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.

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.

Cell Differentiation ; Humans ; Hyperthermia, Induced ; Stem Cells

ObjectiveTo understand the epidemiological characteristics of severe fever with thrombocytopenia syndrome （SFTS） in Yiyuan County， and provide scientific evidence for prevention and control strategies. MethodsDescriptive epidemiological methods were used to analyze the incidence of SFTS in Yiyuan County during 2014—2019. ResultsA total of 130 SFTS cases were documented in Yiyuan County during 2014—2019， of which four were death cases. The annual incidence was determined to be 3.79/10⁵ and the mortality was 3.08%， showing an upward trend in the incidence （ χ T r e n d 2 =9.06， P=0.003）. Majority of the cases occurred between May and August （88.46%）， were more than 50 years old （81.54%）， and farmers （94.62%）. The median duration of time from onset to diagnosis was five days. ConclusionSFTS was widely distributed in Yiyuan County with seasonal pattern. Middle aged and elderly farmers were mainly susceptible. It warrants strengthening prevention and control of SFTS and health education in elderly.

The general data, blood routine, liver and kidney function, glucose metabolism and lipid metabolism of 11 922 participants who underwent physical examination at the Health Management Center of the Second Xiangya Hospital of Central South University from January 2019 to December 2019 were collected. Clinical characteristics and independent factors of patients with discordance between HbA1c and FPG were evaluated and analyzed. The prevalence of HbA1c-defined diabetes and prediabetes (respectively 8.13%, 34.79%) were significantly higher than that in FPG-defined diabetes and prediabetes (respectively 4.70%, 8.97%) (χ2=2 635.940; P<0.001). The prevalence of inconsistence between HbA1c and FPG was 35.65% and increased with increasing age. This inconsistence mainly occurred in population with HbA1c:5.7%-6.0% and FPG<5.6 mmol/L, followed by population with HbA1c:6.1%-6.4% and FPG<5.6 mmol/L. The risk factors of inconsistency included advanced age, overweight or obesity, hypoalbuminemia, dyslipidemia and hyperuricemia. Among these special participants, compared with participants under 45 years old, participants with over 45 years of age ( OR=3.525, 95% CI: 3.216-3.863, P<0.001) were more likely to have inconsistence between HbA1c and FPG; and overweight participants ( OR=1.474, 95% CI: 1.341-1.620, P<0.001) or obese participants ( OR=1.856, 95% CI: 1.633-2.110, P<0.001) are prone to have the inconsistence than those with normal weight.

The general data, blood routine, liver and kidney function, glucose metabolism and lipid metabolism of 11 922 participants who underwent physical examination at the Health Management Center of the Second Xiangya Hospital of Central South University from January 2019 to December 2019 were collected. Clinical characteristics and independent factors of patients with discordance between HbA1c and FPG were evaluated and analyzed. The prevalence of HbA1c-defined diabetes and prediabetes (respectively 8.13%, 34.79%) were significantly higher than that in FPG-defined diabetes and prediabetes (respectively 4.70%, 8.97%) (χ2=2 635.940; P<0.001). The prevalence of inconsistence between HbA1c and FPG was 35.65% and increased with increasing age. This inconsistence mainly occurred in population with HbA1c:5.7%-6.0% and FPG<5.6 mmol/L, followed by population with HbA1c:6.1%-6.4% and FPG<5.6 mmol/L. The risk factors of inconsistency included advanced age, overweight or obesity, hypoalbuminemia, dyslipidemia and hyperuricemia. Among these special participants, compared with participants under 45 years old, participants with over 45 years of age ( OR=3.525, 95% CI: 3.216-3.863, P<0.001) were more likely to have inconsistence between HbA1c and FPG; and overweight participants ( OR=1.474, 95% CI: 1.341-1.620, P<0.001) or obese participants ( OR=1.856, 95% CI: 1.633-2.110, P<0.001) are prone to have the inconsistence than those with normal weight.

Objective:To investigate the clinical efficacy of fixed-bearing unicompartmental knee arthroplasty (UKA) in the treatment of anteromedial knee osteoarthritis or spontaneous osteonecrosis of the femoral condyle.Methods:Between June 2017 and June 2018, 62 consecutive patients were treated at Department of Joint Surgery, Fuzhou Second Hospital Affiliated to Xiamen University for anteromedial knee osteoarthritis or spontaneous osteonecrosis of the femoral condyle using a fixed-bearing UKA system. They were 27 men and 35 women, aged from 58 to 85 years (average, 69.8 years). There were 58 cases of anteromedial knee osteoarthritis and 4 cases of spontaneous osteonecrosis of the femoral condyle. The courses of disease ranged from 2 to 10 years (average, 5.1 years). Medial unicompartmental knee arthroplasty was performed for all the patients on the fixation platform SLED. Recorded were the hip-knee-ankle angle (HKA) of the patients 2 days after operation, Oxford knee score (OKS) and American Knee Society score (KSS) at the final follow-up and post-operative complications.Results:The 62 patients were followed up for 9 to 21 months (average, 15.6 months). Tibial plateau fracture occurred in one case who eventually obtained bony union after open reduction and internal fixation. Another case had a wound healing problem which responded to drainage and debridement with prosthesis preservation. Another case presented prepatellar pain which was improved after physical therapy. In the 62 patients, the HKA 2 days after operation (172.27°±1.61°) was significantly improved compared to the preoperative value (177.79°±1.32°), the OKS at the final follow-up (19.8±2.7) significantly lower than the preoperative value (50.2±3.1), and the KSS at the final follow-up (89.7±2.6) significantly higher than the preoperative value (49.6±5.2) (all P<0.05). Follow-ups revealed no cases of joint infection or prosthetic loosening. Conclusion:Fixed-bearing unicompartmental knee arthroplasty can lead to fine short-term outcomes for anteromedial knee osteoarthritis or spontaneous osteonecrosis of the femoral condyle.

RAP1 is a well-known telomere-binding protein, but its functions in human stem cells have remained unclear. Here we generated RAP1-deficient human embryonic stem cells (hESCs) by using CRISPR/Cas9 technique and obtained RAP1-deficient human mesenchymal stem cells (hMSCs) and neural stem cells (hNSCs) via directed differentiation. In both hMSCs and hNSCs, RAP1 not only negatively regulated telomere length but also acted as a transcriptional regulator of RELN by tuning the methylation status of its gene promoter. RAP1 deficiency enhanced self-renewal and delayed senescence in hMSCs, but not in hNSCs, suggesting complicated lineage-specific effects of RAP1 in adult stem cells. Altogether, these results demonstrate for the first time that RAP1 plays both telomeric and nontelomeric roles in regulating human stem cell homeostasis.