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Aging of the vasculature is associated with detrimental changes in vascular smooth muscle cell (VSMC) mechanosensitivity to extrinsic forces in their surrounding microenvironment. However, how chronological aging alters VSMCs' ability to sense and adapt to mechanical perturbations remains unexplored. Here, we show defective VSMC mechanosensation in aging measured with ultrasound tweezers‐based micromechanical system, force instantaneous frequency spectrum, and transcriptome analyses. The study reveals that aged VSMCs adapt to a relatively inert mechanobiological state with altered actin cytoskeletal integrity, resulting in an impairment in their mechanosensitivity and dynamic mechanoresponse to mechanical perturbations. The aging‐associated decline in mechanosensation behaviors is mediated by hyperactivity of Piezo1‐dependent calcium signaling. Inhibition of Piezo1 alleviates vascular aging and partially restores the loss in dynamic contractile properties in aged cells. Altogether, our study reveals the signaling pathway underlying aging‐associated aberrant mechanosensation in VSMC and identifies Piezo1 as a potential therapeutic mechanobiological target to alleviate vascular aging. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to examine the predictive value of the multiplication of neutrophil and monocyte counts (MNM) in peripheral blood, and develop a new predictive model for the prognosis of patients with aneurysmal subarachnoid hemorrhage (aSAH). Methods: This is a retrospective analysis that included 2 separate cohorts of patients undergoing endovascular coiling for aSAH. The training cohort consisted of 687 patients in the First Affiliated Hospital of Shantou University Medical College; the validation cohort consisted of 299 patients from Sun Yat‐sen University's Affiliated Jieyang People's Hospital. The training cohort was used to develop 2 models to predict unfavorable prognosis (modified Rankin scale of 3–6 at 3 months): one was based on traditional factors (e.g., age, modified Fisher grade, NIHSS score, and blood glucose), and another model that included traditional factors as well as MNM on admission. Results: In the training cohort, MNM upon admission was independently associated with unfavorable prognosis (odds ratio after adjustment, 1.06; 95% confidence interval [CI], 1.03–1.10). In the validation cohort, the basic model that included only traditional factors had 70.99% sensitivity, 84.36% specificity, and 0.859 (95% CI, 0.817–0.901) area under the receiver operating characteristic curve (AUC). Adding MNM increased model sensitivity (from 70.99% to 76.48%), specificity (from 84.36% to 88.63%), and overall performance (AUC 0.859 [95% CI, 0.817–0.901] to 0.879 [95% CI, 0.841–0.917]). Interpretation: MNM upon admission is associated with unfavorable prognosis in patients undergoing endovascular embolization for aSAH. The nomogram including MNM is a user‐friendly tool to help clinicians quickly predict the outcome of patients with aSAH. [ABSTRACT FROM AUTHOR]

Objectives: Large hepatocellular carcinoma (LHCC) is prone to short‐term recurrence and poor long‐term survival after hepatectomy, and there is still a lack of effective neoadjuvant treatments to improve recurrence‐free survival (RFS) and overall survival (OS). We retrospectively analyzed the efficacy of preoperative transcatheter arterial chemoembolization (TACE) in solitary LHCC (≥5 cm). Materials and Methods: A multicenter medical database was used to analyze preoperative TACE's effects on RFS, OS, and perioperative complications in patients with solitary LHCC who received surgical treatment from January 2005 to December 2015. The patients were divided into Group A (5.0–9.9 cm) and Group B (≥10 cm), with 10 cm as the critical value, and the effect of preoperative TACE on RFS, OS and perioperative complications was assessed in each subgroup. Results: In the overall population, patients with preoperative TACE had better RFS and OS than those without preoperative TACE. However, after stratifying the patients into the two HCC groups, preoperative TACE only improved the survival outcomes of patients with Group B (≥10 cm). Multivariate Cox‐regression analysis showed that lack of preoperative TACE was an independent risk factor for RFS and OS in the overall population and in Group B but not in Group A. Conclusions: Preoperative TACE is beneficial for patients with solitary HCC (≥10 cm). [ABSTRACT FROM AUTHOR]

As an advanced task for image synthesis without labelled data, unsupervised image‐to‐image translation refers to the overall conversion of a certain characteristic image domain X to another domain Y. The key point is to learn a mapping relationship that can be transformed between different image domains. Existing methods mainly adopt GANs to generate authentic images. While the discriminators will be abandoned after the training process is completed. In order to avoid this waste of training resources, a feature encoder reusing method is proposed, which could reduce the number of parameters and accelerate the training speed. In addition, we add the adaptive perceptual loss for the purpose of paying more attention to the quality of generated images. This loss directly uses the encoder during training to perform feature‐level constraints, and applies the L1‐norm on the intermediate feature layer of the generated samples. The experiments illustrate that our framework can generate more natural images and provide an effective solution for unsupervised translation. [ABSTRACT FROM AUTHOR]

Background and aims: The existing evidence has indicated that hyperthermia ablation (HA) and HA combined with transarterial chemoembolization (HATACE) are the optimal alternative to surgical resection for patients with hepatocellular carcinoma (HCC) in the COVID‐19 crisis. However, the evidence for decision‐making is lacking in terms of comparison between HA and HATACE. Herein, a comprehensive evaluation was performed to compare the efficacy and safety of HATACE with monotherapy. Materials and Methods: Worldwide studies were collected to evaluate the HATACE regimen for HCC due to the practical need for global extrapolation of applicative population. Meta‐analyses were performed using the RevMan 5.3 software (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark). Results: Thirty‐six studies involving a large sample of 5036 patients were included finally. Compared with HA alone, HATACE produced the advantage of 5‐year overall survival (OS) rate (OR:1.90; 95%CI:1.46,2.46; p < 0.05) without increasing toxicity (p ≥ 0.05). Compared with TACE alone, HATACE was associated with superior 5‐year OS rate (OR:3.54; 95%CI:1.96,6.37; p < 0.05) and significantly reduced the incidences of severe liver damage (OR:0.32; 95%CI:0.11,0.96; p < 0.05) and ascites (OR:0.42; 95%CI:0.20,0.88; p < 0.05). Subgroup analysis results of small (≤3 cm) HCC revealed that there were no significant differences between the HATACE group and HA monotherapy group in regard to the OS rates (p ≥ 0.05). Conclusions: Compared with TACE alone, HATACE was more effective and safe for HCC. Compared with HA alone, HATACE was more effective for non‐small‐sized (>3 cm) HCC with comparable safety. However, the survival benefit of adjuvant TACE in HATACE regimen was not found for the patients with small (≤3 cm) HCC. [ABSTRACT FROM AUTHOR]

Background: There is a lack of targeted therapeutic options for squamous cell lung cancer (SCC). Accelerated hypertension is an issue with many targeted therapies for lung cancer. This study aimed to analyze the efficacy of anlotinib, based on progression‐free survival (PFS) and overall survival (OS) in patients with SCC, stratified by hypertension and Eastern Cooperative Oncology Group (ECOG) score. Methods: This was a post hoc analysis of a multicenter, double‐blind, phase III ALTER0303 randomized controlled trial. Only patients with SCC were included. The occurrence of hypertension during the study period was defined according to CTCAE 4.03. OS and PFS were the primary and secondary endpoints, respectively. The patients were stratified according to hypertension and ECOG score, respectively. Results: The median PFS in the patients who developed hypertension was longer than in those who did not (7.2 (95% CI: 3.5–11.0) versus 3.2 (95% CI: 1.2–5.3) months, p = 0.001; HR (95% CI), 0.4 (0.2–0.8)). In the ECOG 0 patients, the median PFS in the patients who developed hypertension versus those who did not was 5.6 vs. 1.8 months, respectively (Figure 2(d)). In the ECOG 1 patients, the median PFS in the patients who developed hypertension versus those who did not was 7.0 (95% CI: 3.0–11.0) vs. 4.8 (95% CI: 1.2–8.5) months (p = 0.043). No statistically significant differences were found in OS in the stratified analyses. Conclusions: The occurrence of hypertension might be a clinical indicator predicting the efficacy of third‐line anlotinib treatment in patients with SCC. [ABSTRACT FROM AUTHOR]

Objective: The neutrophil to lymphocyte ratio (NLR) has been proposed to capture the inflammatory status of patients with various conditions involving the brain. This retrospective study aimed to explore the association between the NLR and the early growth of traumatic intracerebral haemorrhage (tICH) in patients with traumatic brain injury (TBI). Methods: A multicentre, observational cohort study was conducted. Patients with cerebral contusion undergoing baseline computed tomography for haematoma volume analysis within 6 h after primary injury and follow‐up visits within 48 h were included. Routine blood tests were performed upon admission, and early growth of tICH was assessed. Prediction accuracies of the NLR for the early growth of tICH and subsequent surgical intervention in patients were analysed. Results: There were a total of 1077 patients who met the criteria included in the study cohort. Univariate analysis results showed that multiple risk factors were associated with the early growth of tICH and included in the following multivariate analysis models. The multivariate logistic regression analysis results revealed that the NLR was highly associated with the early growth of tICH (p < 0.001) while considering other risk factors in the same model. The prediction accuracy of the NLR for the early growth of tICH in patients is 82%. Interpretation: The NLR is easily calculated and might predict the early growth of tICH for patients suffering from TBI. [ABSTRACT FROM AUTHOR]

Cover legend: The cover image is based on the Research Article Aging‐associated decline in vascular smooth muscle cell mechanosensation is mediated by Piezo1 channel by Ngoc Luu et al., https://doi.org/10.1111/acel.14036.By Ngoc Luu; Apratim Bajpai; Rui Li; Seojin Park; Mahad Noor; Xiao Ma and Weiqiang ChenReported by Author; Author; Author; Author; Author; Author; Author [Extracted from the article]

Chimeric antigen receptor (CAR) T‐cell transfer is a novel paradigm of adoptive T‐cell immunotherapy. When coming into contact with a target cancer cell, CAR T‐cell forms a nonclassical immunological synapse with the cancer cell and dynamically orchestrates multiple critical forces to commit cytotoxic immune function. Such an immunologic process involves a force transmission in the CAR and a spatiotemporal remodeling of cell cytoskeleton to facilitate CAR activation and CAR T‐cell cytotoxic function. Yet, the detailed understanding of such mechanotransduction at the interface between the CAR T‐cell and the target cell, as well as its molecular structure and signaling, remains less defined and is just beginning to emerge. This article summarizes the basic mechanisms and principles of CAR T‐cell mechanoimmunology, and various lessons that can be comparatively learned from interrogation of mechanotransduction at the immunological synapse in normal cytotoxic T‐cell. The recent development and future application of novel bioengineering tools for studying CAR T‐cell mechanoimmunology is also discussed. It is believed that this progress report will shed light on the CAR T‐cell mechanoimmunology and encourage future researches in revealing the less explored yet important mechanosensing and mechanotransductive mechanisms involved in CAR T‐cell immuno‐oncology. [ABSTRACT FROM AUTHOR]

Background: Anlotinib showed significant survival benefits in advanced non‐small cell lung cancer (NSCLC) patients as a third‐ or further‐line treatment in the ALTER0303 trial. We aimed to evaluate the efficacy of anlotinib in patients with different histologies. Methods: The ALTER0303 trial was a randomized, open‐label, phase 3 study of anlotinib in NSCLC patients previously treated with at least two lines of chemotherapy or a tyrosine kinase inhibitor (TKI) in 31 centers in China. Patients were randomly assigned at a 2:1 ratio to receive anlotinib (12 mg QD from days 1 to 14 of a 21‐day cycle) or placebo until progression or intolerable toxicity. The primary endpoint was overall survival (OS). We assessed the efficacy of anlotinib in histological subgroups in the full analysis set. Results: In the ALTER0303 trial, 336 patients had the histological subtype of adenocarcinoma (ACC), 86 patients had the histological subtype of squamous cell carcinoma (SCC), and 15 patients had another subtype. In the ACC subgroup, the median OS time was significantly improved with anlotinib compared with placebo (9.6 months vs 6.9 months, P =.0051), as was the median progression‐free survival (PFS) time (5.5 months vs 1.4 months, P <.0001). In the SCC subgroup, the median OS time was 10.7 months in the anlotinib group and 6.5 months in the placebo group (P =.2570), and the median PFS time was 4.8 months and 2.7 months (P =.0004), respectively. The common adverse events observed in the SCC and ACC subgroups were similar. Conclusions: Our findings suggest that anlotinib significantly improves PFS and OS in ACC patients and has a tendency to prolong survival in SCC patients. [ABSTRACT FROM AUTHOR]

Background: Anlotinib is an oral tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor, fibroblast growth factor receptor, platelet‐derived growth factor receptor, and stem cell factor receptor (c‐Kit). In the phase III ALTER‐0303 trial (Clinical Trial Registry ID: NCT 02388919), anlotinib significantly improved overall survival versus placebo in advanced non‐small cell lung cancer patients who had received at least two previous chemotherapy and epidermal growth factor receptor/anaplastic lymphoma kinase targeted therapy regimens. This study summarized adverse event management in this trial. Methods: Patients were randomized (2:1) to anlotinib or placebo up to progression or intolerable toxicity. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 and managed by investigators. Key strategies for preventing and managing the most common adverse events included patient education, supportive care, and dose modification. Results: Between February 2015 and August 2016, 294 patients received anlotinib. A total of 170 (57.8%) patients received antihypertensive medications for hypertension, 53 (18.0%) patients received levothyroxine for hypothyroidism, 24 (8.2%) patients received fibrates for hypertriglyceridemia, 11 (3.7%) patients took cortisone cream for hand‐foot syndrome, and 38 (12.9%) patients received anti‐diarrheal medications for diarrhea. Dose reduction and drug discontinuation were required in 24 (8.16%) and 31 (10.54%) patients in the anlotinib group, respectively. Conclusion: Anlotinb‐related adverse events could be controlled by patient education, prophylactic measures, early and active intervention, and dose modification. [ABSTRACT FROM AUTHOR]