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 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.

Objective To investigate the effect of facet joint resection at different ranges under endoscopy on the stability of the cervical spine and provide a biomechanical theoretical basis for clinical surgery.Methods A normal finite element model of the cervical spine C5-6 was established based on CT data,and unilateral facetectomy models with different ranges(0,25％,50％,75％,and 100％)of laminectomy were obtained(Models 1-5)by simulating cervical endoscopic surgery.The ranges of motion(ROMs)of C5-6 and the von Mises stresses of the discs for the models in each group were compared and analyzed.Results Except for flexion,Models 1 and 2 showed insignificant changes in ROMs and disc von Mises stresses in each direction compared with those of the normal model.Model 3 showed a noticeable increase in ROMs and disc von Mises stresses in each direction compared with those of the normal model:ROMs under flexion,extension,left lateral bending,right lateral bending,left rotation,and right rotation increased by 27％,4％,3％,13％,5％,and 16％,respectively,and von Mises stresses increased by 32％,4％,2％,5％,9％,and 5％,respectively.Models 4 and 5 exhibited a significant increase in the ROMs and disc von Mises stresses in each direction compared to the normal model.For Model 4,ROMs were increased by 27％,14％,6％,24％,7％,167％,and von Mises stresses were increased by 33％,13％,3％,32％,10％,130％.For Model 5,ROMs were increased by 27％,17％,6％,25％,7％,167％,and von Mises stresses were increased by 33％,29％,8％,33％,12％,138％.Conclusions As the range of unilateral facetectomy increased,cervical ROM and disc von Mises stress extremum gradually increased.The cervical spine shows a significant ROM increase and stress changes when facet joint resection on one side exceeds 1/2.More than 1/2 of the facet joint should be preserved during surgery to avoid medical instability.

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 evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.

BACKGROUND: Breast cancer patients who are positive for hormone receptor typically exhibit a favorable prognosis. It is controversial whether chemotherapy is necessary for them after surgery. Our study aimed to establish a multigene model to predict the relapse of hormone receptor-positive early-stage Chinese breast cancer after surgery and direct individualized application of chemotherapy in breast cancer patients after surgery. METHODS: In this study, differentially expressed genes (DEGs) were identified between relapse and nonrelapse breast cancer groups based on RNA sequencing. Gene set enrichment analysis (GSEA) was performed to identify potential relapse-relevant pathways. CIBERSORT and Microenvironment Cell Populations-counter algorithms were used to analyze immune infiltration. The least absolute shrinkage and selection operator (LASSO) regression, log-rank tests, and multiple Cox regression were performed to identify prognostic signatures. A predictive model was developed and validated based on Kaplan-Meier analysis, receiver operating characteristic curve (ROC). RESULTS: A total of 234 out of 487 patients were enrolled in this study, and 1588 DEGs were identified between the relapse and nonrelapse groups. GSEA results showed that immune-related pathways were enriched in the nonrelapse group, whereas cell cycle- and metabolism-relevant pathways were enriched in the relapse group. A predictive model was developed using three genes ( CKMT1B , SMR3B , and OR11M1P ) generated from the LASSO regression. The model stratified breast cancer patients into high- and low-risk subgroups with significantly different prognostic statuses, and our model was independent of other clinical factors. Time-dependent ROC showed high predictive performance of the model. CONCLUSIONS A multigene model was established from RNA-sequencing data to direct risk classification and predict relapse of hormone receptor-positive breast cancer in Chinese patients. Utilization of the model could provide individualized evaluation of chemotherapy after surgery for breast cancer patients.
Humans ; Female ; Breast Neoplasms/genetics* ; East Asian People ; Neoplasm Recurrence, Local/genetics* ; Breast ; Algorithms ; Chronic Disease ; Prognosis ; Tumor Microenvironment