Evaluation the role of insulin signaling pathway in reproductive toxicity of dispersed diesel particulate extract under environmental conditions.

Diesel particulate extract (DPE), which is a significant constituent of airborne particle pollution, has a strong association with the development of cancer and respiratory diseases. Fulvic acid (FA), a plentiful organic macromolecule found in water, has the capability to modify particle surface charge and adsorption capacity when combined with minerals. Nevertheless, there is a scarcity of data regarding the influence of their interaction on DPE toxicity. To examine the impact of environmental factor on the toxic effects of DPE, we used the Caenorhabditis elegans (C. elegans) model to investigate the reproductive toxicity of DPE and FA on insulin signaling pathway. C. elegans were subjected to a semi-fluid medium (NGG) containing different concentrations of DPE or DPE + FA in order to assess germline apoptosis and the expression of important genes in the insulin signaling pathway. Through several mutant strains, we found that daf-2, age-1, pdk-1, akt-1 and daf-16 were involved in DPE-induced apoptosis. Furthermore, and the expression levels of these genes significantly altered. The ratio of daf-16 translocation to nucleation, as well as the amount of reactive oxygen species (ROS), exhibited a dose-response relationship, however, the presence of FA could altered these effects. The results revealed that the insulin signaling pathway plays a vital role in mediating the harmful effects caused by DPE, whereas environmental factors have a substantial impact on its toxicity. Moreover, it was noted that semi-fluid medium could effectively replicate three-dimensional exposure circumstances closely resembling those observed in actual situations.

Modified Suture-Button Latarjet Procedure With Coracoacromial Ligament and Pectoralis Minor Preservation Achieves Good Clinical Outcomes at 2-Year Follow-Up: Case Series of Latarjet Technique.

PURPOSE: To evaluate whether the modified suture-button Latarjet procedure with coracoacromial ligament (CAL) and pectoralis minor (PM) preservation could achieve excellent outcomes at the 2-year follow-up. METHODS: During January 2019 to January 2021, the data of patients who underwent modified suture-button Latarjet with CAL and PM preservation in our department were collected. The glenoid bone loss of these patients was greater than 20% or greater than 10% with high demands for exercise. Partial coracoid osteotomy was based on the results of a preoperative 3-dimensional computed tomography evaluation of the glenoid defect area and corresponding coracoid process morphology. The preoperative and postoperative clinical results were assessed. The minimal clinically important difference (MCID) was used to compare improvement in clinical outcomes. Graft-glenoid union and remodeling were assessed using postoperative 3-dimensional computed tomography, and magnetic resonance imaging was performed to confirm the integrity of the CAL and PM postoperatively. RESULTS: In total, 35 patients were included in this study; the mean follow-up time was 26.9 ± 1.9 months. No case of recurrent dislocation or sublaxity. Significant improvements were observed in mean visual analog scale (VAS) scores for pain during motion, American Shoulder and Elbow Surgeons (ASES) score, Rowe score, and Walch-Duplay score (P < .001). The percentage of patients achieving at least an MCID improvement in clinical outcomes was VAS 85.71%, ASES 97.14%, Rowe 100%, and Walch-Duplay 97.14%. Thirty-three patients (94.3% of all cases) were able to return to their preoperative sport levels, 34 grafts (97.1%) achieved bone union (1 soft union) in 6.3 ± 2.2 months, and the coracoid grafts restored 97.1 ± 4.0% of the perfect-fitting circle at the last follow-up. Postoperative computed tomography scan showed that 31 grafts (88.6%) were placed ideally in vertical view. In the axial view, 25 grafts (82.9%) were flushed to the glenoid, whereas 1 and 5 grafts were fixed medially and laterally, respectively. The CAL and PM were visualized postoperatively. No arthropathy was observed in any patient at the last follow-up. CONCLUSIONS: The modified suture-button Latarjet procedure with CAL and PM preservation obtained good clinical and radiological results without recurrence or complications. A substantial number of patients (>85%) achieved the MCID for the VAS, ASES, Rowe, and Walch-Duplay scores. In addition, the malpositioned graft (17.1%) did not cause arthropathy of the joints at 2-year follow-up. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Intersection of Race, Rurality, and Income in Defining Access to Minimally Invasive Lung Surgery.

BACKGROUND: Race is a potent influencer of health care access. Geography and income may exert equal or greater influence on patient outcomes. We sought to define the intersection of race, rurality, and income and their influence on access to minimally invasive lung surgery in Medicare beneficiaries. METHODS: Centers for Medicare and Medicaid Services data were used to evaluate patients with lung cancer who underwent right upper lobectomy, by open, robotic-assisted thoracic surgery (RATS), or video-assisted thoracic surgery (VATS) between 2018 and 2020. International Classification of Diseases, 10th Edition, was used to define diagnoses and procedures. We excluded sublobar, segmental, wedge, bronchoplasty, or reoperative patients with nonmalignant or metastatic disease or a history of neoadjuvant chemotherapy. Risk adjustment was performed using inverse probability of treatment weighting (IPTW) propensity scores with generalized linear models and Cox proportional hazards models. RESULTS: The cohort comprised 13,404 patients, 4291 open (32.1%), 4317 RATS (32.2%), and 4796 VATS (35.8%). Black/urban patients had significantly higher RATS and VATS rates (P < .001), longer long-term survival (P = .007), fewer open resections (P < .001), and lower overall mortality (P = .007). Low-income Black/urban patients had higher RATS (P = .002), VATS (P < .001), longer long-term survival (P = .005), fewer open resections (P < .001), and lower overall mortality compared with rural White patients (P = .005). CONCLUSIONS: Rural White populations living close to the federal poverty line may suffer a burden of disparity traditionally observed among poor Black people. This suggests a need for health policies that extend services to impoverished, rural areas to mitigate social determinants of health.

Mechanical digit sensory stimulation: a randomized control trial on neurological and motor recovery in acute stroke.

Background: Mechanical digit sensory stimulation (MDSS) is a novel therapy designed to accelerate the recovery of upper limb (including hand) function in patients with hemiplegia following a stroke. The primary goal of this study was to investigate the effect of MDSS on patients with acute ischemic stroke (AIS). Methods: Sixty-one inpatients with AIS were randomly divided into conventional rehabilitation group (RG) and stimulation group (SG), and the latter group received MDSS therapy. A healthy group consisting of 30 healthy adults was also included. The interleukin-17A (IL-17A), vascular endothelial growth factor A (VEGF-A), and tumor necrosis factor-alpha (TNF-α) plasma levels were measured in all subjects. The neurological and motor functions of patients were evaluated using the National Institutes of Health Stroke Scale (NIHSS), Mini-Mental State Examination (MMSE), Fugel-Meyer Assessment (FMA), and Modified Barthel Index (MBI). Results: After 12 days of intervention, the IL-17A, TNF-α, and NIHSS levels were significantly decreased, while the VEGF-A, MMSE, FMA, and MBI levels were significantly increased in both disease groups. No significant difference was observed between both disease groups after intervention. The levels of IL-17A and TNF-α were positively correlated with NIHSS but negatively correlated with MMSE, FMA, and MBI. The VEGF-A levels were negatively correlated with NIHSS but positively correlated with MMSE, FMA, and MBI. Conclusion: Both MDSS and conventional rehabilitation significantly reduce the production of IL-17A and TNF-α, increase the VEGF-A levels, and effectively improve cognition and motor function of hemiplegic patients with AIS, and the effects of MDSS and conventional rehabilitation are comparable.

Molecular dynamics study on defect evolution during the plastic deformation of nickel-based superalloy GH4169 single crystal under different rolling temperatures.

Nickel-based superalloy GH4169 is widely used as an important material in the aviation field. The rolling forming process can improve its surface quality and performance. Therefore, conducting an extensive investigation into the microscopic plastic deformation defect evolution process of nickel-based single crystal alloys during the rolling process is crucial. This study can offer valuable insights for optimizing rolling parameters. In this paper, a nickel-based superalloy GH4169 single crystal alloy was rolled at different temperatures from the atomic scale using the molecular dynamics (MD) method. The crystal plastic deformation law, dislocation evolution and defect atomic phase transition under different temperature rolling were studied. The results show that the dislocation density of nickel-based single crystal alloys increases as the temperature increases. When the temperature continues to increase, it is accompanied by an increase in vacancy clusters. When the rolling temperature is below 500 K, the atomic phase transition of the subsurface defects of the workpiece is mainly a Close-Packed Hexagonal (HCP) structure; when the temperature continues to increase, the amorphous structure begins to increase, and when the temperature reaches 900 K, the amorphous structure increases significantly. This calculation result is expected to provide a theoretical reference for the optimization of rolling parameters in actual production.

Adjuvant chemotherapy is associated with an overall survival benefit regardless of age in ER+/HER2- breast cancer pts with 1-3 positive nodes and oncotype DX recurrence score 20 to 25: an NCDB analysis.

Background: The RxPONDER trial found that among breast cancer patients with estrogen receptor positive (ER+) breast cancer, 1-3 positive axillary nodes, and a recurrence score of ≤25, only pre-menopausal women benefitted from adjuvant chemoendocrine therapy; postmenopausal women with similar characteristic did not benefit from adjuvant chemotherapy. We aimed to replicate the RxPonder trial using a larger patient cohort with real world data to determine whether a RS threshold existed where adjuvant chemotherapy was beneficial regardless of age. Methods: The National Cancer Database (NCDB) was queried for women with ER+, human epidermal growth factor receptor 2 (HER2) negative breast cancer, 1-3 positive axillary nodes, and RS ≤25 who received endocrine (ET) only or chemo-endocrine therapy (CET). Cox regression interaction was explored between CET and age as a surrogate for menopausal status. Results: The final analytic cohort included 28,427 eligible women: 7,487 (26.3%) received adjuvant CET and 20,940 (73.7%) ET. In the entire cohort, RS had a normal distribution, with a median score of 14. After correcting for demographic and clinical variables, a threshold effect was observed with RS >20 being associated with a significantly inferior overall survival (OS) (P value range: < 0.001-0.019). In women with RS of 20-25, CET was associated with a significant improvement in OS compared to ET alone, regardless of age (age <=50: HR = 0.334, P=0.002; age>50: HR=0.521, P=0.019). Conclusion: Among women with ER+/HER2- breast cancer with 1-3 positive nodes, and a RS of 20-25-in contrast to the RxPONDER trial-we observed that CET was associated with an OS benefit in women regardless of age.

Metabolite Comparison between Spleen-Deficiency and Healthy Children.

Objective: From the perspective of metabolomics, this study compares the metabolomics characteristics of feces and urine between children with spleen-deficiency and healthy children to explain the scientific connotation of children with spleen-deficiency susceptibility to digestive system diseases from the metabolic level and provide a scientific basis for further research. Methods: This study included 20 children with spleen-deficiencies and 17 healthy children. Children's symptom scores, height, and weight were recorded in groups, and feces and urine samples were collected. The samples were detected using ultrahigh-performance liquid chromatography-mass spectrometry. The data were analyzed using multivariate statistical analysis such as principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA). Related differential metabolites were identified through database comparisons between two groups based on the MS and KEGG. Results: Compared to healthy children, the metabolites glucuronic acid, xanthine, and indole-3-acetaldehyde tend to be reduced in children with spleen-deficiency. Moreover, these children showed an increase in metabolites such as quinic acid, adenine, 4-methyl-5-thiazole-ethanol, 3-formyl indole, and 5-hydroxy indole-3-acetic acid. The condition affected many of the critical metabolic pathways, including the metabolism of tryptophan, cysteine, methionine, and pentose phosphate. Conclusion: The children with spleen-deficiency had disorders at the metabolic level, which might be due to factors such as diet, personal preferences, and genes, leading to various symptoms, making spleen-deficiency children more prone to suffer from digestive diseases than healthy children. The results set a basis for the research on children's TCM constitution, which can be a reference to further studies to deal with the spleen-deficiency.

Morbidity After Esophagectomy Is Higher for Benign Than Malignant Disease.

BACKGROUND: Esophagectomy carries a high risk of morbidity and mortality. The most common indication for esophagectomy is esophageal cancer, with fewer than 5% of esophagectomies performed for benign disease. We hypothesized that esophagectomy for benign disease is associated with a higher risk of operative and postoperative complications. METHODS: A retrospective study of The Society of Thoracic Surgeons database was performed to identify all patients who had an esophagectomy from 2010 to 2018. Patients who had an emergent or palliative esophagectomy were excluded. Patients were compared based on the indication for operation, malignant vs benign disease. A 1:1 propensity score matching of The Society of Thoracic Surgeons risk factors was performed and outcomes compared between the matched cohorts. RESULTS: Of 16,392 patients, 14,871 (91%) had malignant disease and 1521 (9%) had benign disease that met inclusion criteria. Patients with malignant disease were older (P < .001), more likely to be male (83% vs 56%, P < .001), and had more comorbidities (P < .001). There were 1362 propensity-matched pairs. Malignant esophagectomies were more likely to be performed with a minimally invasive vs an open approach (P < .001). Benign operations had more intraoperative blood transfusions (P < .001). Patients undergoing esophagectomy for benign disease had more prolonged intubations (P = .02) and postoperative blood transfusions (P = .001). Benign disease had more major morbidities (P = .001) but similar postoperative mortality (P = .62). CONCLUSIONS: Esophagectomy for benign disease is associated with worse perioperative morbidity compared with esophagectomy for malignant disease. Given these findings patients should be counseled on expected outcomes, and this variable should be considered for inclusion in the composite score for risk assessment.

Controllable Majorana vortex states in iron-based superconducting nanowires.

To reveal the non-Abelian braiding statistics of Majorana zero modes (MZMs), it is crucial to design a Majorana platform, in which MZMs can be easily manipulated in a broad topological nontrivial parameter space. This is also an essential step to confirm their existence. In this study, we propose an iron-based superconducting nanowire system with Majorana vortex states to satisfy desirable conditions. This system has a radius-induced topological phase transition, giving a lower bound for the nanowire radius. In the topological phase, the iron-based superconducting nanowires have only one pair of MZMs over a wide range of radii, chemical potential and external magnetic fields. The wave function of MZMs has a sizable distribution at the side edge of the nanowires. This property enables the control of the interaction of MZMs in neighboring vortex nanowires and paves the way for Majorana fusion and braiding.

KIAA0101 and IL2RA Were Identified as Core Genes in Hormone-Resistant Nephropathy.

Objectives: To analyze the tissue heterogeneity of hormone-sensitive and drug-resistant nephrotic syndrome genes using a bioinformatics approach and to analyze gene-related functional pathways. Methods: The limma package of R software was used to screen differential genes from the nephropathy datasets GSE145969 and GSE189734. The differential genes were analyzed for functional and pathway enrichment in terms of biological processes, cellular components, and molecular functions. The Metascape tool was used to construct protein networks for the differential genes, and the results were imported into Cytoscape software for visualization. The genes were identified as key modules and genes using the MCODE plug-in. Gene set enrichment analysis was performed for the HALLMARK analysis of the two microarray key genes to obtain the relevant pathways. Results: GSE145969 screened 351 differential genes, 168 upregulated genes, and 183 downregulated genes. The differential genes were enriched in biological processes, cellular components, and molecular functions, such as myocardial contraction, intracellular nonmembrane organelles, and structural molecular activities. The protein-protein interaction (PPI) network contained 140 nodes, with the highest-scoring module containing seven genes, and the MCODE plug-in calculated the downseed. The key gene was KIAA0101, whose HALLMARK pathway was significantly enriched in the mTORC1 signaling pathway. A total of 263 differential genes were screened by GSE189734, and they were enriched in biological processes, molecular functions, and cellular components, such as immune system processes, signaling receptor binding, and the cytoplasmic matrix. The PPI network contained 253 nodes, with the highest-scoring module containing 37 genes. The seed gene obtained through the MCODE plug-in calculation was IL2RA, whose HALLMARK pathway was significantly enriched in the KRAS signaling pathway. Conclusion: By analyzing the gene sets of different tissues in nephropathy, two key genes, namely KIAA0101 and IL2RA, were obtained. Their gene function enrichment is related to cell growth, development, and reproduction. Therefore, IL2RA and KIAA0101 can be used as diagnostic markers for hormone-resistant nephropathy.

Treatment of membranous nephropathy with crescent nephritis by rituximab: A case report.

BACKGROUND: Crescent formation is rare in primary membranous nephropathy (MN). The mechanism of crescent formation is unknown and the treatments are tentative. PATIENT CONCERNS: A 71-year-old woman presented with nephrotic syndrome, hematuria, and rapidly progressive kidney dysfunction. DIAGNOSIS: Kidney biopsy was performed, and the diagnosis was MN in combination with crescentic glomerulonephritis. Circulating anti-PLA2R was detected of a high level. INTERVENTIONS: The patient received rituximab besides corticosteroids. OUTCOMES: The patient achieved complete remission of proteinuria and recovery of kidney function. CONCLUSION: Our case suggests that there is a pathologic feature of MN and crescents in the absence of known immunologic factors as well as rituximab could serve as an effective cure and could be considered in serious MN conditions.

Role of insulin signaling pathway in apoptosis induced by food chain delivery of nano-silver under the action of environmental factors.

OBJECTIVE: To investigate how the environmental factor affects the delivery of nano silver through food chain, we set up a two-stage food delivery chain model of Escherichia coli and Caenorhabditis elegans system. METHODS: Through a two-stage food delivery chain model of E. coli and C. elegans, the mRNA expression levels of DAF-2, age-1, PDK-1, Akt-1 and DAF-16 in the insulin growth factor 1 signaling pathway in nematode gonad cells which occurs AgNPs induced apoptosis were evaluated and the apoptosis of gonad cells in the mutant strains of the above key genes were detected. RESULTS: DAF-2, age-1, PDK-1 and Akt-1 could significantly negatively regulate the apoptosis of nematode cells induced by AgNPs, while DAF-16 could significantly promote the apoptosis induced by AgNPs. The DAF-16 up-regulated expression was a protective effect on the body and the phenomenon of DNA double-strand breaks was significantly increased. The damage effect induced by AgNPs was significantly enhanced in the presence of the environmental factor fulvic acid. CONCLUSION: The damage effect induced by AgNPs after food delivery involves the regulation of the insulin growth factor 1 signaling pathway and environmental factors have a significant impact on the biological effects.

Cancer spheroids derived exosomes reveal more molecular features relevant to progressed cancer.

Cancer cell spheroids have been shown to be more physiologically relevant to native tumor tissue than monolayer 2D culture cells. Due to enhanced intercellular communications among cells in spheroids, spheroid secreted exosomes which account for transcellular transportation should exceed those from 2D cell culture and may display a different expression pattern of miRNA or protein. To test this, we employed a widely used pancreatic cancer cell line, PANC-1, to create 3D spheroids and compared exosomes generated by both 2D cell culture and 3D PANC-1 spheroids. We further measured and compared exosomal miRNA and GPC-1 protein expression with qRT-PCR and enzyme-linked immunosorbent assay, respectively. It showed that PANC-1 cells cultured in 3D spheroids can produce significantly more exosomes than PANC-1 2D cells and exosomal miRNA and GPC-1 expression derived from spheroids show more features relevant to the progression of pancreatic cancer. These findings point to the potential importance of using spheroids as in vitro model to study cancer development and progression.

Neuroprotective Effect of Fructus broussonetiae on APP/PS1 Mice via Upregulation of AKT/ß-Catenin Signaling.

OBJECTIVE: To evaluate the mechanisms underlying the protective effect of Chinese herbal medicine Fructus broussonetiae (FB) in both mouse and cell models of Alzheimer's disease (AD). METHODS: APP/PS1 mice treated with FB for 2 months and vehicle-treated controls were run through the Morris water maze and object recognition test to evaluate learning and memory capacity. RNA-Seq, Western blotting, and immunofluorescence staining were also conducted to evaluate the effects of FB treatment on various signaling pathways altered in APP/PS1 mice. To further explore the mechanisms underlying FB's protective effect, PC-12 cells were treated with Aß25-35 in order to establish an in vitro model of AD. RESULTS: FB-treated mice showed improved learning and memory capacity on both the Morris water maze and object recognition tests. RNA-seq of hippocampal tissue from APP/PS1 mice showed that FB had effects on multiple signaling pathways, specifically decreasing cell apoptotic signaling and increasing AKT and ß-catenin signaling. Similarly, FB up-regulated both AKT and ß-catenin signaling in PC-12 cells pre-treated with Aß25-35, in which AKT positively regulated ß-catenin signaling. Further study showed that AKT promoted ß-catenin signaling via enhancing ß-catenin (Ser552) phosphorylation. Moreover, AKT and ß-catenin signaling inhibition both resulted in the attenuated survival of FB-treated cells, indicating the AKT/ß-catenin signaling is a crucial mediator in FB promoted cell survival. CONCLUSIONS: FB exerted neuroprotective effects on hippocampal cells of APP/PS1 mice, as well as improved cell viability in an in vitro model of AD. The protective actions of FB occurred via the upregulation of AKT/ß-catenin signaling.

Identification of Latent Diagnostic Biomarkers and Biological Pathways in Dermatomyositis Based on WGCNA.

INTRODUCTION: Dermatomyositis (DM) is a chronic autoimmune disease of predominantly lymphocytic infiltration mainly involving the transverse muscle. Its pathogenesis is remaining unknown. This research is designed to probe the latent pathogenesis of dermatomyositis, identify potential biomarkers, and reveal the pathogenesis of dermatomyositis through information biology analysis of gene chips. METHODS: In this study, we utilised the GSE14287 and GSE11971 datasets rooted in the Gene Expression Omnibus (GEO) databank, which included a total of 62 DM samples and 9 normal samples. The datasets were combined, and the differentially expressed gene sets were subjected to weighted gene coexpression network analysis, and the hub gene was screened using a protein interaction network from genes in modules highly correlated with dermatomyositis progression. RESULTS: A total of 3 key genes-myxovirus resistance-2 (MX2), oligoadenylate synthetase 1 (OAS1), and oligoadenylate synthetase 2 (OAS2)-were identified in combination with cell line samples, and the expressions of the 3 genes were verified separately. The results showed that MX2, OAS1, and OAS2 were highly expressed in LPS-treated cell lines compared to normal cell lines. The results of pathway enrichment analysis of the genes indicated that all 3 genes were enriched in the cytosolic DNA signalling and cytokine and cytokine receptor interaction signalling pathways; the results of functional enrichment analysis showed that all 3 were enriched in interferon-α response and interferon-γ response functions. CONCLUSIONS: This is important for the study of the pathogenesis and objective treatment of dermatomyositis and provides important reference information for the targeted therapy of dermatomyositis.

Exosomes Secreted From Bone Marrow Mesenchymal Stem Cells Attenuate Oxygen-Glucose Deprivation/Reoxygenation-Induced Pyroptosis in PC12 Cells by Promoting AMPK-Dependent Autophagic Flux.

Background: Cerebral ischemia-reperfusion (I/R) injury can lead to severe dysfunction, and its treatment is difficult. It is reported that nucleotide-binding domain and leucine-rich repeat family protein 3 (NLRP3) inflammasome-mediated cell pyroptosis is an important part of cerebral I/R injury and the activation of autophagy can inhibit pyroptosis in some tissue injury. Our previous study found that the protective effects of bone marrow mesenchymal stem cells (BMSCs) in cerebral I/R injury may be associated with the regulation of autophagy. Recent studies have demonstrated that exosomes secreted from BMSCs (BMSC-Exos) may play an essential role in the effective biological performance of BMSCs and the protective mechanism of BMSC-Exos is associated with the activation of autophagy and the remission of inflammation, but it has not been reported in studies of cerebral I/R injury. We aimed to investigate the effects of BMSC-Exos on cerebral I/R injury and determine if the mechanism is associated with the regulation of pyroptosis and autophagic flux. Method: PC12 cells were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) to induce cerebral I/R in vitro and were cocultured with BMSC-Exos. Cell viability was determined with CCK-8 and lactate dehydrogenase (LDH) detection kits. Scanning electron microscopy (SEM), Hoechst 33342/propidium iodide (PI) double staining, 2',7'-dichlorodihydrofluorescein diacetate assay, immunofluorescence, Western blot, and Enzyme-linked immunosorbent assay (ELISA) were used to detect cell pyroptosis. Furthermore, transmission electron microscopy (TEM), GFP-RFP-LC3 adenovirus transfection, and Western blot were used to detect autophagic flux and its influence on pyroptosis. Finally, coimmunoprecipitation was used to detect the binding interaction between NLRP3 and LC3. Results: BMSC-Exos increased cell viability in OGD/R. The inhibitory effect of BMSC-Exos on pyroptosis was comparable to the NLRP3 inhibitor MCC950 and was reversed by NLRP3 overexpression. Furthermore, BMSC-Exos promoted autophagic flux through the AMP-activated kinase (AMPK)/mammalian target of the rapamycin pathway, whereas chloroquine, AMPK silencing, and compound C blocked the inhibitory effect on pyroptosis. Conclusions: BMSC-Exos can protect PC12 cells against OGD/R injury via attenuation of NLRP3 inflammasome-mediated pyroptosis by promoting AMPK-dependent autophagic flux.

Differential Association of Serum BDNF With Poststroke Depression and Poststroke Anxiety.

OBJECTIVES: To investigate the correlation between brain-derived neurotrophic factor (BDNF) and risk factors, as well as functional outcome in poststroke depression (PSD) or poststroke anxiety (PSA). DESIGN: Cohort study. SETTING: Stroke patients admitted to an urban rehabilitation hospital. PARTICIPANTS: Stroke patients (N=162) without any previous history of depression and anxiety. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Sociodemographic information and comorbidities were recorded during hospital admission. Functional outcomes were assessed using FIM scores at time of admission and discharge. The influence of various factors such as BDNF and patient characteristics on functional outcome was investigated. Single-factor effect was examined using simple logistic regression, as was multi-factor effect using multiple logistic regression. The goodness-of-fit of those regression models was evaluated by the integrated area under ROC curve. RESULTS: PSD was diagnosed in 61 (37.7%) patients, and PSA was diagnosed in 40 (24.7%). Multiple logistic analysis showed that BDNF, divorce or separation, and history of smoking were significantly associated with the occurrence of PSD but not with the occurrence of PSA. The model combining low BDNF level and divorce or separation improved the prediction for PSD. Among the variables analyzed for prediction of functional outcome, serum BDNF had a minimum correlation with motor FIM scores in PSD but no significant correlation with motor FIM scores in PSA. CONCLUSIONS: BDNF is a valuable prediction for the occurrence of PSD but not for PSA. More strikingly, ischemic stroke patients who are divorced or separated with low serum BDNF have a much higher risk for PSD. BDNF has a minimum correlation with motor function outcome in PSD but no significant correlation with motor outcome in PSA.

Effects of nimodipine combined with betahistine on CRP and other inflammatory cytokines and vascular endothelial function in patients with hypertensive cerebral vasospasm.

OBJECTIVE: This study aims to investigate the effect of nimodipine combined with betahistine on the levels of CRP and other inflammatory cytokines, as well as vascular endothelial function in patients with hypertensive cerebral vasospasm. METHODS: A total of 80 patients with hypertensive cerebral vasospasm from March 2016 to September 2018 were enrolled and randomly equally divided into two groups. At 1 week before enrollment, the application of all antihypertensive drugs was stopped. Then amlodipine tablets were used in control group, based on which nimodipine tablets were applied in observation group. All the patients included were followed up for 1 month. The changes in the cerebral vasospasm index in the course of treatment as well as inflammatory cytokines and indicators related to vascular endothelial function at 1 month after treatment were measured and compared between the two groups. The correlations of the cerebral vasospasm index with the changes in inflammatory cytokines and vascular endothelial function-related factors in the body were analyzed. Finally, the effective rates of blood pressure regulation and cerebral vasospasm treatment were compared, while the adverse reactions and the overall clinical treatment effect of the two groups were evaluated. RESULTS: The cerebral vasospasm indexes in observation group were significantly lower than those in control group at 3 d, 1 week and 1 month after treatment (p < 0.05). At 1 month after treatment, the levels of inflammatory cytokines such as high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in observation group were significantly reduced compared to those in control group (p < 0.05). As for vascular endothelial function-related indicators, the endothelin-1 (ET-1) level in observation group was markedly lower than that in control group, whereas the level of nitric oxide (NO) was statistically higher than that in control group (p < 0.05). The cerebral vasospasm index was statistically positively correlated with changes in hs-CRP, IL-6, TNF-α and ET-1 (p < 0.05), but negatively correlated with changes in NO (p < 0.05). Besides, the effective rates of blood pressure regulation and cerebral vasospasm treatment in observation group were significantly higher than those in control group (p < 0.05). The overall treatment effective rate in observation group was markedly higher than that in control group (p < 0.05), and there were no significant differences of adverse reactions between the two groups (p > 0.05). CONCLUSION: For the treatment of hypertensive cerebral vasospasm, combined application of betahistine on the basis of nimodipine can effectively reduce the body's aseptic inflammatory responses, improve vascular endothelial function and increase the cerebral circulation blood flow, which offers a favorable strategy for clinical therapy.