Corrigendum:Neuroprotection mediated by the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage

In the article titled“Neuroprotection mediated by the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage,”published on pages 1013-1024,Issue 6,Volume 14 of Neural Regeneration Research(Wang et al.,2019),there are some errors in selecting the appropriate images in Figures 4A,4B,and 5A by authors during assembling the images.

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.

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.

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.

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.

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.

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.

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.

Role of N-formyl peptide receptor 2 in germinal matrix hemorrhage:an intrinsic review of a hematoma resolving pathway

Germinal matrix hemorrhage is one of the leading causes of morbidity,mortality,and acquired infantile hydrocephalus in preterm infants in the United States,with little progress made in its clinical management.Blood clots have been shown to elicit secondary brain injury after germinal matrix hemorrhage,by disrupting normal cerebrospinal fluid circulation and absorption after germinal matrix hemorrhage causing post-hemorrhagic hydrocephalus development.Current evidence suggests that rapid hematoma resolution is necessary to improve neurological outcomes after hemorrhagic stroke.Various articles have demonstrated the beneficial effects of stimulating the polarization of microglia cells into the M2 phenotype,as it has been suggested that they play an essential role in the rapid phagocytosis of the blood clot after hemorrhagic models of stroke.N-formyl peptide receptor 2(FPR2),a G-protein-coupled receptor,has been shown to be neuroprotective after stroke.FPR2 activation has been associated with the upregulation of phagocytic macrophage clearance,yet its mechanism has not been fully explored.Recent literature suggests that FPR2 may play a role in the stimulation of scavenger receptor CD36.Scavenger receptor CD36 plays a vital role in microglia phagocytic blood clot clearance after germinal matrix hemorrhage.FPR2 has been shown to phosphorylate extracellular-signal-regulated kinase 1/2(ERK1/2),which then promotes the transcription of the dual-specificity protein phosphatase 1(DUSP1)gene.In this review,we present an intrinsic outline of the main components involved in FPR2 stimulation and hematoma resolution after germinal matrix hemorrhage.

Prevention and Treatment of Hemorrhage during Laparoscopic Splenectomy and Devascularization for Portal Hypertension

This study was aimed to explore prevention and treatment of hemorrhage during laparoscopic splenectomy plus devascularization（LSD） for portal hypertension by modified and simplified operation. From June 2012 to June 2014, LSD was performed on 138 patients with portal hypertension. The patients were allocated into two groups： earlier stage（ES） group, in which 45 patients received traditional LSD from June 2012 to Sep. 2012; later stage（LS） group, in which 93 patients underwent modified LSD from Jan. 2013 to June 2014. Perioperative variables were compared between the two groups. Laparoscopic operations were successfully performed in all but two patients in ES group who were converted to laparotomy（total conversion rate： 1.4%）. There was no perioperative death or reoperation, and all patients recovered and were discharged from hospital with no serious complications in the six months of postoperative follow-up. The average time in the ES group was longer than that in the LS group（335.1 min vs. 201.3 min, P〈0.05）. LS group outperformed ES group in terms of blood loss（705.4 m L vs. 910.4 mL, P〈0.05）. The average operation time to oral diet intake after surgery（40.5 h vs. 50.3 h, P〈0.05） and postoperative hospital stay（7.4 d vs. 9.0 days, P〈0.05） were much less in the LS group than in the ES group. The overall complication rate（4.3 % vs. 11.1 %, P〈0.05） and conversion rate（0% vs. 4.4%, P〈0.05） were lower in the LS group than in the ES group. It was concluded that prevention and treatment of hemorrhage are the key points of LSD for portal hypertension. By creating a tunnel above the splenic pedicle and a tunnel behind the lower esophagus, the simplified and modified LSD can reduce hemorrhage and improve success of surgery dramatically, and splenomegaly and severe varices are not contraindications.

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.

Preventive and therapeutic effect of simvastatin on secondary inflammatory damage of rats with cerebral hemorrhage

Objective:To investigate the preventive and therapeutic effect and mechanism of simvastatin on secondary inflammatory damage of rats with cerebral hemorrhage.Methods:Sixty SD rat aged 9-12 weeks were chosen and divided into the control group,model group and simvastatintreated group randomly with 20 rats in each group.Rats in the model group and simvastatintreated group were infused with autologous fresh uncoagulated blood to the right brain tissue of the basal ganglia to build the cerebral hemorrhage model,while rats in the control group were treated with the same amount of normal saline.Then,rats in the simvastatin-treated group were given a gavage of 3 mg/kg of simvastatin once a day after modeling.Rats in the three groups were given nerve dysfunction score(NDS) and wet-dry weighting method was used to detect the brain water content(BWC) of brain tissues around the lesion of the rats.Then Nissl staining was conducted and the undamaged neurons were counted.Immunohistochemical SP method was applied to count the number of NF-d the immuno fluorκB,TLR4 and IL-1escence method wasβ positive cells in brain tissues around the lesions,an employed to determine the expression levels of NF-κB,TLR4 and IL-1me points were aβ proteins.Results:The NDS results of the simvastatin-treated group at all till significantly higher than those of the model group(P < 0.05);the BWC values of the simvastatin-treated group at all time points were all significantly lower than those of the model group at the same periods(P < 0.05);the number of the undamaged neurons around the lesions of the simvastatin-treated group at all time points were all significantly higher than those of the model group(P < 0.05);seven days after treatment,the number of the NF-κB,TLR4 and IL-1β positive cells in brain tissues around the lesions of the simvastatin-treated group were all significantly lower than those of the model group(P < 0.05),and its expression levels of NF-ower than those of the model group(κB,TLR4 and IL-1P < 0.05).Conclusioβ protein were also significantly lns:Simvastatin can inhibit the expressions of NF-κB,TLR4 and IL-1β proteins in rats with cerebral hemorrhage,and protect neurons and reduce secondary inflammatory damages by down-regulating the above protein-mediated inflammatory responses.

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.

Cerebral arterial blood flow,attention,and executive and cognitive functions in depressed patients after acute hypertensive cerebral hemorrhage

BACKGROUND Intracerebral hemorrhage mainly occurs in middle-aged and elderly patients with hypertension,and surgery is currently the main treatment for hypertensive cerebral hemorrhage,but the bleeding caused by surgery will cause damage to the patient's nerve cells,resulting in cognitive and motor dysfunction,resulting in a decline in the patient's quality of life.AIM To investigate associations between cerebral arterial blood flow and executive and cognitive functions in depressed patients after acute hypertensive cerebral hemorrhage.METHODS Eighty-nine patients with depression after acute hypertensive cerebral hemorrhage who were admitted to our hospital between January 2019 and July 2021 were selected as the observation group,while 100 patients without depression who had acute hypertensive cerebral hemorrhage were selected as the control group.The attention span of the patients was assessed using the Paddle Pin Test while executive function was assessed using the Wisconsin Card Sorting Test(WCST)and cognitive function was assessed using the Montreal Cognitive Assessment Scale(MoCA).The Hamilton Depression Rating Scale(HAMD-24)was used to evaluate the severity of depression of involved patients.Cerebral arterial blood flow was measured in both groups.RESULTS The MoCA score,net scores I,II,III,IV,and the total net score of the scratch test in the observation group were significantly lower than those in the control group(P<0.05).Concurrently,the total number of responses,number of incorrect responses,number of persistent errors,and number of completed responses of the first classification in the WCST test were significantly higher in the observation group than those in the control group(P<0.05).Blood flow in the basilar artery,left middle cerebral artery,right middle cerebral artery,left anterior cerebral artery,and right anterior cerebral artery was significantly lower in the observation group than in the control group(P<0.05).The basilar artery,left middle cerebral artery,right middle cerebral artery,left anterior cerebral artery,and right anterior cerebral artery were positively correlated with the net and total net scores of each part of the Paddle Pin test and the MoCA score(P<0.05),and negatively correlated with each part of the WCST test(P<0.05).In the observation group,the post-treatment improvement was more prominent in the Paddle Pin test,WCST test,HAMD-24 score,and MoCA score compared with those in the pre-treatment period(P<0.05).Blood flow in the basilar artery,left middle cerebral artery,right middle cerebral artery,left anterior cerebral artery,and right anterior cerebral artery significantly improved in the observation group after treatment(P<0.05).CONCLUSION Impaired attention,and executive and cognitive functions are correlated with cerebral artery blood flow in patients with depression after acute hypertensive cerebral hemorrhage and warrant further study.

Oral esomeprazole vs injectable omeprazole for the prevention of hemorrhage after endoscopic submucosal dissection

AIM To evaluate the effectiveness of oral esomeprazole(EPZ) vs injectable omeprazole(OPZ) therapy to prevent hemorrhage after endoscopic submucosal dissection(ESD).METHODS A case-control study was conducted using a quasirandomized analysis with propensity score matching. A total of 258 patients were enrolled in this study. Patients were treated with either oral EPZ or injectable OPZ. The endpoint was the incidence of hemorrhage after ESD.RESULTS Data of 71 subjects treated with oral EPZ and 172 subjects treated with injectable OPZ were analyzed. Analysis of 65 matched samples revealed no difference in the incidence of hemorrhage after ESD between the oral EPZ and injectable OPZ groups(OR = 0.89, 95%CI:0.35-2.27, P ≥ 0.99).CONCLUSION We conclude that oral EPZ therapy is a useful alternative to injectable PPI therapy for the prevention of hemorrhage after ESD.

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.

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.

D-Dimer: Predictor of Postpartum Hemorrhage among Pre-Eclampsia at Kilimanjaro Christian Medical Centre

Background: Postpartum hemorrhage (PPH) is the major contributor to maternal mortality and morbidity worldwide as well as in Tanzania. Studies have shown Pre-eclampsia as a risk indicator for Postpartum hemorrhage and D-dimer tends to rise in women with pre-eclampsia. Few studies that have shown the association between D-dimer and PPH have been controversial and differ according to ethnicity and lifestyle. Hence there is no suitable reference interval for D-dimer in predicting Postpartum hemorrhage among women with pre-eclampsia. Broad Objective: This study aimed to assess the association, sensitivity, and specificity of D-dimer as a laboratory predictor of postpartum hemorrhage among women with pre-eclampsia at KCMC hospital. Methodology: This was a hospital-based analytical cross-sectional study conducted at KCMC Hospital in Northern Tanzania from September 2022 to March 2023. A total of 195 women with pre-eclampsia were included in this study. Plasma D-dimer levels were taken from women with pre-eclampsia pre-delivery. Haematocrit was compared before and after delivery, and a fall of 10% was considered as Postpartum hemorrhage together with clinical assessment of the patient. Participants were divided among those who had severe features and those who did not have severe features and were further categorized into those who had PPH and those who did not have PPH. Logistic regression was used to determine the association between D-dimer and PPH adjusting for other factors. The Receiver Operating Curve (ROC) was used to evaluate the predictive value. Results: Higher median D-dimer levels were seen among women who had PPH compared to those who had no PPH. D-dimer was seen to be associated with PPH, thus for every unit increase of µg/ml of D-dimer among women who had pre-eclampsia without severe features there was a 14% significant increase in the odds of having postpartum hemorrhage and a 45% significant increase of having postpartum hemorrhage among those who had pre-eclampsia with severe features. Furthermore, the cut-off point of a D-dimer level of 0.66 µg/ml significantly predicts postpartum hemorrhage with a sensitivity of 75% and specificity of 55%. For those who had no severe features the cut-off point was 0.53 µg/ml with a sensitivity of 95% and specificity of 53%, and for those who had severe features the cut-off point was 3.58 µg/ml with a sensitivity of 50% and specificity of 96%. Conclusion: D-dimer can be used to predict postpartum hemorrhage among pre-eclampsia, especially among those who have severe features. This shows that D-dimer has specificity in predicting PPH in women with pre-eclampsia and can be applied in clinical services to save women from maternal morbidity and mortality. Blood products such as fresh frozen plasma, platelets, and whole blood together with tranexamic acid should be readily available in women with pre-eclampsia especially those with severe features with a D-dimer level of 3.58 µg/ml and above during delivery as they are at high risk of developing PPH.

Tripartite intensive intervention for prevention of rebleeding in elderly patients with hypertensive cerebral hemorrhage

BACKGROUND Hypertensive cerebral hemorrhage(HICH)is the rupture and bleeding of vessels of the cerebral parenchyma caused by continuously elevated or violently fluctuating blood pressure.The condition is characterized by high disability and high mortality.Hematoma formation and resulting space-occupying effects following intracerebral hemorrhage are among the key causes of impaired neurological function and disability.Consequently,minimally invasive clearance of the hematoma is undertaken for the treatment of HICH because it can effectively relieve intracranial hypertension.Therefore,special attention should be given to the quality of medical and nursing interventions in the convalescent period after minimally invasive hematoma clearance.AIM The study aim was to determine the value of intensive intervention,including doctors,nurses,and patient families,for the prevention of rebleeding in elderly patients with HICH during the first hospitalization for rehabilitation after the ictal event METHODS A total of 150 elderly HICH patients with minimally invasive hematoma evacuation in our hospital between May 2018 and May 2020 were selected and equally divided into two groups of 75 each by their planned intervention.The control group was given conventional nursing intervention and the observation group was given tripartite intensive intervention.The length of hospital stay,cost,complication rate,satisfaction rate,and rebleeding rate during hospitalization were recorded.Changes in cerebral blood flow indicators were recorded in both groups.Changes in the National Institutes of Health Stroke Scale(NIHSS)score,quality of life index(QLI)score,and health behavior score were evaluated at the National Institutes of Health.RESULTS Duration of hospitalization was shorter in the in the observation group than in the control group,the hospitalization cost was less than in the control group,and the rate of rebleeding during hospitalization was lower than in the control group(all P<0.05).There were no significant differences between the two groups before treatment(all P>0.05).The mean flow rate(Qmean)and mean velocity(Vmean)of the two groups increased(P<0.05),and the dynamic resistance and peripheral resistance decreased(P<0.05).The Qmean and Vmean in the intervention group were higher than those in the control group(P<0.05).Moreover,the dynamic resistance and peripheral resistance of the blood vessels were also lower in the intervention group than in the control group(P<0.05).The difference in health behavior scores between the two groups before treatment was not significant(P>0.05).In both groups,the scores for healthy behaviors such as emotion control,medication adherence,dietary management,exercise management,and selfmonitoring were higher after than before treatment(P<0.05),and the scores of healthy behaviors in the intervention group were higher than those in the control group(P<0.05).There was no significant difference in the NIHSS and QLI scores between the two groups before treatment(P>0.05).The QLI scores of the two groups increased(P<0.05),and the NIHSS scores decreased(P<0.05).The QLI scores of the intervention group were higher than those of the control group(P<0.05),and the NIHSS score was correspondingly lower than that of the control group(P<0.05).The incidence of respiratory infections,pressure sores,central hyperpyrexia,and deep venous thrombosis was lower in the intervention group than in the control group.Accordingly,the satisfaction rate was higher in the treatment group than that in the control group(P<0.05).CONCLUSION Intensive intervention by doctors,nurses,and families of elderly patients with HICH reduced the rate of rebleeding during hospitalization.It also reduced the incidence of complications,promoted rehabilitation,improved the quality of life,and enhanced nerve function.Additionally,it improved satisfaction and promoted healthy behaviors.