Publications by authors named "X Bai"

5,411 Publications

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Mannosylated gelatin nanoparticles enhanced inactivated PRRSV targeting dendritic cells and increased T cell immunity.

Vet Immunol Immunopathol 2021 Apr 5;235:110237. Epub 2021 Apr 5.

College of Life Science and Technology, Dalian University, Dalian, 116622, PR China; Institute of Immunology, Dalian University, Dalian, 116622, PR China. Electronic address:

The objective of the present work was to evaluate the efficacy of a novel antigen carrier using mannosylated gelatin nanoparticles with entrapped inactivated porcine reproductive and respiratory syndrome virus (PRRSV) in inducing T cell mediated immunity in vitro. Gelatin nanoparticles (GNP) were modified with mannose to form mannosylated gelatin nanoparticles (MnGNP), which can efficiently and specifically target monocyte derived dendritic cells (MoDCs). The inactivated PRRSV was encapsulated in the MnGNP and GNP, referred to as MnGNP-PRRSV and GNP-PRRSV, respectively. All these prepared nanometer particles were characterized for size, surface charge, drug encapsulation efficiency, and drug release. The efficacy of MnGNP in targeting MoDCs was investigated, as well as the subsequent MoDCs maturation and T cell mediated cytotoxicity. The developed MnGNP-PRRSV particle was characterized with a nanometric size of 302.67 ± 3.2 nm, surface charge of 23.81 ± 1.26 mV, and PRRSV encapsulation efficiency of 63.2 ± 1.85 %. The maximum uptake of MnGNP in MoDCs in vitro was 15.5 times higher than GNP with a shorter reaction time that peaked 4 h earlier. The uptake of MnGNP-PRRSV induced maturation of MoDCs and significantly enhanced expression of SWC-3a, CD80, CD1, SLA I, SLA II on MoDCs, compared to PRRSV (p < 0.001). The cytokine secretion of IL-1β, IL-6, IL-10, and IL-12 was also increased in MoDCs when treated with MnGNP-PRRSV, compared to PRRSV (p < 0.05). The matured MoDCs triggered T lymphocytes in autologous peripheral blood mononuclear cells (PBMCs) activation, proliferation, and differentiation into effector cytotoxic T lymphocyte, suggesting increased amount of activated T cells after MnGNP-PRRSV treatment. Additionally, the function of T cells to kill PRRSV infected cells was 83.98 ± 2.62 % when triggered by MnGNP-PRRSV, compared to 60 ± 4.7 % in PRRSV group (p < 0.001). These results indicate that MnGNP with entrapped inactivated PRRSV can effectively and specifically target dendritic cells for maturation and activation, and subsequently improve T cell activation, proliferation and function to kill PRRSV infected cells.
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http://dx.doi.org/10.1016/j.vetimm.2021.110237DOI Listing
April 2021

Association between VPS13C rs2414739 polymorphism and Parkinson's disease risk: A meta-analysis.

Neurosci Lett 2021 Apr 7:135879. Epub 2021 Apr 7.

Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, China. Electronic address:

Objective: We aimed to estimate the role of vacuolar protein sorting 13C (VPS13C) gene single nucleotide polymorphism (SNP) rs2414739 variant in the risk of PD by meta-analysis.

Methods: Five eligible case-control studies including 2796 PD cases and 4138 health controls involved in this meta-analysis. The fixed or random effect model was selected based on the heterogeneity of the included studies which detected by I and Q tests. The association between rs2414739 polymorphism and the risk of PD was evaluated using the pooled odds ratios (OR) and 95% confidence interval (95%CI). Sensitivity analysis was used to test the stability of the results. Funnel plot and Begg's test were employed to verified publication bias.

Results: The results of our meta-analysis showed a significant correlation between VPS13C rs2424739 gene polymorphism and PD susceptibility in Allele model (A versus vs. G: OR = 1.14, 95%CI = 1.05-1.23, p = 0.002), dominant model (GG + AG vs. AA: OR = 0.86, 95%CI = 0.78-0.95, p = 0.004), heterozygote model (AG vs. AA: OR = 0.87, 95%CI = 0.77-0.99, p = 0.04), homozygote model (GG vs. AA: OR = 0.76, 95%CI = 0.60-0.96, p = 0.02). Surprisingly, we did not find a significant statistical difference between VPS13C rs2414739 polymorphism and PD risk in Chinese cohort in the regional stratified analysis.

Conclusions: This meta-analysis suggests that VPS13C rs2414739 polymorphism might act as a genetic predisposition factor for PD, whereas does not include Chinese population.
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http://dx.doi.org/10.1016/j.neulet.2021.135879DOI Listing
April 2021

FABP5 enhances malignancies of lower-grade gliomas via canonical activation of NF-κB signaling.

J Cell Mol Med 2021 Apr 9. Epub 2021 Apr 9.

Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Low-grade gliomas (LGGs) are grade III gliomas based on the WHO classification with significant genetic heterogeneity and clinical properties. Traditional histological classification of gliomas has been challenged by the improvement of molecular stratification; however, the reproducibility and diagnostic accuracy of LGGs classification still remain poor. Herein, we identified fatty acid binding protein 5 (FABP5) as one of the most enriched genes in malignant LGGs and elevated FABP5 revealed severe outcomes in LGGs. Functionally, lentiviral suppression of FABP5 reduced malignant characters including proliferation, cloning formation, immigration, invasion and TMZ resistance, contrarily, the malignancies of LGGs were enhanced by exogenous overexpression of FABP5. Mechanistically, epithelial-mesenchymal transition (EMT) was correlated to FABP5 expression in LGGs and tumour necrosis factor α (TNFα)-dependent NF-κB signalling was involved in this process. Furthermore, FABP5 induced phosphorylation of inhibitor of nuclear factor kappa-B kinase α (IKKα) thus activated nuclear factor kappa-B (NF-κB) signalling. Taken together, our study indicated that FABP5 enhances malignancies of LGGs through canonical activation of NF-κB signalling, which could be used as individualized prognostic biomarker and potential therapeutic target of LGGs.
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http://dx.doi.org/10.1111/jcmm.16536DOI Listing
April 2021

Are medical record front page data suitable for risk adjustment in hospital performance measurement? Development and validation of a risk model of in-hospital mortality after acute myocardial infarction.

BMJ Open 2021 Apr 9;11(4):e045053. Epub 2021 Apr 9.

National Clinical Research Center of Cardiovascular Diseases, NHC Key Laboratory of Clinical Research for Cardiovascular Medications, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovascular Diseases, Beijing, China

Objectives: To develop a model of in-hospital mortality using medical record front page (MRFP) data and assess its validity in case-mix standardisation by comparison with a model developed using the complete medical record data.

Design: A nationally representative retrospective study.

Setting: Representative hospitals in China, covering 161 hospitals in modelling cohort and 156 hospitals in validation cohort.

Participants: Representative patients admitted for acute myocardial infarction. 8370 patients in modelling cohort and 9704 patients in validation cohort.

Primary Outcome Measures: In-hospital mortality, which was defined explicitly as death that occurred during hospitalisation, and the hospital-level risk standardised mortality rate (RSMR).

Results: A total of 14 variables were included in the model predicting in-hospital mortality based on MRFP data, with the area under receiver operating characteristic curve of 0.78 among modelling cohort and 0.79 among validation cohort. The median of absolute difference between the hospital RSMR predicted by hierarchical generalised linear models established based on MRFP data and complete medical record data, which was built as 'reference model', was 0.08% (10th and 90th percentiles: -1.8% and 1.6%). In the regression model comparing the RSMR between two models, the slope and intercept of the regression equation is 0.90 and 0.007 in modelling cohort, while 0.85 and 0.010 in validation cohort, which indicated that the evaluation capability from two models were very similar.

Conclusions: The models based on MRFP data showed good discrimination and calibration capability, as well as similar risk prediction effect in comparison with the model based on complete medical record data, which proved that MRFP data could be suitable for risk adjustment in hospital performance measurement.
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http://dx.doi.org/10.1136/bmjopen-2020-045053DOI Listing
April 2021

[Analysis of the incidence of syncope and the influencing factors of death in patients with cardiovascular critical emergency].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2021 Mar;33(3):324-328

Laboratory of Cardiac Physiology, Nanyang Second General Hospital, Nanyang 473012, Henan, China.

Objective: To observe the incidence of syncope in patients with acute and critical cardiovascular diseases and to explore the risk factors of death.

Methods: 925 cases of acute heart failure, acute myocardial infarction, pulmonary embolism, arrhythmia and aortic dissection rupture who participated in Prospective, Multi-Center Registered Research Project for Chinese Syncope Patients from March 2018 to March 2020, admitted to the department of emergency of Nanyang Second General Hospital were selected as the research objects. The incidence and mortality of syncope were recorded, and the patients were divided into syncope group and non-syncope group according to whether they were accompanied by syncope or not. The incidence of syncope in male and female patients with different cardiovascular critical diseases, the age and mortality of cardiovascular critical patients with syncope or not were analyzed and compared. Multivariate Logistic regression analysis was used to analyze the risk factors of death, and receiver operating characteristic curve (ROC curve) was drawn to evaluate the predictive value of risk factors on the prognosis of patients.

Results: The incidence of syncope in 5 kinds of cardiovascular critical patients from high to low was: acute myocardial infarction 3.03% (28/925), arrhythmia 2.70% (25/925), pulmonary embolism 1.51% (14/925), aortic dissection rupture 1.41% (13/925), acute heart failure 0.65% (6/925), with statistically significant differences (χ = 10.765, P = 0.010). There was no significant difference in the incidence of syncope between male and female patients with pulmonary embolism, aortic dissection rupture, acute myocardial infarction, arrhythmia and acute heart failure. The age of patients with aortic dissection rupture, acute myocardial infarction and arrhythmia in syncope group were significantly higher than those in non-syncope group [aortic dissection rupture (years old): 66.29±15.64 vs. 57.63±14.23, acute myocardial infarction (years old): 69.55±15.13 vs. 62.10±15.75, arrhythmia (years old): 70.48±14.93 vs. 60.29±16.31, all P < 0.05]. The mortality of patients with pulmonary embolism, aortic dissection rupture, acute myocardial infarction, arrhythmia, acute heart failure in syncope group were significantly higher than those in non-syncope group [pulmonary embolism: 5.81% (5/86) vs. 0.95% (8/839), aortic dissection rupture: 4.65% (4/86) vs. 0.60% (5/839), acute myocardial infarction: 4.65% (4/86) vs. 1.19% (10/839), arrhythmia: 2.33% (2/86) vs. 0.95% (8/839), acute heart failure: 2.33% (2/86) vs. 0.60% (5/839), all P < 0.05]. Multivariate Logistic regression analysis showed that age [odds ratio (OR) = 2.158, 95% confidence interval (95%CI) was 0.921-4.785, P = 0.000], pulmonary embolism (OR = 15.391, 95%CI was 8.904-27.314, P = 0.001), aortic dissection rupture (OR = 13.079, 95%CI was 6.237-25.509, P = 0.000), acute myocardial infarction (OR = 18.826, 95%CI was 10.420-32.921, P = 0.000), syncope (OR = 4.940, 95%CI was 1.764-9.287, P = 0.000) were risk factors for the prognosis of patients with acute and critical cardiovascular diseases. ROC curve analysis showed that syncope had a certain predictive value for 28-day prognosis of patients [the area under the ROC curve (AUC) = 0.760, P = 0.000], when the cut-off value was 4.12, the sensitivity was 88.51%, the specificity was 78.05%, the positive predictive value was 81.31%, and the negative predictive value was 84.27%.

Conclusions: Syncope is an independent risk factor of death in patients with acute and critical cardiovascular diseases. For patients with syncope as the chief complaint, we should quickly identify the types of acute and critical diseases and assess the risk of sudden death.
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http://dx.doi.org/10.3760/cma.j.cn121430-20201028-00691DOI Listing
March 2021

Application of Infusion Control System Based on Internet of Things Technology in Joint Orthopedics Nursing Work.

J Healthc Eng 2021 26;2021:6691258. Epub 2021 Mar 26.

Department of Spinal Surgery, The Fourth People's Hospital of Jinan, Jinan, Shandong 250031, China.

In recent years, the Internet of Things technology has flourished, and there have been corresponding practical results in various fields. In medical care, the introduction of Internet of Things technology must also be a new trend in the development of hospital informatization, and it is the development stage of the digital medical process. The traditional infusion system shows that the infusion bottle is not replaced in time, the infusion waiting time is too long, the infusion efficiency is too low, and the existing medical staff is far from meeting the needs of the huge infusion population. Therefore, this article proposes a technology based on the Internet of Things application of the infusion control system in joint orthopedics nursing work to improve the efficiency of infusion in nursing work. This article deeply learns and uses the Internet of Things technology to build a new infusion management and control system, which is applied to joint orthopedics nursing treatment. This paper designs the application research experiment of the infusion control system. Through the Internet of Things technology, the relevant data in the infusion process are uploaded and sent to the network center of the hospital. Nursing staff can directly see the infusion situation directly through the computer console. This article compares and analyzes two different infusion systems and draws conclusions. The infusion ringing rate of the control group was 81.3%, and the infusion ringing rate of the IoT group was 29.8%; the time for timely replacement of the infusion bottle after IoT data control was 13.89 min, compared to 19.76 min before. A variety of data results show that the infusion management and control system based on the Internet of Things technology has played a great role in joint orthopedics care, which can greatly improve the efficiency of infusion, replace the infusion or deal with failures in time for patients, and improve patient satisfaction.
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http://dx.doi.org/10.1155/2021/6691258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018849PMC
March 2021

Establishment of bovine expanded potential stem cells.

Proc Natl Acad Sci U S A 2021 Apr;118(15)

The State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, 010070 Hohhot, China;

Embryonic stem cells (ESCs) and induced pluripotent stem cells have the potential to differentiate to all cell types of an adult individual and are useful for studying development and for translational research. However, extrapolation of mouse and human ESC knowledge to deriving stable ESC lines of domestic ungulates and large livestock species has been challenging. In contrast to ESCs that are usually established from the blastocyst, mouse expanded potential stem cells (EPSCs) are derived from four-cell and eight-cell embryos. We have recently used the EPSC approach and established stem cells from porcine and human preimplantation embryos. EPSCs are molecularly similar across species and have broader developmental potential to generate embryonic and extraembryonic cell lineages. We further explore the EPSC technology for mammalian species refractory to the standard ESC approaches and report here the successful establishment of bovine EPSCs (bEPSCs) from preimplantation embryos of both wild-type and somatic cell nuclear transfer. bEPSCs express high levels of pluripotency genes, propagate robustly in feeder-free culture, and are genetically stable in long-term culture. bEPSCs have enriched transcriptomic features of early preimplantation embryos and differentiate in vitro to cells of the three somatic germ layers and, in chimeras, contribute to both the embryonic (fetal) and extraembryonic cell lineages. Importantly, precise gene editing is efficiently achieved in bEPSCs, and genetically modified bEPSCs can be used as donors in somatic cell nuclear transfer. bEPSCs therefore hold the potential to substantially advance biotechnology and agriculture.
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http://dx.doi.org/10.1073/pnas.2018505118DOI Listing
April 2021

Turn-on fluorescent probe for dopamine detection in solutions and live cells based on in situ formation of aminosilane-functionalized carbon dots.

Anal Chim Acta 2021 May 13;1157:338394. Epub 2021 Mar 13.

Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, 610041, China. Electronic address:

Dopamine (DA) is a critical biomarker for a variety of neurological diseases. Methods for simple and rapid DA detection are crucial for clinical diagnosis and treatments for those diseases. In this work, we developed a novel pretreatment-free method for dopamine detection using carbon dots as a turn-on fluorescent probe synthesized in situ. The aminosilane-functionalized carbon dots (SiCDs) were produced in a mild condensation reaction between N-[3-(Trimethoxysilyl)propyl]ethylenediamine (AEATMS) and dopamine, which were directly used for probing of dopamine. The prepared SiCDs exhibited green fluorescence with excitation/emission maximum at 380/495 nm, the intensity of which can be measured to quantify the DA present in the reaction mixture. The linear range of the assay was between 0.1 and 100 μM with a limit of detection (LOD) of 56.2 nM. The probe is of good selectivity and the recoveries of the developed method were in the range of 101.77-119.91% with RSDs within 3.67% in human serum sample tests. The SiCDs were also synthesized within MN9D cells under 37 °C and generated bright fluorescence, which can probe the DA's distribution in the cells. The described method exhibit potential in DA detection and live-cell imaging for its feature of facility, inexpensiveness, and sensitivity.
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http://dx.doi.org/10.1016/j.aca.2021.338394DOI Listing
May 2021

The complete chloroplast genome of Mill. (Fagaceae).

Mitochondrial DNA B Resour 2021 Mar 28;6(3):1249-1250. Epub 2021 Mar 28.

Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing, PR China.

Mill. is mainly grown in the temperate regions of continental Europe, and it has a considerable economic value. In this study, the complete chloroplast genome sequence of was characterized. Leaves were collected from the National Botanical Garden of Latvia. The chloroplast genome was determined to be 160,938 bp in length. It contained large single-copy (LSC) and small single-copy (SSC) regions of 90,519 and 18,967 bp, respectively, which were separated by a pair of 25,726 bp inverted repeat (IR) regions. The genome is predicted to contain 130 genes, including 83 protein-coding genes, 37 genes, eight genes, and two pseudo genes. The overall GC content of the genome is 36.8%. A phylogenetic tree reconstructed by 34 chloroplast genomes reveals that is most closely related to the clade including , and .
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http://dx.doi.org/10.1080/23802359.2021.1903359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009113PMC
March 2021

The complete chloroplast genome of 'Chuizhili'.

Mitochondrial DNA B Resour 2021 Mar 26;6(3):1160-1161. Epub 2021 Mar 26.

Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing, China.

The 'Chuizhili' is an important variety of in breeding for dwarf chestnut and ornamental trees due to the weeping characteristic in China. In this study, the complete chloroplast genome of 'Chuizhili' was identified and sequenced by using Illumina sequencing data. The genome size is 160,799 bp, with a large single-copy (LSC, 90,430 bp) region, a small single-copy (SSC, 18,997 bp) region, and separated by a pair of 25,686 bp inverted repeat (IR) regions. A total of 130 genes are successfully annotated, including 83 protein-coding genes, 37 tRNA genes, 8 rRNA genes, and 2 pseudo-genes. The phylogenetic relationships revealed that 'Chuizhili' is closely related to in Fagaceae.
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http://dx.doi.org/10.1080/23802359.2021.1903360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008883PMC
March 2021

Dual Antibacterial Effect of In Situ Electrospun Curcumin Composite Nanofibers to Sterilize Drug-Resistant Bacteria.

Nanoscale Res Lett 2021 Apr 7;16(1):54. Epub 2021 Apr 7.

Collaborative Innovation Center for Nanomaterials and Devices, College of Physics, Qingdao University, Qingdao, 266071, China.

Bacterial infection especially caused by multidrug-resistant bacteria still endangers human life. Photodynamic therapy (PDT) can effectively kill bacteria, and nanofiber-based PDT can effectively reduce damage to normal tissues. However, current photosensitizers coated on the surfaces of fibers would release to the wound, causing some side effects. And nanofibers prepared by traditional method exhibit poor adhesion on the wound, which severely reduces the PDT effect due to its short-range effect. Herein, core-shell curcumin composite nanofibers are prepared by in situ electrospinning method via a self-made portable electrospinning device. The obtained composite nanofibers show superior adhesiveness on different biological surface than that of traditional preparation method. Upon 808-nm irradiation, these composite nanofibers effectively produced singlet oxygen (O) without curcumin falling off. After these composite nanofibers' exposure to drug-resistant bacteria, they exhibit dual antibacterial behaviors and efficiently kill the drug-resistant bacteria. These dual antibacterial nanofiber membranes with excellent adhesiveness may benefit the application of wound infection as antibacterial dressing.
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http://dx.doi.org/10.1186/s11671-021-03513-2DOI Listing
April 2021

Regulator of calcineurin 1 gene isoform 4 in pancreatic ductal adenocarcinoma regulates the progression of tumor cells.

Oncogene 2021 Apr 6. Epub 2021 Apr 6.

Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Therapeutic strategies to treat pancreatic ductal adenocarcinoma (PDAC) remain unsatisfying and limited. Therefore, it is imperative to fully determine the mechanisms underlying PDAC progression. In the present study, we report a novel role of regulator of calcineurin 1, isoform 4 (RCAN1.4) in regulating PDAC progression. We demonstrated that RCAN1.4 expression was decreased significantly in PDAC tissues compared with that in para-cancerous tissues, and correlated with poor prognosis of patients with pancreatic cancer. In vitro, stable high expression of RCAN1.4 could suppress the metastasis and proliferation and angiogenesis of pancreatic tumor cells. In addition, interferon alpha inducible protein 27 (IFI27) was identified as having a functional role in RCAN1.4-mediated PDAC migration and invasion, while VEGFA play a vital role in RCAN1.4-mediated PDAC angiogenesis. Analysis of mice with subcutaneously/orthotopic implanted xenograft tumors and liver metastasis model confirmed that RCAN1.4 could modulate the growth, metastasis, and angiogenesis of tumors via IFI27/VEGFA in vivo. In conclusion, our results suggested that RCAN1.4 suppresses the growth, metastasis, and angiogenesis of PDAC, functioning partly via IFI27 and VEGFA. Importantly, our results provided possible diagnostic criteria and therapeutic targets for PDAC.
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http://dx.doi.org/10.1038/s41388-021-01763-zDOI Listing
April 2021

Creating polar antivortex in PbTiO/SrTiO superlattice.

Nat Commun 2021 Apr 6;12(1):2054. Epub 2021 Apr 6.

International Center for Quantum Materials, Peking University, Beijing, China.

Nontrivial topological structures offer a rich playground in condensed matters and promise alternative device configurations for post-Moore electronics. While recently a number of polar topologies have been discovered in confined ferroelectric PbTiO within artificially engineered PbTiO/SrTiO superlattices, little attention was paid to possible topological polar structures in SrTiO. Here we successfully create previously unrealized polar antivortices within the SrTiO of PbTiO/SrTiO superlattices, accomplished by carefully engineering their thicknesses guided by phase-field simulation. Field- and thermal-induced Kosterlitz-Thouless-like topological phase transitions have also been demonstrated, and it was discovered that the driving force for antivortex formation is electrostatic instead of elastic. This work completes an important missing link in polar topologies, expands the reaches of topological structures, and offers insight into searching and manipulating polar textures.
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http://dx.doi.org/10.1038/s41467-021-22356-0DOI Listing
April 2021

Method of Tumor Pathological Micronecrosis Quantification via Deep Learning from Label Fuzzy Proportions.

IEEE J Biomed Health Inform 2021 Apr 6;PP. Epub 2021 Apr 6.

The presence of necrosis is associated with tumor progression and patient outcomes in many cancers, but existing analyses rarely adopt quantitative methods because the manual quantification of histopathological features is too expensive. We aim to accurately identify necrotic regions on hematoxylin and eosin (HE)stained slides and to calculate the ratio of necrosis with minimal annotations on the images. An adaptive method named Learning from Label Fuzzy Proportions (LLFP) was introduced to histopathological image analysis. Two datasets of liver cancer HE slides were collected to verify the feasibility of the method by training on the internal set using cross validation and performing validation on the external set, along with ensemble learning to improve performance. The models from cross validation performed relatively stably in identifying necrosis, with a Concordance Index of the Slide Necrosis Score (CISNS) of 0.91650.0089 in the internal test set. The integration model improved the CISNS to 0.9341 and achieved a CISNS of 0.8278 on the external set. There were significant differences in survival (p=0.0060) between the three groups divided according to the calculated necrosis ratio. The proposed method can build an integration model good at distinguishing necrosis and capable of clinical assistance as an automatic tool to stratify patients with different risks or as a cluster tool for the quantification of histopathological features. We presented a method effective for identifying histopathological features and suggested that the extent of necrosis, especially micronecrosis, in liver cancer is related to patient outcomes.
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http://dx.doi.org/10.1109/JBHI.2021.3071276DOI Listing
April 2021

Pollution characteristics and ecological risks associated with heavy metals in the Fuyang river system in North China.

Environ Pollut 2021 Mar 29;281:116994. Epub 2021 Mar 29.

CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, & CAS-HKU Joint Laboratory of Metallomics on Health and Environment, & Beijing Metallomics Facility, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, China.

The Fuyang River system (FRS) in north China, for a long time, is seriously polluted with organic compounds and heavy metals due to industrialization. However, the information on heavy metal pollution in this area is still limited, and health risks raised by trace elements are neglected up to now. To characterize the heavy metal pollutants and assess their potential ecological risks scientifically in FRS, surface sediments were collected from 66 sampling sites selected according to the hydrological and anthropogenic conditions along the river. A total of twelve metal pollutants (e.g., Cr, As, and Hg) in the sediments were detected among the distributaries. A combining application of geoaccumulation index (I), ratio of secondary phase and primary phase (RSP), and the ecological risk factor (Er) in this study gave systematic assessment results of single or combined pollution status raised by heavy metals in this area. The results show that Cr, Ni, Cu, As, Cd, Co, and Sn are mainly dispersed in the river reaches of Xingtai City and pose potential health risks in midstream, as per the geoaccumulation index and Pearson's correlation analyses. In particular, Cd accumulates strongly in sediments of Ming River and Aixinzhuang dam from Xingtai City. In upstream and downstream of FRS, the potential ecological risk is low, except in Yongnian County where high ecological risk was caused by Cd and Hg. These findings provide new insights into the pollution characteristics and assessment of the potential ecological risks induced by heavy metals along FRS, which suggest new directions should strategically tend to typical pollutants control by policy formulation and taking effective measures to prevent and manage heavy metal pollution in North China.
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http://dx.doi.org/10.1016/j.envpol.2021.116994DOI Listing
March 2021

N-Acetylcysteine Combined With Dexamethasone Treatment Improves Sudden Sensorineural Hearing Loss and Attenuates Hair Cell Death Caused by ROS Stress.

Front Cell Dev Biol 2021 18;9:659486. Epub 2021 Mar 18.

Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Sudden sensorineural hearing loss (SSNHL) is a common emergency in the world. Increasing evidence of imbalance of oxidant-antioxidant were found in SSNHL patients. Steroids combined with antioxidants may be a potential strategy for the treatment of SSNHL. In cochlear explant experiment, we found that N-acetylcysteine (NAC) combined with dexamethasone can effectively protect hair cells from oxidative stress when they were both at ineffective concentrations alone. A clinic trial was designed to explore whether oral NAC combined with intratympanic dexamethasone (ITD) as a salvage treatment has a better therapeutic effect. 41 patients with SSNHL were randomized to two groups. 23 patients in control group received ITD therapy alone, while 18 patient s in NAC group were treated with oral NAC and ITD. The patients were followed-up on day 1st (initiation of treatment) and day 14th. Overall, there was no statistical difference in final pure-tone threshold average (PTA) improvement between those two groups. However, a significant hearing gain at 8,000 Hz was observed in NAC group. Moreover, the hearing recovery rates of NAC group is much higher than that in control group. These results demonstrated that oral NAC in combination with ITD therapy is a more effective therapy for SSNHL than ITD alone.
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http://dx.doi.org/10.3389/fcell.2021.659486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014036PMC
March 2021

SPTBN1 Prevents Primary Osteoporosis by Modulating Osteoblasts Proliferation and Differentiation and Blood Vessels Formation in Bone.

Front Cell Dev Biol 2021 19;9:653724. Epub 2021 Mar 19.

Department of Endocrinology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.

Osteoporosis is a common systemic skeletal disorder that leads to increased bone fragility and increased risk of fracture. Although βII-Spectrin (SPTBN1) has been reported to be involved in the development of various human cancers, the function and underlying molecular mechanisms of SPTBN1 in primary osteoporosis remain unclear. In this study, we first established a primary osteoporosis mouse model of senile osteoporosis and postmenopausal osteoporosis. The results showed that the expression of SPTBN1 was significantly downregulated in primary osteoporosis mice model compared with the control group. Furthermore, silencing of SPTBN1 led to a decrease in bone density, a small number of trabecular bones, wider gap, decreased blood volume fraction and number of blood vessels, as well as downregulation of runt-related transcription factor 2 (Runx2), Osterix (Osx), Osteocalcin (Ocn), and vascular endothelial growth factor (VEGF) in primary osteoporosis mice model compared with the control group. Besides, the silencing of SPTBN1 inhibited the growth and induced apoptosis of mouse pre-osteoblast MC3T3-E1 cells compared with the negative control group. Moreover, the silencing of SPTBN1 significantly increased the expression of TGF-β, Cxcl9, and the phosphorylation level STAT1 and Smad3 in MC3T3-E1 cells compared with the control group. As expected, overexpression of SPTBN1 reversed the effect of SPTBN1 silencing in the progression of primary osteoporosis both and . Taken together, these results suggested that SPTBN1 suppressed primary osteoporosis by facilitating the proliferation, differentiation, and inhibition of apoptosis in osteoblasts via the TGF-β/Smad3 and STAT1/Cxcl9 pathways. Besides, overexpression of SPTBN1 promoted the formation of blood vessels in bone by regulating the expression of VEGF. This study, therefore, provided SPTBN1 as a novel therapeutic target for osteoporosis.
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http://dx.doi.org/10.3389/fcell.2021.653724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017174PMC
March 2021

A Practical Nomogram to Predict Early Death in Advanced Epithelial Ovarian Cancer.

Front Oncol 2021 19;11:655826. Epub 2021 Mar 19.

Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.

Ovarian cancer is a common gynecological malignancy, most of which is epithelial ovarian cancer (EOC). Advanced EOC is linked with a higher incidence of premature death. To date, no effective prognostic tools are available to evaluate the possibility of early death in patients with advanced EOC. Advanced (FIGO stage III and IV) EOC patients who were enrolled in the Surveillance, Epidemiology, and End Results database between 2004 and 2015 were regarded as subjects and studied. We aimed to construct a nomogram that can deliver early death prognosis in patients with advanced EOC by identifying crucial independent factors using univariate and multivariate logistic regression analyses to help deliver accurate prognoses. In total, 13,403 patients with advanced EOC were included in this study. Three hundred ninety-seven out of a total of 9,379 FIGO stage III patients died early. There were 4,024 patients with FIGO stage IV, 414 of whom died early. Nomograms based on independent prognostic factors have the satisfactory predictive capability and clinical pragmatism. The internal validation feature of the nomogram demonstrated a high level of accuracy of the predicted death. By analyzing data from a large cohort, a clinically convenient nomogram was established to predict premature death in advanced EOC. This tool can aid clinicians in screening patients who are at higher risk for tailoring treatment plans.
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http://dx.doi.org/10.3389/fonc.2021.655826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017286PMC
March 2021

Treatment of collagen-induced arthritis rat model by using Notch signalling inhibitor.

J Orthop Translat 2021 May 17;28:100-107. Epub 2021 Mar 17.

Center for Translational Medicine Research and Development, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, 518055, China.

Background: The Notch signalling pathway has been reported to play a key role in rheumatoid arthritis (RA) development. Thus, inhibition of the activation of this signalling pathway may be a promising approach to the treatment of RA. In this study, the Notch signalling inhibitor LY411575, which can inhibit both Notch1 and Notch3, was used for the treatment of collagen-induced arthritis (CIA) rats.

Methods: Wistar rats were immunised with bovine type II collagen (CII) to establish rats CIA model. The inhibitory effects of LY411575 on Notch1 intracellular domain (N1ICD) and Notch3 intracellular domain (N3ICD) protein was verified by western blot (WB) . CIA rats were treated with different doses of LY411575 for 15 and 28 days, respectively. Methotrexate and sodium carboxymethyl cellulose (CMC-Na) were used as positive and negative (vehicle) control respectively. Destruction of the rat ankle joint and the bone loss on the periarticular side were evaluated by micro-computed tomography (Micro-CT). In addition, destruction of the ankle articular cartilage and the osteoclast numbers were determined by histology. Expression of N1ICD and N3ICD in the ankle joint was detected by immunohistochemistry.

Results: LY411575 could significantly inhibit the expression of N1ICD and N3ICD . Micro-CT test showed that the ankle joint destruction significantly improved after treatment with LY411575 (5 ​mg/kg and 10 ​mg/kg, respectively). The bone quality in the LY411575 (5 ​mg/kg and 10 ​mg/kg, respectively) groups were improved compared with the vehicle group. Histological analysis showed that LY411575 (5 ​mg/kg and 10 ​mg/kg, respectively) treatment reduced the severity of ankle joint inflammation in CIA rats (including ankle joint destruction, pannus formation, and cartilage damage) and reduced the expression of N1ICD and N3ICD in CIA rats ankle joints significantly.

Conclusion: The inhibitor of Notch signalling LY411575 is an effective treatment for CIA.

The Translational Potential Of This Article: Our study provides new evidence to support the potential clinical application of Notch signalling pathway inhibitor LY411575 as a drug candidate for the treatment of RA.
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http://dx.doi.org/10.1016/j.jot.2021.01.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995347PMC
May 2021

Disruption of Epithelial Barrier of Caco-2 Cell Monolayers by Excretory Secretory Products of Might Be Related to Serine Protease.

Front Microbiol 2021 17;12:634185. Epub 2021 Mar 17.

Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Institute of Zoonosis, Jilin University, Changchun, China.

The physical barrier is composed of epithelial cells which are joined together through intercellular connections. It serves to prevent pathogenic microorganisms from departing the intestinal lumen to invade the host. The excretory secretory (ES) products of are critical for invasion. However, whether ES products of can act on the intestinal barrier is still unknown. In this study, the role of ES products of muscle larvae (-ML-ES) in host invasion was studied by establishing an cell monolayers model. Barrier integrity analysis by a transmembrane resistance test and a paracellular permeability assay revealed that the -ML-ES was able to destroy barrier function. It occurred a reduction in the expression of tight junction (TJ) proteins, which was induced by serine protease. Furthermore, Western bolt analysis indicated that -ML-ES reduced the expression of TJ proteins the MAPK signaling pathway. Based on these data, we conclude that serine protease are likely the main factors from -ML-ES that affect host intestinal barrier integrity by reducing the expression of TJs the P38-MAPK signaling pathway. Serine protease in -ML-ES might be a key invasion factor in .
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http://dx.doi.org/10.3389/fmicb.2021.634185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013981PMC
March 2021

Association between age-related kidney function and vascular subclinical state in a healthy Chinese population.

Chin Med J (Engl) 2021 Mar 31. Epub 2021 Mar 31.

Department of Gerontology and Geriatrics, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519099, China Department of Gerontology and Geriatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China Department of Kidney, General Hospital of Chinese People's Liberation Army, Beijing 100853, China.

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http://dx.doi.org/10.1097/CM9.0000000000001422DOI Listing
March 2021

18β-Glycyrrhetinic acid alleviates demyelination by modulating the microglial M1/M2 phenotype in a mouse model of cuprizone-induced demyelination.

Neurosci Lett 2021 Apr 1:135871. Epub 2021 Apr 1.

Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, Wuhan University School of Pharmaceutical Sciences, Wuhan University, Wuhan, Hubei, PR China. Electronic address:

This research aimed to examine the nutritious supplementary function of 18β-Glycyrrhetinic acid (18β-GA) in moderating the myelin sheath destruction and behavioral impairments observed in the cuprizone model of demyelination. Mice were fed daily on food containing cuprizone (0.3%) and given doses of 18β-GA (5 or 1 mg/kg) for a period of five weeks. The groups treated with 18β-GA exhibited improvements in exploratory behavior, locomotive activity, and weight. As assessed using luxol-fast blue and myelin basic protein (MBP) staining, which were used to detect demyelination in the brain, 18β-GA both reduced and prevented instances of cuprizone-induced demyelinating lesions; treatment with 18β-GA also caused the MBP level in the corpus callosum to increase. Furthermore, alongside these positive results following 18β-GA treatment, microglial polarisation was also observed to shift towards the beneficial M2 phenotype. The results of this research thus indicate the potential clinical application of 18β-GA for the prevention of myelin damage and behavioral dysfunction.
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http://dx.doi.org/10.1016/j.neulet.2021.135871DOI Listing
April 2021

Selection and Validation of Reference Genes for qRT-PCR Analysis in the Oil-Rich Tuber Crop Tiger Nut () Based on Transcriptome Data.

Int J Mol Sci 2021 Mar 4;22(5). Epub 2021 Mar 4.

CAS Key Laboratory of Tropical Plant Resources and Sustainable Use, Xishuangbanna Tropical Botanical Garden, Innovation Academy for Seed Design, Chinese Academy of Sciences, Menglun, Mengla 666303, China.

Tiger nut (), a perennial C plant of the family, is an unconventional crop that is distinguished by its oil-rich tubers, which also possesses the advantages of strong resistance, wide adaptability, short life periods, and large biomass. To facilitate studies on gene expression in this species, we identified and validated a series of reference genes (RGs) based on transcriptome data, which can be employed as internal controls for qRT-PCR analysis in tiger nut. Fourteen putative candidate RGs were identified and evaluated across nine different tissues of two cultivars, and the RGs were analyzed using three different algorithms (geNorm, NormFinder, and BestKeeper). The stability rankings of the candidate RGs were merged into consensus lists with RankAggreg. For the below-ground storage organ of tiger nut, the optimal RGs were and in different developmental stages of tubers. and were the most stably expressed RGs among all tissues, while and exhibited the lowest expression stability. , and were compared to normalize the expression levels of the () and () genes across the same tissues. Our results showed that the RGs identified in this study, which exhibit more uniform expression patterns, may be utilized for the normalization of qRT-PCR results, promoting further research on gene expression in various tissues of tiger nut.
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http://dx.doi.org/10.3390/ijms22052569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961719PMC
March 2021

Cloudy Apple Juice Fermented by Prevents Obesity via Modulating Gut Microbiota and Protecting Intestinal Tract Health.

Nutrients 2021 Mar 17;13(3). Epub 2021 Mar 17.

College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China.

Obesity and hyperglycemia are two serious chronic diseases that are increasing in incidence worldwide. This research aimed to develop a fermented cloudy apple juice with good hyperglycemia intervention activities. Here, cloudy apple juice (CAJ), cloudy apple juice rich in polyphenols (CAJP) and fermented cloudy apple juice rich in polyphenols (FCAJP) were prepared sequentially, and then the effects of the three apple juices on weight, lipid level, gut microbiota composition and intestinal tract health were evaluated for obese mice induced by a high-fat diet. The research findings revealed that the FCAJP showed potential to inhibit the weight gain of mice, reduce fat accumulation, and regulate the blood lipid levels of obese mice by decreasing the ratio of the Firmicutes/Bacteroidotas, improving the Sobs, Ace, and Chao indexes of the gut microbiota and protecting intestinal tract health. In addition, the FCAJP augmented the abundance of Akkermansia and Bacteroides, which were positively related to SCFAs in cecal contents. This study inferred that FCAJP could be developed as a healthy food for preventing obesity and hyperglycemia.
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http://dx.doi.org/10.3390/nu13030971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002442PMC
March 2021

A Versatile Optoelectronic Tweezer System for Micro-Objects Manipulation: Transportation, Patterning, Sorting, Rotating and Storage.

Micromachines (Basel) 2021 Mar 6;12(3). Epub 2021 Mar 6.

School of Mechanical Engineering & Automation, Beihang University, Beijing 100191, China.

Non-contact manipulation technology has a wide range of applications in the manipulation and fabrication of micro/nanomaterials. However, the manipulation devices are often complex, operated only by professionals, and limited by a single manipulation function. Here, we propose a simple versatile optoelectronic tweezer (OET) system that can be easily controlled for manipulating microparticles with different sizes. In this work, we designed and established an optoelectronic tweezer manipulation system. The OET system could be used to manipulate particles with a wide range of sizes from 2 μm to 150 μm. The system could also manipulate micro-objects of different dimensions like 1D spherical polystyrene microspheres, 2D rod-shaped euglena gracilis, and 3D spiral microspirulina. Optical microscopic patterns for trapping, storing, parallel transporting, and patterning microparticles were designed for versatile manipulation. The sorting, rotation, and assembly of single particles in a given region were experimentally demonstrated. In addition, temperatures measured under different objective lenses indicate that the system does not generate excessive heat to damage bioparticles. The non-contact versatile manipulation reduces operating process and contamination. In future work, the simple optoelectronic tweezers system can be used to control non-contaminated cell interaction and micro-nano manipulation.
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http://dx.doi.org/10.3390/mi12030271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000357PMC
March 2021

Association between use of Qingfei Paidu Tang and mortality in hospitalized patients with COVID-19: A national retrospective registry study.

Phytomedicine 2021 Feb 28;85:153531. Epub 2021 Feb 28.

National Clinical Research Center for Cardiovascular Diseases, State Key, Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for, Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union, Medical College, Beijing, People's Republic of China; Central China Subcenter of the National Center for Cardiovascular Diseases, Zhengzhou, People's Republic of China; Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen, People's Republic of China. Electronic address:

Background: Qingfei Paidu Tang (QPT), a formula of traditional Chinese medicine, which was suggested to be able to ease symptoms in patients with Coronavirus Disease 2019 (COVID-19), has been recommended by clinical guidelines and widely used to treat COVID-19 in China. However, whether it decreases mortality remains unknown.

Purpose: We aimed to explore the association between QPT use and in-hospital mortality among patients hospitalized for COVID-19.

Study Design: A retrospective study based on a real-world database was conducted.

Methods: We identified patients consecutively hospitalized with COVID-19 in 15 hospitals from a national retrospective registry in China, from January through May 2020. Data on patients' characteristics, treatments, and outcomes were extracted from the electronic medical records. The association of QPT use with COVID-19 related mortality was evaluated using Cox proportional hazards models based on propensity score analysis.

Results: Of the 8939 patients included, 28.7% received QPT. The COVID-19 related mortality was 1.2% (95% confidence interval [CI] 0.8% to 1.7%) among the patients receiving QPT and 4.8% (95% CI 4.3% to 5.3%) among those not receiving QPT. After adjustment for patient characteristics and concomitant treatments, QPT use was associated with a relative reduction of 50% in-hospital COVID-19 related mortality (hazard ratio, 0.50; 95% CI, 0.37 to 0.66 p < 0.001). This association was consistent across subgroups by sex and age. Meanwhile, the incidences of acute liver injury (8.9% [95% CI, 7.8% to 10.1%] vs. 9.9% [95% CI, 9.2% to 10.7%]; odds ratio, 0.96 [95% CI, 0.81% to 1.14%], p = 0.658) and acute kidney injury (1.6% [95% CI, 1.2% to 2.2%] vs. 3.0% [95% CI, 2.6% to 3.5%]; odds ratio, 0.85 [95% CI, 0.62 to 1.17], p = 0.318) were comparable between patients receiving QPT and those not receiving QPT. The major study limitations included that the study was an observational study based on real-world data rather than a randomized control trial, and the quality of data could be affected by the accuracy and completeness of medical records.

Conclusions: QPT was associated with a substantially lower risk of in-hospital mortality, without extra risk of acute liver injury or acute kidney injury among patients hospitalized with COVID-19.
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http://dx.doi.org/10.1016/j.phymed.2021.153531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914374PMC
February 2021

Delayed immune-related adverse events with anti-PD1-based immunotherapy in melanoma.

Ann Oncol 2021 Mar 30. Epub 2021 Mar 30.

Melanoma Institute Australia, The University of Sydney, Sydney, Australia;; Royal North Shore and Mater Hospitals, Sydney, Australia.

Background: IrAEs typically occur within 4 months of starting anti-PD1-based therapy (anti-PD1 +/- anti-CTLA4), but delayed irAEs (onset >12 months after commencement) can also occur. This study describes the incidence, nature and management of delayed irAE in patients receiving anti-PD1-based immunotherapy.

Methods: Patients with delayed irAEs from 20 centres were studied. The incidence of delayed irAEs was estimated as a proportion of melanoma patients treated with anti-PD1-based therapy and surviving >1 year. Onset, clinical features, management and outcomes of irAEs were examined.

Results: 118 patients developed a total of 140 delayed irAEs (20 after initial combination with anti-CTLA4); with an estimated incidence of 5.3% (95% CI 4.0-6.9, 53/999 patients at sites with available data). The median onset of delayed irAE was 16 months (range 12-53). 87 patients (74%) were on anti-PD1 at irAE onset, 15 patients (12%) were <3 months from last dose, 16 patients (14%) were >3 months from last dose of anti-PD1. The most common delayed irAEs were colitis, rash and pneumonitis; 55 of all irAEs (39%) were ≥G3. Steroids were required in 80 patients (68%), as well as an additional immunosuppressive agent in 27 patients (23%). There were two irAE-related deaths: encephalitis with onset during anti-PD1, and a multiple organ-irAE with onset 11 months after ceasing anti-PD1. Early irAEs (<12 months) had also occurred in 69 patients (58%), affecting a different organ from the delayed irAE in 59 patients (86%).

Conclusions: Delayed irAEs occur in a small but relevant subset of patients. Delayed irAEs are often different from previous irAE, may be high grade and can lead to death. They mostly occur in patients still receiving anti-PD1. The risk of delayed irAE should be considered when deciding duration of treatment in responding patients. However, patients who stop treatment may also rarely develop delayed irAE.
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http://dx.doi.org/10.1016/j.annonc.2021.03.204DOI Listing
March 2021

Treatment of secondary central nervous system involvement in systemic aggressive B cell lymphoma using R-MIADD chemotherapy: a single-center study.

Chin Neurosurg J 2021 Apr 2;7(1):20. Epub 2021 Apr 2.

Department of Hematology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Background: Secondary central nervous system lymphoma (SCNSL) is defined as lymphoma involvement within the central nervous system (CNS) that originated elsewhere, or a CNS relapse of systemic lymphoma. Prognosis of SCNSL is poor and the most appropriate treatment is still undetermined.

Methods: We conducted a retrospective study to assess the feasibility of an R-MIADD (rituximab, high-dose methotrexate, ifosfamide, cytarabine, liposomal formulation of doxorubicin, and dexamethasone) regimen for SCNSL patients.

Results: Nineteen patients with newly diagnosed CNS lesions were selected, with a median age of 58 (range 20 to 72) years. Out of 19 patients, 11 (57.9%) achieved complete remission (CR) and 2 (10.5%) achieved partial remission (PR); the overall response rate was 68.4%. The median progression-free survival after CNS involvement was 28.0 months (95% confidence interval 11.0-44.9), and the median overall survival after CNS involvement was 34.5 months. Treatment-related death occurred in one patient (5.3%).

Conclusions: These single-centered data underscore the feasibility of an R-MIADD regimen as the induction therapy of SCNSL, further investigation is warranted.
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http://dx.doi.org/10.1186/s41016-021-00238-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017776PMC
April 2021

LC-MS/MS analysis and pharmacokinetics of daidzein and its 7-O-glucuronide in rats after oral administration of 7-O-L-valyl carbamate prodrug.

Bioanalysis 2021 Apr 1. Epub 2021 Apr 1.

Wuya College of Innovation, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.

A valine carbamate prodrug (7-P) was designed to enhance the low bioavailability of daidzein due to its low water solubility and membrane permeability. Here, we developed a high-throughput HPLC-MS/MS method to measure daidzein and its 7-O-glucuronide after oral administration of daidzein or 7-P. A HPLC-MS/MS method was validated and successfully applied to assess the pharmacokinetic behavior of daidzein and its 7-O-glucuronide after orally administrating daidzein or 7-P. The validated method on selectivity, linearity (r ≥ 0.995), precision (relative standard deviation <11.4%), accuracy (relative error <7.1%), extraction recovery (>92.4%), matrix effect (<8.2%) and stability were satisfied. The proposed economical, rapid and sensitive method will be an alternative analytical procedure for daidzein and its metabolite in biological samples.
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http://dx.doi.org/10.4155/bio-2020-0276DOI Listing
April 2021

Critical roles of Rad54 in tolerance to apigenin-induced Top1-mediated DNA damage.

Exp Ther Med 2021 May 18;21(5):505. Epub 2021 Mar 18.

Department of Pharmacology, Key Laboratory of Drug-Targeting and Drug Delivery Systems of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041, P.R. China.

Apigenin (APG), a flavone sub-class of flavonoids, possesses a diverse range of biological activities, including anti-cancer and anti-inflammatory effects. Previous studies identified the genotoxicity of APG in certain cancer cells, which may be associated with its anticancer effect. However, the DNA damage repair mechanism induced by APG has remained elusive. In order to clarify the molecular mechanisms, the present study determined the toxicity of APG to the wild-type () DT40 chicken B-lymphocyte cell line, as well as to DT40 cells with deletions in various DNA repair genes, and their sensitivities were compared. It was demonstrated that cells deficient of Rad54, a critical homologous recombination gene, were particularly sensitive to APG. Cell-cycle analysis demonstrated that APG caused an increase in the G/M-phase population of cells that was greater than that in cells. Furthermore, it was demonstrated by immunofluorescence assay that cells exhibited significantly increased numbers of γ-phosphorylated H2AX variant histone foci and chromosomal aberrations compared to the cells in response to APG. Of note, the complex of enzyme assay indicated that APG induced increased topoisomerase I (Top1) covalent protein DNA complex in cells compared to cells. Finally, these results were verified using the TK6 human lymphoblastoid cell line and it was demonstrated that, as for DT40 cells, Rad54 deficiency sensitized TK6 cells to APG. The present study demonstrated that Rad54 was involved in the repair of APG-induced DNA damage, which was associated with Top1 inhibition.
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http://dx.doi.org/10.3892/etm.2021.9936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005727PMC
May 2021