ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally， the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome， such as oral ulcers， sore throat， and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation， oxidative stress， and energy metabolism in the early phase， Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting （XGBoost） algorithm was used to develop a prediction model for main symptom classification， with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers， sore throat， and overall symptoms， with significant effects observed especially in sore throat and overall symptom analyses （P<0.01）. Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement， were also called "heat-related biomarkers"， including succinic acid， α-ketoglutaric acid， glycine， lactic acid， adenosine monophosphate （AMP）， tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-10 （IL-10）， and so on. Conversely， clinical biomarkers negatively correlated with symptom severity， were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan， including malic acid， fumaric acid， cis-aconitic acid， adrenocorticotropic hormone （ACTH）， IL-1β， IL-4， IL-8， succinic acid， and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables， with importance scores of 0.081 and 0.080， respectively. After screening out 14 key variables and optimizing the parameters， model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables， confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established， achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.

ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally， the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome， such as oral ulcers， sore throat， and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation， oxidative stress， and energy metabolism in the early phase， Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting （XGBoost） algorithm was used to develop a prediction model for main symptom classification， with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers， sore throat， and overall symptoms， with significant effects observed especially in sore throat and overall symptom analyses （P<0.01）. Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement， were also called "heat-related biomarkers"， including succinic acid， α-ketoglutaric acid， glycine， lactic acid， adenosine monophosphate （AMP）， tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-10 （IL-10）， and so on. Conversely， clinical biomarkers negatively correlated with symptom severity， were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan， including malic acid， fumaric acid， cis-aconitic acid， adrenocorticotropic hormone （ACTH）， IL-1β， IL-4， IL-8， succinic acid， and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables， with importance scores of 0.081 and 0.080， respectively. After screening out 14 key variables and optimizing the parameters， model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables， confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established， achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.

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Atherosclerosis, a chronic inflammatory disease, is markedly influenced by both immune and inflammatory reactions throughout its progression. Dendritic cells, as pivotal antigen-presenting entities, play a crucial role in the initiation of immune responses and the preservation of immunological homeostasis. Accumulating data indicates that dendritic cells are present in healthy arteries and accumulate significantly in atherosclerotic plaques. Novel immunotherapeutic approaches and vaccination protocols have yielded substantial clinical advancements in managing chronic inflammatory diseases, with dendritic cell-centric modalities emerging for atherosclerotic management. In this review, we delineate the essential functions and underlying mechanisms of dendritic cells and their subsets in the modulation of atherosclerotic inflammation and immune responses. We underscore the immense promise of dendritic cell-based immunotherapeutic strategies, including vaccines and innovative combinations with nanotechnological drug delivery platforms for atherosclerosis treatment. We also discuss the challenges associated with dendritic cell immunotherapy and provide perspectives on the future direction of this field.

Alzheimer disease(AD)is a progressive neurodegenerative disorder characterized by cognitive dysfunction and declining learning and memory abilities,significantly impacting daily lives and behavioral capacities of the patients.The mitogen-activated protein kinase(MAPK)signaling pathway,primarily composed of extracellular signal-regulated kinase,p38 MAPK,and c-Jun N-terminal kinase.Mounting evidence suggests that the MAPK signaling path-way is intimately linked to the pathogenesis of AD,providing crucial insights into the disease's progression.In recent years,traditional Chinese medicine(TCM)has demonstrated promising potential in treating AD,with its advantages of personalized therapy and multi-target regulation garnering increasing research attention.This study aims to review the ex-perimental research landscape of TCM interventions targeting the MAPK signaling pathway for the prevention and treat-ment of AD over the past five years.The findings reveal that effective compounds and herbal formulas in TCM,such as isorhamnetin,nobiletin,parthenolide,Glehnia littoralis,Ishige okamurae,shikonin,artemisinin,kaempferol,myrice-tin,and Tripterygium glycosides,can alleviate AD symptoms by modulating the MAPK signaling pathway.These interven-tions mitigate Aβ-induced neuronal damage,reduce Tau protein hyperphosphorylation,and suppress neuroinflammatory responses.The objective of this review is to provide a scientific and theoretical reference for the clinical prevention and treatment of AD and to inform the development of novel therapeutic agents.

Objective:To investigate the distribution of CGG repeat numbers in the FMR1 gene among reproductive-age women in China, providing data reference for carrier screening and genetic counseling of Fragile X syndrome. Methods:This cross-sectional study recruited 16 610 reproductive-age women from 12 medical institutions between July 2022 and October 2023. Peripheral venous blood samples (3 mL) were collected, and genomic DNA was extracted. The number of CGG repeats in the FMR1 gene was determined using the triplet-primed polymerase chain reaction (TP-PCR) combined with capillary electrophoresis technology. Statistical analyses were performed to assess the prevalence and distribution of CGG repeat expansions. Results:Among 16 610 women of childbearing age, 5 684 (34.220%) women had the same number of CGG repeats in the two alleles of FMR1 gene, and 10 926 (65.780%) women had different numbers of repeats in the two alleles. Among the 33 220 FMR1 alleles in 16 610 women of reproductive age, the most common CGG repeat numbers were 29 [48.645% (16 160/33 220)] and 30 [26.276% (8 729/33 220)], while the most frequent CGG genotype was CGG 29/29 [24.726% (4 107/16 610)]. The CGG repeat numbers of FMR1 gene were normal in 16 498 women (99.326%). Among the 112 women (0.674%) with CGG repeat abnormities, 96 (0.578%) women were classified as intermediate carriers, 15 (0.090%) as premutation carriers, and 1 (0.006%) as a full mutation carrier, whose CGG genotype was (36, >200). Conclusion:In the general reproductive-age female population in China, the normal CGG repeat numbers of the FMR1 gene account for 99.326%, while the intermediate carrier rate is 0.578%, and the combined carrier rate of the premutation and full mutation types is 0.096%.

BACKGROUND:In recent years,the application of surgical robots has become a research hotspot in the field of spinal surgery,but there is still a lack of literature visualization analysis of spinal surgical robots in China.OBJECTIVE:To conduct literature visualization analysis on the research hotspots of spinal surgical robots for the treatment of spinal diseases to provide a useful reference for the research and development of spinal surgical robots in China.METHODS:The Web of Science core set database was applied to search for relevant literature on spinal surgical robots for the treatment of spinal diseases,and 900 articles were finally included. Visualization analysis was conducted on number of publications,journals,institutions,countries,keywords,co-cited documents and highly cited documents of the included literature using VOSviewer 1.6.19 software.RESULTS AND CONCLUSION:(1) The literature in the field of spinal surgical robots for the treatment of spinal diseases has been increasing year by year,especially in 2023,when the number of publications reached a peak. United States,China,and Germany are the research hotspots in this field. National Natural Science Foundation of China is the main fund in this field. (2) Beijing Jishuitan Hospital,China and Hospital for Special Surgery in United States have made great publications to the research in this field. (3) World Neurosurgery,Spine,and Operative Neurosurgery are the main publication journals in this field. (4) Keyword analysis showed that the research mainly focused on the accuracy of robot-assisted spinal surgery,minimally invasive surgery,robotic spinal surgery,and navigation technology. (5) The results of the co-citation analysis of the literature exhibit that robot-assisted technology has significant advantages in spinal surgery. Compared with traditional surgery,spinal surgical robots such as ROSA? Spine,ExcelsiusGPS,Mazor X,and TiRobot have the advantages of high-precision navigation,precise pedicle screw placement,and real-time feedback. They reduce X-ray radiation exposure during surgery,diminish the risk of complications for patients,and improve the success rate of surgery,showing their application prospects in the field of spinal surgery. (6) Despite this,the application and accuracy of related technologies still need to accumulate experience for improvement. Robotic surgery technology has shown cost-effectiveness in reducing surgical radiation exposure and enhancing surgical accuracy. However,it is needed to explore its accuracy in pedicle screw placement surgery,the impact of surgical time,and economic benefits. (7) The results of the analysis of highly cited literature from 2021 to 2024 further show that the latest research hotspots in this field are currently focused on the application of virtual reality and augmented reality technologies,the improvement of the accuracy of robot-assisted pedicle screw placement,and the application of navigation robot spinal surgery platforms. For example,innovative technologies such as organic electrochemical neurons provide new integrated solutions for brain-computer interfaces,prosthetics,and intelligent soft robotics. Simultaneously,virtual reality and augmented reality technologies have shown broad application prospects in areas such as spinal deformity correction.

BACKGROUND: The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation. METHODS: We conducted a kidney xenotransplantation in a brain-dead human recipient using a porcine kidney with five gene edits (5GE) on March 25, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22 days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation. RESULTS: The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24 h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient. CONCLUSIONS 5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.
Transplantation, Heterologous/methods* ; Kidney Transplantation/methods* ; Heterografts/pathology* ; Immunoglobulins, Intravenous/administration & dosage* ; Graft Survival/immunology* ; Humans ; Animals ; Sus scrofa ; Graft Rejection/prevention & control* ; Kidney/pathology* ; Gene Editing ; Species Specificity ; Immunosuppression Therapy/methods* ; Plasma Exchange ; Brain Death ; Biopsy ; Male ; Aged

Alzheimer disease(AD)is a neurodegenerative disorder characterized by the abnormal deposition of amyloid β-protein(Aβ).Inflammation plays a significant role in promoting this abnormal deposition.Toll-like receptor 4(TLR4)is recognized as a"primary regulator"of the inflammatory response,facilitating the activation of microglia and interacting with various pathways,including nuclear factor-κB and nucleotide-binding oligomerization domain-like recep-tor protein 3.This interaction can lead to an inflammatory cascade that accelerates the progression of AD.Numerous pro-spective studies have demonstrated that traditional Chinese medicine can modulate the TLR4 signaling pathway,effective-ly addressing both the onset and progression of AD.However,a comprehensive review of how Chinese medicine regulates this pathway in the treatment of AD is currently lacking.Therefore,this paper aims to detail the latest findings related to TLR4 in the prevention and treatment of AD,drawing from recent literature.It will explore the mediation of traditional Chinese medicine,preserving its essence,and provide references and a basis for clinical practices aimed at preventing and treating AD.

Objective To observe the effects of Xuanfei Tongfu formula on the prognosis of patients with severe pneumonia.Methods Sixty patients with severe pneumonia admitted to the First People's Hospital of Fuyang District,Hangzhou City from June 1,2022 to April 1,2024 were selected as the research subjects.Patients were divided into control group(31 cases)and observation group(29 cases)by randomly number table method.Upon hospital admission,the control group received conventional Western medicine treatment,while the observation group received Xuanfei Tongfu formula in addition to conventional Western medicine treatment[Rhubarb 8 g(decocted later),Aurantii Fructus Immaturus 12 g,Magnoliae Officinalis Cortex 12 g,Agastache Rugosa 10 g,Tatarian Aster Root 15 g,Natrii Sulfas Exsiccatus 10 g(dissolved in water),decocted to 150 mL each time and taken],once a day for 5 days.Observe the changes of inflammatory indicators such as serum levels of C-reactive protein(CRP),procalcitonin(PCT),interleukin-6(IL-6)in both groups before and after treatment.To evaluate the severity indicators of diseases such as acute physiology and chronic health evaluationⅡ(APACHEⅡ)and sequential organ failure assessment(SOFA),as well as the clinical efficacy after treatment.Record the duration of mechanical ventilation,intensive care unit(ICU)length of stay and total hospitalization length of the two groups,calculate the oxygenation index level,and statistically analyze the 28-day survival rate.Results Compared with before treatment,the levels of inflammatory indicators CRP,PCT,and IL-6,as well as the scores of APACHEⅡand SOFA in both groups were significantly lower than those after treatment,the oxygenation index was significantly higher than that before treatment,and the changes in the observation group were more obvious than those in the control group[CRP(mg/L):28±17 vs.50±34,PCT(μg/L):2.0±1.5 vs.4.1±2.7,IL-6(ng/L):52±28 vs.97±61,APACHEⅡscore:12.8±5.1 vs.16.1±6.1,SOFA score:3.9±1.8 vs.6.2±2.7,oxygenation index(mmHg,1 mmHg≈0.133 kPa):302±57 vs.252±85,all P<0.05].Compared with the control group,the observation group exhibited a markedly reduced duration of mechanical ventilation(days:8.3±3.8 vs.11.4±6.4,P<0.05),and a significantly higher total effective rate of clinical efficacy[82.76%(24/29)vs.54.84%(17/31),P<0.05].Conclusion The application of Xuanfei Tongfu formula can effectively enhance the clinical treatment outcomes for severe pneumonia,reduce systemic inflammatory responses,promote organ function recovery,and improve the prognosis of patients.