Characteristic changes in blood routine and peripheral blood lymphocyte subpopulations in recipients of different types of rejection. / ä¸åŒç±»åž‹æŽ’æ–¥ååº”å—è€ è¡€å¸¸è§„åŠå¤–å‘¨è¡€æ·‹å·´ç»†èƒžäºšç¾¤ç‰¹å¾æ€§å˜åŒ–.

OBJECTIVES: Rejection remains the most important factor limiting the survival of transplanted kidneys. Although a pathological biopsy of the transplanted kidney is the gold standard for diagnosing rejection, its limitations prevent it from being used as a routine monitoring method. Recently, peripheral blood lymphocyte subpopulation testing has become an important means of assessing the body's immune system, however, its application value and strategy in the field of kidney transplantation need further exploration. Additionally, the development and utilization of routine test parameters are also important methods for exploring diagnostic strategies and predictive models for kidney transplant diseases. This study aims to explore the correlation between peripheral blood lymphocyte subpopulations and T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR), as well as their diagnostic value, in conjunction with routine blood tests. METHODS: A total of 154 kidney transplant recipients, who met the inclusion and exclusion criteria and were treated at the Second Xiangya Hospital of Central South University from January to December, 2021, were selected as the study subjects. They were assigned into a stable group, a TCMR group, and an ABMR group, based on the occurrence and type of rejection. The basic and clinical data of these recipients were retrospectively analyzed and compared among the 3 groups. The transplant kidney function, routine blood tests, and peripheral blood lymphocyte subpopulation data of the TCMR group and the ABMR group before rejection treatment were compared with those of the stable group. RESULTS: The stable, TCMR group, and ABMR group showed no statistically significant differences in immunosuppressive maintenance regimens or sources of transplanted kidneys (all P>0.05). However, the post-transplant duration was significantly longer in the ABMR group compared with the stable group (P<0.001) and the TCMR group (P<0.05). Regarding kidney function, serum creatinine levels in the ABMR group were higher than in the stable group and the TCMR group (both P<0.01), with the TCMR group also showing higher levels than the stable group (P<0.01). Both TCMR and ABMR groups had significantly higher blood urea nitrogen levels than the stable group (P<0.01), with no statistically significant difference between TCMR and ABMR groups (P>0.05). The estimated glomerular filtration rate (eGFR) was lower in both TCMR and ABMR groups compared with the stable group (both P<0.01). In routine blood tests, the ABMR group had lower hemoglobin, red blood cell count, and platelet count than the stable group (all P<0.05). The TCMR group had higher neutrophil percentage (P<0.05) and count (P<0.05) than the stable group, and the ABMR group had a higher neutrophil percentage than the stable group (P<0.05). The eosinophil percentage and count in the TCMR group were lower than in the stable and ABMR groups (all P<0.05). Both TCMR and ABMR groups had lower basophil percentage and count, as well as lower lymphocyte percentage and count, compared with the stable group (all P<0.05). There were no significant differences in monocyte percentage and count among the 3 groups (all P>0.05). In lymphocyte subpopulations, the TCMR and ABMR groups had lower counts of CD45+ cells and T cells compared with the stable group (all P<0.05). The TCMR group also had lower counts of CD4+ T cells, NK cells, and B cells than the stable group (all P<0.05). There were no significant differences in the T cell percentage, CD4+ T cell percentage, CD8+ T cell percentage and their counts, CD4+/CD8+ T cell ratio, NK cell percentage, and B cell percentage among the stable, TCMR, and ABMR groups (all P>0.05). CONCLUSIONS: The occurrence of rejection leads to impaired transplant kidney function, accompanied by characteristic changes in some parameters of routine blood tests and peripheral blood lymphocyte subpopulations in kidney transplant recipients. The different characteristics of changes in some parameters of routine blood tests and peripheral blood lymphocyte subpopulations during TCMR and ABMR may help predict and diagnose rejection and differentiate between TCMR and ABMR.

Comparative efficacy of different exercise types on inflammatory markers in women with overweight and obesity: A systematic review and network meta-analysis of randomized controlled trials.

OBJECTIVES: This study aimed to compare and rank the effectiveness of aerobic exercise, resistance training, combined aerobic and resistance exercise, and high-intensity interval training on inflammatory marker levels in women with overweight and obesity by using network meta-analysis. DESIGN: Systematic review with network meta-analysis and Grading Recommendations Assessment, Development, and Evaluation of the evidence. METHODS: Literature as of April 2023 was searched from databases such as Cochrane, Embase, Pubmed, Web of Science, and EBSCO, and English-language randomized controlled trials that meet the inclusion criteria were selected. A random-effects network meta-analysis was performed within a frequentist framework. RESULTS: A total of 75 articles and 4048 participants were included. Resistance training was the most recommended type of exercise to decrease C-reactive protein levels (surface under cumulative ranking = 90.1; standardized mean difference = -0.79, 95 % confidence interval: -1.17, -0.42); aerobic exercise was the most effective exercise type to reduce tumor necrosis factor-α levels (surface under cumulative ranking = 87.9; standardized mean difference = -0.79, 95 % confidence interval: -1.19, -0.39); combined aerobic and resistance exercise was the most effective type of exercise to reduce interleukin-6 levels (surface under cumulative ranking = 75.8; standardized mean difference = -0.77, 95 % confidence interval: -1.38, -0.16) and leptin levels (surface under cumulative ranking = 77.1; standardized mean difference = -0.96, 95 % confidence interval: -1.72, -0.20), and high-intensity interval training was the type of exercise that was well suited to increase adiponectin levels (surface under cumulative ranking = 87.2; standardized mean difference = 0.99, 95 % confidence interval: 0.27, 1.71). CONCLUSIONS: This network meta-analysis based on randomized controlled trials confirmed that different exercise types have different efficacies on inflammation indicators among women with overweight and obesity. The findings may provide clinicians and healthcare professionals with insights into the implementation of exercise programs for women struggling with overweight and obesity.

The Impact of SARS-CoV-2 Infection on the Length of Stay in the Neuro-ICU:A Prospective Multicenter Cohort Study in Eight Neuro-ICU, China Between February and April 2023.

Purpose: The SARS-CoV-2 infection cases are increasing rapidly in neuro-intensive care units (neuro-ICUs) at the beginning of 2023 in China. We aimed to characterize the prevalence, risk factors, and prognosis of critically ill patients treated in neuro-ICUs. Materials and Methods: In the prospective, multicenter, observational registry study, critically ill patients with intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), and traumatic brain injury (TBI) admitted to eight Chinese neuro-ICUs between Feb 16, 2023, to Apr 30, 2023 were enrolled for the study. Mortality and ICU stay day were used as the primary outcomes. Results: 131 patients were finally included and analyzed (mean age 60.36 years [SD 13.81], 64.12% male, 39.69% SARS-CoV-2 infected). The mortality is higher in the SARS-CoV-2 infection group without statistical signification (7.69% vs 5.06%, p>0.05). The length of stay (LOS) in neuro-ICUs was significantly longer among the SARS-CoV-2 infection patients (7(1-12) vs 4(1-8), p<0.01), with increased viral pneumonia occurrence (58.54% vs 7.32%, p<0.01). SARS-CoV-2 infection, surgery, and low GCS scores were independent risk factors for prolonged LOS, and respiratory/renal failure were independent risk factors for death. Conclusion: Based on the present neuro-ICU cohort, SARS-CoV-2 infection was a significant risk for the prolonged LOS of neuro-critically ill patients. Trial Registration: Registered with Chictr.org.cn (ChiCTR2300068355) at 16 February 2023, Prospective registration. https://www.chictr.org.cn/showproj.html?proj=188252.

A new minimally invasive, nonexcisional, surgical browlift technique with minimal scarring: a protocol for a prospective observational study.

Background: The aim of this study is to prospectively evaluate the new minimal invasive (MINE) browlift technique with possibly superior results and minimal visible scarring. Study design: A prospective observational study will be performed on all available data from patients who will undergo a browlift procedure in the HMC from 1 June 2021 till 31 May 2024. Our goal is to include at least 50 patients. Inclusion criteria are: patients with medical (i.e. brow ptosis and facial paralysis) or cosmetic indication, patients with sufficient understanding of the Dutch or English language and willingness to participate in extra study specific follow-up moments and filling in of questionnaires. Exclusion criteria are: less than 18 years of age and patients with previous brow or eyelid surgery. Patients will be photographed preoperatively and postoperatively using the VECTRA camera. Outcome measurements: Scarring after procedure; functionality of eyebrow movement; amount of correction in brow ptosis, measured in VECTRA; longevity of procedure in months; aesthetic result as assessed by questionnaires and adverse effects of procedure will be measured. Ethics and dissemination: The database management software 'Castor' will be used to store and collect the data from the questionnaire. The Medical Research Ethics Committee found this study not eligible to be submitted to the Dutch Medical Research Involving Human Subjects Acts (WMO). Written consent will be obtained from all patients.

Monitoring of Perioperative Microcirculation Dysfunction by Near-Infrared Spectroscopy for Neurological Deterioration and Prognosis of Aneurysmal Subarachnoid Hemorrhage: An Observational, Longitudinal Cohort Study.

INTRODUCTION: No evidence has established a direct causal relationship between early microcirculation disturbance after aneurysmal subarachnoid hemorrhage (aSAH) and neurological function prognosis, which is the key pathophysiological mechanism of early brain injury (EBI) in patients with aSAH. METHODS: A total of 252 patients with aSAH were enrolled in the Neurosurgical Intensive Care Unit of Southwest Hospital between January 2020 and December 2022 and divided into the no neurological deterioration, early neurological deterioration, and delayed neurological deterioration groups. Indicators of microcirculation disorders in EBI included regional cerebral oxygen saturation (rSO2) measured by near-infrared spectroscopy (NIRS), brain oxygen monitoring, and other clinical parameters for evaluating neurological function and determining the prognosis of patients with aSAH. RESULTS: Our data suggest that the rSO2 is generally lower in patients who develop neurological deterioration than in those who do not and that there is at least one time point in the population of patients who develop neurological deterioration where left and right cerebral hemisphere differences can be significantly monitored by NIRS. An unordered multiple-classification logistic regression model was constructed, and the results revealed that multiple factors were effective predictors of early neurological deterioration: reoperation, history of brain surgery, World Federation of Neurosurgical Societies (WFNS) grade 4-5, Fisher grade 3-4, SAFIRE grade 3-5, abnormal serum sodium and potassium levels, and reduced rSO2 during the perioperative period. However, for delayed neurological deterioration in patients with aSAH, only a history of brain surgery and perioperative RBC count were predictive indicators. CONCLUSIONS: The rSO2 concentration in patients with neurological deterioration is generally lower than that in patients without neurological deterioration, and at least one time point in the population with neurological deterioration can be significantly monitored via NIRS. However, further studies are needed to determine the role of microcirculation and other predictive factors in the neurocritical management of EBI after aSAH, as these factors can reduce the incidence of adverse outcomes and mortality during hospitalization.

Downregulation of nutrition sensor GCN2 in macrophages contributes to poor wound healing in diabetes.

Poor skin wound healing, which is common in patients with diabetes, is related to imbalanced macrophage polarization. Here, we find that nutrition sensor GCN2 (general control nonderepressible 2) and its downstream are significantly upregulated in human skin wound tissue and mouse skin wound macrophages, but skin wound-related GCN2 expression and activity are significantly downregulated by diabetes and hyperglycemia. Using wound healing models of GCN2-deleted mice, bone marrow chimeric mice, and monocyte-transferred mice, we show that GCN2 deletion in macrophages significantly delays skin wound healing compared with wild-type mice by altering M1 and M2a/M2c polarization. Mechanistically, GCN2 inhibits M1 macrophages via OXPHOS-ROS-NF-κB pathway and promotes tissue-repairing M2a/M2c macrophages through eukaryotic translation initiation factor 2 (eIF2α)-hypoxia-inducible factor 1α (HIF1α)-glycolysis pathway. Importantly, local supplementation of GCN2 activator halofuginone efficiently restores wound healing in diabetic mice with re-balancing M1 and M2a/2c polarization. Thus, the decreased macrophage GCN2 expression and activity contribute to poor wound healing in diabetes and targeting GCN2 improves wound healing in diabetes.

Comparisons of procedural characteristics and clinical outcomes between SMARTTOUCH SURROUNDFLOW catheter and other catheters for atrial fibrillation radiofrequency catheter ablation: a systematic literature review.

BACKGROUND: SMARTTOUCH SURROUNDFLOW (STSF) catheter is the new generation of SMARTTOUCH (ST) catheter with an upgraded irrigation system for radiofrequency catheter ablation (RFCA) in patients with atrial fibrillation (AF). METHODS: This systematic literature review searched the major English and Chinese bibliographic databases from 2016 to 2022 for any original clinical studies assessing the STSF catheter for RFCA in AF patients. Meta-analysis with a random effects model was used for evidence synthesis. RESULTS: Pooled outcomes from 19 included studies indicated that STSF catheter was associated with a significantly shorter procedure time (weighted mean difference (WMD): -17.4 min, p<0.001), shorter ablation time (WMD: -6.6 min, p<0.001) and lower catheter irrigation fluid volume (WMD: -492.7 mL, p<0.001) than ST catheter. Pooled outcomes from four included studies with paroxysmal AF patients reported that using the STSF catheter for RFCA was associated with a significantly shorter ablation time (WMD: -5.7 min, p<0.001) and a lower risk of 1-year postablation arrhythmia recurrence (rate ratio: 0.504, p<0.001) than the SURROUNDFLOW (SF) catheter. Significant reductions in procedure time and ablation time associated with the STSF catheter were also reported in the other four studies using non-ST/SF catheters as the control. Overall complications of STSF catheter and control catheters were comparable. CONCLUSIONS: Using the STSF catheter was superior to using the ST catheter to conduct RFCA for AF by significantly reducing procedure time, ablation time, fluoroscopy time and irrigation fluid volume. The superiority of the STSF catheter over the SF catheter and other non-ST/SF catheters for RFCA needs further confirmation.

Effect of exercise on inflammatory markers in postmenopausal women with overweight and obesity: A systematic review and meta-analysis.

IMPORTANCE: Postmenopausal women affected by overweight and obesity are susceptible to a variety of diseases due to inflammation. Exercise may reduce the risk of disease by attenuating low-grade chronic inflammation. OBJECTIVE: We conducted a systematic review and meta-analysis to investigate the effects of exercise on inflammatory markers in postmenopausal women struggling with overweight and obesity. METHOD: Literature as of May 2023 was searched from databases such as Cochrane, Embase, Pubmed, Web of Science, and EBSCO and English-language randomized controlled trials (RCTs) that meet the inclusion criteria were selected. Studies were included based on the following criteria: (A) Written in English; (B) RCTs; (C) Postmenopausal women impacted by overweight and obesity as research objects; (D) Outcome measurements include CRP, TNF-α, IL-6, and adiponectin; (E) Duration of the exercise intervention is eight weeks. RESULTS: A total of 34 articles and 2229 participants were included. Exercise can significantly reduce the level of C-reactive protein (CRP) (MD: -0.59, 95 % CI: -0.87 to -0.31, p < 0.00001), tumor necrosis factor-α (TNF-α) (MD: -0.65, 95 % CI: -0.94 to -0.35, p < 0.00001), interleukin-6 (IL-6) (MD: -0.48, 95 % CI: -0.75 to -0.21, p < 0.00001), and exercise can significantly increase the level of adiponectin (MD: 0.33, 95 % CI: 0.02 to 0.65, p = 0.04) in women impacted by overweight and obesity. CONCLUSION: These results suggest that exercise may be an effective intervention for reducing pro-inflammatory markers and increasing adiponectin in postmenopausal women impacted by overweight and obesity. The findings may provide clinicians and healthcare professionals with insights into the implementation of exercise programs for postmenopausal women living with overweight and obesity.

Hemophagocytic lymphohistiocytosis secondary to virus infection and followed by lupus nephritis recurrence in a renal transplantation pediatric recipient: a case report.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening disorder characterized by systemic inflammation and organ failure as a result of dysregulated immune cell activation. HLH can be induced by a variety of factors including infection, tumours and autoimmune disease and can also occur in patients following solid organ transplantation. Occurrence of HLH and lupus nephritis (LN) successively within a short period of time after renal transplantation is uncommon. CASE PRESENTATION: We described an 11-year-old female post-transplant patient who presented with hemocytopenia, fever, elevated serum ferritin, splenomegaly, hyperlipidemia, and hypofibrinemia, and was clinically diagnosed with HLH. After comprehensive treatment with corticosteroids, intravenous immunoglobulin (IVIG), and reducing immunosuppressants, her condition improved, but then hematuria ensued. The transplant kidney biopsy showed LN. She was treated with hydroxychloroquine and methylprednisolone while intensive immunosuppressive agents were given. She has remained in remission for two years until now. CONCLUSIONS: The main inducing factors of HLH should be identified as early as possible, and accurate treatment plans should be taken. The long-course IVIG regimen may be one of the effective treatments for virus-induced HLH. After remission of HLH, we need to be alert to the recurrence of autoimmune diseases in patients with underlying diseases, and timely increase immunosuppressants.

Evaluation of Preoperative Microvascular Invasion in Hepatocellular Carcinoma Through Multidimensional Parameter Combination Modeling Based on Gd-EOB-DTPA MRI.

Background and Aims: The study established and compared the efficacy of the clinicoradiological model, radiomics model and clinicoradiological-radiomics hybrid model in predicting the microvascular invasion (MVI) of hepatocellular carcinoma (HCC) using gadolinium ethoxybenzyl diethylene triaminepentaacetic acid (Gd-EOB-DTPA) enhanced MRI. Methods: This was a study that enrolled 602 HCC patients from two institutions. Least absolute shrinkage and selection operator (Lasso) method was used to screen for the most important clinicoradiological and radiomics features that predict MVI pre-operatively. Three machine learning algorithms were used to establish the clinicoradiological, radiomics, and clinicoradiological-radiomics hybrid models. Area under the curve (AUC) of receiver operating characteristic (ROC) curves and Delong's test were used to compare and quantify the predictive performance of the models. Results: The AUCs of the clinicoradiological model in training and validation cohorts were 0.793 and 0.701, respectively. The radiomics signature of arterial phase (AP) images alone achieved satisfying predictive efficacy for MVI, with AUCs of 0.671 and 0.643 in training and validation cohort, respectively. The combination of clinicoradiological factors and fusion radiomics signature of AP and VP images achieved AUCs of 0.824 and 0.801 in training and validation cohorts, 0.812 and 0.805 in prospective validation and external validation cohorts, respectively. The hybrid model provided the best prediction results. The results of the Delong test revealed that there were statistically significant differences among the clinicoradiological-radiomics hybrid model, clinicoradiological model, and radiomics model (p<0.05). Conclusions: The combination of clinicoradiological factors and fusion radiomics signature of AP and VP images based on Gd-EOB-DTPA-enhanced MRI can effectively predict MVI.

TRAPPC1 is essential for the maintenance and differentiation of common myeloid progenitors in mice.

Myeloid cell development in bone marrow is essential for the maintenance of peripheral immune homeostasis. However, the role of intracellular protein trafficking pathways during myeloid cell differentiation is currently unknown. By mining bioinformatics data, we identify trafficking protein particle complex subunit 1 (TRAPPC1) as continuously upregulated during myeloid cell development. Using inducible ER-TRAPPC1 knockout mice and bone marrow chimeric mouse models, we demonstrate that TRAPPC1 deficiency causes severe monocyte and neutrophil defects, accompanied by a selective decrease in common myeloid progenitors (CMPs) and subsequent cell subsets in bone marrow. TRAPPC1-deleted CMPs differentiate poorly into monocytes and neutrophils in vivo and in vitro, in addition to exhibiting enhanced endoplasmic reticulum stress and apoptosis via a Ca2+ -mitochondria-dependent pathway. Cell cycle arrest and senescence of TRAPPC1-deleted CMPs are mediated by the activation of pancreatic endoplasmic reticulum kinase and the upregulation of cyclin-dependent kinase inhibitor p21. This study reveals the essential role of TRAPPC1 in the maintenance and differentiation of CMPs and highlights the significance of protein processing and trafficking processes in myeloid cell development.

Changes in the peripapillary vasculature and macular thickness after cataract surgery using two phacoemulsification systems with optical coherence tomography angiography.

AIM: To assess the changes in the peripapillary vasculature and macular thickness after cataract surgery using two phacoemulsification systems with optical coherence tomography angiography (OCTA). METHODS: Fifty-two eyes of 52 patients with age-related cataract were randomized into two groups for phacoemulsification: Infiniti group (26 patients) using the Infiniti phacoemulsification system with gravity-fluidics and Centurion group (26 patients) using the Centurion phacoemulsification system with active-fluidics. The peripapillary vessel density (PVD) and macular thickness were examined using OCTA at baseline and at 1d, 1 and 3mo after cataract surgery. RESULTS: In the Infiniti group, the PVD was significantly reduced at 1d after the cataract surgery (P<0.001). However, the retinal nerve fiber layer (RNFL) thickness showed no significant change during the follow-up. Change in PVD 1d postoperatively was significantly negatively correlated to the cumulative dissipated energy (CDE), estimated fluid usage (EFU), effective phacoemulsification time (EPT), intraocular pressure (IOP), and total operating time (TOT; P<0.05). The macular thickness was significantly increased in all regions after the cataract surgery (P<0.05). However, no significant changes were found in the macular vessel density (VD) during the follow-up (P>0.05). In the Centurion group, the VD and thickness in the optic papilla and macula did not significantly change in all regions during the follow-up (all P>0.05). The best-corrected visual acuity (BCVA) significantly improved in both groups postoperatively (P<0.001). CONCLUSION: Using the Infiniti phacoemulsification system, OCTA provides a promising analysis of retinal vascular alterations, demonstrating a reduction of the PVD and an increase in the macular thickness. The Centurion phacoemulsification system can provide better retinal vasculature preservation during cataract surgery.

[Analysis of risk factors of multiple fractures of limbs complicated with pleural effusion].

OBJECTIVE: To explore the risk factors of limb fracture complicated with pleural effusion, and to provide reference for the prevention of pleural effusion. METHODS: From January 2010 to December 2019, 137 patients with multiple limb fractures were treated surgically, including 102 males and 35 females, aged 16 to 92(48.34±15.85) years. Multiple limb fractures were defined as more than two limb fractures in the whole body, so the selected patients had complete clinical, impact and laboratory examination data before operation, including preoperative chest CT, gender, age, body mass index(BMI), hematocrit(HCT), American Society of Anesthesiologists(ASA), injury severity score (ISS), smoking history of operation, history of diabetes, history of hypertension, admission to operation time, fracture site, platelet count, albumin, C-reactive protein and D-dimer. Whether the patient was complicated with pleural effusion, calculate the amount of pleural effusion were recorded, and the relevant risk factors were statistically analyzed. RESULTS: All limb fractures received surgical treatment. The incision healed well after operation, and there were no complications such as wound infection, acute lung injury or acute respiratory distress syndrome. Multivariate regression analysis showed that ISS higher than 16(P=0.000), smoking history(P=0.001) and rib fracture(P=0.000) were the risk factors of multiple limb fractures complicated with pleural effusion. Multivariate linear regression analysis showed that smoking history, ISS and rib fracture were the risk factors for the increase of pleural effusion in multiple limb fractures. CONCLUSION: Multiple fractures of limbs combined with pleural effusion are related to ISS, smoking history and rib fracture;the amount of pleural effusion was related to smoking history, ISS and rib fracture. Patients with multiple fractures with ISS greater than 16, smoking history or rib fracture should be vigilant and intervene as soon as possible to reduce the risk of pleural effusion.

Schisandra chinensis (Turcz.) Baill. essential oil exhibits antidepressant-like effects and against brain oxidative stress through Nrf2/HO-1 pathway activation.

The present study aimed to evaluate the antidepressant-like effect of essential oils from Schisandra chinensis (Turcz.) Baill. (SEO) and its possible mechanisms of SEO. The behavioral despair mouse model in vivo and H2O2-induced PC12 cells model in vitro were employed. And the potential effective components were identified by the spectrum-effect relationships analysis. SEO significantly decreased the immobility time in the forced swimming test and tail suspension test, which indicated a promising antidepressant-like effect of SEO in depressed mice. The decreased levels of SOD, GSH, and CAT, and increased levels of MDA were significantly reversed by SEO treatment, which showed good antioxidant activities both in vitro and in vivo. Besides, SEO significantly promoted the nuclear translocation of Nrf2 and the expression of HO-1 in depressed mice and H2O2-induced PC12 cells. The histopathological examination results showed a potential neuronal protective effect of SEO in the hippocampus and cortex. Furthermore, the upregulation of PI3K/AKT/GSK3ß signaling was observed after SEO treatment in the H2O2-induced PC12 cells. Additionally, based on the spectrum-effect relationship analysis, 9 peaks were identified as positively correlated with the antioxidant activity of SEO. These results suggested that SEO promoted Nrf2/HO-1 pathway to improve the oxidative stress status and exerted the antidepressant-like effects.

Preoperative Assessment of Abdominal Adipose Tissue to Predict Microvascular Invasion in Small Hepatocellular Carcinoma.

Background and Aims: Microvascular invasion (MVI) affects recurrence after treatment of small hepatocellular carcinoma (sHCC) of ≤3 cm in size. The present study aimed to investigate whether abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and intermuscular adipose tissue (IMAT) are associated with MVI in patients with sHCC. Methods: A total of 124 patients with pathologically-confirmed sHCC diagnosed on surgical resection at the First Hospital Affiliated to Army Military University were recruited and divided into two groups according to MVI classification criteria (i.e., MVI-positive or MVI-negative). The SAT, VAT, and IMAT areas at the lumbar 3 vertebral level were imaged with abdominal computed tomography and measured using ImageJ software. Their association with MVI in sHCC was analyzed. Results: Of the 124 patients with sHCC, 67 were MVI-positive and 57 were MVI-negative. Univariate analysis revealed a significant difference in the abdominal VAT and SAT between the MVI-positive and MVI-negative groups (p<0.05), with an area under the receiver operating characteristic curve of 0.76 and 0.65, respectively. Conclusions: The results of this study suggest that the areas of abdominal SAT and VAT are of significant clinical value because they can effectively predict the MVI status in patients with sHCC.

Associating Preoperative MRI Features and Gene Expression Signatures of Early-stage Hepatocellular Carcinoma Patients using Machine Learning.

BACKGROUND AND AIMS: The relationship between quantitative magnetic resonance imaging (MRI) imaging features and gene-expression signatures associated with the recurrence of hepatocellular carcinoma (HCC) is not well studied. METHODS: In this study, we generated multivariable regression models to explore the correlation between the preoperative MRI features and Golgi membrane protein 1 (GOLM1), SET domain containing 7 (SETD7), and Rho family GTPase 1 (RND1) gene expression levels in a cohort study including 92 early-stage HCC patients. A total of 307 imaging features of tumor texture and shape were computed from T2-weighted MRI. The key MRI features were identified by performing a multi-step feature selection procedure including the correlation analysis and the application of RELIEFF algorithm. Afterward, regression models were generated using kernel-based support vector machines with 5-fold cross-validation. RESULTS: The features computed from higher specificity MRI better described GOLM1 and RND1 gene-expression levels, while imaging features computed from lower specificity MRI data were more descriptive for the SETD7 gene. The GOLM1 regression model generated with three features demonstrated a moderate positive correlation (p<0.001), and the RND1 model developed with five variables was positively associated (p<0.001) with gene expression levels. Moreover, RND1 regression model integrating four features was moderately correlated with expressed RND1 levels (p<0.001). CONCLUSIONS: The results demonstrated that MRI radiomics features could help quantify GOLM1, SETD7, and RND1 expression levels noninvasively and predict the recurrence risk for early-stage HCC patients.

External fixation with bone cement implantation for open calcaneal fractures: A case series.

OBJECTIVE: The purpose of this study was to retrospectively evaluate patients who had open reduction, external fixation and bone cement implantation of open calcaneal fractures. METHODS: The records of 14 patients with open calcaneus fractures from January 2015 to January 2019 were reviewed retrospectively. Clinical evaluations consisting of AOFAS, MFS and EQ-5D VAS scores and radiological evaluations consisting of the height, width and length of the calcaneus as well as Bohler's and Gissane angle performed at 3 months, 1 year and the last follow-up postoperatively. Time to surgery, wound complications were recorded. RESULTS: Our study sample consisted of 9 males and 5 females with a mean age of 38.5 ± 9.8 years and a mean follow-up of 31.4 ± 7.7 months. The mean period from injury to surgery was 5.4 ± 1.9 days and the mean duration of hospitalization was 13.2 ± 4.5 days. The AOFAS, MFS and EQ-5D VAS scores were 92.5 ± 10.3, 84.1 ± 9.7 and 86.4 ± 15.1 respectively at the final follow-up. The Bohler's angle increased from (12.9 ± 3.1)° preoperatively to (28.5 ± 6.3)° at the final follow-up (P < 0.001), with the Gissane's angle from (104.5 ± 9.7)° to (116.4 ± 8.9)° (P < 0.001). One patients (7.1%) developed pin infections and one patient (7.1%) suffered from dorso-lateral hindfoot hypoaesthesia. There was complete fracture healing without secondary loss of reduction in all cases. CONCLUSION: External fixation with bone cement implantation is a valid alternative treatment for the management of displaced open calcaneal fractures with a low rate of complications. LEVEL OF EVIDENCE: IV, retrospective case series.

2-Phenylcyclopropylmethylamine Derivatives as Dopamine D2 Receptor Partial Agonists: Design, Synthesis, and Biological Evaluation.

Partial agonist activity at the dopamine D2 receptor (D2R) is the primary pharmacological feature of the third-generation antipsychotics─aripiprazole, brexpiprazole, and cariprazine. However, all these drugs share a common phenyl-piperazine moiety as the primary pharmacophore. In this study, we designed and synthesized a series of novel compounds based on the 2-phenylcyclopropylmethylamine (PCPMA) scaffold and studied their pharmacological activity at the D2R. A number of potent D2R partial agonists were identified through binding affinity screening and functional activity profiling in both G protein and ß-arrestin assays. The structure-functional activity relationship results showed that the spacer group is crucial for fine-tuning the intrinsic activity of these compounds. Compounds (+)-14j and (+)-14l showed good pharmacokinetic properties and an unexpected selectivity against the serotonin 2A (5-HT2A) receptor. Preliminary suppressive effects in a mouse hyperlocomotion model proved that these PCPMA-derived D2R partial agonists are effective as potential novel antipsychotics.

High-sensitive photometric microplate assay for tumor necrosis factor-alpha based on Fe@BC nanozyme.

Optical immunoassay for the detection of protein biomarker tumor necrosis factor-α (TNF-α) is reported based on core-shell Fe@BC structure nanozyme as label. The nanozyme is composed of Fe nanoparticles as core and carbon layer as shell with element B doped into the carbon shell. The nanozyme displays good peroxidase-like activity that can oxidize 3,3',5,5'-tetramethylbenzidine (TMB) to oxTMB in the presence of H2O2, generating blue colored compound. The detection of TNF-α was following the ELISA protocol by replacing traditional enzyme horseradish peroxidase (HRP) with nanozyme Fe@BC. The assay can be finished by about 2 h and has wide linear range for TNF-α from 5 pg/mL to 1 ng/mL with limit of detection of 2 pg/mL. The assay was applied for the detection of TNF-α in human serum samples with detection results comparable to commercial ELISA.

The Development and Survival of Thymic Epithelial Cells Require TSC1-Dependent Negative Regulation of mTORC1 Activity.

Thymic epithelial cells (TECs) are critical for the development and generation of functionally competent T cells. Until now, the mechanism that regulates the survival of TECs is poorly understood. In the current study, we found that Tsc1 controls the homeostasis of medullary TECs (mTECs) by inhibiting lysosomal-mediated apoptosis pathway in mice. TEC-specific deletion of Tsc1 predominately decreased the cell number of mTECs and, to a lesser content, affected the development cortical TECs. The defect of mTECs caused by Tsc1 deficiency in mice impaired thymocyte development and peripheral T cell homeostasis. Mechanistically, Tsc1 deficiency did not affect the cell proliferation of mTECs but increased the apoptosis of mTECs significantly. RNA-sequencing analysis showed that pathways involved in lysosomal biogenesis, cell metabolism, and apoptosis were remarkably elevated in Tsc1-deficient mTECs compared with their wild-type counterparts. Tsc1-deficient mTECs exhibited overproduction of reactive oxygen species and malfunction of lysosome, with lysosome membrane permeabilization and the release of cathepsin B and cathepsin L to the cytosol, which then lead to Bid cleaved into active truncated Bid and subsequently intrinsic apoptosis. Finally, we showed that the impaired development of mTECs could be partially reversed by decreasing mTORC1 activity via haploinsufficiency of Raptor Thus, Tsc1 is essential for the homeostasis of mTECs by inhibiting lysosomal-mediated apoptosis through mTORC1-dependent pathways.