Characteristics of nonvariceal upper gastrointestinal hemorrhage in patients with chronic kidney disease

AIM:To evaluate the clinical characteristics of nonvariceal upper gastrointestinal hemorrhage(NGIH)in patients with chronic kidney disease(CKD).METHODS:From 2003 to 2010,a total of 72 CKD patients(male n=52,72.2%;female n=20,27.8%)who had undergone endoscopic treatments for NGIH were retrospectively identified.Clinical findings,endoscopic features,prognosis,rebleeding risk factors,and mortality-related factors were evaluated.The characteristics of the patients and rebleeding-related data were recorded for the following variables:gender,age,alcohol use and smoking history,past hemorrhage history,endoscopic findings(the cause,location,and size of the hemorrhage and the hemorrhagic state),therapeutic options for endoscopy,endoscopist experience,clinical outcomes,and mortality.RESULTS:The average size of the hemorrhagic site was 13.7±10.2 mm,and the most common hemorrhagic site in the stomach was the antrum(n=21,43.8%).The most frequent method of hemostasis was combination therapy(n=32,44.4%).The incidence of rebleeding was 37.5%(n=27),and 16.7%(n=12)of patients expired due to hemorrhage.In a multivariate analysis of the risk factors for rebleeding,alcoholism(OR=11.19,P=0.02),the experience of endoscopists(OR=0.56,P=0.03),and combination endoscopic therapy(OR=0.06,P=0.01)compared with monotherapy were significantly related to rebleeding after endoscopic therapy.In a risk analysis of mortality after endoscopic therapy,only rebleeding was related to mortality(OR=7.1,P=0.02).CONCLUSION:Intensive combined endoscopic treatments by experienced endoscopists are necessary for the treatment of NGIH in patients with CKD,especially when a patient is an alcoholic.

Artificial kidney: Challenges and opportunities

This review aims to present the developments occurring in the field of artificial organs and particularly focuses on the presentation of developments in artificial kidneys.The challenges for biomedical engineering involved in overcoming the potential difficulties are showcased,as well as the importance of interdisciplinary collaboration in this marriage of medicine and technology.In this review,modern artificial kidneys and the research efforts trying to provide and promise artificial kidneys are presented.But what are the problems faced by each technology and to what extent is the effort enough to date?

Translation and cross-cultural adaptation of the Kidney Transplant Questionnaire 25 to Greek

BACKGROUND Kidney transplantation leads to continuous improvement in the survival rates of kidney transplant recipients(KTRs)and has been established as the treatment of choice for patients with end-stage kidney disease.Health-related quality of life(HRQoL)has become an important outcome measure.It is highly important to develop reliable methods to evaluate HRQoL with disease-specific questionnaires.AIM To translate the disease-specific instrument Kidney Transplant Questionnaire 25(KTQ-25)to the Greek language and perform a cross-cultural adaptation.METHODS The translation and adaptation of the original English version of the KTQ-25 to the Greek language were performed based on the International Quality of Life RESULTS Eighty-four KTRs(59 males;mean age 53.5±10.7 years;mean estimated glomerular filtration rate 47.7±15.1 mL/min/1.73 m2;mean transplant vintage 100.5±83.2 months)completed the Greek version of the KTQ-25 and the 36-item Short-Form Health Survey,and the results were used to evaluate the reliability of the Greek KTQ-25.The Cronbach alpha coefficients for all the KTQ-25 dimensions were satisfactory(physical symptoms=0.639,fatigue=0.856,uncertainty/fear=0.661,appearance=0.593,emotions=0.718,total score=0.708).The statistically significant correlation coefficients among the KTQ-25 dimensions ranged from 0.226 to 0.644.The correlation coeffi-cients of the KTQ-25 dimensions with the SF-36 physical component summary(PCS)ranged from 0.196 to 0.550;the correlation coefficients of the KTQ-25 with the SF-36 mental component summary(MCS)ranged from 0.260 to 0.655;and the correlation coefficients of the KTQ-25 with the total scores with the SF-36 PCS and MCS were 0.455 and 0.613,respectively.CONCLUSION According to the findings,the Greek version of the KTQ-25 is valid and reliable for administration among kidney transplant patients in Greece.

Application and management of continuous glucose monitoring in diabetic kidney disease

Diabetic kidney disease(DKD)is a common complication of diabetes mellitus that contributes to the risk of end-stage kidney disease(ESKD).Wide glycemic var-iations,such as hypoglycemia and hyperglycemia,are broadly found in diabetic patients with DKD and especially ESKD,as a result of impaired renal metabolism.It is essential to monitor glycemia for effective management of DKD.Hemoglobin A1c(HbA1c)has long been considered as the gold standard for monitoring glycemia for>3 months.However,assessment of HbA1c has some bias as it is susceptible to factors such as anemia and liver or kidney dysfunction.Continuous glucose monitoring(CGM)has provided new insights on glycemic assessment and management.CGM directly measures glucose level in interstitial fluid,reports real-time or retrospective glucose concentration,and provides multiple glycemic metrics.It avoids the pitfalls of HbA1c in some contexts,and may serve as a precise alternative to estimation of mean glucose and glycemic variability.Emerging studies have demonstrated the merits of CGM for precise monitoring,which allows fine-tuning of glycemic management in diabetic patients.Therefore,CGM technology has the potential for better glycemic monitoring in DKD patients.More research is needed to explore its application and management in different stages of DKD,including hemodialysis,peritoneal dialysis and kidney transplantation.

Complexity and Management of Chronic Kidney Disease

Chronic Kidney Disease (CKD) is ongoing damage of the kidneys, which affects their ability to filter the blood the way they should. Worldwide CKD is considered as the 16th leading cause of death and affects 8% - 16% of the population. CKD often goes unnoticed and is revealed as an incidental finding. Healthcare providers diagnose the condition as CKD based on persistent abnormal kidney function tests revealing kidney damage markers > 3 months, urine albumin creatinine ratio (UACR) > or equal to 30 mg/g per 24 hours, and GFR < 60 mL/min/1.73m2. In this article, we have discussed chronic kidney disease in terms of kidney physiology, chronic kidney disease pathophysiology, etiology, diagnosis, signs and symptoms, and management.

Experimental models for preclinical research in kidney disease

Acute kidney injury(AKI)and chronic kidney disease(CKD)are significant public health issues associated with a long-term increase in mortality risk,resulting from various etiologies including renal ischemia,sepsis,drug toxicity,and diabetes mellitus.Numerous preclinical models have been developed to deepen our understanding of the pathophysiological mechanisms and therapeutic approaches for kidney diseases.Among these,rodent models have proven to be powerful tools in the discovery of novel therapeutics,while the development of kidney organoids has emerged as a promising advancement in the field.This review provides a comprehensive analysis of the construction methodologies,underlying biological mechanisms,and recent therapeutic developments across different AKI and CKD models.Additionally,this review summarizes the advantages,limitations,and challenges inherent in these preclinical models,thereby contributing robust evidence to support the development of effective therapeutic strategies.

Pathological mechanism of immune disorders in diabetic kidney disease and intervention strategies

Diabetic kidney disease is one of the most severe chronic microvascular complications of diabetes and a primary cause of end-stage renal disease.Clinical studies have shown that renal inflammation is a key factor determining kidney damage during diabetes.With the development of immunological technology,many studies have shown that diabetic nephropathy is an immune complex disease,and that most patients have immune dysfunction.However,the immune response associated with diabetic nephropathy and autoimmune kidney disease,or caused by ischemia or infection with acute renal injury,is different,and has a complicated pathological mechanism.In this review,we discuss the pathogenesis of diabetic nephropathy in immune disorders and the intervention mechanism,to provide guidance and advice for early intervention and treatment of diabetic nephropathy.

Incidental renal cell carcinoma post bilateral nephrectomy in autosomal dominant polycystic kidney disease

BACKGROUND Renal cell carcinoma(RCC)is more common in patients with autosomal dominant polycystic kidney disease(ADPKD)than in the general population.Diagnosing RCC in ADPKD is challenging due to the presence of multiple renal cysts,often leading to delays and difficulties in distinguishing RCC from cyst infection or hemorrhage.A total of 38 kidneys were excised from 19 patients,with a mean age of 56.8 years and an average hemodialysis duration of 84.2 months.Eight patients underwent open nephrectomies,and 11 underwent hand-assisted laparoscopic nephrec-tomies.RCC was detected in 15.8%of kidneys,affecting 21.1%of patients.Two patients had multifocal RCC in both kidneys.All RCC cases were pT1 stage,with the largest lesion averaging 16.5 mm in diameter.The average operative duration was 120 minutes,with intraoperative blood loss averaging 184.2 mL.Five patients required blood transfusions.Postoperative complications occurred in five patients,with a mean hospital stay of 17.1 days.The mean follow-up period was 28.1 months.CONCLUSION The prevalence of RCC is higher in patients with ADPKD with ESRD than in those with ESRD alone.Thus,clinicians should be cautious and implement surveillance programs to monitor the development of RCC in patients with ADPKD,particularly those on dialysis.

Utilising continuous glucose monitoring for glycemic control in diabetic kidney disease

In this editorial,we comment on the article by Zhang et al.Chronic kidney disease(CKD)presents a significant challenge in managing glycemic control,especially in diabetic patients with diabetic kidney disease undergoing dialysis or kidney transplantation.Conventional markers like glycated haemoglobin(HbA1c)may not accurately reflect glycemic fluctuations in these populations due to factors such as anaemia and kidney dysfunction.This comprehensive review discusses the limitations of HbA1c and explores alternative methods,such as continuous glucose monitoring(CGM)in CKD patients.CGM emerges as a promising technology offering real-time or retrospective glucose concentration measure-ments and overcoming the limitations of HbA1c.Key studies demonstrate the utility of CGM in different CKD settings,including hemodialysis and peritoneal dialysis patients,as well as kidney transplant recipients.Despite challenges like sensor accuracy fluctuation,CGM proves valuable in monitoring glycemic trends and mitigating the risk of hypo-and hyperglycemia,to which CKD patients are prone.The review also addresses the limitations of CGM in CKD patients,emphasizing the need for further research to optimize its utilization in clinical practice.Altogether,this review advocates for integrating CGM into managing glycemia in CKD patients,highlighting its superiority over traditional markers and urging clinicians to consider CGM a valuable tool in their armamentarium.

Clinical efficacy and safety of flexible ureteroscopy and percutaneous nephrolithotomy for large kidney stones:A retrospective comparative study

BACKGROUND Renal stones ranging 20–40 mm are very common in China.Although no largesample clinical studies have confirmed the clinical efficacy and safety of this method,there is also a lack of comparative data with traditional treatment.AIM To investigate the clinical efficacy of flexible ureteroscopy(FURS)and percutaneous nephrolithotomy(PCNL)by postoperative stone clearance and changes in soluble vascular cell adhesion molecule 1(sVCAM-1)and kidney injury molecule 1(KIM-1)levels in patients with large kidney stones(>2 cm in diameter).METHODS This single-center observational study was performed at a Chinese hospital between January 1,2021,and October 30,2023.All 250 enrolled patients were diagnosed with large kidney stones(>2 cm)and divided into a FURS group(n=145)and a PCNL group(n=105)by the surgical method.The FURS group was treated with flexible ureteroscopy and the PCNL group was treated with percutaneous nephrolithotomy.The operation time,time to palinesthesia,intraoperative blood loss,drop in hemoglobin,length of hospital stay,stone clearance rate,and complications were recorded in the two groups.Preoperative and postoperative serum sVCAM-1 levels,erythrocyte sedimentation rate(ESR),urine KIM-1 levels,preoperative and postoperative pain visual analog scale(VAS)and Wisconsin Stone Quality of Life Questionnaire(WISQOL)scores were also documented.RESULTS All 250 eligible patients completed the follow-up.There were no significant differences in baseline characteristics between the two groups(P>0.05).The operation time in the FURS group was significantly greater than that in the PCNL group.The time to ambulation,intraoperative blood loss,decrease in hemoglobin,and length of hospital stay were significantly lower in the FURS group than in the PCNL group.The FURS group also had a significantly higher stone clearance rate and a lower incidence of postoperative complications.There was no significant difference in antibiotic use between the groups.Postoperative serum sVCAM-1 levels,urine KIM-1 levels,and VAS scores were lower in the FURS group than in the PCNL group,but postoperative ESR and WISQOL scores were greater in the FURS group than in the PCNL group.CONCLUSION FURS demonstrated superior clinical efficacy in treating large kidney stones(>2 cm in diameter)compared PCNL.It not only improved the postoperative stone clearance rate and reduced complications and recovery time but also positively affected serum SCM-1,ESR,and urine KIM-1 levels,subsequent improvement of patient quality of life.

Potential efficacy and mechanism of medicinal plants on chronic kidney disease-associated vascular calcification:a review

Vascular calcification is a crucial risk factor that affects the incidence and mortality of cardiovascular disease in chronic kidney disease patients.Modern medicine relies on calcium-phosphorus binding agents,calcium mimetics,active vitamin D,and hemodialysis to prevent and treat vascular calcification,however,their efficacy is unsatisfactory and adverse reactions often occur.Medical plant therapy can act as an integrative regulator in patients with chronic kidney disease-associated vascular calcification,which can significantly improve patients’symptoms,but its specific mechanism has not been fully elucidated yet.In this paper,we reviewed the domestic and international theoretical studies on the pathogenesis mechanism of chronic kidney disease-associated vascular calcification in recent years,summarized eight active ingredients of medicinal plants as well as four compound formulas for improving chronic kidney disease-associated vascular calcification,and explored the mechanism of action of herbal medicine,which will provide a new strategy for promoting the prevention and treatment of vascular calcification.

Clinical Observation on the Treatment of Diabetic Kidney Disease with Damp-heat Stasis Syndrome in Clinical Proteinuria Stage by Kunkui Kidney Preserving Paste

[Objectives]To evaluate the clinical efficacy and safety of Kunkui Kidney Preserving Paste in the treatment of diabetic kidney disease(DKD)patients with damp-heat stasis syndrome in the clinical proteinuria stage.[Methods]Retrospective analysis was made on 30 patients with DKD who were diagnosed with damp-heat stasis syndrome in the clinical proteinuria stage from March 2021 to March 2023 in Jiangsu Province Hospital of Chinese Medicine,and who took Kunkui Kidney Preserving Paste continuously for six months.The urinary albumin/creatinine ratio(UACR),urinary complement C3,and urea nitrogen(BUN)of DKD patients before and after treatment were compared,and estimated glomerular filtration rate(eGFR),blood creatinine(Scr),and cystatin C(CysC)were estimated,and the therapeutic effects on renal function and urinary protein were evaluated.[Results]After treatment,UACR significantly decreased(P<0.01),and urinary complement C3 and Scr decreased(P<0.05),while other indicators showed no significant statistical difference(P>0.05).In terms of evaluating the efficacy of urinary protein therapy,8 cases showed recent relief;8 cases showed significant effect;9 cases were effective,and 5 cases were invalid after treatment,with a total effective rate of 83.33%.In terms of renal function efficacy evaluation,8 cases showed significant effect;4 cases were effective;11 cases were stable,and 7 cases were invalid,with a total effective rate of 76.67%.In the safety evaluation,there were no obvious adverse reactions.[Conclusions]The Kunkui Kidney Preserving Past has significant clinical efficacy and safety in treating DKD patients with damp-heat stasis syndrome in the clinical proteinuria period.It has significant advantages in reducing urinary protein and protecting renal function,which is worthy of clinical promotion.

Innovative approaches beyond periprocedural hydration for preventing contrast-induced acute kidney injury

Contrast-induced acute kidney injury(CI-AKI)is a major concern in clinical practice,particularly among high-risk patients with preexisting renal and cardiovascular conditions.Although periprocedural hydration has long been the primary approach for CI-AKI prevention,recent advancements have led to the development of novel approaches such as RenalGuard and contrast removal systems.This editorial explores these emerging approaches and highlights their potential for enhancing CI-AKI prevention.By incorporating the latest evidence into clinical practice,health-care professionals can more effectively maintain renal function and improve outcomes for patients undergoing contrast-enhanced procedures.

Patterns of kidney diseases diagnosed by kidney biopsy and the impact of the COVID-19 pandemic in Yogyakarta,Indonesia:A single-center study

BACKGROUND Glomerular diseases rank third among the causes of chronic kidney disease worldwide and in Indonesia,and its burden continues to increase,especially regarding the sociodemographic index.Kidney biopsy remains the gold standard for the diagnosis and classification of glomerular diseases.It is crucial for developing treatment plans,determining the degree of histologic changes,and identifying disease relapse.AIM To describe the patterns of biopsy-proven kidney diseases in adult patients.METHODS We retrospectively reviewed the demographic,histopathologic,clinical,and laboratory data of 75 adult patients with biopsy-proven kidney diseases at our institution recorded from 2017 to 2022.RESULTS Among the patients,43(57.3%)were females,and the mean age was 31.52 years±11.70 years.The most common histopathologies were lupus nephritis(LN)(33.3%),minimal change disease(MCD)(26.7%),and focal segmental glomerulosclerosis(10.7%).LN(41.7%)was frequently diagnosed in women and MCD(28.1%)in men.The most common cause of nephritic syndrome was LN(36.7%)and of nephrotic syndrome was MCD(40%).CONCLUSION Different kidney disease patterns were observed in different sexes,age categories,clinical syndromes,and biopsy dates relative to the coronavirus disease 2019 pandemic.

Cerebral venous sinus thrombosis presenting with subarachnoid hemorrhage and intracerebral hemorrhage:a case report

Objective:To explore the clinical and pathological characteristics of cerebral venous sinus thrombosis(CVST)with subarachnoid hemorrhage(SAH)and intracerebral hemorrhage(ICH),and to investigate the diagnosis,radiographic changes,and prognosis over the course of treatment.Methods:The clinical data and radiographic findings of a young male CVST patient,who presented with initial symptoms of SAH and ICH,were collected and analyzed.The relevant literature was also reviewed.Results:The patient had no specific clinical symptoms except for headache.The brain computed tomography(CT)scan revealed SAH,a high-density shadow in the right posterior fossa and cerebellar hemisphere,and ICH in the left frontal lobe.Magnetic resonance venography(MRV)further revealed bilateral thrombosis in the transverse and sigmoid sinuses.Conclusion:CVST with SAH and ICH is rare and difficult to diagnose.Careful radiological study and clinical analysis are important for the correct and early diagnosis of this condition.Anticoagulation therapy is considered the primary treatment for CVST.

Supportive care in transplantation: A patient-centered care model to better support kidney transplant candidates and recipients

Kidney transplantation(KT),although the best treatment option for eligible patients,entails maintaining and adhering to a life-long treatment regimen of medications,lifestyle changes,self-care,and appointments.Many patients experience uncertain outcome trajectories increasing their vulnerability and symptom burden and generating complex care needs.Even when transplants are successful,for some patients the adjustment to life post-transplant can be challenging and psychological difficulties,economic challenges and social isola-tion have been reported.About 50%of patients lose their transplant within 10 years and must return to dialysis or pursue another transplant or conservative care.This paper documents the complicated journey patients undertake before and after KT and outlines some initiatives aimed at improving patient-centered care in transplantation.A more cohesive approach to care that borrows its philosophical approach from the established field of supportive oncology may improve patient experiences and outcomes.We propose the"supportive care in transplantation"care model to operationalize a patient-centered approach in transplantation.This model can build on other ongoing initiatives of other scholars and researchers and can help advance patient-centered care through the entire care continuum of kidney transplant recipients and candidates.Multi-dimensionality,multi-disciplinarity and evidence-based approaches are proposed as other key tenets of this care model.We conclude by proposing the potential advantages of this approach to patients and healthcare systems.Core Tip:Kidney transplant recipients and candidates face several uncertainties in their care journey and have several expressed unmet healthcare needs.We recommend a structured and comprehensive approach to transplant care across the entire continuum of a transplant patient’s journey similar to what has been developed in the field of oncology.The supportive care in transplantation model can operationalize patient-centered care and build on the efforts of other researchers in the field.We postulate that such a model would significantly improve care delivery and patients’experiences and outcomes and potentially decrease healthcare utilization and cost.INTRODUCTION Patients with kidney failure benefit from(KT)[1,2],and experience improved survival rates when compared with dialysis[3-6].KT studies,using validated instruments,have also consistently demonstrated that kidney transplant recipients(KTRs)experience better health-related quality of life and several improvements in other disease-specific domains when compared with dialysis[7].In countries where dialysis is out of reach for many,the diagnosis of kidney failure would be futile without KT[8].Thus,increasing KT has been a priority for the nephrology and transplant communities.This priority has been reflected in recent global trends:Of the 79 countries where data were available,the International Society of Nephrology’s Global Kidney Atlas reported that the prevalence of KTRs in 2023 was 279 per million population which represented an increase of 9.4%from the data published four years prior[8].Despite this growth,KT can be a challenging journey for many patients and it is sometimes regarded as a‘cure’,which does not conform with the reality that many patients experience[9-13].KTRs must maintain a life-long treatment regimen of medications,lifestyle changes,self-care and medical appointments[14-17].As poignantly stated by a young female transplant recipient,“I thought everything would change once I got my kidney.I thought I would be healthy again”but after experiencing multiple side effects of immunosuppressive medications and graft loss,she stated,“I am just a different kind of patient now”[18].Indeed,a significant proportion of patients experience graft failure and return to dialysis;it is estimated that over 50%return to dialysis within 10 years of KT[19-23].Patients are often not prepared for this outcome and report several psychosocial and physical ramifications of graft failure[24,25].Overall,high symptom burden,adverse effects of immunosuppressants,risk of graft rejection or failure and mortality,contribute to complex needs,vulnerability and uncertainties for patients,increasing their care needs and treatment burden[26-30].In this paper,we highlight the complex journey that KTRs and candidates undertake that can generate varied outcome trajectories and complex healthcare needs.We highlight the need for a comprehensive patient-centered approach to care and conclude with a proposal for a“supportive care in transplantation”care model.

Impact of bisphosphonate treatment on bone mineral density after kidney transplant

BACKGROUND Mineral bone disease is associated with chronic kidney disease and persists after kidney transplantation.Immunosuppressive treatment contributes to the patho-genesis of this disease.Bisphosphonate treatments have shown positive but inde-finite results.AIM To evaluate the effectiveness and safety of bisphosphonate treatment on post kidney transplantation bone mineral density(BMD).METHODS We included kidney transplant recipients(KTRs)whose BMD was measured after the operation but before the initiation of treatment and their BMD was measured at least one year later.We also evaluated the BMD of KTRs using two valid mea-surements after transplantation who received no treatment(control group).RESULTS Out of 254 KTRs,62(39 men)were included in the study.Bisphosphonates were initiated in 35 KTRs in total(20 men),1.1±2.4 years after operation and for a period of 3.9±2.3 years while 27(19 men)received no treatment.BMD improved significantly in KTRs who received bisphosphonate treatments(from-2.29±1.07 to-1.66±1.09,P<0.0001).The control group showed a non-significant decrease in BMD after 4.2±1.4 years of follow-up after surgery.Kidney function was not affected by bisphosphonate treatment.In KTRs with established osteoporosis,active treatment had a similar and significant effect on those with osteopenia or normal bone mass.CONCLUSION In this retrospective study of KTRs receiving bisphosphonate treatment,we showed that active treatment is effective in preventing bone loss irrespective of baseline BMD.

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.