Vegetation Length is Associated with Long-term Survival in Patients Treated Surgically for Infective Endocarditis.

Background: The impact of vegetation length on therapeutic decision-making and prediction of long-term survival of patients with infective endocarditis is a highly topical issue. The aim of the study was to clarify the impact of vegetation length greater than 10 mm on long-term survival treated surgically for infective endocarditis. Methods: Patients treated surgically for infective endocarditis in our hospital from January 2006 to November 2022 and were successfully followed up were included in the retrospective analysis. Results: 814 survivors discharged from our medical center were successfully followed up to the date of death or the end date of the research and allocated to a group with vegetation length <10 mm (n = 432) or ≥10 mm (n = 382). The average follow-up time was 75.1 ± 1.8 months. Multivariate analysis indicated vegetation length ≥10 mm was associated with 1-year and 5-year mortality. Multivariate analysis of Cox regression identified vegetation length ≥10 mm to be associated with all-time mortality. Multivariate analysis identified male gender, long time between symptoms and surgery, more preoperative left ventricular ejection fraction (LVEF) and more preoperative aortic regurgitation to be associated with vegetation length ≥10 mm in infective endocarditis. Conclusions: Our study indicated that vegetation length ≥10 mm was associated with long-term survival in patients treated surgically for infective endocarditis.

A longitudinal multimodal MRI study of the visual network in postoperative delirium.

Although structural and functional damage to the brain is considered to be an important neurobiological mechanism of postoperative delirium (POD), alterations in the visual cortical network related to this vulnerability have not yet been determined. In this study, we investigated the impact of alterations in the visual network (VN), as measured by structural and functional magnetic resonance imaging (MRI), on the development of POD. Thirty-six adult patients with frontal glioma who underwent elective craniotomy were recruited. The primary outcome was POD 1-7 days after surgery, as assessed by the Confusion Assessment Method. Cognition before surgery was measured by a battery of neuropsychological tests. Then, we evaluated preoperative and postoperative gray matter volume (GMV) and functional connectivity (FC) alterations by voxel-based morphometry and resting-state functional MRI (rs-fMRI) between the POD and non-POD groups. Multiple logistic regression models were used to investigate the associations between neuroimaging biomarkers and the occurrence of POD. Compared to those in the non-POD group, a decreased GMV in the fusiform gyrus (0.181 [0.018] vs. 0.207 [0.022], FDRp = 0.001) and decreased FC between the fusiform gyrus and VN (0.351 [0.153] vs. 0.610 [0.197], GFRp < 0.001) were observed preoperatively in the POD group, and increased FC between the fusiform gyrus and ventral attentional network (0.538 [0.180] vs. 0.452 [0.184], GFRp = < 0.001) was observed postoperatively in the POD group. According to our multiple logistic regression analysis, age (Odds ratio [OR]: 1.141 [1.015 to 1.282], P = 0.03) and preoperative fusiform-VN FC (OR 0.001 [0.001 to 0.067], P = 0.01) were significantly related to risk of POD. Our findings suggested that preoperative functional disconnectivity between fusiform and VN might be highly involved in the development of POD. These findings may allow for the discovery of additional underlying mechanisms.

Observational and genetic association of non-alcoholic fatty liver disease and calcific aortic valve disease.

Background: Non-alcoholic fatty liver disease (NAFLD) has emerged as a predominant driver of chronic liver disease globally and is associated with increased cardiovascular disease morbidity and mortality. However, the association between NAFLD and calcific aortic valve disease remains unclear. We aimed to prospectively investigate the association between NAFLD and incident aortic valve calcification (AVC), as well as its genetic relationship with incident calcific aortic valve stenosis (CAVS). Methods: A post hoc analysis was conducted on 4226 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) database. We employed the adjusted Cox models to assess the observational association between NAFLD and incident AVC. Additionally, we conducted two-sample Mendelian randomization (MR) analyses to investigate the genetic association between genetically predicted NAFLD and calcific aortic valve stenosis (CAVS), a severe form of CAVD. We repeated the MR analyses by excluding NAFLD susceptibility genes linked to impaired very low-density lipoprotein (VLDL) secretion. Results: After adjustment for potential risk factors, participants with NAFLD had a hazard ratio of 1.58 (95% CI: 1.03-2.43) for incident AVC compared to those without NAFLD. After excluding genes associated with impaired VLDL secretion, the MR analyses consistently showed the significant associations between genetically predicted NAFLD and CAVS for 3 traits: chronic elevation of alanine aminotransferase (odds ratio = 1.13 [95% CI: 1.01-1.25]), imaging-based NAFLD (odds ratio = 2.81 [95% CI: 1.66-4.76]), and biopsy-confirmed NAFLD (odds ratio = 1.12 [95% CI: 1.01-1.24]). However, the association became non-significant when considering all NAFLD susceptibility genes. Conclusions: NAFLD was independently associated with an elevated risk of incident AVC. Genetically predicted NAFLD was also associated with CAVS after excluding genetic variants related to impaired VLDL secretion.

Acute hematologic toxicity prediction using dosimetric and radiomics features in patients with cervical cancer: does the treatment regimen matter?

Background: Acute hematologic toxicity (HT) is a prevalent adverse tissue reaction observed in cervical cancer patients undergoing chemoradiotherapy (CRT), which may lead to various negative effects such as compromised therapeutic efficacy and prolonged treatment duration. Accurate prediction of HT occurrence prior to CRT remains challenging. Methods: A discovery dataset comprising 478 continuous cervical cancer patients (140 HT patients) and a validation dataset consisting of 205 patients (52 HT patients) were retrospectively enrolled. Both datasets were categorized into the CRT group and radiotherapy (RT)-alone group based on the treatment regimen, i.e., whether chemotherapy was administered within the focused RT duration. Radiomics features were derived by contouring three regions of interest (ROIs)-bone marrow (BM), femoral head (FH), and clinical target volume (CTV)-on the treatment planning CT images before RT. A comprehensive model combining the radiomics features as well as the demographic, clinical, and dosimetric features was constructed to classify patients exhibiting acute HT symptoms in the CRT group, RT group, and combination group. Furthermore, the time-to-event analysis of the discriminative ROI was performed on all patients with acute HT to understand the HT temporal progression. Results: Among three ROIs, BM exhibited the best performance in classifying acute HT, which was verified across all patient groups in both discovery and validation datasets. Among different patient groups in the discovery dataset, acute HT was more precisely predicted in the CRT group [area under the curve (AUC) = 0.779, 95% CI: 0.657-0.874] than that in the RT-alone (AUC = 0.686, 95% CI: 0.529-0.817) or combination group (AUC = 0.748, 95% CI: 0.655-0.827). The predictive results in the validation dataset similarly coincided with those in the discovery dataset: CRT group (AUC = 0.802, 95% CI: 0.669-0.914), RT-alone group (AUC = 0.737, 95% CI: 0.612-0.862), and combination group (AUC = 0.793, 95% CI: 0.713-0.874). In addition, distinct feature sets were adopted for different patient groups. Moreover, the predicted HT risk of BM was also indicative of the HT temporal progression. Conclusions: HT prediction in cervical patients is dependent on both the treatment regimen and ROI selection, and BM is closely related to the occurrence and progression of HT, especially for CRT patients.

Modifiable risk factors of immediate and long-term outcomes in the operable and inoperable with left-sided infective endocarditis.

Objectives: To evaluate the outcomes of left-sided infective endocarditis that can be operated on and cannot be operated on, and to focus on modifiable risk factors for immediate and long-term mortality. Methods: This study retrospectively investigated patients with left-sided infective endocarditis who occurred in our medical center between January 2006 and November 2022. Results: 48 in-hospital deaths occurred (5.8 %, 48/832). We identified time from symptoms to admission and symptomatic neurological complications to be risk factors for multiple organ failure upon admission. Time from symptoms to admission and vegetation size in group of isolated medical treatment were significantly shorter than those in the group of heart operation. We also found that preoperative neurological complications, annulus destruction, levels of serum creatinine at 24 and 48 h post heart operation, and perivalvular leakage are risk factors for in-hospital mortality post heart operation. With 148 µmol/L as a cutoff level, the diagnostic sensitivity and specificity of serum creatinine level 48 h post surgery for in-hospital mortality post cardiac surgery are 100 % and 81.6 %, respectively. We found that vegetation size, ICU stay, postoperative serum creatinine at 48 h, left ventricular end diastolic size postoperative, and red blood cell transfusion were associated with all-time mortality. Conclusions: Early diagnosis and treatment, improvement of surgical techniques, good protection for heart, kidney and blood and close follow-up are advocated to conduce to better immediate and long-term outcomes of the operable and inoperable with left-sided infective endocarditis.

Distance-specific functional connectivity strength alterations in human immunodeficiency virus asymptomatic neurocognitive impairment patients: a cross-sectional study.

Background: Asymptomatic neurocognitive impairment (ANI) is the mildest form of human immunodeficiency virus (HIV)-associated neurocognitive disorders (HANDs), and functional connectivity strength (FCS) alternations have been observed in the ANI stage. However, it is not clear whether the FCS alterations are influenced by the anatomical distance. This study sought to investigate distance-specific FCS changes in HIV ANI patients. Methods: In total, 29 patients with HAND and 32 healthy controls (HCs) were enrolled in the study. Between-group differences were detected for short, middle and long range anatomical distance FCS. A correlation analysis was performed to examine the relationship between distance-specific FCS and immunological parameters and neuropsychological tests. A receiver operating characteristic (ROC) analysis was conducted to examine the discriminative performance for HIV ANI patients. Results: In comparison to the HCs, the HAND patients showed increased short-range FCS in the left inferior parietal lobule (IPL), middle-range FCS in the superior temporal gyrus (STG), long-range FCS in the left precuneus (PCC), and decreased FCS in the right postcentral gyrus (PCG) (cluster P<0.05, voxel significance P<0.001). Further, the long-range FCS in the right PCG was negatively correlated with the CD4/CD8 ratio (r=-0.479, 95% confidence interval (CI): -0.735 to -0.104, P=0.015), and the distance-specific FCS also showed good classification performance between the HAND patients and HCs. The left IPL, left STG, right PCG, and left PCC had areas under the curve (AUCs) of 0.875 [95% confidence interval (CI): 0.758-0.949, P<0.0001], 0.806 (95% CI: 0.677-0.900, P<0.0001), 0.855 (95% CI: 0.734-0.935, P<0.0001), and 0.852 (95% CI: 0.754-0.950, P<0.0001), respectively. There was no significant relationship between the distance-specific FCS and the neuropsychological tests. Conclusions: Distance-specific FCS could be used to examine subtle alternations in HIV-infected patients in the ANI stage and help to explain the possible neurophysiological mechanism of HAND.

Intracranial mesenchymal tumor with multiple extracranial metastases: A case report and literature review.

This study presents a rare case of an older woman with an intracranial mesenchymal tumor in the right frontal and parietal lobes. Despite prompt surgical intervention, her condition rapidly deteriorated because of tumor dissemination, leading to her demise. We highlight the tumor's marked invasiveness and heterogeneity, coupled with a propensity for distant systemic metastasis, which negatively impacted the patient's prognosis. This particular clinical behavior had not been previously reported, making this a novel observation. Thus, through a comprehensive review of relevant literature, we aim to provide valuable insights for further understanding, diagnosing, and treating such tumors.

Sanhuang Xiexin Decoction Ameliorates TNBC By Modulating JAK2-STAT3 and Lipid Metabolism.

OBJECTIVE: To investigate the therapeutic effect of Sanhuang Xiexin Decoction (SXD) on triple-negative breast cancer (TNBC) in mice and its underlying mechanism. METHODS: The high-performance liquid chromatography (HPLC) was used to quantitate and qualify SXD. A total of 15 female BALB/c mice were inoculated subcutaneously on the right hypogastrium with 3×105 of 4T1-Luc cells to establish TNBC mouse model. All mice were divided randomly into 3 groups, including phosphate buffered solution (PBS), SXD and doxorubicin (DOX) groups (positive drug). Additionally, tumor growth, pathological changes, serum lipid profiles, expression of Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) signaling pathway and its key targets including inflammatory factors, cell cycle and epithelial-mesenchymal transition (EMT) markers were investigated. Besides, the biosafety of SXD was also evaluated in mice. RESULTS: Rhein, coptisine, berberine hydrochloride and baicalin were all found in SXD, and the concentrations of these 4 components were 0.57, 2.61, 2.93, and 46.04 mg/g, respectively. The mouse experiment showed that SXD could notably suppress the development of tumors and reduce the density of tumor cells (P<0.01). The serum lipid analysis and Oil-Red-O staining both showed the differences, SXD group exhibited higher serum adiponectin and HDL-C levels with lower TC and LDL-C levels compared to the PBS and DOX groups (P<0.05 or P<0.01), respectively. SXD also decreased the levels of phospho-JAK2 (p-JAK2), phospho-STAT3 (p-STAT3) expressions and its downstream factors, including mostly inflammatory cytokine, EMT markers, S phase of tumor cells and vascular endothelial growth factor (VEGF) expression (P<0.05 or P<0.01), respectively. The biosafety assessment of SXD revealed low levels of toxicity in mice. CONCLUSION: SXD could inhibit TNBC by suppressing JAK2-STAT3 phosphorylation which may be associated with modulation of lipid metabolism.

Risk factors of prolonged intensive care unit stay following cardiac surgery for infective endocarditis.

INTRODUCTION: Prolonged intensive care unit (ICU) stay is common in serious patients undergoing cardiac surgery. Prolonged ICU stay is associated with increased mortality and worse prognosis. This study was conducted to determine the risk factors for prolonged ICU stay after cardiac surgery for infective endocarditis (IE) and we try to decrease the operative risk of mortality and morbidity of cardiac surgery for IE. METHODS: The retrospective study of patients with IE undergoing cardiac surgery between January 2006 and November 2022 at our hospital was performed. RESULTS: 896 patients undergoing cardiac surgery were divided into group of ICU stay ≤ 3d (n = 416) and group p of ICU stay > 3d (n = 480). There were 48 operative deaths (5.4%). Univariable and multivariable analyses showed that factors are associated with prolonged ICU stay following cardiac surgery for IE, including male (P < .001), age (P < .001), weight (P = .009), vegetation length (P < .001), paravalvular leak (P < .001), aortic cross-clamp time (P < .001), cardiopulmonary bypass (CPB) time (P < .001), mechanical ventilation time (P < .001), hospitalized time postoperative (P = .032), creatinine of serum before surgery (P < .001), creatinine of serum 24h after surgery (P = .005), creatinine of serum 48h after surgery (P < .001), fluid balance on operation day (P < .001), postoperative acute kidney injury (P < .001), left ventricular end diastolic dimension (LVEDD) preoperative (P < .001), LVEDD postoperative (P < .001), chest drainage (P = .032), frozen plasma (P = .016), preoperative aortic insufficiency (P < .001), and packed red cells (P < .001). CONCLUSIONS: In our study, shortness of ICU stay and optimization of pre-, peri-, and postoperative factors that can shorten ICU stay, therefore, contribute to a better postoperative outcome and leads to lower rates of mortality and morbidity.

Surgical treatment of left-sided infective endocarditis with symptomatic neurological complications before surgery in China.

Introduction: We aimed to investigate surgical treatment of left-sided infective endocarditis with symptomatic neurological complications before surgery. Methods: This was a retrospective study of patients with left-sided infective endocarditis and symptomatic neurological complications before surgery undergoing cardiac surgery between January 2006 and November 2022 at our hospital. Results: Eight hundred thirty-two patients were divided into group with symptomatic neurological complications before surgery (n = 112) and without symptomatic neurological complications before surgery (n = 720). There were 48 operative deaths (5.4%). Univariate and multivariate analyses showed that symptomatic neurological complications before surgery is statistically significantly associated with in-hospital mortality following cardiac surgery and prolonged intubation time. Conclusions: Our study showed that symptomatic neurological complications before surgery are associated with increased in-hospital mortality following cardiac surgery and prolonged intubation time.

Probing bundle-wise abnormalities in patients infected with human immunodeficiency virus using fixel-based analysis: new insights into neurocognitive impairments.

BACKGROUND: Changes in white matter (WM) underlie the neurocognitive damages induced by a human immunodeficiency virus (HIV) infection. This study aimed to examine using a bundle-associated fixel-based analysis (FBA) pipeline for investigating the microstructural and macrostructural alterations in the WM of the brain of HIV patients. METHODS: This study collected 93 HIV infected patients and 45 age/education/handedness matched healthy controls (HCs) at the Beijing Youan Hospital between January 1, 2016 and December 30, 2016.All HIV patients underwent neurocognitive evaluation and laboratory testing followed by magnetic resonance imaging (MRI) scanning. In order to detect the bundle-wise WM abnormalities accurately, a specific WM bundle template with 56 tracts of interest was firstly generated by an automated fiber clustering method using a subset of subjects. Fixel-based analysis was used to investigate bundle-wise differences between HIV patients and HCs in three perspectives: fiber density (FD), fiber cross-section (FC), and fiber density and cross-section (FDC). The between-group differences were detected by a two-sample t -test with the false discovery rate (FDR) correction ( P <0.05). Furthermore, the covarying relationship in FD, FC and FDC between any pair of bundles was also accessed by the constructed covariance networks, which was subsequently compared between HIV and HCs via permutation t -tests. The correlations between abnormal WM metrics and the cognitive functions of HIV patients were explored via partial correlation analysis after controlling age and gender. RESULTS: Among FD, FC and FDC, FD was the only metric that showed significant bundle-wise alterations in HIV patients compared to HCs. Increased FD values were observed in the bilateral fronto pontine tract, corona radiata frontal, left arcuate fasciculus, left corona radiata parietal, left superior longitudinal fasciculus III, and right superficial frontal parietal (SFP) (all FDR P <0.05). In bundle-wise covariance network, HIV patients displayed decreased FD and increased FC covarying patterns in comparison to HC ( P <0.05) , especially between associated pathways. Finally, the FCs of several tracts exhibited a significant correlation with language and attention-related functions. CONCLUSIONS: Our study demonstrated the utility of FBA on detecting the WM alterations related to HIV infection. The bundle-wise FBA method provides a new perspective for investigating HIV-induced microstructural and macrostructural WM-related changes, which may help to understand cognitive dysfunction in HIV patients thoroughly.

Impact of Vegetation Length on Clinical Complications During Surgical Intervention and Long-Term Survival in Infective Endocarditis.

We aimed to investigate the impact of vegetation length on clinical complications during surgical intervention and long-term survival in infective endocarditis. This was a retrospective study of patients with infective endocarditis who underwent cardiac surgery between January 2006 and November 2022 at our hospital. 896 patients were divided into 2 groups: group I (vegetation length <10 mm, n = 448) and group II (vegetation length ≥10 mm, n = 448). There were 48 operative deaths (5.4%). Univariate and multivariate analyses showed that vegetation length is statistically significantly associated with destruction of the annulus (p <0.001), neurological complications before surgery (p <0.001), acute renal injury (p <0.001), prolonged intubation time (intubation time >24 hours) (p <0.001), prolonged intensive care unit (ICU) retention time (ICU retention time >3 days) (p <0.001), and in-hospital mortality (p <0.001), respectively. Our study showed that vegetation length is statistically significantly associated with destruction of the annulus, neurological complications before surgery, acute renal injury, prolonged intubation time, prolonged ICU retention time, in-hospital mortality, and 1-year mortality, respectively.

Rubiginosin B selectively inhibits Treg cell differentiation and enhances anti-tumor immune responses by targeting calcineurin-NFAT signaling pathway.

BACKGROUND: The accumulation of CD4+Foxp3+ regulatory T cells (Tregs) in the tumor microenvironment (TME) dampens anti-tumor immune responses and promotes tumor progression. Therefore, the elimination of Tregs has become a strategy to enhance the efficacy of tumor immunotherapy, although it is still a daunting challenge. Rhododendron brachypodum (R. brachypodum) is a perennial shrub mainly distributed in Southwestern China, whereas the chemical constituents in this plant remain elusive. PURPOSE: To identify small-molecule inhibitors of Tregs from R. brachypodum. METHODS: Meroterpenoids in R. brachypodum were isolated by column chromatography under the guidance of LCMS analyses. The structures of isolates were identified by spectroscopic data and quantum calculations. The activities of compounds were first evaluated on CD4+ T cell differentiation by flow cytometry in Th1, Th2, Th17, and Treg polarizing conditions, and then on CT26 and MC38 murine colorectal carcinoma cells-allografted mice models. The mechanism of action was first investigated by determining Foxp3 degradation in Jurkat T cells transfected with pLVX-TetOne-Puro-Foxp3-tGFP, and then through analyses of Foxp3 expression on several pre-transcriptional signaling molecules. RESULTS: Two new prenylated phenolic acids (1 and 2) and a chromane meroterpenoid, rubiginosin B (RGB, 3) were obtained from R. brachypodum. The structure of S-anthopogochromene C (1) was rectified according to the electronic circular dichroism (ECD) experiment, and rhodobrachypodic acid (2) was proposed as the precursor of RGB by photochemical transformation. In this investigation, we first found that RGB (3) selectively suppressed the de novo differentiation of TGFß-induced CD4+Foxp3+ regulatory T cells (iTregs), overcome the immunosuppressive TME, and consequently inhibited the growth of tumor in mouse models. The mechanistic study revealed that RGB could target calcineurin, inhibited the nuclear factor of activated T cells (NFAT) dephosphorylation, and down-regulated Foxp3 expression. The hypothetical binding modes of RGB with calcineurin were predicted by molecular docking, and the interactions were mainly hydrophobic effects and hydrogen bonds. CONCLUSION: These results suggest that RGB enhances anti-tumor immune responses by inhibiting Treg cell differentiation through calcineurin-NFAT signaling pathway, and therefore RGB or its analogs may be used as adjuvant agents meriting further investigation.

Missense mutation of c.635 T > C in CAPN3 impairs muscle injury repair in a Limb-Girdel Muscular Dystropy Model.

Limb-girdle muscular dystrophy recessive 1 (LGMDR1), previously known as LGMD2A, is a specific LGMD caused by a gene mutation encoding the calcium-dependent neutral cysteine protease calpain-3 (CAPN3). In our study, the compound heterozygosity with two missense variants c.635 T > C (p.Leu212Pro) and c.2120A > G (p.Asp707Gly) was identified in patients with LGMDR1. However, the pathogenicity of c.635 T > C has not been investigated. To evaluate the effects of this novel likely pathogenic variant to the motor system, the mouse model with c.635 T > C variant was prepared by CRISPR/Cas9 gene editing technique. The pathological results revealed that a limited number of inflammatory cells infiltrated the endomyocytes of certain c.635 T > C homozygous mice at 10 months of age. Compared with wild-type mice, motor function was not significantly impaired in Capn3 c. 635 T > C homozygous mice. Western blot and immunofluorescence assays further indicated that the expression levels of the Capn3 protein in muscle tissues of homozygous mice were similar to those of wild-type mice. However, the arrangement and ultrastructural alterations of the mitochondria in the muscular tissues of homozygous mice were confirmed by electron microscopy. Subsequently, muscle regeneration of LGMDR1 was simulated using cardiotoxin (CTX) to induce muscle necrosis and regeneration to trigger the injury modification process. The repair of the homozygous mice was significantly worse than that of the control mice at day 15 and day 21 following treatment, the c.635 T > C variant of Capn3 exhibited a significant effect on muscle regeneration of homozygous mice and induced mitochondrial damage. RNA-sequencing results demonstrated that the expression levels of the mitochondrial-related functional genes were significantly downregulated in the mutant mice. Taken together, the results of the present study strongly suggested that the LGMDR1 mouse model with a novel c.635 T > C variant in the Capn3 gene was significantly dysfunctional in muscle injury repair via impairment of the mitochondrial function.

Radiation hematologic toxicity prediction for locally advanced rectal cancer using dosimetric and radiomics features.

BACKGROUND: Hematologic toxicity (HT) is a common adverse tissue reaction during radiotherapy for rectal cancer patients, which may lead to various negative effects such as reduced therapeutic effect, prolonged treatment period and increased treatment cost. Therefore, predicting the occurrence of HT before radiotherapy is necessary but still challenging. PURPOSE: This study proposes a hybrid machine learning model to predict the symptomatic radiation HT in rectal cancer patients using the combined demographic, clinical, dosimetric, and Radiomics features, and ascertains the most effective regions of interest (ROI) in CT images and predictive feature sets. METHODS: A discovery dataset of 240 rectal cancer patients, including 145 patients with HT symptoms and a validation dataset of 96 patients (63 patients with HT) with different dose prescription were retrospectively enrolled. Eight ROIs were contoured on patient CT images to derive Radiomics features, which were then, respectively, combined with the demographic, clinical, and dosimetric features to classify patients with HT symptoms. Moreover, the survival analysis was performed on risky patients with HT in order to understand the HT progression. RESULTS: The classification models in ROIs of bone marrow and femoral head exhibited relatively high accuracies (accuracy = 0.765 and 0.725) in the discovery dataset as well as comparable performances in the validation dataset (accuracy = 0.758 and 0.714). When combining the two ROIs together, the model performance was the best in both discovery and validation datasets (accuracy = 0.843 and 0.802). In the survival analysis test, only the bone marrow ROI achieved statistically significant performance in accessing risky HT (C-index = 0.658, P = 0.03). Most of the discriminative features were Radiomics features, and only gender and the mean dose in Irradvolume was involved in HT. CONCLUSION: The results reflect that the Radiomics features of bone marrow are significantly correlated with HT occurrence and progression in rectal cancer. The proposed Radiomics-based model may help the early detection of radiotherapy induced HT in rectal cancer patients and thus improve the clinical outcome in future.

Influence of mixed ventilation on particulate-gas diffusion and distribution of diesel engine exhaust in fully mechanized excavation face.

Tail gas emitted by underground trackless rubber wheel cars poses a serious threat to the health and safety of underground workers. To effectively reduce the tail gas concentration of a comprehensive excavation face, this study adopted a numerical simulation method to investigate the influence of air suction volume Q and distance L between trackless rubber wheel cars and headfaces on the diffusion law of diesel particulate matter, CO, and NOx under long suction and short pressure ventilation. The results showed that under the condition of L = 20 m, the trackless rubber wheel car is closer to the suction air duct. At this point, when Q = 600 m3/min, the tail gas control effect in the roadway is optimum. In addition, under the condition of L = 40 m, the trackless rubber wheel car is in the middle of the roadway. At this point, when Q = 300 m3/min, the tail gas control effect in the roadway is optimum. When L = 60 m and Q = 200 m3/min, the ventilation mode in the roadway is mainly pressure-in ventilation. The high-volume-fraction NOx region and the medium-volume-fraction NOx region under this air volume are small.

Long-term ANT-DBS effects in pilocarpine-induced epileptic rats: A combined 9.4T MRI and histological study.

Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) appears to be effective against seizures in animals and humans however, its therapeutic mechanisms remain elusive. This study aimed to combine 9.4T multimodal magnetic resonance imaging (MRI) with histology to investigate the longitudinal effects of long-term ANT-DBS in pilocarpine-induced epileptic rats. Status epilepsy (SE) was induced by LiCl-pilocarpine injection in 11 adult male Sprague-Dawley rats. Four weeks after SE, chronic epileptic rats underwent either ANT-DBS (n = 6) or sham-DBS (n = 5) surgery. Electroencephalography (EEG) and spontaneous recurrent seizures (SRS) were recorded for 1 week. The T2-weighted image and images from resting-state functional MRI (rs-fMRI) were acquired at three states: before SE, at 4 weeks post-SE, and at 5 weeks post-DBS. Volumes of the hippocampal subregions and hippocampal-related functional connectivity (FC) were compared longitudinally. Finally, antibodies against neuronal nuclei (NeuN) and glial fibrillary acidic proteins were used to evaluate neuronal loss and astrogliosis in the hippocampus. Long-term ANT-DBS significantly reduced seizure generalization in pilocarpine-induced epileptic rats. By analyzing the gray matter volume using T2-weighted images, long-term ANT-DBS displayed morphometric restoration of the hippocampal subregions. Neuronal protection of the hippocampal subregions and inhibition of astrogliosis in the hippocampal subregions were observed in the ANT-DBS group. ANT-DBS caused reversible regulation of FC in the insula-hippocampus and subthalamic nucleus-hippocampus. Long-term ANT-DBS provides comprehensive protection of hippocampal histology, hippocampal morphometrics, and hippocampal-related functional networks.

Results of the inoperable and operable with aortic valve endocarditis.

Objectives: To evaluate the results of the inoperable and operable with aortic valve endocarditis, focus on risk factors, significance, and management of destruction of the aortic annulus in aortic valve endocarditis. Methods: The retrospective study was completed to investigate patients with aortic valve endocarditis undergoing cardiac surgery between January 2006 and November 2022 at our hospital. Results: 512 patients were divided into group with destruction of the aortic annulus (n = 80) and without destruction of the aortic annulus (n = 432). There were 32 operative deaths (6.3%, 32/512). By univariate and multivariate analysis, destruction of the aortic annulus is found to be statistically significantly associated with in-hospital mortality (P < 0.001), prolonged mechanical ventilation time (mechanical ventilation time > 96 h, P = 0.018), early aortic paravalvular leak (P < 0.001), and 1-year mortality following cardiac surgery (P < 0.001), respectively. Conclusions: In our study, destruction of the aortic annulus increases mortality and health care costs. Optimization of pre-, peri-, and postoperative factors can reduce mortality and morbidity in aortic valve endocarditis. Aortic root replacement could be recommended as the best practice choice for aortic valve endocarditis with periannular abscess and destruction of the aortic annulus.

Distepharinamide, a novel dimeric proaporphine alkaloid from Diploclisia glaucescens, inhibits the differentiation and proliferative expansion of CD4+Foxp3+ regulatory T cells.

BACKGROUND: CD4+Foxp3+ regulatory T cells (Tregs) represent the primary cellular mechanism of tumor immune evasion. Elimination of Treg activity by the pharmacological agent may enhance anti-tumor immune responses. However, Treg-eliminating agents, especially those with small molecules, are rarely reported. PURPOSE: To identify small molecule inhibitors of Treg cells from natural products. METHODS: Compounds from Diploclisia glaucescens were isolated by column chromatography, and structures were identified by spectroscopic evidence and quantum calculations. The tet-On system for Foxp3-GFP expression in Jurkat T cells was generated to screen Treg inhibitors based on Foxp3 expression. The effect of the compound on TNF-induced proliferative expansion of naturally occurring Tregs (nTregs) and TGF-ß-induced generation of Tregs (iTregs) from naive CD4+ Tcells was further examined. RESULTS: A novel dimeric proaporphine alkaloid, designated as distepharinamide (DSA) with a symmetric structure isolated from the stems of D. glaucescens, restrained the doxycycline (Doxy)-induced Foxp3-tGFP expression, decreased the half-life of Foxp3 mRNA as well as reduced the mRNA levels of chemokine receptors (CCR4, CCR8 and CCR10) in Jurkat T cells with inducible Foxp3-tGFP expression. In lymphocytes or purified Tregs from wild-type C57BL/6 mice or from C57BL/6-Tg(Foxp3-DTR/EGFP)23.2Spar/Mmjax mice, DSA markedly inhibited TNF-induced proliferative expansion of Tregs present in the unfractionated CD4+ T cells, accompanied by the down-regulation of TNFR2, CD25 and CTLA4 expression on Tregs. Furthermore, DSA potently inhibited TGF-ß-induced differentiation of Foxp3-expressing iTregs. Importantly, the expression of Foxp3 mRNA by both nTregs and iTregs was decreased by DSA treatment. Nevertheless, DSA at the same concentrations did not inhibit the proliferation of conventional CD4+ and CD8+ T cells stimulated by anti-CD3/CD28 antibodies. CONCLUSION: DSA, a novel dimeric proaporphine alkaloid, potently inhibited the expansion of nTregs and generation of iTregs. Therefore, DSA or its analogs may merit further investigation as novel immunotherapeutic agents.

Alteration of default mode network: association with executive dysfunction in frontal glioma patients.

OBJECTIVE: Patients with frontal gliomas often experience executive dysfunction (EF-D) before surgery, and the changes in brain plasticity underlying this effect remain obscure. In this study, the authors aimed to assess whole-brain structural and functional alterations by using structural MRI and resting-state functional MRI (rs-fMRI) in frontal glioma patients with or without EF-D. METHODS: Fifty-seven patients with frontal gliomas were admitted prospectively to the authors' institution and assigned to one of two groups: 1) the normal executive function (EF-N) group and 2) the EF-D group, based on patient results for the Trail Making Test, Part B and Stroop Color-Word Test, Part C. Twenty-nine baseline-matched healthy controls were also recruited. All participants underwent multimodal MRI examination. Cortical surface thickness, surface-based resting-state activity (fractional amplitude of low-frequency fluctuation [fALFF] and regional homogeneity [ReHo]), and edge-based network functional connectivity (FC) were measured with FreeSurfer and fMRIPrep. The correlation between altered MRI parameters and executive function (EF) was assessed using Pearson correlation and receiver operating characteristic (ROC) analysis. RESULTS: Demographic characteristics (sex, age, and education level) and clinical characteristics (location, volume, grade of tumor, and preoperative epilepsy) were not significantly different between the groups, but the Karnofsky Performance Scale score was worse in the EF-D group. There was no significant difference in cortical surface thickness between the EF-D and EF-N groups. In both low-grade and high-grade glioma patients the fALFF value (permutation test + threshold-free cluster enhancement, p value after family-wise error correction < 0.05) and ReHo value (t-test, p < 0.001) of the left precuneus cortex in the EF-D group were greater than those in the EF-N group, which were negatively correlated with EF (p < 0.05) and enabled prediction of EF (area under the ROC curve 0.826 for fALFF and 0.855 for ReHo, p < 0.001). Compared with the EF-N group, the FCs between the default mode network (DMN) from DMN node to DMN node (DMN-DMN) and from the DMN to the central executive network (DMN-CEN) in the EF-D group were increased significantly (network-based statistics corrected p < 0.05) and negatively correlated with EF (Pearson correlation, p < 0.05). CONCLUSIONS: Apart from local disruption, the abnormally activated DMN in the resting state is related to EF-D in frontal glioma patients. DMN activity should be considered during preoperative planning and postoperative neurorehabilitation for frontal glioma patients to preserve EF. Clinical trial registration no.: NCT03087838 (ClinicalTrials.gov).