Colorectal cancer(CRC) is one of the most common malignant tumors worldwide, primarily originating from recurrent inflammatory bowel disease(IBD). Therefore, blocking the inflammation-cancer transformation in the colon has become a focus in the early prevention and treatment of CRC. The inflammation-cancer transformation in the colon involves multiple types of cells and complex pathological processes, including inflammatory responses and tumorigenesis. In this complex pathological process, immune cells(including non-specific and specific immune cells) and non-immune cells(such as tumor cells and fibroblasts) interact with each other, collectively promoting the progression of the disease. In traditional Chinese medicine(TCM), inflammation-cancer transformation in the colon belongs to the categories of dysentery and diarrhea, with the main pathogenesis being cold and heat in complexity. This paper first elaborates on the complex molecular mechanisms involved in the inflammation-cancer transformation process in the colon from the perspectives of inflammation, cancer, and their mutual influences. Subsequently, by comparing the pathogenic characteristics and clinical manifestations between inflammation-cancer transformation and the TCM pathogenesis of cold and heat in complexity, this paper explores the intrinsic connections between the two. Furthermore, based on the correlation between inflammation-cancer transformation in the colon and the TCM pathogenesis, this paper delves into the importance of the interaction between inflammation and cancer. Finally, it summarizes and discusses the clinical and basic research progress in the TCM intervention in the inflammation-cancer transformation process, providing a theoretical basis and treatment strategy for the treatment of CRC with integrated traditional Chinese and Western medicine.
Humans ; Colon/pathology* ; Integrative Medicine ; Animals ; Cold Temperature ; Cell Transformation, Neoplastic/drug effects* ; Medicine, Chinese Traditional ; Hot Temperature ; Inflammation ; Drugs, Chinese Herbal/therapeutic use* ; Colonic Neoplasms/drug therapy*

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

Objective To investigate the screening and prevalence of tuberculosis among freshmen in different schools in Baoding City,and provide reference for tuberculosis control in schools.Methods Screening data of tu-berculosis and tuberculin test(PPD)of freshmen from 156 schools in different regions of Baoding City from Septem-ber 2021 to March 2022 were collected.PPD screening results of students from different regions and different school stages were analyzed and compared.Results A total of 68 177 freshmen from 156 schools were investigated for suspected symptoms and close contact history of pulmonary tuberculosis.PPD screening was conducted on 63 939 students.13 821 students were PPD positive,with a positive rate of 21.62％.3 083 students were strongly posi-tive,with a strong positive rate of 4.82％.15 cases of tuberculosis were found,and the reported incidence was 23.46/100 000.PPD positive rate and strong positive rate as well as incidence of tuberculosis in students in different school stages presented statistically significant differences(all P＜0.01).Positive rate and strong positive rate in students in different school stages showed upward trends(all P＜0.01).PPD positive rate and strong positive rate of students from schools in plain and mountainous areas presented statistically significant differences([22.28％vs 17.89％];[4.85％vs 3.62％],both P＜0.01).PPD positive rate and strong positive rate between students from boarding junior school and non-boarding junior school were significantly different,respectively([23.94％vs 21.60％];[5.07％vs 3.56％],both P＜0.01).Conclusion It is necessary to strengthen tuberculosis screening and health education for freshmen,especially those from boarding schools in plain areas,screening latent Mycobac-terium tuberculosis infection as early as possible,take corresponding measures to prevent and control the spread of tuberculosis,and reduce the risk of tuberculosis.

Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing. Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing. Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

To explore the mechanism by which vinegar-processed Euphorbiae Pekinensis Radix regulates gut microbiota and reduces intestinal toxicity, this study aimed to identify key microbial communities related to vinegar-induced detoxification and verify their functions. Using a derivatization method, the study measured the content of short-chain fatty acids(SCFAs) in feces before and after vinegar-processing of Euphorbiae Pekinensis Radix. Combined with the results of previous gut microbiota sequencing, correlation analysis was used to identify key microbial communities related to SCFAs content. Through single-bacterium transplantation experiments, the role of key microbial communities in regulating SCFAs metabolism and alleviating the intestinal toxicity of Euphorbiae Pekinensis Radix was clarified. Fecal extracts were then added to a co-culture system of Caco-2 and RAW264.7 cells, and toxicity differences were evaluated using intestinal tight junction proteins and inflammatory factors as indicators. Additionally, the application of a SCFAs receptor blocker helped confirm the role of SCFAs in reducing intestinal toxicity during vinegar-processing of Euphorbiae Pekinensis Radix. The results of this study indicated that vinegar-processing of Euphorbiae Pekinensis Radix improved the decline in SCFAs content caused by the raw material. Correlation analysis revealed that Bifidobacterium was positively correlated with the levels of acetic acid, propionic acid, isobutyric acid, n-butyric acid, isovaleric acid, and n-valeric acid. RESULTS:: from single-bacterium transplantation experiments demonstrated that Bifidobacterium could mitigate the reduction in SCFAs content induced by raw Euphorbiae Pekinensis Radix, enhance the expression of tight junction proteins, and reduce intestinal inflammation. Similarly, cell experiment results confirmed that fecal extracts from Bifidobacterium-transplanted mice alleviated inflammation and increased the expression of tight junction proteins in intestinal epithelial cells. The use of the free fatty acid receptor-2 inhibitor GLPG0974 verified that this improvement effect was related to the SCFAs pathway. This study demonstrates that Bifidobacterium is the key microbial community responsible for reducing intestinal toxicity in vinegar-processed Euphorbiae Pekinensis Radix. Vinegar-processing increases the abundance of Bifidobacterium, elevates the intestinal SCFAs content, inhibits intestinal inflammation, and enhances the expression of tight junction proteins, thereby improving the intestinal toxicity of Euphorbiae Pekinensis Radix.
Animals ; Mice ; Humans ; Acetic Acid/chemistry* ; Gastrointestinal Microbiome/drug effects* ; Fatty Acids, Volatile/metabolism* ; Bifidobacterium/genetics* ; Caco-2 Cells ; Intestines/microbiology* ; Drugs, Chinese Herbal/chemistry* ; Euphorbia/toxicity* ; RAW 264.7 Cells ; Male ; Feces/chemistry* ; Intestinal Mucosa/drug effects*

Objective: To investigate the expression and significance of protease activated receptor 2 (PAR2) in ovarian epithelial carcinoma. Methods: PAR2 mRNA expression levels in 410 cases of epithelial ovarian carcinoma and 88 cases of human normal ovary were analyzed from cancer Genome Atlas (TCGA) database and tissue genotypic expression database (GTEx). Immunohistochemical (IHC) staining of PAR2 protein was performed in 149 patients with ovarian cancer who underwent primary surgical treatment at Cancer Hospital of Chinese Academy of Medical Sciences. Then the relationship between mRNA/protein expression of PAR2 and clinicopathological features and prognosis was analyzed. Gene functions and related signaling pathways involved in PAR2 were studied by enrichment analysis. Results: The mRNA expression of PAR2 in epithelial ovarian carcinoma was significantly higher than that in normal ovarian tissue (3.05±0.72 vs. 0.33±0.16, P=0.004). There were 77 cases showing positive and 19 showing strong positive of PAR2 IHC staining among the 149 patients, accounting for 64.4% in total. PAR2 mRNA/protein expression was closely correlated with tumor reduction effect and initial therapeutic effect (P<0.05). Survival analysis showed that the progression free survival time (P=0.033) and overall survival time (P=0.011) in the group with high PAR2 mRNA expression was significantly lower than that in the low PAR2 mRNA group. Multivariate analysis showed tumor reduction effect, initial therapeutic effect were independent prognostic factors on both progression-free survival and overall survival (P<0.05). The progression-free survival (P=0.016) and overall survival (P=0.038) of the PAR2 protein high expression group was significantly lower than that of the low group. Multivariate analysis showed PAR2 expression, initial treatment effect and chemotherapy resistance were independent prognostic factors on both progression-free survival and overall survival (P<0.05). Based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), PAR2 target genes were mainly enriched in function related to intercellular connection, accounting for 40%. Gene enrichment analysis (GSEA) showed that the Wnt/β-catenin signaling pathway (P=0.023), the MAPK signaling pathway (P=0.029) and glycolysis related pathway (P=0.018) were enriched in ovarian cancer patients with high PAR2 mRNA expression. Conclusions: PAR2 expression is closely related to tumor reduction effect, initial treatment effect and survival of ovarian cancer patients. PAR2 may be involved in Wnt/β-catenin signaling pathway and intercellular connection promoting ovarian cancer invasion and metastasis.
Female ; Humans ; Carcinoma, Ovarian Epithelial ; Receptor, PAR-2 ; Ovarian Neoplasms/pathology* ; Prognosis ; RNA, Messenger/metabolism*

OBJECTIVE To study the possible effects and mechanism of Jinxin oral liquid and its main ingredient baicalin on Re-spiratory syncytial virus(RSV)-induced abnormal cardiolipin metabolism.METHODS BALB/c mice were randomly divided into control group,RSV group and Jinxin oral liquid treatment group.Mice were nasally administrated of RSV suspension to establish RSV infection model at the first 3 days.Then Jinxin oral liquid 27.6 g·kg-1·d-1 was administrated intragastrically for the next 3 days from the afternoon of the third day.Raw264.7 cells were infected by RSV to establish an in vitro infection model and baicalin(100 mg·kg-1·d-1)was given for intervention.The changes of cardiolipin metabolism profiles in mice lung tissue and Raw264.7 cells were detected by chromatography-mass spectrometry.Transcriptional mRNA levels of RSV surface proteins RSV-F and RSV-G,inflammatory cytokines IL-6,IL-1β and Tnf-α,cardiolipin metabolic enzymes Tafazzin(TAZ),Cardiolipin Synthase 1(Crls1),Phospholipid Scramblase 3(PLSCR3)and autophagy-related protein p62 were detected by qPCR.The protein level of p62 was detec-ted by Western blot.Molecular docking was used to detect the binding ability of p62 to CL14 ∶ 0-16 ∶ 1-16 ∶ 1-18 ∶ 2.RESULTS The expression of IL-6,IL-1β,and Tnf-α mRNA increased in RSV-infected mice and cell models(P<0.05,P<0.01,P<0.001).Jinxin oral liquid and baicalin plays a certain restoration effect.The cardiolipin metabolism profile changes after RSV infec-tion,and Jinxin oral liquid and baicalin can play a certain regulatory role.The expression of Crls1 and TAZ mRNA in the lung tissue of mice in the model group was significantly up-regulated(P<0.01),after administration of Jinxin oral liquid,the expression of Crls1 and TAZ mRNA was significantly reduced(P<0.01);the expression of Crls1 mRNA in the cell model group was significantly in-creased(P<0.001),and after baicalin intervention,the expression of Crls1 mRNA was significantly reduced(P<0.000 1).The ex-pression of p62 protein in the lung tissue of RSV-infected mice was significantly reduced(P<0.001),and the expression of p62 pro-tein was significantly increased after administration of Jinxin oral liquid(P<0.01).The p62 protein expression in the Raw264.7 cell model group increased significantly(P<0.05),and the p62 protein level further increased significantly after administration of baicalin(P<0.000 1).Molecular docking results showed that cardiolipin CL14 ∶ 0-16 ∶ 1-16 ∶ 1-18 ∶ 2 can threshold-bind with the UBA structure of p62.CONCLUSION Jinxin oral liquid and baicalin can improve RSV-induced cardiolipin metabolism disorder,regulate mitochondrial function,and thus exert anti-RSV infection effects.

Objectives: To study the association between metals mixture exposure and DNA oxidative damage using mixture analysis methods, and to explore the most significant exposure factors that cause DNA oxidative damage. Methods: Workers from steel enterprises were recruited in Shandong Province. Urinary metals were measured by using the inductively coupled plasma mass spectrometry method. The level of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) was determined by using the ultra-high performance liquid chromatography-mass spectrometry method. Bayesian kernel machine regression (BKMR), elastic net regression and quantile g-computation regression were used to analyze the association between urinary metals and urinary 8-OHdG. Results: A total of 768 subjects aged (36.15±7.40) years old were included in the study. BKMR, elastic net regression and quantile g-computation all revealed an overall positive association between the mixture concentration and increased urinary 8-OHdG. The quantile g-computation results showed that with a 25% increase in metal mixtures, the urinary 8-OHdG level increased by 77.60%. The elastic net regression showed that with a 25% increase in exposure risk score, the urinary 8-OHdG level increased by 26%. The BKMR summarized the contribution of individual exposures to the response, and selenium, zinc, and nickel were significant contributors to the urinary 8-OHdG elevation. Conclusion: Exposure to mixed metals causes elevated levels of DNA oxidative damage, and selenium, zinc, and nickel are significant exposure factors.
Humans ; Adult ; Nickel/toxicity* ; Selenium ; Bayes Theorem ; Metals/toxicity* ; 8-Hydroxy-2'-Deoxyguanosine ; Oxidative Stress/physiology* ; Zinc ; DNA Damage

Objective: To investigate the mechanism of signal transducer and activator of transcription 3 (STAT3) and cancer associated fibroblasts (CAF) jointly generate chemo-resistance in epithelial-ovarian cancer and their effect on prognosis. Methods: A total of 119 patients with high-grade ovarian serous cancer who received surgery in Cancer Hospital of Chinese Academy of Medical Sciences from September 2009 to October 2017 were collected. The clinico-pathological data and follow-up data were complete. Multivariate Cox regression model was used to analyze the prognostic factors. Ovarian cancer tissue chips of patients in our hospital were prepared. EnVision two-step method immunohistochemistry was used to detect the protein expression levels of STAT3, the specific markers of CAF activation, fibroblast activating protein (FAP), and type Ⅰ collagen (COL1A1) secreted by CAF. The relationship between the expression of STAT3, FAP, COL1A1 protein and drug resistance and prognosis of ovarian cancer patients was analyzed, and the correlation between the expression of three proteins was analyzed. These results were verified through the gene expression and prognostic information of human ovarian cancer tissues collected in the GSE26712 dataset of gene expression omnibus (GEO) database. Results: (1) Multivariate Cox regression model analysis showed that chemotherapy resistance was an independent risk factor for overall survival (OS) of ovarian cancer (P<0.001). (2) The expression levels of STAT3, FAP, and COL1A1 proteins in chemotherapy resistant patients were significantly higher than those in chemotherapy sensitive patients (all P<0.05). Patients with high expression of STAT3, FAP, and COL1A1 had significantly shorter OS than those with low expression (all P<0.05). According to the human ovarian cancer GSE26712 dataset of GEO database, patients with high expression of STAT3, FAP, and COL1A1 also showed shorter OS than patients with low expression (all P<0.05), the verification results were consistent with the detection results of ovarian cancer patients in our hospital. (3) Correlation analysis showed that the protein level of STAT3 was positively correlated with FAP and COL1A1 in our hospital's ovarian cancer tissue chips (r=0.47, P<0.001; r=0.30, P=0.006), the analysis of GEO database GSE26712 dataset showed that the expression of STAT3 gene and FAP, COL1A1 gene were also significantly positively correlated (r=0.31, P<0.001; r=0.52, P<0.001). Conclusion: STAT3 and CAF could promote chemotherapy resistance of ovarian cancer and lead to poor prognosis.
Female ; Humans ; Cancer-Associated Fibroblasts/pathology* ; Carcinoma, Ovarian Epithelial ; Ovarian Neoplasms/pathology* ; Prognosis ; STAT3 Transcription Factor/metabolism* ; Drug Resistance, Neoplasm