Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,...Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,and necroptosis.Oligomerization of mitochondrial voltage-dependent anion channel 1 is an important pathological event in regulating cell death in retinal ischemia–reperfusion injury.However,its role in PANoptosis remains largely unknown.In this study,we demonstrated that voltage-dependent anion channel 1 oligomerization-mediated mitochondrial dysfunction was associated with PANoptosis in retinal ischemia–reperfusion injury.Inhibition of voltage-dependent anion channel 1 oligomerization suppressed mitochondrial dysfunction and PANoptosis in retinal cells subjected to ischemia–reperfusion injury.Mechanistically,mitochondria-derived reactive oxygen species played a central role in the voltagedependent anion channel 1-mediated regulation of PANoptosis by promoting PANoptosome assembly.Moreover,inhibiting voltage-dependent anion channel 1 oligomerization protected against PANoptosis in the retinas of rats subjected to ischemia–reperfusion injury.Overall,our findings reveal the critical role of voltage-dependent anion channel 1 oligomerization in regulating PANoptosis in retinal ischemia–reperfusion injury,highlighting voltage-dependent anion channel 1 as a promising therapeutic target.展开更多
AIM:To analyze the effect of conbercept treatment on different types of macular edema secondary to retinal vein occlusion(RVO-ME)using optical coherence tomography(OCT)images.METHODS:This retrospective study included ...AIM:To analyze the effect of conbercept treatment on different types of macular edema secondary to retinal vein occlusion(RVO-ME)using optical coherence tomography(OCT)images.METHODS:This retrospective study included patients who first received conbercept injections for RVO-ME at Yijishan Hospital of Wannan Medical College from December 1,2017,to March 31,2022.Data on disease duration,age,hypertension,OCT images,central macular thickness(CMT),and best-corrected visual acuity(BCVA)were collected before and at 4-6 wk after treatment.Patients were divided into 4 groups according to different types of macular edema:cystoid macular edema(CME),sponge-like diffuse retinal thickening(SDRT),serous retinal detachment(SRD),and mixed type(FULL).Changes in CMT and visual acuity before and after treatment were compared among the groups to analyze differences in the effect of conbercept treatment on different ME types,and the effect of baseline CMT and visual acuity on post-treatment visual acuity.RESULTS:Totally 139 patients(139 eyes)were classified as having macular edema,including 62 males(44.6%)and 77 females(55.4%),with a mean age of 58.9±10.9 years,and they were divided into 4 groups based on different types of macular edema,including 54 cases(54 eyes)(mean age 59.6±11.1 years)in the CME group,23 cases(23 eyes;mean age 56.6±10.2 years)in the SDRT group,22 cases(22 eyes;mean age 57.8±12.0 years)in the SDR group,and 40 cases(40 eyes;mean age 60.0±10.7 years)in the FULL group.There were no significant differences in the duration of disease or age between groups(P>0.05).There was a significant difference in preoperative CMT between groups(P=0.01,one-way ANOVA),with the CMT in the FULL group being significantly greater than that in the SDRT group(P=0.03).There were no significant differences in pre-treatment visual acuity between the four groups(P=0.26).After conbercept treatment,the macular central recess thickness was reduced and visual acuity was improved in all four groups,among which the CMT in the CME and FULL groups was reduced significantly compared with the other two groups(P<0.05),and the visual acuity in the CME and SRD groups was improved significantly compared with the other two groups(P<0.05).Postoperative visual acuity was negatively correlated with preoperative CMT(P=0.044)and positively correlated with preoperative visual acuity(P<0.01).CONCLUSION:The efficacy of intravitreal conbercept in the treatment of RVO and macular edema may be related to the type of edema observed on OCT images,in which the efficacy is best in patients with CME but poor in patients with SDRT.展开更多
AIM:To evaluate the therapeutic effects of ranibizumab on optic disc and macular microvascular perfusion in central retinal vein occlusion(CRVO)with macular edema(ME).METHODS:Optical coherence tomography angiology(OCT...AIM:To evaluate the therapeutic effects of ranibizumab on optic disc and macular microvascular perfusion in central retinal vein occlusion(CRVO)with macular edema(ME).METHODS:Optical coherence tomography angiology(OCTA)parameters,including optic disc vessel density(VD;including whole-disc VD,intra-disc VD,and peripapillary VD),superficial/deep capillary plexus(SCP/DCP)VD,and central macular thickness(CMT)were analyzed.Additional assessments included best-corrected visual acuity(BCVA)via Early Treatment Diabetic Retinopathy Study(ETDRS)chart and hemorheological profiling.CRVO patients received monthly intravitreal ranibizumab injections for three consecutive months.Pre-and post-treatment parameters were statistically compared.RESULTS:The study comprised 60 CRVO-ME patients(28 males;32 females),aged 50-78y(mean 63.3±7.6y)and 60 age-/sex-matched healthy controls.As compared with participants exhibiting normal funduscopic findings,CRVO patients demonstrated significantly elevated levels of low-shear-rate whole blood viscosity(LSR-WBV),high-shearrate whole blood viscosity(HSR-WBV),and aggregation index(AI,all P<0.05).In CRVO-affected eyes,vertical cupto-disc(C/D)ratio and optic cup volume were significantly smaller,whereas retinal nerve fiber layer(RNFL)thickness was significantly greater,compared to both unaffected contralateral eyes and normal control eyes(all P<0.05).Following treatment,VD of the entire optic disc(P<0.05),intra-disc VD(P<0.05),and peripapillary VD(P<0.05)all increased significantly relative to baseline.CMT decreased significantly(P<0.05),whereas macular SCP-VD and macular DCP-VD showed non-significant slight reductions(P>0.05).At baseline,BCVA of CRVO eyes correlated with whole-disc VD(r=-0.276,P=0.033),intra-disc VD(r=-0.342,P=0.009),and peripapillary VD(r=-0.335,P=0.007),with intra-disc VD demonstrating the strongest association.Besides,BCVA improvement,after the treatment,correlated positively with whole-disc VD(r=0.342,P=0.008)and intradisc VD(r=0.396,P=0.002).CONCLUSION:Optic disc blood perfusion is more closely associated with visual acuity than macular perfusion,suggesting intra-disc VD may serve as a potential biomarker for monitoring visual acuity changes in CRVO.Multiple ranibizumab injections significantly improve optic disc perfusion but may have exerted detrimental effects on the macula.CRVO patients shows higher hemorheological parameters than those with normal fundi.Reduced vertical C/D ratio and optic cup volume may be linked to CRVO incidence,potentially acting as susceptibility factors.展开更多
To address the issues of frequent identity switches(IDs)and degraded identification accuracy in multi object tracking(MOT)under complex occlusion scenarios,this study proposes an occlusion-robust tracking framework ba...To address the issues of frequent identity switches(IDs)and degraded identification accuracy in multi object tracking(MOT)under complex occlusion scenarios,this study proposes an occlusion-robust tracking framework based on face-pedestrian joint feature modeling.By constructing a joint tracking model centered on“intra-class independent tracking+cross-category dynamic binding”,designing a multi-modal matching metric with spatio-temporal and appearance constraints,and innovatively introducing a cross-category feature mutual verification mechanism and a dual matching strategy,this work effectively resolves performance degradation in traditional single-category tracking methods caused by short-term occlusion,cross-camera tracking,and crowded environments.Experiments on the Chokepoint_Face_Pedestrian_Track test set demonstrate that in complex scenes,the proposed method improves Face-Pedestrian Matching F1 area under the curve(F1 AUC)by approximately 4 to 43 percentage points compared to several traditional methods.The joint tracking model achieves overall performance metrics of IDF1:85.1825%and MOTA:86.5956%,representing improvements of 0.91 and 0.06 percentage points,respectively,over the baseline model.Ablation studies confirm the effectiveness of key modules such as the Intersection over Area(IoA)/Intersection over Union(IoU)joint metric and dynamic threshold adjustment,validating the significant role of the cross-category identity matching mechanism in enhancing tracking stability.Our_model shows a 16.7%frame per second(FPS)drop vs.fairness of detection and re-identification in multiple object tracking(FairMOT),with its cross-category binding module adding aboute 10%overhead,yet maintains near-real-time performance for essential face-pedestrian tracking at small resolutions.展开更多
BACKGROUND：The intestinal lymphatic pathway and intestinal ischemia/reperfusion are mainly involved in mesenteric lymph duct ligation or drainage; moreover,intervention by reducing the lymph liquid reflux might relie...BACKGROUND：The intestinal lymphatic pathway and intestinal ischemia/reperfusion are mainly involved in mesenteric lymph duct ligation or drainage; moreover,intervention by reducing the lymph liquid reflux might relieve lung and other organ dysfunction induced by intestinal ischemia/reperfusion; however,research addressing mesenteric lymph reperfusion （MLR） and brain injury has not yet to be reported.OBJECTIVE：To observe the effect of MLR on brain tissue in a rat model of superior mesenteric artery occlusion （SMAO） shock,and to explore the molecular mechanism of MLR.DESIGN,TIME AND SETTING：A randomized,controlled,animal experiment at a neuro-pathophysiology level was performed at the Institute of Microcirculation,Hebei North University; Department of Pathophysiology,Basic Medical College; Department of Pathology,the First Hospital of Hebei North University between December 2007 and March 2009.MATERIALS：Adenosine triphosphate （ATP） standard was provided by the National Institute for the Control of Pharmaceutical and Biological Products; lactic acid （LA）,superoxide dismutase （SOD）,malonaldehyde （MDA）,nitrogen monoxidum （NO）,nitric oxide synthase （NOS）,myeloperoxidase （MPO） and ATPase assay kits were provided by Nanjing Jiancheng Bioengineering Institute,China.METHODS：A total of 24 male Wistar rats were randomly divided into four groups.In the sham-surgery group （n = 6）,both the mesenteric lymph duct and the superior mesenteric artery were not blocked; in the MLR group （n = 6）,the mesenteric lymph duct was occluded for 1 hour followed by 2-hour reperfusion; in the SMAO group （n = 6）,the superior mesenteric artery was occluded for 1 hour followed by 2-hour reperfusion; in the MLR ＋ SMAO group （n = 6）,both the mesenteric lymph duct and superior mesenteric artery were occluded for 1 hour followed by 2-hour reperfusion.MAIN OUTCOME MEASURES：Mean arterial blood pressure prior to and following ischemia/reperfusion; brain tissue morphology levels of LA,MDA,SOD,NO,NOS,MPO,ATPase and ATP following reperfusion.RESULTS：MLR did not cause changes in mean arterial blood pressure,brain tissue morphology,LA,MDA,NO,ATP,SOD,NOS,MPO and ATPase.However,SMAO caused a rapid decrease and gradual increase of mean arterial blood pressure.Neuronal necrosis,degeneration and swelling were observed in brain tissue.Contents of MDA,NO,LA and ATP as well as activities of NOS and MPO were significantly increased （P〈 0.05）,but activities of SOD and Na＋-K＋-ATPase were significantly decreased （P 〈 0.05）.MLR aggravated neuronal damage in a rat model of SMAO shock.Following MLR,mean arterial blood pressure was significantly decreased （P 〈 0.05）,contents of MDA and NO as well as activities of NOS and MPO were significantly increased （P 〈0.05）,but activities of Ca2＋-ATPase,Mg2＋-ATPase and Ca2＋-Mg2＋-ATPase as well as ATP content were significantly decreased （P〈 0.05）.CONCLUSION：MLR aggravates brain injury in a rat model of SMAO shock,which correlates with oxygen-derived free radical injury,NO synthesis and release,sequestration of neutrophilic granulocytes,decreasing activity of cell membrane pumps and energy metabolism dysfunction.Pathogenesis of the intestinal lymphatic pathway should be thoroughly investigated to prevent ischemia/reperfusion injury.展开更多
BACKGROUND： Previous studies have shown that mesenteric lymph reperfusion （MLR） exacerbates brain injury in a rat model of superior mesenteric artery occlusion （SMAO） shock. However, little is known about the inf...BACKGROUND： Previous studies have shown that mesenteric lymph reperfusion （MLR） exacerbates brain injury in a rat model of superior mesenteric artery occlusion （SMAO） shock. However, little is known about the influence of MLR on neurotransmitter expression in brain tissue. OBJECTIVE： To observe the effect of MLR on brain tissue injury by measuring monoamine and cholinergic neurotransmitter levels. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Institute of Microcirculation, Hebei North University, China; Research Room of Microcirculation and Laboratory of Biochemistry, Department of Pathophysiology, Basic Medical College, Hebei North University between December 2007 and March 2009. MATERIALS： Choline acetyltransferase （CHAT） and acetylcholine esterase （ACHE） kits were provided by Nanjing Jiancheng Bioengineering Institute, China; dopamine （DA） and noradrenalin （NE） standards were provided by the National Institute for the Control of Pharmaceutical and Biological Products; HP1100 chromatograph of liquid was provided by Agllent, USA. METHODS： A total of 24 male, Wistar rats were randomly assigned to 4 groups： sham-surgery, MLR SMAO, and MLR ＋ SMAO groups, with 6 rats in each group. In the MLR or SMAO groups, the mesenteric lymph duct or superior mesenteric artery was blocked for 1 hour. In the MLR ＋ SMAO group, the mesenteric lymph duct and superior mesenteric artery were occluded for 1 hour, followed by 2-hour repeffusion. ChAT and AChE levels were measured using the synthesized and hydrolyzed acetylcholine method, respectively. Liquid chromatography was employed to quantitatively analyze DA and NE levels, using relative retention time and the external standard method. MAIN OUTCOME MEASURES： CHAT, ACHE, DA, and NE levels. RESULTS： AChE levels were significantly increased, but ChAT levels were significantly decreased in the MLR and MLR ＋ SMAO groups following 2-hour repeffusion （P〈 0.01）. However, AChE activity in the MLR ＋ SMAO group was greater than in the MLR group （P 〈 0.05）. DA and NE levels were significantly decreased in the SMAO and MLR ＋ SMAO groups （P〈 0.01）, while DA levels in the MLR ＋ SMAO group were less than in the SMAO group （P 〈 0.05）. CONCLUSION： MLR exacerbated brain injury in a rat model of SMAO shock, which correlated with the intestinal lymphatic pathway. MLR decreased DA levels, but increased AChE activity, in a rat model of SMAO shock.展开更多
Aim:The effects of tirofiban combined with nicorandil on effective reperfusion,and the levels of interleukin-4(IL-4)and soluble intercellular adhesion molecule-1(sICAM-1)after percutaneous coronary intervention(PCI)fo...Aim:The effects of tirofiban combined with nicorandil on effective reperfusion,and the levels of interleukin-4(IL-4)and soluble intercellular adhesion molecule-1(sICAM-1)after percutaneous coronary intervention(PCI)for chronic coronary total occlusion(CTO)were investigated.Method:From January 1,2017,to June 31,2019,a total of 40 patients with CTO receiving PCI in Shandong Qian-foshan Hospital were randomly divided into a control group(treated with single tirofiban)and a cocktail group(treated with nicorandil combined with tirofiban).Effective reperfusion was compared between groups.In addition,differences in coronary serum IL-4 and sICAM-1 levels before and 10 min after the operation were compared between groups,and the incidence rates of adverse reactions were observed.Finally,patient follow-up occurred at 1 month and 6 months,and the total incidence rates of adverse cardiac events in both groups were assessed.Results:The levels of IL-4 and sICAM-1 in the cocktail group significantly decreased after the operation(P<0.05).In addition,after the operation,significantly greater decreases in the IL-4 and sICAM-1 levels were observed in the cocktail group than the control group(P<0.05).The Seattle Angina Scale(SAQ)score of the cocktail group,compared with the control group,showed a significant improvement after vessel opening in the patients with CTO.At the 1-month follow-up,the SAQ score of the cocktail group,compared with the control group,indicated further improvements in terms of angina attack frequency.No significant differences were observed in the incidence rates of adverse reactions between groups(P>0.05).Conclusion:The treatment of patients with CTO undergoing PCI with nicorandil and tirofiban alleviated the inflam-matory response,improved the SAQ scores,and decreased the occurrence of angina pectoris in patients.Moreover,this treatment is safe and reliable,and has important clinical significance.展开更多
OBJECTIVE To investigate regulatory effects of hyperoside(Hyp)on IP3/PKC/TRPV4 pathway in rat cerebral basilar artery(CBA)subjected to global cerebral ischemia-reperfusion(I/R).METHODS The model of global cerebral I/R...OBJECTIVE To investigate regulatory effects of hyperoside(Hyp)on IP3/PKC/TRPV4 pathway in rat cerebral basilar artery(CBA)subjected to global cerebral ischemia-reperfusion(I/R).METHODS The model of global cerebral I/R in rats was established by four-vessel occlusions methods.The treated rats were administrated with Hyp(50 mg·kg^-1)group,Hyp(50 mg·kg^-1)+HC-067047(10 mg·kg^-1),Hyp(50 mg·kg^-1)+2APB(2 mg·kg^-1),Hyp(50 mg·kg^-1)+BisI(2.5 mg·kg^-1),Hyp(50 mg·kg^-1)+2APB(2 mg·kg^-1)+BisI(2.5 mg·kg^-1).Hematoxylin-eosin(HE)and Nissl staining were performed and the contents of methane dicarboxylic aldehyde(MDA),neuron-specific enolase(NSE),S100β and the activity of lactic dehydrogenase(LDH)in serum were measured by enzyme-linked immunosorbnent assay(ELISA).The specific blocker N-nitro-L-arginine-methyl-ester(L-NAME)and indomethacin(Indo)were used to delete the prostacyclin(PGI2)and nitric oxide(NO)dependent relaxation.The protein expression level of TRPV4 was detected by Western blotting.Ca2+intensity in vascular smooth muscle cells was measured by confocal laser scanning microscope and flow cytometry was performed to observe the apoptosis of CBA endothelial cells after in vivo administration.RESULTS Hyp induced a dose-dependent relaxation of CBA in IR rats via a PGI2 and NO independent manner,as evidenced by alleviated patho⁃logical changes and up-regulated expression of TRPV4 protein in the endothelial cells from cerebral vessels.Hyp signifi⁃cantly reduced the contents of MDA,NSE,S100βand the activity of LDH in serum and decreased the fluorescence intensity of Ca2+in cerebral vascular smooth muscle cells by in vivo administration.The apoptotic rate of endothelial cells in Hyp treated group was significantly less than that in IR group.CONCLUSION Hyp does in fact ameliorate I/R injury by regulatingIP3/PKC/TRPV4 pathway.展开更多
The stable gastric pentadecapeptide BPC 157 counteracts various venous occlusion-induced syndromes.Summarized are all these arguments,in the Robert’s cytoprotection concept terms,to substantiate the resolution of dif...The stable gastric pentadecapeptide BPC 157 counteracts various venous occlusion-induced syndromes.Summarized are all these arguments,in the Robert’s cytoprotection concept terms,to substantiate the resolution of different major vessel occlusion disturbances,in particular ischemia-reperfusion injury following the Pringle maneuver and Budd-Chiari syndrome,which was obtained by BPC 157 therapy.Conceptually,there is new point(bypassed occluded or ruptured vessel,the equation endothelium maintenance→epithelium maintenance=blood vessel recruitment and activation towards defect or bypassing vessel occlusion),the recruitment of collateral blood vessels to compensate for vessel occlusion and reestablish blood flow.In this paper,we summarize the evidence of the native cytoprotective gastric pentadecapeptide BPC 157,which is stable in the human gastric juice,is a membrane stabilizer and counteracts gut-leaky syndrome.As a particular target,it is distinctive from the standard peptide growth factors,with particular molecular pathways involved,controlling VEGF and NO pathways.In the early 1990s,BPC 157 appeared as a late outbreak of the Robert’s and Szabo’s cytoprotection-organoprotection concept,epithelium,endothelium protection as previous theoretical/practical breakthrough in the 1980s,and brain-gut axis and gut-brain axis.As the time went on,with its reported effects,it is likely most useful theory practical implementation and justification.Meantime,several reviews suggest that BPC 157,which does not have a lethal dose(LD1),has profound cytoprotective activity,used to be demonstrated in ulcerative colitis and invented to multiple sclerosis trials.Likely,it may bring the theory to practical application,starting with the initial argument,no degradation in human gastric juice for more than 24 h,and thereby,the therapeutic effectiveness(including therapeutic per-oral regimen)and pleiotropic beneficial effects.展开更多
Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion injury.Autophagy occurs within hours after cereb...Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion injury.Autophagy occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains unclear.In this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion injury.We found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced autophagy.Furthermore,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating autophagy.Blocking autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion injury.Findings from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.展开更多
Reperfusion following cerebral ischemia causes both structural and functional damage to brain tissue and could aggravate a patient's condition;this phenomenon is known as cerebral ischemia-reperfusion injury.Curre...Reperfusion following cerebral ischemia causes both structural and functional damage to brain tissue and could aggravate a patient's condition;this phenomenon is known as cerebral ischemia-reperfusion injury.Current studies have elucidated the neuroprotective role of the sirtuin protein family(Sirtuins)in modulating cerebral ischemia-reperfusion injury.However,the potential of utilizing it as a novel intervention target to influence the prognosis of cerebral ischemia-reperfusion injury requires additional exploration.In this review,the origin and research progress of Sirtuins are summarized,suggesting the involvement of Sirtuins in diverse mechanisms that affect cerebral ischemia-reperfusion injury,including inflammation,oxidative stress,blood-brain barrier damage,apoptosis,pyroptosis,and autophagy.The therapeutic avenues related to Sirtuins that may improve the prognosis of cerebral ischemia-reperfusion injury were also investigated by modulating Sirtuins expression and affecting representative pathways,such as nuclear factor-kappa B signaling,oxidative stress mediated by adenosine monophosphate-activated protein kinase,and the forkhead box O.This review also summarizes the potential of endogenous substances,such as RNA and hormones,drugs,dietary supplements,and emerging therapies that regulate Sirtuins expression.This review also reveals that regulating Sirtuins mitigates cerebral ischemia-reperfusion injury when combined with other risk factors.While Sirtuins show promise as a potential target for the treatment of cerebral ischemiareperfusion injury,most recent studies are based on rodent models with circadian rhythms that are distinct from those of humans,potentially influencing the efficacy of Sirtuinstargeting drug therapies.Overall,this review provides new insights into the role of Sirtuins in the pathology and treatment of cerebral ischemia-reperfusion injury.展开更多
Nitric oxide(NO)is a gaseous molecule produced by 3 different NO synthase(NOS)isoforms:Neural/brain NOS(nNOS/bNOS,type 1),endothelial NOS(eNOS,type 3)and inducible NOS(type 2).Type 1 and 3 NOS are constitutively expre...Nitric oxide(NO)is a gaseous molecule produced by 3 different NO synthase(NOS)isoforms:Neural/brain NOS(nNOS/bNOS,type 1),endothelial NOS(eNOS,type 3)and inducible NOS(type 2).Type 1 and 3 NOS are constitutively expressed.NO can serve different purposes:As a vasoactive molecule,as a neurotransmitter or as an immunomodulator.It plays a key role in cerebral ischemia/reperfusion injury(CIRI).Hypoxic episodes simulate the production of oxygen free radicals,leading to mitochondrial and phospholipid damage.Upon reperfusion,increased levels of oxygen trigger oxide synthases;whose products are associated with neuronal damage by promoting lipid peroxidation,nitrosylation and excitotoxicity.Molecular pathways in CIRI can be altered by NOS.Neuroprotective effects are observed with eNOS activity.While nNOS interplay is prone to endothelial inflammation,oxidative stress and apoptosis.Therefore,nNOS appears to be detrimental.The interaction between NO and other free radicals develops peroxynitrite;which is a cytotoxic agent.It plays a main role in the likelihood of hemorrhagic events by tissue plasminogen activator(t-PA).Peroxynitrite scavengers are currently being studied as potential targets to prevent hemorrhagic transformation in CIRI.展开更多
The chronic occlusion of intracranial arteries generally has no or mild clinical symptoms,and the clinical symptoms of acute cerebral artery occlusion are mostly manifested as severe cerebral infarction symptoms,which...The chronic occlusion of intracranial arteries generally has no or mild clinical symptoms,and the clinical symptoms of acute cerebral artery occlusion are mostly manifested as severe cerebral infarction symptoms,which often make early diagnosis difficult,thus losing the best treatment opportunity.Once cerebral infarction occurs,the consequences are difficult to recover.This is also an important reason for the high misdiagnosis rate and mortality of this disease.In this paper,the characteristics of the disease were analyzed to provide clinical reference.展开更多
BACKGROUND The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined.METHODS All CTO vesse...BACKGROUND The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined.METHODS All CTO vessels treated with successful anatomical PCI in patients from PANDA Ⅲ trial were retrospectively measured for postPCI QFR.The primary outcome was 2-year vessel-oriented composite endpoints (VOCEs,composite of target vessel-related cardiac death,target vessel-related myocardial infarction,and ischemia-driven target vessel revascularization).Receiver operator characteristic curve analysis was conducted to identify optimal cutoff value of post-PCI QFR for predicting the 2-year VOCEs,and all vessels were stratified by this optimal cutoff value.Cox proportional hazards models were employed to calculate the hazard ratio (HR) with 95% CI.RESULTS Among 428 CTO vessels treated with PCI,353 vessels (82.5%) were analyzable for post-PCI QFR.31 VOCEs (8.7%) occurred at 2 years.Mean value of post-PCI QFR was 0.92±0.13.Receiver operator characteristic curve analysis shown the optimal cutoff value of post-PCI QFR for predicting 2-year VOCEs was 0.91.The incidence of 2-year VOCEs in the vessel with post-PCI QFR<0.91 (n=91) was significantly higher compared with the vessels with post-PCI QFR≥0.91 (n=262)(22.0%vs.4.2%,HR=4.98,95%CI:2.32–10.70).CONCLUSIONS Higher post-PCI QFR values were associated with improved prognosis in the PCI practice for coronary CTO.Achieving functionally optimal PCI results (post-PCI QFR value≥0.91) tends to get better prognosis for patients with CTO lesions.展开更多
Ferroptosis is a novel form of non-apoptotic cell death that has been widely studied in recent years and is involved in a variety of pathophysiological processes.The core treatment goal of ischemic stroke is to restor...Ferroptosis is a novel form of non-apoptotic cell death that has been widely studied in recent years and is involved in a variety of pathophysiological processes.The core treatment goal of ischemic stroke is to restore blood flow as early as possible,while the pathological mechanism of reperfusion injury after restoring blood flow is complex,involving oxidative stress,calcium overload,and inflammatory response.In recent years,more and more studies have found that ferroptosis mediation is involved in the occurrence and development of cerebral ischemia-reperfusion injury.This paper elaborates on the concept,mechanisms,and regulation of ferroptosis,detailing its role in cerebral ischemia-reperfusion injury and potential inhibition strategies.The aim is to deepen the understanding of ferroptosis in this pathological process and provide insights for possible targeted therapies.展开更多
Cerebral ischemia/reperfusion(I/R)injury is an important pathophysiological condition of ischemic stroke that involves a variety of physiological and pathological cell death pathways,including autophagy,apoptosis,necr...Cerebral ischemia/reperfusion(I/R)injury is an important pathophysiological condition of ischemic stroke that involves a variety of physiological and pathological cell death pathways,including autophagy,apoptosis,necroptosis,and phagoptosis,among which autophagy is the most studied.We have reviewed studies published in the past 5 years regarding the association between autophagy and cerebral I/R injury.To the best of our knowledge,this is the first review article summarizing potential candidates targeting autophagic pathways in the treatment of I/R injury post ischemic stroke.The findings of this review may help to better understand the pathogenesis and mechanisms of I/R events and bridge the gap between basic and translational research that may lead to the development of novel therapeutic approaches for I/R injury.展开更多
AIM:To assess the relationship between serological parameters and the prognosis of young patients with retinal vein occlusion(RVO)after intravitreal conbercept injection(IVC).METHODS:This study enrolled 100 young pati...AIM:To assess the relationship between serological parameters and the prognosis of young patients with retinal vein occlusion(RVO)after intravitreal conbercept injection(IVC).METHODS:This study enrolled 100 young patients(≤50 years old)diagnosed with RVO-related macular edema(RVO-ME)who had been undergoing IVC at the 474 Hospital in Xinjiang between January 2022 and October 2023.Patients were categorized into two groups:70 eyes in the effective group and 30 eyes in the ineffective group.The effective group comprised patients exhibiting a visual acuity improvement of≥2 lines at the last follow-up,with resolved ME and central macular thickness(CMT)<300μm.Conversely,the ineffective group included patients with visual acuity improvement of<1 line,persistent ME,and CMT≥300μm at the last follow-up.Serological parameters,including white blood cell count,neutrophil count,lymphocyte count,monocyte count,and mean platelet volume were assessed before treatment.The correlation between bestcorrected visual acuity(BCVA)and neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),systemic immune inflammation index(SII),and systemic immune response index(SIRI)was analyzed.Additionally,the association between these serological parameters and the efficacy of IVC was explored.RESULTS:Three months after treatment,the effective group demonstrated a significant improvement in BCVA from 0.82±0.20 to 0.36±0.10,with a concurrent decrease in CMT from 661.28±163.90 to 200.61±82.45μm(P<0.001).Conversely,the ineffective group exhibited minimal changes in BCVA(0.86±0.25 to 0.82±0.14)and CMT(669.84±164.95 to 492.13±138.67μm,P<0.001).The differences in BCVA and CMT between the two groups were statistically significant(P<0.001).According to subgroup analysis,in patients with central RVO(CRVO),BCVA improved from 0.82±0.23 to 0.49±0.12 in the effective group and from 0.80±0.18 to 0.76±0.22 in the ineffective group(P<0.001).The CMT changes followed a similar pattern.In patients with branch RVO(BRVO),comparable trends in BCVA and CMT changes were observed between the effective and ineffective groups(P<0.001).Additionally,the effective group exhibited higher PLR and SII values than the ineffective group(P<0.05).Further CRVO and BRVO subgroups analysis exhibited consistent PLR and SII value trends.CONCLUSION:Compared to other inflammatory factors,elevated PLR and SII levels before treatment are better predictors of outcomes in young RVO-ME patients undergoing IVC treatment.展开更多
AIM:To explore the morphological and functional parameters to evaluate the effectiveness of intravitreal injections of ranibizumab(IVR)in treating macular edema(ME)secondary to retinal vein occlusion(RVO).METHODS:This...AIM:To explore the morphological and functional parameters to evaluate the effectiveness of intravitreal injections of ranibizumab(IVR)in treating macular edema(ME)secondary to retinal vein occlusion(RVO).METHODS:This retrospective study involved 65 RVO patients(65 eyes)who received IVR and were followedup for more than 3mo.ME was categorized into cystoid macular edema(CME),diffuse retinal thickening(DRT),and serous retinal detachment(SRD)according to optical coherence tomography(OCT)images.The comparison of best corrected visual acuity(BCVA;logMAR)and central macular thickness(CMT)among different follow-up points and those among 3 groups were performed by Kruskal-Wallis test.The correlation between BCVA and baseline parameters during treatment was analyzed using Spearman correlation analysis.RESULTS:BCVA tended to improve in all groups,with marked improvement in CME and DRT groups.CMT showed the greatest reduction after 1wk,and remained stable over the following 3mo.DRT patients had the worst BCVA and the highest CMT at baseline,but the differences became smaller after IVR treatment.CMT in SRD group was significantly better than in CME and DRT groups 3mo after IVR.Most patients of CME and SRD groups transitioned to a normal pattern at 3mo follow-up.DRT patients were most likely to transform into the other morphological groups,while SRD patients showed minimal transitions.BCVA at baseline was identified as the most important prognostic indicator in all 3 groups.Additionally,DRT patients with a longer clinical course,higher CMT and central retinal vein occlusion(CRVO)tend to exhibit worse BCVA after treatment.In addition,CRVO patients are more likely to have worse BCVA at 2 and 3mo follow-up compared with branch retinal vein occlusion(BRVO)patients in CME group.SRD patients with higher baseline CMT were prone to experiencing worse BCVA after treatment.CONCLUSION:The effectiveness of IVR is strongly correlated with baseline BCVA in all 3 groups.Baseline parameters including clinical course,CMT,and RVO position are also useful in predicting the BCVA at different time points after treatment.展开更多
Objective:Acute kidney injury(AKI)is a clinical syndrome characterized by sudden deterioration of renal function,with ischemia reperfusion injury(IRI)being the most common cause.Long noncoding RNA(lncRNA)regulate cell...Objective:Acute kidney injury(AKI)is a clinical syndrome characterized by sudden deterioration of renal function,with ischemia reperfusion injury(IRI)being the most common cause.Long noncoding RNA(lncRNA)regulate cell fate through interactions with microRNA(miRNA)and messenger RNAs(mRNA),but the mechanisms and regulatory networks underlying lncRNA AK154753(AK154753)in IRI-induced AKI remain unclear.This study aims to investigate the role of AK154753 in acute renal IRI and to elucidate the molecular mechanism of the AK154753 via miR-345-3p/Bcl-2 homologous antagonist/killer(Bak)and miR-708-5p/Bcl-2 interacting mediator of cell death(Bim)axis.Methods:A bilateral renal artery ischemia model was established in mice(30 minutes ischemia followed by 24 hours and 48 hours reperfusion).Kidney tissues were analyzed using microarray-based transcriptomic sequencing to identify differentially expressed lncRNAs,miRNAs,and mRNAs.RNA levels of AK154753,miR-345-3p,miR-708-5p,Bak,and Bim were validated using real-time reverse transcription PCR(real-time RTPCR).Oxygen and glucose deprivation/reperfusion(OGD/R)models were constructed in mouse proximal renal tubular epithelial BUMPT cells to simulate in vitro IRI conditions.Adeno-associated virus(AAV)-mediated shRNA was used to silence AK154753 in vivo.Apoptosis was assessed using TUNEL staining and flow cytometry.Protein levels of Bak,Bim,and cleaved-caspase-3 were measured using Western blotting.Fluorescence in situ hybridization(FISH)was used to determine intracellular localization of AK154753.Binding relationships between AK154753 and miR-345-3p/Bak and miR-708-5p/Bim were verified using dual-luciferase reporter assays.MiRNA mimics and inhibitors were used to evaluate regulatory-network integrity.Results:IRI significantly elevated serum blood urea nitrogen(BUN)and serum creatinine(Scr),accompanied by tubular-structure damage and increased cell apoptosis(all P<0.05).Transcriptome profiling and real-time RT-PCR validation demonstrated that lncRNA AK154753,along with the pro-apoptotic proteins Bak and Bim,was significantly upregulated after IRI,whereas miR-345-3p and miR-708-5p were markedly downregulated(P<0.01).In vitro,OGD/R treatment significantly induced AK154753 expression in renal tubular epithelial cells and suppressed the expression of miR-345-3p and miR-708-5p,while markedly increasing the protein levels of Bak,Bim,and cleaved-caspase 3,resulting in a significant increase in apoptosis(all P<0.01).Silencing AK154753 significantly attenuated OGD/R-induced apoptosis,reduced the expression of Bak,Bim,and cleaved caspase 3,and decreased cell apoptosis(all P<0.01),while significantly upregulating miR-345-3p and miR-708-5p expression(P<0.01).In vivo,adeno-associated virus(AAV)-mediated knockdown of AK154753 significantly improved renal function in IRI mice,alleviated tubular injury,and suppressed renal tissue apoptosis,as evidenced by reduced BUN and Scr levels,improved histopathological injury scores,and decreased expression of Bak,Bim,and cleaved caspase-3(all P<0.01),accompanied by significant upregulation of miR-345-3p and miR-708-5p(all P<0.01).Luciferase reporter assays further confirmed that miR-345-3p directly binds to the 3'-untranslated region(3'-UTR)of AK154753 and Bak,whereas miR-708-5p directly binds to the 3'-UTRs of AK154753 and Bim.Inhibition of miR-345-3p or miR-708-5p abolished the anti-apoptotic effects induced by AK154753 silencing and restored Bak and Bim expression levels(all P<0.01).Conclusion:AK154753 is upregulated in acute renal IRI and promotes apoptosis by suppressing miR-345-3p and miR-708-5p,thereby upregulating Bak and Bim,and participates in the initiation and progression of acute renal IRI.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82172196(to KX),82372507(to KX)the Natural Science Foundation of Hunan Province,China,No.2023JJ40804(to QZ)the Key Laboratory of Emergency and Trauma(Hainan Medical University)of the Ministry of Education,China,No.KLET-202210(to QZ)。
文摘Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,and necroptosis.Oligomerization of mitochondrial voltage-dependent anion channel 1 is an important pathological event in regulating cell death in retinal ischemia–reperfusion injury.However,its role in PANoptosis remains largely unknown.In this study,we demonstrated that voltage-dependent anion channel 1 oligomerization-mediated mitochondrial dysfunction was associated with PANoptosis in retinal ischemia–reperfusion injury.Inhibition of voltage-dependent anion channel 1 oligomerization suppressed mitochondrial dysfunction and PANoptosis in retinal cells subjected to ischemia–reperfusion injury.Mechanistically,mitochondria-derived reactive oxygen species played a central role in the voltagedependent anion channel 1-mediated regulation of PANoptosis by promoting PANoptosome assembly.Moreover,inhibiting voltage-dependent anion channel 1 oligomerization protected against PANoptosis in the retinas of rats subjected to ischemia–reperfusion injury.Overall,our findings reveal the critical role of voltage-dependent anion channel 1 oligomerization in regulating PANoptosis in retinal ischemia–reperfusion injury,highlighting voltage-dependent anion channel 1 as a promising therapeutic target.
文摘AIM:To analyze the effect of conbercept treatment on different types of macular edema secondary to retinal vein occlusion(RVO-ME)using optical coherence tomography(OCT)images.METHODS:This retrospective study included patients who first received conbercept injections for RVO-ME at Yijishan Hospital of Wannan Medical College from December 1,2017,to March 31,2022.Data on disease duration,age,hypertension,OCT images,central macular thickness(CMT),and best-corrected visual acuity(BCVA)were collected before and at 4-6 wk after treatment.Patients were divided into 4 groups according to different types of macular edema:cystoid macular edema(CME),sponge-like diffuse retinal thickening(SDRT),serous retinal detachment(SRD),and mixed type(FULL).Changes in CMT and visual acuity before and after treatment were compared among the groups to analyze differences in the effect of conbercept treatment on different ME types,and the effect of baseline CMT and visual acuity on post-treatment visual acuity.RESULTS:Totally 139 patients(139 eyes)were classified as having macular edema,including 62 males(44.6%)and 77 females(55.4%),with a mean age of 58.9±10.9 years,and they were divided into 4 groups based on different types of macular edema,including 54 cases(54 eyes)(mean age 59.6±11.1 years)in the CME group,23 cases(23 eyes;mean age 56.6±10.2 years)in the SDRT group,22 cases(22 eyes;mean age 57.8±12.0 years)in the SDR group,and 40 cases(40 eyes;mean age 60.0±10.7 years)in the FULL group.There were no significant differences in the duration of disease or age between groups(P>0.05).There was a significant difference in preoperative CMT between groups(P=0.01,one-way ANOVA),with the CMT in the FULL group being significantly greater than that in the SDRT group(P=0.03).There were no significant differences in pre-treatment visual acuity between the four groups(P=0.26).After conbercept treatment,the macular central recess thickness was reduced and visual acuity was improved in all four groups,among which the CMT in the CME and FULL groups was reduced significantly compared with the other two groups(P<0.05),and the visual acuity in the CME and SRD groups was improved significantly compared with the other two groups(P<0.05).Postoperative visual acuity was negatively correlated with preoperative CMT(P=0.044)and positively correlated with preoperative visual acuity(P<0.01).CONCLUSION:The efficacy of intravitreal conbercept in the treatment of RVO and macular edema may be related to the type of edema observed on OCT images,in which the efficacy is best in patients with CME but poor in patients with SDRT.
基金Central High-Level Traditional Chinese Medicine Hospital Project of Eye Hospital China Academy of Chinese Medical Science(No.GSP5-83,No.GSP4-02No.GSP5-06)+1 种基金Supported by National Natural Science Foundation of China(General ProgramNo.82474582).
文摘AIM:To evaluate the therapeutic effects of ranibizumab on optic disc and macular microvascular perfusion in central retinal vein occlusion(CRVO)with macular edema(ME).METHODS:Optical coherence tomography angiology(OCTA)parameters,including optic disc vessel density(VD;including whole-disc VD,intra-disc VD,and peripapillary VD),superficial/deep capillary plexus(SCP/DCP)VD,and central macular thickness(CMT)were analyzed.Additional assessments included best-corrected visual acuity(BCVA)via Early Treatment Diabetic Retinopathy Study(ETDRS)chart and hemorheological profiling.CRVO patients received monthly intravitreal ranibizumab injections for three consecutive months.Pre-and post-treatment parameters were statistically compared.RESULTS:The study comprised 60 CRVO-ME patients(28 males;32 females),aged 50-78y(mean 63.3±7.6y)and 60 age-/sex-matched healthy controls.As compared with participants exhibiting normal funduscopic findings,CRVO patients demonstrated significantly elevated levels of low-shear-rate whole blood viscosity(LSR-WBV),high-shearrate whole blood viscosity(HSR-WBV),and aggregation index(AI,all P<0.05).In CRVO-affected eyes,vertical cupto-disc(C/D)ratio and optic cup volume were significantly smaller,whereas retinal nerve fiber layer(RNFL)thickness was significantly greater,compared to both unaffected contralateral eyes and normal control eyes(all P<0.05).Following treatment,VD of the entire optic disc(P<0.05),intra-disc VD(P<0.05),and peripapillary VD(P<0.05)all increased significantly relative to baseline.CMT decreased significantly(P<0.05),whereas macular SCP-VD and macular DCP-VD showed non-significant slight reductions(P>0.05).At baseline,BCVA of CRVO eyes correlated with whole-disc VD(r=-0.276,P=0.033),intra-disc VD(r=-0.342,P=0.009),and peripapillary VD(r=-0.335,P=0.007),with intra-disc VD demonstrating the strongest association.Besides,BCVA improvement,after the treatment,correlated positively with whole-disc VD(r=0.342,P=0.008)and intradisc VD(r=0.396,P=0.002).CONCLUSION:Optic disc blood perfusion is more closely associated with visual acuity than macular perfusion,suggesting intra-disc VD may serve as a potential biomarker for monitoring visual acuity changes in CRVO.Multiple ranibizumab injections significantly improve optic disc perfusion but may have exerted detrimental effects on the macula.CRVO patients shows higher hemorheological parameters than those with normal fundi.Reduced vertical C/D ratio and optic cup volume may be linked to CRVO incidence,potentially acting as susceptibility factors.
基金supported by the confidential research grant No.a8317。
文摘To address the issues of frequent identity switches(IDs)and degraded identification accuracy in multi object tracking(MOT)under complex occlusion scenarios,this study proposes an occlusion-robust tracking framework based on face-pedestrian joint feature modeling.By constructing a joint tracking model centered on“intra-class independent tracking+cross-category dynamic binding”,designing a multi-modal matching metric with spatio-temporal and appearance constraints,and innovatively introducing a cross-category feature mutual verification mechanism and a dual matching strategy,this work effectively resolves performance degradation in traditional single-category tracking methods caused by short-term occlusion,cross-camera tracking,and crowded environments.Experiments on the Chokepoint_Face_Pedestrian_Track test set demonstrate that in complex scenes,the proposed method improves Face-Pedestrian Matching F1 area under the curve(F1 AUC)by approximately 4 to 43 percentage points compared to several traditional methods.The joint tracking model achieves overall performance metrics of IDF1:85.1825%and MOTA:86.5956%,representing improvements of 0.91 and 0.06 percentage points,respectively,over the baseline model.Ablation studies confirm the effectiveness of key modules such as the Intersection over Area(IoA)/Intersection over Union(IoU)joint metric and dynamic threshold adjustment,validating the significant role of the cross-category identity matching mechanism in enhancing tracking stability.Our_model shows a 16.7%frame per second(FPS)drop vs.fairness of detection and re-identification in multiple object tracking(FairMOT),with its cross-category binding module adding aboute 10%overhead,yet maintains near-real-time performance for essential face-pedestrian tracking at small resolutions.
基金the National Natural Science Foundation of China,No. 30370561,30770845the Natural Science Foundation of Hebei Province,No. C2004000649,C2008000503+1 种基金the Science & Technology Pillar Program of Hebei Province,No. 09276101D-31Science and Technology Program of Zhangjiakou,No. 0711046D-3
文摘BACKGROUND：The intestinal lymphatic pathway and intestinal ischemia/reperfusion are mainly involved in mesenteric lymph duct ligation or drainage; moreover,intervention by reducing the lymph liquid reflux might relieve lung and other organ dysfunction induced by intestinal ischemia/reperfusion; however,research addressing mesenteric lymph reperfusion （MLR） and brain injury has not yet to be reported.OBJECTIVE：To observe the effect of MLR on brain tissue in a rat model of superior mesenteric artery occlusion （SMAO） shock,and to explore the molecular mechanism of MLR.DESIGN,TIME AND SETTING：A randomized,controlled,animal experiment at a neuro-pathophysiology level was performed at the Institute of Microcirculation,Hebei North University; Department of Pathophysiology,Basic Medical College; Department of Pathology,the First Hospital of Hebei North University between December 2007 and March 2009.MATERIALS：Adenosine triphosphate （ATP） standard was provided by the National Institute for the Control of Pharmaceutical and Biological Products; lactic acid （LA）,superoxide dismutase （SOD）,malonaldehyde （MDA）,nitrogen monoxidum （NO）,nitric oxide synthase （NOS）,myeloperoxidase （MPO） and ATPase assay kits were provided by Nanjing Jiancheng Bioengineering Institute,China.METHODS：A total of 24 male Wistar rats were randomly divided into four groups.In the sham-surgery group （n = 6）,both the mesenteric lymph duct and the superior mesenteric artery were not blocked; in the MLR group （n = 6）,the mesenteric lymph duct was occluded for 1 hour followed by 2-hour reperfusion; in the SMAO group （n = 6）,the superior mesenteric artery was occluded for 1 hour followed by 2-hour reperfusion; in the MLR ＋ SMAO group （n = 6）,both the mesenteric lymph duct and superior mesenteric artery were occluded for 1 hour followed by 2-hour reperfusion.MAIN OUTCOME MEASURES：Mean arterial blood pressure prior to and following ischemia/reperfusion; brain tissue morphology levels of LA,MDA,SOD,NO,NOS,MPO,ATPase and ATP following reperfusion.RESULTS：MLR did not cause changes in mean arterial blood pressure,brain tissue morphology,LA,MDA,NO,ATP,SOD,NOS,MPO and ATPase.However,SMAO caused a rapid decrease and gradual increase of mean arterial blood pressure.Neuronal necrosis,degeneration and swelling were observed in brain tissue.Contents of MDA,NO,LA and ATP as well as activities of NOS and MPO were significantly increased （P〈 0.05）,but activities of SOD and Na＋-K＋-ATPase were significantly decreased （P 〈 0.05）.MLR aggravated neuronal damage in a rat model of SMAO shock.Following MLR,mean arterial blood pressure was significantly decreased （P 〈 0.05）,contents of MDA and NO as well as activities of NOS and MPO were significantly increased （P 〈0.05）,but activities of Ca2＋-ATPase,Mg2＋-ATPase and Ca2＋-Mg2＋-ATPase as well as ATP content were significantly decreased （P〈 0.05）.CONCLUSION：MLR aggravates brain injury in a rat model of SMAO shock,which correlates with oxygen-derived free radical injury,NO synthesis and release,sequestration of neutrophilic granulocytes,decreasing activity of cell membrane pumps and energy metabolism dysfunction.Pathogenesis of the intestinal lymphatic pathway should be thoroughly investigated to prevent ischemia/reperfusion injury.
基金the National Natural Science Foundation of China, No. 30370561, 30770845the Natural Science Foundation of Hebei Province, No. C2004000649, C2008000503+1 种基金the Science & Technology Pillar Program of Hebei Province, No. 09276101D-31Science and Technology Program of Zhangjiakou, No. 0711046D-3
文摘BACKGROUND： Previous studies have shown that mesenteric lymph reperfusion （MLR） exacerbates brain injury in a rat model of superior mesenteric artery occlusion （SMAO） shock. However, little is known about the influence of MLR on neurotransmitter expression in brain tissue. OBJECTIVE： To observe the effect of MLR on brain tissue injury by measuring monoamine and cholinergic neurotransmitter levels. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Institute of Microcirculation, Hebei North University, China; Research Room of Microcirculation and Laboratory of Biochemistry, Department of Pathophysiology, Basic Medical College, Hebei North University between December 2007 and March 2009. MATERIALS： Choline acetyltransferase （CHAT） and acetylcholine esterase （ACHE） kits were provided by Nanjing Jiancheng Bioengineering Institute, China; dopamine （DA） and noradrenalin （NE） standards were provided by the National Institute for the Control of Pharmaceutical and Biological Products; HP1100 chromatograph of liquid was provided by Agllent, USA. METHODS： A total of 24 male, Wistar rats were randomly assigned to 4 groups： sham-surgery, MLR SMAO, and MLR ＋ SMAO groups, with 6 rats in each group. In the MLR or SMAO groups, the mesenteric lymph duct or superior mesenteric artery was blocked for 1 hour. In the MLR ＋ SMAO group, the mesenteric lymph duct and superior mesenteric artery were occluded for 1 hour, followed by 2-hour repeffusion. ChAT and AChE levels were measured using the synthesized and hydrolyzed acetylcholine method, respectively. Liquid chromatography was employed to quantitatively analyze DA and NE levels, using relative retention time and the external standard method. MAIN OUTCOME MEASURES： CHAT, ACHE, DA, and NE levels. RESULTS： AChE levels were significantly increased, but ChAT levels were significantly decreased in the MLR and MLR ＋ SMAO groups following 2-hour repeffusion （P〈 0.01）. However, AChE activity in the MLR ＋ SMAO group was greater than in the MLR group （P 〈 0.05）. DA and NE levels were significantly decreased in the SMAO and MLR ＋ SMAO groups （P〈 0.01）, while DA levels in the MLR ＋ SMAO group were less than in the SMAO group （P 〈 0.05）. CONCLUSION： MLR exacerbated brain injury in a rat model of SMAO shock, which correlated with the intestinal lymphatic pathway. MLR decreased DA levels, but increased AChE activity, in a rat model of SMAO shock.
基金supported by research grants from the Natural Science Foundation of Shandong Province[grant number ZR2017BH114],the National Natural Science Foundation of China[grant number 81700334],and Jinan Science and Technology Plan Project[grant number 201805058].
文摘Aim:The effects of tirofiban combined with nicorandil on effective reperfusion,and the levels of interleukin-4(IL-4)and soluble intercellular adhesion molecule-1(sICAM-1)after percutaneous coronary intervention(PCI)for chronic coronary total occlusion(CTO)were investigated.Method:From January 1,2017,to June 31,2019,a total of 40 patients with CTO receiving PCI in Shandong Qian-foshan Hospital were randomly divided into a control group(treated with single tirofiban)and a cocktail group(treated with nicorandil combined with tirofiban).Effective reperfusion was compared between groups.In addition,differences in coronary serum IL-4 and sICAM-1 levels before and 10 min after the operation were compared between groups,and the incidence rates of adverse reactions were observed.Finally,patient follow-up occurred at 1 month and 6 months,and the total incidence rates of adverse cardiac events in both groups were assessed.Results:The levels of IL-4 and sICAM-1 in the cocktail group significantly decreased after the operation(P<0.05).In addition,after the operation,significantly greater decreases in the IL-4 and sICAM-1 levels were observed in the cocktail group than the control group(P<0.05).The Seattle Angina Scale(SAQ)score of the cocktail group,compared with the control group,showed a significant improvement after vessel opening in the patients with CTO.At the 1-month follow-up,the SAQ score of the cocktail group,compared with the control group,indicated further improvements in terms of angina attack frequency.No significant differences were observed in the incidence rates of adverse reactions between groups(P>0.05).Conclusion:The treatment of patients with CTO undergoing PCI with nicorandil and tirofiban alleviated the inflam-matory response,improved the SAQ scores,and decreased the occurrence of angina pectoris in patients.Moreover,this treatment is safe and reliable,and has important clinical significance.
基金National Natural Science Foundation of China(81173596)Natural Science Foundation of the Department of Education of Anhui Province(KJ2015A157)
文摘OBJECTIVE To investigate regulatory effects of hyperoside(Hyp)on IP3/PKC/TRPV4 pathway in rat cerebral basilar artery(CBA)subjected to global cerebral ischemia-reperfusion(I/R).METHODS The model of global cerebral I/R in rats was established by four-vessel occlusions methods.The treated rats were administrated with Hyp(50 mg·kg^-1)group,Hyp(50 mg·kg^-1)+HC-067047(10 mg·kg^-1),Hyp(50 mg·kg^-1)+2APB(2 mg·kg^-1),Hyp(50 mg·kg^-1)+BisI(2.5 mg·kg^-1),Hyp(50 mg·kg^-1)+2APB(2 mg·kg^-1)+BisI(2.5 mg·kg^-1).Hematoxylin-eosin(HE)and Nissl staining were performed and the contents of methane dicarboxylic aldehyde(MDA),neuron-specific enolase(NSE),S100β and the activity of lactic dehydrogenase(LDH)in serum were measured by enzyme-linked immunosorbnent assay(ELISA).The specific blocker N-nitro-L-arginine-methyl-ester(L-NAME)and indomethacin(Indo)were used to delete the prostacyclin(PGI2)and nitric oxide(NO)dependent relaxation.The protein expression level of TRPV4 was detected by Western blotting.Ca2+intensity in vascular smooth muscle cells was measured by confocal laser scanning microscope and flow cytometry was performed to observe the apoptosis of CBA endothelial cells after in vivo administration.RESULTS Hyp induced a dose-dependent relaxation of CBA in IR rats via a PGI2 and NO independent manner,as evidenced by alleviated patho⁃logical changes and up-regulated expression of TRPV4 protein in the endothelial cells from cerebral vessels.Hyp signifi⁃cantly reduced the contents of MDA,NSE,S100βand the activity of LDH in serum and decreased the fluorescence intensity of Ca2+in cerebral vascular smooth muscle cells by in vivo administration.The apoptotic rate of endothelial cells in Hyp treated group was significantly less than that in IR group.CONCLUSION Hyp does in fact ameliorate I/R injury by regulatingIP3/PKC/TRPV4 pathway.
文摘The stable gastric pentadecapeptide BPC 157 counteracts various venous occlusion-induced syndromes.Summarized are all these arguments,in the Robert’s cytoprotection concept terms,to substantiate the resolution of different major vessel occlusion disturbances,in particular ischemia-reperfusion injury following the Pringle maneuver and Budd-Chiari syndrome,which was obtained by BPC 157 therapy.Conceptually,there is new point(bypassed occluded or ruptured vessel,the equation endothelium maintenance→epithelium maintenance=blood vessel recruitment and activation towards defect or bypassing vessel occlusion),the recruitment of collateral blood vessels to compensate for vessel occlusion and reestablish blood flow.In this paper,we summarize the evidence of the native cytoprotective gastric pentadecapeptide BPC 157,which is stable in the human gastric juice,is a membrane stabilizer and counteracts gut-leaky syndrome.As a particular target,it is distinctive from the standard peptide growth factors,with particular molecular pathways involved,controlling VEGF and NO pathways.In the early 1990s,BPC 157 appeared as a late outbreak of the Robert’s and Szabo’s cytoprotection-organoprotection concept,epithelium,endothelium protection as previous theoretical/practical breakthrough in the 1980s,and brain-gut axis and gut-brain axis.As the time went on,with its reported effects,it is likely most useful theory practical implementation and justification.Meantime,several reviews suggest that BPC 157,which does not have a lethal dose(LD1),has profound cytoprotective activity,used to be demonstrated in ulcerative colitis and invented to multiple sclerosis trials.Likely,it may bring the theory to practical application,starting with the initial argument,no degradation in human gastric juice for more than 24 h,and thereby,the therapeutic effectiveness(including therapeutic per-oral regimen)and pleiotropic beneficial effects.
基金supported by the National Natural Science Foundation of China,Nos.82260245(to YX),81660207(to YX),81960253(to YL),82160268(to YL),U1812403(to ZG)Science and Technology Projects of Guizhou Province,Nos.[2019]1440(to YX),[2020]1Z067(to WH)+1 种基金Cultivation Foundation of Guizhou Medical University,No.[20NSP069](to YX)Excellent Young Talents Plan of Guizhou Medical University,No.(2022)101(to WH)。
文摘Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion injury.Autophagy occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains unclear.In this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion injury.We found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced autophagy.Furthermore,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating autophagy.Blocking autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion injury.Findings from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.
文摘Reperfusion following cerebral ischemia causes both structural and functional damage to brain tissue and could aggravate a patient's condition;this phenomenon is known as cerebral ischemia-reperfusion injury.Current studies have elucidated the neuroprotective role of the sirtuin protein family(Sirtuins)in modulating cerebral ischemia-reperfusion injury.However,the potential of utilizing it as a novel intervention target to influence the prognosis of cerebral ischemia-reperfusion injury requires additional exploration.In this review,the origin and research progress of Sirtuins are summarized,suggesting the involvement of Sirtuins in diverse mechanisms that affect cerebral ischemia-reperfusion injury,including inflammation,oxidative stress,blood-brain barrier damage,apoptosis,pyroptosis,and autophagy.The therapeutic avenues related to Sirtuins that may improve the prognosis of cerebral ischemia-reperfusion injury were also investigated by modulating Sirtuins expression and affecting representative pathways,such as nuclear factor-kappa B signaling,oxidative stress mediated by adenosine monophosphate-activated protein kinase,and the forkhead box O.This review also summarizes the potential of endogenous substances,such as RNA and hormones,drugs,dietary supplements,and emerging therapies that regulate Sirtuins expression.This review also reveals that regulating Sirtuins mitigates cerebral ischemia-reperfusion injury when combined with other risk factors.While Sirtuins show promise as a potential target for the treatment of cerebral ischemiareperfusion injury,most recent studies are based on rodent models with circadian rhythms that are distinct from those of humans,potentially influencing the efficacy of Sirtuinstargeting drug therapies.Overall,this review provides new insights into the role of Sirtuins in the pathology and treatment of cerebral ischemia-reperfusion injury.
文摘Nitric oxide(NO)is a gaseous molecule produced by 3 different NO synthase(NOS)isoforms:Neural/brain NOS(nNOS/bNOS,type 1),endothelial NOS(eNOS,type 3)and inducible NOS(type 2).Type 1 and 3 NOS are constitutively expressed.NO can serve different purposes:As a vasoactive molecule,as a neurotransmitter or as an immunomodulator.It plays a key role in cerebral ischemia/reperfusion injury(CIRI).Hypoxic episodes simulate the production of oxygen free radicals,leading to mitochondrial and phospholipid damage.Upon reperfusion,increased levels of oxygen trigger oxide synthases;whose products are associated with neuronal damage by promoting lipid peroxidation,nitrosylation and excitotoxicity.Molecular pathways in CIRI can be altered by NOS.Neuroprotective effects are observed with eNOS activity.While nNOS interplay is prone to endothelial inflammation,oxidative stress and apoptosis.Therefore,nNOS appears to be detrimental.The interaction between NO and other free radicals develops peroxynitrite;which is a cytotoxic agent.It plays a main role in the likelihood of hemorrhagic events by tissue plasminogen activator(t-PA).Peroxynitrite scavengers are currently being studied as potential targets to prevent hemorrhagic transformation in CIRI.
基金Supported by the Science and Technology Program of Nantong Health Committee,No.MA2019003 and No.MA2021017Kangda College of Nanjing Medical University,No.KD2021JYYJYB025,No.KD2022KYJJZD019,and No.KD2022KYJJZD022+1 种基金Research Project of Nantong Health and Health Commission,No.MS2023041the Science and Technology Program of Nantong City,No.Key003 and No.JCZ2022040.
文摘The chronic occlusion of intracranial arteries generally has no or mild clinical symptoms,and the clinical symptoms of acute cerebral artery occlusion are mostly manifested as severe cerebral infarction symptoms,which often make early diagnosis difficult,thus losing the best treatment opportunity.Once cerebral infarction occurs,the consequences are difficult to recover.This is also an important reason for the high misdiagnosis rate and mortality of this disease.In this paper,the characteristics of the disease were analyzed to provide clinical reference.
基金supported by the CAMS Innovation Fund for Medical Sciences(No.2021-I2M-1-008)the National High Level Hospital Clinical Research Funding(No.2023-GSP-GG-2&No.2023-GSP-QN-34&No.2023-GSPRC-05).
文摘BACKGROUND The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined.METHODS All CTO vessels treated with successful anatomical PCI in patients from PANDA Ⅲ trial were retrospectively measured for postPCI QFR.The primary outcome was 2-year vessel-oriented composite endpoints (VOCEs,composite of target vessel-related cardiac death,target vessel-related myocardial infarction,and ischemia-driven target vessel revascularization).Receiver operator characteristic curve analysis was conducted to identify optimal cutoff value of post-PCI QFR for predicting the 2-year VOCEs,and all vessels were stratified by this optimal cutoff value.Cox proportional hazards models were employed to calculate the hazard ratio (HR) with 95% CI.RESULTS Among 428 CTO vessels treated with PCI,353 vessels (82.5%) were analyzable for post-PCI QFR.31 VOCEs (8.7%) occurred at 2 years.Mean value of post-PCI QFR was 0.92±0.13.Receiver operator characteristic curve analysis shown the optimal cutoff value of post-PCI QFR for predicting 2-year VOCEs was 0.91.The incidence of 2-year VOCEs in the vessel with post-PCI QFR<0.91 (n=91) was significantly higher compared with the vessels with post-PCI QFR≥0.91 (n=262)(22.0%vs.4.2%,HR=4.98,95%CI:2.32–10.70).CONCLUSIONS Higher post-PCI QFR values were associated with improved prognosis in the PCI practice for coronary CTO.Achieving functionally optimal PCI results (post-PCI QFR value≥0.91) tends to get better prognosis for patients with CTO lesions.
基金Natural Science Basic Research Program of Shaanxi Province(Project No.:2021JM-554)。
文摘Ferroptosis is a novel form of non-apoptotic cell death that has been widely studied in recent years and is involved in a variety of pathophysiological processes.The core treatment goal of ischemic stroke is to restore blood flow as early as possible,while the pathological mechanism of reperfusion injury after restoring blood flow is complex,involving oxidative stress,calcium overload,and inflammatory response.In recent years,more and more studies have found that ferroptosis mediation is involved in the occurrence and development of cerebral ischemia-reperfusion injury.This paper elaborates on the concept,mechanisms,and regulation of ferroptosis,detailing its role in cerebral ischemia-reperfusion injury and potential inhibition strategies.The aim is to deepen the understanding of ferroptosis in this pathological process and provide insights for possible targeted therapies.
基金Shanghai Rehabilitation Medical Association,Grant/Award Number:2023JGKT24China Rehabilitation Medical Association,Grant/Award Number:KFKT-2023Shanghai“14th Five-Year Plan”Traditional Chinese Medicine Specialty and Traditional Chinese Medicine Emergency Capacity Improvement Project,Grant/Award Number:ZYTSZK2-7。
文摘Cerebral ischemia/reperfusion(I/R)injury is an important pathophysiological condition of ischemic stroke that involves a variety of physiological and pathological cell death pathways,including autophagy,apoptosis,necroptosis,and phagoptosis,among which autophagy is the most studied.We have reviewed studies published in the past 5 years regarding the association between autophagy and cerebral I/R injury.To the best of our knowledge,this is the first review article summarizing potential candidates targeting autophagic pathways in the treatment of I/R injury post ischemic stroke.The findings of this review may help to better understand the pathogenesis and mechanisms of I/R events and bridge the gap between basic and translational research that may lead to the development of novel therapeutic approaches for I/R injury.
基金Supported by Youth Cultivation Research Program of Beijing Road Medical Area,Xinjiang Military Region General Hospital,Xinjiang,China(No.2022jzbj105)Science and Technology Program of Urumqi Municipal Health and Wellness Commission(No.202360).
文摘AIM:To assess the relationship between serological parameters and the prognosis of young patients with retinal vein occlusion(RVO)after intravitreal conbercept injection(IVC).METHODS:This study enrolled 100 young patients(≤50 years old)diagnosed with RVO-related macular edema(RVO-ME)who had been undergoing IVC at the 474 Hospital in Xinjiang between January 2022 and October 2023.Patients were categorized into two groups:70 eyes in the effective group and 30 eyes in the ineffective group.The effective group comprised patients exhibiting a visual acuity improvement of≥2 lines at the last follow-up,with resolved ME and central macular thickness(CMT)<300μm.Conversely,the ineffective group included patients with visual acuity improvement of<1 line,persistent ME,and CMT≥300μm at the last follow-up.Serological parameters,including white blood cell count,neutrophil count,lymphocyte count,monocyte count,and mean platelet volume were assessed before treatment.The correlation between bestcorrected visual acuity(BCVA)and neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),systemic immune inflammation index(SII),and systemic immune response index(SIRI)was analyzed.Additionally,the association between these serological parameters and the efficacy of IVC was explored.RESULTS:Three months after treatment,the effective group demonstrated a significant improvement in BCVA from 0.82±0.20 to 0.36±0.10,with a concurrent decrease in CMT from 661.28±163.90 to 200.61±82.45μm(P<0.001).Conversely,the ineffective group exhibited minimal changes in BCVA(0.86±0.25 to 0.82±0.14)and CMT(669.84±164.95 to 492.13±138.67μm,P<0.001).The differences in BCVA and CMT between the two groups were statistically significant(P<0.001).According to subgroup analysis,in patients with central RVO(CRVO),BCVA improved from 0.82±0.23 to 0.49±0.12 in the effective group and from 0.80±0.18 to 0.76±0.22 in the ineffective group(P<0.001).The CMT changes followed a similar pattern.In patients with branch RVO(BRVO),comparable trends in BCVA and CMT changes were observed between the effective and ineffective groups(P<0.001).Additionally,the effective group exhibited higher PLR and SII values than the ineffective group(P<0.05).Further CRVO and BRVO subgroups analysis exhibited consistent PLR and SII value trends.CONCLUSION:Compared to other inflammatory factors,elevated PLR and SII levels before treatment are better predictors of outcomes in young RVO-ME patients undergoing IVC treatment.
基金Supported by the Suzhou Medical Innovation Application Research Project(SZM2023027).
文摘AIM:To explore the morphological and functional parameters to evaluate the effectiveness of intravitreal injections of ranibizumab(IVR)in treating macular edema(ME)secondary to retinal vein occlusion(RVO).METHODS:This retrospective study involved 65 RVO patients(65 eyes)who received IVR and were followedup for more than 3mo.ME was categorized into cystoid macular edema(CME),diffuse retinal thickening(DRT),and serous retinal detachment(SRD)according to optical coherence tomography(OCT)images.The comparison of best corrected visual acuity(BCVA;logMAR)and central macular thickness(CMT)among different follow-up points and those among 3 groups were performed by Kruskal-Wallis test.The correlation between BCVA and baseline parameters during treatment was analyzed using Spearman correlation analysis.RESULTS:BCVA tended to improve in all groups,with marked improvement in CME and DRT groups.CMT showed the greatest reduction after 1wk,and remained stable over the following 3mo.DRT patients had the worst BCVA and the highest CMT at baseline,but the differences became smaller after IVR treatment.CMT in SRD group was significantly better than in CME and DRT groups 3mo after IVR.Most patients of CME and SRD groups transitioned to a normal pattern at 3mo follow-up.DRT patients were most likely to transform into the other morphological groups,while SRD patients showed minimal transitions.BCVA at baseline was identified as the most important prognostic indicator in all 3 groups.Additionally,DRT patients with a longer clinical course,higher CMT and central retinal vein occlusion(CRVO)tend to exhibit worse BCVA after treatment.In addition,CRVO patients are more likely to have worse BCVA at 2 and 3mo follow-up compared with branch retinal vein occlusion(BRVO)patients in CME group.SRD patients with higher baseline CMT were prone to experiencing worse BCVA after treatment.CONCLUSION:The effectiveness of IVR is strongly correlated with baseline BCVA in all 3 groups.Baseline parameters including clinical course,CMT,and RVO position are also useful in predicting the BCVA at different time points after treatment.
基金supported by the National Natural Science Foundation of China(81770692)。
文摘Objective:Acute kidney injury(AKI)is a clinical syndrome characterized by sudden deterioration of renal function,with ischemia reperfusion injury(IRI)being the most common cause.Long noncoding RNA(lncRNA)regulate cell fate through interactions with microRNA(miRNA)and messenger RNAs(mRNA),but the mechanisms and regulatory networks underlying lncRNA AK154753(AK154753)in IRI-induced AKI remain unclear.This study aims to investigate the role of AK154753 in acute renal IRI and to elucidate the molecular mechanism of the AK154753 via miR-345-3p/Bcl-2 homologous antagonist/killer(Bak)and miR-708-5p/Bcl-2 interacting mediator of cell death(Bim)axis.Methods:A bilateral renal artery ischemia model was established in mice(30 minutes ischemia followed by 24 hours and 48 hours reperfusion).Kidney tissues were analyzed using microarray-based transcriptomic sequencing to identify differentially expressed lncRNAs,miRNAs,and mRNAs.RNA levels of AK154753,miR-345-3p,miR-708-5p,Bak,and Bim were validated using real-time reverse transcription PCR(real-time RTPCR).Oxygen and glucose deprivation/reperfusion(OGD/R)models were constructed in mouse proximal renal tubular epithelial BUMPT cells to simulate in vitro IRI conditions.Adeno-associated virus(AAV)-mediated shRNA was used to silence AK154753 in vivo.Apoptosis was assessed using TUNEL staining and flow cytometry.Protein levels of Bak,Bim,and cleaved-caspase-3 were measured using Western blotting.Fluorescence in situ hybridization(FISH)was used to determine intracellular localization of AK154753.Binding relationships between AK154753 and miR-345-3p/Bak and miR-708-5p/Bim were verified using dual-luciferase reporter assays.MiRNA mimics and inhibitors were used to evaluate regulatory-network integrity.Results:IRI significantly elevated serum blood urea nitrogen(BUN)and serum creatinine(Scr),accompanied by tubular-structure damage and increased cell apoptosis(all P<0.05).Transcriptome profiling and real-time RT-PCR validation demonstrated that lncRNA AK154753,along with the pro-apoptotic proteins Bak and Bim,was significantly upregulated after IRI,whereas miR-345-3p and miR-708-5p were markedly downregulated(P<0.01).In vitro,OGD/R treatment significantly induced AK154753 expression in renal tubular epithelial cells and suppressed the expression of miR-345-3p and miR-708-5p,while markedly increasing the protein levels of Bak,Bim,and cleaved-caspase 3,resulting in a significant increase in apoptosis(all P<0.01).Silencing AK154753 significantly attenuated OGD/R-induced apoptosis,reduced the expression of Bak,Bim,and cleaved caspase 3,and decreased cell apoptosis(all P<0.01),while significantly upregulating miR-345-3p and miR-708-5p expression(P<0.01).In vivo,adeno-associated virus(AAV)-mediated knockdown of AK154753 significantly improved renal function in IRI mice,alleviated tubular injury,and suppressed renal tissue apoptosis,as evidenced by reduced BUN and Scr levels,improved histopathological injury scores,and decreased expression of Bak,Bim,and cleaved caspase-3(all P<0.01),accompanied by significant upregulation of miR-345-3p and miR-708-5p(all P<0.01).Luciferase reporter assays further confirmed that miR-345-3p directly binds to the 3'-untranslated region(3'-UTR)of AK154753 and Bak,whereas miR-708-5p directly binds to the 3'-UTRs of AK154753 and Bim.Inhibition of miR-345-3p or miR-708-5p abolished the anti-apoptotic effects induced by AK154753 silencing and restored Bak and Bim expression levels(all P<0.01).Conclusion:AK154753 is upregulated in acute renal IRI and promotes apoptosis by suppressing miR-345-3p and miR-708-5p,thereby upregulating Bak and Bim,and participates in the initiation and progression of acute renal IRI.
