Publications by authors named "Yun He"

488 Publications

Effects of mechanosensitive ion channel Piezo1 on proliferation and osteogenic differentiation of human dental follicle cells.

Ann Anat 2021 Oct 20:151847. Epub 2021 Oct 20.

Oral and Maxillofacial Reconstruction and Regeneration Laboratory, Southwest Medical University, Luzhou 646000, China; Department of Oral and Maxillofacial Surgery, The Affiliated Stomatology Hospital of Southwest Medical University, Luzhou 646000, China; Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China. Electronic address:

Background: To explore the role of the mechanosensitive ion channel Piezo1 in the proliferation and osteogenic differentiation of human dental follicle cells (hDFCs), and its mechanism, so as to provide the basis for the use of hDFCs to achieve bone regeneration.

Methods: hDFCs were obtained from fresh dental follicle tissues by enzymatic digestion, and cell phenotype and multipotential differentiation were identified. Identification of the expression of mechanosensitive ion channel Piezo1 was performed by immunofluorescence and immunohistochemistry. CCK-8 was used to determine the optimal concentration of the Piezo1 agonist, Yoda1. Then, according to the obtained results, Alizarin red staining, RT-PCR quantitative analysis and Western blot were used to further observe the osteogenic differentiation of hDFCs and its probable mechanism via Wnt/β-catenin signalling. The data were analysed by SPSS 22.0 software.

Results: The results of the concentration gradient experiments indicated that 0.5µM Piezo1 agonist (Yoda1) enhanced the proliferation of hDFCs. Compared with the control group, a considerable number of calcium nodules showed that activating Piezo1 could promote the osteogenic differentiation of hDFCs. The relative mRNA and protein expression of Piezo1, ALP, RUNX2, OCN and BMP2 in the Piezo1 agonist group were higher than that of the control group. Furthermore, the expression of Wnt3a and β-catenin related to the classical osteogenic pathway were significantly up-regulated in the Piezo1 agonist group.

Conclusion: Activating mechanosensitive ion channel Piezo1 with an appropriate concentration of Yoda1 has a positive effect on the proliferation and osteogenic differentiation of hDFCs. This mechanism of promoting osteogenic differentiation may be mediated by the Wnt/β-catenin pathway.
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http://dx.doi.org/10.1016/j.aanat.2021.151847DOI Listing
October 2021

All-trans retinoic acid plus low-dose rituximab vs low-dose rituximab in corticosteroid-resistant or relapsed ITP.

Blood 2021 Oct 19. Epub 2021 Oct 19.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.

The study aimed to compare the efficacy and safety of all-trans retinoic acid (ATRA) plus low-dose rituximab (LD-RTX) with LD-RTX monotherapy in corticosteroid-resistant or relapsed immune thrombocytopenia (ITP) patients. Recruited patients were randomized at a ratio of 2:1 into 2 groups: 112 patients received LD-RTX plus ATRA and 56 patients received LD-RTX monotherapy. Overall response (OR), defined as achieving a platelet count of ≥ 30 × 109/L confirmed on at least two separate occasions (at least 7 days apart), at least a doubling of the baseline platelet count without any other ITP-specific treatment and the absence of bleeding within 1 year after enrollment, was observed in more patients in the LD-RTX plus ATRA group (80%) than in the LD-RTX monotherapy group (59%) (between-group difference, 0.22; 95% CI, 0.07 to 0.36). Sustained response (SR), defined as maintenance of a platelet count > 30 x 109/L, an absence of bleeding, and no requirement for any other ITP-specific treatment for 6 consecutive months after achievement of OR during 1 year following enrollment, was achieved by 68 (61%) patients in the combination group and 23 (41%) patients in the monotherapy group (between-group difference, 0.20; 95% CI, 0.04 to 0.35). The 2 most common AEs for the combination group were dry skin and headache or dizziness. Our findings demonstrated that ATRA plus LD-RTX significantly increased the overall and sustained response, indicating a promising treatment option for corticosteroid-resistant or relapsed adult ITP. This study is registered at www.clinicaltrials.gov as #NCT03304288.
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http://dx.doi.org/10.1182/blood.2021013393DOI Listing
October 2021

Activation of Toll-like receptor 2 enhances peripheral and tumor-infiltrating CD8 T cell cytotoxicity in patients with gastric cancer.

BMC Immunol 2021 10 7;22(1):67. Epub 2021 Oct 7.

Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277 Yanta West Rd, Xi'an, 710061, Shaanxi Province, China.

Background: Toll-like receptors (TLRs) play central roles in the initiation of innate immune response, and also control adaptive immunity activation. Thus, the aim of the study was to investigate the regulation of TLR activation to CD8 T cells has not been fully elucidated in gastric cancer (GC).

Materials And Methods: Thirty-two GC patients and twenty-three healthy controls were enrolled. Expression profile of TLRs in peripheral and tumor-infiltrating CD8 T cells was investigated. Purified CD8 T cells were stimulated with Pam3Csk4, an agonist of TLR2, and cytotoxic and co-inhibitory molecules in CD8 T cells was measured. Direct and indirect contact coculture system between CD8 T cells and AGS cells was set up. Modulation of TLR2 activation to CD8 T cells was assessed by measuring lactate dehydrogenase release and cytokine secretion.

Results: TLR2 mRNA and TLR2 cell percentage was down-regulated in GC derived peripheral and tumor-infiltrating CD8 T cells. CD8 T cells from GC patients showed exhausted phenotype, which presented as decreased perforin/granzyme B, increased programmed death-1, and reduced cytotoxicity to AGS cells. TLR2 activation by Pam3Csk4 enhanced perforin and granzyme B expression in CD8 T cells, however, did not affect either proinflammatory cytokine production or co-inhibitory molecules expression. Pam3Csk4 stimulation enhanced cytolytic activation of peripheral and tumor-infiltrating CD8 T cells from GC, but not those from healthy individuals.

Conclusion: The present data revealed an important immunomodulatory activity of TLR2 to CD8 T cells in GC patients.
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http://dx.doi.org/10.1186/s12865-021-00459-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8499526PMC
October 2021

Exosomal hsa-miR-21-5p is a biomarker for breast cancer diagnosis.

PeerJ 2021 17;9:e12147. Epub 2021 Sep 17.

Department of Clinical Laboratory, Affiliated Hospital of Guizhou Medical UniversityGuiyang, Guizhou Province, China.

Purpose: Breast cancer (BC) is characterized by concealed onset, delayed diagnosis, and high fatality rates making it particularly dangerous to patients' health. The purpose of this study was to use comprehensive bioinformatics analysis and experimental verification to find a new biomarker for BC diagnosis.

Methods: We comprehensively analyzed microRNA (miRNA) and mRNA expression profiles from the Gene Expression Omnibus (GEO) and screened out differentially-expressed (DE) miRNAs and mRNAs. We used the miRNet website to predict potential DE-miRNA target genes. Using the Database for Annotation, Visualization and Integrated Discovery (DAVID), we performed Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses on overlapping potential target genes and DE-mRNAs. The protein-protein interaction (PPI) network was then established. The miRNA-mRNA regulatory network was constructed using Cytoscape and the analysis results were visualized. We verified the expression of the most up-regulated DE-miRNA using reverse transcription and a quantitative polymerase chain reaction in BC tissue. The diagnostic value of the most up-regulated DE-miRNA was further explored across three levels: plasma-derived exosomes, cells, and cell exosomes.

Results: Our comprehensive bioinformatics analysis and experimental results showed that hsa-miR-21-5p was significantly up-regulated in BC tissue, cells, and exosomes. Our results also revealed that tumor-derived hsa-miR-21-5p could be packaged in exosomes and released into peripheral blood. Additionally, when evaluating the diagnostic value of plasma exosomal hsa-miR-21-5p, we found that it was significantly up-regulated in BC patients. Receiver operating characteristic (ROC) analysis also confirmed that hsa-miR-21-5p could effectively distinguish healthy people from BC patients. The sensitivity and specificity were 86.7% and 93.3%, respectively.

Conclusion: This study's results showed that plasma exosomal hsa-miR-21-5p could be used as a biomarker for BC diagnosis.
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http://dx.doi.org/10.7717/peerj.12147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8451442PMC
September 2021

Synthesis of 6-phenylbenzo[]quinolines photoinduced dehydrogenative annulation of ()-2-phenyl-3-styrylpyridines.

Org Biomol Chem 2021 Oct 14;19(39):8554-8558. Epub 2021 Oct 14.

School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an 710119, China.

A concise and environmentally friendly protocol was developed for the synthesis of 6-phenylbenzo[]quinolines. 6-Phenylbenzo[]quinolines were obtained in good yields irradiation of ()-2-phenyl-3-styrylpyridines with a 254 nm UV light (64 W) in EtOH under an argon atmosphere in the presence of TFA. The reaction is a dehydrogenative annulation reaction that proceeds through 6π-electrocyclization, a [1,5]-H shift, 1,3-enamine tautomerization, and elimination of a hydrogen molecule to afford 6-phenylbenzo[]quinolines. The described protocol not only avoids the usage of a transition metal catalyst and an oxidant but also has the advantages of high atom efficiency and mild reaction conditions.
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http://dx.doi.org/10.1039/d1ob01674aDOI Listing
October 2021

Characterization of Urine Derived Stem Cells from Patients with End-Stage Liver Diseases and Application to Induced Acute and Chronic Liver Injury of Nude Mice Model.

Stem Cells Dev 2021 Sep 22. Epub 2021 Sep 22.

Chongqing Medical University Affiliated Children's Hospital, 159456, Chongqing, China;

Urine-derived stem cells (USCs) are adult stem cells isolated from urine with strong proliferative ability and differentiation potentials. Cell transplantation of USCs could partly repair liver injury. It has been reported that the proliferative ability of bone mesenchymal stem cells in patients with chronic liver failure is significantly lower than in patients without liver disease. The aim of this study was therefore to evaluate the biological characteristics of USCs from end-stage liver disease patients (LD-USCs) compared to those from normal healthy individuals (N-USCs), with a view to determining whether autologous USCs can be applied to the treatment of liver disease. In this study USCs were isolated from urine samples of male patients with end-stage liver disease. Adherent USCs exhibit a spindle- or rice grain-like morphology, and express CD24, CD29, CD73, CD90, and CD146 surface markers, but not CD31, CD34, CD45, and CD105. We observed no differences in cell morphology or cell surface marker profile between LD-USCs and N-USCs. LD-USCs exhibited similar proliferative, colony-forming, apoptotic, and migratory abilities to N-USCs. Both USCs demonstrated similar capacities for osteogenic, adipogenic, and chondrogenic differentiation. When USCs were transplanted into CCl4 treatment-induced acute and chronic liver fibrosis mouse models, we observed a decrease in liver index, recovery of ALT and AST levels, alleviation of liver tissue injury, and dramatic improvement of liver tissue structure. USC transplantation can effectively recover liver function and improve liver tissue damage in acute or chronic liver injury mouse models. According to the results, we concluded that the biological characteristics of LD-USCs are not affected by basic liver disease. This study provides further evidence of the stem cell characteristics and liver repair function of LD-USCs, which may serve as a theoretical and experimental foundation for autologous USC transplantation technology in the treatment of liver failure and end-stage liver diseases.
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http://dx.doi.org/10.1089/scd.2021.0137DOI Listing
September 2021

A prognostic model (BATAP) with external validation for patients with transplant-associated thrombotic microangiopathy.

Blood Adv 2021 Sep 10. Epub 2021 Sep 10.

Peking University People's Hospital, Peking University Institute of Hematology;National Clinical Research Center for Hematologic Disease;Beijing Key Laboratory of Hematopoietic Stem Cell Transplanta, Beijing, China.

Transplant-associated thrombotic microangiopathy (TA-TMA) is a potentially life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Information on markers for early prognostication remains limited, and no predictive tools for TA-TMA are available. We attempt to develop and validate a prognostic model for TA-TMA. A total of 507 patients who developed TA-TMA following allo-HSCT were retrospectively identified and separated into a derivation cohort and a validation cohort according to the time of transplantation to perform external temporal validation. Patient age (OR 2.371, 95% CI 1.264-4.445), anemia (OR 2.836, 95% CI 1.566-5.138), severe thrombocytopenia (OR 3.871, 95% CI 2.156-6.950), elevated total bilirubin (OR 2.716, 95% CI 1.489-4.955) and proteinuria (OR 2.289, 95% CI 1.257-4.168) were identified as independent prognostic factors for the 6-month outcome of TA-TMA. A risk score model termed BATAP (Bilirubin, Age, Thrombocytopenia, Anemia, Proteinuria) was then constructed according to the regression coefficients. The validated c-statistics were 0.816 (95% CI 0.766-0.867) and 0.756 (95% CI 0.696-0.817) in the internal and external validation, respectively. Calibration plots indicated that the model-predicted probabilities correlated well with the actual observed frequencies. This predictive model may facilitate the prognostication of TA-TMA and contribute to the early identification of high-risk patients.
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http://dx.doi.org/10.1182/bloodadvances.2021004530DOI Listing
September 2021

Prenatal hypoxia induced ETR activation and abnormal ROS signalling in pulmonary artery cells of rat offspring.

Reprod Toxicol 2021 Oct 31;105:91-100. Epub 2021 Aug 31.

Institute for Fetology, First Hospital of Soochow University, Suzhou, China; Wuxi Maternal & Child Health Hospital, Jiangsu, China. Electronic address:

Pulmonary arterial hypertension is a progressive disorder characterized by remodeling and increased small pulmonary arteries resistance. Endothelin-1 (ET-1) was related to PAH and ET-1 receptors were up-regulated selectively in the lung when exposed to toxic factor hypoxia. However, the role of ET-1 signaling in the pathogenesis of prenatal hypoxia-induced pulmonary abnormalities remains to be elucidated. Pregnant rats were divided into prenatal hypoxia (10.5 % O from gestational day 4-21) and control group. Their three-month-old offspring male rats were tested for vascular functions and molecular analysis, DNA methylation was assessed for cellular hypoxia. Functional testing showed that ET-1-mediated vasoconstriction was enhanced, and the expressions of endothelin A receptor/B receptor (ETR/ETR), inositol 1,4,5-trisphosphate receptor, type 1, and the sensitivity of calcium channels were increased in the small pulmonary arteries following prenatal hypoxia. q-PCR and DHE staining showed that the expressions of NADPH oxidase 1/4 (Nox1/4) were up-regulated, along with the increased production of superoxide anion. Furthermore, superoxide anion promoted ET-1-mediated pulmonary artery contraction. In the pulmonary artery smooth muscle cell experiments, q-PCR, Western Blot, CCK8 and DHE staining showed that the expressions of ETR, Nox1/4, and superoxide anion were increased by hypoxia, along with promoted cell proliferation. 2,2,6,6-Tetramethyl-1-piperidinyloxy reversed hypoxia-induced cell proliferation. ETR antagonist BQ788 inhibited hypoxia-increased expressions of Nox1/4, superoxide anion production, and proliferation of cells. Moreover, methylation analysis indicated that hypoxia decreased the methylation levels of the ETR promoter in the pulmonary artery smooth muscle cells. The results indicated that prenatal toxic factor hypoxia resulted in abnormal ETR activation, which enhanced ET-1-mediated vasoconstriction of pulmonary arteries and pulmonary artery smooth muscle cell proliferation through ETR/Nox1/4-derived ROS pathway.
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http://dx.doi.org/10.1016/j.reprotox.2021.08.009DOI Listing
October 2021

A Hybrid Ionic and Electronic Conductive Coating Layer for Enhanced Electrochemical Performance of 4.6 V LiCoO.

ACS Appl Mater Interfaces 2021 Sep 3;13(36):42917-42926. Epub 2021 Sep 3.

Materials Genome Institute, Shanghai University, Shanghai 200444, China.

The LiCoO cathode undergoes undesirable electrochemical performance when cycled with a high cut-off voltage (≥4.5 V versus Li/Li). The unstable interface with poor kinetics is one of the main contributors to the performance failure. Hence, a hybrid Li-ion conductor (LiAlGePO) and electron conductor (Al-doped ZnO) coating layer was built on the LiCoO surface. Characterization studies prove that a thick and conductive layer is homogeneously covered on LiCoO particles. The coating layer can not only enhance the interfacial ionic and electronic transport kinetics but also act as a protective layer to suppress the side reactions between the cathode and electrolyte. The modified LiCoO (HC-LCO) achieves an excellent cycling stability (77.1% capacity retention after 350 cycles at 1C) and rate capability (139.8 mAh g at 10C) at 3.0-4.6 V. Investigations show that the protective layer can inhibit the particle cracks and Co dissolution and stabilize the cathode electrolyte interface (CEI). Furthermore, the irreversible phase transformation is still observed on the HC-LCO surface, indicating the phase transformation of the LiCoO surface may not be the main factor for fast performance failure. This work provides new insight of interfacial design for cathodes operating with a high cut-off voltage.
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http://dx.doi.org/10.1021/acsami.1c12882DOI Listing
September 2021

Prediction of Genetic Alterations in Oncogenic Signaling Pathways in Squamous Cell Carcinoma of the Head and Neck: Radiogenomic Analysis Based on Computed Tomography Images.

J Comput Assist Tomogr 2021 Aug 31. Epub 2021 Aug 31.

From the Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning GE Healthcare, Shanghai, China.

Objective: This study investigated the role of radiomics in evaluating the alterations of oncogenic signaling pathways in head and neck cancer.

Methods: Radiomics features were extracted from 106 enhanced computed tomography images with head and neck squamous cell carcinoma. Support vector machine-recursive feature elimination was used for feature selection. Support vector machine algorithm was used to develop radiomics scores to predict genetic alterations in oncogenic signaling pathways. The performance was evaluated by the area under the curve (AUC) of the receiver operating characteristic curve.

Results: The alterations of the Cell Cycle, HIPPO, NOTCH, PI3K, RTK RAS, and TP53 signaling pathways were predicted by radiomics scores. The AUC values of the training cohort were 0.94, 0.91, 0.94, 0.93, 0.87, and 0.93, respectively. The AUC values of the validation cohort were all greater than 0.7.

Conclusions: Radiogenomics is a new method for noninvasive acquisition of tumor molecular information at the genetic level.
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http://dx.doi.org/10.1097/RCT.0000000000001213DOI Listing
August 2021

A Medical Pedagogy Reform by Integration of Biomedical Research into the Clinical Medicine Program.

Med Sci Educ 2020 Dec 14;30(4):1569-1576. Epub 2020 Oct 14.

Queen Mary School, Nanchang University, 461 Ba Yi Avenue, Nanchang, China.

Purpose: The objective of this study is to assess the effectiveness of integrating research-based biomedical sciences into a clinical medicine program. This reform aims to enable medical students to conduct both clinical and independent research work at an early stage and to consider human disease through a mechanistic and evidence-based perspective.

Method: We designed this innovative medical program using modules that are different from those used in traditional medical programs in both China and Western countries. Thus, in this new program, we incorporated biomedical sciences components including essential theoretical and practical elements, active learning, and research skills training in the first 3 years of a 5-year program. We also offered students opportunities for oral presentation, teamwork, and leadership training.

Results: We find that students are actively engaged in this program and are enthusiastic about medical research, academically competent, and confident at expression and presentation of their data. They demonstrate leadership and teamwork skills that are essential for contemporary medical practice and prepare them by developing these skills at this early stage as they embark on their medical career. We show that students who train through this reformed program perform well at various nationwide and province-wide academic contests and show increased competitiveness in applications onto post-graduate programs.

Conclusion: Overall, we provide evidence that this new program is proving to be successful and is a worthwhile reform establishing a new paradigm for Chinese medical education. Furthermore, we suggest it is a reform that would be of interest to other countries whose medical education is not delivering the desired output of research- and evidence-based-driven doctors.
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http://dx.doi.org/10.1007/s40670-020-01105-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8368868PMC
December 2020

DNA Damage Repair Profiles Alteration Characterize a Hepatocellular Carcinoma Subtype With Unique Molecular and Clinicopathologic Features.

Front Immunol 2021 12;12:715460. Epub 2021 Aug 12.

Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and displays high heterogeneity of molecular phenotypes. We investigated DNA damage repair (DDR) alterations in HCC by integrating multi-omics data. HCC patients were classified into two heterogeneous subtypes with distinct clinical and molecular features: the DDR-activated subtype and the DDR-suppressed subtype. The DDR-activated subgroup is characterized by inferior prognosis and clinicopathological features that result in aggressive clinical behavior. Tumors of the DDR-suppressed class, which have distinct clinical and molecular characteristics, tend to have superior survival. A DDR subtype signature was ultimately generated to enable HCC DDR classification, and the results were confirmed by using multi-layer date cohorts. Furthermore, immune profiles and immunotherapy responses are also different between the two DDR subtypes. Altogether, this study illustrates the DDR heterogeneity of HCCs and is helpful to the understanding of personalized clinicopathological and molecular mechanisms responsible for unique tumor DDR profiles.
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http://dx.doi.org/10.3389/fimmu.2021.715460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387599PMC
August 2021

Nanofiber Composite for Improved Water Retention and Dendrites Suppression in Flexible Zinc-Air Batteries.

Small 2021 Oct 24;17(39):e2103048. Epub 2021 Aug 24.

Department of Chemical and Biological Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, 999077, China.

Water loss of the gel polymer electrolytes (GPEs) and dendrites growth on Zn anode are overriding obstacles to applying flexible zinc-air batteries (ZABs) for wearable electronic devices. Nearly all previous efforts aim at developing novel GPEs with enhanced water retention and therefore elongate their lifespan. Herein, a facile interface engineering strategy is proposed to retard the water loss of GPE from the half-open structured air cathode. In detail, the poly(ethylene vinyl acetate)/carbon powder (PEVA-C) nanofiber composite interface layer with features of hydrophobicity, high conductivity, air permeability, and flexibility are prepared on the carbon cloth and set up between the GPE and electrode. The as-assembled ZAB with simple alkaline PVA GPE exhibits an impressive cycle life of 230 h, which outperforms ZAB without the PEVA-C nanofibers interface layer by 14 times. Additionally, the growth of Zn dendrites can be suppressed due to the tardy water loss of GPE.
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http://dx.doi.org/10.1002/smll.202103048DOI Listing
October 2021

A novel D2D-MEC method for enhanced computation capability in cellular networks.

Sci Rep 2021 Aug 19;11(1):16918. Epub 2021 Aug 19.

School of Communication and Information Engineering, Chongqing University of Posts and Telecommunications, Chongqing, 400065, China.

Device-to-device (D2D) communications and mobile edge computing (MEC) used to resolve traffic overload problems is a trend in the cellular network. By jointly considering the computation capability and the maximum delay, resource-constrained terminals offload parts of their computation-intensive tasks to one nearby device via a D2D connection or an edge server deployed at a base station via a cellular connection. In this paper, a novel method of cellular D2D-MEC system is proposed, which enables task offloading and resource allocation meanwhile improving the execution efficiency of each device with a low latency. We consider the partial offloading strategy and divide the task into local and remote computing, both of which can be executed in parallel through different computational modes. Instead of allocating system resources from a macroscopic view, we innovatively study both the task offloading strategy and the computing efficiency of each device from a microscopic perspective. By taking both task offloading policy and computation resource allocation into consideration, the optimization problem is formulated as that of maximized computing efficiency. As the formulated problem is a mixed-integer non-linear problem, we thus propose a two-phase heuristic algorithm by jointly considering helper selection and computation resources allocation. In the first phase, we obtain the suboptimal helper selection policy. In the second phase, the MEC computation resources allocation strategy is achieved. The proposed low complexity dichotomy algorithm (LCDA) is used to match the subtask-helper pair. The simulation results demonstrate the superiority of the proposed D2D-enhanced MEC system over some traditional D2D-MEC algorithms.
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http://dx.doi.org/10.1038/s41598-021-96284-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377034PMC
August 2021

Biodegradable and renewable UV-shielding polylactide composites containing hierarchical structured POSS functionalized lignin.

Int J Biol Macromol 2021 Oct 8;188:323-332. Epub 2021 Aug 8.

Department of Materials Science and Engineering, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, China.

The demand for biodegradable and renewable UV-shielding materials is ever increasing due to the rising concern for the environment. In this paper, biobased lignin was functionalized by polyhedral oligomeric silsesquioxane (POSS) with an epoxy substituent. Then the POSS decorated lignin (lignin-POSS) was mixed with polylactide (PLA) to act as UV-shielding filler by melt compounding. The SEM observation revealed that the presence of POSS contributed to improving the homogeneous dispersion of lignin-POSS in the PLA matrix with good compatibility when the content of lignin-POSS was lower than 5 wt%. The synergistic effects of lignin and POSS endowed PLA composite films with a good balance of UV-shielding ability and transparency in the visible light region. With the addition of 5 wt% lignin-POSS, the PLA composite film absorbed almost all UV irradiation across the entire UV spectrum. In addition, the presence of lignin-POSS could serve as a nucleating agent to increase the degree of crystallinity of PLA. The dynamical rheological tests revealed that the lignin-POSSS reduced the complex viscosity and storage modulus of PLA composites, improving the flowability of PLA composites. This work presents a viable pathway to prepare biodegradable and renewable UV-shielding materials for potential packaging applications.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.08.033DOI Listing
October 2021

A Comparative Insight on the Newly Emerging Rifamycins: Rifametane, Rifalazil, TNP-2092 and TNP-2198.

Curr Med Chem 2021 Aug 6. Epub 2021 Aug 6.

Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, Chongqing. China.

Rifamycins are considered a milestone for tuberculosis (TB) treatment because of their proficient sterilizing ability. Currently, available TB treatments are complicated and need a long duration, which ultimately leads to failure of patient compliance. Some new rifamycin derivatives, i.e., rifametane, TNP-2092 (rifamycin-quinolizinonehybrid), and TNP-2198 (rifamycin-nitromidazole hybrid) are under clinical trials, which are attempting to overcome the problems associated with TB treatment. The undertaken review is intended to compare the pharmacokinetics, pharmacodynamics and safety profiles of these rifamycins, including rifalazil, another derivative terminated in phase II trials, and already approved rifamycins. The emerging resistance of microbes is an imperative consideration associated with antibiotics. Resistance development potential of microbial strains against rifamycins and an overview of chemistry, as well as structure-activity relationship (SAR) of rifamycins, are briefly described. Moreover, issues associated with rifamycins are discussed as well. We expect that newly emerging rifamycins shall appear as potential tools for TB treatment in the near future.
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http://dx.doi.org/10.2174/0929867328666210806114949DOI Listing
August 2021

CT Radiomics for the Prediction of Synchronous Distant Metastasis in Clear Cell Renal Cell Carcinoma.

J Comput Assist Tomogr 2021 Sep-Oct 01;45(5):696-703

From the Departments of Medical Ultrasound.

Purpose: The aim of this study was to construct and verify a computed tomography (CT) radiomics model for preoperative prediction of synchronous distant metastasis (SDM) in clear cell renal cell carcinoma (ccRCC) patients.

Methods: Overall, 172 patients with ccRCC were enrolled in the present research. Contrast-enhanced CT images were manually sketched, and 2994 quantitative radiomic features were extracted. The radiomic features were then normalized and subjected to hypothesis testing. Least absolute shrinkage and selection operator (LASSO) was applied to dimension reduction, feature selection, and model construction. The performance of the predictive model was validated through analysis of the receiver operating characteristic curve. Multivariate and subgroup analyses were performed to verify the radiomic score as an independent predictor of SDM.

Results: The patients randomized into a training (n = 104) and a validation (n = 68) cohort in a 6:4 ratio. Through dimension reduction using LASSO regression, 9 radiomic features were used for the construction of the SDM prediction model. The model yielded moderate performance in both the training (area under the curve, 0.89; 95% confidence interval, 0.81-0.97) and the validation cohort (area under the curve, 0.83; 95% confidence interval, 0.69-0.95). Multivariate analysis showed that the CT radiomic signature was an independent risk factor for clinical parameters of ccRCC. Subgroup analysis revealed a significant connection between the SDM and radiomic signature, except for the lower pole of the kidney subgroup.

Conclusions: The CT-based radiomics model could be used as a noninvasive, personalized approach for SDM prediction in patients with ccRCC.
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http://dx.doi.org/10.1097/RCT.0000000000001211DOI Listing
October 2021

Incomplete thermal ablation-induced up-regulation of transcription factor nuclear receptor subfamily 2, group F, member 6 (NR2F6) contributes to the rapid progression of residual liver tumor in hepatoblastoma.

Bioengineered 2021 12;12(1):4289-4303

Department of Medical Ultrasonics, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P.R. China.

Hepatoblastoma is a kind of extreme malignancy frequently diagnosed in children. Although surgical resection is considered as the first-line treatment for hepatoblastoma, a relatively large population of patients have lost the preferred opportunity for surgery. Administration of locoregional ablation enables local tumor control but with the deficiency of insufficient ablation, residual tumor, and rapid progression. In this study, we integrated 219 hepatoblastoma and 121 non-cancer liver tissues to evaluate the expression of NR2F6, from which a higher NR2F6 level was found in hepatoblastoma compared with non-cancer livers with a standard mean difference (SMD) of 1.04 (95% CI: 0.79, 1.29). The overexpression of NR2F6 also appeared to be an efficient indicator in distinguishing hepatoblastoma tissues from non-cancer liver tissues from the indication of a summarized AUC of 0.90, with a pooled sensitivity of 0.76 and a pooled specificity of 0.89. Interestingly, nude mouse xenografts provided direct evidence that overexpressed NR2F6 was also detected in residual tumor compared to untreated hepatoblastoma. Chromatin immunoprecipitation-binding data in HepG2 cells and transcriptome analysis of HepG2 xenografts were combined to identify target genes regulated by NR2F6. We finally selected 150 novel target genes of NR2F6 in residual tumor of incomplete ablation, and these genes appeared to be associated with the biological regulation of lipid metabolism-related pathway. Accordingly, targeting NR2F6 holds a therapeutic promise in treating residual recurrent hepatoblastoma after incomplete ablation.
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http://dx.doi.org/10.1080/21655979.2021.1945521DOI Listing
December 2021

Pan-cancer analysis of clinical significance and associated molecular features of glycolysis.

Bioengineered 2021 12;12(1):4233-4246

Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.

Tumor glycolysis is a major promoter of carcinogenesis and cancer progression. Given its complex mechanisms and interactions, comprehensive analysis is needed to reveal its clinical significance and molecular features. On the basis of a well-established glycolysis gene expression signature, we quantified 8633 patients with different cancer types from the Cancer Genome Atlas (TCGA) and evaluated their prognostic associations. High tumor glycolytic activity correlated with inferior overall survival in the pan-cancer patients (hazard ratio: 1.70, 95% confidence interval: 1.20-2.40, P = 0.003). The prognostic value of glycolysis correlated with the molecular subtypes and was stable regardless of clinical parameters. The prognostic significance of glycolysis was validated using three independent datasets. In addition, genome, transcriptome, and proteome profiles were utilized to characterize the distinctive molecular features associated with glycolysis. Mechanistically, glycolysis fulfilled the fundamental needs of tumor proliferation in multiple ways. Exploration of the relationships between glycolysis and tumor-infiltrating immune cells showed that glycolysis enabled the immune evasion of tumor cells. Mammalian target of rapamycin (mTOR) inhibitors and dopamine receptor antagonists can effectively reverse the glycolytic status of cancers. Overall, our study provides an in-depth molecular understanding of tumor glycolysis and may have practical implications for clinical cancer therapy.
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http://dx.doi.org/10.1080/21655979.2021.1955510DOI Listing
December 2021

Development and Validation of a Radiomic Nomogram for Predicting the Prognosis of Kidney Renal Clear Cell Carcinoma.

Front Oncol 2021 6;11:613668. Epub 2021 Jul 6.

Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.

Purpose: The present study aims to comprehensively investigate the prognostic value of a radiomic nomogram that integrates contrast-enhanced computed tomography (CECT) radiomic signature and clinicopathological parameters in kidney renal clear cell carcinoma (KIRC).

Methods: A total of 136 and 78 KIRC patients from the training and validation cohorts were included in the retrospective study. The intraclass correlation coefficient (ICC) was used to assess reproducibility of radiomic feature extraction. Univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) as well as multivariate Cox analysis were utilized to construct radiomic signature and clinical signature in the training cohort. A prognostic nomogram was established containing a radiomic signature and clinicopathological parameters by using a multivariate Cox analysis. The predictive ability of the nomogram [relative operating characteristic curve (ROC), concordance index (C-index), Hosmer-Lemeshow test, and calibration curve] was evaluated in the training cohort and validated in the validation cohort. Patients were split into high- and low-risk groups, and the Kaplan-Meier (KM) method was conducted to identify the forecasting ability of the established models. In addition, genes related with the radiomic risk score were determined by weighted correlation network analysis (WGCNA) and were used to conduct functional analysis.

Results: A total of 2,944 radiomic features were acquired from the tumor volumes of interest (VOIs) of CECT images. The radiomic signature, including ten selected features, and the clinical signature, including three selected clinical variables, showed good performance in the training and validation cohorts [area under the curve (AUC), 0.897 and 0.712 for the radiomic signature; 0.827 and 0.822 for the clinical signature, respectively]. The radiomic prognostic nomogram showed favorable performance and calibration in the training cohort (AUC, 0.896, C-index, 0.846), which was verified in the validation cohort (AUC, 0.768). KM curves indicated that the progression-free interval (PFI) time was dramatically shorter in the high-risk group than in the low-risk group. The functional analysis indicated that radiomic signature was significantly associated with T cell activation.

Conclusions: The nomogram combined with CECT radiomic and clinicopathological signatures exhibits excellent power in predicting the PFI of KIRC patients, which may aid in clinical management and prognostic evaluation of cancer patients.
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http://dx.doi.org/10.3389/fonc.2021.613668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290524PMC
July 2021

Integrated multi-omics analysis of the clinical relevance and potential regulatory mechanisms of splicing factors in hepatocellular carcinoma.

Bioengineered 2021 12;12(1):3978-3992

Department of Medical Ultrasonics, First Affiliated Hospital of Guangxi Medical University, Nanning, P. R. China.

Splicing factors (SFs) have been increasingly documented to perturb the genome of cancers. However, little is known about the alterations of SFs in hepatocellular carcinoma (HCC). This study comprehensively delineated the genomic and epigenomic characteristics of 404 SFs in HCC based on the multi-omics data from the Cancer Genome Atlas database. The analysis revealed several clinically relevant SFs that could be effective biomarkers for monitoring the onset and prognosis of HCC (such as, HSPB1, DDX39A, and NELFE, which were the three most significant clinically relevant SFs). Functional enrichment analysis of these indicators showed the enrichment of pathways related to splicing and mRNA processes. Furthermore, the study found that SF copy number variation is common in HCC and could be a typical characteristic of hepato-carcinogenesis; the complex expression regulation of SFs was significantly affected by copy number variant and methylation. Several SFs with significant mutation patterns were identified (such as, RNF213, SF3B1, SPEN, NOVA1, and EEF1A1), and the potential regulatory network of SFs was constructed to identify their potential mechanisms for regulating clinically relevant alternative splicing events. Therefore, this study established a foundation to uncover the broad molecular spectrum of SFs for future functional and therapeutic studies of HCC.
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http://dx.doi.org/10.1080/21655979.2021.1948949DOI Listing
December 2021

Optical properties of aerosol and cloud particles measured by a single-line-extracted pure rotational Raman lidar.

Opt Express 2021 Jul;29(14):21947-21964

Conventional lidar methods for deriving particle optical properties suffer from the fact that two unknowns (backscatter and extinction coefficients) need to be determined from only one lidar equation. Thus, additional assumptions (constant lidar ratio or Ångström relationship) have to be introduced to settle this problem. In contrast, a single-line-extracted pure-rotational-Raman (PRR) lidar method allows the strict retrieval of backscatter and extinction coefficients without additional assumptions. Based on the observations of our single-line-extracted PRR lidar from February 2016 to December 2017, the optical properties (backscatter coefficient, extinction coefficient and lidar ratio) of continental polluted aerosols, dust aerosols, and cirrus cloud particles over Wuhan (30.5°N, 114.4°E) are well characterized. The mean values of the measured lidar ratios are respectively 60 ± 7 sr for continental polluted aerosols, 47 ± 4 sr for dust aerosols and 22 ± 4 sr for cirrus cloud particles. The backscatter and extinction coefficients measured by the single-line-extracted PRR lidar deviate as a whole by 7-13% and 13-16%, respectively, from those retrieved by the traditional Fernald method. The optical properties measured by the single-line-extracted PRR lidar can serve as observational standards for particle optical properties (backscatter/extinction coefficient and lidar ratio) at 532 nm wavelength.
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http://dx.doi.org/10.1364/OE.427864DOI Listing
July 2021

Data Mining of Differentially Expressed Genes in Ovarian Epithelial Carcinoma: Implications in Precise Medicine.

Curr Top Med Chem 2021 Oct;21(14):1285-1300

Key Laboratory of Biomedical Information Engineering, Ministry of Education, Mitochondrial Biomedical Research Institute, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China.

Background: Epithelial Ovarian Carcinoma (EOC) is a ubiquitous gynecological malignancy with complicated pathogenesis. Genetic risk factors and pathways involved in the prognosis of this cancer are not yet understood completely. Determining genetic markers with diagnostic and prognostic values would pave the way for efficient management of cancer.

Objective: This study aimed to investigate the genes and the regulatory networks involved in the occurrence and prognosis of EOC through different bioinformatics analysis tools. In addition, recent advances in using bioinformatic analysis approaches based on the genes and regulatory networks, particularly Differentially Expressed Genes (DEGs) in improving the diagnosis and prognosis of EOC, are discussed.

Methods: The gene expression profiles of GSE18520, GSE54388, and GSE27651 were downloaded from the Gene Expression Omnibus (GEO) database and further analyzed with different analyses in R language. Current literature on using bioinformatics based on DEGs and associated regulatory networks to improve the diagnosis and prognosis of EOC was reviewed.

Results: Analyses of the gene expression levels between the malignant tissue against normal tissue unveiled 163 DEGs. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed on the target genes using cluster profile package and Cytoscape package was employed to assess the protein interaction network of these genes. The protein-protein interaction network was analyzed using the CytoHubba plug-in to identify 20 hub genes. In addition, we analyzed the prognosis of the hub genes using the Kaplan-Meier survival analysis that revealed evident differences in the prognosis of 13 genes. The malignant tissues exhibited a differential expression of 12 genes against healthy tissues as shown by Gene Expression Profiling Interactive Analysis (GEPIA) analysis.

Conclusion: Findings of this study revealed 12 genes to be significantly up-regulated and the prognosis was significantly different, which could be employed to potentially target EOC in clinical practice.
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http://dx.doi.org/10.2174/1568026621666210708093649DOI Listing
October 2021

Magnetic resonance imaging (MRI) radiomics of papillary thyroid cancer (PTC): a comparison of predictive performance of multiple classifiers modeling to identify cervical lymph node metastases before surgery.

Radiol Med 2021 Oct 8;126(10):1312-1327. Epub 2021 Jul 8.

Department of Medical Ultrasonics, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Guangxi Zhuang Autonomous Region, Nanning, People's Republic of China.

Purpose: To compare predictive efficiency of multiple classifiers modeling and establish a combined magnetic resonance imaging (MRI) radiomics model for identifying lymph node (LN) metastases of papillary thyroid cancer (PTC) preoperatively.

Materials And Methods: A retrospective analysis based on the preoperative MRI scans of 109 PTC patients including 77 patients with LN metastases and 32 patients without metastases was conducted, and we divided enroll cases into trained group and validation group. Radiomics signatures were selected from fat-suppressed T2-weighted MRI images, and the optimal characteristics were confirmed by spearman correlation test, hypothesis testing and random forest methods, and then, eight predictive models were constructed by eight classifiers. The receiver operating characteristic (ROC) curves analysis were performed to demonstrate the effectiveness of the models.

Results: The area under the curve (AUC) of ROC based on MRI texture diagnosed LN status by naked eye was 0.739 (sensitivity = 0.571, specificity = 0.906). Based on the 5 optimal signatures, the best AUC of MRI radiomics model by logistics regression classifier had a considerable prediction performance with AUCs 0.805 in trained group and 0.760 in validation group, respectively, and a combination of best radiomics model with visual diagnosis of MRI texture had a high AUC as 0.969 (sensitivity = 0.938, specificity = 1.000), suggesting combined model had a preferable diagnostic efficiency in evaluating LN metastases of PTC.

Conclusion: Our combined radiomics model with visual diagnosis could be a potentially effective strategy to preoperatively predict LN metastases in PTC patients before clinical intervention.
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http://dx.doi.org/10.1007/s11547-021-01393-1DOI Listing
October 2021

Mechanism underlying Polygonum capitatum effect on Helicobacter pylori-associated gastritis based on network pharmacology.

Bioorg Chem 2021 Sep 5;114:105044. Epub 2021 Jun 5.

Department of Basic Clinical Laboratory Medicine, School of Clinical Laboratory Science, Guizhou Medical University, No. 9 Beijing Road, Yunyan District, Guiyang 550004, China; Department of Clinical Laboratory, Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang 550004, China. Electronic address:

Helicobacter pylori (H. pylori) infection is a common disease that can cause H. pylori-associated gastritis (HAG), peptic ulcers, and gastric cancer. As a traditional Chinese medicine, Polygonum capitatum (PC) manifests its unique advantages in the prevention and treatment of complex diseases and chronic diseases, due to its ability to clear heat, detoxify and relieve pain, promote blood circulation, and remove blood stasis. In order to explore the molecular mechanism of PC for HAG, the study collected the predicted targets of active compounds, conducted functional analysis by the STRING database, collected HAG differential expression genes, and conducted KEGG enrichment analysis on the intersection of predicted targets and differential expression genes of gastritis by Cluego. The results show that PC works mainly by affecting phosphorylation of IκBα, NF-κB p65, p38MAPK, and ERK1/2 and nuclear transposition of NF-κB p65 and p-p38MAPK, which has been proved by in vivo and in vitro experiments. These results suggest that PC may act on HAG with multiple targets and pathways, and play a key role in the process of HAG treatment.
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http://dx.doi.org/10.1016/j.bioorg.2021.105044DOI Listing
September 2021

Ameliorated biomechanical properties of carotid arteries by puerarin in spontaneously hypertensive rats.

BMC Complement Med Ther 2021 Jun 22;21(1):173. Epub 2021 Jun 22.

Department of Anatomy, Hubei University of Medicine, Shiyan, 442000, China.

Background: An emerging body of evidence indicates that puerarin (PUE) plays an important role in the treatment of angina pectoris, myocardial ischemia-reperfusion injury, hypertension and other cardiovascular diseases, but how PUE affects the vascular remodeling of hypertensive rats has not been reported yet. This study aimed to investigate the effect and mechanism of PUE on carotid arteries of spontaneously hypertensive rats (SHR) to provide the basis for the clinical application of PUE.

Methods: Thirty male SHR and six male Wistar Kyoto rats (WKY) aged 3 months were used in this study, SHR rats were randomly divided into 5 groups, PUE(40 or 80 mg/kg/d, ip) and telmisartan (TELMI) (30 mg/kg/d, ig) were administrated for 3 months. We use DMT myography pressure-diameter system to investigate biomechanical properties of carotid arteries, 10 μM pan-classical transient receptor potential channels (TRPCs) inhibitor SKF96365, 200 nM specific TRPC6 inhibitor SAR7334 and 100 μM Orai1 inhibitor ANCOA4 were used in the mechanical test.

Results: PUE can significantly decrease systolic and diastolic blood pressure, long-term administration of PUE resulted in a mild reduction of thickness and inner diameter of carotid artery. PUE ameliorate NE-response and vascular remodeling mainly through inhibiting TRPCs channel activities of VSMC.

Conclusion: PUE can ameliorate biomechanical remodeling of carotid arteries through inhibiting TRPCs channel activities of VSMC in spontaneously hypertensive rats.
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http://dx.doi.org/10.1186/s12906-021-03345-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216761PMC
June 2021

Increased infiltration of CD8 T cells in recurrent glioblastoma patients is a useful biomarker for assessing the response to combined bevacizumab and lomustine therapy.

Int Immunopharmacol 2021 Aug 4;97:107826. Epub 2021 Jun 4.

Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, China. Electronic address:

Purpose: Treatment options for recurrent glioblastoma (rGBM) remain scarce, which may be due to the limited understanding of its molecular characteristics.

Methods: Based on gene expression profiling, the infiltration scores of 26 immune cell types were calculated using gene set variation analysis. The differences between rGBM and other cancer subtypes were estimated to characterize the specific immune characteristics of rGBM, and the prognostic value of immune cells in rGBM was estimated using univariate and multivariate Cox analysis. Subgroup analyses and Kaplan-Meier analyses were performed to identify whether CD8 T-cell infiltration could be useful in selecting treatment options for rGBM patients.

Results: We found that rGBM patients were associated with enrichment of activated CD8 T cells, and high CD8 T-cell infiltration was associated with superior overall survival. Patients exhibiting high CD8 T-cell infiltration who received treatment with bevacizumab and lomustine combination therapy experienced a significant benefit in overall survival and progression-free survival, whereas patients with low CD8 T-cell infiltration did not experience such a benefit. CD8 T cells remained an independent prognostic factor in multivariate analyses (cohort 1: hazard ratio [HR] = 0.546, 95% confidence interval [CI]: 0.316-0.945, P = 0.031; cohort 3: HR = 0.615, 95% CI: 0.387-0.978, P = 0.040) after adjusting for clinicopathological and molecular factors.

Conclusions: Activated CD8 T-cells is a promising biomarker for predicting overall survival in rGBM patients and could be used for assisting treatment selection.
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http://dx.doi.org/10.1016/j.intimp.2021.107826DOI Listing
August 2021

Preoperative combi-elastography for the prediction of early recurrence after curative resection of hepatocellular carcinoma.

Clin Imaging 2021 Nov 31;79:173-178. Epub 2021 May 31.

Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, China. Electronic address:

Purpose: To estimate the prognostic value of preoperative combi-elastography for early recurrence (ER) of hepatocellular carcinoma (HCC) after radical resection.

Methods: A total of 94 HCC patients undergoing hepatectomy from January to August 2019 were included. The combined elastography (ARIETTA 850, Hitachi Healthcare) was used for real-time tissue elastography and shear wave measurement analysis. Six elastography related indicators were calculated. The patients were randomly divided into a training and a validation group in a 7:3 ratio and prediction model was assessed about discrimination capability by using area under the receiver operating curve. Univariate and multivariate analyses were performed to determine the prognostic value of clinicopathological factors, laboratory tests, and elastography for HCC ER.

Results: The Vs, E, F, and A indexes were significantly higher in patients with ER than in those without ER (P = 0.002, P = 0.002, P < 0.001, and P < 0.001, respectively). Multivariate logistic regression analysis indicated that microvascular invasion (MVI, odds ratio [OR] = 3.964, 95% confidence interval [CI] = 1.326-11.845; P = 0.010) and the F index (OR = 9.533, 95%CI = 1.921-47.296; P = 0.006) were independent predictors of ER in HCC. A ER prediction model based on laboratory tests, MVI and F index were moderate [area under curves (AUCs) in training and validation cohort were 0.829(95%CI: 0.723-0.935; P < 0.001) and 0.846 (95%CI: 0.699-0.994; P = 0.002), respectively].

Conclusion: Preoperative combi-elastography analysis could be used as a potential prognostic tool for HCC ER and assist in clinical decision-making.
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http://dx.doi.org/10.1016/j.clinimag.2021.05.020DOI Listing
November 2021

Virologic Response to Very Early HIV Treatment in Neonates.

J Clin Med 2021 May 12;10(10). Epub 2021 May 12.

Gertrude H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.

Factors that influence viral response when antiretroviral therapy (ART) is initiated in neonates are not well characterized. We assessed if there is consistency in predictive factors when operationalizing viral response using different methods. Data were collected from a clinical study in South Africa that started ART in neonates within 14 days of birth (2013-2018). Among 61 infants followed for ≥48 weeks after ART initiation, viral response through 72 weeks was defined by three methods: (1) clinical endpoints (virologic success, rebound, and failure); (2) time to viral suppression, i.e., any viral load (VL: copies/mL) <400, <50, or target not detected (TND) using time-to-event methods; and (3) latent class growth analysis (LCGA) to empirically estimate discrete groups with shared patterns of VL trajectories over time. We investigated the following factors: age at ART initiation, sex, birthweight, preterm birth, mode of delivery, breastfeeding, pre-treatment VL and CD4, maternal ART during pregnancy, and maternal VL and CD4 count. ART was initiated 0-48 h of birth among 57.4% of the infants, 48 h-7 days in 29.5% and 8-14 days in 13.1%. By Method 1, infants were categorized into 'success' (54.1%), 'rebound' (21.3%), and 'failure' (24.6%) for viral response. For Method 2, median time to achieving a VL <400, <50, or TND was 58, 123, and 331 days, respectively. For Method 3, infants were categorized into three trajectories: 'rapid decline' (29.5%), 'slow decline' (47.5%), and 'persistently high' (23.0%). All methods found that higher pre-treatment VL, particularly >100,000, was associated with less favorable viral outcomes. No exposure to maternal ART was associated with a better viral response, while a higher maternal VL was associated with less favorable viral response and higher maternal CD4 was associated with better viral response across all three methods. The LCGA method found that infants who initiated ART 8-14 days had less favorable viral response than those who initiated ART earlier. The other two methods trended in a similar direction. Across three methods to operationalize viral response in the context of early infant treatment, findings of factors associated with viral response were largely consistent, including infant pre-treatment VL, maternal VL, and maternal CD4 count.
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http://dx.doi.org/10.3390/jcm10102074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151270PMC
May 2021

Chimeric Phi29 DNA polymerase with helix-hairpin-helix motifs shows enhanced salt tolerance and replication performance.

Microb Biotechnol 2021 07 19;14(4):1642-1656. Epub 2021 May 19.

Research Center of Molecular Diagnostics and Sequencing, Research Institute of Tsinghua University in Shenzhen, Shenzhen, Guangdong, 518057, China.

Phi29 DNA polymerase (Phi29 Pol) has been successfully applied in DNA nanoball-based sequencing, real-time DNA sequencing from single polymerase molecules and nanopore sequencing employing the sequencing by synthesis (SBS) method. Among these, polymerase-assisted nanopore sequencing technology analyses nucleotide sequences as a function of changes in electrical current. This ionic, current-based sequencing technology requires polymerases to perform replication at high salt concentrations, for example 0.3 M KCl. Nonetheless, the salt tolerance of wild-type Phi29 Pol is relatively low. Here, we fused helix-hairpin-helix (HhH) domains E-L (eight repeats in total) of topoisomerase V (Topo V) from the hyperthermophile Methanopyrus kandleri to the Phi29 Pol COOH terminus, designated Phi29EL DNA polymerase (Phi29EL Pol). Domain fusion increased the overall enzyme replication efficiency by fourfold. Phi29EL Pol catalysed rolling circle replication in a broader range of salt concentrations than did Phi29 Pol, extending the KCl concentration range for activity up to 0.3 M. In addition, the mutation of Glu to Ser or Gln increased Phi29EL Pol activity in the presence of KCl. In this work, we produced a salt-tolerant Phi29 Pol derivative by means of (HhH) domain insertion. The multiple advantages of this insertion make it a good substitute for Phi29 Pol, especially for use in nanopore sequencing or other circumstances that require high salt concentrations.
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http://dx.doi.org/10.1111/1751-7915.13830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313265PMC
July 2021
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