Objective To investigate the protective effect and mechanism of Polygonatum sibiricum polysaccharides(PSP)on diabetic cardiomyopathy(DCM).Methods Forty SPF-grade male Sprague-Dawley rats were divided randomly into Control,Model,PSP,and metformin groups.After 4 weeks of feeding a high-fat diet,streptozotocin was injected intraperitoneally to establish a rat model of diabetes mellitus.The drug was administered by gavage for 12 weeks,and body mass and blood glucose were recorded every 2 weeks.Cardiac function was detected by non-invasive echocardiography at week 16.Myocardial histopathological changes and the degree of myocardial fibrosis were assessed by hematoxylin and eosin and Masson staining.Serum interleukin(IL)-6,IL-1β,IL-18,tumor necrosis factor-α(TNF-α),triglycerides,total cholesterol,low-density lipoprotein,and high-density lipoprotein were detected by enzyme-linked immunosorbent assay.Expression levels of the fibrosis-related proteins transforming growth factor(TGF)-β1,Smad2,Collagen-Ⅰ,Collagen-Ⅲ,and the pyroptosis-related proteins NOD-like receptor thermal protein domain associated protein 3(NLRP3),apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),and Caspase-1 were detected in rat myocardial tissues by Western blot.Cellular experiments were performed by exposing H9c2 cells to high glucose(40 mmol/L)to mimic the in vitro DCM model,cell viability was detected by Cell Counting Kit-8 assay,and the apoptotic cell ratio was detected by flow cytometry.Results Rats in the treatment group had significantly lower blood glucose,lipid,and serum inflammatory factor levels compared with the model group(P＜0.05),significantly higher ejection fraction and fractional shortening values(P＜0.05),and improved cardiac function.Myocardial fibers were better aligned and collagen fiber accumulation was reduced,and myocardial tissue levels of NLRP3,ASC,Caspase-1,Collagen-Ⅰ,Collagen-Ⅲ,TGF-β1,and Smad2 were significantly reduced(P＜0.05).In the cellular assay,PSP increased the viability and decreased the proportion of apoptotic cells in high glucose-induced H9c2 cardiomyocytes.Conclusions PSP can improve glucose-lipid metabolism,protect cardiac function,and delay the occurrence of myocardial fibrosis in diabetic rats,and can also improve the viability of cardiomyocytes.Its mechanism of action may be related to the inhibition of cellular pyroptosis and delayed occurrence of ventricular remodeling.

Objective To investigate the protective effect and mechanism of Polygonatum sibiricum polysaccharides(PSP)on diabetic cardiomyopathy(DCM).Methods Forty SPF-grade male Sprague-Dawley rats were divided randomly into Control,Model,PSP,and metformin groups.After 4 weeks of feeding a high-fat diet,streptozotocin was injected intraperitoneally to establish a rat model of diabetes mellitus.The drug was administered by gavage for 12 weeks,and body mass and blood glucose were recorded every 2 weeks.Cardiac function was detected by non-invasive echocardiography at week 16.Myocardial histopathological changes and the degree of myocardial fibrosis were assessed by hematoxylin and eosin and Masson staining.Serum interleukin(IL)-6,IL-1β,IL-18,tumor necrosis factor-α(TNF-α),triglycerides,total cholesterol,low-density lipoprotein,and high-density lipoprotein were detected by enzyme-linked immunosorbent assay.Expression levels of the fibrosis-related proteins transforming growth factor(TGF)-β1,Smad2,Collagen-Ⅰ,Collagen-Ⅲ,and the pyroptosis-related proteins NOD-like receptor thermal protein domain associated protein 3(NLRP3),apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),and Caspase-1 were detected in rat myocardial tissues by Western blot.Cellular experiments were performed by exposing H9c2 cells to high glucose(40 mmol/L)to mimic the in vitro DCM model,cell viability was detected by Cell Counting Kit-8 assay,and the apoptotic cell ratio was detected by flow cytometry.Results Rats in the treatment group had significantly lower blood glucose,lipid,and serum inflammatory factor levels compared with the model group(P＜0.05),significantly higher ejection fraction and fractional shortening values(P＜0.05),and improved cardiac function.Myocardial fibers were better aligned and collagen fiber accumulation was reduced,and myocardial tissue levels of NLRP3,ASC,Caspase-1,Collagen-Ⅰ,Collagen-Ⅲ,TGF-β1,and Smad2 were significantly reduced(P＜0.05).In the cellular assay,PSP increased the viability and decreased the proportion of apoptotic cells in high glucose-induced H9c2 cardiomyocytes.Conclusions PSP can improve glucose-lipid metabolism,protect cardiac function,and delay the occurrence of myocardial fibrosis in diabetic rats,and can also improve the viability of cardiomyocytes.Its mechanism of action may be related to the inhibition of cellular pyroptosis and delayed occurrence of ventricular remodeling.

Objective:To investigate the application of (4R)-4-(3-[ 18F]fluoranyl-5-fluorophenyl)-1-((3-methylpyridin-4-yl)methyl)pyrrolidin-2-one( 18F-SynVesT-1), a synaptic vesicle glycoprotein 2A (SV2A) radioactive tracer, in patients with Alzheimer′s disease (AD). Methods:A total of 20 AD patients (2 males, 18 females, age (66.4±8.1) years) with positive β-amyloid (Aβ) deposition and 20 normal controls (NC; 9 males, 11 females, age (62.6±8.6) years ) without Aβ deposition were retrospectively recruited from Huashan Hospital, Fudan University between December 2021 and December 2022. All of them underwent 18F-SynVesT-1 PET/MR and 18F-Florbetapir (AV45) PET/CT scans. Preprocessing of brain 18F-SynVesT-1 PET images was carried out using statistical parametric mapping (SPM). The differences of the uptke of 18F-SynVesT-1 (synaptic density) between two groups based on ROI were compared by using either the independent-sample t test or Mann-Whitney U test. Spearman rank correlation analysis was performed to assess the relationship between synaptic density and cognitive performance. For voxelwise analysis, a general linear model was constructed to analyze differences in synaptic density between the two groups using the independent-sample t test. Furthermore, a multiple linear regression model was developed to explore the relationship between synaptic density and cognitive performance. Results:Compared to the NC group, the AD group exhibited significant widespread reduction in synaptic density across the cortical regions ( P<0.05, false discovery rate (FDR)-corrected), particularly in the medial temporal lobe (0.84±0.09 vs 1.04±0.09; t=-6.95, P<0.001), lateral temporal lobe (1.15±0.13 vs 1.31±0.08; t=-4.56, P<0.001), and lateral parietal lobe (1.24(1.04, 1.26) vs 1.32(1.23, 1.39); z=-3.25, P=0.001). Moreover, synaptic density in extensive cortical regions showed a positive correlation with mini-mental state examination (MMSE) and Montreal cognitive assessment-basic (MoCA-B) scores ( P<0.05, FDR-corrected). Notably, significant associations were observed between MMSE and MoCA-B scores and synaptic density in the lateral temporal lobe ( rs values: 0.71, 0.74, both P<0.001) and medial temporal lobe ( rs values: 0.71, 0.74, both P<0.001). Conclusions:18F-SynVesT-1 PET imaging is a valuable tool for evaluating synaptic density, specifically in the context of AD. The observed widespread reduction in synaptic density across cortical regions of patients with AD are closely related to cognitive decline.

OBJECTIVE To investigate the effect of a new variety of Sambucus williamsii Hance Yandan on the healing in rats with fractures.METHODS SD rats were randomly allocated to sham surgery group,model group,Zhonghua dieda pill group(0.54 g/kg),wild S.williamsii group(5.4 g/kg,using raw drug dosage),and high-,medium-,and low-dose groups of Yandan(10.8,5.4,2.7 g/kg,using raw drug dosage),with 12 rats in each group.Except for the sham surgery group,the remaining groups were prepared with a femoral fracture model.Starting from the second day after surgery,each group was intubated with the corresponding drugs and distilled water once daily for 8 consecutive weeks.At 2,4,and 8 weeks after administration,the levels of calcium,phosphorus,alkaline phosphatase(ALP),and osteocalcin(OCN)in rat serum were detected.Micro-CT scanning was used to evaluate the morphology and bone microstructural parameters of the fractured femur[bone mineral density(BMD),bone volume/tissue volume(BV/TV),trabecular number(Tb.N),trabecular separation(Tb.Sp),trabecular thickness(Tb.Th)],and hematoxylin-eosin staining was adopted to observe the morphological changes at the bone fracture site.RESULTS Compared with the model group,the levels of calcium in rat serum were significantly decreased(except at 4 weeks after administration),and the levels of phosphorus,ALP,and OCN were significantly increased(P＜0.05)at 2,4,and 8 weeks after administration in the high-dose group of Yandan;bone callus formation,connection of fracture ends,gradual blurring or disappearance of the fracture line,and opening of the marrow cavity were observed in the bone repair process,and a large amount of granulation tissue,fibroblasts,chondrocytes,new trabeculae,and new bone plates were visible at the fracture site of bone tissue;after 8 weeks of administration,BMD,BV/TV,Tb.N,and Tb.Th were significantly increased,and Tb.Sp was significantly decreased(P＜0.05).Most of the above indicators in the wild S.williamsii Hance group showed no significant changes.CONCLUSIONS Yandan has the effect of promoting fracture healing in rats,and its effect is superior to that of wild S.williamsii.

Objective:To explore the β-amyloid (Aβ) deposition pattern of subjects with the preclinical Alzheimer′s disease (AD), community-derived amnestic mild cognitive impairment (aMCI) and normal cognition (NC) from communities of Shanghai.Methods:According to the inclusion and exclusion criteria, 273 subjects (104 males, 169 females; age (64.2±7.6) years) were recruited from Shanghai community and memory clinics from December 2018 to July 2020. All subjects underwent MRI, 18F-AV45 PET imaging and neuropsychological scale tests and were grouped into AD, aMCI and NC groups based on clinical diagnosis. Differences in demographic information, the neuropsychological scale tests′ scores and positive rate of Aβ deposition among each group were analyzed by one-way analysis of variance or χ2 test. Aβ deposition patterns of AD and MCI groups were analyzed at voxel level, and the differences of Aβ deposition among different groups were compared. Results:Among 273 patients, the positive rates of Aβ deposition in AD, aMCI and NC groups were 84.4%(38/45), 36.4%(20/55) and 23.1%(40/173), respectively ( χ2=58.37, P<0.001). Among AD, aMCI, NC and NC (Aβ-) groups ( n=132), the education years of AD group was the lowest ((9.7±4.6) years; F=8.86, P<0.001). In addition, there were significant differences in the scores of several neuropsychological scale tests among AD, aMCI, NC groups and NC (Aβ-) group ( F values: 27.68-235.50, all P<0.001). Compared with subjects in NC(Aβ-) group, the Aβ depositions in the aMCI and AD groups were widely distributed in the whole cerebral cortex; and AD group had higher Aβ deposition in bilateral frontal, parietal, temporal, occipital lobe, cingulate gyrus and precuneus than aMCI group. Conclusions:The positive rate of Aβ deposition in the preclinical AD population from the Shanghai community is obtained. There are significant different Aβ deposition patterns in subjects at different stages of AD.

Objective:To explore the association of the impaired cognition and the deposition of β-amyloid (Aβ) in normal cognitive (NC) and mild cognitive impairment (MCI).Methods:From December 2018 to January 2021, 305 subjects (113 males, 192 females; age (64.0±7.7) years) who completed neuropsychological tests and MRI in Shanghai Sixth People′s Hospital, Shanghai Jiao Tong University and 18F-florbetapir (AV45) PET imaging in Huashan Hospital, Fudan University were retrospectively analyzed. The subjects were divided into MCI group and NC group based on neuropsychological tests, and each group was further divided into Aβ-positive and Aβ-negative based on PET imaging results. Independent-sample t test, Mann-Whitney U test and χ2 test were used to analyze the data. Results:There were 118 subjects in MCI group and 187 subjects in NC group. The Aβ-positive rate in MCI group (37.3%, 44/118) was higher than that in NC group (26.2%, 49/187; χ2=4.19, P=0.041). The assessment performances of MCI group in general cognitive function, memory function, language function and executive function were inferior to those of NC group ( t values: from -10.63 to -6.31, z values: from -11.01 to -6.03, all P<0.001). The Auditory Verbal Learning Test-Long Delay Recall (AVLT-LDR) score of Aβ-positive subjects was lower than that of Aβ-negative subjects in MCI group (1.00(0.00, 3.00) and 3.00(1.00, 4.00); z=-2.49, P=0.013). The Montreal Cognitive Assessment Basic (MoCA-B) score of Aβ-positive subjects was lower than that of Aβ-negative subjects in NC group (25.29±2.67 and 26.36±2.42; t=-2.61, P=0.010). Conclusion:Compared to Aβ-negative subjects, MCI patients with Aβ-positive perform worse on memory tests, and NC subjects with Aβ-positive perform worse on general cognitive function.

Objective:We evaluated frailty in elderly hospitalized patients with atrial fibrillation and analyzed the relevance, consistency, and diagnostic power of different frailty tools.Methods:From September 2018 to April 2019, a total of 197 elderly patients with atrial fibrillation aged ≥ 65 years in Beijing Hospital, Chinese PLA General Hospital, and Beijing Tsinghua Changgung Hospital were prospectively enrolled.Five frailty tools, including the clinical frailty scale(CFS), FRAIL scale(FRAIL), Fried frailty phenotype(Fried), Edmonton frail scale(EFS), and comprehensive geriatric assessment-frailty index(CGA-FI), were used for frailty assessment.Results:A total of 197 hospitalized elderly patients with atrial fibrillation were enrolled, with an average age of(77.5±7.1)years old(57.4% male). The prevalence of frailty, according to the five frailty tools, were 25.4%(FRAIL), 27.9%(EFS), 34.5%(Fried), 40.6%(CFS), and 42.6%(CGA-FI), respectively.CFS had a good correlation(correlation coefficient 0.80)and and consistency(Kappa value 0.71, 95% CI 0.61~0.81)with CGA-FI.The combined frailty index was used as the gold standard for frailty diagnosis.The results showed that CFS and CGA-FI had high diagnostic sensitivity(95.9 % and 98.0 %, respectively)and specificity(77.7 % and 75.7 %, respectively). Conclusions:Frailty is common in elderly hospitalized patients with atrial fibrillation, showing multidimensional features, and physical weakness is not prominet.CFS and CGA-FI are recommended for the assessment of frailty in patients with atrial fibrillation, which had good correlation and consistency.

Objective:To investigate the tau deposition pattern in Alzheimer′s disease (AD) and its correlation with cognition by 18F-MK6240 PET imaging. Methods:From August 2021 to February 2022, 46 elderly people over 55 years old (16 males, 30 females; age (68.9±7.7) years) were included from outpatient and community in Shanghai. Structural brain MRI, β-amyloid (Aβ) PET imaging, tau-PET imaging and comprehensive neuropsychological tests batteries were conducted. The subjects were divided into AD group ( n=16) and normal cognition (NC) group ( n=30) according to the 2018 National Institute on aging and Alzheimer′s Association (NIA-AA) diagnostic criteria. Quantitative analysis was conducted to investigate the tau deposition pattern in AD after preprocessing 18F-MK6240 PET images with MRI images. SUV ratio (SUVR) of brain regions such as entorhinal cortex, hippocampus, parahippocampal gyrus, amygdala, insular lobe, frontal lobe, precuneus, occipital lobe, thalamus and putamen were analyzed, with cerebellum as reference region. The differences of tau deposition in brain regions between AD and NC groups were analyzed by independent-sample t test. The associations between SUVR and Mini-Mental State Examination (MMSE) score and Montreal Cognitive Assessment-Basic (MoCA-B) score were analyzed by Pearson correlation analysis. Results:AD displayed a significant tau deposition in frontal lobes, temporal lobes and parietal lobes compared with NC. SUVR of brain regions in AD group were higher than those in NC group ( t values: 3.37-9.61, all P<0.05). SUVR in brain regions were negatively correlated with MMSE score ( r values: from -0.735 to -0.350, all P<0.05) and MoCA-B score ( r values: from -0.723 to -0.367, all P<0.05). Conclusion:18F-MK6240 PET can demonstrate the tau deposition in the brain of AD patients, and the tau deposition is related to cognitive function.

ObjectiveTo investigate the preventive and curative effect of Chaishao Liujunzi Tang （CSLJZT） on colonic mucosal injury induced by dextran sulfate sodium （DSS） in mice with ulcerative colitis （UC） and its mechanism. MethodFifty Balb/c male mice were randomly divided into normal group， model group， CSLJZT low-dose group， CSLJZT high-dose group， and sulfasalazine group. Except for the normal group， other groups were given 2.5% DSS freely for 7 d， and were given drug intervention after successful modeling for 7 d. Bodyweight， feces， and other general physiological statuses of mice were recorded every day， and disease activity index （DAI） scores were calculated.The colon length was measured， and stained by hematoxylin-eosin （HE） staining to observe the morphological changes of the colon.The enzyme-linked immunosorbent assay （ELISA） was used to determine the content of interleukin-1β （IL-1β）， myeloperoxidase （MPO）， and superoxide dismutase （SOD） in the serum. Western blot was used to determine the protein expression levels of Toll-like receptor 4 （TLR4）， myeloid differentiation factor 88 （MyD88）， nuclear factor kappa B （NF-κB）， inhibitor-kappa binding protein （IκB）， Caspase-1， and nucleotide-binding oligomerization domain-like receptor 3 （NLRP3） in the colon tissues. ResultAs compared with the normal group， mice in the model group had significantly decreased body weight （P<0.01）， severe diarrhea and hematochezia， and significantly increased DAI score （P<0.01）. As compared with the model group， the decreasing trend of body weight was significantly alleviated in the CSLJZT groups （P<0.01）， diarrhea and hematochezia were significantly improved， DAI score was significantly decreased （P<0.01）， and colon length increased （P<0.05）. HE staining showed that the pathological damage of colon tissue was significantly improved and the inflammatory cell infiltration was reduced in the CSLJZT groups as compared with the model group. As compared with the normal group， the serum levels of IL-1β and MPO were significantly higher （P<0.01） and SOD levels were significantly lower （P<0.01） of mice in the model group.Compared with the model group， the treated group reduced the serum IL-1β and MPO levels （P<0.01）， and raised the SOD level （P<0.01）. The results of Western blot showed that as compared with the normal group， the expression levels of TLR4， MyD88， NF-κB， Ccaspase-1， and NLRP3 proteins were significantly increased （P<0.01）， whereas the expression level of IκB protein was significantly decreased （P<0.01） in the colonic tissue of mice in the model group. As compared with the model group， the expression levels of TLR4， MyD88， NF-κB， Caspase-1， and NLRP3 proteins were decreased （P<0.01）， whereas the expression level of IκB protein was increased （P<0.01） in the colonic tissue of mice in the CSLJZT groups. ConclusionCSLJZT improves the inflammatory injury of the colon tissue in DSS-induced UC mice through TLR4/MyD88/NF-κB signaling pathway.

Objective To discuss the correlation between histological evaluation of primary lesions and prognosis of gastric cancer patients treated with neoadjuvant chemotherapy.Methods A total of 117 patients with stage Ⅱ-Ⅲ gastric cancer who received neoadjuvant chemotherapy in our hospital from January 2006 to December 2012 were enrolled.All patients received 2 courses of neoadjuvant chemotherapy and underwent CT,gastrointestinal radiography or endoscopic examination to evaluate the response to neoadjuvant chemotherapy,and the histochemical staining results of the surgical specimens were also used for chemotherapy responsive validation.Kappa (κ) coefficient was used to analyzed the consistency of different evaluation methods for chemotherapy reactivity.The 5-year survival rate was used for compared the effective assessments in three different approaches.Results There were 38 cases (32.5％),78 cases (66.7％) and 43 cases (36.8％) were considered to be CT,gastrointestinal radiography or endoscopic examination and histologic responders,respectively.Histological evaluation of primary lesions was less correlated with CT,gastrointestinal radiography or endoscopic evaluation (κ values were 0.10 and 0.19 respectively).Based on CT evaluation,the median survival time of patients with chemotherapy response was longer than 60 months,and the median survival time of patients without response was 43 months,and the difference was not statistically significant (x2 =2.978,P =0.076).Based on gastrointestinal radiography or endoscopy evaluation,the median survival time of patients with chemotherapy response was longer than 60 months,and the median survival time of patients without response was 29 months,and the difference was not statistically significant (x2 =1.230,P =0.239).Based on histological evaluation,the median survival time of patients with chemotherapy response was longer than 60 months,and the median survival time of patients without response was 18.5 months,and the difference was statistically significant (x2 =29.020,P ＜ 0.001).Multivariate Cox regression analysis showed that nonrespond of adjuvant chemotherapy under histologic evaluation (HR =4.021,95％ CI:1.548-8.767,P =0.002) and non-respond of gastrointestinal radiography or endoscopic examination (HR =8.210,95％ CI:4.333-17.980,P ＜ 0.001) were independent risk factors for poor prognosis in patients with gastric cancer,and intestinal gastric cancer (HR =0.241,95％ CI:0.080-0.871,P =0.019) was an independent predictor of survival improvement in patients with gastric cancer.Conclusion The degree of neoadjuvant chemotherapy response assessed by histological evaluation of primary lesions can effectively predict the long-term survival outcomes for gastric cancer patients.