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Few studies have reported the roles of the complement system in concomitant idiopathic membranous nephropathy and IgA nephropathy (IMN-IgAN). Complement factor B (CFB) is a crucial factor that involved in the alternative complement pathway. We aimed to evaluate the association between disease activity (eGFR, anti-PLA2R antibody levels and 24 h urinary protein excretion), progression and serum CFB levels of IMN-IgAN patients. In total, 39 IMN-IgAN patients (median follow-up, 46.6 months), 99 IMN patients and 92 IgAN patients participated in this study. The disease progression event was defined as end-stage renal disease (ESRD) or a 30% decline in estimated glomerular filtration rate (eGFR). The serum CFB concentration was measured by enzyme-linked immunosorbent assay. Serum CFB levels were lower in IMN-IgAN patients than in patients with IgAN only (P

Hypertension is a complex disease which is mainly influenced by genetic factors. Recently, genome-wide association study (GWAS) found three novel endothelial dysfunction-related sites: Vascular endothelial growth factor A (VEGFA) rs9472135, Faciogenital dysplasia 5 (FGD5) rs11128722, Zinc Finger C3HC-type Containing 1 (ZC3HC1) rs11556924. Endothelial dysfunction is one of the early events in pathophysiology of essential hypertension. To investigate the association of endothelial dysfunction-related genes with essential hypertension, we conducted a case-control study of 431 patients with hypertension and 345 controls. The polymorphisms were detected using Taqman Probe. The alleles and genotypes of ZC3HC1 rs11556924 and VEGFA rs9472135 were not statistically different between the two groups, while the allele of FGD5 rs11128722 was different [P = 0.045, OR = 1.265, 95% CI = (1.009–1.586)], especially in the male [P = 0.035, OR = 1.496, 95% CI = (1.037–2.158)]. Analyzing the different of genotype distribution of 3 SNPs in the two groups under different genetic models, the genotypes of FGD5 rs11128722 showed difference in male under dominant model [P = 0.049, OR = 1.610, 95% CI = (1.018–2.544)]. The polymorphism of FGD5 rs11128722 had a significant difference in Body Mass Index (BMI) among different genotypes; In the additive genetic model, BMI of GA genotype was higher than that of GG (P = 0.038); GA + AA was higher than GG in the dominant genetic model (P = 0.011). In our study, we found that the polymorphisms of VEGFA rs9472135 and ZC3HC1 rs11556924 may not significantly associated with the risk of essential hypertension, and FGD5 rs11128722 may increase the risk of it, especially in elderly men.

Objective To compare the degree of agreement and consistency of urodynamic studies (UDS) with low urinary tract symptoms (LUTS) questionnaires for evaluating LUTS in cervical cancer patients following radical hysterectomy (RH) and pelvic lymphadenectomy. Methods From January 2012 to March 2015, 204 cervical cancer patients who underwent RH in 13 hospitals were evaluated using the Incontinence Questionnaire-Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) and the Overactive Bladder Symptom Score (OABSS). Urodynamic tests were also performed on these patients during the same period. Results Study participants’ age ranged from 23 to 75 years, with a mean (standard deviation) of 48.0 ​± ​9.3 years. Using questionnaires, the prevalence of patients with LUTS symptoms, including storage symptoms, voiding symptoms, stress urinary incontinence (SUI) and overactive bladder (OAB) was 86.3%, 77.0%, 62.7%, 52.9% and 14.7%, respectively. For UDS, the corresponding prevalence was 89.7%, 70.1%, 66.7%, 46.6% and 13.2%, respectively. The diagnostic concordance of questionnaires and UDS for storage symptoms, voiding symptoms, SUI and OAB was 79.9%, 66.7%, 66.7%, 57.4% and 79.9%, respectively. For voiding symptoms, the correlation coefficient was 0.272, which was higher than that of storage symptoms, SUI and OAB. Conclusions In cervical cancer patients who have undergone RH, there was a moderate degree of agreement between UDS and symptom questionnaires in evaluating LUTS, but the consistency was poor. Medical personnel should be adequately trained in UDS to ensure LUTS are adequately diagnosed in patients.

Background:. It has been a global trend that increasing complications related to pelvic floor surgeries have been reported over time. The current study aimed to outline the development of Chinese pelvic floor surgeries related to pelvic organ prolapse (POP) over the past 14 years and investigate the potential influence of enhanced monitoring conducted by the Chinese Association of Urogynecology since 2011. Methods:. A total of 44,594 women with POP who underwent pelvic floor surgeries between October 1, 2004 and September 30, 2018 were included from 22 tertiary academic medical centers. The data were reported voluntarily and obtained from a database. We compared the proportion of each procedure in the 7 years before and 7 years after September 30, 2011. The data were analyzed by performing Z test (one-sided). Results:. The number of different procedures during October 1, 2011−September 30, 2018 was more than twice that during October 1, 2004−September 30, 2011. Regarding pelvic floor surgeries related to POP, the rate of synthetic mesh procedures increased from 38.1% (5298/13,906) during October 1, 2004–September 30, 2011 to 46.0% (14,107/30,688) during October 1, 2011–September 30, 2018, whereas the rate of non-mesh procedures decreased from 61.9% (8608/13,906) to 54.0% (16,581/30,688) (Z = 15.53, P

Objective Bevacizumab has an important and evolving role in improving outcomes in patients with metastatic colorectal cancer (mCRC) worldwide and was approved in China in 2010. However, there are limited real-world data on the efficacy and safety of chemotherapy regimens combined with bevacizumab in Chinese patients with mCRC. This observational, phase IV trial study aimed to obtain more experience on the efficacy and safety of bevacizumab combined with chemotherapy in Chinese mCRC patients. Methods Between September 2013 and November 2016, patients with histologically confirmed mCRC were enrolled in a prospective, multicenter, observational, non-interventional phase IV trial at 26 centers across China. Eligible patients received different chemotherapeutic regimens combined with bevacizumab. The efficacy and safety data in the intention-to-treat study population were analyzed. Results A total of 611 patients were included in the efficacy analysis. The median overall survival and median progression-free survival was 18.00 and 10.05 months, respectively. The objective response rate was 21.00% and disease control rate was 89.40%. In subgroup analyses, the survival differences were observed according to metastatic status, duration of treatment and elevation in blood pressure. A total of 613 patients were evaluable for safety assessments. And 569 (92.82%) patients reported at least one adverse event (AE), and 151 (24.63%) experienced grade 3 or higher AEs. The incidence of bevacizumab-associated AEs of special interest was reported in 31 (5.06%) patients with hypertension (n=12), abscesses and fistulae (n=7), bleeding (n=6), proteinuria (n=3), gastrointestinal perforation (n=2) and venous thrombotic events (n=1). Conclusions This observational phase IV trial broadens our experience and knowledge of bevacizumab in the Chinese population and provides a good indication of its overall efficacy and safety. Bevacizumab in combination with chemotherapy offers clinical benefits to Chinese patients with mCRC and has an acceptable and manageable safety profile.

Background The cognitive impairment pattern of deficit schizophrenia (DS) is centered on an impaired attention function. Previous studies have suggested that the exploratory eye movement (EEM) tests reflect attention deficits in patients with schizophrenia. However, no study has investigated the characteristics of eye movement in DS in the Chinese Han population. This study aimed to investigate the pattern of eye movement characteristics in DS patients and to examine whether eye movement characteristic is associated with serious negative symptoms and cognitive decline in this schizophrenia subtype. Methods A total of 86 male patients [37 DS and 49 non-deficit schizophrenia (NDS)] and 80 healthy controls (HC) participated in this study. Clinical symptoms were assessed using the Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the Assessment of Negative Symptoms (SANS). Cognitive function was assessed using the Mattis Dementia Rating Scale (MDRS-2). Eye movement data of subjects were collected using an eye movement tracking analyzer. Results There were significant differences in the overall eye movement data and cognitive test scores among the three groups (all P P P = 0.001) and structure factor of cognitive (r = − 0.389, P = 0.023), the affective flattening factor of SANS was negatively correlated with TESL (r = − 0.353, P = 0.041) and initiation/retention factor of cognitive (r = − 0.376,P = 0.028). TESL was found to positively correlate with the MDRS-2 total score (r = 0.427, P = 0.012), attention factor (r = 0.354, P = 0.040), and memory factor (r = 0.349, P = 0.043) in the DS group, whereas the mean of eye scanning length (MESL) positively correlated with cognitive impairments in the NDS group. The negative symptoms showed no significant correlation with cognition in the NDS group. Conclusions Total of eye scanning length may be a characteristic eye movement symptom in DS patients, which is associated with serious negative symptoms and cognitive impairment in this schizophrenia subtype.

Simple Summary Cisplatin is a broadly used chemotherapy drug, but its use and efficacy are limited by its nephrotoxicity. Autophagy protects against kidney injury during cisplatin exposure but may reduce the efficacy of chemotherapy by protecting cancer cells. In this review, we describe the role and regulation of autophagy in cisplatin-induced nephrotoxicity and discuss the therapeutic advances and challenges of targeting autophagy in chemotherapy. Abstract Cisplatin is a widely used chemotherapeutic agent but its clinical use is often limited by nephrotoxicity. Autophagy is a lysosomal degradation pathway that removes protein aggregates and damaged or dysfunctional cellular organelles for maintaining cell homeostasis. Upon cisplatin exposure, autophagy is rapidly activated in renal tubule cells to protect against acute cisplatin nephrotoxicity. Mechanistically, the protective effect is mainly related to the clearance of damaged mitochondria via mitophagy. The role and regulation of autophagy in chronic kidney problems after cisplatin treatment are currently unclear, despite the significance of research in this area. In cancers, autophagy may prevent tumorigenesis, but autophagy may reduce the efficacy of chemotherapy by protecting cancer cells. Future research should focus on developing drugs that enhance the anti-tumor effects of cisplatin while protecting kidneys during cisplatin chemotherapy.

Recently, several novel therapeutic drugs (NTDs) were found to have therapeutic potential in treating chronic heart failure (CHF). This network meta-analysis aimed to compare and rank different NTDs in patients with CHF. We searched Medline/PubMed, Embase and Cochrane Library of Clinical Trials database through February 9, 2021, for RCTs comparing the NTDs with standard of care (SOC) in adult patients with CHF. Trials of angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose transporter 2 (SGLT2) inhibitors, ivabradine, non-steroidal mineralcorticoid receptor antagonists (MRA), soluble guanylate cyclase (SGC) stimulators and cardiac myosin activators (CMA) were included. We performed a Bayesian network meta-analysis to indirectly compare the mortality, HF hospitalization and adverse events of the NTDs. Thirty-three studies enrolling 63614 patients were included in this analysis. The results showed none of the NTDs was associated with a significant superiority in reducing all-cause mortality, composite outcome of cardiovascular mortality or HF hospitalization and HF hospitalization alone. For cardiovascular mortality alone, ARNI was superior to ivabradine and CMA, while SGLT2 inhibitors were superior to CMA. For adverse events, SGLT2 inhibitors were associated with a lower risk of serious adverse events than ivabradine and CMA. ARNI and SGLT2 inhibitors were recommended as better choices in reducing CV mortality, while SGLT2 inhibitors performed better regarding serious adverse event.

Background: The pathogenesis of obstructive sleep apnea (OSA) remains not fully understood. This study aimed to explore the mechanism of OSA by assessing the association between the human tandem of P domains in a weak inwardly rectifying K+ channel (TWIK)-related acid-sensitive K+ channel-1 (TASK-1) gene and OSA. Methods: A total of 164 patients with severe OSA and 171 patients without OSA were recruited from the Center for Hypertension of People’s Hospital of Xinjiang Uygur Autonomous Region (China) from April to December in 2016. Two single nucleotide polymorphisms (rs1275988 and rs2586886) in the TASK-1 gene were selected and genotyped using a kompetitive allele specific polymerase chain reaction genotyping system. Clinical-pathological characteristics and genotype data were compared between the severe and non-OSA groups to explore the association between TASK-1 gene polymorphism and severe OSA. Results: There were no significant differences in genotype distribution, allele frequency, and the recessive and dominant model of the two selected single nucleotide polymorphisms (rs1275988 and rs2586886) between the severe and non-OSA groups in the total population (P < 0.05). However, for patients with a body mass index (BMI) ≥28 kg/m2, the distribution of genotypes and alleles, and the recessive model (GG + GA vs. AA) exhibited significant differences between the severe and non-OSA group (for genotypes: P = 0.014 and P = 0.026; for alleles: P = 0.006 and P = 0.011; for the recessive model: P = 0.005 and P = 0.009, respectively). The simple logistic regression analysis revealed that the GG genotype was a risk factor for OSA. The odds ratio (OR) and 95% confidence intervals (CI) were 4.902 (1.582–15.186, P = 0.006) for rs1275988 and 4.420 (1.422–13.734, P = 0.010) for rs2586886, respectively. In multivariate logistic regression analysis, the combination of GG genotypes of rs1275988 with BMI ≥28 kg/m2 increased the risk of severe OSA (OR = 8.916, 95% CI 4.506–17.645, P < 0.001). Conclusion: Both the GG genotype of rs1275988 and GG genotype of rs2586886 in the TASK-1 gene may play as potential risk factors in obese patients with OSA. Key words: Potassium channels; Obstructive sleep apnea; Single nucleotide polymorphism; Body mass index

Decreased expression of the renal aquaporin (AQP) protein family is associated with hydronephrosis in adult humans and animals. However, the expression of AQPs, especially subtypes AQP1–3, which play a core role in the urinary concentration function, in hydronephrotic human fetuses is not clear. The aim of this study is to investigate the expression of the AQP1–3 in normal and hydronephrotic human fetal kidneys. Twenty-one normal and six hydronephrotic kidney (HK) samples were harvested from abortive fetuses. Meanwhile, seven normal adult human kidney samples were collected as positive controls. Quantitative real-time PCR, western blotting, and immunohistochemistry were used to analyze the expression of AQP1–3. Both the protein and messenger mRNA expression levels of AQP1–3 increased with gestational age in the normal fetuses, but the levels were significantly lower than those in the adult tissues and significantly higher than those in the hydronephrotic fetuses at the same gestational age. The increased expression of AQP1–3 with gestational age in the fetal kidney may indicate maturation of the urinary concentrating ability. The lower expression of AQP1–3 in HKs may reflect a maturation obstacle with regard to urinary concentration in human hydronephrotic fetuses.

For compression fracture, vertebral body height loss (VBHL) and kyphotic angle (KA) are two important imaging parameters for determining the prognosis and appropriate treatment. This study used previous measurement methods to assess the degree of VBHL and KA, compare and examine differences between various measurement methods, and examine the correlation between relevant measurement parameters and intravertebral cleft (IVC) in the vertebral body. The radiographic images (lateral view of the T-L spine) of 18 patients with a single-level vertebral compression fracture were reviewed. We measured 9 characteristic lengths and angles on plain radiographs, including anterior vertebral height (AVH) and AVH of the adjacent upper and lower levels, middle vertebral height (MVH) and MVH of the adjacent upper and lower levels, posterior vertebral height (PVH), and vertebral body width, and assessed 6 parameters, including vertebral compression ratio (VBCR), percentage of anterior height compression (PAHC), percentage of middle height compression (PMHC), kyphotic angle (KA), calculated kyphotic angle (CKA), and IVC. The results showed that VBCR is a simple and rapid method of VBHL assessment, but it may result in an underestimation of the degree of VBHL compared to PAHC. WhenPMHC<40%orkyphotic angle>15°, the probability of IVC occurring on the vertebral body was higher which means the higher risk of vertebral body instability. The results of this study could provide a reference for surgeons when using imaging modalities to assess the degree of vertebral body collapse.

Background The benefit of systemic treatments in esophageal squamous cell carcinoma (ESCC) which has progressed after chemotherapy is still uncertain and optimal regimens based on randomized trials have not yet been established. We aimed to compare the efficacy of irinotecan plus S-1 with S-1 monotherapy in recurrent or metastatic ESCC patients who had resistance to platinum- or taxane-based chemotherapy. Methods We conducted a prospective randomized, multicenter, open-label, phase 3 trial in 15 centers across China. Eligible patients were adults with histologically confirmed recurrent or metastatic ESCC, and were randomly assigned (ratio, 1:1) to receive either irinotecan plus S-1 (intravenous infusion of irinotecan [160 mg/m2] on day 1 and oral S-1 [80–120 mg] on days 1–10, repeated every 14 days) or oral S-1 monotherapy (80–120 mg/day on days 1–14, repeated every 21 days) using a central computerized minimization procedure. The primary endpoint was progression-free survival (PFS). Results Between December 23, 2014 and July 25, 2016, we screened 148 patients and randomly assigned 123 patients to receive either irinotecan plus S-1 regimen (n = 61) or S-1 monotherapy (n = 62). After a median follow-up of 29.2 months (95% confidence interval [CI] 17.5–40.9 months), the median PFS was significantly longer in the irinotecan plus S-1 group than in the S-1 monotherapy group (3.8 months [95% CI 2.9–4.3 months] vs. 1.7 months [95% CI 1.4–2.7 months], hazard ratio = 0.58, 95% CI 0.38–0.86, P = 0.006). The objective response rates were 24.6% in the irinotecan plus S-1 group and 9.7% in the S-1 monotherapy group (P = 0.002). The patients in the irinotecan plus S-1 group presented with increased rates of grade 3–4 leukopenia (16.4% vs. 0%), neutropenia (14.8% vs. 1.6%), and nausea (4.9% vs. 0%). No significant difference in grade 3–4 diarrhea and no treatment-related deaths were observed in both groups. Conclusions The combination of irinotecan with S-1 was similarly tolerable but significantly prolonged PFS compared to S-1 monotherapy as a second- or third-line treatment in patients with recurrent or metastatic ESCC. Clinical Trial Registration NCT02319187. Registered on December 9, 2014 Electronic supplementary material The online version of this article (10.1186/s40880-019-0359-7) contains supplementary material, which is available to authorized users.

Background: Computer-aided diagnosis using deep learning algorithms has been initially applied in the field of mammography, but there is no large-scale clinical application.Methods: This study proposed to develop and verify an artificial intelligence model based on mammography. Firstly, retrospectively collected mammograms from six centers were randomized to a training dataset and a validation dataset for establishing the model. Secondly, the model was tested by comparing 12 radiologists’ performance with and without it. Finally, prospectively multicenter mammograms were diagnosed by radiologists with the model. The detection and diagnostic capabilities were evaluated using the free-response receiver operating characteristic (FROC) curve and ROC curve.Results: The sensitivity of model for detecting lesion after matching was 0.908 for false positive rate of 0.25 in unilateral images. The area under ROC curve (AUC) to distinguish the benign from malignant lesions was 0.855 (95% CI: 0.830, 0.880). The performance of 12 radiologists with the model was higher than that of radiologists alone (AUC: 0.852 vs. 0.808, P = 0.005). The mean reading time of with the model was shorter than that of reading alone (80.18 s vs. 62.28 s, P = 0.03). In prospective application, the sensitivity of detection reached 0.887 at false positive rate of 0.25; the AUC of radiologists with the model was 0.983 (95% CI: 0.978, 0.988), with sensitivity, specificity, PPV, and NPV of 94.36%, 98.07%, 87.76%, and 99.09%, respectively.Conclusions: The artificial intelligence model exhibits high accuracy for detecting and diagnosing breast lesions, improves diagnostic accuracy and saves time.Trial registration: NCT, NCT03708978. Registered 17 April 2018, https://register.clinicaltrials.gov/prs/app/ NCT03708978

Background Data focusing on the synergistic effect of programmed cell death 1 (PD-1) inhibitors and brain radiotherapy for brain metastases (BMs) in lung cancer is scarce. Methods A total of 60 lung cancer patients receiving PD-1 inhibitors with or without brain radiotherapy were identified in this retrospective study. The primary endpoints were intracranial progression-free survival (iPFS), extracranial progression-free survival (PFS), and overall survival (OS) among three groups. Results Twenty-one patients received PD-1 inhibitors and concurrent brain radiotherapy, 20 patients were treated with PD-1 inhibitors and non-concurrent brain radiotherapy, and the other 19 patients were treated with PD-1 inhibitors alone. Patients in the concurrent group achieved a higher intracranial objective response rate (iORR, 61.1% vs. 29.4% vs. 25.0%) and a higher intracranial disease control rate (iDCR, 83.3% vs. 58.8% vs. 56.3%) compared with those in the non-concurrent group and PD-1 inhibitors alone group. The median iPFS was significantly longer in the concurrent group than the non-concurrent group and the PD-1 inhibitors alone group (9.8, 5.7, and 4.8 months, P=0.039, respectively). The median PFS were 9.2, 5.7 and 4.6 months (P=0.347) in the concurrent group, non-concurrent group and PD-1 inhibitors alone group. And the median OS were not reached, 12.1 and 6.9 months (P=0.206), respectively. Multivariate analysis revealed that the lack of concurrent brain radiotherapy was independently associated with a shorter iPFS. Conclusions PD-1 inhibitors with concurrent brain radiotherapy achieved a higher iORR, iDCR, and iPFS in lung cancer patients with treated or newly diagnosed BMs.

The kidneys play an indispensable role in glucose homeostasis via glucose reabsorption, production, and utilization. Conversely, aberrant glucose metabolism is involved in the onset, progression, and prognosis of kidney diseases, including acute kidney injury (AKI). In this review, we describe the regulation of glucose homeostasis and related molecular factors in kidneys under normal physiological conditions. Furthermore, we summarize recent investigations about the relationship between glucose metabolism and different types of AKI. We also analyze the involvement of glucose metabolism in kidney repair after injury, including renal fibrosis. Further research on glucose metabolism in kidney injury and repair may lead to the identification of novel therapeutic targets for the prevention and treatment of kidney diseases.

Background Aberrant DNA hypermethylation of CpG islands (CGIs) occurs frequently and is genome-wide in human gastric cancer (GC). A DNA methylation approach in plasma cell-free DNA (cfDNA) is attractive for the noninvasive detection of GC. Here, we performed genome-scale cfDNA methylation analysis in patients with GC. Methods We used MCTA-Seq, a genome-scale DNA methylation analysis method, on the plasma samples of patients with GC (n = 89) and control participants (n = 82), as well as 28 pairs of GC and adjacent noncancerous tissues. The capacity of the method for detecting GC and discriminating GC from colorectal cancer (CRC) and hepatocellular carcinoma (HCC) was assessed. Results We identified 153 cfDNA methylation biomarkers, including DOCK10, CABIN1, and KCNQ5, for detecting GC in blood. A panel of these biomarkers gave a sensitivity of 44%, 59%, 78%, and 100% for stage I, II, III, and IV tumors, respectively, at a specificity of 92%. CpG island methylation phenotype (CIMP) tumors and NON-CIMP tumors could be distinguished and detected effectively. We also identified several hundreds of cfDNA biomarkers differentially methylated between GC, CRC, and HCC, and showed that MCTA-Seq can discriminate early-stage GC, CRC, and HCC in blood by using a high specificity (approximately 100%) algorithm. Conclusions Our comprehensive analyses provided valuable data on cfDNA methylation biomarkers of GC and showed the promise of cfDNA methylation for the blood-based noninvasive detection of GC.

With the rapid development of new energy and DC, new technologies such as energy storage are emerging, and the characteristics of power grids are becoming more and more complex. The traditional dispatching mode of "source following load" has been difficult to deal with this situation. Considering the characteristics of the existing domestic power grid automation and information systems, a coordinated and optimized structure of source-network-load-storage integration of power information and physical integration is proposed, and then a technical solution based on the "State Grid Cloud Platform + Data Center" system architecture is formed, and compared with the traditional smart grid-based dispatch control system function expansion plan, Pros and cons of the plan are analyzed from the three aspects of system operation safety, inputoutput ratio and system maintenance cost. Two key technologies are given for multi-dimensional aggregation model construction and ubiquitous coordination and optimization of source-networkload-storage interaction. The developed ubiquitous dispatching control system with multiple coordinated source, grid, load and storage was put into operation in the East China Electric Power Control Sub-center of State Grid. The construction cost is relatively small, the effect of renewable energy consumption is obvious, and the grid operation is safe and reliable. The scheme has important reference significance for the coordination and optimization construction of the multiple coordination of the source network.

This retrospective study was conducted to analyze the associations between ring finger protein 213 p.R4810K variant, clinical features and long-term outcomes in patients with moyamoya disease (MMD) after encephaloduroarteriosynangiosis treatment.A total of 2,545 patients with MMD in China were included in this study (median of follow-up duration: 32.00 months). Multiple Cox regression models were used to assess the associations between p.R4810K variant, clinical features and long-term outcomes.For all patients, in multivariate Cox analysis, no association was observed between p.R4810K and long-term outcomes. Pediatric onset (HR, 0.38; 95%CI, 0.25-0.59) and headache (HR, 0.26; 95%CI, 0.08-0.83) were inversely and hypertension (HR, 1.43 95%CI, 1.06-1.94), diabetes (HR, 1.55; 95%CI, 1.00-2.40), bilateral lesions (HR, 2.73; 95%CI, 1.12-6.65) and posterior cerebral artery involvement (HR, 1.44; 95%CI, 1.08-1.90) were positively associated with follow-up stroke (all P0.05). Pediatric onset (HR, 0.46; 95%CI, 0.26-0.82) was inversely and hyperlipidemia (HR, 1.83; 95%CI, 1.23-2.73), smoking (HR, 1.86; 95%CI, 1.13-3.07), high Suzuki angiographic stage (HR, 1.71, 95%CI, 1.09-2.70), poor admission neurologic status (HR, 8.93; 95%CI, 6.49-12.29) and follow-up stroke (HR, 8.31; 95%CI, 6.01-11.49) were positively associated with poor neurologic outcome at the last follow-up visit (all P0.05). The factors were not consistent in the different groups of age at onset.In our study, p.R4810K may play no role in long-term outcomes in Chinese MMD. Clinical features including age at onset, initial symptoms, risk factors of stroke, imaging, poor admission neurologic status were associated with poor outcomes in MMD after EDAS.

Background Crazy-paving patterns are rarely reported as radiological manifestations of pulmonary cryptococcosis. Case presentation Herein, we presented a very rare case of a crazy-paving pattern as a radiological manifestation of pulmonary cryptococcosis in a patient with primary ciliary dyskinesia. The diagnosis of pulmonary cryptococcosis and primary ciliary dyskinesia was ultimately confirmed by bronchoscopic biopsy, fungus culture, whole exome sequencing of blood, etc. The patient received flucytosine (PO, 5 g per day) and amphotericin B (IV, 70 mg per day) during hospitalization and sequential therapy with voriconazole (PO, 200 mg twice a day) after discharge. He recovered during follow-up. Conclusions We concluded that pulmonary cryptococcosis should be considered a possible cause of crazy-paving patterns in chest CT scans.

Aims: To determine the risk of liver injury associated with the use of different intravenous lipid emulsions (LEs) in large populations in a real-world setting in China.Methods: A prescription sequence symmetry analysis was performed using data from 2015 Chinese Basic Health Insurance for Urban Employees. Patients newly prescribed both intravenous LEs and hepatic protectors within time windows of 7, 14, 28, 42, and 60 days of each other were included. The washout period was set to one month according to the waiting-time distribution. After adjusting prescribing time trends, we quantify the deviation from symmetry of patients initiating LEs first and those initiating hepatic protectors first, by calculating adjusted sequence ratios (ASRs) and relevant 95% confidence intervals. Analyses were further stratified by age, gender, and different generations of LEs developed.Results: In total, 416, 997, 1,697, 2,072, and 2,342 patients filled their first prescriptions with both drugs within 7, 14, 28, 42, and 60 days, respectively. Significantly increased risks of liver injury were found across all time windows, and the strongest effect was observed in the first 2 weeks [ASR 6.97 (5.77–8.42) ∼ 7.87 (6.04–10.61)] in overall patients. In subgroup analyses, female gender, age more than 60 years, and soybean oil-based and alternative-LEs showed higher ASRs in almost all time windows. Specially, a lower risk for liver injury was observed in the first 14 days following FO-LEs administration (ASR, 3.42; 95% CI, 0.81–14.47), but the risk started to rise in longer time windows.Conclusion: A strong association was found between LEs use and liver injury through prescription sequence symmetry analysis in a real-world setting, which aligns with trial evidence and clinical experience. Differences revealed in the risks of liver injury among various LEs need further evaluation.

It is essential for an automated vehicle in the field to perform discretionary lane changes with appropriate roadmanship - driving safely and efficiently without annoying or endangering other road users - under a wide range of traffic cultures and driving conditions. While deep reinforcement learning methods have excelled in recent years and been applied to automated vehicle driving policy, there are concerns about their capability to quickly adapt to unseen traffic with new environment dynamics. We formulate this challenge as a multi-Markov Decision Processes (MDPs) adaptation problem and developed Meta Reinforcement Learning (MRL) driving policies to showcase their quick learning capability. Two types of distribution variation in environments were designed and simulated to validate the fast adaptation capability of resulting MRL driving policies which significantly outperform a baseline RL.

Simple Summary Cisplatin is a widely used chemotherapy drug, but its use and efficacy are limited by its nephrotoxicity. HIF has protective effects against kidney injury during cisplatin chemotherapy, but it may attenuate the anti-cancer effect of cisplatin. In this review, we describe the role and regulation of HIF in cisplatin-induced nephrotoxicity and highlight the therapeutic potential of targeting HIF in chemotherapy. Abstract Cisplatin is a highly effective, broad-spectrum chemotherapeutic drug, yet its clinical use and efficacy are limited by its side effects. Particularly, cancer patients receiving cisplatin chemotherapy have high incidence of kidney problems. Hypoxia-inducible factor (HIF) is the “master” transcription factor that is induced under hypoxia to trans-activate various genes for adaptation to the low oxygen condition. Numerous studies have reported that HIF activation protects against AKI and promotes kidney recovery in experimental models of cisplatin-induced acute kidney injury (AKI). In contrast, little is known about the effects of HIF on chronic kidney problems following cisplatin chemotherapy. Prolyl hydroxylase (PHD) inhibitors are potent HIF inducers that recently entered clinical use. By inducing HIF, PHD inhibitors may protect kidneys during cisplatin chemotherapy. However, HIF activation by PHD inhibitors may reduce the anti-cancer effect of cisplatin in tumors. Future studies should test PHD inhibitors in tumor-bearing animal models to verify their effects in kidneys and tumors.

In view of the current inefficient oral English teaching and low quality of learners' oral output, this paper attempts to apply information technology in the English education, to build an effective English oral output teaching mode under the guidance of multimodal discourse theory. This paper first clarifies three concepts: multimodal discourse, effective teaching, and the cloud environment. Then it puts forward three components for the construction of a new oral English teaching mode from three aspects: making the teaching process more effective, applying multi-modal teaching activities and building a cloud environment for oral English teaching.

Aim To identify common drug-related problems (DRPs) during pharmacy intervention and consultation in an intensive care unit (ICU); to explore the gap between physicians and pharmacists on their understanding of each other's capabilities and needs. Method We conducted a single-center prospective study in the ICU of a tertiary academic hospital for 21 months. A pharmaceutical care (PC) model was implemented by a pharmacy team, and data were collected during pharmacy intervention and consultation. Data analysis was performed on identified DRPs, causes and their relationships. DRPs' frequency during intervention and consultation was compared. Problem-level descriptive analysis and network analysis were conducted using R 3.6.3. Result Implementation of PC model greatly improved the efficacy of pharmacists in both interventions proposed to solve DRPs (from 13.6 to 20.1 cases per month) and number of patients being closely monitored (from 7.7 to 16.9 per month). Pharmacists identified 427 DRPs during pharmacy intervention with primarily adverse drug events (ADEs, 34.7%) and effect of treatment not optimal (25.5%), and 245 DRPs during consultation (mainly ADEs, 58.4%). About three-fifths DRPs were caused by antibiotics. Comparing DRPs identified during pharmacy intervention and consultation, physicians consulted pharmacists more on questions related to medication safety, while pharmacists also paid attention to treatment effectiveness, which was consulted less commonly. Conclusion Implementation of PC model is beneficial in guiding pharmacy practice and improving efficacy especially under limited human resources. Physicians and pharmacists shall continue ensuring drug safety and be familiar with the scope of PC and clinical need for a better cooperation.

BackgroundCOVID-19 has been affecting global health since the end of 2019 and so far, no any sign shows the relief of the pandemic. The major issue for controlling the infection disease is lacking efficient prevention and therapeutic approaches. Chloroquine (CQ) and Hydroxychloroquine (HCQ) has been reported to treat the disease, but underlying mechanism still keeps controversial. Purpose: The objective of this study was to investigate whether CQ and HCQ could be an ACE2 blocker to inhibit COVID-19 infection.MethodsIn our study, we used CCK-8 stain, flow cytometry and immunofluorescent stain to evaluated the toxicity and autophagy of CQ and HCQ respectively on ACE2 high expressed HEK293T cells (ACE2h cells). We further analyzed the binding character of CQ and HCQ to ACE2 by molecular docking, surface plasmon resonance (SPR) assays and molecule docking, and COVID-19 spike pseudotype virus was also used to observe the viropexis effect of CQ and HCQ in ACEh cells.ResultsResults showed that HCQ is slightly more toxic to ACE2h cells than CQ, both CQ and HCQ could bind to ACE2 with KD (7.31±0.62)e-7 and (4.82±0.87)e-7, respectively. They also exhibit equivalent suppression effect for the entrance of COVID-19 spike pseudotype virus into ACE2h cells.ConclusionsCQ and HCQ both inhibite the entrance COVID-19 virus into cell by blocking the binding of the virus with ACE2. Our finding provides a novel insight into the molecular mechanism of CQ and HCQ treatment effect on the virus infection.

Summary IgA nephropathy (IgAN) is the leading cause of kidney failure due to an incomplete understanding of its pathogenesis. We perform single-cell RNA sequencing (RNA-seq) on kidneys and CD14+ peripheral blood mononuclear cells (PBMCs) collected from IgAN and normal samples. In IgAN, upregulation of JCHAIN in mesangial cells provides insight into the trigger mechanism for the dimerization and deposition of IgA1 in situ. The pathological mesangium also demonstrates a prominent inflammatory signature and increased cell-cell communication with other renal parenchymal cells and immune cells, suggesting disease progress from the mesangium to the entire kidney. Specific gene expression of kidney-resident macrophages and CD8+ T cells further indicates abnormal regulation associated with proliferation and inflammation. A transitional cell type among intercalated cells with fibrosis signatures is identified, suggesting an adverse outcome of interstitial fibrosis. Altogether, we systematically analyze the molecular events in the onset and progression of IgAN, providing a promising landscape for disease treatment.

Background and purpose The MRI-assessed tumor regression grade (mrTRG) is limited due to its subjectivity and poor consistency on pathological tumor regression grade (pTRG). A new MRI criterion was established to predict the prognosis of locally advanced rectal cancer (LARC). Materials and methods The new MRI criterion magnetic resonance imaging tumor response score (mrTRS) was based on the retrospective sample of 214 LARC patients (unpublished data). Subsequently, 878 LARC patients were enrolled for a prospective, multicenter study. Baseline and postoperative MRI were obtained, and imaging features were measured by collecting the pathological, clinical and follow-up data. Kaplan-Meier method with log-rank estimate and multivariate cox regression model was used to determine the prognosis of mrTRS in LARC patients with neoadjuvant chemoradiotherapy (NACRT). The predictive capability of 3-year prognosis between mrTRS and mrTRG was determined by time-dependent ROC curves. Results The results demonstrated that mrTRS acted as an independent predictor of survival outcomes. mrTRS stratified by good and moderate responders showed significantly lower risk of death (HR = 0.04, 95%CI 0.01–0.31; HR = 0.35, 95%CI 0.23–0.52), distant metastasis (HR = 0.25, 95%CI 0.13–0.52; HR = 0.42, 95%CI 0.30–0.58), and local recurrence when compared with poor responders(HR = 0.01 95%CI 0.23–0.52;HR = 0.38, 95%CI 0.16–0.90). In contrast, no significant difference was observed among mrTRG stratified groups. Excellent and substantial interobserver agreement for mrTRS and mrTRG evaluation was observed (κ = 0.92 and 0.62), respectively. Conclusion mrTRS can serve as an effective predictor for assessing tumor regression grade in LARC patients with NACRT.

EGFR-TKIs are confronted with big challenge of everlasting activated EGFR mutations which lack effective binding sites; this barrier is the dark side that largely limits the outcome of NSCLC patients in the clinic. Combination strategies show impressive anti-tumor efficacy that compared with EGFR-TKI mono-treatment, especially targeting both stem cells and non-stem cells. SHP2 (Src homology 2-containing phosphotyrosine phosphatase 2) plays an important role in regulating various malignant biology through hyper-activating intracellular pathways due to either overexpression or catalytical mutation. Some pathways, in which SHP2 was involved, were overlapped with EGFR downstream, and others were not subject to EGFR. Interestingly, SHP2 suppression was reported to destroy the stemness of cancer. Therefore, we hypothesize that SHP2 inhibitor might be a promising drug that could synergistically enhance or sensitize the anti-tumor efficacy of EGFR-TKIs in EGFR mutated NSCLC patients. Here, we summarized the mechanisms of SHP2 in regulating EGFR mutated NSCLC patients, and attempted to reveal the potential synergistic file://localhost/C/:Program%20Files%20(x86):Youdao:Dict:7.5.2.0:resultui:dict:%3Fkeyword=effects of SHP2 inhibitor combined with EGFR-TKIs.

Located in the subtropics, Taiwan is one of the major epidemic areas for dengue fever, with severe epidemics occurring in recent years. Dengue fever has become a serious health threat to Taiwan&rsquo, s residents and a potentially serious economic cost to society. This study recruited 730 random participants and adopted the contingent valuation method to understand the factors influencing the populace&rsquo, s willingness to pay (WTP) to reduce the health risk of dengue fever. The results show that high-income women with children and people with higher preventive perceptions and behavior are more willing to invest in preventive measures against dengue fever. In the evaluation of WTP for preventive treatment for health risks, each person was willing to pay on average NT$751 annually to lower psychological health risks, NT$793 annually to lower the risk of illness, and NT$1086 annually to lower the risk of death.

Near-infrared (NIR) phosphors, promising non-destructive measurement materials for food, have attracted extensive attention worldwide. Herein, we designed a low-cost rare-earth free Mg2B2O5:Cr3+ phosphor. Under the excitation of 450 nm, the Mg2B2O5:Cr3+ phosphors show a broadband near-infrared emission at 800 nm, for 4T2 (4F) → 4A2 transition. The optimal concentration of Cr3+ was about 0.003 and a higher concentration will lead to concentration quenching owing to dipole-dipole interaction. Moreover, considering the unequal substitution of Mg2+ by Cr3+, charge compensation had been applied to improve the photoluminescence. The mechanism of alkali charge compensation and its effect on polyhedron distortion had been illustrated. The relationship between decay lifetime and charge compensation had been discussed. Finally, the activation energy for thermal quenching of as-prepared samples was calculated. The increasing polyhedron distortion result in worse thermal stability, which was explained by the configurational coordinate model. The above results are helpful in the development of low-cost near-infrared phosphors and the enhancement of photoluminescence intensity.

Yield stress is one of the main performance parameters of magnetorheological fluid (MRF). In order to satisfy the magnetic field requirement of yield stress test device, a magnetic circuit with current excitation is designed, and the finite element software is used to simulate the magnetic circuit. The test bench is built, and the magnetic field loading test is carried out. The magnetic induction intensity of the working gap of MRF is tested, and its B–I curve is obtained. Under the same current, there is a certain error between the magnetic induction intensity and the simulation result, and the maximum relative error is within 6%.

ObjectivesUnderstanding the molecular mechanisms underlying human cartilage degeneration and regeneration is helpful for improving therapeutic strategies for treating osteoarthritis (OA). Here, we report the molecular programmes and lineage progression patterns controlling human OA pathogenesis using single-cell RNA sequencing (scRNA-seq).MethodsWe performed unbiased transcriptome-wide scRNA-seq analysis, computational analysis and histological assays on 1464 chondrocytes from 10 patients with OA undergoing knee arthroplasty surgery. We investigated the relationship between transcriptional programmes of the OA landscape and clinical outcome using severity index and correspondence analysis.ResultsWe identified seven molecularly defined populations of chondrocytes in the human OA cartilage, including three novel phenotypes with distinct functions. We presented gene expression profiles at different OA stages at single-cell resolution. We found a potential transition among proliferative chondrocytes, prehypertrophic chondrocytes and hypertrophic chondrocytes (HTCs) and defined a new subdivision within HTCs. We revealed novel markers for cartilage progenitor cells (CPCs) and demonstrated a relationship between CPCs and fibrocartilage chondrocytes using computational analysis. Notably, we derived predictive targets with respect to clinical outcomes and clarified the role of different cell types for the early diagnosis and treatment of OA.ConclusionsOur results provide new insights into chondrocyte taxonomy and present potential clues for effective and functional manipulation of human OA cartilage regeneration that could lead to improved health.

DNA methylation, chromatin states and their interrelationships represent critical epigenetic information, but these are largely unknown in human early embryos. Here, we apply single-cell chromatin overall omic-scale landscape sequencing (scCOOL-seq) to generate a genome-wide map of DNA methylation and chromatin accessibility at single-cell resolution during human preimplantation development. Unlike in mice, the chromatin of the paternal genome is already more open than that of the maternal genome at the mid-zygote stage in humans, and this state is maintained until the 4-cell stage. After fertilization, genes with high variations in DNA methylation, and those with high variations in chromatin accessibility, tend to be two different sets. Furthermore, 1,797 out of 5,155 (35%) widely open chromatin regions in promoters closed when transcription activity was inhibited, indicating a feedback mechanism between transcription and open chromatin maintenance. Our work paves the way for dissecting the complex, yet highly coordinated, epigenetic reprogramming during human preimplantation development.

This paper presents the mathematical modeling of the nonlinear vibration behavior of a hybrid laminated plate composed of carbon nanotube reinforced functionally graded (CNTR-FG) layers and conventional fiber reinforced composite (FRC) layers. Three type symmetric distributions of single walled carbon nanotubes (SWCNTs) through the thickness of layers are considered. The cracks are modeled as aligned slit cracks across the ply thickness and transverse to the laminate plane. The distribution of cracks is assumed to be statistically homogeneous corresponding to an average crack density. The obtained partial differential equations are solved by the element-free kp-Ritz method, and the iteration process is dealt with using the linearized updated mode method. Detailed parametric studies are conducted investigate the effects of matrix crack density, CNTs distributions, CNT volume fraction, plate aspect ratio and plate length-to-thickness ratio, boundary conditions and number of layers on the frequency-amplitude responses of hybrid laminated plates containing CNTR-FG layers.

Three-dimensional (3D) printing of continuous fiber-reinforced composites (FRCs) and automated fiber placement (AFP) technology have enabled the fabrication of variable stiffness composites (VSCs), a kind of advanced composite materials reinforced by curvilinear fibers, which have been demonstrated with superior global mechanical properties. However, the fracture behaviors, an indispensable factor in the engineering structure design, of the VSC are still unclear due to a lack of research. To fill in the gap, the paper presents a multi-phase-field approach to perform the failure analyses of VSC laminae at mesoscale through which the VSC lamina is modeled as an anisotropic while nonhomogenous brittle material. The proposed model is validated against experimental results of fracture behaviors of single edge cracked and open-hole FRC laminae. Then a systematic investigation of the failure analyses of the pre-cracked and open-hole VSC laminae under different designs is performed. The results reveal that the propagations of cracks are always along with the fiber orientations in notched VSC laminae. In addition, a progressive failure mode demonstrated by the load–displacement curve can be amazingly observed in some designs. Moreover, the guidance in the design of VSCs with discontinuities is also provided based on the modeling results. Our presented fundamental insights in designing the novel fracture-resistant FRCs may promote the application of VSCs in automotive and aerospace structures.

A first known study on the mechanical behavior of laminated CNT-reinforced quadrilateral composite plates due to a sudden transverse dynamic load is performed. In this study, a moderately thick plate is considered; therefore, the first-order shear deformation theory (FSDT) is employed in the formulation. The numerical analysis of the problem is carried out using the IMLS-Ritz method. The Newmark- β method is employed for the numerical time integration of the dynamic problem. The Mori-Tanaka approach is adopted for predicting the properties of CNT-composites. The numerical stabilities and accuracies of the IMLS-Ritz method are examined. The convergence properties are illustrated through solving an isotropic square plate and a laminated CNT-composite quadrilateral plate by varying their node numbers and support sizes. A comprehensive parametric study has been carried out to examine the dynamic behavior of symmetric and asymmetric CNT-composite plates.

We examine the aeroelastic behavior of a cylindrical nanocomposite (i.e. CNT-reinforced composite) shell in a supersonic airflow under thermal environments. Meanwhile, using piezoelectric materials, active flutter control of the cylindrical nanocomposite shell is conducted. Reddy’s high-order shear deformation theory is applied in the structural modeling, and the displacement fields of piezoelectric patches are derived according to the geometrical deformation relationship. The partial differential equation of motion is formulated by way of Hamilton’s principle and then is discretized by the assumed mode method. The active controller is designed by the displacement feedback and linear quadratic regular (LQR) methods. The aerothermoelastic properties of the cylindrical shell are analyzed using the frequency-domain method. The flutter bounds of the cylindrical shell are computed using the third-order shear deformation theory (TSDT), and the first-order shear deformation theory (FSDT) is compared in order to verify the necessity of the high-order shear deformation theory in the vibration analysis of thick nanocomposite structures. The influences of temperature change, CNT distribution and CNT volume fraction on the aeroelastic stability of the nanocomposite cylindrical shell are investigated. The active flutter control effects of different control methods are performed. The influence of thickness of the cylindrical shell on the flutter control effects is examined.

Estimating the quality of an electrical discharge machining (EDM) workpiece is challenging when attempting to extract features from the stochastic and time-consuming processes. To solve this problem, an intelligent sensing unit for EDM (ISU-EDM) is proposed to extract key machining features for estimating workpiece roughness. During machining, the ISU-EDM simultaneously samples the signals of both the discharge current and voltage, while automatically segmenting the signals according to tool location and discharge effectiveness. Furthermore, the machining features could be extracted from the segmented data by a genetic-algorithm-based distribution fitting method. After applying the features to an automated virtual metrology system, experimental results show that the mean absolute percentage error of roughness estimation is less than 15%.

This paper presents the first known mechanical behavior of laminated CNT-reinforced composite skew plates subjected to a transverse sudden dynamic load. The plate is composed of multilayers of nanocomposite reinforced with single-walled carbon nanotubes (SWCNTs). The problem is formulated using the first-order shear deformation theory (FSDT), and solution to the problem is obtained through the element-free IMLS-Ritz method. The elastodynamic behavior is furnished by employing the Newmark-β method. Material properties of CNT-reinforced composites are predicted through the Mori–Tanaka approach. The stability and precision of the IMLS-Ritz method are validated by convergence and comparison studies. The effects of skew angles, width-to-thickness ratio, CNT-volume fraction, CNT-distribution along the layer thickness, CNT-fiber orientation and boundary conditions on the elastodynamic responses of laminated CNT-reinforced composite skew plates are examined.

Additive manufacturing (AM) or 3D printing has been hailed as the third industrial revolution as it has caused a paradigm shift in the way objects have been manufactured. Conventionally, converting a raw material to a fully finished and assembled, usable product comprises several steps which can be eliminated by using this process as functional products can be created directly from the raw material at a fraction of the time originally consumed. Thus, AM has found applications in several sectors including automotive, aerospace, printed electronics, and healthcare. AM is increasingly being used in the healthcare sector, given its potential to fabricate patient-specific customized implants with required accuracy and precision. Implantable heart valves, rib cages, and bones are some of the examples where AM technologies are used. A vast variety of materials including ceramics, metals, polymers, and composites have been processed to fabricate intricate implants using 3D printing. The applications of AM in dentistry include maxillofacial implants, dentures, and other prosthetic aids. It may also be used in surgical training and planning, as anatomical models can be created at ease using AM. This article gives an overview of the AM process and reviews in detail the applications of 3D printing in dentistry. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2058-2064, 2018.

To the best of our knowledge, the available literature investigating the impact analysis of functionally graded carbon nanotube reinforced composite (CNTRC) plates is very limited and missing in the case of utilizing any of the element-free methods. In this paper, a novel element-free IMLS-Ritz model in association with Reddy’s higher-order shear deformation theory is presented to study the impact analysis of CNTRC plates with both uniform and functionally graded carbon nanotubes (CNTs) distributions. The modified non-linear Hertz contact law is used to define the contact force between the CNTRC target plates and the spherical impactor during the impact duration. Newmark time integration method is employed to identify the dynamic response of the CNTRC plates and the impactor displacement. Two Mori–Tanaka methods are utilized to calculate the effective material properties of the composites reinforced with randomly oriented or aligned straight CNTs. The current approach accuracy is validated with the available open literature results showing a clear agreement. Detailed parametric studies are performed to study the effects of CNTs distributions, plate’s width-to-thickness ratio, impactor’s initial velocity, impactor’s radius and CNTs volume fraction on the results. Furthermore, a comparison between the results obtained by the two Mori-Tanka methods is presented.

A first attempt to investigate bending and vibration behaviors of carbon nanotube (CNT) reinforced functionally graded composite skew plates using the isogeometric analysis is performed. The formulation of the plate is based on Reddy’s higher order shear deformation theory (HSDT). The effect of CNT orientation angle on the mechanical behavior of CNT-reinforced composite plates with varying skew angles is investigated. The optimum fiber orientations for CNT-reinforced composite skew plates with simply supported, clamped and cantilevered boundary conditions are found. It is shown that selecting the correct fiber orientation angle is of crucial importance in obtaining the desired static and dynamic responses of CNT-reinforced composite skew plates.

A comprehensive study on elastodynamic behavior of regular polygonal carbon nanotube (CNT) reinforced functionally graded composite plates subjected to a sudden transverse dynamic load is presented in this paper. This analysis uses as its base the first-order shear deformation theory (FSDT) and the element-free IMLS-Ritz method, to conduct a numerical simulation. A numerical time integration for the dynamic problems is performed using the Newmark-β method. Convergence studies are carried out for an isotropic square plate with different support sizes and different numbers of nodes. Parametric studies are further carried out to investigate the effect of four special regular polygons with different CNT volume fractions, CNT distribution types, plate apothem-to-thickness ratios and boundary conditions on the dynamic behaviors of regular polygonal CNT-reinforced composite plates.

This paper presents a first know study of the effect of orientation angle of carbon nanotubes (CNTs), embedded in a single-ply polymer-based CNT-reinforced composite, on buckling behavior of skew plates using an isogeometric analysis. The plate model is based on Reddy’s higher-order shear deformation theory (HSDT). Four in-plane loading conditions together with simply supported and cantilevered boundary conditions have been considered. The optimum CNT fiber orientations for CNT-reinforced composite rhombic plates with varying skew angles and boundary conditions are presented. Moreover, the effect of width-to-thickness ratio on optimum CNT orientation is explored. The results show that the efficiency of the skew plate structures can be significantly improved by simply placing the CNTs in the correct orientation.

Background From December 2019 to February 2020, 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a serious outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China. Related clinical features are needed. Methods We reviewed 69 patients who were hospitalized in Union hospital in Wuhan between 16 January and 29 January 2020. All patients were confirmed to be infected with SARS-CoV-2, and the final date of follow-up was 4 February 2020. Results The median age of 69 enrolled patients was 42.0 years (interquartile range 35.0–62.0), and 32 patients (46%) were men. The most common symptoms were fever (60 [87%]), cough (38 [55%]), and fatigue (29 [42%]). Most patients received antiviral therapy (66 [98.5%] of 67 patients) and antibiotic therapy (66 [98.5%] of 67 patients). As of 4 February 2020, 18 (26.9%) of 67 patients had been discharged, and 5 patients had died, with a mortality rate of 7.5%. According to the lowest SpO2 during admission, cases were divided into the SpO2 ≥ 90% group (n = 55) and the SpO2 < 90% group (n = 14). All 5 deaths occurred in the SpO2 < 90% group. Compared with SpO2 ≥ 90% group, patients of the SpO2 < 90% group were older and showed more comorbidities and higher plasma levels of interleukin (IL) 6, IL10, lactate dehydrogenase, and C reactive protein. Arbidol treatment showed tendency to improve the discharging rate and decrease the mortality rate. Conclusions COVID-19 appears to show frequent fever, dry cough, and increase of inflammatory cytokines, and induced a mortality rate of 7.5%. Older patients or those with underlying comorbidities are at higher risk of death.

Traditional intelligent product design usually focuses on functional design, aiming to generate appropriate structures that would provide required functions. Design specifications are mainly formulized into technical descriptions or values that are related to certain functional or usability requirements. In today’s global market, to in-crease user satisfaction, the appearance design of a product become vital for users to make purchasing decisions. This is particularly true of today’s consumer products such as mobile phones, digital cameras, and other electronic products. In intelligent product appearance design, design specifications are merely described as basic geometric dimensions and types of surface materials. Additionally, the aesthetic considerations and emotional needs of product appearance are seldom discussed when establishing design specifications for product appearance design. In this regard, the objective of this study is to propose a design specification representation framework for intelligent product appearance design considering both emotional and aesthetic aspects. The framework be-gins to investigate user needs by acquiring user aesthetic experience. Based on the notion of aesthetic experience, a detailed representation model of appearance design specifications is provided for satisfying user emotional and aesthetic needs. Finally, a case study of the appearance design of digital cameras is provided to demonstrate the acquisition of user needs and establishment of design specifications based on the proposed framework.