OBJECTIVE To investigate the potential therapeutic effect of the sporoderm-removed Ganoderma lucidum spore tablet "Xianzhi No.3" from the perspective of immunomodulation and cardioprotection. METHODS Chemical components of the sporoderm-removed Ganoderma lucidum spore tablet "Xianzhi No.3" were analyzed by UPLC-Q-TOF-MS and colorimetric methods. Examined tablet’s effects on zebrafish models of macrophage reduction, heart failure, H2O2-induced oxidative stress in myocardial and endothelial cells, and a microglial inflammation model induced by lipopolysaccharide. Immune regulation and cardioprotective effects were evaluated through multiple indicators, including macrophage formation and phagocytosis abilities, anti-neuroinflammation ability, cardiac systolic and diastolic functions, and anti-oxidative stress injury ability in myocardial and endothelial cells. RESULTS The sporoderm-removed Ganoderma lucidum spore tablet "Xianzhi No.3" improved macrophage formation and phagocytosis, cardiac systolic and diastolic functions, reduced neuroinflammation, and alleviated oxidative stress in myocardial and endothelial cells, resulting in immunomodulatory and cardioprotective effects. CONCLUSION The sporoderm-removed Ganoderma lucidum spore tablet "Xianzhi No.3" maybe a potential therapeutic agent for regulating the immune system and protecting cardiac function.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Under the background of high-intensity fattening,probiotics have gradually become wide-ly used feed additives.It can inhibit the proliferation of pathogenic bacteria,maintain the microeco-logical balance in the digestive tract,and improve the host immune function.In order to screen lac-tic acid bacteria strains with potential probiotic effects,23 acid-producing strains were isolated from rumen fluid of healthy Duolang sheep by CaCO3-MRS solid medium.Safe strains were re-screened through primary screening and hemolysis tests.Acid tolerance tests and bile salt tests were used to screen the strains that were relatively adapted to the rumen environment.The survival rate of the strain M2 was 93.80％under pH3.0 and 59.72％under bile salt concentration of 0.30％and the survival rate is higher than other strains under high temperature conditions.Subsequently,morphological observation,molecular biological identification,testing of pathogen antagonism,antibiotic tolerance analysis,growth characteristics detection and other methods were used to fur-ther explore the characteristics of the strain.The results showed that the strain to be tested was Gram-positive bacillus.After 16S rRNA gene sequence comparison,the strain was identified as Lactobac illus salivus,which could be used as a candidate strain to develop probiotics.The research results laid a foundation for its application in Duolang sheep breeding.

Objective:To examine the effectiveness of thin struct bare stents for the treatment of spontaneous isolated dissection of the superior mesenteric artery (SIDSMA).Methods:The data of 32 patients admitted to First Hospital of Jiaxing (20 cases) and Jinling Hospital (12 cases) with SIDSMA from January 2016 to January 2021 were retrospectively analyzed. There were 27 males and 5 females, aging (54.8±9.4) years (range: 36 to 75 years). All patients were treated with thin struct bare stents. Controllable spring coils were used to fulfill the false lumen in 2 cases. Symptoms, vascular remodeling pattern at the SIDSMA lesion, and patency of the stents were observed during follow-up.Results:The surgical success rate was 100%. According to the length of the lesions and stents, the number of stents implanted was 1 in 17 cases, 2 in 11 cases and 3 in 4 cases. The angiography showed that blood flow in the stent was smooth. The numerical rating scale for abdominal pain decreased from 6.1±1.5 (range: 4 to 10) preoperatively to 1.0 (1.0) (range: 0 to 3) 1 hour postoperatively ( W=528, P<0.01). The compression rate of the true lumen of the superior mesenteric artery decreased from (92.3±6.7)% (range: 25% to 94%) preoperatively to 0.8 (1.2)% (range: 0 to 3.2%) 1 month postoperatively ( W=528, P<0.01). The primary patency rate of CT angiography at 1 month postoperatively was 100%. The vascular remodeling rate was (92.3±6.7)% (range: 80% to 100%). All patients were followed for (46.3±17.0) months (range: 24 to 76 months). The cumulative patency rates in 1, 2 and 5 years were all 100%. Conclusion:The use of thin struct bare stents for SIDSMA could obtained the expected safety and efficacy.

Objective:To examine the effectiveness of thin struct bare stents for the treatment of spontaneous isolated dissection of the superior mesenteric artery (SIDSMA).Methods:The data of 32 patients admitted to First Hospital of Jiaxing (20 cases) and Jinling Hospital (12 cases) with SIDSMA from January 2016 to January 2021 were retrospectively analyzed. There were 27 males and 5 females, aging (54.8±9.4) years (range: 36 to 75 years). All patients were treated with thin struct bare stents. Controllable spring coils were used to fulfill the false lumen in 2 cases. Symptoms, vascular remodeling pattern at the SIDSMA lesion, and patency of the stents were observed during follow-up.Results:The surgical success rate was 100%. According to the length of the lesions and stents, the number of stents implanted was 1 in 17 cases, 2 in 11 cases and 3 in 4 cases. The angiography showed that blood flow in the stent was smooth. The numerical rating scale for abdominal pain decreased from 6.1±1.5 (range: 4 to 10) preoperatively to 1.0 (1.0) (range: 0 to 3) 1 hour postoperatively ( W=528, P<0.01). The compression rate of the true lumen of the superior mesenteric artery decreased from (92.3±6.7)% (range: 25% to 94%) preoperatively to 0.8 (1.2)% (range: 0 to 3.2%) 1 month postoperatively ( W=528, P<0.01). The primary patency rate of CT angiography at 1 month postoperatively was 100%. The vascular remodeling rate was (92.3±6.7)% (range: 80% to 100%). All patients were followed for (46.3±17.0) months (range: 24 to 76 months). The cumulative patency rates in 1, 2 and 5 years were all 100%. Conclusion:The use of thin struct bare stents for SIDSMA could obtained the expected safety and efficacy.

Objective:To investigate the clinical significance of fluid-attenuated inversion recovery (FLAIR) vascular hyperintensities (FVHs) in patients with chronic atherosclerotic middle cerebral artery occlusion.Methods:From July 2016 to November 2020, patients admitted to the Department of Neurology, Jiangdu People's Hospital of Yangzhou and first found chronic atherosclerotic middle cerebral artery occlusion were enrolled. The demographic, clinical and MRI imaging data were collected. According to the presence or absence of acute cerebral infarction, they were divided into the non-acute cerebral infarction group and the acute cerebral infarction group. According to the modified Rankin Scale score at 3 months after the onset, patients with acute cerebral infarction were further divided into the good outcome group (≤2) and the poor outcome group (>2). A multivariate logistic regression model was used to analyze the independent correlation between FVHs and the risk of cerebral infarction in patients with chronic atherosclerotic middle cerebral artery occlusion and the outcome in patients with cerebral infarction. Results:A total of 94 patients with chronic atherosclerotic middle cerebral artery occlusion were enrolled, including 38 with non-acute cerebral infarction (40.4%) and 56 with acute cerebral infarction (59.6%). In patients with acute cerebral infarction, 13 (23.2%) had a poor outcome, and 43 (76.8%) had a good outcome. The fibrinogen level, the proportion of patients with FVHs and the FVHs score in the cerebral infarction group were significantly higher than those in the non-cerebral infarction group (all P<0.05). Multivariate logistic regression analysis showed that the FVHs score was significantly, independently, and positively correlated with the risk of acute cerebral infarction (odds ratio 2.524, 95% confidence interval 1.400-4.552; P=0.002). The National Institutes of Health Stroke Scale score at admission, the modified Rankin Scale score at admission, and FVHs score in the poor outcome group were significantly higher than those in the good outcome group (all P<0.05). Multivariate logistic regression analysis showed that there was a significant independent negative correlation between the FVHs score and the outcome of patients with cerebral infarction (odds ratio 0.144, 95% confidence interval 0.045-0.459; P=0.001). Conclusions:FVHs suggest that the blood supply is in a state of decompensation. When FVHs are present, the risk of cerebral infarction in patients with chronic middle cerebral artery occlusion is significantly increased; the wider the range of FVHs, the higher the risk of poor outcome after cerebral infarction.

FLASH radiotherapy (FLASH-RT) is a treatment modality that delivers ultra-high dose rate and ultra-fast radiation for cancer treatment. Compared to conventional dose rate radiotherapy, FLASH-RT can yield similar efficacy for tumors and achieve normal tissue protection, translating to an increased therapeutic window. Due to this unique feature, FLASH-RT is attracting increasing attention from the radiotherapy community, both academia and industry. Due to its unique Bragg peak as well as intrinsic high dose rate, application of FLASH has more value and profound significance in proton therapy while achieving highly conformal dose deposition simultaneously. This article reviews research progress on FLASH-RT, relevant cell and animal studies, experimental conditions and results. Moreover, this article also investigates the potential biological mechanisms, technical challenges for implementation and potential clinical applications of FLASH-RT.

Objective:To investigate the role of nucleotide-binding oligomerization domain-like receptor protein 12 (NLRP12) in diabetic patients with coronary heart disease.Methods:From Jun. 2017 to Oct. 2018, 40 patients with type 2 diabetes mellitus (T2DM) in our hospital were selected as simple diabetes group, 80 patients with coronary heart disease as simple coronary heart disease group, 80 patients with T2DM and coronary heart disease as diabetes mellitus complicated with coronary heart disease group, and 60 healthy people in the same period as control group. Peripheral blood mononuclear cells were isolated and cultured. The levels of NLRP12, apoptosis-related spot-like protein, Caspase-3 mRNA and protein expression were detected by RT-PCR and Western blot. The plasma was separated and the content of IL-18 was detected by ELISA.Results:The relative expressions of NLRP12, apoptosis-related spot-like protein, Caspase-3 mRNA and protein in peripheral blood mononuclear cells of diabetes mellitus group, coronary heart disease group and diabetes mellitus complicated with coronary heart disease group were significantly higher than those of the control group ( P<0.05) . The apoptosis-related spot-like protein and Caspase-3 mRNA in peripheral blood mononuclear cells of diabetes mellitus complicated with coronary heart disease group were significantly higher than those of the control group ( P<0.05) . The relative expression of NLRP12 was significantly higher than that of diabetes mellitus group and coronary heart disease group ( P<0.05) . There was no significant difference in the relative expression of NLRP12 gene and protein between diabetes mellitus group, coronary heart disease group and diabetes mellitus complicated with coronary heart disease group ( P>0.05) . The plasma levels of IL-18 in diabetes mellitus group, coronary heart disease group and diabetes mellitus complicated with coronary heart disease group were significantly higher than those in the control group ( P<0.01) ; the plasma levels of IL-18 in diabetes complicated with coronary heart disease group were significantly higher than those in diabetes mellitus group and coronary heart disease group ( P<0.05) . The correlation analysis showed that plasma IL-18 level was positively correlated with NLRP12, apoptosis-related spot-like protein, Caspase-3 mRNA and relative protein expression. Conclusion:The abnormal activation of NLRP12 promotes the maturation and release of downstream inflammatory factor IL-18 by activating the expression of apoptosis related spot like protein and Caspase-3, and participates in the occurrence and development of diabetes mellitus complicated with coronary heart disease.

Objective:Serum cytokines and chemokines in patients with fever with thrombocytopenia syndrome (SFTS) and the severity of the disease was studied.Methods:Serum of 47 SFTS patients from 2014 to 2017 in Jinan city was collected. Serum of 11 dead patients and 36 survivors were selected as the survival group and serum of 10 healthy people was selected as the control group. Luminex liquid phase chip was used to detect and analyze the expression levels of 40 cytokines and chemokines in peripheral blood.Results:The expression levels of 27 cytokines and chemokines in the death group were significantly higher than those in the control group ( P<0.05). The expression level of 33 cytokines and chemokines in the death group was significantly higher than that in the survival group ( P<0.05). The expression level of 12 cytokines and chemokines in the survival group was significantly higher than that in the control group ( P<0.05). The expression levels of 10 cytokines and chemokines in the patients were increased in different degrees during the recovery period compared with the acute period ( P<0.05). The expression levels of 5 cytokines and chemokines were lower in the recovery period than in the acute period ( P<0.05). Receiver operating characteristic curve (ROC curve) analysis showed that 22 factors were statistically significant and could be used as biomarkers to predict the severity of the disease. Conclusions:The expression levels of various cytokines and chemokines in serum of SFTS patients changed significantly during the development of the disease and the cytokine storm caused by SFTS may be the cause of death.

BACKGROUND: The tyrosine kinase inhibitors (TKI) treatment of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation may have a positive effect, but most patients may develop drug resistance, therefore, the detection of the developing time in drug resistance and the research of the mechanism of drug resistance are need to be solved. While the emerge of next generation sequencing (NGS) have make it possible. The aim of this study is to monitor the efficacy of targeted therapy by studying the variation of circulating tumor DNA (ctDNA) mutation frequency and gene mutation spectrum through the targeted therapy. METHODS: Our center enrolled 22 patients with EGFR mutation detected by tissue or peripheral blood, and collect 8 mL of peripheral blood of the patients for ctDNA sequencing in different phases, before systematic prior treatment, followed-up by 2 months and disease progression after TKI administration. RESULTS: Patients with EGFR gene mutation may acquire a longer median survival time after receiving targeted drug therapy, due to the drop of mutation abundances, while the therapy may have a minor effect in patients which their mutation abundances have slightly decreased compared to the statistics before the cession (P=0.015,3). The significantly reduced group median progression was associated with a longer survival [progression free survival (PFS)=390 d]. At the same time, we found out that when related to TP-53 gene mutation, the effect of targeted drug therapy for EGFR-sensitive mutation was unsatisfactory (the median PFS was 120 d compared with 630 d, P=0.000,2). CONCLUSIONS Patients who has lower mutation abundance with EGFR sensitive mutations after TKI treatment may have a longer survival period (P<0.05), and the mutation abundance were not significantly dropping or accompanied by other mutations may indicating TKI resistance.