Colorectal tumorigenesis generally progresses from adenoma to adenocarcinoma, accompanied by dynamic changes in the tumor microenvironment (TME). A randomized controlled trial has confirmed the efficacy and safety of Shen-Bai-Jie-Du decoction (SBJDD) in preventing colorectal tumorigenesis. However, the mechanism remains unclear. In this study, we employed single-cell RNA sequencing (scRNA-seq) to investigate the dynamic evolution of the TME and validated cell infiltration with multiplex immunohistochemistry and flow cytometry. Bulk RNA sequencing was utilized to assess the underlying mechanisms. Our results constructed the mutually verifiable single-cell transcriptomic atlases in Apc ^Min/+ mice and clinical patients. There was a marked accumulation of CCL22⁺ dendritic cells (DCs) and an enhanced immunosuppressive action, which SBJDD and berberine reversed. Combined treatment with cholesterol and lipopolysaccharide induced characteristic gene expression of CCL22⁺ DCs, which may represent "exhausted DCs". Intraperitoneal injection of these DCs after SBJDD treatment eliminated its therapeutic effects. TMEM131 derived CCL22⁺ DCs generation by TNF signaling pathway and may be a potential target of berberine in retarding colorectal tumorigenesis. These findings emphasize the role of exhausted DCs and the regulatory mechanisms of SBJDD and berberine in colorectal cancer (CRC), suggesting that the multi-component properties of SBJDD may help restore TME homeostasis and offer novel cancer therapy.

OBJECTIVE To explore the molecular mechanism of Xijiao Dihuang Decoction(XJDHT)in inhibiting inflammatory response in sepsis based on network pharmacology,molecular docking and in vitro and in vivo experiments.METHODS Active com-ponents of XJDHT were screened using the TCMSP and HERB databases.Sepsis-related targets and histone H3K36 trimethylation(H3K36me3)-associated targets were retrieved from GeneCard,OMIM,and DisGeNet databases.A protein-protein interaction(PPI)network was constructed using the STRING database,and core targets were identified via Cytoscape 3.9.1.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed to predict potential mechanisms.Mo-lecular docking validated ligand-receptor binding affinity.A cecal ligation and puncture(CLP)model was established in mice to evalu-ate 24-hour sepsis scores(MSS)and survival rates.Blood routine parameters were analyzed using an automated hematology analyzer.Serum IL-1β and TNF-α levels were measured by ELISA.Liver histopathology was assessed via HE staining,and H3K36me3 expression in Kupffer cells was detected by immunofluorescence.In vitro,LPS-induced THP-1 cells were used as an in-flammatory model.ChIP-qPCR evaluated H3K36me3 enrichment at IL-1β and TNF-α gene loci.Western blot analyzed HIF-1α,EGFR,and AKT1 pathway proteins.RESULTS A total of 28 active components of XJDHT were identified,corresponding to 987 gene targets,with 189 overlapping sepsis-related targets.Core targets included TNF,IL1B,and GAPDH.Enriched pathways includ-ed EGFR tyrosine kinase inhibitor resistance.Molecular docking confirmed strong binding between core components and key targets.In vivo,compared to the sham group,the CLP group exhibited significantly reduced 24-hour survival(P<0.01),elevated MSS(P<0.01),immune imbalance,and increased serum IL-1β and TNF-α levels(P<0.01).High-and low-dose XJDHT intervention im-proved survival(P<0.01),reduced MSS(P<0.01),restored immune homeostasis,and dose-dependently suppressed IL-1β and TNF-α(P<0.01).CLP mice showed elevated H3K36me3 in Kupffer cells and severe hepatic inflammation,while XJDHT dose-de-pendently reduced H3K36me3(P<0.05)and attenuated liver injury.In peritoneal macrophages,CLP upregulated H3K36me3,IL-1β,TNF-α,HIF-1α,p-AKT1/AKT1,and EGFR(P<0.01),which were reversed by XJDHT(P<0.05,P<0.01).In vitro,LPS increased H3K36me3 and IL-1β and TNF-α expression(P<0.01),with ChIP-qPCR confirming H3K36me3 enrichment at IL-1β lo-ci(P<0.01).Treatment with 15%XJDHT-containing serum for 24 h reduced H3K36me3(P<0.01),diminished its recruitment to IL-1β loci(P<0.01),and inhibited LPS-induced activation of EGFR,HIF-1α,and p-AKT1/AKT1(P<0.05,P<0.01).HIF-1α agonist Dimethyloxallyl Glycine(DMOG)further validated that XJDHT suppressed H3K36me3-mediated epigenetic remodeling via HIF-1α-related pathways.CONCLUSION XJDHT inhibits inflammatory responses,regulates immune homeostasis,and improves sepsis prognosis,potentially by modulating H3K36me3 epigenetic modifications at IL-1β loci.

OBJECTIVE To explore the molecular mechanism of Xijiao Dihuang Decoction(XJDHT)in inhibiting inflammatory response in sepsis based on network pharmacology,molecular docking and in vitro and in vivo experiments.METHODS Active com-ponents of XJDHT were screened using the TCMSP and HERB databases.Sepsis-related targets and histone H3K36 trimethylation(H3K36me3)-associated targets were retrieved from GeneCard,OMIM,and DisGeNet databases.A protein-protein interaction(PPI)network was constructed using the STRING database,and core targets were identified via Cytoscape 3.9.1.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed to predict potential mechanisms.Mo-lecular docking validated ligand-receptor binding affinity.A cecal ligation and puncture(CLP)model was established in mice to evalu-ate 24-hour sepsis scores(MSS)and survival rates.Blood routine parameters were analyzed using an automated hematology analyzer.Serum IL-1β and TNF-α levels were measured by ELISA.Liver histopathology was assessed via HE staining,and H3K36me3 expression in Kupffer cells was detected by immunofluorescence.In vitro,LPS-induced THP-1 cells were used as an in-flammatory model.ChIP-qPCR evaluated H3K36me3 enrichment at IL-1β and TNF-α gene loci.Western blot analyzed HIF-1α,EGFR,and AKT1 pathway proteins.RESULTS A total of 28 active components of XJDHT were identified,corresponding to 987 gene targets,with 189 overlapping sepsis-related targets.Core targets included TNF,IL1B,and GAPDH.Enriched pathways includ-ed EGFR tyrosine kinase inhibitor resistance.Molecular docking confirmed strong binding between core components and key targets.In vivo,compared to the sham group,the CLP group exhibited significantly reduced 24-hour survival(P<0.01),elevated MSS(P<0.01),immune imbalance,and increased serum IL-1β and TNF-α levels(P<0.01).High-and low-dose XJDHT intervention im-proved survival(P<0.01),reduced MSS(P<0.01),restored immune homeostasis,and dose-dependently suppressed IL-1β and TNF-α(P<0.01).CLP mice showed elevated H3K36me3 in Kupffer cells and severe hepatic inflammation,while XJDHT dose-de-pendently reduced H3K36me3(P<0.05)and attenuated liver injury.In peritoneal macrophages,CLP upregulated H3K36me3,IL-1β,TNF-α,HIF-1α,p-AKT1/AKT1,and EGFR(P<0.01),which were reversed by XJDHT(P<0.05,P<0.01).In vitro,LPS increased H3K36me3 and IL-1β and TNF-α expression(P<0.01),with ChIP-qPCR confirming H3K36me3 enrichment at IL-1β lo-ci(P<0.01).Treatment with 15%XJDHT-containing serum for 24 h reduced H3K36me3(P<0.01),diminished its recruitment to IL-1β loci(P<0.01),and inhibited LPS-induced activation of EGFR,HIF-1α,and p-AKT1/AKT1(P<0.05,P<0.01).HIF-1α agonist Dimethyloxallyl Glycine(DMOG)further validated that XJDHT suppressed H3K36me3-mediated epigenetic remodeling via HIF-1α-related pathways.CONCLUSION XJDHT inhibits inflammatory responses,regulates immune homeostasis,and improves sepsis prognosis,potentially by modulating H3K36me3 epigenetic modifications at IL-1β loci.

Objective To determine the epidemiological and etiological characteristics of hand，foot，and mouth disease （HFMD） in Pujiang County from 2008 through 2020， so as to provide scientific evidence for prevention and control measures. Methods Descriptive epidemiological analysis was used to analyze HFMD cases retrieved in the Chinese Information System for Disease Control and Prevention in Pujiang County during 2008‒2020. Results From 2008 through 2020， a total of 9 393 cases were documented in Pujiang County， with an annual incidence of 182.3 per 100 000， showing a trend of alternating high-incidence and low-incidence years. The seasonal distribution was bimodal， and the incidence peaked in May-July and November-December. The incidence of HFMD in urban areas was significantly higher than that in rural areas， and the incidence was positively correlated with population density. Majority of cases （94.9%） were children under 5 years old， of which boys had higher incidence than girls. The number of documented cases was the highest among preschool children living in families and kindergartens， accounting for 97.3%. Totally， 558 cases were laboratory confirmed in Pujiang County in 2008-2020， of which severe cases were all caused by EV71 infection. Conclusion Enterovirus serotypes in HFMD have continually changed from 2008 through 2020 in Pujiang County. However， severe HFMD remains principally attributable to EV71 infection， suggesting that it is necessary to strengthen the surveillance on the etiology of HFMD. In addition， it warrants further promotion of EV71 vaccination.

Objective To analyze the clinical factors for pathologic complete response ( pCR) after preoperative neoadjuvant chemoradiotherapy ( neo?CRT) for locally advanced rectal cancer. Methods From 2005 to 2012, 297 patients with locally advanced rectal cancer and complete clinical data were enrolled as subjects. Those patients were diagnosed with biopsy and treated with neo?CRT ( radiotherapy by 3?dimonsional conformal radiotherapy or volumetric?modulated arc therapy) followed by radical surgery. The logistic regression model was used for the multivariate analyses of the correlation of pCR with age, gender, distance between tumor and the anal verge, serum level of carcinoembryonic antigen ( CEA ) before treatment, hemoglobin level before treatment, cT staging, and cN staging. Results In all patients, 78 ( 26?7%) patients had pCR after treatment. The numbers of patients with pCR were 42( 34?4%) in patients with stage T1?T3 disease and 37(21?1%) in patients with stage T4 disease. In the patients with serum CEA levels no higher than 5?33 ng/ml, 55(36?4%) had pCR after treatment, while in the patients with serum CEA levels higher than 5?33 ng/ml, only 24( 16?4%) had pCR. The univariate analysis revealed that age, gender, distance between tumor and the anal verge, anemia before treatment, or cN staging were not related to pCR. The multivariate analysis showed that stage cT1?T3 and a serum CEA level no higher than 5?33 ng/ml before treatment were influencing factors for pCR after neo?CRT for locally advanced rectal cancer ( P=0?031,P=0?000) . Conclusions The clinical staging and the serum CEA level before treatment are influencing factors for pCR after neo?CRT for locally advanced rectal cancer. The serum CEA level before treatment can be considered as a predictor of pCR after neo?CRT for locally advanced rectal cancer.

This paper presents a unit free-form deformation (FFD) method applied to rapid three-dimensioanl (3D) bone reconstruction, which was based on traditional FFD. With the femur as an example, we reconstructed a 3D model of femur from two X-ray images and a standardized model by taking advantage of unit FFD algorithm. The X-ray images and its parameters were taken by C-arm device. Those parameters and X-ray contour are contributed to 3D reconstruction. The out contours of X-ray image and standard model were connected by point matching algorithm. The unit-FFD lattice was built to reconstruct standard model and finally made the contour of X-ray image and standard model exactly the same. Experiments on shape accuracy, robustness and time consuming, carried out by 35 specimen from cadaver, showed that mean error of shape (0. 52 mm) and mean construction time (112 s) were lower than those using traditional method (0.7-2.6 mm, 8-20 min). The method proposed in this paper shows a good prospect in clinical application and related research.
Algorithms ; Femur ; anatomy & histology ; diagnostic imaging ; Humans ; Imaging, Three-Dimensional ; Models, Anatomic ; Radiography

This paper is aimed to focus on the joint prosthesis failure event, to collect the statistic data about the failure of artificial joints issued by authoritative organizations at home and aboard, and to compare the functions of different types of the artificial joints. We generalized and compared current study analyzing the failure reason and type of joint prosthesis, and categorized the failure events according to the failure occurring time, i. e. short-term, medium-term and long-term. This paper could be helpful for improving and summarizing of artificial joint replacement surgery, and could put forward the requirements for the future artificial joints.
Arthroplasty, Replacement ; adverse effects ; statistics & numerical data ; Arthroplasty, Replacement, Hip ; adverse effects ; statistics & numerical data ; Arthroplasty, Replacement, Knee ; adverse effects ; statistics & numerical data ; Humans ; Joint Prosthesis ; Prosthesis Failure ; etiology

A whole technical way of reconstructing 3D model of the scoliotic spine from two X-ray images was proposed. From the experimental results of 30 patients with mild to severe scoliosis, we can conclude that the accuracy of locating vertebrae is 0.5 mm, the orientation accuracy was 1.5. After comparing the results with those using the previous methods, we found that the method proposed in this paper can get higher resolution with less computational time, making it suitable for clinical routine use.
Humans ; Imaging, Three-Dimensional ; methods ; Models, Statistical ; Radiography ; Scoliosis ; diagnostic imaging ; Spine ; diagnostic imaging

Identifying the origin of body fluids left at a crime scene can give a significant insight into crime scene reconstruction by supporting a link betw een sample donors and actual criminal acts. How ev-er, the conventional body fluid identification methods are prone to various limitations, such as time con-sumption, intensive labor, nonparallel manner, varying degrees of sensitivity and limited specificity. Re-cently, the analysis of cell-specific messenger RNA expression (mRNA profiling) has been proposed to supplant conventional methods for body fluid identification. Since 2011, the collaborative exercises have been organized by the European DNA Profiling Group (EDNAP ) in order to evaluate the robustness and reproducibility of mRNA profiling for body fluid identification. The major advantages of mRNA profil-ing, compared to the conventional methods, include higher sensitivity, greater specificity, the ability of detecting several body fluids in one multiplex reaction, and compatibilitywith current DNA extraction and analysis procedure. In the current review ,we provided an overview of the present know ledge and detection methodologies of mRNA profiling for forensic body fluid identification and discussed its possi-ble practical application to forensic casew ork.

This paper focused on the joint prosthesis failure event, through survey and investigation in different kinds of case studies, generalized and analyzed the failure reason of joint prosthesis. The failure reason been categorized according to the failure occurring time: short-term, medium-term and long-term, and for each category, the characteristics and root causes are discussed, and the corresponding countermeasures put forward.
Arthroplasty, Replacement ; instrumentation ; Equipment Failure Analysis ; Humans ; Joint Prosthesis ; Prosthesis Failure