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Abstract Introduction To assess the safety and efficacy of repeated intravitreal injections of RC28-E, a novel bispecific antibody that simultaneously binds vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in patients with neovascular age-related macular degeneration (AMD). This was a prospective, multicenter, open-label clinical trial; 37 patients with choroidal neovascularization secondary to AMD and best-corrected visual acuity (BCVA) letter scores between 73 and 34 were enrolled. Methods Treatment regimens consisted of a 3-month loading phase and a pro re nata (PRN) maintenance phase. This study included three treatment groups: the 0.5, 1.0, and 2.0 mg RC28-E groups, with escalating doses ranging from 0.5 to 2.0 mg. Patients were evaluated monthly for 48 weeks. Safety was assessed based on ocular and systemic adverse events (AEs), pharmacokinetic characteristics, and the presence of anti-RC28-E antibodies. Efficacy was assessed using the mean change in BCVA and central subfield thickness (CST) from baseline to week 48. Results Most AEs were mild or moderate. The most common AE was a minor injection-related subconjunctival hemorrhage (16.2%). The AEs did not increase with dose or repeated injections. At week 48, mean improvements in BCVA from baseline in the 0.5, 1.0, and 2.0 mg groups were 6.1 ± 8.3, 9.9 ± 10.7, and 7.6 ± 9.38 letters, respectively; mean reductions in CST in the three groups were 112.1 ± 160.5, 175.1 ± 212.4, and 128.7 ± 145.8 μm, respectively. The serum RC28-E concentrations in 95% of the patients were below the quantification limit of the assay. No significant change from baseline was observed in the mean plasma concentrations of VEGF or FGF over the 48 weeks of treatment. Pre-treatment antibodies to RC28-E were detected in 1 of the 37 patients. Antibodies to RC28-E were detected in two patients after dosing with RC28-E for 48 weeks. Conclusion RC28-E was well tolerated and exhibited an overall favorable safety profile with evidence of improvements in BCVA and anatomical parameters.

Abstract Objective To investigate the effect of bone cement on the vertebral body and biomechanical properties in percutaneous cement discoplasty (PCD) for degenerative lumbar disc disease. Methods Three-dimensional reconstruction of L2 ~ L3 vertebral bodies was performed in a healthy volunteer, and the corresponding finite element model of the spine was established. Biomechanical analysis was performed on the changes in stress distribution in different groups of models by applying quantitative loads. Results Models with percutaneous discoplasty (PCD) showed improved stability under various stress conditions, and intervertebral foraminal heights were superior to models without discoplasty. Conclusion Cement discoplasty can improve the stability of the vertebral body to a certain extent and restore a certain height of the intervertebral foramen, which has a good development prospect and potential.

BackgroundIntervertebral Disc Degeneration (IDD) is a major cause of lower back pain and a significant global health issue. However, the specific mechanisms of IDD remain unclear. This study aims to identify key genes and pathways associated with IDD using bioinformatics and machine learning algorithms.MethodsGene expression profiles, including those from 35 LDH patients and 43 healthy volunteers, were downloaded from the GEO database (GSE124272, GSE150408, GSE23130, GSE153761). After merging four microarray datasets, differentially expressed genes (DEGs) were selected for GO and KEGG pathway enrichment analysis. Weighted Gene Co-expression Network Analysis (WGCNA) was then applied to the merged dataset to identify relevant modules and intersect with DEGs to discover candidate genes with diagnostic value. A LASSO model was established to select appropriate genes, and ROC curves were drawn to elucidate the diagnostic value of genetic markers. A Protein-Protein Interaction (PPI) network was constructed and visualized to determine central genes, followed by external validation using qRT-PCR.ResultsDifferential analysis of the preprocessed dataset identified 244 genes, including 183 upregulated and 61 downregulated genes. WGCNA analysis revealed the most relevant module intersecting with DEGs, yielding 9 candidate genes. The lasso-cox method was used for regression analysis, ultimately identifying 6 genes: ASPH, CDC42EP3, FOSL2, IL1R1, NFKBIZ, TCF7L2. A Protein-Protein Interaction (PPI) network created with GENEMANIA identified IL1R1 and TCF7L2 as central genes.ConclusionOur study shows that IL1R1 and TCF7L2 are the core genes of IDD, offering new insights into the pathogenesis and therapeutic development of IDD.

Insulin resistance (IR) is becoming a worldwide medical and public health challenge as an increasing prevalence of obesity and metabolic disorders. Accumulated evidence has demonstrated a strong relationship between IR and a higher incidence of several dramatically vision-threatening retinal diseases, including diabetic retinopathy, age-related macular degeneration, and glaucoma. In this review, we provide a schematic overview of the associations between IR and certain ocular diseases and further explore the possible mechanisms. Although the exact causes explaining these associations have not been fully elucidated, underlying mechanisms of oxidative stress, chronic low-grade inflammation, endothelial dysfunction and vasoconstriction, and neurodegenerative impairments may be involved. Given that IR is a modifiable risk factor, it may be important to identify patients at a high IR level with prompt treatment, which may decrease the risk of developing certain ocular diseases. Additionally, improving IR through the activation of insulin signaling pathways could become a potential therapeutic target.

Differential evolution algorithm is a very powerful and recently proposed evolutionary algorithm. Generally, only a mutation operator and predefined parameter values of differential evolution algorithm are utilized to solve various optimization problems, which limits the performance of the algorithm. In this paper, six commonly used mutation operators are divided into three categories according to their own features. A mutation pool is established based on the three categories. A parameter pool with three predefined values is designed. During evolution, three mutation operators are randomly chosen from the three categories, and three parameter values are also randomly selected from the parameter pool. The three groups of mutation operators and parameter values are employed to produce trial vectors. The proposed algorithm makes good use of different mutation operators. Three recently proposed differential evolution variants and three non-differential evolution algorithms are used to make comparisons on the 29 testing functions from CEC. The experimental results have demonstrated that the proposed algorithm is very competitive. The proposed algorithm is utilized to solve three real applications, and the results are superior.

Background. Psoriasis, a systemic disorder mediated by the immune system, can appear on the skin, joints, or both. Individuals with cutaneous psoriasis (PsC) have an elevated risk of developing psoriatic arthritis (PsA) during their lifetime. Despite this known association, the cellular and molecular mechanisms underlying this progression remain unclear. Methods. We performed high-dimensional, in-depth immunophenotyping of peripheral blood mononuclear cells (PBMCs) in patients with PsA and psoriasis vulgaris (PsV) by mass cytometry. Blood samples were collected before and after therapy for a longitudinal study. Then three sets of comparisons were made here: active PsA vs. active PsV, untreated PsV vs. treated PsV, and untreated PsA vs. treated PsA. Results. Marked differences were observed in multiple lymphocyte subsets of PsA related to PsV, with expansion of CD4+ T cells, CD16− NK cells, and B cells. Notably, two critical markers, CD28 and CD127, specifically differentiated PsA from PsV. The expression levels of CD28 and CD127 on both Naïve T cells (TN) and central memory CD4+ T cells (TCM) were considerably higher in PsA than PsV. Meanwhile, after treatment, patients with PsV had higher levels of CD28hi CD127hi CD4+ TCM cells, CD28hi CD127hi CD4+ TN cells, and CD16− NK cells. Conclusion. In the circulation of PsA patients, the TN and CD4+ TCM are characterized with more abundant CD28 and CD127, which effectively distinguished PsA from PsV. This may indicate that individuals undergoing PsV could be stratified at high risk of developing PsA based on the circulating levels of CD28 and CD127 on specific cell subsets.

Abstract Purpose To investigate early changes in the intraocular pressure (IOP) and macular microvascular structure in eyes with branch retinal vein occlusion (BRVO) treated with intravitreal Ranibizumab injection. Methods This study enrolled 30 patients (one eye per patient) who received intravitreal injections (IVI) of ranibizumab for macular edema secondary to BRVO. IOP were measured before, 30 min (min) and 1 month following IVI. Changes in macular microvascular structure were examined via assessment of foveal avascular zone (FAZ) parameters, vascular density (VD) of superficial vascular complex (SVC), and deep vascular complex (DVC) in whole macula, central fovea and parafovea area which were measured automatically by optical coherence tomography angiography (OCTA) on the same time as IOP examinations. Paired t test and Wilcoxon test were used to compare pre- and post-injection values. The correlation between IOP and OCTA findings was assessed. Results IOP Measurements at 30 min post-IVI (17.91 ± 3.36 mmHg) increased significantly from baseline (15.07 ± 2.58 mmHg, p 0.05). There were no significant correlations between IOP and OCTA findings no matter 30 min or 1 month post-IVI (P > 0.05). Conclusions Transient IOP elevation and decreased superficial macular capillary perfusion density were detected 30 min post-IVI, however, no potential continual macular microvascular damage was suspected.

BackgroundThis study aimed to develop deep learning models using macular optical coherence tomography (OCT) images to estimate axial lengths (ALs) in eyes without maculopathy.MethodsA total of 2,664 macular OCT images from 444 patients’ eyes without maculopathy, who visited Beijing Hospital between March 2019 and October 2021, were included. The dataset was divided into training, validation, and testing sets with a ratio of 6:2:2. Three pre-trained models (ResNet 18, ResNet 50, and ViT) were developed for binary classification (AL ≥ 26 mm) and regression task. Ten-fold cross-validation was performed, and Grad-CAM analysis was employed to visualize AL-related macular features. Additionally, retinal thickness measurements were used to predict AL by linear and logistic regression models.ResultsResNet 50 achieved an accuracy of 0.872 (95% Confidence Interval [CI], 0.840–0.899), with high sensitivity of 0.804 (95% CI, 0.728–0.867) and specificity of 0.895 (95% CI, 0.861–0.923). The mean absolute error for AL prediction was 0.83 mm (95% CI, 0.72–0.95 mm). The best AUC, and accuracy of AL estimation using macular OCT images (0.929, 87.2%) was superior to using retinal thickness measurements alone (0.747, 77.8%). AL-related macular features were on the fovea and adjacent regions.ConclusionOCT images can be effectively utilized for estimating AL with good performance via deep learning. The AL-related macular features exhibit a localized pattern in the macula, rather than continuous alterations throughout the entire region. These findings can lay the foundation for future research in the pathogenesis of AL-related maculopathy.

To explore the temporal and spatial characteristics of the torrential rain in Huaihe River basin,this article analyzed the average trend and period of the rainstorm frequency and intensity by the empirical mode decomposition method,and then analyzed the comprehensive danger and return period by the Copulas function based on the torrential rain days and maximum daily precipitation data for each year at 68 meteorological stations from 1951 to 2017. The results are as follows. (1) The rainstorm frequency of the whole basin firstly decreased and then increased in the study period,and the turning point occurred around 1980. The intensity has been showing a significant linear upward trend. The main periods of rainstorm frequency and intensity are both subject to 2 a. (2) For more than 90% of the torrential rain,the frequency is 3 days or less and the intensity is less than 100 mm. The increasing rate slows down significantly when exceeding these thresholds. The return period of torrential rain increases with the two single indexes increasing,and the rate gets faster gradually. (3) The high values of the spatial pattern of the average change trend for the two indicators are consistent. And the area ratios of the rising and falling trends of the two indicators are similar. (4) The spatial pattern of the mean and minimum values of the joint probability of the rainstorm is consistent,while the distribution of its maximum values is relatively dispersed. Although the frequency and intensity of rainstorms in some cities show downward trends,the mean and minimum values of the danger of the rainstorm hazard evaluated by joint probability are very high.

Abstract Background At present, intraocular injection of anti-VEGF (vascular endothelial growth factor) drugs has replaced traditional laser therapy as the first-line treatment for DME (diabetic macular edema). However, ranibizumab, a commonly used anti-VEGF drug, is expensive and requires multiple intraocular injections. It places a heavy economic burden on patients with DME. Micropulse laser is safer than conventional laser and can reduce edema. Combined treatment with anti-VEGF may reduce the number of intraocular injections. This study will compare the efficacy of micropulse laser combined with ranibizumab treatment to ranibizumab monotherapy in the treatment of DME, providing a new regimen for future DME treatment. Methods This study is a prospective randomized double-blind controlled clinical trial (RCT) in patients with DME. After 1-year follow-up, visual acuity and macular edema regression will be compared between micropulse laser combined with ranibizumab group and ranibizumab monotherapy group to determine whether the efficacy of micropulse laser combined with ranibizumab treatment was not lower than that of ranibizumab monotherapy in the treatment of DME. Visual acuity measured by the ETDRS chart is the primary outcome measure. The secondary outcome measures are CMT (central macular thickness) measured by OCT (optical coherence tomography) and the number of injections of two groups. Changes in visual acuity and CMT of the two groups will be compared at 12-month follow-up. Before patients are recruited, we provide them with informed consent, in which we explain to them the purpose and process of the study. Discussion Micropulse laser combined with anti-VEGF drugs in the treatment of DME can reduce the number of intravitreal anti-VEGF injections, not only relieve the pain of the patients, but also ease the economic and psychological burden of patients, bringing great benefits. However, there is no treatment consensus for the parameters and specific methods of micropulse laser treatment for DME. There is a lack of clinical research data reference of micropulse laser combined with anti-VEGF therapy in clinical practice. This study intends to provide a new direction for clinical DME treatment and also provide a realistic consideration for the application of micropulse laser in DME treatment. Trial registration ClinicalTrials.gov NCT03690947. Registered on 1 October 2018.

Objective: To investigate whether mineralized collagen modified polymethyl methacrylate (MC-PMMA) bone cement impacts the implanted vertebral body and adjacent segments and the feasibility of biomechanical properties compared with common bone cement in the treatment of osteoporotic vertebral compression fractures (OVCF).Methods: A healthy volunteer was selected to perform a three-dimensional reconstruction of the T11-L1 vertebral body to establish the corresponding finite element model of the spine, and the changes in the stress distribution of different types of cement were biomechanically analyzed in groups by applying quantitative loads.Results: The stress distribution of the T11-L1 vertebral body was similar between the two bone types of cement under various stress conditions.Conclusion: Mineralized collagen modified bone cement had the advantages of promoting bone regeneration, good biocompatibility, good transformability, and coupling, and had support strength not inferior to common PMMA bone cement, indicating it has good development prospects and potential.

PurposeA systematic review and meta-analysis was conducted to investigate changes in retinal and choroidal microvasculature in patients with multiple sclerosis (MS) using optical coherence tomography angiography (OCTA).MethodsPubMed and Google Scholar were searched for studies that compared retinal and choroidal microvasculature between MS and healthy controls (HC) with OCTA. MS patients were divided into 2 groups: MS with (MSON) or without optic neuritis (MSNON).ResultsTotally, 13 studies including 996 MS eyes and 847 HC eyes were included. Compared with the HC, the vessel density of the whole superficial vascular complex (SVC) was reduced by 2.27% and 4.30% in the MSNON and MSON groups, respectively. The peripapillary vessel density was 2.28% lower and 4.96% lower in the MSNON and MSON groups, respectively, than in the HC. Furthermore, the MSON group had significant lower vessel density of the SVC (mean difference [MD] = −2.17%, P < 0.01) and lower peripapillary vessel density (MD = −2.02%, P = 0.02) than the MSNON group. No significant difference was found in the deep vascular complex or choriocapillaris densities among MSNON, MSON or HC groups (P > 0.05). Meta-regression analyses suggested that illness duration and the Expanded Disability Status Scale scores of MS patients were possible sources of heterogeneity (P < 0.05).ConclusionThe retinal SVC and peripapillary vessel density decreased significantly in MS eyes, especially in eyes with optic neuritis. Retinal microvasculature is a potential biomarker of disease progression in MS.

This study proposes a new combined cooling, heating and power (CCHP) system applied for geothermal energy. In the proposed system, a water heater is introduced to utilize the exhaust geothermal water for supplying heating, and the throttled valve of the basic flash cycle is replaced by an ejector for cooling output. To evaluate the system performance, detailed mathematic models are established and validated. Based on the basic condition (170°C geothermal water), the exergy efficiency of the proposed system is 44.34% and the sum of the power, cooling output and heating output is 10,283.68 kW. Also, the exergy loss analysis demonstrates that the component of the water heater, ejector, turbine, condenser and flasher has a large improved space to reduce the exergy destructions for system performance enhancement. At last, the parametric analysis results suggest that there exists an optimal flash pressure (around 140 kPa) to maximize the exergy efficiency. Within the discussed ranges, both the increase of the outlet temperature of water heater and condenser temperature will damage the system exergy efficiency, while a higher evaporator temperature is beneficial for the system exergy efficiency.

The Arrhenius temperature integral is typically used in non-isothermal kinetic analysis, which is widely applied in gas–solid reactions in separation processes. In previous studies, researchers provided various methods to solve the temperature integral, but the error usually became significant when the value of x (x = Ea/RT) was too large or too small. In this paper, we present a new series method and design a computer program to calculate the temperature integral. According to the precise calculation of the temperature integral, we first reveal the relationship among the integral, the temperature, and the activation energy, and we find an interesting phenomenon in which the 3-D image of the temperature integral is of self-similarity according to fractal theory. The work is useful for mechanism and theoretical studies of non-isothermal kinetics.

Abstract In recent years, in Space-Ground-Sea Wireless Networks, the rapid development of image recognition also promotes the development of images fusion. For example, the content of a single-mode medical image is very single, and the fused image contains more image information, which provides a more reliable basis for diagnosis. However, in wireless communication and medical image processing, the image fusion effect is poor and the efficiency is low. To solve this problem, an image fusion algorithm based on fast finite shear wave transform and convolutional neural network is proposed for wireless communication in this paper. This algorithm adopts the methods such as fast finite shear wave transform (FFST), reducing the dimension of the convolution layer, and the inverse process of fast finite shear wave transform. The experimental results show that the algorithm has a very good effect in both objective indicators and subjective vision, and it is also very feasible in wireless communication.

Abstract Background How to obtain a small interfering RNA (siRNA) vector has become a moot point in recent years. Exosomes (Exo) show advantages of long survival time in vivo, high transmission efficiency, and easy penetration across the blood-spinal cord barrier, renowned as excellent carriers of bioactive substances. Methods We applied mesenchymal stem cell (MSC)-derived exosomes as the delivery of synthesized siRNA, which were extracted from rat bone marrow. We constructed exosomes-siRNA (Exo-siRNA) that could specifically silence CTGF gene in the injury sites by electroporation. During the administration, we injected Exo-siRNA into the tail vein of SCI rats, Results In vivo and in vitro experiments showed that Exo-siRNA not only effectively inhibited the expressions of CTGF gene, but quenched inflammation, and thwarted neuronal apoptosis and reactive astrocytes and glial scar formation. Besides, it significantly upregulated several neurotrophic factors and anti-inflammatory factors, acting as a facilitator of locomotor recovery of rats with spinal cord injury (SCI). Conclusions In conclusion, this study has combined the thoroughness of gene therapy and the excellent drug-loading characteristics of Exo for the precise treatment of SCI, which will shed new light on the drug-loading field of Exo.

Abstract Background To investigate the changes in retinal nerve fiber layer thickness and macular blood flow density during the preclinical stage of diabetic retinopathy and their relationship with blood glucose. Methods In this cross-sectional study, 97 diabetic patients (total of 188 eyes; 144 eyes in no diabetic retinopathy group, 44 eyes in mild diabetic non-proliferative retinopathy group) and 35 healthy people (70 eyes) were enrolled, All the subjects were divided into different groups based on their HbA1c levels, and they underwent optical coherence tomography angiography. We compared the optical coherence tomography angiography parameters and retinal nerve fiber layer thickness among the different glucose groups. Results The parafoveal vessel density and the temporal retinal nerve fiber layer thickness were lower (p

When disasters happen, victims suffer from lots of miseries. Vehicles are used to carry relief supplies for these victims. However, these vehicles are subject to threats as roads and bridges are often destroyed by these disasters. To dispatch vehicles safely and minimize the misery of victims, a disaster emergency vehicle path planning model is proposed by introducing the deprivation cost function and two constraints. One constraint is the risk of the route, and the other is the angle of the vehicle. A differential evolution algorithm based on the exponential selection is developed to optimize the model. The proposed algorithm uses the exponential ranking method, making individuals have exponential probability as parents enter into the mutation stage. The approach improves the exploitation capacity while maintain the exploration ability of the algorithm. Three disaster scenarios in three-dimension are used to do simulations. The experimental results have verified that our proposed model can deal well with the vehicle path planning problem in disaster emergency management. The proposed algorithm has acquired superior performances compared with differential evolution variant algorithms.

Abstract Background Nontraumatic osteonecrosis of the femoral head (NONFH) is a highly disabling orthopedic disease in young individuals. Plasminogen activator inhibitor 1 (PAI-1) has been reported to be positively associated with NONFH. We aimed to investigate the dysregulating PAI-1 in bone marrow mesenchymal stem cells (BMMSCs) and vascular cells in rabbit steroid-induced NONFH. Methods To verify the hypothesis that BMMSCs could promote thrombus formation in a paracrine manner, we collected exosomes from glucocorticoid-treated BMMSCs (GB-Exo) to determine their regulatory effects on vascular cells. microRNA sequencing was conducted to find potential regulators in GB-Exo. Utilizing gain-of-function and knockdown approaches, we testified the regulatory effect of microRNA in exosomes. Results The expression of PAI-1 was significantly increased in the local microenvironment of the femoral head in the ONFH model. GB-Exo promoted PAI-1 expression in vascular smooth muscle cells and vascular endothelial cells. We also revealed that miR-451-5p in GB-Exo plays a crucial role for the elevated PAI-1. Moreover, we identified miR-133b-3p and tested its role as a potential inhibitor of PAI-1. Conclusions This study provided considerable evidence for BMMSC exosomal miR-mediated upregulation of the fibrinolytic regulator PAI-1 in vascular cells. The disruption of coagulation and low fibrinolysis in the femoral head will eventually lead to a disturbance in the microcirculation of NONFH. We believe that our findings could be of great significance for guiding clinical trials in the future.

Abstract Background It is not clear whether macular laser combined with anti-vascular endothelial growth factor (VEGF) can reduce the number of anti-VEGF injections in the treatment of macular edema (ME) secondary to branch retinal vein occlusion (BRVO). Our study aimed to investigate the effects of intravitreal ranibizumab with or without macular laser for ME secondary to BRVO and its associated number of anti-VEGF injections. Methods This is a prospective, randomized, double-blind, monocentric trial.80 patients were enrolled and 64 patients fulfilled the study requirements. All patients received a minimum of 3 initial monthly ranibizumab injections, pro re nata (PRN) dosing thereafter VA and CRT stabilization criteria-driven PRN treatment. Laser was given 7 days after third ranibizumab injection in ranibizumab with laser group. The follow-up time of this study was 1 year. Best corrected visual acuity (BCVA) improvement, central retinal thickness (CRT) reduction and number of injections of patients were compared between two groups. T-test, non-parametric Wilcoxon test and chis-square tests were adopted for between-group comparisons. Results Thirty patients received intravitreal ranibizumab 0.5 mg alone and 34 patients received intravitreal ranibizumab 0.5 mg with macular laser. At 52 week, BCVA increased significantly and CRT decreased significantly in both groups (P 0.05). Conclusions Our study suggests that ranibizumab combined with macular laser is effective in the treatment of ME secondary to BRVO after 1 year of treatment with 3 + PRN regimen. However, combination of macular grid photocoagulation showed no beneficial anatomical or functional effect during follow-up period, nor did it reduce the number of ranibizumab injections, either in ischemic group or non-ischemic group. We suggest that there is no need to combine macular grid photocoagulation in the treatment of ME secondary to BRVO in the future. Trial registration Clinical Trials NCT03054766. https://register.clinicaltrials.gov .Prospectively registered.

Interactions among spinal dorsal horn neurons and microglia contribute to the induction and maintenance of neuropathic pain after peripheral nerve injury. The authors show that depletion of macrophages in the dorsal root ganglia prevents and reverses ongoing nerve injury-induced hypersensitivity.

Background. To study the changes of retinal vascular density (VD), retinal thickness (RT), and their correlations with visual acuity (VA) in branch retinal vein occlusion (BRVO) patients with retinal atrophy after resolution of macular oedema (MO). Methods. This is a retrospective study consisting of 46 patients diagnosed with BRVO at Beijing Hospital from 2015 to 2019. Patients’ 46 affected eyes and 39 fellow eyes were included. The affected eyes were further divided into the atrophy group and the nonatrophy group. Optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) images obtained when MO completely resolved after treatment with ranibizumab were analyzed. We quantitatively measured foveal avascular zone (FAZ) parameters, the disruption extent of ellipsoid zone (EZ), RT, and VD of superficial vascular complex (SVC), and deep vascular complex (DVC) in central fovea and the minimal-VD quadrant. Paired t-tests, independent t-tests, Mann–Whitney U tests, Wilcoxon tests, Pearson correlation analyses, Spearman correlation analyses, and single and multiple linear regression models were adopted. Results. Compared with nonatrophy eyes, the minimal-VD quadrantal (quadrantal for short) SVC-VD (25.76 ± 4.57% versus 36.21 ± 6.47%, P

Abstract Background There is no consensus on the optimal initial treatment for polypoidal choroidal vasculopathy (PCV). Our study aimed to report the efficacy of repeated injections of intravitreal ranibizumab with or without photodynamic therapy for the treatment of PCV and to determine the possible factors predictive of visual outcomes. Methods The results of the initial treatment of 40 patients with PCV with 3 monthly injections of ranibizumab were retrospectively reviewed. We compared the results in terms of the best corrected visual acuity (BCVA), the central retinal thickness (CRT), the number of injections, the regression rates of polyps and the rates of the reduction of subretinal fluid. Results At the 3-month follow-up, the mean BCVA was significantly increased by 7.3 ± 12.4 letters compared to baseline (p 0.05). The mean CRT at the 12-month follow-up was 593.58 ± 243.64 μm, with an average decrease of 101.55 ± 256.07 μm compared to baseline (p

Abstract. Molecular and cellular interactions among spinal dorsal horn neurons and microglia, the resident macrophages of the central nervous system, contribute to the induction and maintenance of neuropathic pain after peripheral nerve injury. Emerging evidence also demonstrates that reciprocal interactions between macrophages and nociceptive sensory neurons in the dorsal root ganglion contribute to the initiation and persistence of nerve injury-induced mechanical hypersensitivity (allodynia). We previously reported that sensory neuron-derived colony-stimulating factor 1 (CSF1), by engaging the CSF1 receptor (CSF1R) that is expressed by both microglia and macrophages, triggers the nerve injury-induced expansion of both resident microglia in the spinal cord and macrophages in the dorsal root ganglion and induces their respective contributions to the neuropathic pain phenotype. Here, we review recent research and discuss unanswered questions regarding CSF1/CSF1R-mediated microglial and macrophage signaling in the generation of neuropathic pain.

Purpose. To observe the changes in macular microvascular structure and the correlation between anatomy and visual function in patients with macular edema secondary to branch retinal vein occlusion (BRVO) treated with antivascular endothelial growth factor for one year. Methods. This prospective study enrolled 39 patients (one eye per patient) who received intravitreal injections of ranibizumab for macular edema secondary to BRVO. All patients received a minimum of 3 initial monthly ranibizumab injections and criteria-driven pro re nata (PRN) dosing thereafter for visual acuity (VA) and central retinal thickness (CRT) stabilization. The follow-up period of this study was one year. The vascular density (VD) of the superficial retinal capillary plexus (SCP) and deep retinal capillary plexus (DCP), the foveal avascular zone (FAZ) area, the FAZ perimeter, the VD within a 300 μm wide ring surrounding the FAZ (FD-300), and the acircularity index (AI) were measured automatically by optical coherence tomography angiography (OCTA) at baseline, month 6, and month 12. Results. Compared with those before treatment, the VD of the SCP significantly decreased 6 months after treatment (P0.05). The change in BCVA was negatively correlated with the VD of the SCP at 12 months (P=0.0447, r = −0.3233). There was a relationship between the DBP and AI, and CRT was related to VD of DCP at baseline (P=0.028, 0.0209; r = 0.383, −0.384). The PERIM and AI at 12 months were significantly associated with the recurrence of macular edema, and the changes in vascular density in the SCP and PERIM were significantly associated with the number of injections within 12 months (P

Green finance is considered to be the financial support for green growth. It acts on the environmental protection industry through financial activities to reduce greenhouse gas emissions. It is a new financial model that combines financial and environmental protection activities. In order to explore the origin and development of this new financial model, namely, green finance, this study adopts the method of bibliometrics. Based on the database based on the Science Citation Index Expanded and Social Sciences Citation Index databases, the historical evolution of green finance and the classification of research hotspots are explored. The results show that green finance research has gone through three stages: the budding stage, the stable development stage, and the booming development stage. The research topics have also changed from the establishment of the green financial system to the difficulties faced by the green financial systems of various countries to the empirical evidence of the vigorous development of green finance. In addition, we have also established a three-dimensional framework (i.e., purpose, process, and participants, or 3P) of research hotspots in green finance to show a road map for future research directions.

Adhesive properties of leukemia cells shape the degree of organ infiltration and the extent of leukocytosis. CD44 and the integrin VLA-4, a CD49d/CD29 heterodimer, are important factors of progenitor cell adhesion in bone marrow (BM). Here, we report their cooperation in acute myeloid leukemia (AML) by a novel non-classical CD44-mediated way of inside-out VLA-4 activation. In primary AML BM samples from patients and the OCI-AML3 cell line, CD44 engagement by hyaluronan induced inside-out activation of VLA-4 resulting in enhanced leukemia cell adhesion on VCAM-1. This was independent from VLA-4 affinity regulation but based on ligand-induced integrin clustering on the cell surface. CD44-induced VLA-4 activation could be inhibited by the Src family kinase inhibitor PP2 and the multikinase inhibitor midostaurin. In further consequence, the increased adhesion on VCAM-1 allowed AML cells to strongly bind stromal cells. Thereby VLA-4/VCAM-1 interaction promoted activation of Akt, MAPK, NF-kB and mTOR signaling and decreased AML cell apoptosis. Collectively, our investigations provide a mechanistic description of an unusual CD44 function in regulating VLA-4 avidity in AML, supporting AML cell retention in the supportive BM microenvironment.

Cuckoo Search (CS) is one of the heuristic algorithms that has gradually drawn public attention because of its simple parameters and easily understood principle. However, it still has some disadvantages, such as its insufficient accuracy and slow convergence speed. In this paper, an Adaptive Guided Spatial Compressive CS (AGSCCS) has been proposed to handle the weaknesses of CS. Firstly, we adopt a chaotic mapping method to generate the initial population in order to make it more uniform. Secondly, a scheme for updating the personalized adaptive guided local location areas has been proposed to enhance the local search exploitation and convergence speed. It uses the parent’s optimal and worst group solutions to guide the next iteration. Finally, a novel spatial compression (SC) method is applied to the algorithm to accelerate the speed of iteration. It compresses the convergence space at an appropriate time, which is aimed at improving the shrinkage speed of the algorithm. AGSCCS has been examined on a suite from CEC2014 and compared with the traditional CS, as well as its four latest variants. Then the parameter identification and optimization of the photovoltaic (PV) model are applied to examine the capacity of AGSCCS. This is conducted to verify the effectiveness of AGSCCS for industrial problem application.

As one of the most promising forms of renewable energy, solar energy is increasingly deployed. The simulation and control of photovoltaic (PV) systems requires identification of their parameters. A Hybrid Adaptive algorithm based on JAYA and Differential Evolution (HAJAYADE) is developed to identify these parameters accurately and reliably. The HAJAYADE algorithm consists of adaptive JAYA, adaptive DE, and the chaotic perturbation method. Two adaptive coefficients are introduced in adaptive JAYA to balance the local and global search. In adaptive DE, the Rank/Best/1 mutation operator is put forward to boost the exploration and maintain the exploitation. The chaotic perturbation method is applied to reinforce the local search further. The HAJAYADE algorithm is employed to address the parameter identification of PV systems through five test cases, and the eight latest meta-heuristic algorithms are its opponents. The mean RMSE values of the HAJAYADE algorithm from five test cases are 9.8602 × 10−4, 9.8294 × 10−4, 2.4251 × 10−3, 1.7298 × 10−3, and 1.6601 × 10−2. Consequently, HAJAYADE is proven to be an efficient and reliable algorithm and could be an alternative algorithm to identify the parameters of PV systems.

We describe a case of facial skin infection and sinusitis caused by Mycobacterium marseillense in an immunocompetent woman in China in 2018. The infection was cleared with clarithromycin, moxifloxacin, and amikacin. Antimicrobial drug treatments could not be predicted by genetic analyses; further genetic characterization would be required to do so.

Abstract Background Insulin‐like growth factor‐1 (IGF‐1) promotes osteoblast differentiation and mineralization. The objective of this study was to investigate the effects of IGF‐1 on proliferation, mineralization, alkaline phosphatase (ALP) synthesis, and gene expression of osteoblast differentiation in MC3T3‐E1 osteoblasts cells, and to explore gene expression profiling differential genes. Methods MC3T3‐E1 osteoblasts cells were cultured in medium with or without IGF‐1. The ALP assay was employed to determine the osteoblast mineralization, and Alizarin red S to stain for calcium deposits, which were the indicators of mature osteocytes. The living cell number was assessed by the Cell Counting Kit‐8 method. RNA‐seq analysis was applied to identify genes that were differentially expressed in with or without IGF‐1 as well as genes that varied between these two groups. The expression of osteogenic marker genes was determined by quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blot analysis. Result The cell number of osteoblasts exposed to IGF‐1 at 200 μg/L significantly increased compared with the control group. The ALP activity in IGF‐1‐treated cells was higher than that in the control group. IGF‐1 can increase ALP synthesis in osteoblasts in vitro. RNA‐seq analysis showed that 677 triggered differentially expressed genes by IGF, of which 383 genes were downregulated and 294 genes were upregulated. Gene ontology (GO) analysis showed that IGF‐1 caused a significant change in gene expression patterns. Conclusions This result suggested that IGF‐1 could probably promote the synthesis of organic matrix and mineralize action of bone. Osteogenic‐related genes (DMP1, PHEX, SOST, BMP2, RUNX2, OPN, and OCN) were significantly upregulated both in GO analysis and in pathway analysis to perform qRT‐PCR. Western blot analysis demonstrated that the Notch pathway was highly upregulated in MC3T3‐E1 cells.

Fibrodysplasia Ossificans Progressiva (FOP) is an ultra-rare but debilitating disorder characterized by spontaneous, progressive, and irreversible heterotopic ossifications (HO) at extraskeletal sites. FOP is caused by gain-of-function mutations in the Activin receptor Ia/Activin-like kinase 2 gene (Acvr1/Alk2), with increased receptor sensitivity to bone morphogenetic proteins (BMPs) and a neoceptor response to Activin A. There is extensive literature on the skeletal phenotypes in FOP, but a much more limited understanding of non-skeletal manifestations of this disease. Emerging evidence reveals important cardiopulmonary and neurologic dysfunctions in FOP including thoracic insufficiency syndrome, pulmonary hypertension, conduction abnormalities, neuropathic pain, and demyelination of the central nervous system (CNS). Here, we review the recent research and discuss unanswered questions regarding the cardiopulmonary and neurologic phenotypes in FOP.

In this paper, direct coal liquefaction residue was prepared from Shen-dong coal, and the solubility of the residue in five organic solvents was studied. Then, an experimental device was set up to recover molybdenum (Mo) compounds from the direct coal liquefaction residue after extraction, and the influences of sublimation temperature and duration on recycling efficiency were examined. The recycled Mo-based products were characterized using scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), and a thermal analyzer. The results reveal that the optimum extraction conditions were obtained through ultrasonic extraction with a quinoline solvent and the highest recycling efficiency occurred for sublimation at 900 °C for 30 min. The recycled products are identified to be α-MoO3 crystals. Moreover, the α-MoO3 crystal is thermally stable before the temperature reaches its melting point.

Background & Aims Accumulating research has addressed the linkage between the changes to gut microbiota structure and type 2 diabetes (T2D). Inulin is one type of soluble dietary fiber that can alleviate T2D. As a prebiotic, inulin cannot be digested by humans, but rather is digested by probiotics. However, whether inulin treatment can benefit the entire gut bacteria community remains unknown. In this study, we evaluated the differences in gut microbiota composition among diabetic, inulin-treated diabetic, normal control, and inulin-treated normal control rats. Methods A diabetic rat model was generated by a high-fat diet and streptozotocin injections (HF/STZ). Inulin was orally administered to normal and diabetic rats. To determine the composition of the gut microbiota, fecal DNA extraction and 16S rRNA gene 454 pyrosequencing were performed. Results We found that inulin treatment reduced fasting blood glucose levels and alleviated glucose intolerance and blood lipid panels in diabetic rats. Additionally, inulin treatment increased the serum glucagon-like peptide-1 (GLP-1) level, reduced serum IL-6 level, Il6 expression in epididymal adipose tissue, and Pepck, G6pc expression in liver of diabetic rats. Pyrophosphate sequencing of the 16s V3–V4 region demonstrated an elevated proportion of Firmicutes and a reduced abundance of Bacteroidetes at the phylogenetic level in diabetic rats compared to normal control rats. The characteristics of the gut microbiota in control and inulin-treated rats were similar. Inulin treatment can normalize the composition of the gut microbiota in diabetic rats. At the family and genus levels, probiotic bacteria Lactobacillus and short-chain fatty acid (SCFA)-producing bacteria Lachnospiraceae, Phascolarctobacterium, and Bacteroides were found to be significantly more abundant in the inulin-treated diabetic group than in the non-treated diabetic group. In addition, inulin-treated rats had a lower abundance of Desulfovibrio, which produce lipopolysaccharide (LPS). The abundance of Lachnospiraceae was negatively correlated with the blood glucose response after a glucose load. Conclusion In summary, diabetic rats have different gut microbiota from control rats. Inulin treatment can alleviate gut microbiota dysbiosis in T2D model rats. Moreover, inulin treatment enhanced serum GLP-1 level to suppress IL-6 secretion and production and hepatic gluconeogenesis, resulted in moderation of insulin tolerance.

Purpose. To assess the morphology of idiopathic choroidal neovascularization (ICNV) by optical coherence tomography angiography (OCTA) and determine the therapeutic effects of intravitreal antivascular endothelial growth factor (anti-VEGF). Method. Patients with naive ICNV were assessed by spectral domain optical coherence tomography (SD-OCT) and OCTA in this observational study. The timing of observation was before treatment, 1 day after treatment with intravitreal anti-VEGF injection, and 1 month after the treatment. The central retina thickness (CRT) on SD-OCT, selected CNV area, and flow area on OCTA were measured. Results. A total of 17 eyes from 17 patients with ICNV were included in this study. OCTA showed visible irregular choroidal neovascularization with “tree-in-bud” form on outer retinal layer. After treatment, as well as in the 1-day follow-up, CNV decreased in size from the periphery, and the vessel density was reduced. As shown on OCTA, the selected CNV area and flow area were significantly reduced compared to pretreatment. The rate of CNV vessel area changes was higher on OCTA than the changes in CRT on SD-OCT at 1-day and 1-month follow-up. Conclusion. Intravitreal injection of anti-VEGF is effective for idiopathic choroidal neovascularization, and the treatment outcomes are observable after 1 day. OCTA provides a useful approach for monitoring and evaluating the treatment of intravitreal anti-VEGF for CNV.

Purpose. To observe the effect of intravitreal ranibizumab injection on wet age-related macular degeneration (wAMD) over 5 years in Chinese patients. Methods. Thirty-seven patients who were diagnosed with wAMD in our hospital from June 2007 to June 2014 were retrospectively reviewed. The PRN regimen and the treatment and extend regimen were applied. Best corrected visual acuity (BCVA), number of ranibizumab injections, and changes in the choroidal neovascularization (CNV) lesion over 5 years were analyzed. Results. The mean BCVA measured by the ETDRS chart at baseline was 47.4 and 5 years after the treatment it was 34.89 letters, which was significantly different (p=0.013). Fourteen eyes (37.8%) had improved visual acuity after 5 years. The number of injections in 5 years was 11.53, and most of the injections were in the first two years. Seventeen (45.9%) cases developed fibrous lesions, and 2 (5.4%) cases had atrophic lesions after 5 years. The fibrosis/atrophy was significantly correlated with the injection numbers (Pearson, r=0.663, and p=0.000). Conclusion. Most of the patients can maintain visual acuity treated by ranibizumab in the first 3 years. After 5 years, some patients can still improve or maintain visual acuity. Fibrous scarring of the lesion is the main reason for a decrease in vision of wAMD patients.

Particle swarm optimization (PSO) is a stochastic search technique for solving optimization problems, which has been proven to be efficient and effective in wide applications. However, the PSO can easily fly into the local optima and lack the ability to jump out of the local optima. A novel adaptive PSO is proposed by evaluating convergence of the fitness value. The novel mechanism is to ensure the diversity of particles. Simulations for benchmark test functions have illustrated that the proposed algorithm possesses better ability to find the global optima than other variants and is an effective global optimization tool.

Particle swarm optimization (PSO) and differential evolution (DE) are both efficient and powerful population-based stochastic search techniques for solving optimization problems, which have been widely applied in many scientific and engineering fields. Unfortunately, both of them can easily fly into local optima and lack the ability of jumping out of local optima. A novel adaptive hybrid algorithm based on PSO and DE (HPSO-DE) is formulated by developing a balanced parameter between PSO and DE. Adaptive mutation is carried out on current population when the population clusters around local optima. The HPSO-DE enjoys the advantages of PSO and DE and maintains diversity of the population. Compared with PSO, DE, and their variants, the performance of HPSO-DE is competitive. The balanced parameter sensitivity is discussed in detail.

Now, there are a lot of multiobjective evolutionary algorithms (MOEAs) available and these MOEAs argue that they are competitive. In fact, these results are generally unfair and unfaithful. In order to make fair comparison, comprehensive performance index system is established. The weights among the performance index system are solved by an adaptive differential evolution (ADE) algorithm. An approach is proposed to estimate MOEAs based on box plots and fuzzy TOPSIS. Box plots are employed to depict features of performance indicators and fuzzy TOPSIS is used to make evaluation. Experiments have been tested on IEEE CEC2009. The experiment results have revealed that the evaluation approach is effective, fair, and faithful when evaluating MOEAs.

Aiming to reduce the impact of substation noise on the lives of surrounding residents, improving the low and middle frequencies acoustic performance of traditional resistive mufflers in indoor substations is significant. The paper is based on the resonance sound absorption mechanism, and for the first time applies multi-frequency resonance noise reduction technology to the research field of indoor substation noise control, proposing a multi-frequency resonant muffling structure. The acoustic performance of the proposed muffler unit is investigated through theoretical and numerical analysis. The measured noise data of the indoor substation is used as sound excitation in the numerical analysis. The results show that at frequencies of 100 Hz, 200 Hz, 300 Hz, 400 Hz, and 500 Hz, the noise in indoor substations is significantly reduced by the multi-frequency resonant muffling structure. The paper provides references for the application of multi-frequency resonant mufflers in the field of noise control of indoor substations. [ABSTRACT FROM AUTHOR]