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Background and Purpose: Intraluminal thrombus (ILT) is an emerging imaging marker in acute ischemic stroke. We aimed to investigate the association of ILT with outcomes of acute large vessel occlusion (LVO) patients receiving endovascular treatment. Methods: Acute LVO stroke patients who underwent endovascular treatment within 24 hours, in a prospective, nationwide registry were enrolled. Pretreatment digital subtraction angiography was reviewed for the presence of ILT. The primary outcome was 90-day functional dependence (modified Rankin Scale scores, 3–6). Secondary outcomes included 24-hour LVO, 90-day death, and symptomatic intracranial hemorrhage. Results: Among 711 patients enrolled, 75 (10.5%) with ILT were less likely to have 90-day functional dependence compared with those without ILT (adjusted odds ratio, 0.53 [95% CI, 0.31–0.90]; P =0.021). The same trend was found among those with successful reperfusion (modified Thrombolysis in Cerebral Infarction 2b–3; P =0.008) but not in those without successful reperfusion ( P =0.107). Presence of ILT was also independently associated with a lower rate of 24-hour LVO (adjusted odds ratio 0.34 [95% CI, 0.13–0.89]; P =0.028). However, those with or without ILT had similar risks of symptomatic intracranial hemorrhage and 90-day death. Conclusions: Among acute LVO patients receiving endovascular treatment, pretreatment ILT-positive patients may have a better 90-day functional outcome (versus ILT-negative) but similar risk of death and symptomatic intracranial hemorrhage. The possibly favorable effect of ILT patients remained in those with successful reperfusion. Registration: URL: http://www.chictr.org.cn ; Unique identifier: ChiCTR1900022154.

Background and purposeCurrent randomised controlled trials (RCTs) showed an uncertain benefit of haemostatic therapy on preventing haematoma expansion and improving the outcome in patients with intracerebral haemorrhage (ICH). This meta-analysis aims to systematically evaluate the effect of haemostatic agents on the prevention of haemorrhage growth in patients with high-risk spontaneous ICH predicted by CT signs in RCTs.MethodsA comprehensive search of PubMed, EMBASE and Cochrane library from 1 January 2005 to 30 June 2021 was conducted. RCTs that compared haemostatic agents with placebo for the treatment of spontaneous patients with ICH with high-risk haemorrhage growth were included. The primary endpoint was haematoma expansion at 24 hours. Other major endpoints of interest included 90-day functional outcome and mortality.ResultsThe meta-analysis included four RCTs that randomised 2666 patients with ICH with high-risk haemorrhage growth. Haemostatic therapy reduced the rate of haematoma expansion at a marginally statistically significant level when compared with placebo (OR 0.84; 95% CI 0.70 to 1.00; p=0.051). Subgroup analysis for patients with black hole sign on CT revealed a significant reduction of haematoma expansion with haemostatic therapy (OR 0.61; 95% CI 0.39 to 0.94; p=0.03). However, both the primary analysis and subgroup analyses showed that haemostatic therapy could not reduce the rate of poor functional outcome (modified Rankin Scale >3) or death.ConclusionsHaemostatic therapy showed a marginally significant benefit in reducing early haematoma expansion in patients with high-risk spontaneous ICH predicted by markers on CT scan. However, no significant improvement in functional outcome or reduction of mortality was observed.

Background and Purpose: We aimed to evaluate the impact of cortical microinfarcts (CMIs) on functional outcome after endovascular treatment in patients with acute ischemic stroke. Methods: In a multicenter registration study for RESCUE-RE (a registration study for Critical Care of Acute Ischemic Stroke After Recanalization), eligible patients with large vessel occlusion stroke receiving endovascular treatment, who had undergone 3T magnetic resonance imaging on admission or within 24 hours after endovascular treatment were analyzed. We evaluated the presence and numbers of CMIs with assessment of axial T1, T2-weighted images, and fluid-attenuated inversion recovery images. The primary outcome was functional dependence or death defined as modified Rankin Scale scores of 3 to 6 at 90 days. Secondary outcomes included early neurological improvement, any intracranial hemorrhage, symptomatic intracranial hemorrhage, and mortality. We investigated the independent associations of CMIs with the outcomes using multivariable logistic regression in overall patients and in subgroups. Results: Among 414 patients (enrolled from July 2018 to May 2019) included in the analyses, 96 (23.2%) patients had at least one CMI (maximum 6). Patients with CMI(s) were more likely to be functionally dependent or dead at 90 days, compared with those without (55.2% versus 37.4%; P P =0.04) and multiple CMIs (CMIs ≥2; adjusted odds ratio, 7.41 [95% CI, 2.48−22.17]; P Conclusions: Acute large vessel occlusion stroke patients receiving endovascular treatment with CMI(s) were more likely to have a poor functional outcome at 90 days, independent of patients’ characteristics. Such associations may be dose-dependent. Registration: URL: http://www.chictr.org.cn ; Unique identifier: ChiCTR1900022154.

Cancer cells acquire genetic heterogeneity to escape from immune surveillance during tumor evolution, but a systematic approach to distinguish driver from passenger mutations is lacking. Here we investigate the impact of different immune pressure on tumor clonal dynamics and immune evasion mechanism, by combining massive parallel sequencing of immune edited tumors and CRISPR library screens in syngeneic mouse tumor model and co-culture system. We find that the core microRNA (miRNA) biogenesis and targeting machinery maintains the sensitivity of cancer cells to PD-1-independent T cell-mediated cytotoxicity. Genetic inactivation of the machinery or re-introduction of ANKRD52 frequent patient mutations dampens the JAK-STAT-interferon-γ signaling and antigen presentation in cancer cells, largely by abolishing miR-155-targeted silencing of suppressor of cytokine signaling 1 (SOCS1). Expression of each miRNA machinery component strongly correlates with intratumoral T cell infiltration in nearly all human cancer types. Our data indicate that the evolutionarily conserved miRNA pathway can be exploited by cancer cells to escape from T cell-mediated elimination and immunotherapy., Dysregulation of the microRNA machinery has crucial roles in cancer development. Here the authors show that inactivation of proteins involved in microRNA-mediated gene silencing, such as ANKRD52 or AGO2, confers resistance to T cell-mediated immune response in a preclinical cancer model.

BackgroundThis study aimed to assess the prognostic value of various diagnostic immunohistochemical (IHC) markers and develop an IHC-based classifier to predict the disease-free survival (DFS) of patients with bladder cancer undergoing radical cystectomy.MethodsIHC was performed on tumor specimens from 366 patients with transitional cell bladder cancer. The least absolute shrinkage and selection operator (LASSO) Cox regression model was used to develop a multi-marker classifier for predicting DFS of patients with bladder cancer. The Kaplan–Meier estimate was performed to assess DFS, and unadjusted and adjusted Cox regression models were used to identify independent risk factors to predict DFS of patients with bladder cancer.ResultsBased on the LASSO Cox regression model, nine prognostic markers were identified in the training cohort. Patients were stratified into low- and high-risk groups using the IHC-based classifier. In the training cohort, the 10-year DFS was significantly better in low-risk patients (71%) compared with high-risk patients (18%) (p < 0.001); in the validation cohort, the 10-year DFS was 86% for the low-risk group and 20% for the high-risk group (p < 0.001). Multivariable Cox regression analyses showed that the high-risk group based on the classifier was associated with poorer DFS adjusted by clinicopathological characteristics. Finally, a nomogram comprising the classifier and clinicopathological factors was developed for clinical application.ConclusionThe nine-IHC-based classifier is a reliable prognostic tool, which can eventually guide clinical decision making regarding treatment strategy and follow-up scheduling of bladder cancer.

Background To investigate whether collateral status could modify the associations between post‐thrombectomy blood pressure (BP) measures and outcomes. Methods and Results Patients with anterior‐circulation large‐vessel‐occlusion successfully recanalized in a multicenter endovascular thrombectomy registry were enrolled. Pretreatment collateral status was graded and dichotomized (good/poor) in angiography. Maximum, minimum, and mean systolic BP (SBP) and BP variability (assessed by the SD, coefficient of variation) during the initial 24 hours after endovascular thrombectomy were obtained. The primary outcome was unfavorable 90‐day outcome (modified Rankin Scale score 3–6). Secondary outcomes included symptomatic intracranial hemorrhage and 90‐day mortality. Adjusted odds ratios (aOR) of BP parameters over the outcomes were obtained in all patients and in patients with good/poor collaterals. Among 596 patients (mean age 66 years; 59.9% males), 302 (50.7%) patients had unfavorable 90‐day outcome. In multivariable analyses, higher mean SBP (aOR, 1.59 per 10 mm Hg increment; 95% CI, 1.26–2.02; P 140 mm Hg (versus ≤120 mm Hg; aOR, 4.27; 95% CI, 1.66–10.97; P =0.002), and higher SBP SD (aOR, 1.08 per 1‐SD increment; 95% CI, 1.01–1.16; P =0.02) were respectively associated with unfavorable 90‐day outcome in patients with poor collateral but not in those with good collateral. A marginal interaction between SBP coefficient of variation tertiles and collaterals on 90‐day functional outcome ( P for interaction, 0.09) was observed. A significant interaction between SBP coefficient of variation tertiles and collaterals on 90‐day mortality ( P for interaction, 0.03) was observed. Conclusions Higher postprocedural BP is associated with 90‐day unfavorable outcomes after successful endovascular thrombectomy in patients with poor collateral. Registration URL: https://www.chictr.org.cn ; Unique identifier: ChiCTR1900022154.

Objectives: This study aims to investigate whether the machine learning algorithms could provide an optimal early mortality prediction method compared with other scoring systems for patients with cerebral hemorrhage in intensive care units in clinical practice.Methods: Between 2008 and 2012, from Intensive Care III (MIMIC-III) database, all cerebral hemorrhage patients monitored with the MetaVision system and admitted to intensive care units were enrolled in this study. The calibration, discrimination, and risk classification of predicted hospital mortality based on machine learning algorithms were assessed. The primary outcome was hospital mortality. Model performance was assessed with accuracy and receiver operating characteristic curve analysis.Results: Of 760 cerebral hemorrhage patients enrolled from MIMIC database [mean age, 68.2 years (SD, ±15.5)], 383 (50.4%) patients died in hospital, and 377 (49.6%) patients survived. The area under the receiver operating characteristic curve (AUC) of six machine learning algorithms was 0.600 (nearest neighbors), 0.617 (decision tree), 0.655 (neural net), 0.671(AdaBoost), 0.819 (random forest), and 0.725 (gcForest). The AUC was 0.423 for Acute Physiology and Chronic Health Evaluation II score. The random forest had the highest specificity and accuracy, as well as the greatest AUC, showing the best ability to predict in-hospital mortality.Conclusions: Compared with conventional scoring system and the other five machine learning algorithms in this study, random forest algorithm had better performance in predicting in-hospital mortality for cerebral hemorrhage patients in intensive care units, and thus further research should be conducted on random forest algorithm.

A total of two postpartum women with no noteworthy medical history presented with persistent headache. Brain magnetic resonance imaging (MRI) of both revealed extensive cerebral venous thrombosis, concurrently with abnormal signals of the splenium of the corpus callosum (SCC): The splenium appeared hyperintense on T2-weighted sequences, fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging (DWI) imaging, and hypointense on T1 sequences and apparent diffusion coefficient (ADC) map. The patients were given thrombolytic therapy. Clinically, both patients achieved recovery with no neurologic sequelae, and follow-up MRI revealed complete resolution of the lesion in the SCC at day 36 and day 37 after initial presentation, respectively.

Early diagnosis and treatment for cancer is a key to reduce the mortality of cancer. Based on confocal back scatter micro-spectroscopic system, micro-spectra of normal stomach epithelial cells and cancerous cells were collected. In order to discriminate the two types of cells, the micro-spectra of cells were analyzed with principal component analysis in which the first two scores of the principal components were utilized. The results showed this method could clearly distinguish the confocal back scattering micro-spectra of the normal stomach epithelial cells and cancerous cells. This might provide a new method for early diagnosis of stomach cancer, which is fast, accurate and low-cost at single-cell scale.

Research has identified that epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) possess large benefits for adenocarcinoma (ADC), although little benefit for squamous cell carcinoma (SCC). The aim of the present study was to investigate the percentage of patients with SCC with the EGFR mutations subset and the benefits of EGFR TKIs in SCC. In the present study, the EGFR mutations subset was detected with an amplification refractory mutation system in 1,359 clinical SCC tissues. The association of the EGFR mutations subset with clinicopathological parameters was evaluated using the Mann-Whitney U test, and Kruskal-Wallis H. Kaplan-Meier survival analysis was used to estimate the effect of the EGFR mutations subset on SCC patient survival rates. A total of 94 out of 1,359 SCC patients were identified as having EGFR mutations, an EGFR mutation rate of 6.92%. The EGFR mutations subset in the 94 cases was identified as follows: 37.2% (35/94) in exon 19; 39.4% (37/94) in L858R; 5.3% (5/94) in T790M; 4.3% (4/94) in G719X; 2.1% (2/94) in L861Q; and 11.7% (11/94) in other mutations. Kaplan-Meier survival analysis identified that the differentiation, pathological tumor, node, metastasis stage, lymph node metastasis and distant metastases were significantly associated with patients' survival (P>0.05; log-rank test), and no significant difference was observed between TKI therapy and chemotherapy in terms of patient survival rates (P>0.05). In addition, the overall discordant rate of the EGFR mutations subset in SCC patients was relatively low. Due to the non-significant difference between TKI therapy and chemotherapy in terms of patient survival and the lower discordance rate of the EGFR mutations subset in SCC patients, EGFR TKIs could be a recommended treatment for SCC.

Elucidating mechanisms of natural organofluorine biosynthesis is essential for a basic understanding of fluorine biochemistry in living systems as well as for expanding biological methods for fluorine incorporation into probe or therapeutic molecules. To meet this goal we have combined massively parallel sequencing technologies, genetic knockout, and in vitro biochemical approaches to investigate the fluoride response of the only known genetic host of an organofluorine producing pathway, Streptomyces cattleya. Interestingly, we have discovered that the major mode of S. cattleya’s resistance to the fluorinated toxin it produces, fluoroacetate, may be due to temporal control of production rather than the ability of the host’s metabolic machinery to discriminate between fluorinated and non–fluorinated molecules. Indeed, neither the acetate kinase/phosphotransacetylase acetate assimilation pathway nor the TCA cycle enzymes (citrate synthase and aconitase) exclude fluorinated substrates based on in vitro biochemical characterization. Furthermore, disruption of the fluoroacetate resistance gene encoding a fluoroacetyl–CoA thioesterase (FlK) does not appear to lead to an observable growth defect related to organofluorine production. By showing that a switch in central metabolism can mediate and control molecular fluorine incorporation, our findings reveal a new potential strategy toward diversifying simple fluorinated building blocks into more complex products.

SUMMARY Aims: To analyze and compare the value of different treatment methods for acute aneurysmal subarachnoid hemorrhage (aSAH)-related vasospasm. Cerebral hemodynamic variables’ changes were evaluated by transcranial Doppler (TCD) in aSAH patients within 14 days after onset. Methods: Thirty aSAH patients were enrolled in the study within 72 h after onset. Baseline CT and TCD were used for assessment. Patients were divided into three groups according to SAH severity and patients’ discretion: nonsurgical group, endovascular coiling, and neurosurgical clipping. TCD hemodynamic parameters were measured and Lindegaard index was calculated daily from onset to 14th day after SAH. The group mean cerebral blood velocity (MBFV) and Lindegaard index were compared using repeated measures analysis of variance (reANOVA). Least Significant Difference (LSD) test was used for post hoc comparison. All 30 patients were followed for 90 days after onset for outcome assessment. Results: The values of MBFV and Lindegaard index of anterior cerebral artery (ACA)/middle cerebral artery (MCA) from high to low is nonsurgical group, clipping and coiling (ACA: P= 0.0001/P= 0.006; MCA: P= 0.243/P= 0.317). Conclusions: These results indicate that both neurosurgical clipping and endovascular coiling management may relieve the severity of cerebral vasospasm in acute aSAH.

lin s.-c., tsai k.-w., chen m.-w. & koo m. (2012) Association between fatigue and Internet addiction in female hospital nurses. Journal of Advanced Nursing69(2), 374–383. doi: 10.1111/j.1365-2648.2012.06016.x Abstract Aims. To report a study conducted to examine the association between fatigue and Internet addiction among female hospital nurses. Background. The Internet provides unprecedented convenience for social interaction and information retrieval. Although excessive Internet use has been demonstrated to correlate with fatigue in adolescents, no studies have examined whether it is associated with fatigue in nurses. Design. Cross-sectional survey. Methods. The study was conducted in August 2010. Female Registered Nurses working in a regional teaching hospital in southern Taiwan were asked to complete a paper-based questionnaire. The questionnaire included questions on demographics, the Chen Internet Addiction Scale and the Chalder Fatigue Scale. Multiple linear regression analysis was performed using Chalder fatigue scale as the dependent variable. Results. Of the 564 (79% response) valid questionnaires returned, 6 and 10% of the participants were classified as diagnostic cases and possible cases of Internet addiction, respectively. Fatigue levels, adjusting for other potential confounders including work unit, shift work, regular self-medication, and self-perceived health status, was significantly associated with both possible cases of Internet addiction and diagnostic cases of Internet addiction. Conclusion. This study is the first in reporting a statistically significant association between fatigue levels and Internet addiction in female hospital nurses. Relevance to clinical practice. Nurses should pay attention to their Internet activity and whether it adds to their fatigue levels. Addictive behaviour should promptly be dealt with to ensure that the best care is provided to patients.

OBJECTIVE To investigate the effects of Liangxue Tongyu Formula (LXTYF), a compound traditional Chinese herbal medicine, on brain edema in rats with intracerebral hemorrhage and to explore the mechanism. METHODS Intracerebral hemorrhage was induced by using the intrastriatal autologous blood injection. Rats were randomized into sham-operated (SO) group, intracerebral hemorrhage (ICH) group and LXTYF group. Rats in the LXTYF group were intragastrically administered with LXTYF every day while the other two groups were given normal saline. Brain water content was determined at 24, 48, 72, and 120 h after intracerebral hemorrhage. Matrix metalloproteinase-9 (MMP-9) level, and MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA expressions in perihematoma area were detected by gelatin zymography and fluorescence quantitative real-time polymerase chain reaction at the four time points, respectively. RESULTS Water content in the ICH group was highly elevated after intracerebral hemorrhage, and reached to the peak at 72 h. Compared with the ICH group, the LXTYF group had lower water contents at 48, 72 and 120 h after intracerebral hemorrhage (P

Objectives: Self-report is considered the gold standard of pain measurement. Physiological measures are valuable in situations where self-report measures are more difficult to administer. This investigation assesses pain intensity in patients with musculoskeletal pain before and after the first session of physical therapy by evaluating the visual analog scale [VAS] and verbal rating scale [VRS] and analyzing the heart rate variability [HRV], and examines their relationships.Methods: A short-term electrocardiogram signal, VAS, and VRS of patients experiencing musculoskeletal pain were gathered before and after physical therapy and HRV was analyzed. The normal-to-normal [NN] intervals were obtained from electrocardiogram via Tompkins algorithm, followed by time-domain analyses. Additionally, the power spectrum density was determined via Fast Fourier Transform and frequency-domain analyses were conducted. Differences in each parameter before and after physical therapy were studied with paired t-test or Wilco...

In traditional oriental medicine, Yin-Chen-Hao decoction is used for the remedy of liver diseases such as hepatitis, fatty liver, hepatocirrhosis and jaundice. However, despite extensive pharmacological study, the molecular mechanism of the anti-inflammatory effect of Yin-Chen-Hao decoction is poorly understood. In this study, we have investigated the pharmacological action on the mechanism of concanavalin A-induced T cell-dependent hepatitis in mice. Concanavalin A administration resulted in a severe liver injury. This was shown through increased levels of serum transaminase and lactic dehydrogenase, and increased liver DNA fragmentation and caspase-3 activity. Pretreatment with the aqueous extract from Yin-Chen-Hao decoction dose-dependently inhibited the elevation in transaminase and lactic dehydrogenase activity, and reduced liver DNA fragmentation and caspase-3 levels. There was an improvement in histological changes including inflammatory infiltration, hepatocyte necrosis and degeneration, and Kupffer cell hyperplasia. In addition, Yin-Chen-Hao decoction significantly inhibited tumour necrosis factor-α (TNF-α) production in-vitro and in-vivo. Moreover, the activation of nuclear factor kappa B (NF-kB), which regulates TNF-α production, was blocked by Yin-Chen-Hao decoction in-vitro and in-vivo. In conclusion, Yin-Chen-Hao decoction was capable of regulating T-cell-mediated liver injury in-vivo. This event may have depended on the decrease of TNF-α production through the inhibition of NF-kB activation.

This paper describes the diagnostic techniques and experimental methods used for investigating the properties of implosion compression in direct drive . Several diagnostic techniques with fine time, space and spectrum resolution are employed to obtain the information concerning implosion, such as radiation un iformity on the capsule, compression symmetry, volume compression ratio, implosi on time, implosion velocity and average electron temperature of the capsule shell. Some of the typical results measured in the experiments are presented and as imple discussion is also given.

BackgroundStudies show tranexamic acid can reduce the risk of death and early neurological deterioration after intracranial haemorrhage. We aimed to assess whether tranexamic acid reduces haematoma expansion and improves outcome in intracerebral haemorrhage patients susceptible to haemorrhage expansion.MethodsWe did a prospective, double-blind, randomised, placebo-controlled trial at 10 stroke centres in China. Acute supratentorial intracerebral haemorrhage patients were eligible if they had indication of haemorrhage expansion on admission imaging (eg, spot sign, black hole sign or blend sign), and were treatable within 8 hours of symptom onset. Patients were randomly assigned (1:1) to receive either tranexamic acid or a matching placebo. The primary outcome was intracerebral haematoma growth (>33% relative or >6 mL absolute) at 24 hours. Clinical outcomes were assessed at 90 days.ResultsOf the 171 included patients, 124 (72.5%) were male, and the mean age was 55.9±11.6 years. 89 patients received tranexamic acid and 82 received placebo. The primary outcome did not differ significantly between the groups: 36 (40.4%) patients in the tranexamic acid group and 34 (41.5%) patients in the placebo group had intracranial haemorrhage growth (OR 0.96, 95% CI 0.52 to 1.77, p=0.89). The proportion of death was lower in the tranexamic acid treatment group than placebo group (8.1% vs 10.0%), but there were no significant differences in secondary outcomes including absolute intracranial haemorrhage growth, death and dependency.ConclusionsAmong patients susceptible to haemorrhage expansion treated within 8 hours of stroke onset, tranexamic acid did not significantly prevent intracerebral haemorrhage growth. Larger studies are needed to assess safety and efficacy of tranexamic acid in intracerebral haemorrhage patients.