Publications by authors named "Wei Wang"

16,911 Publications

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Expression of angiogenesis-related proteins in bone marrow mesenchymal stem cells induced by osteoprotegerin during osteogenic differentiation in rats.

Authors:
Wei Wang Bo Wang

Int Immunopharmacol 2021 Jun 9;98:107821. Epub 2021 Jun 9.

Department of Orthopaedic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. Electronic address:

This study aimed to discuss the expression of angiogenesis-related proteins in bone marrow mesenchymal stem cells (BMSCs) induced by osteoprotegerin (OGP) during osteogenic differentiation in rats, and to analyze the effect of fracture healing inflammatory factor TNF-ɑ on the osteogenic differentiation of BMSCs of rats. BMSCs isolated and cultured from the third generation rats were taken as the research object. According to the addition amount of OGP, BMSCs were divided into control group, OGP (10 mol/L) group, OGP (10 mol/L) group, and OGP (10 mol/L) group. The cell growth and morphological characteristics of each group were observed by inverted phase contrast microscope, the cell proliferation rate was measured by MTT method, angiogenesis-related markers (platelet growth factor (VEGF), cingulate protein 5 (Fbln5), and angiogenin-like protein 4 (Angptl4)) were quantitatively detected by Western blot, and the effect of TNF-ɑ on osteogenic differentiation was detected by CCK. Compared with the control group, MTT results showed that the value-added rate of cells in the OGP (10 mol/L) group reached the maximum at 9 days (P < 0.05). The ALP activity in osteoblasts in the OGP (10 mol/L) group reached the maximum at 9 days (P < 0.01). The OGP (10 mol/L) group had the highest expression of vascular regeneration proteins (VEGF, Fbln5, and Angptl4) (P < 0.05). CCK analysis showed that the TNF-ɑ (1.0 ng/mL) group showed a significant increase in absorbance compared with the control group on 6 days (P < 0.05), and the OD value of the TNF-ɑ (10 ng/mL) group decreased at all time points (P < 0.05). Overall, 10 mol/L OGP can induce the proliferation and osteogenic differentiation of MSCs, and promote the expression of angiogenesis-related proteins (VEGF, Fbln5, and Angptl4) during osteogenic differentiation. Besides, 1.0 ng/mL of TNF-ɑ can also promote osteogenesis differentiation of BMSCs in the short term.
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http://dx.doi.org/10.1016/j.intimp.2021.107821DOI Listing
June 2021

Nanographene-Osmapentalyne Complexes as a Cathode Interlayer in Organic Solar Cells Enhance Efficiency over 18.

Adv Mater 2021 Jun 12:e2101279. Epub 2021 Jun 12.

Shenzhen Grubbs Institute and Department of Chemistry, Southern University of Science and Technology, Shenzhen, 518055, China.

Interface engineering is a critical method by which to efficiently enhance the photovoltaic performance of nonfullerene solar cells (NFSC). Herein, a series of metal-nanographene-containing large transition metal involving d -p conjugated systems by way of the addition reactions of osmapentalynes and p-diethynyl-hexabenzocoronenes is reported. Conjugated extensions are engineered to optimize the π-conjugation of these metal-nanographene molecules, which serve as alcohol-soluble cathode interlayer (CIL) materials. Upon extension of the π-conjugation, the power conversion efficiency (PCE) of PM6:BTP-eC9-based NFSCs increases from 16% to over 18%, giving the highest recorded PCE. It is deduced by X-ray crystallographic analysis, interfacial contact methods, morphology characterization, and carrier dynamics that modification of hexabenzocoronenes-styryl can effectively improve the short-circuit current density (J ) and fill factor of organic solar cells (OSCs), mainly due to the strong and ordered charge transfer, more matching energy level alignments, better interfacial contacts between the active layer and the electrodes, and regulated morphology. Consequently, the carrier transport is largely facilitated, and the carrier recombination is simultaneously impeded. These new CIL materials are broadly able to enhance the photovoltaic properties of OSCs in other systems, which provides a promising potential to serve as CILs for higher-quality OSCs.
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http://dx.doi.org/10.1002/adma.202101279DOI Listing
June 2021

Quantifying Bone Marrow Fat Fraction and Iron by MRI for Distinguishing Aplastic Anemia from Myelodysplastic Syndromes.

J Magn Reson Imaging 2021 Jun 11. Epub 2021 Jun 11.

Radiology Department, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.

Background: Bone marrow of patients with aplastic anemia (AA) is different from that of patients with myelodysplastic syndrome (MDS) and is difficult to identify by blood examination. IDEAL-IQ (iterative decomposition of water and fat with echo asymmetry and least-squares estimation) imaging might be able to quantify fat fraction (FF) and iron content in bone tissues.

Purpose: To determine if IDEAL-IQ measurements of bone marrow FF and iron content can distinguish between patients with AA and MDS.

Study Type: Retrospective.

Population: Fifty-seven patients with AA, 21 patients with MDS, and 24 healthy controls.

Field Strength/sequence: 3.0 T, IDEAL-IQ sequence.

Assessment: Three independent observers evaluated the IDEAL-IQ images and measured FF and R2* in the left posterior superior iliac spine.

Statistical Tests: Kruskal-Wallis test, linear correlations, and Bland-Altman analysis were used. A P-value of <0.05 was considered statistically significant.

Results: The FF in patients with AA (79.46% ± 15.00%) was significantly higher than that in patients with MDS (42.78% ± 30.09%) and control subjects (65.50% ± 14.73%). However, there was no significant difference in FF between control subjects and patients with MDS (P = 0.439). The R2* value of AA, MDS, and controls was 145.38 ± 53.33, (171.13 ± 100.89, and 135.99 ± 32.41/second, respectively, with no significant difference between the three groups (P = 0.553).

Data Conclusion: Quantitative IDEAL-IQ magnetic resonance imaging may facilitate the diagnosis of AA and distinguish it from MDS.

Level Of Evidence: 3 TECHNICAL EFFICACY STAGE: 2.
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http://dx.doi.org/10.1002/jmri.27769DOI Listing
June 2021

Transcriptional response to prolonged perchlorate exposure in the methanogen Methanosarcina barkeri and implications for Martian habitability.

Sci Rep 2021 Jun 11;11(1):12336. Epub 2021 Jun 11.

Department of Geosciences, Princeton University, Princeton, NJ, USA.

Observations of trace methane (CH) in the Martian atmosphere are significant to the astrobiology community given the overwhelming contribution of biological methanogenesis to atmospheric CH on Earth. Previous studies have shown that methanogenic Archaea can generate CH when incubated with perchlorates, highly oxidizing chaotropic salts which have been found across the Martian surface. However, the regulatory mechanisms behind this remain completely unexplored. In this study we performed comparative transcriptomics on the methanogen Methanosarcina barkeri, which was incubated at 30˚C and 0˚C with 10-20 mM calcium-, magnesium-, or sodium perchlorate. Consistent with prior studies, we observed decreased CH production and apparent perchlorate reduction, with the latter process proceeding by heretofore essentially unknown mechanisms. Transcriptomic responses of M. barkeri to perchlorates include up-regulation of osmoprotectant transporters and selection against redox-sensitive amino acids. Increased expression of methylamine methanogenesis genes suggest competition for H with perchlorate reduction, which we propose is catalyzed by up-regulated molybdenum-containing enzymes and maintained by siphoning diffused H from energy-conserving hydrogenases. Methanogenesis regulatory patterns suggest Mars' freezing temperatures alone pose greater constraints to CH production than perchlorates. These findings increase our understanding of methanogen survival in extreme environments and confers continued consideration of a potential biological contribution to Martian CH.
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http://dx.doi.org/10.1038/s41598-021-91882-0DOI Listing
June 2021

High-throughput functional screening for next-generation cancer immunotherapy using droplet-based microfluidics.

Sci Adv 2021 Jun 11;7(24). Epub 2021 Jun 11.

State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin, China.

Currently, high-throughput approaches are lacking in the isolation of antibodies with functional readouts beyond simple binding. This situation has impeded the next generation of cancer immunotherapeutics, such as bispecific T cell engager (BiTE) antibodies or agonist antibodies against costimulatory receptors, from reaching their full potential. Here, we developed a highly efficient droplet-based microfluidic platform combining a lentivirus transduction system that enables functional screening of millions of antibodies to identify potential hits with desired functionalities. To showcase the capacity of this system, functional antibodies for CD40 agonism with low frequency (<0.02%) were identified with two rounds of screening. Furthermore, the versatility of the system was demonstrated by combining an anti-Her2 × anti-CD3 BiTE antibody library with functional screening, which enabled efficient identification of active anti-Her2 × anti-CD3 BiTE antibodies. The platform could revolutionize next-generation cancer immunotherapy drug development and advance medical research.
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http://dx.doi.org/10.1126/sciadv.abe3839DOI Listing
June 2021

The comparison of Nice knots and traditional methods as an auxiliary reduction-fixation technique in pre-contoured locking plate fixation for comminuted Robinson type 2B clavicle fracture: A retrospective study.

Medicine (Baltimore) 2021 Jun;100(23):e26282

Department of Orthopaedic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Abstract: Open reduction and pre-contoured locking plate fixation is a popular treatment option for displaced midshaft clavicle fracture. Lag screw and cerclage are 2 main intraoperative techniques to reduce and fix fragments. However, both lag screw and metallic cerclage have disadvantages. The doubled-suture Nice knot has been reported in many areas of orthopedic surgery for its effectiveness. This study aims to compare the outcomes of comminuted mid-shaft clavicle fractures reduced by Nice knots vs traditional techniques (lag screw or/and metallic cerclage) when bridged with pre-contoured locking plates.We retrospectively reviewed 101 patients (65 females and 36 males) diagnosed with midshaft clavicle fractures with at least one wedge fragment reduced by either Nice knots or traditional methods and bridged with pre-contoured locking plates between December 2016 and April 2019. Operation time, functional outcomes, pain, patient satisfaction, fracture healing, and complications were assessed at a follow-up of 12 to 40 months.The mean age of all the patients was 50.8 years. There were 52 and 49 patients in the Nice knot group and traditional group respectively, and no differences between 2 groups were found in general patient characteristics, fracture type, follow up and injury-to-surgery duration. The Nice knot group had significant less operation time (P < .01) than the traditional group (mean and standard deviation [SD], 78.6 ± 19.0 compared with 94.4 ± 29.9 minutes, respectively). For healing time, functional score, pain, satisfaction and complications, there were no significant differences between groups, despite the Nice knot group had slightly better results.Both Nice knots and traditional methods treated for comminuted Robinson type 2B clavicle fractures were effective and safe. And the Nice knots seemed to be superior with significant less operation time.
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http://dx.doi.org/10.1097/MD.0000000000026282DOI Listing
June 2021

Search for Light Dark Matter-Electron Scattering in the PandaX-II Experiment.

Phys Rev Lett 2021 May;126(21):211803

Research Center for Particle Science and Technology, Institute of Frontier and Interdisciplinary Science, Shandong University, Qingdao 266237, Shandong, China.

We report constraints on light dark matter through its interactions with shell electrons in the PandaX-II liquid xenon detector with a total 46.9  tonnes/day exposure. To effectively search for these very low energy electron recoils, ionization-only signals are selected from the data. 1821 candidates are identified within an ionization signal range between 50 and 75 photoelectrons, corresponding to a mean electronic recoil energy from 0.08 to 0.15 keV. The 90% C.L. exclusion limit on the scattering cross section between the dark matter and electron is calculated with systematic uncertainties properly taken into account. Under the assumption of point interaction, we provide the world's most stringent limit within the dark matter mass range from 15 to 30  MeV/c^{2}, with the corresponding cross section from 2.5×10^{-37} to 3.1×10^{-38}  cm^{2}.
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http://dx.doi.org/10.1103/PhysRevLett.126.211803DOI Listing
May 2021

Effect of Rongchang capsule on seizure behavior, cognitive impairment, and hippocampal DNA damage and inflammatory factors in epileptic rat.

J Tradit Chin Med 2021 Jun;41(3):438-446

Department of pediatrics, Graduate School of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.

Objective: To observe the behavioral changes and changes in DNA fragments and related inflammatory factors in the hippocampus of epileptic rats pretreated with Rongchang capsule ().

Methods: Eighty Sprague-Dawley rats were randomly divided into the normal group (NG), model group (MG), sodium valproate group (VG), and Rongchang capsule group (RG) (n = 20 in each group). Pentylentetrazol was administered to the MG, VG, and RG to induce epilepsy. The VG and RG were pretreated with 1/2 the therapeutic dose of sodium valproate and Rongchang capsule, respectively. Changes in convulsion behavior and water maze learning were observed. Single cell gel electrophoresis was used to detect changes in the DNA in the hippocampus. The tail length (TL) and Olive tail moment (OTM) of cells were analyzed by GASP software. The expression of interleukin-1β (IL-1β), high mobility group box 1 (HMGB1), transforming growth factor-β (TGF-β), and CCL4 in the hippocampus was determined by Western blotting.

Results: Rongchang capsule had a weaker effect on convulsive latency than sodium valproate, but significantly reduced seizure susceptibility. The spatial learning ability of the RG was better than that of the VG (P ≤ 0.01). The TL and OTM were significantly higher in the MG than the NG (P < 0.01). The RG had a better TL and OTM than the VG (P < 0.01). Combined with the microscopy results, DNA damage was most pronounced in the MG. Drug intervention decreased the DNA damage in the VG and RG. The expressions of IL-1β, CCL4, and HMGB1 in the hippocampus were significantly greater in the MG than the NG (P < 0.01), and were significantly reduced in the RG and VG compared with the MG (P < 0.01); however, there was no intergroup difference in the expression of TGF-β. The average values for the expression of inflammatory factors in the hippocampus were higher in the RG than in the VG; thus, Rongchang capsule may have a weaker effect on reducing the expression of inflammatory factors in the hippocampus than sodium valproate.

Conclusion: Pretreatment with Rongchang capsule prevents or delays cognitive impairment in rats with induced epilepsy, reduces hippocampal DNA damage, and decreases the hippocampal expressions of IL-1β, CCL4, and HMGB1.
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http://dx.doi.org/10.19852/j.cnki.jtcm.2021.03.012DOI Listing
June 2021

Local Efficacy of Corticosteroids as an Adjuvant for Periarticular Cocktail Injection in Simultaneous Bilateral Total Knee Arthroplasty: A Prospective Randomized Double-Blind Controlled Trial.

Pain Res Manag 2021 19;2021:5595095. Epub 2021 May 19.

Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.

Multimodal cocktail periarticular injections comprising corticosteroids are the most suggested therapy for postoperative discomfort and swelling following total knee arthroplasty (TKA). Nevertheless, previous findings cannot be applied to instances of unilateral total knee arthroplasty on bilateral knees. This randomized, prospective, double-blind, controlled clinical study examines the efficacy as well as safety of periarticular multimodal cocktail injection along or sans corticosteroids in certain situations. The 60 patients (120 knees) that experienced concurrent bilateral total knee arthroplasty were provided periarticular injections along additional betamethasone (7 mg) in the randomized knee, as well as the other knee, where corticosteroid was not administered. Key results were "pain scores at rest as well as in action" on a visual analogue scale of 11 pt. Other results included motion range, swelling of the thigh, Hospital for Special Surgery score (HSS score), and adverse effects were measured between the two sides. No statistically promising variations were found in the visual analogue scale ranking, motion range, girth of the thigh, and HSS score, as well as complications between the two sides. The impact on treatment outcomes was maintained between the knees on postoperative day 3 or at 3 months of follow-up. Multimodal periarticular injection without corticosteroid will alleviate postoperative swelling and pain. More studies are needed for the use of betamethasone as a corticosteroid in periarticular multimodal cocktail injections. This Chinese Clinical Trial Registry is registered with ChiCTR-OPC-17013503, dated 2017-11-23, available from http://www.chictr.org.cn/showproj.aspxproj=23146.
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http://dx.doi.org/10.1155/2021/5595095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154299PMC
May 2021

Persistent Discrimination of TB in Southeastern China: Results from Four Repeated Population-Based Surveys During the Period of 2006-2018.

Risk Manag Healthc Policy 2021 3;14:2333-2344. Epub 2021 Jun 3.

Department of Tuberculosis Control and Prevention, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, People's Republic of China.

Objective: To analyze the changes in discriminatory attitudes and isolated behaviors of the public toward tuberculosis (TB) in the Zhejiang Province and to determine the associated factors with TB discrimination.

Methods: Data were obtained from four cross-sectional population-based investigations from 2006 to 2018. A total of 26,246 respondents were interviewed using unified questionnaires that measured knowledge, attitudes, and behaviors regarding TB. The changes in public attitudes and behaviors towards TB over time were analyzed. The effect of socio-demographic factors and the level of TB awareness on TB discriminatory attitudes and isolated behaviors were evaluated.

Results: The results of these four cross-sectional studies found that TB discrimination had not changed much over the decade. Overall, discriminatory attitudes were present in 63.5% of the respondents who knew about TB (81.2%). Nearly 31.2% of those who reported being surrounded by people with TB (5.8%) showed isolated behaviors. Older respondents, those with a low education level, and farmers were prone to having discriminatory attitudes or behaviors. Those aware of the infectiousness and transmission routes of TB, and those who felt that TB was serious were more likely to discriminate against TB ( < 0.001). Those aware that TB can be cured were non-discriminatory (aOR = 0.77, 95% CI: 0.72-0.82).

Conclusion: Discriminatory attitudes and isolated behaviors toward TB have not changed significantly in southeastern China over the survey years, and persistent discrimination against TB still exists among the public. The multiple causes of discrimination cannot be addressed through basic health education. Tailor-made strategies, relevant policy measures, and an enabling social environment for TB are urgently required.
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http://dx.doi.org/10.2147/RMHP.S311869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184293PMC
June 2021

Macrophage biomimetic nanocarriers for anti-inflammation and targeted antiviral treatment in COVID-19.

J Nanobiotechnology 2021 Jun 10;19(1):173. Epub 2021 Jun 10.

Center for Infection and Immunity, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong, China.

Background: The worldwide pandemic of COVID-19 remains a serious public health menace as the lack of efficacious treatments. Cytokine storm syndrome (CSS) characterized with elevated inflammation and multi-organs failure is closely correlated with the bad outcome of COVID-19. Hence, inhibit the process of CSS by controlling excessive inflammation is considered one of the most promising ways for COVID-19 treatment.

Results: Here, we developed a biomimetic nanocarrier based drug delivery system against COVID-19 via anti-inflammation and antiviral treatment simultaneously. Firstly, lopinavir (LPV) as model antiviral drug was loaded in the polymeric nanoparticles (PLGA-LPV NPs). Afterwards, macrophage membranes were coated on the PLGA-LPV NPs to constitute drugs loaded macrophage biomimetic nanocarriers ([email protected]). In the study, [email protected] could neutralize multiple proinflammatory cytokines and effectively suppress the activation of macrophages and neutrophils. Furthermore, the formation of NETs induced by COVID-19 patients serum could be reduced by [email protected] as well. In a mouse model of coronavirus infection, [email protected] exhibited significant targeted ability to inflammation sites, and superior therapeutic efficacy in inflammation alleviation and tissues viral loads reduction.

Conclusion: Collectively, such macrophage biomimetic nanocarriers based drug delivery system showed favorable anti-inflammation and targeted antiviral effects, which may possess a comprehensive therapeutic value in COVID-19 treatment.
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http://dx.doi.org/10.1186/s12951-021-00926-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190731PMC
June 2021

Long noncoding RNA PM maintains cerebellar synaptic integrity and Cbln1 activation via Pax6/Mll1-mediated H3K4me3.

PLoS Biol 2021 Jun 10;19(6):e3001297. Epub 2021 Jun 10.

Department of Geriatrics, Gerontology Institute of Anhui Province, The First Affiliated Hospital, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Recent studies have shown that long noncoding RNAs (lncRNAs) are critical regulators in the central nervous system (CNS). However, their roles in the cerebellum are currently unclear. In this work, we identified the isoform 204 of lncRNA Gm2694 (designated as lncRNA-Promoting Methylation (lncRNA-PM)) is highly expressed in the cerebellum and derived from the antisense strand of the upstream region of Cerebellin-1 (Cbln1), a well-known critical cerebellar synaptic organizer. LncRNA-PM exhibits similar spatiotemporal expression pattern as Cbln1 in the postnatal mouse cerebellum and activates the transcription of Cbln1 through Pax6/Mll1-mediated H3K4me3. In mouse cerebellum, lncRNA-PM, Pax6/Mll1, and H3K4me3 are all associated with the regulatory regions of Cbln1. Knockdown of lncRNA-PM in cerebellum causes deficiencies in Cbln1 expression, cerebellar synaptic integrity, and motor function. Together, our work reveals an lncRNA-mediated transcriptional activation of Cbln1 through Pax6-Mll1-H3K4me3 and provides novel insights of the essential roles of lncRNA in the cerebellum.
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http://dx.doi.org/10.1371/journal.pbio.3001297DOI Listing
June 2021

Adversarial Caching Training: Unsupervised Inductive Network Representation Learning on Large-Scale Graphs.

IEEE Trans Neural Netw Learn Syst 2021 Jun 10;PP. Epub 2021 Jun 10.

Network representation learning (NRL) has far-reaching effects on data mining research, showing its importance in many real-world applications. NRL, also known as network embedding, aims at preserving graph structures in a low-dimensional space. These learned representations can be used for subsequent machine learning tasks, such as vertex classification, link prediction, and data visualization. Recently, graph convolutional network (GCN)-based models, e.g., GraphSAGE, have drawn a lot of attention for their success in inductive NRL. When conducting unsupervised learning on large-scale graphs, some of these models employ negative sampling (NS) for optimization, which encourages a target vertex to be close to its neighbors while being far from its negative samples. However, NS draws negative vertices through a random pattern or based on the degrees of vertices. Thus, the generated samples could be either highly relevant or completely unrelated to the target vertex. Moreover, as the training goes, the gradient of NS objective calculated with the inner product of the unrelated negative samples and the target vertex may become zero, which will lead to learning inferior representations. To address these problems, we propose an adversarial training method tailored for unsupervised inductive NRL on large networks. For efficiently keeping track of high-quality negative samples, we design a caching scheme with sampling and updating strategies that has a wide exploration of vertex proximity while considering training costs. Besides, the proposed method is adaptive to various existing GCN-based models without significantly complicating their optimization process. Extensive experiments show that our proposed method can achieve better performance compared with the state-of-the-art models.
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http://dx.doi.org/10.1109/TNNLS.2021.3084195DOI Listing
June 2021

Self-Training Enhanced: Network Embedding and Overlapping Community Detection With Adversarial Learning.

IEEE Trans Neural Netw Learn Syst 2021 Jun 10;PP. Epub 2021 Jun 10.

Network embedding (NE) aims to encode the relations of vertices into a low-dimensional space. After NE, we can obtain the learned vectors of vertices that preserve the proximity of network structures for subsequent applications, e.g., vertex classification and link prediction. In existing NE models, they usually exploit the skip-gram with a negative sampling method to optimize their objective functions. Generally, this method learns the vertex representation only from the local connectivity of vertices (i.e., neighbors). However, there is a larger scope of vertex connectivity in real-world scenarios: a vertex may have multifaceted aspects and should belong to overlapping communities. Taking a social network as the overlapping example, a user may subscribe to the channels of politics, economy, and sports simultaneously, but the politics share more common attributes with the economy and less with the sports. In this article, we propose an adversarial learning approach (ACNE) for modeling overlapping communities of vertices. Specifically, we map the association between communities and vertices into an embedding space. Moreover, we take further research on enhancing our ACNE with the following two operations. First, in the initialization stage, we adopt a walking strategy with perception to obtain paths containing more possible boundary vertices to improve overlapping community detection. Then, after representation learning with ACNE, we use soft community assignments from a simple classifier as supervision to update the weights of ACNE. This self-training mechanism referred to as ACNE-ST can help ACNE to achieve better performance. Experimental results demonstrate that the proposed methods, including ACNE and ACNE-ST, can outperform the state-of-the-art models on the subsequent tasks of vertex classification and overlapping community detection.
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http://dx.doi.org/10.1109/TNNLS.2021.3083318DOI Listing
June 2021

Ibrutinib Plus Venetoclax for First-line Treatment of Chronic Lymphocytic Leukemia: A Nonrandomized Phase 2 Trial.

JAMA Oncol 2021 Jun 10. Epub 2021 Jun 10.

Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston.

Importance: Oral targeted therapies have advanced the treatment of chronic lymphocytic leukemia (CLL). These therapies include Bruton tyrosine kinase inhibitors, used as monotherapy, and the Bcl-2 inhibitor venetoclax, typically combined with the CD20 monoclonal antibody. Preclinical studies have shown synergy between Bruton tyrosine kinase inhibitors and the Bcl-2 inhibitor venetoclax.

Objective: To examine the rate of complete remission, complete remission with incomplete count recovery, and bone marrow-undetectable measurable residual disease (U-MRD) after treatment with the combination of ibrutinib and venetoclax.

Design, Setting, And Participants: A single-center, phase 2 nonrandomized trial enrolled patients from August 17, 2016, to June 5, 2018. Participants included previously untreated patients with CLL who met International Workshop on CLL 2008 criteria for treatment indication. Patients were required to have at least 1 of the following features: del(17p), TP53-mutated CLL, del(11q), unmutated immunoglobulin heavy-chain variable gene, or age 65 years or older.

Interventions: Therapy consisted of ibrutinib, 420 mg/d, monotherapy for 3 cycles, thereafter combined with venetoclax (standard weekly dose ramp-up to 400 mg/d) for a total of 24 cycles of combination treatment. Responses were assessed at serial points according to International Workshop on CLL 2008 criteria. Measurable residual disease (MRD) was assessed by multicolor flow cytometry with a sensitivity of 10-4.

Main Outcomes And Measures: Outcomes included complete remission, complete remission with incomplete count recovery, and bone marrow U-MRD rate.

Results: Eighty patients (57 [71%] men) were treated; median age was 65 years (range, 26-83 years). The median follow-up for all 80 patients was 38.5 months (range, 5.6-51.1 months). Five patients discontinued the study during the ibrutinib monotherapy phase; the remaining 75 patients received combination therapy. On an intent-to-treat analysis of combined treatment, 45 (56%) patients achieved bone marrow U-MRD remission at 12 cycles and 53 (66%) patients achieved bone marrow U-MRD remission at 24 cycles. Overall, 60 (75%) patients achieved bone marrow U-MRD remission as their best response. Responses were seen across all high-risk subgroups, independent of the immunoglobulin heavy-chain variable gene mutation status, fluorescence in situ hybridization category, or TP53 mutation. The 3-year progression-free survival was 93%, and 3-year overall survival was 96%. No patient had CLL progression; 2 patients developed Richter transformation.

Conclusions And Relevance: The findings of this study suggest that combination therapy with ibrutinib and venetoclax might be beneficial for previously untreated patients with CLL. Remissions appeared to be durable during a follow-up of more than 3 years, with activity seen across high-risk disease subgroups, including those with del(17p)/TP53-mutated CLL.

Trial Registration: ClinicalTrials.gov Identifier: NCT02756897.
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http://dx.doi.org/10.1001/jamaoncol.2021.1649DOI Listing
June 2021

ARGONAUTE 2 increases rice susceptibility to rice black-streaked dwarf virus infection by epigenetically regulating HEXOKINASE 1 expression.

Mol Plant Pathol 2021 Jun 10. Epub 2021 Jun 10.

Key Laboratory of Food Quality and Safety, Institute of Plant Protection, Jiangsu Academy of Agricultural Sciences, Nanjing, Jiangsu Province, China.

ARGONAUTE (AGO) proteins play crucial roles in plant defence against virus invasion. To date, the role of OsAGO2 in rice antiviral defence remains largely unknown. In this study, we determined that the expression of OsAGO2 in rice was induced upon rice black-streaked dwarf virus (RBSDV) infection. Using transgenic rice plants overexpressing OsAGO2 and Osago2 mutants generated through transposon-insertion or CRISPR/Cas9 technology, we found that overexpression of OsAGO2 enhanced rice susceptibility to RBSDV infection. Osago2 mutant lines exhibited strong resistance to RBSDV infection through the elicitation of an early defence response, including reprogramming defence gene expression and production of reactive oxygen species (ROS). Compared to Nipponbare control, the expression level of OsHXK1 (HEXOKINASE 1) increased significantly, and the methylation levels of its promoter decreased in the Osago2 mutant on RBSDV infection. The expression profile of OsHXK1 was the opposite to that of OsAGO2 during RBSDV infection. Overexpression of OsHXK1 in rice also induced ROS production and enhanced rice resistance to RBSDV infection. These results indicate that OsHXK1 controls ROS accumulation and is regulated by OsAGO2 through epigenetic regulation. It is noteworthy that the Osago2 mutant plants are also resistant to southern rice black-streaked dwarf virus infection, another member of the genus Fijivirus. Based on the results presented in this paper, we conclude that OsAGO2 modulates rice susceptibility to fijivirus infection by suppressing OsHXK1 expression, leading to the onset of ROS-mediated resistance. This discovery may benefit future rice breeding programmes for virus resistance.
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http://dx.doi.org/10.1111/mpp.13091DOI Listing
June 2021

Novel Multifunctional Stimuli-Responsive Nanoparticles for Synergetic Chemo-Photothermal Therapy of Tumors.

ACS Appl Mater Interfaces 2021 Jun 10. Epub 2021 Jun 10.

School of Chemical Engineering, Sichuan University, Chengdu 610065, Sichuan, China.

In this study, a novel class of multifunctional responsive nanoparticles is designed and fabricated as drug nanocarriers for synergetic chemo-photothermal therapy of tumors. The proposed nanoparticles are composed of a thermo-/pH-responsive poly(-isopropylacrylamide--acrylic acid) (PNA) nanogel core, a polydopamine (PDA) layer for photothermal conversion, and an outer folic acid (FA) layer as a targeting agent for the folate receptors on tumor cells. The fabricated nanoparticles show good biocompatibility and outstanding photothermal conversion efficiency. The proposed nanoparticles loaded with doxorubicin (DOX) drug molecules are stable under physiological conditions with low leakage of drugs, while rapidly release drugs in environments with low pH conditions and at high temperature. The experimental results show that the drug release process is mainly governed by Fickian diffusion. In vitro cell experimental results demonstrate that the [email protected] nanoparticles can be phagocytized by 4T1 tumor cells and release drugs in tumor cell acidic environments, and confirm that the combined chemo and photothermal therapeutic efficacy of [email protected] nanoparticles is higher than the photothermal therapeutic efficacy or the chemotherapeutic efficacy alone. The proposed multifunctional responsive nanoparticles in this study provide a novel class of drug nanocarriers as a promising tool for synergetic chemo-photothermal therapy of tumors.
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http://dx.doi.org/10.1021/acsami.1c05330DOI Listing
June 2021

BRD7 Promotes Cell Proliferation and Tumor Growth Through Stabilization of c-Myc in Colorectal Cancer.

Front Cell Dev Biol 2021 24;9:659392. Epub 2021 May 24.

NHC Key Laboratory of Carcinogenesis, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.

BRD7 functions as a crucial tumor suppressor in numerous malignancies. However, the effects of BRD7 on colorectal cancer (CRC) progression are still unknown. Here, based on the BRD7 knockout (BRD7) and BRD7 (BRD7) mouse models constructed in our previous work, we established an azoxymethane/dextran sodium sulfate (AOM/DSS)-induced mouse model. BRD7 mice were found to be highly susceptible to AOM/DSS-induced colitis-associated CRC, and BRD7 significantly promoted cell proliferation and cell cycle G1/S transition but showed no significant effect on cell apoptosis. Furthermore, BRD7 interacted with c-Myc and stabilized c-Myc by inhibiting its ubiquitin-proteasome-dependent degradation. Moreover, restoring the expression of c-Myc in BRD7-silenced CRC cells restored cell proliferation, cell cycle progression, and tumor growth and . In addition, BRD7 and c-Myc were both significantly upregulated in CRC patients, and high expression of these proteins was associated with clinical stage and poor prognosis in CRC patients. Collectively, BRD7 functions as an oncogene and promotes CRC progression by regulating the ubiquitin-proteasome-dependent stabilization of c-Myc protein. Targeting the BRD7/c-Myc axis could be a potential therapeutic strategy for CRC.
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http://dx.doi.org/10.3389/fcell.2021.659392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181413PMC
May 2021

Exploration of Crucial Mediators for Carotid Atherosclerosis Pathogenesis Through Integration of Microbiome, Metabolome, and Transcriptome.

Front Physiol 2021 24;12:645212. Epub 2021 May 24.

Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

Background: Carotid atherosclerosis (CAS) is an important cause of stroke. Although interactions between the gut microbiome and metabolome have been widely investigated with respect to the pathogenesis of cardiovascular diseases, information regarding CAS remains limited.

Materials And Methods: We utilized 16S ribosomal DNA sequencing and untargeted metabolomics to investigate the alterations in the gut microbiota and plasma metabolites of 32 CAS patients and 32 healthy controls. The compositions of the gut microbiota differed significantly between the two groups, and a total of 11 differentially enriched genera were identified. In the metabolomic analysis, 11 and 12 significantly changed metabolites were screened in positive (POS) and negative (NEG) modes, respectively. α-N-Phenylacetyl-L-glutamine was an upregulated metabolite in CAS patients detected in both POS and NEG modes and had the highest | log(fold change)| in POS mode. In addition, transcriptomic analysis was performed using the GSE43292 dataset.

Results: A total of 132 differentially expressed genes (DEGs) were screened. Among the upregulated DEGs in CAS patients, FABP4 exhibited the highest | log(fold change)|. Furthermore, FABP4 was positively associated with and had the highest Spearman's correlation coefficient and the most significant -value among the microbiota-DEG pairs.

Conclusion: In this study, we investigated the potential "microbiota-metabolite-gene" regulatory axis that may act on CAS, and our results may help to establish a theoretical basis for further specialized study of this disease.
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http://dx.doi.org/10.3389/fphys.2021.645212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181762PMC
May 2021

Fast-spreading SARS-CoV-2 variants: challenges to and new design strategies of COVID-19 vaccines.

Signal Transduct Target Ther 2021 06 9;6(1):226. Epub 2021 Jun 9.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, PR China.

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http://dx.doi.org/10.1038/s41392-021-00644-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187888PMC
June 2021

Prevention of dementia using mobile phone applications (PRODEMOS): protocol for an international randomised controlled trial.

BMJ Open 2021 Jun 9;11(6):e049762. Epub 2021 Jun 9.

Beijing Key Laboratory of Clinical Epidemiology, Capital Medical University School of Public Health, Beijing, China.

Introduction: Profiles of high risk for future dementia are well understood and are likely to concern mostly those in low-income and middle-income countries and people at greater disadvantage in high-income countries. Approximately 30%-40% of dementia cases have been estimated to be attributed to modifiable risk factors, including hypertension, smoking and sedentary lifestyle. Tailored interventions targeting these risk factors can potentially prevent or delay the onset of dementia. Mobile health (mHealth) improves accessibility of such prevention strategies in hard-to-reach populations while at the same time tailoring such approaches. In the current study, we will investigate the effectiveness and implementation of a coach-supported mHealth intervention, targeting dementia risk factors, to reduce dementia risk.

Methods And Analysis: The prevention of dementia using mobile phone applications (PRODEMOS) randomised controlled trial will follow an effectiveness-implementation hybrid design, taking place in the UK and China. People are eligible if they are 55-75 years old, of low socioeconomic status (UK) or from the general population (China); have ≥2 dementia risk factors; and own a smartphone. 2400 participants will be randomised to either a coach-supported, interactive mHealth platform, facilitating self-management of dementia risk factors, or a static control platform. The intervention and follow-up period will be 18 months. The primary effectiveness outcome is change in the previously validated Cardiovascular Risk Factors, Ageing and Incidence of Dementia dementia risk score. The main secondary outcomes include improvement of individual risk factors and cost-effectiveness. Implementation outcomes include acceptability, adoption, feasibility and sustainability of the intervention.

Ethics And Dissemination: The PRODEMOS trial is sponsored in the UK by the University of Cambridge and is granted ethical approval by the London-Brighton and Sussex Research Ethics Committee (reference: 20/LO/01440). In China, the trial is approved by the medical ethics committees of Capital Medical University, Beijing Tiantan Hospital, Beijing Geriatric Hospital, Chinese People's Liberation Army General Hospital, Taishan Medical University and Xuanwu Hospital. Results will be published in a peer-reviewed journal.

Trial Registration Number: ISRCTN15986016.
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http://dx.doi.org/10.1136/bmjopen-2021-049762DOI Listing
June 2021

Applications of single-cell sequencing in cancer research: progress and perspectives.

J Hematol Oncol 2021 Jun 9;14(1):91. Epub 2021 Jun 9.

Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 Dong'An Road, Shanghai, 200032, China.

Single-cell sequencing, including genomics, transcriptomics, epigenomics, proteomics and metabolomics sequencing, is a powerful tool to decipher the cellular and molecular landscape at a single-cell resolution, unlike bulk sequencing, which provides averaged data. The use of single-cell sequencing in cancer research has revolutionized our understanding of the biological characteristics and dynamics within cancer lesions. In this review, we summarize emerging single-cell sequencing technologies and recent cancer research progress obtained by single-cell sequencing, including information related to the landscapes of malignant cells and immune cells, tumor heterogeneity, circulating tumor cells and the underlying mechanisms of tumor biological behaviors. Overall, the prospects of single-cell sequencing in facilitating diagnosis, targeted therapy and prognostic prediction among a spectrum of tumors are bright. In the near future, advances in single-cell sequencing will undoubtedly improve our understanding of the biological characteristics of tumors and highlight potential precise therapeutic targets for patients.
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http://dx.doi.org/10.1186/s13045-021-01105-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190846PMC
June 2021

Analysis of External Quality Assessment of Maternal Serum Prenatal Screening for Down Syndrome in the First Trimester in China.

Clin Lab 2021 Jun;67(6)

Background: We analyzed the 2019 external quality assessment (EQA) results to evaluate the analytical performance of maternal serum prenatal screening for Down Syndrome (DS) in the first trimester in China.

Methods: In each round, five lyophilized EQA samples with detailed clinical information were distributed to participants and used to test the concentration of human chorionic gonadotropin free beta subunits (free β-HCG) and pregnancy-associated plasma protein-A (PAPP-A) to calculate the risk value of DS. The robust coefficient of variability (CV) was calculated or test results for free β-HCG and PAPP-A using analytes and major measurement platforms. For DS risk values, the robust CV was calculated using a professional calculation platform. Failed EQA results were analyzed using serum marker testing results and DS risk values.

Results: EQA results were collected from 242 laboratories in round 1 and 239 laboratories in round 2. Total acceptable rates of testing results for free β-HCG and PAPP-A ranged from 95.04% to 97.91%. Overall acceptable rates of DS risk values ranged from 97.52% to 97.90%. The proportion of laboratories exhibiting satisfactory performance was higher in round 2 than in round 1 for serum marker testing results and DS risk values. The robust CV for risk values for each sample were significantly higher than those of serum markers. Three EQA result failure types were found, including result reporting errors, serum marker concentration testing errors, and DS risk calculation errors.

Conclusions: The analytical performance of maternal serum prenatal screening for DS in the first trimester in China can be improved further.
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http://dx.doi.org/10.7754/Clin.Lab.2020.201004DOI Listing
June 2021

The Impact of hyperuricemia on long-term clinical outcomes of renal transplant recipients: a systematic review and meta-analysis.

J Pharm Pharm Sci 2021 ;24:292-307

Purpose: To evaluate the effect of hyperuricemia on clinical outcomes of renal transplant recipients (RTRs).

Methods: A literature search of PubMed, Cochrane, Embase was conducted up to March 20, 2020. The primary outcome was the estimated glomerular filtration rate (eGFR). The second outcomes were the risk of graft loss, death, cardiovascular event and the level of triglyceride. The following search terms were utilized: ((Hyperuricemic group) OR (Hyperuricaemia) OR (Hyperuric) OR (Urea acid) OR (Uric acid) OR (Acid urate) OR (Urate) OR (Gout)) and ((Transplantation) OR (Transplantations) OR (Transplant) OR (Transplants) OR (Graft)).

Results: 28 studies with 18224 patients were eligible for inclusion. There was no significant difference in eGFR (<12 months, p=0.07), the risk of graft loss (<60 months, p=0.07) and death (<60months, p=0.19) between the hyperuricemic and normouricemic group in the early post-transplantation period. But increased uric acid levels contributed to the long-term decline of eGFR, the risk of graft loss and death increased after transplantation. Hyperuricemia increased the risk of cardiovascular event with no significant difference in the level of triglyceride between the two groups.

Conclusions: Increased uric acid levels contributed to the long-term decline of eGFR, increased risk of graft loss and death after transplantation. Although there was no significant effect on triglyceride, hyperuricemia increased the risk of cardiovascular event.
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http://dx.doi.org/10.18433/jpps31620DOI Listing
January 2021

A Novel Multiparameter Scoring Model for Noninvasive Early Prediction of Ischemic Colitis: A Multicenter, Retrospective, and Real-World Study.

Clin Transl Gastroenterol 2021 Jun 9;12(6):e00370. Epub 2021 Jun 9.

Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Introduction: Ischemic colitis (IC) is a common gastrointestinal ischemic disease caused by hypoperfusion or reperfusion injury. However, there are few studies on risk factors associated with poor prognoses of the disease. This study aimed to determine the predictors of poor prognoses in patients with IC and establish a prognostic scoring method with good internal and external validity for identifying severe cases in an early stage.

Methods: We established a prognosis model by conducting a multicenter, retrospective study of patients hospitalized with IC between November 2008 and May 2020. Predictive power was tested using 5-fold internal cross-validation and external validation.

Results: The following 6 factors were included in the prognostic model: neutrophil count, D-dimer level, ischemia of the distal ileum, ischemia of the hepatic flexure, ulceration, and luminal stenosis. The area under the receiver-operating characteristic curve for internal cross-validation of the prediction model was 86%, and that for external validation was 95%. During internal validation, our model correctly identified 88.08% of the patients. It was further found that patients younger than 65 years with a higher neutrophil-to-lymphocyte ratio and higher heart rate had poor prognoses. Patients aged 65 years and older with ischemia of terminal ileum, hepatic flexure, splenic flexure, and intestinal stenosis had poor prognoses.

Discussion: Patients with ischemia in the hepatic flexure and the distal ileum, endoscopic evidence of ulcer or stenosis, higher neutrophil counts, and higher D-dimer levels have worse prognoses. This information could aid in the selection of timely and appropriate treatment.
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http://dx.doi.org/10.14309/ctg.0000000000000370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189633PMC
June 2021

[Clinical Characteristics and Prognostic Analysis of Extranodal NK/T-Cell Lymphoma Patients Treated with Pegaspargase Based Chemotherapy].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Jun;29(3):735-740

Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730,

Objective: To investigate the clinical characteristics of patients with extranodal NK/T-cell lymphoma (ENKL), and to analyze the factors that affecting the survival and prognostic of patients treated with pegaspargase based chemotherapy.

Methods: The clinical data of 61 ENKL patients treated in Peking Union Medical College Hospital from January 2015 to June 2019 were enrolled and retrospectively analyzed. The clinical characteristics, survival rate and influencing factors of prognostic in patients were investigated.

Results: The male and female ratio in the whole group was 2.8∶1. The median age was 46 years old (range, 17-67 years old). 30 patients were in stage I/II, while 31 patients were in stage III/IV. The ratio of nasal and non-nasal type was 4.1∶1. The common sites of extranodal involvement were skin and subcutaneous tissue (26.2%), liver (14.8%), lung (13.1%) and gastrointestinal tract (13.1%). 9.8% of patients showed central nervous system involvement and 11.5% showed bone marrow involvement. The median follow-up time was 22 months (range, 1-53 months). The 2-year PFS and OS rates of patients in the whole group were 51.6% and 53.2%, respectively. The 2-year OS rate of patients at stage I/II was 87.5%, while that of patients at stage III/IV was only 21.2%, the difference showed statistically significant (P<0.0001). Patients with non-nasal type disease showed a higher proportion in adverse factors of prognosis, of whom the median OS was only 3 months. Multivariate analysis showed that age>60 years old and Ann Arbor stage III-IV were the independent adverse factors that affecting the prognosis of PFS and OS (HR=3.681, 95% CI 1.322-10.250; HR=4.611, 95% CI 1.118-19.009).

Conclusion: The survival of ENKL patients has been significantly improved by pegaspargase based chemotherapy. Patients with stage I/II disease have achieved a relatively good 2-year OS rate of 87.5%, but the prognosis of stage III/IV and non-nasal type patients are still poor. Age>60 years old and Ann Arbor stage III/IV are independent adverse prognostic factors for ENKL patients.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2021.03.014DOI Listing
June 2021

Treatment and outcome patterns of patients with Waldenström's macroglobulinemia: a large, multicenter retrospective review in China.

Leuk Lymphoma 2021 Jun 9:1-8. Epub 2021 Jun 9.

Department of Hematology, Hubei, China.

In this study, we aimed to investigate treatment options and the prognosis of patients with WM in China. This retrospective study included 1141 patients diagnosed with symptomatic WM between January 2003 and December 2019 at 35 tertiary hospitals in 22 provinces of China. Fifty-four patients (7.3%) received monotherapy, 264 (36.0%) received chemoimmunotherapy, 395 (53.8%) received other combination regimens without rituximab, and 21 (2.9%) received ibrutinib. Using a multivariable Cox regression model, age > 65 years old, platelets <100 × 10/L, serum albumin <3.5 g/dl, β2 microglobulin concentration ≥4 mg/L and LDH ≥250 IU/L predicted poor OS. In summary, our study showed that frontline treatment choices for WM are widely heterogeneous. We validated most of the established prognostic factors in the rIPSS (age >65 years, LDH ≥250 IU/L, ALB <3.5 g/dl and β2 microglobulin ≥4 mg/L) together with PLT ≤ 100 × 10/L indicate a poor prognosis for patients with WM.
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http://dx.doi.org/10.1080/10428194.2021.1938030DOI Listing
June 2021

Migrant experiences of living with type 2 diabetes in Western Sydney, Australia: a multilingual pilot research project.

Public Health Res Pract 2021 Jun 9;31(2). Epub 2021 Jun 9.

School of Languages and Cultures, University of Sydney, NSW, Australia.

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http://dx.doi.org/10.17061/phrp3122109DOI Listing
June 2021

Identification of Molecular Characteristics and New Prognostic Targets for Thymoma by Multiomics Analysis.

Biomed Res Int 2021 19;2021:5587441. Epub 2021 May 19.

Department of Thoracic Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.

Background: Thymoma is a heterogeneous tumor originated from thymic epithelial cells. The molecular mechanism of thymoma remains unclear.

Methods: The expression profile, methylation, and mutation data of thymoma were obtained from TCGA database. The coexpression network was constructed using the variance of gene expression through WGCNA. Enrichment analysis using clusterProfiler R package and overall survival (OS) analysis by Kaplan-Meier method were carried out for the intersection of differential expression genes (DEGs) screened by limma R package and important module genes. PPI network was constructed based on STRING database for genes with significant impact on survival. The impact of key genes on the prognosis of thymoma was evaluated by ROC curve and Cox regression model. Finally, the immune cell infiltration, methylation modification, and gene mutation were calculated.

Results: We obtained eleven coexpression modules, and three of them were higher positively correlated with thymoma. DEGs in these three modules mainly involved in MAPK cascade and PPAR pathway. LIPE, MYH6, ACTG2, KLF4, SULT4A1, and TF were identified as key genes through the PPI network. AUC values of LIPE were the highest. Cox regression analysis showed that low expression of LIPE was a prognostic risk factor for thymoma. In addition, there was a high correlation between LIPE and T cells. Importantly, the expression of LIPE was modified by methylation. Among all the mutated genes, GTF2I had the highest mutation frequency.

Conclusion: These results suggested that the molecular mechanism of thymoma may be related to immune inflammation. LIPE may be the key genes affecting prognosis of thymoma. Our findings will help to elucidate the pathogenesis and therapeutic targets of thymoma.
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http://dx.doi.org/10.1155/2021/5587441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159640PMC
May 2021

A clinical study on plasma biomarkers for deciding the use of adjuvant corticosteroid therapy in bronchopulmonary dysplasia of premature infants.

Int J Med Sci 2021 29;18(12):2581-2588. Epub 2021 Apr 29.

Department of Neonatology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu, China.

The study was designed to investigate some plasma markers which help us to decide the use of adjuvant corticosteroid therapy in bronchopulmonary dysplasia (BPD) of premature infants. Thirty BPD infants were treated by dexamethasone. Among these cases, dexamethasone was significant effective in 10 cases, and no significant effective in 20 cases. These patients were divided into two groups as the significant effect (SE) group (n=10) and the non-significant effect (NE) group (n=20) according to the curative effect of dexamethasone. Fifteen non-BPD infants with gestational age and gender matching were selected as the control group. Plasma samples before and after dexamethasone treatment were collected from three infants chosen randomly from SEG for the data-independent acquisition (DIA) analysis. ELISA was further used to detect the levels of differential proteins LRP1 and S100A8 in all individuals, including SE, NE and control groups. DIA analysis results showed that after dexamethasone treatment, there were a total of 52 plasma proteins that showed significant differences, of which 43 proteins were down-regulated and 9 proteins were up-regulated. LRP1 and S100A8 were two plasma proteins that were significantly changed after dexamethasone treatment. Compared with the control group, plasma LRP1 was significantly increased in BPD. Interestingly, the plasma concentration of LRP1 in the NE group was significantly higher than that in the SE group. S100A8, as an indicator of plasma inflammation, was significantly higher in BPD than the control group. Unlike LRP1, there was no significantly difference between the SE and NE group (P=0.279) before dexamethasone treatment. Elevated plasma LRP1 and S100A8 in BPD infants are two indicators that correlated with the efficacy of dexamethasone, and might be used as biomarkers for deciding the use of adjuvant corticosteroids therapy in the BPD.
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http://dx.doi.org/10.7150/ijms.58650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176188PMC
April 2021