Publications by authors named "Jing Zhang"

9,119 Publications

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Assessment of the effects of four crosslinking agents on gelatin hydrogel for myocardial tissue engineering applications.

Biomed Mater 2021 May 11. Epub 2021 May 11.

College of Biomedical Engineering, Sichuan University, No.24 South Section 1, Yihuan Road,, Chengdu, 610065, CHINA.

Cardiomyocyte (CM) transplantation is a promising option for regenerating infarcted myocardium. However, poor cell survival and residence rates reduce the efficacy of cell transplantation. Gelatin (GA) hydrogel as a frequently-used cell carrier is a possible approach to increase the survival rate of CMs. In this study, microbial transglutaminase (mTG) and chemical crosslinkers glutaraldehyde (GTA), genipin (GP), and 1-ethyl-3-(3-dimethyl aminopropyl)-carbodiimide (EDC) were employed to prepare GA hydrogels. The mechanical properties and degradation characteristics of these hydrogels were then evaluated. Neonatal rat CMs (NRCMs) were isolated and inoculated on the surface of these hydrogels or encapsulated in mTG- hydrogels. Cellular growth morphology and beating behavior were observed. Cellular viability and immunofluorescence were analyzed. Intracellular Ca2+ transient and membrane potential propagation were detected using fluorescence dyes (Fluo-3 and di-4-ANEPPS, respectively). Results showed that the chemical crosslinkers exhibited high cytotoxicity and resulted in high rates of cell death. By contrast, mTG- hydrogels showed excellent cell compatibility. The CMs cultured in mTG-hydrogels for a week expressed CM maturation markers. The NRCMs begun independently beating on the third day of culture, and their beating synchronized after a week of culture. Furthermore, intracellular Ca2+ transient events with periodicity were observed. In conclusion, the novel mTG-crosslinked GA hydrogel synthesized herein has good biocompatibility, and it supports CM adhesion, growth, and maturation.
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http://dx.doi.org/10.1088/1748-605X/abfff2DOI Listing
May 2021

Low-dose aspirin can downregulate progesterone resistance and increase the expression of LIF in endometriosis during the implantation window.

Gynecol Endocrinol 2021 May 11:1-5. Epub 2021 May 11.

Department of Obstetrics and Gynaecology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China.

Aim: Study the effect of low-dose aspirin on the endometrial receptivity in endometriosis rat models.

Materials And Methods: This study is to explore the expressions of progesterone receptor and LIF among three groups of endometriosis rat models: control group ( = 12), EMs group ( = 15), and aspirin group ( = 17). The expressions of progesterone receptor (PR), PRA, PRB, and leukemia inhibitory factor receptor (LIFR) in eutopic endometrium were determined using immunohistochemistry technology, western blot, and qRT-PCR. The levels of LIF in eutopic endometrium and serum were detected by western blot, qRT-PCR, and ELISA.

Results: The expressions of PR, PRA, and PRB protein were significantly increased in the eutopic endometrium after low-dose aspirin treatment, and the level of PRB mRNA was also increased while the ratio of PRA/PRB mRNA was decreased in the eutopic endometrium. The levels of LIF in eutopic endometrium and serum were increased compared with the untreated endometriosis rats. However, the expression of LIFR was not statistically different among the three groups.

Conclusions: The results suggest that the low-dose aspirin treatment could downregulate progesterone resistance and increase the expression of LIF of endometriosis rats during the implantation window, which could improve endometrial receptivity and enhance the pregnant rate of endometriosis. It may provide a potential treatment method for endometriosis-related infertility.
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http://dx.doi.org/10.1080/09513590.2021.1918663DOI Listing
May 2021

[Significance and case analysis of FMR1 mutation screening during early and middle pregnancy].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 May;38(5):450-453

The Fourth Hospital of Shijiazhuang, Shijiazhuang, Hebei 050011, China.

Objective: To screen for mutations of fragile X mental retardation 1 (FMR1) gene during early and middle pregnancy and provide prenatal diagnosis for those carrying high-risk CGG trinucleotide expansions.

Methods: Peripheral blood samples of 2316 pregnant women at 12 to 21(+6) gestational weeks were collected for the extraction of genomic DNA. CGG repeats of the FMR1 gene were detected by fluorescence PCR and capillary electrophoresis. Genetic counseling and prenatal diagnosis were provided for 3 women carrying the premutations.

Results: The carrier rate of CGG repeats of the FMR1 gene was 1 in 178 for the intermediate type and 1 in 772 for the premutation types. The highest frequency allele of CGG was 29 repeats, which accounted for 49.29%, followed by 30 repeats (28.56%) and 36 repeats (8.83%). In case 1, the fetus had a karyotype of 45,X, in addition with premutation type of CGG expansion of the FMR1 gene. Following genetic counseling, the couple chose to terminate the pregnancy through induced labor. The numbers of CGG repeats were respectively 70/- and 29/30 for the husband and wife. In case 2, amniocentesis was performed at 20 weeks of gestation. The number of CGG repeats of the FMR1 gene was 29/-. No abnormality was found in the fetal karyotype and chromosomal copy number variations. The couple chose to continue with the pregnancy. Case 3 refused prenatal diagnosis after genetic counseling and gave birth to a girl at full term, who had a birth weight of 2440 g and no obvious abnormality found during follow-up.

Conclusion: Pregnant women should be screened for FMR1 gene mutations during early and middle pregnancy, and those with high-risk CGG expansions should undergo prenatal diagnosis, genetic counseling and family study.
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http://dx.doi.org/10.3760/cma.j.cn511374-20200319-00181DOI Listing
May 2021

Oxidation of Pd(II) with disilane in a palladium-catalyzed disilylation of aryl halides: a theoretical view.

Dalton Trans 2021 May 11. Epub 2021 May 11.

School of Chemistry and Chemical Engineering, and Chongqing Key Laboratory of Theoretical and Computational Chemistry, Chongqing University, Chongqing 400030, P. R. China. and Green Catalysis Center, and College of Chemistry Zhengzhou University Zhengzhou, Henan 450001, China.

Density functional theory (DFT) calculation has been used to reveal the mechanism of the Pd-catalyzed disilylation reaction of aryl halides. The DFT calculations indicate that the reaction starts with the oxidative addition of the C-I bond to the Pd(0) catalyst. Concerted metalation-deprotonation (CMD) can then generate a five-membered palladacycle. Insertion of Pd(ii) into the Si-Si bond in disilane followed by two sequential steps of reductive eliminations yields the disilylation product and regenerates the Pd(0) catalyst. According to the NPA charge analysis along the reaction coordinates, the formal oxidative addition of the Si-Si bond to palladium could be considered as the insertion of palladium into the Si-Si bond. However, the conventional oxidative addition of the C-I bond to palladium is exactly an oxidation process with the electron transfer from the palladium atom to the C-I bond. Therefore, electron rich Pd(0) is beneficial for the oxidation process, and Pd(ii) prone to acquire electrons is beneficial for the insertion process.
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http://dx.doi.org/10.1039/d1dt00399bDOI Listing
May 2021

Tolerability, Safety, Pharmacokinetics, and Immunogenicity of a Novel SARS-CoV-2 Neutralizing Antibody, Etesevimab in Chinese Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled, First-In-Human Phase 1 Study.

Antimicrob Agents Chemother 2021 May 10. Epub 2021 May 10.

Phase 1 Clinical Research Center, Huashan Hospital, Fudan University, Shanghai, China

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to spread rapidly worldwide. This study is the first to report the tolerability, safety, pharmacokinetics (PK), and immunogenicity of a recombinant human anti-SARS-CoV-2 monoclonal antibody, etesevimab (CB6, JS016, LY3832479 or LY-CoV016), in healthy adults. This paper involves a randomized, double-blind, placebo-controlled, phase 1 study. A total of 40 participants were enrolled to receive a single intravenous dose of either etesevimab or a placebo in one of four sequential ascending intravenous dose cohorts. All 40 participants completed the study. Seventeen (42.5%) participants experienced 22 treatment emergent adverse events (TEAEs) that were drug-related, and the rates of these TEAEs among different dose cohorts were numerically comparable. No difference was observed between the combined etesevimab group and the placebo group. The exposure after etesevimab infusion increased in an approximately proportional manner as the dose elimination half-life cohorts and was estimated to be around 4 weeks. Etesevimab was well tolerated after administration of a single dose at a range of 2.5 mg/kg to 50 mg/kg in healthy Chinese adults. The PK profiles of etesevimab in healthy volunteers showed typical monoclonal antibody distribution and elimination characteristics. (This study has been registered at ClinicalTrials.gov under identifier NCT04441918.).
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http://dx.doi.org/10.1128/AAC.00350-21DOI Listing
May 2021

Fasudil ameliorates cognitive deficits, oxidative stress and neuronal apoptosis via inhibiting ROCK/MAPK and activating Nrf2 signalling pathways in APP/PS1 mice.

Folia Neuropathol 2021 ;59(1):32-49

Department of Neurology, First Affiliated Hospital, Shanxi Medical University, Taiyuan, P.R. China.

Alzheimer's disease (AD) is a severe neurodegenerative disorder of the central nervous system (CNS) characterized by neuron loss and dementia. Previous abundant evidence demonstrates that the first critical step in the course of AD is the state of oxidative stress and the neuronal loss is closely related to the interaction of several signalling pathways. The neuroprotective efficacy of Rho-associated protein kinase (ROCK) inhibitor in the treatment of AD has been reported, but its exact mechanism has not been well elucidated. The purpose of this study is to investigate the therapeutic effects of Fasudil on amyloid precursor protein/presenilin-1 (APP/PS1) mice and to discover the potential underlying mechanism. Sixteen 8-month-old APP/PS1 mice were divided into model and Fasudil treatment groups and 8 wild-type mice were used as a normal control group. After the behavioural test, all mice were sacrificed for immunofluorescence and other biochemical tests. The results showed that the administration of Fasudil improved learning and memory ability, elevated the concentration of antioxidative substances and decreased lipid peroxides, as well as inhibited neuronal apoptosis by increasing the expression of B-cell lymphoma-2 (Bcl-2) (p < 0.05), reducing Bcl-2 Associated X (Bax) (p < 0.05) and cleaved caspase-3 (p < 0.05) of APP/PS1 mice. Moreover, Fasudil treatment also ameliorated the phosphorylation of p38 (p < 0.01), c-Jun N-terminal kinase (JNK) (p < 0.001) and extracellular regulated protein kinases (ERK) (p < 0.001), and accelerated the nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) (p < 0.01) expression and its antioxidative downstream molecules (p < 0.05, p < 0.05, and p < 0.05, respectively). Data from the present study demonstrate that Fasudil significantly restored cognitive function, restrained oxidative stress and reduced neuronal apoptosis in the hippocampus, probably by inhibiting ROCK/MAPK and activating Nrf2 signalling pathways in APP/PS1 mice.
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http://dx.doi.org/10.5114/fn.2021.105130DOI Listing
January 2021

Spirosoma profusum sp. nov., and Spirosoma validum sp. nov., radiation-resistant bacteria isolated from soil in South Korea.

Antonie Van Leeuwenhoek 2021 May 10. Epub 2021 May 10.

Department of Bio and Environmental Technology, College of Natural Science, Seoul Women's University, Seoul, 139-774, Republic of Korea.

Two novel Gram-negative, rod-shaped bacterial strains BT702 and BT704 were isolated from soil collected in Jeongseon (37° 22' 45″ N, 128° 39' 53″ E), Gangwon province, South Korea. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strains BT702 and BT704 belong to distinct lineage within the genus Spirosoma (family Cytophagaceae, order Cytophagales, class Cytophagia and phylum Bacteroidetes). The strain BT702 was closely related to Spirosoma flavus 15J11-2 (96.7% 16S rRNA gene similarity) and Spirosoma metallilatum TX0405 (93.3%). The strain BT704 was closely related to Spirosoma koreense 15J8-5 (94.6%), Spirosoma endophyticum DSM 26130 (93.8%) and Spirosoma humi S7-4-1 (93.8%). The genome sizes of type strains BT702 and BT704 are 8,731,341 bp and 8,221,062 bp, respectively. The major cellular fatty acids of strains BT702 and BT704 were C ω5c and summed feature 3 (C ω6c/C ω7c). The strains were found to have the same quinone system, with MK-7 as the major respiratory quinone. The major polar lipids of strain BT702 was identified to be phosphatidylethanolamine (PE), aminophospholipid (APL) and aminolipid (AL), while that of strain BT704 consisted of phosphatidylethanolamine (PE) and aminophospholipid (APL). Based on the polyphasic analysis (phylogenetic, chemotaxonomic and biochemical), strains BT702 and BT704 can be suggested as two new bacterial species within the genus Spirosoma and the proposed names are Spirosoma profusum and Spirosoma validum, respectively. The type strain of Spirosoma profusum is BT702 (= KCTC 82115 = NBRC 114859) and type strain of Spirosoma validum is BT704 (= KCTC 82114 = NBRC 114966).
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http://dx.doi.org/10.1007/s10482-021-01585-9DOI Listing
May 2021

Multiple nerve root metastasis of breast carcinoma: a report of two cases.

Gland Surg 2021 Apr;10(4):1542-1546

Department of Neurosurgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

Nerve root metastases are extremely rare with only a handful of cases ever reported. Metastasis to sites other than the primary site is common in malignant tumors whereas spinal ganglion metastasis is extremely rare and has been only reported in individual cases. The lumbar spine tends to be more common areas of presentation whereas breast cancer metastasis has been rarely reported. We herein reported two cases of breast carcinoma metastasis to multiple spinal nerve roots. The metastasis sites were S1 nerve root in Case 1 and left L5 and bilateral cervical nerve roots in Case 2. On magnetic resonance imaging (MRI), the nerve roots in the intervertebral foramen zones appeared thickened and contrast-enhanced MRI exhibited intense enhancement. Pathological examination showed that these primary lesions were breast cancer in both cases, and there were intracranial multiple metastases in both cases, including preoperative metastasis to multiple nerve roots (lumbar and cervical) and postoperative recurrence. The clinical course was characterized by worsening radicular symptoms-especially intractable pain. The radiologic appearance might mimic a neurogenic tumor, which is performed intervertebral foraminal area lesion, and the corresponding ganglion/nerve root became thickened and was enhanced significantly. Surgical intervention with tumor debulking followed by radiotherapy provides local tumor control and palliation from pain, but it is palliative. Therefore, for patients with radiological manifestations of radiculopathy, the possibility of metastatic tumors should be considered.
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http://dx.doi.org/10.21037/gs-20-708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102223PMC
April 2021

Potential Networks Regulated by MSCs in Acute-On-Chronic Liver Failure: Exosomal miRNAs and Intracellular Target Genes.

Front Genet 2021 23;12:650536. Epub 2021 Apr 23.

Department of Infectious Diseases, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Acute-on-chronic liver failure (ACLF) is a severe syndrome associated with high mortality. Alterations in the liver microenvironment are one of the vital causes of immune damage and liver dysfunction. Human bone marrow mesenchymal stem cells (hBMSCs) have been reported to alleviate liver injury via exosome-mediated signaling; of note, miRNAs are one of the most important cargoes in exosomes. Importantly, the miRNAs within exosomes in the hepatic microenvironment may mediate the mesenchymal stem cell (MSC)-derived regulation of liver function. This study investigated the hepatocyte exosomal miRNAs which are regulated by MSCs and the target genes which have potential in the treatment of liver failure. Briefly, ACLF was induced in mice using carbon tetrachloride and primary hepatocytes were isolated and co-cultured (or not) with MSCs under serum-free conditions. Exosomes were then collected, and the expression of exosomal miRNAs was assessed using next-generation sequencing; a comparison was performed between liver cells from healthy ACLF animals. Additionally, to identify the intracellular targets of exosomal miRNAs in humans, we focused on previously published data, i.e., microarray data and mass spectrometry data in liver samples from ACLF patients. The biological functions and signaling pathways associated with differentially expressed genes were predicted using gene ontology and Kyoto Encyclopedia of Genes and Genomics enrichment analyses; hub genes were also screened based on pathway analysis and the prediction of protein-protein interaction networks. Finally, we constructed the hub gene-miRNA network and performed correlation analysis and qPCR validation. Importantly, our data revealed that MSCs could regulate the miRNA content within exosomes in the hepatic microenvironment. MiR-20a-5p was down-regulated in ACLF hepatocytes and their exosomes, while the levels of chemokine C-X-C Motif Chemokine Ligand 8 (CXCL8; interleukin 8) were increased in hepatocytes. Importantly, co-culture with hBMSCs resulted in up-regulated expression of miR-20a-5p in exosomes and hepatocytes, and down-regulated expression of CXCL8 in hepatocytes. Altogether, our data suggest that the exosomal miR-20a-5p/intracellular CXCL8 axis may play an important role in the reduction of liver inflammation in ACLF in the context of MSC-based therapies and highlights CXCL8 as a potential target for alleviating liver injury.
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http://dx.doi.org/10.3389/fgene.2021.650536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102832PMC
April 2021

Effects of nurse-led web-based interventions on people with type 2 diabetes mellitus: A systematic review and meta-analysis.

J Telemed Telecare 2021 May 9:1357633X211010019. Epub 2021 May 9.

School of Nursing, Lanzhou University, China.

Introduction: Diabetes mellitus is an expanding global health problem. Currently, the home management of diabetes is mainly led by a multidisciplinary team based on telemedicine. However, the role nurses play in it remains inconclusive. This study aimed to investigate the effectiveness of nurse-led web-based intervention on glycated haemoglobin, blood pressure and lipid profile in patients with type 2 diabetes.

Methods: An exhaustive systematic literature search was undertaken using the following databases: PubMed, Web of Science, Embase, The Cochrane Central Register of Controlled Trials and CINAHL. Two investigators independently extracted data and assessed the quality of the studies by examining the risk of bias and using Modified Jadad Score system. We conducted a meta-analysis of randomized controlled trials that had been published from inception to July 2020, using Review Manager 5.3.

Results: Eleven randomized controlled trials were selected that included 2063 participants. Meta-analyses results indicated significant effects on not only glycated haemoglobin (pooled mean difference (MD) = -0.40, 95% confidence interval (CI): -0.5 to -0.26,  < 0.00001), but also on systolic blood pressure (pooled MD = -1.91, 95% CI: -3.73 to -0.09,  = 0.04) and low density lipoprotein (pooled standardized MD = -0.29, 95% CI: -0.44 to -0.15,  < 0.0001). There were no effects of nurse-led web-based intervention on fasting blood glucose, diastolic blood pressure, high density lipoprotein, body mass index and triglycerides.

Discussion: Nurse-led web-based intervention is a promising way to complement routine clinical care. However, the specific intervention content and intervention media still need to carry out large-scale well-designed randomized controlled trials. Systematic review registration: PROSPERO CRD 42020204565.
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http://dx.doi.org/10.1177/1357633X211010019DOI Listing
May 2021

Discovery of pyrazolones as novel carboxylesterase 2 inhibitors that potently inhibit the adipogenesis in cells.

Bioorg Med Chem 2021 Apr 30;40:116187. Epub 2021 Apr 30.

Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address:

Carboxylesterase 2 (CES2) is one of the most important Phase I drug metabolizing enzymes in the carboxylesterase family. It plays crucial roles in the bioavailability of oral ester prodrugs and the therapeutic effect of some anticancer drugs such as irinotecan (CPT11) and capecitabine. In addition to the well-known roles of CES2 in xenobiotic metabolism, the enzyme also participates in endogenous metabolism and the production of lipids. In this study, we synthesized a series of pyrazolones and assayed their inhibitory effects against CES2 in vitro. Structure-activity relationship analysis of these pyrazolones reveals that the introduction of 4-methylphenyl unit (R), 4-methylbenzyl (R) and cyclohexyl (R) moieties are beneficial for CES2 inhibition. Guided by these SARs results, 1-cyclohexyl-4-(4-methylbenzyl)-3-p-tolyl-1H- pyrazol-5(4H)-one (27) was designed and synthesized. Further investigations demonstrated that the compound 27 exhibited stronger CES2 inhibition activity with a lower IC value (0.13 μM). The inhibition kinetic study demonstrated that compound 27 inhibited the hydrolysis of CES2-fluorescein diacetate (FD) through non-competitive inhibition. In addition, the molecular docking showed that the core of pyrazolone, the cyclohexane moiety, 4-methylbenzyl and 4-methylphenyl groups in compound 27 all played important roles with the amino acid residues of CSE2. Also, compound 27 could inhibit adipocyte adipogenesis induced by mouse preadipocytes. In brief, we designed and synthesized a novel pyrazolone compound with a strong inhibitory ability on CES2 and could inhibit the adipogenesis induced by mouse preadipocytes, which can be served as a promising lead compound for the development of more potent pyrazolone-type CES2 inhibitors, and also used as a potential tool for exploring the biological functions of CES2 in human being.
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http://dx.doi.org/10.1016/j.bmc.2021.116187DOI Listing
April 2021

Utility of liquid-based cytology on residual needle rinses collected from core needle biopsy for lung nodule diagnosis.

Cancer Med 2021 May 7. Epub 2021 May 7.

Department of Anorectal Surgery, The First Affiliated Hospital of University of South China, Hengyang, China.

Background: Core needle biopsy (CNB) has become the most common tissue sampling modality for pathological diagnosis of peripheral lung nodules. However, approximately 10% of pulmonary CNB specimens cannot be unambiguously diagnosed, even with auxiliary techniques. This retrospective study investigated the diagnostic value of liquid-based cytology on residual pulmonary CNB material collected from needle rinses.

Methods: Computed tomography-guided pulmonary CNB specimens and relevant cytology of CNB needle rinses (CNR) from July 2017 to June 2020 were reviewed. A total of 406 patients, each of whom underwent a CNB procedure, were included in the study.

Results: Of the 406 cases, a more serious diagnosis was rendered by CNR in 6.4% (n = 26) of cases. Furthermore, among these 26 cases, 13 malignancies were confirmed only from CNR. Of the remaining 13 patients with uncertain lesions identified from CNR, six were diagnosed with definite benign lesions from tissue samples, five were found to harbor malignant neoplasms through repeated CNB or follow-up examination, and two had tuberculosis. The sensitivity (320/332, 96.4%) of combined CNR/CNB (both CNR and CNB) in distinguishing malignancies from benign lesions was higher than that of CNB alone (307/332, 92.5%). A total of 320 malignant neoplasms included 198 cases of primary lung adenocarcinoma and 71 cases of primary lung squamous cell carcinoma.

Conclusions: CNR with higher nuclear and cytoplasmic resolution than CNB exhibited a high diagnostic efficacy for differentiating malignant from benign lesions in the lung. Moreover, combined CNR/CNB achieved optimal results in reducing the false-negative rate and the subtyping of non-small cell lung cancer.
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http://dx.doi.org/10.1002/cam4.3949DOI Listing
May 2021

Multiple intravenous tranexamic acid doses in total knee arthroplasty in patients with rheumatoid arthritis: a randomized controlled study.

BMC Musculoskelet Disord 2021 May 7;22(1):425. Epub 2021 May 7.

Shanghai University of Traditional Chinese Medicine, Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, 200052, CN, China.

Background: We aimed to determine the efficacy and safety of multiple doses of intravenous tranexamic acid (IV-TXA) on perioperative blood loss in patients with rheumatoid arthritis (RA) who had undergone primary unilateral total knee arthroplasty (TKA).

Methods: For this single-center, single-blind randomized controlled clinical trial, 10 male and 87 female participants with RA, aged 50-75 years, who underwent unilateral primary TKA were recruited. The patients received one dose of 1 g IV-TXA 10 min before skin incision, followed by articular injection of 1.5 g tranexamic acid after cavity suture during the surgery. The patients were randomly assigned (1:1) into two groups and received an additional single dose of IV-TXA (1 g) for 3 h (group A) or three doses of IV-TXA (1 g) for 3, 6, and 12 h (group B) postoperatively. Primary outcomes were total blood loss (TBL), hidden blood loss (HBL), and maximum hemoglobin (Hb) level decrease. Secondary outcomes were transfusion rate and D-dimer levels. All parameters were measured postoperatively during inpatient hospital stay.

Results: The mean TBL, HBL, and maximum Hb level decrease in group B (506.1 ± 227.0 mL, 471.6 ± 224.0 mL, and 17.5 ± 7.7 g/L, respectively) were significantly lower than those in group A (608.8 ± 244.8 mL, P = 0.035; 574.0 ± 242.3 mL, P = 0.033; and 23.42 ± 9.2 g/L, P = 0.001, respectively). No episode of transfusion occurred. The D-dimer level was lower in group B than in group A on postoperative day 1 (P <  0.001), and the incidence of thromboembolic events was similar between the groups (P > 0.05).

Conclusion: In patients with RA, three doses of postoperative IV-TXA further facilitated HBL and Hb level decrease without increasing the incidence of adverse events in a short period after TKA.

Trial Registration: The trial was registered in the Chinese Clinical Trial Registry ( ChiCTR1900025013 ).
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http://dx.doi.org/10.1186/s12891-021-04307-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105956PMC
May 2021

Effects of doping high-valence transition metal (V, Nb and Zr) ions on the structure and electrochemical performance of LIB cathode material LiNiCoMnO.

Phys Chem Chem Phys 2021 May 7. Epub 2021 May 7.

College of Chemistry, Fuzhou University, Fuzhou, Fujian, 350116, P. R. China. and State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou, Fujian, 350116, China and Fujian Provincial Key Laboratory of Theoretical and Computational Chemistry (FTCC), Xiamen University, Xiamen, Fujian, 61005, China.

Ni-rich layered oxides, like LiNi0.8Co0.1Mn0.1O2 (NCM811), have been widely investigated as cathodes due to their high energy density. However, gradual structural transformation during cycling can lead to capacity degradation and potential decay of cathode materials. Herein, we doped high-valence transition metal (TM) ions (V5+, Nb5+, and Zr4+) at the Ni site of NCM811 by first principles simulations and explored the mechanism of doping TMs in NCMs for enhancing the electrochemical performance. Analysis of the calculations shows that doping V, Nb and Zr has an efficient influence on alleviating the Ni oxidation, reducing the loss of oxygen, and facilitating Li+ migration. Moreover, V doping can further suppress the lattice distortion due to the radius of V5+ being close to the radius of Mn4+. In particular, compared with the barrier of the pristine NCM in Li divacancy, the barrier of V-doped NCM reaches the lowest. In conclusion, V is the most favorable dopant for NCM811 to improve the electrochemical properties and achieve both high capacity and cycling stability.
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http://dx.doi.org/10.1039/d1cp00426cDOI Listing
May 2021

Response to first-line treatment predicts progression-free survival benefit of small-cell lung cancer patients treated with anlotinib.

Cancer Med 2021 May 6. Epub 2021 May 6.

Department of Oncology, General Hospital of Chinese PLA, Beijing, China.

Background: Anlotinib significantly extended progression-free survival (PFS) and overall survival (OS) in small-cell lung cancer (SCLC) as third or later line treatment.

Methods: In this study, we retrospectively analyzed the efficacy and safety of anlotinib in the clinical practice and aimed to identify risk factors for predicting the clinical benefit of anlotinib in SCLC patients. 29 SCLC patients treated with anlotinib monotherapy or combination therapy as second or later line treatment were included. PFS, OS, objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were analyzed.

Results: In whole patients, the median PFS was 2.1 months (95% confidence interval (CI): 1.1-3.2 months); The ORR and DCR were 10.3% and 48.3%, respectively; The median OS was 7.2 months (95%CI: 3.2-11.2 months). Cox regression analysis demonstrated that response to first-line treatment was the independent risk factor for PFS. The ORR (20.0% vs. 0%) and DCR (53.3% vs. 42.9%) were promoted in patients treated with anlotinib combination therapy comparing to anlotinib monotherapy. The most common AEs were hoarseness, fatigue, decreased appetite, oral mucositis, and anemia. No treatment-related AEs graded 3 or more.

Conclusion: Anlotinib is an effective option for SCLC patients with tolerable toxicity as second or later line treatment. Patients sensitive to first-line treatment had longer PFS when treated with anlotinib. Anloitnib combined with other therapy increased the efficacy without adding toxicity.
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http://dx.doi.org/10.1002/cam4.3941DOI Listing
May 2021

Transbronchial mediastinal cryobiopsy in the diagnosis of mediastinal lesions: a randomised trial.

Eur Respir J 2021 May 6. Epub 2021 May 6.

Department of Respiratory Disease, Xinqiao Hospital, Third Military Medical University, Chongqing, China.

Background: Guidelines recommend endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) as an initial investigation technique for mediastinal nodal staging in lung cancer. However, EBUS-TBNA can be limited by the inadequacy of intact tissues, which might restrict its diagnostic yield in mediastinal lesions of certain etiologies. We have previously shown that EBUS-guided transbronchial mediastinal cryobiopsy can provide intact samples with greater volume.

Methods: This randomised study determined the diagnostic yield and safety of transbronchial mediastinal cryobiopsy monitored by endosonography for the diagnosis of mediastinal lesions. Patients with mediastinal lesion of 1 cm or more in the short axis were recruited. Following identification of the mediastinal lesion by linear EBUS, fine-needle aspiration and cryobiopsy were sequently performed in a randomised order. Primary endpoints were diagnostic yield defined as the percentage of patients for whom mediastinal biopsy provided a definite diagnosis, and procedure-related adverse events.

Results: One hundred and ninety-seven patients were enrolled and randomly allocated. The overall diagnostic yield was 79.9% and 91.8% for TBNA and transbronchial mediastinal cryobiopsy, respectively (p=0.001). Diagnostic yields were similar for metastatic lymphadenopathy (94.1% 95.6%, p=0.58), while cryobiopsy was more sensitive than TBNA in uncommon tumors (91.7% 25.0%, p=0.001) and benign disorders (80.9% 53.2%, p=0.004). No significant differences in diagnostic yield were detected between TBNA first and cryobiopsy first groups. We observed 2 cases of pneumothorax and 1 case of pneumomediastinum.

Conclusions: Transbronchial cryobiopsy performed under EBUS guidance is a safe and useful approach that offers diagnostic histological samples of mediastinal lesions.
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http://dx.doi.org/10.1183/13993003.00055-2021DOI Listing
May 2021

Glyphosate exposure attenuates testosterone synthesis via NR1D1 inhibition of StAR expression in mouse Leydig cells.

Sci Total Environ 2021 Apr 25;785:147323. Epub 2021 Apr 25.

Northwest A&F University, Yangling 712100, Shaanxi, China; Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, China; Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University, Yangling 712100, Shaanxi, China. Electronic address:

Glyphosate is a broad-spectrum herbicide that impairs testosterone synthesis in mammals. Leydig cells (LCs), the primary producers of testosterone, demonstrate rhythmic expression of circadian clock genes both in vivo and in vitro. The nuclear receptor NR1D1 is an important clock component that constitutes the subsidiary transcriptional/translational loop in the circadian clock system. Nr1d1 deficiency resulted in diminished fertility in both male and female mice. However, whether NR1D1 is involved in the glyphosate-mediated inhibition of testosterone synthesis in LCs remains unclear. Here, the involvement of NR1D1 in glyphosate-mediated inhibition of testosterone synthesis was investigated both in vitro and in vivo. Glyphosate exposure of TM3 cells significantly increased Nr1d1 mRNA levels, but decreased Bmal1, Per2, StAR, Cyp11a1, and Cyp17a1 mRNA levels. Western blotting confirmed elevated NR1D1 and reduced StAR protein levels following glyphosate exposure. Glyphosate exposure also reduced testosterone production in TM3 cells. In primary LCs, glyphosate exposure also upregulated Nr1d1 mRNA levels and downregulated the mRNA levels of other clock genes (Bmal1 and Per2) and steroidogenic genes (StAR, Cyp17a1, Cyp11a1, and Hsd3b2), and inhibited testosterone synthesis. Moreover, glyphosate exposure significantly reduced the amplitude and shortened the period of PER2::LUCIFERASE oscillations in primary LCs isolated from mPer2 knock-in mice. Four weeks of oral glyphosate upregulated NR1D1 at both the mRNA and protein levels in mouse testes, and this was accompanied by a reduction in StAR expression. Notably, serum testosterone levels were also drastically reduced in mice treated with glyphosate. Moreover, dual-luciferase reporter and EMSA assays revealed that in TM3 cells NR1D1 inhibits the expression of StAR by binding to a canonical RORE element present within its promoter. Together, these data demonstrate that glyphosate perturbs testosterone synthesis via NR1D1 mediated inhibition of StAR expression in mouse LCs. These findings extend our understanding of how glyphosate impairs male fertility.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147323DOI Listing
April 2021

Modulating Mechanical and Shape-Memory Properties while Mitigating Degradation-Induced Inflammation of Polylactides by Pendant Aspirin Incorporation.

ACS Appl Mater Interfaces 2021 May 6. Epub 2021 May 6.

Department of Orthopedics & Physical Rehabilitation, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01655, United States.

Synergistically modulating mechanical properties and improving shape-memory performance while mitigating degradation-induced chronic inflammation of polylactide (PLA)-based implants for biomedical applications remain elusive. We test the hypothesis that copolymerizing aspirin-functionalized glycolide with d,l-lactide could enhance the thermal processing, toughness, and shape-memory efficiency of the copolymer while mitigating local inflammatory responses upon its degradation. The content of pendant aspirin was readily modulated by monomer feeds during ring-opening polymerization, and the copolymers with ∼10% or less aspirin pendants exhibited gigapascal-tensile moduli at body temperature and significantly improved fracture toughness and energy dissipation that positively correlated with the aspirin pendant content. The copolymers also exhibited excellent thermal-healing and shape-memory efficacy, achieving a >97% temporary shape fixing ratio at room temperature and facile shape recovery at 50-65 °C. These drastic improvements were attributed to the dynamic hydrophobic aggregations among aspirin pendants that strengthen glassy-state physical entanglement of PLA while readily dissociating under stress/thermal activation. When subcutaneously implanted, the copolymers mitigated degradation-induced inflammation due to concomitant hydrolytic release of aspirin without suppressing early acute inflammatory responses. The incorporation of aspirin pendants in PLA represents a straightforward and innovative strategy to enhance the toughness, shape-memory performance, and safety of this important class of thermoplastics for biomedical applications.
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http://dx.doi.org/10.1021/acsami.1c06178DOI Listing
May 2021

Tumor-associated Stromal Cellular Density as a Predictor of Recurrence and Mortality in Breast Cancer: Results from Ethnically-diverse Study Populations.

Cancer Epidemiol Biomarkers Prev 2021 May 5. Epub 2021 May 5.

Division of Cancer Epidemiology and Genetics, National Cancer Institute.

Background: Tumor-associated stroma is comprised of fibroblasts, tumor infiltrating lymphocytes (TILs), macrophages, endothelial, and other cells, that interactively influence tumor progression through inflammation and wound repair. Although gene expression signatures reflecting wound repair predict breast cancer survival, it is unclear whether combined density of tumor-associated stromal cells, a morphological proxy for inflammation and wound repair signatures on routine hematoxylin and eosin (H&E)-stained sections, is of prognostic relevance.

Methods: By applying machine learning to digitized H&E-stained sections for 2,084 breast cancer patients from China (n=596; 24-55years), Poland (n=810; 31-75years), and the United States (n=678; 55-78years), we characterized tumor-associated stromal cellular density (SCD) as the percentage of tumor-stroma that is occupied by nucleated cells. Hazard ratios (HR) and 95% confidence intervals (CI) for associations between SCD and clinical outcomes (recurrence (China); mortality (Poland and United States)) were estimated using Cox proportional hazard regression, adjusted for clinical variables.

Results: SCD was independently predictive of poor clinical outcomes in hormone receptor-positive (luminal) tumors from China (multivariable HR(95%CI)fourth(Q4) vs first(Q1) quartile=1.86(1.06-3.26);Ptrend=0.03), Poland (HR(95%CI)Q4 vs Q1=1.80(1.12-2.89);Ptrend=0.01), and United States (HR(95%CI)Q4 vs Q1=2.42(1.33-4.42);Ptrend=0.002). In general, SCD provided more prognostic information than most classical clinicopathologic factors, including grade, size, PR, HER2, IHC4, and TILs, predicting clinical outcomes irrespective of menopausal or lymph nodal status. SCD was not predictive of outcomes in hormone receptor-negative tumors.

Conclusions: Our findings support the independent prognostic value of tumor-associated SCD among ethnically-diverse luminal breast cancer patients.

Impact: Assessment of tumor-associated SCD on standard H&E could help refine prognostic assessment and therapeutic decision-making in luminal breast cancer.
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http://dx.doi.org/10.1158/1055-9965.EPI-21-0055DOI Listing
May 2021

Coronary artery bypass grafting in a patient with situs inversus totalis and Hodgkin lymphoma: Three-year follow-up report and systematic literature review.

Asian J Surg 2021 May 2. Epub 2021 May 2.

Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China. Electronic address:

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http://dx.doi.org/10.1016/j.asjsur.2021.03.043DOI Listing
May 2021

PD-1 blockade combined with IL-33 enhances the antitumor immune response in a type-1 lymphocyte-mediated manner.

Cancer Treat Res Commun 2021 Apr 23;28:100379. Epub 2021 Apr 23.

Department of Immunology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China; Jiangsu Key Laboratory of Clinical Immunology, Soochow University, Suzhou 215006, China; Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China. Electronic address:

PD-1 immune checkpoint blockade and cytokine IL-33 have shown significant therapeutic effects in tumor immunotherapy. These therapies promote CD8 T cell activation, proliferation, and effector functions. However, there were few research about the combined therapy efficacy. In this study, we established B16-empty vector and B16-IL33 melanoma mouse models and treated with PD-1 monoclonal antibody. We reported that PD-1 blockade combined with cytokine IL-33 further inhibited tumor progression and prolonged the survival of tumor-bearing mice. Mechanistically, the combination therapy was found to further facilitate CD4 and CD8 T lymphocytes accumulation, and enhance the antitumor effects of CD4or CD8tumor-infiltrating lymphocytes by promoting type-1 immune response within the tumor microenvironment using flow cytometry and quantitative real time polymerase chain reaction. Thus, PD-1 blockade combined with IL-33 has application potential in tumor immunotherapy. Further, this study provides a new promising strategy and theoretical basis for tumor combination immunotherapy.
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http://dx.doi.org/10.1016/j.ctarc.2021.100379DOI Listing
April 2021

An efficient localized catalytic hairpin assembly-based DNA nanomachine for miRNA-21 imaging in living cells.

Analyst 2021 May;146(9):3041-3051

Research Center of Analytical Instrumentation, Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry & Materials Science, Northwest University, Xi'an, 710069, Shaanxi, P.R. China.

As an enzyme-free isothermal amplification strategy, catalytic hairpin assembly (CHA) is a very promising method for cell imaging. However, the practical application of CHA on intracellular miRNA imaging is limited by slow kinetics, insufficient amplification efficiency and strong interference in living cells. Herein, a localized catalytic hairpin assembly-based DNA nanomachine (LCHA nanomachine) was developed for the rapid, efficient and reliable fluorescence resonance energy transformation (FRET) imaging of miRNA-21 in living cells. The nanomachine was simply constructed by a one-step self-assembly process of a stator strand, a pair of hairpin probes from CHA and an AS1411 aptamer. Benefiting from the spatial-confinement effect, a pair of hairpin probes with high collision frequency was rapidly and efficiently assembled using miRNA-21 as the catalyst on a stator strand in every nanomachine. Compared with the free-CHA nanomachine, the LCHA nanomachine shortened the reaction time by 4.5-fold for reaching a plateau and significant improved the sensitivity by 7.6-fold for miRNA-21 detection in vitro. Importantly, the nanomachine was successfully applied for miRNA-21 imaging in living cells. With the assistance of an AS1411 aptamer and stator strand, the pair of hairpin probes with the ratio of 1 : 1 synchronously transported into a co-site of the cytoplasm, which ensures efficient imaging of trace miRNA-21. The signal output of the ratio of 6-carboxy-fluorescein (FAM) to tetramethyl rhodamine (TAMRA) intensities guaranteed reliability through avoiding the interference from different amounts of the nanomachine that enters into cells. Notably, the nanomachine can distinguish the miRNA-21 expression level in different kinds of cancer cells. By virtue of the advantages of simplicity, efficiency and reliability, the proposed strategy provides a powerful method for exploring the functions of miRNA and diagnosis of disease.
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http://dx.doi.org/10.1039/d1an00001bDOI Listing
May 2021

Analysis of Brugada syndrome loci reveals that fine-mapping clustered GWAS hits enhances the annotation of disease-relevant variants.

Cell Rep Med 2021 Apr 20;2(4):100250. Epub 2021 Apr 20.

Department of Medical Sciences, School of Medicine, Universitat de Girona, Girona, Spain.

Genome-wide association studies (GWASs) are instrumental in identifying loci harboring common single-nucleotide variants (SNVs) that affect human traits and diseases. GWAS hits emerge in clusters, but the focus is often on the most significant hit in each trait- or disease-associated locus. The remaining hits represent SNVs in linkage disequilibrium (LD) and are considered redundant and thus frequently marginally reported or exploited. Here, we interrogate the value of integrating the full set of GWAS hits in a locus repeatedly associated with cardiac conduction traits and arrhythmia, -. Our analysis reveals 5 common 7-SNV haplotypes (Hap1-5) with 2 combinations associated with life-threatening arrhythmia-Brugada syndrome (the risk Hap and protective Hap genotypes). Hap1 and Hap2 share 3 SNVs; thus, this analysis suggests that assuming redundancy among clustered GWAS hits can lead to confounding disease-risk associations and supports the need to deconstruct GWAS data in the context of haplotype composition.
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http://dx.doi.org/10.1016/j.xcrm.2021.100250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080235PMC
April 2021

The Landscape of Cell-free HBV Integrations and Mutations in Cirrhosis and Hepatocellular Carcinoma Patients.

Clin Cancer Res 2021 May 4. Epub 2021 May 4.

Berry Oncology Corporation, Beijing, China.

Purpose: Intratumoral hepatitis B virus (HBV) integrations and mutations are related to hepatocellular carcinoma (HCC) progression. Circulating cell-free DNA (cfDNA) has shown itself as a powerful non-invasive biomarker for cancer. However, the HBV integration and mutation landscape on cfDNA remains unclear.

Experimental Design: A cSMART (Circulating Single-Molecule Amplification and Resequencing Technology)-based method (SIM) was developed to simultaneously investigate HBV integration and mutation landscapes on cfDNA with HBV-specific primers covering the whole HBV genome. 481 HCC and 517 liver cirrhosis (LC) patients were recruited in the study.

Results: A total of 6,861 integration breakpoints including TERT and KMT2B were discovered in HCC cfDNA, more than in LC. The concentration of circulating tumor DNA (ctDNA) was positively correlated with the detection rate of these integration hotspots and total HBV integration events in cfDNA. To track the origin of HBV integrations in cfDNA, whole-genome sequencing (WGS) was performed on their paired tumor tissues. The paired comparison of WGS data from tumor tissues and SIM data from cfDNA confirmed most recurrent integration events in cfDNA originated from tumor tissue. The mutational landscape across the whole HBV genome was firstly generated for both HBV genotype C and B. A region from nt1100 to nt1500 containing multiple HCC risk mutation sites (OR>1) was identified as a potential HCC-related mutational hot-zone.

Conclusions: Our study provides an in-depth delineation of HBV integration/mutation landscapes at cfDNA level and did a comparative analysis with their paired tissues. These findings shed light on the possibilities of non-invasive detection of virus insertion/mutation.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-0002DOI Listing
May 2021

Celastrol inhibit the proliferation, invasion and migration of human cervical HeLa cancer cells through down-regulation of MMP-2 and MMP-9.

J Cell Mol Med 2021 May 4. Epub 2021 May 4.

Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China.

The present study evaluated the anticancer potential of celastrol through down-regulation of matrix metalloproteinase-2 (MMP-2) and MMP-9. HeLa cells were incubated with different concentrations of celastrol (1, 10 and 100 µM) for 48h. Doxorubicin was used as a reference drug. Cancer cell migration, apoptosis, cell viability and mitochondrial fragmentation were evaluated following celastrol treatment. In addition, the expression level of MMP-2, MMP-9 and caspase-3 was evaluated following celastrol treatment. HeLa cell viability was 94.1 ± 7, 53.4 ± 4 and 36.3 ± 2% at 1-100 µM of celastrol, respectively. Apoptotic cell numbers were increased, and inhibition of larger wounds in cancer cells was observed following celastrol treatment. Celastrol-treated cells showed condensed nuclei and clumped mitochondria. Reduced expression of MMP-2 and MMP-9 and increased expression of caspase-3 were observed following celastrol treatment. Based on the experimental results, we are concluding that the celastrol was effective against HeLa cervical cancer cells.
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http://dx.doi.org/10.1111/jcmm.16488DOI Listing
May 2021

Titanium dioxide nanotubes as drug carriers for infection control and osteogenesis of bone implants.

Drug Deliv Transl Res 2021 May 3. Epub 2021 May 3.

Frontiers Science Center for Flexible Electronics, Xi'an Institute of Flexible Electronics (IFE), and Xi'an Institute of Biomedical Materials & Engineering (IBME), Northwestern Polytechnical University, 127 West Youyi Road, Xi'an, 710072, China.

Titanium implants have been widely used as one of the most effective treatments of bone defects. However, the lack of osteogenesis and bacteria-resistant activities result in high infection and loosening rates of titanium implants. Anodic oxidation could easily construct titanium dioxide nanotubes (TNTs) array on the surface of titanium, and the rough surface of TNTs is beneficial to the growth of osteoblast-related cells on the surface. And TNTs could be excellent drug carriers because of their single-entry tubular hollow structure. In this review, we aim at detailing the application of TNTs as drug carriers in the field of bone implants. Starting from the topography of TNTs, we illustrated the biological activity of the TNTs surface, the drugs for loading in TNTs, and the controlled and responsive release strategies of drug-loaded TNTs, respectively. At the end of this review, the shortcomings of TNTs as the drug carrier in the field of bone implants are discussed, and the development direction of this research field is also prospected.
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http://dx.doi.org/10.1007/s13346-021-00980-zDOI Listing
May 2021

Making Aggregation-Induced Emission Luminogen More Valuable by Gold: Enhancing Anticancer Efficacy by Suppressing Thioredoxin Reductase Activity.

ACS Nano 2021 May 3. Epub 2021 May 3.

Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction and Institute for Advanced Study, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong 999077, China.

Gold complexes have been recognized as potential anticancer agents against various kinds of diseases due to their inherent suppressions of antioxidant thioredoxin reductase (TrxR) activity. Herein, a powerful aggregation-induced emission luminogen (AIEgen), TBP-Au, was designed and synthesized by integrating an anticancer Au(I) moiety with an AIE-active photosensitizer (TBP), in which both the production and consumption routes of reactive oxygen species (ROS) were elaborately considered simultaneously to boost the anticancer efficacy. It has been demonstrated that TBP-Au could realize superior two-photon fluorescence imaging in tumor tissues with high resolution and deep penetration as well as long-term imaging in live animals due to its AIE property. In addition, the introduction of a special Au(I) moiety could tune the organelle specificity and efficiently facilitate the ROS-determined photodynamic therapy (PDT). More impressively, TBP-Au could efficiently eliminate cancer cells under light irradiation through the preconceived synergetic approaches from the PDT and the effective suppression of TrxR, demonstrating that TBP-Au holds great potential for precise cancer theranostics.
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http://dx.doi.org/10.1021/acsnano.1c02882DOI Listing
May 2021

Clinical relevance of serum immunoglobulin G4 in glucocorticoid therapy of Graves' ophthalmopathy.

Clin Endocrinol (Oxf) 2021 May 3. Epub 2021 May 3.

Department of Endocrinology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, P.R. China.

Objective: Previous studies suggested IgG4 levels were associated with the development of Graves' ophthalmopathy (GO). The present study investigated the role of IgG4 levels in glucocorticoid (GC) treatment in GO patients.

Methods: Sixty-nine GO patients were enrolled. Serum thyroid hormones, thyroid antibodies, IgG, IgG4, ophthalmological examinations and orbital MRI were performed. The clinical outcomes (a composite response endpoint including the clinical activity score (CAS), proptosis, vision, diplopia, and lid width) after high-dose intravenous GC treatment in 32 active moderate-to-severe GO patients were compared.

Results: A total of 33.3% of GO patients (23/69) had elevated IgG4 levels. IgG4 levels positively correlated with GO severity and activity. After GC therapy, IgG4, IgG4/IgG, vision and CAS improved significantly in GO patients. Patients with high IgG4 levels had a significantly reduced extraocular muscle area (EOMs) and better clinical outcomes than patients with normal IgG4 levels.

Conclusions: Our results suggest a possible subgroup of elevated IgG4 GO patients with more severe ophthalmopathy and better response to GC treatment compared to normal IgG4 GO patients.
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http://dx.doi.org/10.1111/cen.14493DOI Listing
May 2021

Systemic Lupus Erythematosus Complicated with Hypertrophic Cardiomyopathy: A Case Report and Literature Review.

Case Rep Cardiol 2021 11;2021:6633085. Epub 2021 Apr 11.

Department of Cardiology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China.

A 32-year-old female with systemic lupus erythematosus (SLE) for more than 7 years, and long-term treatment with cyclophosphamide, cyclosporine, methotrexate, and tacrolimus, later found to be combined with hypertrophic cardiomyopathy (HCM) for one year. The patient denied a family history of cardiomyopathy and sudden cardiac death (SCD). Echocardiography suggested that uneven thickening of the left ventricle (LV), mainly in the lower middle segment. Cardiac magnetic resonance (CMR) showed that the walls of the left ventricular (LV) were significantly thickened, as about 21 mm, mainly in the middle and lower segments. Genetic tests showed no known or suspected pathogenic variations were found and no significant enhancement in CMR, so secondary HCM was diagnosed clinically. After symptomatic treatment, the patient was discharged, and long-term follow-up was conducted. The diagnosis of HCM, which combined with SLE or second to usage of tacrolimus, was based on symptoms, echocardiography, and CMR; no endomyocardial biopsies were performed.
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http://dx.doi.org/10.1155/2021/6633085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055423PMC
April 2021

3D bioprinting of integral ADSCs-NO hydrogel scaffolds to promote severe burn wound healing.

Regen Biomater 2021 Mar 25;8(3):rbab014. Epub 2021 Apr 25.

Department of Plastic and Aesthetic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Tianhe District, Guangzhou 510630, China.

Severe burns are challenging to heal and result in significant death throughout the world. Adipose-derived mesenchymal stem cells (ADSCs) have emerged as a promising treatment for full-thickness burn healing but are impeded by their low viability and efficiency after grafting . Nitric oxide (NO) is beneficial in promoting stem cell bioactivity, but whether it can function effectively is still largely unknown. In this study, we bioprinted an efficient biological scaffold loaded with ADSCs and NO (3D-ADSCs/NO) to evaluate its biological efficacy in promoting severe burn wound healing. The integral 3D-ADSCs/NO hydrogel scaffolds were constructed via 3D bioprinting. Our results shown that 3D-ADSCs/NO can enhance the migration and angiogenesis of Human Umbilical Vein Endothelial Cells (HUVECs). Burn wound healing experiments in mice revealed that 3D-ADSCs/NO accelerated the wound healing by promoting faster epithelialization and collagen deposition. Notably, immunohistochemistry of CD31 suggested an increase in neovascularization, supported by the upregulation of vascular endothelial growth factor (VEGF) mRNA in ADSCs in the 3D biosystem. These findings indicated that 3D-ADSC/NO hydrogel scaffold can promote severe burn wound healing through increased neovascularization via the VEGF signalling pathway. This scaffold may be considered a promising strategy for healing severe burns.
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http://dx.doi.org/10.1093/rb/rbab014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071097PMC
March 2021