Objective To investigate the expression of carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) in esophageal squamous cell carcinoma (ESCC) and analyze its correlation with immune cell infiltration and patient prognosis. Methods Three ESCC datasets (GSE161533, GSE26886, and GSE23400) from the GEO database were analyzed to identify differentially expressed genes. CEACAM6 was identified as a key gene through survival analysis. Its expression, prognostic value, and relationship with immune cell infiltration were further explored using databases, such as TIMER. Tissue samples were collected from 162 patients with ESCC. Immunohistochemistry was performed to detect the expression of CEACAM6, immune cell markers (CD4, CD8, CD20, and CD56), and immune checkpoint molecules (HHLA2 and CD40LG). Correlations between CEACAM6 expression and clinicopathological features, immune cell infiltration, and immune checkpoints were analyzed. Results Bioinformatic analysis and clinical sample validation confirmed that CEACAM6 expression was significantly upregulated in ESCC tissues compared with adjacent nontumor tissues (P<0.05). High CEACAM6 expression was closely associated with advanced clinical stage (AJCC Ⅲ-Ⅳ), high T stage (T3-T4), lymph node metastasis, nonulcerative type, and poor prognosis. Furthermore, CEACAM6 expression levels were positively correlated with the infiltration density of CD8⁺ T cells, CD4⁺ T cells, and CD20⁺ B cells within the tumor microenvironment and with the expression of the immune checkpoint molecules HHLA2 and CD40LG (all P<0.05). Conclusion CEACAM6 serves as an independent poor prognostic factor for ESCC. Its high expression is implicated in the modulation of the tumor immune microenvironment by correlating with specific immune cell infiltration and immune checkpoint molecules, suggesting its potential as a novel prognostic biomarker and immunotherapeutic target for ESCC.

BACKGROUND:Cervical rotation-traction manipulation is effective and safe in the treatment of cervical spondylotic radiculopathy,and has been widely used in clinical work.However,its effects on the biomechanics of cervical vertebra and intervertebral disc and the area of intervertebral foramen have not been systematically clarified. OBJECTIVE:Based on the finite element analysis technique,a relevant research and analysis were carried out to provide digital evidence for the mechanism of effect of cervical rotation-traction manipulation in the treatment of cervical spondylotic radiculopathy. METHODS:The CT image data of a volunteer with no neck diseases were selected as the finite element model material at its left-handed physiological limit position.The initial construction of the finite element model was completed by Mimics 19.0 software,Geomagic Studio 2013 software,Hypermash 14.0 software,and ANSYS Workbench 2020 R2 software,respectively.Based on the literature,the grid division of cervical structure and the assignment of elastic modulus and elastic coefficient were completed.Based on the previous work of the team,the mechanical effects of cervical rotation-traction manipulation were simulated on the model.Effects of cervical rotation-traction manipulation on the mechanical parameters of each vertebral body and intervertebral disc in C3-T1 segment and on the cervical lateral foramen area were analyzed. RESULTS AND CONCLUSION:(1)During cervical rotation-traction manipulation,the stress of bone structure was significantly higher than that of soft tissue such as intervertebral disc.(2)When operating the technique,the stress at the top of each cervical vertebra was higher,the stress at the bottom was lower,and the stress at the facet joint and transverse process was lower.The stress at the top of the intervertebral disc was lower,the stress at the bottom was higher,but the highest point of the intervertebral disc stress was outside the top.(3)In addition,after loading the lifting force,the projected area of the C6/C7 intervertebral foramen increased significantly compared with that before loading.(4)It is indicated that the cervical rotation-traction manipulation has the mechanical characteristics of changing the stress structure of the cervical spine itself,and can expand the C6/7 intervertebral cervical foramen area on the opposite side of the patient's cervical rotation,so as to achieve the purpose of treating cervical spondylotic radiculopathy.

Lymph node metastasis (LNM) is a crucial risk factor influencing an unfavorable prognosis in specific cancers. Fundamental research illuminates our understanding of tumor behavior and identifies valuable therapeutic targets. Nevertheless, the exploration of fundamental theories and the validation of clinical therapies hinge on preclinical experiments. Preclinical models, in this context, serve as the conduit connecting fundamental theories to clinical outcomes. In vivo models established in animals offer a valuable platform for comprehensively observing interactions between tumor cells and organisms. Using various experimental animals, including mice, diverse methods, such as carcinogen-induced tumorigenesis, tumor cell line or human tumor transplantation, genetic engineering, and humanization, have been used effectively to construct numerous models for tumor LNM. Carcinogen-induced models simulate the entire process of tumorigenesis and metastasis. Transplantation models, using human tumor cell lines or patient-derived tumors, offer a research platform closely mirroring the histology and clinical behavior of human tumors. Genetically engineered models have been used to delve into the mechanisms of primary tumorigenesis within an intact microenvironment. Humanized models are used to overcome barriers between human and murine immune systems. Beyond mouse models, various other animal models have unique advantages and limitations, all contributing to exploring LNM. This review summarizes existing in vitro and animal preclinical models, identifies current bottlenecks in preclinical research, and offers an outlook on forthcoming preclinical models.
Animals ; Humans ; Mice ; Lymphatic Metastasis/pathology* ; Disease Models, Animal ; Cell Line, Tumor

Objective To establish a prediction model for the occurrence of non-occupational carbon monoxide poisoning events in Beijing, and to provide scientific basis and theoretical support for the prevention and warning of poisoning events. Methods Based on the monitoring data of non-occupational carbon monoxide poisoning events in Beijing from 2016 to 2024, the seasonal ARIMA model and seasonal index model were established to analyze the data and predict the occurrence of events. Results Between 2016 and 2024, a total of 436 cases of non-occupational carbon monoxide poisoning were reported in Beijing, showing a downward trend. The established SARIMA model and seasonal index model were SARIMA (1,0,0) (1,1,0) 12, Yt = (-0.0339t+5.8863) × St, and the average relative errors were 65.42% and 29.19%, respectively. In terms of months, the SARIMA model had better predictive performance during April and summer (June to August), while the seasonal index model was superior in other months. By combining the two models, the predicted number of events in 2025 was as follows: 3, 2, 2, 3, 1, 5, 2, 7, 1, 1, 1, and 2. Conclusion The seasonal index model has the best prediction effect on the non-occupational carbon monoxide poisoning events in Beijing throughout the year, and the number of summer events predicted by SARIMA model is closer to the actual values. The two models can be combined to predict the trend of non-occupational carbon monoxide poisoning, which provides a scientific basis for the prevention and control of carbon monoxide poisoning in the future.

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

Objective:To establish a monitoring and evaluation index system for the building project of national children′s regional medical centre (shorted as the evaluation system), so as to provide quantitative supports for output hospitals to fulfil their primary responsibilities and offer guidance for project hospitals to implement target management.Methods:From April to June 2024, through searching literature and policy document, and combining with the actual situation of national regional medical center construction, the initial indicators of the evaluation system were screened. An evaluation system were constructed using two rounds of Delphi method, and the weights of indicators were determined by analytic hierarchy process.Results:This study invited 17 experts. The participation rates of experts in the two rounds of consultation exceeded 90.00%, with an expert authority coefficient of 0.96. The final evaluation system comprised 2 primary indicators, 8 secondary indicators, and 52 tertiary indicators. The primary indicators included project implementation status and project outcomes, with relative weights of 44.44% and 55.56% respectively. Project implementation status included 4 secondary indicators: project organisation, resource allocation, project progress, and safeguard mechanisms. Project outcomes encompassed 4 secondary indicators: healthcare service capacity, regional talent development outreach, and collaborative innovation.Conclusions:The evaluation system established in this study demonstrated a high degree of scientificity and feasibility. It could effectively supported the process management and outcome evaluation of establishing the national children′s regional medical centre. This system provided a scientific basis for enhancing the quality and efficiency of children′s healthcare services, optimising policy formulation and resource allocation.

AIM To investigate the effects of Jisuishang Formula on neurological function and ferroptosis in a rat model of cervical spondylotic myelopathy(CSM).METHODS The CSM rat models were established and randomly assigned to the model group,the Fer-1 group(2 g/kg Ferrostatin-1 via intraperitoneal injection),the low-dose(9.7 g/kg,intragastrically),medium-dose(19.4 g/kg,intragastrically)and high-dose(38.8 g/kg,intragastrically)Jisuishang Formula groups,and the sham operation group,with 6 rats in each group.Following 4 weeks of treatment administration,BBB locomotor scores and oblique plate test result were recorded to assess their neurological function in rats.Histopathological evaluation utilized HE staining for spinal cord tissue pathology,Nissl staining for Nissl body visualization,and Prussian blue staining for iron ion deposition analysis.Protein expressions of Nrf2,SLC7A11,GPX4,HO-1,TFRC and Cox2 in spinal cord tissues was detected by immunofluorescence and Western blot,while mRNA expressions were quantified using RT-qPCR.RESULTS Compared to the sham group,the CSM model group exhibited significantly reduced BBB locomotor scores and inclined plane test performance at 1,2 and 4 weeks post-operation(P＜0.05);obvious tissue cavitation,cellular edema and Prussian blue positive iron deposition in spinal cord tissues;downregulated protein and mRNA expressions of Nrf2,SLC7A11,GPX4,HO-1(P＜0.05);and upregulated protein and mRNA expressions of TFRC and Cox2(P＜0.05).Compared to the model group,the Jisuishang Formula and Fer-1 intervention groups showed significantly improved BBB scores and inclined plane test result at 1,2 and 4 weeks post-operation(P＜0.05);reduced tissue cavitation,attenuated cellular edema and decreased Prussian blue positive iron deposition in spinal cord tissues;upregulated protein and mRNA expression of Nrf2,SLC7A11,GPX4 and HO-1 in spinal cord tissues(P＜0.05);and downregulated protein and mRNA expressions of TFRC and Cox2(P＜0.05).CONCLUSION Targeting the Nrf2/SLC7A11/GPX4 signaling pathway,Jisuishang Formula potentially suppresses ferroptosis and alleviates iron accumulation in spinal cord neurons,thereby improving neurological recovery in CSM rats.

Oral squamous cell carcinoma(OSCC)is a malignant lesion originating from the oral mucosal squamous epithelium,account-ing for over 80％of oral and maxillofacial malignancies.Key etiological factors include tobacco,alcohol abuse,and betel quid chewing.In China,its incidence has shown an overall upward trend,posing a significant threat to public health.OSCC exhibits high local invasive-ness,making early diagnosis critical for improving prognosis.Its clinical management requires close multidisciplinary collaboration among oral and maxillofacial surgery,head and neck surgery,radiation oncology,medical oncology,reconstructive surgery,radiology,patholo-gy,and nutritional support teams.Given the increasing disease burden of OSCC and rapid development of multidisciplinary collaborative models,an expert panel has formulated this integrated management consensus based on evidence-based medicine and extensive deliber-ation.Centered on the'Prevention-Screening-Diagnosis-Treatment-Rehabilitation'framework,the consensus provides comprehensive guidance for the entire disease course of OSCC patients,aiming to standardize clinical practice.

ObjectiveTo explore the potential mechanism of action of the combination of Sanguisorbae Radix-Sophorae Flos （DH） in the treatment of ulcerative colitis （UC） using network pharmacology methods and molecular docking technology. MethodsNetwork pharmacology analysis was utilized to predict the potential targets of DH for the treatment of UC. The therapeutic effects were experimentally validated by inducing a UC model in mice with 3% dextran sulfate sodium （DSS）. The experimental groups were the normal group， the model group， the salazosulfapyridine group （100 mg·kg^-1）， and the low， medium， and high dose groups of DH （1.2， 2.4， and 4.8 g·kg^-1）. The efficacy of the treatment was assessed through the general condition of the mice， histopathological examination， and the expression levels of inflammatory markers in the colon. The effect of DH on angiogenesis was explored by messenger RNA （mRNA） detection of colonic angiogenesis-related mediators， vascular endothelial growth factor （VEGF） immunohistochemistry， microvessel density （MVD） detection， and transmission electron microscopy. The phosphatidylinositol-3-kinase （PI3K）-protein kinase B （Akt） signaling pathway proteins were quantitatively analyzed through Western blot to assess whether the suppression of pathological angiogenesis by DH is associated with this pathway. ResultsNetwork pharmacological analysis yielded 112 potential core therapeutic targets for the treatment of UC with DH， of which the core targets were tumor protein 53 （TP53）， JUN， interleukin （IL）-6， Akt1， and tumor necrosis factor （TNF）. Compared with the normal group， mice in the model group showed significant weight loss， colon shortening， and high DAI score， increased expression of inflammatory factors IL-6， IL-1β， and TNF-α， as well as increased mRNA expression levels of angiogenesis-related mediators VEGF， vascular cell adhesion molecule 1 （VCAM1）， angiotensin 1 （Ang1）， matrix metalloproteinase （MMP）-1， MMP-2， and MMP-9. The positive expression of CD31 and VEGF in colonic tissue increased， and the protein expression of the PI3K/Akt pathway was increased （P<0.05）. The endothelial cells of the colonic mucosa and the colonic vasculature were severely damaged. Compared with the model group， mice in the DH groups had significantly reduced weight loss and colon shortening， lower DAI scores， and a significant decrease in mRNA expression of inflammatory factors and angiogenesis-related mediators. In addition， there was decreased positive expression of CD31 and VEGF in colonic tissue and decreased protein expression of the PI3K/Akt pathway （P<0.05）. ConclusionNetwork pharmacology， molecular docking， and experimental validation are applied to explore the mechanism of action of DH in the treatment of UC， and it is found that DH is able to improve the symptoms of colitis and inhibit the pathological angiogenesis in UC mice. Its action might be related to affecting the PI3K/Akt pathway.

ObjectiveTo explore the potential mechanism of action of the combination of Sanguisorbae Radix-Sophorae Flos （DH） in the treatment of ulcerative colitis （UC） using network pharmacology methods and molecular docking technology. MethodsNetwork pharmacology analysis was utilized to predict the potential targets of DH for the treatment of UC. The therapeutic effects were experimentally validated by inducing a UC model in mice with 3% dextran sulfate sodium （DSS）. The experimental groups were the normal group， the model group， the salazosulfapyridine group （100 mg·kg^-1）， and the low， medium， and high dose groups of DH （1.2， 2.4， and 4.8 g·kg^-1）. The efficacy of the treatment was assessed through the general condition of the mice， histopathological examination， and the expression levels of inflammatory markers in the colon. The effect of DH on angiogenesis was explored by messenger RNA （mRNA） detection of colonic angiogenesis-related mediators， vascular endothelial growth factor （VEGF） immunohistochemistry， microvessel density （MVD） detection， and transmission electron microscopy. The phosphatidylinositol-3-kinase （PI3K）-protein kinase B （Akt） signaling pathway proteins were quantitatively analyzed through Western blot to assess whether the suppression of pathological angiogenesis by DH is associated with this pathway. ResultsNetwork pharmacological analysis yielded 112 potential core therapeutic targets for the treatment of UC with DH， of which the core targets were tumor protein 53 （TP53）， JUN， interleukin （IL）-6， Akt1， and tumor necrosis factor （TNF）. Compared with the normal group， mice in the model group showed significant weight loss， colon shortening， and high DAI score， increased expression of inflammatory factors IL-6， IL-1β， and TNF-α， as well as increased mRNA expression levels of angiogenesis-related mediators VEGF， vascular cell adhesion molecule 1 （VCAM1）， angiotensin 1 （Ang1）， matrix metalloproteinase （MMP）-1， MMP-2， and MMP-9. The positive expression of CD31 and VEGF in colonic tissue increased， and the protein expression of the PI3K/Akt pathway was increased （P<0.05）. The endothelial cells of the colonic mucosa and the colonic vasculature were severely damaged. Compared with the model group， mice in the DH groups had significantly reduced weight loss and colon shortening， lower DAI scores， and a significant decrease in mRNA expression of inflammatory factors and angiogenesis-related mediators. In addition， there was decreased positive expression of CD31 and VEGF in colonic tissue and decreased protein expression of the PI3K/Akt pathway （P<0.05）. ConclusionNetwork pharmacology， molecular docking， and experimental validation are applied to explore the mechanism of action of DH in the treatment of UC， and it is found that DH is able to improve the symptoms of colitis and inhibit the pathological angiogenesis in UC mice. Its action might be related to affecting the PI3K/Akt pathway.