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The clinical utility of Dixon water-fat separation coronary MR angiography (CMRA) with compressed sensing (CS) reconstruction has not been determined in a patient population. This study was designed to evaluate the performance of 3.0 T non-contrast-enhanced Dixon water-fat separation CS whole-heart CMRA sequence in vitro and in vivo.In vitro phantom MRI, we compared key parameters of the SENSE and CS images. And in this prospective in vivo study, from November 2019 to October 2020, 94 participants were recruited for 3.0 T non-contrast-enhanced Dixon water-fat separation CS whole-heart CMRA. The accuracy of CMRA for detecting a ≥ 50% reduction in diameter was determined using X-ray coronary angiography (CA) as the reference method.Compared with SENSE, CS with an appropriate acceleration factor offers both higher SNR/CNR (p0.05) and a shortened acquisition. Fifty-eight patients successfully completed the CMRA and CA. The sensitivity, specificity, positive predictive values, negative predictive values, and accuracy of 3.0 T non-contrast-enhanced Dixon water-fat separation CS whole-heart CMRA according to a patient-based analysis were 96.4%, 66.7%, 73.0%, 95.2% and 81.0%, respectively. The area under the receiver-operator characteristic (ROC) curve (AUC) of 3.0 T non-contrast-enhanced Dixon water-fat separation CS whole-heart CMRA for detecting significant coronary artery stenosis is 0.908, 0.895, and 0.904 in patient-, vessel-, and segment-based analyses respectively.3.0 T non-contrast-enhanced Dixon water-fat separation whole-heart CMRA using appropriate CS is a promising noninvasive and radiation-free technique to detect clinically significant coronary stenosis on patients with suspected CAD.

To develop and validate a radiomics nomogram for differentiating between malignant pulmonary nodules and benign nodules.56 benign and 51 malignant nodules from 96 patients were analyzed using manual segmentation of the T2-fBLADE-TSE, while the nodules signal intensity (SIlesion), lesion muscle ratio (LMR) and nodule size were all measured and recorded. The maximum relevance and minimum redundancy (mRMR) and the least absolute shrinkage and selection operator (LASSO) were used to select nonzero coefficients and develop the model in pulmonary nodules diagnosis. The radiomics nomogram was also developed. The clinical prediction value was determined by the decision curve analysis (DCA).The nodule size, SIlesion and LMR of the benign group were 1.78 ± 0.57 cm, 227.50 ± 81.39 and 2.40 ± 1.27 respectively, in contrast to the 2.00 ± 0.64 cm, 232.87 ± 82.21 and 2.17 ± 0.91, respectively, in the malignant group (P = 0.09, 0.60 and 0.579). A total of 13 radiomics features were retained. The Rad-score of the benign nodules group was lower than that of the malignant nodules group (P0.0010.049, trainingtest set). The AUC of radiomics signature for nodules diagnosis was 0.82 (95% CI, 0.73-0.91) in the training set and 0.71 (95% CI, 0.51-0.90) in the test set. A nomogram, consisting of 13 radiomics features and nodule size, produced good prediction in the training set (AUC, 0.82; 95% CI, 0.73-0.91), which was significantly better than that of T2-based quantitative parameters (AUC, 0.62; 95% CI, 0.50-0.75, P = 0.003). In the test set, the performance of radiomics nomogram (AUC, 0.70; 95% CI, 0.51-0.90) was also better than that of T2-based quantitative parameters (AUC, 0.46; 95% CI, 0.25-0.67) (P = 0.145). The DCA showed that radiomics nomogram and T2-based quantitative parameter had overall net benefits, while the performance of nomogram was better.We constructed and validated a T2-fBLADE-TSE-based radiomics nomogram that can help to differentiate between malignant pulmonary nodules and benign nodules.

Detrimental tumor microenvironment (TME) relies on distorted tumor vasculature for further tumor expansion. Vascular normalization therapy partly improves TME through vessel repairing, while these therapies enter an unbreakable Mobius ring due to each attempt hindered by pro-angiogenic factors from TME, leading to limited duration and extent of vascular normalization. Here, we developed a nanosystem including FLG and MAR/MPA nanodrugs to regulate both tumor vasculature and TME. FLG nanodrugs were constructed by connecting VEGF/VEGFR2 inhibitory low molecular weight heparin and gambogic acid with F3 peptide decoration for directly regulating on vascular endothelial cells and inducing vascular normalization. Meanwhile, MAR/MPA nanodrugs encapsulating CCL5/CCR5 blocker maraviroc were designed to restrict cytokine functions of angiogenesis and TME deterioration, contributing to vasculature repairing and TME reconstruction. Our results demonstrated this combined nanosystem synergistically induced vascular normalization window lasting 9 days and restored vascular permeability and oxygen supply in Panc-1 tumor. Furthermore, in melanoma, our nanosystem achieved immune improvements with increased infiltration of CD4+ and CD8+T cells in a remodeled TME. The two nanodrugs assisting each other in terms of both vascular repairing and TME improvements successfully reversed the vicious crosstalk to a positive one, achieving overall TME remodeling and promoting therapeutic efficiency.

Background The long-term prognostic value of coronary CT angiography (CCTA) in asymptomatic adults with hepatic steatosis (HS) remains unknown. Purpose To evaluate the long-term prognostic value of CCTA in asymptomatic adults with HS. Materials and Methods Between January 2009 and December 2013, consecutive asymptomatic adults who underwent CCTA evaluation and unenhanced abdominal CT were prospectively enrolled. All participants were divided into two groups-with HS and without HS according to abdominal CT results. The primary end point was major adverse cardiovascular events (MACEs), defined as cardiac death, stroke, myocardial infarction, and angina requiring hospitalization. Multivariable Cox regression analysis and Kaplan-Meier analysis were used to compare survival rates. Results One thousand thirteen participants with HS and 1940 participants without HS who completed the follow-up were included (mean age, 66 years ± 10 [standard deviation] [range, 29-90 years]; 1940 men). During a median of 7.2 years of follow-up (interquartile range, 6.3-8.1), MACEs were observed in 96 of 1013 participants with HS (10%), whereas 80 of 1940 participants without HS (4%) had MACEs. In participants with a Coronary Artery Disease Reporting and Data System (CAD-RADS) category of 0, both participants with and without HS had a similar 8.8-year event-free survival rate (99.2% event-free survival rate in participants with HS vs 99.0% event-free survival rate in participants without HS, P = .77). As for participants with CAD-RADS categories 1 or 2 or 3-5, the 8.8-year event-free survival rate was lower in participants with HS than in those without HS (70.6% vs 85.2%, P < .001; 51.4% vs 71.7%, P = .03, respectively). The risk of MACEs was higher for participants with HS than for those without HS in CAD-RADS categories 1 and 2 (adjusted hazard ratio = 2.3; 95% CI: 1.4, 3.9; P < .001) and CAD-RADS categories 3-5 (adjusted HR = 2.1; 95% CI: 1.2, 3.6; P = .006) but not in the setting of CAD-RADS category 0 (adjusted HR = 5.1; 95% CI: 0.1, 398; P = .47). Conclusion Asymptomatic participants with hepatic steatosis (HS) had a worse prognosis than those without HS in the presence of coronary artery disease (CAD) at coronary CT angiography, whereas participants with HS and without CAD might have excellent clinical outcomes during a median follow-up of 7.2 years. © RSNA, 2021 Online supplemental material is available for this article.

Background Artificial intelligence can assist in cardiac image interpretation. Here, we achieved a substantial reduction in time required to read a cardiovascular magnetic resonance (CMR) study to estimate left atrial volume without compromising accuracy or reliability. Rather than deploying a fully automatic black-box, we propose to incorporate the automated LA volumetry into a human-centric interactive image-analysis process. Methods and results Atri-U, an automated data analysis pipeline for long-axis cardiac cine images, computes the atrial volume by: (i) detecting the end-systolic frame, (ii) outlining the endocardial borders of the LA, (iii) localizing the mitral annular hinge points and constructing the longitudinal atrial diameters, equivalent to the usual workup done by clinicians. In every step human interaction is possible, such that the results provided by the algorithm can be accepted, corrected, or re-done from scratch. Atri-U was trained and evaluated retrospectively on a sample of 300 patients and then applied to a consecutive clinical sample of 150 patients with various heart conditions. The agreement of the indexed LA volume between Atri-U and two experts was similar to the inter-rater agreement between clinicians (average overestimation of 0.8 mL/m2 with upper and lower limits of agreement of − 7.5 and 5.8 mL/m2, respectively). An expert cardiologist blinded to the origin of the annotations rated the outputs produced by Atri-U as acceptable in 97% of cases for step (i), 94% for step (ii) and 95% for step (iii), which was slightly lower than the acceptance rate of the outputs produced by a human expert radiologist in the same cases (92%, 100% and 100%, respectively). The assistance of Atri-U lead to an expected reduction in reading time of 66%—from 105 to 34 s, in our in-house clinical setting. Conclusions Our proposal enables automated calculation of the maximum LA volume approaching human accuracy and precision. The optional user interaction is possible at each processing step. As such, the assisted process sped up the routine CMR workflow by providing accurate, precise, and validated measurement results.

PURPOSE Strict clinical criteria used by Medicare for germline testing for Lynch syndrome (LS) could lead to missed diagnoses of hereditary cancer syndromes given variable individual and family phenotypes. The aim of this study was to compare rates and spectrum of pathogenic or likely pathogenic (P/LP) variants in LS and other hereditary cancer genes on the basis of meeting Medicare LS testing criteria. METHODS Retrospective review of Medicare beneficiaries who had multigene panel testing with an indication of personal or family history of colorectal cancer (CRC) was performed. Ordering providers determined if Medicare LS criteria were met. The results of genetic testing were compared on the basis of whether or not Medicare testing criteria were met. RESULTS Among 639 Medicare beneficiaries, 495 (77.5%) met testing criteria. Overall rates of P/LP variant identification were similar between those meeting and not meeting testing criteria (18.4% v 11.8%; P = .06). LS was diagnosed more frequently among those meeting testing criteria (10.1% v 4.9%; P = .05). No statistical differences were found in rates of P/LP variant identification for non-LS CRC genes (5.3% v 5.6%; P = .89) or non-CRC genes (4.2% v 2.1%; P = .23). PMS2, MUTYH, and ATM P/LP variants were found at higher rates among those outside of criteria. CONCLUSION Among Medicare beneficiaries undergoing genetic testing for suspected LS, rates of P/LP variants in actionable cancer genes were similar regardless of whether testing criteria were met. Current testing criteria fail to identify individuals with P/LP variants in PMS2 and other actionable cancer genes. Relaxing LS testing criteria could improve identification of individuals with hereditary cancer syndromes among Medicare beneficiaries.

Objective: Based on the data mining method, explore the medication rules of Chinese patent medicines for the treatment of digestive system tumors. Method: Based on the "Chinese Traditional Medicine Prescription Database" in https://db.yaozh.com/, collect Chinese patent medicines for the treatment of digestive system tumors, establish an Excel table, and use the ancient and modern medical case cloud platform (V2.2.1) to perform frequency statistics, association rules, and drugs on the data Clustering and complex network analysis. Results: A total of 36 Chinese patent medicines for the treatment of digestive system tumors were screened. The medicinal properties were mainly warm and cold, the taste was bitter and sweet, and the meridians were mainly liver and spleen meridians. High frequency Chinese medicine include Astragalus, Scutellaria-barbata, Ginseng, Curcuma, Triangle, Atractylodes, Hedyotis diffusa, etc. Correlation analysis obtained 17 drug combinations, High-frequency drug pairs include Scutellaria-barbata-Astragalus, Ginseng-Astragalus, Curcuma-Astragalus, Scutellaria-barbata-Curcuma, etc. Cluster analysis found 3 types of drugs. The core drug network is composed of 27 drugs, and the core compatibility network consists of 3 groups of drugs. Conclusion: The Chinese patent compound medicine for the treatment of digestive system tumors has the characteristics of combining cold and warming, replenishing and reducing treatment, and treating the liver and spleen at the same time. The medicine is mainly used to replenish qi and invigorate the spleen, promote blood circulation and remove blood stasis, and clear away heat and detoxification. Replenish qi, nourish yin, invigorate blood, and detoxify are mainly compatible with each other, reflecting the pathogenesis characteristics of "deficiency, stasis, and toxin" in digestive system tumors. Data mining can provide references for the prescription and compatibility of Chinese patent medicines.

Objective: This study aims to identify key genes and pathways associated with the molecular biological mechanisms of major depressive disorder through bioinformatics analysis in the Gene Expression Omnibus (GEO) public database of the National Center for Biotechnology Information (NCBI) website. Methods: The whole-transcriptome brain expression profile dataset (GSE101521) was obtained from the GEO database. Differentially-expressed genes (DEGs) in normal group (non-psychiatric human) and MDD group (depressive patients) were identified applying Networkanalyst online database. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to function annotation and enrichment analysis. After that, STRING online database was conducted to protein–protein interaction (PPI) network, and Cytoscape.3.7.2 software was performed to module analysis. Results: Out of the 41 DEGs identified from normal tissue samples and MDD, 39 were upregulated and 2 were downregulated. GO enrichment analysis discovered that DEGs were primarily involved in inflammatory response, and KEGG pathway analysis suggested that the most chiefly pathway related to MDD were IL-17 signaling pathway, TNF signaling pathway and NOD-like receptor signaling pathway. Six hub genes (IL6, CXCL8, IL1B, FOS, CCL2 and CXCL2) were identified by PPI network and module analysis. Conclusion: Our current study detected novel markers and targets involved immune system, which are involved in pivotal biological mechanisms related to the pathogenesis of major depression. Looking forward, these findings still need to be validated in future experimental studies.

There are around 300 million adolescent pregnancies worldwide, accounting for 11% of all births worldwide. Accumulating evidence demonstrates that many adverse perinatal outcomes are associated with adolescent pregnancies. However, how and why these abnormalities occur remain to be defined. In this study, pregnancy at different stages was compared between 25- and 30- day-old and mature female mice. We found that the litter size of adolescent pregnancy is significantly decreased from F1 to F3 generations compared to mature pregnancy. On days 8 and 12 of pregnancy, multiple abnormalities in decidual and placental development appear in F3 adolescent pregnancy. On days 5 and 8, uterine endoplasmic reticulum stress is dysregulated in F3 adolescent pregnancy. Embryo implantation and decidualization are also compromised in adolescent pregnancy. Many genes are abnormally expressed in adolescent estrous uteri. The abnormal endocrine environment and abnormal implantation from uterine immaturity may result in multiple pregnancy failures in adolescent pregnancy. The aim of this study is to shed light on human adolescent pregnancy.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by pulmonary microvascular endothelial barrier dysfunction. Mesenchymal stem cell-secreted hepatocyte growth factor (HGF) has positive effects of lipopolysaccharide- (LPS-) induced pulmonary endothelial barrier. Studies have exhibited the mammalian TORC1 (mTORC1) signaling is of potent angiogenesis effects. The mTOR protein kinase has two distinct multiprotein complexes mTORC1 and mTORC2 that regulate different branches of the mTOR network. However, detailed mTORC2 mechanisms of HGF protective effects remain poorly defined. Therefore, the aim of this study was to determine whether mTORC2 mediated protective effects of MSC-secreted HGF against LPS-induced pulmonary microvascular endothelial barrier dysfunction activated like mTORC1 activation. We introduced MSC-PMVEC coculture transwell system and recombinant murine HGF on LPS-induced endothelial cell barrier dysfunction in vitro and then explored potential mechanisms by lentivirus vector-mediated HGF, mTORC1 (raptor), and mTORC2 (rictor) gene knockdown modification. Endothelial paracellular and transcellular permeability, adherent junction protein (VE-Cadherin), cell proliferation, apoptosis, and mTOR-associated proteins were tested. These revealed that HGF could promote quick reestablishment of adherent junction VE-cadherin and decrease endothelial paracellular and transcellular permeability during LSP-induced endothelial dysfunction with the involvement of mTORC2 (rictor) and mTORC1 (raptor) pathways. Raptor and rictor knockdown in LPS-induced PMEVECs with stimulation of HGF increased apoptosis ratio, activated Cleaved-Caspase-3 expression, and downregulated cell proliferation. Moreover, mTORC2/Akt but not mTORC2/PKC had significance on HGF endothelial protective effects. Taken together, these highlight activation mTORC2 pathway could also contribute to vascular endothelial barrier recovery by MSC-secreted HGF in LPS stimulation.

Background To test the advantages of positron emission tomography and computed tomography (PET/CT) for diagnosing lymph nodes and staging nasopharyngeal carcinoma and to investigate its benefits for survival and treatment decisions. Methods The performance of PET/CT and magnetic resonance imaging (MRI) in diagnosis was compared based on 460 biopsied lymph nodes. Using the propensity matching method, survival differences of T3N1M0 patients with (n = 1093) and without (n = 1377) PET/CT were compared in diverse manners. A radiologic score model was developed and tested in a subset of T3N1M0 patients. Results PET/CT performed better than MRI with higher sensitivity, accuracy, and area under the receiver operating characteristic curve (96.7% vs. 88.5%, p p p p p = 0.006) for the high-risk patients selected by the model but not for those without risk stratification (p = 0.78). Conclusion PET/CT showed advantages in staging nasopharyngeal carcinoma due to a more accurate diagnosis of lymph nodes and this contributed to a survival benefit. PET/CT combined with MRI provided prognostic factors that could identify high-risk patients and guide individualized treatment.

Jia Liu,1,&ast; Jun-Fei Zhang,2,&ast; Han-Ning Ma,2 Ke Feng,2 Zhong-Wei Chen,2 Li-Shan Yang,2 Bin Mei,3 Jun-Jian Zhang4 1Medical Experimental Center, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750000, People’s Republic of China; 2Department of Emergency Medical, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750000, People’s Republic of China; 3Department of Social Medical Development, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China; 4Department of Neurology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhong-Wei Chen; Li-Shan Yang Email 13995390007@163.com; nyfyyls@126.comObjective: Information regarding the epidemiology and clinical features of mild to moderate patients caused by COVID-19 in Fangcang Hospital is scarce. Through a retrospective cohort study, the clinical characteristics of COVID-19 patients in Dongxihu Fangcang shelter hospitals were analyzed, and the factors that affected the disease progression of COVID-19 patients were explored.Methods: The clinical characteristics of 714 patients with COVID-19 were retrospectively analyzed at Dongxihu Fangcang Hospital between February 7 and March 8, 2020. We described the clinical characteristics and distribution of discharge or transfer times for each patient. According to the disease progression of COVID-19 patients, we divided all patients into Non-Deteriorated group and Deteriorated group. Furthermore, binary logistic regression was used for a single outcome and multiple response variables.Results: We treated 789 patients with mild and moderate COVID-19, of which 714 were included in this study, which included 326 (45.66%) deteriorated patients and 388 (54.34%) non-deteriorated patients. The mean age of the study population was 48.16± 12.44 years. Of all patients, 319 (44.7%) were men and 395 (55.3%) were women. The average length of the patient’s stay was 16.08± 5.13 days. The most common clinical feature on admission was fever (593 of 714, 83.05%). It is worth noting that 80 (11.20%) of the 714 patients were asymptomatic from exposure to admission. Multivariate logistic regression analysis showed that gender, age, diabetes, respiratory system disease, fever, dyspnea, and nasal congestion were risk factors associated with deterioration in cases with COVID-19 patients, and asymptomatic (OR: 0.058; 95% CI: 0.022– 0.155; P< 0.001) was the protective factor for deterioration of COVID-19 patients.Conclusion: Accompanied by chronic diseases, old age, fever, nasal congestion, and dyspnea were factors that influenced the aggravation of COVID-19 patients, and more attention and treatment should be given to these patients.Keywords: clinical characteristics, mild to moderate, makeshift (fangcang) hospital, influence factors

Pei Shan Yang,1,2 Sophia Delpe,2 Casey G Kowalik,2 W Stuart Reynolds,2 Melissa R Kaufman,2 Roger R Dmochowski2 1Department of Urologic Surgery, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan; 2Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN, USACorrespondence: Pei Shan YangDepartment of Urologic Surgery, Chang Gung Memorial Hospital and Chang Gung University, No. 5, Fuxing Street, Guishan District, Taoyuan, 333, TaiwanTel +886 328-1200Email dr.yang.uro@gmail.comIntroduction: Pubovaginal sling is an efficient and safe procedure for stress urinary incontinence without the complications of synthetic sling. Urine retention and de novo urgency are bothersome aftermath of this procedure. We aim to identify potential risk factors for de novo urgency after autologous pubovaginal sling.Methods: From 2013 to 2016, 347 patients underwent autologous pubovaginal sling. Age, BMI, pelvic irradiation, use of anticholinergic medication, previous vaginal related surgical histories, “over-tight” technique, and concomitant surgeries were examined for potential risk factors. De novo urgency/urge incontinence was defined as treatment (medication, botulinum toxin injection, sacral neuromodulation) for urge postoperatively and was not noted before surgery. Chi-square and fisher’s exact tests were used as statistical analysis.Results: A total of 109 patients underwent autologous rectus fascia pubovaginal sling, after excluding status post urethral diverticulectomy, concomitant diverticulectomy, and concomitant abdominal surgery. Twenty-three (21.1%) patients were treated for de novo urge/urge incontinence, 18 (78.2%) with anticholinergic, 4 (17.3%) with botox injection and 2 (8.69%) with sacral neuromodulation. None but prior pelvic organ prolapse surgery was associated with developing de novo urge/urge incontinence (p=0.026).Discussion: Patients with prior pelvic organ prolapse surgery were more likely to be at risk of de novo urgency after autologous pubovaginal sling. This study provided more information for preoperative consultation for patients undergoing incontinence surgery.Keywords: autologous fascial sling, de novo urgency, stress urinary incontinence, urge urinary incontinence

Summary Most rare clinical missense variants cannot currently be classified as pathogenic or benign. Deficiency in human 5,10-methylenetetrahydrofolate reductase (MTHFR), the most common inherited disorder of folate metabolism, is caused primarily by rare missense variants. Further complicating variant interpretation, variant impacts often depend on environment. An important example of this phenomenon is the MTHFR variant p.Ala222Val (c.665C>T), which is carried by half of all humans and has a phenotypic impact that depends on dietary folate. Here we describe the results of 98,336 variant functional-impact assays, covering nearly all possible MTHFR amino acid substitutions in four folinate environments, each in the presence and absence of p.Ala222Val. The resulting atlas of MTHFR variant effects reveals many complex dependencies on both folinate and p.Ala222Val. MTHFR atlas scores can distinguish pathogenic from benign variants and, among individuals with severe MTHFR deficiency, correlate with age of disease onset. Providing a powerful tool for understanding structure-function relationships, the atlas suggests a role for a disordered loop in retaining cofactor at the active site and identifies variants that enable escape of inhibition by S-adenosylmethionine. Thus, a model based on eight MTHFR variant effect maps illustrates how shifting landscapes of environment- and genetic-background-dependent missense variation can inform our clinical, structural, and functional understanding of MTHFR deficiency.

MicroRNA-221 (miRNA-221) is upregulated in several malignant tumors and is associated with poor patient prognosis. Therefore, the present study aimed to investigate the role and underlying mechanism of miRNA-221 in doxorubicin (DOX) resistance in osteosarcoma cells. We constructed DOX-resistant Saos-2/DOX cells and treated them with DOX. Cell viability was determined by performing a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cells were transfected with either miRNA-221 mimic or miRNA-221 inhibitor; quantitative (q)RT-PCR was performed to detect the expression of miRNA-221. Flow cytometry and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick-end labeling (TUNEL) staining were used to detect cell apoptosis. The immunofluorescence method was also used to detect cell signal transduction and activator of transcription 3 (Stat3) protein expression distribution. In addition, Western blotting was used to detect changes in the expression of each protein. We found that miRNA-221 was upregulated in Saos-2/DOX cells. Moreover, the miRNA-221 mimic induced DOX resistance in Saos-2 cells, whereas the miRNA-221 inhibitor enhanced DOX sensitivity in Saos-2/DOX cells. The miRNA-221 mimic upregulated the expression of phosphorylated-Stat3, P-glycoprotein (P-gp), and B-cell lymphoma-2 (Bcl-2) proteins in Saos-2 cells and induced the entry of Stat3 into the nucleus, whereas the miRNA-221 inhibitor exerted the opposite effect. Pretreatment with the Stat3 chemical inhibitor, STAT3-IN-3, significantly inhibited the upregulation of P-gp and Bcl-2 protein expression induced by the miRNA-221 mimic in Saos-2 cells; it also caused the Saos-2 cells to overcome DOX resistance induced by the miRNA-221 mimic. Thus, miRNA-221 increased the expression of P-gp and Bcl-2 by activating the Stat3 pathway to promote DOX resistance in osteosarcoma cells, indicating a potential use of miRNA-221 in osteosarcoma treatment.

Urea/1-ethyl-3-methylimidazolium chloride (urea-EMIC) was developed to electrodeposit Cu from Cu2O at room temperature. Density, viscosity and conductivity of this urea-EMIC system were obtained. The cyclic voltammograms illustrated that the electroreduction of copper ion (Cu(I) ion) involves a quasi-reversible and one-step single electron transfer process. Chronoamperometric studies showed that the copper electrodeposition proceeds a three-dimensional (3D) progressive model. With an increase in temperature, on voltammograms the onset potentials for copper ion reduction shifted anodically and the diffusion coefficient determined using chronoamperometry increased from 5.40 × 10−11 m2 s−1 at 333 K to 1.02 × 10−10 m2 s−1 at 363 K. Also, potentiostatic electrolysis was conducted on tungsten substrates at − 0.65 V (vs. Ag) and 363 K. Then spherical metallic copper electrodeposits were obtained.

Background: Increased IL-6 level, M2 macrophages and PD-1+CD8+ T cells in tumor microenvironments (TME) have been identified to correlate with resistance to checkpoint blockade immunotherapy, yet the mechanism remains poorly understood. Rab small GTPase-mediated trafficking of cytokines is critical in immuno-modulation. We have previously reported dysregulation of Rab37 in lung cancer cells, whereas the roles of Rab37 in tumor-infiltrating immune cells and cancer immunotherapy are unclear. Methods: The tumor growth of the syngeneic mouse allograft in wild type or Rab37 knockout mice was analyzed. Imaging analyses and vesicle isolation were conducted to determine Rab37-mediated IL-6 secretion. STAT3 binding sites at PD-1 promoter in T cells were identified by chromatin immunoprecipitation assay. Multiplex fluorescence immunohistochemistry was performed to detect the protein level of Rab37, IL-6 and PD-1 and localization of the tumor-infiltrating immune cells in allografts from mice or tumor specimens from lung cancer patients. Results: We revealed that Rab37 regulates the secretion of IL-6 in a GTPase-dependent manner in macrophages to trigger M2 polarization. Macrophage-derived IL-6 promotes STAT3-dependent PD-1 mRNA expression in CD8+ T cells. Clinically, tumors with high stromal Rab37 and IL-6 expression coincide with tumor infiltrating M2-macrophages and PD1+CD8+ T cells that predicts poor prognosis in lung cancer patients. In addition, lung cancer patients with an increase in plasma IL-6 level are found to be associated with immunotherapeutic resistance. Importantly, combined blockade of IL-6 and CTLA-4 improves survival of tumor-bearing mice by reducing infiltration of PD1+CD8+ T cells and M2 macrophages in TME. Conclusions: Rab37/IL-6 trafficking pathway links with IL-6/STAT3/PD-1 transcription regulation to foster an immunosuppressive TME and combined IL-6/CTLA-4 blockade therapy exerts potent anti-tumor efficacy.

Objective:Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been discovered in Wuhan and spread rapidly across China and worldwide. Characteristics of infected patients are needed to get insight into the full spectrum of the disease.Methods:Epidemiological and clinical information of 1738 diagnosed patients during February 7-26, 2020 in Wuhan Dongxihu Fangcang Hospital were analyzed. A total of 709 patients were followed up on symptom, mental health, isolation site, and medication after discharge.Results:There were 852 males and 886 females in the cohort. The average age of the patients was 48.8 y. A total of 79.98% of the patients were from Wuhan, Hubei Province. The most common initial symptoms were fever, cough, and shortness of breath. Among all the patients, 1463 had complications, with respiratory distress as the most common complication. The average duration of hospitalization was 15.95 ± 14.69 d. The most common postdischarge symptom is cough. After discharge, most patients were full of energy and chose hotel as their self-isolation site. Coronavirus disease 2019 (COVID-19) Chinese medicine No.2 prescription is the medication used most commonly by the patients after discharge.Conclusions:The population is generally susceptible to SARS-CoV-2. After receiving aggressive treatment of combined Chinese and Western medicine, most patients had a good prognosis and mental health after discharge.

This article presents a digital ultraviolet (UV) beam lithography system for fabricating microstructures of arbitrary patterns on a roller mold. This roller mold can then be used in roller imprinting for fast and large-area replication of microstructures on substrates. This digital optomechanical system consists of a UV light source, a digital micromirror device (DMD) and its electronic controller, a high-precision image lens, a fiber array integrated with microlenses on both ends, and a two-axis ( x – θ ) servo-controlled motion stage. It exposes a photoresist (PR) layer coated on the cylindrical surface of a roller with a linear array of 192 small UV spots focused by a microlens/fiber array. On the other end of the fibers, UV light is fed by DMD's micromirrors so that the UV light can be dynamically modulated. Finally, by synchronizing the electronics of DMD chip and the mechanical movement (rotation and translation) of the roller, one can achieve arbitrary UV patterning on the roller's PR layer in a digital and maskless manner. This system can successfully achieve UV patterning with a smallest linewidth of 8 μ m, a pattern resolution of 2.5 μ m, and a total patterning width of 192 mm on a roller with a diameter of 100 mm.

Background and Purpose As magnetic resonance imaging (MRI) signs of normal pressure hydrocephalus (NPH) may precede clinical symptoms we sought to evaluate an algorithm that automatically detects this pattern. Methods A support vector machine (SVM) was trained in 30 NPH patients treated with ventriculoperitoneal shunts and 30 healthy controls. For comparison, four neuroradiologists visually assessed sagittal MPRAGE images and graded them as no NPH pattern, possible NPH pattern, or definite NPH pattern. Results Human accuracy to visually detect a NPH was between 0.85 and 0.97. Interobserver agreement was substantial (κ = 0.656). Accuracy of the SVM algorithm was 0.93 and AUROC 0.99. Among 272 prespecified regions, gray matter and CSF volumes of both caudate, the right parietal operculum, the left basal forebrain, and the 4th ventricle showed the highest discriminative power to separate a NPH and a no NPH pattern. Conclusion A NPH pattern can be reliably detected using a support vector machine (SVM). Its role in the work-up of asymptomatic patients or neurodegenerative disease has to be evaluated.

Increasing circRNAs have attracted a lot of attention because of their significant biological effects in many diseases. It has been reported that circ_0008305 can modulate lung cancer progression. However, the association between circ_0008305 and hepatocellular carcinoma (HCC) needs to be well explored. In this current research, we studied the molecular function and potential mechanism of circ_0008305 in HCC progression. First, it was demonstrated that circ_0008305 was greatly increased in HCC tissues and cells. Moreover, we observed silencing circ_0008305 markedly repressed HCC cells in vitro growth and reduced tumor growth in vivo. Additionally, it was identified that circ_0008305 can act as a sponge of miR‐660 while miR‐660 targeted Bcl‐2‐associated athanogene 5 (BAG5). BAG5 belongs to a member of BAG family and it is involved in multiple diseases. We reported that circ_0008305 contributed to the inhibition of miR‐660, which resulted in an upregulated expression of BAG5 in HCC. Subsequently, rescue assays were conducted and it was indicated that loss of BAG5 reversed the effects of miR‐660 inhibitors on HCC partially. To sum up, it was illustrated by our study that circ_0008305‐mediated miR‐660‐5p/BAG5 axis triggered HCC progression, which could provide a novel insight on the underlying mechanism of HCC progression., circ_0008305 was greatly increased in HCC tissues and cells. circ_0008305 can act as a sponge of miR‐660. miR‐660 targeted Bcl‐2‐associated athanogene 5 (BAG5).

Jun-Fei Zhang,1,* Jia Liu,2,* Han-Ning Ma,1 Ke Feng,1 Zhong-Wei Chen,1 Li-Shan Yang,1 Bin Mei,3 Jun-Jian Zhang4 1Department of Emergency Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750000, People’s Republic of China; 2Medical Experiment Center, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750000, People’s Republic of China; 3Department of Social Medical Development, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, People’s Republic of China; 4Department of Neurology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhong-Wei Chen; Li-Shan Yang Email 13995390007@163.com; nyfyyls@126.comRationale: Currently, the “gold standard” is real-time reverse transcriptase–polymerase chain reaction (RT-PCR) amplification of the viral DNA for diagnosis of COVID-19 infection. However, early reports of test performance in the Wuhan outbreak showed variable sensitivities. Therefore, the simple use of RT-PCR as a discharge standard for COVID-19 patients may be risky. Early discussions suggested that CT should be the preferred modality for the diagnosis of COVID-19. However, the use of CT for COVID-19 discharge is controversial. In the Fangcang hospital, we performed multiple nucleic acid tests and chest CT examinations in all patients. For discharged patients, we performed multiple nucleic acid tests and chest CT scans on the basis of discharge standards to minimize the incidence of false negatives in nucleic acid tests.Patient Concerns: Two 42-year-old male patients with mild to moderate COVID-19 were treated in the Fangcang Hospital According to the treatment, one patient was cured and discharged, while the other patient was sent to a higher-level hospital for further treatment.Diagnoses: Real-time reverse transcriptase–polymerase chain reaction amplification of the viral DNA for diagnosis of COVID-19 infection.Interventions: The patients received Chinese medicine and antiviral treatment in the Fangcang Hospital.Outcomes: At follow-up, both patients were cured after treatment and returned to normal life after 2 weeks of home isolation and a negative nucleic acid test.Lessons: The use of nucleic acid testing combined with chest CT examination can quickly diagnose patients with COVID-19 infection and evaluate their treatment in the Fangcang Hospital.Keywords: case report, COVID-19, CT, Fangcang Hospital

Background: Huangqi Guizhi Wuwu decoction (HQGZWW) exhibits good effects when administered to treat multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Understanding the precise mechanism of this decoction is thus important. Based on the findings of our previous study, the aim of the present study was to understand the role of antigen-specific CD8+ T-cells on the pathogenesis of MS/EAE when HQGZWW is administered as treatment. Methods: Myelin oligodendrocyte glycoprotein (MOG) 35-55-induced mice were administered distilled water, prednisone, and high dose or low dose HQGZWW. After purified CD4+ and CD8+ T-cells were stimulated with the MOG35-55 peptide, proliferation and cytokine secretion assays were performed. To establish the adoptive transfer EAE model, naive mice were injected with MOG35-55 -CD8+ or CD4+ T-cells. Results: Significant improvements in EAE score and pathology were observed in the high dose HQGZWW and prednisone groups. Compared to the low dose HQGZWW and distilled water groups, lower antigen-specific responses, lower levels of interferon-gamma, and higher levels of interleukin (IL)-4 and IL-10 from CD8+ and CD4+ T cells were observed in the high dose HQGZWW and prednisone groups. Finally, the EAE score was observed to be similar between the high dose HQGZWW group and prednisone group; however, this finding was not observed in the low dose HQGZWW group. Conclusion: Our findings suggest that high dose HQGZWW has similar effects on cell proliferation, cytokine secretion, and EAE score to prednisone, while low dose HQGZWW does not have such effect. The protective role of HQGZWW against EAE might thus depend on the Th2 cytokine secretion profile induced by either MOG35-55 specific CD8+ or CD4+ T-cells.

The failure to treat and control the growth of metastases is the main cause of death in breast cancer (BC) patients. Compared to the traditional method of analyzing circulating tumor DNA (ctDNA), capturing intact circulating tumor cells (CTCs) allows us to more accurately characterize mutations and identify suitable targeted therapies. We used CellCollector to collect peripheral CTCs. Thirty metastatic breast cancer (MBC) patients were enrolled, and 17 were analyzed with next-generation sequencing (NGS) methods. Clinical characteristics were analyzed along with the CTCs enumeration and detection rates. Whole-genome amplification (WGA) was used to amplify the CTC genomic DNA of 127 genes. Patients younger than 45 years old, with brain metastasis, with three or more metastatic sites, or with HER2-positive had the highest number of CTCs collected. The CTCs detection rate was also correlated to the number of metastasis sites. Different metastasis sites such as the brain, viscus, bone, and soft tissue contained specific high-frequency gene mutations. AKT3, MYC, and NT5C2 mutations were only found in brain metastases. APC, BCL2L11, ESRP1, FLT3 mutations were only in the visceral metastases. KEAP1, KIT, MET were the specific mutation genes in patients with bone and soft tissue metastases. These findings provide evidence that we can detect gene mutation information for obtaining the biological characteristics by CTCs using CellCollector. Different metastasis sites contain specific high-frequency mutation genes, which provide guidance to the accurate gene therapy.