Publications by authors named "Mei Zhang"

1,692 Publications

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Effect of Tetrahedral Framework Nucleic Acids on Neurological Recovery via Ameliorating Apoptosis and Regulating the Activation and Polarization of Astrocytes in Ischemic Stroke.

ACS Appl Mater Interfaces 2022 Aug 11. Epub 2022 Aug 11.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, P. R. China.

Astrocytes, as the most plentiful subtypes of glial cells, play an essential biphasic function in ischemic stroke (IS). However, although having beneficial effects on stroke via promoting nerve restoration and limiting lesion extension, astrocytes can unavoidably cause exacerbated brain damage due to their participation in the inflammatory response. Therefore, seeking an effective and safe drug/strategy for protecting and regulating astrocytes in stroke is urgent. Here, we employ tetrahedral framework nucleic acid (tFNA) nanomaterials for astrocytes in stroke, considering their excellent biological properties and outstanding biosafety. In vitro, tFNA can inhibit calcium overload and ROS regeneration triggered by oxygen-glucose deprivation/reoxygenation (OGD/R), which provides a protective effect against astrocytic apoptosis. Furthermore, morphological changes such as hyperplasia and hypertrophy of reactive astrocytes are restrained, and the astrocytic polarization from the proinflammatory A1 phenotype to the neuroprotective A2 phenotype is facilitated by tFNA, which further alleviates cerebral infarct volume and facilitates the recovery of neurological function in transient middle cerebral artery occlusion (tMCAo) rat models. Moreover, the TLRs/NF-κB signaling pathway is downregulated by tFNA, which may be the potential mechanism of tFNA for protecting astrocytes in stroke. Collectively, we demonstrate that tFNA can effectively mediate astrocytic apoptosis, activation, and polarization to alleviate brain injury, which represents a potential intervention strategy for IS.
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http://dx.doi.org/10.1021/acsami.2c10364DOI Listing
August 2022

Role and mechanism of the zinc finger protein ZNF580 in foam-cell formation.

Exp Ther Med 2022 Sep 19;24(3):579. Epub 2022 Jul 19.

Department of Cardiac Thoracic Surgery, Characteristic Medical Center of People's Armed Police Force, Tianjin 300309, P.R. China.

Coronary atherosclerotic heart disease poses a significant threat to human health. The pathological basis is atherosclerosis and foam-cell formation is the key factor in the initiation of atherosclerosis. In the present study, foam cell models were established using 50 ng/ml oxidized low-density lipoprotein to stimulate cultures of THP-1 cells for 72 h. The expression of zinc finger protein 580 (ZNF580), a Cys2-His2 zinc finger protein containing 172 amino acids that was originally cloned by screening a human aortic cDNA library, was measured in foam cells and its interaction with various regulatory factors during foam-cell formation was investigated. Oil red O staining was used to observe cell morphology and intracellular lipid levels. Lentivirus transfection was employed to either overexpress or silence ZNF580 in THP-1 cells, and an inverted fluorescence microscope was used to observe the distribution of ZNF580 immunofluorescence to determine the transfection rate. RNA and total protein were extracted and the expression levels of ZNF580, CD36, peroxisome proliferator-activated receptor-γ (PPAR-γ), ATP-binding cassette transporter A1 (ABCA1) and apolipoprotein E (ApoE) were measured by reverse transcription-quantitative PCR. The protein levels were examined by western blot analysis to evaluate the interaction between ZNF580 and associated regulatory factors. ZNF580 was able to significantly increase the expression levels of ApoE and ABCA1 and significantly decrease the expression levels of CD36 and PPAR-γ, suggesting that ZNF580-mediated inhibition of foam-cell formation is associated with the PPAR-γ-CD36 signalling pathway. Based on these findings, ZNF580 may be a potential therapeutic candidate for the treatment of coronary atherosclerotic heart disease.
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http://dx.doi.org/10.3892/etm.2022.11516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353537PMC
September 2022

Data Resource Profile: A Protocol of China National Diabetic Chronic Complications Study.

Biomed Environ Sci 2022 Jul;35(7):633-640

Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai 200233, China.

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http://dx.doi.org/10.3967/bes2022.078DOI Listing
July 2022

Melanopsin retinal ganglion cells mediate light-promoted brain development.

Cell 2022 Aug 8. Epub 2022 Aug 8.

Brain Research Center, Third Military Medical University, and Chongqing Institute for Brain and Intelligence, Guangyang Bay Laboratory, Chongqing 400038, China.

During development, melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) become light sensitive much earlier than rods and cones. IpRGCs project to many subcortical areas, whereas physiological functions of these projections are yet to be fully elucidated. Here, we found that ipRGC-mediated light sensation promotes synaptogenesis of pyramidal neurons in various cortices and the hippocampus. This phenomenon depends on activation of ipRGCs and is mediated by the release of oxytocin from the supraoptic nucleus (SON) and the paraventricular nucleus (PVN) into cerebral-spinal fluid. We further characterized a direct connection between ipRGCs and oxytocin neurons in the SON and mutual projections between oxytocin neurons in the SON and PVN. Moreover, we showed that the lack of ipRGC-mediated, light-promoted early cortical synaptogenesis compromised learning ability in adult mice. Our results highlight the importance of light sensation early in life on the development of learning ability and therefore call attention to suitable light environment for infant care.
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http://dx.doi.org/10.1016/j.cell.2022.07.009DOI Listing
August 2022

Effect of Solitaire FR Stent Thrombectomy Combined with the Suction Thrombus on the Clinical Effect and Prognosis of Acute Middle Cerebral Artery Occlusion.

Evid Based Complement Alternat Med 2022 30;2022:9227790. Epub 2022 Jul 30.

School of Medicine, Anhui University of Science and Technology, Huainan 232001, Anhui, China.

To determine the curative effect and prognosis of Solitaire FR stent thrombectomy integrated with the suction thrombus on the treatment of acute middle cerebral artery occlusion (AMCAO). Based on the treatment, patients suffering from AMCAO were separated into the Solitaire FR group (Solitaire FR stent + suction thrombus) and suction group (suction thrombus). Modified thrombolysis in cerebral infarction grading, National Institutes of Health Stroke Scale (NIHSS) score, modified Rankin Scale score, and safety performance were compared between the two groups. The operation time in the suction group was obviously shorter than the Solitaire FR group ( < 0.05). Significant differences were observed in the NIHSS scores 1 week and 4 weeks after the operation between the Solitaire FR group and the suction group ( < 0.05). The NIHSS scores 1 week and 4 weeks after operation were significantly lower than those before operation ( < 0.05). NIHSS scores 1 week after operation did not show obvious difference ( > 0.05). The Solitaire FR group showed obvious lower NIHSS scores than the suction group 4 weeks after surgery ( < 0.05). Statistically obvious difference in cerebral infarction grading of modified thrombolysis between the Solitaire FR group and the suction group were observed ( < 0.05). The recanalization rate of the Solitaire FR group was obviously higher than the suction group ( < 0.05). The difference in the monthly modified Rankin Scale score was obvious ( < 0.05). The good prognosis rate of the Solitaire FR group was obviously higher than the suction group ( < 0.05). No obvious differences in the incidence of internal bleeding, reocclusion, and 3-month postoperative mortality were observed ( > 0.05). These results showed that the treatment of the Solitaire FR stent + suction thrombus in AMCAO patients has a good thrombus recanalization rate and is helpful in improving the prognosis and safety performance.
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http://dx.doi.org/10.1155/2022/9227790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356800PMC
July 2022

Elevated monocyte-to-HDL cholesterol ratio predicts post-stroke depression.

Front Psychiatry 2022 22;13:902022. Epub 2022 Jul 22.

Department of Neurology, People's Hospital of Lixin County, Bozhou, China.

Objectives: Inflammation plays an important role in the development of depression after stroke. Monocyte-to-HDL Cholesterol Ratio (MHR) recently emerged as a novel comprehensive inflammatory indicator in recent years. This study aimed to investigate whether there is a relationship between MHR levels and post-stroke depression (PSD).

Methods: From February 2019 to September 2021, patients with acute ischemic stroke (AIS) were recruited within 7 days post-stroke from the two centers and blood samples were collected after admission. The 17-item Hamilton Depression Scale (HAMD-17) was used to measure depressive symptoms at 3 months after stroke. Patients were given the DSM-V criteria for diagnosis of PSD.

Results: Of the 411 enrolled patients, 92 (22.38%) patients were diagnosed with PSD at 3-months follow-up. The results also showed significantly higher level of MHR in patients with depression [0.81 (IQR 0.67-0.87) vs. 0.61 (IQR 0.44-0.82), < 0.001] at admission than patients without depression. Multivariate logistic regression revealed that MHR (OR 6.568, 95% CI: 2.123-14.565, = 0.015) was an independent risk factor for the depression at 3 months after stroke. After adjustment for potential confounding factors, the odds ratio of PSD was 5.018 (95% CI: 1.694-14.867, = 0.004) for the highest tertile of MHR compared with the lowest tertile. Based on the ROC curve, the optimal cut-off value of MHR as an indicator for prediction of PSD was projected to be 0.55, which yielded a sensitivity of 87% and a specificity of 68.3%, with the area under the curve at 0.660 (95% CI: 0.683-0.781; = 0.003).

Conclusion: Elevated level of MHR was associated with PSD at 3 months, suggesting that MHR might be a useful Inflammatory markers to predict depression after stroke.
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http://dx.doi.org/10.3389/fpsyt.2022.902022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354071PMC
July 2022

Myocardial work: the analytical methodology and clinical utilities.

Hellenic J Cardiol 2022 Aug 2. Epub 2022 Aug 2.

The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qala Hospital, CeeLo College of Medicine, Shandong University, Shandong, China. Electronic address:

The evaluation of left ventricular (LV) systolic function is an essential part of the clinical practice of cardiology. Although left ventricular ejection fraction (LVEF) is the most validated and widely used parameter, it has fundamental limitations. LV strain is more sensitive to detect subtle myocardial dysfunction when LVEF was preserved, but it is load-dependent. Invasive left ventricular pressure-volume loop (LV-PVL) is the reliable standard to evaluate cardiac function, but its wide clinical application is limited by the risk of invasive LV pressure detection. Until the advent of non-invasive LV pressure-strain loop (LV-PSL), things have changed. LV-PSL is in good agreement with regional myocardial oxygen consumption and metabolism. Compared with traditional echocardiographic parameters or LV strain, myocardial work (MW) derived from LV-PSL is a more advanced tool that combines deformation as well as hemodynamics through integration of global longitudinal strain and non-invasive LV systolic pressure. In recent years, researches on MW are going on in full swing and show many advantages of MW. This review described the method and discussed the applications, advantages, limitations, and prospects of MW in multiple cardiovascular diseases. The goal is to provide the readers new insights for evaluating LV systolic function and promote the incorporation of MW into daily practice.
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http://dx.doi.org/10.1016/j.hjc.2022.07.007DOI Listing
August 2022

Biological variation of cardiovascular biochemical markers in patients with Type 2 Diabetes Mellitus.

Clin Chim Acta 2022 Aug 1;534:161-166. Epub 2022 Aug 1.

Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China. Electronic address:

Background: Type 2 diabetes mellitus (T2DM) is a well-established risk factor for cardiovascular diseases. We aimed to identify the biological variation of ten cardiovascular biochemical markers in T2DM patients to aid in their interpretation.

Methods: Blood samples for evaluating ten biomarkers were collected biweekly from 23 T2DM patients (10 men, 13 women) for three months. The analytical variability and variations of within-subject (CV) and between-subject (CV) levels were calculated, as well as the analytical performance specifications, reference change value (RCV), and index of individuality (II).

Results: The levels of total cholesterol (CHOL), apolipoprotein A (apoA), homocysteine (HCY), high-sensitivity troponin T (hsTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) differed between males and females (P < 0.05). The CVs or CVs of the biomakers were higher than those of healthy participants in Westgard online database, except for hsTnT. Triglyceride (TG), lipoprotein (a) [Lp(a)] and NT-proBNP had relatively high CV, CV and RCV, whereas CHOL, high-density lipoprotein cholesterol (HDL-C), apoA and HCY showed low variation. Moreover, the II of HDL-C, LP(a), apoA, HCY and hsTnT was <0.6 and other biochemical markers was between 0.6 and 1.4.

Conclusion: The cardiovascular biochemical markers in T2DM patients showed higher CV or CV, except for hsTnT. ApoA had the lowest CV and CV values. Population-based reference intervals should be used with caution in clinical decision-making for T2DM patients.
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http://dx.doi.org/10.1016/j.cca.2022.07.017DOI Listing
August 2022

An injectable thermosensitive hydrogel with a self-assembled peptide coupled with an antimicrobial peptide for enhanced wound healing.

J Mater Chem B 2022 Aug 4. Epub 2022 Aug 4.

College of Animal Science, Jilin University, Changchun, 130012, China.

A wound dressing based on a thermosensitive hydrogel shows advantages over performed traditional dressings, such as rapid reversible sol-gel-sol transition properties and the capacity to fill an irregular-shaped wound area. Herein, RA-Amps was fabricated by coupling a self-assembled peptide RADA16 with an antibacterial peptide (Amps) and incorporated into a PNIPAM hydrogel containing an MGF E peptide to develop a multi-functional composite hydrogel with thermo-response properties, good biocompatibility, good mechanical properties, and antibacterial and carrier functions for wound healing. PNI/RA-Amps is an injectable thermo-reversible system with a phase transition temperature of ∼32 °C, and exhibits a rapid reversible sol-gel-sol transition of ∼23 s, which makes it conducive to sealing the wound area and avoiding sol diffusion caused by a lengthy gel time. MGF E peptide was loaded into a hydrogel and released continuously to promote fibroblast proliferation. Rat full-thickness skin experiments revealed that the PNI/RA-Amps/E hydrogel accelerates wound healing significantly by accelerating epithelialization, the generation of new blood vessels and promoting the generation of collagen fiber compared with commercial dressing. Thus, our findings establish a new candidate for use as an injectable wound dressing for the clinical treatment of wounds.
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http://dx.doi.org/10.1039/d2tb00644hDOI Listing
August 2022

Time-resolved transcriptome analysis of Scenedesmus obliquus HTB1 under 10% CO condition.

Microb Biotechnol 2022 Aug 1. Epub 2022 Aug 1.

Institute of Marine and Environmental Technology, University of Maryland Center for Environmental Science, Baltimore, Maryland, USA.

Certain microalgal species can grow under high CO concentrations providing potential for mitigating CO pollution in flue gas produced by power plants. Microalga Scenedesmus obliquus strain HTB1 was isolated from the Chesapeake Bay and grow rapidly in a high level of CO . However, little is known about the molecular responses of HTB1 to high CO levels. Here, we investigated how HTB1 responds to 10% CO using the time-resolved transcriptome analysis. Gene expression profiles indicated that HTB1 responds quickly (in 2 h) and becomes adaptive within 12 h when exposed to 10% CO . Interestingly, certain genes of light-harvesting, chlorophyll synthesis and carbon fixation (i.e. rbcS) were up-regulated at 10% CO , and these functional responses are consistent with the increased photosynthesis efficiency and algal biomass under 10% CO . Nitrate assimilation was strongly enhanced, with amino acid biosynthesis and aminoacyl tRNA biosynthesis genes being markedly up-regulated, indicating that HTB1 actively takes up nitrogen and accelerates protein synthesis at 10% CO . Carbon metabolism including fatty acid biosynthesis and TCA cycle was enhanced at 10% CO , supporting the earlier observation of increased lipid content of Scenedesmus sp. under high CO levels. Interestingly, key genes like RuBisCO (rbcL) and carbonic anhydrase in carboxysomes did not respond actively to 10% CO , implying that exposure to 10% CO has little impact on the carbon concentrating mechanisms and CO fixation of the Calvin cycle. It appears that HTB1 can grow rapidly at 10% CO without significant metabolic changes in carbon fixation and ATP synthesis.
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http://dx.doi.org/10.1111/1751-7915.14100DOI Listing
August 2022

Evaluation of the reliability of MS1-based approach to profile naturally occurring peptides with clinical relevance in urine samples.

Rapid Commun Mass Spectrom 2022 Jul 29:e9369. Epub 2022 Jul 29.

Institute for Cell Analysis, Shenzhen Bay Laboratory, Shenzhen, China.

Rationale: Natural urinary peptides profiling are valuable indicators of kidney condition. While front-end separation limits the speed of peptidomic profiling, MS1-based results suffer from limited peptide coverage and specificity. Clinical studies on chronic kidney disease require an effective strategy to balance the trade-off between identification depth and throughput.

Methods: CKD273, a urinary proteome classifier associated with chronic kidney disease in samples from diabetic nephropathy patients were profiled in parallel using CE-MS, LC-MS and MALDI-MS, respectively. Through cross-comparison of results from MS1 of unfractionated peptides and elution-time-revolved survey MS1 as well as MS/MS in LC- and CE-MS approaches, we evaluated the contribution of false positive identification to MS1-based identification and quantitation, and analyzed the benefit of front-end separation in terms of accuracy and efficiency.

Results: In LC- and CE-MS, although MS1 data resulted in higher identifications than MS/MS, elution-time-dependent analysis revealed extensive presence of interference by non-CKD273 peptides, which would contribute up to 50% to quantitation should they be unseparated from genuine CKD273 peptides. In the absence of separation, MS1 data resulted in lower identifications and abundance pattern that significantly deviated from those by LC- or CE-MS/MS. CE showed higher identification efficiency at low sample consumption or short separation duration.

Conclusions: To ensure the reliability of MS1-based urinary peptide profiling, front-end separation should not be omitted, and elution time should be used in addition to intact mass for identification. Including MS/MS in data acquisition does not compromise the speed or identification number, while benefiting data reliability by providing real-time sequence verification.
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http://dx.doi.org/10.1002/rcm.9369DOI Listing
July 2022

Genomic Analysis of Abnormal DNAM Methylation in Parathyroid Tumors.

Int J Endocrinol 2022 16;2022:4995196. Epub 2022 Jul 16.

Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University &Shandong Provincial Qianfoshan Hospital, No 16766 Jingshi Road, Jinan, Shandong, China.

Background: Parathyroid tumors are common endocrine neoplasias associated with primary hyperparathyroidism. Although numerous studies have studied the subject, the predictive value of gene biomarkers nevertheless remains low.

Methods: In this study, we performed genomic analysis of abnormal DNA methylation in parathyroid tumors. After data preprocessing, differentially methylated genes were extracted from patients with parathyroid tumors by using -tests.

Results: After refinement of the basic differential methylation, 28241 unique CpGs (634 genes) were identified to be methylated. The methylated genes were primarily involved in 7 GO terms, and the top 3 terms were associated with cyst morphogenesis, ion transport, and GTPase signal. Following pathway enrichment analyses, a total of 10 significant pathways were enriched; notably, the top 3 pathways were cholinergic synapses, glutamatergic synapses, and oxytocin signaling pathways. Based on PPIN and ego-net analysis, 67 ego genes were found which could completely separate the diseased group from the normal group. The 10 most prominent genes included POLA1, FAM155 B, AMMECR1, THOC2, CCND1, CLDN11, IDS, TST, RBPJ, and GNA11. SVM analysis confirmed that this grouping approach was precise.

Conclusions: This research provides useful data to further explore novel genes and pathways as therapeutic targets for parathyroid tumors.
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http://dx.doi.org/10.1155/2022/4995196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9308548PMC
July 2022

Dual-targeted enzyme-sensitive hyaluronic acid nanogels loading paclitaxel for the therapy of breast cancer.

Carbohydr Polym 2022 Oct 28;294:119785. Epub 2022 Jun 28.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address:

In this study, a CD44 and biotin receptors dual-targeted enzyme-sensitive hyaluronic acid nanogel loading paclitaxel (PTX/Bio-NG) for targeting breast cancer was constructed. Spherical nanogels with a mean particle size of 149.1 ± 1.6 nm, higher entrapment efficiency (90.17 ± 0.52 %) and drug loading (15.28 ± 0.10 %) were obtained. PTX/Bio-NG quickly released drugs under the catalysis of hyaluronidase and/or lipase. Cell studies revealed that the uptake of Bio-NG by 4T1 cells was mediated by CD44 receptor and Bio-specific receptor. Compared with PTX-loaded biotin-free NG (PTX/NG), PTX/Bio-NG had higher cytotoxicity against breast cancer cells (4T1 cells). The rats pharmacokinetic profile indicated higher AUC but lower clearance rates of PTX/NG (6.24 times and 15.96 %, respectively) and PTX/Bio-NG (6.66 times and 14.89 %, respectively) than control group (Taxol). In vivo studies showed that PTX/Bio-NG possessed excellent therapeutic efficacy in 4T1 tumor-bearing Balb/c mice, which suggest that PTX/Bio-NG could be an excellent candidate for the treatment of breast cancer.
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http://dx.doi.org/10.1016/j.carbpol.2022.119785DOI Listing
October 2022

Proteomic Analysis Reveals the Vital Role of Synaptic Plasticity in the Pathogenesis of Temporal Lobe Epilepsy.

Neural Plast 2022 11;2022:8511066. Epub 2022 Jul 11.

Department of Clinical Pharmacology, Key Laboratory of Molecular Target & Clinical Pharmacology, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, Guangdong 511436, China.

Temporal lobe epilepsy (TLE) is a chronic neurological disorder that is often resistant to antiepileptic drugs. The pathogenesis of TLE is extremely complicated and remains elusive. Understanding the molecular mechanisms underlying TLE is crucial for its diagnosis and treatment. In the present study, a lithium-pilocarpine-induced TLE model was employed to reveal the pathological changes of hippocampus in rats. Hippocampal samples were taken for proteomic analysis at 2 weeks after the onset of spontaneous seizure (a chronic stage of epileptogenesis). Isobaric tag for relative and absolute quantization (iTRAQ) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique was applied for proteomic analysis of hippocampus. A total of 4173 proteins were identified from the hippocampi of epileptic rats and its control, of which 27 differentially expressed proteins (DEPs) were obtained with a fold change > 1.5 and < 0.05. Bioinformatics analysis indicated 27 DEPs were mainly enriched in "regulation of synaptic plasticity and structure" and "calmodulin-dependent protein kinase activity," which implicate synaptic remodeling may play a vital role in the pathogenesis of TLE. Consequently, the synaptic plasticity-related proteins and synaptic structure were investigated to verify it. It has been demonstrated that CaMKII-, CaMKII-, and GFAP were significant upregulated coincidently with proteomic analysis in the hippocampus of TLE rats. Moreover, the increased dendritic spines and hippocampal sclerosis further proved that synaptic plasticity involves in the development of TLE. The present study may help to understand the molecular mechanisms underlying epileptogenesis and provide a basis for further studies on synaptic plasticity in TLE.
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http://dx.doi.org/10.1155/2022/8511066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9293557PMC
July 2022

Fibroblast growth factor 21 and bone homeostasis.

Authors:
Yan Tang Mei Zhang

Biomed J 2022 Jul 15. Epub 2022 Jul 15.

Department of Laboratory Medicine, West China Hospital, Sichuan University, No.37,Guoxue Lane, Chengdu, Sichuan, 610041,China. Electronic address:

Fibroblast growth factor 21 (FGF21), a member of the FGF subfamily, is produced primarily in the liver and adipose tissue. The main function of FGF21 is to regulate energy metabolism of carbohydrates and lipids in the body through endocrine and other means, making FGF21 have potential clinical value in the treatment of metabolic disorders. Although FGF21 and its receptors play a role in the regulation of bone homeostasis through a variety of signaling pathways, a large number of studies have reported that the abuse of FGF21 and its analogues and the abnormal expression of FGF21 in vivo may be associated with bone abnormalities. Due to limited research information on the effect of FGF21 on bone metabolism regulation, the role of FGF21 in the process of bone homeostasis regulation and the mechanism of its occurrence and development have not been fully clarified. Certainly, the various roles played by FGF21 in the regulation of bone homeostasis deserve increasing attention. In this review, we summarize the basic physiological knowledge of FGF21 and the effects of FGF21 on metabolic homeostasis of the skeletal system in animal and human studies. The information provided in this review may prove beneficial for the intervention of bone diseases.
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http://dx.doi.org/10.1016/j.bj.2022.07.002DOI Listing
July 2022

Efficacy of Traditional Chinese Exercise in Improving Gait and Balance in Cases of Parkinson's Disease: A Systematic Review and Meta-analysis.

Front Aging Neurosci 2022 30;14:927315. Epub 2022 Jun 30.

The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China.

Background: The efficacy of traditional Chinese exercise (TCE)-based intervention in the improvement of motor function in patients with Parkinson's disease (PD) is controversial. The present study aimed to assess the effects of TCE on balance and gait outcomes, as well as motor symptoms in individuals with PD, and evaluate potential discrete moderators such as TCE dosage-related variables.

Method: PubMed, Embase, Cochrane's Library, Web of Science, Medline, and Scopus were systematically searched from their dates of inception to February 2022. All studies were randomized controlled trials (RCTs) of TCE-based interventions for PD. The treatment effects were estimated using a random-effect meta-analysis model with standardized mean differences (Hedges' g). The Physiotherapy Evidence Database was used to evaluate the methodological quality of the study.

Result: Fifteen studies involving a total of 873 participants were included in the final analysis. The meta-analytic findings revealed significant improvements in balance outcomes [Berg Balance Scales (BBS) ( = 0.83, 95% CI = 0.37-1.29, = 0.000, I = 84%), time up and go (TUG) ( = -0.80, 95% CI = -1.13- -0.47, = 0.000, I = 81%), and the one legged blind balance test ( = 0.49, 95% CI = 0.13-0.86, = 0.01, I = 10%)], as well as gait outcomes [gait velocity ( = 0.28, 95% CI = 0.02-0.54, = 0.04, I = 64%), 6-min walking test (6MWT) ( = 0.32, 95% CI 0.01-0.62, = 0.04, = 15%), stride length ( = 0.25, 95% CI = 0.08-0.41, = 0.003, I = 42%)], and motor symptoms [Unified Parkinson's Disease Rating Scale part III (UPDRS-III) ( = -0.77, 95% CI = -1.06- -0.48, = 0.000, I = 76%)]. However, cadence ( = -0.03) and step length ( = 0.02) did not differ significantly. The moderator shows that the effects of TCE on BBS and gait velocity were moderated by Pedro score, exercise type, control group type, and number of sessions. Meta-regression found that TCE (exercise duration, number of sessions, and session duration) was significantly associated with improved UPDRS-III and BBS scores.

Conclusion: These findings provide evidence for the therapeutic benefits of TCE as an adjunct therapy for patients with PD. TEC dosage (high-intensity long sessions) may moderate some favorable effects.

Systematic Review Registration: PROSPERO, identifier CRD42022314686.
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http://dx.doi.org/10.3389/fnagi.2022.927315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9285003PMC
June 2022

β-cell function and insulin sensitivity contributions on incident diabetes in patients with endogenous Cushing's syndrome.

Diabetes Res Clin Pract 2022 Jul 14;190:109994. Epub 2022 Jul 14.

Department of Endocrinology, the First Affiliated Hospital with Nanjing Medical University, Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China. Electronic address:

Objective: To evaluate the relative contributions of β-cell function and insulin sensitivity on the deterioration of glucose tolerance from OGTT in patients with endogenous CS.

Methods: We retrospectively analyzed the data of 60 patients with CS and determined the glucose metabolism and β-cell function through OGTT. Their general characteristics were retrieved. A series of parameters for assessing insulin sensitivity and β-cell function was calculated. The logistic regression model was used to investigate insulin sensitivity and β-cell function contributions on incident diabetes.

Results: Of the 60 patients with CS, 10 (16.7%), 21 (35%), and 29 (48.3%) were classified as CS/ normal glucose tolerance (NGT), CS/prediabetes, and CS/diabetes mellitus (DM). Compared with the HCs, the CS/NGT patients had higher HOMA-IR and lower ISI-Matsuda but with a compensatory increase in HOMA-β. Significant decreasing trends were observed in HOMA-β, AUC and ΔI/ΔG among CS/NGT, CS/prediabetes and CD/DM groups. The OR of incident diabetes compared with the high AUC/high ISI group was significant in the low AUC/high ISI group.

Conclusion: Impairment of the β-cell function had a more profound effect on incident diabetes than decreased insulin sensitivity. An approach based on an OGTT has utility for diagnosing dysglycaemia and β-cell dysfunction in patients with CS.
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http://dx.doi.org/10.1016/j.diabres.2022.109994DOI Listing
July 2022

Efficacy and Safety of Dupilumab Versus Omalizumab in Chronic Rhinosinusitis With Nasal Polyps and Asthma: EVEREST Trial Design.

Am J Rhinol Allergy 2022 Jul 15:19458924221112211. Epub 2022 Jul 15.

Sanofi, Bridgewater, New Jersey, USA.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma are chronic type 2 inflammatory diseases that are frequently associated with each other. Dupilumab inhibits the dual signaling pathways of interleukin (IL)-4 and IL-13, which are key and central drivers of type 2 inflammation in CRSwNP. Omalizumab blocks the action of immunoglobulin E. Head-to-head studies are required to investigate the comparative efficacy and safety of these interventions. EVEREST (EValuating trEatment RESponses of dupilumab vs omalizumab in Type 2 patients) trial is designed to evaluate whether the efficacy of dupilumab is superior to omalizumab in treating patients with CRSwNP and comorbid asthma (ClinicalTrials.gov Identifiers: NCT04998604).

Objective: Here, we describe the EVEREST study design to compare the efficacy and safety of dupilumab compared to omalizumab over 24 weeks of treatment in patients with severe CRSwNP and comorbid asthma.

Methods: EVEREST is a global, phase 4 multicenter, randomized (1:1), double-blind, active-controlled trial. Approximately 422 adult patients with severe CRSwNP, symptoms of nasal congestion and loss of smell, and coexisting asthma will be recruited across 15 countries. The primary objective is to assess the efficacy of dupilumab compared to omalizumab in reducing the nasal polyp size and improving the sense of smell. The key secondary objectives are to evaluate the comparative efficacy in improving CRSwNP symptoms (eg, nasal congestion) and lung function. The safety will be evaluated in terms of treatment-emergent adverse events (AEs), serious AEs, and AEs of special interest.

Conclusions: EVEREST is the first head-to-head trial assessing the comparative efficacy and safety of 2 biologics in patients with severe CRSwNP and comorbid asthma. The study will provide evidence to help optimize treatment plans for patients that suffer from severe CRSwNP and comorbid asthma.
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http://dx.doi.org/10.1177/19458924221112211DOI Listing
July 2022

Influence of neutrophil-to-lymphocyte ratio and mean platelet volume on severity and short-term prognosis of acute ischemic stroke.

Am J Transl Res 2022 15;14(6):4066-4073. Epub 2022 Jun 15.

Department of Neurology, First Affiliated Hospital of Anhui University of Science and Technology, First People's Hospital of Huainan No. 203, Huaibin Road, Tianjia'an District, Huainan 232007, Anhui Province, China.

Objective: To investigate the influence of neutrophil-to-lymphocyte ratio (NLR) and mean platelet volume (MPV) on the severity and short-term prognosis of acute ischemic stroke (AIS).

Methods: A retrospective analysis was made on 188 AIS patients treated in our hospital from June 2019 to June 2021. They were divided into mild stroke group and severe stroke group based on NIHSS score. In view of the modified Rankin score (mRS) on 14th day after stroke, patients were divided into good prognosis group and bad prognosis group. The clinical data, NLR and MPV data of each group were compared, and the independent risk factors of short-term poor prognosis of AIS patients were analyzed by multivariate Logistic regression.

Results: NLR and MPV in patients with mild stroke were lower than those with severe stroke (P<0.05). In addition, NLR and MPV of patients with good prognosis were lower than those with poor prognosis (P<0.05). Regression analysis revealed that high NLR and MPV were independent predictors of short-term poor prognosis of AIS patients. The AUC of NLR in predicting the poor prognosis of patients after 14 days of stroke was 0.904, and the specificity and sensitivity were 70.55% and 97.62%. A. AUC of MPV was 0.904, and the specificity and sensitivity were 92.47% and 85.71%. B. Pearson correlation analysis revealed that NLR was positively correlated with MPV (r=0.452, P<0.001).

Conclusion: The elevation of NLR and MPV may be independent risk factors of AIS, but it is related to the severity of stroke and short-term prognosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9274605PMC
June 2022

Development of monoclonal antibody based IgG and IgM ELISA for diagnosis of severe fever with thrombocytopenia syndrome virus infection.

Braz J Infect Dis 2022 Jul 11;26(4):102386. Epub 2022 Jul 11.

Guizhou Provincial People's Hospital, Guiyang, China; NHC Key Laboratory of Pulmonary Immunological Diseases, Guizhou Provincial People's Hospital, Guiyang, China. Electronic address:

Introduction: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a newly emerged virus that poses a great threat to human health because of high fatality rate.

Methods: To develop sensitive and specific sero-diagnostic systems for SFTSV infections, monoclonal antibodies (MAbs) against recombinant SFTSV nucleocapsid (rSFTSV-N) protein were developed by immunizing BALB/C mice with rSFTSV-N protein and fusing the spleen cells with SP2/0 myeloma cells. Three hybridoma cell lines secreting MAbs against rSFTSV-N were obtained. MAb based IgG sandwich enzyme linked immunosorbent assay (ELISA) and IgM capture ELISA systems were established by using the newly developed MAbs. One hundred fifteen clinical suspected SFTS patients serum samples were used to evaluate the newly established systems by comparing with the total antibody detecting sandwich ELISA system and indirect ELISA systems.

Results: The MAbs based sandwich IgG ELISA was perfectly matched with that of the total antibody sandwich ELISA and the indirect IgG ELISA. IgM capture ELISA results perfectly matched with that of the total antibody sandwich ELISA while detecting eight additional positive samples missed by the indirect IgM ELISA.

Conclusions: The MAbs against rSFTSV-N protein offer new tools for SFTSV studies and our newly developed MAb-based IgG and IgM capture ELISA systems would offer safe and useful tools for diagnosis of SFTS virus infections and epidemiological investigations.
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http://dx.doi.org/10.1016/j.bjid.2022.102386DOI Listing
July 2022

Pregnancy and Adverse Obstetric Outcomes After Hysteroscopic Resection: A Systematic Review and Meta-Analysis.

Front Surg 2022 27;9:889696. Epub 2022 Jun 27.

School of Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China.

Objective: Although the randomized controlled trial (RCT) of the efficacy of hysteroscopic resection in women with uterine septum has not shown any significant correlation in recent research, motivation for deeper study remains insufficient. In this study, the objective was to determine pregnancy-related outcomes, along with adverse obstetric outcomes, following hysteroscopic resection and also to determine whether women with hysteroscopic resection bear the same outcomes as women with normal uterine cavities.

Search Methods: From January 1995 to February 2022, a systematic literature review was conducted to identify all studies published concerning the gestation outcomes of women with and without hysteroscopic resection while comparing the gestation outcomes of women after hysteroscopic resection and with a normal uterine cavity. Our primary outcome was the live birth rate (LBR). The secondary outcomes were term delivery, preterm delivery, spontaneous miscarriage, malpresentation, cesarean section, and other adverse obstetric outcomes.

Results: 22 studies were included in this meta-analysis. The control groups of 14 studies were treated women, and the control groups of the other 8 studies were patients bearing a normal uterine cavity. Hysteroscopic resection was related to a higher rate of term delivery (OR = 2.26, 95% CI, 1.26-4.05), and a lower rate of spontaneous abortion (OR = 0.50, 95% CI, 0.27-0.93), and a lower rate of malpresentation (OR = 0.31, 95% CI, 0.19-0.50). Nevertheless, in comparison with the normal uterus group, the rates of preterm birth, cesarean section, and postpartum hemorrhage after resection did not return to normal levels.

Conclusion: Hysteroscopic resection can effectively reduce the risk of abortion and malpresentation in patients possessing a uterine septum while increasing the term delivery rate. Although well-designed RCTs should confirm our meta-analysis, it still bears recommending to patients.
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http://dx.doi.org/10.3389/fsurg.2022.889696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271824PMC
June 2022

Upregulation of SQLE Contributes to Poor Survival in Head and Neck Squamous Cell Carcinoma.

Int J Biol Sci 2022 16;18(9):3576-3591. Epub 2022 May 16.

Key laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, 98West 5th Road, Xi'an, Shaanxi 710004, China.

Recently, increasing attention has been paid to the role of Squalene epoxidase (SQLE) in several types of cancers. However, its functional role in tumor progression of head and neck squamous cell carcinoma (HNSCC) is still unclear. We performed bioinformatic analyses and relative experiments to assess the potential mechanism of SQLE-mediated HNSCC malignancy. And the results showed that SQLE was significantly upregulated in tumor samples compared with peritumor samples. Mechanistically, miR-584-5p downregulation may lead to the upregulation of SQLE in HNSCC. Moreover, high SQLE expression in HNSCC was associated with TNM stage, distant metastasis, and poor survival, indicating that SQLE be involved in the progression of HNSCC. Furtherly, SQLE boosted proliferation, migration, invasion of HNSCC cells and . Bioinformatic studies showed that PI3K/Akt signaling participated in HNSCC progression mediated by SQLE overexpression, which is confirmed by and analysis. Particularly, treatment with terbinafine, an inhibitor of SQLE widely used in the treatment of fungal infections, showed a therapeutic influence on HNSCC. Our findings demonstrate that SQLE plays a vital role in HNSCC progression, providing research evidence for SQLE as a prospective HNSCC therapeutic target and for terbinafine as a candidate drug of HNSCC treatment in the future.
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http://dx.doi.org/10.7150/ijbs.68216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9254471PMC
July 2022

Association Between Urinary Sodium and Potassium Excretion and Blood Pressure Among Non-Hypertensive Adults - China, 2018-2019.

China CDC Wkly 2022 Jun;4(24):522-526

Division of NCD and Risk Factor Surveillance, National Center for Chronic and Non-communicable Disease Control and Prevention, China CDC, Beijing, China.

What Is Already Known About This Topic?: High sodium and low potassium in 24 h urinary excretion were associated with elevated blood pressure.

What Is Added By This Report?: With increasing body mass index levels, decreasing unit urinary sodium excretion was more effective in reducing systolic and diastolic blood pressure, and increasing unit urinary potassium excretion was more effective in reducing diastolic blood pressure.

What Are The Implications For Public Health Practice?: Reducing sodium and increasing potassium intake was more effective in reducing blood pressure in overweight and obese non-hypertensive adults compared to underweight and normal weight adults.
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http://dx.doi.org/10.46234/ccdcw2022.066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9257692PMC
June 2022

Efficacy and safety of potassium-competitive acid blockers versus proton pump inhibitors as Helicobacter pylori eradication therapy: a meta-analysis of randomized clinical trials.

Clinics (Sao Paulo) 2022 Jul 7;77:100058. Epub 2022 Jul 7.

Gastroenterology Department, Xuanwu Hospital Capital Medical University, Beijing, China. Electronic address:

Background And Aims: Potassium-Competitive Acid Blockers (P-CABs) have been used in Helicobacter pylori (H. pylori) eradication therapies in recent years. However, the efficacy and safety of P-CABs compared to Proton-Pump Inhibitors (PPIs) in this setting remain controversial.

Methods: The efficacy and safety of P-CABs and PPIs for H. pylori eradication were compared in a meta-analysis based on a systematic literature search of major electronic databases for relevant Randomized Controlled Trials (RCTs).

Results: Seven studies and 1,168 patients were included. The pooled eradication rate determined by Intention-To-Treat (ITT) analysis was 90.2% for P-CAB-based and 75.5% for PPI-based triple therapy (pooled RR [95% CI] = 1.17 [1.08-1.28], p < 0.001). The Per-Protocol (PP) analysis also demonstrated significant superiority of P-CABs (pooled eradication rate = 92.4% vs. 77.8%; pooled RR [95% CI] = 1.14 [1.03-1.26], p < 0.01). In a subgroup evaluation, P-CABs were significantly better than PPIs as a first-line eradication therapy, in both the ITT analysis (pooled eradication rate = 91.8% vs. 76.4%; pooled RR [95% CI] = 1.18 [1.10-1.28], p < 0.0001) and the PP analysis (pooled eradication rate = 93.0% vs. 78.6%; pooled RR [95% CI] = 1.13 [1.02-1.26], p < 0.05). However, P-CABs were not superior to PPIs when administered as salvage therapy, as determined in the ITT (75.0% vs. 66.0%, pooled RR [95% CI] = 1.11 [0.69-1.78], p = 0.66) and PP (85.7% vs. 70.0%, pooled RR [95% CI] = 1.20 [0.82-1.75], p = 0.34) analyses. In a subgroup analysis limited to Japanese patients, both the ITT analysis (pooled eradication rate = 89.6% vs. 73.9%; RR [95% CI] = 1.21 [1.14-1.29], p < 0.01) and the PP analysis (pooled eradication rate = 92.0% vs. 75.7%; RR [95% CI] = 1.18 [1.06-1.32], p < 0.01) showed that P-CABs were significantly superior compared to PPIs as triple eradication therapy. However, in the subgroup analysis of patients from other countries, there was no significant difference in either the ITT analysis (pooled eradication rate = 93.8% vs. 85.2%; RR [95% CI] = 1.10 [0.99-1.22], p = 0.07) or PP analysis (pooled eradication rate = 95.0% vs. 90.8%; RR [95% CI] = 1.05 [0.98-1.14], p = 0.17). The incidence of adverse events associated with the two regimens did not significantly differ (P-CABs vs. PPIs: 33.6% vs. 40.0%; RR [95% CI] = 0.84 [0.71‒1.00], p = 0.05). The incidence of serious adverse events and dropout rate due to adverse events also did not differ (p = 0.44 and p = 0.67, respectively).

Conclusions: The efficacy of P-CAB-based triple therapy is superior to that of PPI-based triple therapy as a first-line approach to H. pylori eradication, particularly in Japanese patients. As salvage therapy, the efficacy of the two treatments did not significantly differ. The tolerability of P-CAB-based and PPI-based triple therapy was comparable, as was the incidence of adverse events.
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http://dx.doi.org/10.1016/j.clinsp.2022.100058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9278030PMC
July 2022

Ultrasensitive electrochemiluminescence aptasensor based on ABEI reduced silver nanoparticles for the detection of profenofos.

Sci Total Environ 2022 Jul 5:157184. Epub 2022 Jul 5.

Food Toxicology and Contaminants Dept., Division of Food Industries and Nutrition, National Research Centre, 33 El-Bohouth St., Dokki, Cairo 12622, Egypt.

An ultrasensitive electrochemiluminescence (ECL) aptasensor for detection of profenofos was constructed by the reducibility and chemiluminescence property of N-(aminobutyl)-N-(ethylisoluminol) (ABEI). ABEI was used to reduce silver nitrate (AgNO) to silver nanoparticles (AgNPs), which could be adsorbed on the lattice of graphene oxide (GO) to form ABEI-AgNPs-GO complex. This compound could achieve excellent luminescence. The aptamer (Apt) modified (5') by sulfhydryl groups could be immobilized on AgNPs to capture profenofos. When profenofos was present, the ECL signal of the aptasensor would be weakened. To further demonstrate the successful construction of the aptasensor, cyclic voltammetry tests were performed on an electrochemical workstation and an ECL analyzer, respectively. The standard curve and specificity experiment both showed that the sensor had the advantages of low limit of detection (LOD) and good specificity. Under the optimal conditions, the aptasensor had a good linear response for profenofos in the range of 1 × 10-1 × 10 ng/mL. It also had a LOD of 6.7 × 10 ng/mL and a correlation coefficient (R) of 0.9991. The aptasensor had been successfully applied to the detection of profenofos in vegetables. The recovery range of the proposed ECL aptasensor was 98 % ~ 107.4 %.
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http://dx.doi.org/10.1016/j.scitotenv.2022.157184DOI Listing
July 2022

Corrigendum to "Gax gene transfer inhibits vascular remodeling induced by adventitial inflammation in rabbits" [Atherosclerosis 212(2) (2010) 398-405].

Atherosclerosis 2022 Jul 4. Epub 2022 Jul 4.

The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University, Qilu Hospital, Jinan, Shandong, 250012, China. Electronic address:

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http://dx.doi.org/10.1016/j.atherosclerosis.2022.06.1024DOI Listing
July 2022

The effects of glucagon-like peptide-1 receptor agonists on adipose tissues in patients with type 2 diabetes: A meta-analysis of randomised controlled trials.

PLoS One 2022 7;17(7):e0270899. Epub 2022 Jul 7.

Department of Endocrinology, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, China.

Aims: Glucagon‑like peptide 1 receptor agonist (GLP-1RA) treatment can improve adipose distribution. We performed this meta-analysis to investigate whether GLP-1RAs preferentially reduce visceral adipose tissue (VAT) over subcutaneous adipose tissue (SAT) in patients with type 2 diabetes.

Materials And Methods: We searched MEDLINE and the Cochrane Library for randomised controlled trials explicitly reporting changes in VAT and SAT. A random-effects model was performed to estimate the weighted mean difference (MD) for VAT and SAT. Heterogeneity among the studies was assessed using I2 statistics, and publication bias was assessed using Egger's tests. Meta-regression was performed to identify the correlation between changes in adipose tissues and changes in body weight and glycated haemoglobin level.

Results: Ten trials with 924 patients were enrolled in the meta-analysis. GLP-1RA treatment led to similar absolute area (cm2) reductions in VAT (MD -21.13 cm2, 95% CI [-29.82, -12.44]) and SAT (MD -22.89 cm2, 95% CI [-29.83, -15.95]). No significant publication bias was detected, and this result was stable in the sensitivity and subgroup analyses. Moreover, GLP-1RA treatment resulted in a greater reduction in VAT and SAT in the subgroup with a greater reduction in body weight. The absolute area reduction in VAT was significantly correlated with the reduction in body weight (r = 6.324, p = 0.035).

Conclusions: GLP-1RA treatment leads to significant and similar absolute reductions in VAT and SAT, and the reduction in adipose tissues may be correlated with the reduction in body weight.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0270899PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262225PMC
July 2022

Multifunctional 3D sponge-like macroporous cryogel-modified long carbon fiber reinforced polyetheretherketone implants with enhanced vascularization and osseointegration.

J Mater Chem B 2022 Jul 20;10(28):5473-5486. Epub 2022 Jul 20.

Key Laboratory of High Performance Plastics, Ministry of Education, College of Chemistry, Jilin University, Changchun 130012, P. R. China.

Long carbon fiber reinforced polyetheretherketone (LCFRPEEK), a newly developed high-performance composite material, is being investigated as a possible orthopedic implant. However, its inability of angiogenesis and osseointegration after implantation makes it difficult for use as a long-term osteogenic fixation implant, which limits its scope of clinical application. Therefore, we design and construct a multifunctional 3D sponge-like macroporous cryogel to modify sulfonated LCFRPEEK using a cryogelation method based on free radical photopolymerization. The cryogel is mainly composed of graphene oxide-hydroxyapatite (GO-HAP) nanocomposites and gelatin methacrylate/polyethylene glycol diacrylate (GelMA/PEGDA). The results reveal that the multifunctional LCFRPEEK implant shows excellent biocompatibility and osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) due to the incorporation of HAP nanoparticles into GO-HAP nanocomposites. Systematic animal studies further confirm that the multifunctional surface improves the bone remodeling and osseointegration of the LCFRPEEK implant. Additionally, the characteristic 3D sponge-like macroporous structures of cryogels promote the ingrowth and migration of human umbilical vein endothelial cells (HUVECs) and GO in the GO-HAP also boosts HUVEC migration and tube formation showing that they are beneficial for vascularization during osteogenesis. Therefore, the developed 3D sponge-like macroporous GelMA/PEGDA/GO-HAP cryogel fabricated on sulfonated LCFRPEEK implants with enhanced angiogenesis and osseointegration capabilities has great potential for clinical use as an orthopedic implant material.
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http://dx.doi.org/10.1039/d2tb00725hDOI Listing
July 2022

Association between physical activity energy expenditure and cardiometabolic risk factor clustering among Chinese adults in 2015.

Sports Med Health Sci 2022 Jun 12;4(2):105-111. Epub 2022 Apr 12.

National Center for Chronic and Non-communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.

To understand the association between cardiometabolic risk factor (CMRF) clustering and physical activity (PA) levels, we included 86520 Chinese adults aged 18-64 years having at least one CMRF (hypertension, diabetes, dyslipidemia, or obesity) from the China Chronic Disease and Nutrition Surveillance survey in 2015, a nationally and provincially representative investigation with a multistage clustering sampling design. Self-reported PA information was collected with the Global Physical Activity Questionnaire through face-to-face interviews. In view of the obesity epidemic in CMRF patients, PA energy expenditure (PAEE) per kilogram body weight was used, and was defined into four categories: (i) inactivity: 0 ​kJ/kg/day; (ii) low activity: 0-5 ​kJ/kg/day; (iii) moderate activity: 6-11 ​kJ/kg/day; and (iv) vigorous activity: ≥ 12 ​kJ/kg/day. The estimated weighted prevalence (95% confidence interval []) of having 1, 2, 3, and 4 CMRFs was 60.57% (59.48%-61.67%), 28.10% (27.40%-28.79%), 9.82% (9.22%-15.42%) and 1.50% (1.37%-1.63%), respectively. The rate (95%) of inactivity, low activity, moderate activity, and vigorous activity was 34.52% (32.69%-36.35%), 22.22% (21.37%-23.37%), 15.98% (15.38%-16.58%) and 27.28% (26.02%-28.53%), respectively. For those having 2, 3 and 4 CMRFs (compared to those having 1 CMRF), the adjusted odds ratio (95%) for moderate activity and vigorous activity were 0.91 (0.85-0.98) and 0.92 (0.85-0.99), 0.87 (0.80-0.95) and 0.84 (0.77-0.92), and 0.77 (0.67-0.89) and 0.85 (0.72-1.00), respectively. In conclusion CMRF clustering was a pandemic among Chinese adults in 2015 and was inversely associated with PA level. PAEE (in kJ/kg/day) may be introduced into PA management practice, especially for populations with high body weight.
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http://dx.doi.org/10.1016/j.smhs.2022.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9219286PMC
June 2022

A novel antibody-TCR (AbTCR) T-cell therapy is safe and effective against CD19-positive relapsed/refractory B-cell lymphoma.

J Cancer Res Clin Oncol 2022 Jul 1. Epub 2022 Jul 1.

Eureka Therapeutics, Inc., Emeryville, CA, USA.

Purpose: A barrier to widespread adoption of chimeric antigen receptor (CAR) T-cell therapy is toxicity. To address this, we recently developed a novel antibody-T-cell receptor (AbTCR) platform (trademarked as ARTEMIS) which was designed to leverage natural immune receptor signaling and regulation. The AbTCR platform includes a gamma/delta (γδ) TCR-based AbTCR construct and a separate co-stimulatory molecule, both engineered to be tumor-specific. Here, we aim to assess the safety and preliminary efficacy of a CD19-directed AbTCR T-cell therapy.

Methods: We generated ET019003 T cells, which are autologous CD19-directed AbTCR T cells. We then conducted an early phase I study to evaluate the safety and preliminary efficacy of ET019003 T cells for the treatment of CD19-positive relapsed/refractory (r/r) B-cell lymphoma.

Results: Sixteen patients enrolled in this study and 12 patients were treated. Of the 12 patients treated, 6 patients (50%) achieved a complete response (CR), and 4 (33%) achieved a partial response (PR) (best objective response rate [ORR] of 83%). CRs were durable, including 2 patients with ongoing CRs for 22.7 months and 23.2 months. ET019003 was well-tolerated with an attractive safety profile. No patients experienced severe (grade ≥ 3) cytokine release syndrome (CRS) and only 1 patient experienced immune effector cell-associated neurotoxicity syndrome (ICANS) of any grade. Significant elevations of cytokine levels were not seen, even in patients with marked expansion of ET019003 T cells.

Conclusion: This study provides initial clinical validation of the AbTCR platform as a novel cancer treatment with the potential to provide durable clinical benefit with low toxicity.

Trial Registration: NCT03642496; Date of registration: August 22, 2018.
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http://dx.doi.org/10.1007/s00432-022-04132-9DOI Listing
July 2022
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