Publications by authors named "Zhigang Zhao"

417 Publications

Untargeted GC-MS metabolomics reveals the metabolic responses in the gills of Chinese mitten crab (Eriocheir sinensis) subjected to air-exposure stress.

Ecotoxicol Environ Saf 2022 Jan 12;231:113159. Epub 2022 Jan 12.

Department of Marine Technology, School of Marine and Biological Engineering, Yancheng Institute of Technology, Yancheng 224051, China.

Desiccation is a common stress experienced by crabs during aquaculture and transportation. In China, the crustacean, Chinese mitten crab (Eriocheir sinensis), is economically important. However, little is known about the molecular pathways underlying physiological stress. Here, by using untargeted gas chromatography-mass spectrometry metabolomics, we investigated the metabolic responses of the gills of E. sinensis subjected to air-exposure stress by six biological replicates of the control group (CG) and the air-exposure stress group (AG). Metabolomic analysis identified 43 differential metabolites in the AG versus the CG that could be potential biomarkers of desiccation stress. In addition, integrated analysis of key metabolic pathways revealed the involvement of histidine metabolism; glycine, serine and threonine metabolism; the pentose phosphate pathway; the citrate cycle (TCA cycle); and nicotinate and nicotinamide metabolism. These findings indicated the special physiological responses to air-exposure stresses in this species.
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http://dx.doi.org/10.1016/j.ecoenv.2021.113159DOI Listing
January 2022

Biomimetic porous scaffolds containing decellularized small intestinal submucosa and Sr/Feco-doped hydroxyapatite accelerate angiogenesis/osteogenesis for bone regeneration.

Biomed Mater 2022 Jan 13. Epub 2022 Jan 13.

Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei, 430000, CHINA.

The design of bone scaffolds is predominately aimed to well reproduce the natural bony environment by imitating the architecture/composition of host bone. Such biomimetic biomaterials are gaining increasing attention and acknowledged quite promising for bone tissue engineering. Herein, novel biomimetic bone scaffolds containing decellularized small intestinal submucosa matrix (SIS-ECM) and Sr/Feco-doped hydroxyapatite (SrFeHA) are fabricated for the first time by the sophisticated self-assembled mineralization procedure, followed by cross-linking and lyophilization post-treatments. The results indicate the constructed SIS/SrFeHA scaffolds are characterized by highly porous structures, rough microsurface and improved mechanical strength, as well as efficient releasing of bioactive Sr/Feand ECM components. These favorable physico-chemical properties endow SIS/SrFeHA scaffolds with an architectural/componential biomimetic bony environment which appears to be highly beneficial for inducing angiogenesis/osteogenesis both in vitro and in vivo. In particular, the cellular functionality and bioactivity of endotheliocytes/osteoblasts are significantly enhanced by SIS/SrFeHA scaffolds, and the cranial defects model further verifies the potent ability of SIS/SrFeHA to accelerate in vivo vascularization and bone regeneration following implantation. In this view these results highlight the considerable angiogenesis/osteogenesis potential of biomimetic porous SIS/SrFeHA scaffolds for inducing bone regeneration and thus may afford a new promising alternative for bone tissue engineering.
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http://dx.doi.org/10.1088/1748-605X/ac4b45DOI Listing
January 2022

A Systematic Review of Population Pharmacokinetic Models of Methotrexate.

Eur J Drug Metab Pharmacokinet 2022 Jan 5. Epub 2022 Jan 5.

Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, 119 Nansihuan West Road, Fengtai District, Beijing, 100070, People's Republic of China.

Background And Objectives: Methotrexate (MTX) is widely used for the treatment of a variety of neoplastic and autoimmune diseases. However, its toxicity and efficacy varied greatly among individuals, and they could be predicted by its pharmacokinetics. Many population pharmacokinetic models have been published to describe MTX pharmacokinetics. The objective of this systematic review was to summarize and discuss covariates with significant influence on MTX pharmacokinetics.

Methods: We searched PubMed and EMBASE databases from their inception to April 2021 for population pharmacokinetic of MTX. The articles were screened by inclusion and exclusion criteria. The characteristics of studies and information for model construction and validation were extracted, summarized and discussed.

Results: Thirty-five articles were included. The two-compartment model well described the pharmacokinetic behavior of MTX. For inter-individual variability, an exponential distribution error model was usually used for high-dose MTX population pharmacokinetic models, while a proportional distribution error model was used for low-dose MTX population pharmacokinetic models. Proportional and combined proportional and additive error models were used to describe residual error. Renal function was an independent indicator of MTX clearance. Body weight, age, gene polymorphisms (SLCO1B1, ABCC2, ABCB1, ABCG2 and MTHFR) and co-medications (proton pump inhibitors, non-steroidal anti-inflammatory drug, dexamethasone, vancomycin, penicillin and salicylic acid) could influence MTX clearance. Body weight, body surface area, age and dosage regimen have significant influence on MTX central compartment volume. Internal bootstrap test, external validation and visual predictive check were used to evaluate model predictive ability.

Conclusions: Various covariates could affect MTX pharmacokinetics, and their relationships have been summarized and discussed. This review will be helpful for researchers to develop their own population pharmacokinetic models and select appropriate models for individualized therapy of MTX.
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http://dx.doi.org/10.1007/s13318-021-00737-6DOI Listing
January 2022

Ultrathin Two-Dimensional Metal-Organic Framework Nanosheets with Activated Ligand-Cluster Units for Enhanced SERS.

ACS Appl Mater Interfaces 2022 Jan 27;14(1):2326-2334. Epub 2021 Dec 27.

School of Nano-Tech and Nano-Bionics, University of Science and Technology of China, Hefei 230026, China.

Ultrathin two-dimensional (2D) metal-organic framework (MOF) nanosheets (MOFNs) comprise an emerging family of attractive materials with excellent potential for use in different catalytic, electrochemical, and sensing applications owing to their striking features such as ultrathin thickness, a large surface area, and highly ordered network structures. However, to the best of our knowledge, the ligand-cluster units activated through exfoliation into the MOFNs have rarely been realized, which is indeed crucial for surface-enhanced Raman scattering (SERS) analysis. Herein, we emphasize that the activated ligand-cluster units are based on the accessible coordination sites at the exposed cluster nodes accompanied by a complete excitation of the ligand-cluster units under incident photons, which make MOFNs highly effective SERS substrates, significantly outperforming their bulk counterparts. The SERS enhancement of MOFNs is further illustrated by an efficient integration of the inherent ligand-cluster charge-transfer (LCCT) transitions in MOFNs into interfacial charge-transfer processes through an "L"-type charge-transfer (CT) pathway, as further evidenced by an ultrahigh degree (0.98) of CT contributed to the SERS enhancement. This study provides an efficient strategy of exfoliating MOFs into ultrathin nanosheets for the design of highly efficient MOF-based SERS substrates.
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http://dx.doi.org/10.1021/acsami.1c20353DOI Listing
January 2022

17 β-Estradiol alleviates oxidative damage in osteoblasts by regulating miR-320/RUNX2 signaling pathway.

J Biosci 2021 ;46

Department of Orthopaedics, Wuhan Fourth Hospital, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430033, China.

The aim of this study is to investigate the effect and mechanism of 17 β-estradiol (E2) on oxidative stress in the osteoblasts. An oxidative stress-induced damage model was established using HO in MC3T3-E1 cells, and HO-induced cells were treated with E2. The results indicated that E2 attenuated oxidative stress in HO- induced MC3T3-E1 cells. In addition, HO upregulated the expression of miR-320-3p and downregulated that of RUNX2, but these changes were counteracted by E2. Thereafter, we verified the interactive relationship between miR-320-3p and RUNX2. Then, HO-induced MC3T3-E1 cells were transfected with miR-320-3p mimics or inhibitors and treated with E2. The results indicated that miR-320-3p inhibition suppressed HO- induced inflammation, apoptosis, and oxidative stress and promoted the osteogenic differentiation of MC3T3- E1 cells by regulating RUNX2, ALP, and OCN, and this effect was further strengthened by E2. In conclusion, the findings suggest that E2 alleviates oxidative damage in osteoblasts by regulating the miR-320/RUNX2 signaling.
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January 2021

The potential roles of Nrf2/Keap1 signaling in anticancer drug interactions.

Curr Res Pharmacol Drug Discov 2021 4;2:100028. Epub 2021 May 4.

State Key Laboratory of Natural and Biomimetic Drugs; Department of Molecular and Cellular Pharmacology, Peking University School of Pharmaceutical Sciences, Beijing, 100191, PR China.

Nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2), together with its suppressive binding partner Kelch-like ECH-associated protein 1 (Keap1), regulates cellular antioxidant response and drug metabolism. The roles of Nrf2/Keap1 signaling in the pathology of many diseases have been extensively investigated, and small molecules targeting Nrf2/Keap1 signaling have been developed to prevent or treat diseases such as multiple sclerosis, chronic kidney disease and cancer. Notably, Nrf2 plays dual roles in cancer development and treatment. Activation of Nrf2/Keap1 signaling in cancer cells has been reported to promote cancer progression and result in therapy resistance. Since cancer patients are often suffering comorbidities of other chronic diseases, anticancer drugs could be co-administrated with other drugs and herbs. Nrf2/Keap1 signaling modulators, especially activators, are common in drugs, herbs and dietary ingredients, even they are developed for other targets. Therefore, drug-drug or herb-drug interactions due to modulation of Nrf2/Keap1 signaling should be considered in cancer therapies. Here we briefly summarize basic biochemistry and physiology functions of Nrf2/Keap1 signaling, Nrf2/Keap1 signaling modulators that cancer patients could be exposed to, and anticancer drugs that are sensitive to Nrf2/Keap1 signaling, aiming to call attention to the potential drug-drug or herb-drug interactions between anticancer drugs and these Nrf2/Keap1 signaling modulators.
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http://dx.doi.org/10.1016/j.crphar.2021.100028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8663926PMC
May 2021

From Green Super Rice to green agriculture: Reaping the promise of functional genomics research.

Mol Plant 2022 01 6;15(1):9-26. Epub 2021 Dec 6.

National Key Laboratory of Crop Genetic Improvement, Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan 430070, China. Electronic address:

Producing sufficient food with finite resources to feed the growing global population while having a smaller impact on the environment has always been a great challenge. Here, we review the concept and practices of Green Super Rice (GSR) that have led to a paradigm shift in goals for crop genetic improvement and models of food production for promoting sustainable agriculture. The momentous achievements and global deliveries of GSR have been fueled by the integration of abundant genetic resources, functional gene discoveries, and innovative breeding techniques with precise gene and whole-genome selection and efficient agronomic management to promote resource-saving, environmentally friendly crop production systems. We also provide perspectives on new horizons in genomic breeding technologies geared toward delivering green and nutritious crop varieties to further enhance the development of green agriculture and better nourish the world population.
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http://dx.doi.org/10.1016/j.molp.2021.12.001DOI Listing
January 2022

Geographic Variation in the Petiole-Lamina Relationship of 325 Eastern Qinghai-Tibetan Woody Species: Analysis in Three Dimensions.

Front Plant Sci 2021 28;12:748125. Epub 2021 Oct 28.

State Key Laboratory of Grassland Agro-ecosystems, School of Life Sciences, Lanzhou University, Lanzhou, China.

The petiole-lamina relationship is central to the functional tradeoff between photosynthetic efficiency and the support/protection cost. Understanding environmental gradients in the relationship and its underlying mechanisms remains a critical challenge for ecologists. We investigated the possible scaling of the petiole-lamina relationships in three dimensions, i.e., petiole length (PL) vs. lamina length (LL), petiole cross sectional area (PCA) vs. lamina area (LA), and petiole mass (PM) vs. lamina mass (LM), for 325 Qinghai-Tibetan woody species, and examined their relation to leaf form, altitude, climate, and vegetation types. Both crossspecies analysis and meta-analysis showed significantly isometric, negatively allometric, and positively allometric scaling of the petiole-lamina relationships in the length, area, and mass dimensions, respectively, reflecting an equal, slower, and faster variation in the petiole than in the lamina in these trait dimensions. Along altitudinal gradients, the effect size of the petiole-lamina relationship decreased in the length and mass dimensions but increased in the area dimension, suggesting the importance of enhancing leaf light-interception and nutrient transport efficiency in the warm zones in petiole development, but enhancing leaf support/protection in the cold zones. The significant additional influences of LA, LM, and LA were observed on the PL-LL, PCA-LA, and PM-LM relationships, respectively, implying that the single-dimension petiole trait is affected simultaneously by multidimensional lamina traits. Relative to simple-leaved species, the presence of petiolule in compound-leaved species can increase both leaf light interception and static gravity loads or dynamic drag forces on the petiole, leading to lower dependence of PL variation on LL variation, but higher biomass allocation to the petiole. Our study highlights the need for multidimension analyses of the petiole-lamina relationships and illustrates the importance of plant functional tradeoffs and the change in the tradeoffs along environmental gradients in determining the relationships.
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http://dx.doi.org/10.3389/fpls.2021.748125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8583490PMC
October 2021

MiR-629-5p Promotes Prostate Cancer Development and Metastasis by Targeting AKAP13.

Front Oncol 2021 15;11:754353. Epub 2021 Oct 15.

Department of Urology & Andrology, Minimally Invasive Surgery Center, Guangdong Provincial Key Laboratory of Urology, The First Affiliated Hospital of GuangZhou Medical University, Guangzhou, China.

Prostate cancer (PCa) has become the most frequently occurring cancer among western men according to the latest report, and patients' prognosis is often poor in the event of tumor progression, therefore, many researches are devoted to exploring the molecular mechanism of PCa metastasis. MicroRNAs (miRNA) have proved to play an important role in this process. In present study, by combining clinical samples with public databases, we found that miR-629-5p increased to varying degrees in primary localized PCa tissues and metastatic PCa tissues compared with adjacent normal tissues, and bioinformatics analysis suggested that high level of miR-629-5p was related to poor prognosis. Functionally, miR-629-5p drove PCa cell proliferation, migration and invasion , and promoted growth of PCa cells . Moreover, A-kinase Anchor Protein 13 (AKAP13) was screened as a direct target of miR-629-5p, that expression was negatively correlated with the malignant phenotype of tumor cells. In the end, through verification in clinical specimens, we found that AKAP13 could be independently used as a clinical prognostic indicator. Overall, the present study indicates that miR-629-5p plays an oncogenic role in PCa by targeting AKAP13, which provides a new idea for clinical diagnosis and treatment of complex refractory PCa.
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http://dx.doi.org/10.3389/fonc.2021.754353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8554144PMC
October 2021

Heterogeneous alterations in thalamic subfields in major depression disorder.

J Affect Disord 2021 12 4;295:1079-1086. Epub 2021 Sep 4.

Key Laboratory for Biomedical Engineering of Ministry of Education, Department of Biomedical Engineering, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China.

Background: It is well known that the thalamus is not a unitary and homogeneous entity but a complex and highly connected archeocortical structure. Although many neuroimaging studies have reported alterations in the thalamus in major depressive disorder (MDD), the structural alterations in thalamic subfields remain unclear. This study aimed to investigate changes in gray matter volume (GMV) in thalamic subfields in MDD patients.

Methods: The present study included structural images of 848 MDD patients and 794 age-matched normal controls (NC) from 17 study sites of the REST-meta-MDD consortium. We performed voxel-based morphometric analyses to calculate the GMV in the entire thalamus and its subfields using three different automated anatomical labeling atlases and subsequently compared the differences between first-episode drug-naïve major depressive disorder (FEDN), recurrent major depressive disorder (RMDD), and NC groups. We also evaluated the relationships between thalamic GMV and clinical symptoms in MDD patients.

Results: Compared to NC, the FEDN patients showed increased GMV in thalamic subfields but not in the entire thalamus, while RMDD patients showed no significant alterations in GMV in the entire thalamus and its subfields. Moreover, the mean GMV in the right anterior thalamus and left anteroventral thalamus in RMDD patients were mildly positively correlated with the Hamilton Anxiety Rating Scale scores.

Limitations: The main limitations are a single-modal analysis based on T1-weighted MR images and a cross-sectional design.

Conclusions: Our findings suggest that FEDN and RMDD patients show heterogeneous alterations across thalamic subfields, which may help us understand the pathophysiological mechanisms of MDD.
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http://dx.doi.org/10.1016/j.jad.2021.08.115DOI Listing
December 2021

A longitudinal sampling study of transcriptomic and epigenetic profiles in patients with thrombocytopenia syndrome.

Nat Commun 2021 09 24;12(1):5629. Epub 2021 Sep 24.

College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, China.

Severe fever with thrombocytopenia syndrome (SFTS) is a novel tick-borne infectious disease caused by a new type of SFTS virus (SFTSV). Here, a longitudinal sampling study is conducted to explore the differences in transcript levels after SFTSV infection, and to characterize the transcriptomic and epigenetic profiles of hospitalized patients. The results reveal significant changes in the mRNA expression of certain genes from onset to recovery. Moreover, mA-seq reveals that certain genes related with immune regulation may be regulated by mA. Besides the routine tests such as platelet counts, serum ALT and AST levels testing, distinct changes in myocardial enzymes, coagulation function, and inflammation are well correlated with the clinical data and sequencing data, suggesting that clinical practitioners should monitor the above indicators to track disease progression and guide personalized treatment. In this study, the transcript changes and RNA modification may lend a fresh perspective to our understanding of the SFTSV and play a significant role in the discovery of drugs for effective treatment of this disease.
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http://dx.doi.org/10.1038/s41467-021-25804-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463551PMC
September 2021

Surface Enhanced Raman Scattering Revealed by Interfacial Charge-Transfer Transitions.

Innovation (N Y) 2020 Nov 13;1(3):100051. Epub 2020 Oct 13.

Key Lab of Nanodevices and Applications, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences (CAS), Suzhou 215123, China.

Surface enhanced Raman scattering (SERS) is a fingerprint spectral technique whose performance is highly dependent on the physicochemical properties of the substrate materials. In addition to the traditional plasmonic metal substrates that feature prominent electromagnetic enhancements, boosted SERS activities have been reported recently for various categories of non-metal materials, including graphene, MXenes, transition-metal chalcogens/oxides, and conjugated organic molecules. Although the structural compositions of these semiconducting substrates vary, chemical enhancements induced by interfacial charge transfer are often the major contributors to the overall SERS behavior, which is distinct from that of the traditional SERS based on plasmonic metals. Regarding charge-transfer-induced SERS enhancements, this short review introduces the basic concepts underlying the SERS enhancements, the most recent semiconducting substrates that use novel manipulation strategies, and the extended applications of these versatile substrates.
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http://dx.doi.org/10.1016/j.xinn.2020.100051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8454671PMC
November 2020

Quadratus lumborum block for postoperative analgesia after cesarean section: a meta-analysis of randomized controlled trials with trial sequential analysis.

Sci Rep 2021 09 13;11(1):18104. Epub 2021 Sep 13.

Department of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Qingchun East Road No. 3, Hangzhou, 310020, China.

The aim of this study was to assess the analgesic efficacy of QLB versus controls in women undergoing cesarean section (CS). We systematically searched Cochrane Library, PUBMED, EMBASE, VIP, WANFANG, and China National Knowledge Infrastructure. Trials were eligible if parturients received QLB during CS. GRADE system was used to assess the certainty of evidence and Trial sequential analyses (TSA) were performed to determine whether the results are supported by sufficient data. Thirteen studies involving 1269 patients were included. Compared to controls, QLB significantly reduced the cumulative postoperative intravenous opioid consumption (in milligram morphine equivalents) at 24 h (MD, - 11.51 mg; 95% CI - 17.05 to - 5.96) and 48 h (MD, - 15.87 mg; 95% CI - 26.36 to - 5.38), supported by sufficient data confirmed by TSA. The postoperative pain scores were significantly reduced by QLB at 4 h, 6 h, 12 h, 24 h, and 48 h postoperatively by QLB compared with control. Moreover, the time to first request for rescue analgesic and the incidence of PONV were also significantly reduced by QLB. The quality of evidence of most results were low and moderate assessed by GRADE.
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http://dx.doi.org/10.1038/s41598-021-96546-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438068PMC
September 2021

Flavor mystery of Chinese traditional fermented baijiu: The great contribution of ester compounds.

Food Chem 2022 Feb 21;369:130920. Epub 2021 Aug 21.

Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, China; Beijing Engineering and Technology Research Center of Food Additives, Beijing Technology and Business University, Beijing 100048, China; Key Laboratory of Brewing Molecular Engineering of China Light Industry, Beijing Technology and Business University, Beijing 100048, China. Electronic address:

Chinese traditional fermented baijiu is a famous alcoholic beverage with unique flavor. Despite its consumption for millennia, the flavor mystery behind baijiu is still unclear. Studies indicate that esters are the most important flavor substances, and bring health benefits. However, the aroma contribution and formation mechanism of esters still need to be clarified to reveal the flavor profile of baijiu. This review systematically summarizes all the 510 esters and finds 9 ethyl esters contribute greatly to the flavor of baijiu. The 508 different microbial species that have been identified affect the synthesis of esters through fatty acid and amino acid metabolism. The determination of minimum functional microbial groups and the analysis of their metabolic characteristics are crucial to reveal the mechanism of formation of baijiu flavor, and ensure the reproducible formation of flavor substances.
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http://dx.doi.org/10.1016/j.foodchem.2021.130920DOI Listing
February 2022

Increased MALAT1 expression predicts poor prognosis in primary gastrointestinal diffuse large B-cell lymphoma.

Clin Exp Med 2021 Aug 24. Epub 2021 Aug 24.

Key Laboratory of Cancer Prevention and Therapy, Department of Hematology, National Clinical Research Center for Cancer, Tianjin Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People's Republic of China.

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is involved in the pathogenesis and progression of several cancers. However, the potential effect of MALAT1 in primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL) has not been elucidated. This study aimed to explore the prognostic value of MALAT1 in patients with PGI-DLBCL. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine the expression of MALAT1 in 90 patients with PGI-DLBCL. MALAT1 was remarkably upregulated in PGI-DLBCL tissues compared to paired adjacent non-tumor tissues (P < 0.001), and the area under the receiver operating characteristic (ROC) curve (AUC) was 0.838. MALAT1 expression was further increased in the non-germinal center B-cell-like (non-GCB), advanced stage (stages IIE-IV) and International Prognostic Index (IPI) score (3-5) groups (P = 0.01, P < 0.001 and P < 0.001, respectively). Furthermore, Kaplan-Meier analysis showed that elevated MALAT1 expression correlated with inferior overall survival (OS) and progression-free survival in PGI-DLBCL patients (P < 0.001 and P < 0.001, respectively), and our multivariate analysis results suggested that upregulation of MALAT1 and high IPI score (3-5) were two unfavorable prognostic factors for PGI-DLBCL. In conclusion, our results demonstrate that MALAT1 may serve as a novel prognostic biomarker and an ideal therapeutic target for patients with PGI-DLBCL.
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http://dx.doi.org/10.1007/s10238-021-00748-2DOI Listing
August 2021

Catheter-Based Adrenal Ablation Remits Primary Aldosteronism: A Randomized Medication-Controlled Trial.

Circulation 2021 08 16;144(7):580-582. Epub 2021 Aug 16.

Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Army Medical University, Chongqing Institute of Hypertension, China (Z. Zhao, X.L, H. Zhang, Q.L., H.H., Z.Y., F.S., Y.L., X.Z., X.B., H.W., Z. Zhu).

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http://dx.doi.org/10.1161/CIRCULATIONAHA.121.054318DOI Listing
August 2021

An investigation of pharmacovigilance and reporting of adverse drug reactions in hospitals: a cross-sectional study in China.

Curr Med Res Opin 2021 11 27;37(11):2001-2006. Epub 2021 Aug 27.

Department of Pharmacovigilance, Chinese Society of Toxicology, Beijing, China.

Background: Pharmacovigilance is a science that plays a significant role in reducing ADRs and helps predict adverse reactions to drugs in community. To safely use drugs in treatment and prevention of disease, adverse drug reaction has been paid more attention.

Objectives: To evaluate the future needs of existing systems, the paper investigated the current state of pharmacovigilance and the reporting of ADR in Chinese hospitals.

Methods: This cross-sectional, questionnaire-based study involved 10,063 pharmacists, doctors, and nurses from primary, secondary, and tertiary hospitals in all 31 provinces of China. It was commissioned by the National Centre for ADR Monitoring of China and conducted in March 2020. Three areas were assessed: sociodemographic characteristics of participants, awareness of the pharmacovigilance system, and the current state of hospitals' reporting of ADRs. Chi-square tests were used to calculate P values.

Results: Health care professionals had heard the term "pharmacovigilance" previously (89.40%) and knew the reporting object (68.47%), content (65.94%), and range (64.83%) of pharmacovigilance. Most hospitals dispatched responsible professionals (87.64%) and departments (86.25%) to monitor ADR reporting. A total of 58.66% of tertiary medical, 45.25% of secondary, and 38.90% of primary hospitals extracted ADRs from a hospital information system. Moreover, 53.09% of tertiary medical, 38.93% of secondary, and 23.89% of primary hospitals had established a prescription automatic screening system to warn about risks for ADRs. Health care professionals' reports (99.92%) and patient feedback (77.99%) were included in most hospitals' ADR reporting.

Conclusions: Chinese health care professionals generally have good awareness of pharmacovigilance, and pharmacovigilance is relatively more advanced in China compared to other developing countries.
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http://dx.doi.org/10.1080/03007995.2021.1967114DOI Listing
November 2021

Electrochromic Metamaterials of Metal-Dielectric Stacks for Multicolor Displays with High Color Purity.

Nano Lett 2021 08 6;21(16):6891-6897. Epub 2021 Aug 6.

Key Lab of Nanodevices and Applications, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences (CAS), Suzhou 215123, China.

Inorganic electrochromic (EC) materials with vibrant multicolor change that are compatible with large-scale processing have been at the forefront of EC technology and are crucial in a wide range of applications, such as displays and camouflage. However, limited strategies are available to realize such inorganic materials, and challenges such as low color purity are yet to be overcome. Here, we demonstrate multilayered metal-dielectric metamaterials (MMDMs) as a new family of inorganics-based EC materials to achieve dynamic alternation among multicolors with high contrast and high color purity, which are structurally realized by significantly enhancing the confinement of the incident light in specific optical frequencies. This multilayer structure renders high reflectivity (75%), high quality factor (7.4), and a full width at half-maximum of 60 nm before coloration and presents a color gamut at least 40% wider than that of previously reported metamaterials after coloration, indicating good color quality.
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http://dx.doi.org/10.1021/acs.nanolett.1c02030DOI Listing
August 2021

Arbidol is associated with increased in-hospital mortality among 109 patients with severe COVID-19: A multicenter, retrospective study.

J Glob Health 2021 17;11:05017. Epub 2021 Jul 17.

Emergency Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.

Background: The antiviral therapy has been considered as an ordinary intervention for COVID-19 patients. However, the effectiveness of antiviral therapy is uncertain. This study was designed to determine the association between the antiviral therapy and in-hospital mortality among severe COVID-19 patients.

Methods: This study enrolled severe COVID-19 patients admitted to four designated hospitals in Wuhan, China. The use of antiviral treatments, demographics, laboratory variables, co-morbidities, complications, and other treatments were compared between survival and fatal cases. The association between antiviral agents and in-hospital mortality were analyzed.

Results: In total, 109 severe COVID-19 patients (mean age 65.43) were enrolled for analysis, among which, 61 (56.0%) patients were discharged alive, and 48 (44.0%) died during hospitalization. We found no association between lopinavir/ritonavir (LPV/r) treatment and the in-hospital mortality (odds ratio (OR) = 0.195, 95% confidence interval (CI) = 0.023-1.679). Besides, ribavirin (OR = 0.738, 95% CI = 0.344-1.582), oseltamivir (OR = 0.765, 95% CI = 0.349-1.636), and interferon-alpha (IFN-α) (OR = 0.371, 95% CI = 0.112-1.236) were not associated with the in-hospital mortality. However, arbidol monotherapy (OR = 5.027, 95% CI = 1.795-14.074) or the combination of arbidol and oseltamivir (OR = 5.900, 95% CI = 1.190-29.247) was associated with an increased in-hospital mortality. In addition, the multiple logistic regression identified a significant association between the use of arbidol and the in-hospital mortality (adjusted OR = 4.195, 95% CI = 1.221-14.408).

Conclusions: Our findings indicated that LPV/r, IFN-α, ribavirin, or oseltamivir have no beneficial effects on the prognosis of severe COVID-19 patients, whereas the use of arbidol is associated with increased in-hospital mortality.
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http://dx.doi.org/10.7189/jogh.11.05017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284661PMC
August 2021

Reply to Comment on "miR-199b-5p-DDR1-ERK signalling axis suppresses prostate cancer metastasis via inhibiting epithelial-mesenchymal transition".

Br J Cancer 2021 08 20;125(4):620-621. Epub 2021 Jul 20.

Department of Urology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China.

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http://dx.doi.org/10.1038/s41416-021-01493-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8367950PMC
August 2021

Human mesenchymal stromal cells small extracellular vesicles attenuate sepsis-induced acute lung injury in a mouse model: the role of oxidative stress and the mitogen-activated protein kinase/nuclear factor kappa B pathway.

Cytotherapy 2021 10 13;23(10):918-930. Epub 2021 Jul 13.

Center of Pulmonary and Critical Care Medicine, Chinese People's Liberation Army General Hospital, Chinese People's Liberation Army Medical College, Beijing, China. Electronic address:

Background Aims: Acute lung injury (ALI) secondary to sepsis is a complex disease associated with high morbidity and mortality. Mesenchymal stem cells (MSCs) and their conditioned medium have been demonstrated to reduce alveolar inflammation, improve lung endothelial barrier permeability and modulate oxidative stress in vivo and in vitro. Recently, MSCs have been found to release small extracellular vesicles (sEVs) that can deliver functionally active biomolecules into recipient cells. The authors' study was designed to determine whether sEVs released by MSCs would be effective in sepsis-induced ALI mice and to identify the potential mechanisms.

Methods: A total of 6 h after cercal ligation and puncture, the mice received saline, sEV-depleted conditioned medium (sEVD-CM) or MSC sEVs via the tail vein.

Results: The administration of MSC sEVs improved pulmonary microvascular permeability and inhibited both histopathological changes and the infiltration of polymorphonuclear neutrophils into lung tissues. In addition, the activities of antioxidant enzymes were significantly increased in the group treated with sEVs compared with the saline and sEVD-CM groups, whereas lipid peroxidation was significantly decreased. Furthermore, sEVs were found to possibly inhibit phosphorylation of the mitogen-activated protein kinase/nuclear factor kappa B (MAPK/NF-κB) pathway and degradation of IκB but increase the activities of nuclear factor erythroid 2-related factor 2 and heme oxygenase 1.

Conclusions: These findings suggest that one of the effective therapeutic mechanisms of sEVs against sepsis-induced ALI may be associated with upregulation of anti-oxidative enzymes and inhibition of MAPK/NF-κB activation.
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http://dx.doi.org/10.1016/j.jcyt.2021.05.009DOI Listing
October 2021

Association between SNPs and hepatotoxicity in patients with primary central nervous system lymphoma on high-dose methotrexate therapy.

J Pharm Pharmacol 2021 Oct;73(11):1480-1490

Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, P.R. China.

Objectives: This study aims to evaluate the association between polymorphisms of methotrexate pathway genes and high-dose methotrexate-related hepatotoxicity in Chinese patients with primary central nervous system lymphoma.

Methods: Sixty-five patients in 411 treatment courses were enrolled and their toxicities were evaluated. The association between 30 candidate SNPs from 20 methotrexate pathway genes and high-dose methotrexate-related hepatotoxicity was analysed by PLINK and logistic regression.

Key Findings: TYMS 6 bp DI + II (rs151264360; OR, 0.41; 95% CI, 0.25-0.66; P = 0.00029), MTHFD1 1958 GA + AA (rs2236225; OR, 0.55; 95% CI, 0.33-0.91; P = 0.020) and CCND1 870 GA + GG (rs9344; OR, 0.42; 95% CI, 0.24-0.73; P = 0.0024) had less risk of hepatotoxicity compared with their homozygotes (DD, GG and AA, respectively), while ABCC2 intron 29 GA + GG (rs3740065; OR, 3.14; 95% CI, 1.89-5.20; P = 0.00001) was more prevalent in patients with hepatotoxicity than TT.

Conclusions: TYMS 6 bp DI + II, MTHFD1 1958 GA + AA, CCND1 870 GA + GG genotypes were associated with a lower probability of hepatotoxicity in patients with primary central nervous system lymphoma on high-dose methotrexate therapy, and ABCC2 intron 29 GA + GG was correlated with increased risk of hepatotoxicity.
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http://dx.doi.org/10.1093/jpp/rgab099DOI Listing
October 2021

Activation of Glucagon-Like Peptide-1 Receptor Ameliorates Cognitive Decline in Type 2 Diabetes Mellitus Through a Metabolism-Independent Pathway.

J Am Heart Assoc 2021 07 10;10(14):e020734. Epub 2021 Jul 10.

Center for Hypertension and Metabolic Diseases Department of Hypertension and Endocrinology Daping Hospital Army Medical University Chongqing China.

Background Patients with hypertension and diabetes mellitus are susceptible to dementia, but regular therapy fails to reduce the risk of dementia. Glucagon-like peptide-1 receptor agonists have neuroprotective effects in experimental studies. We aimed to assess the effect of liraglutide, a glucagon-like peptide-1 receptor agonist, on cognitive function and whether its effect was associated with metabolic changes in patients with type 2 diabetes mellitus. Methods and Results Fifty patients with type 2 diabetes mellitus were recruited in this prospective study. All patients underwent cognitive assessment and brain activation monitoring by functional near-infrared spectroscopy. At 12 weeks, patients in the glucagon-like peptide-1 group acquired better scores in all cognitive tests and showed remarkable improvement in memory and attention (=0.040) test compared with the control group after multivariable adjustment. Compared with the control group, liraglutide significantly increased activation of the dorsolateral prefrontal cortex and orbitofrontal cortex brain regions (=0.0038). After liraglutide treatment, cognitive scores were significantly correlated with changes in these activating brain regions (<0.05), but no correlation was observed between the changes in cognitive function and changes of body mass index, blood pressure, and glycemic levels. Conclusions We concluded that liraglutide improves cognitive decline in patients with type 2 diabetes mellitus. This beneficial effect is independent of its hypoglycemic effect and weight loss. The optimal intervention should be targeted to cognitive decline in the early stages of dementia. Registration URL: https://www.ClinicalTrials.gov; Unique identifier: NCT03707171.
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http://dx.doi.org/10.1161/JAHA.120.020734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8483500PMC
July 2021

Characterization of a carbapenem-resistant coharbouring and genes.

J Med Microbiol 2021 Jun;70(6)

The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang, PR China.

Members of the genus are facultative anaerobic Gram-negative bacilli belonging to the [Janda 1994; 32(8):1850-1854; Arens 1997;3(1):53-57]. Formerly, were occasionally reported as nosocomial pathogens with low virulence [Pepperell 2002;46(11):3555-60]. Now, they are consistently reported to cause nosocomial infections of the urinary tract, respiratory tract, bone, peritoneum, endocardium, meninges, intestines, bloodstream and central nervous system. Among species, the most common isolates are and , while has seldom been isolated [Janda 1994; 32(8):1850-1854; Marak 2017;49(7):532-9]. Further, spp. are usually susceptible to carbapenems, aminoglycosides, tetracyclines and colistin [Marak 2017;49(7):532-9]. As is rare, only one clinical isolate, coharbouring carbapenem resistance gene and quinolone resistance gene , has been reported. To characterize a carbapenem-resistant strain from PR China coharbouring and . Three hundred and forty nonrepetitive carbapenem-resistant (CRE) strains were collected during 2011-2018. A carbapenem-resistant strain was detected and confirmed using a VITEK mass spectrometry-based microbial identification system and 16S rRNA sequencing. Minimum inhibitory concentrations (MICs) for clinical antimicrobials were obtained by the broth microdilution method. Whole-genome sequencing (WGS) was performed for antibiotic resistance gene analysis, and a phylogenetic tree of strains was constructed using the Bacterial Pan Genome Analysis (BPGA) tool. The transferability of the resistance plasmid was verified by conjugal transfer. A rare carbapenem-resistant strain (CA71) was recovered from a patient with cerebral obstruction and the sequences of 16S rRNA gene shared more than 99 % similarity with CITRO86, FDAARGOS 165. CA71 is resistant to β-lactam, quinolone and aminoglycoside antibiotics, and even imipenem and meropenem (MICs of 2 and 4 mg l respectively), and is only sensitive to polymyxin B and tigecycline. Six antibiotic resistance genes were detected via WGS, including the β-lactam genes , and , the quinolone gene , and the aminoglycoside genes . Interestingly, and coexist on an IncN1-type plasmid (pCA71-IMP) and successfully transferred to J53 via conjugal transfer. Phylogenetic analysis showed that CA71 is most similar to strain CJ25 and belongs to the same evolutionary cluster along with seven other strains. To the best of our knowledge, this is the first report of a carbapenem-resistant isolate coharbouring and .
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http://dx.doi.org/10.1099/jmm.0.001364DOI Listing
June 2021

Correlation between white blood cell count at admission and mortality in COVID-19 patients: a retrospective study.

BMC Infect Dis 2021 Jun 14;21(1):574. Epub 2021 Jun 14.

Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China.

Background: Coronavirus disease-19 (COVID-19) has become a world health threaten. Its risk factors with death were still not known. White blood cells (WBC) count as a reflection of inflammation has played a vital role in COVID-19, however its level with death is not yet investigated.

Methods: In this retrospective, single-center study, all confirmed patients with COVID-19 at West Branch of Union Hospital from Jan 29 to Feb 28, 2020 were collected and analyzed. Demographic and clinical data including laboratory examinations were analyzed and compared between recovery and death patients.

Results: A total of 163 patients including 33 death cases were included in this study. Significant association was found between WBC count and death (HR = 1.14, 95%CI: 1.09-1.20, p < 0.001). The regression analysis results showed there was a significant association between WBC count and death (HR = 5.72, 95%CI: 2.21-14.82, p < 0.001) when use the second quartile as a cutoff value (> 6.16 × 10^9/L). The difference was still exist after adjusting for confounding factors (HR = 6.26, 95%CI: 1.72-22.77, p = 0.005). In addition, Kaplan-meier survival analysis showed that there was a significant decline of the cumulative survival rate (p < 0.001) in those with WBC count ≥6.16 × 10^9/L.

Conclusion: WBC count at admission is significantly corelated with death in COVID-19 patients. Higher level of WBC count should be given more attention in the treatment of COVID-19.
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http://dx.doi.org/10.1186/s12879-021-06277-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202964PMC
June 2021

Levels of Fibrin Degradation Products at Admission With Acute Ischemic Stroke Correlate With the NIH Stroke Scale Score 1 h After Intravenous Thrombolysis.

Front Neurol 2021 28;12:651867. Epub 2021 May 28.

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

Fibrin degradation products (FDPs) are fragments released by the plasmin-mediated degradation of fibrinogen or fibrin. Whether plasma levels of these fragments can predict the thrombolytic effect of recombinant tissue plasminogen activator (r-tPA) remains unknown. We performed a hospital-based study of patients with acute ischemic stroke (AIS) to explore the relationship between FDP levels at admission and the NIH Stroke Scale (NIHSS) score 1 h after thrombolysis treatment. In this retrospective, single-center study, the data of all patients with AIS who received r-tPA treatment at Beijing Tiantan Hospital from January 2019 to October 2020 were collected and analyzed. Demographic and clinical data, including laboratory examinations, were also analyzed. A total of 339 patients with AIS were included in this study. Of these, 151 showed favorable effects of r-tPA, and 188 showed unsatisfactory effects at 1 h after thrombolysis. Overall, we found an inverse relationship between the FDPs levels at admission and the NIHSS score. A significant difference was observed when using the interquartile range of the FDPs levels (1.31 μg/mL) as a cutoff value ( = 0.003, odds ratio [OR] = 1.95, 95% confidence interval [CI]: 1.26-3.01), even after adjusting for confounding factors ( = 0.003, OR = 2.23, 95% CI: 1.31-3.77). In addition, significant associations were observed in the tertile (T3) and quartile (Q3, Q4) FDP levels when compared with T1 or Q1. A nomogram was also employed to create a model to predict an unsatisfactory effect of r-tPA. We found that FDP levels, white blood cell count, age, D-dimer level, and body mass index could influence the thrombolytic effect of r-tPA. In conclusion, the present study demonstrated that the levels of FDPs at admission can be used as a prognostic factor to predict the curative effect of r-tPA.
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http://dx.doi.org/10.3389/fneur.2021.651867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194400PMC
May 2021

Morphological Effect of Vitamin D Deficiency on Globular Substances in Mice.

Otol Neurotol 2021 10;42(9):e1313-e1317

Department of Otolaryngology/Head and Neck Surgery, The First Affiliated Hospital, Harbin Medical University.

Objective: Many authors, including us, elucidated that vitamin D deficiency was a risk factor for benign paroxysmal position vertigo. We speculated vitamin D deficiency was likely to intervene otoconia formation by globular substance (GS).

Methods: Kunming mice were randomly divided into three groups: vitamin D sufficient group (12-wk standard control diet), vitamin D deficiency group (16-wk vitamin D deficiency diet), and vitamin D supplement group (16-wk vitamin D deficiency diet and followed 8-wk standard control diet). At 12, 16, and 24 weeks, blood was collected for measuring vitamin D and macula utriculi were obtained for research under scanning electron microscope (SEM). We randomly selected 10 SEM photographs of macula utriculi in each mouse, counted cilium and GS, and measured diameters of counted GS. The ratio of the number of GS to cilium in each SEM photograph was defined as density of GS.

Results: The diameter and density of GS were larger and higher in vitamin D deficiency group than sufficient group (p < 0.05; p < 0.05). There was no significant difference in density and diameters of GS between vitamin D deficiency and supplement group. The rough and grainy surface became smoother and smoother along with vitamin D deficiency, and reappeared after vitamin D supplement for 8 weeks.

Conclusion: GS secreted as a precursor of mature otoconia is affected by vitamin D deficiency and vitamin D supplementation can mitigate the effects in mice. The density of GS, a quantitative method we designed, can quantify GS well.
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http://dx.doi.org/10.1097/MAO.0000000000003229DOI Listing
October 2021

Transcriptional dynamics of transposable elements when converting fibroblast cells of Macaca mulatta to neuroepithelial stem cells.

BMC Genomics 2021 Jun 4;22(Suppl 3):405. Epub 2021 Jun 4.

State Key Laboratory of Primate Biomedical Research; Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, 650500, China.

Background: Transposable elements (TE) account for more than 50% of human genome. It has been reported that some types of TEs are dynamically regulated in the reprogramming of human cell lines. However, it is largely unknown whether some TEs in Macaca mulatta are also regulated during the reprogramming of cell lines of monkey.

Results: Here, we systematically examined the transcriptional activities of TEs during the conversion of Macaca mulatta fibroblast cells to neuroepithelial stem cells (NESCs). Hundreds of TEs were dynamically regulated during the reprogramming of Macaca mulatta fibroblast cells. Furthermore, 48 Long Terminal Repeats (LTRs), as well as some integrase elements, of Macaca endogenous retrovirus 3 (MacERV3) were transiently activated during the early stages of the conversion process, some of which were further confirmed with PCR experiments. These LTRs were potentially bound by critical transcription factors for reprogramming, such as KLF4 and ETV5.

Conclusion: These results suggest that the transcription of TEs are delicately regulated during the reprogramming of Macaca mulatta fibroblast cells. Although the family of ERVs activated during the reprogramming of fibroblast cells in Macaca mulatta is different from those in the reprogramming of human fibroblast cells, our results suggest that the activation of some ERVs is a conserved mechanism in primates for converting fibroblast cells to stem cells.
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http://dx.doi.org/10.1186/s12864-021-07717-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176597PMC
June 2021

Determination of adrenal hypersecretion in primary Aldosteronism without aldosterone-production adenomas.

BMC Endocr Disord 2021 May 31;21(1):114. Epub 2021 May 31.

Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Daping Hospital, Army Medical University of PLA, Chongqing, 400042, China.

Background: Primary aldosteronism (PA) is highly prevalent in hypertensive population. Adrenal vein sampling (AVS) is the only procedure to assess adrenal aldosterone hypersecretion in PA. PA patients without aldosterone-producing adenomas (APA) frequently have unilateral aldosterone hypersecretion (UAH). These patients could bear inappropriate adrenalectomy without AVS. This study aims to identify which clinical characteristics should be recommended to perform AVS in these PA patients.

Methods: This study was performed from January 2018 to July 2019 at a center for hypertension and metabolic diseases. Adrenal computed tomography (CT) scan, biochemical evaluation, and AVS were performed.

Results: Total 141 patients were included in this study. Aldosterone to renin ratio (ARR) after confirmatory test is highly associated with adrenal laterality. The specificity of ARR > 10 (ng/dL)/(mU/L) after confirmatory test is 100%. After confirmatory test, patients with ARR > 10 (ng/dL)/(mU/L) had higher plasma aldosterone concentration and incidences of ischemic heart diseases and renal damage(p < 0.05).

Conclusions: After confirmatory tests, ARR > 10 (ng/dL)/(mU/L) indicates adrenal laterality, with increasingly cardiorenal damage in PA patients without APA. Thus, AVS should be recommended in these patients before surgery.

Trial Registration: NCT03398785 , Date of Registration: December 24, 2017.
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http://dx.doi.org/10.1186/s12902-021-00770-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167985PMC
May 2021

Methotrexate Polyglutamates Analysis by Chromatography Methods in Biological Matrices: A Review.

Anal Sci 2021 Dec 21;37(12):1655-1664. Epub 2021 May 21.

Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University.

Methotrexate (MTX) is used as an immunosuppressant and antineoplastic drug in clinical practice. MTX is a parent drug and converts to MTX polyglutamates (MTXPGs) to exhibit its biological activity. Clinical studies found that MTXPG levels were associated with MTX response and toxicities, especially at low doses. Due to huge variance of MTX response and toxicities between individuals, therapeutic drug monitoring is necessary for its use in individualized therapy. Various chromatography methods coupled with ultraviolet-visible detector, fluorescence detector and mass spectrometry have been reported for MTXPG analysis in various biological matrices. The aim of this paper is to review the chromatographic based methods for the measurement of total and/or individual MTXPGs. We searched Embase, Science Direct and PubMed databases using "methotrexate polyglutamate" and "chromatography" as search terms, and found 745 articles. Of those, 14 articles were extracted for this study. The key steps for method development (sample pretreatment, parameter optimization of liquid chromatography and mass spectrometry, selection of internal standard) and validation (lower limit of quantitation, accuracy, precision, recovery, matrix effect and stability) were analyzed and summarized, which might be helpful for researchers to develop their own methods.
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http://dx.doi.org/10.2116/analsci.21R001DOI Listing
December 2021
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