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.

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.

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 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.

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.

Platelet-endothelial cell interactions modulate smooth muscle cell phenotype in an in vitro model of type 2 diabetes mellitus.

Platelet (PLT)-endothelial cell (EC) interaction appears to contribute to phenotypic transition of vascular smooth muscle cells (VSMCs), which play an important role in the physiological and pathological process of vascular complications in type 2 diabetes mellitus (DM2). However, the precise mechanisms by which interactions between PLTs and ECs affect VSMC phenotype have largely remained unclear. We determined the effect of diabetic PLT-EC interaction to influence VSMC migration, proliferation, and phenotypic transformation in triple-cell coculture models using the quantitative real-time PCR, Western blot, fluorescence microscopy, wound scratch assays, CCK-8 assays, and gelatin zymography assays. Our results revealed DM2 PLT-EC interaction to be associated with a significant downregulation of VSMC-specific contractile phenotypic genes and proteins, including SM22α, smooth muscle actin, Smoothelin-B, and smooth muscle-myosin heavy chain. Inversely, VSMC-specific proliferative phenotype gene and protein levels, including cyclin D1 and 2, nonmuscle myosin heavy chain B, and PCNA were in upregulation. Furthermore, the DM2-originated PLT-EC interaction promoted the expression level of transforming growth factor-ß1, and the PI3K/Akt and matrix metalloproteinase 9 signaling pathway was activated subsequently. Finally, these reactions contributed to a synthetic phenotype of VSMCs, including the proliferation, migration, and gelatinolytic activities. These findings suggest that PLT-EC interaction modulates the phenotypic transition of VSMCs between a contractile and proliferative/synthetic phenotype under diabetic conditions, conceivably providing important implications regarding the mechanisms controlling the VSMC phenotypic transition and the development of cardiovascular complications.

PGK1 is a Potential Survival Biomarker and Invasion Promoter by Regulating the HIF-1α-Mediated Epithelial-Mesenchymal Transition Process in Breast Cancer.

BACKGROUND/AIMS: Glycolysis, a multi-step enzymatic reaction, is considered to be the root of cancer development and progression. The aim of this study is to figure out which glycolysis enzyme participates in the progression of breast cancer and its possible mechanisms. MATERIALS: We firstly screened out PGK1 by performing an RT-PCR array of glycolysis-related genes in three paired breast cancer samples, and further investigated PGK1 using TCGA and our own database. The effect and mechanism of PGK1 on cell invasion was further explored both in vitro and using patient samples. RESULTS: PGK1 was most upregulated in T3N0 with distant metastases compared to those with no metastases. In the TCGA database, high PGK1 expression predicted poor overall survival (OS) in breast cancer and some other cancers (P< 0.001). In the validation cohort, high PGK1 expression was significantly correlated with larger tumor size (P=0.011) and advanced TNM stage (P=0.033), and PGK1 expression was an independent prognostic factor for OS and disease free survival (DFS) in both univariate and multivariate regression analyses (P< 0.05). Functional studies indicated that knockdown of PGK1 expression significantly inhibited invasion and reversed the epithelial-mesenchymal transition process in breast cancer cells (P< 0.05). Mechanistically, PGK1 increased HRE luciferase activity in a dose-dependent manner, while silencing PGK1 expression decreased HRE activity. CONCLUSION: High PGK1 expression was associated with poor prognosis in breast cancer, because PGK1 and HIF-1α formed a positive feed-forward loop and thus stimulated breast cancer progression and metastases. Based on these results, PGK1 may serve as a promising biomarker and target therapy for breast cancer.

HMGB2 is associated with malignancy and regulates Warburg effect by targeting LDHB and FBP1 in breast cancer.

BACKGROUND: High-mobility group box 2 (HMGB2) is implicated in tumorigenesis in various cancers. However, the clinical significance of HMGB2 signaling in human breast cancer progression remains unknown. METHODS: We investigated HMGB2 expression in 185 cases of primary breast cancer and matched normal breast tissue specimens, and explored the underlying mechanisms of altered HMGB2 expression as well as the impact of this altered expression on breast cancer growth and on aerobic glycolysis using in vitro and animal models of breast cancer. RESULTS: HMGB2 was more highly expressed in tumor-cell nuclei of breast cancer cells than in the adjacent normal breast tissues (P < 0.05). Higher HMGB2 expression correlated with larger tumor size (P = 0.003) and advanced tumor stage (P = 0.033). A Cox proportional hazards model revealed that HMGB2 expression was an independent prognostic factor for breast cancer after radical resection (P < 0.05). Experimentally, knockdown of HMGB2 expression by stable transfected shRNA significantly decreased the growth and glycolysis of breast cancer cells both in vitro and in mouse models. Mechanically, promotion of breast cancer progression by HMGB2 directly and significantly correlated with activation of LDHB expression and inactivation of FBP1 expression. CONCLUSIONS: These results disclose a novel role for HMGB2 in reprogramming the metabolic process in breast cancer cells by targeting LDHB and FBP1 and provide potential prognostic predictors for breast cancer patients.

Expression and prognostic value of miR-92a in patients with gastric cancer.

MicroRNA (miR)-92 expression is often aberrant in human cancers. However, its expression in gastric carcinoma and its relation to clinicopathological features and prognosis are unclear.Tissue microarrays were constructed from 180 patients with gastric cancer (GC), who were undergoing radical resection. MiR-92a expression was detected using miRNA-locked nucleic acid in situ hybridization, and its correlation with clinicopathological features and overall survival was analyzed. MiR-92a expression was decreased in 13.9 % (25/180) of GC, increased in 81.1 % (146/180), and unchanged in 5.0 % (9/180), compared with paracancerous normal tissue (P < 0.001). Univariate analysis showed that high miR-92a expression, tumor stage, tumor status, node status, and tumor size were significant negative prognostic predictors for overall survival in patients with GC (P < 0.001, P < 0.001, P = 0.008, P < 0.001, and P = 0.001, respectively). High miR-92a expression still remained a significant predictor of shorter survival in stage II (n = 56, P = 0.001) and stage III (n = 92, P = 0.009) GC. Multivariate regression analysis demonstrated that tumor status (hazard ratio [HR], 3.10; 95 % confidence interval [CI], 1.51-6.37; P = 0.002), stage (HR, 3.54; 95 % CI, 1.65-7.63; P = 0.000), lymph node metastasis (HR, 2.83; 95 % CI, 1.88-4.28; P = 0.000), high expression of miR-92a (HR, 2.94; 95 % CI, 2.01-4.31; P = 0.000), and tumor size (HR, 2.34; 95 % CI, 1.45-3.79; P = 0.002) predicted shorter OS.High expression of miR-92a compared with adjacent normal tissues was associated with shorter OS. MiR-92a may thus be useful for evaluating prognosis and may provide a novel treatment target in patients with GC.

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.

Accelerating the Rate-Determining Steps of Sulfur Conversion Reaction for Lithium-Sulfur Batteries Working at an Ultrawide Temperature Range.

Wide operation temperature is the crucial objective for an energy storage system that can be applied under harsh environmental conditions. For lithium-sulfur batteries, the "shuttle effect" of polysulfide intermediates will aggravate with the temperature increasing, while the reaction kinetics decreases sharply as the temperature decreasing. In particular, sulfur reaction mechanism at low temperatures seems to be quite different from that at room temperature. Here, through in situ Raman and electrochemical impedance spectroscopy studies, the newly emerged platform at cryogenic temperature corresponds to the reduction process of Li2S8 to Li2S4, which will be another rate-determining step of sulfur conversion reaction, in addition to the solid-phase conversion process of Li2S4 to Li2S2/Li2S at low temperatures. Porous bismuth vanadate (BiVO4) spheres are designed as sulfur host material, which achieve the rapid snap-transfer-catalytic process by shortening lithium-ion transport pathway and accelerating the targeted rate-determining steps. Such promoting effect greatly inhibits severe "shuttle effect" at high temperatures and simultaneously improves sulfur conversion efficiency in the cryogenic environment. The cell with the porous BiVO4 spheres as the host exhibits excellent rate capability and cycle performance under wide working temperatures.

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.

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.

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.

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.

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.

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.

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.