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 assess the association of cytotoxic T lymphocyte-associated antigen-4 ( CTLA-4) gene polymorphisms with the prognosis of patients with Bladder urothelial carcinoma (BUC). Methods:From February 2019 to October 2020, 256 BUS patients treated at the Xinxiang Central Hospital were selected as the study group, whilst 250 healthy individuals were selected as the control group. Genotypes of rs5742909 (-318C/T), rs231775 (+ 49A/G) and rs4553808 (-1661A/G) were determined by PCR-restriction fragment length polymorphism assay. The frequencies of genotypes and alleles of the CTLA-4 gene were compared between the two groups. All patients had undergone surgical treatment and were followed up for 3 years and divided into good prognosis group ( n=166) and poor prognosis group ( n=86) based on the status of disease. The distribution of alleles and genotypes were compared, and Kaplan-Meier analysis was used to assess the association of genetic polymorphisms with the prognosis. Results:No significant difference was found in the gender, age, BMI, smoking history and alcohol use between the two groups ( P>0.05). The frequencies of GG genotype and G allele for the rs231775 (+ 49A/G) and rs4553808 (-1661A/G) loci were significantly higher in the study group compared with the control group ( P<0.05), whilst no statistical difference was found in the genotypic and allelic frequency for the rs5742909 locus between the two groups ( P>0.05). Among the 252 subjects who had completed follow-up, 86 had poor prognosis and 166 had good prognosis. The frequencies of GG genotype and G allele at the rs231775 (+ 49A/G) and rs4553808 (-1661A/G) loci were significantly lower in the good prognosis group compared with the poor prognosis group ( P<0.05). Kaplan-Meier survival curve analysis showed that the survival time of patients with GG genotype for the rs231775 (+ 49A/G) and rs4553808 (-1661A/G) loci was significantly shorter than patients with AA or AG genotypes (Log Rank 2 = 13.654, 9.974, P<0.001). Conclusion:The polymorphisms of the rs231775 and rs4553808 loci of the CTLA-4 gene are associated with genetic susceptibility and poor prognosis for BUC, and a higher GG genotypic frequency may increase the risk for infection and poor prognosis of the patients.

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 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: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.

Objective:To explore the abnormal brain metabolic pattern and connectivity in temporal lobe epilepsy (TLE) patients.Methods:18F-FDG PET images of 75 patients diagnosed as drug resistant unilateral TLE from January 2014 to December 2016 in Huashan Hospital of Fudan University were collected retrospectively, including 41 (22 males, 19 females, age (28.4±8.7) years) left TLE (LTLE) and 34 (13 males, 21 females, age (28.5±8.8) years) right TLE (RTLE). Forty-four healthy controls (24 males, 20 females, age (31.2±6.2) years) were also enrolled. The cerebral glucose metabolism in TLE patients and the controls were analyzed with statistical parametric mapping (SPM) 12. The brain connectivity based on glucose metabolism were analyzed with bilateral hippocampus and amygdala as seeds. Permutation test with 1 000 permutations was used to analyze data. Results:Compared to control group, in both LTLE and RTLE groups, hypometabolism was found in affected hippocampus, amygdala, insula and temporal gyrus and hypermetabolism was observed in health hippocampus, parahippocampal gyrus, amygdala, lenticular nucleus and thalamus. In addition, hypometabolism was also found in affected superior/middle frontal gyrus and hypermetabolism was also found in bilateral frontal-orbital gyrus, bilateral cerebellum, affected lenticular nucleus and thalamus in LTLE group. In both TLE groups, affected seeds exhibited increased connectivity with affected superior frontal gyrus, lingual gyrus, fusiform gyrus, superior/middle temporal gyrus and temporal pole (all P<0.05); affected seeds exhibited increased connectivity with health superior frontal gyrus ( P=0.005), lingual gyrus ( P=0.018) and transverse temporal gyrus ( P=0.016) in RTLE group in addition. Besides, affected seeds exhibited decreased connectivity with bilateral default mode network (DMN) (all P<0.05), affected caudate nucleus ( P=0.015) and health thalamus ( P=0.008), in a uniform distribution pattern in LTLE group, and with bilateral cerebral cortex in an irregular distribution pattern in RTLE group (all P<0.05). In LTLE group, health seeds exhibited more increased connections with superior ( P=0.005)/middle frontal gyrus ( P=0.042), health hippocampus ( P=0.038), parahippocampal gyrus ( P=0.019), amygdala ( P=0.038), posterior cingulate gyrus ( P=0.004), and bilateral fusiform gyrusand ( P=0.048) compared with RTLE group; while, in RTLE group, health seeds exhibited more decreased connections with health superior ( P=0.047), inferior frontal gyrus ( P<0.001), orbital frontal gyrus ( P<0.001) and rectus gyrus ( P=0.016) compared with LTLE group. Conclusion:Altered brain glucose metabolism and connectivity pattern are found and will elucidate the underlying metabolic pattern of TLE.

Objective:To explore the efficacy and safety of posterior retroperitoneoscopic adrenalectomy (PRA) in the prone position.Methods:The clinical data of 74 patients who underwent PRA in the prone position in our hospital from January 2019 to February 2021 were reviewed. There were 36 males and 38 females, with an average age was (54.4±12.5) years old. The body mass index was (24.03±3.5) kg/m 2. CT scans of the adrenal glands were performed before operation. There were 39 cases of adrenal tumors on the left side, 33 cases on the right side, and 2 cases on both sides. The diameter of adrenal tumors shown on CT was (2.4±1.3) cm. Among them, 22 cases were diagnosed of non-functional adrenal tumors, 21 cases were primary aldosteronism, 8 cases were Cushing syndrome, and 23 cases were pheochromocytoma . The PRA in the prone position were performed in all 74 patients(76 sides). Results:The operation was performed successfully in all 74 patients(76 sides), of which 42 cases underwent unilateral adrenalectomy, 30 cases underwent unilateral partial adrenalectomy and 2 cases underwent bilateral adrenalectomy. The operation time was (53.2±16.1) min for 76 sides, and the time of two bilateral cases was 70 min and 115 min respectively. The median time of rainage tube indwelling was 3(0, 4) d, and the hospital stay was (4.2±0.9) d. The pathological diagnosis: there were 32 cases of adrenal cortical adenoma, 8 cases of adrenal cortical hyperplasia nodule, 5 cases of adrenal cyst, 7 cases of adrenal medullary lipoma, and 22 cases of adrenal pheochromocytoma. No adverse complications occurred during the perioperative period. The patients were followed-up for (12.5±2.7) months, and no tumor recurrence or long-term complications occurred.Conclusions:Posterior retroperitoneoscopic adrenalectomy in the prone position has the advantages of reducing bleeding and exudation, and rapid recovery after surgery, which provides a safe and effective surgical method for the treatment of adrenal tumors.

Objective To explore the impact of mindfulness on sleep and the mediating role of resilience.Methods A total of 540 medical staff in a three first-class hospital were assessed by five facet mindfulness questionnaire (FFMQ),Pittsburgh sleep quality index(PSQI) and Connor-Davidson resilience scale(CD-RISC).Results The average PSQI scores of medical staff was (6.67±3.20),of which the total score was equal or above 8 accounting for 37.04％.The positive rate of each factor of PSQI (factor score ≥2) was 51.67％ for daytime function,37.22％ for sleeping time,and 24.07％ for subjective sleep quality.The total score of PSQI was (6.67±3.20),the score of FFMQ was (119.55±9.90),and the score of CDRISC was (59.50± 12.77).PSQI was negatively correlated with FFMQ and CD-RISC (r=-0.29,-0.24;both P＜0.01),and there was a significant positive correlation between FFMQ and CD-RISC (r=0.48,P＜0.01).The factors of FFMQ associated with CD-RISC were followed by the description of mindfulness,the action of awareness,the non-reaction and the observation of mindfulness.The multi-linear regression analysis showed that resilience played a part mediating role between mindfulness and sleep quality,with a mediating effect of 20.9％.Conclusion Mindfulness has a positive impact on the quality of sleep of medical staff through resilience.