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Background The insidious nature of BCG-osteomyelitis makes it challenging for clinicians to detect it early on. Methods This 12-year retrospective analysis was conducted at a single tertiary hospital in central Taiwan. Electronic medical records of pediatric patients treated for BCG-osteomyelitis were reviewed. Demographics, clinical features, and laboratory findings were compared with patients diagnosed with culture-proven pyogenic osteomyelitis. Results In total, eight patients fulfilled our inclusion criteria. Their median age was 16 months, and no obvious gender prevalence was found. Six of the eight patients had lesions involving the lower extremities. When compared with the pyogenic osteomyelitis group, age of disease onset was found to be significantly younger in the BCG osteomyelitis group (p=0.038). Absence of fever and pain in the BCG osteomyelitis group was found to be statistically significant when compared with the pyogenic group (p=0.002 and p=0.026 respectively). CRP and ESR were found to be significantly higher in the pyogenic osteomyelitis group (p=0.000 and p=0.004 respectively). Conclusion BCG-related osteomyelitis must be considered when evaluating an afebrile child presenting with an unexplainable swelling or limp, and especially when the lesion is located on a lower limb. Laboratory studies may reveal normal WBC and CRP, with a normal to modest elevation of ESR. Imaging studies, including plain radiographs, magnetic resonance imaging (MRI), or computed tomography (CT) should be employed to rule out BCG-related osteomyelitis. Early diagnosis help minimize inappropriate antibiotics use, and may lead to a better outcome.

Background The causative pathogen of pediatric osteomyelitis is often unidentified despite culturing attempts. This study evaluated and compared the clinical characteristics, therapeutic approach, and outcomes of osteomyelitis caused by unknown pathogens and identified microorganisms. Method This 17-year retrospective study was conducted at a tertiary hospital in central Taiwan. Medical records of children aged less than 18 years with a diagnosis of osteomyelitis between 2003 and 2019 were reviewed. Result In total, 70 patients (median age = 6.4 years; male = 65.7%) fulfilled the inclusion criteria, of whom 33 (47.1%) were culture negative. Staphylococcus aureus was the main pathogen (67.6% of identified bacteria). The proportion of methicillin-resistant S. aureus (MRSA) was 44% and 54.5% of the MRSA isolates exhibited clindamycin resistance. Compared to children with culture-positive osteomyelitis, those with culture-negative osteomyelitis had a lower rate of concomitant septic arthritis (40.5% vs. 15.2%, p = 0.019) and leukocytosis on presentation (45.9% vs. 21.2%, p = 0.030); they also required fewer surgical interventions (56.8% vs. 24.2%, p = 0.006) and received a shorter course of total antibiotic therapy (49.0 vs. 43.0 days, p = 0.045). In the culture-negative group, the MRSA coverage rate was 18.8% during initial empirical therapy and increased to 59.4% during further adjusted therapy. The overall complication rate was 18.6% and was lower in the culture-negative group (32.4% vs. 3.0%, p = 0.002). Conclusion In areas where community-associated MRSA and clindamycin resistance strains are a concern, empirical glycopeptide-based therapy is suggested in pediatric osteomyelitis, particularly in those with culture-negative infections.

Drawing from models of successful psychopathy, self-determination theory, and personality theory, we investigated how the facets of the triarchic model of psychopathy are related to subjective well-being. We hypothesized that boldness was positively while meanness and disinhibition were negatively related to subjective well-being. We further hypothesized boldness as a protective factor that tempers negative effects of meanness. Participants, enrolled in part-time university courses for working adults in Singapore, provided self-ratings on the psychopathy facets (at Time 1) and on their job satisfaction, life satisfaction, positive affect, and negative affect (at Time 2). Hierarchical moderated regression analyses were used to test the hypotheses. Findings generally supported the hypotheses, demonstrating the differential contribution of the psychopathy facets to subjective well-being and highlighting the role of boldness as a protective factor in successful psychopathy. Practical implications for counselors and organizational decision makers are discussed.

A novel Egeria najas driven-biochar was activated by loading ferric chloride onto surface (FeCl3@EN-BC). The synthesized composite was evaluated for its physicochemical properties and Cr(VI) adsorption behavior and mechanism. The result of SEM showed that the modified biochar is less porous than raw Egeria najas biochar, but loaded with γ-Fe2O3 and Fe3O4 crystals. In addition, the results of FTIR, XRD and XPS also confirmed that Fe was successfully loaded on the Egeria najas biochar. Cr(VI) was efficiently removed by FeCl3@EN-BC within the pH range from 2.5–8.5. The thermodynamics parameters suggested that the adsorption processes of Cr(VI) were all spontaneous and endothermic. The overall removal mechanism was regarded as adsorption, surface complex formation, reduction and ion exchange reaction. Therefore, this modified biochar derived from Egeria najas has a potential of practical application in the removal of Cr(VI) from wastewater.

Tao Li,1,2 Kai Sen Tan,2– 5 Yan Yi Tu,1,2 Li Zhao,6 Jing Liu,2,3 Hsiao Hui Ong,2,3 De Yun Wang,2,3 Li Shi1 1Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 2Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; 3National University Health System Infectious Diseases Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; 4Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; 5Biosafety level 3 Core Facility, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore, Singapore; 6Department of Otolaryngology, The Second Hospital of Shandong University, Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Li ShiDepartment of Otolaryngology, Shandong Provincial ENT Hospital, Cheeloo College of Medicine, Shandong University, Duanxing West Road, Jinan, Shandong, 250033, People’s Republic of ChinaTel +86 531 83086279Fax +86 531 87980304Email shili126@sina.comDe Yun WangDepartment of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, Singapore, 119228 Tel +65 67725373Fax +65 67753820Email entwdy@nus.edu.sgBackground: Nasal inverted papilloma (NIP) is defined based on its histological characteristic of inverted epithelium growth into the stroma. The inversion can result in epithelial growth in the underlying connective tissue stroma when the basement membrane completely separates from the epithelial layer. To date, such inversion mechanism underlying NIP’s pathological phenomenon is unknown. Therefore, we hypothesized that mediators and soluble proteins released by neutrophils, the most predominant infiltrating cells in NIP, is vital in causing the epithelial changes and pathogenesis of NIP.Methods: We collected 37 NIP tissues from patients who underwent surgical removal of NIP and performed hematoxylin–eosin (HE), immunohistochemical, and immunofluorescence staining to analyze in-depth the basic characteristics of NIP, including detecting the expression and distribution of MMPs and associated factors in NIP. Western blotting and quantitative real-time PCR were further performed to analyze the protein and mRNA expression levels of specific factors including MMPs, HIF-1α, and tissue inhibitors of metalloproteinases (TIMPs).Results: We observed finger-like projections that insert into the epithelium in NIP tissue as its main characteristics. The projections contain fibroblasts, extracellular matrix, capillaries, and infiltrating inflammatory cells. We found abundant neutrophils clustered at the finger-like projection of NIP, and also noted MMP-1 and MMP-9 were up-regulated in NIP (p< 0.05), whereas TIMP-1/3 was decreased. The expression level of HIF-1α was also found to be increased in NIP tissue. We further showed that MMP-9 and HIF-1α were mainly expressed by neutrophils and were predominantly observed in the finger-like projections that contribute to the NIP pathology.Conclusion: Upregulation and release of MMP-9 and HIF-1α from infiltrating neutrophils may cause damage to the epithelial basement membrane and epithelial clefts, forming finger-like projections with angiogenesis and fibroblasts insertion, resulting in epithelial growth in the tissue stroma, a typical histo-pathological characteristic in NIP.Keywords: nasal inverted papilloma, finger-like projection, MMP-9, HIF-1α, pathogenesis, neutrophils

The newly emerging coronavirus SARS-CoV-2 causes severe lung disease and substantial mortality. How the virus evades host defense for efficient replication is not fully understood. In this report, we found that the SARS-CoV-2 nucleocapsid protein (NP) impaired stress granule (SG) formation induced by viral RNA. SARS-CoV-2 NP associated with the protein kinase PKR after dsRNA stimulation. SARS-CoV-2 NP did not affect dsRNA-induced PKR oligomerization, but impaired dsRNA-induced PKR phosphorylation (a hallmark of its activation) as well as SG formation. SARS-CoV-2 NP also targeted the SG-nucleating protein G3BP1 and impaired G3BP1-mediated SG formation. Deficiency of PKR or G3BP1 impaired dsRNA-triggered SG formation and increased SARS-CoV-2 replication. The NP of SARS-CoV also targeted both PKR and G3BP1 to impair dsRNA-induced SG formation, whereas the NP of MERS-CoV targeted PKR, but not G3BP1 for the impairment. Our findings suggest that SARS-CoV-2 NP promotes viral replication by impairing formation of antiviral SGs, and reveal a conserved mechanism on evasion of host antiviral responses by highly pathogenic human betacoronaviruses.

OBJECTIVE Women with type 1 diabetes (T1D) are thought to experience menopause earlier than women without diabetes, although not all studies agree. We assessed metabolic predictors of the age at which natural menopause occurs among women with T1D participating in the Epidemiology of Diabetes Complications study. METHODS Women with childhood-onset (

Background Internal jugular vein (IJV) and axillary vein/subclavian vein (AxV/SCV) are commonly used for implantable venous access port (IVAP) implantation in breast cancer (BC) patients with chemotherapy. Previous studies focused on complications between these different approaches and ignored patient comfort. In this study, we aim to compare patient comfort between IJV and AxV/SCV approaches, as well as surgery duration and complications. Methods This is a single-center prospective randomized controlled clinical trial. A total of 200 patients diagnosed with invasive BC will be enrolled in this study. After signing written informed consent, patients schedule to undergo IVAP implantation will be randomized at a 1:1 ratio to receive central venous catheters (CVC) with either IJV or AxV/SCV approaches. Baseline as well as demographic data and procedure time of port implantation will be recorded. All patients will receive assessment of comfort with a comfort scale table at days 1, 2 and 7 after implantation surgery. Patients will be followed up and complications will be recorded until devices are removed at the end of the treatment period, or in case of complications. Patient comfort, procedure time of implantation and complications will be compared and analyzed between these two arms. Discussion To the best of our knowledge, this is the first study to compare patient comfort as primary outcome measure between IJV and AxV/SCV puncture. This study will further confirm the benefits of ultrasound guidance and may provide a better choice of IVAP implantation for BC patients. Trial registration This study has been registered at Chinese Clinical Trial Registry (ChiCTR, www. chictr.org.cn) and Chinese Ethics Committee of Registering Clinical Trials (No. ChiCTR2000034986).

Background The optimization of myocardial CT perfusion (CTP) assessment remains inconsistent and uncertain. Our aim was to explore the superior analysis selection and incremental improvement of myocardial blood flow (MBF) assessment on CTP in diagnosing hemodynamically significant coronary artery disease (CAD). Methods Sixty patients (43 men and 17 women; 61.38 ± 8.01 years) were prospectively recruited and underwent stress dynamic myocardial CTP examinations. Absolute and relative MBF was used for ischemia evaluation with the invasive coronary angiography and fractional flow reserve were used as the reference standard. Areas under the receiver operating characteristic curves (AUCs) and cutoff values were calculated and compared. Results There were 151 vessels in 60 patients finally enrolled for analysis. The sensitivity, specificity, PPV, NPV and diagnostic accuracy for the absolute MBF value and relative MBF ratio were 82.76%, 98.92%, 97.96%, 90.20%, and 92.72% and 74.14%, 93.56%, 87.76%, 85.29%, and 86.09%, respectively. The absolute MBF value was superior than the relative MBF ratio in detecting ischemia (AUC, 0.955 [95%CI: 0.919–0.990] vs.0.906 [95%CI:0.857–0.954])(P = 0.02). For territories with both sensitivity and specificity ≤90%, the diagnostic accuracy increased from 79.1% to 88.4% when the specific data were assessed using the absolute MBF value instead of the relative MBF ratio. Conclusions The absolute MBF value from the endocardial myocardium on stress dynamic myocardial CTP showed superior diagnostic performance compared to the relative MBF ratio for the detection of myocardial ischemia in intermediate-to-high risk patients. The absolute MBF value provides an incremental benefit toward diagnostic performance for the relative MBF ratio evaluation.

Proteasome inhibitors, such as bortezomib and carfilzomib, have shown efficacy in anti-cancer therapy in hematological diseases but not in solid cancers. Here, we found that liposarcomas (LPS) are susceptible to proteasome inhibition, and identified drugs that synergize with carfilzomib, such as selinexor, an inhibitor of XPO1-mediated nuclear export. Through quantitative nuclear protein profiling and phospho-kinase arrays, we identified potential mode of actions of this combination, including interference with ribosome biogenesis and inhibition of pro-survival kinase PRAS40. Furthermore, by assessing global protein levels changes, FADS2, a key enzyme regulating fatty acids synthesis, was found down-regulated after proteasome inhibition. Interestingly, SC26196, an inhibitor of FADS2, synergized with carfilzomib. Finally, to identify further combinational options, we performed high-throughput drug screening and uncovered novel drug interactions with carfilzomib. For instance, cyclosporin A, a known immunosuppressive agent, enhanced carfilzomib’s efficacy in vitro and in vivo. Altogether, these results demonstrate that carfilzomib and its combinations could be repurposed for LPS clinical management. Electronic supplementary material The online version of this article (10.1007/s00018-020-03620-w) contains supplementary material, which is available to authorized users.

To investigate the diagnostic performance of 70-kVp stress dynamic myocardial CT perfusion (CTP) as a low-dose, one-stop cardiac CT examination in clinical application. Consecutive symptomatic patients were prospectively recruited and scanned with stress dynamic myocardial CTP. The CTP phase with the best enhancement of the coronary arteries was selected and extracted as the CTP-derived single-phase coronary CT angiography (SP-CTA). The diagnostic performance of CTP and CTP+SP-CTA for functionally significant CAD was assessed. Invasive coronary angiography and fractional flow reserve were used as the reference standard for the myocardial ischemia evaluation. In total, 71 patients (43 men and 28 women; 63.6 ± 8.8 years old) underwent the stress dynamic myocardial CTP; 63 vessels (36.2%) from 42 of the patients (59.2%) were identified as causing ischemia. On a per-vessel basis, the sensitivity, specificity, PPV, NPV, and diagnostic accuracy for CTP and CTP+SP-CTA were 77.8%, 93.7%, 87.5%, 88.1%, and 87.9% and 84.1%, 93.7%, 88.3%, 91.2%, and 90.2%, respectively. The area under the curve (AUC) of CTP+SP-CTA (AUC = 0.963; 95%CI, 0.938–0.989) was significantly superior to that of CTP (AUC = 0.922; 95%CI, 0.880–0.964) and that of SP-CTA (AUC = 0.833; 95%CI, 0.765–0.900) alone (all p

Hematopoietic stem cell (HSC) gene therapy has the potential to cure many genetic, malignant, and infectious diseases. We have shown in a nonhuman primate gene therapy and transplantation model that the CD34+CD90+ cell fraction was exclusively responsible for multilineage engraftment and hematopoietic reconstitution. In this study, we show the translational potential of this HSC-enriched CD34 subset for lentivirus-mediated gene therapy. Alternative HSC enrichment strategies include the purification of CD133+ cells or CD38low/– subsets of CD34+ cells from human blood products. We directly compared these strategies to the isolation of CD90+ cells using a good manufacturing practice (GMP) grade flow-sorting protocol with clinical applicability. We show that CD90+ cell selection results in about 30-fold fewer target cells in comparison to CD133+ or CD38low/– CD34+ hematopoietic stem and progenitor cell (HSPC) subsets without compromising the engraftment potential in vivo. Single-cell RNA sequencing confirmed nearly complete depletion of lineage-committed progenitor cells in CD90+ fractions compared to alternative selections. Importantly, lentiviral transduction efficiency in purified CD90+ cells resulted in up to 3-fold higher levels of engrafted gene-modified blood cells. These studies should have important implications for the manufacturing of patient-specific HSC gene therapy and gene-engineered cell products., Graphical Abstract, Current CD34-mediated hematopoietic stem cell (HSC) gene therapy approaches are untargeted and expensive. Purification and targeting of the HSC-enriched CD34+CD90+ subset is less expensive and more efficient with predictable results ex vivo and in vivo. Modifying CD34+CD90+ cells can overcome current roadblocks for the routine clinical use of HSC gene therapy.

The methods for calculating the optimal myocardial blood flow (MBF) relative parameters in stress dynamic myocardial CT perfusion (CTP) in the detection of hemodynamically significant coronary artery disease (CAD) are non-uniform and lack standards.A total of 86 patients who were prospectively recruited underwent APT stress dynamic myocardial CTP. The relative MBF perfusion parameters were calculated as av_Ratio, Q3av_Ratio and hi_Ratio according to the three types of reference MBF values, respectively: (1) average segmental MBF value, (2) the third quartile of the average segmental MBF value, and (3) highest segmental MBF value. All the data were derived from both the endocardial and transmural layers of the myocardium. Invasive coronary angiography and fractional flow reserve (ICA/FFR) were used as the reference standards for myocardial ischemia evaluation.A total of 151 vessels of 60 patients (43 men and 17 women; 61.38 ± 8.01 years) were enrolled in the analysis. The performance of the endocardial layer was superior to that of the transmural layer (all P 0.05). The hi_Ratio of the endocardial myocardium (AUC = 0.906, 95% CI: 0.857-0.954), for which the highest segmental value was selected as the reference MBF, was superior to both av_Ratio and Q3av_Ratio for ischemia detection (AUC, 0.906 vs.0.879, P 0.05; 0.906 vs.0.891, P = 0.18), and the sensitivity, specificity, PPV, NPV and diagnostic accuracy were 74.1%, 93.6%, 87.8%, 85.3% and 86.1%, respectively. The cutoff value of hi_Ratio was 0.675.The relative MBF parameter of the endocardial myocardium using the highest segmental MBF value as a reference provided optimal diagnostic accuracy for the detection of hemodynamically significant CAD.

Hibiscus cannabinus L. or commonly known as kenaf is a multipurpose crop with various medicinal and nutritional properties. The aim of this study was to determine the antioxidant, nutritional, and functional properties of kenaf leaves powder. In addition, the effect of kenaf leaves powder fortification in bread properties and consumer acceptability were evaluated by production of three formulations of bread with 0% (control), 4% and 8% substitution of kenaf leaves powder per weight of flour used. From the sensory evaluation, 4% leaves powder bread was the most preferred by the panelists followed by 0% leaves powder bread then 8% leaves powder bread. Therefore, 4% leaves powder bread was chosen as the best formulation for this study and it showed significantly higher value of DPPH free radical scavenging capacity (8.05 mg TE/100 g), total phenolic content (12.9 mg GAE/100 g) and total flavonoid content (13.3 mg QE/100 g) compared to control bread (1.38 mg TE/100 g, 8.17 mg GAE/100 g and 8.77 mg QE/100 g, respectively). Besides, 4% leaves powder bread also showed improvement in calcium and total dietary fibre compared to control bread. Given these results, kenaf leaves powder can be used in baking formulation up to 4% with flour to enhance the functional properties of baking formulation without compromising eating quality.

Most hereditary diseases are incurable, but their deterioration could be delayed or stopped if diagnosed timely. It is thus imperative to explore the state-of-the-art and high-efficient diagnostic techniques for precise analysis of the symptoms or early diagnosis of pre-symptoms. Diagnostics based on clinical presentations, hard to distinguish different phenotypes of the same genotype, or different genotypes displaying similar phenotypes, are incapable of pre-warning the disease status. Molecular diagnosis is ahead of harmful phenotype exhibition. However, conventional gold-standard molecular classifications, such as karyotype analysis, Southern blotting (SB) and sequencing, suffer drawbacks like low automation, low throughput, prolonged duration, being labor intensive and high cost. Also, deficiency in flexibility and diversity is observed to accommodate the development of precise and individualized diagnostics. The aforementioned pitfalls make them unadaptable to the increasing clinical demand for detecting and interpreting numerous samples in a rapid, accurate, high-throughput and cost-effective manner. Nevertheless, capillary electrophoresis based on genetic information analysis, with advantages of automation, high speed, high throughput, high efficiency, high resolution, digitization, versatility, miniature and cost-efficiency, coupled with flexible-designed PCR strategies in sample preparation (PCR-CE), exhibit an excellent power in deciphering cryptic molecular information of superficial symptoms of genetic diseases, and can analyze in parallel a large number of samples in a single PCR-CE, thereby providing an alternative, accurate, customized and timely diagnostic tool for routine screening of clinical samples on a large scale. Thus, the present study focuses on CE-based nucleic acid analysis used for inherited disease diagnosis. Also, the limitations and challenges of this PCR-CE for diagnosing hereditary diseases are discussed.

Background Gastric cancer (GC) is a malignant tumour originating from the gastric mucosa epithelium that seriously threatens human health. DCLK1, miR-15b and lncRNA SNHG1 play potential roles in the occurrence of GC, but the mechanism remains unclear. Methods Gene expression of DCLK1, miR-15b and lncRNA SNHG1 was investigated by qRT-PCR. Protein expression was detected by Western blotting. Migration and invasion of gastric cancer cells was tested by a Transwell assay and wound healing assay. Cell proliferation was measured by an MTT assay. Finally, the correctness of the prediction results was confirmed by a dual-luciferase reporter assay. Results The expression of DCLK1, Notch1, and SNHG1 was increased in GC tissues, while the expression of miR-15b was decreased. Overexpression of lncRNA SNHG1 promoted the expression of DCLK1 and Nothc1 in GC cells. Moreover, miR-15b targeted DCLK1 to regulate Notch1 expression and inhibited the EMT process in GC cells. SNHG1 enhanced the effects of DCLK1/Notch1 on the EMT process through regulating miR-15b expression. Conclusion SNHG1 enhances the EMT process in GC cells through DCLK1-mediated Notch1 pathway, which can be a potential target for treating GC.

Objectives The aim of this study was to validate the feasibility of a novel structural and computational fluid dynamics–based fractional flow reserve (FFR) algorithm for coronary computed tomography angiography (CTA), using alternative boundary conditions to detect lesion-specific ischemia. Background A new model of computed tomographic (CT) FFR relying on boundary conditions derived from structural deformation of the coronary lumen and aorta with transluminal attenuation gradient and assumptions regarding microvascular resistance has been developed, but its accuracy has not yet been validated. Methods A total of 338 consecutive patients with 422 vessels from 9 Chinese medical centers undergoing CTA and invasive FFR were retrospectively analyzed. CT FFR values were obtained on a novel on-site computational fluid dynamics–based CT FFR (uCT-FFR [version 1.5, United-Imaging Healthcare, Shanghai, China]). Performance characteristics of uCT-FFR and CTA in detecting lesion-specific ischemia in all lesions, intermediate lesions (luminal stenosis 30% to 70%), and “gray zone” lesions (FFR 0.75 to 0.80) were calculated with invasive FFR as the reference standard. The effect of coronary calcification on uCT-FFR measurements was also assessed. Results Per vessel sensitivities, specificities, and accuracies of 0.89, 0.91, and 0.91 with uCT-FFR, 0.92, 0.34, and 0.55 with CTA, and 0.94, 0.37, and 0.58 with invasive coronary angiography, respectively, were found. There was higher specificity, accuracy, and AUC for uCT-FFR compared with CTA and qualitative invasive coronary angiography in all lesions, including intermediate lesions (p 0.80; p = 0.397) and in patients with “gray zone” versus FFR ≤0.75 (p = 0.633) and versus FFR >0.80 (p = 0.364), respectively. No significant difference in the diagnostic performance of uCT-FFR was found between patients with calcium scores ≥400 and Conclusions This novel computational fluid dynamics–based CT FFR approach demonstrates good performance in detecting lesion-specific ischemia. Additionally, it outperforms CTA and qualitative invasive coronary angiography, most notably in intermediate lesions, and may potentially have diagnostic power in gray zone and highly calcified lesions.

Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats1–4. Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans5–7. Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV., Characterization of full-length genome sequences from patients infected with a new coronavirus (2019-nCoV) shows that the sequences are nearly identical and indicates that the virus is related to a bat coronavirus.

In December 2019, a novel coronavirus (2019-nCoV) caused an outbreak in Wuhan, China, and soon spread to other parts of the world. It was believed that 2019-nCoV was transmitted through respiratory tract and then induced pneumonia, thus molecular diagnosis based on oral swabs was used for confirmation of this disease. Likewise, patient will be released upon two times of negative detection from oral swabs. However, many coronaviruses can also be transmitted through oral–fecal route by infecting intestines. Whether 2019-nCoV infected patients also carry virus in other organs like intestine need to be tested. We conducted investigation on patients in a local hospital who were infected with this virus. We found the presence of 2019-nCoV in anal swabs and blood as well, and more anal swab positives than oral swab positives in a later stage of infection, suggesting shedding and thereby transmitted through oral–fecal route. We also showed serology test can improve detection positive rate thus should be used in future epidemiology. Our report provides a cautionary warning that 2019-nCoV may be shed through multiple routes.

Context Shuxuening injection (SXNI), derived from the leaf of Ginkgo biloba L. (Ginkgoaceae), is widely used to treat cardio-cerebral vascular system related disease due to the efficacy of dilating the blood vessels and improving the function of microcirculation. Nevertheless, SXNI induces immediate hypersensitivity reactions in clinics and the molecular mechanisms are unknown. Objective The present study investigates the molecular mechanism of SXNI mediated hypersensitivity reactions. Materials and methods Naive male ICR mice (n = 10) were administered (i.v.) with negative control combined with Evans blue (EB) (CTL-EB), SXNI (14 or 70 mg/kg) combined with EB (SXNI/1-EB or SXNI/4-EB), vascular leakage was evaluated, ears and lungs were collected for histopathological analysis. In vitro, TSC1 was knockdown in human umbilical vein endothelial cells (HUVECs). HUVECs were incubated with SXNI, and the alterations of endothelial cell permeability were observed. Rapamycin (mTOR inbibitor) was used to investigate SXNI-induced hypersensitivity reactions both in mice and HUVECs. Results SXNI (70 mg/kg) induced vascular leakage in mice. Slight oedema and microvascular dilation in the ears, and broaden of alveolar septal and monocyte infiltration in the lungs were observed in SXNI (70 mg/kg) treated mice. mTOR inhibitor alleviates SXNI mediated vascular endothelial hyperpermeability both in vitro and in vivo. Discussion and conclusions SXNI stimulates pseudo-allergic reactions through hyperactivation of mTOR signalling pathway. Our work provides the new molecular mechanism of drug related pseudo-allergic reactions, and a potential drug to prevent and treat SXNI mediated hypersensitivity reactions.

Coronavirus disease 2019 (COVID-19) is an emerging life-threatening pulmonary disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which originated in Wuhan, Hubei Province, China, in December 2019. COVID-19 develops after close contact via inhalation of respiratory droplets containing SARS-CoV-2 during talking, coughing, or sneezing by asymptomatic, presymptomatic, and symptomatic carriers. This virus evolved over time, and numerous genetic variants have been reported to have increased disease severity, mortality, and transmissibility. Variants have also developed resistance to antivirals and vaccination and can escape the immune response of humans. Reverse transcription polymerase chain reaction (RT–PCR) is the method of choice among diagnostic techniques, including nucleic acid amplification tests (NAATs), serological tests, and diagnostic imaging, such as computed tomography (CT). The limitation of RT–PCR is that it cannot distinguish fragmented RNA genomes from live transmissible viruses. Thus, SARS-CoV-2 isolation by using cell culture has been developed and makes important contributions in the field of diagnosis, development of antivirals, vaccines, and SARS-CoV-2 virology research. In this research, two SARS-CoV-2 strains were isolated from four RT–PCR-positive nasopharyngeal swabs using VERO E6 cell culture. One isolate was cultured successfully with a blind passage on day 3 post inoculation from a swab with a Ct > 35, while the cells did not develop cytopathic effects without a blind passage until day 14 post inoculation. Our results indicated that infectious SARS-CoV-2 virus particles existed, even with a Ct > 35. Cultivable viruses could provide additional consideration for releasing the patient from quarantine. The results of the whole genome sequencing and bioinformatic analysis suggested that these two isolates contain a spike 68-76del+spike 675-679del double-deletion variation. The double deletion was confirmed by amplification of the regions spanning the spike gene deletion using Sanger sequencing. Phylogenetic analysis revealed that this double-deletion variant was rare (one per million in public databases, including GenBank and GISAID). The impact of this double deletion in the spike gene on the SARS-CoV-2 virus itself as well as on cultured cells and/or humans remains to be further elucidated.

Nuclear import, mediated in part by karyopherin-α (KPNA)/importin-α subtypes, regulates transcription factor access to the genome and determines cell fate. However, the cancer-specific changes of KPNA subtypes and the relevancy in cancer biology remain largely unknown. Here, we report that KPNA4, encoding karyopherin-α4 (KPNA4), is exclusively amplified and overexpressed in head and neck of squamous cell carcinoma (HNSCC). Depletion of KPNA4 attenuated nuclear localization signal-dependent transport activity and suppressed malignant phenotypes and induced epidermal differentiation. Mechanistically, KPNA4-mediated nuclear transport of Ras-responsive element-binding protein (RREB1), which sustains Ras/ERK pathway signaling through repressing miR-143/145 expression. Notably, MAPK signaling enhanced trafficking activity of KPNA4 via phosphorylation of KPNA4 at Ser60. These data reveal that KPNA4 establishes a feed-forward cascade that potentiates Ras/ERK signaling in HNSCC.

Endoscopy may be used for early screening of various cancers, such as nasopharyngeal cancer, esophageal adenocarcinoma, gastric cancer, colorectal cancer, and bladder cancer, and performing minimal invasive surgical procedures, such as laparoscopy surgery. During this procedure, an endoscope is used; it is a long, thin, rigid, or flexible tube having a light source and a camera at the tip, which facilitates visualization inside the affected organs on a screen and helps doctors in diagnosis.

Objectives: The objective of this study was to explore the diagnostic value of deep learning-based image reconstruction (DLR) and hybrid iterative reconstruction (HIR) for calcification-related obstructive coronary artery disease (CAD) evaluation by using coronary CT angiography (CCTA) images and subtraction CCTA images.Methods: Forty-two consecutive patients with known or suspected coronary artery disease who underwent coronary CTA on a 320-row CT scanner and subsequent invasive coronary angiography (ICA), which was used as the reference standard, were enrolled. The DLR and HIR images were reconstructed as CTADLR and CTAHIR, and, based on which, the corresponding subtraction CCTA images were established as CTAsDLR and CTAsHIR, respectively. Qualitative images quality comparison was performed by using a Likert 4 stage score, and quantitative images quality parameters, including image noise, signal-to-noise ratio, and contrast-to-noise ratio were calculated. Diagnostic performance on the lesion level was assessed and compared among the four CCTA approaches (CTADLR, CTAHIR, CTAsDLR, and CTAsHIR).Results: There were 166 lesions of 86 vessels in 42 patients (32 men and 10 women; 62.9 ± 9.3 years) finally enrolled for analysis. The qualitative and quantitative image qualities of CTAsDLR and CTADLR were superior to those of CTAsHIR and CTAHIR, respectively. The diagnostic accuracies of CTAsDLR, CTADLR, CTAsHIR, and CTAHIR to identify calcification-related obstructive diameter stenosis were 83.73%, 69.28%, 75.30%, and 65.66%, respectively. The false-positive rates of CTAsDLR, CTADLR, CTAsHIR, and CTAHIR for luminal diameter stenosis ≥50% were 15%, 31%, 24%, and 34%, respectively. The sensitivity and the specificity to identify ≥50% luminal diameter stenosis was 90.91% and 83.23% for CTAsDLR.Conclusion: Our study showed that deep learning–based image reconstruction could improve the image quality of CCTA images and diagnostic performance for calcification-related obstructive CAD, especially when combined with subtraction technique.

Diabetic peripheral neuropathy (DPN) is the most common microvascular complication of diabetes that affects approximately half of the diabetic population. Up to 53% of DPN patients experience neuropathic pain, which leads to a reduction in the quality of life and work productivity. Tocotrienols have been shown to possess antioxidant, anti-inflammatory, and neuroprotective properties in preclinical and clinical studies. This study aimed to investigate the effects of tocotrienol-rich vitamin E (Tocovid SuprabioTM) on nerve conduction parameters and serum biomarkers among patients with type 2 diabetes mellitus (T2DM). A total of 88 patients were randomized to receive 200 mg of Tocovid twice daily, or a matching placebo for 12 months. Fasting blood samples were collected for measurements of HbA1c, renal profile, lipid profile, and biomarkers. A nerve conduction study (NCS) was performed on all patients at baseline and subsequently at 2, 6, 12 months. Patients were reassessed after 6 months of washout. After 12 months of supplementation, patients in the Tocovid group exhibited highly significant improvements in conduction velocity (CV) of both median and sural sensory nerves as compared to those in the placebo group. The between-intervention-group differences (treatment effects) in CV were 1.60 m/s (95% CI: 0.70, 2.40) for the median nerve and 2.10 m/s (95% CI: 1.50, 2.90) for the sural nerve. A significant difference in peak velocity (PV) was also observed in the sural nerve (2.10 m/s, 95% CI: 1.00, 3.20) after 12 months. Significant improvements in CV were only observed up to 6 months in the tibial motor nerve, 1.30 m/s (95% CI: 0.60, 2.20). There were no significant changes in serum biomarkers, transforming growth factor beta-1 (TGFβ-1), or vascular endothelial growth factor A (VEGF-A). After 6 months of washout, there were no significant differences from baseline between groups in nerve conduction parameters of all three nerves. Tocovid at 400 mg/day significantly improve tibial motor nerve CV up to 6 months, but median and sural sensory nerve CV in up to 12 months of supplementation. All improvements diminished after 6 months of washout.

INTRODUCTION Frailty is associated with adverse health outcomes and can be measured using the FRAIL scale. In Singapore, its use has been studied in tertiary hospitals but not in community hospitals. A tool to predict rehabilitation outcomes would allow for better risk stratification and allocation of resources. We aimed to determine whether the FRAIL scale is associated with rehabilitation outcomes in patients admitted to the community hospital setting, where post-acute care and rehabilitation are primarily delivered. METHODS This was a retrospective cohort study. The FRAIL scale was utilised to screen 560 older adults who were admitted to a community hospital for rehabilitation. Data were analysed to determine the relationship between baseline characteristics and frailty status, with rehabilitation outcome measures of absolute functional gain, rehabilitation effectiveness, rehabilitation efficiency, length of stay and discharge destination. RESULTS The combined score of the FRAIL scale showed significant negative association with absolute functional gain (p < 0.001), rehabilitation effectiveness (p < 0.001) and rehabilitation efficiency (p < 0.001), whereas it was positively associated with increased length of stay (p < 0.05) and a need for continued support in increased care settings (p < 0.001). Individual components of the FRAIL scale, in particular, the 'fatigue', 'ambulation' and 'loss of weight' components, appeared to be highly associated with rehabilitation effectiveness and efficiency, especially among pre-frail patients. CONCLUSION The utility of the FRAIL scale as an indicator of frailty status and its association with rehabilitative outcomes in the post-acute care setting were demonstrated. Moreover, the FRAIL scale may better predict the rehabilitative progress of pre-frail patients.

Background Respiratory tract infections (RTIs) represent a major cause of clinical visits worldwide. Viral epidemiology of RTIs in adults has been less studied compared to children. FilmArray respiratory panel (FA-RP), a multiplex, real time polymerase chain reaction method can simultaneously detect the nucleic acids of multiple pathogens. The purpose of this study is to analyze the epidemiology and clinical presentations of an RTI cohort. Methods This retrospective cohort study was conducted at China Medical University Hospital (CMUH) and China Medical University Children's Hospital (CMUCH), from January 2020 to June 2020. The FA-RP results were collected and analyzed according to upper versus lower RTIs. Results Among 253 respiratory samples tested, 135 (53.4%) were from adults and 118 (46.6%) from children. A total positive rate of 33.9% (86/253) was found, with 21.48% (29/135) in adults and 48.31% (57/118) in children. Human rhinovirus/Enterovirus (HRV/EV) was detected in most of the age groups and was more common in URIs. HRV/EV was found as a frequent co-detection virus. Among children, HRV/EV was the most detected pathogen of URIs, while the most predominant pathogen in LRIs was Mycoplasma pneumoniae. Conclusions FA-RP has the potential to improve the detection rate of respiratory pathogens. The positive rate of FA-RP was higher in children compared to adults, which likely corresponds to the higher incidence of viral RTIs in children. Different pathogens may lead to different types of respiratory infections.

Previous reports demonstrated that aristolochic acids (AAs) exposure-induced nephrotoxicity, mutations, and tumorigenesis are mainly due to aristolochic acid I (AAI). Notably, the chemical structure of aristolochic acid IVa (AAIVa), which exists at higher levels in many Aristolochiaceae herbs, is extremely similar to AAI. In lack of toxicological data, it is unknown whether AAIVa exposure leads to aristolochic acid nephropathy (AAN), mutations, and tumorigenesis as of AAI. To answer these questions, mice were administered AAIVa by single or repeated long-term gavage, while AAI was used as a positive control. We found that single gavage of 40 mg/kg of AAIVa exhibited no obvious toxicity. Also, there were no tumors or death in mice administrated with 1 and 10 mg/kg of AAIVa for 6 months followed by a 12-month recovery time. There were no noteworthy alterations in gene mutation frequency in the kidney, liver, and stomach between the AAIVa and control mice. Fascinatingly, AA-associated mutational signatures, adenine-to-thymine (A>T) transversions, were absent in AAIVa-treated mice. Nonetheless, 10 mg/kg of AAIVa triggered lymphocytic infiltration and slight fibrous hyperplasia in the kidney at the 6th month; however, these were alleviated at the 12th and 18th months. On the contrary, AAI (positive control) caused severe diffuse fibrosis, tubular atrophy, necrosis, tumors in the forestomach and kidney, and death after the 6th month. It seems that long-term AAIVa exposure induced mild renal lesions could be due to the activation of the canonical or noncanonical transforming growth factor-β (TGFβ) pathway. Overall, these findings suggest that the mutagenicity and carcinogenic risk of AAIVa are very low.

BACKGROUND: Long noncoding RNAs (lncRNAs) play a central role in the pathogenesis of various tumors, including hepatocellular carcinoma (HCC). TMPO antisense RNA 1 (TMPO-AS1) has been reported in many tumors. Nevertheless, the underlying mechanism whereby TMPO-AS1 influences HCC remains unclear. Our research aimed to reveal the molecular mechanism governing the function of TMPO-AS1 in HCC. METHODS: TMPO-AS1 expression levels in HCC tissues/cells were evaluated using reverse transcriptase-polymerase chain reaction. The effect of TMPO-AS1 on the progression of HCC was observed by Cell Counting Kit-8 (CCK8), clone formation, wound healing, and transwell. The direct interaction between TMPO-AS1 and microRNA (miR)-126-3p was observed using a dual-luciferase reporter. RESULTS: We found TMPO-AS1 expression to be remarkably higher in HCC specimens and associated with poor prognosis. Silencing of TMPO-AS1 not only inhibited HCC cell proliferation but also significantly reduced epithelial-to-mesenchymal transition-induced invasion and migration to a remarkable degree. According to the results from the online database analysis tools implemented to identify if TMPO-AS1 could target miR-126-3p, we found that miR-126-3p had a negative relationship with TMPO-AS1 in HCC specimens. Meanwhile, the luciferase reporter assay confirmed that TMPO-AS1 could directly act on miR-126-3p. Moreover, the silencing of miR-126-3p dramatically abolish the inhibitive influence of sh-TMPO-AS1 on HCC development. CONCLUSIONS: Our research demonstrated that TMPO-AS1 acts as a sponge for the tumor suppressor miR-126-3p in HCC and promotes the expression of LRP6 indirectly. Taken together, our results show that TMPO-AS1 may be regarded as a novel therapeutic target in the treatment of liver cancer.

IL6 is one of the most elevated cytokines during chimeric antigen receptor (CAR) T cell cytokine release syndrome (CRS), and IL6R blockade by Tocilizumab has successfully relieved the most life-threatening aspects of CRS in patients. In addition, latest studies demonstrated the essential role of IL1 in driving CART induced neurotoxicity in mouse models. Here we present a clinical investigation (ChiCTR2000032124; ChiCTR2000031868) of anti-CD19 and anti-BCMA CART (41BBζ) secreting an anti-IL6 scFv and IL1 receptor antagonist (IL1RA) in treating patients with hematologic malignancy. Our results revealed that IL6 and IL1B were maintained at low levels without significant elevation during CRS, rendering Tocilizumab dispensable. Moreover, treated patients did not show neurotoxicity during CRS and exhibited mild to moderate CRS. Notably, we observed high rate of complete response (CR) and significant CART expansion during treatment. In sum, we conclude that CART-secreting anti-IL6 scFv and IL1RA could self-neutralize IL6 storm and maintain low levels of IL1B during CART therapy to minimize IL6- and IL1-associated cytokine toxicity and neurotoxicity without impairing therapeutic efficacy.

In this digital era, young children spend a considerable amount of time looking at telephone, tablet, computer and television screens. However, preventative eye health behavior education could help avoid and relieve asthenopia. The effects of parental influence on their children’s eye health behavior through the preschool eye health education intervention program were examined. The Health Belief Model was used to develop parental involvement strategy and eye health curriculum. The study was conducted in a large public preschool with five branches in Beijing, China. A total of 248 parent–child pairs participated in the baseline and follow-up surveys, of which 129 were in the intervention group and 119 were in the comparison group. The generalized estimating equation analysis results indicated that parental involvement in preschool-based eye health intervention on screen uses had positive influence on parents’ eye health knowledge, cues to action, and parenting efficacy. The intervention program also had positive effects on the increasing level of children’s eye health knowledge, beliefs, cues to action, self-efficacy, and behaviors. The results supported the implementation of a preschool-based eye health intervention program with parental involvement, which could potentially enhance children’s and parents’ eye health beliefs and practices.

Purpose: This study aimed to investigate the relationship of triglyceride glucose-body mass index (TyG-BMI) with bone mineral density, femoral neck geometry, and risk of fracture in middle-aged and elderly Chinese individuals. Methods: A total of 832 nondiabetic individuals (474 men aged ≥50 years and 358 postmenopausal women) were selected from the prospective population-based HOPE cohort. All individuals underwent dual-energy X-ray absorptiometry for assessment of bone mineral density (BMD) at the lumbar spine, femoral neck, and total hip, as well as femoral neck geometry. The 10-year probabilities of major osteoporotic fractures (MOFs) and hip fractures (HFs) were calculated. Correlations of TyG-BMI with BMD at different sites, femoral neck geometry, and risk of fractures were examined in men and women. Results: Cortical thickness (CT), compression strength index (CSI), cross-sectional moment of inertia (CSMI), cross-sectional area (CSA), section modulus (SM), and 25(OH)D levels were significantly lower in women (all P < 0.001). The presence of osteoporosis was related to age, BMI, BMD and femoral neck geometry, TyG-BMI index and TyG index, MOF and HF in both sex. TyG-BMI was positively correlated with BMD at femoral neck, lumber spine, and total hip and with femoral neck geometry parameters in men, Similar significant association was also present in women. In men, TyG-BMI showed significant negative correlation with HF but not with MOF. In women, TyG-BMI showed significant negative correlation with both factors only after adjusting for other variable. The various geometric indices of the femoral neck were 3 significantly impaired in individuals with low TyG-BMI. the TyG-BMI index was found to be significantly associated with osteoporosis after adjusting for confounders. Conclusion: TyG-BMI is positively associated with BMD and femoral neck geometry, and negatively associated with risk of fracture in nondiabetic middle-aged and elderly Chinese men and women.

NAP1L1 has been reported to be significantly involved in the carcinogenesis of hepatocellular carcinoma (HCC). Yet, its detailed molecular basis is still to be determined. Based on the analysis of The Cancer Genome Atlas (TCGA) database, NAP1L1 mRNA was found to be upregulated and predicted the poor prognosis initially. Subsequently, consistent with the prediction, the upregulated expression of NAP1L1 mRNA and protein levels was confirmed by quantitative polymerase chain reaction (qPCR), Western blot, and immunohistochemistry assays. Upregulated NAP1L1 protein positively promoted the disease progression and poor prognosis of HCC. In addition, NAP1L1 protein expression was considered as an independent prognostic factor in HCC. Inhibition of NAP1L1 expression by siRNA or shRNA pathway significantly reduced the cell proliferation and cell cycle transformation in vitro and in vivo. Mechanism analysis first showed that the function of NAP1L1 was to recruit hepatoma-derived growth factor (HDGF), an oncogene candidate widely documented in tumors. Furthermore, the latter interacted with c-Jun, a key oncogenic transcription factor that can induce the expression of cell cycle factors and thus stimulate the cell growth in HCC. Finally, transfecting HDGF or c-Jun could reverse the suppressive effects on HCC growth in NAP1L1-suppressed HCC cells. Our data indicate that NAP1L1 is a potential oncogene and acts via recruiting HDGF/c-Jun in HCC.

Radiotherapy is one of the standard treatments for cervical cancer and head and neck cancer. However, the clinical efficacy of this treatment is limited by radioresistance. The discovery of effective prognostic biomarkers and the identification of new therapeutic targets have helped to overcome the problem of radioresistance. In this study, we show that in the context of PIK3CA mutation or amplification, high expression of fascin actin-bundling protein 1 (FSCN1) (using the median as the cut-off value) is associated with poor prognosis and radiotherapy response in cancer patients. Silencing FSCN1 enhances radiosensitivity and promotes apoptosis in cancer cells with PIK3CA alterations, and this process may be associated with the downregulation of YWHAZ. These results reveal that FSCN1 may be a key regulator of radioresistance and could be a potential target for improving radiotherapy efficacy in cervical cancer and head and neck cancer patients with PIK3CA alterations.

The purpose of this study was to evaluate the impact of artificial intelligence (AI)-based noise reduction algorithm on aorta computed tomography angiography (CTA) image quality (IQ) at 80 kVp tube voltage and 40 mL contrast medium (CM).After obtaining institutional review board approval and 8 written informed consents, 60 patients (35 men, 25 women; age range: 18 to 85 y) referred for aorta CTA examination were assigned to 2 groups at random. Group A underwent an 80 kVp protocol with 40 mL CM (320 mg I/mL). Group A reconstructed with iterative reconstruction was named as group A1 and further AI-based noise reduction was named as group A2. Group B was scanned with standard 120 kVp, 80 mL CM, and iterative reconstruction algorithm. The quantitative assessment of IQ included aorta CT attenuation, noise, signal-to-noise ratio, and contrast-to-noise ratio. A 5-point scale (5-excellent, 1-poor) was used by 2 radiologists independently for qualitative IQ analysis.The image noise significantly decreased while signal-to-noise ratio and contrast-to-noise ratio significantly increased in the order of group A1, B, and A2 (all P0.05). Compared with group B, the subjective IQ score of group A1 was significantly lower (P0.05), while that of group A2 had no significant difference (P0.05). The effective dose and CM volume of group A were reduced by 79.18% and 50%, respectively, than that of group B.The AI-based noise reduction could improve the IQ of aorta CTA with low kV and reduced CM, which achieved the potential of radiation dose and contrast media reduction compared with conventional aorta CTA protocol.

Four ruthenium(II) arene complexes containing mono-carbonyl analogues of curcumin (MAC) functioning as pendant or bridging ligands as well as chlorido ancillary ligands have been synthesized and structurally characterized by IR and 1H NMR spectroscopies, ESI mass spectrometry and elemental analysis. Anti-proliferative activity of the complexes determined on MOLT-4 human leukemia cells revealed good to moderate activity. Two of the compounds, 3b and 4b, both of which incorporated cyclohexanone as part of the MAC structural motif, displayed potency comparable to cisplatin. In intercalative binding studies, while the organic MACs did not display any interaction with quadruplex DNA, the ruthenium complexes were found to be able to stabilize quadruplex DNA, with 3b and 4b displaying the greatest selectivity for HTelo over c-myc. Compound 4b, in which the MAC ligand is bridged by two organoruthenium centres, bound to HTelo more tightly than 3b, in which the MAC functions as a pendant ligand towards a single ruthenium arene core. These results suggest that minor changes to the structural motif of the MAC ligand, as well as the presence of the ruthenium arene moiety play an important role in achieving selective quadruplex DNA stabilization.

Two novel ruthenium(II) polypyridyl complexes [Ru(bpy)2(ETPIP)](ClO4)2 (Ru(II)-1) and [Ru(phen)2(ETPIP)](ClO4)2 (Ru(II)-2) (bpy = 2,2′-bipyridine, ETPIP = 2-(4-(thiophen-2-ylethynyl)phenyl)-1H-imidazo[4,5-f][1,10]phenanthroline, phen = 1,10-phenanthroline) have been synthesized and characterized. The DNA binding behaviors were evaluated using electronic absorption titration, luminescence spectra and viscosity measurement, revealing an intercalative mode. The cytotoxicity of the ligand and Ru(II) complexes toward A549, HepG-2, SGC-7901 and Hela was assayed by MTT ((3-(4,5-dimethylthiazo-2-yl)-2,5-diphenyltetrazolium bromide)) method. Notably, ETPIP shows no anticancer activity against selected cell lines, and complexes Ru(II)-1 (IC50 = 18.4 ± 2.1 μM) and Ru(II)-2 (IC50 = 16.5 ± 1.7 μM) were found to be slightly more effective against HepG-2 cells than cisplatin (IC50 = 26.4 ± 2.6 μM). Evaluation of cell invasion was performed with the Boyden chamber invasion assay. Additionally, the cell cycle distribution of HepG-2 cells was carried out by flow cytometry. Most importantly, the further anticancer mechanism of the Ru(II) complexes was explored by apoptosis, intracellular reactive oxygen species (ROS) levels and mitochondrial membrane potentials. These results reveal that complexes Ru(II)-1 and Ru(II)-2 could induce apoptosis in HepG-2 cells via a ROS-mediated mitochondrial dysfunction pathway.

Purpose To evaluate the diagnostic performance of coronary computed tomography angiography derived fractional flow reserve (CT-FFR) with invasive fractional flow reserve (FFR) in patients with coronary artery disease" before "with invasive fractional flow reserve serving as the reference standard. Materials and methods CT-FFR values based on a machine learning algorithm (cFFRML) in 183 vessels of 136 patients from four centers were measured with invasive FFR as reference standard. The diagnostic performance from our multicenter study was combined into a meta-analysis following a literature search in Web of Science, PubMed, Cochrane library to identify studies comparing diagnostic performance of coronary computed tomography angiography (CCTA) and CT-FFR. Sensitivity, specificity, accuracy were analyzed on both per-vessel and per-patient basis for intermediate lesions and by algorithm. Results Our multicenter study demonstrated sensitivities, specificities, and accuracies of cFFRML and CCTA of 0.85, 0.94, 0.90, and 0.95, 0.28, 0.55 on a per-vessel basis, respectively. For our meta-analysis, pooled sensitivities, specificities, and accuracies of CT-FFR and CCTA were 0.85, 0.82, 0.82, and 0.85, 0.57, 0.65 with AUC of 0.86 (95%CI: 0.83˜0.89) and 0.83 (95%CI: 0.79˜0.86) on a per-vessel basis, respectively. The sensitivity, specificity and accuracy for intermediate lesions using cFFRML were 0.84, 0.92, and 0.89. No significant difference was found among different algorithms of CT-FFR (P Conslusion This multicenter study with meta-analysis showed that CT-FFR had a high diagnostic accuracy in determining ischemia-specific lesions and intermediate lesions. There was no significant difference when comparing the combined diagnostic performance of different algorithms of CT-FFR with invasive FFR as the reference standard.

Large numbers of previously published studies show the importance of Metabolic syndrome (MetS) in the development of endometrial cancer (EC), the most common gynecologic malignancy in the United States. Defining the association between EC and MetS is complicated by inconsistencies among the MetS definitions used in EC. The aim of this study was to identify the MetS definition that is most practical for EC patients, as well as to estimate the prevalence of MetS using each definition in EC patients. A systematic literature search of PubMed and Embase was conducted to identify studies published between 1988 and 2018 and reporting the components of MetS in EC patients. Relevant studies were selected based on the presence of key MetS components, including central obesity, dyslipidemia, elevated blood pressure, and impaired glucose metabolism. Two independent reviewers extracted information from these articles. Our literature search has identified 400 articles, 8 of which were used for the final analyses. In this systematic review, the prevalence of MetS in EC patients varied based on the definition used, ranging from 6% for International Diabetes Federation (IDF) to 62% for Harmonized. IDF and Harmonized of MetS were the most practical definitions for women with EC. While our review included different approaches to diagnosing MetS and linking it to EC, we argue that there is a need for single and practical MetS definition criteria to improve diagnostics, decrease the inconsistencies across the future EC studies, and foster a cohesive understanding of the evidence regarding the association between MetS and EC.

In recent years, ruthenium complexes have attracted extensive attention as new anticancer drugs. In this paper, three new ruthenium complexes [Ru(dmb)2(HMNPIP)](PF6)2 (1), [Ru(bpy)2(HMNPIP)](PF6)2 (2) and [Ru(phen)2(HMNPIP)](PF6)2 (3) (HMNPIP = 2-hydroxy-3-methoxy-5-nitrophenylimidazo[4,5-f][1,10]phenanthroline) were synthesized and characterized by elemental analysis, ESI-MS, 1H NMR and 13C NMR. The MTT assays showed that the complexes have no cytotoxic activity in vitro. However, upon irradiation with white light, the complexes display high anticancer activity toward A549 cells. The cell cycle distribution and apoptosis of A549 cells induced by the complexes were investigated by flow cytometry. The intracellular ROS and calcium ion levels were studied. The change of mitochondrial membrane potential, cell invasion were also investigated. The expression of caspase 3, p53 and Bcl-2 family proteins was explored by western blot. The complexes induce apoptosis in A549 cells through intrinsic pathway.

The aim of the present study was to investigate the performance of low keV mono-energetic reconstructions in spectral coronary computed tomography angiography (CCTA) using spectral detector CT (SDCT) with reduced contrast media and radiation dose.Sixty patients were randomly assigned to Groups A and B (both n = 30) to undergo CCTA on a dual-layer SDCT with tube voltage 120 kVp and 100 kVp (average tube current: 108.5 and 73.8 mAs, respectively), with contrast media volume of 36 mL used in both groups. The mono-energetic 40-80 keV and conventional 120 kVp images in Group A and conventional 100 kVp images in Group B were reconstructed. Quantitative and qualitative image quality (IQ) were evaluated in the aortic root and distal segments of the coronary arteries.The patient characteristics were not significantly different between the two groups (all P≥ 0.47), nor was the effective radiation dose (1.5 ± 0.3 and 1.4 ± 0.3 mSv, P = 0.20). The quantitative IQ in aorta and coronary arteries of mono-energetic 40-60 keV was superior to conventional 120 kVp and 100 kVp images (all P 0.8).The mono-energetic 40-50 keV reconstructions from spectral CCTA using SDCT provide improved IQ compared to conventional techniques while facilitating reduced radiation dose and contrast media.