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1.
World J Gastroenterol ; 30(30): 3564-3573, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39193574

RESUMEN

BACKGROUND: Biliary tract cancers (BTCs) are a heterogeneous group of tumors with high malignancy, poor prognosis, and limited treatment options. AIM: To explore the efficacy and safety of nab-paclitaxel plus capecitabine as first-line treatment for advanced and metastatic BTCs. METHODS: This open-label, non-randomized, double-center, phase II clinical trial recruited systemic therapy-naive patients with unresectable or metastatic BTCs between April 2019 and June 2022 at Beijing Cancer Hospital and the First Hospital of China Medical University. Eligible patients were administered nab-paclitaxel (150 mg/m2, day 1) and capecitabine (2000 mg/m2, twice daily, days 1-7) in 14-day cycles until experiencing intolerable toxicity or disease progression. The primary outcome was the objective response rate (ORR). The secondary outcomes included the disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and safety. RESULTS: A total of 44 patients successfully completed the trial, with a median age of 64.00 years (interquartile range, 35.00-76.00), and 26 (59.09%) were females. Tumor response assessment was impeded for one patient due to premature demise from tumor hemorrhage. Among the remaining 43 patients undergoing at least one imaging assessment, the ORR was 23.26% [95% confidence interval (CI): 11.80%-38.60%], and the DCR was 69.77% (95%CI: 53.90%-82.80%). The median OS was 14.1 months (95%CI: 8.3-19.9), and the median PFS was 4.4 months (95%CI: 2.5-6.3). A total of 41 patients (93.18%) experienced at least one adverse event (AE), with 10 patients (22.73%) encountering grade ≥ 3 AEs, and the most frequent AEs of any grade were alopecia (79.50%), leukopenia (54.55%), neutropenia (52.27%), and liver dysfunction (40.91%), and no treatment-related deaths were documented. CONCLUSION: Nab-paclitaxel plus capecitabine may be an effective and safe first-line treatment strategy for patients with advanced or metastatic BTCs.


Asunto(s)
Albúminas , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias del Sistema Biliar , Capecitabina , Paclitaxel , Supervivencia sin Progresión , Humanos , Femenino , Persona de Mediana Edad , Masculino , Capecitabina/administración & dosificación , Capecitabina/efectos adversos , Capecitabina/uso terapéutico , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Albúminas/administración & dosificación , Albúminas/efectos adversos , Albúminas/uso terapéutico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Adulto , Neoplasias del Sistema Biliar/tratamiento farmacológico , Neoplasias del Sistema Biliar/mortalidad , Neoplasias del Sistema Biliar/patología , Resultado del Tratamiento
2.
Nat Commun ; 15(1): 4977, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38862531

RESUMEN

Quantum processor architectures must enable scaling to large qubit numbers while providing two-dimensional qubit connectivity and exquisite operation fidelities. For microwave-controlled semiconductor spin qubits, dense arrays have made considerable progress, but are still limited in size by wiring fan-out and exhibit significant crosstalk between qubits. To overcome these limitations, we introduce the SpinBus architecture, which uses electron shuttling to connect qubits and features low operating frequencies and enhanced qubit coherence. Device simulations for all relevant operations in the Si/SiGe platform validate the feasibility with established semiconductor patterning technology and operation fidelities exceeding 99.9%. Control using room temperature instruments can plausibly support at least 144 qubits, but much larger numbers are conceivable with cryogenic control circuits. Building on the theoretical feasibility of high-fidelity spin-coherent electron shuttling as key enabling factor, the SpinBus architecture may be the basis for a spin-based quantum processor that meets the scalability requirements for practical quantum computing.

3.
Nat Med ; 30(8): 2224-2234, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38830992

RESUMEN

Claudin18.2 (CLDN18.2) is highly expressed with the development of various malignant tumors, especially gastrointestinal cancers, and is emerging as a new target for cancer treatment. Satricabtagene autoleucel (satri-cel)/CT041 is an autologous chimeric antigen receptor (CAR) T cell targeting CLDN18.2, and the interim results of the CT041-CG4006 trial were reported in June 2022. Here we present the final results of this single-arm, open-label, phase 1 trial, which evaluated the safety and efficacy of satri-cel in patients with CLDN18.2-positive advanced gastrointestinal cancers. This trial included a dose-escalation stage (n = 15) and a dose-expansion stage in four different cohorts (total n = 83): cohort 1, satri-cel monotherapy in 61 patients with standard chemotherapy-refractory gastrointestinal cancers; cohort 2, satri-cel plus anti-PD-1 therapy in 15 patients with standard chemotherapy-refractory gastrointestinal cancers; cohort 3, satri-cel as sequential treatment after first-line therapy in five patients with gastrointestinal cancers; and cohort 4, satri-cel monotherapy in two patients with anti-CLDN18.2 monoclonal antibody-refractory gastric cancer. The primary endpoint was safety; secondary endpoints included efficacy, pharmacokinetics and immunogenicity. A total of 98 patients received satri-cel infusion, among whom 89 were dosed with 2.5 × 108, six with 3.75 × 108 and three with 5.0 × 108 CAR T cells. Median follow-up was 32.4 months (95% confidence interval (CI): 27.3, 36.5) since apheresis. No dose-limiting toxicities, treatment-related deaths or immune effector cell-associated neurotoxicity syndrome were reported. Cytokine release syndrome occurred in 96.9% of patients, all classified as grade 1-2. Gastric mucosal injuries were identified in eight (8.2%) patients. The overall response rate and disease control rate in all 98 patients were 38.8% and 91.8%, respectively, and the median progression-free survival and overall survival were 4.4 months (95% CI: 3.7, 6.6) and 8.8 months (95% CI: 7.1, 10.2), respectively. Satri-cel demonstrates therapeutic potential with a manageable safety profile in patients with CLDN18.2-positive advanced gastrointestinal cancer. ClinicalTrials.gov identifier: NCT03874897 .


Asunto(s)
Claudinas , Neoplasias Gastrointestinales , Inmunoterapia Adoptiva , Receptores Quiméricos de Antígenos , Humanos , Masculino , Neoplasias Gastrointestinales/inmunología , Neoplasias Gastrointestinales/terapia , Neoplasias Gastrointestinales/patología , Femenino , Persona de Mediana Edad , Anciano , Adulto , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia Adoptiva/métodos , Receptores Quiméricos de Antígenos/inmunología , Claudinas/inmunología , Resultado del Tratamiento , Linfocitos T/inmunología , Linfocitos T/trasplante
4.
BMC Public Health ; 24(1): 1063, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38627707

RESUMEN

OBJECTIVE: This study aims to elucidate the dose‒response relationship between 24-h activity behaviors and body fat percentage (BFP) in Chinese preschool children using a compositional isotemporal substitution model (ISM). METHODS: In a cross-sectional design, 881 children aged 3-6 from urban and rural areas of Jiangxi Province were sampled. Activity behaviors, including sedentary behavior (SB), low-intensity physical activity (LPA), and moderate- to high-intensity physical activity (MVPA), were measured using accelerometers. Sleep patterns were assessed through questionnaires, and BFP was determined by bioelectrical impedance analysis (BIA). The study employed compositional data analysis (CoDA) and ISM to estimate the impact of reallocating durations of different activity behaviors on BFP. RESULTS: Higher BFP was found in urban vs. rural children, decreasing with age. Overweight and obesity rates were 10.6% and 7.6%, respectively, above national averages. MVPA and LPA were negatively correlated with BFP, while SB was positively correlated. A 30-min MVPA reduction significantly increased zBFR, particularly in overweight children. Gender-specific nuances revealed that boys' MVPA negatively influenced zBFP (ß = -0.155), P < 0.05), while girls' SB positively impacted zBFP (ß = 0.636, P < 0.01). Isotemporal simulations emphasized amplified effects in overweight children, with boys' zBFR rising rapidly when MVPA was substituted and girls displaying a notable substitution effect between SB and LPA. CONCLUSION: BFP is closely linked to 24-h activity behaviors, notably in overweight and obese preschoolers. ISM identified MVPA as a critical influencer, with a 30-min reduction substantially increasing BFP. Gender disparities were evident, implicating MVPA in boys and LPA and SB in girls.


Asunto(s)
Ejercicio Físico , Sobrepeso , Masculino , Femenino , Humanos , Preescolar , Estudios Transversales , Ejercicio Físico/fisiología , Obesidad , Tejido Adiposo , Acelerometría
5.
Infect Drug Resist ; 17: 1041-1049, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38511153

RESUMEN

Purpose: This study aimed to investigate awareness of tuberculosis control among post-treatment tuberculosis patients, in order to provide a basis for future preventive and control work in this population. Patients and Methods: A cross-sectional descriptive study was conducted on post-treatment patients with tuberculosis in seven districts of Jinan City between July 2021 and December 2022. A face-to-face or telephone interviews using structured questionnaires for the research subjects were conducted by data collectors. Analyses were carried out first for all subjects, and then separately for male and female subjects. Results: A total of 837 valid questionnaires were collected, of which 495 were males and 342 were females. The awareness rate of the core TB knowledge was 82.46%. The ≥65 year group in the total group (OR=0.43, 95% CI: (0.28, 0.68)), male (OR=0.47, 95% CI: (0.27, 0.83)) and female group (OR=0.40, 95% CI: (0.19, 0.86)) was lower than that of the control group. Educational level and monthly income are the main factors of TB cognition in total group. People with university or higher education (OR=2.05, 95% CI: (1.38, 3.05)) and with a monthly income of ≥6,000 (OR=1.89, 95% CI: (1.10, 3.25)) had a higher awareness rate. The group with current residence in the city was more aware than the reference group. Conclusion: In the future, the communication of the main transmission route, suspicious symptoms, and cure of TB needs to be strengthened for the post-treatment TB patients. The elderly, those with secondary school education or below, agricultural workers and low-income people are the groups with weak knowledge of TB, and they are also the groups that need to be focused on health education. The above information should be focused on the above groups of people in order to educate them in a way that is easily acceptable to them.

6.
Nat Commun ; 15(1): 2296, 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38485971

RESUMEN

The connectivity within single carrier information-processing devices requires transport and storage of single charge quanta. Single electrons have been adiabatically transported while confined to a moving quantum dot in short, all-electrical Si/SiGe shuttle device, called quantum bus (QuBus). Here we show a QuBus spanning a length of 10 µm and operated by only six simply-tunable voltage pulses. We introduce a characterization method, called shuttle-tomography, to benchmark the potential imperfections and local shuttle-fidelity of the QuBus. The fidelity of the single-electron shuttle across the full device and back (a total distance of 19 µm) is (99.7 ± 0.3) %. Using the QuBus, we position and detect up to 34 electrons and initialize a register of 34 quantum dots with arbitrarily chosen patterns of zero and single-electrons. The simple operation signals, compatibility with industry fabrication and low spin-environment-interaction in 28Si/SiGe, promises long-range spin-conserving transport of spin qubits for quantum connectivity in quantum computing architectures.

7.
Nat Ecol Evol ; 8(4): 717-728, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38383853

RESUMEN

Viruses are crucial in shaping soil microbial functions and ecosystems. However, studies on soil viromes have been limited in both spatial scale and biome coverage. Here we present a comprehensive synthesis of soil virome biogeographic patterns using the Global Soil Virome dataset (GSV) wherein we analysed 1,824 soil metagenomes worldwide, uncovering 80,750 partial genomes of DNA viruses, 96.7% of which are taxonomically unassigned. The biogeography of soil viral diversity and community structure varies across different biomes. Interestingly, the diversity of viruses does not align with microbial diversity and contrasts with it by showing low diversity in forest and shrubland soils. Soil texture and moisture conditions are further corroborated as key factors affecting diversity by our predicted soil viral diversity atlas, revealing higher diversity in humid and subhumid regions. In addition, the binomial degree distribution pattern suggests a random co-occurrence pattern of soil viruses. These findings are essential for elucidating soil viral ecology and for the comprehensive incorporation of viruses into soil ecosystem models.


Asunto(s)
Suelo , Virus , Suelo/química , Ecosistema , Viroma , Microbiología del Suelo , Ecología , Virus/genética
8.
Nat Commun ; 15(1): 1325, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38351007

RESUMEN

Long-ranged coherent qubit coupling is a missing function block for scaling up spin qubit based quantum computing solutions. Spin-coherent conveyor-mode electron-shuttling could enable spin quantum-chips with scalable and sparse qubit-architecture. Its key feature is the operation by only few easily tuneable input terminals and compatibility with industrial gate-fabrication. Single electron shuttling in conveyor-mode in a 420 nm long quantum bus has been demonstrated previously. Here we investigate the spin coherence during conveyor-mode shuttling by separation and rejoining an Einstein-Podolsky-Rosen (EPR) spin-pair. Compared to previous work we boost the shuttle velocity by a factor of 10000. We observe a rising spin-qubit dephasing time with the longer shuttle distances due to motional narrowing and estimate the spin-shuttle infidelity due to dephasing to be 0.7% for a total shuttle distance of nominal 560 nm. Shuttling several loops up to an accumulated distance of 3.36 µm, spin-entanglement of the EPR pair is still detectable, giving good perspective for our approach of a shuttle-based scalable quantum computing architecture in silicon.

10.
Nat Commun ; 14(1): 7318, 2023 11 11.
Artículo en Inglés | MEDLINE | ID: mdl-37951952

RESUMEN

Soil harbors a vast expanse of unidentified microbes, termed as microbial dark matter, presenting an untapped reservo)ir of microbial biodiversity and genetic resources, but has yet to be fully explored. In this study, we conduct a large-scale excavation of soil microbial dark matter by reconstructing 40,039 metagenome-assembled genome bins (the SMAG catalogue) from 3304 soil metagenomes. We identify 16,530 of 21,077 species-level genome bins (SGBs) as unknown SGBs (uSGBs), which expand archaeal and bacterial diversity across the tree of life. We also illustrate the pivotal role of uSGBs in augmenting soil microbiome's functional landscape and intra-species genome diversity, providing large proportions of the 43,169 biosynthetic gene clusters and 8545 CRISPR-Cas genes. Additionally, we determine that uSGBs contributed 84.6% of previously unexplored viral-host associations from the SMAG catalogue. The SMAG catalogue provides an useful genomic resource for further studies investigating soil microbial biodiversity and genetic resources.


Asunto(s)
Microbiota , Suelo , Microbiota/genética , Metagenoma/genética , Biodiversidad , Genómica , Microbiología del Suelo
11.
Nanomaterials (Basel) ; 13(13)2023 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-37446501

RESUMEN

In order to improve laser transmission efficiency at 1053 nm and 527 nm, a potassium deuterium phosphate (DKDP) crystal (a key component of high-power laser systems) needs a bi-layer antireflection coating system on its incident surface. UV-curable polysiloxane coatings with a refractive index varying from 1.500 to 1.485 were prepared through the polycondensation of a methacryloxy propyl trimethoxylsilane (MPS) monomer with a controllable degree of hydrolysis. Additionally, the influence rule of the coating structure on the refractive index was intensively studied, and the primary factors that dominate the hydrolysis process were discussed. Further refractive index adjustment was achieved using only a small amount of dopant based on the polysiloxane coating with refractive index of 1.485, allowing for high antireflection of the bi-layer coating system at desired wavelengths to be achieved. In addition, high laser damage resistance and remarkable mechanical properties of the coating were simultaneously realized through the incorporation of a minor quantity of dopants, which benefited from the successful modulation of the intrinsic refractive index of the polysiloxane coating.

12.
Sci Total Environ ; 896: 165187, 2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37391143

RESUMEN

The phyllosphere provides a habitat for a large sum of microorganisms which are modulated by numerous biotic and abiotic factors. While it is logical that host lineage must have some effect on the phyllosphere habitat, it is unclear if phyllospheres harbor similar microbial core communities across multiple ecosystems at the continental-scale. Here we collected 287 phyllosphere bacterial communities from seven ecosystems (including paddy field, dryland, urban area, protected agricultural land, forest, wetland, and grassland) in east-China to identify the regional core community and to characterize the importance of such communities in maintaining phyllosphere bacterial community structure and function. Despite significantly different bacterial richness and structure, the seven studied ecosystems contained a similar regional core community of 29 OTUs that comprised 44.9 % of the total bacterial abundance. The regional core community was less affected by environmental variables and less connected in the co-occurrence network compared with other non-core OTUs (the whole minus regional core community). Furthermore, the regional core community also had a large proportion (>50 %) of a constrained set of nutrient metabolism related functional potentials and less functional redundancy. This study suggests there is a robust regional core phyllosphere community regardless of ecosystem or spatial and environmental heterogeneity, and supports the argument that core communities are pivotal in maintaining microbial community structure and function.


Asunto(s)
Bosques , Microbiota , Bacterias , Agricultura , China
13.
Trends Biotechnol ; 41(10): 1227-1236, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37183053

RESUMEN

Synthetic microbial community (SynCom) biosensors are a promising technology for detecting and responding to environmental cues and target molecules. SynCom biosensors use engineered microorganisms to create a more complex and diverse sensing system, enabling them to respond to stimuli with enhanced sensitivity and accuracy. Here, we give a definition of SynCom biosensors, outline their construction workflow, and discuss current biosensing technology. We also highlight the challenges and future for developing and optimizing SynCom biosensors and the potential applications in agriculture and food management, biotherapeutic development, home sensing, urban and environmental monitoring, and the One Health foundation. We believe SynCom biosensors could be used in a real-time and remote-controlled manner to sense the chaos of constantly dynamic environments.


Asunto(s)
Técnicas Biosensibles , Microorganismos Modificados Genéticamente
14.
Sci Rep ; 13(1): 3451, 2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36859452

RESUMEN

The purpose of this study is to analyze the damage of antireflective (AR) coating over potassium dihydrogen phosphate (KDP) crystal subjected to multi-pulse laser irradiation at low flux under vacuum. Fresh silica AR was characterized as a reference; Atomic Force Microscope (AFM), Scanning Electron Microscopy (SEM), profilometer, and Scanning Near-Field Optical Microscope Photo-induced Force Microscope (SNOM-PiFM) were employed to analyze the characteristics of coatings. The experimental results indicated that the damage of AR coating over the KDP crystal was mainly caused by partial exfoliation, which exposed silica particles beneath the surface. It was found that the accumulated tensile stress led to coating damage with the increase of laser pulse. The initial coating damage was observed to extend and interconnect to form large-area exfoliation. Splitting mechanism of SiO-Si TO3 was observed at vibration mode peaks of 1064 cm-1 and 1096 cm-1showing progressing irradiation damage. Based on this study, it would be helpful to suppress the damage probability of AR coating over KDP crystal applied in high-power laser systems. Moreover, the applicability of SNOM-PiFM method to study the Infrared Radiation (IR) spectra of ultra-thin coatings with transparent substrates was proposed.

15.
Exp Eye Res ; 228: 109392, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36717050

RESUMEN

A20, also called TNFAIP3, is a crucial regulator of inflammation in various diseases but has not evidenced its function in the cornea. We aimed to evaluate the existence and the functions of A20 in human corneal epithelial (HCE-T) cells. After being treated with lipopolysaccharide (LPS) in different concentrations or at separate times, cells were collected to analyze A20 expressions. We then constructed the A20 knockdown system by siRNA and the A20 overexpressing system by lentivirus transduction. Systems were further exposed to medium with or without LPS for indicated times. Next, we evaluated the production of inflammatory cytokines (IL-6 and IL-8) by qRT-PCR and ELISA. Also, the translocation of P65 and the phosphorylation of P65, P38 and JNK were observed in two systems. In addition, we used the nuclear factor kappa-B (NF-κB) antagonist TPCA-1 for the pretreatment in cells and then detected the A20 expressions. We found a low basal expression of A20 in HCE-T cells, and the expressions could be dose-dependently induced by LPS, peaking at 4 h in protein level after stimulation. Both the A20 knockdown and A20 overexpressing systems were confirmed to be effective. After the LPS treatment, productions of IL-6 and IL-8 were enhanced in the A20 knockdown system and reduced in the A20 overexpressing system. A20 reduced the translocation of P65 into the nucleus and the phosphorylation of P65, P38 and JNK. Furthermore, TPCA-1 pretreatment reduced the expression of A20 in cells. We concluded that A20 is a potent regulator for corneal epithelium's reaction to inflammation, and it thus is expected to be a potential therapy target for ocular surface diseases.


Asunto(s)
Interleucina-6 , Lipopolisacáridos , Humanos , Células Epiteliales/metabolismo , Inflamación/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Lipopolisacáridos/farmacología , FN-kappa B/metabolismo
16.
Dig Dis Sci ; 68(4): 1339-1350, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36002675

RESUMEN

AIM: Pancreatic fibrosis is the main pathological characteristic of chronic pancreatitis (CP) and pancreatic cancer. Pancreatic stellate cells (PSCs) play a critical role in pancreatic fibrosis. Any targets that may have an impact on the activation of PSCs could become potential treatment candidates for CP and pancreatic cancer. Our goal was to investigate the effect of P-element-induced wimpy-testis (PIWI) protein 1 (PIWIL1) on PSC activation. METHODS: Lentivirus-based RNA interference (RNAi) and overexpression vector construction were used to knock down and over-express the PIWIL1 protein. Immunocytofluorescent staining, western blotting, wound healing assay, transwell assay, and phalloidin staining were used to investigate the effects of PIWIL1 on the secretion of extracellular matrix components (EMC), actin cytoskeleton, and on the invasion and migration abilities of primary PSCs isolated from C57BL/6 mice. Moreover, pancreatic fibrosis was induced by L-arginine in C57BL/6 mice. The expression of PIWIL1 and collagen deposition in vivo were tested by western blotting and Sirius red staining. RESULTS: Expression levels of collagen I, collagen III, and α-smooth muscle actin were significantly decreased in the LV-PIWIL1 group. Compared with the si-PIWIL1 group, significant differences were observed in the expression of desmin, p-PI3K, p-AKT, and p-mTOR in the LV-PIWIL1 group. Furthermore, PIWIL1 suppressed the PSCs' invasion and migration abilities. In a rescue experiment, the PI3K/AKT/mTOR signaling pathway was found to be the underlying mechanism in PSCs activation mediated by PIWIL1. CONCLUSIONS: Our findings suggest that PIWIL1 inhibits the activation of PSCs via the PI3K/AKT/mTOR signaling pathway. PIWIL1 is a potential therapeutic target for pancreatic fibrosis.


Asunto(s)
Enfermedades Pancreáticas , Neoplasias Pancreáticas , Pancreatitis Crónica , Masculino , Ratones , Animales , Páncreas/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Células Estrelladas Pancreáticas/patología , Testículo/metabolismo , Testículo/patología , Células Cultivadas , Ratones Endogámicos C57BL , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Neoplasias Pancreáticas/patología , Pancreatitis Crónica/inducido químicamente , Enfermedades Pancreáticas/patología , Colágeno/metabolismo , Fibrosis , Neoplasias Pancreáticas
17.
Front Cell Infect Microbiol ; 12: 1009894, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36389157

RESUMEN

Objectives: To summarize the clinical characteristics of patients infected by SARS-CoV-2 omicron variant and explore the risk factors affecting the progression in a Fangcang hospital, Shanghai, China. Methods: A total of 25,207 patients were retrospectively enrolled. We described the clinical characteristics and performed univariate and multivariate logistic regression analysis to identify the risk factors for non-severe to severe COVID-19 or death. Results: According to the outcomes, there were 39 severe patients (including 1 death) and 25,168 non-severe patients enrolled in this study. Among the 25,207 cases, the median age was 45 years (IQR 33-54), and 65% patients were male. Cough (44.5%) and expectoration (38.4%) were the most two common symptoms. Hypertension (10.4%) and diabetes (3.5%) were most two common comorbidities. Most patients (81.1%) were fully vaccinated. The unvaccinated and partially vaccinated patients were 15.1% and 3.9%, respectively. The length of viral shedding time was six days (IQR 4-9) in non-severe patients. Multivariate logistic regression analysis suggested that age (OR=1.062, 95%CI 1.034-1.090, p<0.001), fever (OR=2.603, 95%CI 1.061-6.384, p=0.037), cough (OR=0.276, 95%CI 0.119-0.637, p=0.003), fatigue (OR=4.677, 95%CI 1.976-11.068, p<0.001), taste disorders (OR=14.917, 95%CI 1.884-118.095, p=0.010), and comorbidity (OR=2.134, 95%CI 1.059-4.302, p=0.034) were predictive factors for deterioration of SARS-CoV-2 omicron variant infection. Conclusions: Non-critical patients have different clinical characteristics from critical patients. Age, fever, cough, fatigue, taste disorders, and comorbidity are predictors for the deterioration of SARS-CoV-2 omicron variant infection.


Asunto(s)
COVID-19 , Humanos , Masculino , Persona de Mediana Edad , Femenino , Estudios Retrospectivos , COVID-19/epidemiología , SARS-CoV-2 , Tos , China/epidemiología , Factores de Riesgo , Hospitales , Trastornos del Gusto , Fatiga , Progresión de la Enfermedad
18.
FASEB J ; 36(11): e22569, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36183339

RESUMEN

Ferroptosis is an iron-dependent form of nonapoptotic cell death characterized by the accumulation of lipid peroxides in cells. In recent years, extensive attention has been dedicated to exploring safe and effective natural ferroptosis regulators which can provide novel treatment strategies for ferroptosis-related diseases. This study identified galangin, a natural flavonoid, as an effective inhibitor of ferroptosis, which could increase cell viability in RSL3-inhibited HT1080 cells, decrease levels of lipid ROS and MDA, improve PTGS2 mRNA expression, and enhance the expression of glutathione peroxidase 4 (GPX4). Ferroptosis is widely present in ischemia-reperfusion (IR) injury. This study found that galangin significantly ameliorated the pathological damage of liver tissue in mice with IR, reduced levels of serum ALT, AST, and MDA, and increased the expression of GPX4. The results of RNA-seq exhibited ferroptosis was significant and the PI3K/AKT pathway deserved to explore the inhibition effects of galangin on ferroptosis. Indeed, galangin treatment significantly rescued RSL3-inhibited phosphorylation levels of PI3K, AKT, and CREB proteins, and the ferroptosis inhibitory effects of galangin were counteracted by PI3K inhibitor LY294002. These findings indicated that galangin may exert its anti-ferroptosis effects via activating the PI3K/AKT/CREB signaling pathway and it will hopefully serve as a promising effective measure to attenuate IR injury by inhibiting ferroptosis.


Asunto(s)
Fosfatidilinositol 3-Quinasas , Daño por Reperfusión , Animales , Ciclooxigenasa 2 , Flavonoides/farmacología , Hierro/metabolismo , Peróxidos Lipídicos , Ratones , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Mensajero , Especies Reactivas de Oxígeno/metabolismo
19.
Phytother Res ; 36(11): 4101-4114, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36043374

RESUMEN

The purpose of this meta-analysis is to explore whether the supplement of sea buckthorn affects the factors related to metabolic syndrome. The related RCTs from five databases were systematically searched and comprehensively random effects model was used to calculate SMD and 95% CI. The Cochrane deviation risk tool was used to evaluate the deviation risk. Fifteen studies were involved in the meta-analysis. First, sea buckthorn supplementation reduced triglycerides [-0.722 (-1.129, -0.316); p < .001], total cholesterol [-0.345 (-0.639, -0.051); p = .021], low density lipoprotein cholesterol [-0.396 (-0.755, -0.037); p = .031], and increased high density lipoprotein cholesterol [0.370 (0.056, 0.684); p = .021] in overall subjects. Second, subgroup analysis showed that sea buckthorn supplementation reduced lipids only in people with abnormal lipid metabolism. Third, sea buckthorn had no effect on blood sugar, blood pressure, and BMI of the overall subjects. Sea buckthorn may affect the lipid metabolism in circulation, but it cannot affect blood glucose, blood pressure, and BMI. These indicators are closely associated with metabolic syndrome. This study may contribute to the development and utilization of sea buckthorn, and may provide a new and safer way for the prevention and treatment of metabolic syndrome. The limitation of this study is high heterogeneity, even if subgroup analysis is used. However, more clinical studies are needed to determine the real effect of sea buckthorn on metabolic syndrome.


Asunto(s)
Hippophae , Síndrome Metabólico , Humanos , Síndrome Metabólico/tratamiento farmacológico , Triglicéridos , LDL-Colesterol , Suplementos Dietéticos , Glucemia , Frutas , Ensayos Clínicos Controlados Aleatorios como Asunto
20.
J Clin Transl Hepatol ; 10(3): 458-466, 2022 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-35836768

RESUMEN

Background and Aims: It is challenging to predict the 90-day outcomes of patients infected with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) via prevailing predictive models. This study aimed to develop an innovative model to enhance the analytical efficacy of 90-day mortality in HBV-ACLF. Methods: In this study, 149 HBV-ACLF patients were evaluated by constructing a death risk prediction nomogram. Bootstrap resampling and an independent validation cohort comprising 31 patients from June 2019 to February 2020 were assessed for model confirmation. Results: The nomogram was constructed by entering and identifying five factors (age, total bilirubin, prothrombin activity (PTA), lymphocyte (L)%, and monocyte (M)%. Healthy refinement was achieved from the nomogram analysis, where the area under the receiver operating characteristic curve was 0.864 for the training cohort and 0.874 was achieved for the validation cohort. There was admirable concordance between the predicted and true results in the equilibrium curve. The decision curve assessment revealed the useful clinical application of the nomogram. Conclusions: We constructed an innovative nomogram and validated it for the prediction of 90-day HBV-ACLF patient outcomes. This model might help develop optimized treatment protocol recommendations for HBV-ACLF patients.

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