To analyze the disease burden, temporal trends, and attributable risk factors of early-onset female breast cancer (EOBC) in China and globally from 1990 to 2021.

Objective　To analyze the epidemiological characteristics and infection sources of six human Streptococcus suis infection outbreaks in Shenzhen in 2023, and to provide a reference for effective prevention and control of the epidemic. Methods　Field epidemiological methods were used to investigate the disease onset and medical consultation process, exposure history of household and farmer market pork stalls, and other relevant factors. Data on patient demographics, clinical profiles, epidemiological characteristics, and common exposure cases were collected. Blood, cerebrospinal fluid, and environmental samples were collected for pathogen detection and genotyping. Spatial-geographical analysis of infection characteristics was performed using the professional mapping software ArcMap. Results　In 2023, a total of six cases were reported in Shenzhen, all of which were severe hospitalized cases with no deaths. Among them, five cases were of the meningitis type, and one was of the common type. All patients improved and were discharged after treatment. All six cases were male, with a median age of 47.5 years, and all had a history of direct exposure to raw pork through hand-skin wounds. Two cases were engaged in raw pork sales, while four were non-occupationally exposed individuals. Of the six cases, four were identified as Streptococcus suis serotype 2, and two were serotype 14. The positive rate of raw pork and environmental samples was 8.45% (6/71). Field epidemiological investigation found these six outbreaks were mainly directed toward three slaughterhouses in Guangming District, Bao'an District, and Longgang District. However, different genetic typing results suggested sporadic cases. Conclusions　These six outbreaks in Shenzhen in 2023 were all sporadic individual cases, showing characteristics such as multiple-point sporadic occurrences, diversified case composition, and primarily meningitis-type clinical manifestations. Although the genetic typing of the samples varied, the epidemiological investigation indicated three slaughterhouses as potential sources, providing a scientific basis for source control. In infectious disease epidemic source tracing, gene sequencing combined with field epidemiological surveys is more conducive to determining the source of infection and the relationship between transmission.

Objective : To explore the effect and mechanism of CD151 on vascular permeability by regulating vesicle internalization and recycling. Methods: Wild-type mice and CD151 knockout mice were divided into WT-con group, WT-model group, KO-con group and KO-model group, with 6 mice in each group. WT-model group and KO-model group were intraperitoneally injected with LPS to prepare sepsis ALI model, and WT-con group and KO-con group were intraperitoneally injected with phosphate buffer saline(PBS) as a control. 24 h after modeling, pulmonary vascular permeability was measured by Miles test. The siRNA silencing CD151 expression(si-CD151) and negative control si-NC were transfected into EA.hy 926 cells. The permeability of endothelial cell layer to FITC-dextran at different time points was observed under basic conditions and vascular endothelial growth factor-A(VEGF-A) stimulation conditions. Transcriptome sequencing of endothelial cells in si-CD151 group and si-NC group; the distribution and internalization of CD151 in each group were measured using immunofluorescence. Western blot and real-time quantitative RT-qPCR were used to detect the expression of VE-cadherin in si-CD151 groupand other groups. The distribution and internalization of VE-cadherin in each group were measured using immunofluorescence. Results : Miles experiment results indicated that dye exudation in lung tissue of WT-model group was significantly higher than that of WT-con group(P<0.01). The dye exudation in the lung tissue of KO-model group increased compared with WT-model group(P<0.05). The results of endothelial cell layer permeability test showed that the permeability of FITC-dextran in si-CD151 group was significantly higher than that in control group after VEGF-A stimulation for 30, 60 and 120 min(P<0.05). Transcriptome sequencing results suggested that CD151 in endothelial cells was closely related to vesicle-mediated transport. Compared with other groups, protein and mRNA levels of VE-cadherin in CD151 knockdown endothelial cells was significantly lower(allP<0.01). The immunofluorescence assay demonstrated that after VEGF-A stimulation, the decrease of CD151 expression significantly impaired the expression of VE-cadherin at cell-cell contacts and reduced the CD151-VE-cadherin colocalization in the perinuclear region compared with other groups. Conclusion The absence of CD151 affects the internalization and recycling of endothelial cell vesicles, affects the expression and internalization of VE-cadherin, and then influences vascular permeability.

Objective To investigate the prognostic value of optic nerve sheath diameter(ONSD)measured by critical care ultrasound combined with serum biomarkers[S100 calcium-binding protein β(S100β)and neuron-specific enolase(NSE)]in patients with severe traumatic brain injury.Methods A total of 103 adult severe traumatic brain injury patients admitted to the intensive care unit of this hospital from A-pril 1,2023,to April 1,2024 were enrolled.All patients underwent invasive intracranial pressure monitoring after admission,alongside bedside critical care ultrasound measurement of ONSD at 3 mm behind the globe and serum biomarker testing.Baseline data and Glasgow outcome scale(GOS)scores at 90 days after dis-charge were recorded.Patients were divided into the survival and the non-survival groups based on GOS scores.Receiver operating characteristic(ROC)curve analysis and area under the curve(AUC)were used to evaluate the predictive performance of ONSD and serum biomarkers for poor prognosis in severe traumatic brain injury patients.Results Ninety-six patients were ultimately included,with 52(54.1％)in the survival group and 44(45.9％)in the non-survival group.Significant differences were observed in blood glucose,Glas-gow coma scale(GCS)score,acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score,ONSD,NSE,and S100β levels(P＜0.05)between the two groups.Multivariate analysis identified ONSD(OR=4.962,95％CI:3.473-6.254),NSE(OR=2.704,95％CI:1.987-3.033),S100β(OR=2.983,95％CI:1.843-4.571),and APACHE Ⅱ score(OR=3.726,95％CI:2.837-4.592)as independent predictors of mortality in severe traumatic brain injury patients(P＜0.05).The combination of ONSD,NSE,and S100β yielded an AUC of 0.840 for predicting poor prognosis,with a specificity of 88.3％and sensitivity of 98.6％.Conclusion ONSD and serum brain injury biomarkers(NSE,S100β)are associated with in-hospital prognosis in severe traumatic brain injury patients.Their combined detection can effectively predict a poor outcome.

Objective To investigate the expression of Cyclin O(CCNO)in cervical cancer and its molecular mechanism in the progression of cervical cancer.Methods The pathological sections of 60 patients with cervical cancer in the Department of Oncology and Gynecology of the First Affiliated Hospital of Bengbu Medical University from January 2018 to December 2023 were collected,and the expression of CCNO in cervical cancer was detected by immunohistochemistry.The cells were divided into Vector group,CCNO group,siNC group and siCCNO group by transfection technology.CCK-8 assay and colony formation assay were used to evaluate the ability of CCNO to affect cell proliferation.Transwell assay and wound healing assay were used to evaluate the effect of CCNO on cell invasion and migration.Glycolysis assay and Western blot assay were used to evaluate the effect and mechanism of CCNO on glycolysis of cervical cancer cells.Results The results of immunohistochemistry and WB showed that CCNO was highly expressed in cervical cancer(P<0.001).Overexpression of CCNO promoted the proliferation,invasion,migration and glycolysis of cervical cancer cells(P<0.05),whereas the opposite effect inhibited the proliferation,invasion,migration and glycolysis of cervical cancer cells(P<0.05).Bioinformatics analysis and WB results showed that CCNO overexpression may regulate the occurrence of cervical cancer by activating the PI3K/AKT signaling pathway(P<0.05).Conclusion Cyclin O may promote the proliferation and metastasis of cervical cancer cells by regulating glycolysis.

Objective To assess transcriptomic differences between carbon tetrachloride(CCl4)-induced and diethyl 1,4-dihydro-2,4,6-trimethyl-3,5-pyridinedicarboxylate(DDC)diet-induced mouse models of liver fibrosis to provide a framework for future research using mouse liver fibrosis models.Methods Mouse models of liver fibrosis were induced by a 10％ CCl4(2 mL/kg)injection or a 0.1％DDC diet.After 4 weeks of induction,serum levels of ALT,AST,and TBil were measured.HE and Sirius red staining were used to observe hepatic inflammation and collagen deposition.Jamall's method was used to evaluate hydroxyproline(Hyp)content in liver tissues.Hepatic tumor necrosis factor-α(TNF-α),interleukin(IL)-6,and IL-1β were measured by ELISA.Total RNA was extracted from murine liver tissues for RNA-sequencing(RNA-seq).Differentially expressed genes of the two models were analyzed by R software and then GO and KEGG enrichment was performed.Then,genes with significant differences were verified.Results Compared with normal mice,serum levels of ALT,AST,and TBil and hepatic expression of TNF-α,IL-6,and IL-1β were significantly increased in mice that received CCl4 and DDC,while the Alb serum level was decreased.Pathological staining showed that the structures of liver tissues were destroyed and a large number of hepatocytes around the central vein were hyalinized and necrotic in CCl4-treated mice.In DDC diet-treated mice,a large amount of porphyrins had been deposited in the liver and a large number of inflammatory cells had infiltrated into the portal area and bile duct.Different degrees of collagen deposition were observed in the liver tissues of the two model mice.Different genes(DEGs)of CCl4-and DDC diet-treated mice were screened using a filter(|logFC|＞2-fold and P＜0.05).As a result,1820 and 2373 DEGs in CCl4-and DDC diet-treated mice were analyzed,including 1302 and 1978 upregulated genes,and 518 and 395 downregulated genes,respectively.GO annotation showed that the two models had important functions in molecular function,biological process,and cell component.KEGG analysis showed that 22 and 29 signaling pathways were activated in CCl4-and DDC diet-induced models,respectively.Among them,16 signaling pathways,such as extracellular matrix receptor interaction,cell cycle,protein digestion and absorption,focal adhesion,and PI3K-Akt,were significantly enriched in the two models(P＜0.05).Cluster analysis showed that Mup11,Mup15,Mup17,and Mup1 were significantly down-regulated in both models,which were identified by RT-qPCR(P＜0.05).Conclusions This study conducted a comparative analysis of the RNA-Seq transcriptomic features of liver fibrosis models induced by exposure to CCl4 and a DDC diet.It examined the gene expression patterns and the pathways influenced by gene expression.The findings serve as a valuable resource for selecting appropriate animal models for future research on the pathogenesis and treatment of liver fibrosis.

African swine fever(ASF),caused by the African swine fever virus(ASFV),is a highly contagious infectious disease of pigs.This disease has been spread rapidly in China since 2018,po-sing a huge threat to China's pig farming industry.To rapid detect the ASFV,a loop-mediated iso-thermal amplification(LAMP)combined with the disposable nucleic acid visualization test strip was established for visual detection of the nucleic acid of ASFV B646L gene.The method was easy to operate without special instruments and equipment,while it effectively avoided the disadvantage of false positives caused by aerosol contamination.The method was able to detect 1.16 copies/μL of the recombinant plasmid in 50 min at 65 ℃.In addition,the method was specific with no cross-re-action with classical swine fever virus,porcine reproductive and respiratory syndrome virus,por-cine parvovirus,transmissible gastroenteritis virus.The results in this study provides a rapid,con-venient,sensitive and reliable method for early diagnosis and screening for ASFV suspected infec-tion cases.

New approach methodologies(NAMs)based next generation risk assessment for toxicity testing has quietly emerged globally.As an important component of NAMs,quantitative in vitro to in vivo extrapolation(QIVIVE)has come to be one of the significant technologies for chemical toxicity testing and risk assessment,and has gained rapid development and wide applications in the field of toxicology.The implementation of QIVIVE technology relies on two vital branches of computational toxicology:physiologically based toxicokinetics and physiologically based toxicodynamics.The system integrates population research,in vivo/in vitro testing,and computational toxicology research to quantitatively study the nonlinear quantitative relationship between exposure doses and physiological response,providing an efficient and accurate means of toxicity testing for health risk assessment of chemicals.At the same time,utilizing increasingly mature multi omics technologies to obtain high-throughput and effective toxicology information,and drawing a signal network of toxicity occurrence and development in the context of big data can greatly improve the efficiency and range of toxicology research.

Objective To explore the effect of occupational skills relearning programme on hemiplegic arm motor function and ac-tivities of daily living(ADL)in stroke patients. Methods From February,2022 to August,2023,74 stroke patients in Guangdong Work Injury Rehabilitation Hospital were enrolled and randomly divided into control group(n=37)and experimental group(n=37).The control group received conventional rehabilitation training,and the experimental group received additional occupational skills relearning programme,for three weeks.They were assessed with Fugl-Meyer Assessment-Upper Extremi-ties(FMA-UE),Functional Test for the Hemiplegic Upper Extremity-Hong Kong(FTHUE-HK),Motor Activity Log(MAL)-amount of use(AOU)and MAL-quality of movement(QOM),modified Barthel Index(MBI),and Stroke Impact Scale(SIS)-Hand and SIS-ADL before and after treatment. Results The scores in all assessments improved significantly in both groups(|t|>3.597,P<0.05)after treatment,while the scores of FMA-UE,FTHUE-HK,MAL-AOU,MAL-QOM were higher in the experimental group than in the control group(|t|>2.352,P<0.05). Conclusion Occupational skills relearning programme could promote the recovery of hemiplegic arm motor and activity,and facilitate the use of the hemiplegic arm in daily life in stroke patients.

Objective:To explore the efficacy and safety of immunoneoadjuvant therapy with pembrolizumab combined with chemotherapy in locally advanced resectable hypopharyngeal squamous cell carcinoma patients.Methods:This study was a prospective, single arm, single center clinical study that was opened for enrollment in April 2021. Patients who met the inclusion criteria at the Cancer Hospital of the Chinese Academy of Medical Sciences were treated with neoadjuvant therapy of pembrolizumab combined with cisplatin and paclitaxel, and after treatments, received surgery and postoperative adjuvant therapy. The main endpoint of this study was postoperative pathological complete response (pCR), and other observations included adverse reactions and long-term prognoses of patients after neoadjuvant therapy.Results:By September 2023, a total of 23 patients who underwent neoadjuvant therapy and surgery were enrolled in the study and all patients were males aged 49-74 years. All patients were locally advanced stage, including 3 patients in stage Ⅲ and 20 patients in stage Ⅳ. There were 12 cases of primary lesions with posterior ring involvement accompanied by fixation of one vocal cord and 20 cases of regional lymph node metastases classified as N2. Eighteen cases received a two cycle regimen and 5 cases received a three cycle regimen for neoadjuvant therapy. The postoperative pCR rate was 26.1% (6/23), with no surgical delay caused by adverse drug reactions. The laryngeal preservation rate was 87.0% (20/23). Pharyngeal fistula was the main surgical complication, with an incidence of 21.7% (5/23). The median follow-up time was 15 months, and 3 patients experienced local recurrence.Conclusions:The immunoneoadjuvant therapy of pembrolizumab combined with chemotherapy has a high pCR rate in locally advanced resectable hypopharyngeal squamous cell carcinoma, with increased laryngeal preservation rate and no significant impact on surgical safety.