In-situ synthesis Fe3C@C/rGO as matrix for high performance lithium-sulfur batteries at room and low temperatures.

People have been focusing on how to improve the specific capacity and cycling stability of lithium-sulfur batteries at room temperature, however, on some special occasions such as cold cities and aerospace fields, the operating temperature is low, which dramatically hinders the performance of batteries. Here, we report an iron carbide (Fe3C)/rGO composite as electrode host, the Fe3C nanoparticles in the composite have strong adsorption and high catalytic ability for polysulfide. The rGO makes the distribution of Fe3C nanoparticles more disperse, and this specific structure makes the deposition of Li2S more uniform. Therefore, it realizes the rapid transformation and high performance of lithium-sulfur batteries at both room and low temperatures. At room temperature, after 100 cycles at 1C current density, the reversible specific capacity of the battery can be stabilized at 889 ± 7.1 mAh/g. Even at -40 °C, in the first cycle battery still emits 542.9 ± 3.7 mAh/g specific capacity. This broadens the operating temperature for lithium-sulfur batteries and also provides a new idea for the selection of host materials for sulfur in low-temperature lithium-sulfur batteries.

A scientometric review of the growing trends in transcranial alternating current stimulation (tACS).

Objective: The aim of the current study was to provide a comprehensive picture of tACS-related research in the last decade through a bibliometric approach in order to systematically analyze the current status and cutting-edge trends in this field. Methods: Articles and review articles related to tACS from 2013 to 2022 were searched on the Web of Science platform. A bibliometric analysis of authors, journals, countries, institutions, references, and keywords was performed using CiteSpace (6.2.R2), VOSviewer (1.6.19), Scimago Graphica (1.0.30), and Bibliometrix (4.2.2). Results: A total of 602 papers were included. There was an overall increase in annual relevant publications in the last decade. The most contributing author was Christoph S. Herrmann. Brain Stimulation was the most prolific journal. The most prolific countries and institutions were Germany and Harvard University, respectively. Conclusion: The findings reveal the development prospects and future directions of tACS and provide valuable references for researchers in the field. In recent years, the keywords "gamma," "transcranial direct current simulation," and "Alzheimer's disease" that have erupted, as well as many references cited in the outbreak, have provided certain clues for the mining of research prefaces. This will act as a guide for future researchers in determining the path of tACS research.

The characteristics of intestinal microbiota in patients with chronic schistosomiasis japonica-induced liver fibrosis by 16S rRNA gene sequence.

Background: The intestinal microbiota is known to play a role in the development of liver disease, there is a limited understanding of the intestinal microbiota associated with chronic schistosomiasis japonica. This study sought to explore the characteristics of the intestinal microbiota in patients with chronic schistosomiasis japonica and identify potential biomarkers that could aid diagnosis. Methods: A total of 40 residents of Qingshan Island in Yueyang (Hunan, China) were enrolled in this cross-sectional study. These individuals were divided into two groups for analysis of the intestinal microbiota: patients with chronic schistosomiasis japonica-induced liver fibrosis group (CSJ group, n = 10) and a healthy control group (HC group, n = 30). Feces were collected from each participant and analyzed by 16S rRNA gene sequencing, which included species composition analysis at the phylum and family levels, α and ß diversity analysis, LEfSe, Kyoto Encyclopedia of Genes and Genome (KEGG) and Clusters of Orthologous Groups of proteins (COG) analysis. Results: Our results indicated that Schistosoma japonicum infection changed the composition and abundance of intestinal microbiota at the phylum and family levels. Compared with the HC group, the α and ß diversity results showed that CSJ group had low diversity of species of the intestinal microbiome. LEfSe and relative abundance analysis found that the Prevotella 7, Alloprevotella, and Holdemanella genera were significantly higher in the CSJ group than in the HC group. Meanwhile, the ROC analysis showed that the area under the curve (AUC) of Prevotella 7, Alloprevotella, and Holdemanella genera was 0.779, 0.769, and 0.840, respectively. KEGG and COG analysis showed that the Replication and Repair, and Defense Mechanism pathways correlated strongly with chronic schistosomiasis japonica infection. Conclusion: The current study was the first to explore differences in the intestinal microbiota of patients with chronic schistosomiasis japonica-induced liver fibrosis and healthy people from Qingshan Island, which indicated that Prevotella 7, Alloprevotella, and Holdemanella genera could have a potential value in non-invasive diagnosis of chronic schistosomiasis japonica-induced fibrosis.

Single-cell RNA sequencing reveals a peripheral landscape of immune cells in Schistosomiasis japonica.

BACKGROUND: Schistosomiasis, also known as bilharzia, is a devastating parasitic disease. This progressive and debilitating helminth disease is often associated with poverty and can lead to chronic poor health. Despite ongoing research, there is currently no effective vaccine for schistosomiasis, and praziquantel remains the only available treatment option. According to the progression of schistosomiasis, infections caused by schistosomes are classified into three distinct clinical phases: acute, chronic and advanced schistosomiasis. However, the underlying immune mechanism involved in the progression of schistosomiasis remains poorly understood. METHODS: We employed single-cell RNA sequencing (scRNA-seq) to profile the immune landscape of Schistosomiasis japonica infection based on peripheral blood mononuclear cells (PBMCs) from a healthy control group (n = 4), chronic schistosomiasis group (n = 4) and advanced schistosomiasis group (n = 2). RESULTS: Of 89,896 cells, 24 major cell clusters were ultimately included in our analysis. Neutrophils and NK/T cells accounted for the major proportion in the chronic group and the healthy group, and monocytes dominated in the advanced group. A preliminary study showed that NKT cells were increased in patients with schistosomiasis and that CXCR2 + NKT cells were proinflammatory cells. Plasma cells also accounted for a large proportion of B cells in the advanced group. MHC molecules in monocytes were notably lower in the advanced group than in the chronic group or the healthy control group. However, monocytes in the advanced group exhibited high expression of FOLR3 and CCR2. CONCLUSIONS: Overall, this study enhances our understanding of the immune mechanisms involved in schistosomiasis. It provides a transcriptional atlas of peripheral immune cells that may contribute to elimination of the disease. This preliminary study suggests that the increased presence of CCR2 + monocyte and CXCR2 + NKT cells might participate in the progression of schistosomiasis.

IgG persistence showed weak clinical aspects in chronic schistosomiasis patients.

Schistosomiasis is a chronic parasitic disease, which affects the quality of daily life of patients and imposes a huge burden on society. Hepatic fibrosis in response to continuous insult of eggs to the liver is a significant cause of morbidity and mortality. However, the mechanisms of hepatic fibrosis in schistosomiasis are largely undefined. The purpose of our study is to detect the indicator to hepatic fibrosis in schistosomiasis. A total of 488 patients with chronic schistosomiasis japonica were enrolled in our study. The patients were divided into two groups according to liver ultrasound examination, which could indicate liver fibrosis of schistosomiasis with unique reticular changes. Logistic regression analysis showed that globulin, albumin/globulin, GGT levels and anti-Schistosoma IgG were independently associated with liver fibrosis in patients with schistosomiasis and IgG was the largest association of liver fibrosis (OR 2.039, 95% CI 1.293-3.213). We further compared IgG+ patients with IgG- patients. IgG+ patients (ALT 25 U/L, GGT 31 U/L) slightly higher than IgG- patients (ALT 22 U/L, GGT 26 U/L) in ALT and GGT. However, the fibrosis of liver in IgG+ patients (Grade II(19.7%), Grade III(7.3%)) were more severe than that in IgG- patients(Grade II(12.5%), Grade III(2.9%)) according to the grade of liver ultrasonography. Our results showed anti-Schistosoma IgG was independently associated with liver fibrosis in patients with chronic schistosomiasis japonica and patients with persistent anti-Schistosoma IgG might have more liver fibrosis than negative patients despite no obvious clinical signs or symptoms.

Characteristics of peripheral lymphocyte subsets in patients with different stages of schistosomiasis japonica.

Immune cells are important for the development of schistosomiasis japonica and are also critical for the treatment of schistosomiasis. The immune cells in the peripheral blood help assess the immune state. The peripheral lymphocytes in schistosomiasis mansoni were well studied; however, immune cells in patients with different stages of schistosomiasis japonica are not well analysed. Here, we performed a preliminary study to explore characteristics of peripheral lymphocyte subsets in patients with different stages of schistosomiasis japonica. 135 patients with Schistosoma japonicum infection and 25 healthy volunteers were included in this study, including 84 patients with chronic S. japonicum infection and 51 patients with advanced S. japonicum infection. Flow cytometry analysis was performed to evaluate peripheral lymphocytes including T cells, B cells, and natural killer (NK) cells. Blood routine and liver function test data were analysed. Ultrasound examination was used to access liver fibrosis according to the World Health Organization standard about ultrasound in schistosomiasis. Demographic data analysis suggested there was no difference in age and gender in patients with S. japonicum infection and health control group. Liver function tests showed that patients with advanced schistosomiasis had a higher incidence of liver function abnormality and blood lipid than those with chronic schistosomiasis. Blood routine results reflected that haemoglobin, red blood cells, platelets, as well as lymphocytes in the advanced group were significantly less than that in the chronic group. Furthermore, flow cytometry analysis indicated that the percentage of CD4+ T cells was lower in the advanced group, but the percentage of CD19+ B cells was higher in the advanced group. In addition, the number of CD3+ T cells, CD3+ CD4+ T cells, CD3+ CD8+ T cells, and NK cells was less in the advanced group when compared with those in the chronic group. In addition, there was a correlation between the decrease in CD4+ T cells and more severe fibrosis on ultrasound images. Our results indicated that the immune state in the peripheral is different in different stages of S. japonicum infection. Lymphocyte subset analysis has potential to facilitate differential diagnosis of different stages of schistosomiasis japonica and even to be a prognostic factor.

Distribution of the Retinal Microcirculation Based on the Morphology of Peripapillary Atrophy in High Myopia.

INTRODUCTION: The objective of this study was to evaluate the retinal microvasculature of the optic nerve head and macula in high myopia (HM), investigate the association between the vascular parameters and peripapillary atrophy (PPA) deformation, and assess and identify the PPA morphology changes during the development of HM. METHODS: One hundred sixty-seven right eyes from 167 HM patients were enrolled in this cross-sectional study. Using the optical coherence tomography angiography (OCTA) and fundus camera, we evaluated the following parameters: radian and type of PPA, intrapapillary vascular density (IVD), peripapillary vascular density (PVD), macular vascular density (MVD), and foveal avascular zone (FAZ). Based on the PPA radian, subjects were divided into four groups: the non-PPA, temporal PPA, advanced PPA, and annular PPA. At the same time, the above parameters were compared between the groups using analysis of variance (ANOVA) and least significant difference test. RESULTS: Total enrolled patients were divided into the non-PPA group (22 eyes), temporal-PPA group (70 eyes), advanced-PPA group (60 eyes), and annular-PPA group (15 eyes). The results showed that the PVD in the annular-PPA group was smaller than that in the non-PPA group, especially in the superonasal, nasosuperior, nasoinferior, inferotemporal, temporoinferior, and superotemporal directions (F = 4.059, 5.014, 2.830, 4.798, 5.892, 3.439; p < 0.05). Notably, the PVD showcased the highest value in temporal, followed by that in superior and inferior, and the lowest in the nasal. Concerning the fovea deep macular vascular density, FAZ area, and subfoveal choroidal thickness in the annular-PPA group, they were less than those of the rest of the groups (p < 0.05). CONCLUSION: The retinal microvasculature differed significantly in HM according to the PPA morphology. In addition to PVD and SFCT, the PPA can also affect FAZ. Finally, we speculated that PVD demonstrated better predictability of myopic progression than MVD.

MicroRNA regulation of phenotypic transformations in vascular smooth muscle: relevance to vascular remodeling.

Alterations in the vascular smooth muscle cells (VSMC) phenotype play a critical role in the pathogenesis of several cardiovascular diseases, including hypertension, atherosclerosis, and restenosis after angioplasty. MicroRNAs (miRNAs) are a class of endogenous noncoding RNAs (approximately 19-25 nucleotides in length) that function as regulators in various physiological and pathophysiological events. Recent studies have suggested that aberrant miRNAs' expression might underlie VSMC phenotypic transformation, appearing to regulate the phenotypic transformations of VSMCs by targeting specific genes that either participate in the maintenance of the contractile phenotype or contribute to the transformation to alternate phenotypes, and affecting atherosclerosis, hypertension, and coronary artery disease by altering VSMC proliferation, migration, differentiation, inflammation, calcification, oxidative stress, and apoptosis, suggesting an important regulatory role in vascular remodeling for maintaining vascular homeostasis. This review outlines recent progress in the discovery of miRNAs and elucidation of their mechanisms of action and functions in VSMC phenotypic regulation. Importantly, as the literature supports roles for miRNAs in modulating vascular remodeling and for maintaining vascular homeostasis, this area of research will likely provide new insights into clinical diagnosis and prognosis and ultimately facilitate the identification of novel therapeutic targets.

Morphology and microcirculation changes of the optic nerve head between simple high myopia and pathologic myopia.

PURPOSE: To investigate morphological and microcirculation changes of optic nerve head (ONH) in simple high myopia (SHM) and pathologic myopia(PM) to evaluate and identify ONH changes in the development of PM. METHODS: A cross-sectional clinical study was used. Medical records from 193 right eyes of 193 patients with high myopia (HM) were included. Using the Topocon swept source optical coherence tomograph (SS-OCT) and fundus camera to detect the parameters, we have assessed the relative position and size of ONH, tilt and rotation of ONH, angle α (Defined as between retinal temporal arterial vascular arcades was measured from the centre of ONH with 250 pixels' radius), size and type of peripapillary atrophy (PPA), the thickness of peripapillary retinal nerve fiber layer (PRNFL), peripapillary choriodal thickness (PCT) and peripapillary scleral thickness (PST), and peripapillary vessel density (PVD). In addition, subjects were grouped as SHM and PM according to retinopathy, and the above parameters were compared between the two groups. RESULTS: Patients were divided into the SHM group (138 eyes) and the PM group (55 eyes). Paramters like older age, higher diopter and longer axial length (AL) of the PM were compared to SHM (t=-3.585, -8.808, -11.409, all P<0.05). There were no differences in the smallest diameter and area of ONH, rotation angle and ratio, or PST (all P>0.05). The angle α in PM was smaller than that in SHM (t = 2.728, P<0.01). The disc-fovea distance (DFD), the largest diameter, tilt index and ratio, PPA area and radian in PM were larger than in SHM (t=-3.962, Z=-2.525, t=-2.229, Z=-4.303, Z=-2.834, all P<0.05). The superior and inferior PRNFLs in PM were smaller than in SHM (t = 4.172, 4.263, all P<0.01). The temporoinferior PRNFL was the opposite (t=-2.421, P<0.01). The average PCT in PM (93.82 ± 29.96 µm) was smaller than in SHM (108.75 ± 30.70 µm) (P<0.05). The PVD in each direction of PM was smaller than that in SHM (t = 6.398, 4.196, 4.971, 3.267, 5.029, 5.653, 4.202, 5.146, 2.090, all P<0.05). CONCLUSION: Compared with SHM, the PM patients were older, with higher diopter. Their AL and DFD were longer, the angle α was smaller, the tilt index was more extensive, the PPA area and radian were larger, PCT was generally thinner, and PVD was lower. When the PPA area was bigger than the ONH area, this already indicated the presence of PM. Based on these results, we suggest ophthalmologists and myopia patients pay more attention to ONH's morphology and microcirculation changes as there is a possibility that microcirculatory changes precede morphologic changes.

Amblyopic astigmatism characteristics and surgical outcomes in younger children with severe congenital ptosis after frontalis suspension surgery.

BACKGROUND: To examine the astigmatism characteristics and surgical outcomes in patients with unilateral severe congenital ptosis following frontalis suspension surgery. METHODS: We included 53 congenital ptosis patients who underwent frontalis suspension surgery in Hunan Children's Hospital. Each patient underwent a refractive examination before and after surgery to assess astigmatism. We also evaluated the effects and complications associated with the procedure. RESULTS: Degree of astigmatism in ptotic and fellow eyes was - 1.45 ± 0.59 D and - 0.66 ± 0.51 D before surgery. Ratio of severe astigmatism in ptotic and fellow eyes was 51.3 and 12.8%. The fellow eyes presented with with-the-rule astigmatism (WR; 71.8%) and against-the-rule astigmatism (AR; 20.5%) types, with no cases of oblique astigmatism (OA). Ptotic eyes demonstrated higher frequencies of AR (59.0%) and OA (10.2%) than did fellow eyes. Furthermore, the former showed increased astigmatism, followed by a gradual decrease at the 6-month, before significantly decreasing at the 1-year postoperatively. The ratio of postoperative AR and OA astigmatism cases in ptotic eyes decreased to 35.9 and 7.7% 1 month postoperatively. However, there was a postoperative increase in the WR ratio from 30.8 to 56.4% after 1 month. Kaplan-Meier survival analysis showed a success rate of 81.4% at 6 months and 62.9% at 12 months which was influenced by the following complications: suture reaction, epithelial keratopathy, infection and granuloma, lid lag, and recurrence. CONCLUSION: Monocular congenital ptosis could develop severe astigmatism and higher frequency of AR or OA, early surgery may ameliorate astigmatic amblyopia.

Distribution of the Retinal Microcirculation Based on the Morphology of the Optic Nerve Head in High Myopia.

PURPOSE: To explore the retinal microvasculature of the optic nerve head and macula and their associations with the optic nerve head deformation in high myopia. METHODS: One hundred sixty-seven eyes from patients with high myopia (HM) were enrolled in a cross-sectional study. We have evaluated and measured characteristics like the tilt ratio of the optic disc, interpupillary vascular density (IVD), peripapillary vascular density (PVD), macular vascular density (MVD), subfoveal choroidal thickness (SFCT) and foveal avascular zone (FAZ). The subjects were classified as a non-tilt group (control group) and a tilt group based on the tilt index. The above parameters were utilized to compare the two groups. In addition, we collected the data from the subjects' right eyes to analyze variance, the Kruskal-Wallis test, and the least significant difference. RESULTS: The patients were divided into the non-tilt group of ninety-one eyes and the tilt group of seventy-six eyes. We found that the IVD in the tilt group was more significant than in the non-tilt group (t = -2.794, P = .006). On the other hand, the PVD was less in the tilt group than in the non-tilt, especially in the NS, NI and IN directions (tNS = 3.782; tNI = 3.07; tIN = 2.086; P < .05). Interestingly, the values of PVD were the highest in temporal, second in superior and inferior and lowest in nasal. Concerning the fovea-DMVD (including fovea, parafovea and perifovea), we characterized them as more minor in the tilt group when compared to those in the non-tilt group (P < .05). CONCLUSION: Herein, we discovered that the retinal microvasculature differed significantly in patients with HM according to the ONH morphology. In this population, lower PVD and thinner SFCT were associated with higher odds of the tilted optic disc. In addition, the other two characteristics, the IVD and DMVD, were affected by the ONH deformation. Finally, we showed that PVD demonstrated better predictability of rapid myopic progression than MVD.

Changes of optic nerve head microcirculation in high myopia.

AIM: To analyze the correlation of age, spherical equivalent (SE), and axial length (AL) with the microcirculation of optic nerve head (ONH) in high myopia (HM). METHODS: In this cross-sectional clinical study, 164 right eyes were included. Optical coherence tomography angiography (OCTA) was used to detect ONH vessel density. Eyes were classified based on age, SE, and AL. Groups of Age1, Age2, and Age3 were denoted for age classification (Age1<20y, 20y≤Age2<30y, Age3≥30y); Groups SE1, SE2, and SE3 for the SE classification (-9≤SE1<-6 D, -12≤SE2<-9 D, SE3<-12 D); Groups AL1, AL2, AL3, and AL4 for the AL classification (AL1<26 mm, 26≤AL2<27 mm, 27≤AL3<28 mm, AL4≥28 mm). RESULTS: No significant difference was observed in vessel density among the Age1, Age2, and Age3 groups (all P>0.05) and the SE1, SE2, and SE3 groups (all P>0.05). No significant difference was observed in the intrapapillary vascular density (IVD) among AL1, AL2, AL3, and AL4 groups (P>0.05). However, a significant decrease was found in the peripapillary vascular density (PVD) in the AL1, AL2, AL3, and AL4 groups (F=3.605, P=0.015), especially in the inferotemporal (IT; F=6.25, P<0.001), temporoinferior (TI; F=2.865, P=0.038), and temporosuperior (TS; F=6.812, P<0.001) sectors. The IVD was correlated with age (r=-0.190, P<0.05) but not with SE or AL (P>0.05). The PVD was correlated with AL (r=-0.236, P<0.01) but not with age or SE (P>0.05). CONCLUSION: With the increase of AL, the IVD remains stable while the PVD decreases, especially in the three directions of temporal (IT, TI, and TS). The main cause of microcirculation reduction may be related to AL elongation rather than an increase in age or SE.

A Federated Learning System for Histopathology Image Analysis With an Orchestral Stain-Normalization GAN.

Currently, data-driven based machine learning is considered one of the best choices in clinical pathology analysis, and its success is subject to the sufficiency of digitized slides, particularly those with deep annotations. Although centralized training on a large data set may be more reliable and more generalized, the slides to the examination are more often than not collected from many distributed medical institutes. This brings its own challenges, and the most important is the assurance of privacy and security of incoming data samples. In the discipline of histopathology image, the universal stain-variation issue adds to the difficulty of an automatic system as different clinical institutions provide distinct stain styles. To address these two important challenges in AI-based histopathology diagnoses, this work proposes a novel conditional Generative Adversarial Network (GAN) with one orchestration generator and multiple distributed discriminators, to cope with multiple-client based stain-style normalization. Implemented within a Federated Learning (FL) paradigm, this framework well preserves data privacy and security. Additionally, the training consistency and stability of the distributed system are further enhanced by a novel temporal self-distillation regularization scheme. Empirically, on large cohorts of histopathology datasets as a benchmark, the proposed model matches the performance of conventional centralized learning very closely. It also outperforms state-of-the-art stain-style transfer methods on the downstream Federated Learning image classification task, with an accuracy increase of over 20.0% in comparison to the baseline classification model.

Systematic evaluation on the physicochemical characteristics of a series polysaccharides extracted from different edible lilies by ultrasound and subcritical water.

A series polysaccharide samples extracted from three edible lilies (Lilium davidii var. willmottiae, Lilium brownii var. viridulum, and Lilium lancifolium) by subcritical water and ultrasound-assisted extraction were systematically compared. The results showed that extraction method was a more important factor than lily species. Subcritical water extracted lily polysaccharides (S-LP) with higher yield, molecular weight, neutral glucose and uronic acid content as well as apparent viscosity. Ultrasound-assisted extracted lily polysaccharides (U-LP) with higher reducing sugars and protein content. Moreover, due to the degradation of glycosidic bonds, ultrasonic extraction was easier to obtain lower molecular weight polysaccharides. In addition, the extraction method significantly affected the monosaccharide proportion of polysaccharides, but had no effect on type. Glucose was the main component in S-LP, and glucose and mannose were the main components in U-LP. The micromorphology of different polysaccharide samples was similar, and the scanning electron microscope (SEM) images showed regular/irregular particle clusters with different particle sizes. Overall, the relationships between extraction methods, lily species and polysaccharide properties were preliminarily elucidated, providing a reference for the targeted extraction of specific lily polysaccharides (LP).

Case Report: A de novo Variant of CRYGC Gene Associated With Congenital Cataract and Microphthalmia.

Background: Congenital cataract is one of the most common causes of blindness in children. A rapid and accurate genetic diagnosis benefit the patients in the pediatric department. The current study aims to identify the genetic defects in a congenital cataract patient without a family history. Case presentation: A congenital cataract patient with microphthalmia and nystagmus was recruited for this study. Trio-based whole-exome sequencing revealed a de novo variant (c.394delG, p.V132Sfs*15) in CRYGC gene. According to the American College of Medical Genetics and Genomics (ACMG) criteria, the variant could be annontated as pathogenic. Conclusion: Our findings provide new knowledge of the variant spectrum of CRYGC gene and are essential for understanding the heterogeneity of cataracts in the Chinese population.

The Association between Regulatory T Cell Subpopulations and Severe Pneumonia Post Renal Transplantation.

Severe pneumonia accounts for the majority of morbidity and mortality in renal allograft recipients due to immunosuppressant maintenance. Regulatory T cells (Tregs), which are involved in tackling infections under immunosuppressive conditions, are rarely uncovered. We aimed to investigate the relationship between various Treg subpopulations and severe pneumonia after kidney transplantation (KTx). KTx recipients with pneumonia were divided into severe pneumonia and mild pneumonia groups. The frequencies and absolute numbers (Ab No.) of total Tregs (CD4+CD25+FoxP3+), six subsets of Tregs (Helios+/-, CD39+/-, and CD45RA+/-), and T cells, B cells, and NK cells were assessed from peripheral blood via flow cytometry using the t or Mann-Whitney test and receiver operating curve analysis. We also determined the median fluorescence intensity (MFI) of human leukocyte antigen- (HLA-) DR on monocytes and CD64 on neutrophils. Logistic regression was used to identify the risk factors of disease progression, and Pearson's correlation analysis was performed to identify relationships between the measured immune indices and patients' clinical information. Our research indicated that Treg subpopulations were strongly associated with severe pneumonia progression post KTx. Based on the monitoring of Treg subpopulations, better-individualized prevention and therapy might be achieved for patients with severe pneumonia post KTx.

The Expansion of Myeloid-Derived Suppressor Cells Correlates With the Severity of Pneumonia in Kidney Transplant Patients.

BACKGROUND: Pneumonia is one of the most frequent but serious infectious complications post kidney transplantation. Severe pneumonia induces sustained immunosuppression, but few parameters concerning immune status are used to assess the severity of pneumonia. Myeloid-derived suppressor cells (MDSCs) are induced under infection and have the strong immunosuppressive capacity, but the correlation between MDSCs and pneumonia in kidney transplant recipients (KTRs) is unknown. METHODS: Peripheral blood MDSCs were longitudinally detected in 58 KTRs diagnosed with pneumonia using flow cytometry and in 29 stable KTRs as a control. The effectors of MDSCs were detected in the plasma. Spearman's rank correlation analysis was performed to determine the correlation between MDSCs and the severity of pneumonia as well as lymphopenia. RESULTS: The frequency of MDSCs and effectors, including arginase-1, S100A8/A9, and S100A12, were significantly increased in the pneumonia group compared with the stable group. CD11b+CD14+HLA-DRlow/-CD15- monocytic-MDSCs (M-MDSCs) were higher in the pneumonia group but showed no significant difference between the severe and non-severe pneumonia subgroups. CD11b+CD14-CD15+ low-density granulocytic-MDSCs (G-MDSCs) were specifically increased in the severe pneumonia subgroup and correlated with the severity of pneumonia as well as lymphopenia. During the study period of 2 weeks, the frequencies of MDSCs and G-MDSCs were persistently increased in the severe pneumonia subgroup. CONCLUSIONS: MDSCs and G-MDSCs were persistently increased in KTRs with pneumonia. G-MDSCs were correlated with the severity of pneumonia and could thus be an indicator concerning immune status for assessing pneumonia severity.

Influence of polymorphisms in VEGF, TNF-α, and GSTP1 genes on retinopathy of prematurity risk: a Meta-analysis.

PURPOSE: To investigate the influence of polymorphisms in vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), and glutathione S-transferase Pi isoform (GSTP1) genes on retinopathy of prematurity (ROP) risk, we performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant meta-analysis. METHODS: An exhaustive search was conducted in PubMed, Web of Science, and CNKI for genetic studies evaluating the relationship between VEGF (-460 T/C, +936 C/T, -634 G/C, and -2578 C/A), TNF-α (-308 G/A) and GSTP1 (Ile/Val) polymorphisms and ROP risk from inception until November 2019. Odds ratio (OR) with the 95% confidence interval (CI) were used for estimating combined effect size. The quality of the included studies was evaluated using the Newcastle-Ottawa Scale (NOS). RESULTS: A total of 14 studies met the inclusion criteria. The meta-analyses revealed that VEGF - 460 T/C was associated with ROP risk in the allele model (C vs. T, OR = 0.83, 95% CI: 0.74-0.94, POR=0.004), homozygous gene model (CC vs. TT, OR = 0.70, 95% CI: 0.54-0.91, POR=0.008), dominant gene model (CC + TC vs. TT, OR = 0.80, 95% CI: 0.67-0.95, POR = 0.012), and recessive gene model (CC vs. TC + TT, OR = 0.74, 95% CI: 0.59-0.94, POR = 0.014). However, we did not find significant differences in the genotype and allele distribution of VEGF + 936 C/T, -634 G/C, -2578 C/A, TNF-α - 308 G/A and GSTP1 Ile/Val polymorphisms, between ROP and control group (p > .05). CONCLUSIONS: VEGF polymorphism -460 T/C was associated with a lower ROP risk. Further research is warranted to investigate haplotype effects of VEGF polymorphisms on the risk of ROP.

The Role of Apolipoprotein E ε4 in Early and Late Mild Cognitive Impairment.

BACKGROUND: Apolipoprotein E (APOE) ε4 is highly associated with mild cognitive impairment (MCI). However, the specific influence of APOE ε4 status on tau pathology and cognitive decline in early MCI (EMCI) and late MCI (LMCI) is poorly understood. Our goal was to evaluate the association of APOE ε4 with cerebrospinal fluid (CSF) tau levels and cognition in EMCI and LMCI patients in the Alzheimer's Disease Neuroimaging Initiative database, and whether this association was mediated by amyloid-ß (Aß). METHODS: Participants were 269 cognitively normal (CN), 262 EMCI, and 344 LMCI patients. They underwent CSF Aß42 and tau detection, APOE ε4 genotyping, Mini-Mental State Examination, (MMSE), and Alzheimer's disease assessment scale (ADAS)-cog assessments. Linear regressions were used to examine the relation of APOE ε4 and CSF tau levels and cognitive scores in persons with and without Aß deposition (Aß+ and Aß-). RESULTS: The prevalence of APOE ε4 is higher in EMCI and LMCI than in CN (p < 0.001 for both), and in LMCI than in EMCI (p = 0.001). APOE ε4 allele was significantly higher in Aß+ subjects than in Aß- subjects (p < 0.001). Subjects who had a lower CSF Aß42 level and were APOE ε4-positive experienced higher levels of CSF tau and cognitive scores in EMCI and/or LMCI. CONCLUSIONS: An APOE ε4 allele is associated with increased CSF tau and worse cognition in both EMCI and LMCI, and this association may be mediated by Aß. We conclude that APOE ε4 may be an important mediator of tau pathology and cognition in the early stages of AD.

Antagonizing αvß3 Integrin Improves Ischemia-Mediated Vascular Normalization and Blood Perfusion by Altering Macrophages.

Background: αVß3 integrin has been implicated in the physiological processes and pathophysiology of important angiogenesis-related disorders; however, the preclinical and clinical data on integrin αVß3 antagonists have not demonstrated improved outcomes. Our goal was to test the hypothesis that inhibition of αVß3 integrin improves blood flow in a mouse hindlimb ischemia model. Methods: In this study, we examined the effect of cilengitide, an αVß3/αVß5 integrin-specific RGD-mimetic cyclic peptide, on blood perfusion and angiogenesis after hindlimb ischemia. Blood flow was measured using Laser Doppler Scanner. Vascular density, and macrophages infiltration were examined by immunofluorescence. Macrophage polarization was measured by quantitative real time PCR. Results: We found that low-dose, not high-dose, cilengitide increased blood flow perfusion, capillary formation, and pericyte coverage, accompanied by an accumulation of macrophages and increased expression of the chemokine (C-C motif) ligand 2 (CCL2) in ischemic muscles. Macrophage depletion using clodronate liposomes resulted in a reduction in low-dose cilengitide-induced blood flow perfusion, macrophage accumulation, pericyte coverage, and CCL2 expression. Finally, in vitro assays showed that low-dose, not high-dose, cilengitide increased macrophage migration. Conclusion: These studies identified a novel role of the inhibition of αVß3 integrin in modulating ischemia-induced angiogenesis, possibly through effects on macrophage infiltration and polarization, and revealed αVß3 integrin inhibition to be a promising therapeutic strategy for peripheral artery disease.