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In order to build a very-low-level γ ray radiation field and its magnitude transfer system，the scattering contribution caused by different mechanical device structure is researched based on the experimental conditions of the Jinping underground laboratory in China. In this research，the Monte Carlo model of the irradiation device，the magnitude transfer detector，and the internal transmission structure of the shielding box were built in the MCNP5 software. After that，the scattering contribution caused by three spatial variables: the emission angle of the irradiation device，the distance between the detector and the edge of the shielding box，and the distance between the source and the detector，was simulated，and the appropriate device design and layout scheme were obtained. The emission angle of 20°，30° and 40° were used in this research. The energy deposition in sensitive area (with/without the shielding box) was recorded under three different distances between the source and the detector. Three locations of the irradiation device were designed to analyze the change of energy deposition caused by the change of locations. The energy deposition in sensitive area was simulated under more distances between the source and the detector. According to the data，the increase in energy deposition with the emission angle of 20° is less than that caused by the emission angle of 30° and 40°，and the increase in energy deposition is less when the irradiation device is far from the edge of the shielding box. In this research，energy deposition caused by scattering radiation under various irradiation conditions were obtained and analyzed，the device design and layout in the radiation field were optimized，and the idea for establishing an extremely-low-background radiation field was provided.

In order to study the effect of garlic powder on the quality of duck luncheon meat and obtain the best quality products. 0%, 2%, 4%, 6% or 8% garlic powder was added into the production of luncheon meat. The quality of duck luncheon meat were measured by electronic nose, texture instrument, color difference analyzer and LF-NMR. Meanwhile, fuzzy mathematics sensory evaluation was used to comprehensively analyze the quality of duck luncheon meat. The results showed that there was a significant difference in the odor between duck luncheon meat with and without garlic powder added. With the increase of garlic powder addition, the various texture indicators and the L* of duck luncheon meat showed a trend of first increasing and then decreasing, specially all indicators reached their peak when the amount of garlic powder added was 4%. At the same time, the a* of luncheon meat color decreased, while b* significantly increased overall (P

BackgroundGut microbiota is closely related to the occurrence and development of sepsis. However, the causal effects between the gut microbiota and sepsis, and whether circulating inflammatory proteins act as mediators, remain unclear.MethodsGut microbiota, circulating inflammatory proteins, and four sepsis-related outcomes were identified from large-scale genome wide association studies (GWAS) summary data. Inverse Variance Weighted (IVW) was the primary statistical method. Additionally, we investigated whether circulating inflammatory proteins play a mediating role in the pathway from gut microbiota to the four sepsis-related outcomes.ResultsThere were 14 positive and 15 negative causal effects between genetic liability in the gut microbiota and four sepsis-related outcomes. Additionally, eight positive and four negative causal effects were observed between circulating inflammatory proteins and the four sepsis-related outcomes. Circulating inflammatory proteins do not act as mediators.ConclusionsGut microbiota and circulating inflammatory proteins were causally associated with the four sepsis-related outcomes. However, circulating inflammatory proteins did not appear to mediate the pathway from gut microbiota to the four sepsis-related outcomes.

To evaluate the efficacy and safety of flumatinib in the later-line treatment of Chinese patients with Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia (CP-CML previously treated with tyrosine kinase inhibitors (TKIs). Patients with CML-CP were evaluated for the probabilities of responses including complete hematologic response (CHR), cytogenetic response, and molecular response (MR) and adverse events (AEs) after the later-line flumatinib therapy. Of 336 enrolled patients with median age 50 years, median duration of treatment with flumatinib was 11.04 (2-25.23) months. Patients who achieved clinical responses at baseline showed maintenance of CHR, complete cytogenetic response (CCyR)/2-log molecular response (MR2), major molecular response (MMR), and 4-log molecular response or deep molecular response (MR4/DMR) in 100%, 98.9%, 98.6%, and 92.9% patients, respectively. CHR, CCyR/MR2, MMR, and MR4/DMR responses were achieved in 86.4%, 52.7%, 49.6%, and 23.5% patients respectively, which showed the lack of respective clinical responses at baseline. The patients without response at baseline, treated with flumatinib as 2L TKI, having no resistance to prior TKI or only resistance to imatinib, with response to last TKI, and with BCR::ABL ≤10% had higher CCyR/MR2, MMR, or MR4/DMR. The AEs observed during the later-line flumatinib treatment were tolerable and consistent with those reported with the first-line therapy. Flumatinib was effective and safe in patients who are resistant or intolerant to other TKIs. In particular, 2L flumatinib treatment induced high response rates and was more beneficial to patients without previous 2G TKI resistance, thus serving as a probable treatment option for these patients.

BackgroundFollowing COVID-19, reports suggest Long COVID and autoimmune diseases (AIDs) in infected individuals. However, bidirectional causal effects between Long COVID and AIDs, which may help to prevent diseases, have not been fully investigated.MethodsSummary-level data from genome-wide association studies (GWAS) of Long COVID (N = 52615) and AIDs including inflammatory bowel disease (IBD) (N = 377277), Crohn’s disease (CD) (N = 361508), ulcerative colitis (UC) (N = 376564), etc. were employed. Bidirectional causal effects were gauged between AIDs and Long COVID by exploiting Mendelian randomization (MR) and Bayesian model averaging (BMA).ResultsThe evidence of causal effects of IBD (OR = 1.06, 95% CI = 1.00–1.11, p = 3.13E-02), CD (OR = 1.10, 95% CI = 1.01–1.19, p = 2.21E-02) and UC (OR = 1.08, 95% CI = 1.03–1.13, p = 2.35E-03) on Long COVID was found. In MR-BMA, UC was estimated as the highest-ranked causal factor (MIP = 0.488, MACE = 0.035), followed by IBD and CD.ConclusionThis MR study found that IBD, CD and UC had causal effects on Long COVID, which suggests a necessity to screen high-risk populations.

BackgroundLong COVID is a major challenge facing the public. Gut microbiota is closely related to Long COVID. However, the causal effects between gut microbiota and Long COVID remains unclear.MethodsUsing summary statistics from Genome-Wide Association Studies (GWAS), Mendelian randomization (MR) analyses were performed to investigate the relationship between gut microbiota and Long COVID. The primary statistical method employed was Inverse Variance Weighted (IVW). Sensitivity analyses were then conducted to evaluate the reliability of the findings and account for potential confounding variables. Finally, a reverse MR analysis was conducted to examine potential associations between Long COVID and genetically predicted gut microbiota compositions.ResultsThere were 2 positive and 1 negative causal effect between gut microbiota and Long COVID. Meta-analysis results show that genus Parasutterella (OR = 1.145, 95%CI = 1.035 ∼ 1.266, P = 0.008) and genus Oscillospira (OR = 1.425, 95%CI = 1.235 ∼ 1.645, P < 0.001) significantly increased the risk of Long COVID. And genus Eisenbergiella (OR = 0.861, 95%CI = 0.785 ∼ 0.943, P = 0.001) significantly decreased the risk of Long COVID. Neither the pleiotropy nor the heterogeneity was observed. Reverse causal effect does not hold.ConclusionOur research has provided genetic evidence that establishes multiple causal relationships between the gut microbiota and Long COVID, supporting the role of the gut microbiota in Long COVID. It is possible that different taxa play a role in the development of Long COVID. The causal relationships identified in this study require further investigation.

Introduction There is still a lack of therapeutic options for long COVID. Several studies have shown the benefit of hyperbaric oxygen therapy (HBOT) on long COVID. However, the efficacy and safety of HBOT for long COVID remain unclear. Therefore, we will conduct this systematic review to assess the feasibility of HBOT as a primary or complemental therapy for long COVID.Methods and analysis Databases such as Web of Science, PubMed, Embase, Cochrane Database of Systematic Reviews, ClinicalTrials.gov, International Clinical Trials Registry Platform, Wanfang Database, China National Knowledge Infrastructure, SINOMED, VIP Database and the Chinese Clinical Trial Registry will be searched systematically from the establishment to 9 December 2023. All articles will be reviewed by two independent reviewers. Cochrane risk of bias tool will be used to assess the risk of bias in the study. We will evaluate heterogeneity using a visual inspection of the funnel plot. If an available number of studies are identified, we will perform a meta-analysis.Ethics and dissemination No ethical approval is required since this study is based on published articles. The findings will be published in a peer-reviewed journal or disseminated through conference presentations.PROSPERO registration number CRD42023482523.

Zhen-Wu-Tang (ZWT), a conventional herbal mixture, has been recommended for treating lupus nephritis (LN) in clinic. However, its mechanisms of action remain unknown. Here we aimed to define the immunological mechanisms underlying the effects of ZWT on LN and to determine whether it affects renal tissue-resident memory T (TRM) cells. Murine LN was induced by a single injection of pristane, while in vitro TRM cells differentiated with IL-15/TGF-β. We found that ZWT or mycophenolate mofetil treatment significantly ameliorated kidney injury in LN mice by decreasing 24-h urine protein, Scr and anti-dsDNA Ab. ZWT also improved renal pathology and decreased IgG and C3 depositions. In addition, ZWT down-regulated renal Desmin expression. Moreover, it lowered the numbers of CD8+ TRM cells in kidney of mice with LN while decreasing their expression of TNF-α and IFN-γ. Consistent with in vivo results, ZWT-containing serum inhibited TRM cell differentiation induced by IL-15/TGF-β in vitro. Mechanistically, it suppressed phosphorylation of STAT3 and CD122 （IL2/IL-15Rβ）expression in CD8+ TRM cells. Importantly, ZWT reduced the number of total F4/80+CD11b+ and CD86+, but not CD206+, macrophages in the kidney of LN mice. Interestingly, ZWT suppressed IL-15 protein expression in macrophages in vivo and in vitro. Thus, we have provided the first evidence that ZWT decoction can be used to improve the outcome of LN by reducing CD8+ TRM cells via inhibition of IL-15/IL-15R /STAT3 signaling.

Acute myeloid leukemia (AML) with t(16;21)(p11;q22)/FUS::ERG is a rare AML subtype associated with poor prognosis. However, its clinical and molecular features remain poorly defined. We determined the clinicopathological, genomic, and transcriptomic characteristics and outcomes of patients with AML harboring FUS::ERG at our center. Thirty-six AML patients harboring FUS::ERG were identified, with an incidence rate of 0.3%. These patients were characterized by high lactate dehydrogenase levels (median: 838.5 U/L), elevated bone marrow blast counts (median: 71.5%), and a CD56-positive immunophenotype (94.3%). Notably, we found that RTK–RAS GTPase (RAS) pathway genes, including NRAS (33%) and PTPN11 (24%), were frequently mutated in this subtype. Transcriptome analysis revealed enrichment of the phosphatidylinositol-3-kinase-Akt (PI3K-Akt), mitogen-activated protein kinase (MAPK), and RAS signaling pathways and upregulation of BCL2, the target of venetoclax, in FUS::ERG AML compared to RUNX1::RUNX1T1 AML, a more common AML subtype with good prognosis. The median event-free survival in patients with FUS::ERG AML was 11.9 (95% confidence interval [CI]: 9.0–not available [NA]) months and the median overall survival was 18.2 (95% CI: 12.4–NA) months. Allogeneic hematopoietic stem cell transplantation failed to improve outcomes. Overall, the high incidence of RTK–RAS pathway mutations and high expression of BCL2 may indicate promising therapeutic targets in this high-risk AML subset.

Abstract Edible mushrooms are highly valued for both their culinary and medicinal properties. Unlike traditional condiments, the complex flavor of mushrooms is not determined by a single component, but rather by the potential synergistic actions of several different components and chemical interactions. However, only a limited number of edible mushroom flavor compounds have been examined in detail, leading to an incomplete understanding of their overall flavor profile. To address this knowledge gap, it is necessary to conduct further scientific research on edible mushroom flavors to maximize their utilization. This review aims to provide a comprehensive overview of the flavor substances found in edible mushrooms, including both volatile and nonvolatile compounds, as well as the mechanisms by which various processing methods affect flavor. Additionally, we will explore the various factors that hinder the development of edible mushroom flavors and recommend strategies to further advance the technological and theoretical understanding of these unique and valuable food ingredients. In summary, by enhancing our understanding of the complex and unique flavor profile of edible mushrooms, we can better leverage their full potential as a valuable culinary and medicinal resource.

Abstract Background Human respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection and hospitalization, especially in children. Highly mutagenic nature and antigenic diversity enable the RSV to successfully survive in human population. We conducted a molecular epidemiological study during 2017–2021 to investigate the prevalence and genetic characteristics of RSV. Methods A total of 6499 nasopharyngeal (NP) swabs were collected from hospitalized children at Department of Pediatrics, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, Guangdong, China. All NP swab specimens were preliminary screened for common respiratory viruses and then tested for RSV using specific PCR assays. Partial G genes of RSV were amplified for phylogenetic analysis and genetic characterization. Results The overall detection rate for common respiratory viruses was 16.12% (1048/6499). Among those, 405 specimens (6.20%, 405/6499) were found positive for RSV. The monthly distribution of RSV and other respiratory viruses was variable, and the highest incidence was recorded in Autumn and Winter. Based on the sequencing of hypervariable region of G gene, 93 RSV sequences were sub-grouped into RSV-A (56, 60.2%) and RSV-B (37, 39.8%). There was no coinfection of RSV-A and RSV-B in the tested samples. Phylogenetic analysis revealed that RSV-A and RSV-B strains belonged to ON1 and BA9 genotypes respectively, indicating predominance of these genotypes in Guangzhou. Several substitutions were observed which may likely change the antigenicity and pathogenicity of RSV. Multiple glycosylation sites were noticed, demonstrating high selection pressure on these genotypes. Conclusion This study illustrated useful information about epidemiology, genetic characteristics, and circulating genotypes of RSV in Guangzhou China. Regular monitoring of the circulating strains of RSV in different parts of China could assist in the development of more effective vaccines and preventive measures.

Background: Dysfunction in myocardial energy metabolism plays a vital role in the pathological process of Dilated Cardiomyopathy (DCM). However, the precise mechanisms remain unclear. This study aims to investigate the key molecular mechanisms of energy metabolism and potential therapeutic agents in the progression of dilated cardiomyopathy with heart failure.Methods: Gene expression profiles and clinical data for patients with dilated cardiomyopathy complicated by heart failure, as well as healthy controls, were sourced from the Gene Expression Omnibus (GEO) database. Gene sets associated with energy metabolism were downloaded from the Molecular Signatures Database (MSigDB) for subsequent analysis. Weighted Gene Co-expression Network Analysis (WGCNA) and differential expression analysis were employed to identify key modules and genes related to heart failure. Potential biological mechanisms were investigated through Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and the construction of a competing endogenous RNA (ceRNA) network. Molecular docking simulations were then conducted to explore the binding affinity and conformation of potential therapeutic drugs with hub genes.Results: Analysis of the left ventricular tissue expression profiles revealed that, compared to healthy controls, patients with dilated cardiomyopathy exhibited 234 differentially expressed genes and 2 genes related to myocardial energy metabolism. Additionally, Benzoylaconine may serve as a potential therapeutic agent for the treatment of dilated cardiomyopathy.Conclusion: The study findings highlight the crucial role of myocardial energy metabolism in the progression of Dilated Cardiomyopathy. Notably, Benzoylaconine emerges as a potential candidate for treating Dilated Cardiomyopathy, potentially exerting its therapeutic effects by targeted modulation of myocardial energy metabolism through NRK and NT5.

Tea polyphenols possess anti-obesity properties and reduce TMAO levels. However, the variability of tea polyphenols under different processing methods and their preventive efficacy requires further exploration. This study systematically evaluated the antioxidant, hypoglycemic, and hypolipotropic enzyme capacities of GT, YT and DT through UPLC-ESI-MS/MS analysis of catechin profiles. OPLS, correlation analysis, and molecular docking were employed to investigate the compounds and inhibitory mechanisms targeting hypoglycemic, hypolipidemic, and TMAO-producing enzymes. GT exhibited significantly lower IC50 values for biological activity and higher catechins contents compared to YT and DT (p

Several international centers have used and reported pediatric-inspired regimens for adolescent and adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph- ALL). However, there is a lack of prospective data on the Chinese population. Herein, we performed a prospective study with a pediatric-inspired regimen (IH-2014 regimen) in treating adolescent and adult Ph- ALL patients in our center. From 2014 to 2021, a total of 415 patients aged between 14 and 65 years (median age, 27) were included in this study. After a median follow-up of 40.8 months, the 5-year overall survival, disease-free survival, and event-free survival rates were 53.8%, 51.1% and 45.0%, respectively. The regimen was generally well tolerated and safe, and the overall chemotherapy-related mortality was 3.6%. Age ≥ 40 years and persistent detectable minimal residual disease (MRD) post-induction were independent prognostic factors. Traditional risk factors for adult patients combined with MRD post-induction exhibit predictive significance for survival and relapse, which is helpful in the selection of subsequent treatment. Patients with high risk factors who can achieve deep MRD response after induction do not derive benefit from allogeneic hematopoietic stem cell transplantation.

Highlights A nanofiber composite reinforced organohydrogel with multifunctionality is prepared. The composite organohydrogel possesses multiple interfacial bondings and multi-level strengthening and toughening mechanism is proposed. The composite organohydrogel exhibits long-term strain sensing stability and can be used for high performance electromagnetic interference shielding.

Among non-destructive testing (NDT) techniques, fast neutron radiography with a higher penetration capability has achieved rapid advancements. However, the application of the radiography detector in many fast neutron imaging systems is limited by unfavorable detection efficiency and imaging spatial resolution. In this paper, a fast neutron radiography detector was designed, which was composed of a pixelated EJ200 scintillator array, a 16 × 16 silicon photomultiplier (SiPM) array, and capacitive multiplexing network readout electronics. The main parameters of the detector were optimized using Monte Carlo simulations. In addition, the prototype of the detector was fabricated and tested under a 14 MeV D-T neutron source. The preliminary test results demonstrated that the spatial resolution of the prototype reached 1.2 mm. Moreover, the conflict between spatial resolution and detection efficiency could be mitigated by using a pixelated scintillator structure. Overall, SiPMs enabled the extensive application of the imaging system because of their excellent photon detection performance, relatively low price, and joint possibility for large areas.

This study undertakes a comprehensive examination of the intricate link between diet nutrition, age, and metabolic syndrome (MetS), utilizing advanced artificial intelligence methodologies. Data from the National Health and Nutrition Examination Survey (NHANES) spanning from 1999 to 2018 were meticulously analyzed using machine learning (ML) techniques, specifically extreme gradient boosting (XGBoost) and the proportional hazards model (COX). Using these analytic methods, we elucidated a significant correlation between age and MetS incidence and revealed the impact of age-specific dietary patterns on MetS. The study delineated how the consumption of certain dietary components, namely retinol, beta-cryptoxanthin, vitamin C, theobromine, caffeine, lycopene, and alcohol, variably affects MetS across different age demographics. Furthermore, it was revealed that identical nutritional intakes pose diverse pathogenic risks for MetS across varying age brackets, with substances such as cholesterol, caffeine, and theobromine exhibiting differential risks contingent on age. Importantly, this investigation succeeded in developing a predictive model of high accuracy, distinguishing individuals with MetS from healthy controls, thereby highlighting the potential for precision in dietary interventions and MetS management strategies tailored to specific age groups. These findings underscore the importance of age-specific nutritional guidance and lay the foundation for future research in this area.

In this research, the different methods (acid extraction, alkaline extraction and enzymatic extraction) were used to extract soluble dietary fiber (SDF) from pomegranate peel and compared with water extraction. Results revealed that all three extraction methods influenced the structure, physicochemical and functional properties of SDF. Especially, SDF extracted by enzymes (E-SDF) and SDF extracted by alkali (A-SDF) had higher yield (27.30% and 27.17%), molecular weight and thermal stability than SDF extracted by water (W-SDF). Higher oil holding capacity (OHC) was found in SDF extracted by acid (C-SDF) (3.18 g/g), A-SDF (3.18 g/g) and E-SDF (5.36 g/g) compared with W-SDF. In addition, A-SDF showed the smallest particle size, lowest ζ-potential and highest viscosity among the tested samples. E-SDF presented a more porous structure, better glucose adsorption capacity (GAC) and antioxidant activity than C-SDF and A-SDF. To sum up, A-SDF and E-SDF may have great potential to be functional food ingredients in the food industry.

Single-cell multi-omics and deep learning could lead to the inference of biological networks across specific cell types. Here, the authors develop DeepMAPS, a deep learning, graph-based approach for cell-type specific network inference from single-cell multi-omics data that is tested on healthy and tumour tissue datasets.

Background The Wisconsin upper respiratory symptom survey (WURSS) is a validated English questionnaire to evaluate the quality of life and severity of upper respiratory tract infections (URTIs). We aimed to develop a Mandarin Chinese version of WURSS-24 (WURSS-24-C) and evaluate its reliability, validity and minimal important difference (MID). Methods The WURSS-24-C was developed using the forward-backward translation procedure. People with URTIs’ symptoms within 48 h of onset were recruited and asked to fill in the WURSS-24-C daily for up to 14 d. Exploratory and confirmatory factor analyses were used to suggest domains. The 8-Item Short Form Health Survey (SF-8) assessing general mental and physical health was used to assess validity. Reliability estimated by Cronbach’s alpha and mean day-to-day change for those indicating minimal improvement as MID were evaluated. Results The WURSS-24-C was found to be acceptable, relevant, and easy to complete in cognitive debriefing interviews. A total number of 300 participants (age 28.4 ± 9.3, female 70%) were monitored for 2500 person-days. Four domains (activity and function, systemic symptoms, nasal symptoms and throat symptoms) of the WURSS-24-C were confirmed (comparative fit index [CFI] = 0.93). The reliability of this 4-domain-structure is good (Cronbach’s alphas varied from 0.849 to 0.943). Convergent validity is moderate (Pearson correlation coefficients between daily WURSS-24-C and the SF-8 were −0.780 and −0.721, for the SF-8 physical and mental health, respectively). Estimates of MID for individual items varied from −0.41 to −1.14. Conclusions The WURSS-24-C is a reliable and valid questionnaire for assessing illness-specific quality-of-life health status in Chinese-speaking patients with URTIs.Key messages The Wisconsin upper respiratory symptom survey (WURSS) series are patient-oriented questionnaire instruments assessing the quality of life and severity of upper respiratory tract infections (URTIs). The WURSS-24 was translated into Mandarin Chinese using the forward-backward translation procedure, and evaluated its validity, reliability and minimal important difference (MID) in 300 Chinese participants with URTIs. The WURSS-24 Chinese version (WURSS-24-C) seems to be a reliable and valid questionnaire for assessing illness-specific quality-of-life health status in Chinese patients with URTIs.

Background Resembling acute promyelocytic leukemia (APL) is a unique subtype of APL who sharing clinical, morphological, and immunophenotypic features with typical APL, but lacking evidence of PML-RARA fusion gene and usually insensitive to arsenic trioxide (ATO) and all-trans retinoic acid (ATRA). For years, RARA, RARB and RARG rearrangement were found in resembling APL continually. The confirmed partner genes of RARG rearrangement included CPSF6, NUP98, NPM1, PML, and HNRNPC. These patients were a group of resembling APL with rare molecular genetic abnormality and unfavorable prognosis. They usually were resistant to ATO and ATRA but partially sensitive to anthracycline-based chemotherapy.Case presentation We reported a 25-year-old female patient with a novel fusion gene RARG-HNRNPM (RARG chr12:53606869: –; HNRNPM chr19: 8527413: + based on GRCh37/hg19 Assembly) through RNA-seq as resembling APL. The patient with RARG-HNRNPM was benefited from a combined chemotherapy homoharringtonine, cytarabine, and aclacinomycin (HAA) regimen with no relapse.Discussion and conclusions RARG rearrangement resembling APL are various. The treatment should be switched from ATRA/ATO to AML combined chemotherapy regimen early.

BackgroundAnti-type 2 inflammation therapy has been proposed as a treatment strategy for eosinophil-associated chronic airway disorders that could reduce exacerbations and improve lung function. We performed a meta-analysis of randomized controlled trials to assess the effectiveness of type 2 monoclonal antibodies (anti-T2s) for eosinophil-associated chronic airway disorders.MethodsPubMed, Embase, Web of Science, and Cochrane Library were searched from their inception to 21 August 2022. Randomized clinical trials evaluating the effectiveness of anti-T2s versus placebo in the treatment of chronic airway diseases were selected. The outcomes were exacerbation rate and change in pre-bronchodilator forced expiratory volume in 1 s (FEV1) from baseline. The Cochrane Risk of Bias Assessment Tool 1.0 was used to evaluate the risk of bias, and the random-effects or fixed-effect model were used to pool the data.ResultsThirty-eight articles concerning forty-one randomized clinical trials with 17,115 patients were included. Compared with placebo, anti-T2s therapy yielded a significant reduction in exacerbation rate in COPD and asthma (Rate Ratio (RR)=0.89, 95%CI, 0.83-0.95, I2 = 29.4%; RR= 0.59, 95%CI, 0.52-0.68, I2 = 83.9%, respectively) and improvement in FEV1 in asthma (Standard Mean Difference (SMD)=0.09, 95%CI, 0.08-0.11, I2 = 42.6%). Anti-T2s therapy had no effect on FEV1 improvement in COPD (SMD=0.05, 95%CI, -0.01-0.10, I2 = 69.8%).ConclusionDespite inconsistent findings across trials, anti-T2s had a positive overall impact on patients’ exacerbation rate in asthma and COPD and FEV1 in asthma. Anti-T2s may be effective in treating chronic airway illnesses related to eosinophils.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022362280.

Influenza pneumonia has challenged public health and social development. One of the hallmarks of severe influenza pneumonia is overproduction of pro-inflammatory cytokines and chemokines, which result from the continuous activation of intracellular signaling pathways, such as the NF-κB pathway, mediated by the interplay between viruses and host pattern recognition receptors (PRRs). It has been reported that traditional Chinese medicines (TCMs) can not only inhibit viral replication and inflammatory responses but also affect the expression of key components of PRRs and NF-κB signaling pathways. However, whether the antiviral and anti-inflammatory roles of TCM are related with its effects on NF-κB signaling pathway activated by PRRs remains unclear. Here, we reviewed the mechanism of PRRs-mediated activation of NF-κB signaling pathway following influenza virus infection and summarized the influence of anti-influenza TCMs on inflammatory responses and the PRRs/NF-κB signaling pathway, so as to provide better understanding of the mode of action of TCMs in the treatment of influenza pneumonia.

17-4PH martensitic steel is usually used as valve stems in nuclear power plants and it suffers from thermal aging embrittlement due to long-time service in a high-temperature and high-pressure environment. Here, we characterized the evolution of microstructures at the nano-scale in 17-4PH steel by in situ small-angle neutron scattering (SANS) with a thermo-mechanically coupled loading device. The device could set different temperatures and tensile so that an in situ SANS experiment could dynamically characterize the process of nanoscale structural changes. The results showed that with increasing thermal aging time, the ε-Cu phase precipitates and grows as the temperature is 475 °C and 590 °C, and the ε-Cu phase is spherical at 475 °C but became elongated cylinders at 590 °C. Moreover, the loading stress could aid in the growth of the ε-Cu phase at 475 °C.

ObjectivesEvidence from systematic reviews/meta-analyses about the efficacy and safety of Qishen Yiqi (QSYQ) dripping pills in chronic heart failure (CHF) remains unclear. This study comprehensively reviewed available systematic reviews on latest evidence to provide reliable information for the clinical use of QSYQ in CHF.MethodsThe systematic review was performed on studies retrieved from six major medical databases. Eligible studies were evaluated in terms of methodological quality and quality of evidence using the Assessment of Multiple Systematic review 2 (AMSTAR-2) tool, the Risk of Bias in Systematic Reviews (ROBIS) was used to assess the risk of bias, and the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) 2020 was utilized for assessing reporting quality. In addition, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to determine primary outcome indicators’ evidence quality.ResultsA total of 14 systematic reviews were included in this study, based on which it could be concluded that QSYQ combined with conventional medicine (CM) treatment tended to be superior to CM treatment alone in terms of improving cardiac function-related indices (e.g., increasing the left ventricular ejection fraction [LVEF] and reducing the left ventricular end-diastolic dimension [LVEDD] and left ventricular end-systolic internal diameter [LVESD]), improving the total effective rate and 6-min walking distance (6MWD), and reducing N-terminal pro-brain natriuretic peptide (NT-proBNP). Overall, no serious QSYQ-related adverse events were observed. However, the GRADE results showed “very low” to “moderate” evidence for these outcomes, with no high-quality evidence supporting them. Unsatisfactory results were obtained in terms of methodological quality, risk of bias and reporting quality after assessment using the AMSTAR-2, ROBIS, and PRISMA 2020, limited mainly by deficiencies in the following areas: registration of study protocols, explanation of the inclusion of randomized controlled trials (RCTs), complete and detailed search strategy, list of excluded literature, description of funding sources for inclusion in RCTs, investigation of the impact of risk of bias on the results of meta-analysis, and reporting of potential conflicts of interest.ConclusionThe efficacy and safety of QSYQ adjuvant therapy in CHF remain to be further clarified due to the lack of high-quality evidence provided by current systematic reviews.

Abstract Background Human Adenoviruses (HAdVs) cause a wide array of illnesses in all age groups. They particularly cause frequent morbidity among children. In China, human adenovirus types 3, 4, 7, 11, 14, 21, and 55 have caused at least seven outbreaks since 2000. However, limited studies are available regarding the epidemiological patterns and diversity of HAdVs types among hospitalized patients with respiratory tract infections (RTIs). Methods To understand the epidemiology and subtype distribution of HAdV infections associated with RTIs in China, nasal swab (NS) clinical samples were collected from 4129 patients in a Guangzhou hospital between August 2017 and October 2019. PCR, sequencing, and phylogenetic analysis were performed on these specimens to identify HAdV subtypes. Results HAdV was successfully sequenced in 99 (2.4%) of the 4129 NS specimens, with the highest HAdV prevalence (6.3%) found in children between the ages of 5 and 10 years. Among HAdV-positive specimens, the most prevalent genotypes identified were HAdV-B3 (55.6%) and HAdV-B7 (25.3%). The most common symptoms in the HAdV-infected patients were fever (100%), cough (80.8%), and rhinorrhea (71.8%). HAdV infections were detected throughout the year with a relatively higher prevalence in summer. Conclusion All ages suffer adenovirus infections, but young children are at the greatest risk. This study data demonstrates that at least three species of HAdVs (species B, C, and E) are circulating in Guangzhou City, China. As antiviral therapies and type-specific vaccines become available, such epidemiological data will be useful in guiding therapy and public health interventions.

BackgroundThe neutrophil-to-lymphocyte ratio (NLR) is a biomarker reflecting the balance between inflammation (as indicated by the neutrophil count) and adaptive immunity (as indicated by the lymphocyte count). We aimed to estimate ability of NLR at admission and at day 1 for predicting stroke outcome after two reperfusion therapies: intravenous thrombolysis (IVT) and mechanical thrombectomy (MT).MethodsA retrospective analysis was performed on patients who received recombinant human tissue plasminogen activator (IVT) and/or underwent MT for acute ischemic stroke (AIS) at the First Affiliated Hospital of Wenzhou Medical University (Wenzhou, China) from January 2018 to December 2020. Blood samples were taken on admission to hospital and on day 1 after stroke onset. Binary logistic regression models were applied to investigate potential associations between NLR at admission or day 1 and the following outcomes: symptomatic intracerebral hemorrhage (sICH), dependence, and mortality at 90 days. The ability of NLR to predict AIS outcome was analyzed using receiver operating characteristic (ROC) curves.ResultsData for 927 patients (576 IVT and 351 MT) were reviewed. High admission NLR was associated with dependence in IVT treatment [adjusted odds ratio (OR) 1.21, 95% confidence interval (CI) 1.14–1.23] and 90-day mortality in MT patients (OR 1.09, 95% CI 1.04–1.13). In IVT patients, high NLR at day 1 predicted dependence (OR 1.09, 95% CI 1.02–1.11), sICH (OR = 1.07, 95% CI 1.01–1.12), and 90-day mortality (OR 1.06, 95% CI 1.01–1.15). In MT patients, high NLR at day 1 also predicted dependence (OR 1.08, 95% CI 1.02–1.11) and sICH (OR 1.03, 95% CI 1.01–1.09). ROC analysis confirmed that NLR at day 1 could predict dependence (cut-off 4.2; sensitivity 68.7%; specificity 79.6%), sICH (cut-off 5.1; sensitivity 57.9%, specificity 73.5%), and death (cut-off 5.4; sensitivity 78.8%; specificity 76.4%) in IVT patients. Z values of area under the curves were compared between admissioin and day 1 NLR in IVT patients and showed day 1 NLR can better predict dependence (Z = 2.8, p = 0.004) and 90-day death (Z = 2.8, p = 0.005).ConclusionsNLR is a readily available biomarker that can predict AIS outcome after reperfusion treatment and day 1 NLR is even better than admission NLR.

BackgroundIt has been proven that the ratio of albumin to globulin (A/G) is a typical biomarker for monitoring inflammation and nutritional status. But the potential role of A/G in stroke-associated pneumonia (SAP) after acute ischemic stroke (AIS) remained unknown.Patients and methodsFollowing inclusion criteria, 5,173 AIS patients were included and segmented into SAP (n = 897) and non-SAP (n = 4,276) groups. The differences in variables between groups were compared. The logistic regression model was used to determine the association between A/G and SAP, and a forest plot was drawn.ResultsCompared with the non-SAP group, the SAP group had a lower A/G level (P < 0.001). Then, A/G was divided into quartiles. In comparison to Q3 (A/G = 1.25–1.39), logistic regression revealed that patients with a lower A/G (A/G ≤ 1.09) had a higher risk of SAP (OR = 1.96, 95% CI, 1.56–2.46, P < 0.001). On the contrary, those with a higher A/G (A/G ≥ 1.4) had a lower SAP risk (OR = 0.73, 95% CI, 0.54–0.97, P = 0.029).ConclusionThe study revealed that a low A/G level was associated with an increased SAP risk. Appropriate preventative measures for SAP should be taken in AIS patients with a low A/G level.

In this study, ultrasound-assisted extraction of polyphenols from C. cicadae was optimized by response surface methodology (RSM). The optimized conditions were determined as extraction time of 39 min, liquid-to-solid ratio of 1:29 g/mL, extraction temperature of 69 °C and ethanol concentration of 55% with a yield of 21.9 mg gallic acid equivalent/g dry weight. Four resins were used for polyphenol purification. D101 resin had the highest ratio of adsorption and was further applied in polyphenol purification test. A total of 19 different phenolic compounds were identified by LC-MS, including 12 phenolic acids and 7 organic acids. In addition, C. cicadae polyphenols displayed higher antioxidant activity in vitro and anti-aging activity of C. elegans in vivo. Lastly, C. cicadae polyphenols showed the potential to protect DNA from oxidative damage. Overall, our results suggest that polyphenols from C. cicadae may be considered as novel sources of anti-oxidation, anti-aging and recommended as reagents to protect DNA from oxidative damage in food and pharmaceutical industries.

The polysaccharides from C. cicadae were extracted by ultrasonically-assisted enzymatic extraction (UAEE). Response surface analysis was used to determine the optimum parameters as follows: addition of enzymes, 0.71%; extraction temperature, 60°C; extraction time, 18 min; liquid-solid ratio, 46:1 (mL/g). The extraction yield of polysaccharide was 3.66 ± 0.87%. A novel polysaccharide fraction (JCH-a1) from C. cicadae was extracted and then purified by cellulose DEAE-32 and Sephadex G-100 anion exchange chromatography. The analysis results showed that the molar ratio of galactose, glucose, and mannose in JCH-a1 cells (60.7 kDa) was 0.89:1:0.39. JCH-a1 with a triple helix contains more α-glycosides and has strong thermal stability. Moreover, JCH-a1 showed strong antioxidant activity and acted as a strong inhibitor of α-glucosidase in vitro. In addition, JCH-a1 can prolong the lifespan of C. elegans. The present study might provide a basis for further study of JCH-a1 as an antioxidant and hypoglycemic food or drug.

Abstract Acute leukemias of ambiguous lineage, not otherwise specified (ALAL-NOS) is a rare type of acute leukemia. Management of relapse/refractory (R/R) patients is still challenging.traditional chemotherapy treatment is not effective. In this paper, we reported 6 R/R patients diagnosed as ALAL-NOS in our hospital, who were treated with venetoclax based treatment (venetoclax combining with azacitidine or chemotherapy). All 6 patients achieved CR. Five of the six patients received allo-HSCT, four patients were still alive in CR until the follow-up day. Our data provide preliminary evidence and show that venetoclax based regimens are effective and safety in patients with R/R ALAL-NOS.

Objective: This study aimed to clarify the efficacy and safety of Xinbao pill (XBP) as an adjunctive treatment for chronic heart failure (CHF).Methods: Randomized controlled trials (RCTs) on the efficacy and safety of XBP in the treatment of CHF were searched from the six databases. The risk of bias assessment tool recommended by Cochrane Handbook 5.1 were used to assess the methodological quality of the included studies. RevMan 5.3 software was used for meta-analysis. The subgroup and sensitivity analyses were also performed. The grading recommendations assessment, development, and evaluation (GRADE) technique were used to assess the evidence’s certainty.Results: Nine RCTs with a total of 882 patients were identified in this study. The meta-analysis demonstrated that XBP as adjunctive therapy was superior to conventional medicine alone for the treatment of CHF in improving the left ventricular ejection fraction (LVEF; MD = 5.34; 95% CI 4.68 to 5.99; p < 0.001), the total effective rate (RR = 1.21; 95% CI, 1.14 to 1.29; p < 0.001), the cardiac output (MD = 0.56; 95% CI 0.42 to 0.70; p < 0.001), the stroke volume (MD = 3.42; 95% CI 2.03 to 4.81; p < 0.001) and the 6-min walking distance (6-MWD; MD = 31.95; 95% CI 21.83 to 42.06; p < 0.001), meanwhile reducing the left ventricular end-diastolic diameter (LVEDD; MD = −3.22; 95% CI −4.03 to −2.42; p < 0.001) and left ventricular end-systolic dimension (LVESD; MD = −2.93; 95% CI −3.80 to −2.06; p < 0.001). Regarding safety, a total of 2.4% (11/456) adverse reactions occurred in the XBP groups while 3.9% (18/456) in the control group. The outcomes’ evidentiary quality ranged from “very low” to “moderate”.Conclusion: This study indicated that XBP as adjunctive therapy combined with conventional medicine seemed to be safe and more effective than conventional medicine alone in treating CHF. However, due to the poor methodological quality of the included RCTs, further well-designed RCTs are required to confirm the efficacy and safety of XBP.

Background: Post-traumatic stress disorder (PTSD) is the most common psychiatric sequelae among novel coronavirus disease (COVID-19) patients. The aim of this study was to determine the prevalence of PTSD symptoms, PTSD-related factors, and its relationship with quality of life at long-term follow-up in hospitalized COVID-19 survivors.Methods: A cross-sectional study was undertaken to evaluate the health consequences of hospitalized COVID-19 survivors. All participants were interviewed face-to-face through a series of questionnaires: a researcher-developed symptom questionnaire, the Post-traumatic Stress Disorder Checklist–Civilian Version, the Generalized Anxiety Disorder 7-item, and the 36-item Short Form.Results: A total of 574 participants were enrolled with an average age of 57 years. The median follow-up time post-discharge was 193.9 days (SD = 15.32). Among the participants, 77.9% of survivors presented with at least one symptom, where fatigue or muscle weakness (47.9%) was reported the most frequently, followed by chest distress (29.4%) and sleep difficulty (29.4%). The prevalence of PTSD was 11.15% [95% confidence interval (CI): 8.56, 13.73] with a cut-off score of 44. Factors such as respiratory symptoms [odds ratio (OR): 3.53; 95% CI: 1.68–7.42], anxiety (OR: 14.64; 95% CI: 7.09–30.21), and sleep difficulty (OR: 2.17; 95% CI: 1.14–4.16) were positively related to PTSD. Those COVID-19 survivors with potential PTSD had significantly lower quality of life than those without (P < 0.05).Conclusion: Our study illustrated that a significant number of COVID-19 survivors were suffering from physical or mental distress to varying degrees at 6 months post-discharge. People with PTSD were more likely to experience persistent respiratory symptoms and sleep difficulty, as well as anxiety and a decreased quality of life. Such survivors require greater attention to their mental health, particularly the PTSD symptoms at the early phase, which may play an important role in the recovery of both the physical and psychological health of COVID-19 survivors.

Abstract Diabetes mellitus (DM) refers to a group of metabolic disorders that are characterized by hyperglycemia. Oral subcutaneously administered antidiabetic drugs such as insulin, glipalamide, and metformin can temporarily balance blood sugar levels, however, long‐term administration of these therapies is associated with undesirable side effects on the kidney and liver. In addition, due to overproduction of reactive oxygen species and hyperglycemia‐induced macrovascular system damage, diabetics have an increased risk of complications. Fortunately, recent advances in nanomaterials have provided new opportunities for diabetes therapy and diagnosis. This review provides a panoramic overview of the current nanomaterials for the detection of diabetic biomarkers and diabetes treatment. Apart from diabetic sensing mechanisms and antidiabetic activities, the applications of these bioengineered nanoparticles for preventing several diabetic complications are elucidated. This review provides an overall perspective in this field, including current challenges and future trends, which may be helpful in informing the development of novel nanomaterials with new functions and properties for diabetes diagnosis and therapy.

The prevention of the COVID-19 pandemic is highly complicated by the prevalence of asymptomatic and recurrent infection. Many previous immunological studies have focused on symptomatic and convalescent patients, while the immune responses in asymptomatic patients and re-detectable positive cases remain unclear. Here we comprehensively analyzed the peripheral T-cell receptor (TCR) repertoire of 54 COVID-19 patients in different courses, including asymptomatic, symptomatic, convalescent, and re-detectable positive cases. We identified a set of V–J gene combinations characterizing the upward immune responses through asymptomatic and symptomatic courses. Furthermore, some of these V–J combinations could be awakened in the re-detectable positive cases, which may help predict the risk of recurrent infection. Therefore, TCR repertoire examination has the potential to strengthen the clinical surveillance and the immunotherapy development for COVID-19.

Nowadays, a large number of deep convolutional neural network (CNN) models are applied to image classification tasks. However, the authors find that the most widely used evaluation indicator, the Top‐N Accuracy indicator, cannot discriminate these models effectively. In this study, they propose a new indicator called Maximum‐Spanning‐Confusion‐Tree indicator to solve this problem. The Maximum‐Spanning‐Confusion‐Tree indicator is computed based on the hierarchical structure of the Maximum Spanning Confusion Tree of the deep CNN model on the dataset and reflect the ability of deep CNN models to discriminate confused categories in the dataset. The hierarchical structure of the Maximum Spanning Confusion Tree can reveal the confused category set of one selected category in the dataset efficiently and flexibly. Experiments show that they can discriminate ten different deep CNN models more accurately with the Maximum Spanning Confusion Tree indicator than the Top‐N Accuracy indicator and the Maximum Spanning Confusion Tree intuitively shows the distribution of confused category sets in the dataset so they can find out the weakness of deep CNN models effectively.

Abstract Background Coronary heart disease (CHD) is a clinical syndrome caused by coronary atherosclerosis (AS) or functional changes in coronary arteries. We have previously reported that astragaloside IV (in astragalus) and tanshinone IIA (in Salvia miltiorrhiza) improve myocardial ischemic injury. Methods This study will employ the randomized, blinded, prospective, single-center experiments approach. Briefly, a total of 160 eligible patients will be equally randomized into three treatment groups and placebo control groups. Patients will receive appropriate treatments every 24 h for seven days after enrollment and followed up for 28 days. The main evaluation indicators will be cell count, serum high-sensitivity C-reactive protein (hs-CRP) level, monocyte chemoattractant protein 1 (MCP-1), interleukin-6 (IL-6), interleukin-1β (IL-1β), interleukin-8 (IL-8), interleukin-18 (IL-18), interleukin-10 (IL-10), tumor necrosis factor (TNF)-α, oxidized low density lipoprotein (OX-LDL), angina grade, and Traditional Chinese Medicine (TCM) symptom changes scale. Secondary indicators to be evaluated will include B-type natriuretic peptide (BNP) levels, troponin (cTn), muscle enzyme isoenzyme (CK-MB), heart-type fatty acid binding protein (H-FABP), liver and renal functions, as well as blood coagulation. Close monitoring of adverse events during the trial will also be conducted. Discussion This randomized controlled trial of Chinese herbal extracts for the treatment of coronary heart disease will generate results that are expected to provide valuable clinical evidence to inform future development of therapies towards management of CHD. Trial registration China Clinical Trial Registration Center, ChiCTR1900021590 . Registered on 28 February 2019.

Introduction: Accumulating evidence had demonstrated that females had a higher risk of deep vein thrombosis (DVT) than males, but the mechanism was still unknown. Vitamin D was found to play an essential role in DVT, and gender may influence the serum vitamin D levels. This study aimed to explore whether vitamin D played a role in the gender difference in DVT.Materials and Methods: A total of 444 patients with acute stroke were recruited, which were divided into the DVT group (n = 222) and the non-DVT group (n = 222). Serum vitamin D levels were measured after admission and were split into three categories, including deficiency (

A uniform magnetic field is required to establish and preserve the spin-polarized state in noble gases with non-zero nuclear spins. Such spin-polarized noble gases, e.g. 3He and 129Xe, exhibit unique properties that are interesting in scientific and medical imaging applications. The balance of field uniformity, spatial accessibility, size and feasibility of construction is vital in the design and optimization of such magnet systems. magcoilcalc is an open-source Python library that enables users to efficiently model, simulate and optimize magnets consisting of axisymmetric circular current loops, such as solenoid coils and Helmholtz coils and their variants.

The objective of this study was to evaluate the diversity of endophytic fungi of different parts of Ligusticum chuanxiong Hort (CX) and further characterize their biological activities and identify chemical compounds produced by these endophytic fungi. A total of 21 endophytic fungi were isolated and identified from CX. Penicillium oxalicum, Simplicillium sp., and Colletotrichum sp. were identified as promising strains by the color reaction. Comparing different organic extracts of the three strains, it was observed that the ethyl acetate extract of Penicillium oxalicum and Simplicillium sp. and the n-butanol extract of Colletotrichum sp. showed significant antioxidant and antibacterial activities. The ethyl acetate extracts of Penicillium oxalicum had outstanding antioxidant and antibacterial effects, and its radical scavenging rates for ABTS and DPPH were 98.43 ± 0.006% and 90.11 ± 0.032%, respectively. At the same time, their IC50 values were only 0.18 ± 0.02 mg/mL and 0.04 ± 0.003 mg/mL. The ethyl acetate extract of Penicillium oxalicum showed MIC value of only 0.5 mg/mL against Escherichia coli and Staphylococcus aureus. By liquid chromatography-mass spectrometry (LC-MS), we found that Penicillium oxalicum could produce many high-value polyphenols, such as hesperidin (36.06 μmol/g), ferulic acid (1.17 μmol/g), and alternariol (12.64 μmol/g), which can be a potential resource for the pharmaceutical industry. In conclusion, these results increase the diversity of CX endophytic fungi and the antioxidant and antibacterial activities of their secondary metabolites.

Arabinoxylan (AX) has been associated with alleviating intestinal barrier damage, and different structures of AX give rise to different effects on the intestinal barrier. This study investigated the main structural characteristics of AX, whose functional properties are attributed to alleviating intestinal barrier damage, and clarified their underlying mechanisms. An in vitro Caco-2 cell model was established to investigate the intestinal barrier effects of AX with various degrees of substitution (Ds) and molecular weight (Mw), with an added MyD88 inhibitor to verify the signaling pathways. Arabinoxylan treated with endo-1,4-β-xylanase (AXX) with higher Ds and Mw showed stronger physiological activity, which might be correlated with the uronic acid and bound ferulic acid contents in AXX. Moreover, AXX alleviated the intestinal barrier damage by upregulating the transepithelial electrical resistance (TER) and alleviating the decrease of claudin-1 (p < 0.05). AXX regulated the expression of inflammatory factors IL-2, TNF-α, IL-6 and IL-10 (p < 0.05). In addition, AXX reduced the intestinal barrier damage induced via inhibiting the TLRs/MyD88/NF-κB pathway and activating the TLRs/PKC pathway. Thus, AX with higher Ds and Mw might be better in alleviating intestinal barrier damage, and MyD88 might be the key point of AXX to identify these signaling pathways.

Background: Real-world evidence on the effectiveness of inactivated vaccines against the Delta and Omicron (BA.2.38) variants remains scarce. Methods: A retrospective cohort study was conducted to estimate the adjusted vaccine effectiveness (aVE) of one, two, and three doses of inactivated vaccines in attenuating pneumonia, severe COVID-19, and the duration of viral shedding in Delta and Omicron cases using modified Poisson and linear regression as appropriate. Results: A total of 561 COVID-19 cases were included (59.2% Delta and 40.8% Omicron). In total, 56.4% (184) of Delta and 12.0% (27) of Omicron cases had COVID-19 pneumonia. In the two-dose vaccinated population, 1.4% of Delta and 89.1% of Omicron cases were vaccinated for more than 6 months. In Delta cases, the two-dose aVE was 52% (95% confidence interval, 39–63%) against pneumonia and 61% (15%, 82%) against severe disease. Two-dose vaccination reduced the duration of viral shedding in Delta cases, but not in booster-vaccinated Omicron cases. In Omicron cases, three-dose aVE was 68% (18%, 88%) effective against pneumonia, while two-dose vaccination was insufficient for Omicron. E-values were calculated, and the E-values confirmed the robustness of our findings. Conclusions: In Delta cases, two-dose vaccination within 6 months reduced pneumonia, disease severity, and the duration of viral shedding. Booster vaccination provided a high level of protection against pneumonia with Omicron and should be prioritized.

Background Functional fermented beverages are popular worldwide due to their potential to promote health. Starter culture is the main determinant of the final quality and flavor of fermented beverages. The co-cultivation of lactic acid bacteria (LAB) and yeast makes a significant contribution to the safe flavor of fermented beverages. However, the research on the potential of antioxidant, antimicrobial, and anti-biofilm formation of strawberry fermented beverage obtained by combining the LAB and yeast as starter cultures has not been well explored. Methods In this study, LAB and yeast were combined as starter culture to obtain strawberry fermented beverage. Fourier transform infrared (FTIR ) spectroscopy was used for the qualitative analysis of the fresh strawberry juice and fermented beverage. From the changes in antioxidant content, free radical scavenging ability, total superoxide dismutase (T-SOD) activity and total antioxidant capacity (T-AOC) to evaluate the antioxidant capacity of fermented beverage in vitro. The antibacterial ability was tested by the Oxford cup method. The biofilms of Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 6538 under fermented beverages treatment was observed by Fluorescence microscope. In addition, sensory analysis was conducted in this study. Results In this study, the absorption peaks of Fourier transform infrared between 1,542 cm−1 and 976 cm−1, suggest the existence of organic acids, sugars and ethanol. The total phenols and total flavonoids content decreased by 91.1% and 97.5%, respectively. T-SOD activity increased by 33.33%.The scavenging ability of fermented beverage on superoxide anion free radicals was enhanced, and the scavenging ability on DPPH free radicals, hydroxyl free radicals, and ABTS free radicals was weakened. However, the T-AOC increased from 4.15 ± 0.81 to 8.43 ± 0.27 U/mL. Fermented beverage shows antibacterial activity against four pathogens. The minimum inhibitory concentration (MIC) values of Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 6538 were 0.05 mL/mL and 0.025 mL/mL, respectively, and the minimum bactericidal concentration (MBC) were both 0.2 mL/mL. It was observed by fluorescence microscope that the green fluorescence area of the two biofilms is greatly reduced after being treated with fermented beverage. Sensory analysis results show that the average scores of fermented beverage in color, appearance and taste were increased. The overall impression and flavor were decreased. Conclusion These results demonstrated that strawberry fermented beverage has potential benefits such as an antioxidant, antibacterial, and anti-biofilm formation, providing the potential for the fermented beverage to become promising candidates for natural antioxidants, antibacterial agents and anti-biofilm agents.

To systematically explore potential biomarkers which can predict disease severity in COVID-19 patients and prevent the occurrence or development of severe COVID-19, the levels of 440 factors were analyzed in patients categorized according to COVID-19 disease severity; including asymptomatic, mild, moderate, severe, convalescent and healthy control groups. Factor candidates were validated by ELISA and functional relevance was uncovered by bioinformatics analysis. To identify potential biomarkers of occurrence or development of COVID-19, patient sera from three different severity groups (moderate, severe, and critical) at three time points (admission, remission, and discharge) and the expression levels of candidate biomarkers were measured. Eleven differential factors associated with disease severity were pinpointed from 440 factors across 111 patients of differing disease severity. The dynamic changes of GDF15 reflect the progression of the disease, while the other differential factors include TRAIL R1, IGFBP-1, IGFBP-4, VCAM-1, sFRP-3, FABP2, Transferrin, GDF15, IL-1F7, IL-5Rα, and CD200. Elevation of white blood cell count, neutrophil count, neutrophil-lymphocyte ratio (NLR), Alanine aminotransferase and Aspartate aminotransferase, low lymphocyte and eosinophil counts in the severe group were associated with the severity of COVID-19. GDF15 levels were observed to be associated with the severity of COVID-19 and the dynamic change of GDF15 levels was closely associated with the COVID-19 disease progression. Therefore, GDF15 might serve as an indicator of disease severity in COVID-19 patients.

The existence of asymptomatic and re-detectable positive coronavirus disease 2019 (COVID-19) patients presents the disease control challenges of COVID-19. Most studies on immune responses in COVID-19 have focused on moderately or severely symptomatic patients; however, little is known about the immune response in asymptomatic and re-detectable positive (RP) patients. Here we performed a comprehensive analysis of the transcriptomic profiles of peripheral blood mononuclear cells (PBMCs) from 48 COVID-19 patients which included 8 asymptomatic, 13 symptomatic, 15 recovered and 12 RP patients. The weighted gene co-expression network analysis (WGCNA) identified six co-expression modules, of which the turquoise module was positively correlated with the asymptomatic, symptomatic, and recovered COVID-19 patients. The red module positively correlated with symptomatic patients only and the blue and brown modules positively correlated with the RP patients. The analysis by single sample gene set enrichment analysis (ssGSEA) revealed a lower level of IFN response and complement activation in the asymptomatic patients compared with the symptomatic, indicating a weaker immune response of the PBMCs in the asymptomatic patients. In addition, gene set enrichment analysis (GSEA) analysis showed the enrichment of TNFα/NF-κB and influenza infection in the RP patients compared with the recovered patients, indicating a hyper-inflammatory immune response in the PBMC of RP patients. Thus our findings could extend our understanding of host immune response during the progression of COVID-19 disease and assist clinical management and the immunotherapy development for COVID-19.

Although pediatric-like treatment regimen has remarkably improved the survival rates of adults with acute lymphoblastic leukemia (ALL), the outcome of some adult patients is still poor owing to adverse genetic features. These molecular abnormalities, especially gene deletions, may be considered for the prognosis assessment for adult patients with ALL. In this study, using multiplex ligation-dependent probe amplification (MLPA) method, gene deletions were analyzed in from 211 adult B-ALL patients treated in our center. The data showed that 68.2% (144/211) adult B-ALL patients carried gene deletions, and the frequency is much higher in Ph+B-ALL patients. IKZF1 gene deletion is the most common gene deletion in adult B-ALL, followed by CDKN2A/B deletion. In Ph-B-ALL patients, the overall survival of patients with gene deletions is inferior to that of patients without any gene deletions. More obviously, patients with IKZF1 or CDKN2A/B deletion had a worse prognosis, whereas, allogeneic hematopoietic stem cell transplantation could improve OS in patients with IKZF1 deletion, but not in patients with CDKN2A/B deletion. Moreover, the outcome of Ph-B-ALL patients with double deletion of IKZF1and CDKN2A/B may be much worse than that of patients with IKZF1 or CDKN2A/B alone. Minimal residual disease (MRD) was also analyzed together with gene deletions and demonstrated that gene deletions have a negative impact on survival only in MRD positive Ph-B-ALL patients. In conclusion, gene deletions are closely related with the prognosis of adult Ph-B-ALL patients.

Abstract The aim of this study was to demonstrate the effect of arabinoxylan on colonic mucosal barrier and metabolomic profiles in high‐fat diet‐induced rats. A total of 20 six‐week‐old male rats were arranged randomly to two groups (n = 10/group), including a high‐fat diet (HFD) group and a high‐fat supplemented with arabinoxylan diet (AXD) group. Results showed that feeding AXD reduced serum lipopolysaccharide in rats after 5 weeks. In colonic digesta, Escherichia coli population was reduced, while Lactobacillus, Bifidobacterium, and Bacteroidetes populations were increased in AXD group. Metabolomics assay found that the different abundances of 84 metabolites were observed, involving lipid, carbohydrate, and nitrogenous metabolism in colonic digesta. In colonic mucosa, AXD up‐regulated gene level of tight‐junction‐related proteins. Meanwhile, lower TNF‐α and IL‐1β levels were related to TLR4/NF‐κB/MyD88 pathway in AXD group. In conclusion, arabinoxylan could change colonic microbial metabolism and improve the colonic mucosal barrier via modulating intestinal microflora and tight junction proteins.

The effect of diet on skin aging has become an interesting research topic. Previous studies have mostly focused on the beneficial effects of collagen peptides derived from marine organisms on the aging skin when administered orally, while the beneficial effects of collagen peptides derived from poultry on aging skin have been rarely reported. In this study, collagen peptides were prepared from chicken bone by enzymatic hydrolysis, and the effect and mechanism of action of orally administered collagen peptides on alleviating skin aging induced by UV combined with D-galactose were investigated. The results showed that the chicken bone collagen had typical characteristics of collagen, and the chicken bone collagen peptides (CPs) were mainly small molecular peptides with a molecular weight of