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Peroxisomes and pexophagy have gained increasing attention in their role within the central nervous system (CNS) in recent years. In this review, we comprehensively discussed the physiological and pathological mechanisms of peroxisomes and pexophagy in neurological diseases. Peroxisomes communicate with mitochondria, endoplasmic reticulum, and lipid bodies. Their types, sizes, and shapes vary in different regions of the brain. Moreover, peroxisomes play an important role in oxidative homeostasis, lipid synthesis, and degradation in the CNS, whereas its dysfunction causes various neurological diseases. Therefore, selective removal of dysfunctional or superfluous peroxisomes (pexophagy) provides neuroprotective effects, which indicate a promising therapeutic target. However, pexophagy largely remains unexplored in neurological disorders. More studies are needed to explore the pexophagy's crosstalk mechanisms in neurological pathology.

Abstract Background Survival prognosis of patients with gastric cancer (GC) often influences physicians’ choice of their follow-up treatment. This study aimed to develop a positron emission tomography (PET)-based radiomics model combined with clinical tumor-node-metastasis (TNM) staging to predict overall survival (OS) in patients with GC. Methods We reviewed the clinical information of a total of 327 patients with pathological confirmation of GC undergoing 18 F-fluorodeoxyglucose (18 F-FDG) PET scans. The patients were randomly classified into training (n = 229) and validation (n = 98) cohorts. We extracted 171 PET radiomics features from the PET images and determined the PET radiomics scores (RS) using the least absolute shrinkage and selection operator (LASSO) and random survival forest (RSF). A radiomics model, including PET RS and clinical TNM staging, was constructed to predict the OS of patients with GC. This model was evaluated for discrimination, calibration, and clinical usefulness. Results On multivariate COX regression analysis, the difference between age, carcinoembryonic antigen (CEA), clinical TNM, and PET RS in GC patients was statistically significant (p

Intratumoral microbiota (IM) has emerged as a significant component of the previously thought sterile tumor microenvironment (TME), exerting diverse functions in tumorigenesis and immune modulation. This review outlines the historical background, classification, and diversity of IM, elucidating its pivotal roles in oncogenicity, cancer development, and progression, alongside its influence on anti-tumor immunity. The signaling pathways through which IM impacts tumorigenesis and immunity, including reactive oxygen species (ROS), β-catenin, stimulator of interferon genes (STING), and other pathways [NF-κB, Toll-like receptor (TLR), complement, RhoA/ROCK, PKR-like ER kinase (PERK)], are discussed comprehensively. Furthermore, we briefly introduce the clinical implications of IM, emphasizing its potential as a target for novel cancer therapies, diagnostic biomarkers, and prognostic indicators. Notably, microbe-based therapeutic strategies such as fecal microbiome transplantation (FMT), probiotics regulation, bacteriotherapy, bacteriophage therapy, and oncolytic virotherapy are highlighted. These strategies hold promise for enhancing the efficacy of current cancer treatments and warrant further exploration in clinical settings.

Purpose: To evaluate the efficacy of two novel indices, the hole closure index (HCI) and the hole healing index (HHI), in predicting both the anatomic outcome and postoperative visual acuity following surgical intervention for idiopathic macular holes. Methods: A total of 38 patients diagnosed with idiopathic macular hole (IMH) were included. All patients underwent standard surgical treatment, including vitrectomy, internal limiting membrane (ILM) peeling, and gas tamponade. Preoperative and postoperative spectral-domain optical coherence tomography (SD-OCT) was utilized to assess the anatomical status of the macular hole (MH). The maximum distance between the tips of the external limiting membrane (ELM) was designated as the hole size (HS). HHI, calculated as the ratio of hole height to HS, and HCI, calculated as the ratio of hole height to the average of minimum diameter and base diameter, were determined. Postoperative reconstruction of ELM and ellipsoid zone (EZ) was evaluated, along with analysis of best-corrected visual acuity (BCVA) on a logarithm of the minimum angle of resolution (logMAR) scale. Regression analysis was performed to evaluate the relationship between anatomical outcomes, postoperative visual acuity, and optical coherence tomography (OCT) parameters. Receiver operating characteristic (ROC) curves were generated for both HHI and HCI. Results: Regression analyses revealed significant correlations between HCI and the restoration of ELM and EZ at 6 months after surgery (P = 0.002 and P = 0.014, respectively). In addition, a significant correlation was found between HHI and postoperative BCVA better than logMAR 0.52 also at 6 months after surgery (P = 0.033). The area under the ROC curve (AUC) for HCI based on ELM and EZ reconstruction was high, with values of 0.942 and 0.842, respectively. AUC for HHI, determined by ROC curve analysis of postoperative BCVA, was 0.704. Conclusions: In conclusion, our findings indicate that HCI may be the most accurate predictor of type 1 closure, while HHI could be considered a potential predictor of postoperative visual acuity.

Abstract Purpose To evaluate the repeatability and agreement of Fourier-domain optical coherence tomography (AOCT-1000 M and RTVue XR) and partial coherence interferometry biometer (IOL Master 500) in measuring corneal thickness mapping and axial length respectively. Methods Corneal thickness was measured by AOCT-1000 M and RTVue XR. Axial lengths were measured by AOCT-1000 M and IOL Master 500. The repeatability and agreement of corneal thickness and axial length were calculated in two groups of devices. The intraclass correlation coefficient (ICC) was used to verify the repeatability of the device. The 95% confidence interval of the difference compared to the set cut-off value was used to verify the agreement between the two devices. Results A total of 60 subjects with 58 eyes were included. The central corneal thickness measured by AOCT-1000 M and RTVue XR were 504.46 ± 42.53 μm and 504.43 ± 42.89 μm respectively. The average difference between groups was 0.03 ± 4.58 μm, and the 95% confidence interval was (-1.17, 1.24), which was far less than the set threshold value of 15 μm (P

The role of glial scar after intracerebral hemorrhage (ICH) remains unclear. This study aimed to investigate whether microglia-astrocyte interaction affects glial scar formation and explore the specific function of glial scar. We used a pharmacologic approach to induce microglial depletion during different ICH stages and examine how ablating microglia affects astrocytic scar formation. Spatial transcriptomics (ST) analysis was performed to explore the potential ligand-receptor pair in the modulation of microglia-astrocyte interaction and to verify the functional changes of astrocytic scars at different periods. During the early stage, sustained microglial depletion induced disorganized astrocytic scar, enhanced neutrophil infiltration, and impaired tissue repair. ST analysis indicated that microglia-derived insulin like growth factor 1 (IGF1) modulated astrocytic scar formation via mechanistic target of rapamycin (mTOR) signaling activation. Moreover, repopulating microglia (RM) more strongly activated mTOR signaling, facilitating a more protective scar formation. The combination of IGF1 and osteopontin (OPN) was necessary and sufficient for RM function, rather than IGF1 or OPN alone. At the chronic stage of ICH, the overall net effect of astrocytic scar changed from protective to destructive and delayed microglial depletion could partly reverse this. The vital insight gleaned from our data is that sustained microglial depletion may not be a reasonable treatment strategy for early-stage ICH. Inversely, early-stage IGF1/OPN treatment combined with late-stage PLX3397 treatment is a promising therapeutic strategy. This prompts us to consider the complex temporal dynamics and overall net effect of microglia and astrocytes, and develop elaborate treatment strategies at precise time points after ICH.

Accurately predicting fracture initiation pressure is crucial for successfully applying hydraulic fracturing technology in layered reservoirs. However, existing models overlook the effects of rock anisotropy and borehole deformation. In this study, we simplified the layered reservoir to a transversely isotropic medium and developed a model to estimate borehole deformation precisely. Based on this estimated deformation, we created a model to predict fracture initiation pressure in hydraulic fracturing. By comparing previous models and experimental data, we validated the effectiveness of these proposed models. We examined the impacts of various factors on borehole deformation, fracture initiation pressure, and initiation angle. The results revealed that circular boreholes in layered reservoirs deform into elliptical boreholes under in situ stress, with the major axis not aligning with the principal stress direction, which highlights the significant impact of rock anisotropy on borehole deformation. Furthermore, the fracture initiation pressure of hydraulic fracturing either increases or decreases following borehole deformation, depending on specific geological parameters. The calculated initiation angle after borehole deformation is within 10°, closer to previous experimental results, underscoring the notable effect of borehole deformation on hydraulic fracturing. Our research indicates that the impact of borehole deformation on hydraulic fracturing is significant and should not be overlooked. This finding will offer fresh avenues for further study in the field of hydraulic fracturing.

Abstract The albumin‐bilirubin (ALBI) score was originally used to accurately assess liver dysfunction and predict the prognoses of patients with hepatocellular carcinoma. Following its more recent application to patients with gastrointestinal tumors, this study analyzed the prognostic value of the ALBI score in Chinese patients with advanced resectable (tumor‐node‐metastasis [TNM] stages I–III) gastric cancer (GC). This study investigated 1185 patients with advanced GC, including 429 with TNM stage I. The patients were divided into training and verifications groups (593 and 592 patients, respectively) in which these patients were classified as high risk (ALBI score ≥ −2.65) or low risk (ALBI score < −2.65). Univariate and multivariate Cox regression analyses were performed, and a visual survival prediction model (nomogram) was created. On Kaplan–Meier analysis, patients who were low‐risk and high‐risk according to their ALBI scores had significantly different survival rates in both the training and verification groups (p

The influence of interdisciplinary research has become a trending topic in library and information science. However, research examining the influence of interdisciplinarity on scholars is still limited. This current study examines the interdisciplinarity from the author co-citation network approach. We focus on the field of social networking sites (SNS) research, namely studies about online platforms that people use for networking (e.g., Facebook), and examine whether interdisciplinarity would promote academic impact. About 2,489 articles in the field of SNS published from 2014 to 2016 were retrieved, with 611 first authors cited by those articles identified. The interdisciplinarity of the scholar was assessed in the author co-citation networks using two indexes: betweenness centrality and constraint. We identified four primary disciplines of SNS research in 2014 to 2016. Interdisciplinarity indexes were used to predict the scholarly impact in this field in the next 3-year interval (2017–2019), measured by citation counts. We found that citation number was predicted by betweenness centrality but not by constraint. Theoretical and practical implications of interdisciplinarity in research activities are discussed.

Abstract Subarachnoid hemorrhage (SAH) is a devastating subtype of stroke with high mortality and disability rate. Meningeal lymphatic vessels (mLVs) are a newly discovered intracranial fluid transport system and are proven to drain extravasated erythrocytes from cerebrospinal fluid into deep cervical lymph nodes after SAH. However, many studies have reported that the structure and function of mLVs are injured in several central nervous system diseases. Whether SAH can cause mLVs injury and the underlying mechanism remain unclear. Herein, single‐cell RNA sequencing and spatial transcriptomics are applied, along with in vivo/vitro experiments, to investigate the alteration of the cellular, molecular, and spatial pattern of mLVs after SAH. First, it is demonstrated that SAH induces mLVs impairment. Then, through bioinformatic analysis of sequencing data, it is discovered that thrombospondin 1 (THBS1) and S100A6 are strongly associated with SAH outcome. Furthermore, the THBS1‐CD47 ligand‐receptor pair is found to function as a key role in meningeal lymphatic endothelial cell apoptosis via regulating STAT3/Bcl‐2 signaling. The results illustrate a landscape of injured mLVs after SAH for the first time and provide a potential therapeutic strategy for SAH based on mLVs protection by disrupting THBS1 and CD47 interaction.

BackgroundMetabolic syndrome (MetS) is associated with poor prognosis in many cancers. However, the relationship between metabolic syndrome and overall survival (OS) in patients with colorectal cancer (CRC) remains unclear. We aimed to comprehensively analyze whether MetS could affect postoperative complications and long-term survival in patients with CRC.MethodsWe included patients who underwent CRC resection at our center between January 2016 and December 2018. Bias was reduced through propensity score matching analysis. Patients with CRC were divided into the MetS and non-MetS groups based on whether they had MetS. Univariate and multivariate analyses were used to identify risk factors affecting OS.ResultsWe included 268 patients; among them, 120 were included for further analysis after propensity score matching. There were no significant between-group differences in the clinicopathological features after matching. Compared with the non-MetS group, the MetS group had a shorter OS (P = 0.027); however, there was no significant between-group difference in postoperative complications. Multivariate analysis revealed that MetS (hazard ratio [HR] = 1.997, P = 0.042), tumor-node-metastasis stage (HR = 2.422, P = 0.003), and intestinal obstruction (HR = 2.761, P = 0.010) were independent risk factors for OS.ConclusionsMetS affects the long-term survival of patients with CRC without affecting postoperative complications.

CO2 geological storage (CGS) is considered to be an important technology for achieving carbon peak and carbon neutralization goals. Injecting CO2 into deep unminable coal seams can achieve both CGS and enhance coalbed methane (ECBM) production. Therefore, the deep unminable coal seams are considered as promising geological reservoirs. CO2 exists in a supercritical CO2 (ScCO2) when it was injected into deep unminable coal seams. The injection of ScCO2 can induce changes in the seepage characteristics and microstructure of deep water-bearing coal seams. In this study, typical bituminous coal from Shenmu, Shanxi Province was used to investigate the effects of ScCO2 on seepage characteristics, pore characteristics, and mineral composition through experiments such as seepage tests, low-temperature liquid nitrogen adsorption, and X-ray diffraction (XRD). The results indicate that ScCO2 treatment of dry and saturated coal samples caused a significant increase in clay mineral content due to the dissolution of carbonates, leading to the conversion of adsorption pores to seepage pores and an improvement in seepage pore connectivity. Therefore, the Brunauer-Emmett-Teller (BET) specific surface area and pore volume of the two coal samples both decreased after ScCO2 treatment. Moreover, the permeability of dry and saturated coal samples increased by 191.53% and 231.71% at 10 MPa effective stress respectively. In semi-saturated coal samples, a large amount of dolomite dissolved, leading to the precipitation of Ca2+ and CO32- to form calcite. This caused pore throats to clog and macropores to divide. The results show that the pore volume and average pore size of coal samples decrease, while the specific surface area increases after ScCO2 treatment, providing more space for gas adsorption. However, the pore changes also reduced the permeability of the coal samples by 32.21% and 7.72% at effective stresses of 3 MPa and 10 MPa, respectively. The results enhance our understanding of carbon sequestration through ScCO2 injection into water-bearing bituminous coal seams.

Abstract Background Sarcopenia is an age-related syndrome that may have negative impact on surgical outcomes and long-term survival of patients with gastric cancer. Serum creatinine/cystatin C (Cr/CysC) ratio has attracted attention as a surrogate marker for sarcopenia but has not been adequately studied in patients with gastric cancer. The purpose of this study was to investigate the validity of serum Cr/CysC ratio as a predictor of sarcopenia, evaluate a statistical cut-off value, and assess the relationship between Cr/CysC ratio and prognosis of patients with gastric cancer. Methods We retrospectively studied 327 patients who underwent surgery for gastric cancer from June 2009 to October 2021. The skeletal muscle mass index was calculated using computed tomography (CT). We determined the relevance of serum Cr/CysC ratio as a surrogate maker for sarcopenia by comparing it with various biomarkers. The Concordance index (C-index) was calculted to measure whether the Cr/CysC ratio can prognosis of patients with gastric cancer. Results Serum Cr/CysC was significantly correlated with with Skeletal Muscle Index (SMI) (r = 0.221, p

BackgroundFew studies have compared the prognosis of different reconstruction methods after gastrectomy for gastric cancer (GC) patients with obesity. The aim of the present study was to compare postoperative complications and overall survival (OS) between the following reconstruction methods: Billroth I (B-I), Billroth II (B-II), and Roux-en-Y (R-Y) after gastrectomy for GC patients with visceral obesity (VO).MethodsWe performed a double-institutional dataset study of 578 patients who underwent radical gastrectomy with B-I, B-II, and R-Y reconstructions between 2014 and 2016. VO was defined as a visceral fat area at the level of the umbilicus greater than 100 cm2. Propensity score-matching analysis was performed to balance the significant variables. Postoperative complications and OS were compared between the techniques.ResultsVO was determined in 245 patients, of which 95, 36, and 114 underwent B-I, B-II, and R-Y reconstructions, respectively. B-II and R-Y were fused into the Non-B-I group due to the similar incidence of overall postoperative complications and OS. Therefore, 108 patients were enrolled after matching. The overall postoperative complications incidence and overall operative time in the B-I group were significantly lower than those in the non-B-I group. Further, multivariable analysis showed that B-I reconstruction was an independent protective factor for overall postoperative complications (odds ratio (OR) 0.366, P=0.017). However, no statistical difference in OS was found between the two groups (hazard ratio (HR) 0.644, P=0.216).ConclusionsB-I reconstruction was associated with decreased overall postoperative complications, rather than OS, in GC patients with VO who underwent gastrectomy.

The migration of light non-aqueous phase liquids (LNAPLs) trapped in porous media is a complex phenomenon. Groundwater table fluctuation can not only affect contaminant migration but also redox conditions, bacterial communities, and contaminant degradation. Understanding LNAPLs’ (e.g., benzene, toluene, ethylbenzene, and xylene (BTEX)) behavior within porous media is critical for the high efficiency of most in situ remediation systems. A laboratory study of single- and double-lithology soil column investigation of the groundwater table fluctuation effect on BTEX transport, using benzene and toluene as typical compounds, in a typical representative model of aquifers subjected to water table fluctuation was undertaken in this study. The results show that benzene and toluene migration in single-lithology soil columns packed with sand was mainly affected by flushing due to the hydraulic force induced by water table fluctuations and that the double-lithology soil column packed with sand and silt was significantly affected by retention due to the higher adsorption induced by 10 cm of silt. The dissolution mainly correlated with the BTEX migration in saturated zones, and the contaminant concentration increased when the water table fell and decreased when the water table rose. For a contaminated site with a single-lithology structure consisting of sand, more attention should be paid to organic contaminant removal within the groundwater, and a double-lithology structure containing silt is more suited to the removal of organic contaminants from the silt layer. The difference in biodegradation kinetics between the groundwater table fluctuation (GTF) zone and the saturated zone should be better understood for the remediation of BTEX compounds.

As defined by the Global Leaders Malnutrition Initiative (GLIM), malnutrition is strongly associated with a lower quality of life and poor prognosis in gastric cancer patients. However, few studies have precisely explored the predictors of malnutrition, as defined by the GLIM, for overall survival (OS) after gastric cancer surgery in subgroups of patients stratified according to population characteristics. Our research aimed to analyze whether the predictors of malnutrition defined by the GLIM for postoperative OS in gastric cancer patients differ across subgroups. Patients who underwent radical gastric cancer surgery at our center between July 2014 and February 2019 were included in the study. Propensity score matching (PSM) was used to minimize bias. The study population was divided into malnourished and normal groups based on whether they were malnourished as defined by the GLIM. Univariate and multivariate analyses were performed to identify the risk factors affecting OS. The Kaplan–Meier curve and log-rank test were performed to determine the survival rate difference between subgroups. Overall, 1,007 patients were enrolled in the research. Multivariate analysis showed that malnutrition among the patients was 33.47%. Additionally, GLIM-defined malnutrition was an independent risk factor [hazard ratio (HR): 1.429, P = 0.001] for a shorter OS in gastric cancer patients. Furthermore, subgroup analysis showed that the GLIM was more appropriate for predicting OS in older aged patients (≥65 years), females, those with comorbidities (Charlson comorbidity index ≥ 2), and those with advanced gastric cancer (TNM stage = 3). GLIM-defined malnutrition affects the long-term survival of gastric cancer patients, especially older patients, females, patients with comorbidities, and patients with advanced gastric cancer.

Abstract Direct comparison data on spatial patterns of visual field (VF) defects among primary angle-closure glaucoma (PACG), high-tension glaucoma (HTG) and normal-tension glaucoma (NTG) are not available. We aimed to compare the intraocular asymmetry of VF loss among patients with PACG, NTG and HTG across different severity levels. A total of 162 eyes of 114 patients with PACG, 111 eyes of 74 patients with HTG and 148 eyes of 102 patients with NTG were included. VF defects were categorized into 3 stages (early, moderate, and advanced), and each hemifield was divided into 5 regions according to the Glaucoma hemifield test (GHT). The mean total deviation (TD) of each GHT region was calculated. In the early stage, the paracentral, peripheral arcuate 1 and peripheral arcuate 2 regions in the superior hemifield in the NTG group had significantly worse mean TDs than their corresponding regions in the inferior hemifield. In the advanced stage, the central region in the superior hemifield in the PACG group had a significantly worse mean TD than that in the inferior hemifield. There was no significant difference in the mean TD for any of the five regions between hemifields across all severity levels in the in the HTG group. The superior hemifield was affected more severely than the inferior hemifield in all three subtypes of primary glaucoma. This asymmetric tendency was more pronounced in NTG than in PACG and HTG.

Abstract Background Intracerebral hemorrhage (ICH) can induce excessive accumulation of reactive oxygen species (ROS) that may subsequently cause severe white matter injury. The process of oligodendrocyte progenitor cell (OPC) differentiation is orchestrated by microglia and astrocytes, and ROS also drives the activation of microglia and astrocytes. In light of the potent ROS scavenging capacity of ceria nanoparticles (CeNP), we aimed to investigate whether treatment with CeNP ameliorates white matter injury by modulating ROS-induced microglial polarization and astrocyte alteration. Methods ICH was induced in vivo by collagenase VII injection. Mice were administered with PLX3397 for depleting microglia. Primary microglia and astrocytes were used for in vitro experiments. Transmission electron microscopy analysis and immunostaining were performed to verify the positive effects of CeNP in remyelination and OPC differentiation. Flow cytometry, real-time polymerase chain reaction, immunofluorescence and western blotting were used to detect microglia polarization, astrocyte alteration, and the underlying molecular mechanisms. Results CeNP treatment strongly inhibited ROS-induced NF-κB p65 translocation in both microglia and astrocytes, and significantly decreased the expression of M1 microglia and A1 astrocyte. Furthermore, we found that CeNP treatment promoted remyelination and OPC differentiation after ICH, and such effects were alleviated after microglial depletion. Interestingly, we also found that the number of mature oligodendrocytes was moderately increased in ICH + CeNP + PLX3397-treated mice compared to the ICH + vehicle + PLX3397 group. Therefore, astrocytes might participate in the pathophysiological process. The subsequent phagocytosis assay indicated that A1 astrocyte highly expressed C3, which could bind with microglia C3aR and hinder microglial engulfment of myelin debris. This result further replenished the feedback mechanism from astrocytes to microglia. Conclusion The present study reveals a new mechanism in white matter injury after ICH: ICH induces M1 microglia and A1 astrocyte through ROS-induced NF-κB p65 translocation that hinders OPC maturation. Subsequently, A1 astrocytes inhibit microglial phagocytosis of myelin debris via an astrocytic C3-microglial C3aR axis. Polyethylene glycol-CeNP treatment inhibits this pathological process and ultimately promotes remyelination. Such findings enlighten us that astrocytes and microglia should be regarded as a functional unit in future works.

Abstract Background Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Microglial/macrophage activation and neuroinflammation are key cellular events following TBI, but the regulatory and functional mechanisms are still not well understood. Myeloid-epithelial-reproductive tyrosine kinase (Mer), a member of the Tyro-Axl-Mer (TAM) family of receptor tyrosine kinases, regulates multiple features of microglial/macrophage physiology. However, its function in regulating the innate immune response and microglial/macrophage M1/M2 polarization in TBI has not been addressed. The present study aimed to evaluate the role of Mer in regulating microglial/macrophage M1/M2 polarization and neuroinflammation following TBI. Methods The controlled cortical impact (CCI) mouse model was employed. Mer siRNA was intracerebroventricularly administered, and recombinant protein S (PS) was intravenously applied for intervention. The neurobehavioral assessments, RT-PCR, Western blot, magnetic-activated cell sorting, immunohistochemistry and confocal microscopy analysis, Nissl and Fluoro-Jade B staining, brain water content measurement, and contusion volume assessment were performed. Results Mer is upregulated and regulates microglial/macrophage M1/M2 polarization and neuroinflammation in the acute stage of TBI. Mechanistically, Mer activates the signal transducer and activator of transcription 1 (STAT1)/suppressor of cytokine signaling 1/3 (SOCS1/3) pathway. Inhibition of Mer markedly decreases microglial/macrophage M2-like polarization while increases M1-like polarization, which exacerbates the secondary brain damage and sensorimotor deficits after TBI. Recombinant PS exerts beneficial effects in TBI mice through Mer activation. Conclusions Mer is an important regulator of microglial/macrophage M1/M2 polarization and neuroinflammation, and may be considered as a potential target for therapeutic intervention in TBI.

BackgroundTo determine the association of the retinal capillary plexus (RCP) and ganglion cell complex (GCC) with cognitive impairment using optical coherence tomography angiography (OCTA).MethodsA cross-sectional, community-based study utilizing data from the participants enrolled between August 2019 and January 2020 in the Jidong Eye Cohort Study. We assessed the vessel density in RCP and GCC thickness using OCTA, and cognitive testing using the Montreal Cognitive Assessment (MoCA). Cognitive impairment in this study was defined as MoCA score < 24. We used multivariable analysis to evaluate the association of RCP and GCC with cognitive impairment after adjusting for confounders.ResultsThis study analyzed 1555 participants. The mean age of participants was 52.3 (8.4) years, and 861 (55.4%) were women. Cognitive impairment was observed in 268 (17.2%) participants. The adjusted odds ratio (OR) with 95% confidence interval (95% CI) for parafovea vessel density in the deep RCP with cognitive impairment was 1.20 (1.03–1.39). For vessel area and length density surrounding foveal avascular zone with cognitive impairment, the ORs with 95% CIs were 1.23 (1.07–1.41) and 1.30 (1.13–1.49), respectively. For thickness in the superior GCC with cognitive impairment, the OR with 95% CI was 1.16 (1.01–1.32).ConclusionLower vessel density in the RCP and thinner GCC were associated with cognitive impairment. Our results suggest that alterations in the RCP and GCC could provide further evidence when assessing the cognitive function and may even be potentially useful biomarkers in the detection of cognitive impairment.

Abstract Background China is undergoing a massive transition toward an urban and industrial economy. These changes will restructure the demographics and economy which will eventually influence the future patterns of disease. The risk factors of vision-impairing eye diseases remain ambiguous and poorly understood. Metabolomics is an ideal tool to understand and shed light on the ocular disease mechanisms for earlier treatment. This article aims to describe the design, methodology and baseline data of the Yueqing Ocular Diseases Investigation (YODI), a developed county population-based study to determine the prevalence and primary causes of visual impairment; also with metabonomics analysis we aimed to identify, predict and suggest some preventive biomarkers that cause blindness. Methods A population-based, cross-sectional study. Randomized clustering sampling was used to identify adults aged 50 years and older in Xiangyang Town, Yueqing county-level City. The interviews covered demographic, behavioral, ocular risk factors and mental health state. The ocular examination included visual acuity, autorefraction, intraocular pressure, anterior and posterior segment examinations, fundus photography, retinal tomography and angiography, and visual field testing. Anthropometric measurements included height and weight, waist and hip circumference, blood pressure, pulse rate, electrocardiogram, and abdominal ultrasound scan. A venous blood sample was collected for laboratory tests and metabonomics studies. Results Of the 5319 individuals recruited for the YODI, 4769 (89.7%) subjects were enrolled for analyses. The median age was 62.0 years, and 45.6% were male. The educational level of illiteracy or semi-illiteracy, primary, middle and high school or above was 29.8%, 45.5%, 20.1%, and 3.3%, respectively. Majority of the participants were female, younger, and less educated when compared with nonparticipants. The average body mass index and waist-hip ratios were 24.4 ± 3.4 kg/m2 and 0.9 ± 0.1 respectively. Blood sample collection reached a sample size of 1909 (479 from subjects with self-reported diabetes and 1430 from one-third of the 4290 subjects without self-reported diabetes). Conclusions The YODI provides population-based data with a high response rate (89.7%) on the prevalence and primary causes of major vision-impairing eye diseases in developed county areas in eastern China. Metabonomics analysis from YODI will provide further association of metabolic characteristics with the visual impairment eye diseases. The risk prediction model could be created and has the potential to be generalized to developed eastern areas in China for prevention.

BackgroundCurrently, there are shortcomings in diagnosing gastric cancer with or without serous invasion, making it difficult for patients to receive appropriate treatment. Therefore, we aimed to develop a radiomic nomogram for preoperative identification of serosal invasion.MethodsWe selected 315 patients with gastric cancer, confirmed by pathology, and randomly divided them into two groups: the training group (189 patients) and the verification group (126 patients). We obtained patient splenic imaging data for the training group. A p-value of

Abstract Background Neuroinflammation and oxidative stress play important roles in early brain injury following subarachnoid hemorrhage (SAH). This study is the first to show that activation of apelin receptor (APJ) by apelin-13 could reduce endoplasmic reticulum (ER)-stress-associated inflammation and oxidative stress after SAH. Methods Apelin-13, apelin siRNA, APJ siRNA, and adenosine monophosphate-activated protein kinase (AMPK) inhibitor-dorsomorphin were used to investigate if the activation of APJ could provide neuroprotective effects after SAH. Brain water content, neurological functions, blood-brain barrier (BBB) integrity, and inflammatory molecules were evaluated at 24 h after SAH. Western blotting and immunofluorescence staining were applied to assess the expression of target proteins. Results The results showed that endogenous apelin, APJ, and p-AMPK levels were significantly increased and peaked in the brain 24 h after SAH. In addition, administration of exogenous apelin-13 significantly alleviated neurological functions, attenuated brain edema, preserved BBB integrity, and also improved long-term spatial learning and memory abilities after SAH. The underlying mechanism of the neuroprotective effects of apelin-13 is that it suppresses microglia activation, prevents ER stress from overactivation, and reduces the levels of thioredoxin-interacting protein (TXNIP), NOD-like receptor pyrin domain-containing 3 protein (NLRP3), Bip, cleaved caspase-1, IL-1β, TNFα, myeloperoxidase (MPO), and reactive oxygen species (ROS). Furthermore, the use of APJ siRNA and dorsomorphin abolished the neuroprotective effects of apelin-13 on neuroinflammation and oxidative stress. Conclusions Exogenous apelin-13 binding to APJ attenuates early brain injury by reducing ER stress-mediated oxidative stress and neuroinflammation, which is at least partly mediated by the AMPK/TXNIP/NLRP3 signaling pathway.

Abstract Background To compare the reoperation rate in patients with vitreous hemorrhage (VH) secondary to proliferative diabetic retinopathy (PDR) with or without preoperative intravitreal bevacizumab (IVB). Methods In this retrospective study, 280 patients (362 eyes) with diabetic VH were divided into a group that received preoperative IVB and a group that did not receive preoperative IVB. According to B-scan or color Doppler ultrasonography, the eyes were grouped as a VH group and a tractional retinal detachment (TRD) group. The reoperation rate, visual and anatomical outcomes of treatment were evaluated after 6 months. Results There were 17.4% of eyes in the VH group that did not receive preoperative IVB later required additional vitrectomy, while only 7.7% of the eyes in the VH group that received preoperative IVB required additional vitrectomy (P = 0.025). There were 45.5% of eyes in the TRD group that did not receive preoperative IVB had no reoperation, while only 21.4% of the eyes in the TRD group that received preoperative IVB had no reoperation (P = 0.004). The patients with one operation achieved better vision than those required reoperations in the VH group (P = 0.038) and TRD group (P = 0.019). Conclusions Preoperative IVB significantly reduced the re-vitrectomy rate in patients with VH without TRD, but there was an increase in the reoperation rate in patients with VH combined with TRD.

Preclinical and clinical research has demonstrated that inflammation is a critical factor regulating intracerebral hemorrhage (ICH)-induced brain injury. Growing evidence suggests that myeloid cells and lymphocytes have an effect on the pathophysiological processes associated with ICH, such as inflammation, immune responses, perihematomal edema formation, blood–brain barrier (BBB) integrity, and cell death. However, the underlying mechanisms remain largely unknown. We aimed to explore the role immune cells played at different stages of the ICH. To achieve this, novel bioinformatics algorithms were employed to analyze the gene expression profiles and three different analytical tools were utilized to predict the abundances of cell types. In this study, we found that natural killer (NK) cells infiltrated into the brain parenchyma after ICH. Infiltrating NK cells may mediate brain injury through degranulation and recruitment of other cells. Besides, in the acute phase of ICH, monocytes in peripheral blood carried out phagocytosis and secretion of cytokines. On the other hand, in the subacute stage, non-classical monocytes were activated and showed a stronger ability to carry out heme metabolism, wound healing, and antigen processing and presentation. In conclusion, our findings emphasize the significance of intracerebral infiltrating immunocytes in ICH and demonstrate that ICH is a systemic disease affected by peripheral blood. The hub genes identified might be promising therapeutic targets. We also provide a reference on how to use bioinformatics approaches to explore non-neoplastic immune-related diseases.

Background: Neuronal apoptosis involved in secondary injury following traumatic brain injury (TBI) significantly contributes to the poor outcomes of patients with TBI. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis of tumor cells. Hypoxia factor (HIF) 1α is a controversial factor that mediates the neuronal apoptotic pathway. Herein, we hypothesize that HIF-1α may mediate the TRAIL-induced neuronal apoptosis after TBI.Methods: We used Western blots and immunofluorescence to study the expression and cell localization of TRAIL and death receptor 5 (DR5) after TBI in rats. Soluble DR5 (sDR5) administration was used to block the TRAIL-induced neuronal death and neural deficits. HIF-1α inhibitor 2ME and agonist DMOG were used to study the role of HIF-1α in TRAIL-induced neuronal death. Meanwhile, HIF-1α siRNA was used to investigate the role of HIF-1α in TRAIL-induced neuronal death in vitro.Results: The expressions of microglia-located TRAIL and neuron-located DR5 were significantly upregulated after TBI. sDR5 significantly attenuated TRAIL-induced neuronal apoptosis and neurological deficits. 2ME decreased neuronal apoptosis, lesion area, and brain edema and improved neurological function via increased expression of TRAIL decoy receptor 1 (DcR1), which inhibited TRAIL-induced apoptosis after TBI. The administration of DMOG produced the opposite effect than did 2ME. Similarly, HIF-1α siRNA attenuated TRAIL-induced neuronal death via increased DcR1 expression in vitro.Conclusion: Our findings suggested that the TRAIL/DR5 signaling pathway plays an important role after neuronal apoptosis after TBI. HIF-1α mediates TRAIL-induced neuronal apoptosis by regulating DcR1 expression following TBI.

Background: We intend to assess the efficacies and limitations of collagenase clostridium histolyticum (CCH) and fasciectomy in treating Dupuytren’s contracture, and the associated complications and rate of recurrences aiming to present a treatment algorithm. Methods: A literature search within the PubMed, Web of Sciences, Cochrane Library, and EMBASE databases was performed using the combined key words ‘Dupuytren, palmar aponeurosis contracture, collagenase clostridium histolyticum and fasciectomy’, including all possible studies with a set of predefined inclusion and exclusion criteria. Results: Thirty studies were assessed for eligibility from 215 identified records. Seventeen publications satisfied the inclusion criteria including 2142 joints in 1784 patients. The mean follow-up time was 18.0 months (3–60). Conclusion: Acceptable contractures release was obtained in both techniques. Severe complications associated with fasciectomy outrank those of CCH, whereas the low rate of recurrence favors the fasciectomy technique.

Abstract Background Elbow osteoarthritis (OA) is a common disabling condition because of pain and loss of motion. Open and arthroscopic debridement are the preferred treatment, however there is no consensus on which treatment modality is suited to which category of patient or stage of disease. The objective of this study was to narratively review the literature for a more comprehensive understanding of its treatment options and associated outcomes, trying to provide a better treatment plan. Methods The PubMed database, EMBASE, Cochrane Library, and Google Scholar were searched, using the keywords (elbow [title/abstract] and osteoarthritis [title/abstract] and (surgery or open or arthroscop* or debridement or ulnohumeral arthroplasty) including all possible studies with a set of inclusion and exclusion criteria. Results A total of 229 studies were identified. Twenty-one articles published between 1994 and 2016 satisfied the inclusion and exclusion criteria including 651 elbows in 639 patients. After comparison, mean postoperative improvement in (ROM) was 28.6° and 23.3°,Mayo elbow performance score/index(MEPS/MEPI) 31 and 26.8 and the total complication rate was 37(11.5%), and 18(5.5%) for open and arthroscopic procedure. Conclusions This narrative review could not provide an insight on which surgical procedure is superior to the other due to the poor orthopedics literature. However, from the data we obtained the open and arthroscopic debridement procedures seem to be safe and effective in the treatment of elbow OA. The optimal surgical intervention for the treatment of symptomatic elbow OA should be determined depending on patients’ conditions.

Abstract Neuronal apoptosis chiefly contributes to the cell loss following traumatic brain injury (TBI). CGP3466B is a compound related to the anti-Parkinsonism drug R-(−)-deprenyl. Previous studies have illuminated anti-apoptosis effects of CGP3466B in different cell lines, but the underlying mechanisms have not been fully elucidated. Mammalian sterile 20 (STE20)-like kinase1 (Mst1) is a core component of the Hippo signaling pathway. Protein-L-isoaspartate (D-aspartate) O-methyltransferase (PCMT1) is an enzyme that repairs damaged L-isoaspartyl residues in proteins. The present study was performed to investigate the neuroprotective effects of CGP3466B and to determine a potential PCMT1/Mst1 neuronal anti-apoptotic pathway after TBI. Double immunofluorescence staining demonstrated that PCMT1 and Mst1 are co-located in neurons. Administration of CGP3466B improved neurological function, downregulated the ROS level and alleviated brain edema at 24 h after TBI. CGP3466B alleviates neuronal apoptosis by increasing PCMT1 expression and subsequently inhibiting MST1 activation, resulting in changing the expression levels of Bax, Bcl-2 and active-caspase3. The TUNEL staining results also support the anti-apoptosis effects of CGP3466B. The anti-apoptotic effects of CGP3466B were abolished by chelerythrine, an Mst1 activator, without changing PCMT1 levels. In conclusion, our findings suggest CGP3466B may have a promising therapeutic potential by modulating PCMT1/Mst1 signaling pathway after TBI injury.

Cell death is deeply involved in pathophysiology of brain injury after intracerebral hemorrhage (ICH). Necroptosis, one of the recently discovered forms of cell death, plays an important role in various diseases, including ICH. Previous studies have suggested that a considerable number of neurons undergoes necroptosis after ICH. However, necroptosis of microglia after ICH has not been reported to date. The present study demonstrated for the first time that necroptosis occurred in the microglia surrounding the hematoma after ICH in C57 mice, and melatonin, a hormone that is predominantly synthesized in and secreted from the pineal gland, exerted a neuroprotective effect by suppressing this process. When we further explored the potential underlying mechanism, we found that melatonin inhibits RIP3-mediated necroptosis by regulating the deubiquitinating enzyme A20 (also known as TNFAIP3) expression after ICH. In summary, we have demonstrated the role of microglial necroptosis in the pathogenesis of ICH. More importantly, A20 was identified as a novel target of melatonin, which opens perspectives for future research.

Intracerebral hemorrhage (ICH) is a devastating disease with high rates of mortality and morbidity. The aim of this study was to explore whether Sodium Benzoate (NaB) could reduce neural cell apoptosis and alleviate neurological deficits after ICH. To assess the therapeutic effects of NaB, first, we measured brain water content, neurobehavior, and blood-brain barrier (BBB) integrity at 24 h after ICH in different groups. Then western blot and immunofluorescence staining (IF) were applied to test the levels of different proteins. Transmission electron microscope (TEM) was used to observe ultra-structures within the cells in different groups. The results showed that levels of DJ-1, p-Akt and p-IκB kinase (IKK) increased after ICH and peaked at 24 h. Besides, NaB significantly upregulated DJ-1 in both cytoplasm and mitochondria, and also increased the levels of p-Akt, p-IKK and Bcl-2/Bax ratio, but decreased the levels of caspase-3 and caspase-9. Additionally, NaB decreased reactive oxygen species (ROS) while increased adenosine triphosphate (ATP), which then improving the neurological functions at 24 h and long-term (21 days) memory and spatial learning ability after ICH. However, the results mentioned above could be greatly reversed by MK2206 and rotenone. Therefore, we concluded that NaB could attenuate secondary brain injury via inhibiting neuronal apoptosis and reducing mitochondria-mediated oxidative stress via DJ-1/Akt/IKK/NFκB pathway.

This study aimed to explore the neuroprotective effects and mechanisms of natrium benzoate (NaB) and DJ-1 in attenuating reactive oxygen species (ROS)-induced neuronal apoptosis in traumatic spinal cord injury (t-SCI) in rats. T-SCI was induced by clip compression. The protein expression and neuronal apoptosis was evaluated by Western blotting, double immunofluorescence staining and transmission electron microscope (TEM). ROS level, spinal cord water content (SCWC) and Evans blue (EB) extravasation was also examined. Locomotor function was evaluated by Basso, Beattie, and Bresnahan (BBB) and inclined plane test (IPT) scores. We found that DJ-1 is expressed in spinal cord neurons and increased after t-SCI. At 24 h post-injury, the levels of DJ-1, p-Akt, SOD2, ROS, p-p38 MAPK/p38 MAPK ratio, and CC-3 increased, while the Bcl-2/Bax ratio decreased. NaB upregulated DJ-1, p-Akt, and SOD2, decreased ROS, p-p38 MAPK/p38 MAPK ratio, and CC-3, and increased the Bcl-2/Bax ratio, which were reversed by DJ-1 siRNA. The proportion of CC-3- and TUNEL-positive neurons also increased after t-SCI and was reduced by NaB. These effects were reversed by MK2206. Moreover, the level of oxDJ-1 increased after t-SCI, which was decreased by DJ-1 siRNA, NaB or the combination of them. NaB also reduced mitochondrial vacuolization, SCWC and EB extravasation, and improved locomotor function assessed by the BBB and IPT scores. In conclusion, NaB increased DJ-1, and thus reduced ROS and ROS-induced neuronal apoptosis by promoting Akt phosphorylation in t-SCI rats. NaB shows potential as a therapeutic agent for t-SCI, with DJ-1 as its main target.

Purpose. To investigate the efficacy and safety of combined vitrectomy with tumor resection in the treatment of retinal vasoproliferative tumors (RVPT). Methods. Retrospective study. RVPT patients who underwent vitreous surgery at the Eye Hospital of Wenzhou Medical University from January 2011 to July 2017 were included. The main outcomes included treatment type, tumor activity, and best-corrected visual acuity (BCVA). Results. Altogether, 16 patients with 17 eyes were enrolled with follow-up of no less than 6 months. Eight eyes were in the resection treatment group (Group R) and 9 eyes were in the conservative treatment group (Group C). Female (69%) were more common. The mean age was 50 (49.72 ± 12.92) years. Fifteen patients got unilateral onset and only one patient suffered bilaterally. The common symptoms were decreased visual acuity, floaters, and visual distortion. The preoperative BCVA ranged from hand movement to 20/20, with an average of 0.82 ± 0.75 LogMAR. Patients were all not high myopia, with a mean axial length of 23.27 ± 0.27 mm (21.61 mm to 24.67 mm). Of the retinal diseases, the epiretinal membrane was the most common, followed by vitreous hemorrhage, uveitis, subretinal fluid, and so on. Compared with the baseline BCVA, it improved more at postoperative 6 months and the last visit in Group R than in Group C (P=0.006 and P=0.033). The BCVA-improved 0.2 LogMAR or above in 6 months was 2 eyes in Group C and 7 eyes in Group R. All tumors in Group R were completely resected, whereas three in Group C (33.3%) had definite activity (P=0.008). In all samples, tumors were located on the inner side of the retina and had small vessel wall thickening and hyaline degeneration. The degree of astrocyte proliferation varies widely among different tumors. Conclusions. RVPT was more likely to occur in nonhigh myopia patients. Epiretinal membrane and vitreous hemorrhage were the main causes for vitreous surgery in RVPT patients. Compared with conservative treatment, surgical resection of the tumor is more beneficial to patients on visual acuity recovery and preventing tumor relapse. It is a safe and effective way to treat RVPT.

Stroke is one of the most devastating diseases worldwide. In recent years, a great number of studies have focused on the effects of microRNAs (miRNAs) on stroke and the results demonstrated that the expressions of miRNAs are associated with the prognosis of stroke. In the present study, we review relevant articles regarding miRNAs and stroke and will explain the complex link between both. The miRNAs participate extensively in the pathophysiology following the stroke, including apoptosis, neuroinflammation, oxidative stress, blood–brain barrier (BBB) disruption and brain edema. The information about the stroke–miRNA system may be helpful for therapeutic and diagnostic methods in stroke treatment.

Neuronal apoptosis is an important factor accounting for the poor outcomes of intracerebral hemorrhage (ICH). This study first showed that inhibition of activating transcription factor 6 (ATF6) could alleviate secondary brain injury through anti-apoptosis after ICH in rats. Melatonin, ATF6 and CCAAT/enhancer-binding protein homologous protein (CHOP) siRNAs were applied in this study. Brain edema, neurological functions, blood-brain barrier (BBB) integrity were evaluated at 24 h after ICH. Western blot analysis was used to evaluate the protein level of target proteins (ATF6, CHOP, Bip, Bcl-2, Bax, and cleaved caspase-3). Reverse transcription-polymerase chain reaction (RT-PCR) was used to assess the mRNA level of ATF6, CHOP and cleaved caspase-3. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and caspase-3 immunofluorescence staining were applied to evaluate the neuronal cell death. The results suggested that the levels of ATF6 and its downstream protein, CHOP, were upregulated and reached the peak at 24 h after ICH. ATF6 was highly expressed in neurons. The administration of melatonin significantly decreased the mRNA and protein levels of ATF6, and its downstream targets, CHOP and cleaved caspase-3, but increased the Bcl-2/Bax ratio, which ameliorated the neurological functions. The CHOP siRNA significantly reversed the pro-apoptotic effect induced by the increased ATF6 level after ICH. Melatonin could protect against neuronal apoptosis via suppression of ATF6/CHOP arm of ER-stress-response pathway.

Aim: Sirtuin3 (sirt3) plays a pivotal role in improving oxidative stress and mitochondrial dysfunction which directly induced neuronal apoptosis after intracerebral hemorrhage (ICH). Reactive oxygen species (ROS) is also a critical activator in triggering NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasomes activation which can regulate inflammatory responses in brain. Moreover, hyperglycemia can aggravate the ICH-induced damage. Hence, this study was designed to investigate the mechanisms of neuroprotection of sirt3 in hyperglycemic ICH.Methods: ICH model was established by autologous blood injection. Hyperglycemia was induced by intraperitoneal injection with streptozotocin. Honokiol (HKL, a pharmacological agonist of sirt3) was injected intraperitoneally at doses of 2.5, 5, or 10 mg/kg. Sirt3 small interfering RNA transfection was implemented through intracerebroventricular injection. The expression of sirt3 and its downstream signaling molecules were detected using Western blotting or immunofluorescence staining. Morphological changes of mitochondria were detected by electron microscopy. SH-SY5Y cells were incubated with 10 μM oxyhemoglobin for 48 h to establish an in vitro ICH model, and then JC-1 staining was used to determine mitochondrial membrane potential (Δψm).Results: Hyperglycemia could suppress sirt3 expression after ICH when compared with non-diabetic rats. Sirt3 protein expression was decreased to the minimum at 24 h in perihematoma tissues. Electron microscope analysis indicated that hyperglycemic ICH induced extensive mitochondrial vacuolization. HKL attenuated ROS accumulation, adenosine triphosphate reduction, and Δψm through Sirt3–superoxide dismutase 2 (SOD2) and Sirt3–NRF1–TFAM pathway. Sirt3 knockdown could exacerbate the neuronal apoptosis and reverse the positive effects of HKL. Sirt3 activation could decrease NLRP3 and interleukin-1β levels through deacetylating SOD2 and scavenging ROS.Conclusion: HKL protects against hyperglycemic ICH-induced neuronal injury via a sirt3-dependent manner.

Neuronal apoptosis plays key roles in secondary brain injury caused by intracerebral hemorrhage (ICH). This study first reported the role of mesencephalic astrocyte-derived neurotrophic factor (MANF) in alleviating secondary brain injury through anti-apoptosis in rat model of ICH. The recombinant human-MANF (rh-MANF) and selective Akt inhibitor MK2206 was administrated intracerebroventricularly 1 h after ICH. Brain water content, behavioral assessment, BBB (blood brain barrier) leakage was evaluated 24 h after the induction of ICH. Western blot analysis was used to evaluate the expression level of target proteins (MANF, mouse 3T3 cell double-minute 2 (MDM2), P53, Akt, Bcl-2, Bax, and caspase-3). Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) was applied to evaluate the neuronal cell death. Besides, whether MANF was expressed in neurons was verified with double immunofluorescence staining. The results suggested that the level of MANF, and its downstream proteins, Akt, MDM2 was upregulated and reached peak at 24 h after ICH. MANF was mainly expressed in neurons. The administration of rh-MANF could significantly increase the level of p-Akt, p-MDM2, Bcl/Bax ratio, but reduce the expression of p53, caspase-3 and neuronal death, thus ameliorate the neurological functions at 24 h after ICH. However, these effects of rh-MANF could be obviously reversed by MK2206. MANF could exert its neuronal anti-apoptotic effects via Akt/MDM2/P53 pathways. Therefore, MANF could be a valuable drug target in the treatment of ICH.

Compelling evidence has indicated that imbalance between apoptosis and autophagy may be involved in subarachnoid hemorrhage (SAH). We aimed to investigate the effects and mechanisms of melatonin in the homeostasis of apoptosis and autophagy. One-hundred and forty-eight male Sprague-Dawley rats were intraperitoneally injected with melatonin or vehicle 2 h after SAH induction. Western blotting and an immunofluorescent assay were performed to detect the expression of apoptosis- and autophagy-related proteins. The neuroprotective effect of melatonin attenuating SAH-induced neurological deficit and brain edema may be associated with the suppression of SAH-induced neuronal apoptosis and autophagy. Furthermore, melatonin inhibited the cleavage of mammalian sterile 20-like kinase 1 (MST1) protein by reducing reactive oxygen species (ROS) content. These effects of melatonin on regulating the homeostasis between apoptosis and autophagy could be reversed by an MST1 agonist, chelerythrine, via enhancement of MST1 cleavage. In conclusion, exogenous melatonin alleviates SAH-induced early brain injury (EBI) by suppressing excessive neuronal apoptosis and autophagy. The underlying mechanism may, at least in part, involve the ROS-MST1 pathway.

Ischemic stroke, the most common subtype of stroke, has been one of the leading causes of mobility and mortality worldwide. However, it is still lacking of efficient agents. Stem cell therapy, with its vigorous advantages, has attracted researchers around the world. Numerous experimental researches in animal models of stroke have demonstrated the promising efficacy in treating ischemic stroke. The underlying mechanism involved antiapoptosis, anti-inflammation, promotion of angiogenesis and neurogenesis, formation of new neural cells and neuronal circuitry, antioxidation, and blood-brain barrier (BBB) protection. This review would focus on the types and neuroprotective actions of stem cells and its potential mechanisms for ischemic stroke.

To evaluate the status of and factors associated with long-term health-related quality of life (HRQOL) in adult patients with strabismus following corrective surgery.Prospective cross-sectional study. A total of 122 adults who underwent corrective surgery and were followed up for at least 1 year were recruited. Pre- and post-operative HRQOL were evaluated using the Chinese version of the Adult Strabismus 20 (AS-20). Demographics and clinical characteristics were recorded. Eighty-nine age-matched, normal individuals without a history of strabismus were recruited as a control group.AS-20 scores improved significantly in the psychosocial subscale and total scale after surgery for all122 patients, but not in the function subscale. HRQOL was better in the successful cases than in the non-successful cases (p

Hydraulic fracturing is used widely to stimulate coalbed methane production in coal mines. However, some factors associated with conventional hydraulic fracturing, such as the simple morphology of the fractures it generates and inhomogeneous stress relief, limit its scope of application in coal mines. These problems mean that gas extraction efficiency is low. Conventional fracturing may leave hidden pockets of gas, which will be safety hazards for subsequent coal mining operations. Based on a new drilling technique applicable to drilling boreholes in coal seams, this paper proposes a tree-type fracturing technique for stimulating reservoir volumes. Tree-type fracturing simulation experiments using a large-scale triaxial testing apparatus were conducted in the laboratory. In contrast to the single hole drilled for conventional hydraulic fracturing, the tree-type sub-boreholes induce radial and tangential fractures that form complex fracture networks. These fracture networks can eliminate the “blank area” that may host dangerous gas pockets. Gas seepage in tree-type fractures was analyzed, and gas seepage tests after tree-type fracturing showed that permeability was greatly enhanced. The equipment developed for tree-type fracturing was tested in the Fengchun underground coal mine in China. After implementing tree-type fracturing, the gas extraction rate was around 2.3 times greater than that for traditional fracturing, and the extraction rate remained high for a long time during a 30-day test. This shortened the gas drainage time and improved gas extraction efficiency.

PurposeTo investigate whether the polymorphism rs800292 (184G>A, I62V) in the complement factor H gene is associated with polypoidal choroidal vasculopathy (PCV) and the genetic difference between PCV and neovascular age-related macular degeneration (nAMD), in Asian populations.MethodsA comprehensive literature search was performed in PubMed, Medline, Web of Science, and reference lists. A system review and meta-analysis of the association between I62V and PCV and/or nAMD were performed from 8 studies involving 5,062 subjects. The following data from individual studies were extracted and analyzed: 1) comparison of I62V polymorphisms between PCV and controls; 2) comparison of I62V polymorphisms between PCV and nAMD. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using fixed-effects models. The Q-statistic test was used to assess heterogeneity, and Egger's test was used to evaluate publication bias. Sensitivity analysis and cumulative meta-analysis were also performed.ResultsThe I62V polymorphism showed a significant summary OR1 for genotype GA+GG versus homozygous genotype AA was 3.18 (95% CI, 2.51-4.04, PConclusionsOur analysis provides evidence that the I62V polymorphism is associated with an increased risk of PCV. The variant of I62V could be a promising genetic biomarker of PCV in Asian populations.