Publications by authors named "Di Lu"

434 Publications

Deletion of Mettl3 at the Pro-B Stage Marginally Affects B Cell Development and Profibrogenic Activity of B Cells in Liver Fibrosis.

J Immunol Res 2022 14;2022:8118577. Epub 2022 Jun 14.

Biotherapy Center, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

N6-methyladenosine (mA) modification plays a pivotal role in cell fate determination. Previous studies show that eliminating mA using dramatically impairs B cell development. However, whether disturbing mA modification at later stages affects B cell development and function remains elusive. Here, we deleted mA methyltransferase Mettl3 from the pro-B stage on using ( cKO) and found that the frequency of total B cells in peripheral blood, peritoneal cavity, and liver is comparable between cKO mice and wild-type (WT) littermates, while the percentage of whole splenic B cells slightly increases in cKO individuals. The proportion of pre-pro-B, pro-B, pre-B, immature, and mature B cells in the bone marrow were minimally affected. Loss of resulted in increased apoptosis but barely affected B cells' proliferation and IgG production upon LPS, CD40L, anti-IgM, or TNF- stimulation. Different stimuli had different effects on B cell activation. In addition, B cell-specific Mettl3 knockout had no influence on the pro-fibrogenic activity of B cells in liver fibrosis, evidenced by comparable fibrosis in carbon tetrachloride- (CCl-) treated cKO mice and WT controls. In summary, our study demonstrated that deletion of Mettl3 from the pro-B stage on has minimal effects on B cell development and function, as well as profibrogenic activity of B cells in liver fibrosis, revealing a stage-specific dependence on Mettl3-mediated mA of B cell development.
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http://dx.doi.org/10.1155/2022/8118577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213183PMC
June 2022

Prevalence of autoimmunity and atopy in US adults with glioblastoma and meningioma.

Neuro Oncol 2022 Jun 17. Epub 2022 Jun 17.

Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Palo Alto, California, USA.

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http://dx.doi.org/10.1093/neuonc/noac145DOI Listing
June 2022

Quantitative analysis of polypropylene glycol polymers by liquid chromatography tandem mass spectrometry based on collision induced dissociation technique.

J Chromatogr A 2022 Jun 11;1676:463214. Epub 2022 Jun 11.

School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, 124221, PR China; JenKem Technology Co. LTD, Tianjin, 300450, PR China. Electronic address:

Polypropylene glycol (PPG) is a commonly used synthetic polymer in many fields. Investigating the toxicity and pharmacokinetic behavior of PPG polymers is necessary and important for evaluating their safety in medicine and daily cosmetics. In this study, PPG425, PPG1K and PPG2K were selected as the target polymers for cytotoxicity and cellular pharmacokinetics study of PPG polymers. Structural diversity and polydisperse molecular weights (MWs) are significant challenges for quantification of PPG polymers by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Collision induced dissociation in source or collision cell generated a series of PPG-related product ions at m/z 59.0, 117.1, 175.1, 233.2, 291.2, 349.3, 407.2, 465.3 and 523.5 corresponding to fragments containing 1, 2, 3, 4, 5, 6, 7, 8, 9 repeating propylene oxide subunits. PPG425 was determined by the sum of the MRM acquisitions used the transitions [M+H] precursor ions → product ions. PPG1K and PPG2K were determined by the MRM acquisitions used the transitions [M+H] precursor ions → product ions at m/z 233.2(four subunits)→59.0(one subunit). Based on the collision induced disassociation technique and structural specific product ions, pharmacokinetic studies of PEG425, PPG1K and PPG2K were successfully conducted in McF-7 cells. The experimental results revealed that PPG polymers are not biologically inert and they can enter into McF-7 cells. The safety of PPG polymers should be considered when they are used as pharmaceutical or cosmetic excipients.
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http://dx.doi.org/10.1016/j.chroma.2022.463214DOI Listing
June 2022

Extrahepatic organs in the development of non-alcoholic fatty liver disease in liver transplant patients.

Hepatobiliary Surg Nutr 2022 Jun;11(3):400-411

Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Background And Objective: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in patients who undergo liver transplantation (LT). Whereas there is huge data on NAFLD, little is known about NAFLD in LT. In this review, we aim to explore extrahepatic organs and their potential mechanisms in the development of NAFLD in LT patients and discuss current limitations in preclinical and clinical scenarios with suggestions for future study.

Methods: The following keywords, such as NAFLD, NASH, liver transplant, therapy, pathogenesis and biomarkers, were set for literature retrieval. The articles which were published articles in English till 25th June 2020 in PubMed database were included, and there is no limit for the study design type.

Key Content And Findings: Following LT, there are significant shifts in the microbiota and farnesoid X receptor may be a potential therapeutic target for NAFLD in LT settings. The roles of probiotics and diet on NALFD remain inconclusive in LT background. Nevertheless, the adipokines and cytokines disorder and local insulin resistance of adipose tissue may contribute to NAFLD process. Bariatric surgeries are promising in controlling de novo and recurrent NAFLD with significant reduction in abdominal adipose tissue, despite the optimal timing is inconclusive in LT cases. Furthermore, circumstantial evidence indicates that miRNA-33a may function as a mediator bridging sarcopenia and NAFLD of post-LT. β-Hydroxy-β-Methyl-Butyrate treatment could improve muscle status in graft recipients and shows protective potential for NAFLD in LT settings.

Conclusions: Gut, adipose tissue and muscle are intricately intertwined in promoting NAFLD in LT cases. Further animal studies are needed to deepen our understanding of mechanisms in multi-organ crosstalk. High quality clinical trials are warrant for making guidelines and developing management strategies on NAFLD after LT.
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http://dx.doi.org/10.21037/hbsn-20-568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9186206PMC
June 2022

Wireless implantable optical probe for continuous monitoring of oxygen saturation in flaps and organ grafts.

Nat Commun 2022 May 30;13(1):3009. Epub 2022 May 30.

Department of Materials Science and Engineering, Northwestern University, Evanston, IL, 60208, USA.

Continuous, real-time monitoring of perfusion after microsurgical free tissue transfer or solid organ allotransplantation procedures can facilitate early diagnosis of and intervention for anastomotic thrombosis. Current technologies including Doppler systems, cutaneous O-sensing probes, and fluorine magnetic resonance imaging methods are limited by their intermittent measurements, requirements for skilled personnel, indirect interfaces, and/or their tethered connections. This paper reports a wireless, miniaturized, minimally invasive near-infrared spectroscopic system designed for uninterrupted monitoring of local-tissue oxygenation. A bioresorbable barbed structure anchors the probe stably at implantation sites for a time period matched to the clinical need, with the ability for facile removal afterward. The probe connects to a skin-interfaced electronic module for wireless access to essential physiological parameters, including local tissue oxygenation, pulse oxygenation, and heart rate. In vitro tests and in vivo studies in porcine flap and kidney models demonstrate the ability of the system to continuously measure oxygenation with high accuracy and sensitivity.
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http://dx.doi.org/10.1038/s41467-022-30594-zDOI Listing
May 2022

One Shoot, Two Birds: Alleviating Inflammation Caused by Ischemia/Reperfusion Injury to Reduce the Recurrence of Hepatocellular Carcinoma.

Front Immunol 2022 11;13:879552. Epub 2022 May 11.

Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Inflammation is crucial to tumorigenesis and the development of metastasis. Hepatic ischemia/reperfusion injury (IRI) is an unresolved problem in liver resection and transplantation which often establishes and remodels the inflammatory microenvironment in liver. More and more experimental and clinical evidence unmasks the role of hepatic IRI and associated inflammation in promoting the recurrence of hepatocellular carcinoma (HCC). Meanwhile, approaches aimed at alleviating hepatic IRI, such as machine perfusion, regulating the gut-liver axis, and targeting key inflammatory components, have been proved to prevent HCC recurrence. This review article highlights the underlying mechanisms and promising therapeutic strategies to reduce tumor recurrence through alleviating inflammation induced by hepatic IRI.
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http://dx.doi.org/10.3389/fimmu.2022.879552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9130551PMC
June 2022

Microglial integrin, chemokine receptors, and inflammatory response vary with development.

Biochem Biophys Res Commun 2022 Jul 17;615:94-101. Epub 2022 May 17.

Department of Anatomy and Histology and Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, Yunnan, 650500, China. Electronic address:

Understanding microglia development could improve our understanding of the central nervous system (CNS) and neurological diseases. To explore the immune phenotypic changes that occur in microglia during development, we studied the morphology, inflammatory response, and expression of several important immune-related proteins in normal microglia from the embryonic, neonatal (postnatal day 3), and adult stages. Results showed that implantation of microglia into the CNS until adulthood resulted in dynamic changes in the expression levels of CD11b (α chain of complement receptor 3) and CX3CR1 (a chemokine receptor), which were consistent and correlated. Expression of proinflammatory cytokines in microglia during development is dynamic and highest in perinatal period. The inflammatory response of microglia was more vigorous and intense in the neonatal microglia than in the adult microglia. Furthermore, the morphology and function of neonatal and adult microglia differed, and thus neonatal microglia cannot be used in lieu of adult microglia for functional studies. Taken together, our results suggest that microglial integrin, chemokine receptors, and inflammatory responses vary with developmental age, which is an important finding for studying the role of microglia in different age-related neurological diseases.
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http://dx.doi.org/10.1016/j.bbrc.2022.05.054DOI Listing
July 2022

Coordinated motion of molecular motors on DNA chains with branch topology.

Authors:
Di Lu Bin Chen

Acta Mech Sin 2022 16;38(3):621225. Epub 2022 Feb 16.

Department of Engineering Mechanics, Zhejiang University, Hangzhou, 310058 China.

To understand the macroscopic mechanical behaviors of responsive DNA hydrogels integrated with DNA motors, we constructed a state map for the translocation process of a single FtsK on a single DNA chain at the molecular level and then investigated the movement of single or multiple FtsK motors on DNA chains with varied branch topologies. Our studies indicate that multiple FtsK motors can have coordinated motion, which is mainly due to the force-responsive behavior of individual FtsK motors. We further suggest the potential application of motors of FtsK, together with DNA chains of specific branch topology, to serve as strain sensors in hydrogels.
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http://dx.doi.org/10.1007/s10409-021-09045-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9109741PMC
February 2022

WNT5A promotes the metastasis of esophageal squamous cell carcinoma by activating the HDAC7/SNAIL signaling pathway.

Cell Death Dis 2022 May 20;13(5):480. Epub 2022 May 20.

Department of Thoracic Surgery, Tangdu Hospital, The Air Force Medical University, 1 Xinsi Road, Xi'an, 710038, China.

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide, with high incidence and mortality rates and low survival rates. However, the detailed molecular mechanism of ESCC progression remains unclear. Here, we first showed significantly higher WNT5A and SNAIL expression in ESCC samples than in corresponding paracancerous samples. High WNT5A and SNAIL expression levels correlated positively with lymphatic metastasis and poor prognosis for patients with ESCC based on immunohistochemical (IHC) staining of 145 paired ESCC samples. Spearman's correlation analyses confirmed the strong positive correlation between WNT5A and SNAIL expression, and patients with ESCC presenting coexpression of WNT5A and SNAIL had the worst prognosis. Then, we verified that the upregulation of WNT5A promoted ESCC cell metastasis in vivo and in vitro, suggesting that WNT5A might be a promising therapeutic target for the prevention of ESCC. Furthermore, WNT5A overexpression induced the epithelial-mesenchymal transition via histone deacetylase 7 (HDAC7) upregulation, and HDAC7 silencing significantly reversed WNT5A-induced SNAIL upregulation and ESCC cell metastasis. In addition, we used HDAC7 inhibitors (SAHA and TMP269) to further confirm that HDAC7 participates in WNT5A-mediated carcinogenesis. Based on these results, HDAC7 is involved in WNT5A-mediated ESCC progression, and approaches targeting WNT5A and HDAC7 might be potential therapeutic strategies for ESCC.
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http://dx.doi.org/10.1038/s41419-022-04901-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9122958PMC
May 2022

A new self-immolative colistin prodrug with dual targeting functionalities and reduced toxicity for the treatment of intracellular bacterial infections.

J Biomed Mater Res A 2022 May 20. Epub 2022 May 20.

School of Chemical Engineering and Technology, Key Laboratory of Systems Bioengineering (Ministry of Education), Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin, P. R. China.

Colistin is a potent antibiotic but its severe side effects including nephrotoxicity and neurotoxicity are the roadblock for their wide use in clinics. To solve this problem, we synthesized a new prodrug, mannose-maltose-colistin conjugate, termed MMCC that can reversibly mask the five amines of colistin that are primarily responsible for the toxicity. The deliberated design of disulfide-based self-immolative linker warranted the reversibly release of the pristine amines of colistin on demand without sacrificing antimicrobial efficacy. Once MMCC was delivered in cells, reducing agents cleaves the disulfide bond and release the pristine amines. The targeting ligands of maltose and mannose were grafted on colistin conjugate for targeting delivery of colistin to bacteria and macrophages, respectively. Taken together, MMCC as a new class of antimicrobial biomaterials, demonstrates its great potential for the treatment of intracellular bacterial infections.
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http://dx.doi.org/10.1002/jbm.a.37410DOI Listing
May 2022

Lysine Acetylation/Deacetylation Modification of Immune-Related Molecules in Cancer Immunotherapy.

Front Immunol 2022 2;13:865975. Epub 2022 May 2.

Department of Thoracic Surgery, Tangdu Hospital, The Air Force Military Medical University, Xi'an, China.

As major post-translational modifications (PTMs), acetylation and deacetylation are significant factors in signal transmission and cellular metabolism, and are modulated by a dynamic process two pivotal categories of enzymes, histone acetyltransferases (HATs) and histone deacetylases (HDACs). In previous studies, dysregulation of lysine acetylation and deacetylation has been reported to be associated with the genesis and development of malignancy. Scientists have recently explored acetylation/deacetylation patterns and prospective cancer therapy techniques, and the FDA has approved four HDAC inhibitors (HDACi) to be used in clinical treatment. In the present review, the most recent developments in the area of lysine acetylation/deacetylation alteration in cancer immunotherapy were investigated. Firstly, a brief explanation of the acetylation/deacetylation process and relevant indispensable enzymes that participate therein is provided. Subsequently, a multitude of specific immune-related molecules involved in the lysine acetylation/deacetylation process are listed in the context of cancer, in addition to several therapeutic strategies associated with lysine acetylation/deacetylation modification in cancer immunotherapy. Finally, a number of prospective research fields related to cancer immunotherapy concepts are offered with detailed analysis. Overall, the present review may provide a reference for researchers in the relevant field of study, with the aim of being instructive and meaningful to further research as well as the selection of potential targets and effective measures for future cancer immunotherapy strategies.
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http://dx.doi.org/10.3389/fimmu.2022.865975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108232PMC
May 2022

MicroRNA-27a-3p relieves inflammation and neurologic impairment after cerebral ischaemia reperfusion via inhibiting lipopolysaccharide induced TNF factor and the TLR4/NF-κB pathway.

Eur J Neurosci 2022 May 18. Epub 2022 May 18.

Department of Anesthesiology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.

Cerebral ischaemia reperfusion (CIR) affects microRNA (miR) expression and causes substantial inflammation. Here, we investigated the influence and underlying mechanism of miR-27a-3p in rats with CIR. First, biliverdin treatment relieved cerebral infarction and decreased the levels of serum interleukin (IL)-1β, IL-6, and TNF-α. Through our previous study, we found key miR-27a-3p and its targeted gene LITAF might involve in the molecular mechanism of CIR. Then, the regulation between miR-27a-3p and LITAF was verified by the temporal miR-27a-3p and LITAF expression profiles and luciferase assay. Moreover, intracerebroventricular injection of the miR-27a-3p mimic significantly decreased the LITAF, TLR4, NF-κB, and IL-6 levels at 24 h post-surgery, whereas miR-27a-3p inhibitor reversed these effects. Furthermore, miR-27a-3p mimic could relieve cerebral infarct and neurologic deficit after CIR. In addition, injection of miR-27a-3p mimic decreased neuronal damage induced by CIR. Taken together, our results suggest that miR-27a-3p protects against CIR by relieving inflammation, neuronal damage, and neurologic deficit via regulating LITAF and the TLR4/NF-κB pathway.
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http://dx.doi.org/10.1111/ejn.15720DOI Listing
May 2022

The value of as prognostic and immunological biomarker in pan-cancer.

Ann Transl Med 2022 Apr;10(8):466

Department of Thoracic Surgery, Tangdu Hospital, The Air Force Military Medical University, Xi'an, China.

Background: Finding new immune-related biomarkers is one of the promising research directions for tumor immunotherapy. The gene could stimulate the WNT pathway and regulate the progression of various tumors. Recent studies have partially revealed the relationship between and tumor immunity, but the correlation and underlying mechanisms in pan-cancer remain obscure. Thus, we conducted this study aiming to characterize the prognostic value and immunological portrait of in cancer.

Methods: The data obtained from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE) databases was utilized to analyze expression levels by Kruskal-Wallis test and correlation to prognosis by Cox regression test and Kaplan-Meier test, while the data was also used to study the association between expression and immune microenvironment, immune neoantigens, immune checkpoints, tumor mutational burden (TMB), and microsatellite instability (MSI) in pan-cancer. Gene set enrichment analysis (GSEA) was used to clarify the relevant signaling pathways. The R package was used for data analysis and to create the plots.

Results: The pan-cancer analysis revealed that the expression level of is generally elevated in most tumors (19/34, 55.88%), and high expression was correlated with poor prognosis in esophageal carcinoma (ESCA, P<0.05), low-grade glioma (LGG, P<0.01), adrenocortical carcinoma (ACC, P<0.01), pancreatic adenocarcinoma (PAAD, P<0.01), and head and neck squamous cell carcinoma (HNSC, P<0.05). In addition, expression was positively associated with immune infiltration, stromal score, and immune checkpoints in most cancers, and correlated to immune neoantigens, TMB, and MSI. Finally, GSEA indicated that is implicated in the transforming growth factor β (TGFβ), Notch, and Hedgehog signaling pathways, which may be related to tumor immunity.

Conclusions: The expression of is elevated in most tumors and associated with tumor prognosis. Furthermore, is associated with tumor immunity and may be an immunological biomarker in cancer.
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http://dx.doi.org/10.21037/atm-22-1317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9096401PMC
April 2022

Machine vision-assisted identification of the lung adenocarcinoma category and high-risk tumor area based on CT images.

Patterns (N Y) 2022 Apr 3;3(4):100464. Epub 2022 Mar 3.

School of Data Science, City University of Hong Kong, Hong Kong SAR, China.

Computed tomography (CT) is a widely used medical imaging technique. It is important to determine the relationship between CT images and pathological examination results of lung adenocarcinoma to better support its diagnosis. In this study, a bilateral-branch network with a knowledge distillation procedure (KDBBN) was developed for the auxiliary diagnosis of lung adenocarcinoma. KDBBN can automatically identify adenocarcinoma categories and detect the lesion area that most likely contributes to the identification of specific types of adenocarcinoma based on lung CT images. In addition, a knowledge distillation process was established for the proposed framework to ensure that the developed models can be applied to different datasets. The results of our comprehensive computational study confirmed that our method provides a reliable basis for adenocarcinoma diagnosis supplementary to the pathological examination. Meanwhile, the high-risk area labeled by KDBBN highly coincides with the related lesion area labeled by doctors in clinical diagnosis.
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http://dx.doi.org/10.1016/j.patter.2022.100464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9024012PMC
April 2022

A Chinese Family With Cerebral Cavernous Malformation Caused by a Frameshift Mutation of the Gene: A Case Report and Review of the Literature.

Front Neurol 2022 4;13:795514. Epub 2022 Apr 4.

Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, China.

Background: Familial cerebral cavernous malformation (FCCM) is a vascular malformation disease closely linked to three identified genes: and . Over the past decade, a few cases of cerebral cavernous malformation (CCM) caused by different gene mutations have been reported in Chinese families. Herein, we introduce a Chinese family affected by FCCM due to a kind of frameshift mutation. At the same time, a literature review was conducted to identify case reports of familial cerebral cavernous malformation.

Case Presentation: The proband in the family in question demonstrated a series of clinical symptoms and features, including headache and bleeding. The proband was hospitalized for headache twice and, both times was examined under suspicion of CCM and received surgical treatment. Magnetic resonance imaging results showed that the proband had multiple intracranial vascular lesions, including on the brain, brainstem, and cerebellum. Genetic test results showed that the classic gene in the proband had a pathogenic mutation. The family members of the proband also showed typical cerebral cavernous malformation when considering clinical manifestations, magnetic resonance imaging findings and genetic test results.

Conclusions: We report a case of Chinese FCCM and its associated symptoms with -deletion mutations in China. Our findings deepen our understanding of CCM mutations and related phenotypes, the investigation results of this clinical experiment further show that the gene mutation form we reported plays an important role in human FCCM, and this trial investigation is beneficial for genetic counseling for CCM patients.
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http://dx.doi.org/10.3389/fneur.2022.795514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9013744PMC
April 2022

Facial Stimulation Induces Long-Term Potentiation of Mossy Fiber-Granule Cell Synaptic Transmission GluN2A-Containing -Methyl-D-Aspartate Receptor/Nitric Oxide Cascade in the Mouse Cerebellum.

Front Cell Neurosci 2022 30;16:863342. Epub 2022 Mar 30.

Department of Physiology, College of Basic Medicine, Jilin Medical University, Jilin, China.

Long-term synaptic plasticity in the cerebellar cortex is a possible mechanism for motor learning. Previous studies have demonstrated the induction of mossy fiber-granule cell (MF-GrC) synaptic plasticity under and conditions, but the mechanisms underlying sensory stimulation-evoked long-term synaptic plasticity of MF-GrC in living animals are unclear. In this study, we investigated the mechanism of long-term potentiation (LTP) of MF-GrC synaptic transmission in the cerebellum induced by train of facial stimulation at 20 Hz in urethane-anesthetized mice using electrophysiological recording, immunohistochemistry techniques, and pharmacological methods. Blockade of GABA receptor activity and repetitive facial stimulation at 20 Hz (240 pulses) induced an LTP of MF-GrC synapses in the mouse cerebellar cortical folium Crus II, accompanied with a decrease in paired-pulse ratio (N2/N1). The facial stimulation-induced MF-GrC LTP was abolished by either an -methyl-D-aspartate (NMDA) receptor blocker, i.e., D-APV, or a specific GluNR2A subunit-containing NMDA receptor antagonist, PEAQX, but was not prevented by selective GluNR2B or GluNR2C/D subunit-containing NMDA receptor blockers. Application of GNE-0723, a selective and brain-penetrant-positive allosteric modulator of GluN2A subunit-containing NMDA receptors, produced an LTP of N1, accompanied with a decrease in N2/N1 ratio, and occluded the 20-Hz facial stimulation-induced MF-GrC LTP. Inhibition of nitric oxide synthesis (NOS) prevented the facial stimulation-induced MF-GrC LTP, while activation of NOS produced an LTP of N1, with a decrease in N2/N1 ratio, and occluded the 20-Hz facial stimulation-induced MF-GrC LTP. In addition, GluN2A-containing NMDA receptor immunoreactivity was observed in the mouse cerebellar granular layer. These results indicate that facial stimulation at 20 Hz induced LTP of MF-GrC synaptic transmission the GluN2A-containing NMDA receptor/nitric oxide cascade in mice. The results suggest that the sensory stimulation-evoked LTP of MF-GrC synaptic transmission in the granular layer may play a critical role in cerebellar adaptation to native mossy fiber excitatory inputs and motor learning behavior in living animals.
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http://dx.doi.org/10.3389/fncel.2022.863342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9005984PMC
March 2022

Sequential gastrodin release PU/n-HA composite scaffolds reprogram macrophages for improved osteogenesis and angiogenesis.

Bioact Mater 2023 Jan 1;19:24-37. Epub 2022 Apr 1.

Yunnan Key Laboratory of Stem Cell and Regenerative Medicine, Science and Technology Achievement Incubation Center, Kunming Medical University, Kunming, 650500, China.

Wound healing is a highly orchestrated process involving a variety of cells, including immune cells. Developing immunomodulatory biomaterials for regenerative engineering applications, such as bone regeneration, is an appealing strategy. Herein, inspired by the immunomodulatory effects of gastrodin (a bioactive component in traditional Chinese herbal medicine), a series of new immunomodulatory gastrodin-comprising biodegradable polyurethane (gastrodin-PU) and nano-hydroxyapatite (n-HA) (gastrodin-PU/n-HA) composites were developed. RAW 264.7 macrophages, rat bone marrow mesenchymal stem cells (rBMSCs), and human umbilical vein endothelial cells (HUVECs) were cultured with gastrodin-PU/n-HA containing different concentrations of gastrodin (0.5%, 1%, and 2%) to decipher their immunomodulatory effects on osteogenesis and angiogenesis . Results demonstrated that, compared with PU/n-HA, gastrodin-PU/n-HA induced macrophage polarization toward the M2 phenotype, as evidenced by the higher expression level of pro-regenerative cytokines (CD206, Arg-1) and the lower expression of pro-inflammatory cytokines (iNOS). The expression levels of osteogenesis-related factors (BMP-2 and ALP) in the rBMSCs and angiogenesis-related factors (VEGF and BFGF) in the HUVECs were significantly up-regulated in gastrodin-PU/n-HA/macrophage-conditioned medium. The immunomodulatory effects of gastrodin-PU/n-HA to reprogram macrophages from a pro-inflammatory (M1) phenotype to an anti-inflammatory and pro-healing (M2) phenotype were validated in a rat subcutaneous implantation model. And the 2% gastrodin-PU/n-HA significantly decreased fibrous capsule formation and enhanced angiogenesis. Additionally, 2% gastrodin-PU/n-HA scaffolds implanted in the rat femoral condyle defect model showed accelerated osteogenesis and angiogenesis. Thus, the novel gastrodin-PU/n-HA scaffold may represent a new and promising immunomodulatory biomaterial for bone repair and regeneration.
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http://dx.doi.org/10.1016/j.bioactmat.2022.03.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8980440PMC
January 2023

Olmesartan Attenuates Single-Lung Ventilation Induced Lung Injury Regulating Pulmonary Microbiota.

Front Pharmacol 2022 23;13:822615. Epub 2022 Mar 23.

Department of Thoracic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Single-lung ventilation (SLV) associated acute lung injury is similar to ischemia reperfusion (IR) injury which is usually occurred during lung surgery. Olmesartan (Olm), a novel angiotensin receptor blocker (ARB), has been reported to ameliorate organ IR injury. Several recent studies have shown that lung microbiota may be involved in pulmonary diseases, but the effect of pulmonary microbiota in SLV-induced lung injury has not been reported. This study aims to determine the mechanism of how Olm attenuates SLV induced lung injury. Our data showed that 7 days Olm treatment before modeling markedly alleviated SLV-induced lung injury by suppressing inflammation and reactive oxygen species. Bronchoalveolar lavage fluid samples from the injured side were collected for 16S rRNA gene-based sequencing analysis and 53 different bacteria at the genus and species levels were identified. Furthermore, the injured lung samples were collected for metabolomics analysis using liquid chromatography-mass spectrometry analyses to explore differential metabolites. The Kyoto Encyclopedia of Genes and Genomes (KEGG) was applied to analyze the correlation between differential metabolites and lung microbiota. A total of 38 pathways were identified according to differential metabolites and 275 relevant pathways were enriched via analyzing the microbial community, 24 pathways were both identified by analyzing either metabolites or microbiota, including pyrimidine metabolism, purine metabolism, aminoacyl-tRNA biosynthesis and ATP-binding cassette transporter. Besides classical blockage of the renin-angiotensin II system, Olm could also alleviate SLV-induced lung injury by rewiring the interaction between pulmonary microbiota and metabolites.
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http://dx.doi.org/10.3389/fphar.2022.822615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8984607PMC
March 2022

Dielectric property measurements for the rapid differentiation of thoracic lymph nodes using XGBoost in patients with non-small cell lung cancer: a self-control clinical trial.

Transl Lung Cancer Res 2022 Mar;11(3):342-356

Department of Thoracic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Background: One of the important criteria for thoracic surgeons in making surgical strategies is whether the thoracic lymph nodes (LNs) are metastatic. Frozen section (FS) is widely used as an intraoperative diagnostic method, which is time-consuming and expensive. The dielectric property, including permittivity and conductivity, varies with different tissues. The extreme gradient boosting (XGBoost) is a powerful classifier and widely used. Thus, this study aims to develop the rapid differentiation method combining dielectric property and XGBoost, and assess its efficacy on the thoracic LNs in patients with non-small cell lung cancer (NSCLC).

Methods: This was a single center self-control clinical trial with paraffin pathology section (PPS) results as gold diagnosis. The LNs from the pathologically diagnosed patients with NSCLC were recruited, which were measured by open-ended coaxial probe for the dielectric property within 1-4,000 MHz after removal from the patients and then were sent to perform FS and PPS diagnosis. The XGBoost combining with dielectric property was developed to differentiate malignant LNs from benign LNs. The classified efficacy was determined using the receiver operator characteristic (ROC) curve and area under the curve (AUC).

Results: A total of 204 LNs from 67 NSCLC patients were analyzed. The mean values of the two parameters differed significantly (P<0.001) between benign and malignant LNs. The AUC for permittivity and conductivity were 0.850 [95% confidence interval (CI): 0.786 to 0.915; P<0.001] and 0.887 (95% CI: 0.828 to 0.946; P<0.001), respectively. The AUC was 0.893 (95% CI: 0.834 to 0.951; P<0.001) when the two parameters were combined. After the application of the XGBoost, the AUC was 0.968 (95% CI: 0.918 to 1.000; P<0.001), and the accuracy was 87.80%. Its sensitivity was 58.33% and the specificity was 100%. When the Synthetic Minority Oversampling Technique (SMOTE) algorithm was used, the AUC was 0.954 (95% CI: 0.883 to 1.000; P<0.001) and the accuracy was 92.68%. Its sensitivity was 83.33% and the specificity was 96.55%.

Conclusions: This method might be useful for thoracic surgeons during surgery, for its relatively high efficacy in rapid differentiation of LNs for patients with NSCLC.
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http://dx.doi.org/10.21037/tlcr-22-92DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8988073PMC
March 2022

Ultrafast and high-throughput quantitative analysis of carbamazepine in human plasma by direct analysis in real time tandem mass spectrometry coupled with solid phase extraction to eliminate matrix effects.

J Pharm Biomed Anal 2022 May 5;214:114751. Epub 2022 Apr 5.

School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin 124221, PR China; The First Hospital of Jilin University, Jilin University, Xinmin Street, Changchun 130061, PR China. Electronic address:

Therapeutic drug monitoring of carbamazepine is necessary for its clinical application with the purpose to reach therapeutic concentration and reduce the risk of concentration-dependent toxicity. An ultrafast analytical assay for quantification of carbamazepine in human plasma was developed and validated based on direct analysis in real time tandem mass spectrometry (DART-MS/MS). After reversed phase solid phase extraction with Waters Oasis HLB, carbamazepine and internal standard carbamazepine-DN were monitored by positive ion mode followed by multiple reaction monitoring (MRM) of the transitions at m/z 237.1→194.0 and 240.1→196.2, respectively. The DART-MS/MS method is ultrafast and high-throughput and the analytical time for each sample is only 0.4 min. The assay was linear in the concentration range 0.50-30 μg/mL and intra- and inter-day accuracies were within ± 15% and trueness were < 13.9% at all concentrations. The method was successfully applied to therapeutic drug monitoring of carbamazepine in human plasma.
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http://dx.doi.org/10.1016/j.jpba.2022.114751DOI Listing
May 2022

Percutaneously introduced wireless intramuscular near-infrared spectroscopy device detects muscle oxygenation changes in porcine model of lower extremity compartment syndrome.

J Orthop Res 2022 Apr 5. Epub 2022 Apr 5.

Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, Washington University, St. Louis, Missouri, USA.

Serial examination and direct measurement of intracompartmental pressure (ICP) are suboptimal strategies for the detection of acute compartment syndrome (CS) because they are operator-dependent and yield information that only indirectly reflects intracompartmental muscle perfusion. As a result, instances of unnecessary fasciotomy and unrecognized CS are relatively common. Recently, near-infrared spectroscopy (NIRS)-based systems for compartment monitoring have generated interest as an adjunct tool. Under ideal conditions, NIRS directly measures the oxygenation of intracompartmental muscle (StO ), thereby obviating the challenges of interpreting equivocal clinical examination or ICP data. Despite these potential advantages, existing NIRS sensors are plagued by technical difficulties that limit clinical utility. Most of these limitations relate to their transcutaneous design that makes them susceptible to both interference from intervening skin/subcutaneous tissue, underlying hematoma, and instability of the skin-sensor interface. Here, we present a flexible, wireless, Bluetooth-enabled, percutaneously introducible intramuscular NIRS device that directly and continuously measures the StO of intracompartmental muscle. Proof of concept for this device is demonstrated in a swine lower extremity balloon compression model of acute CS, wherein we simultaneously track muscle oxygenation, ICP, and compartment perfusion pressure (PP). The observed StO decreased with increasing ICP and decreasing PP and then recovered following pressure reduction. The mean change in StO as the PP was decreased from baseline to 30 mmHg was -7.6%. The mean difference between baseline and nadir StO was -17.4%. Cross-correlations (absolute value) describing the correspondence between StO and ICP were >0.73. This novel intramuscular NIRS device identifies decreased muscle perfusion in the setting of evolving CS.
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http://dx.doi.org/10.1002/jor.25339DOI Listing
April 2022

Preexisting frailty and outcomes in older patients with acute myocardial infarction.

Am Heart J 2022 07 24;249:34-44. Epub 2022 Mar 24.

Duke Clinical Research Institute, Cardiovascular Division, Department of Medicine, Duke University, Durham, NC.

Background: Little is known about the prevalence and prognostic impact of preexisting frailty on acute care and in-hospital outcomes in older adults in the setting of acute myocardial infarction (AMI).

Methods: Preexisting frailty was assessed at baseline in consecutive AMI patients ≥65 years of age treated at 778 hospitals participating in the NCDR ACTION Registry between January 1, 2015 to December 31, 2016. Three domains of preexisting frailty (cognition, ambulation, and functional independence) were abstracted from chart review and summed in 2 ways: an ACTION Frailty Scale based on responses to 6 groups adapted from the Canadian Study of Health and Aging Clinical Frailty Scale and an ACTION Frailty Score derived by summing a rank score of 0-2 assigned for each grade (total ranged between 0 to 6). Multivariable logistic regression examined the association between assigned frailty by score or scale and in-hospital mortality.

Results: Among 143,722 older AMI patients, 108,059 (75.2%) were fit and/or well and 6,484 (4.5%) were vulnerable to frailty, while 7,527 (5.2%) had mild, 3,913 (2.7%) had moderate, 2,715 had (1.9%) severe, and 632 (0.4%) had very severe frailty according to the ACTION Frailty Scale, while 14,392 (10.0%) could not be categorized due to incomplete ascertainment. Frail patients were older, more frequently female, of non-white race and/or ethnicity, and less likely to be treated with guideline-recommended therapies. Increasing severity of frailty by this scale was associated with a step-wise higher risk for in-hospital mortality (P-trend < .001). Patient categories of the ACTION Frailty Score provided similar results. After adjustment, each 1-unit increase in Frailty Score was associated with a 12% higher mortality risk (OR 1.12, 95% CI 1.10-1.15).

Conclusions: Among older patients with acute myocardial infarction, frailty is common and independently associated with in-hospital mortality. These findings show the importance of pragmatic evaluation of frailty in hospital-level quality scores, guideline recommendations, and incorporation into other registry data collection efforts.
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http://dx.doi.org/10.1016/j.ahj.2022.03.007DOI Listing
July 2022

CsPbI-Based Phase-Stable 2D Ruddlesden-Popper Perovskites for Efficient Solar Cells.

Nano Lett 2022 Apr 22;22(7):2874-2880. Epub 2022 Mar 22.

The Centre of Nanoscale Science and Technology and Key Laboratory of Functional Polymer Materials, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China.

Inorganic CsPbI perovskite has shown great promise in highly stable perovskite solar cells due to the lack of volatile organic components. However, the inferior phase stability in ambient conditions resulted from the very small Cs, limiting their practical applications. Here, CsPbI-based 2D Ruddlesden-Popper (RP) perovskites were developed using two thiophene-based aromatic spacers, namely, 2-thiophenemethylamine hydroiodide (ThMA) and 2-thiopheneformamidine hydroiodide (ThFA), which significantly improved the phase stability by releasing the large inner stress of black-phase CsPbI. The optimized ThFA-based 2D RP perovskite ( = 5, ThFA-Cs) device achieves a record efficiency of 16.00%. Importantly, the ThFA-Cs devices could maintain an average of 98% of their initial efficiencies after being stored in N at room temperature for 3000 h and 92% of their initial value at 80 °C for 960 h. This work provides a new perspective for exploration of the phase-stable CsPbI-based perovskite with reduced dimensions for high-performance solar cells.
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http://dx.doi.org/10.1021/acs.nanolett.2c00002DOI Listing
April 2022

First-line PD-1/PD-L1 inhibitors plus chemotherapy versus bevacizumab plus chemotherapy for advanced non-squamous non-small cell lung cancer: A Bayesian network meta-analysis of randomized controlled trials.

Cancer Med 2022 May 22;11(10):2043-2055. Epub 2022 Mar 22.

Senior Department of Oncology, The 5th Medical Center of Chinese PLA General Hospital, Beijing, China.

Chemotherapy in combination with immune checkpoint inhibitor (ICI) or bevacizumab has demonstrated a superior effect for non-squamous non-small cell lung cancer (NS-NSCLC). There are still few randomized controlled trials (RCTs) investigating the differences between ICI plus chemotherapy (ICI-chemotherapy) and bevacizumab plus chemotherapy (Bev-chemotherapy) in first-line treatment of NS-NSCLC. We identified RCTs in databases and conference abstracts presented at international conferences by Sep 1, 2021. Bayesian network meta-analysis was performed using randomized effect consistency model to estimate hazard ratio (HR) and odds ratio (OR). The outcomes included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade ≥ 3 treatment-related adverse events (TRAEs). Fifteen RCTs (17 articles) of 6561 advanced NS-NSCLC patients receiving ICI-chemotherapy, Bev-chemotherapy, or chemotherapy at first-line were eligible for analysis. NMA results showed that first-line ICI-chemotherapy prolonged OS (HR 0.79, 0.66-0.94) in patients with advanced NS-NSCLC compared with Bev-chemotherapy, while no differences were in PFS, ORR, and grade ≥ 3 TRAEs (p > 0.05). Ranking plots suggested that ICI-chemotherapy had the most probability to offer the best OS (probability 0.993), PFS (probability 0.658), and ORR (probability 0.565), and Bev-chemotherapy had the most risks of grade ≥ 3 TRAEs (probability 0.833). Therefore, our findings showed that first-line ICI-chemotherapy was associated with better OS than Bev-chemotherapy in patients with advanced NS-NSCLC, and more clinical trials are warranted to confirm these results.
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http://dx.doi.org/10.1002/cam4.4589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9119358PMC
May 2022

Systemic Bioavailability of Sublingual Atropine Ophthalmic Solution: a Phase I Study in Healthy Volunteers with Implications for Use as a Contingency Medical Countermeasure.

J Med Toxicol 2022 Jul 21;18(3):187-197. Epub 2022 Mar 21.

High Point Clinical Trials Center, 4160 Mendenhall Oaks Pkwy #105, High Point, NC, 27265, USA.

Introduction: Atropine sulfate is an FDA-approved medical countermeasure (MCM) for the treatment of organophosphorus nerve agent and organophosphate pesticide toxicity. Sufficient MCM supplies must be available in an incident involving a mass human exposure either from an accidental chemical release or a terrorist attack.

Methods: We performed a randomized, 3-sequence, 3-period phase I crossover study to assess the bioavailability and pharmacokinetics (PK) of a single dose (0.5 mg and 1.0 mg) of 1% ophthalmic atropine sulfate solution administered sublingually to 15 healthy adult volunteers. The primary endpoint was evaluation of the bioavailability of each of the two sublingual doses against a 1.0 mg reference intravenous (IV) atropine dose. Secondary endpoints included the safety and tolerability (xerostomia scale) of atropine sulfate administered sublingually.

Results: Sublingual atropine was safe (no severe AEs or SAEs were reported with either dose) and well tolerated, with a single subject reaching maximum xerostomia on a single dosing day. The geometric mean AUC was 286.40, 493.81, and 816.47 min*ng/mL for the 0.5 mg and 1.0 mg sublingual doses, and the 1.0 mg IV dose, respectively. Compared to IV administration, the 1.0 mg sublingual dose produced 0.60 (90% CI: 0.55-0.66) of the overall concentration of atropine over time (AUC).

Conclusion: Sublingual atropine sulfate 1% ophthalmic solution may be an alternative formulation and route of administration combination which expands the capacity and dosing options of atropine as a nerve agent MCM.
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http://dx.doi.org/10.1007/s13181-021-00873-0DOI Listing
July 2022

Development of a Novel Prognostic Nomogram for High Model for End-Stage Liver Disease Score Recipients Following Deceased Donor Liver Transplantation.

Front Med (Lausanne) 2022 3;9:772048. Epub 2022 Mar 3.

Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Background: A high model of end-stage liver disease (MELD) score (>30) adversely affects outcomes even if patients receive prompt liver transplantation (LT). Therefore, balanced allocation of donor grafts is indispensable to avoid random combinations of donor and recipient risk factors, which often lead to graft or recipient loss. Predictive models aimed at avoiding donor risk factors in high-MELD score recipients are urgently required to obtain satisfactory outcomes.

Method: Data of patients with MELD score >30 who underwent LT at three transplantation institutes between 2015 and 2018 were retrospectively reviewed. Early allograft dysfunction (EAD), length of intensive care unit (ICU) stay, and graft loss were recorded. Corresponding independent risk factors were analyzed using stepwise multivariable regression analysis. A prediction model of graft loss was developed, and discrimination and calibration were measured.

Results: After applying the exclusion criteria, 778 patients were enrolled. The incidence of EAD was 34.8% (271/778). Donor graft macrovesicular steatosis, graft-to-recipient weight ratio (GRWR), warm ischemia time (WIT), cold ischemia time (CIT), and ABO blood incompatibility, together with donor serum albumins, were independent predictors of EAD. The incidence of ICU stay over 10 days was 64.7% (503/778). Donor age, recipient's MELD score, Child score, and CIT were independent predictors of ICU stay. The 3-year graft survival rates (GSRs) in the training and validation cohorts were 64.2 and 59.3%, respectively. The independent predictors of graft loss were recipient's Child score, ABO blood type incompatibility, donor serum total bilirubin over 17.1 μmol/L, and cold CIT. A nomogram based on these variables was internally and externally validated and showed good performance (area under the receiver operating characteristic curve = 70.8 and 66.0%, respectively). For a recipient with a high MELD score, the avoidance of ABO blood type incompatibility and CIT ≥6 h would achieve a 3-year GSR of up to 78.4%, whereas the presence of the aforementioned risk factors would decrease the GSR to 35.4%.

Conclusion: The long-term prognosis of recipients with MELD scores >30 could be greatly improved by avoiding ABO blood type incompatibility and CIT ≥6 h.
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http://dx.doi.org/10.3389/fmed.2022.772048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8927074PMC
March 2022

Incidence and prevalence of COVID-19 within a healthcare worker cohort during the first year of the SARS-CoV-2 pandemic.

Clin Infect Dis 2022 Mar 12. Epub 2022 Mar 12.

Division of Pediatric Infectious Diseases, Stanford University School of Medicine.

Background: Preventing SARS-CoV2 infections in healthcare workers (HCWs) is critical for healthcare delivery. We aimed to estimate and characterize the prevalence and incidence of COVID-19 in a US HCW cohort and to identify risk factors associated with infection.

Methods: We conducted a longitudinal cohort study of HCWs at 3 Bay Area medical centers using serial surveys and SARS-CoV-2 viral and orthogonal serological testing, including measurement of neutralizing antibodies. We estimated baseline prevalence and cumulative incidence of COVID-19. We performed multivariable Cox proportional hazards models to estimate associations of baseline factors with incident infections and evaluated the impact of time-varying exposures on time to COVID-19 using marginal structural models.

Results: 2435 HCWs contributed 768 person years of follow-up time. We identified 21/2435 individuals with prevalent infection, resulting in a baseline prevalence of 0.86% (95% CI, 0.53% to 1.32%). We identified 70/2414 (2.9%) incident infections yielding a cumulative incidence rate of 9.11 cases per 100 person years (95% CI 7.11 to 11.52). Community contact with a known COVID-19 case most strongly correlated with increased hazard for infection (HR 8.1, 95% CI, 3.8, 17.5). High-risk work-related exposures (i.e., breach in protective measures) drove an association between work exposure and infection (HR 2.5, 95% CI, 1.3-4.8). More cases were identified in HCW when community case rates were high.

Conclusion: We observed modest COVID-19 incidence despite consistent exposure at work. Community contact was strongly associated with infections but contact at work was not unless accompanied by high-risk exposure.
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http://dx.doi.org/10.1093/cid/ciac210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8992269PMC
March 2022

Implantable, wireless, self-fixing thermal sensors for continuous measurements of microvascular blood flow in flaps and organ grafts.

Biosens Bioelectron 2022 Jun 6;206:114145. Epub 2022 Mar 6.

Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL, 60208, USA; Department of Mechanical Engineering, Northwestern University, Evanston, IL, 60208, USA; Department of Biomedical Engineering, Northwestern University, Evanston, IL, 60208, USA; Department of Materials Science and Engineering, Northwestern University, Evanston, IL, 60208, USA; Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA; Department of Electrical and Computer Engineering, Northwestern University, Evanston, IL, 60208, USA; Department of Chemistry, Weinberg College of Arts and Sciences, Northwestern University, Evanston, IL, 60208, USA. Electronic address:

Vascular pedicle thrombosis after free flap transfer or solid organ transplantation surgeries can lead to flap necrosis, organ loss requiring re-transplantation, or even death. Although implantable flow sensors can provide early warning of malperfusion and facilitate operative salvage, measurements performed with existing technologies often depend on extrinsic conditions such as mounting methods and environmental fluctuations. Furthermore, the mechanisms for fixing such probes to vascular or skeletal structures may disrupt the normal blood flow or cause unnecessary tissue damage. Requirements for wired connections to benchtop readout systems also increase costs, complicate clinical care and constrain movements of the patient. Here, we report a wireless, miniaturized flow sensing system that exploits sub-millimeter scale, multi-nodal thermal probes, with biodegradable barbs that secure the probes to the surrounding tissues in a manner that facilitates removal after a period of use. These smartphone-readable devices, together with experimentally validated analytical models of the thermal transport physics, enable reliable, accurate flow sensing in ways that are largely immune to variations in temperature and mechanical perturbations. In vivo demonstrations of this technology in porcine myocutaneous flap and kidney malperfusion models highlight the essential capabilities in microsurgical and transplantation-related biomedical application scenarios.
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http://dx.doi.org/10.1016/j.bios.2022.114145DOI Listing
June 2022

Bioinspired Super-Strong Aqueous Synthetic Tissue Adhesives.

Matter 2022 Mar 25;5(3):933-956. Epub 2022 Jan 25.

Aleo BME, Inc., State College, PA 16803, USA.

Existing tissue adhesives and sealants are far from satisfactory when applied on wet and dynamic tissues. Herein, we report a strategy for designing biodegradable super-strong aqueous glue (B-Seal) for surgical uses inspired by an English ivy adhesion strategy and a cement particle packing theory. B-Seal is a fast-gelling, super-strong, and elastic adhesive sealant composed of injectable water-borne biodegradable polyurethane (WPU) nanodispersions with mismatched particle sizes and counterions in its A-B formulation. B-Seal showed 24-fold greater burst pressure than DuraSeal®, 138-fold greater T-pull adhesive strength than fibrin glue, and 16-fold greater lap shear strength than fibrin glue. In vivo evaluation on a rat cerebrospinal fluid (CSF) rhinorrhea model and a porcine craniotomy model validated the safety and efficacy of B-Seal for effective CSF leak prevention and dura repair. The plant-inspired adhesion strategy combined with particle packing theory represents a new direction of designing the next-generation wet tissue adhesives for surgeries.
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http://dx.doi.org/10.1016/j.matt.2021.12.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8896806PMC
March 2022

Hispanic Ethnicity and Social Determinants of Health in Pulmonary Arterial Hypertension: The Pulmonary Hypertension Association Registry.

Ann Am Thorac Soc 2022 Mar 3. Epub 2022 Mar 3.

Stanford University, Medicine, Stanford, California, United States.

Rationale There is a noticeable underrepresentation of minorities in clinical trials and registries in pulmonary arterial hypertension (PAH). Prior studies evaluating the association between Hispanic ethnicity and clinical outcomes in patients with PAH have not assessed the socioeconomic profile of Hispanic individuals or the significance of social determinants of health in clinical outcomes. Objective To determine the association between Hispanic ethnicity, social determinants of health, and clinical outcomes in PAH. Methods Prospective cohort study of adult participants with PAH enrolled in the Pulmonary Hypertension Association Registry, a multicenter US-based registry of patients treated at Pulmonary Hypertension Care Centers. Participants were classified as Hispanics and non-Hispanic Whites, based on self-reported ethnicity. A comparison of baseline clinical and sociodemographic characteristics between groups was performed as well using absolute standardized differences (ASD). The primary outcome of the study was to assess transplant-free survival between Hispanics and non-Hispanic Whites. A Cox proportional hazards model was used for the multivariable analysis after adjusting for age, sex, PAH etiology, annual income, education level and health insurance. Results A total of 683 individuals were included, 98 (14.3%) of Hispanic ethnicity. Hispanic patients had impaired access to health care (31.6% vs. 12.9% Medicaid/uninsured; ASD 0.35), lower education level (72.6% vs. 94.0% high school graduates or higher; ASD 0.60) and lower annual income (32.0% vs. 17.4% with income <20,000 US dollars; ASD 0.47), as compared with non-Hispanic Whites. Hispanic patients had a higher frequency of ER visits and a higher number of hospitalizations, despite having similar disease severity (incidence rate ratio 1.452, 95% CI 1.326 - 1.590 and 1.428, 95% CI 1.292 - 1.577, respectively). While the unadjusted analysis showed a lower transplant/death hazard ratio for Hispanics (HR 0.47, 95% CI 0.24-0.94; p=0.032), there was no association between Hispanic ethnicity and outcome in the multivariable model after adjusting for social determinants of health and other covariates (HR 0.76, 95% CI 0.35-1.62; p=0.474). Conclusions Hispanic ethnicity was not associated with differences in survival after adjusting for social determinants of health and other factors. Social determinants of health are important to consider when assessing the association between ethnicity and outcomes in PAH.
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http://dx.doi.org/10.1513/AnnalsATS.202109-1051OCDOI Listing
March 2022
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