the SSPL group,the SSPM group and the SSPH group,and the cell morphology,cell survival rate and LDH release rate were observed and measured.The content of intracellular reactive ROS was observed and determined by DCFH-DA staining.The content of MDA in the supernatant and the antioxidant index of cells were determined by the reagent kit.Transcriptome technology was employed to analyze the potential mechanisms by which SSP mitigates oxidative damage in IPEC-J2 cells.The results showed that treatment with 625 μmol/L TBHP for 2 h significantly reduced the activity of IPEC-J2 cells,markedly increased LDH release(P＜0.05),inhibited CAT superoxide SOD and glutathione GPX activities(P＜0.05),and significantly elevated MDA and ROS levels(P＜0.05).Compared to the model group,after SSP treatment,intracellular ROS levels were significantly reduced(P＜0.05),while CAT,SOD,and GPX activities were significantly increased(P＜0.05),and MDA content and LDH re-lease were significantly decreased(P＜0.05)in a dose-dependent manner.Transcriptome analysis revealed that TBHP treatment significantly altered the transcriptional profiles of IPEC-J2 cells,while SSP treatment could restore the transcriptional profiles of the damaged cells to a certain ex-tent.Gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)indicated that the differentially expressed genes between the CC and TBHP groups were significantly enriched in oxidative phosphorylation,ribosome,and other pathways.Meanwhile,the differentially expressed genes between the SSP and TBHP groups were mainly enriched in oxidative phosphorylation,ap-optosis,glyoxylate and dicarboxylate metabolism,and other pathways.These results suggest that TBHP may disrupt normal oxidative respiration in IPEC-J2 cells by affecting oxidative phospho-rylation and interfering with metabolism pathways involving glycine,serine,and threonine,leading to oxidative damage in intestinal epithelial cells.Conversely,SSP treatment may potentially restore oxidative phosphorylation processes,alleviate lysosomal damage,reduce cell apoptosis,and miti-gate oxidative damage in intestinal epithelial cells through modulation of oxidative phosphoryla-tion,apoptosis,and lysosomal pathways.This discovery provides a theoretical basis for the clinical application of SSP in alleviating oxidative damage in the porcine intestinal tract.

Objective:To explore the clinical and salivary metabolic component characteristics of patients with OSA combined with LPRD, and to investigate the potential co-morbid mechanisms of LPRD and OSA.Methods:A total of 98 adult patients with OSA (81 males and 17 females) who visited the Department of Otolaryngology of Peking University Third Hospital from March 2024 to May 2024 were consecutively included. The age ranged from 19 to 68 years (mean±standard deviation: 39.44±11.39 years). The severity of OSA was grouped according to the apnea-hypopnea index (AHI) [mild group (29 cases), moderate group (26 cases), and severe group (43 cases)]. Patients with a reflux symptom index score (RSI)>13 points and/or a reflux sign score (RFS)>7 points were considered LPRD positive. Among the 98 OSA patients, 48 had LPRD and 50 did not. All patients were diagnosed with OSA through out of center sleep testing(OCST) or polysomnography (PSG), and general information, laryngoscopic examination images, and RSI scales were collected. The RFS was evaluated based on the laryngoscopic examination results. Saliva samples were collected from both groups for metabolomics analysis. Chi-square test was used for categorical variable comparison, and independent sample t-test or one-way ANOVA analysis of variance was used for continuous variable comparison.Results:Stratified analysis showed that the proportion of male patients in the mild OSA group was significantly lower than that in the moderate or severe OSA groups (58.6%, 92.3%, 93.0%, χ2=16.43, P<0.001), and the BMI was significantly lower in the mild OSA group [(25.80±4.41)kg/m 2, (27.53±3.88)kg/m 2, (28.99±3.65)kg/m 2, F=6.91, P=0.002]. There was no statistically significant difference in the prevalence of LPRD among patients with different severity of OSA. The BMI of OSA patients with LPRD was higher than that of patients with OSA alone [(28.65±4.75)kg/m 2, (26.94±3.16)kg/m 2, t=-2.07, P=0.041], but there were no statistically significant differences in gender composition, age, AHI, and minimum blood oxygen saturation between the two groups. The metabolomics results of saliva samples from both groups showed significant differences in the levels of tryptophan pathway metabolites. The salivary serotonin metabolite level in patients with LPRD combined with OSA was significantly lower than that in patients with OSA alone (relative abundance 0.12±0.019 vs 0.22±0.046, t=2.04, P=0.045). Conclusion:Patients with OSA combined with LPRD have a greater BMI and significantly lower serotonin, a tryptophan metabolite component of saliva, which may be a potential co-morbidity mechanism between OSA and LPRD.

Aim To investigate the role of triggering receptor expressed on myeloidcells 2(TREM2)in syn-aptic plasticity induced by cocaine addiction.Methods C57BL/6J mice and Trem2 knockout mice were uti-lized in this study to evaluate the alterations in postsyn-aptic density protein 95(PSD-95)and synapsin 1(SYN1)within the cortex and hippocampus of co-caine-addicted mice by using immunological tech-niques.Results HE staining and Nissl staining showed increased neuronal damage in the hippocampus and cortex of mice after cocaine addiction.The results of immunohistochemistry and fluorescence of PSD-95 and SYN1 were consistent with the expression trend of Western blot.In the wild type mouse model,the ex-pression level of PSD-95 in the hippocampus and cortex was lower than that in the saline group,and the ex-pression of SYN1 was higher than that in the saline group.In the knockout mouse model,the expression levels of PSD-95 and SYN1 in the hippocampus and cortex were significantly higher than those in the saline group after cocaine addiction.The expression levels of PSD-95 and SYN1 in the hippocampus and cortex of cocaine knockout mice were higher than those of co-caine wild type mice.Conclusion Cocaine addiction can change the synaptic plasticity,and TREM2 plays a regulatory role in the synaptic plasticity of hippocampus and cortex in mice with cocaine injury.TREM2 is ex-pected to be a new target for studying the mechanism of cocaine addiction.

Aim To explore the mechanism of action of Guizhi Jia Gegen decoction(GGD)in treating pneu-monia-enteritis induced by H1N1 influenza virus infec-tion in a mouse model,using network pharmacology and molecular docking techniques,followed by in vivo verification.Methods A pneumonia-enteritis mouse model was established,and the intervention effects of GGD on the model mice were evaluated using indica-tors such as body weight,rectal temperature,lung in-dex,colon length,H1N1 M gene expression,relative mRNA expression levels of inflammatory cytokines,and pathological sections of the lung and intestine.The targets of the blood-absorbed components of GGD were identified using the Swiss Target Prediction platform,and the disease targets were retrieved from the Gene-Cards platform.The intersecting targets were analyzed through PPI network analysis using the STRING data-base to identify core targets.GO analysis and KEGG pathway enrichment analysis were performed using the Metascape database.RT-qPCR was employed to vali-date the core targets and pathways.Molecular docking was conducted using AutoDock Tools software to verify the interactions between blood-absorbed components and key targets.Results GGD demonstrated signifi-cant therapeutic effects on the pneumonia-enteritis mouse model.The results of network pharmacology in-dicated that the therapeutic effects of GGD were strong-ly associated with targets such as TNF,ALB,PTGS2,MMP9,EGFR,ESR1,SRC,HSP90AA1,PPARG and MMP2.RT-qPCR results indicated that GGD could intervene in pneumonia-enteritis by regulating the targets TNF,ALB,EGFR and the related targets of the NF-κB pathway.Molecular docking results re-vealed that blood-absorbed components such as puerar-in and liquiritin could stably bind to TNF,ALB and EGFR.Conclusion Components such as puerarin and liquiritin in GGD may exert therapeutic effects on pneumonia-enteritis induced by H1N1 influenza virus infection by acting on targets such as TNF,ALB and EGFR.

Background::Computer-aided detection (CAD) software has been introduced to automatically interpret digital chest X-rays. This study aimed to evaluate the performance of CAD software (JF CXR-1 v3.0, which was developed by a domestic Hi-tech enterprise) in tuberculosis (TB) case finding in China.Methods::In 2019, we conducted an internal evaluation of the performance of JF CXR-1 v3.0 by reading standard images annotated by a panel of experts. In 2020, using the reading results of chest X-rays by a panel of experts as the reference standard, we conducted an on-site prospective study to evaluate the performance of JF CXR-1 v3.0 and local radiologists in TB case finding in 13 township health centers in Zhongmu County, Henan Province.Results::Internal assessment results based on 277 standard images showed that JF CXR-1 v3.0 had a sensitivity of 85.94% (95% confidence interval [CI]: 77.42%, 94.45%) and a specificity of 74.65% (95% CI: 68.81%, 80.49%) to distinguish active TB from other imaging conditions. In the on-site evaluation phase, images from 3705 outpatients who underwent chest X-ray detection were read by JF CXR-1 v3.0 and local radiologists in parallel. The imaging diagnosis of local radiologists for active TB had a sensitivity of 32.89% (95% CI: 22.33%, 43.46%) and a specificity of 99.28% (95% CI: 99.01%, 99.56%), while JF CXR-1 v3.0 showed a significantly higher sensitivity of 92.11% (95% CI: 86.04%, 98.17%) ( p < 0.05) and maintained high specificity at 94.54% (95% CI: 93.81%, 95.28%). Conclusions::CAD software could play a positive role in improving the TB case finding capability of township health centers.

The accuracy of medical imaging diagnosis will directly impact the clinical forensic evaluation's scientific validity and objectivity.This study systematically analyzed the primary causes of misdiagnosis and missed diagnosis in imaging examinations,focusing on representative cases,including rib fractures,traumatic subarachnoid hemorrhage,joint injuries with ligament damage,nasal fractures,congenital skeletal variations,and epiphyseal injuries.Key contributing factors encompassed limitation of imaging technologies,the insufficient interpretive experience of examiners,the complexity of injury mechanisms,and inadequate post-traumatic dynamic imaging follow-up.To address these issues,improvement strategies are proposed,which were establishing standardized imaging review protocols,implementing multimodal imaging approaches,rigorous evaluation of original imaging data,and enhancing professional knowledge regarding anatomical variations and injury differentiation.These measures aim to elevate the quality of forensic imaging diagnosis,providing more precise and reliable strategies for forensic clinical identifications.

Objective:To explore the influence of initial high-risk cytogenetic abnormalities on the outcomes of children with acute myeloid leukemia (AML) after post-transplant Cyclophosphamide (PTCy)-based allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:A retrospective cohort study.AML children who underwent PTCy-based allo-HSCT after the first complete remission at Wuhan Children′s Hospital, Tongji Medical College, Huazhong University of Science and Technology between April 2017 and April 2024 were enrolled.Patients were divided into intermediate-risk and high-risk groups based on their initial cytogenetic features.These patients were further divided into complex karyotype, 11q23 rearrangement, and other karyotype groups.Clinical characteristics and survival outcomes were compared among these groups.Measurement and count data were analyzed using Wilcoxon rank-sum/Kruskal-Wallis and χ2 tests, respectively.Survival and risk factor analyses were performed using Kaplan-Meier and Cox proportional hazards methods, respectively. Results:A total of 51 AML children who underwent allo-HSCT were included in this study.The median age at transplantation was 3.2 years and the median follow-up time was 4.6 years.There were 26 cases in the intermediate-risk group and 25 cases in the high-risk group; 8 cases in the complex karyotype group, 14 cases in the 11q23 rearrangement group, and 29 cases in the other karyotype groups.By the end of the follow-up on November 30, 2024, 11 patients relapsed, 8 patients died, and 13 patients developed grades Ⅱ-Ⅳ acute graft-versus-host disease (GVHD).The 3-year overall survival (OS), relapse-free survival (RFS), and grades Ⅱ-Ⅳ acute GVHD-free and relapse-free survival (GRFS) were 84.0% (95% CI: 74.4%-94.8%), 74.5% (95% CI: 63.4%-87.5%), and 58.8% (95% CI: 46.7%-74.0%), respectively.The 3-year OS of the high-risk group was significantly lower than that of the intermediate-risk group (71.8% vs.96.2%, P=0.022), while differences in 3-year RFS and GRFS between the 2 groups were not statistically significant (68.0% vs.80.8%, P=0.400; 52.0% vs.65.4%, P=0.420).The 3-year OS, RFS and GRFS of the complex karyotype group were significantly lower than those of 11q23 rearrangement and other karyotype groups (50.0% vs.85.7%, 93.1%, P=0.009; 37.5% vs.85.7%, 79.3%, P=0.022; 25.0% vs.64.3%, 65.5%, P=0.049).Multivariate analysis showed that a complex karyotype was an independent prognostic factor affecting 3-year OS and GRFS [OS: HR=6.79 (95% CI: 1.13-43.80), P=0.044; GRFS: HR=3.72(95% CI: 1.13-12.20), P=0.030]. Conclusions:High-risk cytogenetic features are significant predictors of survival outcomes in pediatric AML patients undergoing PTCy-based allo-HSCT.

This study was aimed at determining the molecular characteristics of Yersinia pestis in the natural plague foci around Qinghai Lake through single nucleotide polymorphism technology,to lay a foundation for molecular epidemiological and source-tracing analysis of Y.pestis in this area.Using the whole genome sequencing technology,we obtained the whole genome sequences of 84 representative Y.pestis strains.Using the sequences of Y.pestis and Yersinia pseudotuberculosis IP32953 from the NCBI database as references,we compared and analyzed the 2 298 SNP loci of these strains.From 1957 to 2020,84 representative strains of Y.pestis from the natural plague foci around Qinghai Lake were divided into two clades:1.IN2 and 3.ANT1.The 1.IN2 clade was the characteristic population of Y.pestis throughout all epidemic years in this area.Additionally,analysis of the SNP distribution and hosts in the region indicated that the 1.IN2 clade was located in five counties except Wulan,whereas the 3.ANT1 clade was isolated from Himalayan marmot and dog in two counties.In conclusion,the population structure of SNP of Y.pestis in the natural plague foci around Qinghai Lake is relatively simple,and SNP analysis of Y.pestis provided a scientific basis for tracing plague epidemic sources and formulating plague prevention and control measures in this area.