Publications by authors named "Jia Zhong"

144 Publications

Stepwise Fabrication of Co-Embedded Porous Multichannel Carbon Nanofibers for High-Efficiency Oxygen Reduction.

Nanomicro Lett 2019 Apr 6;11(1):33. Epub 2019 Apr 6.

Jiangsu Key Laboratory of Materials and Technology for Energy Conversion, College of Materials Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing, 210016, People's Republic of China.

A novel nonprecious metal material consisting of Co-embedded porous interconnected multichannel carbon nanofibers (Co/IMCCNFs) was rationally designed for oxygen reduction reaction (ORR) electrocatalysis. In the synthesis, ZnCoO was employed to form interconnected mesoporous channels and provide highly active CoO/Co core-shell nanoparticle-based sites for the ORR. The IMC structure with a large synergistic effect of the N and Co active sites provided fast ORR electrocatalysis kinetics. The Co/IMCCNFs exhibited a high half-wave potential of 0.82 V (vs. reversible hydrogen electrode) and excellent stability with a current retention up to 88% after 12,000 cycles in a current-time test, which is only 55% for 30 wt% Pt/C.
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http://dx.doi.org/10.1007/s40820-019-0264-2DOI Listing
April 2019

Establishment and characterization of a rat intestinal microvascular endothelial cell line.

Tissue Cell 2021 Jun 9;72:101573. Epub 2021 Jun 9.

Division of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, PR China. Electronic address:

Intestinal microvascular endothelial cell (IMVEC) is a fundamental and essential component of gut-vascular barrier which is closely associated with intestinal disorders However, there is still a lack of established intestinal microvascular endothelial cell line. In the present study, a newly established rat intestinal microvascular endothelial cell line termed RIMVEC-11 was described and characterized which has been stably cultured for more than 90 passages so far. RIMVEC-11 was characterized by endothelial features with the cobblestone morphology under light microscopy, the Weibel-Palade body and rich vesicles in the cytoplasm on the ultrastructural level, and positive endothelial specific markers CD31 and von Willebrand factor by immunocytochemistry analysis. Meanwhile, RIMVEC-11 maintained the fundamental physiological function of the microvascular endothelial cells. Tube formation assay confirmed that RIMVEC-11 retained the potential for capillaries formation. Scratch assay confirmed the endothelial cell migration potential of RIMVEC-11. Thus, a novel IMVEC cell line RIMVEC-11 was established, which could be used as a promising model for the gut-vascular barrier research.
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http://dx.doi.org/10.1016/j.tice.2021.101573DOI Listing
June 2021

Efficacy and Safety of Combination Treatment With Apatinib and Osimertinib After Osimertinib Resistance in Epidermal Growth Factor Receptor-Mutant Non-small Cell Lung Carcinoma-A Retrospective Analysis of a Multicenter Clinical Study.

Front Mol Biosci 2021 5;8:639892. Epub 2021 May 5.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology, Peking University Cancer Hospital and Institute, Beijing, China.

Currently, there are limited treatment options for patients who developed resistance to osimertinib, a third-generation epidermal growth factor receptor (EGFR) inhibitor. Resistance to EGFR inhibitors is frequently associated with enhanced vascular endothelial growth factor (VEGF) levels. This multicenter, retrospective study aimed to evaluate the efficacy of the combination treatment with apatinib and osimertinib in 39 patients with EGFR-mutant non-small cell lung carcinoma (NSCLC) who developed osimertinib resistance. The patients received the combination of oral apatinib 250 mg qd and osimertinib 80 mg qd. The efficacy was evaluated after the first month then every 2 months thereafter. The primary endpoint was progression-free survival (PFS). The overall response rate (ORR) and the disease control rate (DCR) of the combination of apatinib and osimertinib was 12.8% (5/39) and 79.5% (31/39), respectively. The median PFS was 4 months [95% confidence interval (CI): 3.5-4.5 months]. Fourteen patients were administered with at least 6 months of combination therapy, and 11 of them remained on treatment programs. The 6-month PFS rate was 38%. Nine patients underwent biopsies after failing osimertinib treatment, and five of six patients with TP53 mutations had PFS of less than 3 months. The spectrum of resistance to osimertinib mechanisms included c-mesenchymal-epithelial transition factor (c-Met) amplification, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gain-of-function mutation, phosphatase and tensin homolog (PTEN) loss-of-function mutation, Erb-B2 receptor tyrosine kinase 2 (ERBB2) amplification, and insulin-like growth factor 1 receptor (IGF1R) mutation. The most common adverse events were hypertension (30.7%, 12/39), diarrhea (15.4%, 6/39), and proteinuria (12.8%, 5/39). The combination of apatinib and osimertinib improved the ORR and the DCR of patients with osimertinib-refractory EGFR-positive NSCLC, thus making it a reasonable treatment choice after the development of osimertinib resistance.
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http://dx.doi.org/10.3389/fmolb.2021.639892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131525PMC
May 2021

Naringenin prevents TNF-α-induced gut-vascular barrier disruption associated with inhibiting the NF-κB-mediated MLCK/p-MLC and NLRP3 pathways.

Food Funct 2021 Mar 5;12(6):2715-2725. Epub 2021 Mar 5.

Division of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, P. R. China.

The microvasculature endothelium accurately regulates the passage of molecules across the gut-vascular barrier (GVB), which plays an essential role in intestinal immunity. Naringenin is reported to have therapeutic potential against several intestinal disorders. However, the effect of naringenin on GVB disruption has been rarely studied. This study aims to investigate the effect of naringenin on GVB function and the potential mechanism. In the present study, the in vitro GVB disruption of rat intestinal microvascular endothelial cells (RIMVEC) was induced by 50 ng mL of tumor necrosis factor-α (TNF-α). The integrity of the in vitro GVB was determined by Evans blue (EB)-albumin efflux assay and trans-endothelial electrical resistance (TER). Meanwhile, the expression of tight junction proteins and the related NF-κB, MLCK/p-MLC and NLRP3 pathways were determined using enzyme-linked immunosorbent assay (ELISA), real-time quantitative polymerase chain reaction (RT-qPCR), western blot analysis and immunofluorescence. The results show that naringenin (100 μM) inhibits TNF-α-induced interleukin (IL)-6 hypersecretion, alleviates GVB disruption and mitigates the change in the tight junction protein expression pattern. Naringenin inhibits the GVB-disruption-associated activation of the MLCK/p-MLC system and TLR4/NF-κB/NLRP3 pathways. Furthermore, naringenin shows a similar effect to that of NF-κB inhibitor Bay 11-7082 in reducing the TNF-α-induced activation of NLRP3, p-MLC and secondary GVB disruption. The results suggest that naringenin evidently alleviates TNF-α-induced in vitro GVB disruption via the maintenance of a tight junction protein pattern, partly with the inhibition of the NF-κB-mediated MLCK/p-MLC and NLRP3 pathway activation.
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http://dx.doi.org/10.1039/d1fo00155hDOI Listing
March 2021

Genome sequences reveal global dispersal routes and suggest convergent genetic adaptations in seahorse evolution.

Nat Commun 2021 02 17;12(1):1094. Epub 2021 Feb 17.

CAS Key Laboratory of Tropical Marine Bio-Resources and Ecology, South China Sea Institute of Oceanology, Innovation Academy of South China Sea Ecology and Environmental Engineering, Chinese Academy of Sciences, Guangzhou, China.

Seahorses have a circum-global distribution in tropical to temperate coastal waters. Yet, seahorses show many adaptations for a sedentary, cryptic lifestyle: they require specific habitats, such as seagrass, kelp or coral reefs, lack pelvic and caudal fins, and give birth to directly developed offspring without pronounced pelagic larval stage, rendering long-range dispersal by conventional means inefficient. Here we investigate seahorses' worldwide dispersal and biogeographic patterns based on a de novo genome assembly of Hippocampus erectus as well as 358 re-sequenced genomes from 21 species. Seahorses evolved in the late Oligocene and subsequent circum-global colonization routes are identified and linked to changing dynamics in ocean currents and paleo-temporal seaway openings. Furthermore, the genetic basis of the recurring "bony spines" adaptive phenotype is linked to independent substitutions in a key developmental gene. Analyses thus suggest that rafting via ocean currents compensates for poor dispersal and rapid adaptation facilitates colonizing new habitats.
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http://dx.doi.org/10.1038/s41467-021-21379-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889852PMC
February 2021

Plasma cytokines interleukin-18 and C-X-C motif chemokine ligand 10 are indicative of the anti-programmed cell death protein-1 treatment response in lung cancer patients.

Ann Transl Med 2021 Jan;9(1):33

Department of Immunology, School of Basic Medical Sciences, Peking University, and NHC Key Laboratory of Medical Immunology (Peking University), Beijing, China.

Background: Although programmed cell death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) checkpoint inhibitors have shown prominent efficacy for treatment of advanced lung cancer, the outcomes of metastatic lung cancer remain poor throughout the world. Although progression-free survival (PFS) and overall survival (OS) have improved in the first- and second-line therapy settings for advanced lung cancer, the response rates to PD-1/PD-L1 inhibition range from 20% to 40%. Furthermore, patients may be at risk for immune-related adverse events (irAEs); hence, appropriate patient selection is crucial. This study aimed to identify a panel of plasma cytokines representing prognostic and predictive biomarkers of the response to anti-PD-1/PD-L1 treatment.

Methods: We prospectively studied 32 lung cancer patients who received anti-PD-1/PD-L1 antibody immunotherapy. Plasma cytokines in peripheral blood samples were evaluated and analyzed using flow cytometry at the time of diagnosis and at 2 months after the initiation of PD-1/PD-L1 inhibition.

Results: The baseline plasma concentrations of interleukin-18 (IL-18) and C-X-C motif chemokine ligand 10 (CXCL10) were correlated with the degree of tumor response. Moreover, the magnitude of plasma IL-18 and CXCL10 level fluctuations were correlated significantly with the objective tumor response to anti-PD-1/PD-L1 immunotherapy, and patients with high CXCL10 expression had significantly shorter PFS than those with low CXCL10 expression. A strong positive correlation between the fluctuation of IL-18 and interleukin-8 (IL-8) levels was detected, as was a negative correlation between the fluctuation of IL-18 and CXCL10 levels. The level of plasma C-C motif chemokine ligand 5 (CCL5) was significantly higher in patients with irAEs than in those without irAEs.

Conclusions: Plasma cytokines are related to the clinical efficacy of PD-1/PD-L1 inhibitors. IL-18 and CXCL10 are potential predictive markers for anti-PD-1/PD-L1 therapy in lung cancer patients and may play an important role in selecting patients who would benefit from PD-1/PD-L1 inhibitors.
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http://dx.doi.org/10.21037/atm-20-1513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859784PMC
January 2021

Corrigendum to "Comparative study of EGFR mutations detected in malignant pleural effusion, plasma and tumor tissue in patients with adenocarcinoma of the lung" [Lung Cancer 135 (2019) 116-122].

Lung Cancer 2021 Mar 3;153:196. Epub 2021 Feb 3.

National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 17 Panjiayuan South Lane, District Chaoyang, Beijing, China. Electronic address:

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http://dx.doi.org/10.1016/j.lungcan.2021.01.008DOI Listing
March 2021

Water Quality Effects of Economically Viable Land Use Change in the Mississippi River Basin under the Renewable Fuel Standard.

Environ Sci Technol 2021 02 12;55(3):1566-1575. Epub 2021 Jan 12.

DOE Center for Advanced Bioenergy and Bioproducts Innovation, University of Illinois at Urbana-Champaign, 1206 West Gregory Drive, Urbana, Illinois 61801, United States.

Demand for biofuel production driven by the Renewable Fuel Standard (RFS2) has coincided with increased land in corn production and increasing nitrogen (N) loss to the Gulf of Mexico. Diversifying cropland with perennial energy crops (miscanthus and switchgrass) may reduce N loss and improve water quality. However, the extent of these benefits depends on the mix of biomass feedstocks (corn stover, perennials) incentivized by the RFS2 and the extent to which energy crops displace N-intensive row crops. We developed an integrated economic-biophysical model to quantify the water quality impacts of three potential policy scenarios that provided corn ethanol at levels before the RFS2 (RFS1 baseline); 15 billion gallons of corn ethanol (corn ethanol only); or 16 billion gallons of cellulosic ethanol in addition to corn ethanol (corn + cellulosic ethanol). Our results showed that economically optimal locations for perennial energy crop production were distributed across idle cropland with lower intrinsic N loss than active cropland. We found stover removal incentivized by the RFS2 offset N loss benefits of perennial energy crops. This finding suggests that targeted incentives for N loss reduction are needed to supplement the RFS2 to induce displacement of N-intensive row crops with energy crops to reduce N losses.
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http://dx.doi.org/10.1021/acs.est.0c04358DOI Listing
February 2021

Non-Invasive Estimation of Glioma Mutation and Expression by Histogram Analysis of Dynamic Contrast-Enhanced MRI.

Front Oncol 2020 8;10:593102. Epub 2020 Dec 8.

Department of Medical Imaging, Affiliated Hospital of Nantong University, Nantong, China.

Objectives: To investigate whether glioma isocitrate dehydrogenase () 1 mutation and vascular endothelial growth factor () expression can be estimated by histogram analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).

Methods: Chinese Glioma Genome Atlas (CGGA) database was wined for differential expression of in gliomas with different genotypes. The expression and  genotypes of 56 glioma samples in our hospital were assessed by immunohistochemistry. Preoperative DCE-MRI data of glioma samples were reviewed. Regions of interest (ROIs) covering tumor parenchyma were delineated. Histogram parameters of volume transfer constant ( ) and volume of extravascular extracellular space per unit volume of tissue ( ) derived from DCE-MRI were obtained. Histogram parameters of , and expression of mutant type ( ) gliomas were compared with the wildtype ( ) gliomas. Receiver operating characteristic (ROC) curve analysis was performed to differentiate from gliomas. The correlation coefficients were determined between histogram parameters of , and expression in gliomas.

Results: In CGGA database, expression in gliomas was lower as compared to wildtype counterpart. The immunohistochemistry of glioma samples in our hospital also confirmed the results. Comparisons demonstrated statistically significant differences in histogram parameters of and [mean, standard deviation (SD), 50th, 75th, 90th. and 95th percentile] between and gliomas ( < 0.05, respectively). ROC curve analysis revealed that 50th percentile of (0.019 min) and (0.039) provided the perfect combination of sensitivity and specificity in differentiating gliomas with from . Irrespective of mutation, histogram parameters of and were correlated with expression in gliomas ( < 0.05, respectively).

Conclusions: expression is significantly lower in gliomas as compared to the wildtype counterpart, and it is non-invasively predictable with histogram analysis of DCE-MRI.
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http://dx.doi.org/10.3389/fonc.2020.593102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793903PMC
December 2020

Estimating the Effect of Elagolix Treatment for Endometriosis on Postmenopausal Bone Outcomes: A Model Bridging Phase III Trials to an Older Real-World Population.

JBMR Plus 2020 Dec 7;4(12):e10401. Epub 2020 Nov 7.

Mercy Health Osteoporosis and Bone Health Services Cincinnati OH USA.

Elagolix, a gonadotrophin-releasing hormone antagonist, is used in premenopausal women with endometriosis. There is a risk of bone loss with elagolix, but the long-term effects of BMD loss later in life cannot be directly assessed and has not been quantified. To address this gap in knowledge, this study indirectly estimated the impact of elagolix on postmenopausal fracture risk. BMD change in premenopausal women with endometriosis treated with elagolix was modeled from the phase III program data (elagolix group) and used to simulate treatment effects on (fracture risk assessment tool estimated) 10-year risks of hip and major osteoporotic fracture in women ages 50 to 79 years from the 2005-2010 National Health and Nutrition Examination Survey (NHANES; = 2303). Change in the proportion of women reaching risk-based antiosteoporotic treatment thresholds was also estimated. For elagolix versus NHANES, median 10-year risk of major osteoporotic fracture was 4.73% versus 4.70% in women ages 50 to 59 years, 7.03% versus 6.97% in women ages 60 to 69 years, and 10.83% versus 10.68% in women ages 70 to 79 years. Median 10-year risk of hip fracture in these same groups was 0.19% versus 0.18% for women ages 50 to 59 years, 0.51% versus 0.49% for women 60 to 69 years, and 2.22% versus 2.14% for women 70 to 79 years. The proportion of women reaching risk-based antiosteoporotic treatment thresholds caused by elagolix 150 mg daily for 12 months was 0.36% higher at age 50 to 59 years, 0.23% at age 60 to 69 years, and 1.79% at age 70 to 79 years. The number needed to harm was 643 for one additional hip fracture and 454 for one additional major osteoporotic fracture. Results were similar for elagolix 200 mg twice a day for 3 months. In the modeled scenarios, elagolix had minimal impact on long-term risk of fracture and reaching risk-based treatment thresholds. © 2020 The Authors. published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research © 2020 The Authors. published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbm4.10401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745882PMC
December 2020

Clinical outcomes of acute displaced posterior cruciate ligament tibial avulsion fracture: A retrospective comparative study between the arthroscopic suture and EndoButton fixation techniques.

Orthop Traumatol Surg Res 2021 04 16;107(2):102798. Epub 2020 Dec 16.

Department of Orthopaedics, The Bone Trauma Special Hospital of LiJingHua, China.

Background: Tibial avulsion fracture of the posterior cruciate ligament is not rare in the clinic. Arthroscopic treatment is increasingly accepted, but the choice of fixation has been debated. This study aims to compare the clinical outcomes of suture and EndoButton fixation under arthroscopy for acute displaced posterior cruciate ligament avulsion fractures.

Methods: A total 68 of 83 PCL tibial avulsion fracture cases from 2009 to 2016 were retrospectively reviewed. Some patients received arthroscopic suture initially, and later the others received arthroscopic EndoButton fixation. Associated lesions were treated if present. The Lysholm and International Knee Documentation Committee (IKDC) scores, KT-1000 arthrometry and plain radiography were evaluated at follow-up. The assessment data at two years of follow-up were used for comparing the two different fixation groups.

Results: The follow-up time of 63 patients was more than 2 years. In total, 32 of the 63 patients were in the suture group, and 31 were in the EndoButton group. At two years of follow-up, knee function according to the Lysholm score was a mean of 92.5 with a 95% confidence interval [CI] of 89.45 to 96.40 in the suture group and a mean of 93.5 with a 95% CI of 90.52 to 97.28 in the EndoButton group (P=.785). More than 90% of patients in both groups rated their knee function as normal or nearly normal on IKDC subjective evaluation. KT-1000 arthrometry showed that there was no difference between the two groups, with 0 to 3mm of laxity in 91% of the cases in the suture group versus 90% of cases in the EndoButton group. All patients achieved bony healing within 3 months. No significant complications were noted in the study.

Conclusions: Both the arthroscopic suture and EndoButton fixation methods for acute displaced posterior cruciate ligament avulsion fractures resulted in comparably good clinical outcomes, radiologic healing, and stable knees at mid-term follow-up.

Level Of Evidence: III; retrospective comparative study.
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http://dx.doi.org/10.1016/j.otsr.2020.102798DOI Listing
April 2021

Differential RNA Editing and Intron Splicing in Soybean Mitochondria during Nodulation.

Int J Mol Sci 2020 Dec 9;21(24). Epub 2020 Dec 9.

School of Biological Sciences, University of Hong Kong, Pokfulam, Hong Kong, China.

Nitrogen fixation in soybean consumes a tremendous amount of energy, leading to substantial differences in energy metabolism and mitochondrial activities between nodules and uninoculated roots. While C-to-U RNA editing and intron splicing of mitochondrial transcripts are common in plant species, their roles in relation to nodule functions are still elusive. In this study, we performed RNA-seq to compare transcript profiles and RNA editing of mitochondrial genes in soybean nodules and roots. A total of 631 RNA editing sites were identified on mitochondrial transcripts, with 12% or 74 sites differentially edited among the transcripts isolated from nodules, stripped roots, and uninoculated roots. Eight out of these 74 differentially edited sites are located on the transcript, of which the degrees of RNA editing were the highest in the nodule sample. The degree of mitochondrial intron splicing was also examined. The splicing efficiencies of several introns in nodules and stripped roots were higher than in uninoculated roots. These include introns 2/3/4, intron 3, introns 2/3, intron 1, and intron 1. A greater splicing efficiency of intron 1, a higher NAD4 protein abundance, and a reduction in supercomplex I + III were also observed in nodules, although the causal relationship between these observations requires further investigation.
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http://dx.doi.org/10.3390/ijms21249378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764374PMC
December 2020

Prediction of the VeriStrat test in first-line therapy of pemetrexed-based regimens for advanced lung adenocarcinoma patients.

Cancer Cell Int 2020 Dec 9;20(1):590. Epub 2020 Dec 9.

Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/ Beijing), Department of Thoracic Medical Oncology, Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China.

Background: Although advanced non-squamous non-small cell lung cancer (NSCLC) patients have significantly better survival outcomes after pemetrexed based treatment, a subset of patients still show intrinsic resistance and progress rapidly. Therefore we aimed to use a blood-based protein signature (VeriStrat, VS) to analyze whether VS could identify the subset of patients who had poor efficacy on pemetrexed therapy.

Methods: This study retrospectively analysed 72 advanced lung adenocarcinoma patients who received first-line pemetrexed/platinum or combined with bevacizumab treatment.

Results: Plasma samples from these patients were analysed using VS and classified into the Good (VS-G) or Poor (VS-P) group. The relationship between efficacy and VS status was further investigated. Of the 72 patients included in this study, 35 (48.6%) were treated with pemetrexed plus platinum and 37 (51.4%) were treated with pemetrexed/platinum combined with bevacizumab. Among all patients, 60 (83.3%) and 12 (16.7%) patients were classified as VS-G and VS-P, respectively. VS-G patients had significantly better median progression-free survival (PFS) (Unreached vs. 4.2 months; P < 0.001) than VS-P patients. In addition, the partial response (PR) rate was higher in the VS-G group than that in the VS-P group (46.7% vs. 25.0%, P = 0.212). Subgroup analysis showed that PFS was also significantly longer in the VS-G group than that in the VS-P group regardless of whether patients received chemotherapy alone or chemotherapy plus bevacizumab.

Conclusions: Our study indicated that VS might be considered as a novel and valid method to predict the efficacy of pemetrexed-based therapy and identify a subset of advanced lung adenocarcinoma patients who had intrinsic resistance to pemetrexed based regimens. However, larger sample studies are still needed to further confirm this result.
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http://dx.doi.org/10.1186/s12935-020-01662-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724790PMC
December 2020

An overview of patients with haemophilia A in China: Epidemiology, disease severity and treatment strategies.

Haemophilia 2021 Jan 27;27(1):e51-e59. Epub 2020 Nov 27.

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Hematological Disorders, Institute of Hematology & Blood Diseases Hospital, Tianjin Laboratory of Blood Disease Gene Therapy, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.

Introduction: Haemophilia A (HA) is a rare X chromosome-linked bleeding disorder resulting in missing or defective clotting factor VIII (FVIII) and causes large disease burden.

Aim: As a member of World Federation of Hemophilia, China seeks to understand the current epidemiology, disease profile and treatment landscape of patients with HA through the Hemophilia Treatment Center Collaboration Network of China (HTCCNC).

Methods: The HTCCNC enabled data collection on patients with HA from 166 member hospitals (2007-2019) across China. The distribution of patients across 31 divisions was summarized using a heat map. Patient demographics, disease severity and clinical and treatment information were summarized using descriptive statistics.

Results: HTCCNC identified 17,779 patients with HA during 2007-2019. Patients were predominantly male (99.99%), and 28.3% had a known family history of haemophilia. Among patients with lab-measured disease severity (N = 13,116), 6,519 had severe HA (49.7%), 4,788 had moderate HA (36.5%), and 1,809 had mild HA (13.8%). Among patients with information on the delays, delays in diagnosis and in treatment initiation were observed in 1,437 (28.8%) and 1,750 (39.2%) patients, respectively. On average, those patients had an 8.4 years gap between the first bleed and HA diagnosis and a delay of 8.6 years from the first bleed to treatment initiation. Additionally, 44.33% of patients relied solely on episodic treatments, and 16.2% received any prophylaxis treatments.

Conclusions: Using data from the largest haemophilia registry in China, this study indicated that delayed diagnosis and treatment, together with low utilization of prophylaxis, are key challenges for patients with HA.
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http://dx.doi.org/10.1111/hae.14217DOI Listing
January 2021

The cost-effectiveness of low-dose budesonide as a Step 2 treatment for pediatric asthma in China.

J Comp Eff Res 2020 Nov 6. Epub 2020 Nov 6.

Renji Hospital, Shanghai, 200127, China.

To compare the cost-effectiveness of low-dose budesonide versus montelukast among patients aged 1-5 years from a Chinese patient and healthcare payer perspective. A Markov model based on exacerbation states was developed. Exacerbation was defined as the need for rescue therapy (mild exacerbation) or hoscopitalization (moderate-to-severe exacerbation). Inputs including efficacy (i.e., exacerbation rates), mortality, utilities, costs and treatment adherence were obtained from literature. Compared with montelukast, low-dose budesonide led to fewer exacerbation events (1.44 vs 2.15), lower costs (¥3675 vs 4130) and slightly more quality-adjusted life years (0.974 vs 0.967) over 1 year. These findings may improve the use of low-dose budesonide, an economically and clinically preferable treatment to montelukast in pediatric patients.
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http://dx.doi.org/10.2217/cer-2020-0102DOI Listing
November 2020

Shifts in bird ranges and conservation priorities in China under climate change.

PLoS One 2020 8;15(10):e0240225. Epub 2020 Oct 8.

China Birdwatching Association, Yunnan, Kunming, China.

Climate change is one of the most significant causes of species range shift and extinction. Based on a citizen science dataset of birds in China, the Bird Report, we developed a high-resolution map of bird species richness in China, and simulated the range shifts and area changes of the 1,042 birds through the year 2070 using three different General Circulation Models and two different Representative Concentration Pathways (RCPs, including RCP 2.6 and RCP 8.5). It was found that 241-244 (under different scenarios) bird species would lose a portion of their distribution ranges; and that most species in China would move to either higher elevations or northward. The other 798-801 species would experience range expansion. Compared to resident species (n = 516), migratory birds (n = 526) may undergo more limited range expansion but a longer range shift distance on average. The species diversity of birds will considerably increase in areas higher than 1,500 m in elevation under both RCPs. Conservation priorities with higher species richness were also identified using the Zonation model. The existing national nature reserves are not sufficient for protecting important bird habitats, especially after range shifts. Significant gaps in protected areas were observed in the northern Xinjiang, southern Tibet, Greater Khingan, Sanjiang Plain, Songnen Plain, northern Bohai Rim, and southeastern coastline areas. Many of these areas are characterized by high human populations and intensive development, and establishing sizable protected areas has become difficult. Inclusive conservation mechanisms that include restoring habitats in urban parks and sharing habitats in farmland areas, may be a feasible solution.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240225PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544134PMC
December 2020

Cost-effectiveness analysis of double low-dose budesonide and low-dose budesonide plus montelukast among pediatric patients with persistent asthma receiving Step 3 treatment in China.

J Med Econ 2020 Dec 14;23(12):1630-1639. Epub 2020 Oct 14.

Renji Hospital, Shanghai, China.

Aims: For children aged 1-5 years with persistent asthma, double low-dose inhaled corticosteroids (ICS) are recommended as the preferred Step 3 treatment and low-dose ICS plus leukotriene receptor antagonists (LTRA) as an alternative. Budesonide inhalation suspension (0.5 mg daily) and montelukast (4.0 mg daily) are commonly used low-dose ICS and LTRA, respectively, among children in China. This study compared the cost-effectiveness of double low-dose budesonide vs. low-dose budesonide plus montelukast from a Chinese healthcare payer's perspective.

Methods: A Markov model was constructed with four health states (i.e. no exacerbation, mild exacerbation, moderate-to-severe exacerbation, and death). Transition probabilities were estimated based on exacerbation rates, case-fatality of hospitalized patients due to exacerbation, and natural mortality. Treatment adherence was considered and assumed to impact both drug costs and exacerbation rates. Costs (in 2019 Chinese Yuan [¥]) included drug costs and exacerbation management costs. Cost inputs and utilities for each health state were obtained from a public database and the literature. In-depth interviews were conducted with a health economics expert to validate the model, and a clinical expert to verify inputs and assumptions related to clinical practice. Costs and quality-adjusted life-years (QALYs) were estimated over a year. Deterministic and probabilistic sensitivity analyses were performed.

Results: Compared with low-dose budesonide plus montelukast, double low-dose budesonide was associated with lower costs (¥1,534 vs. ¥2,327), fewer exacerbation events (0.43 vs. 1.67) and slightly better QALYs (0.98 vs. 0.97). Sensitivity analyses supported the robustness of the results and the generalizability of findings across geographic regions in China.

Conclusion: The cost-effectiveness analysis suggests that double low-dose budesonide is a dominant Step 3 treatment strategy compared with low-dose budesonide plus montelukast for patients aged 1-5 years with persistent asthma in China.
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http://dx.doi.org/10.1080/13696998.2020.1830410DOI Listing
December 2020

Volume-based histogram analysis of dynamic contrast-enhanced MRI for estimation of gliomas IDH1 mutation status.

Eur J Radiol 2020 Oct 27;131:109247. Epub 2020 Aug 27.

Department of Medical Imaging, Affiliated Hospital of Nantong University, NO. 20 Xisi Road Nantong 226001, Jiangsu, People's Republic of China. Electronic address:

Purpose: The study aimed to investigate whether isocitrate dehydrogenase 1 (IDH1) mutation status in gliomas can be estimated by volume-based histogram analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).

Materials And Methods: Preoperative DCE-MRI data of 85 pathologically confirmed glioma patients including 33 carrying IDH1 mutant type (IDH1) and 52 with IDH1 wildtype (IDH1) were reviewed in a retrospective approach. Regions of interest (ROI) covering entire tumor volume were manually delineated using O.K. software (OmniKinetics, GE Healthcare, China). Histogram parameters of volume transfer constant (K) and volume of extravascular /extracellular space per unit volume of tissue (V) derived from DCE-MRI were obtained. Mann-Whitney U tests were made to compare the differences in histogram parameters of K and V between IDH1 and IDH1 in all gliomas and high-grade gliomas (HGGs, grade III and IV). Receiver operator characteristic (ROC) analysis were implemented to assess the diagnostic performance.

Results: In histogram parameters of K and V, pairwise comparisons demonstrated statistically significant differences in mean, standard deviation (SD), 90th and 95th percentiles (90%, 95%) values between IDH1 and IDH1 in all cases of gliomas and HGGs (P < 0.05, respectively). The ROC analysis revealed that the cut-off values of 95% value of K (0.097 min) and mean value of V (0.099) provided the best combination of sensitivity and specificity to distinguish all gliomas with IDH1 from IDH1. In HGGs, the cut-off values of mean value of K and V (0.044 min, 0.099) played similar role.

Conclusion: Volume-based histogram analysis of DCE-MRI performs well in identification of IDH1 gliomas.
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http://dx.doi.org/10.1016/j.ejrad.2020.109247DOI Listing
October 2020

Nomogram model for predicting cause-specific mortality in patients with stage I small-cell lung cancer: a competing risk analysis.

BMC Cancer 2020 Aug 24;20(1):793. Epub 2020 Aug 24.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Thoracic Medical Oncology, Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China.

Background: The five-year cumulative incidence rate in patients diagnosed with stage I small-cell lung cancer (SCLC) who were instructed to undergo surgery was from 40 to 60%.The death competition influence the accuracy of the classical survival analyses. The aim of the study is to investigate the mortality of stage I small-cell lung cancer (SCLC) patients in the presence of competing risks according to a proportional hazards model, and to establish a competing risk nomogram to predict probabilities of both cause-specific death and death resulting from other causes.

Methods: The study subjects were patients diagnosed with stage I SCLC according to ICD-O-3. First, the cumulative incidence functions (CIFs) of cause-specific death, as well as of death resulting from other causes, were calculated. Then, a proportional hazards model for the sub-distribution of competing risks and a monogram were constructed to evaluate the probability of mortality in stage I SCLC patients.

Results: 1811 patients were included in this study. The five-year probabilities of death due to specific causes and other causes were 61.5 and 13.6%, respectively. Tumor size, extent of tumor, surgery, and radiotherapy were identified as the predictors of death resulting from specific causes in stage I SCLC. The results showed that surgery could effectively reduce the cancer-specific death, and the one-year cumulative incidence dropped from 34.5 to 11.2%. Like surgery, chemotherapy and radiotherapy improved the one-year survival rate.

Conclusions: We constructed a predictive model for stage I SCLC using the data from the SEER database. The proportional sub-distribution models of competing risks revealed the predictors of death resulting from both specific causes and other causes. The competing risk nomogram that we built to predict the prognosis showed good reliability and could provide beneficial and individualized predictive information for stage I SCLC patients.
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http://dx.doi.org/10.1186/s12885-020-07271-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445928PMC
August 2020

Clinical Characteristics and Outcomes of Patients With Primary Mediastinal Germ Cell Tumors: A Single-Center Experience.

Front Oncol 2020 16;10:1137. Epub 2020 Jul 16.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology-I, Peking University Cancer Hospital and Institute, Beijing, China.

Primary mediastinal germ cell tumors (PMGCTs) are rare. The natural history and optimal treatment strategies still need to be defined. The aim of the study was to summarize the clinical characteristics, treatment outcomes, and prognostic factors of PMGCTs. Twenty-four patients with PMGCTs who were treated from December 2008 to January 2019 were evaluated retrospectively. The Kaplan-Meier method and Cox regression analysis were used to evaluate factors associated with prognosis. The study population consisted of 23 male patients and 1 female patient. Five patients were diagnosed with seminoma and 19 patients were diagnosed with nonseminoma. The median follow-up time for all patients was 15.8 (3.9-114.5) months. The 5-year overall survival (OS) and progression free survival (PFS) rates for all patients were 65.2 and 44.3%. For nonseminoma and seminoma, the 5-year OS rates were 54.1 and 100% ( = 0.093), respectively, and the 5-year PFS rates were 28.7 and 100%, respectively ( = 0.044). In patients with nonseminoma, first-line radiotherapy indicated superior OS and PFS ( = 0.037 and 0.027, respectively). The median survival time after recurrence was 4.3 months and the 1-year survival rate after recurrence was 23.4%. These results indicated that in PMGCTs, the prognosis of seminoma is superior to that of nonseminoma. Radiotherapy may be an essential treatment in patients with nonseminoma. Patients with relapse have unfavorable prognosis.
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http://dx.doi.org/10.3389/fonc.2020.01137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378816PMC
July 2020

A nomogram model to predict death rate among non-small cell lung cancer (NSCLC) patients with surgery in surveillance, epidemiology, and end results (SEER) database.

BMC Cancer 2020 Jul 17;20(1):666. Epub 2020 Jul 17.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Thoracic Medical Oncology, Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China.

Background: This study aimed to establish a novel nomogram prognostic model to predict death probability for non-small cell lung cancer (NSCLC) patients who received surgery..

Methods: We collected data from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute in the United States. A nomogram prognostic model was constructed to predict mortality of NSCLC patients who received surgery.

Results: A total of 44,880 NSCLC patients who received surgery from 2004 to 2014 were included in this study. Gender, ethnicity, tumor anatomic sites, histologic subtype, tumor differentiation, clinical stage, tumor size, tumor extent, lymph node stage, examined lymph node, positive lymph node, type of surgery showed significant associations with lung cancer related death rate (P < 0.001). Patients who received chemotherapy and radiotherapy had significant higher lung cancer related death rate but were associated with significant lower non-cancer related mortality (P<0.001). A nomogram model was established based on multivariate models of training data set. In the validation cohort, the unadjusted C-index was 0.73 (95% CI, 0.72-0.74), 0.71 (95% CI, 0.66-0.75) and 0.69 (95% CI, 0.68-0.70) for lung cancer related death, other cancer related death and non-cancer related death.

Conclusions: A prognostic nomogram model was constructed to give information about the risk of death for NSCLC patients who received surgery.
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http://dx.doi.org/10.1186/s12885-020-07147-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367407PMC
July 2020

The outcomes of one-stage treatment for multiple knee ligament injuries combined with extensor apparatus rupture.

BMC Musculoskelet Disord 2020 Jul 9;21(1):450. Epub 2020 Jul 9.

Department of Orthopaedics, The People's Hospital of LongChuan County, Dehong, China.

Background: Multiple knee ligament injuries combined with extensor apparatus rupture are serious and complex knee injuries that are rare in clinical practice. The management is extremely challenging and controversial. The aim of this study is to describe a patient collective with multiple knee ligament injuries combined with extensor apparatus injuries in detail and to report the mid-term outcomes of a one-stage surgical treatment regarding subjective outcome scores, complications, knee instability, and ROM.

Methods: Eleven of 425 patients with multiple knee ligament injuries combined with extensor apparatus injuries admitted to our hospital were reviewed from July 2008 to May 2017. All patients underwent one-stage repair and reconstruction of multiple knee ligaments and extensor apparatus. The Lysholm knee score and the International Knee Documentation Committee (IKDC) score were adopted to evaluate the surgical effect preoperatively and at a minimum of 2 years' follow-up. Clinical data, including range of motion and knee stability, were also recorded at the final follow-up.

Results: Ten patients were followed up with a mean time of 40 (range, 24-60) months. At the last follow-up, 8 patients had joint flexion range of motion greater than or equal to120 degrees, 2 patients had joint flexion range of motion of 100-120 degrees, and 1 patient had active knee extension limitation of 5 degrees. Stress radiographs showed that the mean differences in posterior displacement were reduced from 10.8 ± 3.0 mm preoperatively to 2.0 ± 2.5 mm at the last follow-up. There were significant improvements in stress radiographs from pre- to postoperative states for all patients with multiple knee ligament injuries. The Lysholm score ranged from 85 to 96, with a mean of 92.1 (compared with 33 before surgery, P < 0.05). The final IKDC scores were A in 2 patients (20%), B in 7 (70%), and C in 1 (10%). Nine of the 10 patients (90%) returned to their former activity level.

Conclusion: Multiple knee ligament injuries combined with extensor apparatus rupture are rare. Single-stage management of the repair and reconstruction of multiple knee ligaments and extensor apparatus with proper rehabilitation is an effective and reliable procedure to restore knee stability and function.

Level Of Evidence: Level IV, therapeutic case series.
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http://dx.doi.org/10.1186/s12891-020-03470-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350637PMC
July 2020

Prevalence and economic burden of hyperkalemia in the United States Medicare population.

Curr Med Res Opin 2020 08 12;36(8):1333-1341. Epub 2020 Jun 12.

Analysis Group, Inc, Boston, MA, USA.

To estimate the prevalence and economic burden of hyperkalemia in the United States (US) Medicare population. Patients were selected from a 5% random sample of Medicare beneficiaries (01 January 2010-31 December 2014) to estimate the prevalence and economic burden of hyperkalemia. The prevalence for each calendar year was calculated as the number of patients with hyperkalemia divided by the total number of eligible patients per year. To estimate the economic burden of hyperkalemia, patients with hyperkalemia (cases) were matched 1:1 to patients without hyperkalemia (controls) on age group, chronic kidney disease [CKD] stage, dialysis treatment, and heart failure. The incremental 30-day and 1-year resource utilization and costs (2016 USD) associated with hyperkalemia were estimated. The estimated prevalence of hyperkalemia was 2.6-2.7% in the overall population and 8.9-9.3% among patients with CKD and/or heart failure. Patients with hyperkalemia had higher 1-year rates of inpatient admissions (1.28 vs. 0.44), outpatient visits (30.48 vs. 23.88), emergency department visits (2.01 vs. 1.17), and skilled nursing facility admissions (0.36 vs. 0.11) than the matched controls (all  < .001). Patients with hyperkalemia incurred on average $7208 higher 30-day costs ($8894 vs. $1685) and $19,348 higher 1-year costs ($34,362 vs. $15,013) than controls (both  < .001). Among patients with CKD and/or heart failure, the 30-day and 1-year total cost differences between cohorts were $7726 ($9906 vs. $2180) and $21,577 ($41,416 vs. $19,839), respectively (both  < .001). Hyperkalemia had an estimated prevalence of 2.6-2.7% in the Medicare population and was associated with markedly high healthcare costs.
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http://dx.doi.org/10.1080/03007995.2020.1775072DOI Listing
August 2020

Model of Short- and Long-Term Outcomes of Emicizumab Prophylaxis Treatment for Persons with Hemophilia A.

J Manag Care Spec Pharm 2020 Sep 26;26(9):1109-1120. Epub 2020 May 26.

CHOC Children's Hospital, Orange, California.

Background: Hemophilia A (HA) can result in bleeding events because of low or absent clotting factor VIII (FVIII). Prophylactic treatment for severe HA includes replacement FVIII infusions and emicizumab, a bispecific factor IXa- and factor X-directed antibody.

Objective: To develop an economic model to predict the short- and long-term clinical and economic outcomes of prophylaxis with emicizumab versus short-acting recombinant FVIII among persons with HA in the United States.

Methods: A Markov model was developed to compare clinical outcomes and costs of emicizumab versus FVIII prophylaxis among persons with severe HA from U.S. payer and societal perspectives. Patients started prophylaxis at age 1 year in the base case. Mutually exclusive health states considered were "no arthropathy," "arthropathy," "surgery," and "death." Serious adverse events, breakthrough bleeds, and inhibitor development were simulated throughout the modeled time horizon. In addition to the prophylaxis drug costs, patients could incur other direct costs related to breakthrough bleeds treatment, serious adverse events, development of inhibitors, arthropathy, and orthopedic surgery. Indirect costs associated with productivity loss (i.e., missed work or disabilities) were applied for adults. Model inputs were obtained from the HAVEN 3 trial, published literature, and expert opinion. The model used a lifetime horizon, and results for 1 year and 5 years were also reported. Deterministic sensitivity analyses and scenario analyses were conducted to assess robustness of the model.

Results: Over a lifetime horizon, the cumulative number of all treated bleeds and joint bleeds avoided on emicizumab versus FVIII prophylaxis were 278.2 and 151.7, respectively. Correspondingly, arthropathy (mean age at onset: 12.9 vs. 5.4 years) and FVIII inhibitor development (mean age at development: 13.9 vs. 1.1 years) were delayed. Total direct and indirect costs were lower for emicizumab versus FVIII prophylaxis for all modeled time horizons ($97,159 vs. $331,610 at 1 year; $603,146 vs. $1,459,496 at 5 years; and $15,238,072 vs. $22,820,281 over a lifetime horizon). The sensitivity analyses indicated that clinical outcomes were sensitive to efficacy inputs, while economic outcomes were driven by the discount rate, dosing schedules, and treatments after inhibitor development. Results for moderate to severe patients were consistent with findings in the severe HA population.

Conclusions: The model suggests that emicizumab prophylaxis confers additional clinical benefits, resulting in a lower number of bleeding events and delayed onset of arthropathy and inhibitor development across all time assessment horizons. Compared with short-acting recombinant FVIII, emicizumab prophylaxis leads to superior patient outcomes and cost savings from U.S. payer and societal perspectives.

Disclosures: Funding for this study was provided by Genentech. Raimundo and Patel are employees of Genentech and own stock or stock options. Zhou, Han, Ji, Fang, Zhong, and Betts are employees of Analysis Group, which received consultancy fees from Genentech for conducting this study. Mahajerin received consultancy fees from Genentech for work on this study. Portions of this research were presented as a poster at the 2018 American Society of Hematology Conference; December 1-4, 2018; San Diego, CA.
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http://dx.doi.org/10.18553/jmcp.2020.19406DOI Listing
September 2020

Analysis of MET kinase domain rearrangement in NSCLC.

Lung Cancer 2020 07 15;145:140-143. Epub 2020 May 15.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department I of Thoracic Oncology, Peking University Cancer Hospital & Institute, No.52, Fucheng Road, Haidian District, Beijing, China. Electronic address:

Objectives: Many MET rearrangements have been identified in various tumor types. However, the frequencies and characteristics of MET rearrangements are not well defined in non-small-cell lung cancer (NSCLC). We sought to illustrate the distribution of MET kinase domain rearrangements (KDREs) in NSCLC, and to uncover novel targets for further drug development in these patients.

Materials And Methods: Targeted sequencing using a 1021-gene panel or a 59-gene panel was performed in 5965 NSCLC cases. We sequenced all MET exons and used bioinformatics techniques to identify fusions.

Results: Fifteen MET KDREs were identified from all patients. The incidence of MET KDRE was 0.26% (15/5695) in the cohort; 60% (9/15) of the fused partners were the genes upstream or downstream of MET. All the fusions of the MET gene with upstream genes or specific regions within them were due to inversions, while the fusions with downstream genes or their encompassed regions were caused by duplications or intra-chromosomal translocations. In the MET KDRE-positive NSCLC cases who did not receive targeted therapies, 75% (6/8) harbored no actionable mutation referring to the NCCN guideline.

Conclusion: Our study illustrated the MET KDRE in NSCLC cases among the Chinese population and unearthed novel targets to develop new effective therapies for patients with MET KDRE.
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http://dx.doi.org/10.1016/j.lungcan.2020.04.040DOI Listing
July 2020

Role of MicroRNA, LncRNA, and Exosomes in the Progression of Osteoarthritis: A Review of Recent Literature.

Orthop Surg 2020 Jun 20;12(3):708-716. Epub 2020 May 20.

Department of Orthopaedics, Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine, Changsha, China.

Osteoarthritis (OA) is a common clinical degenerative disease characterized by the destruction of articular cartilage, which has an increasing impact on people's lives and social economy. The pathogenesis of OA is complex and unclear, and there is no effective way to block its progress. The study of the pathogenesis of OA is the prerequisite for the early diagnosis and effective treatment of OA. To define the pathogenesis of OA, this review considers the pathological mechanism of OA that involves microRNA, lncRNA, and exosomes. More and more evidence shows that microRNA, lncRNA, and exosomes are closely related to OA. MicroRNA inhibits the target gene by binding to the 3'- untranslated region of the targets. LncRNA usually competes with microRNA to regulate the expression level of downstream genes, while exosomes, as a carrier of intercellular information transfer, transmit the biological information of mother cells to target cells, and the effect of exosomes secreted by different cells on OA are different. In this review, we emphasized that different microRNA, lncRNA, and exosomes have different regulatory effects on chondrocyte proliferation and apoptosis, extracellular matrix degradation and inflammation. Besides, we classified and analyzed these molecules according to their effects on the progress of OA. Based on the analysis of the reported literature, this review reveals some pathogenesis of OA, and emphasizes that microRNA, lncRNA, and exosomes have great potential to assist early diagnosis and effective treatment of OA.
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http://dx.doi.org/10.1111/os.12690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307224PMC
June 2020

Real-world analysis of haemophilia patients in China: A single centre's experience.

Haemophilia 2020 Jul 20;26(4):584-590. Epub 2020 May 20.

State Key Laboratory of Experimental Hematology, Tianjin Laboratory of Blood Disease Gene Therapy, CAMS Key Laboratory of Gene Therapy for Blood Diseases, National Clinical Research Center for Hematological Disorders, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.

Introduction: The management of haemophilia is critical to minimize the risk of disability and reduce the burden on China's healthcare system.

Aim: This study was based on a single centre in China and was conducted to understand the evolution of real-world haemophilia care over the past 15 years.

Methods: We retrospectively analysed clinical characteristics, diagnosis, treatment and medical expenditures of 428 patients with haemophilia from January 2004 to December 2018 from the Institute of Hematology & Blood Diseases Hospital in Tianjin, China.

Results: The delayed diagnosis time significantly decreased from 13.3 ± 5.1 years before 2004 to 0.4 ± 0.4 year in 2014-2018 (P < .05). Among children and adults receiving prophylactic treatment, the annual factor consumption increased from 2004-2008 (168.8 IU/kg in children and 120.7 IU/kg in adults) to 2009-2013 (389.2 IU/kg in children and 316.2 IU/kg in adults) and 2014-2018 (1328.0 IU/kg in children and 878.8 IU/kg in adults, P < .001). The annual medical insurance expenditure for haemophilia had increased steadily over the past 10 years. The number of patients tested regularly for inhibitors increased from 2004 (1.9% [2/105]) to 2018 (21.5% [59/275]). The seroprevalence of hepatitis C virus (HCV) was 33.8% during the years examined, while the incidence rates of HCV among patients significantly decreased (7.3% in 2008 to 0.4% in 2018).

Conclusion: Significant improvements in the management of haemophilia were observed from 2004 to 2018. These results highlight the joint effort of the reimbursement policy and drug regulatory management paving the way for a better future for patients with haemophilia in China.
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http://dx.doi.org/10.1111/hae.14029DOI Listing
July 2020

Effects of Surgery on Survival of Early-Stage Patients With SCLC: Propensity Score Analysis and Nomogram Construction in SEER Database.

Front Oncol 2020 24;10:626. Epub 2020 Apr 24.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Thoracic Medical Oncology, Peking University Cancer Hospital & Institute, Beijing, China.

We aimed to assess the survival benefit of surgery for patients with stage IA-IIB small cell lung cancer (SCLC) and construct a nomogram for predicting overall survival (OS). Patients who had been diagnosed with stage IA-IIB SCLC between 2004 and 2014 and who had received active treatment were selected from the Surveillance, Epidemiology, and End Results database. The primary endpoint was OS. Cox proportional hazards models and propensity score (PS) analyses were used to compare the associations between surgery and OS. The probability of 1- and 3-year OS was predicted using a nomogram. We reviewed 2,246 patients. The median OS of the surgery and non-surgery groups was 35 months and 19 months, respectively. Multivariable Cox proportional hazards models showed a survival benefit in the surgery group (hazards ratio [HR], 0.642; 95% confidence interval [CI], 0.557-0.740; < 0.001). To balance the between-group measurable confounders, the impact of surgery on OS was assessed using PS matching. After PS matching, OS analysis still favored surgical resection. The PS-stratification, PS-weighting, and PS-adjustment models showed similar results to demonstrate a statistically significant benefit for surgery. Further, the nomogram was well calibrated and had good discriminative ability (Harrell's -index = 0.645). Our analysis suggests that surgery is a viable option for patients with early-stage SCLC. Our nomogram is a viable tool for quantifying treatment trade-off assumptions and may assist clinicians in decision-making. Future work is needed to validate our results and improve our tools.
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http://dx.doi.org/10.3389/fonc.2020.00626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193096PMC
April 2020

Huai hua san alleviates dextran sulphate sodium-induced colitis and modulates colonic microbiota.

J Ethnopharmacol 2020 Sep 5;259:112944. Epub 2020 May 5.

Division of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Yuan Ming Yuan West Road No. 2, Haidian District, 100193, People's Republic of China. Electronic address:

Ethnopharmacological Relevance: Huai hua san (HHS) is a traditional Chinese herbal formula which is firstly documented in the ancient Chinese classic medical work "Pu Ji Ben Shi Fang" in 1132 AD. It has been widely used in the treatment of lower gastrointestinal disorders such as acute colitis and hematochezia for more than 800 years. However, scientific evidence of the efficacy and the exact mechanism of HHS against colitis has not yet been reported.

Aim Of The Study: The aim of this study is to investigate the potential effects of HHS in the alleviation of dextran sulphate sodium (DSS)-induced colitis and the alteration of colonic microbiota composition and structure.

Materials And Methods: HHS solution was orally administrated to 5% DSS-challenged rats once a day for 8 days. Colitis clinical symptoms of colitis were collected, together with colonic mucosal damage assessed at histomorphometric and ultrastructural levels. The protein levels of inflammatory mediators TNF-α and CRP were detected by ELISA. The colonic vascular permeability was evaluated by Evans blue extravasation. Meanwhile, The effects of the HHS therapy on the colonic microbiota were evaluated by analyzing the V3 and V4 regions of the 16S rRNA gene by Illumina sequencing and multivariate statistical methods.

Results: Daily oral administration of HHS markedly alleviated DSS-induced colitis, as evidenced by decreased colitis disease activity index (DAI) score, reduced colonic inflammation and normalization of colonic vascular hyperpermeability. Moreover, the 16S rRNA gene sequencing analysis demonstrated that HHS treatment during colitis prevented the colitis-associated alteration of colonic microbial community at operational taxonomic unit level, together with the DSS-induced colonic microbiota dysbiosis at taxonomic levels. In addition, HHS therapy reduced colitis-associated high increased ratio of Bacteroidetes to Firmicutes to a normal level.

Conclusion: HHS could attenuate ulcerative colitis and ameliorate gut microbial dysbiosis.
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http://dx.doi.org/10.1016/j.jep.2020.112944DOI Listing
September 2020

Synthesis and Biological Evaluation of HDAC Inhibitors With a Novel Zinc Binding Group.

Front Chem 2020 15;8:256. Epub 2020 Apr 15.

College of Pharmacy, Hebei Medical University, Shijiazhuang, China.

Vorinostat (SAHA) with great therapeutic potential has been approved by the FDA for the treatment of cutaneous T-cell lymphoma as the first HDACs inhibitor, but the drawbacks associated with hydroxamic acid group (poor stability, easy metabolism, weak binding ability to class IIa isozymes, and poor selectivity) have been exposed during the continuous clinical application. Based on the pharmacophore of HDAC inhibitors, two series of compounds with novel zinc binding group (ZBG) were designed and synthesized, and the antitumor bioactivities were evaluated in four human cancer cell lines (A549, Hela, HepG2, and MCF-7). Among the synthesized compounds, compounds , , , , and exhibited promising inhibitory activities against the selected tumor cell lines, especially compounds and on Hela's cytostatic activity (: IC = 11.15 ± 3.24 μM; : IC = 13.68 ± 1.31 μM). The enzyme inhibition assay against Hela extracts and HDAC1&6 subtypes showed that compound had a certain broad-spectrum inhibitory activity, while compound had selective inhibitory activity against HDAC6, which was consistent with Western blot results. In addition, the inhibitory mechanism of compounds and in HDAC1&6 were both compared through computational approaches, and the binding interactions between the compounds and the enzymes target were analyzed from the perspective of energy profile and conformation. In summary, the compounds with novel ZBG exhibited certain antitumor activities, providing valuable hints for the discovery of novel HDAC inhibitors.
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http://dx.doi.org/10.3389/fchem.2020.00256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174758PMC
April 2020