Publications by authors named "Weimin Wang"

405 Publications

Enhanced Sinks of Polycyclic Aromatic Hydrocarbons Due to Kuroshio Intrusion: Implications on Biogeochemical Processes in the Ocean-Dominated Marginal Seas.

Environ Sci Technol 2021 May 4. Epub 2021 May 4.

State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen 361102, China.

The biogeochemical processes of polycyclic aromatic hydrocarbons (PAHs) in the South China Sea (SCS) are influenced by the exchanges of water masses, energies, and materials between this marginal sea and the Pacific Ocean. To investigate the impact of oceanic water intrusion on semivolatile compounds, we collected seawater samples in the Western Pacific, northern, and central SCS in 2017 and analyzed for dissolved PAHs. PAH concentrations in the water columns of the Pacific Ocean and SCS were 1.7-11 and 1.1-7.3 ng L, respectively, showing spatial distinctions in terms of the composition and source characteristics. A common depletion for three-ring PAHs was found in the northern SCS by comparing the modeling results of conservative mixing by Kuroshio intrusion. Kuroshio water increased the levels of temperature, dissolved oxygen, and nutrients when intruding into the northern SCS and was likely to enhance the bioavailability of PAHs and stimulate their biodegradation process. In the water column, the most effective layer under the Kuroshio intrusion impact is different for three- and four-ring PAHs, where the three-ring PAHs' depletion was most significant at the surface; however, for four-ring PAHs, that was at the deep chlorophyll maximum layer. This study highlighted the effect of ocean currents on PAHs for their water-column processes both from physical and biogeochemical perspectives.
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http://dx.doi.org/10.1021/acs.est.1c01009DOI Listing
May 2021

Development of an Electrostatic Comb-Driven MEMS Scanning Mirror for Two-Dimensional Raster Scanning.

Micromachines (Basel) 2021 Apr 1;12(4). Epub 2021 Apr 1.

State Key Laboratory of Optical Technologies on Nano-Fabrication and Micro-Engineering, Institute of Optics and Electronics, Chinese Academy of Sciences, Chengdu 610209, China.

Microelectromechanical System (MEMS)-based scanning mirrors are important optical devices that have been employed in many fields as a low-cost and miniaturized solution. In recent years, the rapid development of Light Detection and Ranging (LiDAR) has led to opportunities and challenges for MEMS scanners. In this work, we propose a 2D electrostatically actuated micro raster scanner with relatively large aperture. The 2D scanner combines a resonant scanning axis driven by an in-plane comb and a quasistatic scanning axis driven by a vertical comb, which is achieved by raising the moving comb finger above the fixed comb finger through the residual stress gradient. The analytic formula for the resonant axis frequency, based on the mechanical coupling of two oscillation modes, is derived and compared with finite element simulation. A prototype is designed, fabricated, and tested, and an overall optical Field-of-View (FoV) of about 60° × 4° is achieved. Finally, some possibilities for further improvement or optimization are discussed.
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http://dx.doi.org/10.3390/mi12040378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066418PMC
April 2021

Determination of 1-methylcyclopropene residues in vegetables and fruits based on iodine derivatives.

Food Chem 2021 Apr 20;358:129854. Epub 2021 Apr 20.

Pesticide Safety Evaluation Research Center, Institute for Agro-food Standards and Testing Technology, Shanghai Academy of Agricultural Sciences, Shanghai 2011106, China. Electronic address:

An innovative method was established for the determination of 1-methylcyclopropene (1-MCP) in vegetables and fruits. Due to its small molecular weight and low boiling point, it was difficult to obtain quantitative analysis for 1-MCP, especially at the residual level. In this work, based on its iodine derivatives, 1-MCP was derived to 1,2-diiodo-1-methylcyclopropane, which was much easier for trace and accurate chromatographic analysis. During the method validation, the method validation results were satisfactory in terms of linearity (4 ~ 400 µg/L, and R ≥ 0.959), matrix effect (-89% ~ -13%), accuracy (80 ~ 100%), sensitivity (limits of quantification, 5 μg/kg) and precision (relative standard deviations ≤ 19%), which was in accordance with the Chinese guidelines for the testing of pesticide residues in crops. Finally, the proposed analytical method was used to monitor the 1-MCP residue levels in commercially available samples, and all the values were below 5 µg/kg, which satisfied the EU or Japan MRLs of 1-MCP.
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http://dx.doi.org/10.1016/j.foodchem.2021.129854DOI Listing
April 2021

Silymarin ameliorates the disordered glucose metabolism of mice with diet-induced obesity by activating the hepatic SIRT1 pathway.

Cell Signal 2021 Apr 24;84:110023. Epub 2021 Apr 24.

Department of Endocrinology, Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital, Nanjing, Jiangsu, China. Electronic address:

Obesity-induced insulin resistance is the principal cause of type 2 diabetes worldwide. The use of natural products for the treatment of diabetes is increasingly attracting attention. Silymarin (SLM) is a flavonolignan compound that has been shown to have promise for the treatment of diabetes. In the present study, we aimed to investigate the mechanisms underlying its therapeutic effects. C57BL/6 mice were fed a high-fat diet (HFD) for 12 weeks and then orally administered SLM (30 mg/kg) daily for 1 month. The effects of SLM were also investigated in HepG2 cells that had been rendered insulin resistant by palmitic acid (PA) treatment. SLM ameliorated the dyslipidemia, hepatic steatosis, and insulin resistance of the HFD-fed mice. HFD-feeding and PA treatment reduced the expression of sirtuin-1 (SIRT1) in the livers of the mice and in HepG2 cells, respectively. SLM increased the phosphorylation of AKT and FOXO1, and reduced the level of FOXO1 acetylation in PA-treated cells. However, SIRT1 knockdown by RNA interference reduced these effects of SLM. Moreover, the results of molecular dynamic simulation and in vitro activity assays indicated that SLM may directly bind to SIRT1 and increase its enzymatic activity. These findings suggest that hepatic SIRT1 may be an important pharmacological target of SLM and mediate effects on insulin resistance and gluconeogenesis, which may underlie its anti-diabetic activity.
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http://dx.doi.org/10.1016/j.cellsig.2021.110023DOI Listing
April 2021

Rapid collagen-directed mineralization of calcium fluoride nanocrystals with periodically patterned nanostructures.

Nanoscale 2021 Apr 23. Epub 2021 Apr 23.

State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Luoshi Road No. 122, Wuhan, 430070, China.

Collagen fibrils present periodic structures, which provide space for intrafibrillar growth of oriented hydroxyapatite nanocrystals in bone and contribute to the good mechanical properties of bone. However, there are not many reports focused on bioprocess-inspired synthesis of non-native inorganic materials inside collagen fibrils and detailed forming processes of crystals inside collagen fibrils remain poorly understood. Herein, the rapid intrafibrillar mineralization of calcium fluoride nanocrystals with a periodically patterned nanostructure is demonstrated. The negatively charged calcium fluoride precursor phase infiltrates collagen fibrils through the gap zones creating an intricate periodic mineralization pattern. Later, the nanocrystals initially filling the gap zones only expand gradually into the remaining space within the collagen fibrils. Mineralized tendons with organized calcium fluoride nanocrystals acquire mechanical properties (indentation elastic modulus ∼25.1 GPa and hardness ∼1.5 GPa) comparable or even superior to those of native human dentin and lamellar bone. Understanding the mineral growth processes in collagen may facilitate the development of tissue engineering and repairing.
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http://dx.doi.org/10.1039/d1nr00789kDOI Listing
April 2021

Systemic immune-inflammation index predicts postoperative acute kidney injury in hepatocellular carcinoma patients after hepatectomy.

Medicine (Baltimore) 2021 Apr;100(14):e25335

Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan.

Abstract: The systemic immune-inflammation index (SII) is an independent prognostic predictor of hepatocellular carcinoma (HCC). The present investigation examined whether an association exists between preoperative SII value and postoperative acute kidney injury (pAKI) in HCC patients.The study included 479 hepatitis B virus (HBV)-associated HCC patients undergoing hepatectomy. The SII was calculated as P × N/L, where P, N, and L represent the counts of platelets, neutrophils, and lymphocytes in routine blood test, respectively. After propensity score matching, logistic regression analysis was used to explore independent predictors of pAKI in HCC patients.pAKI was confirmed in 51 patients (10.8%). The average SII value was higher in patients with pAKI than patients without pAKI. After multivariate logistic regression analysis, SII, history of hypertension, and tumor size, among others, were found to be predictors of pAKI. The optimal threshold value of SII for predicting pAKI was found to be 547.84 × 109/L. Multivariate analysis performed after propensity score matching confirmed that SII ≥ 547.84 × 109/L was an independent predictor of pAKI.The preoperative SII qualifies as a novel, independent predictor of pAKI in HCC patients with HBV infection who underwent hepatectomy.
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http://dx.doi.org/10.1097/MD.0000000000025335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036044PMC
April 2021

A composite risk model predicts disease progression in early stages of COVID-19: A propensity score-matched cohort study.

Ann Clin Biochem 2021 Apr 21:45632211011194. Epub 2021 Apr 21.

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

Background: Recently, studies on COVID-19 have focused on the epidemiology of the disease and clinical characteristics of patients, as well as on the risk factors associated with mortality during hospitalization in critical COVID-19 cases. However, few research has been performed on the prediction of disease progression in particular group of patients in the early stages of COVID-19.

Methods: The study included 338 patients with COVID-19 treated at two hospitals in Wuhan, China, from December 2019 to March 2020. Predictors of the progression of COVID-19 from mild to severe stages were selected by the logistic regression analysis.

Results: COVID-19 progression to severe and critical stages was confirmed in 78 (23.1%) patients. The average value of the neutrophil-to-lymphocyte ratio (NLR) was higher in patients in the disease progression group than in the improvement group. Multivariable logistic regression analysis revealed that elevated NLR, LDH and IL-10 were independent predictors of disease progression. The optimal cut-off value of NLR was 3.75. The values of the area under the curve, reflecting the accuracy of predicting COVID-19 progression by NLR was 0.739 (95%CI: 0.605-0.804). The risk model based on NLR, LDH and IL-10 had the highest area under the ROC curve.

Conclusions: The performed analysis demonstrates that high concentrations of NLR, LDH and IL-10 were independent risk factors for predicting disease progression in patients at the early stage of COVID-19. The risk model combined with NLR, LDH and IL-10 improved the accuracy of the prediction of disease progression in patients in the early stages of COVID-19.
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http://dx.doi.org/10.1177/00045632211011194DOI Listing
April 2021

The ubiquitin ligase MDM2 sustains STAT5 stability to control T cell-mediated antitumor immunity.

Nat Immunol 2021 Apr 25;22(4):460-470. Epub 2021 Mar 25.

Department of Surgery, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USA.

Targeting the p53-MDM2 pathway to reactivate tumor p53 is a chemotherapeutic approach. However, the involvement of this pathway in CD8 T cell-mediated antitumor immunity is unknown. Here, we report that mice with MDM2 deficiency in T cells exhibit accelerated tumor progression and a decrease in tumor-infiltrating CD8 T cell survival and function. Mechanistically, MDM2 competes with c-Cbl for STAT5 binding, reduces c-Cbl-mediated STAT5 degradation and enhances STAT5 stability in tumor-infiltrating CD8 T cells. Targeting the p53-MDM2 interaction with a pharmacological agent, APG-115, augmented MDM2 in T cells, thereby stabilizing STAT5, boosting T cell immunity and synergizing with cancer immunotherapy. Unexpectedly, these effects of APG-115 were dependent on p53 and MDM2 in T cells. Clinically, MDM2 abundance correlated with T cell function and interferon-γ signature in patients with cancer. Thus, the p53-MDM2 pathway controls T cell immunity, and targeting this pathway may treat patients with cancer regardless of tumor p53 status.
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http://dx.doi.org/10.1038/s41590-021-00888-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026726PMC
April 2021

148-W single-frequency Nd:YAG Innoslab μs-amplifier at 1064 nm with high efficiency.

Opt Express 2021 Feb;29(4):5687-5693

In this paper, a single-frequency quasi-continuous-wave partially pumped slab (Innoslab) amplifier at 1064 nm is reported. The 4.4-W single-frequency seed laser was amplified to 148.1 W with optical-optical efficiency of 30.4%. The output pulse duration was 141.4 μs at the repetition of 500 Hz. The beam quality factors of M2 were 1.41 and 1.37 in the horizontal and vertical direction respectively. The experimental results match well with the numerical simulation. To the best of our knowledge, this is the first report on single-frequency Nd:YAG Innoslab amplifier with such a high output power and efficiency.
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http://dx.doi.org/10.1364/OE.414808DOI Listing
February 2021

300  W two-stage Nd:YAG Innoslab microsecond amplifier.

Appl Opt 2021 Feb;60(4):971-975

In this paper, a two-stage partially pumped slab (Innoslab) microsecond amplifier at 1064 nm is reported. The 4.4-W single-frequency seed laser is amplified to 303.6 W, with an overall optical-optical efficiency of 25.7%. The overlapping efficiency of the first- and second- amplifier stage is 67% and 55.6%, respectively. The pulse width is 145.0 µs, at a repetition rate of 500 Hz, and the beam quality factor of is 1.84 and 1.71 in the horizontal and vertical directions, respectively. With higher overlap between the pump volume and the seed laser mode, the output power and optical-optical efficiency can be further improved.
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http://dx.doi.org/10.1364/AO.414813DOI Listing
February 2021

Role of vitronectin-rich protein corona on tumor-specific siRNA delivery and transfection with lipid nanoparticles.

Nanomedicine (Lond) 2021 03 8;16(7):535-551. Epub 2021 Mar 8.

Department of Pharmaceutical Sciences, Bouvé College of Health Sciences, Northeastern University, Boston, MA 02115, USA.

To evaluate the role of vitronectin-enriched protein corona on systemic delivery of siRNA-encapsulated cationic lipid nanoparticles (LNPs) to αvβ3 integrin expressing solid tumors. 1,2-Dioleoyl-3-trimethylammonium-propane LNPs were formulated, protein corona formed in nude mice serum and its impact on drug delivery were analyzed. 1,2-Dioleoyl-3-trimethylammonium-propane-containing LNP led to enhanced recruitment of vitronectin and showed preferential transfection to αvβ3-expressed cells relative to controls. Upon systemic administration in mice, the LNPs accumulated in the αvβ3-expressing endothelial lining of the tumor blood vessels before reaching tumor cells. These results present an optimized LNP that selectively recruits endogenous proteins to its corona which may lead to enhanced delivery and transfection in tissues of interest.
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http://dx.doi.org/10.2217/nnm-2020-0428DOI Listing
March 2021

Concomitant KIAA1549-BRAF fusion and IDH mutation in Pediatric spinal cord astrocytoma: a case report and literature review.

Brain Tumor Pathol 2021 Apr 28;38(2):132-137. Epub 2021 Feb 28.

Department of Pathology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Primary tumors of the spinal cord are rare, accounting for 3-6% of tumors in the central nervous system, particularly in children. KIAA1549-BRAF fusion is more common in pilocytic astrocytoma (PA) and IDH1 R132H mutation is rare in infratentorial tumors. Here, we report a 10-year-old male patient who presented with weakness in lower limbs that progressed to difficulty walking. Magnetic resonance imaging (MRI) revealed an intramedullary solid-cystic lesion from the medulla oblongata to the thoracic spin 4 level, with the expansion of the spinal cord. The lesion exhibited patchy enhancement at C4-T1, indicating a tentative diagnosis of astrocytoma. The patient underwent resection of the lesion in the spinal canal from the cervical 6 level to the thoracic 2 level. Histopathology confirmed diagnosis of astrocytoma, WHO grade 2. Genetic analysis showed both IDH1 R132H mutation and KIAA1549-BRAF fusion. Therefore, our integrated diagnosis was astrocytoma, IDH mutation, WHO grade 2. Its molecular analyses include IDH1 R132H mutation and KIAA1549-BRAF fusion. After the operation, the patient did not receive chemo- or radiotherapy, and underwent an aggressive rehabilitation regiment. Follow up 10 months later, symptoms improved. To our best knowledge, this is the first case of concomitant IDH mutation and BRAF fusion in pediatric spinal cord astrocytoma.
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http://dx.doi.org/10.1007/s10014-021-00394-2DOI Listing
April 2021

Transcriptome profiling towards understanding of the morphogenesis in the scale development of blunt snout bream (Megalobrama amblycephala).

Genomics 2021 Feb 25;113(3):983-991. Epub 2021 Feb 25.

College of Fisheries, Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education/Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan 430070, China. Electronic address:

Skin appendages in vertebrates have individual morphological differences, but share the same evolutionary origin. In this study, we used Megalobrama amblycephala as a fish model to study the developmental regulation mechanism of a common skin appendage in fish: scales. By combining in-toto live imaging method and transcriptomic analysis during the scale development, we elucidated core features of scale patterning containing three distinct regions and experiencing four stages. Differentially expressed genes in skin tissues at the initial site before and after scale development were analyzed and some key regulatory genes (Wnt3, Wnt6, Fgf8, Fgf10, Fgf16, Fgfr1a, Ihhb and BMP6) which are crucial for scale morphogenesis were selected. This study provides a strong reference for further exploration of the function of genes related to the molecular regulation mechanism of scale development in M. amblycephala, as well as in other fishes.
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http://dx.doi.org/10.1016/j.ygeno.2020.12.043DOI Listing
February 2021

Loss of optineurin drives cancer immune evasion via palmitoylation-dependent IFNGR1 lysosomal sorting and degradation.

Cancer Discov 2021 Feb 24. Epub 2021 Feb 24.

Department of Surgery, University of Michigan Medical School

Mutations in IFN- and MHC-signaling genes endow immunotherapy resistance. Colorectal cancer patients infrequently exhibit IFN- and MHC-signaling gene mutations, and are generally resistant to immunotherapy. In exploring the integrity of the IFN- and MHC-signaling in colorectal cancer, we found that optineurin was a shared node between the two pathways, and predicted colorectal cancer patient outcome. Loss of optineurin occurred in early stage human colorectal cancer. Immunologically, optineurin deficiency attenuated IFNGR1 and MHC-I expression, impaired T cell-immunity, and diminished immunotherapy efficacy in murine cancer models and cancer patients. Mechanistically, IFNGR1 was S-palmitoylated on Cys122, and AP3D1 bound with and sorted palmitoylated-IFNGR1 to lysosome for degradation. Unexpectedly, optineurin interacted with AP3D1 to prevent palmitoylated-IFNGR1 lysosomal sorting and degradation - thereby maintaining IFNy- and MHC-I-signaling integrity. Furthermore, pharmacologically targeting IFNGR1-palmitoylation stabilized IFNGR1, augmented tumor immunity, and sensitized checkpoint therapy. Thus, loss of optineurin drives immune evasion and intrinsic immunotherapy resistance in colorectal cancer.
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http://dx.doi.org/10.1158/2159-8290.CD-20-1571DOI Listing
February 2021

Residue behavior and dietary risk assessment of six pesticides in pak choi using QuEChERS method coupled with UPLC-MS/MS.

Ecotoxicol Environ Saf 2021 Apr 18;213:112022. Epub 2021 Feb 18.

Shanghai Agriculture Technical Extension Service Center, Shanghai 201103, PR China.

A reliable and simple modified QuEChERS method with UPLC-MS/MS was developed for the simultaneous determination of six pesticides (dimethomorph, imidaclothiz, lufenuron, methoxyfenozide, pyridaben, spinetoram) and their metabolites in pak choi. Method validation indicated good linearity (R ≥ 0.99), accuracy (recoveries of 75%-112%), sensitivity (limits of quantification, 0.002-0.01 mg kg), and precision (relative standard deviations ≤ 21%), and matrix effects were -36-28%. The half-lives of the six pesticides in pak choi were 2.2-12 d under open field and greenhouse conditions. Considering the short growth cycle of pak choi, the terminal residue levels (0.046-7.8 mg kg) and the relevant maximum residue limits (MRLs) of some countries, 5 d was recommended as the pre-harvest interval for the six pesticides on pak choi. Dietary risk assessment revealed that the risk quotients were 3.1%-58% for different gender and age groups in China, indicating none unacceptable public health risk for general population. The results showed that all the six pesticides degraded faster and the terminal residues were much lower under open field conditions than those under greenhouse conditions, which was mainly due to the influence of rainfall, sunlight and other environmental factors. This work was thus significant in assessing the dissipation fate and food safety risks of the six pesticides on pak choi and facilitated the establishment of maximum residue limits.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112022DOI Listing
April 2021

Polymorphisms in ovine ME1 and CA1 genes and their association with feed efficiency in Hu sheep.

J Anim Breed Genet 2021 Feb 15. Epub 2021 Feb 15.

College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, China.

Improving feed efficiency would increase profitability for producers. The objective of this study was to detect the expression levels of ME1 and CA1 and the polymorphisms of ME1 and CA1 associated with the feed conversion ratio (FCR) and residual feed intake (RFI) of Hu sheep by using qRT-PCR, pooled DNA sequencing and KASPar assay. The qRT-PCR results indicated that the expression levels of ME1 and CA1 were significantly higher in the liver tissues of low-RFI sheep than in those of the high-RFI sheep (p <.01). Association analysis demonstrated that the polymorphism ME1 g.453 C > T was significantly associated with FCR and RFI (p <.05). The polymorphism CA1 g.199 C > T had a significantly associated with FCR (p <.05) and no association with RFI (p >.05). Significant differences were observed between the combined genotypes and FCR and RFI at different measurement periods (p <.05). Thus, we propose the use of these two polymorphisms as new candidate molecular markers for improving feed efficiency in sheep populations.
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http://dx.doi.org/10.1111/jbg.12541DOI Listing
February 2021

Breath-by-breath measurement of intraoperative propofol by unidirectional anisole-assisted photoionization ion mobility spectrometry via real-time correction of humidity.

Anal Chim Acta 2021 Mar 21;1150:338223. Epub 2021 Jan 21.

CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning, 116023, People's Republic of China. Electronic address:

Humidity as a major issue affects the quantitative performance of ion mobility spectrometry (IMS) in field applications. According to the kinetic equations of ion-molecular reaction, the intensity ratio of the product ion peak (PIP) over the reactant ion peak (RIP) is proposed as a quantitative factor to correct real-time humidity variation. By coupling this method with a unidirectional anisole-assisted photoionization IMS, direct breath-by-breath measurement of intraoperative propofol was achieved for the first time, which provided more clinical information for studying the anesthetics pharmacokinetics. Although the signal intensities of the RIP and the propofol PIP both declined along with the increase of humidity, the intensity ratio of Propofol/(RIP + Propofol) kept almost constant in a wide relative humidity range of 0%-98%, enabling direct quantitation of exhaled propofol with varying humidity. Furthermore, interfering ion peaks resulted from the high concentration humidity and anesthetics in single exhalation were eliminated during the balanced anesthesia as the exhaled sample was diluted by the unidirectional gas flow scheme. As a demonstration, breath-by-breath variation profiles of propofol were obtained via monitoring end-tidal propofol concentration of intraoperative anesthetized patients (n = 7). The analyses were quantitative, corrected for humidity in real-time, without measuring the humidity content of each breath sample during operation, which show potential for the quantitative analysis of other high humidity samples.
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http://dx.doi.org/10.1016/j.aca.2021.338223DOI Listing
March 2021

Stanniocalcin 1 is a phagocytosis checkpoint driving tumor immune resistance.

Cancer Cell 2021 Apr 28;39(4):480-493.e6. Epub 2021 Jan 28.

Department of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USA; Department of Pathology, University of Michigan School of Medicine, Ann Arbor, MI, USA; Graduate Program in Immunology, University of Michigan School of Medicine, Ann Arbor, MI, USA; Graduate Program in Cancer Biology, University of Michigan School of Medicine, Ann Arbor, MI, USA. Electronic address:

Immunotherapy induces durable clinical responses in a fraction of patients with cancer. However, therapeutic resistance poses a major challenge to current immunotherapies. Here, we identify that expression of tumor stanniocalcin 1 (STC1) correlates with immunotherapy efficacy and is negatively associated with patient survival across diverse cancer types. Gain- and loss-of-function experiments demonstrate that tumor STC1 supports tumor progression and enables tumor resistance to checkpoint blockade in murine tumor models. Mechanistically, tumor STC1 interacts with calreticulin (CRT), an "eat-me" signal, and minimizes CRT membrane exposure, thereby abrogating membrane CRT-directed phagocytosis by antigen-presenting cells (APCs), including macrophages and dendritic cells. Consequently, this impairs APC capacity of antigen presentation and T cell activation. Thus, tumor STC1 inhibits APC phagocytosis and contributes to tumor immune evasion and immunotherapy resistance. We suggest that STC1 is a previously unappreciated phagocytosis checkpoint and targeting STC1 and its interaction with CRT may sensitize to cancer immunotherapy.
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http://dx.doi.org/10.1016/j.ccell.2020.12.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044011PMC
April 2021

Alcohol-and-HIV-Induced Lysosomal Dysfunction Regulates Extracellular Vesicles Secretion and in Liver-Humanized Mice.

Biology (Basel) 2021 Jan 5;10(1). Epub 2021 Jan 5.

Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA.

Background: Alcohol abuse is common in people living with HIV-1 and dramaticallyenhances the severity of HIV-induced liver damage by inducing oxidative stress and lysosomaldysfunction in the liver cells. We hypothesize that the increased release of extracellular vesicles(EVs) in hepatocytes and liver humanized mouse model is linked to lysosome dysfunction.

Methods: The study was performed on primary human hepatocytes and human hepatoma RLWXP-GFP (Huh7.5 cells stably transfected with CYP2E1 and XPack-GFP) cells and validated on ethanol-fed liverhumanizedfumarylacetoacetate hydrolase (Fah)-/-, Rag2-/-, common cytokine receptor gamma chainknockout (FRG-KO) mice. Cells and mice were infected with HIV-1ADA virus.

Results: We observedan increase in the secretion of EVs associated with a decrease in lysosomal activity and expressionof lysosomal-associated membrane protein 1. Next-generation RNA sequencing of primary humanhepatocytes revealed 63 differentially expressed genes, with 13 downregulated and 50 upregulatedgenes in the alcohol-HIV-treated group. Upstream regulator analysis of differentially expressedgenes through Ingenuity Pathway Analysis identified transcriptional regulators affecting downstreamgenes associated with increased oxidative stress, lysosomal associated disease, and function andEVs biogenesis. Our in vitro findings were corroborated by in vivo studies on human hepatocytetransplantedhumanized mice, indicating that intensive EVs' generation by human hepatocytes andtheir secretion to serum was associated with increased oxidative stress and reduction in lysosomalactivities triggered by HIV infection and ethanol diet.

Conclusion: HIV-and-ethanol-metabolisminducedEVs release is tightly controlled by lysosome status in hepatocytes and participates in thedevelopment of double-insult-induced liver injury.
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http://dx.doi.org/10.3390/biology10010029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824801PMC
January 2021

Simultaneous enantioselective analysis of illicit drugs in wastewater and surface water by chiral LC-MS/MS: A pilot study on a wastewater treatment plant and its receiving river.

Environ Pollut 2021 Jan 8;273:116424. Epub 2021 Jan 8.

State Key Laboratory of Environmental Criteria and Risk Assessment, State Environmental Protection Key Laboratory of Ecological Effect and Risk Assessment of Chemicals, Chinese Research Academy of Environmental Sciences, Beijing, 100012, China; College of Water Sciences, Beijing Normal University, Beijing, 100875, China. Electronic address:

An enantioselective method for quantifying amphetamine-type chiral illicit drugs (CIDs) in wastewater and surface water was developed, validated, and applied to samples from a wastewater treatment plant (WWTP) and its effluent-receiving river in Beijing, China. Water samples were subjected to solid-phase extraction (SPE) and then quantified via liquid chromatography-tandem mass spectrometry. The enantioseparation of CIDs was performed with a CHIRALPAK CBH column. Chromatographic parameters, including mobile phase composition and flow rates, were tested to identify the satisfactory enantiomeric resolution. The SPE method was optimized by evaluating variables, including SPE cartridge types, extraction solvents, and solvent volumes. The Oasis HLB sorbent showed good performance with recoveries exceeding 60% and matrix effects ranging from -19.6% to 26.6% for most target enantiomers, except for norephedrine (NE), in three different aquatic matrixes. The established method was superior to previously reported methods and had a low limit of detection, low limit of quantification, and short runtime (<45 min). The repeatability and reproducibility of the method reached 19.1% and 17.8%, respectively. The method was successfully utilized to monitor the daily variations in CIDs in the influent, effluent, and effluent-receiving river of a WWTP in Beijing over 1 week. The common occurrence of 1 R,2 S-(-)-ephedrine (1 R,2 S-(-)-EPH), 1 S,2 S-(+)-pseudoephedrine (1 S,2 S-(+)-PEPH), R-(-)-methamphetamine (METH), and S-(+)-METH in wastewater samples was observed. Ephedrines (1 R,2 S-(-)-EPH and 1 S,2 S-(+)-PEPH) were the most abundant CIDs in the influent, effluent, upstream, and downstream samples with concentrations of 725.8 ± 181.2 ng/L, 22.9 ± 4.9 ng/L, 12.96 ± 0.79 ng/L, and 11.6 ± 6.7 ng/L, respectively. METH was detectable in most water samples and was present in excess in S-enantiomer form in the influent and in R-enantiomer form in the effluent and surface water. R-(-)-MDMA was detected at a concentration of up to 2.4 ng/L in the influent. The metabolites norketamine (NK), amphetamine(AMP), MDA, and NE were not detected in water samples given the low concentration of their parent drugs.
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http://dx.doi.org/10.1016/j.envpol.2021.116424DOI Listing
January 2021

Ribonuclease1 contributes to the antibacterial response and immune defense in blunt snout bream (Megalobrama amblycephala).

Int J Biol Macromol 2021 Mar 14;172:309-320. Epub 2021 Jan 14.

College of Fisheries, Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education/Key laboratory of Freshwater Animal Breeding, Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan 430070, China. Electronic address:

Ribonuclease 1 (RNase1) is a vertebrate-specific enzyme that mainly performs digestive activity in herbivorous mammals. Here we used bacterial viability assays to explore its antimicrobial activity in blunt snout bream (Megalobrama amblycephala). The results showed that Ma-RNase1 rapidly killed Gram-negative and Gram-positive bacteria at micromolar concentrations. Ma-RNase1 increased the permeability of bacterial outer and inner membranes, thus reducing the integrity of bacterial cell wall and membrane. Moreover, Ma-RNase1 effectively counteracted the tissue damage and apoptosis caused by Aeromonas hydrophila infection. Quantitative real-time PCR and immunoblot analysis indicated that RNase1 mRNA and protein were up-regulated in the kidney and gut during infection. Furthermore, A. hydrophila infection significantly induced Tnf-α and Il-1β mRNA expression in liver, but not in the RNase1 pre-treatment group. In addition, a significant increase in the expression of immune-related genes (Nf-κb and Tlr4) was found in liver, kidney and gut of A. hydrophila-infected fish, while a decrease in Myd88 and Tlr4 levels was found in liver, spleen, kidney and gut in the group pre-treated with RNase1. Collectively, these data suggest that Ma-RNase1 has antimicrobial function both in vitro and in vivo, and contributes to the protective effect and immune defense of blunt snout bream.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.01.066DOI Listing
March 2021

CD133+/CD166+ human gastric adenocarcinoma cells present the properties of neoplastic stem cells and emerge more malignant features.

Life Sci 2021 Mar 12;269:119021. Epub 2021 Jan 12.

Institute of Translational Medicine, Medical College, Yangzhou University, The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of the State Administration of Traditional Chinese Medicine, Yangzhou 225001, China. Electronic address:

Aims: The recurrence and metastasis of gastric cancer has always been an important factor affecting the prognosis of gastric cancer. Cancer stem cells can promote the recurrence and growth of gastric cancer. The identification and isolation of gastric cancer stem cells contribute to the origin, progress and treatment strategy of gastric cancer. The aim of this study was to identify and isolate gastric cancer stem cells, and provide targets for the treatment of gastric cancer.

Methods: Magnetic-activated cell sorting was used to isolate CD133+/CD166+ cell populations from human gastric adenocarcinoma cell lines (BGC-823 and SGC-7901). Sphere formation, cell proliferation, resistance to chemotherapy, colony formation, migration invasion and tumorigenicity in vivo of these cell populations were evaluated. Moreover, RT-qPCR and Western blot were used to investigate the expression level of the stem cell markers Nanog, Sox2, Oct-4, and c-Myc.

Results: CD133+/CD166+ cell subpopulations presented more malignant features than CD133-/CD166-, CD133-/CD166+, CD133+/CD166- cell populations and parental cells. Moreover, the mRNA and protein expression level of Oct-4 and c-Myc were higher in CD133+/CD166+ cells than in parental cells or other cell populations.

Conclusion: The CD133+/CD166+ populations of human gastric cancer cell lines BGC-823 and SGC-7901 have cancer stem cell characteristics.
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http://dx.doi.org/10.1016/j.lfs.2021.119021DOI Listing
March 2021

Expression of JWA and XRCC1 as prognostic markers for gastric cancer recurrence.

Int J Clin Exp Pathol 2020 1;13(12):3120-3127. Epub 2020 Dec 1.

Department of Oncology, Yixing Hospital Affiliated to Medical College of Yangzhou University, Yangzhou University Yixing, Jiangsu, China.

Gastric cancer is one of the common gastrointestinal tumors. Tumor recurrence leads to a high death rate of gastric cancer. It is very important to find markers to effectively predict gastric cancer recurrence. We constructed a gastric cancer tissue microarray containing 89 tumors and corresponding normal tissues to explore the relationship between some proteins' expression and gastric cancer recurrence. The expression of JWA, Cullin1, p53, XRCC1, CHIP, FAK, MMP-2, MDM2 and p21 was determined on the microarray by immunohistochemistry. The relationship between the expression of these proteins and gastric cancer recurrence was analyzed. Tumor diameter, lymph node metastasis, and TNM stage were closely related with gastric cancer recurrence by Fisher's exact test (P<0.05). We used the univariate Cox regression analysis to find that JWA, XRCC1 were related to gastric cancer recurrence (P<0.05); Lymph node metastasis and TNM stage were closely related to gastric cancer recurrence (P<0.05). Multivariate Cox regression analysis revealed that XRCC1 or lymph node metastasis were independent risk factors of gastric cancer recurrence (P<0.05). Kaplan-Meier survival curve assay indicated that patients with low JWA or XRCC1 expression in gastric cancer had significantly shorter DFS than those with high-expressed proteins (P<0.05). JWA or XRCC1 may be effective markers to predict gastric cancer recurrence.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791389PMC
December 2020

Bioinspired 3D Printable, Self-Healable, and Stretchable Hydrogels with Multiple Conductivities for Skin-like Wearable Strain Sensors.

ACS Appl Mater Interfaces 2021 Jan 7;13(2):2952-2960. Epub 2021 Jan 7.

State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan 430070, P. R. China.

Bioinspired hydrogels have promising prospects in applications such as wearable devices, human health monitoring equipment, and soft robots due to their multifunctional sensing properties resembling natural skin. However, the preparation of intelligent hydrogels that provide feedback on multiple electronic signals simultaneously, such as human skin receptors, when stimulated by external contact pressure remains a substantial challenge. In this study, we designed a bioinspired hydrogel with multiple conductive capabilities by incorporating carbon nanotubes into a chelate of calcium ions with polyacrylic acid and sodium alginate. The bioinspired hydrogel consolidates self-healing ability, stretchability, 3D printability, and multiple conductivities. It can be fabricated as an integrated strain sensor with simultaneous piezoresistive and piezocapacitive performances, exhibiting sensitive (gauge factor of 6.29 in resistance mode and 1.25 kPa in capacitance mode) responses to subtle pressure changes in the human body, such as finger flexion, knee flexion, and respiration. Furthermore, the bioinspired strain sensor sensitively and discriminatively recognizes the signatures written on it. Hence, we expect our ideas to provide inspiration for studies exploring the use of advanced hydrogels in multifunctional skin-like smart wearable devices.
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http://dx.doi.org/10.1021/acsami.0c19512DOI Listing
January 2021

Role of Nanocrystallites of Al-Based Glasses and HO in Degradation Azo Dyes.

Materials (Basel) 2020 Dec 24;14(1). Epub 2020 Dec 24.

Key Laboratory for Liquid-Solid Structural Evolution and Processing of Materials (Ministry of Education), School of Materials Science and Engineering, Shandong University, Jinan 250061, China.

Al-based metallic glasses have a special atomic structure and should have a unique degradation ability in azo dye solutions. The AlNiY (Y3), AlNiY (Y6) and AlNiY (Y9) glassy ribbons are melt spun and used in degrading methyl orange (MO) azo dye solution with adding HO. With increasing , the as-spun ribbons have an increasing GFA (glass formability) and gradually decreased the degradation rate of MO solution. TEM (transmission electron microscopy) results show that the Y3 ribbon has nano-scale crystallites, which may form the channels to transport elements to the surface for degrading the MO solution. After adding HO, the degradation efficiency of Al-based glasses is improved and the Y6 ribbon has formed nano-scale crystallites embedded in the amorphous matrix and it has the largest improvement in MO solution degradation. These results indicate that forming nano-scale crystallites and adding HO are effective methods to improve the degradation ability of Al-based glasses in azo dye solutions.
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http://dx.doi.org/10.3390/ma14010039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796186PMC
December 2020

Whole-exome sequencing identifies prognostic mutational signatures in gastric cancer.

Ann Transl Med 2020 Nov;8(22):1484

Department of Gastro-intestine Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.

Background: Gastric cancer (GC) is a heterogeneous disease, and is a leading cause of cancer deaths in Eastern Asia. Genomic analysis, such as whole-exome sequencing (WES), can help identify key genetic alterations leading to the malignancy and diversity of GC, and may help identify new drug targets.

Methods: We identified genomic alterations in a cohort of 38 GC patients, including 26 metastatic and 12 non-metastatic patients. We analyzed the association between novel gene mutations and copy number variations (CNVs) with tumor metastasis and patient survival.

Results: A number of significantly mutated genes in somatic and germline cells were identified. Among them, somatic mutation, a potential biomarker of immunotherapy in stomach cancers, was associated with better patient survival (P=0.0939) and metastasis (P=0.074). germline variation was correlated with shorter overall survival (OS; P=0.0100). Novel CNVs were also identified and can potentially be used as biomarkers. These included 9p24.1 deletion (P=0.0376) and 16p11.2 amplification (P=0.0066), which were both associated with shorter OS. CNVs of several genes including , , and were found to be significantly related to metastasis (P<0.05).

Conclusions: We characterized the mutational landscape of 38 GC patients and discovered several potential new predictive markers of survival and metastasis in GC.
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http://dx.doi.org/10.21037/atm-20-6620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729362PMC
November 2020

Twelve tips for teaching medical students online under COVID-19.

Med Educ Online 2021 Dec;26(1):1854066

University of Massachusetts , Amherst, Massachusetts, USA.

Universities worldwide are pausing in an attempt to contain COVID-19's spread. In February 2019, universities in China took the lead, cancelling all in-person classes and switching to virtual classrooms, with a wave of other institutes globally following suit. The shift to online platform poses serious challenges to medical education so that understanding best practices shared by pilot institutes may help medical educators improve teaching. Provide 12 tips to highlight strategies intended to help on-site medical classes moving completely online under the pandemic. We collected 'best practices' reports from 40 medical schools in China that were submitted to the National Centre for Health Professions Education Development. Experts' review-to-summary cycle was used to finalize the best practices in teaching medical students online that can benefit peer institutions most, under the unprecedented circumstances of the COVID-19 outbreak. The 12 tips presented offer-specific strategies to optimize teaching medical students online under COVID-19, specifically highlighting the tech-based pedagogy, counselling, motivation, and ethics, as well as the assessment and modification. Learning experiences shared by pilot medical schools and customized properly are instructive to ensure a successful transition to e-learning.
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http://dx.doi.org/10.1080/10872981.2020.1854066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723018PMC
December 2021

Ultrasonic-assisted extraction of polysaccharides from Auricularia auricula and effects of its acid hydrolysate on the biological function of Caenorhabditis elegans.

Int J Biol Macromol 2021 Jan 27;167:423-433. Epub 2020 Nov 27.

College of Life Sciences, China Jiliang University, Hangzhou, Zhejiang 310018, China. Electronic address:

The present study was designed to explore the in vivo-antioxidant capacity and the probable mechanism of AAPs-H, prepared from Auricularia auricula polysaccharides with the optimal extraction conditions by Box-Behnken design and acid hydrolysis, using Caenorhabditis elegans as a model organism. The effects of AAPs-H on the locomotion behavior, life span, antioxidant-related enzymes activities, and antioxidants levels in C. elegans were studied. Furthermore, the potentials of AAPs-H in up-regulating the expression of antioxidant-related genes in C. elegans, such as skn-1, sod-3 and sir-2.1, were also discussed. AAPs-H demonstrated a highly significant protective effect against the damage caused by paraquat, could significantly increase U-Turn frequency of worms (p < 0.01), extend their lifespan, enhance antioxidant systems including GR by 63.96% (p < 0.05), GSH-Px by 71.16% (p < 0.01), SOD by 78.65% (p < 0.01) and CAT by 98.52% (p < 0.01), increase the level of GSH by 28.12% (p < 0.05), and decrease the level of MDA by 39.29% (p < 0.01). The qRT-PCR results showed that AAPs-H could up regulate mRNA expression levels of skn-1, sod-1, sod-2, sod-3 and sir-2.1 in wild-type C. elegans (>1.6 fold) when treated with the concentration of 0.4 mg/mL (p < 0.05 or p < 0.01). Our studies provide evidence that AAPs-H improves antioxidant defense system, and up-regulation of oxidative stress related genes for prevention of stress damage in C. elegans.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.11.160DOI Listing
January 2021

Structural Study of MgAlON (0 < < 0.5, 0 < < 1) Spinel Probed by X-ray Diffraction, Al MAS NMR, and First-Principles Calculations.

Inorg Chem 2020 Dec 20;59(23):17009-17017. Epub 2020 Nov 20.

State Key Lab of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan 430070, China.

The deep understanding of the crystal structure and composition-structure relationship is important for modifying and designing solids to obtain functional materials with customized properties. However, because of multiple compositions and complex structures in some spinel solid solutions, the composition-structure relationship is unknown, or becomes very complicated and difficult to be controlled. In this work, the solid-state magic-angle spinning nuclear magnetic resonance (MAS NMR) technique and powder X-ray diffraction (XRD) Rietveld refinement were combined to characterize the crystal structure of quaternary disordered MgAlON solid solutions in detail, which was supported by the first-principles density functional theory calculations. Diffraction data indicate that Mg ions preferentially enter the tetrahedron structure in MgAlON solid solutions because the sum of the bond valence in tetrahedron is closer to the atomic valence of Mg. With the compositional change, the coordination polyhedra in the crystal structure will also adjust the volume according to the changes in lattice parameter, anion parameter, and inversion parameter. In addition, the populations, chemical shifts, and quadrupole coupling constants of Al located in different coordinated environments of the solid solutions were detected through the simulation and integration of Al MAS NMR spectra, which were related to the structural parameters by the bond valence method. It turns out that Al MAS NMR parameters are highly sensitive to the subtle changes in the local environment of Al caused by the preferential occupation of Mg in the tetrahedron. These results provide deep insights into the crystal structural details of novel spinel materials with multiple disorders.
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http://dx.doi.org/10.1021/acs.inorgchem.0c02228DOI Listing
December 2020

Clinical practice guidelines for the management of adult diffuse gliomas.

Cancer Lett 2021 Feb 6;499:60-72. Epub 2020 Nov 6.

Department of Neurosurgery, The Fourth Medical Center of PLA General Hospital, Beijing, 100048, China.

To follow the revision of the fourth edition of WHO classification and the recent progress on the management of diffuse gliomas, the joint guideline committee of Chinese Glioma Cooperative Group (CGCG), Society for Neuro-Oncology of China (SNO-China) and Chinese Brain Cancer Association (CBCA) updated the clinical practice guideline. It provides recommendations for diagnostic and management decisions, and for limiting unnecessary treatments and cost. The recommendations focus on molecular and pathological diagnostics, and the main treatment modalities of surgery, radiotherapy, and chemotherapy. In this guideline, we also integrated the results of some clinical trials of immune therapies and target therapies, which we think are ongoing future directions. The guideline should serve as an application for all professionals involved in the management of patients with adult diffuse glioma and also a source of knowledge for insurance companies and other institutions involved in the cost regulation of cancer care in China and other countries.
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http://dx.doi.org/10.1016/j.canlet.2020.10.050DOI Listing
February 2021