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BACKGROUND: Accurately identifying the branches of pulmonary segmental vessels and bronchi, as well as adjacent structures, and determining the spatial location of lesions within pulmonary segments, are major challenges for thoracic surgeons. The application of three-dimensional reconstruction technology holds promise in addressing this issue. OBJECTIVE: To evaluate the clinical value of three-dimensional reconstruction in thoracoscopic segmental surgery. METHODS: Seventy-seven patients who underwent thoracoscopic segmental surgery combined with three-dimensional reconstruction at our hospital from January 1, 2020, to August 31, 2023, were retrospectively analyzed. Preoperative chest enhanced CT scans were conducted, and MIMICS software aided in reconstructing DICOM format original data for patients with pulmonary nodules to facilitate intraoperative nodule localization. Accurate segmental pneumonectomy was performed by comparing preoperative anatomical identification of target segmental arteries, veins, and bronchi, with surgical details and postoperative outcomes recorded, including intraoperative pulmonary resection distribution, operation time, blood loss, chest tube drainage, extubation time, hospital stay, and complications. RESULTS: Following preoperative three-dimensional reconstruction, successful segmental lung surgeries were performed, predominantly with single segmental resection (92.2%), and a minority with combined segmentectomy (7.8%). Median operation time was 130225 minutes, with intraoperative blood loss at 70100 mL and postoperative chest tube drainage at 347 mL (159690 mL). Median extubation time and hospital stay were 4 days and 7 days, respectively. Complications within the 3-month follow-up affected 11.7% of cases, including persistent pulmonary leakage (7.1%), pulmonary infection (4.3%), atelectasis (4.3%), and pleural effusion (1.4%), with no fatalities. CONCLUSION: Preoperative 3D reconstruction can help the operator to perform safe, efficient and accurate thoracoscopic segmental pneumonectomy, which is worth popularizing in clinic.
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The functions of natural killer (NK) and T cells in innate and adaptive immunity, as well as their functions in tumor eradication, are complementary and intertwined. Here we show that utilization of multi-specific antibodies or nano-antibodies capable of simultaneously targeting both NK and T cells could be a valuable approach in cancer immunotherapy. Here, we introduce a tri-specific Nano-Antibody (Tri-NAb), generated by immobilizing three types of monoclonal antibodies (mAbs), using an optimized albumin/polyester composite nanoparticle conjugated with anti-Fc antibody. This Tri-NAb, targeting PDL1, 4-1BB, and NKG2A (or TIGIT) simultaneously, effectively binds to NK and CD8+ T cells, triggering their activation and proliferation, while facilitating their interaction with tumor cells, thereby inducing efficient tumor killing. Importantly, the antitumor efficacy of Tri-NAb is validated in multiple models, including patient-derived tumor organoids and humanized mice, highlighting the translational potential of NK and T cell co-targeting.
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Anticuerpos Monoclonales , Linfocitos T CD8-positivos , Células Asesinas Naturales , Nanopartículas , Células Asesinas Naturales/inmunología , Animales , Humanos , Ratones , Nanopartículas/química , Anticuerpos Monoclonales/inmunología , Línea Celular Tumoral , Linfocitos T CD8-positivos/inmunología , Inmunoterapia/métodos , Neoplasias/inmunología , Neoplasias/terapia , Antígeno B7-H1/inmunología , Subfamília C de Receptores Similares a Lectina de Células NK/inmunología , Femenino , Miembro 9 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/inmunología , Ratones Endogámicos NODRESUMEN
OBJECTIVES: To observe the effect of acupuncture and moxibustion on arterial elasticity in patients with early carotid atherosclerosis. METHODS: A total of 62 patients with early carotid atherosclerosis were randomly divided into a blank group (12 cases, 1 cases dropped-off), a sham-acupuncture group (25 cases, 5 cases dropped-off) and an acupuncture group (25 cases, 3 cases dropped-off). Patients in the acupuncture group received acupuncture treatment, including â acupunctureï¼Baihui (GV20), Yintang (GV24+), Renying (ST9), Neiguan (PC6), Yanglingquan (GB34)ï¼â¡moxibustionï¼Yinqiguiyuan (Zhongwan ï¼»CV12ï¼½, Xiawan ï¼»CV10ï¼½, Qihai ï¼»CV6ï¼½, Guanyuan ï¼»CV4ï¼½), Sihua (Geshu ï¼»BL17ï¼½, Danshu ï¼»BL19ï¼½)ï¼â¢Intradermal needleï¼Xinshu (BL15), Danshu (BL19). Patients in the sham acupuncture group received placebo acupuncture, moxibustion, an intradermal needle, and the acupoints were the same as the acupuncture group. The above treatments were performed twice a week for 12 weeks. No intervention was given to the patients in the blank group. Diet and lifestyle education was given to the three groups. The ultrafast pulse wave velocity, including beginning-systolic pulse wave velocity (BS) and end-systolic pulse wave velocity (ES), was observed before treatment and 1, 2, 3 months after treatment in the three groups. The blood lipid level and platelet count (PLT) at each time point were observed. The safety of the treatments was also evaluated. RESULTS: Compared with those before treatment, the BS and ES values of both sides in the acupuncture group decreased at 2 and 3 months after treatment (P<0.05). Compared with the blank group, the bilateral ES of the acupuncture group were decreased at 2 months after treatment (P<0.05), and the bilateral BS and ES were decreased at 3 months (P<0.05). Compared with the sham-acupuncture group, the acupuncture group showed a decrease in left BS and left ES after 3 months of treatment (P<0.05), and the overall decrease on the left side of the acupuncture group was better than that on the right side. There were no significant differences between three groups in the levels of blood lipid and PLT at each time point. No serious adverse safety events occurred in the three groups during the treatment. CONCLUSIONS: Acupuncture and moxibustion therapy can improve arterial elasticity in patients with early carotid atherosclerosis, and it is safe and effective.
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Puntos de Acupuntura , Terapia por Acupuntura , Enfermedades de las Arterias Carótidas , Moxibustión , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Enfermedades de las Arterias Carótidas/terapia , Enfermedades de las Arterias Carótidas/fisiopatología , Elasticidad , Adulto , Arterias Carótidas/fisiopatologíaRESUMEN
The construction of C(sp3)-C(sp3) bonds remains one of the most difficult challenges in cross-coupling chemistry. Here, we report a photoredox/nickel dual catalytic approach that enables the simultaneous formation of two C(sp3)-C(sp3) linkages via trimolecular cross-coupling of alkenes with alkyl halides and hypervalent iodine-based reagents. The reaction harnesses a bimolecular homolytic substitution (SH2) mechanism and chemoselective halogen-atom transfer (XAT) to orchestrate the regioselective addition of electrophilic and nucleophilic alkyl radicals across unactivated alkenes without the need for a directing auxiliary. Utility is highlighted through late-stage (fluoro)alkylation and (trideutero)methylation of CâC bonds bearing different substitution patterns, offering straightforward access to drug-like molecules comprising sp3-hybridized carbon scaffolds.
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BACKGROUND: The importance of age on the development of ocular conditions has been reported by numerous studies. Diabetes may have different associations with different stages of ocular conditions, and the duration of diabetes may affect the development of diabetic eye disease. While there is a dose-response relationship between the age at diagnosis of diabetes and the risk of cardiovascular disease and mortality, whether the age at diagnosis of diabetes is associated with incident ocular conditions remains to be explored. It is unclear which types of diabetes are more predictive of ocular conditions. AIM: To examine associations between the age of diabetes diagnosis and the incidence of cataract, glaucoma, age-related macular degeneration (AMD), and vision acuity. METHODS: Our analysis was using the UK Biobank. The cohort included 8709 diabetic participants and 17418 controls for ocular condition analysis, and 6689 diabetic participants and 13378 controls for vision analysis. Ocular diseases were identified using inpatient records until January 2021. Vision acuity was assessed using a chart. RESULTS: During a median follow-up of 11.0 years, 3874, 665, and 616 new cases of cataract, glaucoma, and AMD, respectively, were identified. A stronger association between diabetes and incident ocular conditions was observed where diabetes was diagnosed at a younger age. Individuals with type 2 diabetes (T2D) diagnosed at < 45 years [HR (95%CI): 2.71 (1.49-4.93)], 45-49 years [2.57 (1.17-5.65)], 50-54 years [1.85 (1.13-3.04)], or 50-59 years of age [1.53 (1.00-2.34)] had a higher risk of AMD independent of glycated haemoglobin. T2D diagnosed < 45 years [HR (95%CI): 2.18 (1.71-2.79)], 45-49 years [1.54 (1.19-2.01)], 50-54 years [1.60 (1.31-1.96)], or 55-59 years of age [1.21 (1.02-1.43)] was associated with an increased cataract risk. T2D diagnosed < 45 years of age only was associated with an increased risk of glaucoma [HR (95%CI): 1.76 (1.00-3.12)]. HRs (95%CIs) for AMD, cataract, and glaucoma associated with type 1 diabetes (T1D) were 4.12 (1.99-8.53), 2.95 (2.17-4.02), and 2.40 (1.09-5.31), respectively. In multivariable-adjusted analysis, individuals with T2D diagnosed < 45 years of age [ß 95%CI: 0.025 (0.009,0.040)] had a larger increase in LogMAR. The ß (95%CI) for LogMAR associated with T1D was 0.044 (0.014, 0.073). CONCLUSION: The younger age at the diagnosis of diabetes is associated with a larger relative risk of incident ocular diseases and greater vision loss.
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BACKGROUND: The prognostic association between dysnatremia and outcomes in out-of-hospital cardiac arrest (OHCA) is not well understood. Given hypernatremia is associated with poor outcomes in critical illness and hyponatremia may exacerbate cerebral edema, we hypothesized that dysnatremia on OHCA hospital admission would be associated with worse neurological outcomes. METHODS: We studied adults (≥19 years) with non-traumatic OHCA between 2009 and 2016 who were enrolled in the British Columbia Cardiac Arrest Registry and survived to hospital admission at 2 quaternary urban hospitals. We stratified cases by admission serum sodium into hyponatremic (<135 mmol/L), normonatremic (135-145 mmol/L), and hypernatremic (>145 mmol/L) groups. We used logistic regression models, adjusted for age, sex, shockable rhythm, admission serum lactate, and witnessed arrest, to estimate the association between admission sodium and favorable neurological outcome (cerebral performance category 1-2 or modified Rankin scale 0-3). RESULTS: Of 414 included patients, 63 were hyponatremic, 330 normonatremic, and 21 hypernatremic. In each respective group, 21 (33.3%), 159 (48.2%), and 3 (14.3%) experienced good neurological outcomes. In univariable models, hyponatremia (OR 0.53, 95% CI 0.30-0.93) and hypernatremia (OR 0.19, 95% CI 0.05-0.65) were associated with lower odds of good neurological outcomes compared to the normonatremia group. After adjustment, only hypernatremia was associated with lower odds of good neurological outcomes (OR 0.22, 95% CI 0.05-0.98). CONCLUSIONS: Hypernatremia at admission was independently associated with decreased probability of good neurological outcomes at discharge post-OHCA. Future studies should focus on elucidating the pathophysiology of dysnatremia following OHCA.
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Reanimación Cardiopulmonar , Hipernatremia , Hiponatremia , Paro Cardíaco Extrahospitalario , Adulto , Humanos , Hipernatremia/etiología , Hipernatremia/complicaciones , Hiponatremia/etiología , Hiponatremia/complicaciones , Paro Cardíaco Extrahospitalario/etiología , Paro Cardíaco Extrahospitalario/terapia , Sodio , PronósticoRESUMEN
Background: Despite poor oral hygiene, the Baiku Yao (BKY) ethnic group in China presents a low prevalence of dental caries, which may be related to genetic susceptibility. Due to strict intra-ethnic marriage rule, this ethnic has an advantage in studying the interaction between genetic factors and other regulatory factors related to dental caries. Methods: Peripheral blood from a caries-free adult male was used for whole genome sequencing, and the BKY assembled genome was compared to the Han Chinese genome. Oral saliva samples were collected from 51 subjects for metabolomic and metagenomic analysis. Multiomics data were integrated for combined analysis using bioinformatics approaches. Results: Comparative genomic analysis revealed the presence of structural variations in several genes associated with dental caries. Metabolomic and metagenomic sequencing demonstrated the caries-free group had significantly higher concentration of antimicrobials and higher abundance of core oral health-related microbiota. The functional analysis indicated that cationic antimicrobial peptide resistance and the lipopolysaccharide biosynthesis pathway were enriched in the caries-free group. Conclusions: Our study provided new insights into the specific regulatory mechanisms that contribute to the low prevalence of dental caries in the specific population and may provide new evidence for the genetic diagnosis and control of dental caries.
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Cassava is a crucial crop that makes a significant contribution to ensuring human food security. However, high-quality telomere-to-telomere cassava genomes have not been available up to now, which has restricted the progress of haploid molecular breeding for cassava. In this study, we constructed two nearly complete haploid resolved genomes and an integrated, telomere-to-telomere gap-free reference genome of an excellent cassava variety, 'Xinxuan 048', thereby providing a new high-quality genomic resource. Furthermore, the evolutionary history of several species within the Euphorbiaceae family was revealed. Through comparative analysis of haploid genomes, it was found that two haploid genomes had extensive differences in linear structure, transcriptome features, and epigenetic characteristics. Genes located within the highly divergent regions and differentially expressed alleles are enriched in the functions of auxin response and the starch synthesis pathway. The high heterozygosity of cassava 'Xinxuan 048' leads to rapid trait segregation in the first selfed generation. This study provides a theoretical basis and genomic resource for molecular breeding of cassava haploids.
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When it comes to an efficient catalytic oxygen evolution reaction (OER) in the production of renewable energy and chemicals, the construction of heterogeneous structures is crucial to break the linear scalar relationship of a single catalyst. This heterogeneous structure construction helps creatively achieve high activity and stability. However, the synthesis process of heterogeneous crystalline materials is often complex and challenging to capture and reproduce, which limits their application. Here, the dynamic process of structural changes in Co-MOFs in alkali was captured by in situ powder X-ray diffraction, FT-IR spectroscopy, and Raman spectroscopy, and several self-reconfigured MOF heterogeneous materials with different structures were stably isolated. The created ß-Co(OH)2/Co-MOF heterojunction structure facilitates rapid mass-charge transfer and exposure of active sites, which significantly enhanced OER activity. Experimental results show that this heterogeneous structure achieves a low overpotential of 333 mV at 10 mA cm-2. The findings provide new insights and directions for the search for highly reactive cobalt-based MOFs for sustainable energy technologies.
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Coastal wetlands are highly efficient in blue carbon sequestration. The impacts of climate warming on photosynthetic rates and light response characteristics of wetland plants would change the magnitude of carbon sequestration in coastal wetlands. We constructed warming observation stations in Phragmites australis (Phragmites) wetlands located in the Yellow River Delta in Dongying with dry climate, and in Yancheng by the Yellow Sea with wet climate. By using a Li-6800 photosynthesis system, we investigated the responses of simulated warming on photosynthetic characteristics of Phragmites in both wetlands, and compared the difference between months (June and August) in Dongying wetland. The results showed the photosynthetic rates of Phragmites were higher in June than in August. Warming increased net photosynthetic rate (Pn), transpiration rate (Tr), stomatal conductance (gs) and intercellular carbon dioxide concentration (Ci) in the two months, but the variability of Pn to warming was lower in August. The Pn and water use efficiency (WUE) of Phragmites in the Yancheng wetland were higher than Dongying wetland, and the maximum net photosynthetic rate (Pn max), light saturation point (LSP), apparent quantum efficiency (AQY), and dark respiration rate (Rd) of the former responded more positively to warming. The values of AQY, LSP and Pn max of Phragmites in the Yancheng wetlands were increased by 16.7%, 53.6% and 30.3%, respectively, in the warming plots. Our results suggested that warming could improve the utilization efficiency of weak light, the adaptability to strong light and photosynthetic potential of Phragmites under rainy and humid conditions. This study is of importance for accurately quantifying carbon sequestration of coastal wetlands at the regional and seasonal scales in the context of climate warming.
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Poaceae , Humedales , China , Transporte Biológico , FotosíntesisRESUMEN
Antibiotic resistance caused by biofilm formation is a clinical challenge. Nitric oxide (NO) can effectively disperse a mature biofilm and can also synergistically influence the level of cyclic diguanylate (c-di-GMP), a universal secondary messenger that plays an important role in biofilm formation in bacteria. Based on our previous finding that c-di-GMP G-quadruplex inducers are effective biofilm formation inhibitors, we designed and synthesized a c-di-GMP G-quadruplex inducer-NO donor conjugate (A11@NO) as a bifunctional antibiofilm agent after obtaining the c-di-GMP G-quadruplex inducer (A11), which has an amino group capable of binding to a nitroso group (NO donor). The conjugate A11@NO showed better biofilm inhibition efficiency than A11, and it can also eradicate mature biofilm. Additionally, it exhibited good antimicrobial synergism against Pseudomonas aeruginosa and helped elevate the bactericidal efficiency of tobramycin against biofilm-formed bacteria. In combination with tobramycin, A11@NO also improved the survival rate of Caenorhabditis elegans in a hyperbiofilm environment.
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Donantes de Óxido Nítrico , Pseudomonas aeruginosa , Animales , Donantes de Óxido Nítrico/farmacología , Antibacterianos/farmacología , Tobramicina/farmacología , Óxido Nítrico , Biopelículas , Caenorhabditis elegans , FenotipoRESUMEN
Molecular ferroelectric materials are widely applied in piezoelectric converters, non-volatile memorizers, and photovoltaic devices due to their advantages of adjustable structure, lightweight, easy processing, and environmental friendliness. However, designing multifunctional molecular ferroelectrics with excellent properties has always been a great challenge. Herein, a multiaxial molecular ferroelectric is successfully designed by modifying the quasi-spherical cation dabco with CuBr2 to obtain halogenated [Bretdabco]CuBr4 (Bretdabco = N-bromoethyl-N'-diazabicyclo [2.2.2]octane), which crystallizes in polar point groups (C6). Typical ferroelectric behaviors featured by the P-E hysteresis loop and switched ferroelectric domain are exhibited. Notably, the molecular ferroelectric shows a high TC of 460 K, which is rare in the field and could greatly expand the application range of this material. In addition, the band gap is adjustable through the regulation of halogen. Both the UV absorption spectra and theoretical calculations indicate that the molecular ferroelectrics belong to a direct band gap (2.14 eV) semiconductor. This tunable and narrow band gap semiconductor molecular ferroelectric material with high TC can be utilized more effectively in the study of optoelectronics and sensors, including piezoelectric energy harvesters. This research may provide a promising approach for the development of multiaxial molecular ferroelectrics with a tiny band gap and high TC.
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[This corrects the article DOI: 10.3389/fmicb.2022.1075033.].
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Commercial carriers have been used to prepare monolithic NaBH4 hydrolytic catalysts, but the fixed structure and material limit the application scope and design freedom. Herein, the RuO2-CoP catalyst is coated on the surface of fibrous sepiolite (RuO2-CoP@aSep) by in-situ deposition, annealing in air and phosphating, which is constructed into the aerogel with cellulose nanofiber (CNF) and polyvinyl alcohol (PVA) by freeze drying process. The hydrogen generation rate (HGR) of RuO2-CoP@aSep increases from 3655 to 10713mLmin-1gcatalyst-1 by adjusting the mass ratio of cobalt to ruthenium in RuO2-CoP. Moreover, the optimized composite aerogel can get HGR (5268mLmin-1gcatalyst-1) by regulating its formulation, and the catalytic activity and mass loss rate of the aerogel maintains 76.6 and 0.92 % after five cycles of testing. The synergistic interaction between Ru and Co species, micro-nano porous structure, and structural coupling provide good catalytic activity and cycling performance, and show great potential in the design of controllable NaBH4 hydrolyzed monolithic catalysts.
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Basic requirements for advanced and practical supercapacitors need electrode materials with strong stability, high surface area, well-defined porosity, and enhanced capability of ion insertion and electron transfer. It is worth mentioning that the two-dimensional cluster-based Ni/Co-organic layer (Ni0.7Co0.3-CMOL) inherits high stability from the Kagóme lattice and shows excellent pseudocapacitance behavior. As an optimized atomic composition, this crystalline CMOL exhibits excellent performance and stability both in 1.0 M KOH and All-Solid-State Flexible Asymmetric Supercapacitor (ASCs). The specific capacitance values are 1211 and 394 F g-1 and the energy density is 54.67 Wh kg-1 at 1 A g-1. Good cycling stability is characterized by its capacitance retention, maintained at 92.4% after 5000 cycles in a three-electrode system and 90% after 2000 cycles at 20 A g-1 for assembled All-Solid-State Flexible ASCs. An in situ XRD technique was used in the three-electrode system, which showed that there was no signal of crystalline substance that affected the cyclic stability of the material while charging and discharging. These superior results prove that Ni0.7Co0.3-CMOL is a promising candidate for supercapacitor applications.
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Objective: To investigate the expression of glutathione peroxidase 2 (GPX2) in human lung adenocarcinoma tissues and its effect on the biological function of lung adenocarcinoma A549 cells. Methods: The expression of GPX2 in lung adenocarcinoma and its effect on survival were analyzed by the TCGA database and the GEPIA 2 database. A total of 45 cases of primary lung adenocarcinoma tissue specimens and 45 cases of their paracancerous tissue specimens were collected, and the expression of GPX2 in the two types of tissues was detected by immunohistochemistry. Lung adenocarcinoma A549 cells were divided into the GPX2 overexpression group (GPX2), the GPX2 knockdown group (si-GPX2), the empty vector group (Vector), the siRNA negative control group (si-NC), and the WT group; the mRNA level and protein expression of GPX2 in each group of A549 cells were detected by real-time fluorescence quantitative PCR and Western blotting; the proliferation activity of each group of cells was detected by the CCK-8 assay; the effect of GPX2 on cell migration and invasion ability was detected by the scratch assay and the Transwell invasion assay; the apoptosis of each group of cells was detected by flow cytometry; Western blotting was performed to detect the expression levels of Bax, Bcl-2, E-cadherin, vimentin, and MMP2 and MMP9 proteins in each group of cells. Results: Bioinformatics analysis showed that the expression of GPX2 was strongly correlated with the prognosis of lung adenocarcinoma patients (P < 0.01). The positive expression rates of GPX2 in lung adenocarcinoma and its paracancerous tissues were 66.0% and 15.7%, respectively (P < 0.05). The results of RT-qPCR and Western blotting showed that the expression level of GPX2 mRNA and protein in A549 cells in the GPX2 group increased, which was significantly higher than that in the WT group (P < 0.05); the expression levels of GPX2 mRNA and protein in A549 cells in the si-GPX2 group were the same, that is, significantly lower than the WT group (P < 0.05). GPX2 overexpression promoted the proliferation, migration, and invasion of A549 cells and inhibited their apoptosis; the results in the si-GPX2 group were opposite to those in the GPX2 group. Compared with the WT group, the expression of Bcl-2, vimentin, and MMP2 and MMP9 protein in the GPX2 group increased (P < 0.05), while the expression of Bax and E-cadherin protein decreased in the GPX2 group (P < 0.05); the results in the si-GPX2 group were opposite to those in the GPX2 group. Conclusion: The expression of GPX2 in lung adenocarcinoma is related to the prognosis of patients. It is proved that GPX2 can promote the migration and invasion of lung adenocarcinoma cells and is related to the EMT/ß-catenin pathway. Thus, GPX2 is expected to be an important target for the diagnosis and treatment of lung adenocarcinoma.
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CONTEXT: Viruses have the characteristics of rapid transmission and high mortality. At present, western medicines still lack an ideal antiviral. As natural products, many traditional Chinese medicines (TCM) have certain inhibitory effects on viruses, which has become the hotspot of medical research in recent years. OBJECTIVE: The antiviral active ingredients and mechanisms of TCM against viral diseases was studied in combination with the pathogenesis of viral diseases and antiviral effects. MATERIALS AND METHODS: English and Chinese literature from 1999 to 2021 was collected from databases including Web of Science, PubMed, Elsevier, Chinese Pharmacopoeia 2020 (CP), and CNKI (Chinese). Traditional Chinese medicines (TCM), active ingredients, antiviral, mechanism of action, and anti-inflammatory effect were used as the key words. RESULTS: The antiviral activity of TCM is clarified to put forward a strategy for discovering active compounds against viruses, and provide reference for screening antivirus drugs from TCM. TCM can not only directly kill viruses and inhibit the proliferation of viruses in cells, but also prevent viruses from infecting cells and causing cytophilia. It can also regulate the human immune system, enhance human immunity, and play an indirect antiviral role. DISCUSSION AND CONCLUSION: Based on the experimental study and antiviral mechanism of TCM, this paper can provide analytical evidence that supports the effectiveness of TCM in treating virus infections, as well as their mechanisms against viruses. It could be helpful to provide reference for the research and development of innovative TCMs with multiple components, multiple targets and low toxicity.
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Medicamentos Herbarios Chinos , Virosis , Antivirales/farmacología , Antivirales/uso terapéutico , China , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Medicina Tradicional China , Virosis/tratamiento farmacológicoRESUMEN
BACKGROUND: Elevated blood eosinophil counts are linked to worse outcomes in asthma and COPD, but have yet to be well characterized in CF. We hypothesized that higher stable visit blood eosinophil counts are associated with increased rates of lung function decline and pulmonary exacerbations (PEx). METHODS: We performed a retrospective analysis of adult CF patients (≥19 years) enrolled from 2012 to 2018 in a prospective cohort study focused on blood biomarkers. We included individuals with at least one year of follow-up post-stable visit blood draw and compared clinical characteristics by blood eosinophil count (<300 cells/µL vs. ≥300 cells/µL). We used multivariate mixed-effects linear regression to estimate annual change in ppFEV1. Multivariable poisson and linear regression models were used to estimate rate of PEx requiring IV antibiotics and to compare CF Respiratory Symptom Diary-Chronic Respiratory Infection Symptom Scores (CFRSD-CRISS), respectively. RESULTS: Of 109 patients, 17 (15.6%) had eosinophil counts ≥300 cells/µL. After adjustment for age, sex, BMI, and baseline ppFEV1, there was no association between high vs. low eosinophil group and rates of lung function decline (difference in slope -0.04%/y; 95% CI -1.5 to +1.4) or rates of PEx requiring IV antibiotics (IRR 1.46; 95% CI 0.75 to 2.65). The high eosinophil group had a higher mean CFRSD-CRISS score at stable visit (adjusted mean difference 9.3; 95% CI 2.9 to 16.0). CONCLUSIONS: The high eosinophil group experienced increased respiratory symptoms, but the rates of lung function decline and PEx were comparable between groups.
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Fibrosis Quística , Enfermedad Pulmonar Obstructiva Crónica , Adulto , Humanos , Fibrosis Quística/complicaciones , Fibrosis Quística/diagnóstico , Fibrosis Quística/epidemiología , Eosinófilos , Estudios Retrospectivos , Estudios Prospectivos , Recuento de Leucocitos , Antibacterianos , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/diagnósticoRESUMEN
Circular RNAs (circRNAs) are reported to participate in the development of diverse human malignancies. This work investigated the mechanism of circSKA3 in modulating medulloblastoma progression. A total of 15 cases of medulloblastoma were collected in this work. Daoy cells were used to construct cell models. The expression level of circSKA3, microRNA-520 h (miR-520 h), and cyclin-dependent kinase 6 (CDK6) mRNA in tissues or cells was examined by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot was employed to detect CDK6 protein expression. CCK-8 experiment, Transwell assay, and flow cytometry were applied to detect the regulatory effects of circSKA3 on cell proliferation, migration, invasion, and cell cycle. Dual-luciferase reporter gene experiment was executed to determine the relationship between circSKA3 and miR-520 h, and between miR-520 h and CDK6. circSKA3 was remarkably up-modulated in medulloblastoma tissues. CircSKA3 depletion markedly suppressed Daoy cell viability, migration, invasion, and cell cycle progression. CircSKA3 overexpression induced the opposite effects. circSKA3 could decoyed miR-520 h, which targeted the 3' UTR of CDK6. circSKA3 expression in medulloblastoma tissues was negatively correlated with miR-520 h expression and positively correlated with CDK6 expression. "Rescue" experiments revealed that miR-520 h down-modulation or CDK6 overexpression remarkably counteracted the inhibitory effect of circSKA3 knockdown on Daoy cells. circSKA3 facilitates medulloblastoma progression through miR-520 h/CDK6.