Efficacy and Safety of Surgical Procedures for Congenital Moderate and Severe Blepharoptosis: A Network Meta-analysis.

BACKGROUND: There are various surgical approaches to treat congenital moderate and severe blepharoptosis (CMSBP), but their efficacy and safety remain unclear owing to a lack of high-level evidence. This network meta-analysis aimed to evaluate the efficacy and safety of 3 classical operations: and their modifications frontal muscle flap suspension (FMS), levator palpebrae muscle shortening (LMS), conjoint fascial sheath suspension (CFSS), and modified CFSS. METHODS: We searched the PubMed, MEDLINE, Cochrane Library, CNKI, and Wanfang databases until March 2022. A Bayesian network meta-analysis was conducted for the 5 most common treatments. Outcome indicators were the number of patients with good correction and adverse events. RESULTS: Twenty-one studies were included, with 2402 eyes in 1863 patients. Five surgical methods were evaluated: FMS, LMS, CFSS, and conjoint fascial sheath suspension combined with levator muscle shortening (CFSS+LMS), or with levator palpebrae muscle composite flap suspension (CFS+L). Meta-analysis indicated that CFSS is more effective than LMS and FMS, but inferior to CFSS+LMS and CFS+L. Efficacy rates of CFSS+LMS and CFS+L were comparable. Frontal muscle flap suspension was more effective than LMS. Safety data meta-analysis found CFSS safer than FMS and LMS but with more complications than CFSS+LMS and CFS+L. Complication rates were comparable between CFS+L and CFSS+LMS, and also for FMS and LMS. CONCLUSIONS: When correcting CMSBP, CFSS+LMS, and CFS+L may be better therapeutic strategies for effectiveness and safety. Conjoint fascial sheath suspension also yielded good surgical effects. Plastic surgeons should be cautious about LMS and FMS. LEVEL OF EVIDENCE: Level IV.

Is Pregnancy Following a TRAM or DIEP Flap Safe? A Critical Systematic Review and Meta-analysis.

BACKGROUND: Previous data were not conclusive on the safety of gestation in patients whose abdominal flaps were earlier harvested. We performed a meta-analysis to evaluate the abdominal wall complications and birth mode of pregnancy in post-TRAM or post-DIEP harvested individuals. METHODS: A literature search was performed using the PubMed, Embase, Scopus, and Google scholar database. Heterogeneity was statistically analyzed, and random effect models were applied. Publication bias was assessed by funnel plot. RESULTS: We included 25 papers that captured 56 patients giving birth to 69 healthy babies after elevation of abdominally based flaps, with a pooled abdominal complication rate of 0.00-0.09. The complication incidence in TRAM group was 0.01 (95% CI = [0.00-0.14%]) while 0.00 in the DIEP group (95% CI = [0.00-0.26%]). Discrepancies in incidence following unilaterally or bilaterally based TRAM flaps, following free or pedicled TRAM flaps, following primary sutured or mesh strengthened fascia, following MS free TRAM or conventional free TRAM could not be calculated as statistically significant. TRAM group and DIEP group patients had identical birth modes. CONCLUSIONS: The present meta-analysis did not detect evidence that abdominal walls with the prior harvest of abdominal flaps could affect the process of pregnancy or contraindicate vaginal delivery. No abdominal hernia or bulge occurred with post-DIEP pregnancies. However, such conclusions need to be substantiated by larger sample studies. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine Ratings, please refer to Table of Contents or online Instructions to Authors www.springer.com/00266 .

Microstructure and Mechanical Properties of TaNbVTiAlx Refractory High-Entropy Alloys.

A series of TaNbVTiAlx (x = 0, 0.2, 0.4, 0.6, 0.8, and 1.0) refractory high-entropy alloys (RHEAs) with high specific strength and reasonable plasticity were prepared using powder metallurgy (P/M) technology. This paper studied their microstructure and compression properties. The results show that all the TaNbVTiAlx RHEAs exhibited a single BCC solid solution microstructure with no elemental segregation. The P/M TaNbVTiAlx RHEAs showed excellent room-temperature specific strength (207.11 MPa*cm3/g) and high-temperature specific strength (88.37 MPa*cm3/g at 900 °C and 16.03 MPa*cm3/g at 1200 °C), with reasonable plasticity, suggesting that these RHEAs have potential to be applied at temperatures >1200 °C. The reasons for the excellent mechanical properties of P/M TaNbVTiAl0.2 RHEA were the uniform microstructure and solid solution strengthening effect.

Reversible and Distance-Controllable DNA Scissor: A Regenerated Electrochemiluminescence Biosensing Platform for Ultrasensitive Detection of MicroRNA.

Reversing the switching of DNA scissors with precisely control remains a compelling goal. Herein, based on strand displacement reaction within single step, the DNA scissor realized reversible switching and further controlled the distance of end strands along the movement of DNA scissor, which has been applied for the development of a regenerated sensing platform for the ultrasensitive detection of microRNA-21 (miRNA-21) with the electrochemiluminescence (ECL) complex (PEI-Ru(II)) as luminophores and diethylenetriamine (DETA) as the coreactant. In the presence of ferrocene-labeled DNA (Fc-DNA), the DETA-labeled DNA scissor clockwise switched to "off" state based on strand displacement reaction, resulting in the significant ECL quenching of Ru(II) system. Next, by using miRNA-21 as the motive fuel, the configuration of DNA scissor could be anticlockwise switched, which significantly enhanced the ECL intensity of Ru(II) complex due to the releasing of Fc-DNA and the proximity between DETA and Ru(II) complex. The reversible switching of DNA scissor led to the remarkably enhancing of ECL signal, realizing ultrasensitive detection of miRNA-21 with an excellent detection limit of 0.17 fM, which was also applied in miRNA detection successfully from different cancer cells. Impressively, the reversible switching of DNA scissor biosensor was able to realize the regeneration of the biosensing platform by adding an additional single stranded DNA (ssDNA) based on strand displacement reaction within a single step, providing a novel concept for constructing simple and sensitive regenerated biosensor.

Microstructure and Mechanical Properties of Particulate Reinforced NbMoCrTiAl High Entropy Based Composite.

A novel metal matrix composite based on the NbMoCrTiAl high entropy alloy (HEA) was designed by the in-situ formation method. The microstructure, phase evolution, and compression mechanical properties at room temperature of the composite are investigated in detail. The results confirmed that the composite was primarily composed of body-centered cubic solid solution with a small amount of titanium carbides and alumina. With the presence of approximately 7.0 vol. % Al2O3 and 32.2 vol. % TiC reinforced particles, the compressive fracture strength of the composite (1542 MPa) was increased by approximately 50% compared with that of the as-cast NbMoCrTiAl HEA. In consideration of the superior oxidation resistance, the P/M NbMoCrTiAl high entropy alloy composite could be considered as a promising high temperature structural material.

[Molecular classification of colorectal carcinoma based on integration of gene expression profile and copy number variation].

OBJECTIVE: To classify colorectal carcinoma (CRC) by TNM staging integrated with the gene expression profile and copy number variation (CNV). METHODS: Profile data of gene expression and CNV of CRC were downloaded from public database and processed with batch bias adjustment, quartile normalization, missing value estimation and feature filtration. The processed profiles of mRNA and CNV were introduced into the codes of Bayesian consensus clustering (BCC) method and were used to calculate the subclasses of CRC. With the follow-up information of disease free survival of CRC patients, the prognostic values of the subclasses was investigated and the software of function enrichment analysis was employed to discover the major pathway signaling to each interesting subclass. All statistic analyses were performed under R-3.0.1 environment or by using SPSS 16.0 software. RESULTS: Profile data of gene expression and corresponding CNV from 335 CRC patients with TNM stage Ⅱ-Ⅲ and followed-up information were obtained. After feature filtering, the profiles contained 1578 probes of mRNA and 345 location of CNV. Four CRC subclasses were identified by the integrative analysis with BCC, and the concordances of BCC subclasses and each of gene-based subclasses (Cramer's V=0.49), CNV-based subclasses (Cramer's V=0.51) and Marisa's subclasses (Cramer's V=0.32) were statistically significant (Ps<0.001). Among BCC subclasses, BCC-I had a favorable prognosis, while BCC-Ⅳ had more unfavorable prognosis. The differences of prognosis were significant among BCC-I, BCC-(Ⅱ+Ⅲ) and BCC-Ⅳ with an overall log-rank P<0.001. The top enriched function was DNA damage and repair signaling when BCC-I compared to BCC-Ⅳ, and the new subgroups classified by the genes associated with enriched signaling had the better prognostic value than BCC subclasses but both of them were significantly correlated (Cramer's V=0.39, P<0.001). CONCLUSION: BCC method is effective to integrate multi-type genomic data for molecular classification of colorectal carcinoma, and the BCC-Ⅳ subclass has poor prognosis, which may be associated with the decreased repairing function of DNA damage.

Exploring the NRF2-TP53 Signaling Network Through Machine Learning and Pan-Cancer Analysis: Identifying Potential targets for Cancer Prognosis Related to Oxidative Stress.

Oxidative stress (OXS) is closely related to tumor prognosis and immune response, while TP53 integrated with NRF2 is closely associated with the regulation of cancer-related OXS. Hence, constructing a TP53-NRF2 integrated OXS signature of pan-cancer is essential in predicting survival prognosis and facilitating cancer drug treatment. The pan-cancer analysis acquired the Cancer Genome Atlas (TCGA) transcriptome sequencing data from UCSC Xena, which consisted of 33 cancer types (n = 10 440). The Random Forest, Lasso regression, and Cox regression analyses are used to construct an OXS score based on 25 OXS genes. Following this, based on the OXS signature, patients are categorized into low- and high-risk groups. The disparities between the two cohorts regarding survival prognosis, immune infiltration, and drug sensitivity are delved deeply. The expression level of genes is confirmed using immunohistochemistry. The prognosis of pan-cancer patients is adequately predicted by the OXS signature with the assistance of the machine-learning algorithm. A highly accurate nomogram is developed by combining the OXS signature and clinical features. The presence of immune cells indicated that the OXS signature can be associated with the critical pathways of immunotherapy for all types of cancer, and BCL2 showed promising results. Distinct inter-group differences are observed in the OXS signature for frequently utilized antineoplastic medications in clinical settings, including first-line drugs suggested in the guidelines. In summary, by conducting a thorough analysis of OXS genes, a new model based on OXSscore is successfully developed. This model can predict the clinical prognosis and drug sensitivity of pan-cancer with high accuracy. Potential stars in the field of cancer-related anti-OXS may include drugs that target BCL2.

Prediction of metastases in confusing mediastinal lymph nodes based on flourine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) imaging using machine learning.

Background: For patient management and prognosis, accurate assessment of mediastinal lymph node (LN) status is essential. This study aimed to use machine learning approaches to assess the status of confusing LNs in the mediastinum using positron emission tomography/computed tomography (PET/CT) images; the results were then compared with the diagnostic conclusions of nuclear medicine physicians. Methods: A total of 509 confusing mediastinal LNs that had undergone pathological assessment or follow-up from 320 patients from three centres were retrospectively included in the study. LNs from centres I and II were randomised into a training cohort (N=324) and an internal validation cohort (N=81), while those from centre III patients formed an external validation cohort (N=104). Various parameters measured from PET and CT images and extracted radiomics and deep learning features were used to construct PET/CT-parameter, radiomics, and deep learning models, respectively. Model performance was compared with the diagnostic results of nuclear medicine physicians using the area under the curve (AUC), sensitivity, specificity, and decision curve analysis (DCA). Results: The coupled model of gradient boosting decision tree-logistic regression (GBDT-LR) incorporating radiomic features showed AUCs of 92.2% [95% confidence interval (CI), 0.890-0.953], 84.6% (95% CI, 0.761-0.930) and 84.6% (95% CI, 0.770-0.922) across the three cohorts. It significantly outperformed the deep learning model, the parametric PET/CT model and the physician's diagnosis. DCA demonstrated the clinical usefulness of the GBDT-LR model. Conclusions: The presented GBDT-LR model performed well in evaluating confusing mediastinal LNs in both internal and external validation sets. It not only crossed radiometric features but also avoided overfitting.

Hot Deformation Behavior and Microstructure Evolution of a Graphene/Copper Composite.

Graphene/copper composites are promising in electronic and energy fields due to their superior conductivity, but microstructure control during thermal mechanical processing (TMP) remains a crucial issue for the manufacturing of high-performance graphene/copper composites. In this study, the hot deformation behavior of graphene/copper composites was investigated by isothermal compression tests at deformation temperatures of 700~850 °C and strain rates of 0.01~10 s-1, and a constitutive equation based on the Arrhenius model and hot processing map was established. Results demonstrate that the deformation mechanism of the graphene/copper composites mainly involves dynamic recrystallization (DRX), and such DRX-mediated deformation behavior can be accurately described by the established Arrhenius model. In addition, it was found that the strain rate has a stronger impact on the DRX grain size than the deformation temperature. The optimum deformation temperature and strain rate were determined to be 800 °C and 1 s-1, respectively, with which a uniform microstructure with fine grains can be obtained.

Microstructure and Mechanical Properties of the Powder Metallurgy Nb-16Si-24Ti-2Al-2Cr Alloy.

The Nb-16Si-24Ti-2Al-2Cr alloy was prepared by plasma rotating electrode process (PREP) technology and the hot-pressing (HP) method, and the effects of sintering temperature on the microstructure, mechanical properties and fracture behavior were investigated. The HP alloys sintered at temperatures below 1400 °C are composed of Nbss (Nb solid solution), Nb3Si and Nb5Si3 phases. When the sintering temperature reaches 1450 °C, the Nb3Si phase is completely decomposed into Nbss and Nb5Si3 phases. Meanwhile, the microstructure coarsens significantly. Compared with the cast alloy, the HP alloy shows better mechanical properties. The fracture toughness of the alloy sintered at 1400 °C reaches 20.2 MPa·m1/2, which exceeds the application threshold. The main reason for the highest fracture toughness is attributed to the decomposition of large-sized brittle Nb3Si phase and the formation of a fine microstructure, which greatly increases the number of phase interfaces and improves the chance of crack deflection. In addition, the reduction in the size and content of silicides also reduces their plastic constraints on the ductile Nbss phase.

Therapeutic implication of targeting mitochondrial drugs designed for efferocytosis dysfunction.

Efferocytosis refers to the process by which phagocytes remove apoptotic cells and related apoptotic products. It is essential for the growth and development of the body, the repair of damaged or inflamed tissues, and the balance of the immune system. Damaged efferocytosis will cause a variety of chronic inflammation and immune system diseases. Many studies show that efferocytosis is a process mediated by mitochondria. Mitochondrial metabolism, mitochondrial dynamics, and communication between mitochondria and other organelles can all affect phagocytes' clearance of apoptotic cells. Therefore, targeting mitochondria to modulate phagocyte efferocytosis is an anticipated strategy to prevent and treat chronic inflammatory diseases and autoimmune diseases. In this review, we introduced the mechanism of efferocytosis and the pivoted role of mitochondria in efferocytosis. In addition, we focused on the therapeutic implication of drugs targeting mitochondria in diseases related to efferocytosis dysfunction.

The Function of T Cell Immunity in Lymphedema: A Comprehensive Review.

Lymphedema is a debilitating disease characterized by extremity edema, fibroadipose deposition, impaired lymphangiogenesis, and dysfunctional lymphatics, often with lymphatic injury secondary to the treatment of malignancies. Emerging evidence has shown that immune dysfunction regulated by T cells plays a pivotal role in development of lymphedema. Specifically, Th1, Th2, Treg, and Th17 cells have been identified as critical regulators of pathological changes in lymphedema. In this review, our aim is to provide an overview of the current understanding of the roles of CD4+ T cells, including Th1, Th2, Treg, and Th17 subsets, in the progression of lymphedema and to discuss associated therapies targeting T cell inflammation for management of lymphedema.

Analysis of CD4+ T-helper-associated hub gene signature and immune dysregulation via RNA-sequencing data in a mouse tail model of lymphedema.

Background: T-helper cells play an essential role in the progression of lymphedema. This study aimed to explore the biological significance of T-helper cell-associated genes (THAGs) in a mouse tail model of lymphedema by RNA-sequencing (RNA-seq) data. Methods: The expression profiles of a murine model of secondary lymphedema were obtained from European Nucleotide Archive (ENA) database. Differentially expressed genes (DEGs) were screened and the enrichment analysis of DEGs was conducted. THAGs were constructed by crossing the T-helper-related gene sets obtained from Molecular Signatures Database with DEGs. Protein-protein interaction (PPI) network analysis was utilized to establish T-helper-associated hub genes (THAHGs). Single-sample gene set enrichment analysis (ssGSEA) was employed to decipher differences in immune cell infiltration. The correlation between THAHGs and immune infiltration was calculated by Pearson correlation analysis. Receiver operating characteristic (ROC) curves of THAHGs were drawn to evaluate their diagnostic properties. Additionally, potential drugs and upstream transcription factors (TFs) were predicted based on THAHGs. Results: Enrichment analysis showed that lymphedematous tissue presented higher activation of biological process (BP) of T-helper 1 (Th1), T-helper 2 (Th2), T-helper 17 (Th17). The immune infiltration analysis further calculated that the relative immune abundance of follicular B cells, memory B cells, M1 macrophage, and CD4+ Tm cells was significantly elevated while the relative immune abundance of neutrophils and plasma cells were down-regulated in lymphedema. We established a list of THAHGs consisting of eight hub genes, compassing Cd4, Foxp3, Irf4, Ccr6, Il12rb1, Batf, Il1b, Cd74. THAHGs were shown to be significantly interrelated and related to immune infiltration by Pearson correlation analysis. ROC curves showcased that the area under curve (AUC) values of THAHGs were larger than 0.70. Gata3 was the most potential TF and thalidomide might be the immunoregulatory drug for lymphedema based on THAHGs. Conclusions: Biological pathways associated with T-helpers were significantly enriched in mouse lymphedema tissue. The relative immune infiltration abundance of M1 macrophage, CD4+ Tm cells, and T-helper cells was higher in the lymphedema group. Besides, we identified the THAHGs containing eight genes, namely, Cd4, Foxp3, Irf4, Ccr6, Il12rb1, Batf, Il1b, and Cd74. The THAHGs were closely correlated with immune infiltration results and with good diagnostic properties.

Preparation and Microstructure of High-Activity Spherical TaNbTiZr Refractory High-Entropy Alloy Powders.

High-activity spherical TaNbTiZr refractory high-entropy alloy (REHA) powders were successfully prepared by electrode induction melting gas atomization (EIGA) and plasma rotating electrode process (PREP) methods. Both the EIGAed and PREPed TaNbTiZr RHEA powders have a single-phase body-centered cubic (BCC) structure and low oxygen content. Compared with the EIGAed powders, the PREPed powders exhibit higher sphericity and smoother surface, but larger particle size. The average particle sizes of the EIGAed and PREPed powders are 51.8 and 65.9 µm, respectively. In addition, both the coarse EIGAed and PREPed powders have dendritic structure, and the dendrite size of the EIGAed powders is larger than that of the PREPed powders. Theoretical calculation indicates that the cooling rate of the PREPed powders is one order of magnitude higher than that of the EIGAed powders during the solidification process, and the dendritic structure has more time to grow during EIGA, which is the main reason for the coarser dendrite size of the EIGAed powders.

Effect of Si on Microstructure and Mechanical Properties of FeCrNi Medium Entropy Alloys.

FeCrNi medium entropy alloy (MEA) has been widely regarded for its excellent mechanical properties and corrosion resistance. However, insufficient strength limits its industrial application. Intermetallic particle dispersion strengthening is considered to be an effective method to improve strength, which is expected to solve this problem. In this work, microstructural evolution and mechanical behavior of FeCrNi MEA with different Si content were investigated. We found that the precipitation of fine σ particles can be formed in situ by thermomechanical treatment of Si doping FeCrNi MEAs. The FeCrNiSi0.15 MEA exhibits a good combination of strength and ductility, with yield strength and tensile elongation of 1050 MPa and 7.84%, respectively. The yield strength is almost five times that of the as-cast FeCrNi MEA. The strength enhancement is mainly attributed to the grain-boundary strengthening and precipitation strengthening caused by fine σ particles.

Cu/Fe oxide integrated on graphite felt for degradation of sulfamethoxazole in the heterogeneous electro-Fenton process under near-neutral conditions.

In the heterogeneous electro-Fenton (EF) system, high-efficiency and durable materials have attracted widespread attention as cathodes for degradation of refractory organic pollutants. In this study, a stable Cu/Fe oxide modified graphite felt electrode (Cu0.33Fe0.67NBDC-300/GF) was fabricated via a one-step hydrothermal method and subsequent thermal treatment, which used a bimetallic metal-organic framework (MOF) with 2-aminoterephthalic acid (NH2BDC) ligand as the precursor. The Cu0.33Fe0.67NBDC-300/GF electrode was used as the cathode for sulfamethoxazole (SMX) degradation in the heterogeneous EF process. The coexistence of the FeII/FeIII and CuI/CuII redox couples significantly accelerates the regeneration of FeII and promotes the generation of active free radicals (•OH and •O2-). FeIV was detected during the process, which indicates that the high-valent iron-oxo species was produced in near-neutral pH conditions. The removal efficiency of SMX (10 mg L-1) can reach 100.0% within 75 min over a wide pH range (4.0-9.0). After five cycles, the electrode retained a high stability and an outstanding catalytic capacity. Furthermore, the mechanisms and pathways for SMX degradation were proposed, the products and intermediates of SMX were analyzed, and the toxicity was evaluated. It was found that the toxicity decreased after degradation. This study displays a novel strategy for building an efficient and stable self-supporting electrode for treating antibiotic wastewater.

Microstructure and Mechanical Properties of Novel Lightweight TaNbVTi-Based Refractory High Entropy Alloys.

A series of novel lightweight TaNbVTi-based refractory high entropy alloys (RHEA) were fabricated through ball-milling and spark plasma sintering (SPS). The reinforced phase of TiO precipitates were in-situ formed due to the introduction of Al2O3 ceramic particles. The RHEA with 15% Al2O3 exhibits a high compressive yield strength (1837 MPa) and a low density (7.75 g/cm3) with an adequate ductility retention. The yield strength and density are 32% higher and 15% lower, respectively, compared to the RHEA without Al2O3 addition. The specific yield strength (237 MPa cm3/g) of the RHEAs is much higher than that of other reported RHEAs, and is mainly ascribed to the introduction of high volume fraction of Al2O3 additives, resulting in solid solution strengthening and precipitation strengthening. Meanwhile, the ductile matrix is responsible for the good compressive plasticity.

The Retrotransposition of L1 is Involved in the Reconsolidation of Contextual Fear Memory in Mice.

BACKGROUND: The long interspersed element-1 (L1) participates in memory formation, and DNA methylation patterns of L1 may suggest resilience or vulnerability factors for Post-Traumatic Stress Disorder (PTSD), of which the principal manifestation is a pathological exacerbation of fear memory. However, the unique roles of L1 in the reconsolidation of fear memory remain poorly understood. OBJECTIVE: The study aimed to investigate the role of L1 in the reconsolidation of context-dependent fear memory. METHODS: Mice underwent fear conditioning and fear recall in the observation chambers. Fear memory was assessed by calculating the percentage of time spent freezing in 5 min. The medial prefrontal cortex (mPFC) and hippocampus were removed for further analysis. Open Reading Frame 1 (ORF1) mRNA and ORF2 mRNA of L1 were analyzed by real-time quantitative polymerase chain reaction. After reactivation of fear memory, lamivudine was administered and its effects on fear memory reconsolidation were observed. RESULTS: ORF1 and ORF2 mRNA expressions in the mPFC and hippocampus after recent (24 h) and remote (14 days) fear memory recall exhibited augmentation via different temporal and spatial patterns. Reconsolidation of fear memory was markedly inhibited in mice treated with lamivudine, which could block L1. DNA methyltransferase mRNA expression declined following lamivudine treatment in remote fear memory recall. CONCLUSION: The retrotransposition of L1 participated in the reconsolidation of fear memory after reactivation of fear memory, and with lamivudine treatment, spontaneous recovery decreased with time after recent and remote fear memory recall, providing clues for understanding the roles of L1 in fear memory.