ObjectiveTo explore the effects of different dosage forms of Kaixinsan （KXS） on the morphology and function of mitochondria in rat models of Alzheimer's disease （AD） and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group， model group， treatment groups receiving KXS decoction， powders， and granules （3.08 g·kg^-1）， as well as donepezil group （0.51×10^-3 g·kg^-1）， with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin （STZ）. After 30 days of administration， behavioral assessments were conducted， and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay （ELISA）. Changes in mitochondrial membrane potential were measured via JC-1 staining， and superoxide dismutase （SOD） activity and reactive oxygen species （ROS） levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase （AMPK）， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， and silent information regulator 3 （SIRT3） was detected by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）， and Western blot was used to examine the protein expression levels of optic atrophy protein1 （OPA1）， mitochondrial fission protein 1 （FIS1）， AMPK， p-AMPK， PGC-1α， and SIRT3. ResultsCompared with the sham group， rats in the model group had significantly lower recognition index， spontaneous alternation rate， escape latency， number of platform crossings， time spent in the target quadrant， and percentage of distance traveled in the target quadrant distance （P<0.05， P<0.01）. Significant mitochondrial damage was observed in the hippocampal tissue， with a marked decrease in mitochondrial respiratory chain complex content （P<0.01） and reduced mitochondrial membrane potential （P<0.05）. Additionally， the SOD activity was reduced， while ROS levels were elevated （P<0.01）. The mRNA expression of PGC-1α and SIRT3 was significantly downregulated （P<0.01）， along with decreased protein expression levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， whereas FIS1 protein expression was significantly upregulated （P<0.05， P<0.01）. Compared with the model group， rats in KXS-treated groups （various dosage forms） showed significant improvement in behavioral indexes （P<0.05， P<0.01）， reduced hippocampal mitochondrial damage， and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased （P<0.05， P<0.01）， and mitochondrial membrane potentials were elevated （P<0.05）. SOD activity was elevated， and ROS levels were significantly reduced （P<0.05， P<0.01）. Furthermore， the mRNA expression of PGC-1α and SIRT3 was upregulated， with increased protein levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， while FIS1 protein expression levels were significantly reduced （P<0.05， P<0.01）. Across the KXS-treated groups， the granule group showed a higher spontaneous alternation rate than the decoction and powder groups （P<0.05）. ConclusionKXS decoction， powders， and granules can improve the learning and memory ability of rats， with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway， improvement of the mitochondrial function， and subsequent amelioration of the brain energy metabolism disorders.

ObjectiveTo explore the effects of different dosage forms of Kaixinsan （KXS） on the morphology and function of mitochondria in rat models of Alzheimer's disease （AD） and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group， model group， treatment groups receiving KXS decoction， powders， and granules （3.08 g·kg^-1）， as well as donepezil group （0.51×10^-3 g·kg^-1）， with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin （STZ）. After 30 days of administration， behavioral assessments were conducted， and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay （ELISA）. Changes in mitochondrial membrane potential were measured via JC-1 staining， and superoxide dismutase （SOD） activity and reactive oxygen species （ROS） levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase （AMPK）， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， and silent information regulator 3 （SIRT3） was detected by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）， and Western blot was used to examine the protein expression levels of optic atrophy protein1 （OPA1）， mitochondrial fission protein 1 （FIS1）， AMPK， p-AMPK， PGC-1α， and SIRT3. ResultsCompared with the sham group， rats in the model group had significantly lower recognition index， spontaneous alternation rate， escape latency， number of platform crossings， time spent in the target quadrant， and percentage of distance traveled in the target quadrant distance （P<0.05， P<0.01）. Significant mitochondrial damage was observed in the hippocampal tissue， with a marked decrease in mitochondrial respiratory chain complex content （P<0.01） and reduced mitochondrial membrane potential （P<0.05）. Additionally， the SOD activity was reduced， while ROS levels were elevated （P<0.01）. The mRNA expression of PGC-1α and SIRT3 was significantly downregulated （P<0.01）， along with decreased protein expression levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， whereas FIS1 protein expression was significantly upregulated （P<0.05， P<0.01）. Compared with the model group， rats in KXS-treated groups （various dosage forms） showed significant improvement in behavioral indexes （P<0.05， P<0.01）， reduced hippocampal mitochondrial damage， and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased （P<0.05， P<0.01）， and mitochondrial membrane potentials were elevated （P<0.05）. SOD activity was elevated， and ROS levels were significantly reduced （P<0.05， P<0.01）. Furthermore， the mRNA expression of PGC-1α and SIRT3 was upregulated， with increased protein levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， while FIS1 protein expression levels were significantly reduced （P<0.05， P<0.01）. Across the KXS-treated groups， the granule group showed a higher spontaneous alternation rate than the decoction and powder groups （P<0.05）. ConclusionKXS decoction， powders， and granules can improve the learning and memory ability of rats， with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway， improvement of the mitochondrial function， and subsequent amelioration of the brain energy metabolism disorders.

Objective To rapidly visualize and detect the extracellular vesicles of glial cells in a simulated space environment.Methods By using 2,5 Gy irradiation and 12,24 h microgravity treatment,a damage model of glial cells was established in a simulated space environment.Exosomes extracted from conditioned media with reagent kits were transferred to neurons to elucidate the impact of glial cells on neurons.By performing live-cell fluorescence labeling of exosomes,a visualization monitoring scheme based on fluorescence intensity analysis was developed to characterize the release patterns of extracellular vesicles.The release patterns of exosomes were represented by the fluorescence intensity of the conditioned media.The effects of different storage conditions and duration on the quantity and size of exosomes were investigated.Results The exosomes released from damaged glial cells in the simulated space environment could to some extent protect neurons,with exosomes playing a decisive role in this process,and the neurosystem exosome visualization detection scheme was consistent with the traditional exosome validation scheme.An empirical curve for exosome quantity and size was established for semi-quantitative analysis,providing a new approach for rapid detection of exosomes in cell culture media.Furthermore,the optimal storage conditions for culture medium samples were clarified,laying the foundation for ground/space-based online analysis of culture medium samples after spaceflight.Conclusion Exosome rapid detection and analysis can be achieved through fluorescence labeling and utilized to investigate glial cell injury in a simulated space environment.

Humans ; Hypertension ; Atherosclerosis ; Colorectal Neoplasms ; Risk Factors

Objective:To compare the efficacy of domestic and imported hemostatic clips in preventing delayed post-polypectomy bleeding (DPPB) after endoscopic resection of colorectal polyps ≥ 10 mm.Methods:Clinical data of 789 patients who underwent endoscopic resection of colorectal polyps (polyp diameter ≥10 mm) in Beijing Friendship Hospital, Capital Medical University from January 2018 to December 2019 were collected. The patients were divided into DPPB group ( n=15) and non-DPPB group ( n=774). Univariate and multivariate logistic regression models were used to analyze the influential factors for DPPB. The patients using one type of hemostatic clip were divided into the domestic hemostatic clip group ( n=499) and the imported hemostatic clip group ( n=208). The efficacy of hemostatic clips in preventing DPPB in the two groups was compared. Results:Among the 789 patients undergoing endoscopic resection of colorectal polyps, 1.9% (15/789) suffered from DPPB. Multivariate logistic regression analysis showed that pedunculated polyp was an independent risk factor for DPPB ( OR=6.621, 95% CI: 2.278-19.241, P=0.001), and closure of mucosal defect was an independent protective factor for DPPB ( OR=0.169,95% CI: 0.050-0.570, P=0.004). Regardless of physician experience, there was no significant difference between the domestic and imported hemostatic clip group in preventing DPPB after endoscopic resection of colorectal polyps ≥10 mm [experienced physicians: 1.8% (7/385) VS 0.6% (1/175), χ2=1.314, P=0.445; common physicians: 2.6% (3/114) VS 3.0% (1/33), χ2=0.010, P>0.999]. The domestic hemostatic clip group paid for less medical expenses than the imported hemostatic clip group (experienced physicians: 1 433.51±889.02 yuan VS 3 033.97±1 686.87 yuan, t<0.001 , P<0.001; common physicians: 1 181.58±815.29 yuan VS 3 303.46±1 690.43 yuan, t<0.001 ,P<0.001). Conclusion:Pedunculated polyp is an independent risk factor for DPPB after endoscopic resection of colorectal polyp larger than 10 mm, and clipping can significantly reduce the risk for DPPB. There is no significant difference in the prevention of DPPB between domestic and imported clips, but domestic clips compared with imported clips yield less medical burden, which are suitable for promotion to primary hospitals and major clinical centers.

Objective:To identify key genes and their potential biological mechanisms in the progression of non-alcoholic fatty liver disease (NAFLD) using bioinformatics technology.Methods:Genes differentially expressed in simple non-alcoholic fatty liver disease (NAFL) and non-alcoholic steatohepatitis (NASH) were analyzed by integrating NAFLD-related sequencing datasets GSE135251 and GSE167523 from the Gene Expression Omnibus (GEO) datebase. Gene Ontology (GO) functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome signaling pathway analysis were performed. Key genes were identified by STRING database and Cytoscape3.7.2 software, and the expression of key genes under different fibrosis grades and activity scores was observed. In addition, the expression of key genes in different cell clusters was observed based on the single-cell RNA-seq dataset of NAFLD mice.Results:Bioinformatics methods were used to obtain 97 common differential genes in NAFLD from two datasets. GO functional enrichment analysis was mainly performed in Extracellular Matrix (ECM) tissues. The main signaling pathway is ECM-receptor interaction. Five key genes were identified based on PPI network and Cytoscape software: COL1A1, THBS2, CXCL8, THY1 and LOXL1. The expression of key genes was significantly positively correlated with fibrosis grade and activity score, indicating that they were closely related to the progression of NAFLD. These key genes are highly expressed in hepatic stellate cells (HSCs) and natural killer/T cells (NK/T cells).Conclusion:In this study, bioinformatics technology was used to identify five key genes that may be involved in the NAFL-NASH transformation, suggesting that the ECM-receptor interaction signaling pathway may be a key molecular mechanism of NAFLD disease progression.

Objective:To analyze the risk factors for the most common adverse events, i.e. abdominal pain and distension in sedation-free colonoscopy.Methods:This was a multicenter clinical study, in which clinical data of patients including outpatients and inpatients who underwent selective sedation-free colonoscopy at six gastrointestinal endoscopy centers from July 2017 to December 2019 were collected, including patients' general information, complicating diseases, examination time, examination results, and occurrence of adverse events of abdominal pain and distension. Univariate and multivariate logistic regression was performed to analyze the risk factors for adverse events of abdominal pain and distension during sedation-free colonoscopy.Results:A total of 2 394 patients underwent sedation-free colonoscopy, among whom 690 (28.8%) suffered from abdominal pain, and 1 151 (48.1%) experienced abdominal distension. The results of multivariate logistic analysis showed that overweight ( OR=1.33, 95% CI:1.09-1.62, P=0.005), obesity ( OR=1.55, 95% CI:1.14-2.11, P=0.005) and combination of hypertension ( OR=1.58, 95% CI:1.23-2.02, P<0.001) were independent risk factors for abdominal pain during sedation-free colonoscopy, and overweight ( OR=1.40, 95% CI:1.17-1.68, P<0.001) and combination of hypertension ( OR=1.39,95% CI:1.10-1.76, P=0.006) were independent risk factors for abdominal distension during sedation-free colonoscopy. Conclusion:Obesity, overweight and combination of hypertension are independent risk factors for abdominal pain, and overweight and combination of hypertension are independent risk factors for abdominal distension during sedation-free colonoscopy.

Objective:To determine national trends for breast conserving surgery and to explore the factors affecting the scale of breast conserving surgery in China.Methods:A questionnaire survey was mailed to 110 hospitals with an year′s volume of more than 200 breast cancer surgeries in each center in China concerning hospital variations and percentage of breast conserving surgery.Results:The overall proportion of breast conserving surgery is 21.9% for operable breast cancer in China. There is a significant positive correlation between local Gross Domestic Product (GDP) and the rate of breast conserving surgery ( P=0.001). Hospitals with higher annual operation volume have higher breast-conserving ratios( P=0.042). Compared with non-teaching hospitals, more patients with stage I breast cancer underwent breast conserving surgery in teaching hospitals ( P=0.021). After breast-conserving surgery, the proportion of positive margins needing reoperation had a lower percentage and in cancer hospitals it was the lowest ( P=0.023). The method of pathological evaluation and the remedy strategy for positive margin was not related to per capita GDP and hospital category ( P>0.05). Conclusions:This survey demonstrates the current practices of breast conserving surgery in China. Local GDP, hospital category and tumor stage were factors influencing breast conserving surgery. Breast conserving surgery in China is still at a low level compared with developed countries.

Objective To investigate the safety and efficacy of 177Lu-prostate specific membrane antigen (PSMA)-617 in the treatment of metastatic castration-resistant prostate cancer (mCRPC).Methods From August 2017 to September 2018,11 patients(average age 70.6 years) with mCRPC who underwent 177Lu-PSMA-617 therapy in Nanjing First Hospital were studied.All patients underwent 68Ga-PSMA-11 PET/CT before therapy to assess the tumor radioactive uptake.Blood routine examination and renal function test results were documented before and after therapy to assess the safety.The efficacy was reflected by the changes of prostate specific antigen (PSA) levels and maximum standardized uptake value (SUVmax) on 68Ga-PSMA-11 PET/CT imaging.Paired t test and Wilcoxon's sign rank test were used to analyze the data.Results No acute side effects were observed after therapy of 177Lu-PSMA-617.There were no statistically significant differences after therapy in WBC counts,RBC counts,and PLT,as well as Hb levels (t values:-0.28-1.11,all P＞ 0.05).No kidney toxicity was found.The PSA level after 177Lu-PSMA-617 therapy was significantly lower than that before therapy (80.70 (14.29,1 538.00) μg/L vs 604.60 (88.41,3 980.00) μg/L;u =59,P =0.023).Of the 11 patients,only 2 had elevated PSA levels and disease progression,while the other 9 patients had varying decreases,of which 2/11 decreased by ＞30％ and 7/11 decreased by ＞50％.After therapy,SUVmax of metastatic lesions and metastatic lymph nodes were decreased in 9 and 2 patients respectively.Conclusions 177Lu-PSMA-617 has a good therapeutic value for mCRPC.It is safe and has no obvious side effects.

Objective To investigate the mRNA and protein expression levels of telomeric-repeat binding factor-1 (TRF1) and TRF2 in the peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE),and the relations between these gene expression levels and clinical data of SLE patients were explored.Methods According to disease activity,these SLE patients were divided into the active group (40 cases) and the stable group (67 cases).These patients were also grouped as renal damage group (46 cases) and renal damage-free group (61 cases) based on their renal conditions.Healthy individuals (41 cases) were also included as control.Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to study the mRNA expression of TRF1 and TRF2.The protein levels of TRF1 and TRF2 were measured by Western Blot (WB).Independent-Samples t test or one-way analysis of variance (ANOVA) in conjunction with the Least-Significant Difference method (LSD method) wasperformed if the data were in normal distributions;otherwise,the Kruskal-Wallis test was applied.Spearman's correlation analysis was also used for statistical analysis.Results The mRNA and protein expression levels of TRF1 and TRF2 in the PBMCs of the active group (TRF1:0.003 1±0.003 3;TRF2:0.010 5±0.064 8) and renal damage group (TRF1:0.002 3 ±0.002 6;TRF2:0.004 3 ±0.003 3) were significantly increased compared to the stable group (TRF1:0.001 2±0.001 1;TRF2:0.004 2±0.008 6),the renal damage-free group (TRF1:0.001 3±0.001 8;TRF2:0.003 4±0.007 2) and healthy (TRF1:0.001 2±0.003 0;TRF2:0.003 4±0.002 7) individuals respectively (P＜0.05).In SLE patients,the expression levels of TRF1 mRNA were correlated with erythrocyte sedimentation rate (r=0.365,P＜0.05);the expression levels of TRF2 mRNA were correlated with SLEDAI score (r=0.270,P＜0.05),erythrocyte sedimentation rate (r=0.304,P＜0.05),creatinine (r=0.258,P＜0.05) and 24-hour urinary protein (r=0.344,P＜0.05).Conclusion Altered expression of TRF1 and TRF2 might be involved in the pathogenesis of Systemic lupus erythematosus.The positive correlation between TRF2 and SLEDAI score,24-hour urinary protein suggest that TRF2 might be usedas a biomarker for disease activity or renal damage in