Publications by authors named "Zijun Wang"

159 Publications

Zwitterionic Polymers toward the Development of Orientation-Sensitive Bioprobes.

Langmuir 2022 Aug 18. Epub 2022 Aug 18.

Laboratoire de Physique de la Matière Condensée, Ecole Polytechnique, CNRS, IP Paris, 91128 Palaiseau, France.

Dynamics with an orientational degree of freedom are fundamental in biological events. Probes with polarized luminescence enable a determination of the orientation. Lanthanide-doped nanocrystals can provide more precise analysis than quantum dots due to the nonphotoblinking/bleaching nature and the multiple line-shaped emission. However, the intrinsic polarization property of the original nanocrystals often deteriorates in complex physiological environments because the colloidal stability easily breaks and the probes aggregate in the media with abundant salts and macromolecules. Engineering the surface chemistry of the probes is thus essential to be compatible with biosystems, which has remained a challenging task that should be exclusively addressed for each specific probe. Here, we demonstrate a facile and efficient surface functionalization of lanthanide-doped nanorods by zwitterionic block copolymers. Due to the steric interaction and the intrinsic zwitterionic nature of the polymers, high colloidal stability of the zwitterionic nanorod suspension is achieved over wide ranges of pH and concentration of salts, even giving rise to the lyotropic liquid crystalline behavior of the nanorods in physiological media. The shear-aligned ability is shown to be unaltered by the coated polymers, and thus, the strongly polarized emission of Eu is preserved. Besides, biological experiments reveal good biocompatibility of the zwitterionic nanorods with negligible nonspecific binding. This study is a stepping stone for the use of the nanorods as orientation probes in biofluids and validates the strategy of coupling zwitterions to lanthanide-doped nanocrystals for various bioapplications.
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http://dx.doi.org/10.1021/acs.langmuir.2c01286DOI Listing
August 2022

Effects of different dosages esketamine on cardiac conduction and heterogeneity of Cx43: the epicardial mapping in guinea pigs.

Ann Transl Med 2022 Jul;10(14):772

Department of Anesthesiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.

Background: Esketamine is favored in clinical settings. Relative to other anesthetics it preserves protective airway reflexes, maintains spontaneous respiration, stabilizes hemodynamics, and alleviates neuropathic pain. This study sought to evaluate the cardiac safety of esketamine at 3 sub-anesthetic gradient concentrations.

Methods: We examined the cardiac electrophysiological effects of esketamine with infusion rates of 0.125, 0.25, and 0.5 mg·kg·h. Short-term studies were performed in ventricular myocytes using patch-clamp techniques and optically mapped Langendorff-perfused guinea-pig hearts. Long-term studies were performed using Langendorff-perfused guinea-pig hearts and electrically mapping the receipt of the infusion for 3 hours.

Results: Esketamine changed the action potential (AP) morphology of cardiomyocytes. Notably, it increased the resting membrane potential (RMP), attenuated the amplitude of action potential (APA), reduced the maximum upstroke velocity (Vmax), and shortened the action potential duration (APD) at 30% to 70%, which led to relatively prolonged monophasic action potentials (MAP) triangulation in G and G. All the effects were partially eluted. Optical mapping demonstrated almost equal and heterogeneous conduction. G resulted in an increased heart rate (HR) accompanied by a shortened APD. No detectable arrhythmia was observed at the cycle lengths (CLs) used. Long-term electrical mapping demonstrated the dose-dependent deceleration of the Vmax and APA, but only prolonged the AP parameters in G. Left-ventricular isochronal conduction maps revealed the conduction heterogeneities at G, and conduction velocity (CV) was increased in G and G None of these effects were reversed on drug washout. Electrocardiogram (ECG) traces revealed an accelerated HR with the associated curtailment of QT intervals in G; HRs were decreased in G and G; the PR intervals and QRS duration differed between G and G, G, which elicited electrical alternans. Connexin43 (Cx43) expression were significantly decreased in G, G and G.

Conclusions: These data provide a basic electrophysiology for esketamine. Specifically, we found that (I) various methods of esketamine infusion had different effects on cardiac conduction at different dosages; (II) the heterogeneous expression of Cx43 is associated with spatially dispersed conduction; and (III) potential cardiac risks should be considered for high-risk patients receiving continuous esketamine infusions of high dosages.
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http://dx.doi.org/10.21037/atm-22-2614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9372656PMC
July 2022

Radical footprinting and regularity revealing during the pyrolysis of technical lignins.

Bioresour Technol 2022 Sep 19;360:127648. Epub 2022 Jul 19.

Key Laboratory of Energy Thermal Conversion and Control of Ministry of Education, School of Energy and Environment, Southeast University, Nanjing 210096, PR China. Electronic address:

Revealing radical-mediated reactions is conducive to illustrate lignin pyrolysis and achieve subsequent regulation. Three technical lignins (hot-water-extracted lignin, kraft lignin, and soda lignin) were selected in this study and pyrolyzed from 400 °C to 700 °C, and their pyrolysis radicals in both chars and bio-oils were monitored with the electron paramagnetic resonance spectrometer. Results showed that spin concentrations of char radicals had a volcanic trend against the pyrolysis temperature, and reached the maximum values at 550-600 °C. However, the contents of bio-oil radicals were low during pyrolysis at low and medium temperature, but their spin concentrations exploded abruptly over 600-650 °C. Meanwhile, the bio-oil yields were found to drop after 550-600 °C, and the three inflection temperatures for char radicals, bio-oil radicals, and bio-oil yields were perfectly matched. These findings systematically elucidated the radical regularity in technical lignin pyrolysis and fundamentally contributed to the development of radical-mediated lignin pyrolysis mechanisms.
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http://dx.doi.org/10.1016/j.biortech.2022.127648DOI Listing
September 2022

Developing the RIGHT-COI&F extension for the reporting conflicts of interest and funding in practice guidelines: study protocol.

Ann Transl Med 2022 Jun;10(12):717

Department of Internal Medicine, American University of Beirut, Beirut, Lebanon.

Background: Conflicts of interest (COI) and funding may influence the development of practice guidelines, but there are no internationally endorsed guidelines specifically focusing on the reporting on issues related to COI and funding in practice guidelines. Our aim is to develop an extension of the essential Reporting Items of Practice Guidelines in Healthcare (RIGHT) for COIs and Funding in practice guidelines (i.e., RIGHT-COI&F).

Methods: We will follow the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) network's toolkit for developing a reporting guideline in six stages: (I) identifying the need for the extension; (II) registering the project and setting up working groups; (III) collecting the initial items; (IV) reaching consensus on the items to be included; (V) revision and formulation of the final checklist; and (VI) dissemination and implementation. We intend to form a multidisciplinary international team of experts to collect and evaluate the items and plan to complete the full reporting guideline in about 2 years.

Discussion: The RIGHT-COI&F statement will help guideline developers improve their reporting of issues related to COIs and funding, and subsequently improve the reporting quality of their guidelines. Journals editors, guideline users and evaluators will benefit from a more complete and transparent reporting of COI.

Trial Registration: We have registered the protocol on the EQUATOR network (https://www.equator-network.org/library/reporting-guidelines-under-development/reporting-guidelines-under-development-for-other-study-designs/#RIGHT-COI).
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http://dx.doi.org/10.21037/atm-22-2123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279782PMC
June 2022

Severe Acute Respiratory Syndrome Coronavirus 2 Neutralization After Messenger RNA Vaccination and Variant Breakthrough Infection.

Open Forum Infect Dis 2022 Jul 7;9(7):ofac227. Epub 2022 May 7.

Laboratory of Retrovirology, The Rockefeller University, New York, New York, USA.

The emergence of severe acute respiratory syndrome coronavirus 2 variants that have greater transmissibility and resistance to neutralizing antibodies has increased the incidence of breakthrough infections. We show that breakthrough infection increases neutralizing antibody titers to varying degrees depending on the nature of the breakthrough variant and the number of vaccine doses previously administered. Omicron breakthrough infection resulted in neutralizing antibody titers that were the highest across all groups, particularly against Omicron.
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http://dx.doi.org/10.1093/ofid/ofac227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9129198PMC
July 2022

Highly robust and soft biohybrid mechanoluminescence for optical signaling and illumination.

Nat Commun 2022 07 7;13(1):3914. Epub 2022 Jul 7.

Department of Mechanical and Aerospace Engineering, University of California, San Diego, La Jolla, CA, 92093, USA.

Biohybrid is a newly emerging and promising approach to construct soft robotics and soft machines with novel functions, high energy efficiency, great adaptivity and intelligence. Despite many unique advantages of biohybrid systems, it is well known that most biohybrid systems have a relatively short lifetime, require complex fabrication process, and only remain functional with careful maintenance. Herein, we introduce a simple method to create a highly robust and power-free soft biohybrid mechanoluminescence, by encapsulating dinoflagellates, bioluminescent unicellular marine algae, into soft elastomeric chambers. The dinoflagellates retain their intrinsic bioluminescence, which is a near-instantaneous light response to mechanical forces. We demonstrate the robustness of various geometries of biohybrid mechanoluminescent devices, as well as potential applications such as visualizing external mechanical perturbations, deformation-induced illumination, and optical signaling in a dark environment. Our biohybrid mechanoluminescent devices are ultra-sensitive with fast response time and can maintain their light emission capability for weeks without special maintenance.
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http://dx.doi.org/10.1038/s41467-022-31705-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263131PMC
July 2022

Complement-Opsonized NIR-IIb Emissive Immunotracers for Dynamically Monitoring Neutrophils in Inflammation-Related Diseases.

Adv Mater 2022 Jul 6:e2203477. Epub 2022 Jul 6.

College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, China.

Real-time monitoring of neutrophil dynamics is crucial for timely diagnosis and effective treatment of inflammation-related diseases, which requires a reliable tracer for in vivo tracking of neutrophils. However, immunotracers for neutrophils are extremely limited because of the difficulty in labeling the cells. Inspired by the natural biological function of the complement system, a strategy of enhancing the complement C3 opsonization of lanthanide-doped nanoparticles (LnNPs) by modulating their surface chemistry, thus developing a near infrared-IIb emissive nanotracer for neutrophils, is reported herein. Four kinds of surface-modified LnNPs are fabricated, among which phospholipids DOPG-modified LnNPs ([email protected]) with weak antifouling ability and hydroxyl groups adsorb more complement C3 proteins and form covalent linkages with C3b active fragments under inflammation conditions, inducing enhanced complement C3 opsonization. Therefore, [email protected] with enhanced complement C3 opsonization are capable of efficiently labeling inflammation-stimulated neutrophils in vivo through complement-receptors-mediated phagocytosis and achieve dynamic monitoring neutrophils during cutaneous wound healing and cerebral ischemia/reperfusion.
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http://dx.doi.org/10.1002/adma.202203477DOI Listing
July 2022

Antibody evolution to SARS-CoV-2 after single-dose Ad26.COV2.S vaccine in humans.

J Exp Med 2022 Aug 1;219(8). Epub 2022 Jul 1.

Laboratory of Molecular Immunology, The Rockefeller University, New York, NY.

The single-dose Ad.26.COV.2 (Janssen) vaccine elicits lower levels of neutralizing antibodies and shows more limited efficacy in protection against infection than either of the two available mRNA vaccines. In addition, Ad.26.COV.2 has been less effective in protection against severe disease during the Omicron surge. Here, we examined the memory B cell response to single-dose Ad.26.COV.2 vaccination. Compared with mRNA vaccines, Ad.26.COV.2 recipients had significantly lower numbers of RBD-specific memory B cells 1.5 or 6 mo after vaccination. Despite the lower numbers, the overall quality of the memory B cell responses appears to be similar, such that memory antibodies elicited by both vaccine types show comparable neutralizing potency against SARS-CoV-2 Wuhan-Hu-1, Delta, and Omicron BA.1 variants. The data help explain why boosting Ad.26.COV.2 vaccine recipients with mRNA vaccines is effective and why the Ad26.COV2.S vaccine can maintain some protective efficacy against severe disease during the Omicron surge.
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http://dx.doi.org/10.1084/jem.20220732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9253517PMC
August 2022

Publishing clinical prActice GuidelinEs (PAGE): Recommendations from editors and reviewers.

J Evid Based Med 2022 Jun 29;15(2):136-141. Epub 2022 Jun 29.

Medical Device Regulatory Research and Evaluation Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Transparency Ecosystem for Research and Journals in Medicine (TERM) Working Group summarized the essential recommendations that should be considered to review and publish a high-quality guideline. These recommendations from editors and reviewers included the ten components of essential requirements: systematic review of existing relevant guidelines, guideline registration, guideline protocol, stakeholders, conflicts of interest, clinical questions, systematic reviews, recommendation consensus, guideline reporting, and external review. TERM Working Group abbreviates them as PAGE (essential requirements for Publishing clinical prActice GuidelinEs), recommends guideline authors, editors, and peer reviewers use them for high-quality guidelines.
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http://dx.doi.org/10.1111/jebm.12479DOI Listing
June 2022

Effects of a ketogenic diet in women with PCOS with different uric acid concentrations: a prospective cohort study.

Reprod Biomed Online 2022 08 2;45(2):391-400. Epub 2022 Apr 2.

Department of Obstetrics and Gynecology, Air Force Medical Center, PLA Beijing, China.

Research Question: Do overweight/obese women with PCOS with different uric acid concentrations show different effects after a ketogenic diet intervention?

Design: The study involved women with PCOS with a body mass index (BMI) of ≥24 kg/m. Groups showing different uric acid concentrations were given ketogenic diet guidance for 12 weeks. Weight, BMI, body fat percentage, fasting blood glucose, triacylglyerols, total cholesterol, uric acid and other metabolism-related indexes were measured.

Results: After 12 weeks of the ketogenic diet intervention, body weight (hyperuricaemia group: P=0.001; non-hyperuricaemia group: P<0.001), BMI (hyperuricaemia group: P = 0.025; non-hyperuricaemia group: P<0.001) and body fat percentage (hyperuricaemia group: P<0.001; non-hyperuricaemia group: P<0.001) were decreased in both groups. There was greater weight loss in the non-hyperuricaemia group (hyperuricaemia group 11.2±4.6 kg versus non-hyperuricaemia group 14.7±4.8 kg; P < 0.05). In the non-hyperuricaemia group, uric acid concentrations increased significantly after 6 weeks of the ketogenic diet intervention (week 0: 5.69±0.84 mg/dl versus week 6: 8.41 ± 2.33 mg/dl; P < 0.001) and reached the concentrations of the hyperuricaemia group (week 6: 9.37 ± 2.43 mg/dl; P > 0.05).

Conclusions: A ketogenic diet intervention is beneficial for overweight/obese women with PCOS with different serum uric acid concentrations. Participants with normal basal uric acid concentrations showed a greater fluctuation of serum uric acid concentrations during the ketogenic diet intervention and had a greater weight loss.
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http://dx.doi.org/10.1016/j.rbmo.2022.03.023DOI Listing
August 2022

Loading Drugs in Natural Phospholipid Bilayers of Cell Membrane Shells to Construct Biomimetic Nanocomposites for Enhanced Tumor Therapy.

ACS Appl Mater Interfaces 2022 Jun 15;14(25):28671-28682. Epub 2022 Jun 15.

College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, China.

Drug-based oncotherapy is seriously challenged by insufficient drug accumulation at tumor sites, mainly resulting from low drug loading efficiency and poor tumor-targeting ability of drug carriers. We herein proposed a "one-stone, two-bird" strategy to circumvent both obstacles, utilizing the source cancer cell membrane (CM) as a dual-function carrier to simultaneously achieve sufficient drug loading and homologous tumor targeting. Combining the use of TPGS (d-α-tocopherol polyethylene glycol 1000 succinate) to inhibit the drug efflux process of drug-resistant tumor, we constructed core-shell-structured nanocomposites CMGNPs consisting of ICG (indocyanine green)/DOX (doxorubicin)-loaded, TPGS/OA (oleic acid)-stabilized upconversion nanoparticles as the core and ICG-loaded MCF7/ADR CMs as the shell, for combined chemo/phototherapy of MCF7/ADR tumor. The employment of phospholipid bilayers of CMs as natural pockets for extra drug loading while preserving the homologous targeting ability greatly enhanced drug concentration at tumor sites, endowing CMGNPs with excellent therapeutic efficacy. Our effort provides a versatile approach for facilitating drug delivery in diverse therapeutic systems.
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http://dx.doi.org/10.1021/acsami.2c08587DOI Listing
June 2022

Brain Tumor Cell Membrane-Coated Lanthanide-Doped Nanoparticles for NIR-IIb Luminescence Imaging and Surgical Navigation of Glioma.

Adv Healthc Mater 2022 Aug 19;11(16):e2200521. Epub 2022 Jun 19.

College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, P. R. China.

Intraoperative visualization of the full extent of brain tumor by luminescence imaging helps to improve the degree and accuracy of brain tumor resection, thereby prolonging the survival of patients. However, the limited imaging depth and spatial resolution and the poor blood-brain barrier (BBB) permeability of most currently available luminescent probes restrict the imaging performance and surgical resection efficiency of brain tumor. Here, a brain tumor cell membrane-coated lanthanide-doped nanoparticles (CC-LnNPs) in the near-infrared-IIb window (NIR-IIb, 1500-1700 nm) is designed for brain tumor imaging and surgical navigation. The coating of brain tumor cell membrane endows CC-LnNPs with immune escape, BBB crossing, and homotypic targeting abilities, which are inherited from the source brain tumor cells. In addition, compared with clinically approved imaging agent indocyanine green, CC-LnNPs present higher temporal and spatial resolution, higher stability, and lower background signals, enabling clear visualization of the brain tumor boundary. With the guidance of NIR-IIb fluorescence, the glioma tissue (size < 3 mm, depth > 3 mm) could be clearly visualized and completely removed as a proof of concept. This study offers new insight for the future design of nanoprobe to image brain tumor and to achieve precise diagnosis and surgical navigation of brain tumor.
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http://dx.doi.org/10.1002/adhm.202200521DOI Listing
August 2022

Asymptomatic and pre-symptomatic infection in Coronavirus Disease 2019 pandemic.

Med Rev (Berl) 2022 Feb 24;2(1):66-88. Epub 2022 Feb 24.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.

With the presence of Coronavirus Disease 2019 (COVID-19) asymptomatic infections detected, their proportion, transmission potential, and other aspects such as immunity and related emerging challenges have attracted people's attention. We have found that based on high-quality research, asymptomatic infections account for at least one-third of the total cases, whereas based on systematic review and meta-analysis, the proportion is about one-fifth. Evaluating the true transmission potential of asymptomatic cases is difficult but critical, since it may affect national policies in response to COVID-19. We have summarized the current evidence and found, compared with symptomatic cases, the transmission capacity of asymptomatic individuals is weaker, even though they have similar viral load and relatively short virus shedding duration. As the outbreak progresses, asymptomatic infections have also been found to develop long COVID-19. In addition, the role of asymptomatic infection in COVID-19 remains to be further revealed as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to emerge. Nevertheless, as asymptomatic infections transmit the SARS-CoV-2 virus silently, they still pose a substantial threat to public health. Therefore, it is essential to conduct screening to obtain more knowledge about the asymptomatic infections and to detect them as soon as possible; meanwhile, management of them is also a key point in the fight against COVID-19 community transmission. The different management of asymptomatic infections in various countries are compared and the experience in China is displayed in detail.
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http://dx.doi.org/10.1515/mr-2021-0034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9047649PMC
February 2022

Predictive Nomogram for Unfavorable Outcome of Spontaneous Intracerebral Hemorrhage.

World Neurosurg 2022 Aug 30;164:e1111-e1122. Epub 2022 May 30.

Department of Neurosurgery, Qingdao Municipal Hospital, Qingdao, Shandong, P. R. China. Electronic address:

Background: The goal of this retrospective study was to evaluate the effect of surgical timing on patient outcomes after spontaneous intracerebral hemorrhage (ICH). We also identified risk factors associated with poor prognosis.

Methods: We reviewed all patients who underwent surgery for ICH between January 2014 and January 2021. The outcome was measured using the modified Rankin Scale (mRS) score at 6 months after the surgery. Patients with mRS 0-2 were considered having favorable outcomes, and those with mRS 3-5 were considered having unfavorable outcomes. The relationships of surgical timing with the risk of unfavorable outcomes were identified using the interaction and stratified analyses, and generalized additive and logistic regression models. A nomogram was established and evaluated using a receiver operating characteristic curve analysis, plotted decision curve, and calibration curve.

Results: We identified 53 patients with favorable outcomes and 144 with unfavorable outcomes. The number of cases who underwent surgery at >12 hours and <36 hours in the favorable outcome group was more than that in the unfavorable outcome group (P < 0.001). When the time to operating room (TOR) was less than 21 hours, a shorter TOR was associated with unfavorable outcomes, using the smoothing spline analysis (odds ratio = 0.8, P < 0.001). Finally, we developed a nomogram using systolic blood pressure, Glasgow Coma Scale, midline shift, hematoma volume, and TOR for predicting the unfavorable outcome. The area under the curve, accuracy, specificity, and sensitivity of nomogram were 0.90, 0.87, 0.72, and 0.93, respectively.

Conclusion: Surgical timing between 12 and 26 hours after ICH was associated with favorable outcomes. The nomogram including systolic blood pressure, Glasgow Coma Scale, midline shift, hematoma volume, and TOR was reliable for predicting the ICH outcome.
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http://dx.doi.org/10.1016/j.wneu.2022.05.111DOI Listing
August 2022

Retracted systematic reviews were continued to be frequently cited: a citation analysis.

J Clin Epidemiol 2022 May 28;149:137-145. Epub 2022 May 28.

Evidence-based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China; Research Unit of Evidence-Based Evaluation and Guidelines, Chinese Academy of Medical Sciences (2021RU017), School of Basic Medical Sciences, Lanzhou University Lanzhou, Lanzhou, China; Lanzhou University Institute of Health Data Science, Lanzhou, China; WHO Collaborating Center for Guideline Implementation and Knowledge Translation, Lanzhou, China; Guideline International Network Asia, Lanzhou, China; Chinese GRADE Center, Lanzhou, China. Electronic address:

Background And Objectives: To survey the citations of retracted non-Cochrane systematic reviews (SRs) in scientific literature.

Methods: We searched the Web of Science and Google Scholar from their inception to 30 April 2020 to find the citations of 153 previously identified retracted non-Cochrane SRs. We calculated the numbers of citations before and after retraction separately. We also described how the citation addressed the retraction and how it was used in the article.

Results: A We identified 954 citations of 128 retracted SRs. The number of retracted SRs and citations reached the peak in 2014 and 2016, respectively, and the majority of the citations (n = 580, 60.8%) were in articles published after the SR was retracted. The mean number of citation per retracted SRs was 7.5. 2.6 before and 4.5 after the publication of the retraction notice. Twenty-nine (5.0%) citations indicated the retraction of the SRs in the reference section. Nine of these citations supported the retracted SR's results, and 15 disagreed with them.

Conclusion: Retracted SRs continue to be cited after the publication of the retraction notice. Standardized methods are needed to guide the management of retractions and avoid inappropriate citations of retracted articles.
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http://dx.doi.org/10.1016/j.jclinepi.2022.05.013DOI Listing
May 2022

Study on the performance of a MOF-808-based photocatalyst prepared by a microwave-assisted method for the degradation of antibiotics.

RSC Adv 2021 Oct 6;11(52):32955-32964. Epub 2021 Oct 6.

School of Chemistry and Chemical Engineering, Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, Shihezi University Beisi Road Shihezi Xinjiang 832003 P. R. China +86 15699322089.

In this paper, a simple method was used to rapidly prepare MOF-808 with a large specific surface area and high stability. BiS and MOF-808 were used to design and synthesize high-stability BiS/MOF-808 nanocomposites, which were then used for the photocatalytic degradation of antibiotic tetracyclines. The performance test results showed that the 0.7-808 composite material had good photocatalytic degradation performance for tetracycline under visible-light irradiation, and the degradation rate reached 80.8%, which was 3.21 times and 1.76 times that of MOF-808 and BiS, respectively. This was mainly due to the high photocurrent response and photoluminescence of the BiS/MOF-808 composite material. Therefore, the close contact of n-n BiS/MOF-808 can transfer light-generated electrons and holes to improve the utilization efficiency of photogenerated charges, thereby greatly improving the photocatalytic reaction activity. Particle-capture experiments and ESR confirmed that ˙OH was the main active substance in the photocatalytic degradation.
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http://dx.doi.org/10.1039/d1ra05058cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9042128PMC
October 2021

Application of Ginsenoside Rd in Periodontitis With Inhibitory Effects on Pathogenicity, Inflammation, and Bone Resorption.

Front Cell Infect Microbiol 2022 11;12:813953. Epub 2022 Apr 11.

The State Key Laboratory Breeding Base of Basic Science of Stomatology [Hubei-Ministry of Science and Technology of the People's Republic of China (MOST)] and Key Laboratory of Oral Biomedicine Engineering Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.

Periodontitis is a worldwide oral disease induced by the interaction of subgingival bacteria and host response and is characterized by local inflammation, bone resorption, and tooth loss. Ginsenoside Rd (Rd) is a biologically active component derived from Panax ginseng and has been demonstrated to exert antibacterial and anti-inflammatory activities. This study aims to investigate the inhibitory efficiency of Rd towards (), periodontal inflammatory response, and osteoclastogenesis and to further validate the results in a mouse periodontitis model, thus, evaluate the potential effects of Rd on the control and prevention of periodontitis. According to the results, Rd exerted excellent antibacterial activities against planktonic , along with attenuating virulence and inhibiting its biofilms. Meanwhile, the inflammatory cytokine production and osteoclastogenesis were remarkably inhibited by Rd both and . Furthermore, Rd efficiently ameliorated the subgingival abundance and suppressed the alveolar bone resorption as well. In conclusion, Rd has the potential to be developed as a promising medication in the control and prevention of periodontitis.
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http://dx.doi.org/10.3389/fcimb.2022.813953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9035930PMC
April 2022

Analysis of memory B cells identifies conserved neutralizing epitopes on the N-terminal domain of variant SARS-Cov-2 spike proteins.

Immunity 2022 06 7;55(6):998-1012.e8. Epub 2022 Apr 7.

Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA. Electronic address:

SARS-CoV-2 infection or vaccination produces neutralizing antibody responses that contribute to better clinical outcomes. The receptor-binding domain (RBD) and the N-terminal domain (NTD) of the spike trimer (S) constitute the two major neutralizing targets for antibodies. Here, we use NTD-specific probes to capture anti-NTD memory B cells in a longitudinal cohort of infected individuals, some of whom were vaccinated. We found 6 complementation groups of neutralizing antibodies. 58% targeted epitopes outside the NTD supersite, 58% neutralized either Gamma or Omicron, and 14% were broad neutralizers that also neutralized Omicron. Structural characterization revealed that broadly active antibodies targeted three epitopes outside the NTD supersite including a class that recognized both the NTD and SD2 domain. Rapid recruitment of memory B cells producing these antibodies into the plasma cell compartment upon re-infection likely contributes to the relatively benign course of subsequent infections with SARS-CoV-2 variants, including Omicron.
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http://dx.doi.org/10.1016/j.immuni.2022.04.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8986478PMC
June 2022

Increased memory B cell potency and breadth after a SARS-CoV-2 mRNA boost.

Nature 2022 07 21;607(7917):128-134. Epub 2022 Apr 21.

Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.

The Omicron variant of SARS-CoV-2 infected many vaccinated and convalescent individuals. Despite the reduced protection from infection, individuals who received three doses of an mRNA vaccine were highly protected from more serious consequences of infection. Here we examine the memory B cell repertoire in a longitudinal cohort of individuals receiving three mRNA vaccine doses. We find that the third dose is accompanied by an increase in, and evolution of, receptor-binding domain (RBD)-specific memory B cells. The increase is due to expansion of memory B cell clones that were present after the second dose as well as the emergence of new clones. The antibodies encoded by these cells showed significantly increased potency and breadth when compared with antibodies obtained after the second dose. Notably, the increase in potency was especially evident among newly developing clones of memory cells, which differed from persisting clones in targeting more conserved regions of the RBD. Overall, more than 50% of the analysed neutralizing antibodies in the memory compartment after the third mRNA vaccine dose neutralized the Omicron variant. Thus, individuals receiving three doses of an mRNA vaccine have a diverse memory B cell repertoire that can respond rapidly and produce antibodies capable of clearing even diversified variants such as Omicron. These data help to explain why a third dose of a vaccine that was not specifically designed to protect against variants is effective against variant-induced serious disease.
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http://dx.doi.org/10.1038/s41586-022-04778-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9259484PMC
July 2022

Use of non-steroidal anti-inflammatory drugs and adverse outcomes during the COVID-19 pandemic: A systematic review and meta-analysis.

EClinicalMedicine 2022 Apr 7;46:101373. Epub 2022 Apr 7.

Evidence-based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.

Background: There are concerns that the use of non-steroidal anti-inflammatory drugs (NSAIDs) may increase the risk of adverse outcomes among patients with coronavirus COVID-19. This study aimed to synthesize the evidence on associations between the use of NSAIDs and adverse outcomes.

Methods: A systematic search of WHO COVID-19 Database, Medline, the Cochrane Library, Web of Science, Embase, China Biology Medicine disc, China National Knowledge Infrastructure, and Wanfang Database for all articles published from January 1, 2020, to November 7, 2021, as well as a supplementary search of Google Scholar. We included all comparative studies that enrolled patients who took NSAIDs during the COVID-19 pandemic. Data extraction and quality assessment of methodology of included studies were completed by two reviewers independently. We conducted a meta-analysis on the main adverse outcomes, as well as selected subgroup analyses stratified by the type of NSAID and population (both positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or not).

Findings: Forty comparative studies evaluating 4,867,795 adult cases were identified. Twenty-eight (70%) of the included studies enrolled patients positive to SARS-CoV-2 tests. The use of NSAIDs did not reduce mortality outcomes among people with COVID-19 (number of studies [N] = 29, odds ratio [OR] = 0.93, 95% confidence interval [CI]: 0.75 to 1.14,  = 89%). Results suggested that the use of NSAIDs was not significantly associated with higher risk of SARS-CoV-2 infection in patients with or without COVID-19 ( = 10, OR = 0.96, 95% CI: 0.86 to 1.07,  = 78%;  = 8, aOR = 1.01, 95% CI: 0.94 to 1.09,  = 26%), or an increased probability of intensive care unit (ICU) admission ( = 12, OR = 1.28, 95% CI: 0.94 to 1.75,  = 82% ;  = 4, aOR = 0.89, 95% CI: 0.65 to 1.22,  = 60%), requiring mechanical ventilation ( = 11, OR = 1.11, 95% CI: 0.79 to 1.54,  = 63%;  = 5, aOR = 0.80, 95% CI: 0.52 to 1.24,  = 66%), or administration of supplemental oxygen ( = 5, OR = 0.80, 95% CI: 0.52 to 1.24,  = 63%;  = 2, aOR = 1.00, 95% CI: 0.89 to 1.12,  = 0%). The subgroup analysis revealed that, compared with patients not using any NSAIDs, the use of ibuprofen ( = 5, OR = 1.09, 95% CI: 0.50 to 2.39;  = 4, aOR = 0.95, 95% CI: 0.78 to 1.16) and COX-2 inhibitor ( = 4, OR = 0.62, 95% CI: 0.35 to 1.11;  = 2, aOR = 0.73, 95% CI: 0.45 to 1.18) were not associated with an increased risk of death.

Interpretation: Data suggests that NSAIDs such as ibuprofen, aspirin and COX-2 inhibitor, can be used safely among patients positive to SARS-CoV-2. However, for some of the analyses the number of studies were limited and the quality of evidence was overall low, therefore more research is needed to corroborate these findings.

Funding: There was no funding source for this study.
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http://dx.doi.org/10.1016/j.eclinm.2022.101373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8989274PMC
April 2022

TSPAN31 regulates the proliferation, migration, and apoptosis of gastric cancer cells through the METTL1/CCT2 pathway.

Transl Oncol 2022 Jun 13;20:101423. Epub 2022 Apr 13.

Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjia Yuan Road, Nanjing 210000, Jiangsu, China. Electronic address:

Gastric cancer (GC) is one of the most common human malignancies worldwide, but the molecular mechanism of GC has not been fully elucidated. Tetraspanin 31 (TSPAN31) has been rarely studied in human malignant tumors. This study aimed to investigate the effects of TSPAN31 on GC. We analyzed GC tissues through high-throughput sequencing technology and chose TSPAN31 with high expression. The expression of TSPAN31 in GC was analyzed through bioinformatics website and qRT-PCR. The protein level of TSPAN31 in GC tissues was determined by western blot and immunochemistry. The proliferation, migration, and apoptosis of GC cells were detected by the cell counting kit-8, transwell, and apoptosis experiments. METTL1 and CCT2 that may co-express with TSPAN31 were predicted by the GEPIA database, and analyzed the correlation between the expression levels of TSPAN31, METTL1 and CCT2. The results shows TSPAN31 was highly expressed in GC tissues, and high expression of TSPAN31 was found to result in poor prognosis of patients with GC. TSPAN31 could regulate the proliferation, migration and apoptosis of GC cells. The relative expression levels of TSPAN31, METTL1 and CCT2 in GC were positively correlated. Low expression of TSPAN31 could partially reverse the effect of high expression of METTL1 and CCT2 on the tumor progression of GC cells. In conclusion, TSPAN31 was highly expressed in GC tissues and led to poor prognosis of patients with GC. TSPAN31 may regulate the proliferation, migration, and apoptosis of GC cells. This regulatory mechanism may be achieved through co-expression with METTL1 and CCT2.
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http://dx.doi.org/10.1016/j.tranon.2022.101423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9034387PMC
June 2022

The dry reforming of methane over fly ash modified with different content levels of MgO.

RSC Adv 2021 Apr 14;11(23):14154-14160. Epub 2021 Apr 14.

School of Chemistry and Chemical Engineering, Shihezi University Shihezi Xinjiang 832003 PR China

Large amounts of industrial waste fly ash (FA) have caused serious pollution to the environment. There are a few reports that this kind of material, with its good thermal stability, can be used as a catalyst support for high-temperature catalytic reactions, and it has a certain application space. Upon the alkali treatment of fly ash, its specific surface area is increased, and it has the potential to be a catalyst support. Using treated fly ash as the carrier, a nickel-based catalyst was prepared a sol-gel method, and the catalytic performance changes of catalysts with different MgO content levels in the dry reforming of methane are discussed. Under the conditions of a space velocity of 1.8 × 10 mL g h and a reaction temperature of 750 °C, in the presence of Ni/NaFA-M2 (M2 = 20 wt% MgO), the CH conversion rate can reach 84%, and it has good reaction stability. This will provide a way to use fly ash and carry out more research.
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http://dx.doi.org/10.1039/d1ra01381eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8697673PMC
April 2021

One-step hydrothermal synthesis of a ternary heterojunction g-CN/BiS/InS photocatalyst and its enhanced photocatalytic performance.

RSC Adv 2021 Mar 5;11(17):9788-9796. Epub 2021 Mar 5.

School of Chemistry and Chemical Engineering, Shihezi University Beisi Road Shihezi Xinjiang 832003 PR China +86 15699322089.

In recent years, photoelectrocatalysis has been one of the hotspots of research. Graphite-like carbon nitride (g-CN) is one of the few non-metal semiconductors known and has good potential in the field of photocatalysis due to its simple preparation method and visible light effects. In this study, a method for compounding two semiconductor materials, InS and BiS, on the surface of g-CN a one-step hydrothermal method is reported, and it was found that this resulting material showed remarkable properties. The advantages of this method are as follows: (1) the formation of a heterojunction, which accelerates the separation efficiency of photogenerated carriers; (2) a large number of holes and defects on the surface of g-CN are conducive to the nucleation, crystallisation and growth of InS and BiS. Compared with its counterpart catalysts, the CN/InS/BiS composite catalyst has significantly improved performance. Due to its high degree of crystallinity, the adsorption capacity of the catalyst itself is also significantly improved. In addition, the stability of the composite material maintains 90.9% after four cycles of use, and the structure is not damaged. In summary, CN/BiS/InS composite materials are believed to have broad application potential in the treatment of dye wastewater.
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http://dx.doi.org/10.1039/d1ra00729gDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8695387PMC
March 2021

Switching Diagram of Core-Shell FePt/Fe Nanocomposites for Bit Patterned Media.

Materials (Basel) 2022 Mar 31;15(7). Epub 2022 Mar 31.

Department of Materials Science and Engineering, Xiamen Institute of Technology, Xiamen 361021, Fujian Province, China.

In the current work, a core-shell type exchange coupled composite structure was constructed by micromagnetic simulation with a phase FePt core and an iron shell. Four types of switching loops with magnetic domain structure evolution were demonstrated. Based on the simulation results, a switching type diagram was constructed, which displays various hysteresis loops as a function of core radius and shell thickness. Furthermore, the effects of switching type and composite structure on the coercivity and remanent magnetization were predicted and discussed. This finding indicates that core-shell type FePt/Fe composite structure film has a large advantage in designing exchange-coupled bit patterned media to realize high-density storage devices at the nanoscale.
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http://dx.doi.org/10.3390/ma15072581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9000370PMC
March 2022

Methodology and experiences of rapid advice guideline development for children with COVID-19: responding to the COVID-19 outbreak quickly and efficiently.

BMC Med Res Methodol 2022 04 3;22(1):89. Epub 2022 Apr 3.

Beijing Key Laboratory of Etiology of Viral Diseases in Children, Capital Institute of Pediatrics, Beijing, China.

Background: Rapid Advice Guidelines (RAG) provide decision makers with guidance to respond to public health emergencies by developing evidence-based recommendations in a short period of time with a scientific and standardized approach. However, the experience from the development process of a RAG has so far not been systematically summarized. Therefore, our working group will take the experience of the development of the RAG for children with COVID-19 as an example to systematically explore the methodology, advantages, and challenges in the development of the RAG. We shall propose suggestions and reflections for future research, in order to provide a more detailed reference for future development of RAGs.

Result: The development of the RAG by a group of 67 researchers from 11 countries took 50 days from the official commencement of the work (January 28, 2020) to submission (March 17, 2020). A total of 21 meetings were held with a total duration of 48 h (average 2.3 h per meeting) and an average of 16.5 participants attending. Only two of the ten recommendations were fully supported by direct evidence for COVID-19, three recommendations were supported by indirect evidence only, and the proportion of COVID-19 studies among the body of evidence in the remaining five recommendations ranged between 10 and 83%. Six of the ten recommendations used COVID-19 preprints as evidence support, and up to 50% of the studies with direct evidence on COVID-19 were preprints.

Conclusions: In order to respond to public health emergencies, the development of RAG also requires a clear and transparent formulation process, usually using a large amount of indirect and non-peer-reviewed evidence to support the formation of recommendations. Strict following of the WHO RAG handbook does not only enhance the transparency and clarity of the guideline, but also can speed up the guideline development process, thereby saving time and labor costs.
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http://dx.doi.org/10.1186/s12874-022-01545-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8977048PMC
April 2022

Development process and clinical application of collagenase chemonucleolysis in the treatment of lumbar disc herniation: a narrative review in China.

Postgrad Med J 2022 Mar 14. Epub 2022 Mar 14.

Interventional Radiology and Pain Treatment, The Second Affiliated Hospital of Air Force Medical University, Air Force Medical University, Xi'an, China

Lumbar disc herniation (LDH) is one of the most common causes of lumbocrural pain. In the past 20 years, the incidence of LDH has increased dramatically. There are many treatments for LDH, including conservative treatment (such as acupuncture and physiotherapy), minimally invasive interventional treatment (such as collagenase chemonucleolysis and radiofrequency ablation) and surgical treatment. The main purpose of this paper is to review the development process and application status of collagenase chemonucleolysis in the treatment of LDH at home and abroad and provide a reference for clinical treatment.
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http://dx.doi.org/10.1136/postgradmedj-2021-141208DOI Listing
March 2022

Increased Potency and Breadth of SARS-CoV-2 Neutralizing Antibodies After a Third mRNA Vaccine Dose.

bioRxiv 2022 Feb 15. Epub 2022 Feb 15.

The omicron variant of SARS-CoV-2 infected very large numbers of SARS-CoV-2 vaccinated and convalescent individuals . The penetrance of this variant in the antigen experienced human population can be explained in part by the relatively low levels of plasma neutralizing activity against Omicron in people who were infected or vaccinated with the original Wuhan-Hu-1 strain . The 3 mRNA vaccine dose produces an initial increase in circulating anti-Omicron neutralizing antibodies, but titers remain 10-20-fold lower than against Wuhan-Hu-1 and are, in many cases, insufficient to prevent infection . Despite the reduced protection from infection, individuals that received 3 doses of an mRNA vaccine were highly protected from the more serious consequences of infection . Here we examine the memory B cell repertoire in a longitudinal cohort of individuals receiving 3 mRNA vaccine doses . We find that the 3 dose is accompanied by an increase in, and evolution of, anti-receptor binding domain specific memory B cells. The increase is due to expansion of memory B cell clones that were present after the 2 vaccine dose as well as the emergence of new clones. The antibodies encoded by these cells showed significantly increased potency and breadth when compared to antibodies obtained after the 2 vaccine dose. Notably, the increase in potency was especially evident among newly developing clones of memory cells that differed from the persisting clones in targeting more conserved regions of the RBD. Overall, more than 50% of the analyzed neutralizing antibodies in the memory compartment obtained from individuals receiving a 3 mRNA vaccine dose neutralized Omicron. Thus, individuals receiving 3 doses of an mRNA vaccine encoding Wuhan-Hu-1, have a diverse memory B cell repertoire that can respond rapidly and produce antibodies capable of clearing even diversified variants such as Omicron. These data help explain why a 3 dose of an mRNA vaccine that was not specifically designed to protect against variants is effective against variant-induced serious disease.
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http://dx.doi.org/10.1101/2022.02.14.480394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8863143PMC
February 2022

Potentially effective drugs for the treatment of COVID-19 or MIS-C in children: a systematic review.

Eur J Pediatr 2022 May 22;181(5):2135-2146. Epub 2022 Feb 22.

Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.

The purpose of this systematic review is to evaluate the efficacy and safety of using potential drugs: remdesivir and glucocorticoid in treating children and adolescents with COVID-19 and intravenous immunoglobulin (IVIG) in treating MIS-C. We searched seven databases, three preprint platform, ClinicalTrials.gov, and Google from December 1, 2019, to August 5, 2021, to collect evidence of remdesivir, glucocorticoid, and IVIG which were used in children and adolescents with COVID-19 or MIS-C. A total of nine cohort studies and one case series study were included in this systematic review. In terms of remdesivir, the meta-analysis of single-arm cohort studies have shown that after the treatment, 54.7% (95%CI, 10.3 to 99.1%) experienced adverse events, 5.6% (95%CI, 1.2 to 10.1%) died, and 27.0% (95%CI, 0 to 73.0%) needed extracorporeal membrane oxygenation or invasive mechanical ventilation. As for glucocorticoids, the results of the meta-analysis showed that the fixed-effect summary odds ratio for the association with mortality was 2.79 (95%CI, 0.13 to 60.87), and the mechanical ventilation rate was 3.12 (95%CI, 0.80 to 12.08) for glucocorticoids compared with the control group. In terms of IVIG, most of the included cohort studies showed that for MIS-C patients with more severe clinical symptoms, IVIG combined with methylprednisolone could achieve better clinical efficacy than IVIG alone.

Conclusions: Overall, the current evidence in the included studies is insignificant and of low quality. It is recommended to conduct high-quality randomized controlled trials of remdesivir, glucocorticoids, and IVIG in children and adolescents with COVID-19 or MIS-C to provide substantial evidence for the development of guidelines.

What Is Known: • The efficacy and safety of using potential drugs such as remdesivir, glucocorticoid, and intravenous immunoglobulin (IVIG) in treating children and adolescents with COVID-19/MIS-C are unclear.

What Is New: • Overall, the current evidence cannot adequately demonstrate the effectiveness and safety of using remdesivir, glucocorticoids, and IVIG in treating children and adolescents with COVID-19 or MIS-C. • We are calling for the publication of high-quality clinical trials and provide substantial evidence for the development of guidelines.
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http://dx.doi.org/10.1007/s00431-022-04388-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8861482PMC
May 2022

Sildenafil for adult Asian patients with pulmonary arterial hypertension: a systematic review and meta-analysis.

Ann Palliat Med 2022 Jan;11(1):339-351

Department of Cardiology, Guangdong Provincial People's Hospital, Guangzhou, China.

Background: The prognosis of patients with untreated pulmonary arterial hypertension (PAH) has historically been poor. Previous studies have recommended that sildenafil was beneficial, but the dose varies greatly. In this study, we aimed to evaluate the safety and effectiveness of sildenafil [dose: 20 mg/three times a day (TID)] for adult Asian PAH patients.

Methods: Electronic databases (MEDLINE, Embase, Web of Science, the Cochrane Library, CBM, CNKI, and Wanfang Data) were searched from their inception to January 2022. We recruited all randomized controlled trials and non-randomized studies of interventions that compared sildenafil (20 mg/TID) versus placebo or symptomatic treatment for adult Asian PAH patients.

Results: A total of 10 studies involving 480 participants were included. Compared to symptomatic treatment, sildenafil-treated patients were more likely to walk 57.68 meters further in six-minute walk distance [mean difference (MD) =57.68 m, 95% confidence interval (CI): 41.55 to 73.81], achieve an improvement in systemic arterial oxygen saturation (MD =2.48%, 95% CI: 1.26 to 3.71), and increase the score of the Borg scale for dyspnea (MD =-0.99 points, 95% CI: -1.45 to -0.53). The total number of patients with World Health Organization class III and IV also exhibited a downtrend. Compared to the placebo, sildenafil was associated with a reduction in the mean pulmonary artery pressure (MD =-4.13 mmHg, 95% CI: -6.52 to -1.74) and the level of brain natriuretic peptide (MD =-86.16 pg/mL, 95% CI: -103.39 to -68.93). The most common adverse events were headache, flushing, dyspepsia, and diarrhea, which were relatively mild.

Discussion: Sildenafil at a dose of 20 mg/TID is well tolerated in adult Asian PAH patients, and is associated with statistically significant improvements in exercise capacity, cardio-pulmonary function, and haemodynamic indices. The long-term prognosis still needs to be evaluated and confirmed by further trials.
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http://dx.doi.org/10.21037/apm-21-3979DOI Listing
January 2022

Conserved Neutralizing Epitopes on the N-Terminal Domain of Variant SARS-CoV-2 Spike Proteins.

bioRxiv 2022 Feb 1. Epub 2022 Feb 1.

Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.

SARS-CoV-2 infection or vaccination produces neutralizing antibody responses that contribute to better clinical outcomes. The receptor binding domain (RBD) and the N-terminal domain (NTD) of the spike trimer (S) constitute the two major neutralizing targets for the antibody system. Neutralizing antibodies targeting the RBD bind to several different sites on this domain. In contrast, most neutralizing antibodies to NTD characterized to date bind to a single supersite, however these antibodies were obtained by methods that were not NTD specific. Here we use NTD specific probes to focus on anti-NTD memory B cells in a cohort of pre-omicron infected individuals some of which were also vaccinated. Of 275 NTD binding antibodies tested 103 neutralized at least one of three tested strains: Wuhan-Hu-1, Gamma, or PMS20, a synthetic variant which is extensively mutated in the NTD supersite. Among the 43 neutralizing antibodies that were further characterized, we found 6 complementation groups based on competition binding experiments. 58% targeted epitopes outside the NTD supersite, and 58% neutralized either Gamma or Omicron, but only 14% were broad neutralizers. Three of the broad neutralizers were characterized structurally. C1520 and C1791 recognize epitopes on opposite faces of the NTD with a distinct binding pose relative to previously described antibodies allowing for greater potency and cross-reactivity with 7 different variants including Beta, Delta, Gamma and Omicron. Antibody C1717 represents a previously uncharacterized class of NTD-directed antibodies that recognizes the viral membrane proximal side of the NTD and SD2 domain, leading to cross-neutralization of Beta, Gamma and Omicron. We conclude SARS-CoV-2 infection and/or Wuhan-Hu-1 mRNA vaccination produces a diverse collection of memory B cells that produce anti-NTD antibodies some of which can neutralize variants of concern. Rapid recruitment of these cells into the antibody secreting plasma cell compartment upon re-infection likely contributes to the relatively benign course of subsequent infections with SARS-CoV-2 variants including omicron.
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http://dx.doi.org/10.1101/2022.02.01.478695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8820657PMC
February 2022
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