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Background This study was conducted to assess the survivorship and clinical outcomes of cup-cage reconstruction technique in the revision of THA. Methods PubMed, OVID, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) up to February 2020 were searched. Studies that reported the clinical and radiological follow-up were identified. Results A total of 151 hips (145 patients) in six studies were included. The all-cause revision-free survivorship of cup-cage implant at the end of follow-up was 90.1% (136/151), with a mean follow-up of 64.4 months(range 12–135). The overall complication rate was 23.8% (36 of 151 hips), of which component problem, dislocation, infection and sciatic nerve palsy/injury were relatively common. All included studies reported improved clinical outcomes at the end of follow-up. Conclusion Results suggested that revision of THA with a cup-cage has a favourable implant survivorship and clinical outcomes for the treatment of pelvic discontinuity, despite the high complications occurrence rates.

Background China is a highly endemic area of chronic hepatitis B (CHB). The accuracy of existed noninvasive biomarkers including TE, APRI and FIB-4 for staging fibrosis is not high enough in Chinese cohort. Methods Using liver biopsy as a gold standard, a novel noninvasive indicator was developed using laboratory tests, ultrasound measurements and liver stiffness measurements with machine learning techniques to predict significant fibrosis and cirrhosis in CHB patients in north and east part of China. We retrospectively evaluated the diagnostic performance of the novel indicator named FibroBox, Fibroscan, aspartate transaminase-to-platelet ratio index (APRI), and fibrosis-4 index (FIB-4) in CHB patients from Jilin and Huai’an (training sets) and also in Anhui and Beijing cohorts (validation sets). Results Of 1289 eligible HBV patients who had liver histological data, 63.2% had significant fibrosis and 22.5% had cirrhosis. In LASSO logistic regression and filter methods, fibroscan results, platelet count, alanine transaminase (ALT), prothrombin time (PT), type III procollagen aminoterminal peptide (PIIINP), type IV collagen, laminin, hyaluronic acid (HA) and diameter of spleen vein were finally selected as input variables in FibroBox. Consequently, FibroBox was developed of which the area under the receiver operating characteristic curve (AUROC) was significantly higher than that of TE, APRI and FIB-4 to predicting significant fibrosis and cirrhosis. In the Anhui and Beijing cohort, the AUROC of FibroBox was 0.88 (95% CI, 0.72–0.82) and 0.87 (95% CI, 0.83–0.91) for significant fibrosis and 0.87 (95% CI, 0.82–0.92) and 0.90 (95% CI, 0.85–0.94) for cirrhosis. In the validation cohorts, FibroBox accurately diagnosed 81% of significant fibrosis and 84% of cirrhosis. Conclusions FibroBox has a better performance in predicting liver fibrosis in Chinese cohorts with CHB, which may serve as a feasible alternative to liver biopsy.

Purpose The aim of this study was to determine mid-and-long term follow-up results of patients with early femoral head osteonecrosis who were treated by modified free vascularized fibular grafting combined with core decompression and bone grafting. Methods Forty-four patients at early ONFH were included in this study. Visual analog scale (VAS) pain scores, range of hip motion (ROM), and Harris hip score (HHS) were recorded to assess the clinical outcome; Western Ontario McMaster Osteoarthritis index (WOMAC) scores and Short Form 36 health survey (SF-36) were conducted to measure the living quality; X-ray film or magnetic resonance imaging (MRI) was used to evaluate radiographic progression; survivorship was defined as patients did not undergo the total hip arthroplasty (THA) or fusion at the last follow-up. Median follow-up was 7.4 years (6–8.2 years). Results The mean VAS score, ROM, and HHS were significantly improved at the final follow-up compared with preoperative values (p p Conclusion Modified non-vascularized allogeneic fibula Grafting combined with core decompression and bone grafting could improve the clinical outcomes and enhance the quality of life for patients with early ONFH.

Immune-mediated inflammation plays a key role in the pathology of abdominal aortic aneurysm (AAA). We aimed to use a computational approach to profile the immune infiltration patterns and related core genes in AAA samples based on the overexpression of gene signatures. The microarray datasets of AAA and normal abdominal tissues were acquired from gene expression omnibus (GEO) database. We evaluated the composition of immune infiltrates through microenvironment cell populations (MCP)-counter. Weighted gene correlation network analysis (WGCNA) was employed to construct the co-expression network and extract gene information in the most relevant module. Functional and pathway enrichment analysis was performed and immune infiltration related core genes were screened. AAA tissues had a higher level of infiltration by cytotoxic lymphocytes, NK cells, T cells, fibroblasts, myeloid dendritic cells, and neutrophils than normal aorta. The red module was strongly correlated with the infiltrating levels of T cells and cytotoxic lymphocytes. Gene ontology (GO) and pathway analyses revealed that genes in the most relevant module were mainly enriched in T cell activation, regulation of lymphocyte activation, cytokine-cytokine receptor interaction, and chemokine signaling pathway, etc. The expression of GZMK, CCL5, GZMA, CD2, and EOMES showed significant correlations with cytotoxic lymphocytes, while CD247, CD2, CD6, RASGRP1, and CD48 expression were positively associated with T cell infiltration. In conclusion, we comprehensively analyzed profiles of infiltrated immune cells in AAA tissues and their associated marker genes. Our data may provide a novel clue to indicate the underlying molecular mechanisms of AAA formation in terms of immune infiltration.

Objective To investigate the optimal idarucizumab (dabigatran antagonist) usage strategy for patients with acute pericardial tamponade receiving uninterrupted dabigatran during catheter ablation for atrial fibrillation (AF). Methods Ten patients presenting acute pericardial tamponade while receiving uninterrupted dabigatran during catheter ablation for AF in Beijing Anzhen Hospital from January 2019 to July 2020 were enrolled and retrospectively analyzed. A "wait and see" strategy of idarucizumab was carried out for all patients; in brief, idarucizumab was applied following pericardiocentesis, comprehensive evaluation of bleeding and hemostasis RESULTS: There were 5 males, 5 paroxysmal AF, and the average age of the patients was 64.0 ± 9.8 years. Among the 10 patients, 4 were treated with dabigatran 110 mg, 6 were treated with dabigatran 150 mg, and 1 was simultaneously given clopidogrel. The average time from pericardial tamponade to the last dose of dabigatran was 8.2 ± 3.4 h. All patients underwent pericardiocentesis successfully, and the average drainage volume was 322.5 ml (220.0 ml ± 935.0 ml). For reversal anticoagulation, 6 patients received protamine, and 5 patients received idarucizumab. Of the 5 patients who were treated with idarucizumab, 4 presented exact hemostasis, except for 1 patient who underwent continuous drainage and finally received surgery repair. The average time to restart anticoagulation was 1.1 ± 0.3 days after the procedure, and no rebleeding, embolism or deaths were observed. Conclusion The "wait and see" strategy of idarucizumab for acute pericardial tamponade during the perioperative period of catheter ablation for AF may be safe and feasible. This article is protected by copyright. All rights reserved.

Rationale and Objectives To evaluate possible correlation between changes in apparent diffusion coefficient (ADC) and Ki-67 index as a result of neoadjuvant chemotherapy (NAC) in patients with invasive breast cancer. Methods and Materials Between February 2016 and October 2017, 87 patients with breast cancer underwent diffusion-weighted magnetic resonance imaging (b = 0 and 800 sec/mm2) before and after NAC. ADC and tumor diameter before and after NAC were compared to the Ki-67 index determined from biopsy or surgical specimens. Results Ki-67 index did not correlate significantly with ADC before NAC (p = 0.862) or afterwards (p = 0.292), nor did it correlate with tumor diameter before (p = 0.545) or afterwards (p = 0.478). However, change in ADC as a result of NAC correlated inversely with change in Ki-67 index (r = −0.326, p = 0.002). The percentage change in Ki-67 index did not correlate with the percentage change in ADC (p = 0.404). Similarly, the change in Ki-67 index or percentage change in that index did not correlate with the change in tumor diameter (p = 0.075) or percentage change in tumor diameter (p = 0.233). Conclusion Comparison of pre- and post-NAC ADC can be used to estimate the change in Ki-67 index in patients with invasive breast cancer.

In this work, a class of dual-functional nanoparticles (NPs) were facilely prepared from ZnPc and Fe3O4 NPs for photodynamic therapy (PDT) and magnetic resonance imaging (MRI). The as-synthesized NPs were investigated in terms of size, morphology, zeta potential , biocompatibility, optical and magnetic properties respectively. The aggregation degree of ZnPc in hybrid NPs was found to be considerably meliorated with the presence of Fe 3O4 NPs, corresponding to higher 1O2 generation rate. Based on the dual-functional NPs, MRI and in vitro PDT was carried out, respectively, yielding a high r2 relaxivity value of 152.9 mM−1 s−1 and strong photocytotoxicity. Given the facility of synthesis, such a strategy can be applied to prepare other multifunctional NPs by introducing other small-sized NPs, such as Au NPs (photothermal), quantum dots (fluorescence imaging), etc.

BackgroundIschemic cardiovascular diseases (ICVD) risk predict models are valuable but limited by its requirement for multidimensional medical information including that from blood drawing. A convenient and affordable alternative is in demand.ObjectivesTo develop and validate a deep learning algorithm to predict 10-year ICVD risk using retinal fundus photographs in Chinese population.MethodsWe firstly labeled fundus photographs with natural logarithms of ICVD risk estimated by a previously validated 10-year Chinese ICVD risk prediction model for 390,947 adults randomly selected (95%) from a health checkup dataset. An algorithm using convolutional neural network was then developed to predict the estimated 10-year ICVD risk by fundus images. The algorithm was validated using both internal dataset (the other 5%) and external dataset from an independent source (sample size = 1,309). Adjusted R2and area under the receiver operating characteristic curve (AUC) were used to evaluate the goodness of fit.ResultsThe adjusted R2between natural logarithms of the predicted and calculated ICVD risks was 0.876 and 0.638 in the internal and external validations, respectively. For detecting ICVD risk ≥ 5% and ≥ 7.5%, the algorithm achieved an AUC of 0.971 (95% CI: 0.967–0.975) and 0.976 (95% CI: 0.973–0.980) in internal validation, and 0.859 (95% CI: 0.822–0.895) and 0.876 (95% CI: 0.816–0.837) in external validation.ConclusionsThe deep learning algorithm developed in the study using fundus photographs to predict 10-year ICVD risk in Chinese population had fairly good capability in predicting the risk and may have values to be widely promoted considering its advances in easy use and lower cost. Further studies with long term follow up are warranted.

Background: Screening for hyperthyroidism using gold-standard diagnostic criteria in the general population is not cost-effective, leading to a relatively high rate of undiagnosed and untreated patients. This study aimed to establish a deep learning-based system to detect hyperthyroidism based on retinal photographs. Methods: The multicenter, observational study included retinal photographs taken from participants in two hospitals and 24 health care centers throughout China. We first trained two models to identify hyperthyroidism: in model #1, the non-hyperthyroidism individuals were randomly selected, while in model #2, the non-hyperthyroidism group was matched for age and gender with the hyperthyroidism group. After internal validation, we selected the better model for further evaluation using external validation datasets. Results: The study included 22,940 retinal photographs of 11,409 participants for the model development, and 3862 retinal photographs (1870 participants) which were obtained from two hospitals and four medical centers as the external validation datasets. Model #1 achieved a higher area under the receiver operator curve (AUC) than model #2 (0.907, 95% CI: 0.894-0.918 versus 0.850, 95% CI: 0.832-0.866) in the internal validation so that model #1 was used for further evaluation. In external datasets, model #1 reached AUCs ranging from 0.816 (95% CI 0.789-0.846) to 0.849 (95% CI 0.824-0.874) and achieved accuracies between 0.735 (95% CI 0.700-0.773) and 0.796 (95% CI 0.765-0.824). Heatmaps showed a focus of the DL-algorism on large fundus vessels and the optic nerve head. Conclusions: Retinal fundus photographs may serve for DL systems for a cost-effective and non-invasive method to detect hyperthyroidism. Funding Information: This study was supported by the National Natural Science Foundation of China (82071005); The Special Fund of the Pediatric Medical Coordinated Development Center of Beijing Hospitals Authority (XTCX201824); the Research Foundation of Beijing Friendship Hospital, Capital Medical University (yyqdkt2018-33); the Capital Health Research and Development of Special (2020-1-2052); Science & Technology Project of Beijing Municipal Science & Technology Commission (Z201100005520045, Z181100001818003); the Beijing Municipal Administration of Hospitals’ Ascent Plan (DFL20150201) Declaration of Interests: Authors Lie Ju, Xin Wang, Xin Zhao, Chao He, Yu Zhong Chen, were employed by the company Beijing Eaglevision Technology Co., Ltd, China. Authors Zhao Hui Wang and Jian Xiong Gao were employed by the company iKang Guobin Healthcare Group Co., Ltd, Beijing, China. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Ethics Approval Statement: The Medical Ethics Committee of the Beijing Tongren Hospital, and the Ethics Committee the iKang Corporation approved the study protocol fulfilling the requirements published in the Helsinki declaration. For patients whose fundus images were stored in the retrospective databases at each participating hospital, informed consent was waived by the institutional review boards.

Summary In late December 2019, COVID-19 was firstly recognized in Wuhan, China and spread rapidly to all of the provinces of China. The West Campus of Wuhan Union Hospital, the designated hospital to admit and treat the severe and critically ill COVID-19 cases, has treated a large number of such patients with great success and obtained lots of valuable experiences based on the Chinese guideline (V7.0). To standardize and share the treatment procedures of severe and critically ill cases, Wuhan Union Hospital has established a working group and formulated an operational recommendation, including the monitoring, early warning indicators, and several treatment principles for severe and critically ill cases. The treatment experiences may provide some constructive suggestions for treating the severe and critically ill COVID-19 cases all over the world.

International audience; Deoxynivalenol (DON) is a Fusarium mycotoxin that frequently contaminates the feed of farm animals. Pigs with their monogastric digestive system are in particular sensitive to DON-contaminated feed. At high concentrations, DON causes acute toxic effects, whereas lower concentrations lead to more subtle changes in the metabolism. This applies in particular to the immune system, for which immunosuppressive but also immunostimulatory phenomena have been described. Research in human and rodent cell lines indicates that this may be partially explained by a binding of DON to the ribosome and subsequent influences on cell signaling molecules like mitogen-activated protein kinases. However, a detailed understanding of the influence of DON on functional traits of porcine immune cells is still lacking. In this study, we investigated the influence of DON on transcription factor expression and cytokine production within CD4+, CD8+, and γδ T cells in vitro. At a DON concentration, that already negatively affects proliferation after Concanavalin A stimulation (0.8 μM) an increase of T-bet expression in CD4+ and CD8+ T cells was observed. This increase in T-bet expression coincided with elevated levels of IFN-γ and TNF-α producing T-cell populations. Increases in T-bet expression and cytokine production were found in proliferating and non-proliferating T cells, although increases were more prominent in proliferating cell subsets. Differently, IL-17A production by CD4+ T cells was not influenced by DON. In addition, frequencies of regulatory T cells and their expression of Foxp3 were not affected. In γδ T cells, GATA-3 expression was slightly reduced by DON, whereas T-bet levels were only slightly modulated and hence IFN-γ, TNF-α, or IL-17A production were not affected. Our results show for the single-cell level that DON has the capacity to modulate the expression of transcription factors and related cytokines. In particular, they suggest that for CD4+ and CD8+ T cells, DON can drive T-cell differentiation into a pro-inflammatory type-1 direction, probably depending on the already prevailing cytokine milieu. This could have beneficial or detrimental effects in ongoing immune responses to infection or vaccination. © Copyright © 2020 Vatzia, Pierron, Hoog, Saalmüller, Mayer and Gerner.

BackgroundThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has progressed to a pandemic associated with substantial morbidity and mortality. The WHO and the United States Center for Disease Control and Prevention (CDC) have issued interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19), but there is limited data on the virologic and clinical characteristics for prognosis of severe COVID-19.MethodsA total of 50 patients with severe COVID-19 were divided into good and poor recovery groups. The dynamic viral shedding and serological characteristics of SARS-CoV-2 were explored. The risk factors associated with poor recovery and lung lesion resolutions were identified. In addition, the potential relationships among the viral shedding, the pro-inflammatory response, and lung lesion evolutions were characterized.ResultsA total of 58% of the patients had poor recovery and were more likely to have a prolonged interval of viral shedding. The longest viral shedding was 57 days after symptom onset. Older age, hyperlipemia, hypoproteinemia, corticosteroid therapy, consolidation on chest computed-tomography (CT), and prolonged SARS-CoV-2 IgM positive were all associated with poor recovery. Additionally, the odds of impaired lung lesion resolutions were higher in patients with hypoproteinemia, hyperlipemia, and elevated levels of IL-4 and ferritin. Finally, viral shedding and proinflammatory responses were closely correlated with lung lesion evolutions on chest CT.ConclusionsPatients with severe COVID-19 have prolonged SARS-CoV-2 infection and delayed intermittent viral shedding. Older age, hyperlipemia, hypoproteinemia, corticosteroid usage, and prolonged SARS-CoV-2 IgM positive might be utilized as predicative factors for the patients with poor recovery.

Rhodiola rosea L., a worldwide botanical adaptogen, has been confirmed to possess protective effects of inflammatory injury for many diseases, including cardiovascular diseases, neurodegenerative diseases, diabetes, sepsis, and cancer. This paper is to review the recent clinical and experimental researches about the anti-inflammatory effects and the related mechanisms of Rhodiola rosea L. extracts, preparations, and the active compounds. From the collected information reviewed, this paper will provide the theoretical basis for its clinical application, and provide the evidences or guidance for future studies and medicinal exploitations of Rhodiola rosea L.

The pharmacodynamics of propofol are closely linked to gender. Dexmedetomidine can decrease propofol needs during propofol anesthesia. The aim of this study was to compare the gender differences on the calculated effect site median effective concentration (EC50) of propofol for loss of consciousness (LOC) after pretreatment with different concentrations of dexmedetomidine. In this study 60 male and 60 female patients were randomly allocated to receive dexmedetomidine at target plasma concentrations of 0.0 ng/ml (0.0 group), 0.4 ng/ml (0.4 group), 0.6 ng/ml (0.6 group) and 0.8 ng/ml (0.8 group). Propofol was administered after dexmedetomidine had been intravenously infused for 15 min. The propofol infusion was targeted to provide an initial effect-site concentration of 1.0 μg/ml, followed by increments by 0.2 μg/ml when the effect-site concentration and target concentration of propofol were in equilibrium until LOC was established, where LOC was defined by the observer’s assessment of alertness/sedation scale (OAA/S) score

Psoralen is the main active component of Psoralea corylifolia and is used as a marker to assess its quality. The effects of psoralen on animals have been well characterized. However, the molecular pathway of its toxicity is not fully understood. In this study, the toxic effects of psoralen administration (60 mg/kg) for 7 days in Sprague-Dawley rats were observed. Serum biochemistry and liver histopathology were further investigated. Proton nuclear magnetic resonance was applied to characterize the metabolic profile of liver toxicity induced by psoralen and to find changed metabolites in rat serum and liver. It was revealed that visceral coefficients and serum biochemistry indexes were significantly changed in rats with psoralen-induced liver injury. Furthermore, the histopathological examination exhibited that the liver might be the target organ for psoralen. Metabolic analysis of both serum and liver samples further proved the liver was the target of toxicity of psoralen. Multivariate analysis identified 7 metabolites in serum samples and 15 in liver samples as potential biomarkers in liver injury induced by psoralen. In addition, our results suggest that psoralen can cause a disturbance in amino acid metabolism, especially valine, leucine, and isoleucine biosynthesis in both serum and liver samples. In conclusion, we combined the results of toxicity and metabolomics induced by psoralen and provide useful information about the safety and potential risks of psoralen and Psoralea corylifolia.

Our study aims to elucidate the mechanisms how microRNA-129-5p (miR-129-5p) involved in the neuroprotective effect of dexmedetomidine (DEX) on hypoxic-ischemic brain injury (HIBI) by targeting the type III procollagen gene (COL3A1) through the Wnt/β-catenin signaling pathway in neonatal rats. A total of 120 rats were obtained, among which 15 rats were selected as sham group and rest rats as model, DEX, DEX + negative control (DEX + NC), DEX + miR-129-5p mimics, DEX + miR-129-5p inhibitors, DEX + XAV-939, and DEX + miR-129-5p inhibitors + XAV-939 groups. A dual-luciferase reporter assay was performed for the target relationship between miR-129-5p and COL3A1. Weight rate and water content of cerebral hemisphere were detected. Quantitative real-time polymerase chain reaction and Western blot analysis were conducted to detect miR-129-5p expression and expressions of COL3A1, E-cadherin, T-cell factor (TCF)- 4, and β-catenin. The DEX, DEX + miR-129-5p mimics, DEX + XAV-939 groups had increased weight rate of the cerebral hemisphere, but decreased water content of left cerebral hemisphere, levels of COL3A1, β-catenin, TCF-4, and E-cadherin in the hippocampus compared with the model and DEX + miR-129-5p inhibitors groups. COL3A1 was verified as the target gene of the miR-129-5p. Compared with the DEX + NC and DEX + miR-129-5p inhibitors + XAV-939 groups, the DEX + XAV-939 and DEX + miR-129-5p mimics groups had elevated weight rate of the cerebral hemisphere, but reduced water content of left cerebral hemisphere, levels of COL3A1, β-catenin, TCF-4, and E-cadherin in the hippocampus. Our findings demonstrate that miR-129-5p improves the neuroprotective role of DEX in HIBI by targeting COL3A1 through the Wnt/β-catenin signaling pathway in neonatal rats.

Objective: Approximately 1.6-3.4% and 2-4% of NSCLC patients harbor EGFR or HER2 exon20 insertion mutations, respectively. No targeted therapy has been approved for these patients yet. NIP142 is a novel EGFR/HER2 inhibitor with potent inhibitory activities against above mentioned mutations. Purpose of this study is to provide evidence to support NIP142 as a clinical candidate for treatment of NSCLC driven by EGFR or HER2 exon20 insertion mutations. Method: Enzymatic activities of NIP142 were evaluated in EGFR/HER2 exon20 insertion mutants, including EGFR (D770_N771insNPG) and HER2 (V777_G778ins>CG). Anti-proliferative activities of NIP142 were evaluated in Ba/F3 cell lines with exon20 mutants (such as EGFR(D770_N771insSVD), EGFR(H773_V774insNPH), EGFR(V769_D770insASV), HER2(A775_G776insYVMA)), LU0387(EGFR-H773_V774insNPH), NCI-H1975 (EGFRL858R/T790M) and A431 (EGFRWT) cell lines. In vivo efficacy was evaluated in genetically engineered Ba/F3 (EGFR-D770_N771insSVD) mouse model, and LU0387 (EGFR-H773_V774insNPH) PDX model. Result: NIP142 displayed potent enzymatic inhibition activities in exon20 mutants, such as EGFR (D770_N771insNPG) (IC50 = 0.5 nM), HER2 (V777_G778ins>CG) (IC50 = 0.67 nM) and potent anti-proliferative activities in Ba/F3 cell lines with exon20 mutants, EGFR-D770_N771insSVD (IC50 = 32 nM), EGFR-H773_V774insNPH (IC50 = 32 nM), EGFR-V769_D770insASV (IC50 = 22 nM), HER2 A775_G776insYVMA (IC50 = 30 nM) respectively. NIP142 also exhibited potent anti-proliferative activities in NCI-H1975 (EGFRT790M\L858R) (IC50 = 9.4 nM), LU0387 (EGFR-H773_V774insNPH) (IC50 = 25 nM), and moderate anti-proliferation activity in EGFRWT A431cell line (IC50 = 37 nM). NIP142 was investigated in various CDX models. In particular, NIP142 significantly inhibited tumor growth in the LU0387 (EGFR-H773_V774insNPH) PDX tumor model of NSCLC, and tumor regression was achieved at 15 mg/kg. Conclusion: NIP142 is a potent EGFR/HER2 exon20 insertions inhibitor and showed excellent activities in preclinical in vitro assays and relevant tumor models. These results together with its preclinical safety data (not shown) support NIP142 to enter the clinical research to explore its potential for treating NSCLC with EGFR/HER2 exon20 insertions. Citation Format: Huijun Yin, Xu Yan, Weixue Tian, Guobiao Chu, Zhuo Wang, Xin Zhao, lu zhang, Xile Liu, Charles Z. Ding, Lihong Hu, Chengyuan Li, Gang Bai, Yuanfeng Xia, Chi-Chung Chan, Shuhui Chen. A potent and selective EGFR/HER2 exon 20 mutations inhibitor NIP142 induced tumor regression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2298.

The switch of coal to gas in power generation enterprises is of great significance for tackling air pollution and mitigating climate change. Under China’s emissions trading system, power generation enterprises have incentives to switch to low-carbon clean power, and the cost-benefit of switching is the basis of their decision-making. To this end, this paper studied the impact of changes in carbon and fuel prices on switching prices. The results show that: (1) For per yuan increase in the amount of natural gas, coal, and carbon, the switching price increased 4.768, decreased 5.845 and decreased 0.9994 yuan, respectively. (2) The carbon price is relatively low, and the impact of it on switching price is small. (3) The fluctuation in the carbon price, coal price and the natural gas price has a hysteresis effect on switching price.

Aim Chronic hypoxia leads to right ventricular hypertrophy (RVH). RVH is believed to result from hypoxia-induced pulmonary hypertension. However, if hypoxia impacts RVH directly awaits clarification. Hypoxia triggers oxidative stress, and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) mediates reactive oxygen species (ROS) generation in different cells. Therefore, this study aims to explore whether LOX-1-mediated oxidative stress accounts for hypoxia-induced RVH. Main methods Rats developed RVH after 3 weeks of hypoxia (10% O2). Immunofluorescence staining was performed to evaluate H9C2 cell hypertrophy induced by hypoxia (3% O2). Real-time PCR and Western-blot were performed to assess LOX-1, NADPH oxidases (NOX), collagen I/III, atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) expression. DCFH-DA staining was performed to measure ROS generation. Key findings Hypoxia induced RVH and cardiac fibrosis in rats, as indicated by enlarged cardiomyocytes and deposition of extracellular matrix. Interestingly, hypoxia treatment directly induced H9C2 cardiomyocyte hypertrophy, implying direct effects of hypoxia on cell hypertrophy. Rat and H9C2 hypertrophy model revealed that cell hypertrophy was accompanied by marked increase in LOX-1 expression. Knockdown of LOX-1 significantly ameliorated H9C2 cell hypertrophy. Mechanistically, hypoxia induced prominent oxidative stress in rat right ventricles and H9C2 cells, most likely as a result from increased expression of NOX2/4, contributing to RVH. Knockdown of LOX-1 significantly attenuated H9C2 cell oxidative stress, with a concomitant decrease in NOX2/4 expression. Significance LOX-1/NOX/ROS pathway could represent a novel mechanism underlying hypoxia-induced RVH. Therapeutic targeting of LOX-1 would be exploited to treat RVH owing to chronic hypoxia exposure.

This study is to investigate the protective effect of Acetyl-α-boswellic acid and Acetyl-β-boswellic mixture(α/β-ABA), which is the active ingredients isolated from Frankincense, on actue pancreatitis and its mechanism. Our experimental results showed that 2 μM α/β-ABA reduced production of NO, TNF-α, IL-6, IL-10 and IL-1β in RAW264.7 cells that were stimulated with lipopolysaccharide (LPS) which indicates its anti-inflammatory role. In pancreatitis model induced by caerulein, intra-gastrical administration of 100 mg/kg α/β-ABA relieved inflammatory cells infiltration significantly and attenuated the serum elevation of amylase TNF-α and IL-6 remarkably in mice. Furthermore, α/β-ABA down-regulated mitogen-activated protein kinase (MAPK) family phosphorylated proteins in pancreas, including phosphorylated p38, ERK1/2 and JNK, to reduce the serum inflammatory factors. Finally, α/β-ABA alleviated the pancreatic edema and inflammatory cell infiltration in pancreatitis mice model. This study suggests that α/β-ABA may be targeted for drug development against pancreatitis via modulating MAPKs pathway.

It has well been demonstrated that E3 ubiquitin ligase cullin7 plays important roles in cancer cell growth control via down-regulating p53 expression. The noncanonical function or the pathogenic role of p53 has more recently been implicated in pulmonary vascular remodeling. Therefore, whether cullin7 participates in hypoxia-induced pulmonary vascular remodeling deserves to be elucidated. The present study found that hypoxia up-regulated the expression of cullin7 mRNA and protein in pulmonary arteries and pulmonary artery smooth muscle cells, and knockdown of cullin7 inhibited hypoxia-induced proliferation and migration of pulmonary artery smooth muscle cells and reversed hypoxia-induced inhibition of p53 expression. Notably, administration of proteasome inhibitor MG132 significantly inhibited the expression of cullin7 and up-regulated the expression of p53 in pulmonary arteries concomitantly with improvement of hypoxia-induced pulmonary vascular remodeling. Our study demonstrated that hypoxia induced up-regulation of cullin7 expression resulting to the proliferation and migration of pulmonary artery smooth muscle cells via down-regulating p53 expression, which contributed to pulmonary vascular remodeling.

Background The main bioactive components of Fructus psoraleae, such as psoralen and isopsoralen, are known to be hepatotoxic. However, its underlying mechanism is to be elucidated. Methods To address this, SD rats were randomly divided into control group, 60 mg/kg psoralen group and 60 mg/kg isopsoralen group. Blood was collected to detect serum biochemical indices. RNA was extracted from liver samples, and then, cDNA gene expression profiles were analysed. Results Psoralen administration significantly up-regulated serum AST (aspartate aminotransferase) while addition of isopsoralen increased serum ALT (alanine aminotransferase), AST, TBA (total bile acid) and TG (total triglyceride) levels. A total of 172 differentially expressed genes (DEGs) were acquired between psoralen group and control group while 884 DEGs were screened between isopsoralen group and control group. Chemical Carcinogenesis and Metabolism of Xenobiotics by Cytochrome P450 were the two most significantly enriched pathways as revealed by DEGs. Liver was the most impacted organ, and endoplasmic reticulum was the most impacted organelle in subcellular level. Finally, some kinds of cancers and cytochrome p450 oxidoreductase deficiency were predicted. Taken together, psoralen and isopsoralen might cause hepatotoxicity mainly through cytochrome P450 metabolism of xenobiotics. Furthermore, Cyp1a1, Cyp1a2, Gstm1 and Akr7a3 worked as key genes in hepatotoxicity. Moreover, endoplasmic reticulum was the main target subcellular structure in hepatotoxicity induced by psoralen and isopsoralen.

Tailpipe emissions of gasoline vehicles are one of a main cause of atmospheric environmental problems such as global warming and haze. The substitution of electric vehicles for conventional gasoline vehicles is a promising new way to reduce urban air pollution in many countries such as America, Japan, the EU countries and China. In 2011, Beijing launched a plan that was the substitution of electric vehicles (such as Midi taxis) for gasoline vehicles (such as Hyundai taxis) to low carbon transformations. Our study used local data and LCA based analysis to compare environmental impacts of the transition from Hyundai gasoline vehicles to Midi electric vehicles. We established a life cycle analysis (LCA) model with GaBi6 software and a life cycle assessment integrated model by CML2001 (Problem oriented) and EI99 (Damage oriented) models, which evaluated the comparative environmental impacts of the full life cycle, production stage, use stage and end of life. Finally, we analyzed the key haze-induced factors, key life cycle processes and the sensitivities of lifetime and electric power mix. Our results indicated that in light of the full life cycle assessment, electric vehicles could play significant role in decreasing the potential of Global Warming, Abiotic Depletion and Ozone Layer Depletion; whereas, electric vehicles also exhibited the impacts for increases in the potential of Acidification, Eutrophication, Human Toxicity and Eco-toxicity (marine aquatic and terrestrial). On the basis of inventory data analysis and 2010 Beijing electricity mix, the comparative results of haze-induced pollutants emissions showed that the full life cycle emission of VOCs from a Midi electric vehicle was lower than a Hyundai gasoline vehicle, but the emissions of PM2.5, NOx, SOx of a Midi electric vehicle were higher than a Hyundai gasoline vehicle. These differences are mainly the result of different emissions during the use stages. In addition, the results of sensitivity analysis indicated that the decreased rate of Green House Gas per kilometer (Midi relative to Hyundai) gradually improved with the increase of lifetime and use of cleaner energy; haze-induced pollutants and carbon emissions from EVs could be reduced significantly with the increased use of cleaner energy.

Neutrophils have been recognized as critical response cells during the pathogenesis of endotoxin-induced uveitis (EIU). Apoptosis of neutrophils induced by roscovitine has previously been demonstrated to ameliorate inflammation in several in vivo models. The present study aimed to assess whether roscovitine ameliorates EIU. EIU was induced in female C57BL/6 mice by a single intravitreal injection of lipopolysaccharide (LPS; 250 ng). The mice were divided into three groups as follows: LPS alone, LPS plus vehicle, LPS plus roscovitine (50 mg/kg). The mice were euthanized 12, 24, 48 and 72 h after LPS-induced uveitis. Accumulation of inflammatory cells in the vitreous body was confirmed by immunohistochemistry, and quantified following hematoxylin and eosin staining. Terminal deoxynucleotidyl transferase dUTP nick-end labeling was performed to detect of apoptotic cells. The mRNA levels of inflammatory cytokines were analyzed by reverse transcription-quantitative polymerase chain reaction and the changes in protein levels were analyzed by western blotting. Inflammatory cells accumulated in the vitreous near the optic nerve head and the quantity peaked at 24 h after LPS injection. Immunohistochemistry revealed that the majority of the inflammatory cells were neutrophils. The number of infiltrating cells was similar in the LPS and LPS plus vehicle groups, while there were significantly less in the roscovitine group at 24 h. Apoptosis of neutrophils was observed between 12 and 48 h after roscovitine injection, while no apoptosis was observed in the other groups. The mRNA expression levels of GMCSF, CINC-1 and ICAM-1 peaked at 12 h after LPS injection, and decreased to normal levels at 72 h. This trend in mRNA expression was similar in the LPS and LPS plus vehicle groups; however, the expression levels decreased more quickly in the roscovitine group at 24 and 48 h. Following roscovitine administration, upregulated cleaved caspase 3 expression levels and downregulated Mcl-1 expression levels were observed. In conclusion, roscovitine ameliorates EIU by effecting neutrophil apoptosis. Timely apoptosis of neutrophils may be an effective process to promote the amelioration of EIU.

Artemisia selengensis Turcz (AST) is a perennial herb with therapeutic and economic applications in China. The effects of ultrasound-assisted extraction (UAE) parameters upon extraction yield (EY%), antioxidant and antitumor activities of the polysaccharides extracts were studied by using a factorial design and response surface methodology. The optimal conditions determined were as: ultrasonic power 146 W, extraction time 14.5 min. and extraction temperature 60 °C. The average molecular weights of two homogeneous polysaccharides (APS1 and APS2) purified by DEAE cellulose-52 and Sephadex G-100 column chromatography were 125.4 and 184.1 kDa, respectively. Monosaccharide analysis showed that APS1 and APS2 were composed of five common monomers i.e., galactose, mannose, arabinose, xylose and rhamnose and one different monomer glucose and galacturonic acid respectively, with a most abundant part in molar % of APS1 and APS2 were glucose (83.01 %) and galacturonic acid (48.87 %) while least were xylose (0.80 %) and mannose (1.73 %) respectively. The antioxidant properties were determined by evaluating DPPH, hydroxyl radical scavenging activity and reducing power which indicated both APS1 and APS2 showed strong scavenging activities and anticancer activities on HT-29, BGC823 and antitumor activity on HepG-2. As UAE improved the polysaccharides yield than CSE, meanwhile, no significant difference of polysaccharides chemical compositions. Therefore, the present study suggests that the consumption of AST leaves may beneficial for the treatment of many diseases.

The MADS-box gene family encodes transcription factors with many biological functions that extensively regulate plant growth, development and reproduction. Erigeron breviscapus is a medicinal herb used widely in traditional Chinese medicine, and is believed to improve blood circulation and ameliorate platelet coagulation. In order to gain a detailed understanding of how transcription factor expression may regulate the growth of this potentially important medicinal plant, a genome-wide analysis of the MADS-box gene family of E. breviscapus is needed. In the present study, 44 MADS-box genes were identified in E. breviscapus and categorized into five subgroups (MIKC, Mα, Mβ, Mγ and Mδ) according to their phylogenetic relationships with the Arabidopsis MADS-box genes. Additionally, the functional domain, subcellular location and motif compositions of the E. breviscapus MADS-box gene products were characterized. The expression levels for each of the E. breviscapus MADS-box (EbMADS) genes were analyzed in flower, leaf, stem and root organs, and showed that the majority of EbMADS genes were expressed in flowers. Meanwhile, some MADS genes were found to express high levels in leaf, stem and root, indicating that the MADS-box genes are involved in various aspects of the physiological and developmental processes of the E. breviscapus. The results from gene expression analysis under different pollination treatments revealed that the MADS-box genes were highly expressed after non-pollinated treatment. To the best of our knowledge, this study describes the first genome-wide analysis of the E. breviscapus MADS-box gene family, and the results provide valuable information for understanding of the classification, cloning and putative functions of the MADS-box family.

Recent studies have implied that circHIPK3, an abundant circular RNA (circRNA), participates in tumorigenesis and cancer progression. Its expression and potential functions in human gallbladder cancer were examined in this study. We show that circHIPK3 is upregulated in human gallbladder cancer cells. But its level is low in gallbladder epithelial cells. circHIPK3 silencing by targeted siRNA potently inhibited survival and proliferation of established and primary human gallbladder cancer cells, while inducing cell apoptosis. Conversely, ectopic over-expression of circHIPK3 can further promote cancer cell proliferation. In gallbladder cancer cells, circHIPK3 sponged the tumor-suppressive microRNA-124 (miR-124) to sequester and inhibit its activity, thereby leading to increased expression of miR-124 targets, including ROCK1 (rho-associated protein kinase 1) and CDK6 (rho-associated protein kinase). Ectopic over-expression of miR-124 b y a lentiviral vector mimicked and abolished actions by circHIPK3 siRNA in gallbladder cancer cells. At last, we show that circHIPK3 is upregulated in human gallbladder cancer tissues, which is correlated with miR-124 downregulation and ROCK1-CDK6 upregulation. Together, we conclude that circHIPK3 promotes gallbladder cancer cell growth possibly by sponging miR-124. The over-expressed circHIPK3 could be a novel therapeutic target and diagnosis marker of human gallbladder cancer.

Brachial plexus avulsion (BPA) is one of the major injuries in motor vehicle accidents and may result in neuropathic pain. Accumulating evidence suggests that 30–80% of BPA developed neuropathic pain in human. In our study, complete brachial plexus avulsion (C5–T1) rats model leads to the results that 37.5% of rats had long-lasting (up to 6 months) mechanical allodynia and cold allodynia. We observed the activation of astrocyte and microglial in cervical spinal cord after BPA. Complete brachial plexus avulsion mimics human nerve root traction injury following traffic accidents. The complete BPA rat model approach human injuries and can be used for further investigations.

Laser-induced fluorescence(LIFS), which is one of most effective discrimination methods to identify the material at the molecular level by inducing fluorescence spectrum, has been popularized for its fast and accurate probe’s results. According to the research, violet laser or ultraviolet laser is always used as excitation light source. While, There is no atmospheric window for violet laser and ultraviolet laser, causing laser attenuation along its propagation path. What’s worse, as the laser reaching sample, part of the light is reflected. That is, excitation laser really react on sample to produce fluorescence is very poor, leading to weak fluorescence mingled with the background light collected by LIFS’ processing unit, when it used outdoor. In order to spread LIFS to remote probing under the complex background, study of improving signal-noise ratio for fluorescence channel is a meaningful work. Enhancing the fluorescence intensity and inhibiting background light both can improve fluorescence’ signal-noise ratio. In this article, three different approaches of inhibiting background light are discussed to improve the signal-noise ratio of LIFS. The first method is increasing fluorescence excitation area in the proportion of LIFS’ collecting field by expanding laser beam, if the collecting filed is fixed. The second one is changing field angle base to accommodate laser divergence angle. The third one is setting a very narrow gating circuit to control acquisition circuit, which is shortly open only when fluorescence arriving. At some level, these methods all can reduce the background light. But after discussion, the third one is best with adding gating acquisition circuit to acquisition circuit instead of changing light path, which is effective and economic.