Publications by authors named "Yuliang Zhao"

471 Publications

Pediatric Acute Kidney Injury Survivors Need Risk Stratification and Individualized Follow-Up.

J Am Soc Nephrol 2021 Sep 16. Epub 2021 Sep 16.

Division of Nephrology, West China Hospital of Sichuan University, Chengdu, China.

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http://dx.doi.org/10.1681/ASN.2021060753DOI Listing
September 2021

Diabetes in Patients With Heart Failure With Reduced Ejection Fraction During Hospitalization: A Retrospective Observational Study.

Front Endocrinol (Lausanne) 2021 12;12:727188. Epub 2021 Aug 12.

Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China.

Background: Diabetes is prevalent worldwide including hospitalized patients with heart failure with reduced ejection fraction (HFrEF). This retrospective study investigated the association of diabetes with in-hospital adverse events in patients with HFrEF.

Methods: We analyzed data from electronic medical records of patients hospitalized with HFrEF in West China Hospital of Sichuan University from January 1, 2011, to September 30, 2018. Propensity score matching balances the baseline characteristics between patients with and without diabetes. Logistic and Poisson regressions investigated the association of diabetes with risks of intubation, cardiogenic shock, acute kidney injury (AKI), intensive care unit (ICU) admission and death during hospitalization, and length of ICU and hospital stay in the matched cases.

Results: Among 6,022 eligible patients (including 1,998 with diabetes), 1,930 patient pairs with and without diabetes were included by propensity score matching. Patients with diabetes had a significantly increased risk of intubation (odds ratio [OR], 2.69; 95% confidence interval [CI], 2.25-3.22; <0.001), cardiogenic shock (OR, 2.01; 95% CI, 1.72-2.35; <0.001), AKI at any stage (OR, 1.67; 95% CI, 1.44-1.94; <0.001), ICU admission (OR, 1.89; 95% CI, 1.65-2.15; <0.001), and death (OR, 4.25; 95% CI, 3.06-6.02; <0.001) during hospitalization. Patients with diabetes had longer ICU (median difference, 1.47 days; 95% CI, 0.96-2.08; <0.001) and hospital stay (2.20 days; 95% CI, 1.43-2.86; <0.001) than those without diabetes. There were potential subgroup effects by age and by hypertension, and CKD status on the association of diabetes with risk of AKI at any stage; and subgroup effects by sex and CKD status on the association of diabetes with risk of intubation. The increase in length of hospital stay was larger in patients without hypertension than those with hypertension.

Conclusions: Among patients with HFrEF, those with diabetes have a worse prognosis, including a higher risk of in-hospital intubation, cardiogenic shock, AKI, ICU admission and death during hospitalization, and longer ICU and hospital stay.
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http://dx.doi.org/10.3389/fendo.2021.727188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387582PMC
August 2021

Ultrafast Growth of Large Area Graphene on Si Wafer by a Single Pulse Current.

Molecules 2021 Aug 15;26(16). Epub 2021 Aug 15.

Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing 100190, China.

Graphene has many excellent optical, electrical and mechanical properties due to its unique two-dimensional structure. High-efficiency preparation of large area graphene film is the key to achieve its industrial applications. In this paper, an ultrafast quenching method was firstly carried out to flow a single pulse current through the surface of a Si wafer with a size of 10 mm × 10 mm for growing fully covered graphene film. The wafer surface was firstly coated with a 5-nm-thick carbon layer and then a 25-nm-thick nickel layer by magnetron sputtering. The optimum quenching conditions are a pulse current of 10 A and a pulse width of 2 s. The thus-prepared few-layered graphene film was proved to cover the substrate fully, showing a high conductivity. Our method is simple and highly efficient and does not need any high-power equipment. It is not limited by the size of the heating facility due to its self-heating feature, providing the potential to scale up the size of the substrates easily. Furthermore, this method can be applied to a variety of dielectric substrates, such as glass and quartz.
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http://dx.doi.org/10.3390/molecules26164940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401260PMC
August 2021

Reliability of monitoring acid-base and electrolyte parameters through circuit lines during regional citrate anticoagulation-continuous renal replacement therapy.

Nurs Crit Care 2021 Aug 11. Epub 2021 Aug 11.

Deparment of Nephrology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Background: The current practice involves blood sampling from the circuit line to measure acid-base and electrolyte parameters during continuous renal replacement therapy (CRRT). However, there is limited evidence supporting its reliability due to the effects of anticoagulant mechanism and access recirculation associated with regional citrate anticoagulation (RCA).

Aim: To evaluate the reliability of monitoring acid-base and electrolyte parameters through circuit lines in regular and reversed connections during RCA-CRRT.

Study Design: In this prospective cohort study, we included critically ill patients receiving RCA-CRRT via a double-lumen catheter. During the second hour after CRRT initiation, we collected blood samples to monitor acid-base and electrolyte parameters and their levels were compared between samples from the circuit lines (at 0, 3, and 5 minutes) and those from the central venous catheter (CVC) line (at 0 minute). During this time, CRRT switched to the replacement state as controls.

Results: We observed 128 CRRT circuits in 60 adult patients receiving RCA-CRRT. Ninety-eight (76.6%) circuits had regular connections, while 30 (23.4%) had reversed connections. Among regular connections, no differences were observed in any acid-base or electrolyte parameters between samples from the CVC line and those from the circuit line at all time points (P > .05). Among reversed connections, ionized calcium levels were dramatically decreased at all three time points in samples from the circuit line compared with those from the CVC line (0.65 ± 0.12, 0.72 ± 0.11, and 0.78 ± 0.99 vs 0.98 ± 0.07 mmol/L, P < .001), with comparable levels of other acid-base or electrolyte parameters between the sampling patterns (P > .05).

Conclusions: Acid-base and electrolyte parameters could be reliably monitored through the circuit line during RCA-CRRT in regular connections. However, in reversed connections, pre-filter ionized calcium concentrations determined through the circuit line were lower than those determined through the CVC line.

Relevance To Clinical Practice: We suggest sampling from arterial or CVC lines rather than from the circuit line in a reversed connection during RCA-CRRT.
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http://dx.doi.org/10.1111/nicc.12696DOI Listing
August 2021

[Study on the structural changes of pharyngeal cavity after bariatric surgery in obese patients with obstructive sleep apnea].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2021 Jun;35(6):538-542

Department of Otorhinolaryngology,the Second Hospital of Hebei Medical University,Shijiazhuang,050000,China.

To study whether and how bariatric surgery changes the structure of the pharyngeal cavity in obese patients with obstructive sleep apnea(OSA). Forty-two patients who underwent laparoscopic sleeve gastrectomy were recruited. Morphological indicators(BMI, neck and waist circumference), PSG and acoustic pharyngometry indicators were evaluated pre-operatively and 3, 6, and 12 months post-operatively. All indicators including morphology, pharyngeal cavity structure and OSA severity changed significantly after surgery. Among them, BMI, neck circumference, waist circumference and AHI value were significantly reduced(<0.001), while pharyngeal cavity volume, pharynx volume, oropharyngeal junction area, glottis area and LSaO2 increased significantly(<0.001). The results of multiple comparisons showed that BMI, neck and waist circumference decreased significantly in the first 6 months, and no further decline occurred during 6 to 12 months postoperatively. The decrease in AHI and LSaO2 mainly occurred within the first 3 months postoperatively, while there was no statistically significant difference in these two indicatiors between 3 months vs. 6 months, 6 months vs. 12 months postoperatively. The area of the oropharyngeal junction increased significantly within 0 to 3 months after surgery, while the volume of the pharyngeal cavity and the area of the glottis increased at 6 months and 12 months after surgery. Bariatric surgery can significantly reduce body weight and reduce fat accumulation in the neck. It can also enlarge the volume and cross-sectional area of the pharyngeal cavity, and improve upper airway obstruction, therefore reduce the symptoms of sleep apnea in obese patients with OSA to a certain extent.
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http://dx.doi.org/10.13201/j.issn.2096-7993.2021.06.012DOI Listing
June 2021

Highly Stable Silica-Coated Bismuth Nanoparticles Deliver Tumor Microenvironment-Responsive Prodrugs to Enhance Tumor-Specific Photoradiotherapy.

J Am Chem Soc 2021 Aug 22;143(30):11449-11461. Epub 2021 Jul 22.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics and National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing 100049, P. R. China.

Radiosensitizers are agents capable of amplifying injury to tumor tissues by enhancing DNA damage and fortifying production of radical oxygen species (ROS). The use of such radiosensitizers in the clinic, however, remains limited by an insufficient ability to differentiate between cancer and normal cells and by the presence of a reversible glutathione system that can diminish the amount of ROS generated. Here, to address these limitations, we design an HO-responsive prodrug which can be premixed with lauric acid (melting point ∼43 °C) and loaded around the surface of silica-coated bismuth nanoparticles (BSNPs) for cancer-specific photoradiotherapy. Particularly, silica coating confers BSNPs with improved chemical stability against both near-infrared light and X-rays. Upon photothermal heating, lauric acid is melted to trigger prodrug release, followed by its transformation into -quinone methide via HO stimulation to irreversibly alkylate glutathione. Concurrently, this heat boosts tumor oxygenation and helps relieve the hypoxic microenvironment. Following sequential irradiation by X-rays, BSNPs generate plentiful ROS, which act in combination with these events to synergistically induce cell death via DNA breakage and mitochondria-mediated apoptosis pathways, ultimately enabling effective inhibition of tumor growth with high tumor specificity and reduced side effects. Collectively, this work presents a promising approach for the improvement of other ROS-responsive proalkylating agents, while simultaneously highlighting a robust nanosystem for combining these prodrugs with photoradiosensitizers to realize precision photoradiotherapy.
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http://dx.doi.org/10.1021/jacs.1c03303DOI Listing
August 2021

X-ray-facilitated redox cycling of nanozyme possessing peroxidase-mimicking activity for reactive oxygen species-enhanced cancer therapy.

Biomaterials 2021 09 10;276:121023. Epub 2021 Jul 10.

College of Materials Science and Optoelectronic Technology, University of Chinese Academy of Sciences, Beijing, 100049, China; CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Chinese Academy of Sciences, Beijing, 100190, China; The GBA National Institute for Nanotechnology Innovation, Guangzhou, Guangdong, 510700, China.

Nanomaterials with shifting or mixed redox states is one of the most common studied nanozyme with peroxidase-like activity for chemodynamic therapy (CDT), which can decompose hydrogen peroxide (HO) of tumor microenvironment into highly toxic reactive oxygen species (ROS) by a nano-catalytic way. However, most of them exhibit an insufficient catalytic efficiency due to their dependence on catalytic condition. Herein, a potential methodology is proposed to enhance their enzymatic activity by accelerating the redox cycling of these nanomaterials with shifting or mixed redox states in the presence of X-ray. In this study, the nanocomposite consisting of SnS nanoplates and FeO quantum dots with shifting or mixed redox states (Fe/Fe) is used to explore the strategy. Under external X-ray irradiation, SnS cofactor as electron donor can be triggered to transfer electrons to FeO, which promotes the regeneration of Fe sites on the surface of the FeO. Consequently, the regenerated Fe sites react with the overexpressed HO to persistently generate ROS for enhanced tumor therapy. The designed nanocomposite displays the synergistic effects of radiotherapy and CDT. The strategy provides a new avenue for the development of artificial nanozymes with shifting or mixed redox states in precise cancer treatments based on X-ray-enhanced enzymatic efficacy.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121023DOI Listing
September 2021

The Underlying Function and Structural Organization of the Intracellular Protein Corona on Graphdiyne Oxide Nanosheet for Local Immunomodulation.

Nano Lett 2021 07 9;21(14):6005-6013. Epub 2021 Jul 9.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China.

Nanomaterial-biology interaction is the critical step in the fate of biomedical nanomedicines, influencing the consequent biological outcomes. Herein, we present two-dimensional carbon-based nanomaterials-graphdiyne oxide (GDYO) nanosheets that interact with an intracellular protein corona consisting of signal transducer and activator of transcription 3 (STAT3), inducing the reeducation of immunosuppressive macrophages. The interaction at the GDYO-STAT3 interface, driven by structure matching, hydrogen bonding, and salt bridges, simultaneously triggers the immune response in the tumor microenvironment, facilitating cancer immunotherapy. For the first time, our data reveal an interaction mechanism between the nanoparticle-protein interfaces inevitably formed inside the cells that determines the macrophage phenotype. Our results suggest that GDYO nanosheets could be applied for local immunomodulation due to their function and structural organization of the intracellular protein corona occurred inside macrophages.
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http://dx.doi.org/10.1021/acs.nanolett.1c01048DOI Listing
July 2021

Bacterial cytoplasmic membranes synergistically enhance the antitumor activity of autologous cancer vaccines.

Sci Transl Med 2021 07;13(601)

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center of Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, P. R. China.

Cancer vaccines based on resected tumors from patients have gained great interest as an individualized cancer treatment strategy. However, eliciting a robust therapeutic effect with personalized vaccines remains a challenge because of the weak immunogenicity of autologous tumor antigens. Utilizing exogenous prokaryotic constituents that act as adjuvants to enhance immunogenicity is a promising strategy to overcome this limitation. However, nonspecific stimulation of the immune system may elicit an undesirable immunopathological state. To specifically trigger sufficient antitumor reactivity without notable adverse effects, we developed an antigen and adjuvant codelivery nanoparticle vaccine based on cytoplasmic membranes (EMs) and tumor cell membranes (TMs) from resected autologous tumor tissue. Introduction of the EM into the hybrid membrane nanoparticle vaccines (HM-NPs) induced dendritic cell maturation, thus activating splenic T cells. HM-NPs showed efficacy in immunogenic CT26 colon and 4T1 breast tumor mouse models and also efficiently induced tumor regression in B16-F10 melanoma and EMT6 breast tumor mouse models. Furthermore, HM-NPs provoked a strong tumor-specific immune response, which not only extended postoperative animal survival but also conferred long-term protection (up to 3 months) against tumor rechallenge in a CT26 colon tumor mouse model. Specific depletion of different immune cell populations revealed that CD8 T and NK cells were crucial to the vaccine-elicited tumor regression. Individualized autologous tumor antigen vaccines based on effective activation of the innate immune system by bacterial cytoplasmic membranes hold great potential for personalized treatment of postoperative patients with cancer.
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http://dx.doi.org/10.1126/scitranslmed.abc2816DOI Listing
July 2021

Efficacy and safety of furosemide for prevention of intradialytic hypotension in haemodialysis patients: protocol for a multicentre randomised controlled trial.

BMJ Open 2021 07 5;11(7):e048015. Epub 2021 Jul 5.

Department of Nephrology, West China Hospital, Sichuan University/ West China School of Nursing, Sichuan University, Chengdu, Sichuan, China.

Introduction: Intradialytic hypotension (IDH) is a frequent and serious complication of maintaining haemodialysis (HD) patients and associated with subsequent cardiovascular events and higher mortality. Furosemide is commonly used in non-dialysis chronic kidney disease patients and can effectively manage the volume and blood pressure. However, these agents are often discontinued on initiation of dialysis. Two large observational studies have demonstrated that furosemide can lower the rate of IDH episodes. However, there is still no randomised controlled trial (RCT) to investigate the efficacy and safety of furosemide for prevention of IDH in HD patients. The purpose of this study was to assess the efficacy of furosemide in reducing IDH in HD patients with residual renal function.

Methods And Analysis: A two-arm, parallel, multicente RCT will be conducted at 12 hospitals in China. An estimated sample of 560 HD patients will be recruited. Eligible patients will be randomly assigned to treatment group (patients receive oral furosemide 80 mg/day; after a 2-week treatment, if their urine volume is less than 400 mL/day, the dose of furosemide is adjusted to 160 mg/day) and blank control group via a central randomisation system using 1:1 ratio. The primary outcome is the occurrence of IDH. Outcome assessors and data analysts will be blinded and participants will be asked not to reveal their allocation to assessors. The outcome analyses will be performed both on the intention-to-treat, which includes all patients randomised, and per-protocol population, which includes eligible patients who adhere to the planned treatment and follow-ups.

Ethics And Dissemination: The trial protocol has been approved by the Biomedical Research Ethics Committee of West China Hospital of Sichuan University (2019.385)Results will be presented at national and international conferences and published in peer-reviewed journals.

Trial Registration Number: ChiCTR2000039724.
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http://dx.doi.org/10.1136/bmjopen-2020-048015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258570PMC
July 2021

Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy children and adolescents: a double-blind, randomised, controlled, phase 1/2 clinical trial.

Lancet Infect Dis 2021 Jun 28. Epub 2021 Jun 28.

Sinovac Life Sciences, Beijing, China. Electronic address:

Background: A vaccine against SARS-CoV-2 for children and adolescents will play an important role in curbing the COVID-19 pandemic. Here we aimed to assess the safety, tolerability, and immunogenicity of a candidate COVID-19 vaccine, CoronaVac, containing inactivated SARS-CoV-2, in children and adolescents aged 3-17 years.

Methods: We did a double-blind, randomised, controlled, phase 1/2 clinical trial of CoronaVac in healthy children and adolescents aged 3-17 years old at Hebei Provincial Center for Disease Control and Prevention in Zanhuang (Hebei, China). Individuals with SARS-CoV-2 exposure or infection history were excluded. Vaccine (in 0·5 mL aluminum hydroxide adjuvant) or aluminum hydroxide only (alum only, control) was given by intramuscular injection in two doses (day 0 and day 28). We did a phase 1 trial in 72 participants with an age de-escalation in three groups and dose-escalation in two blocks (1·5 μg or 3·0 μg per injection). Within each block, participants were randomly assigned (3:1) by means of block randomisation to receive CoronaVac or alum only. In phase 2, participants were randomly assigned (2:2:1) by means of block randomisation to receive either CoronaVac at 1·5 μg or 3·0 μg per dose, or alum only. All participants, investigators, and laboratory staff were masked to group allocation. The primary safety endpoint was adverse reactions within 28 days after each injection in all participants who received at least one dose. The primary immunogenicity endpoint assessed in the per-protocol population was seroconversion rate of neutralising antibody to live SARS-CoV-2 at 28 days after the second injection. This study is ongoing and is registered with ClinicalTrials.gov, NCT04551547.

Findings: Between Oct 31, 2020, and Dec 2, 2020, 72 participants were enrolled in phase 1, and between Dec 12, 2020, and Dec 30, 2020, 480 participants were enrolled in phase 2. 550 participants received at least one dose of vaccine or alum only (n=71 for phase 1 and n=479 for phase 2; safety population). In the combined safety profile of phase 1 and phase 2, any adverse reactions within 28 days after injection occurred in 56 (26%) of 219 participants in the 1·5 μg group, 63 (29%) of 217 in the 3·0 μg group, and 27 (24%) of 114 in the alum-only group, without significant difference (p=0·55). Most adverse reactions were mild and moderate in severity. Injection site pain was the most frequently reported event (73 [13%] of 550 participants), occurring in 36 (16%) of 219 participants in the 1·5 μg group, 35 (16%) of 217 in the 3·0 μg group, and two (2%) in the alum-only group. As of June 12, 2021, only one serious adverse event of pneumonia has been reported in the alum-only group, which was considered unrelated to vaccination. In phase 1, seroconversion of neutralising antibody after the second dose was observed in 27 of 27 participants (100·0% [95% CI 87·2-100·0]) in the 1·5 μg group and 26 of 26 participants (100·0% [86·8-100·0]) in the 3·0 μg group, with the geometric mean titres of 55·0 (95% CI 38·9-77·9) and 117·4 (87·8-157·0). In phase 2, seroconversion was seen in 180 of 186 participants (96·8% [93·1-98·8]) in the 1·5 μg group and 180 of 180 participants (100·0% [98·0-100·0]) in the 3·0 μg group, with the geometric mean titres of 86·4 (73·9-101·0) and 142·2 (124·7-162·1). There were no detectable antibody responses in the alum-only groups.

Interpretation: CoronaVac was well tolerated and safe and induced humoral responses in children and adolescents aged 3-17 years. Neutralising antibody titres induced by the 3·0 μg dose were higher than those of the 1·5 μg dose. The results support the use of 3·0 μg dose with a two-immunisation schedule for further studies in children and adolescents.

Funding: The Chinese National Key Research and Development Program and the Beijing Science and Technology Program.
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http://dx.doi.org/10.1016/S1473-3099(21)00319-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238449PMC
June 2021

The immediate trends in atrial electrical remodeling for paroxysmal atrial fibrillation across different modes of catheter ablation.

Clin Cardiol 2021 Jul 1;44(7):938-945. Epub 2021 Jun 1.

Department of Cardiology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.

Background: Catheter ablation has emerged as a major strategy for paroxysmal atrial fibrillation (PAF). Atrial electrical remodeling (AER) plays a critical role in the recurrence of PAF after ablation.

Hypothesis: To characterize the immediate trends of AER during ablations in patients with PAF, and assess the relationship between immediate trends and recurrence.

Methods: We performed this prospective observational study of 135 patients to investigate AER following three ablation modes: radiofrequency ablation (RFA), cryoablation (CA) and 3D mapping-guided cryoablation (3D-CA). The atrial effective refractory period (AERP) and atrial conduction time (ACT) were measured via electrophysiology before and immediately after ablation, and P-wave indices were measured via electrocardiography before and within 24 h after ablation. Follow-up visits were conducted for at least 1 year or until relapse.

Results: Different approaches of ablation caused a fairly significant increase in the shortest P-wave duration and AERP in both the proximal coronary sinus (PCS) and distal coronary sinus (DCS) but caused a shortened P-wave dispersion. No different effect was found at the AERP among the three modes. Compared to patients who received CA, among patients who received RFA, a significant reduction in total ACT and right ACT was seen. Statistically, there was a weakly positive association between changes in total ACT and early recurrence.

Conclusions: Injury during ablation for PAF was associated with an increase in the AERP but not in the ACT. Total ACT and right ACT were shorter after RFA than after CA. The increase in total ACT were slightly predictive of early recurrence.
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http://dx.doi.org/10.1002/clc.23617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259153PMC
July 2021

AI powered electrochemical multi-component detection of insulin and glucose in serum.

Biosens Bioelectron 2021 May 1;186:113291. Epub 2021 May 1.

State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang, 110000, China. Electronic address:

Multi-component detection of insulin and glucose in serum is of great importance and urgently needed in clinical diagnosis and treatment due to its economy and practicability. However, insulin and glucose can hardly be determined by traditional electrochemical detection methods. Their mixed oxidation currents and rare involvement in the reaction process make it difficult to decouple them. In this study, AI algorithms are introduced to power the electrochemical method to conquer this problem. First, the current curves of insulin, glucose, and their mixed solution are obtained using cyclic voltammetry. Then, seven features of the cyclic voltammetry curve are extracted as characteristic values for detecting the concentrations of insulin and glucose. Finally, after training using machine learning algorithms, insulin and glucose concentrations are decoupled and regressed accurately. The entire detection process only takes three minutes. It can detect insulin at the pmol level and glucose at the mmol level, which meets the basic clinical requirements. The average relative error in predicting insulin concentrations is around 6.515%, and that in predicting glucose concentrations is around 4.36%. To verify the performance and effectiveness of the proposed method, it is used to determine the concentrations of insulin and glucose in fetal bovine serum and real clinical serum samples. The results are satisfactory, demonstrating that the method can meet basic clinical needs. This multi-component testing system delivers acceptable detect limit and accuracy and has the merits of low cost and high efficiency, holding great potential for use in clinical diagnosis.
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http://dx.doi.org/10.1016/j.bios.2021.113291DOI Listing
May 2021

Combined application of pharyngeal volume and minimal cross-sectional area may be helpful in screening persons suspected of obstructive sleep apnea (OSA).

Sleep Breath 2021 May 8. Epub 2021 May 8.

Department of Otolaryngology, The second hospital of Hebei Medical University, Shijiazhuang, 050000, China.

Background: Obstructive sleep apnea (OSA) is a common disease that seriously affects human health and daily life. However, the gold standard for its diagnosis, polysomnography (PSG), is expensive resulting in inadequate diagnosis of this disease in primary clinics. Therefore, a simple and rapid method for initial screening for OSA is needed. Acoustic pharyngometry (APh) is an FDA-approved noninvasive method that is gradually being applied to screening for OSA.

Materials And Methods: In this study, we applied analysis with receiver operating characteristic (ROC) curves to explore how APh may play a greater role in the screening of subjects with suspected OSA. Patients admitted into the departments of otolaryngology at our hospital from March 2017 to May 2019 were recruited into the study. All subjects underwent PSG monitor and were separated into two groups according to the apnea-hypopnea index (AHI) from the PSG results: OSA group (AHI ≥ 5) and control group (AHI < 5). APh measurements and other indicators of the subjects, including age, height, and weight; Epworth Sleepiness Scale (ESS) score; and the pharynx examination, including the degree of tonsil enlargement and tongue hypertrophy, were also be recorded.

Results: The t-test results showed that almost all indicators except age and height have significant differences between the OSA group and control group. Subjects with OSA had greater weight, BMI, ESS, higher degree of tonsil enlargement, and tongue hypertrophy, while they had smaller minimal cross-sectional area (mCSA) and pharyngeal volume than the subjects in control group. The correlation analysis revealed that pharyngeal volume and mCSA were two helpful indicators to screen for OSA. Furthermore, we established the ROC curve and calculated the combining predictors (combining predictors = pharyngeal volume + mCSA * (- 2.347)/(- 0.225)). The area under the ROC curve (AUC) of combining predictors was 0.917 (95% CI 0.842-0.991, P < 0.001), which was higher than combinations of other two independent indicators. The cutoff point of combining predictors was found to be 59.84 (AUC = 0.917, sensitivity = 0.80, 1-specificity = 0.06, P < 0.001).

Conclusions: These findings suggest that APh is a simple, rapid, and economical detection method which may be useful in screening for OSA, especially in communities and primary clinics where PSG cannot be performed.
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http://dx.doi.org/10.1007/s11325-021-02358-4DOI Listing
May 2021

Self-Assembly of Copper-DNAzyme Nanohybrids for Dual-Catalytic Tumor Therapy.

Angew Chem Int Ed Engl 2021 06 14;60(26):14324-14328. Epub 2021 May 14.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, China.

Despite the great efforts of using DNAzyme for gene therapy, its clinical success is limited by the lack of simple delivery systems and limited anticancer efficacy. Here, we develop a simple approach for the synthesis of hybrid nanostructures that exclusively consist of DNAzyme and Cu with ultra-high loading capacity. The Cu-DNAzyme nanohybrids allow to effectively co-deliver DNAzyme and Cu into cancer cells for combinational catalytic therapy. The released Cu can be reduced to Cu by glutathione and then catalyze endogenous H O to form cytotoxic hydroxyl radicals for chemodynamic therapy (CDT), while the 10-23 DNAzyme enables the catalytic cleavage of VEGFR2 mRNA and activates gene silencing for gene therapy. We demonstrate that the system can efficiently accumulate in the tumor and exhibit amplified cascade antitumor effects with negligible systemic toxicity. Our work paves an extremely simple way to integrate DNAzyme with CDT for the dual-catalytic tumor treatment.
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http://dx.doi.org/10.1002/anie.202101744DOI Listing
June 2021

GanDTI: A multi-task neural network for drug-target interaction prediction.

Comput Biol Chem 2021 Jun 18;92:107476. Epub 2021 Mar 18.

Department of Mechanical Engineering, Virginia Tech, Blacksburg, VA, 24061, USA.

Drug discovery processes require drug-target interaction (DTI) prediction by virtual screenings with high accuracy. Compared with traditional methods, the deep learning method requires less time and domain expertise, while achieving higher accuracy. However, there is still room for improvement for higher performance with simplified structures. Meanwhile, this field is calling for multi-task models to solve different tasks. Here we report the GanDTI, an end-to-end deep learning model for both interaction classification and binding affinity prediction tasks. This model employs the compound graph and protein sequence data. It only consists of a graph neural network, an attention module and a multiple-layer perceptron, yet outperforms the state-of-the art methods to predict binding affinity and interaction classification on the DUD-E, human, and bindingDB benchmark datasets. This demonstrates our refined model is highly effective and efficient for DTI prediction and provides a new strategy for performance improvement.
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http://dx.doi.org/10.1016/j.compbiolchem.2021.107476DOI Listing
June 2021

Development of a Cancer Vaccine Using In Vivo Click-Chemistry-Mediated Active Lymph Node Accumulation for Improved Immunotherapy.

Adv Mater 2021 May 31;33(20):e2006007. Epub 2021 Mar 31.

CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, China, Beijing, 100190, China.

Due to their ability to elicit a potent immune reaction with low systemic toxicity, cancer vaccines represent a promising strategy for treating tumors. Considerable effort has been directed toward improving the in vivo efficacy of cancer vaccines, with direct lymph node (LN) targeting being the most promising approach. Here, a click-chemistry-based active LN accumulation system (ALAS) is developed by surface modification of lymphatic endothelial cells with an azide group, which provide targets for dibenzocyclooctyne (DBCO)-modified liposomes, to improve the delivery of encapsulated antigen and adjuvant to LNs. When loading with OVA peptide and poly(I:C), the formulation elicits an enhanced CD8 T cell response in vivo, resulting in a much more efficient therapeutic effect and prolonged median survival of mice. Compared to treatment with DBCO-conjugated liposomes (DL)-Ag/Ad without the azide targeting, the percent survival of ALAS-vaccine-treated mice improves by 100% over 60 days. Altogether, the findings indicate that the novel ALAS approach is a powerful strategy to deliver vaccine components to LNs for enhanced antitumor immunity.
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http://dx.doi.org/10.1002/adma.202006007DOI Listing
May 2021

One-Step Synthesis of Single-Stranded DNA-Bridged Iron Oxide Supraparticles as MRI Contrast Agents.

Nano Lett 2021 04 19;21(7):2793-2799. Epub 2021 Mar 19.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China.

Despite progress on DNA-assembled nanoparticle (NP) superstructures, their complicated synthesis procedures hamper their potential biomedical applications. Here, we present an exceptionally simple strategy for the synthesis of single-stranded DNA (ssDNA) assembled FeO supraparticles (DFe-SPs) as magnetic resonance contrast agents. Unlike traditional approaches that assemble DNA-conjugated NPs via Watson-Crick hybridization, our DFe-SPs are formed with a high yield through one-step synthesis and assembly of ultrasmall FeO NPs via ssDNA-metal coordination bridges. We demonstrate that the DFe-SPs can efficiently accumulate into tumors for sensitive MR imaging. By virtue of reversible DNA-metal coordination bridges, the DFe-SPs could be disassembled into isolated small NPs in vivo, facilitating their elimination from the body. This work opens a new avenue for the ssDNA-mediated synthesis of superstructures, which expands the repertoire of DNA-directed NP assembly for biomedical applications.
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http://dx.doi.org/10.1021/acs.nanolett.0c04825DOI Listing
April 2021

X-ray-Based Techniques to Study the Nano-Bio Interface.

ACS Nano 2021 03 2;15(3):3754-3807. Epub 2021 Mar 2.

Mathematics, Informatics, and Natural Sciences (MIN) Faculty, University of Hamburg, 20354 Hamburg, Germany.

X-ray-based analytics are routinely applied in many fields, including physics, chemistry, materials science, and engineering. The full potential of such techniques in the life sciences and medicine, however, has not yet been fully exploited. We highlight current and upcoming advances in this direction. We describe different X-ray-based methodologies (including those performed at synchrotron light sources and X-ray free-electron lasers) and their potentials for application to investigate the nano-bio interface. The discussion is predominantly guided by asking how such methods could better help to understand and to improve nanoparticle-based drug delivery, though the concepts also apply to nano-bio interactions in general. We discuss current limitations and how they might be overcome, particularly for future use .
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http://dx.doi.org/10.1021/acsnano.0c09563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992135PMC
March 2021

Molybdenum derived from nanomaterials incorporates into molybdenum enzymes and affects their activities in vivo.

Nat Nanotechnol 2021 06 18;16(6):708-716. Epub 2021 Feb 18.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing, China.

Many nanoscale biomaterials fail to reach the clinical trial stage due to a poor understanding of the fundamental principles of their in vivo behaviour. Here we describe the transport, transformation and bioavailability of MoS nanomaterials through a combination of in vivo experiments and molecular dynamics simulations. We show that after intravenous injection molybdenum is significantly enriched in liver sinusoid and splenic red pulp. This biodistribution is mediated by protein coronas that spontaneously form in the blood, principally with apolipoprotein E. The biotransformation of MoS leads to incorporation of molybdenum into molybdenum enzymes, which increases their specific activities in the liver, affecting its metabolism. Our findings reveal that nanomaterials undergo a protein corona-bridged transport-transformation-bioavailability chain in vivo, and suggest that nanomaterials consisting of essential trace elements may be converted into active biological molecules that organisms can exploit. Our results also indicate that the long-term biotransformation of nanomaterials may have an impact on liver metabolism.
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http://dx.doi.org/10.1038/s41565-021-00856-wDOI Listing
June 2021

A Bibliometric Analysis of Advanced Healthcare Materials: Research Trends of Biomaterials in Healthcare Application.

Adv Healthc Mater 2021 05 17;10(10):e2002222. Epub 2021 Feb 17.

The First Affiliated Hospital of University of Science and Technology of China, 17 Lujiang Road, Hefei, 230001, China.

In the field of biomaterials for healthcare applications, Advanced Healthcare Materials (AHM) has become one of the leading journals. Since 2011, AHM keeps bringing the latest research results in biomaterial science aimed at promoting human health. Nowadays, bibliometrics, of which methodological approaches can quantitively and qualitatively analyze the research performance of journals or subject fields, has attracted considerable attention among the scientific community. A general bibliometric overview of the research performance of AHM is presented. With the aid of Web of Science Core Collection database and VOSviewer software, the annual publication, the most prolific and influential authors/countries from AHM is identified. In addition, the most cited documents and keyword cooccurrence network analysis allow to recognize the major research topics in AHM. At last, the summary of current research trends based on AHM bibliometric analysis, several considerations for the clinical translation of biomaterials, and prospects to advance the field are also proposed. This editorial presents major research trends in the field of engineered materials for healthcare applications.
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http://dx.doi.org/10.1002/adhm.202002222DOI Listing
May 2021

Reactive Oxygen Species-Regulating Strategies Based on Nanomaterials for Disease Treatment.

Adv Sci (Weinh) 2021 Feb 20;8(3):2002797. Epub 2020 Dec 20.

College of Materials Science and Optoelectronic Technology University of Chinese Academy of Sciences Beijing 100049 China.

Reactive oxygen species (ROS) play an essential role in physiological and pathological processes. Studies on the regulation of ROS for disease treatments have caused wide concern, mainly involving the topics in ROS-regulating therapy such as antioxidant therapy triggered by ROS scavengers and ROS-induced toxic therapy mediated by ROS-elevation agents. Benefiting from the remarkable advances of nanotechnology, a large number of nanomaterials with the ROS-regulating ability are developed to seek new and effective ROS-related nanotherapeutic modalities or nanomedicines. Although considerable achievements have been made in ROS-based nanomedicines for disease treatments, some fundamental but key questions such as the rational design principle for ROS-related nanomaterials are held in low regard. Here, the design principle can serve as the initial framework for scientists and technicians to design and optimize the ROS-regulating nanomedicines, thereby minimizing the gap of nanomedicines for biomedical application during the design stage. Herein, an overview of the current progress of ROS-associated nanomedicines in disease treatments is summarized. And then, by particularly addressing these known strategies in ROS-associated therapy, several fundamental and key principles for the design of ROS-associated nanomedicines are presented. Finally, future perspectives are also discussed in depth for the development of ROS-associated nanomedicines.
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http://dx.doi.org/10.1002/advs.202002797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856897PMC
February 2021

Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy adults aged 60 years and older: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial.

Lancet Infect Dis 2021 06 3;21(6):803-812. Epub 2021 Feb 3.

Sinovac Biotech, Beijing, China. Electronic address:

Background: A vaccine against COVID-19 is urgently needed for older adults, in whom morbidity and mortality due to the disease are increased. We aimed to assess the safety, tolerability, and immunogenicity of a candidate COVID-19 vaccine, CoronaVac, containing inactivated SARS-CoV-2, in adults aged 60 years and older.

Methods: We did a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial of CoronaVac in healthy adults aged 60 years and older in Renqiu (Hebei, China). Vaccine or placebo was given by intramuscular injection in two doses (days 0 and 28). Phase 1 comprised a dose-escalation study, in which participants were allocated to two blocks: block 1 (3 μg inactivated virus in 0·5 mL of aluminium hydroxide solution per injection) and block 2 (6 μg per injection). Within each block, participants were randomly assigned (2:1) using block randomisation to receive CoronaVac or placebo (aluminium hydroxide solution only). In phase 2, participants were randomly assigned (2:2:2:1) using block randomisation to receive either CoronaVac at 1·5 μg, 3 μg, or 6 μg per dose, or placebo. All participants, investigators, and laboratory staff were masked to treatment allocation. The primary safety endpoint was adverse reactions within 28 days after each injection in all participants who received at least one dose. The primary immunogenicity endpoint was seroconversion rate at 28 days after the second injection (which was assessed in all participants who had received the two doses of vaccine according to their random assignment, had antibody results available, and did not violate the trial protocol). Seroconversion was defined as a change from seronegative at baseline to seropositive for neutralising antibodies to live SARS-CoV-2 (positive cutoff titre 1/8), or a four-fold titre increase if the participant was seropositive at baseline. This study is ongoing and is registered with ClinicalTrials.gov (NCT04383574).

Findings: Between May 22 and June 1, 2020, 72 participants (24 in each intervention group and 24 in the placebo group; mean age 65·8 years [SD 4·8]) were enrolled in phase 1, and between June 12 and June 15, 2020, 350 participants were enrolled in phase 2 (100 in each intervention group and 50 in the placebo group; mean age 66·6 years [SD 4·7] in 349 participants). In the safety populations from both phases, any adverse reaction within 28 days after injection occurred in 20 (20%) of 100 participants in the 1·5 μg group, 25 (20%) of 125 in the 3 μg group, 27 (22%) of 123 in the 6 μg group, and 15 (21%) of 73 in the placebo group. All adverse reactions were mild or moderate in severity and injection site pain (39 [9%] of 421 participants) was the most frequently reported event. As of Aug 28, 2020, eight serious adverse events, considered unrelated to vaccination, have been reported by seven (2%) participants. In phase 1, seroconversion after the second dose was observed in 24 of 24 participants (100·0% [95% CI 85·8-100·0]) in the 3 μg group and 22 of 23 (95·7% [78·1-99·9]) in the 6 μg group. In phase 2, seroconversion was seen in 88 of 97 participants in the 1·5 μg group (90·7% [83·1-95·7]), 96 of 98 in the 3 μg group (98·0% [92·8-99·8]), and 97 of 98 (99·0% [94·5-100·0]) in the 6 μg group. There were no detectable antibody responses in the placebo groups.

Interpretation: CoronaVac is safe and well tolerated in older adults. Neutralising antibody titres induced by the 3 μg dose were similar to those of the 6 μg dose, and higher than those of the 1·5 μg dose, supporting the use of the 3 μg dose CoronaVac in phase 3 trials to assess protection against COVID-19.

Funding: Chinese National Key Research and Development Program and Beijing Science and Technology Program.
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http://dx.doi.org/10.1016/S1473-3099(20)30987-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906628PMC
June 2021

Rational Design of Nanomaterials for Various Radiation-Induced Diseases Prevention and Treatment.

Adv Healthc Mater 2021 03 27;10(6):e2001615. Epub 2021 Jan 27.

Center of Materials Science and Optoelectronics Engineering, College of Materials Science and Optoelectronic Technology, University of Chinese Academy of Sciences, Beijing, 100049, China.

Radiation treatments often unfavorably damage neighboring healthy organs and cause a series of radiation sequelae, such as radiation-induced hematopoietic system diseases, radiation-induced gastrointestinal diseases, radiation-induced lung diseases, and radiation-induced skin diseases. Recently, emerging nanomaterials have exhibited good superiority for these radiation-induced disease treatments. Given this background, the rational design principle of nanomaterials, which helps to optimize the therapeutic efficiency, has been an increasing need. Consequently, it is of great significance to perform a systematic summarization of the advances in this field, which can trigger the development of new high-performance nanoradioprotectors with drug efficiency maximization. Herein, this review highlights the advances and perspectives in the rational design of nanomaterials for preventing and treating various common radiation-induced diseases. Furthermore, the sources, clinical symptoms, and pathogenesis/injury mechanisms of these radiation-induced diseases will also be introduced. Furthermore, current challenges and directions for future efforts in this field are also discussed.
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http://dx.doi.org/10.1002/adhm.202001615DOI Listing
March 2021

Organelle-Specific Photoactivation of DNA Nanosensors for Precise Profiling of Subcellular Enzymatic Activity.

Angew Chem Int Ed Engl 2021 04 8;60(16):8923-8931. Epub 2021 Mar 8.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, China.

Understanding of the functions of enzymes in diverse cellular processes is important, but the design of sensors with controllable localization for in situ imaging of subcellular levels of enzymatic activity is particularly challenging. We introduce herein a spatiotemporally controlled sensor technology that permits in situ localization and photoactivated imaging of human apurinic/apyrimidinic endonuclease 1 (APE1) within an intracellular organelle of choice (e.g., mitochondria or nucleus). The hybrid sensor platform is constructed by photoactivatable engineering of a DNA-based fluorescent probe and further combination with an upconversion nanoparticle and a specific organelle localization signal. Controlled localization and NIR-light-mediated photoactivation of the sensor "on demand" effectively constrains the imaging signal to the organelle of interest, with improved subcellular resolution. We further demonstrate the application of the nanosensors for the imaging of subcellular APE1 translocation in response to oxidative stress in live cells.
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http://dx.doi.org/10.1002/anie.202016738DOI Listing
April 2021

Controllable Self-Assembly of Peptide-Cyanine Conjugates In Vivo as Fine-Tunable Theranostics.

Angew Chem Int Ed Engl 2021 03 1;60(14):7809-7819. Epub 2021 Mar 1.

CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Haidian District, Beijing, 100190, China.

The fabrication of functional assemblies with defined structures through controllable molecular packing under physiological conditions is challenging. Here, modularly designed peptide-cyanine conjugates that intracellularly self-assembly into 1D columnar superstructures with controlled cyanine aggregation were designed, and they exhibit distinct imaging or photothermal properties. The peptide backbone is cleaved by caspase-3/7 after entering the cells. Then the self-assembled residue, with a double cyanine substitution (Pr-2Cy), forms a P helical column in which H-aggregated cyanine dyes show 3.4-fold photothermal conversion efficiency compared to free ones. The self-assembled residue with a single cyanine substitution (Pr-1Cy) forms a loose column, in which cyanine dyes with undefined structure have a fluorescence quantum yield of up to 9.5 % (emission at 819 nm in H O). This work provides a simple way to modify in vivo self-assembled peptides with functional molecules for achieving desired bio-applications.
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http://dx.doi.org/10.1002/anie.202015126DOI Listing
March 2021

Assessment of extravascular lung water by measuring the number of pulmonary ultrasound B-lines before and after CBP in patients with MODS.

Medicine (Baltimore) 2021 Jan;100(1):e24181

School of Anesthesiology, Xuzhou Medical University, Xuzhou, China.

Abstract: To determine whether the change in the number of pulmonary ultrasound B-line can accurately assess the extravascular lung water (EVLW) before and after continuous bedside blood purification (CBP) in patients with multiple organ dysfunction syndrome (MODS).Seventy-six patients with MODS who underwent CBP were examined within 24 hours before and after CBP using pulmonary ultrasound to detect the number of ultrasound B-line or using pulse indicator continuous cardiac output method to examine extravascular lung water, blood oxygenation index, and B-type natriuretic peptide (BNP) content. The correlation of the change in the number of B lines before and after CBP treatment with the negative balance of 24 hours liquid, the change of oxygenation index, and BNP content were analyzed.In the 76 patients, CBP treatment significantly decreased EVLW, the number of B-line, and BNP (P < .05 for all), while it significantly increased the oxygenation index (P < .05). Correlation analysis showed that the decrease in B-line number after CBP treatment was positively correlated with the 24 hours negative lung fluid balance, decrease of EVLW, oxygenation index improvement, and decreased BNP content. The change in the numbers of pulmonary ultrasound B-line can accurately assess the change of EVLW before and after CBP treatment and reflect the efficiency of ventilation in the lungs and the risk of heart failure.Thus, it can replace pulse indicator continuous cardiac output as an indicator for evaluating EVLW in patients with MODS treated with CBP.
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http://dx.doi.org/10.1097/MD.0000000000024181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793418PMC
January 2021

3D Imaging and Quantification of the Integrin at a Single-Cell Base on a Multisignal Nanoprobe and Synchrotron Radiation Soft X-ray Tomography Microscopy.

Anal Chem 2021 01 30;93(3):1237-1241. Epub 2020 Dec 30.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100090, China.

The development of three-dimensional (3D) single-cell imaging and protein quantitative methods can provide more comprehensive information for diagnoses. We report the design and synthesis of a multisignal nanoprobe ([email protected]) for single-cell 3D imaging and quantifying the integrin αβ using correlated synchrotron radiation soft X-ray tomography microscopy and an iterative tomographic algorithm termed equally sloped tomography for the first time. Moreover, on the basis of the Au or Gd content of our nanoprobe, the number of integrin αβ on a single cell also can be accurately quantified (1.5 × 10 per cell) via inductively coupled plasma mass spectrometry.
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http://dx.doi.org/10.1021/acs.analchem.0c04662DOI Listing
January 2021

Nanomedicine enables spatiotemporally regulating macrophage-based cancer immunotherapy.

Biomaterials 2021 01 28;268:120552. Epub 2020 Nov 28.

CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Beijing, 100190, PR China; GBA Research Innovation Institute for Nanotechnology, Guangdong, 510700, PR China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, PR China. Electronic address:

Cancer immunotherapy, leveraging the host's coordinated immune system to fight against tumor has been clinically validated. However, the modest response owing to the multiple ways of tumor immune evasion is one of the challenges in cancer immunotherapy. Tumor associated macrophages (TAMs), as a major component of the leukocytes infiltrating in all tumors, play crucial roles in driving cancer initiation, progress and metastasis via multiple mechanisms such as mediating chronic inflammation, promoting angiogenesis, taming protective immune responses, and supporting migration and intravasation. TAMs targeted therapeutics have achieved remarkable successes in clinical trials mostly through the use of small-molecule agents and antibodies. However, efforts for further application have met with challenges of limited efficacy and safety. Nanomaterials can provide versatile approaches to realize the superior spatiotemporal control over immunomodulation to amplify immune responses, ultimately enhancing the therapeutic benefits and reducing toxicity. Here, the potential drugs used in TAM-centered cancer treatment in clinic are summarized and the recent advances of TAMs targeted nanomedicines in this filed are highlighted. More importantly, we focus on how nanomedicine can exert their advantages in spatial and temporal control of immunomodulation.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120552DOI Listing
January 2021

Heart Rate Variability and Prognosis in Hemodialysis Patients: A Meta-Analysis.

Blood Purif 2021 8;50(3):298-308. Epub 2020 Dec 8.

Division of Nephrology, West China Hospital of Sichuan University, Chengdu, China.

Background: Heart rate variability (HRV) means the variation in time of beat-to-beat interval. Lower HRV has been shown to be related with death and cardiovascular events in previous studies. In the last few years, the number of patients with ESRD has increased steadily. Maintenance hemodialysis is the most prevalent renal replacement therapy in patients with ESRD. This study aims to investigate if decreased HRV is an independent predictor of mortality in maintenance hemodialysis patients.

Methods: Pubmed/Medline, EMBASE, Ovid, the Web of Science, and the Cochrane Central Register of Controlled Trials databases were searched up to October 1, 2019, for full-text articles in English. Cohort studies reporting the association between HRV and prognosis in hemodialysis patients were selected. Data extraction was performed by 2 reviewers independently, with adjudication by a third reviewer. Extracted data included the study characteristics, HRV measurement and research outcomes. Hazard ratios (HRs) and 95% confidence interval (CI) were pooled in a random-effects model for outcomes of all-cause and cardiovascular mortality. Heterogeneity assessment, subgroup analyses, and sensitivity analysis were conducted.

Results: A total of 7 studies were eligible. HRV metrics consist of SDNN, SDANN, RMSSD, pNN50, HRVTI, ULF, VLF, LF, HF, LF/HF ratio, HRT, DC, and scaling exponents α1 and α2. Decreased HRV was associated with higher all-cause mortality (HR: 1.63, 95% CI: 1.11-2.39, p = 0.014) and cardiovascular mortality (HR: 1.07, 95% CI: 1.00-1.15, p = 0.045). Among the different HRV metrics, decreased SDANN (p < 0.001) and decreased LF/HF ratio (p = 0.001) were identified as predictors of all-cause death. Decreased SDNN, SDANN, and LF/HF ratio were identified as predictors of cardiovascular death (p = 0.004, p = 0.001, and p = 0.002).

Conclusions: Decreased HRV is associated with higher risk of all-cause and cardiovascular death in the hemodialysis population. Decreased SDANN and LF/HF were identified as predictors of both all-cause and cardiovascular mortality, while the utility of other HRV metrics requires further investigation. The protocol for this study was registered with PROSPERO (CRD42019141886).
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http://dx.doi.org/10.1159/000511723DOI Listing
December 2020
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