Immunotherapy, including immune checkpoint inhibitors, tumor vaccine therapy, oncolytic virotherapy, and adoptive cell therapy, has made remarkably breakthroughs in the field of oncology. Immune checkpoint inhibitors, which block programmed death receptor 1 or programmed death ligand 1, have been included in the first-line clinical treatment for advanced solid tumors, such as non-small cell lung cancer and malignant melanoma. However, primary or secondary drug resistance in tumors severely limits the survival benefits for patients. Immune-related adverse reactions, such as pneumonia, hypothyroidism, hypophysitis, and myocarditis, also greatly affect the quality of life of patients. Fuzheng Jiedu Huayu is an important concept guiding the prevention and treatment of tumors with traditional Chinese medicine (TCM). It is also a curative principle and therapeutic TCM method to reduce the toxicity and enhance the efficacy of immunotherapy. This article summarizes the research progress of immunotherapy and discusses how TCM reduces the toxicity and enhances the efficacy of immunotherapy, hoping to provide a reference for the integrated treatment of tumors with TCM and immunotherapy.

Esophageal squamous cell carcinoma(ESCC)is a common malignant tumor with insidious early symptoms and a poor prognosis.In traditional Chinese medicine(TCM),ESCC is classified as"ye ge."Drawing on clinical experience,we believe that kidney deficiency leads to the deficiency of vital qi and immune dysfunction,providing the foundation for cancerous growth by depleting qi and damaging essence,toxic stasis and stagnation,forming a local hypoxic and acidic microenvironment that promotes tumor invasion,metastasis,and recurrence.Considering the effect of modern comprehensive treatments,the occurrence and development of ESCC are summarized as kidney deficiency being the root cause and toxic stasis being the driving force.The pathogenesis and treatment of ESCC in the preoperative,postoperative,and non-surgical treatment stages are discussed.The pathogenesis of the disease is summarized as follows:preoperatively,toxicity and stasis intertwine,depleting the kidney;postoperatively,the kidney loses its vitality,allowing various pathogenic factors to persist;during non-operative treatment,vital qi and pathogens contend,resulting in entrenched toxicity.During the preoperative neoadjuvant phase,therapy should resolve stasis,eliminate toxins,enhance kidney function,tonify essence,and support the body.During the postoperative adjuvant phase,therapy should strengthen the root and consolidate the foundation while detoxifying and expelling stasis.The non-surgical treatment stage uses"balanced interruption,"targeting tumor progression and metastasis by harmonizing yin and yang,thus preventing recurrence.This article will provide insights into the integrative Chinese-Western management of ESCC.

Objective:To construct a rat model of non-alcoholic fatty liver disease(NAFLD)by choline-deficient high fat diet(CDHFD),and to observe the association between feeding cycle and antioxidant pathway.Methods:The study lasted 16 weeks and was divided into 4 cycles.Detection of pathological changes and expression of antioxidant enzymes in rats liver in different cycles.Results:The early stage of liver steatosis and inflammation in model rats was 2～4 weeks,non-alcoholic steatohepatitis(NASH)stage was 4～8 weeks,and liver fibrosis progression was 8～16 weeks.Mechanistic studies had shown that the expressions of antioxidant enzymes Nrf2,SOD and GSH-Px in the liver of NAFLD rats gradually decreased with the extension of the feeding cycle.Conclusion:Different modeling cycles can successfully induce the pathological changes of steatosis,inflammation and liver fibrosis in rat liver,and the pathological changes are time-dependent with the expressions of antioxidant enzymes.

Objective:To construct a rat model of non-alcoholic fatty liver disease(NAFLD)by choline-deficient high fat diet(CDHFD),and to observe the association between feeding cycle and antioxidant pathway.Methods:The study lasted 16 weeks and was divided into 4 cycles.Detection of pathological changes and expression of antioxidant enzymes in rats liver in different cycles.Results:The early stage of liver steatosis and inflammation in model rats was 2～4 weeks,non-alcoholic steatohepatitis(NASH)stage was 4～8 weeks,and liver fibrosis progression was 8～16 weeks.Mechanistic studies had shown that the expressions of antioxidant enzymes Nrf2,SOD and GSH-Px in the liver of NAFLD rats gradually decreased with the extension of the feeding cycle.Conclusion:Different modeling cycles can successfully induce the pathological changes of steatosis,inflammation and liver fibrosis in rat liver,and the pathological changes are time-dependent with the expressions of antioxidant enzymes.

Objective To explore the effects of cerium-doped mesoporous bioactive glass nanoparticles(Ce-MBGNs)as reactive oxy-gen species(ROS)-responsive nanocarriers on inflammation in pulp and their potential to promote odontogenic differentiation of dental pulp stem cells(DPSCs).Methods The cytotoxicity of Ce-MBGNs was assessed by CCK-8.The expression of mRNA of osteogenic/odontogenic differentiation in DPSCs and that of inflammatory factor in RAW264.7 cells were detected by RT-qPCR.Alkaline phospha-tase and Alizarin Red S staining were utilized to investigate their ability to promote dentin mineralization.The ability of Ce-MBGNs to scavenge ROS was evaluated by immunofluorescence and JC-1 staining was used to assess the membrane potential(MMP)of mitochon-drial.Results Ce-MBGNs exhibited good biocompatibility and significantly increased the expression of osteogenic/odontogenic-related genes in DPSCs,promoting mineralization.Additionally,Ce-MBGNs effectively scavenged intracellular ROS,maintained MMP,inhib-ited the expression of pro-inflammatory factors,and promoted the expression of anti-inflammatory factors.Conclusion Ce-MBGNs can protect DPSCs from oxidative damage by maintaining the MMP of mitochondrial and controlling inflammation,and promote their odonto-blastic differentiation,providing a theoretical basis for the development of novel therapeutic agents for oral treatment.

Objective To explore the effects of cerium-doped mesoporous bioactive glass nanoparticles(Ce-MBGNs)as reactive oxy-gen species(ROS)-responsive nanocarriers on inflammation in pulp and their potential to promote odontogenic differentiation of dental pulp stem cells(DPSCs).Methods The cytotoxicity of Ce-MBGNs was assessed by CCK-8.The expression of mRNA of osteogenic/odontogenic differentiation in DPSCs and that of inflammatory factor in RAW264.7 cells were detected by RT-qPCR.Alkaline phospha-tase and Alizarin Red S staining were utilized to investigate their ability to promote dentin mineralization.The ability of Ce-MBGNs to scavenge ROS was evaluated by immunofluorescence and JC-1 staining was used to assess the membrane potential(MMP)of mitochon-drial.Results Ce-MBGNs exhibited good biocompatibility and significantly increased the expression of osteogenic/odontogenic-related genes in DPSCs,promoting mineralization.Additionally,Ce-MBGNs effectively scavenged intracellular ROS,maintained MMP,inhib-ited the expression of pro-inflammatory factors,and promoted the expression of anti-inflammatory factors.Conclusion Ce-MBGNs can protect DPSCs from oxidative damage by maintaining the MMP of mitochondrial and controlling inflammation,and promote their odonto-blastic differentiation,providing a theoretical basis for the development of novel therapeutic agents for oral treatment.

Esophageal squamous cell carcinoma(ESCC)is a common malignant tumor with insidious early symptoms and a poor prognosis.In traditional Chinese medicine(TCM),ESCC is classified as"ye ge."Drawing on clinical experience,we believe that kidney deficiency leads to the deficiency of vital qi and immune dysfunction,providing the foundation for cancerous growth by depleting qi and damaging essence,toxic stasis and stagnation,forming a local hypoxic and acidic microenvironment that promotes tumor invasion,metastasis,and recurrence.Considering the effect of modern comprehensive treatments,the occurrence and development of ESCC are summarized as kidney deficiency being the root cause and toxic stasis being the driving force.The pathogenesis and treatment of ESCC in the preoperative,postoperative,and non-surgical treatment stages are discussed.The pathogenesis of the disease is summarized as follows:preoperatively,toxicity and stasis intertwine,depleting the kidney;postoperatively,the kidney loses its vitality,allowing various pathogenic factors to persist;during non-operative treatment,vital qi and pathogens contend,resulting in entrenched toxicity.During the preoperative neoadjuvant phase,therapy should resolve stasis,eliminate toxins,enhance kidney function,tonify essence,and support the body.During the postoperative adjuvant phase,therapy should strengthen the root and consolidate the foundation while detoxifying and expelling stasis.The non-surgical treatment stage uses"balanced interruption,"targeting tumor progression and metastasis by harmonizing yin and yang,thus preventing recurrence.This article will provide insights into the integrative Chinese-Western management of ESCC.

Purpose To establish glucose metabolism patterns of Parkinson's disease(PD)at different periods,and to study the changing pattern of target region of interest(ROI)with the period of time,and then explore the relationship between ROIs and cognitive or motor in different periods.Materials and Methods A total of 42 patients with early-stage PD collected from June 2010 to September 2022 in online data from the markers of Parkinson's progression study which included clinical data,and FDG PET imaging was performed at baseline,12,24,36 and 48 months.The data of 8 healthy volunteers were also obtained from the database,and the time range was the same as that of the above-mentioned PD patients.The longitudinal changes of cerebral glucose metabolism in PD patients and the relationship between PD-associated ROI and movement disorder society-sponsored revision of the unified Parkinson's disease rating scale(MDS-UPDRS)score were evaluated.Results PD was relatively reduced activity located in frontal and parietal association areas and relatively increased activity in the cerebellum,the putamen and the cingulate gyrus.In our study of target ROIs over time,FDG uptake in the caudate nucleus,putamen,pallidum,and cerebellum of patients with PD was initially higher than in the normal group,and subsequently decreased.In contrast,the ROI of PD in the anterior cingulate gyrus,posterior cingulate gyrus,the substantia nigra pars compacta and substantia nigra pars reticulata was initially lower than that in healthy controls and subsequently increased.The putamen,pallidum and caudate nucleus metabolic activity showed a positive correlation in 36 month and MDS-UPDRS scores(r=0.659 5,0.678 7,0.716 7,all P<0.05).The caudate nucleus,putamen and pallidum metabolic activity showed a negative correlation in 24 month and baseline(r=-0.541 8,-0.878 9,-0.887 6,all P<0.05).Conclusion We provide 5-year longitudinal data on changes in 18F-FDG imaging outcomes in early PD.In addition,the glucose metabolic activity of caudate nucleus,putamen and globus pallidus are correlated with MDS-UPDRS scores.

Objective To study the mechanism of Sanhuang Decotion in the treatment of ulcerative colitis(UC)under Candida albicans colonization in mice based on Dectin-1-Syk-CARD9 signaling pathway.Methods Mice model of UC with fungal colonization were established with dextran sodium sulfate free drinking and C.albicans intragastric administration.Mice were divided into normal control group,model group,sulfasalazine group,fluconazole group,and Sanhuang Decotion low-and high-dosage groups,and receive corresponding drug interventions.General state of mice were observed,and the disease activity index(DAI)score of mice were calculated.The load of C.albicans in intestine was detected,the length of the colon was measured,and pathological scoring of the colon tissue was performed.The ultrastructural changes of colon epithelium were observed under transmission electron microscopy.The contents of TNF-α,IL-6 and IL-12 in serum and colon tissues were detected by ELISA.The mRNA and protein expression of Dectin-1,Syk,CARD9,NF-κBp65 and inflammation factors in intestinal epithelial cells and colon tissues were detected by qPCR,Western blot and immunohistochemistry.Results Compared with the normal control group,the model group mice showed reduced activity,decreased food intake,accompanied by loose stools,significantly increased DAI score,increased load of C.albicans in the intestine,shortened colon length,and increased histopathological score,with widening of gap between colon epithelial cells,cytoplasmic dissolution,mitochondrial swelling;TNF-α,IL-6 and IL-12 in serum and colon tissue increased,the expressions of Dectin-1 and CARD9 mRNA and protein in colon epithelial cells increased,p-Syk,p-NF-κBp65,CARD9,TNF-α,IL-1β,IL-6 protein expression in colon tissue increased(P<0.01,P<0.05).Compared with the model group,the Sanhuang Decotion high-dosage group mice showed a significant decrease in DAI score,decreased intestinal C.albicans load,increased colon length,decreased histopathological score,more complete and orderly arrangement of microvilli in colon epithelial cells,mild mitochondrial swelling,TNF-α,IL-6 and IL-12 in serum and colon tissue decreased,and the mRNA and protein expression of Dectin-1 and CARD9 in colon tissue increased,the expression of p-Syk,p-NF-κBp65,CARD9,TNF-α,IL-1β,IL-6 protein in colon tissue decreased(P<0.01,P<0.05).Conclusion Sanhuang Decotion may exert an anti C.albicans colonization UC effect by inhibiting the Dectin-1-Syk-CARD9 signaling pathway and reducing the release of inflammatory factors.

The important role of TDP-43 proteinopathy in Alzheimer's disease (AD) has been gradually revealed. High proportion of AD patients have TDP-43 proteinopathy on their postmortem diagnosis. Patients with TDP-43 proteinopathy show more sever hippocampal atrophy and cognitive dysfunction, suggesting that TDP-43 proteinopathy can serve as an important target in AD diagnosis and treatment. Evaluation of TDP-43 proteinopathy in vivo would hold great promise in AD diagnosis, drug development and treatment. In this review, we describe the pathological characteristics of TDP-43 proteinopathy in AD, and summarize the recent progress of TDP-43 proteinopathy in the diagnosis and treatment of AD.