1.Effects of medicated serum of Siwutang on autophagy of ovarian granulosa cells in polycystic ovarian syndrome
Yanshe SHAO ; Xuemei XU ; Baoqin YANG ; Huijuan LI ; Xia JI
China Pharmacy 2025;36(2):185-190
OBJECTIVE To investigate the effects of medicated serum of Siwutang on autophagy of ovarian granulosa cells (KGN cells) in polycystic ovarian syndrome (PCOS) and its underlying mechanism. METHODS Blank serum and different- concentration medicated serum of Siwutang were prepared by intragastric administration of normal saline and different doses of Siwutang [0.52, 1.04, 2.08 g/(kg·d)] in 3-month-old female SD rats. After screening the intervention concentration of Siwutang medicated serum, KGN cells were divided into control group (without any treatment), dehydroepiandrosterone (DHEA) group (treated with 50 μmol/L DHEA for 48 h), blank serum group (treated with 50 μmol/L DHEA for 48 h and with 10% blank serum for 72 h) and medium-concentration of Siwutang medicated serum group (treated with 50 μmol/L DHEA for 48 h and with 10% medium-concentration Siwutang medicated serum for 72 h). The number of autophagosomes was observed in each group, and protein expressions of pathway-related proteins [fructose-1, 6-bisphosphatase 1 (FBP1),mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR)], autophagy-related proteins [p62, microtubule-associated protein 1 light chain 3 (LC3)] and mRNA expression of FBP1 were also detected. The (transfected) cells were further divided into Siwutang group (treated with 10% medium dose of Siwutang medicated serum for 72 h after 48 h intervention with 50 μmol/L DHEA), Siwutang+si-NC group [negative control small interfering RNA (siRNA) transfected cells treated with 50 μmol/L DHEA for 48 h, and then with 10% medium-concentration of Siwutang medicated serum for 72 h] and Siwutang+si-FBP1 group (FBP1 siRNA transfected cells treated with 50 μmol/L DHEA for 48 h, and then with 10% medium-concentration Siwutang medicated serum for 72 h). The effects of knocking down FBP1 on the above-mentioned effects of Siwutang were detected. RESULTS Compared with control group, DHEA group exhibited an increase in the number of autophagosomes, an elevated LC3-Ⅱ/LC3-Ⅰ and p-mTOR/mTOR, as well as increases in protein and mRNA expressions of FBP1, and decreased protein expression of p62 (P<0.05). Compared to both DHEA group and blank serum group, the medium-concentration of Siwutang medicated serum group showed a decrease in the number of autophagosomes, a decrease in LC3-Ⅱ/LC3-Ⅰ, and increases in p-mTOR/mTOR, protein expression of p62, protein and mRNA expressions of FBP1 (P<0.05). After knocking down FBP1, compared with Siwutang+si-NC group, Siwutang+si-FBP1 group showed a significant decrease in cell viability, protein expression of p62 , protein and mRNA expressions of FBP1 as well as p-mTOR/mTOR, and an increase in LC3-Ⅱ/LC3-Ⅰ (P<0.05). CONCLUSIONS Siwutang can promote the phosphorylation of mTOR protein by up- regulating the protein and mRNA expressions of FBP1 in KGN cells, thus inhibiting autophagy of KGN cells.
2.Effects of medicated serum of Siwutang on autophagy of ovarian granulosa cells in polycystic ovarian syndrome
Yanshe SHAO ; Xuemei XU ; Baoqin YANG ; Huijuan LI ; Xia JI
China Pharmacy 2025;36(2):185-190
OBJECTIVE To investigate the effects of medicated serum of Siwutang on autophagy of ovarian granulosa cells (KGN cells) in polycystic ovarian syndrome (PCOS) and its underlying mechanism. METHODS Blank serum and different- concentration medicated serum of Siwutang were prepared by intragastric administration of normal saline and different doses of Siwutang [0.52, 1.04, 2.08 g/(kg·d)] in 3-month-old female SD rats. After screening the intervention concentration of Siwutang medicated serum, KGN cells were divided into control group (without any treatment), dehydroepiandrosterone (DHEA) group (treated with 50 μmol/L DHEA for 48 h), blank serum group (treated with 50 μmol/L DHEA for 48 h and with 10% blank serum for 72 h) and medium-concentration of Siwutang medicated serum group (treated with 50 μmol/L DHEA for 48 h and with 10% medium-concentration Siwutang medicated serum for 72 h). The number of autophagosomes was observed in each group, and protein expressions of pathway-related proteins [fructose-1, 6-bisphosphatase 1 (FBP1),mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR)], autophagy-related proteins [p62, microtubule-associated protein 1 light chain 3 (LC3)] and mRNA expression of FBP1 were also detected. The (transfected) cells were further divided into Siwutang group (treated with 10% medium dose of Siwutang medicated serum for 72 h after 48 h intervention with 50 μmol/L DHEA), Siwutang+si-NC group [negative control small interfering RNA (siRNA) transfected cells treated with 50 μmol/L DHEA for 48 h, and then with 10% medium-concentration of Siwutang medicated serum for 72 h] and Siwutang+si-FBP1 group (FBP1 siRNA transfected cells treated with 50 μmol/L DHEA for 48 h, and then with 10% medium-concentration Siwutang medicated serum for 72 h). The effects of knocking down FBP1 on the above-mentioned effects of Siwutang were detected. RESULTS Compared with control group, DHEA group exhibited an increase in the number of autophagosomes, an elevated LC3-Ⅱ/LC3-Ⅰ and p-mTOR/mTOR, as well as increases in protein and mRNA expressions of FBP1, and decreased protein expression of p62 (P<0.05). Compared to both DHEA group and blank serum group, the medium-concentration of Siwutang medicated serum group showed a decrease in the number of autophagosomes, a decrease in LC3-Ⅱ/LC3-Ⅰ, and increases in p-mTOR/mTOR, protein expression of p62, protein and mRNA expressions of FBP1 (P<0.05). After knocking down FBP1, compared with Siwutang+si-NC group, Siwutang+si-FBP1 group showed a significant decrease in cell viability, protein expression of p62 , protein and mRNA expressions of FBP1 as well as p-mTOR/mTOR, and an increase in LC3-Ⅱ/LC3-Ⅰ (P<0.05). CONCLUSIONS Siwutang can promote the phosphorylation of mTOR protein by up- regulating the protein and mRNA expressions of FBP1 in KGN cells, thus inhibiting autophagy of KGN cells.
3.Efficacy and safety of nicorandil and ticagrelor de-escalation after percutaneous coronary intervention for elderly patients with acute coronary syndrome
Xiang SHAO ; Ning BIAN ; Hong-Yan WANG ; Hai-Tao TIAN ; Can HUA ; Chao-Lian WU ; Bei-Xing ZHU ; Rui CHEN ; Jun-Xia LI ; Tian-Chang LI ; Lu MA
Medical Journal of Chinese People's Liberation Army 2024;49(1):75-81
Objective To explore the efficacy and safety of ticagrelor de-escalation and nicorandil therapy in elderly patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI).Methods A total of 300 elderly patients with ACS were selected from the Sixth and Seventh Medical Center of Chinese PLA General Hospital and Beijing Chaoyang Integrative Medicine Emergency Rescue and First Aid Hospital from November 2016 to June 2019,including 153 males and 147 females,aged>65 years old.All the patients received PCI,and all had double antiplatelet therapy(DAPT)scores≥2 and a new DAPT(PRECISE-DAPT)score of≥25.All patients were divided into two groups by random number table method before operation:ticagrelor group(n=146,ticagrelor 180 mg load dose followed by PCI,and ticagrelor 90 mg bid after surgery)and ticagrelor de-escalation + nicorandil group(n=154,ticagrelor 180 mg load dose followed by PCI,ticagrelor 90 mg bid+nicorandil 5 mg tid after surgery,changed to ticagrelor 60 mg bid+ nicorandil 5 mg tid 6 months later).Follow-up was 12 months.The composite end points of cardiovascular death,myocardial infarction and stroke,the composite end points of mild hemorrhage,minor hemorrhage,other major hemorrhage and major fatal/life-threatening hemorrhage as defined by the PLATO study,and the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding within 12 months in the two groups were observed.Results The comparison of general baseline data between the two groups showed no statistically significant difference(P>0.05).There was also no significant difference in the composite end points of cardiovascular death,myocardial infarction and stroke between the two groups(P>0.05).The cumulative incidence of bleeding events in ticagrelor de-escalation + nicorandil group was significantly lower than that in ticagrelor group(P<0.05),while the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding were also significantly lower than those in tecagrelor group(P<0.05).Conclusion In elderly patients with ACS,the treatment of ticagrelor de-escalation + nicorandil after PCI may not increase the incidence of ischemic events such as cardiovascular death,myocardial infarction or stroke,and it may reduce the incidence of hemorrhagic events.
4.Guiding recommendations for fertility preservation of female patients of reproductive age based on modified Delphi method
Ming-Xia LI ; Shu-Hui HU ; Shu-Yi SHAO ; Ying ZHANG
Fudan University Journal of Medical Sciences 2024;51(2):151-158,165
Objective To obtain guiding recommendations for the development of fertility preservation in female patients of reproductive age,so as to promote the scientific,standardized and orderly implementation of fertility preservation work.Methods A previous questionnaire survey was used to determine the preliminary recommendations,a modified Delphi method was used to invite 18 domestic experts of fertility preservation to conduct two rounds of expert consultation.Then we adjusted and summarized recommendations according to the results of the consultation.Results Finally,14 guiding recommendations for the development of fertility preservation in female patients of reproductive age were obtained according to the results of the Delphi consultation,including 5 recommendations at technical level,5 recommendations at political level and 4 recommendations at educational level.At technical level,it was proposed to establish a standardized operation process;at political level,it was proposed to improve the relevant legislation of fertility preservation in China to protect the safety and interests of patients;at educational level,it was suggested to take various forms to promote the mass dissemination of fertility preservation knowledge.Conclusion Guiding recommendations for fertility preservation in female patients of reproductive age can provide detailed and comprehensive guidance for promoting fertility preservation in female patients of reproductive age in Shanghai,and provide reference for carrying out fertility preservation in other regions.
5.Study on the population genetic structure and phylogenetic relationship of the Han population in Dalian
Wenqian SONG ; Shihang ZHOU ; Nan XIAO ; Lingzi PAN ; Linnan SHAO ; Yuexin XIA ; Ying DUAN ; Yicheng YANG ; Chunxiang LI ; Weijian YU
Chinese Journal of Forensic Medicine 2024;39(1):88-93
Objective To study the population genetic structure and phylogenetic relationships by combining Y-STR haplotype genetic information from the Han population in Dalian with 32 domestic and foreign groups.Methods Blood samples of 958 Han male volunteers from Dalian were collected.Genetic typing of 42 genetic loci was completed using Y-STR fluorescent reagent kits and capillary electrophoresis.Related forensic parameters were calculated.Nei's standard genetic distances among 33 populations based on 17 Y-STR loci were computed,in order to create a principal coordinate analysis as well as construct a phylogenetic tree.Results The analysis of genetic polymorphisms at 42 Y-STR loci revealed 30 unconventional alleles at 10 loci.Genetic analysis of the population based on 17 Y-STR loci confirmed that Dalian's Han population had the closest genetic distance to the Anshan's Han population,followed by populations from Henan,Heilongjiang,Jilin,Shandong,and Chongqing.Furthermore,the genetic distances between the Han population in Dalian and the Qiang population in Beichuan or the Miao population in Guizhou were relatively closer than that to the Manchu population living in Liaoning.Conclusion The genetic distance between the Han population in Dalian and other groups is not entirely proportional to ethnicities and geographical proximity.Both population migration and ethnic assimilation or isolation may have influence on it.
6.Hypericin inhibits the expression of NLRP3 in microglia of Parkinson's disease mice and alleviates the damage of DA-ergic neurons
Li-Shan FAN ; Jia ZHANG ; Si-Xiang NIU ; Qi XIAO ; Hui-Jie FAN ; Lei XU ; Li-Xia YANG ; Lu JIA ; Shao-Chen QIN ; Bao-Guo XIAO ; Cun-Gen MA ; Zhi CHAI
The Chinese Journal of Clinical Pharmacology 2024;40(17):2523-2527
Objective To observe the intervention effect of hypericin(HYP)on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease(PD)mice model and its mechanism.Methods Thirty C57BL/6 mice were randomly divided into normal,model and experimental groups with 10 mice per group.PD mouse model was established after 7 days of intraperitoneal injection of MPTP,and drug intervention was carried out from the first day of modeling.Normal group and model group were intraperitoneally injected with 500 μL·kg·d-1 0.9%NaCl.The experimental group was intraperitoneally injected with 25 mg·kg·d-1 HYP.The three groups of rats were given the drug once each time for 14 days.The expression levels of tyrosine hydroxylase(TH),Nod-like receptor thermal protein domain protein 3(NLRP3)and ionized calcium binding adapter molecule 1(Iba1)in the striatum of nigra were detected by Western blot.Results The climbing time of normal,model and experimental groups was(5.35±0.43),(9.71±1.19)and(8.07±0.34)s;suspension scores were(2.92±0.15),(1.38±0.28)and(1.96±0.28)points;the relative expression levels of TH protein were 1.04±0.06,0.51±0.09 and 0.75±0.07;the relative expression levels of NLRP3 protein were 0.51±0.03,1.00±0.04 and 0.77±0.06;the relative expression levels of Iba1 protein were 0.68±0.10,1.30±0.28 and 0.89±0.05,respectively.The above indexes in the model group were statistically significant compared with the experimental group and the normal group(all P<0.01).Conclusion HYP plays a therapeutic role in PD by inhibiting the expression of NLRP3 inflammasome in PD mice.
7.Coronary artery perforation after using shockwave balloon during percutaneous coronary intervention treatment:a case report
Chen-Ji XU ; Fei LI ; Fa ZHENG ; Bin ZHANG ; Feng-Xia QU ; Jian-Meng WANG ; Ya-Qun ZHOU ; Xian-Liang LI ; Song-Tao WANG ; Yan SHAO ; Chang-Hong LU
Chinese Journal of Interventional Cardiology 2024;32(7):405-408
Coronary perforation is when a contrast agent or blood flows outside a blood vessel through a tear in a coronary artery.In this case,we reported a case of percutaneous coronary intervention for coronary calcified lesions,which led to iatrogenic coronary perforation and cardiac tamponade after the use of Shockwave balloon to treat intracoronary calcified nodules,and the management of PCI-related CAP was systematically reviewed through the literature.
8.Significance of 18F-PI-2620 PET imaging for diagnosing tau protein deposition in patients with different cognitive disorders alongside cognitive correlation analysis
Gan HUANG ; Yan ZHANG ; Cheng WANG ; Mei XIN ; Hongda SHAO ; Yue WANG ; Liangrong WAN ; Ju QIU ; Qun XU ; Jianjun LIU ; Xia LI ; Chenpeng ZHANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(5):273-278
Objective:To evaluate the values of 18F-PI-2620 PET/CT brain imaging with SUV ratio (SUVR) in the assessment of tau protein deposition in the brain of patients with different cognitive disorders and its correlation with cognition. Methods:This was a cross-sectional study. From December 2019 to November 2022, a total of 67 subjects including 54 patients with Alzheimer′s disease (AD; 21 males, 33 females, age (68.6±7.8) years), 7 patients with mild cognitive impairment (MCI; 1 male, 6 females, age (63.1±11.2) years) and 6 healthy controls (HC; 4 males, 2 females, age (69.0±5.8) years) were enrolled retrospectively in Renji Hospital. All participants were examined by 18F-PI-2620 PET/CT. SUVRs of brain regions were obtained, including frontal lobe, temporal lobe, occipital lobe, parietal lobe, insular lobe, whole brain, as well as 10 independent brain ROIs (amygdala, orbitofrontal cortex, cingulate gyrus, superior occipital gyrus, superior parietal gyrus, inferior angular gyrus, precuneus, inferior temporal gyrus, entorhinal cortex and parahippocampal gyrus), with inferior cerebellum cortex as the reference region. All participants were estimated by cognitive scales(mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA)). One-way analysis of variance and the least significant difference t test were used to compare the differences of SUVR in each brain region among HC, MCI and AD groups. ROC curve analysis was used to determine the optimal cut-off values of SUVR in each brain region for the differential diagnosis of AD-MCI and AD-HC. Pearson correlation analysis was employed to examine the correlations of SUVR with cognitive scale scores. Results:The SUVR of whole brain was 1.40±0.31 in AD group, 1.08±0.19 in MCI group, and 1.01±0.12 in HC group. SUVR analysis in the whole brain and each brain region could distinguish AD from HC, AD from MCI ( F values: 1.76-10.09, t values: 2.98-7.47, all P<0.05), but could not distinguish HC from MCI ( t values: 0.17-1.53, all P>0.05). ROC curve analysis showed that the best cut-off value of SUVR was 1.18 for whole brain (AUC=0.89), 1.13 for amygdala (AUC=0.94) and 1.26 for parahippocampal gyrus (AUC=0.94) for differential diagnosis of AD and HC, which was 1.06 for whole brain (AUC=0.82), 1.18 for amygdala (AUC=0.88) and 1.28 (AUC=0.88) for infratemporal gyrus to differential diagnosis of AD and MCI. SUVRs of the whole brain, frontal, occipital, parietal, temporal and insula were significantly negatively correlated with MMSE and MoCA cognitive scale scores ( r values: from -0.64 to -0.40, all P<0.05). Conclusions:SUVR quantitative analysis in 18F-PI-2620 PET imaging can assist the differential diagnosis of AD and HC, AD and MCI. The SUVRs of whole brain and five lobes show negative correlations with MMSE and MoCA scores.
9.Diagnostic efficiency of 18F-FDG PET for Alzheimer′s disease in patients with memory impairment
Yan ZHANG ; Chenpeng ZHANG ; Gan HUANG ; Cheng WANG ; Mei XIN ; Hongda SHAO ; Yue WANG ; Liangrong WAN ; Ju QIU ; Qun XU ; Xia LI ; Jianjun LIU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(12):712-717
Objective:To assess the diagnostic efficiency of 18F-FDG PET for Alzheimer′s disease (AD) in patients with memory impairment. Methods:A retrospective analysis was conducted on 96 patients (40 males, 56 females, age: 69.0(62.8, 74.0) years) initially diagnosed with memory impairment in Renji Hospital, School of Medicine, Shanghai Jiao Tong University between August 2019 and September 2023. The amyloid-tau-neurodegeneration (ATN) criteria, based on 18F-AV45+ 18F-PI-2620 PET/CT+ MRI imaging results, were used as the diagnostic standard for AD. Visual analysis (temporoparietal or posterior cingulate cortex (PCC) hypometabolism) and semi-quantitative analysis methods (PET-SCORE and NeuroQ software analysis (SUV ratio, SUVR)) were applied to evaluate the diagnostic efficiency of 18F-FDG PET imaging for AD. Diagnostic efficiencies of visual assessment and semi-quantitative parameters were compared by χ2 test. Additionally, Pearson correlation analysis was performed to examine the relationship between results of PET-SCORE and cognitive scales. Results:Of the 96 patients initially diagnosed with memory impairment, 61 were clinically diagnosed with AD, while 35 were non-AD patients. Visual assessment of temporoparietal hypometabolism showed the highest sensitivity (91.80%, 56/61), which was significantly different from the sensitivities of PET-SCORE (40.98%(25/61); χ2=29.03, P<0.001) and visual assessment of PCC hypometabolism (77.05%(47/61); χ2=5.82, P=0.016). While semi-quantitative assessment using PET-SCORE demonstrated the highest specificity (100%, 35/35), which was significantly different from the specificities of visual assessment methods (temporoparietal hypometabolism: 17.14%(6/35), χ2=27.03, P<0.001; PCC hypometabolism: 54.29%(19/35), χ2=14.06, P<0.001). PET-SCORE exhibited statistically significant correlations with Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Activities of Daily Living (ADL) scores ( r values: -0.38, -0.36, 0.31, all P<0.01). Conclusions:Among patients initially diagnosed with memory impairment, visual assessment in 18F-FDG PET imaging analysis demonstrates higher sensitivity, while semi-quantitative analysis using PET-SCORE exhibits higher specificity. PET-SCORE shows statistically significant correlation with the severity of cognitive decline.
10.Study of pre-hospital temporary VV-ECMO for the treatment of high-altitude severe blast lung injury based on animal models
Zheng-Bin WU ; Shi-Feng SHAO ; Liang-Chao ZHANG ; Zhao-Xia DUAN ; Yao-Li WANG ; Zong-An LIANG ; Jian-Min WANG
Journal of Regional Anatomy and Operative Surgery 2024;33(5):373-378
Objectives To explore the feasibility of temporary veno-venous extracorporeal membrane oxygenation(VV-ECMO)technology for early on-site treatment,through establishing an animal model of severe blast lung injury in goats by free-field chemical explosion experiments in high-altitude regions.Methods A total of 16 adult goats were selected,and divided into the control group and the treatment group according to the random number table method,with 8 goats in each group.A model of severe blast lung injury was established at an altitude of 4 600 meters above sea level,then the goats in the control group were given respiratory support and the goats in the treatment group were given temporary VV-ECMO treatment.The survival status of the goats 15 minutes after injury was recorded,the vital signs[including body temperature,respiration rate,heart rate,and mean arterial pressure(MAP)]and arterial blood gas analysis indicators[including pH,arterial partial pressure of oxygen(PO2),arterial partial pressure of carbon dioxide(PCO2),oxygen saturation(SaO2),lactate(LAC),calcium(Ca2+),hematocrit(HCT),and hemoglobin(Hb)]before injury and 1 hour,2 hours,3 hours after injury were compared in the two groups.The post-mortem examination was performed on all dead goats and sacrificed goats after treatment,the severity of lung injury was assessed by organ injury scaling(OIS),and the lung injury score was evaluated by abbreviated injury scale(AIS).The wet-to-dry weight ratio(W/D)and lung coefficient were calculated.Results Within 15 minutes after the explosion,4 goats in the control group died and 4 goats survived;and 5 goats in the treatment group died and 3 goats survived.There was no statistically significant difference in the body temperature,respiration rate,heart rate,or MAP before and after injury between the two groups(P>0.05).The PaO2 and SaO2 1 hour,2 hours,and 3 hours after injury in the treatment group were superior than those in the control group(P<0.05),the Ca2+ 2 hours after injury was significantly higher than that in the control group(P<0.05),and there was no statistically significant difference in the pH,PCO2,LAC,HCT or Hb at different time points after injury between the two groups(P>0.05).There was no statistically significant difference in the OIS,AIS or lung coefficient between the two groups(P>0.05),but the W/D of the lung tissue in the control group was lower than that in the treatment group(P<0.05).Conclusion We have established a novel,feasible,and stable treatment effect temporary VV-ECMO animal treatment strategy for the first time in the high-altitude regions,which can provide animal experiment evidence for the early on-site VV-ECMO treatment of severe blast lung injury in high-altitude regions.

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