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Rising human population has increased the utilization of available resources for food, clothes, medicine, and living space, thus menacing natural environment and mounting the gap between available resources, and the skills to meet human desires is necessary. Humans are satisfying their desires by depleting available natural resources. Therefore, multifunctional plants can contribute towards the livelihoods of people, to execute their life requirements without degrading natural resources. Thus, research on multipurpose industrial crops should be of high interest among scientists. Hemp, or industrial hemp, is gaining research interest because of its fastest growth and utilization in commercial products including textile, paper, medicine, food, animal feed, paint, biofuel, biodegradable plastic, and construction material. High biomass production and ability to grow under versatile conditions make hemp, a good candidate species for remediation of polluted soils also. Present review highlights the morphology, adaptability, nutritional constituents, textile use, and medicinal significance of industrial hemp. Moreover, its usage in environmental conservation, building material, and biofuel production has also been discussed.

Background In recent years, a growing body of observational studies suggest that urticaria is associated with a higher risk of rheumatoid arthritis (RA). However, the causal association between urticaria and RA remains unknown. Objective To investigate the causal relationship of urticaria and RA in European populations by Mendelian randomisation (MR) approach. Methods We conducted two-sample MR analyses. Eleven single-nucleotide polymorphisms associated with urticaria were used as instrumental variables. The summary data on urticaria were derived from FinnGen Data Freeze 2. The summary data on RA were obtained from a published meta-analysis using European samples. Four MR methods were applied to the MR estimates. Three heterogeneity tests, including Cochran’s Q test, single variant analysis, and leave-one-out variant analysis, were used. The pleiotropy and horizontal pleiotropy among instrumental variables were assessed with MR-Egger regression intercept, MR pleiotropy residual sum and outlier global test, and PhenoScanner. Results The MR analysis suggested that urticaria was causally associated with RA (odds ratio = 1.114, 95% confidence interval = 1.024–1.211, p = .011). No genetic pleiotropy or horizontal pleiotropy was revealed by MR-Egger regression intercept and MR pleiotropy residual sum and outlier global test. The sensitivity analysis results were relatively robust. Conclusions The MR analysis suggested there was sufficient evidence to indicate urticaria is the cause of RA.

Background: Coronavirus disease 2019 (COVID-19) has caused over 3.8 million deaths globally. Up to date, the number of death in 2021 is more than that in 2020 globally. Here, we aimed to compare clinical characteristics of deceased patients and recovered patients, and analyze the risk factors of death to help reduce mortality of COVID-19. Methods: In this retrospective study, a total of 2719 COVID-19 patients were enrolled, including 109 deceased patients and 2610 recovered patients. Medical records of all patients were collected between February 4, 2020, and April 7, 2020. Clinical characteristics, laboratory indices, treatments, and deep-learning system- assessed lung lesion volumes were analyzed. The effect of different medications on survival time of fatal cases was also investigated. Results: The deceased patients were older (73 years versus 60 years) and had a male predominance. Nausea (10.1% versus 4.1%) and dyspnea (54.1% versus 39.2%) were more common in deceased patients. The proportion of patients with comorbidities in deceased patients was significantly higher than those in recovered patients. The median times from hospital admission to outcome in deceased patients and recovered patients were 9 days and 13 days, respectively. Patients with severe or critical COVID-19 were more frequent in deceased group. Leukocytosis (11.35×109/L versus 5.60×109/L) and lymphocytopenia (0.52×109/L versus 1.58×109/L) were shown in patients who died. The level of prothrombin time, activated partial prothrombin time, D-dimer, aspartate aminotransferase, alanine aminotransferase, urea, creatinine, creatine kinase, glucose, brain natriuretic peptide, and inflammatory indicators were significantly higher in deceased patients than in recovered patients. The volumes of ground-glass, consolidation, total lesions and total lung in all patients were quantified. Complications were more common in deceased patients than in recovered patients; respiratory failure (57.8%), septic shock (36.7%), and acute respiratory distress syndrome (26.6%) were the most common complications in patients who died. Many treatments were more frequent in deceased patients, such as antibiotic therapy (88.1% versus 53.7%), glucocorticoid treatment (70.6% versus 11.0%), intravenous immunoglobin treatment (36.6% versus 4.9%), invasive mechanical ventilation (62.3% versus 3.8%). Antivirals, antibiotics, traditional Chinese medicines and glucocorticoid treatment may significantly increase the survival time of fatal cases. Quantitative computed tomography imaging results were correlated with biochemical markers. Conclusions: Most patients with fatal outcomes were more likely to have common comorbidities. The leading causes of death were respiratory failure and multiple organ dysfunction syndrome. Acute respiratory distress syndrome, respiratory failure and septic shock were the most common serious complications. Antivirals, antibiotics, traditional Chinese medicines, and glucocorticoid treatment may prolong the survival time of deceased patients with COVID-19.

Objective The purpose of the present study is to investigate whether angiopoietin-like 4 (ANGPTL4) can promote angiogenesis and neurogenesis following stroke, as well as to explore the potential underlying mechanisms. Methods ANGPTL4 (40 μg/kg) or a vehicle was administered via tail vein beginning 5 min prior to electrocoagulation-induced stroke in male C57/B6 J mice. Infarct volume was measured via Nissl staining at day 3 post-stroke. Angiogenesis, neurogenesis and activation of microglia were evaluated by immunofluorescence co-labelling bromodeoxyuridine (BrdU) with von Willebrand factor (vWF), doublecortin (DCX), neuronal nuclei (NeuN) and Iba1 at day 7 post-stroke. The levels of p-AKT, T-AKT, VEGF, MPO, Fas and FasL in the ipsilesional brain were detected by Western blot analysis at day 1 post-stroke. Results Compared with the Vehicle group, ANGPTL4 reduced infarct volume significantly at day 3 post-stroke. ANGPTL4 significantly increased the number of BrdU+, BrdU+/vWF+and BrdU+/DCX+ cells in the peri-infarct zone, subventricular zone and subgranular zone and inhibited BrdU+/Iba1+ cells in the peri-infarct zone at day 7 post-stroke. The level of p-AKT and the ratio of phospho-AKT to total-AKT in the ipsilesional brain were significantly elevated, the levels of MPO, Fas and FasL were significantly declined; however, there was no significant difference at day 1 post-stroke between the VEGF and total-AKT levels in both groups. Conclusions ANGPTL4 enhances angiogenesis and neurogenesis post-stroke by upregulating the phosphorylation of AKT, reduces neuronal death and inhibits inflammatory response, which resultes from the inhibition of FasL/Fas expression and its downstream pathway.

Objective The optimal timing for glioma patients to stop taking antiepileptic drugs (AEDs) and the risk factors of seizure relapse have not been determined. Here, we explored the short-term outcomes and risk factors of seizure relapse in glioma patients after withdrawal of AEDs. Methods 91 patients with gliomas who had no seizures at least 2 years after surgery were enrolled in the study. The patients were followed up for 1 year or until the relapse of seizure after AEDs withdrawal. The risk factors of seizure relapse were analyzed by univariate and multivariate analysis. The optimal discrimination point was determined by plotting a receiver operating characteristic (ROC) curve to explore the relationship between the number of risk factors and seizure relapse. Results 28 patients (30.8%) relapsed during the follow-up period while 63 patients (69.2%) remained seizure-free. Of the 28 relapsed patients, 20 (71.4%) relapsed within the first 6 months after the AEDs withdrawal. Multivariate analyses revealed that subtotal resection (p = 0.026), IDH1 mutation (p = 0.019), and combined use of AEDs (p = 0.037) were independent risk factors for seizure relapse in glioma patients. ROC curve based on the seizure relapse showed that the sensitivity was 0.821 and 1–specificity was 0.238, corresponding to 1.5 independent risk factors for each patient. Conclusion To obtain a favorable outcome for glioma patients with preoperative seizures, only patients with less than two independent risk factors for seizure relapse should consider discontinuing AEDs.

Glioma is the most common malignant tumor in the central nervous system. Evidence shows that clinical efficacy of immunotherapy is closely related to the tumor microenvironment. This study aims to establish a microenvironment-related genes (MRGs) model to predict the prognosis of patients with Grade II/III gliomas. Gene expression profile and clinical data of 459 patients with Grade II/III gliomas were extracted from The Cancer Genome Atlas. Then according to the immune/stromal scores generated by the ESTIMATE algorithm, the patients were scored one by one. Weighted gene co-expression network analysis (WGCNA) was used to construct a gene co-expression network to identify potential biomarkers for predicting the prognosis of patients. When adjusting clinical features including age, histology, grading, IDH status, we found that these features were independently associated with survival. The predicted value of the prognostic model was then verified in 440 samples in CGGA part B dataset and 182 samples in CGGA part C dataset by univariate and multivariate cox analysis. The clinical samples of 10 patients further confirmed our signature. Our findings suggested the eight-MRGs signature identified in this study are valuable prognostic predictors for patients with Grade II/III glioma.

Background Collateral status assessed with single- or multiphase CT angiography can be used to predict outcome in patients with acute ischemic stroke (AIS); however, little is known about whether these measures could be comparable with CT perfusion parameters. Purpose To compare the predictive ability of collateral score systems assessed with single- or multiphase CT angiography and CT perfusion parameters in determining clinical outcomes in patients with AIS. Materials and Methods In this retrospective study, data obtained from October 2017 to August 2018 in consecutive patients with AIS caused by isolated anterior circulation large artery occlusion and that were obtained within 24 hours after onset were reviewed. The collateral score was assessed by using established scoring systems described by Menon et al. The correlations between single- and multiphase collateral scores, hypoperfusion, and ischemic core volume and final infarct volume (FIV) determined by follow-up diffusion-weighted imaging or unenhanced CT were studied. Receiver operating characteristic curves and multivariable logistic regression analysis were performed to assess the predictive ability of scoring systems and CT perfusion parameters for a favorable clinical outcome. Results A total of 119 patients (median age, 75 years; interquartile range, 66-82 years; 74 men) were included. Both single- and multiphase Menon scores had a moderate negative correlation with FIV (r = -0.43, P < .001; r = -0.44, P < .001). Receiver operating characteristic curve analysis revealed the multiphase Menon score performed better than the single-phase Menon score (area under the curve [AUC], 0.72 vs 0.64; P = .045) in the prediction of a favorable 90-day modified Rankin scale score. There was no difference between multiphase Menon score and hypoperfusion volume (AUC, 0.72 vs 0.72; P = .97) or ischemic core volume (AUC, 0.72 vs 0.71; P = .94). Multivariable analysis showed multiphase Menon score was an independent predictor of good clinical outcomes (odds ratio = 3.04, P = .001). Conclusion Multiphase Menon score performed better than single-phase Menon score and was comparable with CT perfusion parameters in determining clinical outcomes in patients with acute ischemic stroke. © RSNA, 2020.

The difference in prognosis between genders after abdominoperineal resection (APR) for low rectal cancer (LRC) is unclear. This study aimed to compare survival outcomes between genders in patients with LRC who underwent curative APR. This retrospective cohort study used a database of consecutive colorectal resections. Patients who received curative APR with LRC were grouped according to their gender. Female patients were frequency-matched 1:1 on American Joint Committee on Cancer (AJCC) stage to male patients. Overall survival (OS), disease-free survival (DFS), and their independent risk factors were examined. A total of 140 patients with APR for LRC were included after matching: 70 (50.0%) males and 70 (50.0%) females. No significant differences were found between the groups in terms of age, operation methods, AJCC stage, and adjuvant therapy (all P > 0.05). Median follow-up was 39 (range: 3–128) months. Male gender was independently associated with worse OS (adjusted hazard ratio [HR] = 2.755, 95% CI: 1.507–5.038, P = 0.001) and worse DFS (adjusted HR = 2.440, 95% CI: 1.254–4.746, P = 0.009). Subgroup analysis revealed that female patients with stage III disease had better OS (P = 0.001) and DFS (P

Purpose/aim: Lymphomatosis cerebri (LC) and cauda equina lymphoma are both rare forms of primary central nervous system lymphoma (PCNSL). LC is characterized by diffuse bilateral non-enhancing (or partially enhancing) inltrative lesions without mass effect, which can be easily confused with other forms of leukoencephalopathy and, thus, lead to delays in diagnosis.Case report: For the first time, a case of LC concomitant with cauda equina involvement confirmed by brain stereotactic biopsy is presented.Conclusions: This case highlights the necessity of using a multimodal strategy in diagnosing PCNSL, including multimodal magnetic resonance, cerebral spinal fluid cytology, flow cytometry and fluorodeoxyglucose positron emission tomography/computed tomography.

Breast cancer is the most common type of cancer in women. About 12% of all women in the United States will be diagnosed with breast cancer over their lifetimes. At the same time, incidences of brain metastases (BMs) are increasing and represent an emerging health threat. However, there is no effective chemotherapy for breast cancer brain metastases (BCBMs), which is largely due to lack of efficient delivery of antitumor drugs or drug combinations to the brain. In this study, oleanolic acid (OA), a natural pentacyclic triterpenoid compound with excellent antitumor activity, was found to form nanoparticles (NPs) and efficiently penetrate the brain for BCBMs treatment. On the basis of these findings, we developed a synergistic combinatorial chemotherapeutic regimen by formulating paclitaxel (PTX) into OA NPs and demonstrated that the resulting PTX-OA NPs effectively inhibited primary breast cancer and BCBMs in mouse xenografts. Collectively, this study introduces a new direction to treat primary breast cancer and BCBMs through noninvasive combination chemotherapy.

To explore the predictive factors and short-term outcomes of post-surgical seizures in patients with supratentorial low-grade gliomas (LGGs). A consecutive series of 70 supratentorial LGG patients with seizures were reviewed to determine the predictors and short-term outcomes of seizures. Univariate analyses and multivariate logistic regression analyses were performed to determine the predictive factors associated with postoperative seizure outcomes. We identified the preoperative seizure frequency threshold by plotting a receiver operating characteristic curve. A Kaplan-Meier curve was constructed to illustrate the seizure-free survival rate of our cohort over time. 54 patients who remained seizure -free post-surgery were classified into the Engel class I, and the other 16 patients whose seizures relapsed were classified into Engel classes II–IV. Univariate and multivariate logistic regression analyses showed that the preoperative seizure frequency (X2 = 16.069, P = 0.001), extent of resection (x2 = 5.031, P = 0.025), IDH1 mutation (x2 = 4.435, P = 0.035) and adjuvant chemotherapy of temozolomide (X2 = 4.081, P = 0.043) were related to the postoperative short-term seizure outcome. The ROC curve indicated that the area under the curve for the preoperative seizure frequency test was 0.805 (95% confidence interval 0.690–0.920, p

With the wide application of dynamic compaction, its impact on surrounding buildings has received more and more attention. This paper established a numerical model for dynamic compaction and compared its results with actual experimental data to verify the effectiveness of the model. And the numerical results showed that the vibration isolation trench had an efficient vibration isolation effect during the dynamic compaction process. The study also found that the vibration isolation effect is determined by the width and depth of the vibration isolation trench, and the depth was more sensitive to the final effect. Therefore, this study can provide a theoretical basis for the design of vibration isolation trenches.

Despite being promising, the clinical application of magnetic hyperthermia for brain cancer treatment is limited by the requirement of highly invasive intracranial injections. To overcome this limitation, here we report the development of gallic acid-coated magnetic nanoclovers (GA-MNCs), which allow not only for noninvasive delivery of magnetic hyperthermia but also for targeted delivery of systemic chemotherapy to brain tumors. GA-MNCs are composed of clover-shaped MNCs in the core, which can induce magnetic heat in high efficiency, and polymerized GA on the shell, which enables tumor vessel-targeting. We demonstrate that intravenous administration of GA-MNCs following alternating magnetic field exposure effectively inhibited brain cancer development and preferentially disrupted tumor vasculature, making it possible to efficiently deliver systemic chemotherapy for further improved efficacy. Due to the noninvasive nature and high efficiency in killing tumor cells and enhancing systemic drug delivery, GA-MNCs have the potential to be translated for improved treatment of brain cancer.

As a class of novel biomaterials manufactured by synthetic biology technologies, recombinant collagens are candidates for a variety of medical applications. In this article, a regulatory scientific perspective on recombinant collagens and their medical devices is presented with a focus on the definition, translation, classification and technical review. Recombinant collagens are categorized as recombinant human collagen, recombinant humanized collagen and recombinant collagen-like protein, as differentiated by specific compositions and structures. Based on their intended uses and associated risks, recombinant collagen-based medical devices are generally classified as Class Ⅱ or Ⅲ in China. The regulatory review of recombinant collagen-based medical devices aims to assess their safety and efficacy demonstrated by scientific evidences generated from preclinical and clinical evaluations. Taken together, opportunities as well as challenges for their future clinical translation of recombinant collagen-based medical devices abound, which highlights the essential role of regulatory science to provide new tools, standards, guidelines and methods to evaluate the safety and efficacy of medical products.

Background PLEKHA5 has previously been identified as a novel molecule implicated in melanoma brain metastasis, a disease that continues to portend a poor prognosis. The aim of this study was to further investigate the functional role of PLEKHA5 in disseminated melanoma. Methods The impact of PLEKHA5 on proliferation and tumor growth was examined in vitro and in melanoma xenograft models, including brain-tropic melanomas (melanomas tending to disseminate to the brain). In vitro loss- and gain-of-function studies were used to explore the underlying mechanisms of PLEKHA5-mediated tumor growth and the crosstalk between PLEKHA5 and PI3K/AKT/mTOR or MAPK/ERK signaling. The clinical relevance of PLEKHA5 dysregulation was further investigated in a cohort of matched cranial and extracranial melanoma metastases. Results PLEKHA5 stable knockdown negatively regulated cell proliferation by inhibiting the G1 -to-S cell cycle transition, which coincided with upregulation of the cell cycle regulator PDCD4. Conversely, ectopic PLEKHA5 expression exhibited the inverse effect. PLEKHA5 knockdown significantly inhibited tumor growth, whereas its overexpression upregulated the growth of tumors, which was induced by cranial and subcutaneous inoculation of cells in nude mice. PLEKHA5 modulation affected PDCD4 protein stability and was coupled with changes in PI3K/AKT/mTOR pathway signaling. High PDCD4 expression in cerebral specimens was associated with better overall survival. Conclusions This study further supports the role of PLEKHA5 as a regulator of melanoma growth at distant sites, including the brain. Furthermore, the results highlight the significance of PDCD4 dysregulation in disseminated melanoma and implicate PDCD4 as a possible causal link between PLEKHA5 and cell proliferation and growth.

Objective: To assess the reproducibility of 3.0T high-resolution magnetic resonance imaging for the identification and quantification of atherosclerotic plaques in the middle cerebral artery. Methods: Sixty-nine consecutive patients with ischemic stroke or asymptomatic stenosis (>30%) of the middle cerebral artery underwent 3.0T high-resolution magnetic resonance imaging examinations. Two independent investigators reviewed all images with 1 investigator re-evaluating all images 4 weeks later. Wall characteristics of the middle cerebral artery, including plaque surface morphology, plaque location, plaque components, and burden were identified and measured. Results: Intraobserver and interobserver agreement were all substantial in identifying plaque surface irregularity (k = 0.741, 0.555-0.897; k = 0.685, 0.490-0.843; respectively) and intraplaque hemorrhage (k = 0.654, 0.446-0.838; k = 0.605, 0.369-0.792; respectively). Intraobserver agreement was substantial (k = 0.654) and interobserver agreement was moderate (k = 0.553) for the identification of plaque fibrous caps. The total intraobserver and interobserver reproducibility was almost excellent for the identification of plaque position. With regards to vessel area measurement at the site of maximal lumen narrowing, intraobserver and interobserver reproducibility was excellent (intraclass correlation coefficient was 0.886 and 0.885, respectively) and moderate for lumen area at the site of maximal lumen narrowing (intraclass correlation coefficient was 0.695 and 0.558, respectively). In addition, intraobserver and interobserver reproducibility was excellent for vessel area and lumen area measurements at the reference sites. Conclusions: The reproducibility of 3.0T high-resolution magnetic resonance imaging for the identification and quantification of artery wall characteristics was overall acceptable. However, the reliability for lumen area measurement at the maximum narrowing site and identification of the fibrous cap needs to be improved.

Background Icariin is a major component isolated from Epimedium brevicornum Maxim and has been reported to exhibit anti-tumor activity. However, whether icariin could reverse the acquired drug resistance in breast cancer remains largely unclear. Therefore, this study was designed to explore the antitumor effects of icariin and its underlying mechanisms in a tamoxifen-resistant breast cancer cell line MCF-7/TAM. Methods 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Lactate dehydrogenase (LDH) assay were performed to determine the effects of icariin on cell viability and cell death. Cell cycle progression and apoptosis were detected by flow cytometry analysis. Transmission electron microscopy (TEM) assay was utilized to observe cell autophagy. The downstream protein levels were measured using western blotting. Results Here, we observed that icariin treatment not only inhibited the growth of MCF-7 but also has a potential function to overcome tamoxifen resistance in MCF-7/TAM. Moreover, icariin significantly induced cell cycle G0/G1 phase arrest and apoptosis, as well as suppressed autophagy. At molecular levels, icariin treatment remarkably down-regulated the expression levels of CDK2, CDK4, Cyclin D1, Bcl-2, LC3-1, LC3-II, AGT5, Beclin-1, but upregulated the expression levels of caspase-3, PARP and p62. Most importantly, we found inhibition of autophagy via 3-MA treatment could significantly enhance the effects of icariin on cell viability and apoptosis. Enhanced autophagy via autophagy related 5 (ATG5) overexpression could partially reverse the effects of icariin on cell viability and apoptosis. Conclusion These results revealed that icariin might potentially be useful as an adjuvant agent in cancer chemotherapy to enhance the effect of tamoxifen through suppression of autophagy in vitro and provide insight into the therapeutic potential of icariin for the treatment of chemo-resistant breast cancer.

A residual life prediction method based on the long short-term memory (LSTM) was proposed for remaining useful life (RUL) prediction in this paper. Firstly, feature parameters were extracted from time domain, frequency domain, time–frequency domain and related-similarity features; then three feature evaluation indicators were defined to select feature parameters that could better represent the degradation process of bearings and constructed the feature set with the time factor. The data of the feature set was used to train the LSTM network prediction model, and then the RUL was predicted by the trained neural network. The full life test of rolling bearing was provided to demonstrate that this method could accurately predict the remaining life of the rolling bearing, and the result was compared with the prediction results of BP neural network and support vector regression machine to verify the effectiveness.

Purpose To construct the albumin-bilirubin (ALBI) grade and the Child-Turcotte-Pugh (CTP) score based on nomograms, as well as to develop an artificial neural network (ANN) to compare the prognostic performance of the 2 scores for hepatocellular carcinoma (HCC) that has undergone transarterial chemoembolization. Materials and Methods This multicentric retrospective study included patients with HCC who underwent transarterial chemoembolization monotherapy as an initial treatment at 4 institutions between January 2008 and December 2016. In the training cohort, significant risk factors associated with overall survival (OS) were identified by univariate and multivariate analyses. The prognostic nomograms and ANN were established and then validated in 2 validation cohorts. Results A total of 838 patients (548, 115, and 175 in the training cohort and validation cohorts 1 and 2, respectively) were included. The median OS was 10.4, 15.7, and 9.2 months in the training cohort and validation cohorts 1 and 2, respectively. In the training cohort, both ALBI grade and CTP score were identified as significant risk factors. The ALBI grade and CTP score based on nomograms were established separately and showed similar prognostic performance when assessed externally in validation cohorts (C-index in validation cohort 1: 0.823 vs 0.802, P = .417; in validation cohort 2: 0.716 vs 0.729, P = .793). ANN showed that ALBI grade had higher importance on survival prediction than CTP score. Conclusions ALBI grade performs at least no worse than CTP score regarding survival prediction for HCC receiving transarterial chemoembolization. Considering the easy application, ALBI grade has the potential to be regarded as an alternative to CTP score.

The blood-brain barrier (BBB) prevents antibodies from penetrating the CNS and limits conventional antibody-based approaches to brain tumors. We now show that ENT2, a transporter that regulates nucleoside flux at the BBB, may offer an unexpected path to circumventing this barrier to allow targeting of brain tumors with an anti-DNA autoantibody. Deoxymab-1 (DX1) is a DNA-damaging autoantibody that localizes to tumors and is synthetically lethal to cancer cells with defects in the DNA damage response. We found that DX1 penetrated brain endothelial cells and crossed the BBB, and mechanistic studies identify ENT2 as the key transporter. In efficacy studies, DX1 crosses the BBB to suppress orthotopic glioblastoma and breast cancer brain metastases. ENT2-linked transport of autoantibodies across the BBB has potential to be exploited in brain tumor immunotherapy, and its discovery raises hypotheses on actionable mechanisms of CNS penetration by neurotoxic autoantibodies in CNS lupus.

Background The prognosis of lung cancer with synchronous brain metastasis (LCBM) is very poor, and patients often die within a short time. However, little is known about the early mortality and related factors in patients with LCBM. Methods Patients diagnosed with LCBM between 2010 and 2016 were enrolled from the Surveillance, Epidemiology, and End Result (SEER) database. Univariate and multivariate logistic regression analysis were used to identify significant independent prognostic factors, which were used to construct nomograms of overall and cancer-specific early death. Then, the prediction ability of the model was verified by receiver operating characteristic (ROC) curve. At last, the clinical application value of the model was tested through decision curve analysis (DCA). Results A total of 29,902 patients with LCBM were enrolled in this study. Among them, 13,275 (44.4%) patients had early death, and 11,425 (38.2%) cases died of lung cancer. The significant independent risk factors for overall and cancer-specific early death included age, race, gender, Gleason grade, histological type, T stage, N stage, bone metastasis, liver metastasis and marital status, which were used to construct the nomogram. The ROC curve demonstrated good predictive ability and clinical application value. The areas under the curve (AUC) of the training group was 0.793 (95% CI: 0.788–0.799) and 0.794 (95% CI: 0.788–0.799), in the model of overall and cancer-specific early death respectively. And the AUC of the validation group were 0.803 (95% CI: 0.788–0.818) and 0.806 (95% CI: 0.791–0.821), respectively. The calibration plots of the model showed that the predicted early death is consistent with the actual value. The DCA analysis indicated a good clinical application value of this model. Conclusions We established a comprehensive nomogram to predict early death in lung cancer patients with synchronous brain metastases. Nomograms may help oncologists develop better treatment strategies, such as clinical trials and hospice care.

Xiaonan Zhang,1,&ast; Huimin Fang,1,&ast; Zhigang Zeng,1 Kaijun Zhang,1 Zhanyi Lin,1,2 Gang Deng,1 Weiping Deng,1 Lichang Guan,1 Xuebiao Wei,1 Xinyi Li,2 Lei Jiang,1– 3 Lishu Xu1– 3 1Guangdong Provincial Geriatrics Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 2School of Medicine, South China University of Technology, Guangzhou, 510641, People’s Republic of China; 3The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Jiang; Lishu Xu Tel +86-20-83827812; +86-20-13660032429Email jianglei@smu.edu.cn; xulishu70@163.comPurpose: Gastric cancer is a common tumor type associated with nutritional and immune status. The aim of the current study was to investigate the prognostic value of a preoperative prognostic nutritional index (PNI), composed of nutritional factors and immune factors in elderly patients undergoing gastric cancer surgery.Patients and Methods: A total of 454 patients undergoing gastric cancer surgery were divided into two groups based on preoperative PNI scores: ≤ 45.1 (n = 307) and > 45.1 (n = 147). Survival analysis was performed using the Kaplan–Meier method and Log rank tests. Univariate and multivariate analyses were conducted to identify independent prognostic factors using a Cox proportional hazards model.Results: According to the X-tile program, the optimal cutoff value for predicting overall survival (OS) with the PNI was 45.1. The receiver operating characteristic analysis revealed that PNI exhibited 70.6% sensitivity and 56.5% speci&filig;city for predicting death during long-term follow-up. The cumulative incidence of postoperative 4-year mortality indicated that the risk of death increased significantly for PNI ≤ 45.1. In multivariate analysis, preoperative PNI was a significant independent predictor of mortality. In the age-stratified subgroup analysis, preoperative PNI was more sensitive for the old elderly subgroup than for the young elderly subgroup.Conclusion: Preoperative PNI is a sensitive and specific prognostic predictor among elderly patients undergoing gastric cancer surgery.Keywords: elderly patients, gastric cancer, prognostic nutritional index, radical gastrectomy

BackgroundDespite successful recanalization after endovascular treatment, many patients with acute ischemic stroke due to large vessel occlusion still show functional dependence, namely futile recanalization.MethodsPubMed and Embase were searched up to April 30, 2021. Studies that reported risk factors for futile recanalization following endovascular treatment of acute ischemic stroke were included. The mean difference (MD) or odds ratio (OR) and 95% confidence interval (95% CI) of each study were pooled for a meta-analysis.ResultsTwelve studies enrolling 2138 patients were included. The pooled analysis showed that age (MD 5.81, 95% CI 4.16 to 7.46), female sex (OR 1.40, 95% CI 1.16 to 1.68), National Institutes of Health Stroke Scale (NIHSS) score (MD 4.22, 95% CI 3.38 to 5.07), Alberta Stroke Program Early CT Score (ASPECTS) (MD −0.71, 95% CI −1.23 to –0.19), hypertension (OR 1.73, 95% CI 1.43 to 2.09), diabetes (OR 1.78, 95% CI 1.41 to 2.24), atrial fibrillation (OR 1.24, 95% CI 1.01 to 1.51), admission systolic blood pressure (MD 4.98, 95% CI 1.87 to 8.09), serum glucose (MD 0.59, 95% CI 0.37 to 0.81), internal carotid artery occlusion (OR 1.85, 95% CI 1.17 to 2.95), pre-treatment intravenous thrombolysis (OR 0.67, 95% CI 0.55 to 0.83), onset-to-puncture time (MD 16.92, 95% CI 6.52 to 27.31), puncture-to-recanalization time (MD 12.37, 95% CI 7.96 to 16.79), and post-treatment symptomatic intracerebral hemorrhage (OR 6.09, 95% CI 3.18 to 11.68) were significantly associated with futile recanalization.ConclusionThis study identified female sex, comorbidities, admission systolic blood pressure, serum glucose, occlusion site, non-bridging therapy, and post-procedural complication as predictors of futile recanalization, and also confirmed previously reported factors. Further large-scale prospective studies are needed.

Pancreatic ductal adenocarcinoma (PDCA) is a leading cause of cancer death in the US. Patients diagnosed with PDCA generally present with advanced disease with poor prognosis and limited treatment options. African American patients have higher incidence and mortality of PDCA than Caucasian American or any other ethnic group. Different factors have been attributed to contribute to this health disparity, among them higher incidence of Diabetes Mellitus type 2. To address the need for new therapeutic approaches, we note epidemiologic reports that patients with diabetes mellitus-type 2 treated with the biguanide drug metformin, but not other antidiabetic drugs, have a reduced risk of PDCA and an increased survival rate among those with PDCA. The main physiologic effect of metformin is to lower blood glucose and reduce hyperinsulinemia associated with insulin resistance. In the cell, metformin stimulates AMP-activated protein kinase (AMPK) that in turn inhibits mTORC1 which integrates signals from an array of intracellular pathways to regulate cell growth. Recent clinical trials describe modest antiproliferative effects from use of neoadjuvant metformin, but no significant clinical benefit occurred when metformin was dosed at glycemic control levels in patients with advanced cancers. These findings suggest that development of more potent anticancer analogues of metformin may help to boost clinical benefit and patient survival. Hence, we have designed new biguanide analogues of metformin, and screening of these compounds in preclinical PDCA models show that selected analogues are more efficacious in blocking tumor progression than parental metformin at lower doses. Using proliferation assays in vitro, PDCA cells (Panc 1, MIA Paca-2) were treated 72-hrs with metformin or analogues, and greater dose-dependent inhibition of PDCA cell proliferation was found with analogues as compared to metformin (P

PurposeGiven that the novel coronavirus disease (COVID-19) pandemic has disrupted operations globally, an institution’s ability to repeat transarterial chemoembolization (TACE) for patients with hepatocellular carcinoma (HCC) has also been affected. The aim of this study was to evaluate the impact of the COVID-19 on the intervals and outcomes of TACE in HCC patients.Materials and MethodsThis retrospective study included 154 HCC patients who underwent follow-up after TACE treatment from January 2020 to March 2020 (n = 71, study group) and January 2019 to March 2019 (n = 83, control group) at two institutions in China. The endpoints included the follow-up interval and overall response rate (ORR). Multivariate logistic regression analyses were performed to identify independent risk factors for a worse ORR. The cut-off point was determined to divide follow-up durations into long- and short-intervals.ResultsThe median follow-up interval was 82.0 days (IQR, 61–109) in the study group, which was significantly longer than 66.0 days (IQR, 51–94) in the control group (P = 0.004). The ORR was 23.9 and 39.8% in the study and control group, respectively (P = 0.037). The cut-off value was 95 days. The grouping (OR, 2.402; 95% CI, 1.040–5.546; P = 0.040), long interval (OR, 2.573; 95% CI, 1.022–6.478; P = 0.045), and China liver cancer staging system (OR, 2.500; 95% CI, 1.797–3.480; P <0.001) were independent predictors for the efficacy of TACE treatment.ConclusionsThe COVID-19 pandemic causes a longer follow-up interval in general, which may further lead to a lower ORR in HCC patients. Those with a follow-up interval of >95 days tend to have a worse prognosis.

Background: The prognosis of middle-aged patients with CRC treated by laparoscopic resection (LR) is unclear. This study aimed to evaluate the survival outcomes of LR compared with open resection (OR) for patients with CRC and 45-65 years of age.Methods: This retrospective cohort study used the data from a database of all consecutive colorectal resections performed between January 2009 and December 2017. Propensity score matching (PSM) was done to handle the selection bias based on age, gender, body mass index (BMI), tumor location, AJCC stage, and admission year. Univariate and multivariate COX regression model was used to identify risk factors of overall survival (OS) and progression-free survival (PFS).Results: After PSM, 217 patients were included in each group. There were no differences in OS and PFS between the two groups (all P>0.05). There was less blood loss for LR (PConclusions: In middle-aged patients with CRC, OR and LR have similar survival outcomes and complications.

Background: Aneurysmal subarachnoid hemorrhage (aSAH) leads to severe disability and functional dependence. However, no reliable method exists to predict the clinical prognosis after aSAH. Thus, this study aimed to develop a web-based dynamic nomogram to precisely evaluate the risk of poor outcomes in patients with aSAH.Methods: Clinical patient data were retrospectively analyzed at two medical centers. One center with 126 patients was used to develop the model. Least absolute shrinkage and selection operator (LASSO) analysis was used to select the optimal variables. Multivariable logistic regression was applied to identify independent prognostic factors and construct a nomogram based on the selected variables. The C-index and Hosmer–Lemeshow p-value and Brier score was used to reflect the discrimination and calibration capacities of the model. Receiver operating characteristic curve and calibration curve (1,000 bootstrap resamples) were generated for internal validation, while another center with 84 patients was used to validate the model externally. Decision curve analysis (DCA) and clinical impact curves (CICs) were used to evaluate the clinical usefulness of the nomogram.Results: Unfavorable prognosis was observed in 46 (37%) patients in the training cohort and 24 (29%) patients in the external validation cohort. The independent prognostic factors of the nomogram, including neutrophil-to-lymphocyte ratio (NLR) (p = 0.005), World Federation of Neurosurgical Societies (WFNS) grade (p = 0.002), and delayed cerebral ischemia (DCI) (p = 0.0003), were identified using LASSO and multivariable logistic regression. A dynamic nomogram (https://hu-ping.shinyapps.io/DynNomapp/) was developed. The nomogram model demonstrated excellent discrimination, with a bias-corrected C-index of 0.85, and calibration capacities (Hosmer–Lemeshow p-value, 0.412; Brier score, 0.12) in the training cohort. Application of the model to the external validation cohort yielded a C-index of 0.84 and a Brier score of 0.13. Both DCA and CIC showed a superior overall net benefit over the entire range of threshold probabilities.Conclusion: This study identified that NLR on admission, WFNS grade, and DCI independently predicted unfavorable prognosis in patients with aSAH. These factors were used to develop a web-based dynamic nomogram application to calculate the precise probability of a poor patient outcome. This tool will benefit personalized treatment and patient management and help neurosurgeons make better clinical decisions.

Introduction: Recently, NA1, a peptide designed to protect neurons against NMDA receptor-mediated excitotoxicity, demonstrated promise for acute stroke treatment. Enhanced efficiency of peptide delivery may result in improved efficacy. Hypothesis: The bioactive fragment of NA1 is nine amino acids of the carboxyl tail of GluN2B. Delivery of NR2B9c to cells in the brain is achieved through fusion with TAT, a peptide that binds to biological membranes without selectivity. We hypothesize that enhancing targeted delivery of NA1 to the ischemic brain improve the efficacy of NA1. Methods: We previously identified betulinic acid (BA) forming nanoparticles (NPs) as a novel formulation of stroke treatment delivery. After intravenous administration, BA NP penetrate the ischemic brain, reduce ischemia-induced infarction as an antioxidant agent, and allow for encapsulation and delivery of drugs. In this study, we engineered BA NPs for improved drug delivery preferentially to the ischemic brain through surface conjugation of AMD3100, and for acid-triggered drug release to selectively in the ischemic region, which is known to be acidic, through chemical modification. The resulting acid responsive, stroke- targeting antioxidant NPs, or ARSTA NPs, were evaluated for stroke treatment in the mouse transient middle cerebral artery occlusion (MCAO) model either alone or in combination with NA1, based on changes of infarct volumes, edema, mortality, and outcomes. Results: We found that ARSTA NPs enabled targeted delivery of NA1 preferentially to the ischemic brain and allowed for prompt drug release. We showed that intravenous delivery of 50 ug NA1 (or 1nM/g) encapsulated in 1 mg ARSTAs effectively reduced infarct volumes by 69.8%, edema by 60.3%, mortality (median survival >14 days). In contrast, delivery of ARSTA NPs alone (52.2%, 30.2%, 10) or NA1 (0.7%, 3.3%, 6 days) alone at a comparable dose exhibited significantly less efficacy. Consistently, treatment with NA1-loaded ARSTAs improved neurological outcomes in a degree significantly greater than that by either ARSTA NPs or NA1 alone. Conclusion: BA-NP encapsulating NA-1 may represent a novel platform for improved delivery to the ischemic brain. Improved delivery may result in improved efficacy.

Objective We evaluated the early and midterm results of the endovascular approach with a certain type of bare stent to treat spontaneous isolated visceral artery dissection (SIVAD). Methods 28 patients with symptomatic SIVAD were selected from two hospitals from July 2014 to September 2020. All patients had symptoms of acute persistent abdominal pain accompanied by varying degrees of nausea and vomiting. The diagnosis of SIVAD was made according to the multidetector CT angiography (CTA) findings. We retrospectively analyzed the patients' medical records. According to our previous clinical experience, the Protege EverFlex self-expanding bare stent was used in these patients, and we subsequently followed up the patients to record and analyze their outcomes after surgery. The imaging results before and after the operations were compared. Results All 28 patients were successfully implanted with Protege EverFlex stents. The true lumen blood flow of the SIVAD recovered during the operation. The residual stenosis rate was less than 30%, and the technical success rate was 100%. There were no complications, such as bleeding, intestinal necrosis, digestive tract perforation, liver failure or spleen infarction. The abdominal pain was relieved or eliminated in all patients. Conclusion The Protege EverFlex self-expanding bare stent and the endovascular approach could be a minimally invasive, safe and effective treatment method for SIVAD with a high success rate and a relatively low price.

Coronavirus disease-2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread globally since its first report and become a worldwide pandemic. In response to the outbreak of COVID-19, Center for Medical Device Evaluation, NMPA (CMDE) initiated emergency review and approval procedures to accelerate the process of reviewing emergent medical products and issued the Key Points of Technical Review for the Registration of SARS-CoV-2 Antigen/Antibody Tests (Key Points) to provide the requirements on the technical review of the tests. With uncontrolled spread and evolution of COVID-19 in the world, continuous prevention and measurements are necessary for fighting this pandemic and SARS-CoV-2 antigen/antibody tests are still urgently needed. This article is an attempt to expand clarification of the Key Points to wider audiences based on current understanding of SARS-CoV-2 to facilitate the development and application of SARS-CoV-2 antigen/antibody tests.

Congenital heart disease, particularly cyanotic congenital heart disease (CCHD), may lead to a neurodevelopmental delay through central nervous system injury, more unstable central nervous system development, and increased vulnerability of the nervous system. Neurodevelopmental disease is the most serious disorder of childhood, affecting the quality of life of children and their families. Therefore, the monitoring and optimization of nerve damage treatments are important. The factors contributing to neurodevelopmental disease are primarily related to preoperative, intraoperative, postoperative, genetic, and environmental causes, with intraoperative causes being the most influential. Nevertheless, few studies have examined these factors, particularly the influencing factors during early postoperative care. Children with congenital heart disease may experience brain damage during early heart intensive care due to unstable haemodynamics and total body oxygen transfer, particularly early postoperative inflammatory reactions in the brain, blood glucose levels, and other factors that potentially influence long-term neural development. This study analyses the forms of structural and functional brain damage in the early postoperative period, along with the recent evolution of research on its contributing factors.

BackgroundAlthough increasing evidence shows that immune infiltration plays an essential role in glioblastoma (GBM), current prognostic indicators do not accurately represent the risk of immune cells infiltration in patients. It is therefore critical to identify new prognostic markers for GBM. Here, we investigated the effectiveness of using immunoscore to improve risk stratification and prediction of prognosis in GBM patients receiving chemotherapy.MethodsUsing mRNA microarrays and CIBERSORT, we analyzed 22 types of immune cell fractions in 517 GBM samples and characterized an immunoscore using the least absolute shrinkage and selection operator (LASSO) Cox regression model based on the fraction of immune cell types and patients’ overall survival. The prognostic and predictive accuracy of immunoscore was verified in the validation cohort and the entire cohort.ResultsUsing the LASSO model, an immunoscore was developed to classify patients into High and Low immunoscore groups in the training cohort (P < 0.0001) based on the fraction of eight immune cell types. The immunoscore performance was validated in the validation cohort (P < 0.0001) and the entire cohort (P < 0.0001). Furthermore, a nomogram comprising age, IDH1 status, and immunoscore was generated to predict one- and three-year survival rates in the training cohort. The predictive value of the immunoscore was also confirmed in the validation cohort and the entire cohort (C-index: 0.66, 0.67, and 0.68, respectively). In addition, we concluded that patients in the low-immunoscore group may benefit from adjuvant chemotherapy for GBM.ConclusionImmunoscore, an immune-infiltration-based signature, is a reliable prognostic and predictive tool for GBM.

Cerebral or intracranial aneurysm is a leading cause of subarachnoid hemorrhage. It was initially treated with open surgical clipping but as rapid development of technology a less invasive endovascular coiling technique of aneurysm revolutionized the treatment. Due to tortuous anatomy of parent artery and complicated morphology and location of aneurysm there is ongoing challenge in the complete obliteration of aneurysms. To aid in the advances of treating aneurysm stent assisted endovascular coiling was introduced to give more scaffold support to parent artery and decrease events of coil protrusion from aneurysms. Many types and generation of stents were developed. One of the most recently introduced stent is low profile visualized intraluminal support (LVIS) stent. Due to its low profile nature it can be used in 0.017-inch inner diameter microcatheter and reach small and complex vessels providing high aneurysmal neck coverage which was not possible through other traditional stent. In addition, its braided design with tantalum strands and radiopaque markers make it more visible during stent placement and post procedure stent evaluation. Despite of many advantages of LVIS stent it is related to high rate of thromboembolic complications and technical complications. Aim of this review paper was to evaluate therapeutic safety, effectiveness and feasibility of LVIS stent in endovascular coil embolization of intracranial aneurysms.

With the coming of artificial intelligence and the era of big data, convolutional neural network (CNN) has become one of the research hotspots in many scientific fields. However, there exist serious edge information loss problems in the information transmission process of CNN. Therefore, in order to suppress the loss of important information during the information transmission process, new methods are proposed which use the singular value decomposition (SVD) algorithm based on the phase space reconstruction to analyze the bearing vibration signal. Singular values are regarded as the features for evaluating the bearing's health condition. Then, the features radiate from the center around to form a spiral matrix as the input of the CNN, which can effectively resist information loss problems during the information delivery process. In order to verify the performance of the proposed methods better than the conventional ones, experiments are carried out. This paper shows that the proposed methods have excellent performances in the field of bearing fault diagnosis.

Stroke is a deadly disease without effective pharmacotherapies, which is due to two major reasons. First, most therapeutics cannot efficiently penetrate the brain. Second, single agent pharmacotherapy may be insufficient and effective treatment of stroke requires targeting multiple complementary targets. Here, we set to develop single component, multifunctional nanoparticles (NPs) for targeted delivery of glyburide to the brain for stroke treatment. Methods: To characterize the brain penetrability, we radiolabeled glyburide, intravenously administered it to stroke- bearing mice, and determined its accumulation in the brain using positron emission tomography-computed tomography (PET/CT). To identify functional nanomaterials to improve drug delivery to the brain, we developed a chemical extraction approach and tested it for isolation of nanomaterials from E. ulmoides, a medicinal herb. To assess the therapeutic benefits, we synthesized glyburide-loaded NPs and evaluated them in stroke- bearing mice. Results: We found that glyburide has a limited ability to penetrate the ischemic brain. We identified betulinic acid (BA) capable of forming NPs, which, after intravenous administration, efficiently penetrate the brain and significantly reduce ischemia-induced infarction as an antioxidant agent. We demonstrated that BA NPs enhance delivery of glyburide, leading to therapeutic benefits significantly greater than those achieved by either glyburide or BA NPs. Conclusion: This study suggests a new direction to identify functional nanomaterials and a simple approach to achieving anti-edema and antioxidant combination therapy. The resulting glyburide- loaded BA NPs may be translated into clinical applications to improve clinical management of stroke.

With the rapid development of wireless mobile communication, local content sharing has become the emerging demand for users who are geographically close. Device-to-device (D2D) communication allows two users to communicate directly with each other. In order to achieve more effective content distribution and content spread by allocating better spectrum resources to users with better social networking and content diffusion capabilities, we propose an optimization scheme for resource allocation of the D2D communication by utilizing the potential social relations that are embedded in the communication devices. The degree of intimacy between users is abstracted from the call records to quantify social-relation strengths. Considering the time-varying property of social relations, the auto-regressive integrated moving average model is applied to map the call records into time sequence to predict users’ social relations. Besides, instead of individual utility or the overall network utility, each user aims to maximize its social-community utility which takes other social related D2D users into consideration. Potential game is utilized to solve the social-community utility maximization problem of resource allocation for the D2D communication due to its outstanding mapping nature and always has the Nash equilibrium. Finally, a social-aware distributed resource allocation algorithm is proposed, and the algorithm achieves convergence and stability. Numerical results show that our proposed scheme increases the overall utility over 30% compared with coalition game scheme, and over 50% compared with random selection scheme without loss of the fairness.

We aimed to validate the performance of the hepatitis B-based Hong Kong Liver Cancer (HKLC) staging system compared with the Barcelona Clinic Liver Cancer (BCLC) staging system in Chinese hepatocellular carcinoma (HCC) patients treated with conventional transarterial chemoembolization (TACE) as the initial treatment. The study was approved by the Institutional Review Boards at all participating centers. This retrospective study included 715 patients with HCC who underwent TACE as the initial treatment between January 2008 and December 2016 at three Chinese institutions. All of the patients calculated HCC stage using 5-substage HKLC (HKLC-5), 9-substage HKLC (HKLC-9), and the BCLC system. Based on overall survival (OS), these three staging systems’ performance on treatment outcome prediction were compared using C statistic, Akaike information criterion (AIC), area under the receiver operating characteristic curve (AUC), linear trend Chi-square, likelihood ratio Chi-square, and calibration plots, respectively. The median OS was 10.1 months. Compared with the BCLC system, the HKLC system, especially HKLC-9, showed better performance on survival prediction (HKLC-9: C = 0.689, AIC = 6646.162; HKLC-5: C = 0.683, AIC = 6662.663; BCLC: C = 0.680, AIC = 6654.146), homogeneity (likelihood ratio Chi-square: HKLC-9 = 232.38, HKLC-5 = 215.87, and BCLC = 224.39, P

BACKGROUND Angiopoietin-like 4 (ANGPTL4) is neuroprotective when administered acutely for the treatment of cerebral ischemia. The aim of the present study was to evaluate the preventive effects of ANGPTL4 on the formation of brain edema and to determine whether it promotes the recovery of neurological function following intracerebral hemorrhage (ICH). MATERIAL AND METHODS Recombinant human ANGPTL4 (rhANGPTL4; 40 µg/kg) or a vehicle was administered intraperitoneally 5 min prior to bacterial collagenase-induced ICH in male C57/B6J mice. Behavioral tests were performed prior to ICH and at days 1, 3, 7, 14, 21, and 28 after ICH. Brain edema and hematoma volume were examined separately using the wet weight/dry weight method and hematoxylin-eosin staining. The integrity of the tight and adherens junctions was quantified via immunofluorescence. The ultrastructure of the blood-brain barrier (BBB) was examined using transmission electron microscopy. Vascular endothelial (VE)-cadherin, claudin-5, Src, and phospho-Src in the ipsilateral and contralateral striatum were detected by Western blot analysis. RESULTS RhANGPTL4 reduced brain edema and hematoma volume and improved neurological functional recovery over the subsequent 4 weeks when compared with the control group. rhANGPTL4 significantly increased VE-cadherin and claudin-5-positive areas and relative amounts in the peri‑hematoma region compared with the control group. In addition, ANGPTL4 significantly reduced the ratio of phospho-Src to Src. The significant reduction of Src kinase activity in the peri‑hematoma region of ANGPTL-treated mice was paralleled by a decrease in vascular permeability and edema formation. CONCLUSIONS These results suggest that ANGPTL4 is a relevant target for vasculoprotection and cerebral protection during stroke.

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a recently defined autoimmune meningoencephalomyelitis, associated with GFAP-IgG antibody. A pooled analysis of 324 cases from published literature and a retrospective single-center study were performed, firstly reveals the possibility that patients with myelitic lesions respond better to initial immunotherapy, but are prone to relapse, suggesting a more aggressive and long-term immunosuppressive medication for them. Moreover, our results showed using tacrolimus at maintenance stage exhibited a less tendency to relapse, providing a possibly new choice to future clinical treatments.

BACKGROUND The risk factors for lymph node skip metastasis (LNSM) have not been thoroughly clarified in patients with advanced colorectal cancer (CRC). This study aimed to identify the risk factors for LNSM in CRC patients who underwent laparoscopic radical resection with D3 lymphadenectomy. METHODS This retrospective cohort study included a total of 167 consecutive patients who underwent laparoscopic radical resection with D3 lymphadenectomy for CRC between April 2005 and June 2017. The patients were sorted into the LNSM-positive (skip+ group) and LNSM-negative (skip- group) groups. Logistic regression was used to identify the risk factors for LNSM. RESULTS Compared with the skip- group, the frequency of tumour size

The aim of this study is to investigate the effects of a nitric oxide (NO) donor S-nitrosoglutathione (GSNO) on the metabolism and improvement of preservation quality in apheresis platelets. A GSNO solution with a certain concentration was added into fresh apheresis platelets, and the parameters associated with platelet morphology, metabolism and function were temporally monitored for 7 days. The results showed that the NO level in GSNO group were remarkably higher than those in the control group during the whole storage stage. No significant morphology or function difference was observed between the control and GSNO groups such as Platelet count, platelet distribution width, mean platelet volume and mitochondrial metabolic activity. But in metabolism there are something differences from morphology data: pCO2, pO2, cHCO3 − were also found to have no clear difference between the control and GSNO groups; the lactic acid content, sugar consumption and Lactate dehydrogenase activity in the GSNO group were lower than that in the control group at some time point; and pH values in the GSNO group were higher than the control group. Our study discovered that the NO donor GSNO can reduce the metabolism and maintain the cellular characteristics of platelets in vitro during the platelet storage period.

Background: Transarterial chemoembolization (TACE) may not be repeated “on-demand” timely for hepatocellular carcinoma (HCC) patients in the era of the novel coronavirus disease (COVID-19). We aim to evaluate the impact of the COVID-19 pandemic on the intervals and outcomes of TACE in HCC patients. Methods: This retrospective study included HCC patients who underwent TACE from Jan 1, 2020 to March 31, 2020 (study group) and Jan 1, 2019 to Mar 31, 2019 (control group) at two institutions in China. The endpoints included the TACE interval and the overall response rate (ORR). Uni- and multivariate logistic analyses were performed to identify independent risk factors associated with a worse ORR. The cut-off point was determined to divide repeated TACE time into long- and short- intervals. Findings: 154 patients (71 in the study group, 83 in the control group) were enrolled. The median TACE interval in the study group was 82·0 days (IQR, 61–109), longer than 66·0 days (IQR, 51–94) in the control group (p=0·004). The ORR was 23·9% in the study group, while 39·8% in the control group (p=0·037). The cut-off value was 95 days. The group (OR, 2·402; 95% CI, 1·040–5·546; p=0·040), the long interval (OR, 2·573; 95% CI, 1·022–6·478; p=0·045), and the stage system (OR, 2·500; 95% CI, 1·797–3·480; p

Edge caching can improve the efficiency of content delivery by making full use of the limited storage capacity. Exploiting cooperation between base stations (BSs) could promote the diversity of contents in the whole network and alleviate backhaul traffic. However, prior works mostly overlook the effect of cooperation during caching placement period. In this paper, firstly we propose a local content cloud cooperation scheme to utilize the cache capacity of adjacent BSs. Considering the impact of the capacity of cooperative link and backhaul link, then we formulate an optimizing problem to minimize the average consumption, which consists of content downloading delay and transmission cost. To reduce the complexity and the expenditure of information exchange, we solve the NP-hard problem by the belief propagation method. Meanwhile, simulation shows that the proposed cooperation-based caching placement decreases the average consumption and enhance the hit ratio compared with other strategies.

Background Gingival metastasis from primary hepatocellular cancer (HCC) is rare, highly malignant, and generally has no distinct symptoms. Not performing a biopsy can lead to misdiagnosis. This article reports an 87-year-old male with gingival metastasis from HCC. To gain a better insight into this disease, we also conducted a literature review of 30 cases and discussed the clinical and pathological characteristics, diagnosis, treatment and prognosis of this unusual form of liver cancer. Case presentation An 87-year-old man was hospitalized with a chief complaint of chronic constipation and diffuse lower extremity edema. His past medical history included a three-year hepatitis B infection and a cerebral infarction 17 years prior. Imaging examination detected a massive hepatocellular carcinoma in the right liver lobe and multiple metastases in the lungs. Oral examinations revealed a reddish, cherry-sized exophytic mass on the right upper gum. The mass was tentatively diagnosed as a primary gingival tumor and was ultimately confirmed by biopsy as a metastatic carcinoma originating in the liver. The patient decided, with his guardians, to receive palliative care and not to remove the mass. Unfortunately, the patient accidentally bit the mass open; profuse bleeding ensued and local pressure exerted a poor hemostatic effect. The patient’s condition worsened, and he eventually died of multiple organ failure. We also performed a literature review and discussed 30 cases of gingival metastases from HCC. The findings indicated that these lesions affected males more than females, with a ratio of 6:1, and infiltrated the upper gingivae (63.1%) more than the lower gingivae (36.7%). Survival analysis indicated that the overall survival for patients with upper gingival metastasis was worse than for those with lower gingival metastasis, and patients receiving treatments for primary liver cancer or metastatic gingival tumors had better overall or truncated survival times. Conclusion Gingival metastasis from primary hepatocellular carcinoma is rare, and its diagnosis has presented challenges to clinicians. To avoid a potential misdiagnosis, a biopsy is mandatory regardless of whether a primary cancer is located. Early diagnosis and treatment for primary liver cancer or metastatic gingival lesions may improve survival expectations.

Breast cancers (BCs) with expression of estrogen receptor-alpha (ERα) occur in more than 70% of newly-diagnosed patients in the U.S. Endocrine therapy with antiestrogens or aromatase inhibitors is an important intervention for BCs that express ERα, and it remains one of the most effective targeted treatment strategies. However, a substantial proportion of patients with localized disease, and essentially all patients with metastatic BC, become resistant to current endocrine therapies. ERα is present in most resistant BCs, and in many of these its activity continues to regulate BC growth. Fulvestrant represents one class of ERα antagonists termed selective ER downregulators (SERDs). Treatment with fulvestrant causes ERα down-regulation, an event that helps overcome several resistance mechanisms. Unfortunately, full antitumor efficacy of fulvestrant is limited by its poor bioavailability in clinic. We have designed and tested a new generation of steroid-like SERDs. Using ERα-positive BC cells in vitro, we find that these compounds suppress ERα protein levels with efficacy similar to fulvestrant. Moreover, these new SERDs markedly inhibit ERα-positive BC cell transcription and proliferation in vitro even in the presence of estradiol-17β. In vivo, the SERD termed JD128 significantly inhibited tumor growth in MCF-7 xenograft models in a dose-dependent manner (P

Aims To assess the safety and efficacy of parenchymal‐sparing hepatectomy (PSH) as a treatment of colorectal liver metastases (CLM). Methods A comprehensive medical literature search was performed. Perioperative and long‐term survival outcomes were pooled. Subgroup analysis and meta‐regression analysis were performed to identify potential sources of heterogeneity. Results A total of 18 studies comprising 7081 CLM patients were eligible for this study. The PSH was performed on 3974 (56.1%) patients. We found that the OS (overall survival; hazard ratio [HR] = 1.01, 95% confidence interval [CI]: 0.94‐1.08) and RFS (recurrence‐free survival; HR = 1.00, 95% CI: 0.94‐1.07) were comparable between non‐PSH and PSH group. The perioperative outcomes were better in PSH than in non‐PSH group. Non‐PSH group was significantly associated with longer operative time (standard mean difference [SMD] = 1.17, 95% CI: 0.33‐2.00), increased estimated blood loss (SMD = 1.36, 95% CI: 0.64‐2.07), higher intraoperative transfusion rate (risk ratio [RR] = 2.27, 95% CI: 1.60‐3.23), and more postoperative complications (RR = 1.39, 95% CI: 1.16‐1.66). Meta‐regression analyses revealed that no variable influenced the association between surgical types and the survival outcomes. Conclusions This study shows that PSH is associated with better perioperative outcomes without compromising oncological outcomes. Given the increasing incidence of hepatic parenchyma, the PSH treatment offers a greater opportunity of repeat resection for intrahepatic recurrent tumors. It should be considered as an effective surgical approach for CLM., The present study pooled outcomes of 18 studies to evaluate the safety and effectiveness of parenchymal‐sparing hepatectomy (PSH) for treating colorectal liver metastases (CLM). PSH is associated with potential better perioperative outcomes without compromising oncological outcomes. More future hepatic parenchymal will be preserved in the surgical process of PSH, it offers a greater opportunity of repeat resection for intrahepatic recurrent tumors. The PSH brings the treatment of CLM into personalized precision medicine era.

Photon-counting detector (PCD) can identify absorption features in the multiple ranges of photon energies, which has a great potential in material discrimination. In this paper, we focused on in vivo dual-energy CT imaging to characterize different biomedical compositions. The precision of material decomposition in post-reconstruction space depends on the quality of reconstructed CT images; we used the locally linear embedding (LLE) based online geometric calibration method and GPU-based reconstruction toolbox to reconstruct high-quality CT images. Then, we performed the real experiment and studied materials decomposition with basis material model to discriminate soft tissue and cortical bone of small animal. Finally, the experimental results demonstrated that the proposed method could reconstruct small animal CT images with more slim structures and details, and improve the precision of materials decomposition in dual-energy CT imaging.

Background Spontaneous thrombosis of an intracranial aneurysm is rare but is common in fusiform or large cystic aneurysms, which result in subarachnoid hemorrhage after rupture. This case reports a 47-year-old woman with subarachnoid hemorrhage who developed spontaneous thrombosis of an aneurysm due to rupture of the posterior inferior cerebellar aneurysm. Case Description The patient was admitted to the hospital with history of sudden headache and vomiting for 3 days. According to early imaging findings, she was initially diagnosed as having a cavernous hemangioma with hemorrhage in the left cerebellum, but according to the intraoperative pictures and postoperative pathologic results, the diagnosis was an aneurysm with thrombosis. Conclusions This case represents a rare but important complication of ruptured intracranial aneurysm, which can be easily misdiagnosed or ignored. It should be given great attention and considered in patients with subarachnoid hemorrhage who are negative for imaging examinations.