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Abstract: Spontaneous subarachnoid hemorrhage (SAH), primarily caused by ruptured intracranial aneurysms, remains a prominent clinical challenge with a high rate of mortality and morbidity worldwide. Accumulating clinical trials aiming at the prevention of cerebral vasospasm (CVS) have failed to improve the clinical outcome of patients with SAH. Therefore, a growing number of studies have shifted focus to the pathophysiological changes that occur during the periods of early brain injury (EBI). New pharmacological agents aiming to alleviate EBI have become a promising direction to improve outcomes after SAH. Caspases belong to a family of cysteine proteases with diverse functions involved in maintaining metabolism, autophagy, tissue differentiation, regeneration, and neural development. Increasing evidence shows that caspases play a critical role in brain pathology after SAH. Therefore, caspase regulation could be a potential target for SAH treatment. Herein, we provide an overview pertaining to the current knowledge on the role of caspases in EBI after SAH, and we discuss the promising therapeutic value of caspase-related agents after SAH.

The effects of groundwater table fluctuation (GTF) on the remediation of a petrochemically polluted riverside using soil vapor extraction (SVE) were investigated. The migration and transformation of benzene, toluene, ethylbenzene, and o-xylene (BTEX) in cases of natural attenuation, SVE without GTF, and SVE with GTF were simulated using the TMVOC model. The results showed that the optimized extraction well pressure and influencing radius of the target site were 0.90 atm and 8 m, respectively. The removal rates of BTEX in cases of natural attenuation, SVE without GTF, and SVE with GTF were 11.49%, 85.16%, and 97.33%, respectively. The removal rate of BTEX was maximized in the case of SVE with a GTF amplitude of 0.5 m to 1 m. The removal rates of benzene (99.99%), toluene (99.74%), ethylbenzene (96.37%), and o-xylene (94.72%) were maximized in the case of SVE with GTF. For the cases of SVE without GTF and SVE with GTF, mass losses of BTEX in gaseous (0.05 kg, 0.05 kg, respectively) and aqueous phases (5.46 kg, 5.87 kg, respectively) were consistent. However, the mass loss of BTEX in the non-aqueous phase liquid (NAPL) phase in the case of SVE with GTF (155.13 kg) exceeded that in the case of SVE without GTF (135.41 kg). This is because GTF positively affected both the solubility and volatility of BTEX in the NAPL phase. With the groundwater table decreasing, flows of gas and gaseous pollutants increased by 25% along the vertical section. At this stage, the removal rates of volatile organic compounds can be further improved by increasing the flow of the extraction well.

PurposeGiven the rapid growth in efforts on misinformation correction, the study aims to test how evidence type and veracity interact with news agreement on the effectiveness of fact-checking on how well a corrective message discount a false news information.Design/methodology/approachExperimental participants (N = 511) in Hong Kong were exposed to the same news article and then to a piece of corrective information debunking the news article with variation in the types of evidence (numerical vs narrative) and veracity (no verdict vs half false vs entirely false) in 2019.FindingsAmong the participants who disagreed with the news article, numerical fact-checking was more effective than narrative fact-checking in discounting the news article. Some evidence of the backfire effect was found among participants for whom the article was attitude incongruent.Originality/valueWhen debunking false information with people exposed to attitude-incongruent news, a milder verdict presented in the form of a half-false scale can prompt a more positive perception of the issue at stake than an entirely false scale, implying that a less certain verdict can help in mitigating the backfire effect compared to a certain verdict.

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.

Background: To assess the clinical effectiveness of orthoptic therapy in the postoperative stabilisation and rehabilitation of binocular function in children with intermittent exotropia (IXT) after surgery. Methods: This was a prospective, parallel, randomised controlled trial. A total of 136 IXT patients (aged from 7 to 17 years) who had been successfully corrected at 1 month after surgery were enrolled in this study, and 117 patients (58 controls) completed the 12-month follow-up visit. The primary outcome was established as the proportion of patients with suboptimal surgical outcomes, which were defined as: (1) exodeviation ≥10 prism diopters (PD) at distance or near using the simultaneous prism and cover test (SPCT), or (2) constant esotropia ≥6 PD at distance or near using SPCT, or (3) loss of 2 or more octaves of stereopsis from baseline. The secondary outcomes were the exodeviation at distance and near using the prism and alternate cover test (PACT), stereopsis, fusional exotropia control and convergence amplitude. Results: The cumulative probability of suboptimal surgical outcome by 12 months was 20.5% (14/68) in the orthoptic therapy group and 42.6% (29/68) in the control group. There was a significant difference between these two groups (χ2 = 7.402, p = 0.007). Improvements in stereopsis, fusional exotropia control and fusional convergence amplitude were found in the orthoptic therapy group. A smaller exodrift was found in the orthoptic therapy group at near fixation (t = 2.26, p = 0.025). Conclusions: Early postoperative orthoptic therapy can effectively improve the surgical outcome as well as stereopsis and fusional amplitude.

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.

Jian Jiang,1 Jingjing Xu,1 Yuwen Wang,1 Jingwei Zheng,2 Dan Xu3 1Clinical Optometry Center, Eye Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325027, People’s Republic of China; 2Clinical Research Center, Eye Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325027, People’s Republic of China; 3School of Ophthalmology & Optometry, Wenzhou Medical University, Wenzhou, Zhejiang Province, 325027, People’s Republic of ChinaCorrespondence: Dan XuSchool of Ophthalmology & Optometry, Wenzhou Medical University, Wenzhou, Zhejiang Province, 325027, People’s Republic of ChinaTel +86 577 86689937Email xudammmc@163.comObjective: This study aims to investigate the correlation of dominant eye and refractive error between monozygotic twins.Methods: The data of dominant eye and refractive error of 13 pairs of monozygotic twins who were treated at the Optometry Clinic were collected. The paired chi-square test and Kappa consistency test were used to analyze the data of dominant eye between monozygotic twins, while the paired t test and Pearson correlation analysis were adopted to analyze the refractive error data. SPSS version 22.0 software was used to analyze the above statistics.Results: In the Kappa consistency test of dominant eye between monozygotic twins, Kappa value = 0.451, p = 0.052, p> 0.05, and in the paired chi-square test, p = 0.250. In the spherical equivalent paired t test for the right eye of monozygotic twins, t = 1.491 and p = 0.162, while in the spherical equivalent paired t test for the left eye, t = 0.753 and p = 0.466. In the spherical equivalent correlation analysis of monozygotic twins, for the spherical equivalent refraction of the right eye, the Pearson correlation results were r = 0.901 and p = 0.00, and for the spherical equivalent refraction of the left eye, the Pearson correlation results were r = 0.971 and p = 0.00.Conclusion: The difference in the chi-square test of dominant eye is not statistically significant between monozygotic twins, but dominant eye and refractive error are correlated to some extent. It is suggested that heredity may be the main determinant of the dominant eye. There is no difference in refractive error between identical twins which are highly correlated, however.Keywords: refractive error, dominant eye, monozygotic twins/identical twins, heredity, genes

Objectives We investigate the potential role of BRAF testing in guiding surgical intervention in papillary thyroid carcinoma (PTC). Methods Thyroid fine-needle aspiration (FNA) cases with available BRAF result and follow-up thyroidectomy for PTC were included in the study. Cytology and surgical diagnoses were correlated with BRAF status. Results There were 151 cases of thyroid FNA specimens with BRAF testing (70 mutant and 81 wild-type BRAF) and histologically confirmed unilateral, unifocal PTCs. There were no differences in age, sex, tumor size, or lymphovascular invasion on thyroidectomy specimens between mutant and wild-type BRAF cases. BRAF mutation was significantly associated with cytology diagnosis (P < .001), PTC subtype (P < .001), extrathyroidal extension (ETE) (P = .006), and higher tumor (T) stage (P = .04). However, an analysis within the histologic subtypes of PTC revealed no significant association between BRAF mutation and ETE or higher T stage. There was also no difference in central (P = .847) or lateral (p = 1) neck lymph node (LN) metastasis. Conclusions BRAF mutation identified in thyroid FNA specimens correlates with histologic subtypes but is not an independent factor for predicting PTC biological behavior and should not be used to guide the extent of LN dissection.

Purpose: Metabolic syndrome (MetS) is associated with poor prognosis in many cancers. However, few studies have comprehensively analyzed the relationship between metabolic syndrome and the overall survival of colorectal cancer (CRC) patients. Our study aimed to comprehensively analyze whether MetS could affect postoperative complications and long-term survival in patients with CRC.Patients and methods: We included patients who underwent colorectal cancer resection at our center between January 2016 and December 2018 for this analysis. The propensity score matching analysis was performed to reduce the bias. Dividing CRC patients into MetS and Non-MetS groups based on whether they had MetS. Univariate and multivariate analyses were used to identify the risk factors affecting overall survival (OS).Results: A total of 268 patients were included in the study, of whom 120 patients were included for further analysis after propensity score matching. No significant differences were found in Clinicopathological features between the MetS group and Non-MetS group after matching. Patients with MetS had a shorter OS compared with non-MetS (P=0.027), however the postoperative complications were not significantly different between them. In multivariate analysis, We found MetS (hazard ratio [HR]=1.997, P=0.042), tumor-node-metastasis (TNM) stage (HR=2.422, P=0.003), and intestinal obstruction (HR=2.761, P=0.010) were independent risk factors for OS. Conclusion: Metabolic syndrome affects long-term survival of CRC patients without affecting postoperative complications.

To investigate the association between cigarette smoking and retinal capillary plexus (RCP) using optical coherence tomography angiography (OCTA) and to examine whether potential vascular risk factors could impact their association.This is a cross-sectional, community-based study. The Jidong Eye Cohort Study included participants aged ≥18 years in the Jidong community (Tangshan city, northern China) from August 2019 to January 2020. All participants underwent comprehensive ophthalmic examination and completed detailed smoking questionnaires. Retinal vessel density in the superficial and deep RCP was automatically measured using OCTA.Of the 2598 participants included in the study, 2026 (78.0%) never smoked and 572 (22.0%) had a history of smoking (494 [19.0%] current smokers and 78 [3.0%] former smokers). The median (interquartile range) age was 41 (34-52) years for the non-smoking group and 45 (35-54.5) years for the smoking group. Multivariable analysis showed that smoking history is associated with a low deep RCP vessel density in the parafovea (β, -0.53; 95% confidence interval [CI], -0.82 to -0.24) and four quadrants. Increased smoking pack-years were associated with reduced deep RCP vessel density in the parafovea (p for trend0.001) and four quadrants. The significant interaction between diabetes and smoking only was found for superficial RCP vessel density in the parafovea (p for interaction = 0.014) and four quadrants except for the temporal quadrants.Cigarette smoking is an independent risk factor for reduced deep RCP vessel density. Our findings imply the potential detrimental effect of smoking on the occurrence of ocular diseases.

When hydraulic fractures do not expand in the direction required by a project, it is difficult to enhance coal seam permeability effectively. Slotting–directional hydraulic fracturing (SDHF) has been proposed as a possible alternative, but there is not enough theoretical mechanism to guide the construction. Based on preliminary study of the directional mechanism of single slotted hole, we established a new slotting–directional hydraulic fracturing (NSDHF) mechanical model by using the complex function theory of elasticity, and the influence of stress interference between adjacent slotted holes and non-uniform pore water pressure was considered. We carried out true triaxial double slotted holes SDHF experiments and used large-scale nondestructive computer tomography to scan the fractured samples to ensure accurate measurement of directional distance. The measured directional distance was used to verify the NSDHF model; the maximum deviation was 5.1%. Taking the experimental data in this paper as example, the stress interference between adjacent slotted holes decreased the fracture directional distance by 20.3%, and the non-uniform pore water pressure increased the fracture directional distance by 47.6%. NSDHF mechanical model realized the quantitative description of the influence of non-uniform pore water pressure on directional distance. The contribution of non-uniform pore water pressure to directional distance accounted for more than 25% of the total directional distance; the effect of non-uniform pore water pressure on fracture direction distance was almost twice the stress interference between adjacent slotted holes. The verified NSDHF model was used to study further the influence of horizontal stress difference, azimuth of slotted hole, slotting size and fluid injection pressure on directional distance with different slotting spacing. The work discussed in this paper will contribute to promoting and apply SDHF on a large scale in low-permeability coal mines.

Background This study sought to investigate a novel effect of melatonin in reducing brain injury in an in vivo hyperglycemic intracerebral hemorrhage (ICH) model and further explore the mechanisms of protection. Methods Hyperglycemia ICH was induced in Sprague-Dawley rats by streptozocin injection followed by autologous blood injection into the striatum. A combined approach including RNA-specific depletion, electron microscopy, magnetic resonance, Western blots, and immunohistological staining was applied to quantify the brain injuries after ICH. Results Hyperglycemia resulted in enlarged hematoma volume, deteriorated brain edema, and aggravated neuronal mitochondria damage 3 days after ICH. Post-treatment with melatonin 2 hours after ICH dose-dependently improved neurological behavioral performance lasting out to 14 days after ICH. This improved neurological function was associated with enhanced structural and functional integrity of mitochondria. Mechanistic studies revealed that melatonin alleviated mitochondria damage in neurons via activating the PPARδ/PGC-1α pathway. Promisingly, melatonin treatment delayed until 6 hours after ICH still reduced brain edema and improved neurological functions. Melatonin supplementation reduces neuronal damage after hyperglycemic ICH by alleviating mitochondria damage in a PPARδ/PGC-1α-dependent manner. Conclusion Melatonin may represent a therapeutic strategy with a wide therapeutic window to reduce brain damage and improve long-term recovery after ICH.

Past studies revealed the prognosis differed between aneurysmal subarachnoid hemorrhage (aSAH) patients with surgical clipping and endovascular coiling. We retrospectively reviewed aSAH patients in our institution to investigate the effectiveness of grading scores between two groups. In the surgical clipping group (n = 349), VASOGRADE had a favorable performance for predicting delayed cerebral ischemia (DCI) (area under curve (AUC) > 0.750), and had better results than clinical (World Federation of Neurosurgical Societies (WFNS), Hunt & Hess (HH) and radiological scores (modified Fisher Scale (mFS), Subarachnoid Hemorrhage Early Brain Edema Score) (P 0.750), and had better results than radiological scores (P 0.700, with better performance than mFS (P 0.750), and were better than the radiological scores (P

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.

Ruthenium nanoparticles supported onto aluminum-doped mesoporous silica catalysts (Ru/Al–SBA-15) are fabricated using hydrothermal and impregnation methods for catalysis application. The Ru/Al–SBA-15-3 catalyst at a Si/Al molar ratio of 3 exhibited excellent catalytic performance for the hydrogenation of p-phthalic acid with high conversion efficiency (100.0%) and cis-isomer selectivity (84.0%) in water. Moreover, this system displays exceptional stability and recyclability through preserving the conversion efficiency, as well as a cis-isomer selectivity of 90.2 and 83.3%, respectively, after reusing it fourteen times. Such an exceptional system can also be ideal for the hydrogenation of aromatic dicarboxylic acids and their ester derivatives in water. Strong Lewis acid sites due to doped Al species play significant roles in the hydrogenation reaction. Moreover, isotope labeling studies indicated that water molecules effectively participated in the hydrogenation reaction. Hydrogen and water contributed half of the hydrogen atoms for this hydrogenation reaction. In the end, a plausible mechanistic pathway for the hydrogenation of p-phthalic acid using the Ru/Al–SBA-15-3 catalyst in water is proposed.

The first mandible and maxilla permanent molars are the first permanent teeth that grow next to the deciduous teeth and may decay due to carelessness. Their caries can spread to the pulpal tentacles and cause pulpal and periapical diseases. In the current study, we tried to compare the curative effect of different retrograde filling materials, i.e. white MTA, gray MTA, Portland cement, and IRM, in young permanent molar root canal therapy. Because IL-1β stimulates bone degradation by osteoclasts, IL-1β gene expression was also measured for further evaluation. For this purpose, 400 students (240 boys and 160 girls) aged 8 to 11 years referred to the Pediatric Dental Center for first permanent molar root canal therapy were selected during two years. After recording the demographic characteristics of each patient, the first permanent molar teeth were examined by a general dentist with Abslang and decayed teeth were considered to have both discolorations in their grooves and apparent opacity. The patients, who need root canal therapy, were divided into four groups. The first group was treated with gray MTA. The second group was treated with white MTA. The third group received Portland cement for root canal therapy. The fourth group was treated with IRM. Also, IL-1β gene expression was evaluated by the real-time PCR technique. Relative changes in gene expression in PBMC cells were performed using One Way ANOVA. SPSS 18 software was used to determine the correlation of gene expression in PBMCs. The results showed that there was no significant difference between the groups in terms of age (p = 0.12) and gender (p = 0.24). Also, the need for endodontic treatment in the mandible (n = 278) was higher than the maxilla (n = 85) and both jaws (n = 37). But there was no significant difference between the groups in terms of the need for endodontic treatment (p = 0.32). The results of Pearson correlation coefficients between studied groups in terms of IL-1β gene expression showed that gray MTA and white MTA were not statistically different, but MTAs were generally different from Portland cement and IRM, with higher IL-1β gene expression. In general, the results showed that the teeth in the vicinity of gray MTA and white MTA showed a more appropriate response than Portland cement and IRM, so the use of MTA and its preference over other materials is recommended. In the case of Portland cement, more studies are needed to reach a conclusion comparing this material with MTA.

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.

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 Conclusions Serum Cr/CysC ratio can be used accurately, inexpensively, and easily to evaluate sarcopenia in male patients with gastric cancer. Our study shows that patients with Cr/CysC below 0.67 had possibility of sarcopenia and would be poor prognosis.

Objective: We aimed to evaluate anatomical and functional outcomes and determine posterior scleral contraction (PSC) timing in treating myopic traction maculopathy (MTM). Methods: This is a retrospective study of MTM patients undergoing PSC with genipin cross-linked strip at a single hospital site. Differences in demographic and clinical characteristics were compared among three groups defined by the MTM staging system. All patients were followed up for at least one year postoperatively. The best-corrected visual acuity (BCVA), macular hole diameter, axial length (AL), optical coherence tomography findings, and the complications were evaluated. Additionally, regression analyses were performed to account for confounders. Results: Sixty-one MTM patients (24 eyes at stage 2, 22 eyes at stage 3, and 18 eyes at stage 4) were included. The macular holes were closed in 16 eyes (66.7%), 13 eyes (59.0%), and 11 eyes (61.1%) at stage 2, stage 3, and stage 4, respectively. PSC improved the BCVA in patients at each stage (all P < 0.05). Postoperative BCVA at stage 2 was significantly better than that at stage 4 (P = 0.0069). Preoperative BCVA was associated with postoperative BCVA (P < 0.001). Preoperative AL (OR 0.676, 95% CI 0.480 to 0.951, P = 0.025), AL shortening amount (OR 5.129, 95% CI 1.974 to 13.327, P = 0.001) and macular hole diameter (OR 1.003, 95% CI 1.000 to 1.006, P = 0.030) were associated with macular hole closure. Conclusions: PSC is safe and effective in treating MTM at different stages. Early PSC intervention will have more significant visual benefits.

Jingwei Zheng,1,&ast; Jingsong Huang,2,&ast; Wei Ma,3 Wenqiang Yang,3 Bicheng Hu3 1Clinical Medical College of Jilin University, Changchun, 130012, People’s Republic of China; 2Department of Transfusion, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361101, People’s Republic of China; 3The Central Laboratory, Wuhan No.1 Hospital, the Hospital of Traditional Chinese and Western Medicine Affiliated to Hubei University of Chinese Medicine, Wuhan, 430022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bicheng HuThe Central Laboratory, Wuhan No.1 Hospital, the Hospital of Traditional Chinese and Western Medicine Affiliated to Hubei University of Chinese Medicine, Wuhan, 430022, Hubei, People’s Republic of ChinaTel/Fax +86 27-85332367Email hubicheng211@sina.comBackground: Genetically T cells modified with cancer-specific chimeric antigen receptors (CARs) showed great promise in mediate tumor regression, especially in patients with advanced leukemia. However, the therapeutic effect against solid tumors is not as prominent as anticipated to exhibit potent antitumor efficacy. The underlying mechanism maybe attributed to the inhibitory co-stimulatory pathways such as (PD1/PDL1), which provide tumor cells an escape mechanism from immunosurveillance. Therefore, by exchanging the transmembrane and cytoplasmic tail of PD1 with positive costimulatory molecules, such as CD28 and 4– 1BB signaling domains (PD1-CD28-4-1BB, PD1-CAR), the T cell-negative co-stimulatory PD1/PDL1 signal pathway was thus converted into a positive one. This study aimed to investigate whether the genetically modified CAR-T-PD1 cells activated by SOCS1 silenced DCs have enhanced anti-neoplastic potential in vitro/in vivo.Methods: In order to enhance the antigenicity and reduce transformation activity, a modified HPV16 E7 (HPV16mE7) was employed to load on dendritic cells (DCs) with SOCS1 silenced to improve its antitumor efficiency and targeting ability against cervical cancer. The CAR-T-PD1 cells activated by the generated DCs were transfused into murine models bearing tumor of CaSki cells that expressing PDL1 and HPV16 E6/E7 for in vitro/in vivo antitumor activity assay.Results: The data showed that DC-activated CAR-T-PD1 cells significantly increased the secretion of IL-2, IFN-γ and TNF-α, whilst enhanced cytotoxic activity, suppressed tumor growth and prolong the survival time compared with the controls.Conclusion: These results indicated that the genetically engineered T cells activated by DCs had improved antitumor efficiency and targeting ability. Furthermore, it was suggested that it may have important implications for the improvement of T cell immunotherapy against cervical cancer.Keywords: PD1/PDL1, CAR-T, dendritic cells, suppressor of cytokine signaling 1, cervical cancer

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 ResultsThe diagnostic accuracy of the radiologic tumor invasion score was consistent in the training and verification groups (pConclusionsRadiological tumor invasion index based on splenic imaging combined with other factors accurately predicts serosal invasion of gastric cancer, increases diagnostic precision for the most effective treatment, and is time-efficient.

Identification of risk factors for recurrence of tenosynovial giant cell tumors of the hand is crucial to provide adequate preoperative counseling and tailor surgical treatment. However, the risk factors are still controversial, which are the subject of this research.Recently, we conducted a retrospective cohort study of 135 consecutive patients with giant cell tumors of the tendon sheath of the hand from January 2010 to July 2016. All patients underwent surgical excision, received necessary imaging examinations, and had routine follow-up and thus were identified as those who had recurrence by confirmation of reoperation, and the duration ranged from 24 to 103 months (mean, 53.5 ± 21.4 months). There were 14 local recurrences (10.4%) within 6 to 24 months, respectively, after surgery. Data pertaining to sex, age, tumor sites, tumor size, tumor number, course of disease, bone erosion, tumor growth patterns, anesthesia mode, and the surgeon's experience were all extracted, and Cox regression models were used to estimate recurrence rate with adjustment for potential confounders.According to the Cox regression analysis, the recurrence rate after surgery was significantly higher in patients with a diffused form than in those with a localized one (P = 0.001); in addition, patients with 2 or more tumors had a much higher postoperative recurrence rate than did those with only 1 tumor (P = 0.023).This study suggested that the recurrence rate of tenosynovial giant cell tumors of the hand was closely related to the tumor number and tumor growth patterns.

The aim was to compare the repeatability of subjective accommodative amplitude (AA) measurements obtained using the modified push-up and minus-lens methods and determine the agreement with objective AA by an autorefractor.The right eyes of 47 adults aged 22-30 years (mean 25.1 ± 1.9) were measured by subjective AA using the modified push-up and minus-lens methods. Subjective AAs with first sustained blur and unreadable criteria were obtained with an average of three consecutive measurements. Measurements of the objective AA were simulated by the minus lens using an open-field autorefractor. The repeatability of two subjective AA methods and the agreement among the different methods was assessed.The AA value was dependent on the measuring method (F = 139.68, p 0.001). The AA of the minus-lens method with first sustained blur criterion (10.10 ± 1.71 D) was closest to the objective AA (9.01 ± 1.49 D). The minus-lens method with unreadable criterion had the best repeatability. The agreement between the minus-lens method and the objective methods was better than that between the modified push-up and the objective methods based on the difference and 95 per cent limits of agreement. The agreement was highest between the minus-lens method with the first sustained blur criterion and the objective method, which had the lowest average difference and a narrow 95 per cent limits of agreement.The subjective minus-lens method was more accurate for assessing the subjective AA in adults than the modified push-up method. The minus-lens method with the first sustained blur criterion was the optimal method for subjective AA. The minus-lens method with unreadable criterion can also be applied to clinical measurements, although it was approximately 0.95 D larger than the minus-lens method with the first sustained blur criterion.

Intracerebral hemorrhage (ICH) is a stroke subtype that is associated with high mortality and disability rate. Mitochondria plays a crucial role in neuronal survival after ICH. This study first showed that activation of adiponectin receptor 1 (AdipoR1) by AdipoRon could attenuate mitochondrial dysfunction after ICH. In vivo, experimental ICH model was established by autologous blood injection in mice. AdipoRon was injected intraperitoneally (50 mg/kg). Immunofluorescence staining were performed to explicit the location of AdipoR1, AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-γ coactivator-1a (PGC1α). The PI staining was used to quantify neuronal survival. The expression of AdipoR1 and its downstream signaling molecules were detected by Western blotting. In vitro, 10 μM oxyhemoglobin (OxyHb) was used to induce the neuronal injury in SH-SY5Y cells. Annexin V-FITC/PI staining was used to detect the neuronal apoptosis and necrosis. Mitochondrial membrane potential (Δψm) was measured by a JC-1 kit and mitochondrial mass was quantified by mitochondrial fluorescent probe. In vivo, PI staining showed that the administration of AdipoRon could reduce neuronal death at 72 h after ICH in mice. AdipoRon treatment enhanced ATP levels and reduced ROS levels in perihematoma tissues, and increased the protein expression of AdipoR1, P-AMPK, PGC1α, NRF1 and TFAM. In vitro, the JC-1 staining and Mito-tracker™ Green showed that AdipoRon significantly alleviated OxyHb-induced collapse of Δψm and enhanced mitochondrial mass. Moreover, flow cytometry analysis indicated that the neurons treated with AdipoRon showed low necrotic and apoptotic rate. AdipoRon alleviates mitochondrial dysfunction after intracerebral hemorrhage via the AdipoR1-AMPK-PGC1α pathway.

According to analysing the trends of land use changes in the upper reaches of Minjiang River in the past 30 years and precipitation in the last 50 years, nine types of simulation scenarios were constructed for different precipitation conditions and urbanization development processes. Based on the “five sub-basin selection principles” and “two simulation results evaluation indicators” proposed, the paper studied the influence of the urbanization process on hydrological processes under different precipitation conditions using the SWAT model. The primary conclusions are as follows: (1) the simulation results under the two kinds of land use transfer scenarios show the same laws: (a) when forest land (or grassland) is transferred to urban land, actual evapotranspiration (ET), soil water content (SW), amount of water percolating out of root zone (PERC) and groundwater contribution to streamflow (GW_Q) show a decreasing trend, and the reduction in watershed hydrological indexes is manifested as “high precipitation > average precipitation > low precipitation”. Moreover, surface runoff (SURQ), water yield (WYLD) and annual runoff show an increasing trend, and the increment in SURQ shows “high precipitation > average precipitation > low precipitation”, while the increment in WYLD and the simulated annual runoff show “low precipitation > average precipitation > high precipitation”. (b) Through analysis of the contribution of unit proportion transfer (CUPT) of watershed hydrological indicators, “SURQ > PERC > GW_Q > ET > SW” is observed in all precipitation scenarios. (2) Comparing simulation results between the two kinds of land use transfer scenarios: the CUPT variations of ET, SURQ and WYLD and the contribution of unit area transfer variations of daily flood peak and annual runoff both show “forest land transfer to urban land > grassland transfer to urban land”. Finally, two special phenomena observed in the analysis of the simulation results were discussed. The study results can provide a scientific basis for urban planning and construction for reducing the impact on urban flood.

Numerical simulation models are commonly used to analyze and simulate urban waterlogging risk. However, the computational efficiency of numerical models is too low to meet the requirements of urban emergency management. In this study, a new method was established by combining a long short-term memory neural network model with a numerical model, which can quickly predict the waterlogging depth of a city. First, a numerical model was used to simulate and calculate the ponding depth of each ponding point under different rainfall schemes. Using the simulation results as training samples, the long short-term memory neural network was trained to predict and simulate the waterlogging process. The results showed that the proposed “double model” prediction model appropriately reflected the relationship between the changes in waterlogging depth and the temporal and spatial changes in rainfall, and the accuracy and speed of computation were higher than those of the numerical model alone. The simulation speed of the “double model” was 324,000 times that of the numerical model alone. The proposed “double model” method provides a new idea for the application of artificial intelligence technology in the field of disaster prevention and reduction.

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.

PURPOSE To report the clinical outcomes and evaluate the efficacy of a novel bubble ultra-wide field viewing system for vitreoretinal surgery. DESIGN Prospective, noncomparative, interventional case series. PARTICIPANTS One hundred and fifty-one eyes of 146 consecutive patients with proliferative diabetic retinopathy (PDR), vitreous haemorrhage originating from retinal vein occlusion (VH-RVO), epiretinal membrane (EM), macular hole (MH) or retinal detachment (RD) who underwent vitreoretinal surgery using the bubble ultra-wide field viewing system were included. METHODS A standard phacoemulsification was performed on each patient. Core humour and mid-peripheral vitreous humour were removed using a planoconcave lens. A suitably sized bubble was infused to attach to the posterior capsule or the anterior chamber depending on the integrity of the posterior capsule. The planoconcave lens and the air bubble formed the wide-angle viewing system, through which peripheral vitrectomy was performed. MAIN OUTCOME MEASURES Range of applications, field of view, model validation and complications were recorded. RESULTS The new ultra-wide field viewing system was successfully applied in all eyes, including 34 with PDR, 28 VH-RVO, 28 EM, 25 MH and 36 RD. Peripheral vitrectomy, local or panretinal laser photocoagulation, and removal of the peripheral proliferative membrane were successfully performed while viewing through this system. Maximum peripheral retinal area observable during the procedure was positively correlated with pupil diameter. Model analysis results showed that when the pupil diameter was 6 mm, the maximum field of view was approximately 128.1- 148.0 degrees with this system. Of 142 eyes, the main intraoperative complication was iatrogenic retinal breaks (IRBs) in 8 eyes (5.3%) and posterior capsule injury by vitreous cutter during bubble removal in 6 eyes (4.2%). The postsurgery mean best-corrected visual acuity (BCVA) (0.48 ± 0.39 logMAR) was significantly improved compared with the preoperative mean BCVA (1.60 ± 1.08 logMAR, p

PurposeTo explore the association between constitution types as defined by traditional Chinese medicine (TCM) and risk for normal-tension glaucoma (NTG).DesignPopulation-based cohort study.MethodsPersons were identified in a population cohort aged ≥30 years with NTG, defined as having an untreated mean intraocular pressure measurement ≤21 mm Hg over six separate occasions, with no single reading >24 mm Hg (as in the Collaborative Normal Tension Glaucoma Study). The Body Constitution in Traditional Chinese Medicine Questionnaire was used to assess each participant’s TCM constitution types. The association between various constitutions and visual field progression according to Early Manifest Glaucoma Trial criteria was assessed using Cox regression HR models.ResultsAmong 142 participants (245 eyes), 23 persons (17.6%) and 25 eyes (10.2%) progressed, over a mean (SD) follow-up duration of 3.49 (0.99) years. Progression rates were highest in participants with Yang-deficient constitution (n=19, 13.4%), among whom 7 (36.8%) exhibited worsening fields. After adjusting for sex, age, central corneal thickness, retinal nerve fibre layer thickness and mean deviation on visual field testing, Yang-deficient constitution (HR 4.63, 95% CI 1.77 to 12.1, p=0.002) and higher mean intraocular pressure during follow-up (HR 1.25, 95% CI 1.01 to 1.56, p=0.044) were associated with field progression.ConclusionsYang-deficient constitution and higher intraocular pressure are risk factors for visual field progression in NTG patients. Yang deficiency is characterised by abnormal vasoregulation, and these results may be consistent with prior studies linking NTG progression to Raynaud’s phenomenon and migraine.

The data directly comparing the spatial pattern of VF defects between primary angle-closure glaucoma (PACG), high-tension glaucoma (HTG) and normal-tension glaucoma (NTG) is not available. We aim to compare the asymmetric patterns of VF defects in 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 examinations were performed with standard automated perimetry (HFA, SITA-standard strategy, 24-2), and defects were categorized into 3 stages (early, moderate, and advanced) and each hemifield was divided into 5 regions according to Glaucoma Hemifield Test (GHT). The mean total deviation (TD) of each GHT region was calculated. The relationship between the values of pattern standard deviation (PSD) and mean TD was assessed. In the early stage, nasal region of PACG, central region of HTG and all five regions of NTG in the superior hemifield had significantly worse mean TD than their counterparts in the inferior hemifield. In the moderate stage, three regions of NTG in the superior hemifield had significantly worse mean TD than their inferior counterparts. In the advanced stage, central region of PACG, and central and paracentral regions of HTG in the superior hemifield had significantly worse mean TD than their inferior counterparts. When participants were matched by age, sex and mean deviation, in PACG and HTG eyes, all 5 GHT regions in the superior hemifield had worse mean TD than that that of their inferior-hemifield counterparts; however, the differences were not statistically significant. In NTG eyes, the paracentral, nasal, arcuate 1 and arcuate 2 regions in the superior hemifield had significantly worse mean TDs than their inferior counterparts. The superior hemifield is affected more severely than the inferior hemifield in all 3 subtypes of primary glaucoma. This asymmetric tendency was more pronounced in NTG compared to PACG and HTG.

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.

Background: To develop and validate a risk-scoring model for predicting severe COVID-19 at presentation. Methods: Entire patients with COVID-19 in three cities in Zhejiang, China from December 2019 to February 2020 were analyzed retrospectively. The risk-scoring model was developed with nomogram using multivariate logistic regression and externally validated by the patients from two other cities near Wenzhou. Findings: Severe COVID-19 was detected 58 out of 488 (11·9%) eligible patients in the primary cohort and 24 out of 153 (15·7%) in the validation cohort. The sex (OR 4·11, 95% CI 1·38 to 14·05), body mass index >25 kg/m2 (OR 6·14, 95% CI 2·05 to 21·29), hypertension (OR 4·97, 95% CI 1·73 to 15·37), neutrophil/lymphocyte ratio (3-6) (OR 8·04, 95% CI 2·51 to 29·52), albumin (35-40) g/L (OR 37·96, 95% CI 5·49 to 825·34) and platelets >300×109/L (OR 6·76, 95% CI 1·55 to 32·47) were independent predictors of severe COVID-19. The risk-scoring model-PAINTS performed excellent discrimination with AUC 0·98, 95% CI 0·96 to 1·00 in the primary cohort and AUC 0·78 (95% CI, 0·67 to 0·89) in the validation cohort. Interpretation: PAINTS score may guide clinical decision-making efficiently and allocate limited medical resources reasonably. Funding: The National Key New Drug Creation and Manufacturing Program, Ministry of Science and Technology (CN) [2020ZX09201002]; Wenzhou Science and Technology Key Problem Program [ZY2020001]; The Primary Research and Development Plan of Zhejiang Province [2019C03011] and the Natural Science Foundation of Zhejiang Province [LQ20H150002]. Declaration of Interest: None to declare. Ethical Approval: The study was conducted under the amended Declaration of Helsinki and approved by the Institutional Review Board (IRB) of Wenzhou Medical University (No.2020-002). The written consent was waived by the Institutional Review Board (IRB) of Wenzhou Medical University (No.2020-002)

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.

Additional file 3: Supplementary Figure 3. (A) Low-magnification images indicate the region of interest for immunofluorescent staining of CD16/32 or CD206 (red), Iba-1 (Green) and DAPI (blue) in the ipsilateral cortex from the sham, TBI + Vehicle, TBI + Control siRNA and TBI+Mer siRNA groups on day 3 post-injury, respectively. (B) Low-magnification images indicate the region of interest for Nissl staining in the ipsilateral cortex from the sham, TBI + Vehicle, TBI + Control siRNA and TBI+Mer siRNA groups on day 3 post-injury, respectively. (C) Low-magnification images indicate the region of interest for Fluoro-Jade B (FJB) staining in the ipsilateral cortex from the sham, TBI + Vehicle, TBI + Control siRNA and TBI+Mer siRNA groups on day 3 post-injury, respectively. In A-C, the red dotted area indicates contusion region. * indicates region of interest. Scale bar = 1 mm.

Additional file 6: Supplementary Figure 6. (A) Cerebral edema was measured by brain water content. Quantification analysis showing TBI increased brain edema in the ipsilateral hemisphere on day 3 after TBI, which is significantly alleviated after PS treatment. n = 8 mice per group. (B) Representative images of Nissl staining in the ipsilateral cortex from the sham, TBI + Vehicle (TBI + V), TBI + protein S (TBI + PS) groups, respectively. (C) Quantification analysis showing TBI caused a significant decrease in the number of Nissl-positive cells in the ipsilateral cortex at 3 d post-TBI, and PS application significantly increased the number of Nissl-positive cells in the injured cortex after TBI. n = 6 mice per group. Scale bar = 20 μm. (D) Representative images of Fluoro-Jade B (FJB) staining in the ipsilateral cortex from the sham, TBI + V, TBI + PS groups, respectively. (E) Quantification analysis showing TBI caused a significant increase in the number of FJB-positive cells in the ipsilateral cortex at 3 d post-TBI, and PS application significantly decreased the number of FJB-positive cells in the injured cortex after TBI. n = 6 mice per group. Scale bar = 15 μm. In A, C, E, data are presented as Mean ± SD; **, p < 0.01; ***, p < 0.001. one-way ANOVA followed by Bonferroni’s post-hoc tests.

Additional file 4: Supplementary Figure 4. (A) Modified neurological severity scores (mNSS), (B) foot-fault test, and (C) rotarod test were performed before and 1, 3, and 7 d after TBI. n = 8 mice per group. (D) Representative immunoblots and quantification showing the expression level of Mer protein in the injured cortex at 3 d after TBI or the equivalent area of the sham-operated brains. Data are expressed as fold change compared to sham-operated controls. n = 6 mice per group. M: male; F: female. (E) Quantitative RT-PCR was used to assess the mRNA expression level of Mer in the injured cortex at 3 d after TBI or the equivalent area of the sham-operated brains. Data are expressed as fold change compared to sham-operated controls. n = 6 mice per group. In A-E, data are presented as mean ± SD; ***, p < 0.001; ns, non-significant, p > 0.05. two-way ANOVA followed by Bonferroni’s post-hoc tests.

Additional file 2: Supplementary Figure 2. Experimental design and animal groups. (A) Western blot (WB) and Real-Time Polymerase Chain Reaction (RT-PCR) were performed to evaluate the expression profiles of Mer and M1/M2 polarization markers at different time points after TBI (including 3 h, 12 h, 1 d, 3 d, and 7 d), as well as in the sham group; Besides, immunofluorescence was performed on day 3 after injury. (B) An in vivo knockdown of Mer siRNA was adopted to evaluate the role of Mer in regulating microglial/macrophage M1/M2 polarization after TBI. Mice were randomly distributed into sham, TBI + Vehicle, TBI + Control siRNA, and TBI + Mer siRNA groups. Intracerebroventricular injection (i.c.v.) of siRNA was performed 1 d before and 10 min after TBI. The neurobehavioral functions were assessed before as well as 1, 3, 7 d after TBI. The peri-injured cerebral cortex from each group and the equivalent area in the sham-operated mice was collected for RT-PCR, WB, and immunohistochemistry analysis at 3 d after TBI. Also, contusion volume, brain edema, neuronal damage and degeneration were measured at 3 d after injury. (C) To evaluate the effect of PS on regulating STAT1/SOCSs pathway after TBI, mice were randomly distributed into Sham, TBI + Vehicle, and TBI + recombinant protein S (PS) groups. PS (0.2 mg/kg) was administered via the tail vein at 1 h, 1 d, and 2 d after the CCI. WB, RT-PCR, MACS, neuronal damage and degeneration, brain edema, and neurobehavioral assessments were conducted on day 3 post-injury. (D) Mice were randomly distributed into TBI + Vehicle, TBI + PS + Control siRNA, and TBI + PS + Mer siRNA groups. Mer siRNA (i.c.v.) was administrated 1 d before and 10 min after TBI, and PS was administered via the tail vein at 1 h, 1 d, and 2 d after the injury. WB and neurobehavioral assessments were conducted on day 3 post-injury.

This paper focuses on the use of embedding with global semantic relations to improve the cross modal retrieval. Our method smoothly bridges the heterogeneity gap by graph embedding and then obtains discriminative representation by supervised learning. First, we construct a semantic correlation graph based on the intra-modal similarity and the semantic propagation of pairwise information. Then, embeddings are learnt from the graph semantic structure which enables all the cross-modal data to be mapped into the same space. Second, based on the previous embeddings, we adopt a simple one-branch neural network to enhance the discrimination of the representation by minimizing the discrimination loss and reconstruction loss. Experimental results on three widely-used benchmark datasets clearly demonstrate the improvement of the proposed approach over the state-of-the-art cross-modal retrieval methods.

Additional file 1: Figure S1. Sample size and grouping information. Figure S2. Colloidal stability of PEG-CeNPs and normal CeNPs. Figure S3. Representative images of CD1632/Iba1 and CD206/Iba1 double immunostaining at 7 days post ICH. Lens: 200x; Scale bar: 100 μm. Figure S4. Representative images of CD1632/Iba1 and CD206/Iba1 double immunostaining at 21 days post ICH. Lens: 200x; Scale bar: 100 μm. Figure S5. Representative images of olig2+ cells and EdU+ cells at 7 days post ICH. * p

Additional file 5: Supplementary Figure 5. (A) Fluorescence intensity quantification of Mer expression in CD16/32- and CD206- positive cells in the impacted ipsilateral cortical area at 3 d after TBI. n = 6 per group. (B-G) Quantitative RT-PCR analysis showing mRNA expression of CD16 (B), CD32 (C), iNOS (D), CD206 (E), Arg-1 (F), IL-10 (G) in the injured cortex at 3 d post-TBI. GAPDH: loading control. Data are expressed as fold change compared to the sham group; n = 6 mice per group. In A, data are presented as Mean ± SD; ***, p < 0.001 by Student’s t-test. In B-G, data are presented as Mean ± SD; ***, p < 0.001. one-way ANOVA followed by Bonferroni’s post-hoc tests.

Additional file 1: Supplementary Figure 1. (A-B) The controlled cortical impact (CCI) model of TBI and experimental parameters in mice. (C) A schematic map showing the location of TBI in mice. The center of impact was located at 2 mm medial-lateral (ML) and -2 mm anterior-posterior (AP) to bregma. (D-E) The intracerebroventricular (i.c.v) injection and experimental parameters in mice. (F) A schematic map showing coordinates of i.c.v. injection in mice. The stereotaxic coordinates are 1 mm ML and -0.25 mm AP to bregma, and 2.5 mm dorsoventral (DV) below the skull. LV: lateral ventricle.