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OBJECTIVE: To evaluate the regulatory effect of Diwu Yanggan (DWYG) Decoction on lysoglycerophospholipids (Lyso-GPLs) in circulating exosomes in a mouse model of nonalcoholic fatty liver disease (NAFLD). METHODS: Circulating exosomes isolated from mouse serum by size exclusion chromatography were morphologically characterized using transmission electron microscope and examined for surface markers CD9, CD63 and TSG101 using Western blotting. Twenty-four male Kunming mice were randomized into 3 groups for normal feeding (control, n=8) or high-fat diet feeding for 1 week to induce NAFLD, after which the latter mice were given DWYG decoction (treatment group, n=8) or normal saline (model group, n=8) by gavage for 4 weeks. After the last treatment, blood samples were collected from the mice for testing serum TC, HDL-C, LDL-C, ALT and AST levels and isolating circulating exosomes. Using multivariate statistical analysis based on targeted metabolomics strategy, the potential biomarkers for Lyso-GPLs in the exosomes were screened. RESULTS: The isolated exosomes about 100 nm in size had a typical saucer-like structure with distinct double-layer membranes and a mean particle size of 137.5 nm and expressed the specific surface marker proteins CD9, CD63 and TSG101. The mouse models of NAFLD had significantly increased serum levels of TC, HDL-C, LDL-C and AST and lowered serum ALT level. A total of 43 Lyso-GPLs with significant reduction after DWYG Decoction treatment were identified in NAFLD mice. CONCLUSION: DWYG Decoction can regulate Lyso-GPLs in circulating exosomes in NAFLD mice, which provides a new clue for studying the therapeutic mechanism of DWYG Decoction for liver disease.
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Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Exosomas , Enfermedad del Hígado Graso no Alcohólico , Animales , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/sangre , Exosomas/metabolismo , Ratones , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Masculino , Dieta Alta en Grasa/efectos adversos , Complejos de Clasificación Endosomal Requeridos para el Transporte/metabolismo , Ratones Endogámicos , Tetraspanina 30/metabolismo , Proteínas de Unión al ADN , Factores de Transcripción , Animales no ConsanguíneosRESUMEN
OBJECTIVE: To investigate the prevalence of tick-borne rickettsial infections in selected areas of Liupanshui City, Guizhou Province, 2023, so as to provide insights into the management of tick-borne rickettsioses in the city. METHODS: Ticks were captured from the body surface of bovines and sheep in Gaoxing Village, Dashan Township, Liupanshui City, Guizhou Province during the period between April and June, 2023, and tick species were identified using morphological and molecular biological techniques. In addition, tick-borne Rickettsia was identified using a nested PCR assay, including spotted fever group rickettsiae (SFGR), Coxiella spp., Anaplasma spp., Ehrlichia spp., and Orientia spp., and positive amplified fragments were sequenced and aligned with known sequences accessed in the GenBank database. RESULTS: A total of 200 ticks were collected and all tick species were identified as Rhipicephalus microplus. Nestle PCR assay combined with sequencing identified ticks carrying Candidatus Rickettsia jingxinensis (40.50%), Coxiella burnetii (1.50%), and Coxiella-like endosymbionts (27.00%), and Anaplasma spp., Ehrlichia spp. or Orientsia spp. was not detected. CONCLUSIONS: R. microplus carried Candidatus R. jingxinensis, C. burnetii, and Coxiella-like endosymbionts in selected areas of Liupanshui City, Guizhou Province. Intensified monitoring of tickborne rickettsial infections is needed in livestock and humans to reduce the damages caused by rickettsioses.
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Rickettsia , Animales , Rickettsia/aislamiento & purificación , Rickettsia/genética , China/epidemiología , Ovinos , Bovinos , Infecciones por Rickettsia/epidemiología , Infecciones por Rickettsia/microbiología , Infecciones por Rickettsia/veterinaria , Garrapatas/microbiología , Enfermedades por Picaduras de Garrapatas/microbiología , Enfermedades por Picaduras de Garrapatas/epidemiologíaRESUMEN
BACKGROUND: Patients with Lumbar Spinal Stenosis (LSS) typically complain of back pain and leg pain. These symptoms reduce the quality of life (QoL) and also cause sleep disturbances. This study compares pregabalin and limaprost's efficacy in LSS for pain, disability, QoL, and sleep, aiming to offer insights for medication selection. METHODS: This study was designed as a prospective, randomized, single-center, single-blinded, clinical superiority trial targeting patients with LSS. For 6 weeks, 111 patients per group were administered medication following a standard regimen, after which patient-reported outcomes were measured. The primary outcome was the Visual Analogue Scale (VAS) for back and leg pain, and the secondary outcomes included the Oswestry Disability Index (ODI), European Quality of Life 5 Dimensions (EQ-5D), and sleep quality. RESULTS: After 6 weeks of medication, there were significant improvements over time in the primary outcome, VAS for back pain and leg pain, in both groups, but no significant difference between the 2 groups. Similarly, for the secondary outcomes, ODI and EQ-5D, both groups showed significant improvements, yet there was no significant difference between them. In the subgroup analysis targeting poor sleepers (Pittsburgh sleep quality index, PSQI >5), both groups also exhibited significant improvements in sleep quality, but again, there was no significant difference between the groups. CONCLUSIONS: Efficacy of pregabalin, limaprost in back and leg pain, ODI, EQ-5D, and sleep quality, but there was no significant difference between the 2 groups. Thus, it is advisable to prescribe based on individual drug responses and potential complications.
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Analgésicos , Vértebras Lumbares , Pregabalina , Calidad de Vida , Estenosis Espinal , Humanos , Pregabalina/uso terapéutico , Estenosis Espinal/tratamiento farmacológico , Estenosis Espinal/complicaciones , Masculino , Femenino , Anciano , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Método Simple Ciego , Analgésicos/uso terapéutico , Alprostadil/análogos & derivados , Alprostadil/uso terapéutico , Dimensión del DolorRESUMEN
There is a high unmet need for early detection approaches for diffuse gastric cancer (DGC). We examined whether the stool proteome of mouse models of gastric cancer (GC) and individuals with hereditary diffuse gastric cancer (HDGC) have utility as biomarkers for early detection. Proteomic mass spectrometry of the stool of a genetically engineered mouse model driven by oncogenic KrasG12D and loss of p53 and Cdh1 in gastric parietal cells [known as Triple Conditional (TCON) mice] identified differentially abundant proteins compared with littermate controls. Immunoblot assays validated a panel of proteins, including actinin alpha 4 (ACTN4), N-acylsphingosine amidohydrolase 2 (ASAH2), dipeptidyl peptidase 4 (DPP4), and valosin-containing protein (VCP), as enriched in TCON stool compared with littermate control stool. Immunofluorescence analysis of these proteins in TCON stomach sections revealed increased protein expression compared with littermate controls. Proteomic mass spectrometry of stool obtained from patients with HDGC with CDH1 mutations identified increased expression of ASAH2, DPP4, VCP, lactotransferrin (LTF), and tropomyosin-2 relative to stool from healthy sex- and age-matched donors. Chemical inhibition of ASAH2 using C6 urea ceramide was toxic to GC cell lines and GC patient-derived organoids. This toxicity was reversed by adding downstream products of the S1P synthesis pathway, which suggested a dependency on ASAH2 activity in GC. An exploratory analysis of the HDGC stool microbiome identified features that correlated with patient tumors. Herein, we provide evidence supporting the potential of analyzing stool biomarkers for the early detection of DGC. Prevention Relevance: This study highlights a novel panel of stool protein biomarkers that correlate with the presence of DGC and has potential use as early detection to improve clinical outcomes.
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Biomarcadores de Tumor , Detección Precoz del Cáncer , Heces , Proteómica , Neoplasias Gástricas , Heces/química , Heces/microbiología , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/análisis , Animales , Humanos , Ratones , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patología , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/genética , Detección Precoz del Cáncer/métodos , Femenino , Proteómica/métodos , Masculino , Persona de Mediana Edad , Espectrometría de Masas/métodos , Modelos Animales de EnfermedadRESUMEN
The aim of this preliminary study was to assess the impact of injecting recombinant human bone morphogenetic protein-2 (rhBMP-2) with ß-tricalcium phosphate (ß-TCP) carrier into the uppermost instrumented vertebra (UIV) during surgery to prevent the development of proximal junctional kyphosis (PJK) and proximal junctional failure (PJF). The 25 patients from study group had received 0.5 mg rhBMP-2 mixed with 1.5 g ß-TCP paste injection into the UIV during surgery. The control group consisted of 75 patients who underwent surgery immediately before the start of the study. The incidences of PJK and PJF were analyzed as primary outcomes. Spinopelvic parameters and patient-reported outcomes were analyzed as secondary outcomes. Hounsfield unit (HU) measurements were performed to confirm the effect of rhBMP-2 with ß-TCP on bone formation at preoperative and postoperative at computed tomography. PJK and PJF was more occurred in control group than study group (p = 0.02, 0.29, respectively). The HU of the UIV significantly increased 6 months after surgery. And the increment at the UIV was also significantly greater than that at the UIV-1 6 months after surgery. Injection of rhBMP-2 with ß-TCP into the UIV reduced PJK and PJF rates 6 months after surgery with new bone formation.
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Proteína Morfogenética Ósea 2 , Fosfatos de Calcio , Cifosis , Proteínas Recombinantes , Fusión Vertebral , Factor de Crecimiento Transformador beta , Adulto , Humanos , Estudios Retrospectivos , Complicaciones Posoperatorias/etiología , Cifosis/etiología , Fusión Vertebral/métodosRESUMEN
Background: The T-line hernia mesh is a synthetic, polypropylene mesh specifically designed to prevent anchor point failure by evenly distributing tension through mesh suture extensions. This case series illustrates the first clinical application of the T-line mesh for umbilical hernia repair (UHR). Methods: This study is a retrospective, consecutive cases series of all adult patients presenting to a single surgeon with symptomatic umbilical hernia requiring surgical repair using the T-line hernia mesh. Patient demographics, surgical details, and 30-day postoperative complications were collected. Descriptive statistics were computed in Microsoft Excel (Redmond, Va.). Results: Three patients presented for UHR. All three patients were obese with mean body mass index of 37.5â ±â 6.6. Two patients were former smokers, and two had presented after hernia recurrence. The average defect size was 80.1 cm2 ± 94.0 cm2. Two patients had UHR with onlay mesh placement, whereas one had a transversus abdominus release followed by retrorectus mesh placement. The average mesh size was 192.3 cm2 ± 82.5 cm2. All three cases were classified as clean. There were no intraoperative complications. No patients experienced 30-day postoperative complications or recurrence. Conclusions: We present a case series of three patients presenting with large, symptomatic umbilical hernias who underwent UHR with T-line hernia mesh reinforcement without short term complications or hernia recurrence at last follow-up.
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Background: The COVID-19 pandemic has convoluted hesitancy toward vaccines, including the seasonal influenza (flu) vaccine. Because of COVID-19, the flu season has become more complicated; therefore, it is important to understand all the factors influencing the uptake of these vaccines to inform intervention targets. This article assesses factors related to the uptake of influenza and COVID-19 vaccines among adults in Tennessee. Methods: A cross-sectional, secondary data analysis of 1,400 adults was conducted in Tennessee. The adult sample came from two data sources: Data source 1 completed a baseline survey from January to March 2022, and data source 2 was completed from May to August 2022. Data on vaccine attitudes, facilitators and barriers, and communication needs were collected via random digit dial by Scientific Telephone Samples (STS). Two multivariable logistic regression models were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) to predict sociodemographic and overall vaccine-related factors associated with receipt or non-receipt (referent) of COVID-19 and influenza vaccines. Results: Approximately 78% of the adult sample had received the COVID-19 vaccination. A significant positive association for COVID-19 vaccine uptake was seen among those who were older (aged 50-65) (aOR = 1.9; 95% CI: 1.2-3.2), Black (aOR = 2.0; 95% CI:1.3-2.8), and had a college education and higher (aOR = 2.3; 95% CI: 1.5-3.6). However, there was a significant negative association for persons reporting they were extremely religious (aOR = 0.5; 95% CI:0.3-0.9). Over 56% of the adult sample had received the influenza vaccination this season. Those who had a higher annual household income ($80,000+) (aOR = 1.9; 95% CI: 1.3-2.6) and had health insurance (aOR = 2.6; 95% CI: 1.4-4.8) had a significant positive association with influenza vaccine receipt. However, those who were employed part-time or were unemployed had a significant negative association for influenza vaccine receipt (aOR = 0.7; 95% CI: 0.5-0.9). Both COVID-19 and influenza vaccine receipt had strongly significant positive trends with increasing belief in effectiveness and trust (p < 0.0001) and strongly significant negative trends with higher levels of overall vaccine hesitancy (p < 0.0001). Conclusion: Strategies to increase COVID-19 and influenza vaccination should be age-specific, focus on increasing geographical and financial access, and offer tailored messages to address concerns about these vaccines.
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COVID-19 , Vacunas contra la Influenza , Gripe Humana , Adulto , Humanos , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Vacunas contra la COVID-19 , Estaciones del Año , Tennessee/epidemiología , Estudios Transversales , Pandemias , Cobertura de Vacunación , COVID-19/epidemiología , COVID-19/prevención & control , Conocimientos, Actitudes y Práctica en Salud , VacunaciónRESUMEN
Here we report on the first prospective study evaluating the safety and long-term survival when an escalating dose of inotuzumab ozogamicin (INO) (0.6, 1.2, or 1.8 mg/m2 on day 13) was added to one alkylator-containing conditioning regimen in patients with relapsed CD22 (+) lymphoid malignancies who were candidates for hematopoietic stem cell transplantation (HSCT). Twenty-six patients were enrolled. Six (23%) of these patients entered the phase 1 study: four were treated at an INO dose of 0.6 mg/m2 and two at dose of 1.2 mg/m2. None of these patients experienced dose-limiting toxicities. The remaining 20 (77%) patients entered the phase 2 part of the study at the maximum dose of 1.8 mg/m2. One patient developed VOD; this patient had received nivolumab immediately before HSCT while simultaneously experiencing hyperacute graft-vs-host disease (GVHD). Treatment-related mortality (TRM) at 5 years was 12%. With a median follow-up of 48.7 months, the 5-year overall survival (OS) and progression-free survival (PFS) rates were 84% and 80%, respectively. Compared with a historical cohort who received same conditioning for HSCT but without INO (n = 56), the INO group showed no significant differences in incidence of liver toxicity, engraftment time, TRM, or risk of acute GVHD. Patients with lymphoma who received INO had a trend for a better 5-year OS (93% versus 68%) and PFS (93% versus 58%) than those in the control group. In conclusion, our results showed that INO is safe with no increased risk of VOD when combined with one alkylator-containing regimen of HSCT.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Inotuzumab Ozogamicina , Estudios Prospectivos , Recurrencia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Injerto contra Huésped/etiología , Alquilantes , Acondicionamiento Pretrasplante/métodosRESUMEN
The COVID-19 pandemic highlighted the clear risk that zoonotic viruses pose to global health and economies. The scientific community responded by developing several efficacious vaccines which were expedited by the global need for vaccines. The emergence of SARS-CoV-2 breakthrough infections highlights the need for additional vaccine modalities to provide stronger, long-lived protective immunity. Here we report the design and preclinical testing of small extracellular vesicles (sEVs) as a multi-subunit vaccine. Cell lines were engineered to produce sEVs containing either the SARS-CoV-2 Spike receptor-binding domain, or an antigenic region from SARS-CoV-2 Nucleocapsid, or both in combination, and we tested their ability to evoke immune responses in vitro and in vivo. B cells incubated with bioengineered sEVs were potent activators of antigen-specific T cell clones. Mice immunised with sEVs containing both sRBD and Nucleocapsid antigens generated sRBD-specific IgGs, nucleocapsid-specific IgGs, which neutralised SARS-CoV-2 infection. sEV-based vaccines allow multiple antigens to be delivered simultaneously resulting in potent, broad immunity, and provide a quick, cheap, and reliable method to test vaccine candidates.
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COVID-19 , Vesículas Extracelulares , Vacunas , Animales , Humanos , Ratones , SARS-CoV-2 , PandemiasRESUMEN
OBJECTIVE: This study delves into the role of N-terminal propeptide type III collagen (PIIINP) in the diagnosis and management of liver pathological changes associated with non-alcoholic steatohepatitis (NASH). PATIENTS AND METHODS: We collected baseline information, pathological data, and serum PIIINP levels of 168 patients diagnosed with non-alcoholic fatty liver disease (NAFLD) via ultrasound imaging in our hospital. Based on the non-alcoholic fatty liver disease activity score (NAS), patients with different NAFLD patterns were divided into a Definite NASH group and a Not/borderline group. Differences in PIIINP levels and pathological features between the two groups were compared and analyzed. The diagnostic value of PIIINP for NASH was evaluated using the receiver operating characteristic (ROC) curve. RESULTS: Patients with NASH exhibited significantly higher values of homeostatic model assessment for insulin resistance (HOMA-IR), fibrosis biomarker fibrosis-4 (FIB-4), aminotransferase-to-platelet ratio index (APRI), and serum PIIINP levels than those classified as Not/borderline. A marked increase in the serum concentrations of PIIINP was observed with the severity of fatty degeneration, lobular inflammation, and hepatocellular ballooning. The AUC of PIIINP for diagnosing definite NASH was 0.766 (95% CI: 0.694, 0.839), APRI was 0.634 (95% CI: 0.549, 0.718), and FIB-4 was 0.621 (95% CI: 0.534, 0.708). The AUC of PIIINP for diagnosing definite NASH was significantly higher than that of APRI and FIB-4 (all p<0.05). Utilizing the predetermined threshold values for diagnostic parameters, the PIIINP measure demonstrated a sensitivity of 71.6% and a specificity of 73.6% in diagnosing definitive NASH when its value exceeded 7.72 ng/dL. This yielded a Youden index of 0.45. Similarly, when the APRI measure exceeded 0.21, it exhibited a sensitivity of 60.5% and a specificity of 63.2%, resulting in a Youden index of 0.24. Moreover, when the FIB-4 index surpassed 0.26, it showed a sensitivity of 46.9% and a specificity of 79.3%, culminating in a Youden index of 0.26. CONCLUSIONS: NASH patients in this study exhibited significantly elevated PIIINP serum levels, which were closely associated with hepatocyte pathological changes. PIIINP demonstrated superior competence in diagnosing NASH than APRI and FIB-4 and thus offers a viable alternative for the clinical diagnosis of NASH.
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Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/patología , Colágeno Tipo III , Hígado/patología , Fibrosis , Hepatocitos/patología , Curva ROC , Biomarcadores , Biopsia , Cirrosis HepáticaRESUMEN
This study evaluated carcass attributes, meat and belly qualities in finisher boars (n = 79) selected for feed efficiency (low, intermediate and high) based on estimated breeding value for feed conversion ratio within a Large White dam and sire genetic lines. The sire line had lower trimmed fat proportions and higher lean than the dam line (P < 0.01). Genetic lines expressed slight colour changes and drip losses (P < 0.05), with no differences in pH, marbling and cooking traits (P > 0.05). High-efficient animals presented the highest lean yield (P < 0.01), the lowest trimmed fat proportion (P < 0.01) and no effect on meat and belly quality attributes (P > 0.05) compared with other efficient groups. Interaction between efficiency group and genetic line was only detected for belly weight and thickness (P < 0.01). High-efficient animals offer a greater leanness level, with minimal impact on meat and belly quality traits.
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Carne de Cerdo , Carne Roja , Porcinos/genética , Animales , Masculino , Composición Corporal/genética , Fenotipo , CarneRESUMEN
AIMS: Mounting evidence has shown that caveolin-1 plays a pathological role in the progression of albuminuria. Our study aimed to provide clinical evidence showing whether circulating caveolin-1 levels were associated with microalbuminuria (MAU) in women with overt diabetes mellitus in pregnancy (ODMIP). METHODS: A total of 150 pregnant women were enrolled in different groups, including 40 women with ODMIP and MAU (ODMIP + MAU), 40 women with ODMIP, and 70 women without ODMIP (Non-ODMIP). Plasma caveolin-1 levels were determined by ELISA. The presence of caveolin-1 in the human umbilical vein vascular wall was evaluated by immunohistochemical and western blot analysis, respectively. Albumin transcytosis across endothelial cells was measured using an established nonradioactive in vitro approach. RESULTS: Significantly increased levels of plasma caveolin-1 were detected in ODMIP + MAU women. The Pearson's correlation analysis revealed a positive correlation between plasma caveolin-1 levels and Hemoglobin A1c (HbA1c %) as well as with MAU in the ODMIP + MAU group. Simultaneously, experimental knockdown or overexpression of caveolin-1 significantly decreased or increased the level of albumin transcytosis across both human and mouse glomerular endothelial cells (GECs), respectively. CONCLUSIONS: Our data showed a positive association between plasma caveolin-1 levels and microalbuminuria in ODMIP + MAU.
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Diabetes Mellitus , Embarazo en Diabéticas , Embarazo , Humanos , Femenino , Animales , Ratones , Albuminuria/complicaciones , Caveolina 1 , Células Endoteliales , Albúminas , Factores de RiesgoRESUMEN
Recapitulation of the natural healing process is receiving increasing recognition as a strategy to induce robust tissue regeneration. Endochondral ossification has been recognized as an essential reparative approach in natural jawbone defect healing. However, such an approach has been overlooked in the recent development of cell-based therapeutics for jawbone repair. Therefore, this study aimed to explore a bioinspired stem cell-based strategy for jawbone repair by mimicking the mesenchymal condensation of progenitor cells during the early endochondral ossification process. For this purpose, passage 3 of jawbone periosteum-derived cells (jb-PDCs) was cultured in our previously reported nonadherent microwells (200 µm in diameter, 148 µm in depth, and 100 µm space in between) and self-assembled into spheroids with a diameter of 96.4 ± 5.8 µm after 48 h. Compared to monolayer culture, the jb-PDC spheroids showed a significant reduction of stemness marker expression evidenced by flow cytometry. Furthermore, a significant upregulation of chondrogenic transcription factor SOX9 in both gene and protein levels was observed in the jb-PDC spheroids after 48 h of chondrogenic induction. RNA sequencing and Western blotting analysis further suggested that the enhanced SOX9-mediated chondrogenic differentiation in jb-PDC spheroids was attributed to the activation of the p38 MAPK pathway. Impressively, inhibition of p38 kinase activity significantly attenuated chondrogenic differentiation jb-PDC spheroids, evidenced by a significant decline of SOX9 in both gene and protein levels. Strikingly, the jb-PDC spheroids implanted in 6- to 8-wk-old male C57BL/6 mice with critical-size jawbone defects (1.8 mm in diameter) showed an evident contribution to cartilaginous callus formation after 1 wk, evidenced by histological analysis. Furthermore, micro-computed tomography analysis showed that the jb-PDC spheroids significantly accelerated bone healing after 2 wk in the absence of exogenous growth factors. In sum, the presented findings represent the successful development of cell-based therapeutics to reengineer the endochondral bone repair process and illustrate the potential application to improve bone repair and regeneration in the craniofacial skeleton.
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Células Madre Mesenquimatosas , Ratones , Animales , Masculino , Microtomografía por Rayos X , Ratones Endogámicos C57BL , Osteogénesis/genética , Cartílago/metabolismo , Diferenciación Celular , Condrogénesis/genéticaRESUMEN
Airway remodeling is a major pathological characteristic of chronic obstructive pulmonary disease (COPD). This study aimed to investigate the effect of Abhd2 deficiency on ovalbumin (OVA)-induced airway remodeling and inflammation in vivo. Abhd2-deficient mice were used to establish an OVA-induced asthma model. Lung tissues were analyzed using hematoxylin and eosin (HE) staining, Masson staining, immunohistochemistry, quantitative reverse transcription- polymerase chain reaction (qRT-PCR), and western blotting were used to determine the role of Abhd2 in the regulation of OVA-induced airway remodeling and inflammation. Our findings revealed that the RNA expression of inflammatory factors, including IL-1ß, IL-6, IL-4, and IL-13, was significantly increased in OVA-induced Abhd2 Gt/Gt asthmatic mice. The expression of IFN-γ was decreased significantly in OVA-induced Abhd2 Gt/Gt asthmatic mice. The protein expression of airway remodeling factors, including α-SMA, type I collagen, and Ki67, was also increased in OVA-induced Abhd2 Gt/Gt asthmatic mice compared to that in OVA-induced wild-type (WT) mice. Additionally, Abhd2 deficiency promoted the expression of p-Akt in tissues of the asthma model. These results suggest that Abhd2 deficiency exacerbates airway remodeling and inflammation through the PI3K/Akt pathway in chronic asthma.
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Asma , Animales , Ratones , Remodelación de las Vías Aéreas (Respiratorias) , Asma/inducido químicamente , Asma/genética , Asma/veterinaria , Líquido del Lavado Bronquioalveolar , Modelos Animales de Enfermedad , Inflamación/metabolismo , Inflamación/veterinaria , Pulmón , Ratones Endogámicos BALB C , Ovalbúmina/toxicidad , Ovalbúmina/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
Background: Traditional treatment modalities for vertebral compression fractures (VCFs) include bed rest, pain medications, muscle relaxants, back braces, and physical therapy. In cases where conservative treatment proves ineffective, a new procedure called core decompression of the vertebral body is explored. Core decompression of the vertebral body has the potential to lower and stabilize the intraosseous pressure, resulting in enhanced blood circulation, which contributes to pain reduction. In this trial, we evaluated the efficacy of core decompression of the vertebral body in patients with painful VCFs compared with conventional conservative treatment. Methods: This prospective randomized controlled trial was conducted at a tertiary education hospital between June 2017 and May 2020. The participants were randomly assigned in a 1:1 ratio to one of two treatment groups: the core decompression group and the conservative treatment group. The primary outcome measure was the visual analog scale (VAS) pain score of the back 3 months after the procedure. Secondary outcome measures included the Oswestry Disability Index (ODI) for lumbar disabilities, the European Quality of Life-5 Dimensions (EQ-5D) score for quality of life, and radiographic outcomes such as changes in compression rate. Results: All patients underwent the assigned intervention (48 core decompression and 50 conservative treatments). At both 1 month and 3 months, there were no significant differences between the core decompression group and conservative treatment group in VAS pain score (adjusted treatment effect: -0.1 and 2.0; 95% confidence interval [CI]: -7.5 to 7.3 and -5.6 to 9.6; p = 0.970 and p = 0.601, respectively). In addition, there were no significant inter-group differences in ODI and EQ-5D scores throughout the follow-up period (p = 0.917 and 0.704, respectively). Conclusion: Core decompression of the vertebral body did not demonstrate any significant improvement in pain and disability compared to conventional conservative treatment.
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Fracturas por Compresión , Fracturas de la Columna Vertebral , Humanos , Fracturas por Compresión/cirugía , Tratamiento Conservador , Estudios Prospectivos , Calidad de Vida , Resultado del Tratamiento , Cuerpo Vertebral , Fracturas de la Columna Vertebral/complicaciones , Fracturas de la Columna Vertebral/cirugía , Dolor , DescompresiónRESUMEN
The antiviral restriction factor, tetherin, blocks the release of several different families of enveloped viruses, including the Coronaviridae. Tetherin is an interferon-induced protein that forms parallel homodimers between the host cell and viral particles, linking viruses to the surface of infected cells and inhibiting their release. We demonstrate that SARS-CoV-2 infection causes tetherin downregulation and that tetherin depletion from cells enhances SARS-CoV-2 viral titres. We investigate the potential viral proteins involved in abrogating tetherin function and find that SARS-CoV-2 ORF3a reduces tetherin localisation within biosynthetic organelles where Coronaviruses bud, and increases tetherin localisation to late endocytic organelles via reduced retrograde recycling. We also find that expression of Spike protein causes a reduction in cellular tetherin levels. Our results confirm that tetherin acts as a host restriction factor for SARS-CoV-2 and highlight the multiple distinct mechanisms by which SARS-CoV-2 subverts tetherin function.
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Antígeno 2 del Estroma de la Médula Ósea , COVID-19 , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Liberación del Virus , Humanos , Antígeno 2 del Estroma de la Médula Ósea/antagonistas & inhibidores , Antígeno 2 del Estroma de la Médula Ósea/metabolismo , COVID-19/virología , Proteínas Ligadas a GPI/genética , Proteínas Ligadas a GPI/metabolismo , SARS-CoV-2/fisiología , Glicoproteína de la Espiga del Coronavirus/genéticaRESUMEN
BACKGROUND: Transparency around surgeon level data may align healthcare delivery with quality care for patients. Biliary surgery includes numerous procedures performed by both general surgeons and subspecialists alike. Cholecystectomy is a common surgical procedure and an optimal cohort to measure quality outcomes within a healthcare system. METHODS: Data were collected for 5084 biliary operations performed by 68 surgeons in 11 surgical divisions in a health system including a tertiary academic hospital, two regional community hospitals, and two ambulatory surgery centers. A privacy protected dashboard was developed to compare surgeon performance and cost between July 2018 and June 2022. A sample cohort of patients ≥ 18 years who underwent cholecystectomy were compared by operative time, cost, and 30-day outcomes. RESULTS: Over 4 years, 4568 cholecystectomy procedures were performed by 57 surgeons. Operations were done by 57 surgeons in four divisions and included 3846 (84.2%) laparoscopic cholecystectomies, 601 (13.2%) laparoscopic cholecystectomies with cholangiogram, and 121 (2.6%) open cholecystectomies. Patients were admitted from the emergency room in 2179 (47.7%) cases while 2389 (52.3%) cases were performed in the ambulatory setting. Individual surgeons were compared to peers for volume, intraoperative data, cost, and outcomes. Cost was lowest at ambulatory surgery centers, yet only 4.2% of elective procedures were performed at these facilities. Prepackaged kits with indocyanine green were more expensive than cholangiograms that used iodinated contrast. The rate of emergency department visits was lowest when cases were performed at ambulatory surgery centers. CONCLUSION: Data generated from clinical dashboards can inform surgeons as to how they compare to peers regarding quality metrics such as cost, time, and complications. In turn, this may guide strategies to standardize care, optimize efficiency, provide cost savings, and improve outcomes for cholecystectomy procedures. Future application of clinical dashboards can assist surgeons and administrators to define value-based care.
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Sistema Biliar , Colecistectomía Laparoscópica , Humanos , Estudios Prospectivos , Colecistectomía , Colangiografía , Estudios RetrospectivosRESUMEN
Traditional conditioning regimens for patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) provide suboptimal outcomes, especially for older patients and those with comorbidities. We hypothesized that a fractionated myeloablative busulfan dose delivered over an extended period would reduce nonrelapse mortality (NRM) while retaining antileukemic effects. Here, we performed a phase 2 trial for adults with hematological malignancies receiving matched related or unrelated allo-HCT. Participants received busulfan 80 mg/m2 as outpatients on days -20 and -13 before transplant. Fludarabine 40 mg/m2 was administered on days -6 to -3, followed by busulfan dosed to achieve a target area under the curve of 20 000 mol/min for the whole course. The primary end point was day-100 NRM. Seventy-eight patients were included, with a median age of 61 years (range, 39-70 years), who received transplantation for acute leukemia (24%), myelodysplastic syndrome (27%), or myeloproliferative disease/chronic myeloid leukemia (44%). HCT-specific comorbidity index (HCT-CI) was ≥3 in 34 (44%). With a median follow-up of 36.4 months (range, 2.9-51.5), the 100-day, 1-year, and 3-year NRM rates were 3.8%, 8%, and 9.3%, respectively, without a significant difference in age or HCT-CI score. The 1-year and 3-year relapse incidence was 10% and 18%, respectively. The 3-year overall survival was 80%, without a significant difference in age or HCT-CI score and was similar for patients aged >60 years and those aged <60 years as well as for those with HCT-CI ≥3 and HCT-CI <3. Overall, a myeloablative fractionated busulfan regimen has low NRM without an increase in relapse rate, resulting in promising survival, even in older patients or in patients with comorbidities. This trial was registered at www.clinicaltrials.gov as #NCT02861417.