Objective To observe the repair effect and mechanism of Danhuang Powder-containing serum on high glucose-induced vascular endothelial cell injury.Methods Danhuang Powder-containing serum was prepared.Human umbilical vein endothelial cells(HUVECs)were cultured to be divided into control group,recombinant human epidermal growth factor(called"growth factor"for short)group,Danhuang Powder group,high glucose group,high glucose+growth factor group,and high glucose+Danhuang Powder group.After corresponding intervention in each group for 48 hours,the cell ultrastructure and autophagy were observed under transmission electron microscope,apoptosis was detected by flow cytometry,and the protein expression levels of vascular endothelial growth factor(VEGF),epidermal growth factor(EGF)and basic fibroblast growth factor(bFGF)in the cells were detected by Western Blot.Results(1)The intra-mitochondrial ridges in the control group were clearly visible,autophagosomes and autolysosomes were fewer;mitochondria in the high glucose group were swollen and irregular,and appeared vacuolated;and the more typical autophagy-like structures were seen in the high glucose+Danhuang Powder group.(2)Compared with the high glucose group and high glucose+growth factor group,the apoptosis rate of cells in the high glucose+Danhuang Powder group was significantly decreased(P<0.05).(3)Compared with the high glucose group and the high glucose+growth factor group,the protein expression levels of VEGF,EGF and bFGF in the cells of the high glucose+Danhuang Powder group were significantly increased(P<0.05).Conclusion Danhuang Powder-containing serum can reduce the high glucose-induced damage in HUVEC cells,and its mechanism may be related to the activation of mitochondrial autophagy,and the inhibition of apoptosis,as well as the up-regulation of the expression of VEGF,EGF and bFGF.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

Objective:To study the anti-inflammatory and protective effects of electroacupuncture on rats with cardiopulmo-nary resuscitation based on cholinergic anti-inflammatory pathway(CAP).Methods:Sixty male SD rats were randomly divided into sham operation group(Sham group),cardiopulmonary resuscitation group,electroacupuncture group,antagonist of α7-nicotinic ace-tylcholine receptor(α7nAChR)α Bungarus toxin group(αBGT group,1 μg/kg)and agonist of α7nAChR 3-(2,4-dimethoxybenzyli-dene)anabaseine(GTS-21)group(5 mg/kg),with 12 rats in each group.Model of cardiac arrest was established by inducing ventric-ular fibrillation in rats with percutaneous epicardial electrical stimulation,and routine resuscitation was performed,the defibrillation times,cardiopulmonary resuscitation duration and 72 h survival rate of rats in each group were observed and recorded.Neurological damage of rats in each group was scored(NDS score).Levels of inflammatory factors TNF-α,IL-1β and IL-6 in serum,heart,lung and brain of rats were measured by ELISA.HE staining was applied to evaluate the degree of tissue damage of heart,lung and brain tis-sues of rats in each group.Expressions of α7nAChR,NF-κB/MAPKs signal pathway related proteins in heart,lung and brain of rats in each group were detected by Western blot.Results:Compared with Sham group,the number of defibrillations,duration of cardiopul-monary resuscitation,NDS score,levels of TNF-α,IL-1β and IL-6 in serum,heart,lung and brain tissues,and NF-κB p65 protein in heart,lung and brain tissues in cardiopulmonary resuscitation group increased greatly(P<0.05),the 72 h survival rate,phosphory-lation levels of α7nAChR protein,ERK1/2,JNK and p38MAPK in heart,lung and brain tissues decreased greatly after restoration of spontaneous circulation(P<0.05),cells and neurons in the CA1 region of heart,lung and hippocampus were severely damaged.Com-pared with cardiopulmonary resuscitation group,change trend of relevant indicators in electroacupuncture group was opposite to the above,damage of cells and neurons in rat heart,lung and brain tissue was reduced(P<0.05).αBGT reduced the anti-inflammatory effect of electroacupuncture on cardiopulmonary resuscitation rats(P<0.05).GTS-21 enhanced the anti-inflammatory protection of electroacupuncture on cardiopulmonary resuscitation rats(P<0.05).Conclusion:Electroacupuncture has anti-inflammatory and pro-tective effects on cardiopulmonary resuscitation rats based on CAP,and NF-κB/MAPKs participate in α7nAChR mediated CAP.

Aim To investigate the impact of G pro-tein-coupled estrogen receptor 1(GPER1),also known as GPR30 playing a significant role in the nerv-ous system,on neuronal damage and cognitive dysfunc-tion following epileptic seizures.Methods The pro-tein expression levels of GPER1 and the DNA damage marker γ-H2AX in epileptic rats were assessed using Western blot.The hippocampal neuronal damage and apoptosis in pilocarpine-induced epilepsy models were evaluated using Nissl and TUNEL staining techniques,compared with GPER1 knockdown(GPER1-KD)rats with wild-type(WT)controls.The behavioral activi-ties,including memory and spatial learning,were mo-nitored during the chronic phase of epilepsy using the IntelliCage system.Results Compared to the control group,GPER1 protein expression in the cerebral cortex and hippocampus significantly increased 24 hours post-epilepsy onset.In the GPER1-KD+EP group,hipp-ocampal neuronal damage was more severe,with a sig-nificant increase in apoptotic neurons compared to the WT+EP group.The IntelliCage data revealed that during free exploration,nose contact,position learn-ing,and reverse position learning stages in the GPER1-KD+EP group exhibited fewer visits and a higher error rate than in the WT+EP group.Conclu-sions Deficiency in GPER1 impairs memory and spa-tial learning abilities following epilepsy,potentially due to exacerbated neuronal injury,apoptosis,and inflam-mation.GPER1 represents a promising therapeutic tar-get for mitigating post-epileptic nerve damage and cog-nitive impairment.

AIM:This study aims to investigate the role and mechanism of proprotein convertase subtilisin/kexin type 9(PCSK9)in ovarian cancer.METHODS:We compared the expression levels of PCSK9 between ovarian cancer specimens and their corresponding adjacent non-cancerous tissues,while also assessing its expression in various ovarian cancer cell lines.Using a shRNA strategy,we reduced the expression of PCSK9 in ovarian cancer cell lines cul-tured in vitro,with confirmation via Western blot.The effects of PCSK9 downregulation on the proliferation,migration,and invasion of ovarian cancer cells were evaluated through EdU,colony formation,and Transwell assays.Additionally,we analyzed the impact of PCSK9 down-regulation on the MAPK/ERK signaling pathway using Western blot analysis.RE-SULTS:PCSK9 was significantly upregulated in ovarian cancer tissues and cell lines(P＜0.01).Downregulation of PC-SK9 resulted in a significant decrease in cell proliferation,migration,and invasion(P＜0.01).Western blot analysis dem-onstrated that PCSK9 knockdown led to reduced expression levels of key molecules within the MAPK/ERK signaling path-way(P＜0.01).CONCLUSION:PCSK9 promotes the proliferation and invasion of ovarian cancer cells by activating MAPK/ERK signaling pathway.

Aim To investigate the impact of G pro-tein-coupled estrogen receptor 1(GPER1),also known as GPR30 playing a significant role in the nerv-ous system,on neuronal damage and cognitive dysfunc-tion following epileptic seizures.Methods The pro-tein expression levels of GPER1 and the DNA damage marker γ-H2AX in epileptic rats were assessed using Western blot.The hippocampal neuronal damage and apoptosis in pilocarpine-induced epilepsy models were evaluated using Nissl and TUNEL staining techniques,compared with GPER1 knockdown(GPER1-KD)rats with wild-type(WT)controls.The behavioral activi-ties,including memory and spatial learning,were mo-nitored during the chronic phase of epilepsy using the IntelliCage system.Results Compared to the control group,GPER1 protein expression in the cerebral cortex and hippocampus significantly increased 24 hours post-epilepsy onset.In the GPER1-KD+EP group,hipp-ocampal neuronal damage was more severe,with a sig-nificant increase in apoptotic neurons compared to the WT+EP group.The IntelliCage data revealed that during free exploration,nose contact,position learn-ing,and reverse position learning stages in the GPER1-KD+EP group exhibited fewer visits and a higher error rate than in the WT+EP group.Conclu-sions Deficiency in GPER1 impairs memory and spa-tial learning abilities following epilepsy,potentially due to exacerbated neuronal injury,apoptosis,and inflam-mation.GPER1 represents a promising therapeutic tar-get for mitigating post-epileptic nerve damage and cog-nitive impairment.

Objective:To study the anti-inflammatory and protective effects of electroacupuncture on rats with cardiopulmo-nary resuscitation based on cholinergic anti-inflammatory pathway(CAP).Methods:Sixty male SD rats were randomly divided into sham operation group(Sham group),cardiopulmonary resuscitation group,electroacupuncture group,antagonist of α7-nicotinic ace-tylcholine receptor(α7nAChR)α Bungarus toxin group(αBGT group,1 μg/kg)and agonist of α7nAChR 3-(2,4-dimethoxybenzyli-dene)anabaseine(GTS-21)group(5 mg/kg),with 12 rats in each group.Model of cardiac arrest was established by inducing ventric-ular fibrillation in rats with percutaneous epicardial electrical stimulation,and routine resuscitation was performed,the defibrillation times,cardiopulmonary resuscitation duration and 72 h survival rate of rats in each group were observed and recorded.Neurological damage of rats in each group was scored(NDS score).Levels of inflammatory factors TNF-α,IL-1β and IL-6 in serum,heart,lung and brain of rats were measured by ELISA.HE staining was applied to evaluate the degree of tissue damage of heart,lung and brain tis-sues of rats in each group.Expressions of α7nAChR,NF-κB/MAPKs signal pathway related proteins in heart,lung and brain of rats in each group were detected by Western blot.Results:Compared with Sham group,the number of defibrillations,duration of cardiopul-monary resuscitation,NDS score,levels of TNF-α,IL-1β and IL-6 in serum,heart,lung and brain tissues,and NF-κB p65 protein in heart,lung and brain tissues in cardiopulmonary resuscitation group increased greatly(P<0.05),the 72 h survival rate,phosphory-lation levels of α7nAChR protein,ERK1/2,JNK and p38MAPK in heart,lung and brain tissues decreased greatly after restoration of spontaneous circulation(P<0.05),cells and neurons in the CA1 region of heart,lung and hippocampus were severely damaged.Com-pared with cardiopulmonary resuscitation group,change trend of relevant indicators in electroacupuncture group was opposite to the above,damage of cells and neurons in rat heart,lung and brain tissue was reduced(P<0.05).αBGT reduced the anti-inflammatory effect of electroacupuncture on cardiopulmonary resuscitation rats(P<0.05).GTS-21 enhanced the anti-inflammatory protection of electroacupuncture on cardiopulmonary resuscitation rats(P<0.05).Conclusion:Electroacupuncture has anti-inflammatory and pro-tective effects on cardiopulmonary resuscitation rats based on CAP,and NF-κB/MAPKs participate in α7nAChR mediated CAP.

AIM:This study aims to investigate the role and mechanism of proprotein convertase subtilisin/kexin type 9(PCSK9)in ovarian cancer.METHODS:We compared the expression levels of PCSK9 between ovarian cancer specimens and their corresponding adjacent non-cancerous tissues,while also assessing its expression in various ovarian cancer cell lines.Using a shRNA strategy,we reduced the expression of PCSK9 in ovarian cancer cell lines cul-tured in vitro,with confirmation via Western blot.The effects of PCSK9 downregulation on the proliferation,migration,and invasion of ovarian cancer cells were evaluated through EdU,colony formation,and Transwell assays.Additionally,we analyzed the impact of PCSK9 down-regulation on the MAPK/ERK signaling pathway using Western blot analysis.RE-SULTS:PCSK9 was significantly upregulated in ovarian cancer tissues and cell lines(P＜0.01).Downregulation of PC-SK9 resulted in a significant decrease in cell proliferation,migration,and invasion(P＜0.01).Western blot analysis dem-onstrated that PCSK9 knockdown led to reduced expression levels of key molecules within the MAPK/ERK signaling path-way(P＜0.01).CONCLUSION:PCSK9 promotes the proliferation and invasion of ovarian cancer cells by activating MAPK/ERK signaling pathway.

Objective To investigate the mechanism of sanguinarine(SA)for alleviating ulcerative colitis(UC)induced by dextran sodium sulfate(DSS)in mice.Methods Male C57BL/6 mouse models of 3.5%DSS-induced UC were randomized for treatment with 1,5 and 10 mg/kg SA by gavage,400 mg/kg sulfasalazine by gavage,or 10 mg/kg SA combined with intraperitoneal injection of 30 mg/kg ML385(a Nrf2 inhibitor).The changes in intestinal inflammation was assessed by monitoring weight changes,disease activity index(DAI)score,colon length measurement,and HE staining.After the treatments,the colon tissues were collected for detection of malondialdehyde(MDA)content using colorimetry,mRNA expressions of inflammatory factors using RT-qPCR,and the expressions of Nrf2,HO-1,Keap-1,p-p65,p65,occludin,and ZO-1 proteins were detected using Western blotting.Results SA treatment obviously alleviated weight loss,colon length shortening and DAI score increase and ameliorated structural destruction of the colon glands and colonic crypts in mice with DSS-induced UC.SA intervention significantly decreased the levels of TNF-α,IL-1β and IL-6 mRNA and lowered ROS and MDA levels in the colon tissue of UC mice.The mouse models receiving SA treatment showed significantly increased expressions of Nrf2,HO-1,occludin and ZO-1 and lowered expressions of Keap-1 and P-P65 in the colon tissue without significant changes of p65 expression,and these changes were SA dose-dependent.Treatment with ML385 obviously attenuated the effect of high-dose SA for improving UC in the mouse models.Conclusion SA can improve UC-like enteritis in mice possibly by activating the Nrf2 pathway and inhibiting the NF-κB pathway in the colon tissue.

Objective To investigate the mechanism of sanguinarine(SA)for alleviating ulcerative colitis(UC)induced by dextran sodium sulfate(DSS)in mice.Methods Male C57BL/6 mouse models of 3.5%DSS-induced UC were randomized for treatment with 1,5 and 10 mg/kg SA by gavage,400 mg/kg sulfasalazine by gavage,or 10 mg/kg SA combined with intraperitoneal injection of 30 mg/kg ML385(a Nrf2 inhibitor).The changes in intestinal inflammation was assessed by monitoring weight changes,disease activity index(DAI)score,colon length measurement,and HE staining.After the treatments,the colon tissues were collected for detection of malondialdehyde(MDA)content using colorimetry,mRNA expressions of inflammatory factors using RT-qPCR,and the expressions of Nrf2,HO-1,Keap-1,p-p65,p65,occludin,and ZO-1 proteins were detected using Western blotting.Results SA treatment obviously alleviated weight loss,colon length shortening and DAI score increase and ameliorated structural destruction of the colon glands and colonic crypts in mice with DSS-induced UC.SA intervention significantly decreased the levels of TNF-α,IL-1β and IL-6 mRNA and lowered ROS and MDA levels in the colon tissue of UC mice.The mouse models receiving SA treatment showed significantly increased expressions of Nrf2,HO-1,occludin and ZO-1 and lowered expressions of Keap-1 and P-P65 in the colon tissue without significant changes of p65 expression,and these changes were SA dose-dependent.Treatment with ML385 obviously attenuated the effect of high-dose SA for improving UC in the mouse models.Conclusion SA can improve UC-like enteritis in mice possibly by activating the Nrf2 pathway and inhibiting the NF-κB pathway in the colon tissue.