Mitochondrial dysfunction and quality control lie at the heart of subarachnoid hemorrhage

The dramatic increase in intracranial pressure after subarachnoid hemorrhage leads to a decrease in cerebral perfusion pressure and a reduction in cerebral blood flow.Mitochondria are directly affected by direct factors such as ischemia,hypoxia,excitotoxicity,and toxicity of free hemoglobin and its degradation products,which trigger mitochondrial dysfunction.Dysfunctional mitochondria release large amounts of reactive oxygen species,inflammatory mediators,and apoptotic proteins that activate apoptotic pathways,further damaging cells.In response to this array of damage,cells have adopted multiple mitochondrial quality control mechanisms through evolution,including mitochondrial protein quality control,mitochondrial dynamics,mitophagy,mitochondrial biogenesis,and intercellular mitochondrial transfer,to maintain mitochondrial homeostasis under pathological conditions.Specific interventions targeting mitochondrial quality control mechanisms have emerged as promising therapeutic strategies for subarachnoid hemorrhage.This review provides an overview of recent research advances in mitochondrial pathophysiological processes after subarachnoid hemorrhage,particularly mitochondrial quality control mechanisms.It also presents potential therapeutic strategies to target mitochondrial quality control in subarachnoid hemorrhage.

Mitophagy in intracerebral hemorrhage:a new target for therapeutic intervention

Intracerebral hemorrhage is a life-threatening condition with a high fatality rate and severe sequelae.However,there is currently no treatment available for intracerebral hemorrhage,unlike for other stroke subtypes.Recent studies have indicated that mitochondrial dysfunction and mitophagy likely relate to the pathophysiology of intracerebral hemorrhage.Mitophagy,or selective autophagy of mitochondria,is an essential pathway to preserve mitochondrial homeostasis by clearing up damaged mitochondria.Mitophagy markedly contributes to the reduction of secondary brain injury caused by mitochondrial dysfunction after intracerebral hemorrhage.This review provides an overview of the mitochondrial dysfunction that occurs after intracerebral hemorrhage and the underlying mechanisms regarding how mitophagy regulates it,and discusses the new direction of therapeutic strategies targeting mitophagy for intracerebral hemorrhage,aiming to determine the close connection between mitophagy and intracerebral hemorrhage and identify new therapies to modulate mitophagy after intracerebral hemorrhage.In conclusion,although only a small number of drugs modulating mitophagy in intracerebral hemorrhage have been found thus far,most of which are in the preclinical stage and require further investigation,mitophagy is still a very valid and promising therapeutic target for intracerebral hemorrhage in the long run.

Tumor necrosis factor-stimulated gene-6 ameliorates early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome-mediated astrocyte pyroptosis

Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective treatment.Pyroptosis is a crucial mechanism underlying early brain injury after subarachnoid hemorrhage.Previous studies have confirmed that tumor necrosis factor-stimulated gene-6(TSG-6)can exert a neuroprotective effect by suppressing oxidative stress and apoptosis.However,no study to date has explored whether TSG-6 can alleviate pyroptosis in early brain injury after subarachnoid hemorrhage.In this study,a C57BL/6J mouse model of subarachnoid hemorrhage was established using the endovascular perforation method.Our results indicated that TSG-6 expression was predominantly detected in astrocytes,along with NLRC4 and gasdermin-D(GSDMD).The expression of NLRC4,GSDMD and its N-terminal domain(GSDMD-N),and cleaved caspase-1 was significantly enhanced after subarachnoid hemorrhage and accompanied by brain edema and neurological impairment.To explore how TSG-6 affects pyroptosis during early brain injury after subarachnoid hemorrhage,recombinant human TSG-6 or a siRNA targeting TSG-6 was injected into the cerebral ventricles.Exogenous TSG-6 administration downregulated the expression of NLRC4 and pyroptosis-associated proteins and alleviated brain edema and neurological deficits.Moreover,TSG-6 knockdown further increased the expression of NLRC4,which was accompanied by more severe astrocyte pyroptosis.In summary,our study revealed that TSG-6 provides neuroprotection against early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome activation-induced astrocyte pyroptosis.

Early antiplatelet therapy used for acute ischemic stroke and intracranial hemorrhage

In this editorial we comment on the article published by Zhang et al in the recent issue of World Journal of Clinical Cases.We evaluate their claims on the benefit of use of Aspirin in the early management of patients with ischemic stroke.We also comment on their contention of using aspirin in the early management of patients with intracranial hemorrhage,a practice not seen in modern medicine.Large clinical trials such as the International Stroke Trial and the Chinese Acute Stroke Trial have shown the benefit of Aspirin use within 48 h of patients with Acute Ischemic Stroke.The findings were corroborated in the open-label trial performed by Zhang et al in a smaller sample group of 25 patients where they showed improvement in functional scores at 90 days without an increase in adverse events.As such,this intervention is also recommended by the American Heart Association stroke guidelines from 2021.With regard to Intracranial hemorrhage,traditional practice has been to discontinue or avoid antiplatelet therapy in these patient groups.However,no studies have been done to evaluate this management strategy that is more borne out of the mechanism behind Aspirin’s effect on the coagulation pathway.Zhang et al evaluate the benefits of Aspirin on patients with low-volume intracranial hemorrhage,i.e.,less than 30 mL on computed tomo-graphy imaging,and show no increase in mortality.The caveat of this finding is that all outcomes were pooled into one group for results,and the number of patients was low.While more studies with larger patient groups are required,the data from Zhang et al suggests that patients with small-volume intracranial hemorrhages may benefit from Aspirin administration in the acute phase of management.

Bone marrow-derived mesenchymal stem cell-derived exosomeloaded miR-129-5p targets high-mobility group box 1 attenuates neurological-impairment after diabetic cerebral hemorrhage

BACKGROUND Diabetic intracerebral hemorrhage(ICH)is a serious complication of diabetes.The role and mechanism of bone marrow mesenchymal stem cell(BMSC)-derived exosomes(BMSC-exo)in neuroinflammation post-ICH in patients with diabetes are unknown.In this study,we investigated the regulation of BMSC-exo on hyperglycemia-induced neuroinflammation.AIM To study the mechanism of BMSC-exo on nerve function damage after diabetes complicated with cerebral hemorrhage.METHODS BMSC-exo were isolated from mouse BMSC media.This was followed by transfection with microRNA-129-5p(miR-129-5p).BMSC-exo or miR-129-5poverexpressing BMSC-exo were intravitreally injected into a diabetes mouse model with ICH for in vivo analyses and were cocultured with high glucoseaffected BV2 cells for in vitro analyses.The dual luciferase test and RNA immunoprecipitation test verified the targeted binding relationship between miR-129-5p and high-mobility group box 1(HMGB1).Quantitative polymerase chain reaction,western blotting,and enzyme-linked immunosorbent assay were conducted to assess the levels of some inflammation factors,such as HMGB1,interleukin 6,interleukin 1β,toll-like receptor 4,and tumor necrosis factorα.Brain water content,neural function deficit score,and Evans blue were used to measure the neural function of mice.RESULTS Our findings indicated that BMSC-exo can promote neuroinflammation and functional recovery.MicroRNA chip analysis of BMSC-exo identified miR-129-5p as the specific microRNA with a protective role in neuroinflammation.Overexpression of miR-129-5p in BMSC-exo reduced the inflammatory response and neurological impairment in comorbid diabetes and ICH cases.Furthermore,we found that miR-129-5p had a targeted binding relationship with HMGB1 mRNA.CONCLUSION We demonstrated that BMSC-exo can reduce the inflammatory response after ICH with diabetes,thereby improving the neurological function of the brain.

Optimization of nursing interventions for postoperative mental status recovery in patients with cerebral hemorrhage

BACKGROUND Hypertensive cerebral hemorrhage(HCH),the most common chronic diseases,has become a topic of global public health discussions.AIM To investigate the role of rehabilitative nursing interventions in optimizing the postoperative mental status recovery phase and to provide clinical value for future rehabilitation of patients with HCH.METHODS This randomized controlled study included 120 patients with cerebral HCH who were contained to our neurosurgery department between May 2021–May 2023 as the participants.The participants have randomly sampled and grouped into the observation and control groups.The observation group received the rehabilitation nursing model,whereas the control group have given conventional nursing.The conscious state of the patients was assessed at 7,14,21,and 30 d postoperatively.After one month of care,sleep quality,anxiety,and depression were compared between the two groups.Patient and family satisfaction were assessed using a nursing care model.RESULTS The results showed that the state of consciousness scores of the patients in both groups significantly increased(P<0.05)after surgical treatment.From the 14th day onwards,differences in the state of consciousness scores between the two groups of patients began to appear(P<0.05).After one month of care,the sleep quality,anxiety state,and depression state of patients were significantly better in the observation group than in the control group(P<0.05).Satisfaction with nursing care was higher in the observation group than in the control group(P<0.05).CONCLUSION The rehabilitation nursing model has a more complete system compared to conventional nursing,which can effectively improve the postoperative quality of life of patients with cerebral hemorrhage and improve the efficiency of mental state recovery;however,further analysis and research are needed to provide more scientific evidence.

Spi1 regulates the microglial/macrophage inflammatory response via the PI3K/AKT/mTOR signaling pathway after intracerebral hemorrhage

Preclinical and clinical studies have shown that microglia and macrophages participate in a multiphasic brain damage repair process following intracerebral hemorrhage.The E26 transformation-specific sequence-related transcription factor Spi1 regulates microglial/macrophage commitment and maturation.However,the effect of Spi1 on intracerebral hemorrhage remains unclear.In this study,we found that Spi1 may regulate recovery from the neuroinflammation and neurofunctional damage caused by intracerebral hemorrhage by modulating the microglial/macrophage transcriptome.We showed that high Spi1expression in microglia/macrophages after intracerebral hemorrhage is associated with the activation of many pathways that promote phagocytosis,glycolysis,and autophagy,as well as debris clearance and sustained remyelination.Notably,microglia with higher levels of Soil expression were chara cterized by activation of pathways associated with a variety of hemorrhage-related cellular processes,such as complement activation,angiogenesis,and coagulation.In conclusion,our results suggest that Spi1 plays a vital role in the microglial/macrophage inflammatory response following intracerebral hemorrhage.This new insight into the regulation of Spi1 and its target genes may advance our understanding of neuroinflammation in intracerebral hemorrhage and provide therapeutic targets for patients with intracerebral hemorrhage.

The pivotal role of microglia in injury and the prognosis of subarachnoid hemorrhage

Subarachnoid hemorrhage leads to a series of pathological changes,including vascular spasm,cellular apoptosis,blood–brain barrier damage,cerebral edema,and white matter injury.Microglia,which are the key immune cells in the central nervous system,maintain homeostasis in the neural environment,support neurons,mediate apoptosis,participate in immune regulation,and have neuroprotective effects.Increasing evidence has shown that microglia play a pivotal role in the pathogenesis of subarachnoid hemorrhage and affect the process of injury and the prognosis of subarachnoid hemorrhage.Moreover,microglia play certain neuroprotective roles in the recovery phase of subarachnoid hemorrhage.Several approaches aimed at modulating microglia function are believed to attenuate subarachnoid hemorrhage injury.This provides new targets and ideas for the treatment of subarachnoid hemorrhage.However,an in-depth and comprehensive summary of the role of microglia after subarachnoid hemorrhage is still lacking.This review describes the activation of microglia after subarachnoid hemorrhage and their roles in the pathological processes of vasospasm,neuroinflammation,neuronal apoptosis,blood–brain barrier disruption,cerebral edema,and cerebral white matter lesions.It also discusses the neuroprotective roles of microglia during recovery from subarachnoid hemorrhage and therapeutic advances aimed at modulating microglial function after subarachnoid hemorrhage.Currently,microglia in subarachnoid hemorrhage are targeted with TLR inhibitors,nuclear factor-κB and STAT3 pathway inhibitors,glycine/tyrosine kinases,NLRP3 signaling pathway inhibitors,Gasdermin D inhibitors,vincristine receptorαreceptor agonists,ferroptosis inhibitors,genetic modification techniques,stem cell therapies,and traditional Chinese medicine.However,most of these are still being evaluated at the laboratory stage.More clinical studies and data on subarachnoid hemorrhage are required to improve the treatment of subarachnoid hemorrhage.

Cholesterol metabolism: physiological versus pathological aspects in intracerebral hemorrhage

Cholesterol is an important component of plasma membranes and participates in many basic life functions,such as the maintenance of cell membrane stability,the synthesis of steroid hormones,and myelination.Cholesterol plays a key role in the establishment and maintenance of the central nervous system.The brain contains 20%of the whole body’s cholesterol,80%of which is located within myelin.A huge number of processes(e.g.,the sterol regulatory element-binding protein pathway and liver X receptor pathway)participate in the regulation of cholesterol metabolism in the brain via mechanisms that include cholesterol biosynthesis,intracellular transport,and efflux.Certain brain injuries or diseases involving crosstalk among the processes above can affect normal cholesterol metabolism to induce detrimental consequences.Therefore,we hypothesized that cholesterol-related molecules and pathways can serve as therapeutic targets for central nervous system diseases.Intracerebral hemorrhage is the most severe hemorrhagic stroke subtype,with high mortality and morbidity.Historical cholesterol levels are associated with the risk of intracerebral hemorrhage.Moreover,secondary pathological changes after intracerebral hemorrhage are associated with cholesterol metabolism dysregulation,such as neuroinflammation,demyelination,and multiple types of programmed cell death.Intracellular cholesterol accumulation in the brain has been found after intracerebral hemorrhage.In this paper,we review normal cholesterol metabolism in the central nervous system,the mechanisms known to participate in the disturbance of cholesterol metabolism after intracerebral hemorrhage,and the links between cholesterol metabolism and cell death.We also review several possible and constructive therapeutic targets identified based on cholesterol metabolism to provide cholesterol-based perspectives and a reference for those interested in the treatment of intracerebral hemorrhage.

ATAT1 deficiency enhances microglia/macrophage-mediated erythrophagocytosis and hematoma absorption following intracerebral hemorrhage

MIcroglia/macrophage-mediated erythrophagocytosis plays a crucial role in hematoma clearance after intracerebral hemorrhage.Dynamic cytoskeletal changes accompany phagocytosis.However,whether and how these changes are associated with microglia/macrophage-mediated erythrophagocytosis remain unclear.In this study,we investigated the function of acetylatedα-tubulin,a stabilized microtubule form,in microglia/macrophage erythrophagocytosis after intracerebral hemorrhage both in vitro and in vivo.We first assessed the function of acetylatedα-tubulin in erythrophagocytosis using primary DiO GFP-labeled red blood cells co-cultured with the BV2 microglia or RAW264.7 macrophage cell lines.Acetylatedα-tubulin expression was significantly decreased in BV2 and RAW264.7 cells during erythrophagocytosis.Moreover,silencingα-tubulin acetyltransferase 1(ATAT1),a newly discoveredα-tubulin acetyltransferase,decreased Ac-α-tub levels and enhanced the erythrophagocytosis by BV2 and RAW264.7 cells.Consistent with these findings,in ATAT1-/-mice,we observed increased ionized calcium binding adapter molecule 1(Iba1)and Perls-positive microglia/macrophage phagocytes of red blood cells in peri-hematoma and reduced hematoma volume in mice with intracerebral hemorrhage.Additionally,knocking out ATAT1 alleviated neuronal apoptosis and pro-inflammatory cytokines and increased anti-inflammatory cytokines around the hematoma,ultimately improving neurological recovery of mice after intracerebral hemorrhage.These findings suggest that ATAT1 deficiency accelerates erythrophagocytosis by microglia/macrophages and hematoma absorption after intracerebral hemorrhage.These results provide novel insights into the mechanisms of hematoma clearance and suggest ATAT1 as a potential target for the treatment of intracerebral hemorrhage.

Therapeutic potential of stem cells in subarachnoid hemorrhage

Aneurysm rupture can result in subarachnoid hemorrhage,a condition with potentially severe consequences,such as disability and death.In the acute stage,early brain injury manifests as intracranial pressure elevation,global cerebral ischemia,acute hydrocephalus,and direct blood–brain contact due to aneurysm rupture.This may subsequently cause delayed cerebral infarction,often with cerebral vasospasm,significantly affecting patient outcomes.Chronic complications such as brain volume loss and chronic hydrocephalus can further impact outcomes.Investigating the mechanisms of subarachnoid hemorrhage-induced brain injury is paramount for identifying effective treatments.Stem cell therapy,with its multipotent differentiation capacity and anti-inflammatory effects,has emerged as a promising approach for treating previously deemed incurable conditions.This review focuses on the potential application of stem cells in subarachnoid hemorrhage pathology and explores their role in neurogenesis and as a therapeutic intervention in preclinical and clinical subarachnoid hemorrhage studies.

Human-induced pluripotent stem cell-derived neural stem cell exosomes improve blood-brain barrier function after intracerebral hemorrhage by activating astrocytes via PI3K/AKT/MCP-1 axis

Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)have shown potential for brain injury repair in central nervous system diseases.In this study,we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism.Our results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits,enhanced blood-brain barrier integrity,and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage.Additionally,hiPSC-NSC-Exos decreased immune cell infiltration,activated astrocytes,and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1,macrophage inflammatory protein-1α,and tumor necrosis factor-αpost-intracerebral hemorrhage,thereby improving the inflammatory microenvironment.RNA sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion,thereby improving blood-brain barrier integrity.Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects.In summary,our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity,in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.

Simple procedure for assessing diffuse subarachnoid hemorrhage successfully created using filament perforation method in mice

The murine model of subarachnoid hemorrhage(SAH)is a valuable experimental tool for investigating molecular and cellular mechanisms,and the endovascular filament perforation technique can be used to simulate prominent pathophysiological features observed after human SAH;however,current validation methods for assessing an appropriate SAH model are limited.Here,we introduce a simple procedure for se-lecting a mouse model of diffuse SAH.SAH was induced in 24 mice using a standard filament perforation method.After confirming survival at 24 h,SAH was scored 0-1 based on T2*-weighted images on whole-brain magnetic resonance imaging(MRI)and visual surveillance of the cisterna magna(CM)through the dura mater.The CM-based SAH grading correlated well with a reference parameter defined by extracted brain(r^(2)=0.53,p<0.0001).The receiver operating characteristic curve revealed a sensi-tivity of 85%and a specificity of 91%for detecting diffuse SAH,with a similar area under the curve(0.89±0.06[standard error of the mean])as the MRI-based grading(0.72±0.10,p=0.12).Our data suggest that confirming an SAH clot in the CM is a valuable way to select a clinically relevant diffuse SAH model that can be used in future experimental studies.

Lactiplantibacillus plantarum FRT4 attenuates high-energy low-protein dietinduced fatty liver hemorrhage syndrome in laying hens through regulating gut-liver axis

Background Fatty liver hemorrhage syndrome(FLHS)becomes one of the most major factors resulting in the laying hen death for caged egg production.This study aimed to investigate the therapeutic effects of Lactiplantibacillus plan-tarum(Lp.plantarum)FRT4 on FLHS model in laying hen with a focus on liver lipid metabolism,and gut microbiota.Results The FLHS model of laying hens was established by feeding a high-energy low-protein(HELP)diet,and the treatment groups were fed a HELP diet supplemented with differential proportions of Lp.plantarum FRT4.The results indicated that Lp.plantarum FRT4 increased laying rate,and reduced the liver lipid accumulation by regulating lipid metabolism(lipid synthesis and transport)and improving the gut microbiota composition.Moreover,Lp.plan-tarum FRT4 regulated the liver glycerophospholipid metabolism.Meanwhile,“gut-liver”axis analysis showed that there was a correlation between gut microbiota and lipid metabolites.Conclusions The results indicated that Lp.plantarum FRT4 improved the laying performance and alleviated FLHS in HELP diet-induced laying hens through regulating“gut-liver”axis.Our findings reveal that glycerophospholipid metabolism could be the underlying mechanism for the anti-FLHS effect of Lp.plantarum FRT4 and for future use of Lp.plantarum FRT4 as an excellent additive for the prevention and mitigation of FLHS in laying hens.

Subsequent pregnancy outcomes and fertility rates in the case series that underwent bilateral hypogastric artery ligation(BHGAL)due to severe postpartum hemorrhage

Objective:To evaluate the effect of bilateral hypogastric artery ligation(BHGAL)on women's pregnancy outcomes and fertility rates in cases with severe postpartum hemorrhage.Methods:Patients hospitalized in a tertiary care center between 2007 and 2018 were included in the study.The records of cases were obtained from the hospital database,retrospectively.Maternal demographic data,morbidities or complications associated with BHGAL surgery,any additional haemostatic interventional or surgical procedures,preoperative admission and lowest postoperative haematocrit-hemoglobin values,blood products given,type of anaesthesia,intensive care unit(ICU)and length of hospital stay were recorded.In cases without surgical sterilization,future fertility and subsequent pregnancy outcomes were assessed for at least two years after operation.Information was obtained through face-to-face or telephone interviews with patients whose long-term fertility and subsequent pregnancy outcomes were assessed.Results:Sixty-eight patients with BHGAL surgery history were included in the study.26 Of 37 cases(70%)that did not undergo surgical sterilization had a desire for pregnancy after the surgery.Six of these cases(23%)were diagnosed with secondary infertility.The fertility rate of these cases was 77%,and subsequent pregnancy was detected in 20 women.A total of 25 pregnancies,including first and second pregnancies,developed,and 15 of these pregnancies resulted in term delivery,six preterm births,one stillbirth,and three abortions.Conclusions:The postoperative pregnancy rate was found to be higher than the rate of women with infertility problems,and this surgery does not seem to adversely affect pregnancy outcomes.This is a tertiary center experience and cohort studies with large patient series are needed.

Piezo1 as a potential player in intracranial hemorrhage:From perspectives on biomechanics and hematoma metabolism

Intracranial hemorrhage(ICH)causes numerous neurological deficits and deaths worldwide each year,leaving a significant health burden on the public.The pathophysiology of ICH is complicated and involves both primary and secondary injuries.Hematoma,as the primary pathology of ICH,undergoes metabolism and triggers biochemical and biomechanical alterations in the brain,leading to the secondary injury.Past endeavors mainly aimed at biochemical-initiated mechanisms for causing secondary injury,which have made limited progress in recent years,although ICH itself is also highly biomechanics-related.The discovery of the mechanically-activated cation channel Piezo1 provides a new avenue to further explore the mechanisms underlying the secondary injury.The current article reviews the structure and gating mechanisms of Piezo1,its roles in the physiology/pathophysiology of neurons,astrocytes,microglia,and bone-marrow-derived macrophages,and especially its roles in erythrocytic turnover and iron metabolism,revealing a potential interplay between the biomechanics and biochemistry of hematoma in ICH.Collectively,these advances provide deeper insights into the secondary injury of ICH and lay the foundations for future research.

Intravitreal conbercept injection with panretinal photocoagulation for high-risk proliferative diabetic retinopathy with vitreous hemorrhage

AIM:To assess the clinical efficacy and safety of combining panretinal photocoagulation(PRP)with intravitreal conbercept(IVC)injections for patients with high-risk proliferative diabetic retinopathy(HR-PDR)complicated by mild or moderate vitreous hemorrhage(VH),with or without diabetic macular edema(DME).METHODS:Patients diagnosed with VH with/without DME secondary to HR-PDR and received PRP combined with IVC injections were recruited in this retrospective study.Upon establishing the patient’s diagnosis,an initial IVC was performed,followed by prompt administration of PRP.In cases who significant bleeding persisted and impeded the laser operation,IVC was sustained before supplementing with PRP.Following the completion of PRP,patients were meticulously monitored for a minimum of six months.Laser therapy and IVC injections were judiciously adjusted based on fundus fluorescein angiography(FFA)results.Therapeutic effect and the incidence of adverse events were observed.RESULTS:Out of 42 patients(74 eyes),29 were male and 13 were female,with a mean age of 59.17±12.74y(33-84y).The diabetic history was between 1wk and 26y,and the interval between the onset of visual symptoms and diagnosis of HR-PDR was 1wk-1y.The affected eye received 2.59±1.87(1-10)IVC injections and underwent 5.5±1.02(4-8)sessions of PRP.Of these,68 eyes received PRP following 1 IVC injection,5 eyes after 2 IVC injections,and 1 eye after 3 IVC injections.Complete absorption of VH was observed in all 74 eyes 5-50wk after initial treatment,with resolution of DME in 51 eyes 3-48wk after initial treatment.A newly developed epiretinal membrane was noted in one eye.Visual acuity significantly improved in 25 eyes.No complications such as glaucoma,retinal detachment,or endophthalmitis were reported.CONCLUSION:The study suggests that the combination of PRP with IVC injections is an effective and safe modality for treating diabetic VH in patients with HR-PDR.

Delayed postpancreatectomy hemorrhage as the role of endovascular approach:Four case reports

BACKGROUND Pancreatic resection is still associated with high morbidity rates and delayed postpancreatectomy hemorrhage(PPH)is the most feared complication as it may lead to hemorrhagic shock or serious septic complications.Today,endovascular approach represent safe and efficient method for minimally invasive management of extraluminal PPH.CASE SUMMARY We describe four patients whose postoperative recovery after pancreatic resection was complicated by postoperative pancreatic fistula(POPF)and visceral artery hemorrhage.In all cases endovascular approach was utilized and it resulted in satisfactory outcomes.We discuss modern diagnostic and therapeutic approach in this clinical scenario.CONCLUSION PPH is relatively uncommon,but it is a leading cause of surgical mortality after pancreatic surgery.Careful monitoring and meticulous follow-up are required for all patients post-operatively,especially in the case of confirmed POPF,which is the most significant risk factor for the development of a PPH.Angiography as a diagnostic and therapeutic method may be an optimal first-line treatment for the management of delayed PPHs.In our experience,endovascular treatment for hemorrhagic complications of pancreatic resections has shown satisfactory results.

Fatal intratumoral hemorrhage in a patient with hepatocellular carcinoma following successful treatment with atezolizumab/bevacizumab:A case report

BACKGROUND Atezolizumab/bevacizumab is emerging as the new standard for advanced hepatocellular carcinoma(HCC),with ongoing real-world implementation to study its effectiveness.As the use of atezolizumab/bevacizumab increases,various side effects have been reported in clinical practice,most notably increased bleeding caused by bevacizumab.CASE SUMMARY In this case report,we present a rare and fatal case of intratumoral hemorrhage in a patient with advanced HCC following successful treatment with atezolizumab/bevacizumab.A 63-year-old male diagnosed with HCC initially underwent four cycles of intra-arterial chemotherapy.However,follow-up abdominal computed tomography(CT)revealed disease progression.Subsequently,the treatment plan was modified to atezolizumab/bevacizumab.After the fifth cycle of atezolizumab/bevacizumab,CT showed partial regression of HCC.One week later,he visited the emergency room due to severe abrupt abdominal pain.Abdominal CT revealed focal rupture of HCC in the medial segment inferior portion with active bleeding and a large amount of hemoperitoneum.Angiography was performed on the same day,and embolization of A4 and A8 branches using lipiodol and gelfoam was implemented.Despite successful hemostasis,the patient subsequently developed liver failure and died.CONCLUSION Atezolizumab/bevacizumab for advanced HCC suggests that intratumoral hemorrhage may be crucial despite good tumor response after immunotherapy,emphasizing the continuous monitoring of this side effect.

Predictive model for postpartum hemorrhage requiring hysterectomy in a minority ethnic region

BACKGROUND Postpartum hemorrhage(PPH)is a leading cause of maternal mortality,and hysterectomy is an important intervention for managing intractable PPH.Accurately predicting the need for hysterectomy and taking proactive emergency measures is crucial for reducing mortality rates.AIM To develop a risk prediction model for PPH requiring hysterectomy in the ethnic minority regions of Qiandongnan,China,to help guide clinical decision-making.METHODS The study included 23490 patients,with 1050 having experienced PPH and 74 who underwent hysterectomies.The independent risk factors closely associated with the necessity for hysterectomy were analyzed to construct a risk prediction model,and its predictive efficacy was subsequently evaluated.RESULTS The proportion of hysterectomies among the included patients was 0.32%(74/23490),representing 7.05%(74/1050)of PPH cases.The number of deliveries,history of cesarean section,placenta previa,uterine atony,and placenta accreta were identified in this population as independent risk factors for requiring a hysterectomy.Receiver operating characteristic curve analysis of the prediction model showed an area under the curve of 0.953(95%confidence interval:0.928-0.978)with a sensitivity of 90.50%and a specificity of 90.70%.CONCLUSION The model demonstrates excellent predictive power and is effective in guiding clinical decisions regarding PPH in the ethnic minority regions of Qiandongnan,China.