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The rotating packed bed (RPB) has been widely used in gas-liquid flow systems as a process intensification device, exhibiting excellent mass transfer enhancement characteristics. However, the complex internal structure and the high-speed rotation of the rotor in RPB bring significant challenges to study the intensification mechanism by experiment methods. In the past two decades, Computational Fluid Dynamics (CFD) has been gradually applied to simulate the hydrodynamics and mass transfer characteristics in RPB and instruct the reactor design. This article covers the development of the CFD simulation of gas-liquid flow in RPB. Firstly, the improvement of the simulation method in the aspect of mathematical models, geometric models, and solving methods is introduced. Secondly, new progress of CFD simulation about hydrodynamic and mass transfer characteristics in RPB is reviewed, including pressure drop, velocity distribution, flow pattern, and concentration distribution, etc. Some new phenomena such as the end effect area with the maximum turbulent have been revealed by this works. In addition, the exploration of developing new reactor structures by CFD simulation is introduced and it is proved that such new structures are competitive to different applications. The defects of current research and future development directions are also discussed at last.

To prevent the spread of COVID-19, the Malaysian government implemented a movement control order, an emergency policy that instructed all people in the country to stay home. Being confined in a building for a lengthy period exposes individuals to the risk of having a range of symptoms known as cabin fever. Considering the negative impact of cabin fever, it is crucial to assess cabin fever symptoms among Malaysians. However, there is a lack of validated instruments; hence, this study attempts to develop an instrument for Malaysian adults, named Cabin Fever Scale (CFS). A total of 124 adults (75% females; M = 29.3 years) were recruited via the snowball sampling method to participate in an online survey. Exploratory factor analyses showed that the CFS items were pooled into two factors: behavioural symptoms (six items) and emotional symptoms (four items). Findings show that Malaysians viewed cabin fever as both behavioural and emotional symptoms. The behavioural symptoms comprise food craving, decreased motivation, difficulty waking up, and frequent naps, while emotional symptoms include anxiety, lethargy, depression, impatience, hopelessness, and dissatisfaction. Both CFS subscales demonstrated good internal reliability with Cronbach’s Alpha values of .768 (behavioural symptom) and .908 (emotional symptom). The 10-item CFS is deemed a psychometrically sound instrument for measuring cabin fever in Malaysia.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent responsible for the global coronavirus disease 2019 (COVID-19) pandemic. Numerous studies have demonstrated that cardiovascular disease may affect COVID-19 progression. In the present study, we investigated the effect of hypertension on viral replication and COVID-19 progression using a hypertensive mouse model infected with SARS-CoV-2. Results revealed that SARS-CoV-2 replication was delayed in hypertensive mouse lungs. In contrast, SARS-CoV-2 replication in hypertensive mice treated with the antihypertensive drug captopril demonstrated similar virus replication as SARS-CoV-2-infected normotensive mice. Furthermore, antihypertensive treatment alleviated lung inflammation induced by SARS-CoV-2 replication (interleukin (IL)-1β up-regulation and increased immune cell infiltration). No differences in lung inflammation were observed between the SARS-CoV-2-infected normotensive mice and hypertensive mice. Our findings suggest that captopril treatment may alleviate COVID-19 progression but not affect viral replication.严重急性呼吸系统综合症冠状病毒2型 (SARS-CoV-2) 是导致全球2019冠状病毒病 (COVID-19) 大流行的病原体。大量研究表明，心血管疾病可能会影响COVID-19的进展。在该研究中，我们使用感染了 SARS-CoV-2 的高血压小鼠模型研究了高血压对病毒复制和 COVID-19 进展的影响。结果显示，在高血压小鼠的肺中SARS-CoV-2的复制延迟。相比之下，用抗高血压药物卡托普利治疗的高血压小鼠的SARS-CoV-2 复制与感染了SARS-CoV-2 的正常血压小鼠的病毒复制相似。此外，抗高血压治疗减轻了由 SARS-CoV-2 复制引起的IL-1β上调和免疫细胞浸润增加。在感染 SARS-CoV-2 的血压正常小鼠和高血压小鼠之间没有观察到肺部炎症的差异。因此，我们的研究结果初步表明，卡托普利治疗可能会缓解COVID-19的进展，但不会影响病毒复制。.

The primary outbreak of severe acute respiratory syndrome coronavirus 2, causing pneumonia-like symptoms in patients named coronavirus disease 2019 (COVID-19) had evolved into a global pandemic. COVID-19 has surpassed Middle East respiratory syndrome and severe acute respiratory syndrome in terms of rate and scale causing more than one million deaths. Development of an effective vaccine to fight against the spread of COVID-19 is the main goal of many countries around the world and plant-based vaccines are one of the available methods in vaccine developments. Plant-based vaccine has gained its reputation among researchers for its known effective manufacturing process and cost effectiveness. Many companies around the world are participating in the race to develop an effective vaccine by using the plant system. This review discusses different approaches used as well as highlights the challenges faced by various companies and research groups in developing the plant-based COVID-19 vaccine.

Piebaldism is a rare, autosomal dominant and congenital pigmentary disorder characterized by stable depigmentation of the skin and white forelock. Mutations in KIT or SNAI2 genes result in piebaldism. Most individuals with piebaldism have a family history of the disorder. Herein, we report a 5-month-old Chinese girl with severe piebaldism but no family history thereof. She has white forelock and large patches of depigmentation in the jaw, central anterior trunk, perineum and extremities. We performed whole-exome and Sanger sequencing and identified a de novo KIT mutation (NM_000222.2: c.2657G>A, p.Gly886Val) in exon 18 of KIT in the proband. Currently, this mutation is located in the most extreme C-terminal of the tyrosine kinase domain 2 of the KIT gene amongst all reported mutations and causes a severe clinical phenotype. We further reviewed literature on piebaldism and summarized 79 KIT gene mutations that lead to this disease. Our study may expand knowledge on the genotype-phenotype correlation in piebaldism and serve as a reference for genetic counseling and prenatal diagnosis of affected families.

To observe the therapeutic effect of low-dose amitriptyline (AMT) on epigastric pain syndrome (EPS) in patients with functional dyspepsia. Sixty patients with EPS were randomly divided into the following two groups for a four-week clinical trial: routine treatment with pantoprazole (RT group) and the AMT group. The RT group was treated with 40 mg of pantoprazole once daily. The AMT group received 25 mg of AMT once daily before bedtime. The Nepean Dyspepsia Index (NDI) checklist, Hamilton Rating Scale of Anxiety/Depression (HAMA/HAMD), and Pittsburgh Sleep Quality Index (PSQI) were employed to evaluate dyspepsia symptoms, psychological distress, and sleep, respectively. All items were similar between the two groups before treatment (0 week). After 4 weeks of treatment, the NDI–symptom checklist score as well as the severity and bothersomeness of EPS in the AMT group was significantly decreased compared with those in the RT group (p

Current antiangiogenic therapy is limited by its cytostatic property, scarce drug delivery to the tumor, and side toxicity. To address these limitations, we unveiled the role of ZEB1, a tumor endothelium–enriched zinc-finger transcription factor, during tumor progression. We discovered that the patients who had lung adenocarcinomas with high ZEB1 expression in tumor endothelium had increased prevalence of metastases and markedly reduced overall survival after the diagnosis of lung cancer. Endothelial ZEB1 deletion in tumor-bearing mice diminished tumor angiogenesis while eliciting persistent tumor vascular normalization by epigenetically repressing TGF-β signaling. This consequently led to improved blood and oxygen perfusion, enhanced chemotherapy delivery and immune effector cell infiltration, and reduced tumor growth and metastasis. Moreover, targeting vascular ZEB1 remarkably potentiated the anticancer activity of nontoxic low-dose cisplatin. Treatment with low-dose anti–programmed cell death protein 1 (anti–PD-1) antibody elicited tumor regression and markedly extended survival in ZEB1-deleted mice, conferring long-term protective anticancer immunity. Collectively, we demonstrated that inactivation of endothelial ZEB1 may offer alternative opportunities for cancer therapy with minimal side effects. Targeting endothelium-derived ZEB1 in combination with conventional chemotherapy or immune checkpoint blockade therapy may yield a potent and superior anticancer effect.

Recent interest in the control of bone metabolism has focused on a specialized subset of CD31hiendomucinhi vessels, which are reported to couple angiogenesis with osteogenesis. However, the underlying mechanisms that link these processes together remain largely undefined. Here we show that the zinc-finger transcription factor ZEB1 is predominantly expressed in CD31hiendomucinhi endothelium in human and mouse bone. Endothelial cell-specific deletion of ZEB1 in mice impairs CD31hiendomucinhi vessel formation in the bone, resulting in reduced osteogenesis. Mechanistically, ZEB1 deletion reduces histone acetylation on Dll4 and Notch1 promoters, thereby epigenetically suppressing Notch signaling, a critical pathway that controls bone angiogenesis and osteogenesis. ZEB1 expression in skeletal endothelium declines in osteoporotic mice and humans. Administration of Zeb1-packaged liposomes in osteoporotic mice restores impaired Notch activity in skeletal endothelium, thereby promoting angiogenesis-dependent osteogenesis and ameliorating bone loss. Pharmacological reversal of the low ZEB1/Notch signaling may exert therapeutic benefit in osteoporotic patients by promoting angiogenesis-dependent bone formation., An endothelial cell subtype, expressing endomucin and CD31, has been reported to couple angiogenesis with osteogenesis. Here, the authors show that loss of ZEB1 in these cells epigenetically suppresses Notch signaling, leading to impaired angiogenesis and osteogenesis, and that Zeb1 delivery via liposomes ameliorates bone loss in osteoporotic mice

The aim of the present study was to determine the neuroimaging predictors of poor participation after acute ischemic stroke. A total of 443 patients who had acute ischemic stroke were assessed. At 1-year recovery, the Reintegration to Normal Living Index was used to assess participation restriction. We also assessed the Activities of Daily Living Scale and modified Rankin Scale (mRS) score. Brain MRI measurement included acute infarcts and pre-existing abnormalities such as enlarged perivascular spaces, white matter lesions, ventricular-brain ratio, and medial temporal lobe atrophy (MTLA). The study included 324 men (73.1%) and 119 women (26.9%). In the univariate analysis, patients with poor participation after 1 year were older, more likely to be men, had higher National Institutes of Health Stroke Scale (NIHSS) score on admission, with more histories of hypertension and atrial fibrillation, larger infarct volume, more severely enlarged perivascular spaces and MTLA, and more severe periventricular hyperintensities and deep white matter hyperintensities. Patients with participation restriction also had poor activities of daily living (ADL) and mRS score. Multiple logistic regression showed that, in model 1, age, male gender, NIHSS score on admission, and ADL on follow-up were significant predictors of poor participation, accounting for 60.2% of the variance. In model 2, which included both clinical and MRI variables, male gender, NIHSS score on admission, ADL on follow-up, and MTLA were significant predictors of poor participation, accounting for 61.2% of the variance. Participation restriction was common after acute ischemic stroke despite good mRS score. Male gender, stroke severity, severity of ADL on follow-up, and MTLA may be predictors of poor participation. Trial registration number ChiCTR1800016665.

Objective The aim of this study was to evaluate the predictive factors of central lymph node metastasis (CLNM) and BRAFV600E mutation in Chinese patients with papillary thyroid carcinoma (PTC). Methods A total of 943 PTC patients who underwent thyroidectomy from 2014 to 2016 at our hospital were enrolled. Those patients were divided into PTC > 10 mm and papillary thyroid microcarcinoma (PTMC) groups by tumor size. The BRAFV600E mutation was examined by quantitative real-time PCR. Univariate and multivariate analyses were used to examine risk factors associated with CLNM and the BRAFV600E mutation. Results The frequency of CLNM was 53% (505/943). Both univariate and multivariate analyses suggested that the risk factors for CLNM in PTC patients were male, younger age, and larger tumor size (P < 0.05). Coexistent Hashimoto thyroiditis (HT) was an independent protective factor against CLNM when the tumor was > 10 mm (P = 0.006). Stratified analysis revealed that male, age ≤ 30 years, and tumor size > 5 mm were independent risk factors for CLNM. The BRAFV600E mutation rate was 85%. Multivariate logistic regression analysis revealed that age (P < 0.001) and coexistent HT (P = 0.005) were independent predictive factors of BRAFV600E mutation in PTC patients. Only age was a risk factor for the BRAFV600E mutation when the tumor was > 10 mm (P = 0.004). In the PTMC group, the BRAFV600E mutation was significantly correlated with tumor size (P < 0.001) and coexistent HT (P = 0.03). Stratified analysis revealed that age > 30 years and tumor size > 5 mm were independent predictive factors of BRAFV600E mutation. Furthermore, the incidence of CLNM was significantly higher in BRAFV600E mutation-positive patients (P = 0.009) when the tumor was ≤ 5 mm. Conclusion The factors male, younger age (≤ 30 years), large tumor size (> 5 mm), and coexistent HT are independent predicative factors for CLNM. The BRAFV600E mutation is associated with both large size and without HT in PTMC patients, age > 30 years in the PTC > 10 mm group. The BRAFV600E mutation was an independent risk factor for CLNM when the tumor was ≤ 5 mm. For optimal management, these features should be comprehensively evaluated to determine the initial surgical approach for PTC patients.

Purpose: Impairment of cortical cholinergic pathways (CCP) is an important risk factor for chronic vascular cognitive impairment. However, this phenomenon has rarely been studied in post-stroke cognitive impairment (PSCI). We investigated the relationship between PSCI and CCP lesions assessed by structural magnetic resonance imaging (MRI).Patients and methods: We prospectively enrolled 103 patients within 7 days of ischemic stroke onset. CCP was measured by the cholinergic pathways hyperintensities scale (CHIPS), which semiquantitatively grades MR lesions strategically located on the CCP identified in human brains. We also measured other MRI parameters, including the location and volumes of acute infarcts, cerebral microbleeds, medial temporal lobe atrophy, and white matter lesions. Neuropsychological assessments were performed using the 60-min modified vascular dementia battery (VDB) at 3 months after the index stroke, and PSCI was defined according to VDB as well as ADL.Results: Of all 103 patients, 69 men (67.0%) and 34 women (33.0%) with a mean age of 57.22 ± 12.95 years, 55 patients (53.4%) were judged to have PSCI at 3 months, including 43 (41.7%) patients with PSCI-no dementia and 12 (11.7%) patients with poststroke dementia. According to the VBD assessment, the most commonly impaired cognitive domain was visuomotor speed (27.2%) followed by verbal memory (25.2%). Univariate analysis showed that patients with PSCI were older; had higher informant questionnaire on cognitive decline in the elderly (IQCODE) scores; had more frequent previous stroke history and atrial fibrillation; and had higher CHIPS scores, more severe white matter lesions, and medial temporal lobe atrophy. PSCI patients also had higher depression scores at 3 months. In the multivariate regression analysis, age, IQCODE score, CHIPS score, and Hamilton depression rating scale score were independent predictors of PSCI. Ordinal regression analysis for risk factors of poor functional outcomes revealed that IQCODE scores and cognitive function status were related to mRS score at 3 months after stroke.Conclusion: In patients with early subacute ischemic stroke, the severity of lesions involving the CCP may be associated with cognitive impairment at 3 months.Clinical Trial Registration: Chinese Clinical Trial Registry, identifier: ChiCTR1800014982.

Objective: To evaluate the efficacy of multiparametric magnetic resonance imaging (mp-MRI) using Prostate Imaging Reporting and Data System version 2.0 (PI-RADSv2) definitions in detecting organ-confined prostate cancer. Methods: All patients who underwent radical prostatectomy between January 1, 2014 and December 30, 2014 were identified. All underwent mp-MRI within 180 days before surgery. Those with prior pelvic irradiation or androgen deprivation therapy were excluded. Fully embedded, whole-mount histopathology was centrally reviewed and correlated with imaging for tumour location, Gleason score (GS) and stage. Results: There were 39 patients included, of which 35 (90%) had mp-MRI done post-biopsy. A total of 93 cancer foci were identified on whole-mount pathology, of which mp-MRI detected 63 (68%). Of those detected by mp-MRI, 14 were PI-RADS 3 (n = 6 for GS 6, n = 8 for GS 7, no GS ≥ 8) and 49 were PI-RADS 4–5 (n = 7 for GS 6, n = 33 for GS 7, and n = 9 for GS ≥ 8). There were 30 (32%) cancer foci missed by mp-MRI (n = 15 for GS 6, n = 13 for GS 7 and n = 2 for GS ≥ 8). A lesion classified as PI-RADS 4–5 predicted a higher grade cancer on pathology as compared to PI-RADS 3 (for GS 7 lesions, odds ratio [OR] = 3.53, 95% CI: 0.93–13.45, p = 0.064). The mp-MRI size detection limit was 20 mm2 and 100 mm2 for 50% and 75% probability of cancer, respectively. In associating with radiological and pathologic stage, the weighted Kappa value was 0.69 (p

Objective: To analyze the frequency and spectrum of thalassemia mutations in amniotic fluid samples collected from Han and Li people in Hainan province of China. Methods: We carried out a retrospective analysis on prenatal diagnosis of amniotic fluid samples collected from pregnant women who may have next generation with high risks of medium or severe thalassemia between 2005 and 2016. Diverse fetal thalassemia genotypes and mutated alleles in Han and Li people were analyzed and cmpared. Results: We examined 536 amniotic fluid samples from Han people and 588 from Li people, among which 406 Han and 500 Li samples were found to carry at least one thalassemia gene mutation, with a detection rate of 75.75% and 85.03%, respectively. Among all α- and β-thalassemia mutant alleles detected, the most frequently found mutations in Han and Li samples were SEA-type of α-thalassemia and 41/42 (–CTTT) of β-thalassemia, respectively. A total of 75 severe thalassemia cases were identified in Han samples and 53 in Li samples. In most of these severe cases, parents chose to terminate pregnancy after being informed of thalassemia-related risks. Conclusions: The thalassemia mutations shows ethnic and area specificity, and that prenatal diagnosis for high-risk thalassemia carrier pregnant women is an efficient approach to prevent and control the occurrence of severe thalassemia in the high-prevalence areas.

Objective Postoperative complications adversely affected the prognosis in patients with gastric cancer. This study intends to investigate the feasibility of using machine-learning model to predict surgical outcomes in patients undergoing gastrectomy. Methods In this study, cancer patients who underwent gastrectomy at Shanghai Rui Jin Hospital in 2017 were randomly assigned to a development or validation cohort in a 9:1 ratio. A support vector classification (SVC) model to predict surgical outcomes in patients undergoing gastrectomy was developed and further validated. Results A total of 321 patients with 32 features were collected. The positive and negative outcomes of postoperative complication after gastrectomy appeared in 100 (31.2%) and 221 (68.8%) patients, respectively. The SVC model was constructed to predict surgical outcomes in patients undergoing gastrectomy. The accuracy of 10-fold cross validation and external verification was 78.17% and 78.12%, respectively. Further, an online web server has been developed to share the SVC model for machine-learning-assisted prediction of surgical outcomes in patients undergoing gastrectomy in the future procedures, which is accessible at the web address: http://47.100.47.97:5005/r_model_prediction. Conclusions The SVC model was a useful predictor for measuring the risk of postoperative complications after gastrectomy, which may help stratify patients with different overall status for choice of surgical procedure or other treatments. It can be expected that machine-learning models in cancer informatics research are possibly shareable and accessible via web address all over the world.

The pathophysiology of cardiac hypertrophy is complex and multifactorial. Both the store-operated Ca2+ entry (SOCE) and excessive autophagy are the major causative factors for pathological cardiac hypertrophy. However, it is unclear whether these two causative factors are interdependent. In this study, we examined the functional role of SOCE and Orai1 in angiotensin II (Ang II)-induced autophagy and hypertrophy using in vitro neonatal rat cardiomyocytes (NRCMs) and in vivo mouse model, respectively. We show that YM-58483 or SKF-96365 mediated pharmacological inhibition of SOCE, or silencing of Orai1 with Orail-siRNA inhibited Ang II-induced cardiomyocyte autophagy both in vitro and in vivo. Also, the knockdown of Orai1 attenuated Ang II-induced pathological cardiac hypertrophy. Together, these data suggest that Ang II promotes excessive cardiomyocyte autophagy through SOCE/Orai1 which can be the prime contributing factors in cardiac hypertrophy.

Prior studies have examined the influence of MTHFR C677T on autism susceptibility, however, there are no consensus conclusions and specific analyses of a Chinese population. This meta-analysis included a false-positive report probability (FPRP) test to comprehensively evaluate the association of MTHFR C677T polymorphism with autism susceptibility among a Chinese Han population. A large-scale literature retrieval was conducted using various databases including PubMed, Embase, Wan Fang, and the Chinese National Knowledge Infrastructure (CNKI) up to July 31, 2020, with a total of 2,258 cases and 2,073 controls included. The strength of correlation was assessed by odds ratios (ORs) and 95% confidence intervals (95% CIs). MTHFR C677T showed a significant correlation with increased ASD susceptibility under all genetic models (T vs. C, OR = 1.89, 95% CI 1.28 to 2.79; TT vs. CC: OR = 2.44, 95% CI 1.43 to 4.15; CT vs. CC, OR = 1.73; 95% CI 1.19 to 2.51; CT + TT vs. CC: OR = 2.03, 95% CI 1.31 to 3.15; TT vs. CT + CC, OR = 1.95, 95% CI 1.21 to 3.13). Stratification analysis by region also revealed a consistent association in the Northern Han subgroup, but not in the Southern Han subgroup. Pooled minor allele frequency (MAF) of 30 studies were 45% in Northern Han and 39% in Southern Han. To avoid a possible “false positive report,” we further investigated the significant associations observed in the present meta-analysis using the FPRP test, which consolidated the results. In conclusion, MTHFR C677T polymorphism is associated with the increased risk of autism in China, especially in Northern Han. For those mothers and children who are generally susceptible to autism, prenatal folate and vitamin B12 may reduce the risk that children suffer from autism, especially in Northern Han populations. In the future, more well-designed studies with a larger sample size are expected.

Objective:The aim of the study is to evaluate the association of the BRAFV600E mutation with the clinicopathologic characteristics in Chinese population with papillary thyroid carcinoma (PTC).MethodsA total of 943 PTC patients who underwent thyroidectomy from 2014 to 2016 at Henan Provincial People’s Hospital were included in the present study. The BRAFV600E mutation was examined in each resected specimen by quantitative Real-time PCR (qRT-PCR) technique. Results The PTC patients were subclassified into the overall, PTC>10mm and papillary thyroid microcarcinoma(PTMC) groups. The positive rate of BRAFV600E mutation was 85.4% in Chinese patients with PTC. In both overall PTC and PTC> 10mm groups, the BRAFV600E mutation was much more frequently detected in elderly patients and patients at T1 stage (P< 0.05). In addition, the positive rate of BRAFV600E mutation was significantly higher in PTC patients without concomitant Hashimoto’s thyroiditis in overall PTC and PTMC groups (P< 0.05). Furthermore, logistic regression analysis suggested that the risk of having a larger tumor diameter was increased by 6-fold when BRAFV600E mutation in the PTMC group. No association between the BRAFV600E mutation and other clinicopathologic factors was observed. ConclusionThe BRAFV600E mutation was significantly associated with patients age and T stage. Furthermore, the risk of having a larger tumor size was significantly increased when BRAFV600E mutation in the PTMC group. which suggests that BRAFV600E mutation might play an important role in the activation of early thyroid carcinogenesis, the effect might weaken in the progression of PTC.

Objectives An artificial intelligence model was adopted to identify mild COVID-19 pneumonia from computed tomography (CT) volumes, and its diagnostic performance was then evaluated. Methods In this retrospective multicenter study, an atrous convolution-based deep learning model was established for the computer-assisted diagnosis of mild COVID-19 pneumonia. The dataset included 2087 chest CT exams collected from four hospitals between 1 January 2019 and 31 May 2020. The true positive rate, true negative rate, receiver operating characteristic curve, area under the curve (AUC) and convolutional feature map were used to evaluate the model. Results The proposed deep learning model was trained on 1538 patients and tested on an independent testing cohort of 549 patients. The overall sensitivity was 91.5% (195/213; p < 0.001, 95% CI: 89.2–93.9%), the overall specificity was 90.5% (304/336; p < 0.001, 95% CI: 88.0–92.9%) and the general AUC value was 0.955 (p < 0.001). Conclusions A deep learning model can accurately detect COVID-19 and serve as an important supplement to the COVID-19 reverse transcription–polymerase chain reaction (RT-PCR) test. Key Points • The implementation of a deep learning model to identify mild COVID-19 pneumonia was confirmed to be effective and feasible. • The strategy of using a binary code instead of the region of interest label to identify mild COVID-19 pneumonia was verified. • This AI model can assist in the early screening of COVID-19 without interfering with normal clinical examinations. Supplementary Information The online version contains supplementary material available at 10.1007/s00330-021-07797-x.

Background: Early neurological deterioration (END) is common in acute ischemic stroke (AIS), but its effect on functional outcomes is not well understood. The aim of the present study was to explore the effects of END on multiple dimensions of functional outcomes.Methods: In the present study, 256 patients with AIS were analyzed. All patients were followed up for 1 year. We used the modified Rankin Scale (mRS) to assess body function impairment, the Lawton activities of daily living scale to assess activity limitations, and the reintegration to normal living index (RNLI) to assess participation restrictions. Brain magnetic resonance imaging was performed to identify acute infarcts and preexisting abnormalities, such as white matter lesions, medial temporal lobe atrophy, microbleeds, and silent lacunae. To reduce the effects of a lack of randomization, we conducted a propensity score analysis. Results: The study sample consisted of 185 men (72.3%) and 71 women (27.7%). Sixty-one patients (23.8%) had END. Before matching, patients with END had higher levels of small artery-type stroke, higher National Institutes of Health Stroke Scale scores on arrival, higher systolic blood pressure on admission, and larger infarct volumes. After matching, there were no significant differences between the two groups in any clinical or neuroimaging variables, except for stroke subtype and cortical region infarct. Logistic regression analysis revealed that END was a significant predictor of poor mRS (odds ratio [OR], 3.829; 95% confidence interval [CI], 1.367–10.723, p = 0.011) and poor RNLI (OR, 2.777; 95% CI, 1.133–6.806, p = 0.026) scores after adjusting for confounding factors.Conclusions: END is relatively common in AIS, with an incidence of 23.8%. END might be able to predict poor functional outcomes, including body function impairment and reduced social participation.

Background Low-dose amitriptyline (AMT) is an effective treatment for diarrhea-dominant irritable bowel syndrome (IBS-D). Its efficacy depends upon its serum concentration and the patient's CYP2C19 genotype. Aims To identify the association between serum AMT and nortriptyline (NT) concentration and CYP2C19 polymorphism and the clinical response in IBS-D patients. Methods Ninety IBS-D patients were treated of AMT for 6 weeks. Efficacy was evaluated by the results of the Adequate Relief question each week and an IBS severity scoring system (IBS-SSS) at 0, 3, and 6 weeks. CYP2C19 genotyping was performed by direct sequencing. AMT and NT steady-state serum concentrations were detected by high-performance liquid chromatography. Results The CYP2C19 polymorphism exhibited a significant influence on the NT serum concentration but did not predict the clinical efficacy of AMT for treating IBS-D. The NT steady-state and dose-corrected serum concentrations were significantly correlated with an improvement in the IBS-SSS score after 6 weeks, whereas the AMT serum concentration was not correlated with clinical improvement. The cut-off NT steady-state serum concentration of 2.91 ng/ml may help distinguish responders from non-responders. Conclusions NT serum concentration but not CYP2C19 polymorphism may be correlated with the clinical efficacy of AMT for treating IBS-D, and such a response may occur at the upper NT threshold of 2.91 ng/ml.

Whether autonomic dysfunction contributes to cerebral small vessel disease (CSVD) remains unclear. This study aimed to explore the relationship between CSVD and blood pressure variability (BPV) and heart rate variability (HRV).This case-control study recruited 50 patients with CSVD and 50 non-CSVD hypertensive age- and gender-matched controls. All participants completed a 24-h ambulatory electrocardiogram recording and ambulatory BP monitoring (ABPM). Differences in HRV and BPV between the two groups were examined. BPV indices assessed by ABPM included mean systolic BP (SBP), mean diastolic BP (DBP), coefficient of variation and weighted standard deviation of SBP and DBP.CSVD patients had significant higher 24-h mean systolic BP (SBP), 24-h mean diastolic BP (DBP), daytime mean SBP, nocturnal mean SBP, and nocturnal mean DBP (P.05 for all). CSVD patients had a significant lower nocturnal SBP fall rate compared with controls (median: 1.0 versus 6.2, respectively; P.001) and were more likely to be non-dippers and reverse dippers. There were no differences in HRV variables between the two groups. Five logistic models were built to explore the correlations between BPV indices and CSVD. BPV indices were separately entered into the logistic regression models, together with hyperlipidemia, ischemic stroke history, current use of anti-hypertensive agents, and serum blood urea nitrogen. In models 1-3, 24-h mean SBP and nocturnal mean SBP and DBP were significantly correlated with CSVD (rLower nocturnal SBP fall rate is associated with CSVD. Non-dipper and reverse dipper hypertensive patients have a higher risk of CSVD.

Vascular dementia (VaD), caused by stroke or small vessel disease, is the second-most common type of dementia after Alzheimer's disease (AD). Donepezil is an acetylcholinesterase inhibitor that is currently used in patients with mild to moderate AD, and has recently been shown to improve cognitive performance in patients with VaD. In this study, we evaluated the effects of donepezil on VaD, and investigated the underlying molecular mechanisms of action. VaD was established by ligation of the bilateral common carotid artery occlusion (BCCAO). Executive function was tested by the Morris water maze (MWM) test and the attentional set shifting task (ASST). Our results showed that donepezil improved executive dysfunction and cognitive flexibility in BCCAO rats. In addition, we showed that donepezil treatment decreased the level of Aβ1-42 in BCCAO rats by enzyme-linked immunosorbent assay. Post-translational modifications (PTMs) are known to be critical mechanisms in the regulation of various cellular processes. Furthermore, PTMs have been linked to the central nervous system, which highlights the importance of PTMs in neurodegenerative diseases. In this study, we used western blot analysis to identify several novel PTMs in the hippocampus of BCCAO rats that were treated with or without donepezil. The data revealed that lysine propionylation, 2-hydroxyisobutyrylation, butyrylation, succinylation, and crotonylation were elevated in the hippocampus of BCCAO rats when compared to sham rats. This increase was abolished by donepezil treatment. Taken together, we speculate that donepezil treatment improves cognitive function in our animal model of VaD, possibly by reducing aberrant acyl-PTMs.

Background: Acupuncture points are commonly used by Traditional Chinese Medicine to treat throat discomfort. Transcutaneous electroacupuncture (TEA) is a new therapy combining transcutaneous electrical nerve stimulation with meridian theory. The efficacy and mechanism of Transcutaneous electroacupuncture for globus pharyngeus has not been reported. The aim of our study was to explore the effect and possible mechanisms of TEA at CV22/LI3/LU11/ST36 for patients with globus.Methods: A total of 80 patients with globus pharyngeus were randomly allocated into eight groups. The intervention order in Groups A1/B1/C1/D1 was firstly TEA at CV22/LI3/LU11/ST36 during the first period and sham-TEA in the second period. For participants in Groups A2/B2/C2/D2, the intervention order was the reverse. Before the test, the participants were asked to complete the Glasgow Edinburgh Throat Scale (GETS), visual analog scale (VAS), and the Hamilton Rating Scale Anxiety/Depression and were then asked to test and measure the heart rate variability and serum hormone levels of SP and NPY. At the end of the second period, these tests were manipulated again.Results: D-values of GETS and VAS following stimulation at CV22/LU11 were significantly higher than those of sham-stimulating (CV22: 13.5 ± 13.09 vs. 1 ± 9.68, P

BACKGROUNDThere is little information about the coronavirus disease 2019 (Covid-19) during pregnancy. This study aimed to determine the clinical features and the maternal and neonatal outcomes of pregnant women with Covid-19.METHODSIn this retrospective analysis from five hospitals, we included pregnant women with Covid-19 from January 1 to February 20, 2020. The primary composite endpoints were admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Secondary endpoints included the clinical severity of Covid-19, neonatal mortality, admission to neonatal intensive care unit (NICU), and the incidence of acute respiratory distress syndrome (ARDS) of pregnant women and newborns.RESULTSThirty-three pregnant women with Covid-19 and 28 newborns were identified. One (3%) pregnant woman needed the use of mechanical ventilation. No pregnant women admitted to the ICU. There were no moralities among pregnant women or newborns. The percentages of pregnant women with mild, moderate, and severe symptoms were 13 (39.4%),19(57.6%), and 1(3%). One (3.6%) newborn developed ARDS and was admitted to the NICU. The rate of perinatal transmission of SARS-CoV-2 was 3.6%.CONCLUSIONSThis report suggests that pregnant women are not at increased risk for severe illness or mortality with Covid-19 compared with the general population. The SARS-CoV-2 infection during pregnancy might not be associated with as adverse obstetrical and neonatal outcomes that are seen with the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) infection during pregnancy. (Funded by the National Key Research and Development Program.)

To address the problems of confined space for offshore application, rotating packed bed (RPB) was firstly used to enhance the regeneration of TEG solution in natural gas dehydration process. The performance of the regeneration, which was exhibited in terms of the desorption efficiency and mass transfer coefficient, was investigated experimentally. The effects of various operating parameters, including rotation speed, gas-liquid ratio, liquid flow rate, liquid inlet temperature, and inlet concentration of rich TEG were studied to assess the impacts on the regeneration process. It was found that the purity of regenerated TEG solution by RPB was basically above 99.7% under a common gas-liquid ratio of 45 (volume ratio), and even higher than 99.98% under the optimal conditions. A mass transfer model combined two-film theory and penetration theory was established, which could well predict the TEG solution regeneration performance in RPB. According to the established model and ASPEN simulation result, an RPB and a packed column were designed respectively for a specific TEG regeneration task. It was found the volume reduction factor of RPB was about 8, which showed well adaptation of RPB for the offshore natural gas extraction due to the outstanding mass transfer performance in the TEG regeneration process.

Objectives To study the role of the neutrophil-to-lymphocyte ratio in predicting survival outcomes for patients with advanced bladder cancer. Methods We retrospectively reviewed 150 patients diagnosed with advanced or metastatic bladder cancer between January 2004 and June 2014. The neutrophil-to-lymphocyte ratio was computed on diagnosis and after the first cycle of chemotherapy. A neutrophil-to-lymphocyte ratio cut-off of 3.0 was determined, with a concordance index of 0.89. Kaplan–Meier curves, log–rank tests, Cox proportional hazards and logistic regression models were used to predict the association of the neutrophil-to-lymphocyte ratio with survival outcomes. Results Just five patients were alive at the end of the study; the rest died from metastatic bladder cancer. On multivariate analysis, higher Eastern Cooperative Oncology Group status, lymphadenopathy, visceral metastases and neutrophil-to-lymphocyte ratio ≥3.0 were associated with poorer overall survival (hazard ratio 1.67, P = 0.03; hazard ratio 1.97, P =

Background Antidepressant agents have been shown to be an effective and safe treatment method for patients with globus. However, there are few clinical trials dedicated to studying the effects of antidepressant agents on the natural history and upper oesophageal sphincter (UES) pressure of treated globus patients. Aims To evaluate the effect of paroxetine and amitriptyline to prevent relapses in patients with globus, the simultaneous relationship between changes in UES pressure and improvement of globus symptoms were measured. Methods Globus patients were randomised into amitriptyline, paroxetine and lansoprazole groups for a 6-week treatment period, and follow-up was extended to 12 additional months. Efficacy was evaluated in terms of the Glasgow-Edinburgh Throat Scale (GETS), and UES pressure was measured by standard oesophageal manometry. Results Paroxetine therapy resulted in a higher withdrawal rate due to symptom relapse (15.9% vs 44.1%, P = 0.01; 15.9% vs 64.7, P = 0.001) than amitriptyline and lansoprazole. Furthermore, globus symptoms were alleviated with the decrease of UES pressure after paroxetine and amitriptyline treatment (r = 0.620, P = 0.02; r = 0.575, P = 0.03) Conclusions This follow-up study indicates that paroxetine may alter the natural history of globus and can effectively be used for the long-term management of patients with the disease. Apart from the clinical benefits, paroxetine and amitriptyline can potentially decrease UES pressure.

Ethnopharmacological relevance Diabetic nephropathy (DN) is a major complication of diabetes. The kidney disease develops in nearly 20%–40% of type 2 diabetes (T2D) patients. Ginseng is the root of Panax ginseng C. A. Meyer and has been used in prevention and treatment of diseases for more than 2000 years as a traditional oriental medicine. The 20(R)-ginsenoside Rg3, an active saponin isolated from ginseng, can prevent and treat many diseases. The object of this research was to explore the alleviative effects of 20(R)-Rg3 on DN in mice. Materials and methods The T2D animal model was induced by continuous access to a high fat diet (HFD) combined with a single injection of 100 mg/kg streptozotocin (STZ) in C57BL/6 mice. The mice were treated by oral gavage of the 20(R)-Rg3 (10, 20 mg/kg) for 8 weeks. Functional and histopathological analyses of the kidneys were then performed. Protein expression levels of MAPKs and NF-κB signal pathways in the kidney were evaluated by western blotting. The expressions of HO-1 and NF-κB in the kidney were measured by fluorescent labeling staining. Other assessments including fasting blood glucose (FBG) levels, blood lipids, oxidative indicators, and inflammatory factors were all performed. Results Abnormally elevated FBG levels were observed in HFD/STZ mice, contributing significantly to the occurrence of DN. Simultaneously, HFD/STZ mice showed the rise of serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels, and the decrease in high density lipoprotein cholesterol (HDL-C). DN was evidenced by the overproduction of malondialdehyde (MDA), decreased levels of superoxide dismutase (SOD) and catalase (CAT) enzymatic activities, high levels of serum blood urea nitrogen (BUN) and creatinine (Cr). Simultaneously, the results of the immunofluorescence assay showed an increased expression level in NF-κB p65 while a decrease in antioxidant enzyme HO-1 was observed. Herein, 20(R)-Rg3 treatment for 8 weeks not only attenuated FBG levels and advanced glycation end products (AGEs) levels but also improved insulin (INS) level, blood lipids, oxidative stress, and renal function by regulating MAPKs and NF-κB signal pathways in DN mice. Conclusion Taken together, the findings from the present study explicitly confirmed that 20(R)-Rg3 exerted ameliorative effects on DN mice via improving anti-oxidative activity and reducing renal inflammation.

In order to describe the characteristics of dynamic traffic flow and improve the robustness of its multiple applications, a dynamic traffic temporal-spatial model (DTTS) is established. With consideration of the temporal correlation, spatial correlation and historical correlation, a basic DTTS model is built. And a three-stage approach is put forward for the simplification and calibration of the basic DTTS model. Through critical sections pre-selection and critical time pre-selection, the first stage reduces the variable number of the basic DTTS model. In the second stage, variable coefficient calibration is implemented based on basic model simplification and stepwise regression analysis. Aimed at dynamic noise estimation, the characteristics of noise are summarized and an extreme learning machine is presented in the third stage. A case study based on a real-world road network in Beijing, China, is carried out to test the efficiency and applicability of proposed DTTS model and the three-stage approach.

In order to balance the temporal-spatial distribution of urban traffic flow, a model is established for combined urban traffic signal control and traffic flow guidance. With consideration of the wide use of fixed signal control at intersections, traffic assignment under traffic flow guidance, and dynamic characteristics of urban traffic management, a tri-level programming model is presented. To reflect the impact of intersection delay on traffic assignment, the lower level model is set as a modified user equilibrium model. The middle level model, which contains several definitional constraints for different phase modes, is built for the traffic signal control optimization. To solve the problem of tide lane management, the upper level model is built up based on nonlinear 0-1 integer programming. A heuristic iterative optimization algorithm (HIOA) is set up to solve the tri-level programming model. The lower level model is solved by method of successive averages (MSA), the middle level model is solved by non-dominated sorting genetic algorithm II (NSGA II), and the upper level model is solved by genetic algorithm (GA). A case study is raised to show the efficiency and applicability of the proposed modelling and computing method.

All-trans retinoic acid (ATRA)-based cell differentiation therapy has been successful in treating acute promyelocytic leukemia, a unique subtype of acute myeloid leukemia (AML). However, other subtypes of AML display resistance to ATRA-based treatment. In this study, we screened natural, plant-derived vibsane-type diterpenoids for their ability to induce differentiation of myeloid leukemia cells, discovering that vibsanin A potently induced differentiation of AML cell lines and primary blasts. The differentiation-inducing activity of vibsanin A was mediated through direct interaction with and activation of protein kinase C (PKC). Consistent with these findings, pharmacological blockade of PKC activity suppressed vibsanin A–induced differentiation. Mechanistically, vibsanin A–mediated activation of PKC led to induction of the ERK pathway and decreased c-Myc expression. In mouse xenograft models of AML, vibsanin A administration prolonged host survival and inhibited PKC-mediated inflammatory responses correlated with promotion of skin tumors in mice. Collectively, our results offer a preclinical proof of concept for vibsanin A as a myeloid differentiation-inducing compound, with potential application as an antileukemic agent. Cancer Res; 76(9); 2698–709. ©2016 AACR.

Background The coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2, is a global public health emergency. Data on the effect of coronavirus disease 2019 in pregnancy are limited to small case series. Objective To evaluate the clinical characteristics and outcomes in pregnancy and the vertical transmission potential of severe acute respiratory syndrome coronavirus 2 infection. Study Design Clinical records were retrospectively reviewed for 116 pregnant women with coronavirus disease 2019 pneumonia from 25 hospitals in China between January 20, 2020, and March 24, 2020. Evidence of vertical transmission was assessed by testing for severe acute respiratory syndrome coronavirus 2 in amniotic fluid, cord blood, and neonatal pharyngeal swab samples. Results The median gestational age on admission was 38+0 (interquartile range, 36+0–39+1) weeks. The most common symptoms were fever (50.9%, 59/116) and cough (28.4%, 33/116); 23.3% (27/116) patients presented without symptoms. Abnormal radiologic findings were found in 96.3% (104/108) of cases. Of the 116 cases, there were 8 cases (6.9%) of severe pneumonia but no maternal deaths. One of 8 patients who presented in the first trimester and early second trimester had a missed spontaneous abortion. Of 99 patients, 21 (21.2%) who delivered had preterm birth, including 6 with preterm premature rupture of membranes. The rate of spontaneous preterm birth before 37 weeks’ gestation was 6.1% (6/99). One case of severe neonatal asphyxia resulted in neonatal death. Furthermore, 86 of the 100 neonates tested for severe acute respiratory syndrome coronavirus 2 had negative results; of these, paired amniotic fluid and cord blood samples from 10 neonates used to test for severe acute respiratory syndrome coronavirus 2 had negative results. Conclusion Severe acute respiratory syndrome coronavirus 2 infection during pregnancy is not associated with an increased risk of spontaneous abortion and spontaneous preterm birth. There is no evidence of vertical transmission of severe acute respiratory syndrome coronavirus 2 infection when the infection manifests during the third trimester of pregnancy.

PurposeThe main objectives of this study were to assess the early changes in pulmonary function and intrarenal haemodynamics and to determine the correlation between pulmonary function and intrarenal haemodynamics in patients with type 2 diabetes mellitus (T2DM).Methods96 patients with T2DM (diabetes group) without diabetes kidney disease (DKD) and 33 healthy subjects (control group) were enrolled in studies intended to assess the early changes in pulmonary function and intrarenal haemodynamics associated with diabetes, as well as to determine the correlation between pulmonary function and intrarenal haemodynamics.ResultsPulmonary functional parameters were negatively correlated with HbA1c levels and diabetes duration (P< 0.05). Moreover, renal functional parameters were positively correlated with HbA1c levels and diabetes duration (PConclusionsPatients displayed changes in pulmonary function and intrarenal haemodynamics during the preclinical stages of DKD. Regulating glycaemia may improve intrarenal haemodynamics in the bilateral interlobular renal arteries. Moreover, during the preclinical stages of DKD, the right kidney RI is a effective predictor of early changes in pulmonary function in adult T2DM patients.Trial registrationClinicalTrials.gov (NCT02798198); registered 8 June 2016.

Background: Pre-treated patients with first-line treatment can be offered a second treatment with the aim of improving their poor clinical prognosis. The therapy of metastatic colorectal cancer (CRC) patients who did not respond to first-line therapy has limited treatment options. Recently, many studies have paid much attention to the efficacy of bevacizumab as an adjuvant treatment for metastatic colorectal cancer. Objectives: We aimed to evaluate the efficacy and toxicity of bevacizumab plus chemotherapy compared with bevacizumab-naive based chemotherapy as second-line treatment in people with metastatic CRC. Methods: Electronic databases were searched for eligible studies updated to March 2018. Randomized-controlled trials comparing addition of bevacizumab to chemotherapy without bevacizumab in MCRC patients were included, of which, the main interesting results were the efficacy and safety profiles of the addition of bevacizumab in patients with MCRC as second-line therapy. Result: Five trials were eligible in the meta-analysis. Patients who received the combined bevacizumab and chemotherapy treatment in MCRC as second-line therapy showed a longer overall survival (OS) (OR=0.80,95%CI=0.72-0.89, P Conclusion: Our results suggest that the addition of bevacizumab to the chemotherapy therapy could be an efficient and safe treatment option for patients with metastatic colorectal cancer as second-line therapy and without increasing the risk of an adverse event.

This paper analyzes the development status of the infrared polarization imaging system. According to the application need of medium wave infrared (MWIR) polarization image, this paper proposes a MWIR polarization coaperture optical system. The system is composed of the front co-aperture optical system and the rear sub-aperture optical system. The rear separate aperture optical system includes four polarization channels. Each channel adopts a 1/4 wave plate and a linear polarizers to obtain three line Stokes polarization components and one circularly Stokes polarization components Thus the system could achieve full polarization imaging. According to the detector and the corresponding application needs, the calculation and optical system design were completed. After the design, the MTF of the optical system is more than 0.3@17lp/mm. The maximum RMS spot diameter is less than the size of detector pixel and a single pixel energy concentration is greater than 80%.

The purpose of this study was to observe the hyperplasia trend of scar after the cleft lip surgery in a rabbit animal model, and determine the time-point of the highest hypertrophic degree of scar after cleft lip repair. Forty New Zealand white rabbits from the same offspring were used to establish a cleft lip wound healing model using Millard surgery procedure. The scar volumes were measured and granulation tissues were observed visually in the 2, 3, 4, and 5 weeks after operation. The scar tissues were harvested at the indicated time-points. Immunohistochemical (IHC) and Western Blot analyses were performed to detect the expression level of α-smooth muscle actin (α-SMA) in the scar tissue. The scars shrunk and the volumes reduced at 3 to 4 weeks after surgery; however, at 5 weeks postsurgery, the volumes increased. IHC and Western blot analyses indicated the expression of α-SMA was significantly enhanced 3 to 4 weeks, but reduced in the 5 weeks after surgery. Overall, the degree of scar hyperplasia after cleft lip surgery in rabbits was normally distributed and the scarring was most severe in the 3 to 4 weeks after cleft lip surgery. The study confirms a novel animal model for the assessment of therapies for the treatment of scar hyperplasia of human cleft lip in future.

The nasoalveolar molding (NAM) therapy is advocated to reduce the severity of alveolar cleft and nasal deformity. NAM therapy has demonstrated to be an effective method for reducing cleft and improve nose anatomy. This paper presents a case report of three cleft lip and palate individuals treated with NAM therapy. Furthermore, the paper highlights the advantages of NAM therapy along with an enumeration of literature suggesting in favor of NAM therapy and otherwise. Regardless of controversies and divergent views involved with NAM therapy, the immediate success of NAM therapy facilitating primary lip repair surgery cannot be under-emphasized.

To satisfy the demand of congestion problem solving in intersections, this paper studies the method of automation countermeasure system for intersection optimization (ACSIO). Taking into account the extensive contents and objectives of intersection optimization, this paper puts forward the functions and architecture of ACSIO based on intersection optimization problem statement. Seeking optimal design of intersection channelization and signal control, the main goal of ACSIO is to achieve dynamic and coordination management of intersection. The problem is formulated as a multiobjective program, with each objective corresponding to a different player in the system. Moreover, it presents system design of ACSIO. A case study based on a real-world intersection is implemented to test the efficiency and applicability of the proposed modeling and computing methods.

Passive Q-switching of a diode-pumped Nd:GGG laser is demonstrated using Bi-doped GaAs as saturable absorber. The Bi-doped GaAs wafer is fabricated by ion implantation and subsequent annealing. Compared with the Q-switched laser by undoped GaAs semiconductor saturable absorber, the laser with Bi-doped GaAs as saturable absorber can produce higher output power, shorter pulses, higher single pulse energies and higher peak powers. These results suggest that Bi-doped GaAs can be a promising new candidate of semiconductor saturable absorber in Q-switched laser.

To evaluate the sustainability of an enormous number of urban intersections, a novel assessment model is proposed, along with an indicator system and corresponding methods to determine the indicators. Considering mainly the demands and feelings of the urban residents, the three aspects of safety, functionality, and image perception are taken into account in the indicator system. Based on technologies such as street view picture crawling, image segmentation, and edge detection, GIS spatial data analysis, a rapid automated assessment method, and a corresponding multi-source database are built up to determine the indicators. The improved information entropy method is applied to obtain the entropy weights of each indicator. A case study shows the efficiency and applicability of the proposed assessment model, indicator system and algorithm.

Objective To determine the role of neutrophil-to-lymphocyte ratio (NLR) in prognosticating survival outcomes in patients with advanced/metastatic urothelial bladder cancer. Methods We retrospectively reviewed 84 patients undergoing radical cystectomy (RC) for UCB from January 2002 to June 2012. NLR was computed (median: 5 days) prior to surgery. No patients received neoadjuvant chemotherapy. NLR was analyzed as a continuous variable and a cut-off point of 2.7 was obtained, with a statistical receiver operating characteristics of 0.74. Kaplan–Meier curves, multivariate Cox proportional hazard and logistics regression models were used to predict NLR association with survival outcomes. Results The median follow-up period was 30.1 months (range: 3.2–161.7) owing to high recurrence rate and subsequent mortalities, compared to the median 64.7 months in patients alive at the end of study period. NLR ≥2.7 was associated with worse survival outcomes (5-year disease-specific survival: 22% vs 58%, p = 0.017, 95%CI: 1.193–6.009; 5-year overall survival: 23% vs 60%, p = 0.008, 95%CI: 1.322–6.147). Furthermore, on multivariate analyses, higher NLR was independently associated with higher recurrence rate ( p = 0.007, HR =6.999, 95%CI: 1.712–28.606), higher T staging ( p = 0.021, HR = 3.479, 95%CI: 1.212–9.990) and lymph node involvement ( p = 0.009, HR = 4.534, 95%CI: 1.465–14.034). Conclusion This study suggests that NLR can be an inexpensive novel factor for patients risk stratification pre-operatively. This improves patient counseling and identifies patients who may benefit from multimodal treatment.

Quantum many-body problem with exponentially large degrees of freedom can be reduced to a tractable computational form by neural network method \cite{CT}. The power of deep neural network (DNN) based on deep learning is clarified by mapping it to renormalization group (RG), which may shed lights on holographic principle by identifying a sequence of RG transformations to the AdS geometry. In this essay, we show that any network which reflects RG process has intrinsic hyperbolic geometry, and discuss the structure of entanglement encoded in the graph of DNN. We find the entanglement structure of deep neural network is of Ryu-Takayanagi form. Based on these facts, we argue that the emergence of holographic gravitational theory is related to deep learning process of the quantum field theory., Comment: Received an Honorable Mention on the Gravity Research Foundation's 2017 Essay Competition; v2: typos corrected

The problem of robust fault detection filter is investigated for a class of systems with unknown disturbance and fault inputs. Attention is focused on formulating the design the residuals match with reference model. The robustness of the residual system is proved to be stability. The existence condition of the above filters, which can guarantee the robustness against disturbances and sensitivity against fault are solved by LMI. Finally, an example is given to illustrate the feasibility of the proposed method.

A 25-year-old woman presented with a fever, headache, vomiting and somnolence. Cranial magnetic resonance imaging (MRI) showed multiple lesions in the cerebellum, brainstem, cerebral cortex and subcortex. Oligoclonal bands were positive in the cerebral spinal fluid (CSF). She experienced a good recovery after steroid treatment. Four months later, she developed right vision loss. Repeated MRI showed multiple cranial lesions different from those involved in the first attack in both size and distribution. An abnormal high signal was also observed in the front and intraorbital regions of the right optic nerve. The patient's vision progressively improved, and she obtained a full recovery following the administration of steroids. A diagnosis of multiphasic disseminated encephalomyelitis manifesting with optic neuritis was made.

In this paper, a set of virtual simulation platform for crossbow making is established. First, build a virtual model of Lisu crossbow, optimize the model, accelerate the organization, model generation, modification and editing of the database; then complete the database establishment of the corresponding model, nest the comment entity class and filemeta entity class into the file entity class, store them in a nested data set, and complete the data storage, management and query operations; finally, combined with Kalman filtering, arithmetic average filtering and KNN algorithm are used to build the quest 3D virtual platform to improve the 3D interaction effect with data gloves and complete the construction of the 3D platform.

Multiple myeloma (MM) is the second most commonly hematologic malignancy characterized by proliferation of monoclonal plasmas cells in bone marrow. Despite the availability of new drugs targeting the neoplastic clone and its microenvironment, MM is still an incurable disease, with patients experiencing subsequent phases of remission and relapse, eventually leading to disease resistance and patient death. In the past decades, natural products have attracted increasing attention in the field of anti-myeloma treatment by virtue of their multiple bioactivities and lower toxicity. This review focuses on the research progress and mechanisms through which these natural extracts inhibit tumor cell proliferation and normalize microenvironment in multiple myeloma. These include the induction of apoptosis, inhibition of bone injury and angiogenesis, and reversion of multidrug resistance.