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1.
Ageing Res Rev ; 85: 101842, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36621647

RESUMO

With increasing age, bone tissue undergoes significant alterations in composition, architecture, and metabolic functions, probably causing senile osteoporosis. Osteoporosis possess the vast majority of bone disease and associates with a reduction in bone mass and increased fracture risk. Bone loss is on account of the disorder in osteoblast-induced bone formation and osteoclast-induced bone resorption. As a unique bone resorptive cell type, mature bone-resorbing osteoclasts exhibit dynamic actin-based cytoskeletal structures called podosomes that participate in cell-matrix adhesions specialized in the degradation of mineralized bone matrix. Podosomes share many of the same molecular constitutions as focal adhesions, but they have a unique structural organization, with a central core abundant in F-actin and encircled by scaffolding proteins, kinases and integrins. Here, we conclude recent advancements in our knowledge of the architecture and the functions of podosomes. We also discuss the regulatory pathways in osteoclast podosomes, providing a reference for future research on the podosomes of osteoclasts and considering podosomes as a therapeutic target for inhibiting bone resorption.

2.
Cancer Genet ; 272-273: 9-15, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36640492

RESUMO

Aberrant ubiquitin modifications caused by an imbalance in the activities of ubiquitinases and de-ubiquitinases are emerging as important mechanisms underlying non-small cell lung cancer (NSCLC) progression. The deubiquitinating enzyme ubiquitin-specific peptidase 15 (USP15) has been identified as an important factor in oncogenesis and a potential therapeutic target. However, the expression profile and function of USP15 in NSCLC remain elusive. In the present study, we investigated the expression pattern and the potential biological functions of USP15 in NSCLC both in cells and animal models. Our data revealed that USP15 was highly expressed in NSCLC tissues and cells compared with normal counterpart. We subsequently knocked down USP15 expression in two NSCLC cell lines, which significantly suppressed cell proliferation. In addition, knocking down USP15 expression reduced NSCLC cell migration and invasion according to the results from Matrigel-Transwell analysis. NSCLC animal model results showed that USP15 knockdown also reduced NSCLC size. Biochemical analysis revealed that USP15 knockdown inhibited matrix metalloproteinase (MMP)3 and MMP9 expression. Furthermore, high levels of USP15 and MMP3 expression were associated with poor prognosis in NSCLC. In conclusion, the results from the present study suggest that the high expression of USP15 promotes NSCLC tumorigenesis. Therefore, it is proposed that USP15 and MMPs may represent novel biomarkers for NSCLC progression and prognosis.

3.
Biol Trace Elem Res ; 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36633787

RESUMO

The association between circulating copper and the risk of liver cancer has been investigated by previous studies, while the findings were inconsistent. Thus, we aimed to evaluate the association between circulating copper and liver cancer by using meta-analysis and Mendelian randomization (MR). For meta-analysis, PubMed and Web of Science were searched to identify eligible studies published before April 4, 2022. Standardized mean difference (SMD) with 95% confidence interval (CI) in circulating copper level between liver cancer patients and controls were pooled. Furthermore, we selected genetic instruments for circulating copper from a genome-wide association study (GWAS) to conduct MR analysis. The summary statistics related to liver cancer were obtained from two large independent cohorts, UKBB and FinnGen, respectively. MR analysis was performed mainly by inverse-variance weighted (IVW) approach, followed by maximum-likelihood method as sensitivity analysis. In meta-analysis of eight studies, circulating copper was found to be higher in liver cancer patients (SMD: 1.65; 95% CI: 0.65 to 2.65) with high heterogeneity (I2 = 96.40%, P = 0.001). However, inconsistent findings were observed among subgroups with high evidence. In MR analysis, genetically predicted circulating copper was not significantly associated with the risk of liver cancer by IVW in UKBB (OR: 1.38; 95% CI: 0.72 to 2.65) and FinnGen (OR: 1.10; 95% CI: 0.69 to 1.73) separately, and the pooled results produced similar results (OR: 1.18, 95% CI: 0.81 to 1.72). Moreover, non-significant finding was confirmed by using maximum-likelihood method. There is no sufficient evidence to demonstrate that high levels of circulating copper increase the risks of liver cancer.

4.
Artigo em Inglês | MEDLINE | ID: mdl-36642716

RESUMO

Cucurbitacin B (CuB) is a class of tetracyclic triterpenoids isolated from Cucurbitaceae with a wide range of anti-inflammatory and anti-tumor activities, mainly used in hepatitis and hepatocellular carcinoma, while there is relatively little research and application of this drug for lung cancer. In this study, CuB was administered on A549/DDP cells to observe how it affected the cells and their mechanism of action. CuB demonstrated good anti-tumor activity against A549/DDP cells in a dose-dependent manner and caused changes in the hedgehog (Hh) pathway. The results showed that CuB greatly inhibits the proliferation and the invasion of A549/DDP cells, and promoted apoptosis of A549/DDP cells. Meanwhile, it changed the expression of p53-related genes at the RNA and protein level. In conclusion, this experiment provides a theoretical basis for new applications of CuB and new thoughts on the mechanism of its anti-tumor activity, and provides a direction for deep research.

5.
Biomed Res Int ; 2023: 8956803, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36654870

RESUMO

Percutaneous minimally invasive surgery involving Achilles tendon (AT) repair has the advantages of a low rerupture rate and fewer postoperative complications. However, due to the inability to operate under direct vision, the injury of the small saphenous vein (SSV) and sural nerve (SN) remains largely a high risk involving many challenges. We propose to introduce the preoperative application and advantages of ultrasonography in percutaneous minimally invasive surgery for acute AT rupture. Our results indicated that ultrasonography could locate the position of the SN more accurately and reduce the risk of iatrogenic nerve injury. Compared with the traditional surface markers, the preoperative localization and marking of AT, SSV, and SN in ultrasonography significantly reduced the risk of intraoperative accidental injury to blood vessels and nerves, which could reduce postoperative complications and promote early rehabilitation of patients. We ultimately exploit the properties of ultrasonography in percutaneous minimally invasive surgery to treat Achilles tendon rupture.


Assuntos
Tendão do Calcâneo , Traumatismos dos Tendões , Humanos , Tendão do Calcâneo/diagnóstico por imagem , Tendão do Calcâneo/cirurgia , Tendão do Calcâneo/lesões , Ruptura/diagnóstico por imagem , Ruptura/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Ultrassonografia , Traumatismos dos Tendões/diagnóstico por imagem , Traumatismos dos Tendões/cirurgia , Doença Aguda , Complicações Pós-Operatórias/cirurgia , Resultado do Tratamento , Técnicas de Sutura
6.
ACS Appl Mater Interfaces ; 15(1): 2054-2066, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36579636

RESUMO

Hydrazine and its derivatives are well-known environmental hazards and biological carcinogens; therefore, there is a great need for a powerful workflow solution for protecting the public from unexpected exposure to toxic contaminants. Recently, functional surface-enhanced Raman scattering (SERS) exhibits enormous benefits in sensing trace biochemical substances due to its fingerprint-like identification of individual molecules, making it an ideal method for detecting and quantifying hydrazine. Herein, for the first time, we integrated the orthogonal chemical reporter strategy with SERS to build an intelligent hydrazine detection platform (orthogonal chemical SERS, ocSERS), in which 4-mercaptobenzaldehyde was incorporated on a nanoimprinted gold nanopillar array, which acted as an orthogonal coupling partner of hydrazine to form Raman active benzaldehyde hydrazone, allowing for sensitively detecting hydrazine with a detection limit of 10-13 M in complex circumstances. Particularly, ocSERS could effectively identify the carcinogen N-nitrosodimethylamine (NDMA) after its reduction to dimethylhydrazine (UDMH), enabling ultrasensitive detection of UDMH (10-13 M). Importantly, ocSERS could not only monitor elevated levels of NDMA in ranitidine due to improper storage but also quantify NDMA in urine and blood after oral administration of NDMA-containing drugs, thereby preventing NDMA overexposure. Therefore, ocSERS represents the first click SERS sensor and may open up a new analytical field.


Assuntos
Líquidos Corporais , Nanopartículas Metálicas , Ouro/química , Hidrazinas , Análise Espectral Raman/métodos , Nanopartículas Metálicas/química
7.
Anal Chem ; 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36473082

RESUMO

Aerosols generated by bubble bursting have been proved to promote the extraction of analytes and have ultrahigh electric fields at their water-air interfaces. This study presented a simple and efficient ionization method, carbon dioxide microbubble bursting ionization (CDMBI), without the presence of an exogenous electric field (namely, zero voltage), by simulating the interfacial chemistries of sea spray aerosols. In CDMBI, microbubbles are generated in situ by continuous input of carbon dioxide into an aqueous solution containing low-concentration analytes. The microbubbles extract low- and high-polarity analytes as they pass through the aqueous solution. Upon reaching the water-air interface, these microbubbles burst to produce charged aerosol microdroplets with an average diameter of 260 µm (8.1-10.4 nL in volume), which are immediately transferred to a mass spectrometer for the detection and identification of extracted analytes. The above analytical process occurs every 4.2 s with a stable total ion chromatogram (relative standard deviation: 9.4%) recorded. CDMBI mass spectrometry (CDMBI-MS) can detect surface-active organic compounds in aerosol microdroplets, such as perfluorooctanoic acid, free fatty acids epoxidized by bubble bursting, sterols, and lecithins in soybean and egg, with the limit of detection reaching the level of fg/mL. In addition, coupling CDMBI-MS with an exogenous voltage yields relatively weak gains in ionization efficiency and sensitivity of analysis. The results suggested that CDMBI can simultaneously accomplish both bubbling extraction and microbubble bursting ionization. The mechanism of CDMBI involves bubbling extraction, proton transfer, inlet ionization, and electrospray-like ionization. Overall, CDMBI-MS can work in both positive and negative ion modes without necessarily needing an exogenous high electric field for ionization and quickly detect trace surface-active analytes in aqueous solutions.

8.
Plant Physiol ; 2022 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-36493391

RESUMO

There is a close regulatory relationship between the circadian clock and the abscisic acid (ABA) signaling pathway in regulating many developmental processes and stress responses. However, the exact feedback regulation mechanism between them is still poorly understood. Here, we identified the rice (Oryza sativa) clock component PSEUDO-RESPONSE REGULATOR 95 (OsPRR95) as a transcriptional regulator that accelerates seed germination and seedling growth by inhibiting ABA signaling. We also found that OsPRR95 binds to the ABA receptor gene REGULATORY COMPONENTS OF ABA RECEPTORS10 (OsRCAR10) DNA and inhibits its expression. Genetic analysis showed OsRCAR10 acts downstream of OsPRR95 in mediating ABA responses. In addition, the induction of OsPRR95 by ABA partly required a functional OsRCAR10, and the ABA responsive element (ABRE)-binding factor ABSCISIC ACID INSENSITIVE5 (OsABI5) bound directly to the promoter of OsPRR95 and activated its expression, thus establishing a regulatory feedback loop between OsPRR95, OsRCAR10 and OsABI5. Taken together, our results demonstrated that the OsRCAR10-OsABI5-OsPRR95 feedback loop modulates ABA signaling to fine-tune seed germination and seedling growth, thus establishing the molecular link between ABA signaling and the circadian clock.

10.
Materials (Basel) ; 15(23)2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36499912

RESUMO

In this study, electroless nickel plating and electrodeposition were used to deposit thin films on the polymer lattice template prepared by 3D printing, then seven Octet hollow nickel lattice materials with different structural parameters were synthesized by etching process at the expense of the polymer backbone. The microstructure and properties of the Octet structure nickel lattice were characterized by X-ray diffraction, Electron backscattering diffraction and transmission electron microscopy. According to the results, the average grain size of the electrodeposition Ni lattice material was 429 nm, and (001) weak texture was found along the direction of the film deposition. The lattice deformation mode changed with the increase of the lattice length-to-diameter ratio, and it shifted from the lattice deformation layer-by-layer and the overall deformation to the shear deformation in the 45° direction. The strength, modulus and energy absorption properties of the Octet lattice increased with the density, and they were exponentially related to density. In the relative density range of 0.7~5%, Octet hollow Ni lattices with the same density conditions but different structural parameters showed similar compressive strength and elasticity modulus; the energy absorption capacity, however, was weakened as the length-to-diameter ratio increased.

11.
Opt Express ; 30(26): 46236-46247, 2022 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36558582

RESUMO

A design of a 1 × 2 multimode 3 dB optical power splitter using tapered couplers is proposed and investigated in this paper. As an example, a 1 × 2 splitter processing five-lowest order transverse-electric-polarized modes is designed and optimized by utilizing finite difference time domain method and particle swarm optimization algorithm. To verify the feasibility of this novel design, the optimized device is fabricated on a silicon-on-insulator platform. The coupling lengths of tapered couplers are respectively 6.5 µm, 6.0 µm, 3.5 µm, 5.0 µm, 5.0 µm, 7.5 µm, 6.0 µm, 5.0 µm, and 8.0 µm. Measurement results reveal that, for the fabricated splitter, the power uniformity varies from 0.041 to 0.88 dB, the crosstalk ranges from -23.96 to -14.12 dB, and the insertion loss changes from 0.089 to 1.50 dB within a bandwidth from 1520 to 1600 nm.

12.
Anal Chem ; 2022 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-36562720

RESUMO

The atmospheric oxidation of chemicals has produced many new unpredicted pollutants. A microwave plasma torch-based ion/molecular reactor (MPTIR) interfacing an online mass spectrometer has been developed for creating and monitoring rapid oxidation reactions. Oxygen in the air is activated by the plasma into highly reactive oxygen radicals, thereby achieving oxidation of thioethers, alcohols, and various environmental pollutants on a millisecond scale without the addition of external oxidants or catalysts (6 orders of magnitude faster than bulk). The direct and real-time oxidation products of polycyclic aromatic hydrocarbons and p-phenylenediamines from the MPTIR match those of the long-term multistep environmental oxidative process. Meanwhile, two unreported environmental compounds were identified with an MPTIR and measured in the actual water samples, which demonstrates the considerable significance of the proposed device for both predicting the environmental pollutants (non-target screening) and studying the mechanism of atmospheric oxidative processes.

13.
Front Oncol ; 12: 959892, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36561528

RESUMO

Introduction: Observational studies have reported a relationship between iron status and the risk of prostate cancer. However, it remains uncertain whether the association is causal or due to confounding or reverse causality. To further clarify the underlying causal relationship, we conducted a Mendelian randomization (MR) analysis. Methods: We selected three genetic variants (rs1800562, rs1799945, and rs855791) closely correlated with four iron status biomarkers (serum iron, log-transformed ferritin, transferrin saturation, and transferrin) as instrumental variables. Summary statistics for prostate cancer were obtained from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome consortium including 79,148 cases and 61,106 controls of European ancestry. The inverse-variance weighted (IVW) method was conducted primarily to estimate the association of genetically predicted iron status and the risk of prostate cancer, supplemented with simple-median, weighted-median and maximum-likelihood methods as sensitivity analysis. MR-Egger regression was used to detect directional pleiotropy. We also conducted a meta-analysis of observational studies to assess the associations between iron status and the risk of prostate cancer. Results: Genetically predicted increased iron status was associated with the decreased risk of prostate cancer, with odds ratio of 0.91 [95% confidence interval (CI): 0.84, 0.99; P = 0.035] for serum iron, 0.81 (95% CI: 0.65, 1.00; P = 0.046) for log- transformed ferritin, 0.94 (95% CI: 0.88, 0.99; P = 0.029) for transferrin saturation, and 1.15 (95% CI: 0.98, 1.35; P = 0.084) for transferrin (with higher transferrin levels representing lower systemic iron status), using the inverse-variance weighted method. Sensitivity analyses produced consistent associations, and MR-Egger regression indicated no potential pleiotropy. Our replication analysis based on FinnGen research project showed compatible results with our main analysis. Results from our meta-analysis similarly showed that serum ferritin [standardized mean difference (SMD): -1.25; 95% CI: -2.34, -0.16; P = 0.024] and transferrin saturation (SMD: -1.19; 95% CI: -2.34, -0.05; P = 0.042) were lower in patients with prostate cancer compared with that in controls. Discussion: Our study suggests a protective role of iron in the risk of prostate cancer, further investigations are required to clarify the underlying mechanisms.

14.
Exp Hematol Oncol ; 11(1): 105, 2022 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-36527157

RESUMO

Brain metastasis accounts for a large number of cancer-related deaths. The host immune system, involved at each step of the metastatic cascade, plays an important role in both the initiation of the brain metastasis and their treatment responses to various modalities, through either local and or systemic effect. However, few reliable immune biomarkers have been identified in predicting the development and the treatment outcome in patients with cancer brain metastasis. Here, we provide a focused perspective of immune related biomarkers for cancer metastasis to the brain and a thorough discussion of the potential utilization of specific biomarkers such as tumor mutation burden (TMB), genetic markers, circulating and tumor-infiltrating immune cells, cytokines, in predicting the brain disease progression and regression after therapeutic intervention. We hope to inspire the field to extend the research and establish practical guidelines for developing and validating immune related biomarkers to provide personalized treatment and improve treatment outcomes in patients with metastatic brain cancers.

15.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 34(11): 1222-1226, 2022 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-36567571

RESUMO

Sepsis associated-acute kidney injury (SA-AKI) is a common complication of sepsis, which has a high incidence and is closely related to a poor prognosis. However, delayed diagnosis and non-specific treatments make it difficult to systematically manage SA-AKI. Based on massive clinical data, machine learning could build prediction models, which provide alarms and suggestions for the clinical decision support system. Although there are still many challenges such as poor interpretability, it has shown clinical application value in SA-SKI risk prediction, imaging diagnosis, subtype identification, prognosis assessment, and so on. Based on a brief introduction of machine learning, this article reviews the application, limitations, and future directions of machine learning in the diagnosis and treatment of SA-AKI, and explores the possibility of machine learning in the medical field, in order to promote the development of precision medicine and intelligent medicine.


Assuntos
Injúria Renal Aguda , Sepse , Humanos , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Sepse/complicações , Sepse/diagnóstico , Prognóstico , Aprendizado de Máquina
16.
Front Genet ; 13: 1009589, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36425068

RESUMO

Background: Psoriasis is a common immune-mediated hyperproliferative skin dysfunction with known genetic predisposition. Gene-gene interaction (e.g., between HLA-C and ERAP1) in the psoriasis context has been reported in various populations. As ERAP1 has been recognized as a psoriasis susceptibility gene and plays a critical role in antigen presentation, we performed this study to identify interactions between ERAP1 and other psoriasis susceptibility gene variants. Methods: We validated psoriasis susceptibility gene variants in an independent cohort of 5,414 patients with psoriasis and 5,556 controls. Multifactor dimensionality reduction (MDR) analysis was performed to identify the interaction between variants significantly associated with psoriasis in the validation cohort and ERAP1 variants. We then conducted a meta-analysis of those variants with datasets from exome sequencing, target sequencing, and validation analyses and used MDR to identify the best gene-gene interaction model, including variants that were significant in the meta-analysis and ERAP1 variants. Results: We found that 19 of the replicated variants were identified with p < 0.05 and detected six single-nucleotide polymorphisms of psoriasis susceptibility genes in the meta-analysis. MDR analysis revealed that the best predictive model was that between the rs27044 polymorphism of ERAP1 and the rs7590692 polymorphism of IFIH1 (cross-validation consistency = 9/10, test accuracy = 0.53, odds ratio = 1.32 (95% CI, 1.09-1.59), p < 0.01). Conclusion: Our findings suggest that the interaction between ERAP1 and IFIH1 affects the development of psoriasis. This hypothesis needs to be tested in basic biological studies.

17.
Rev Sci Instrum ; 93(10): 105002, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36319357

RESUMO

Multi-degrees of freedom piezo-driven precision positioning platforms with large working strokes are demanded in many research fields. Although many multi-degrees of freedom piezo-driven positioning platforms have been proposed, few of them can achieve both large working stroke and high speed, which hinders their applications. In this study, a two-degrees of freedom piezo-driven positioning platform was proposed by stacking two identical stick-slip piezoelectric actuators. To simplify the practical implementation of a large working stroke, the actuator employed a special structure, in which the compliant mechanism and the slider were connected together as a mover and the guide rail was fixed as a stator. The working stroke of the actuator can be increased easily by increasing only the length of the guide rail without changing the output performances. By designing a lever-type compliant mechanism (LCM) on the side surface of the slider, a large loading space was obtained. Theoretical calculation and finite element analysis of the LCM were performed in detail. As the structures of these two stick-slip piezoelectric actuators are the same, only the output performances of the upper actuator (x direction) were tested as an example. Experimental results indicated that the upper actuator had a stable bi-direction motion with a working stroke being over 20 cm. The maximum speeds along the positive x and negative x directions reached 17.864 and 18.73 mm/s, and the resolutions were 100 and 230 nm, respectively. Furthermore, the vertical loading capacity was larger than 60 N.

18.
World J Clin Cases ; 10(32): 11955-11966, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36405262

RESUMO

BACKGROUND: Aplastic anemia (AA) complicated with myocardial infarction (MI) is rare and associated with poor prognosis. Here, we present a case of AA with recurrent acute MI (AMI) in a patient treated with cyclosporine A (CsA) and stanozolol. In this patient, we suspect the long-term use of medication linked to platelets hyperfunction. CASE SUMMARY: In 2017, a 45-year-old man was rushed to the emergency department of China-Japan Union Hospital due to precordial pain for 5 h. Based on his symptoms, medical history, blood tests, and findings from coronary angiography (CAG), the patient was diagnosed with acute anterior wall, ST-segment elevated MI, Killip II grade, AA, and dyslipidemia. In 2021, the patient was readmitted to the hospital for 2 h due to chest pain. Because the patient's platelet count was 30 × 109/L and he had severe thrombocytopenia, we performed CAG following platelet transfusion. Optical coherence tomography revealed lipid plaque and thrombus mass in his right coronary artery. The antithrombotic approach was adjusted to employ only anticoagulants (factor Xa inhibitors) and adenosine diphosphate inhibitors (clopidogrel) after assessing the risk of bleeding/thrombotic events. Long-term follow-up revealed that the patient had made a good recovery. CONCLUSION: Patients with AA should be closely monitored for the risk of thrombosis and cardiovascular events, particularly when taking stanozolol or CsA for an extended period of time.

19.
Am J Manag Care ; 28(11): e399-e404, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36374657

RESUMO

OBJECTIVES: To examine the impact of COVID-19 surges on hospital outcomes, particularly among non-COVID-19 patients. STUDY DESIGN: An interrupted time series design. METHODS: Using data from a large insurance claims clearinghouse, the study estimates the impact of the onset of the pandemic and the share of hospital COVID-19 patients on the likelihood of (1) in-hospital death, (2) in-hospital death or discharge to hospice, (3) discharge to other hospitals, (4) discharge to skilled nursing facilities (SNFs), and (5) discharge to home care. RESULTS: The odds of in-hospital death were about 1.7 times that before the onset of the pandemic among all patients and 1.2 times that among non-COVID-19 patients. Increased share of COVID-19 patients was associated with higher odds of in-hospital death among all patients and non-COVID-19 patients. The effects were more pronounced among patients 45 years and older and those with septicemia or pneumonia, and they were also stronger during the months in which COVID-19 cases surged. Although no sizable changes were found in the odds of discharge to other hospitals or SNFs, transfers to home care grew during the pandemic. CONCLUSIONS: The negative impact of the pandemic on mortality among non-COVID-19 patients confirms existing concerns about patient care. No evidence suggests large-scale changes in practices regarding discharge/transfer to other facilities. The findings shed light on future efforts to monitor and improve inpatient care as the pandemic evolves.


Assuntos
COVID-19 , Medicare , Humanos , Estados Unidos/epidemiologia , Mortalidade Hospitalar , COVID-19/epidemiologia , Instituições de Cuidados Especializados de Enfermagem , Alta do Paciente , Hospitais , Readmissão do Paciente
20.
Artigo em Inglês | MEDLINE | ID: mdl-36412196

RESUMO

BACKGROUND: Elevated plasma Lp-PLA2 (lipoprotein-associated phospholipase A2) activity is closely associated with an increased risk of cardiovascular events. However, whether and how Lp-PLA2 is directly involved in the pathogenesis of atherosclerosis is still unclear. To examine the hypothesis that Lp-PLA2 could be a potential preventative target of atherosclerosis, we generated Lp-PLA2 knockout rabbits and investigated the pathophysiological functions of Lp-PLA2. METHODS: Lp-PLA2 KO rabbits were generated using CRISPR/Cas9 system to assess the role of Lp-PLA2 in plasma lipids regulation and identify its underlying molecular mechanisms. Homozygous knockout rabbits along with wild-type rabbits were fed a cholesterol-rich diet for up to 14 weeks and their atherosclerotic lesions were compared. Moreover, the effects of Lp-PLA2 deficiency on the key cellular behaviors in atherosclerosis were assessed in vitro. RESULTS: When rabbits were fed a standard diet, Lp-PLA2 deficiency led to a significant reduction in plasma lipids. The decreased protein levels of SREBP2 (sterol regulatory element-binding protein 2) and HMGCR (3-hydroxy-3-methylglutaryl coenzyme A reductase) in livers of homozygous knockout rabbits indicated that the cholesterol biosynthetic pathway was impaired with Lp-PLA2 deficiency. In vitro experiments further demonstrated that intracellular Lp-PLA2 efficiently enhanced SREBP2-related cholesterol biosynthesis signaling independently of insulin-induced genes (INSIGs). When fed a cholesterol-rich diet, homozygous knockout rabbits exhibited consistently lower level of hypercholesterolemia, and their aortic atherosclerosis lesions were significantly reduced by 60.2% compared with those of wild-type rabbits. The lesions of homozygous knockout rabbits were characterized by reduced macrophages and the expression of inflammatory cytokines. Macrophages of homozygous knockout rabbits were insensitive to M1 polarization and showed reduced DiI-labeled lipoprotein uptake capacity compared with wild-type macrophages. Lp-PLA2 deficiency also inhibited the adhesion between monocytes and endothelial cells. CONCLUSIONS: These results demonstrate that Lp-PLA2 plays a causal role in regulating blood lipid homeostasis and Lp-PLA2 deficiency protects against dietary cholesterol-induced atherosclerosis in rabbits. Lp-PLA2 could be a potential target for the prevention of atherosclerosis.

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