Kidney transplantation is the optimal therapy for end-stage renal disease, yet long-term graft survival remains limited by ischemia-reperfusion injury, rejection, and chronic allograft dysfunction. Accumulating evidence indicates that multiple regulated cell death pathways-including apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagy-are critically involved in transplant injury. These pathways interact extensively, shaping the immune microenvironment, amplifying inflammation, and influencing graft fate. Emerging forms of cell death, such as cuproptosis, parthanatos, and NETosis, further expand the mechanistic landscape of transplant pathology. This review summarizes current mechanistic insights and experimental and clinical evidence linking regulated cell death to kidney transplant outcomes, and discusses therapeutic strategies targeting cell death pathways. Integrating cell death modulation into precision medicine may provide novel avenues to improve graft survival and patient prognosis.

Protein C deficiency is a rare inherited disorder characterized by low levels or impaired function of protein C, a natural anticoagulant protein. Deficiency in protein C activity leads to a hypercoagulable state, predominantly resulting in venous thromboembolism. We report a case of a 69-year-old female with uremia who presented with recurrent heart failure, myocardial infarction, and extensive thromboembolism involving both arterial (coronary, abdominal aorta, renal, iliac, splenic, and femoral arteries) and venous systems (femoral, popliteal, and calf muscle veins). Progressive renal dysfunction led to a diagnosis of uremia, and genetic testing confirmed protein C deficiency. The patient ultimately succumbed to multiple organ failure, intractable ascites, and spontaneous bacterial peritonitis. This case underscores the importance of considering protein C deficiency in patients presenting with unexplained multivessel thromboembolism. For patients presenting with unexplained myocardial infarction, renal/hepatic dysfunction, extensive vascular thrombosis or calcification, acral gangrene, or persistently elevated D-dimer levels, we recommend implementing key diagnostic interventions, including protein C activity assay and genetic screening. This case suggests that protein C deficiency may be a rare potential etiology of type 5 cardiorenal syndrome, an association that requires further validation in larger cohort studies.

Background: The neutrophil percentage-to-albumin ratio (NPAR) is an emerging inflammatory biomarker that has demonstrated a significant association with poor outcomes in patients with cardiovascular diseases. However, the existing evidence regarding its prognostic value in ischemic stroke (IS) patients remains limited. Our study aimed to investigate the potential of the NPAR as a prognostic indicator for all-cause mortality in patients with IS. Methods: This study screened IS patients from the Medical Information Mart for Intensive Care (MIMIC-IV) database and categorized them into two groups based on NPAR values, employing propensity score matching to mitigate confounding factors. The primary outcome assessed was 90‒day mortality, and the secondary outcomes included in-hospital mortality, ICU mortality, and mortality at 30‒day and 1‒year after admission. Cox proportional hazards regression analysis and restricted cubic splines were used to explore the relationship between the NPAR and all-cause mortality in critically ill IS patients, whereas Kaplan‒Meier analysis was used to estimate survival curves. Subgroup analysis and interaction tests were performed to evaluate the robustness of the results. Receiver operating characteristic curves were computed to assess the diagnostic value of the NPAR in predicting outcomes. Results: A total of 706 patients (53.3% male) were included in the study, with in-hospital and ICU mortality rates of 18.2% and 12.6%, respectively. The mortality rates at 30‒day, 90‒day, and 1‒year were 19.2%, 29.7%, and 37.8%, respectively. Restricted cubic splines indicated a nonlinear increase in all-cause mortality as the NPAR increased. Multivariate Cox regression analysis revealed a significant association between a high NPAR and all-cause mortality at 90‒day (hazard ratio [HR]: 1.99; 95% confidence interval [95% CI]: 1.44-2.76, p < 0.001), 30‒day (HR: 2.09; 95% CI: 1.39-3.13, p < 0.001), and 1‒year (HR: 1.77; 95% CI: 1.32-2.37, p < 0.001). The subgroup analysis indicates that a significant interaction was observed between hypertension and mortality risk in IS patients (p for interaction = 0.012), suggesting that hypertension may be an important predictor of poor prognosis in these patients. Receiver operating characteristic curves demonstrated that the NPAR provides a modestly greater ability to predict the risk of death in patients with IS compared to the individual indices of neutrophil percentage and albumin levels, although the specificity (0.567) and sensitivity (0.684) of NPAR were not outstanding overall. Conclusion: Our study revealed an independent association between a high NPAR and increased all-cause mortality at 30‒day, 90‒day, and 1‒year and during hospitalization in patients with IS, reinforcing its status as an independent determinant of mortality risk.

BackgroundGliomas are the most common intracranial malignant tumors. In this study, we aimed to identify the hub genes and investigate the pathophysiological significance of ANXA5 in glioma.MethodsThe differentially expressed genes (DEGs) between tumor and adjacent tissues from glioma patients were acquired from the Gene Expression Omnibus (GEO) database. Functional enrichment analysis and protein-protein interaction (PPI) network construction of overlapping DEGs were performed. The GEPIA and CGGA databases were used to explore hub gene expression. The effect of hub genes on prognosis and tumor-infiltrating immune cells was analyzed via GEPIA, CGGA, and TIMER2 databases. Additionally, ANXA5 expression was measured by qRT-PCR and Western blotting. The effects of ANXA5 were assessed by CCK-8, colony formation, Transwell, and flow cytometry assays. Moreover, the roles of ANXA5 were identified in vivo.ResultsThe DEGs were enriched in cell surface receptor signaling pathway, immune response, and MAPK signaling pathway. The selected hub genes were included ANXA5, STAT1, CD44, CAV1, ANXA2, and MAPT. Among them, expression of ANXA5, STAT1, CD44, CAV1, and ANXA2 was strongly correlated with patient prognosis and was also involved in the tumor microenvironment. Furthermore, ANXA5 knockdown significantly inhibited the migration and proliferation of glioma cells in vitro and in vivo. Meanwhile, we found that the expression of CD44 was monitored by ANXA5, and ANXA5 promoted the migration and proliferation of glioma cells via the MAPK/CD44 pathway.ConclusionTaken together, our data showed that ANXA5 could contribute to cell proliferation and metastasis of glioma by targeting the MAPK/CD44 axis.

Renal fibrosis is a common pathological endpoint of various chronic kidney diseases. Macrophages play an important role in the pathophysiological process of renal fibrosis. However, the exact function and molecular mechanism of macrophages during renal fibrosis remain unclear. In this study, we found an increased expression of RNA demethylase AlkB Homolog 5 (ALKBH5) in macrophages from the mice with unilateral ureteral obstruction (UUO) and TGF-β treatments bone marrow-derived macrophages. Macrophage-specific ALKBH5 knockout could significantly alleviate renal fibrosis in UUO mice and decrease the infiltration of macrophages in the kidneys. Further studies showed that ALKBH5 deficiency reduced M2a macrophage polarization and the expression of TGF-β1, Arg1, and CD206 both in vivo and in vitro. RNA sequencing indicated that Resistin-like alpha (Retnla) was the downstream target of ALKBH5, and treatment with recombinant Retnla abrogated the effect of ALKBH5 deficiency on renal fibrosis. We conclude that ALKBH5-dependent regulation of macrophage and kidney fibrosis progression through Retnla represents a novel strategy for patients with chronic kidney disease.

Neutrophil extracellular trap (NET) formation has been proven to take part in the exacerbation of acute kidney injury (AKI). Ro 106-9920, an effective inhibitor of nuclear factor kappa B (NF-κB) signal, could abrogate the formation of NETs. Herein, we explored whether Ro 106-9920 (Ro) exerts a protective role in AKI by repressing NET formation. The AKI model was induced with 30 min-bilateral renal ischemia followed by reperfusion. After finishing the 7-day treatment of Ro or vehicle, blood and the kidney were collected from each mouse for further analysis. Enzyme-linked immunosorbent assay, H&E, and TUNEL staining, immunohistochemistry, as well as Western blot were carried out to observe the kidney function, renal damage, apoptosis, and inflammation, and to preliminarily uncover the underlying mechanism. Administration with Ro effectively protected against AKI in a dose-dependent manner, as proven by the reduction of serum creatinine, serum neutrophil gelatinase-associated lipocalin, blood urea nitrogen, and serum inflammatory cytokine in AKI models after its administration. Moreover, Ro significantly alleviated morphological damage, kidney cells apoptosis, as well as inflammatory cytokine secretion in renal tissues. Mechanically, phosphorylation of NF-κB and myeloperoxidase activity were observed in renal tissues of AKI models, which suggested NF-κB activation and NETosis occurred in AKI. Notably, Ro treatment could significantly repress the nuclear translocation of NF-κB and the increased myeloperoxidase activity. Ro has a protective potential on ischemia/reperfusion-induced AKI by attenuating apoptosis and inflammation, perhaps by suppressing NF-κB activation and is associated with reduced NETosis.

The interconnected ventricles in the central nervous system are filled with cerebrospinal fluid (CSF) which serves multifaceted roles including bring away metabolic wastes. However, whether there is an inherent 'dislodging' mechanism, in addition to CSF drainage and reabsorption, at play for the removal of microparticles in the CSF is unclear. In this study, we identified a subset of microglia distributed in close proximity to the ependymal wall of ventricles. They differed from parenchymal microglia in morphology, behaviors and transcriptomes. In particular, the paraventricular microglia extended transependymal dendrites into the lumen of ventricles and were proficient in sequestering and phagocytosing intraventricular exogenous particles when present. A specific removal of the paraventricular microglia led to an acute ventriculomegaly due to an increased colloid osmotic pressure in the CSF resulting from protein accumulation. Thus, we identified the paraventricular microglia as specific guardians in monitoring and cleaning the CSF. ### Competing Interest Statement The authors have declared no competing interest.

Hematoma clearance is critical for mitigating intracerebral hemorrhage (ICH)-induced brain injury. Multinucleated giant cells (MGCs), a type of phagocyte, and the complement system may play a pivotal role in hematoma resolution, but whether the complement system regulates MGC formation after ICH remains unclear. The current study investigated the following: (1) the characteristics of MGC formation after ICH, (2) whether it was impacted by complement C3 deficiency in mice and (3) whether it also influenced hematoma degradation (hemosiderin formation). Young and aged male mice, young female mice and C3-deficient and -sufficient mice received a 30 μL injection of autologous whole blood into the right basal ganglia. Brain histology and immunohistochemistry were used to examine MGC formation on days 3 and 7. Hemosiderin deposition was examined by autofluorescence on day 28. Following ICH, MGCs were predominantly located in the peri-hematoma region exhibiting multiple nuclei and containing red blood cells or their metabolites. Aging was associated with a decrease in MGC formation after ICH, while sex showed no discernible effect. C3 deficiency reduced MGC formation and reduced hemosiderin formation. Peri-hematomal MGCs may play an important role in hematoma resolution. Understanding how aging and complement C3 impact MGCs may provide important insights into how to regulate hematoma resolution.

Disruption of blood-brain barrier is a common brain injury in intracerebral hemorrhage. Sufentanil is an analogue of fentanyl, and acts as an opioid analgesic in postsurgical analgesia and anaesthesia. Sufentanil also exerted a neuroprotective effect against cerebral infarction. The role of sufentanil in intracerebral hemorrhage (ICH)-induced blood-brain barrier injury was investigated. Firstly a rat model of intracerebral hemorrhage was established by local injection of collagenase IV into striatum. Rats were then subjected to tail vein injection with sufentanil. Results showed that injection with collagenase IV induced histological damages in brain tissues, increased brain water content and enhanced Evans blue leakage. However, administration with sufentanil attenuated behavioral deficits and histological damages in the brain tissues of rats with intracerebral hemorrhage. Moreover, sufentanil also reduced brain water content and inhibited Evans blue leakage. Sufentanil attenuated collagenase IV-induced increased levels of tumor necrosis factor & alpha; (TNF-& alpha;), interleukin (IL)-6, and IL-1 & beta; in rats with intracerebral hemorrhage. Sufentanil suppressed phosphorylation of c-Jun N-terminal kinase (JNK) and P38 in brain tissues of rats with intracerebral hemorrhage. In conclusion, sufentanil exhibited neuroprotective effects on blood-brain barrier injury in rat with intracerebral hemorrhage, and inhibited neuroinflammation through the inactivation of mitogen-activated protein kinase (MAPK) signaling.

This study investigates the therapeutic potential of electroacupuncture (EA) on obesity, focusing on its influence on autophagy and energy metabolism, utilizing a high-fat diet (HFD)-induced mouse model. Treatment with EA significantly reduces body weight, fat deposition, and lipid accumulation in HFD-fed mice. Additionally, EA effectively ameliorates metabolic imbalances, reducing blood glucose levels and plasma markers of liver function. At the molecular level, EA enhances the expression of thermogenesis-associated genes in brown adipose tissue and decreases p53 expression, suggesting a decrease in apoptosis. Autophagy in white adipose tissue is inhibited by EA, as demonstrated by the suppression of key autophagy-related proteins. Further experiments highlight the critical role of Sirtuin 3 (Sirt3) in EA's anti-obesity effects. Sirt3 supplementation combined with EA results in reduced body weight, fat deposition, and lipid accumulation, along with modulations in key metabolic indicators. Moreover, EA's modulatory effect on uncoupling protein 1 (Ucp1), Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc-1α), and p53 is found to be Sirt3 dependent. In conclusion, EA exerts beneficial effects against obesity through Sirt3-dependent modulation of autophagy and energy metabolism, indicating a potential therapeutic approach for obesity and related metabolic disorders.

ObjectiveThe purpose of this study was to evaluate the curative effect of external therapies of traditional Chinese medicine on constipation in patients with chronic renal failure and to provide scientific theoretical basis for clinical practice.MethodWe searched the English database of PubMed, EMBASE, the Cochrane Library and the Web of Science and Chinese database of CNKI, Wan fang database, VIP Database and China Biomedical Literature Database up to December 2022. Randomized controlled trials (RCTs) involving constipation in patients with CRF that compared external therapies of traditional Chinese medicine and routine treatment to routine treatment were eligible for the analysis. A meta-analysis of the outcome indicators including total efficiency, weekly defecation times, defecation time, defecation difficulty score, patient-assessment of constipation quality of life and adverse events of treatment were performed. The analysis was performed by using Review Manager version 5.3.ResultA total of 23 studies were included, with 1764 patients. Meta-analysis results showed that compared with the control group, the test group could significantly increase weekly defecation times(MD = 0.94, 95%CI(0.70, 1.18), Z = 7.74, P < 0.00001), reduce defecation time(MD = -2.92, 95%CI(-3.69, -2.16), Z = 7.49, P < 0.00001), reduce defecation difficulty score(MD = -1.92, 95%CI(-2.45, -1.39), Z = 7.11, P < 0.00001), improve the quality of life in patients with constipation(MD = -7.57, 95%CI(-10.23, -4.91), Z = 5.58, P < 0.00001) and obtain a higher total effective rate of treatment(OR = 4.53, 95%CI(3.27, 6.29), Z = 9.07, P < 0.00001). In terms of safety, there was no statistical significance in the incidence of adverse events between two groups(OR = 0.35, 95%CI(0.04, 2.95), Z = 0.96, P = 0.34).ConclusionThe combination of external therapies of traditional Chinese medicine and routine treatment could achieve an excellent curative effect, and there was no specific adverse event. However because of the limited level of current evidence, more high-quality trials are needed in the future.5.

The clinical features and risk factors for survival time were analysed in haemodialysis patients complicated with infective endocarditis. A total of 101 infective endocarditis (IE) patients treated at Hangzhou First People's Hospital, from January 1, 2012, to April 1, 2022, were included in the present study. Baseline demographic data and laboratory data were collected for statistical analysis of risk factors and survival time in the IE with haemodialysis group (HD-IE group, n=15) and the IE without haemodialysis group (NHD-IE group, n=86). Haemoglobin, red blood cells, C-reactive protein, procalcitonin, serum albumin, diabetes, invasive procedures, positive blood bacteria culture, heart valve calcification ratio, and left ventricular ejection fraction level were risk factors for infective endocarditis complicated with haemodialysis (P<0.05). Compared with the NHD-IE group, the HD-IE group had an obviously increased risk of mortality (χ2=6.323, P=0.012). The univariate Cox regression analysis showed that age, haemoglobin, red blood cells, serum albumin, left ventricular ejection score, longest vegetation diameter, combined hypotension and diabetes were risk factors for death; furthermore, multivariate Cox regression showed that age (HR=1.187, P=0.015), combined hypotension (HR=0.921, P=0.025) and the longest vegetation diameter (HR=9.191, P=0.004) were independent risk factors affecting the survival of patients. Collectively, the present study revealed that the mortality rate of HD-IE patients was higher than that of NHD-IE patients. Older age, hypotension, and the longest vegetation diameter were independent risk factors affecting the survival of patients. For HD-IE patients, active and effective antibiotic treatment or surgical treatment should be strongly recommended.

Circular RNAs (circRNAs) have been verified as vital regulators in various diseases, including membranous nephropathy (MN). Therefore, the role of circ_CDYL in podocyte apoptosis and MN was investigated. The real-time quantitative polymerase chain reaction was performed to measure the expression of circ_CDYL, microRNA-149-5p (miR-149-5p), and tumor necrosis factor superfamily member 11 (TNFSF11) in podocytes. In addition, angiotensin II (Ang II) was used to induce apoptosis of podocytes. The apoptosis-related protein expression was quantified by western blot assay. The apoptosis of podocytes was evaluated by flow cytometry assay. The interaction relationship between miR-149-5p and circ_CDYL or TNFSF11 was confirmed by dual-luciferase reporter assay. Circ_CDYL was significantly overexpressed in MN patients and Ang II-induced podocytes compared with control groups. Importantly, loss-of-functional experiments indicated that knockdown of circ_CDYL protected podocytes from Ang II-induced apoptosis. MiR-149-5p was verified as target of circ_CDYL and negatively correlated with circ_CDYL expression in MN patients. Knockdown of circ_CDYL-mediated effects on Ang II-induced podocyte cells were abolished by silencing miR-149-5p. Besides, the upregulation of miR-149-5p could suppress apoptosis in Ang II-induced podocyte cells by targeting TNFSF11. Under Ang II stimulation, the upregulation of TNFSF11 could increase the expression of TNFSF11 and induce apoptosis in circ_CDYL-silencing podocytes. Our results confirmed that circ_CDYL specifically targeted miR-149-5p/TNFSF11 pathway to regulate Ang II-induced apoptosis in podocytes, which might be useful diagnostic biomarkers in MN.

Intracerebral hemorrhage (ICH) is a common and highly disabling or fatal neurological disorder in adults. Recent studies have suggested that the platelet derived growth factor (PDGF) signaling pathway plays an important role in the development of ICH. PDGF is involved in vascular remodeling and can be used as a biomarker of cerebral amyloid angiopathy which is one of the major causes of ICH. PDGF and its receptors are involved in the mechanism of the secondary injury after ICH by affecting the integrity of the blood-brain barrier and inflammatory response. PDGF and its receptors may also participate in the mechanism of repair after ICH by promoting angiogenesis. This article reviews the latest research progress on the involvement of PDGF signaling pathway in the pathophysiology of intracerebral hemorrhage, and introduces the relevant antagonists using PDGFR as the therapeutic target, to provide information for the development of therapeutic options for intracerebral hemorrhage.

Ischemia/reperfusion injury (I/R) is the main causes of acute kidney injury (AKI), which is a global health concern. Evidence suggests that asiaticoside plays vital roles on anti-inflammatory and, anti-kidney fibrosis effects, and promotes tissue repair. However, the effects of asiaticoside on AKI caused by ischemia-reperfusion have not been well defined. Herein, we explored the protective effect of asiaticoside on renal ischemia-reperfusion injury (IRI) using in vivo and in vitro studies, and elucidated the potential mechanism of asiaticoside-mediated repair. Results showed that asiaticoside attenuated the levels of blood urea nitrogen (BUN) and serum creatinine (Scr) in the IRI model. Meanwhile, asiaticoside reduced the secretion of IL-6, IL-1β and TNF-α, but increased IL-10 secretion in a dose-dependent manner. Treating Raw264.7 cells with lipopolysaccharide (LPS) induced an inflammatory response, but the LPS-induced effects were attenuated after administering asiaticoside. Furthermore, asiaticoside significantly inhibited the expression of inducible Nitric Oxide Synthase (iNOS) and promoted the expression of Arginase1 induced by LPS, which are the polarization marker proteins. In conclusion, this study shows that asiaticoside possesses protective action in AKI after ischemia-reperfusion, due to the inhibition of inflammatory mediators and promoting transformation of macrophages from M1 type to M2 type.

A cyclic nucleotide-independent protein kinase of human platelets, which phosphorylated histones, myelin basic protein and protamine and did not catalyze the phosphorylation of acidic proteins such as casein, phosvitin and myosin light chain, has been purified approx. 1,500-fold from the crude extract by steps of DEAE-cellulose, Sephadex G-200, hydroxylapatite and phosphoryl cellulose column chromatography. The substrate phosphorylation by this kinase was markedly enhanced by calmodulin even in the absence of Ca2+, when mixed histone was used as a substrate. The interaction of the kinase with mixed histone resulted in an irreversible inactivation of the enzyme. Calmodulin prevented this inactivation, and this compound produced an apparent increase in histone phosphorylation by the kinase. It should be noted that acidic polypeptides such as troponin-C, phospholipids and nucleic acids have a similar ability. The addition of Ca2+ reduced the effect of calmodulin more than the effects of other acidic compounds.

OBJECTIVE:To investigate the initial hemodialysis vascular access in Hangzhou and provide evidence for improving the use of autologous arteriovenous fistula by identifying factors associated with the choice of initial vascular access.METHODS:We retrospectively studied the initial hemodialysis vascular access of 257 patients in five hemodialysis units in Hangzhou of China during a 21-month period (January 2018 to September 2019). A logistic regression was used to identify the risk factors of failing to use an arteriovenous fistula at the initiation of hemodialysis.RESULTS:(1) 257 participants with mean age 67.65 ± 13.43 years old were reviewed, including 165 males (64.2%) and 92 females (35.8%). The etiologies of end-stage renal disease included diabetic nephropathy (37.35%), chronic glomerulonephritis (31.13%), hypertensive nephropathy (14.01%), and other diseases (17.51%). Only 51 patients (19.84%) received arteriovenous fistula, whereas the remaining 206 patients (80.16%) initiated dialysis with a central venous catheter. (2) Logistic regression analysis revealed that the independent risk factors for central venous catheter at the initial hemodialysis were age >70 years old (OR = 4.827, p < 0.01 versus ≤70 years old), chronic glomerulonephritis as the primary etiology (OR = 2.565, p < 0.05 versus nonchronic glomerulonephritis) and eGFR <8.5 mL/min/1.73m2 (OR = 2.283, p < 0.05 versus eGFR ≥8.5 mL/min/1.73m2).CONCLUSION:The proportion of patients using arteriovenous fistula as the initial hemodialysis vascular access in Hangzhou was still low. The choice of vascular access for the first hemodialysis was related to age, eGFR, and the primary etiology of end-stage renal disease. Increasing the proportion of planned vascular access and arteriovenous fistula at the initiation of hemodialysis is still our current goal.

Background and Purpose: Early erythrolysis occurs within the hematoma following intracerebral hemorrhage (ICH), and the release of erythrocyte cytoplasmic proteins such as hemoglobin and Prx2 (peroxiredoxin 2) can cause brain injury. Complement activation can induce erythrolysis. This study determined the function of complement component 3 (C3) in erythrolysis in hematoma and brain injury after ICH in mice. Methods: This study has 3 parts. First, ICH was induced in adult male C3-sufficient and deficient mice and animals were euthanized on days 1, 3, 7, and 28 for immunohistochemistry after magnetic resonance imaging and behavioral testing. Second, C3-sufficient and deficient mice with ICH were euthanized on day 1 for Western blot analysis. Third, C3-sufficient mice received injections of PBS and Prx2. Mice underwent both magnetic resonance imaging and behavioral tests on day 1 and were then euthanized. Brains were harvested for immunohistochemistry and Fluoro-Jade C staining. Results: Erythrolysis occurred in the hematoma in C3-sufficient and deficient mice on day 3 following ICH. C3-deficient mice had less erythrolysis, brain swelling, and neuronal degeneration in the acute phase and less brain atrophy in the chronic phase. There were fewer neurological deficits on days 3, 7, and 28 in C3-deficient mice. C3-deficient mice also had less extracellular Prx2 release. Moreover, Prx2 induced brain edema and brain injury and recruited macrophage scavenger receptor-1- and CD4-positive cells following ICH in mice. Conclusions: C3-deficient mice had less severe erythrolysis and brain injury following ICH compared with C3-sufficient mice. Prx2 released after erythrolysis can cause brain damage and neuroinflammation in mice.

BACKGROUND:Chronic subdural hematoma (CSDH) is a common illness in neurosurgical practice with a substantial recurrence rate. Previous studies found that serum lipids were associated with the risk of stroke and subarachnoid hemorrhage. In the current study, we aimed to identify the relationship between serum lipids and CSDH recurrence.METHODS:The medical records of 274 consecutive surgical patients with CSDH in our department were reviewed and analyzed. Patients were separated into recurrence and non-recurrence groups. Univariable and multivariable Cox proportional hazards regression analyses were performed to identify serum lipids (triglycerides, total cholesterol, LDL, HDL) and other potential predictors associated with CSDH recurrence, and the performance of predictors was assessed with receiver operating characteristic (ROC) curve.RESULTS:Of the 274 patients included in the study, 42 (15.3%) experienced at least 1 recurrence of CSDH. Univariate analysis showed that age, hypertension, diabetes mellitus, anticoagulant use, triglycerides, HDL, and midline shift were all significantly associated with CSDH recurrence. Multivariable Cox regression analysis found that only age, diabetes mellitus, midline shift, and HDL level were independent risk factors for CSDH recurrence. A higher HDL level (HR = 0.929, 95% CI 0.905-0.953) was significantly associated with a lower risk of recurrence, and ROC curve analysis revealed that the optimal HDL cut-off value as a predictor was 37.45 mg/dl.CONCLUSIONS:Low level of high-density lipoprotein is significantly associated with recurrence of chronic subdural hematoma.

Astrocytes are vitally involved in the development of neurodegenerative diseases and brain cancers. In this work, we investigated the potential ameliorative role of microRNA-194-5p (miR-194-5p) against lipopolysaccharide (LPS)-induced astrocytes activation and the mechanism underneath. Astrocytes were transfected with miR-194-5p mimic or inhibitor and subsequently induced with LPS. Cell proliferation was measured using MTT assay while Transwell assay was used for assessing cell migration. The concentrations of cyclooxygenase 2 (COX2) and cytokines (tumor necrosis factor-α (TNF-α), transforming growth factor β (TGF-β), interleukin (IL)-1β and IL-6) were determined by enzyme-linked immunosorbent assay (ELISA). Gene expression was assessed by quantitative reverse transcription PCR (RT-qPCR) while western blotting was used for quantifying relative protein expression. We found that miR-194-5p, downregulated in LPS-induced astrocytes, significantly inhibited LPS-induced cell proliferation and migration. In addition, miR-194-5p inhibited the release of COX2 and pro-inflammatory cytokines (TNF-α, TGF-β, IL-1β and IL-6). Moreover, the silencing of neurexophilin 1 (NXPH1), an in silico and mechanistically confirmed direct target of miR-194-5p, reverted the anti-inflammatory, anti-proliferative and anti-migratory effects of miR-194-5p. We anticipated that miR-194–5 inhibits the proliferation, invasion, and inflammatory reaction in LPS-induced astrocytes by directly targeting NXPH1. These findings hinted that miR-194-5p/NXPH1 axis exerts vital functions in astrocytes activation and neuroinflammation-associated diseases. This finding will open novel avenues for biomedical and neuroscience research.