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AIM: To compare the short-term effectiveness of intelligent navigated laser photocoagulation and 577-nm subthreshold micropulse laser (SML) treatment in patients with chronic central serous chorioretinopathy (cCSC). METHODS: This observational retrospective cohort study included 60 consecutive patients who underwent intelligent navigated laser photocoagulation (n=30) or 577-nm SML treatment (n=30) for cCSC between Jan. 2021 and Oct. 2022. During 3mo follow-up, all patients underwent assessments of best correct visual acuity (BCVA) and optical coherence tomography (OCT). RESULTS: The operation of laser treatment was successful in all cases. At 1mo, BCVA improved significantly more in the intelligent navigated laser photocoagulation group compared to the SML group (P0.05). Central macular thickness (CMT) in the intelligent navigated laser photocoagulation group was lower than in the SML group at 1mo (P0.05). CONCLUSION: Intelligent navigated laser photocoagulation is superior to SML for treating cCSC, leading to better improvements in vision and CMT for short term.

BackgroundFundus vessel segmentation is vital for diagnosing ophthalmic diseases like central serous chorioretinopathy (CSC), diabetic retinopathy, and glaucoma. Accurate segmentation provides crucial vessel morphology details, aiding the early detection and intervention of ophthalmic diseases. However, current algorithms struggle with fine vessel segmentation and maintaining sensitivity in complex regions. Challenges also stem from imaging variability and poor generalization across multimodal datasets, highlighting the need for more advanced algorithms in clinical practice.MethodsThis paper aims to explore a new vessel segmentation method to alleviate the above problems. We propose a fundus vessel segmentation model based on a combination of double skip connections, deep supervision, and TransUNet, namely DS2TUNet. Initially, the original fundus images are improved through grayscale conversion, normalization, histogram equalization, gamma correction, and other preprocessing techniques. Subsequently, by utilizing the U-Net architecture, the preprocessed fundus images are segmented to obtain the final vessel information. Specifically, the encoder firstly incorporates the ResNetV1 downsampling, dilated convolution downsampling, and Transformer to capture both local and global features, which upgrades its vessel feature extraction ability. Then, the decoder introduces the double skip connections to facilitate upsampling and refine segmentation outcomes. Finally, the deep supervision module introduces multiple upsampling vessel features from the decoder into the loss function, so that the model can learn vessel feature representations more effectively and alleviate gradient vanishing during the training phase.ResultsExtensive experiments on publicly available multimodal fundus datasets such as DRIVE, CHASE_DB1, and ROSE-1 demonstrate that the DS2TUNet model attains F1-scores of 0.8195, 0.8362, and 0.8425, with Accuracy of 0.9664, 0.9741, and 0.9557, Sensitivity of 0.8071, 0.8101, and 0.8586, and Specificity of 0.9823, 0.9869, and 0.9713, respectively. Additionally, the model also exhibits excellent test performance on the clinical fundus dataset CSC, with F1-score of 0.7757, Accuracy of 0.9688, Sensitivity of 0.8141, and Specificity of 0.9801 based on the weight trained on the CHASE_DB1 dataset. These results comprehensively validate that the proposed method obtains good performance in fundus vessel segmentation, thereby aiding clinicians in the further diagnosis and treatment of fundus diseases in terms of effectiveness and feasibility.

Abstract Background Chimeric antigen receptor T (CAR‐T) therapy has substantially revolutionized the clinical outcomes of patients with hematologic malignancies, but the cancer‐intrinsic mechanisms underlying resistance to CAR‐T cells remain yet to be fully understood. This study aims to explore the molecular determinants of cancer cell sensitivity to CAR‐T cell‐mediated killing and to provide a better understanding of the underlying mechanisms and potential modulation to improve clinical efficacy. Methods The human whole‐genome CRISPR/Cas9‐based knockout screening was conducted to identify key genes that enable cancer cells to evade CD19 CAR‐T‐cell‐mediated killing. The in vitro cytotoxicity assays and evaluation of tumor tissue and bone marrow specimens were further conducted to confirm the role of the key genes in cancer cell susceptibility to CAR‐T cells. In addition, the specific mechanisms influencing CAR‐T cell‐mediated cancer clearance were elucidated in mouse and cellular models. Results The CRISPR/Cas9‐based knockout screening showed that the enrichment of autophagy‐related genes (ATG3, BECN1, and RB1CC1) provided protection of cancer cells from CD19 CAR‐T cell‐mediated cytotoxicity. These findings were further validated by in vitro cytotoxicity assays in cells with genetic and pharmacological inhibition of autophagy. Notably, higher expression of the three autophagy‐related proteins in tumor samples was correlated with poorer responsiveness and worse survival in patients with relapsed/refractory B‐cell lymphoma after CD19 CAR‐T therapy. Bulk RNA sequencing analysis of bone marrow samples from B‐cell leukemia patients also suggested the clinical relevance of autophagy to the therapeutic response and relapse after CD19 CAR‐T cell therapy. Pharmacological inhibition of autophagy and knockout of RB1CC1 could dramatically sensitize tumor cells to CD19 CAR‐T cell‐mediated killing in mouse models of both B‐cell leukemia and lymphoma. Moreover, our study revealed that cancer‐intrinsic autophagy mediates evasion of CAR‐T cells via the TNF‐α‐TNFR1 axis‐mediated apoptosis and STAT1/IRF1‐induced chemokine signaling activation. Conclusions These findings confirm that autophagy signaling in B‐cell malignancies is essential for the effective cytotoxic function of CAR‐T cells and thereby pave the way for the development of autophagy‐targeting strategies to improve the clinical efficacy of CAR‐T cell immunotherapy.

Our research team previously reported the immunomodulatory effects of kombucha fermentation liquid. This study investigated the protective effects of turmeric kombucha (TK) against lipopolysaccharide (LPS)-induced sepsis and its impact on the intestinal microbiota of mice. A turmeric culture medium without kombucha served as the control (TW). Non-targeted metabolomics analysis was employed to analyze the compositional differences between TK and TW. Qualitative analysis identified 590 unique metabolites that distinguished TK from TW. TK improved survival from 40 to 90%, enhanced thermoregulation, and reduced pro-inflammatory factor expression and inflammatory cell infiltration in the lung tissue, suppressing the NF-κB signaling pathway. TK also altered the microbiome, promoting Allobaculum growth. Our findings shed light on the protective effects and underlying mechanisms of TK in mitigating LPS-induced sepsis, highlighting TK as a promising anti-inflammatory agent and revealing new functions of kombucha prepared through traditional fermentation methods.

ABSTRACT Despite its high mortality, specific and effective drugs for sepsis are lacking. Decoy receptor 3 (DcR3) is a potential biomarker for the progression of inflammatory diseases. The recombinant human DcR3-Fc chimera protein (DcR3.Fc) suppresses inflammatory responses in mice with sepsis, which is critical for improving survival. The Fc region can exert detrimental effects on the patient, and endogenous peptides are highly conducive to clinical application. However, the mechanisms underlying the effects of DcR3 on sepsis are unknown. Herein, we aimed to demonstrate that DcR3 may be beneficial in treating sepsis and investigated its mechanism of action. Recombinant DcR3 was obtained in vitro. Postoperative DcR3 treatment was performed in mouse models of lipopolysaccharide- and cecal ligation and puncture (CLP)-induced sepsis, and their underlying molecular mechanisms were explored. DcR3 inhibited sustained excessive inflammation in vitro, increased the survival rate, reduced the proinflammatory cytokine levels, changed the circulating immune cell composition, regulated the gut microbiota, and induced short-chain fatty acid synthesis in vivo. Thus, DcR3 protects against CLP-induced sepsis by inhibiting the inflammatory response and apoptosis. Our study provides valuable insights into the molecular mechanisms associated with the protective effects of DcR3 against sepsis, paving the way for future clinical studies.IMPORTANCESepsis affects millions of hospitalized patients worldwide each year, but there are no sepsis-specific drugs, which makes sepsis therapies urgently needed. Suppression of excessive inflammatory responses is important for improving the survival of patients with sepsis. Our results demonstrate that DcR3 ameliorates sepsis in mice by attenuating systematic inflammation and modulating gut microbiota, and unveil the molecular mechanism underlying its anti-inflammatory effect.

Background: Gukang Capsule has been used as a complementary and alternative medicine (CAM) for the treatment of primary osteoporosis (POP) in China. The primary aim of this study was to assess the clinical effectiveness and safety of Gukang Capsule in POP patients.Methods: A systematic search was conducted across multiple academic databases including PubMed, Web of science, Cochrane Library, China National Knowledge Infrastructure, Chongqing VIP Information, and Wanfang database to identify randomized controlled trials investigating the Gukang Capsule in the treatment of POP. The screening process, data extraction, and assessment of methodological quality were conducted independently by two reviewers. Statistical analysis was performed using the Rev Man 5.3 software. Subgroup analysis was carried out through the combination of OPF. Subgroup analysis was performed according to whether OPF were combined. Stata 12.0 was used for sensitivity and bias analysis.Results: Nineteen studies were assessed that included 1804 participants. It was found that compared with the control group, the total effective rate (RR = 1.26, 95% CI, 1.20, 1.33), the Medical Outcomes Study Short-form 36 [RR = 1.26, 95% CI(1.20, 1.33)], the bone mineral density (BMD) of lumbar vertebra (SMD = 0.77, 95% CI, 0.48, 1.07), the BMD of femoral neck [SMD = 0.84, 95% CI(0.53, 1.14)], and the BMD of Ward’s triangle (SMD = 0.64, 95% CI, 0.44, 0.85) of the Gukang Capsule experimental group were higher. Compared with the control group, the fracture healing time (SMD = −2.14, 95% CI, −2.45, −1.84), the bone specific alkaline phosphatase (BALP) levels in serum (SMD = −2.00, 95% CI, −2.83, −1.17), the tartrate resistant acid phosphatase 5b (TRACP-5b) levels in serum (SMD = −2.58, 95% CI, −3.87, −1.29) of the Gukang Capsule experimental group were lower. The bone glaprotein (BGP) levels in serum (SMD = −0.22, 95% CI, −1.86, 1.43) and the adverse events (RR = 0.80, 95% CI, 0.40, 1.63) of the experimental group and the control group have no difference.Conclusion: Gukang Capsule, as a CAM for the management of POP, exhibits the potential to enhance BMD and quality of life, expedite the healing time of OPF, diminish levels of BALP and TRACP-5b, and improve the total effective rate without increasing the adverse events.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023477774, PROSPERO CRD42023477774.

Abstract Background The mortality rate of sepsis-associated liver injury (SALI) is relatively high, but there is currently no authoritative prognostic criterion for the outcome of SALI. Meanwhile, lactate-to-albumin ratio (LAR) has been confirmed to be associated with mortality rates in conditions such as sepsis, heart failure, and respiratory failure. However, there is a scarcity of research reporting on the association between LAR and SALI. This study aimed to elucidate the association between LAR and the 28-day mortality rate of SALI. Methods In this retrospective cohort study, data were obtained from the Medical Information Mart for Intensive Care IV (v2.2). Adult patients with SALI were admitted to the intensive care unit in this study. The LAR level at admission was included, and the primary aim was to assess the relationship between the LAR and 28-day all-cause mortality. Results A total of 341 patients with SALI (SALI) were screened. They were divided into a survival group (241) and a non-survival group (100), and the 28-day mortality rate was 29.3%. Multivariable Cox regression analysis revealed that for every 1-unit increase in LAR, the 28-day mortality risk for SALI patients increased by 21%, with an HR of 1.21 (95% CI 1.11 ~ 1.31, p

Background: The COVID-19 pandemic has required teachers and students to suddenly transition from face-to-face formats to distance education (DE). The uniqueness of nursing discipline is that it requires both theoretical and skills-based learning. Therefore, it is necessary to explore the influencing factors and effectiveness of DE in nursing education. This exploration can guide teaching practice and provide a basis for the future application of DE in nursing education. Aims: To describe the current distance education readiness and depth of learning among undergraduate nursing students and explore possible influencing factors. To determine the relationship between students’ distance education readiness and the depth of learning. Design: This is a descriptive and cross-sectional online study. Settings: School of Nursing in a traditional Chinese medicine university, Beijing, China. Participants: A total of 222 undergraduate nursing students from a traditional Chinese medicine university were recruited. Methods: A questionnaire, which is composed of information form, the Online Learning Readiness Scale, and the Scale of Students Making Deep Learning, was used for data collection. Frequency, percentage, arithmetic mean, standard deviation, t-test, one-way ANOVA, and Pearson correlations were used in the analysis of the data. Result: Undergraduate nursing students have lower averages in distance education readiness and higher averages in the depth of learning. Significant differences in distance education readiness and depth of learning between different grade groups. A positive correlation was found between distance education readiness and depth of learning (r = 0.894, p

Not available.

Abstract Background Infection is the most common adverse event of acute lymphoblastic leukemia (ALL) treatment and is also one of the main causes of death. Methods To investigate the clinical characteristics and risk factors of severe infections during the maintenance phase of ALL treatment, we conducted a retrospective study. Results A total of 181 children were eligible and 46 patients (25.4%) suffered from 51 events of severe infection, most of which occurred in the first half year of the maintenance phase (52.9%). The most common infection was pulmonary infection (86.3%) followed by bloodstream infection (19.6%). The main symptoms of ALL patients with pulmonary infection were fever, cough, and shortness of breath. The main manifestations of computer tomography (CT) were ground glass shadow (56.8%), consolidation shadow (27.3%), and streak shadow (25%). Multivariate binary logistic regression analysis showed that agranulocytosis, agranulocytosis ≥7 days, anemia, and low globulin level were independent risk factors for severe infection during the maintenance phase (all p

The hydrophilic and porous structure of cement-based concrete materials makes it vulnerable to various harmful ions dissolved in water in the environment or during the freeze–thaw cycle, resulting in a significant decline in durability. Therefore, the introduction of hydrophobic hydroxyl silicone oil with good chemical stability and excellent hydrophobic properties during the process of concrete preparation to achieve the hydrophobic modification of its internal holes has very positive significance in terms of improving its durability. In order to disperse the hydrophobic hydroxyl silicone oil evenly in the internal pores of the concrete, synthetic non-ionic polyether-modified silicone oil was used as an emulsifier to make it a water-soluble emulsion. The influences of the composition of the emulsifier on the dispersion, water contact angle, water absorption, porosity, and compressive strength of cement mortar were investigated. The results show that when the emulsion content is 0.5%, the pore volume of the cement mortar decreases by 15%, and the maximum contact angle reaches 128°, which is conducive to improving the anti-erosion and anti-freezing properties of concrete and provides a new solution for the preparation of high-durability concrete. However, the introduction of polyether-modified silicone oil increases the number of large holes in the cement mortar, and leads to an increase in water absorption and a decrease in compressive strength. It is necessary to further optimize the composition of emulsifier in future work.

Abstract Background A prospective study of multiple small samples found that idiopathic pulmonary fibrosis (IPF) is often accompanied by a deficiency in Vitamin D levels. However, the causal relationship between the two remains to be determined. Therefore, our study aims to investigate the causal effect of serum 1,25-hydroxyvitamin D (25(OH)D) on the risk of IPF through a two-sample Mendelian randomization (MR) analysis. Methods Through data analysis from two European ancestry-based genome-wide association studies (GWAS), including 401,460 individuals for 25(OH)D levels and 1028 individuals for IPF, we primarily employed inverse-variance weighted (IVW) to assess the causal effect of 25(OH)D levels on IPF risk. MR-Egger regression test was used to determine pleiotropy, and Cochran’s Q test was conducted for heterogeneity testing. Leave-one-out analysis was conducted to examine the robustness of the results. Results 158 SNPs related to serum 25(OH)D were used as instrumental variables (IVs). The MR analyses revealed no evidence supporting a causal association between the level of circulating 25(OH)D and the risk of IPF. The IVW method [OR 0.891, 95%CI (0.523–1.518), P = 0.670]; There was no significant level of heterogeneity, pleiotropy and bias in IVs. Cochran’s Q test for heterogeneity (MR Egger P = 0.081; IVW P = 0.089); MR-Egger regression for pleiotropy (P = 0.774). Conclusions This MR Study suggests that genetically predicted circulating vitamin D concentrations in the general population are not causally related to IPF.

Summary: Background: Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne pathogen that causes severe hemorrhagic fever in humans, but no FDA-approved specific antivirals or vaccines are available to treat or prevent SFTS. Methods: The plasmids construction and transfection were performed to generate the recombinant SFTSV harboring the nanoluciferase gene (SFTSV-Nluc). Immunostaining plaque assay was performed to measure viral titers, and DNA electrophoresis and Sanger sequencing were performed to evaluate the genetic stability. Luciferase assay and quantitative RT-PCR were performed to evaluate the efficacy of antivirals in vitro. Bioluminescence imaging, titration of virus from excised organs, hematology, and histopathology and immunohistochemistry were performed to evaluate the efficacy of antivirals in vivo. Findings: SFTSV-Nluc exhibited high genetic stability and replication kinetics similar to those of wild-type virus (SFTSVwt), then a rapid high-throughput screening system for identifying inhibitors to treat SFTS was developed, and a nucleoside analog, 4-FlU, was identified to effectively inhibit SFTSV in vitro. SFTSV-Nluc mimicked the replication characteristics and localization of SFTSVwt in counterpart model mice. Bioluminescence imaging of SFTSV-Nluc allowed real-time visualization and quantification of SFTSV replication in the mice. 4-FlU was demonstrated to inhibit the replication of SFTSV with more efficiency than T-705 and without obvious adverse effect in vivo. Interpretation: The high-throughput screening system based on SFTSV-Nluc for use in vitro and in vivo revealed that a safe and effective antiviral nucleoside analog, 4-FlU, may be a basis for the strategic treatment of SFTSV and other bunyavirus infections, paving the way for the discovery of antivirals. Funding: This work was supported by grants from the National Key Research and Development Plan of China (2021YFC2300700 to L. Zhang, 2022YFC2303300 to L. Zhang), Strategic Priority Research Program of Chinese Academy of Sciences (XDB0490000 to L. Zhang), National Natural Science Foundation of China (31970165 to L. Zhang, U22A20379 to G. Xiao), the Science and Technology Commission of Shanghai Municipality (21S11903100 to Y. Xie), Hubei Natural Science Foundation for Distinguished Young Scholars (2022CFA099 to L. Zhang).

ABSTRACTBackground Acute megakaryoblastic leukemia (AMKL) without Down syndrome (non-DS-AMKL) usually a worse outcome than DS-AMKL. Acquired trisomy 21(+21) was one of the most common cytogenetic abnormalities in non-DS-AMKL. Knowledge of the difference in the clinical characteristics and prognosis between non-DS-AMKL with +21 and those without +21 is limited.Objective Verify the clinical characteristics and prognosis of non-DS-AMKL with +21.Method We retrospectively analyzed 33 non-DS-AMKL pediatric patients and 118 other types of AML, along with their clinical manifestations, laboratory data, and treatment response.Results Compared with AMKL without +21, AMKL with +21 has a lower platelet count (44.04 ± 5.01G/L) at onset (P > 0.05). Differences in remission rates between AMKL and other types of AML were not significant. Acquired trisomy 8 in AMKL was negatively correlated with the long-term OS rate (P

Using panel data of Chinese manufacturing enterprises listed in Shanghai and Shenzhen A-shares from 2015 to 2021, we examine the effects of heterogeneous environmental regulations on the green transformation of Chinese manufacturing enterprises under “Double Carbon” target, and reveal the mediating role played by managers' green perception in the process from an intra-firm perspective. We find that three environmental regulation tools, namely environmental administrative supervision, environmental economic regulation and environmental soft constraint, all contribute significantly to the green transformation of manufacturing enterprises. Among them, environmental economic regulation is the most effective in promoting the green transformation of manufacturing enterprises, followed by environmental soft constraint and environmental administrative supervision. The mechanism analysis shows that managers' green perception is partially mediated between heterogeneous environmental regulations and the green transformation of manufacturing enterprises. Moreover, environmental administrative supervision is the most effective in raising managers' green perception among them, followed by environmental economic regulation and environmental soft constraint. Further analysis shows that the positive effect of heterogeneous environmental regulations on the green transformation of Chinese manufacturing enterprises is more significant when the enterprises locate in regions with high policy uncertainty, in the eastern part of the country, or when the enterprises are state-owned enterprises. The conclusions provide a theoretical basis for Chinese environmental policymakers to flexibly adopt differentiated environmental regulation tools.

Abstract Background T cell receptor (TCR)-T cells possess similar effector function, but milder and more durable signal activation compared with chimeric antigen receptor-T cells. TCR-T cell therapy is another active field of cellular immunotherapy for cancer. Methods We previously developed a human anti-CD19 antibody (ET190L1) and generated novel CD19-specific γ/δ TCR-T cells, ET019003, by fusing the Fab fragment of ET190L1 with γ/δ TCR constant chain plus adding an ET190L1-scFv/CD28 co-stimulatory molecule. ET019003 cells were tested in preclinical studies followed by a phase 1 clinical trial. Results ET019003 cells produced less cytokines but retained comparable antitumor potency than ET190L1-CAR-T cells in vivo and in vitro. In the first-in-human trial, eight patients with relapsed or refractory DLBCL were treated. CRS of grade 1 was observed in three (37.5%) patients; ICANS of grade 3 was noted in one (12.5%) patient. Elevation of serum cytokines after ET019003 infusion was almost modest. With a median follow-up of 34 (range 6–38) months, seven (87.5%) patients attained clinical responses and six (75%) achieved complete responses (CR). OS, PFS and DOR at 3 years were 75.0%, 62.5%, and 71.4%, respectively. Notably, patient 1 with primary CNS lymphoma did not experience CRS or ICANS and got an ongoing CR for over 3 years after infusion, with detectable ET019003 cells in CSF. ET019003 showed striking in vivo expansion and persisted in 50% of patients at 12 months. Three patients received a second infusion, one for consolidation therapy after CR and two for salvage therapy after disease progression, but no response was observed. ET019003 expansion was striking in the first infusion, but poor in the second infusion. Conclusions CD19-specific γ/δ TCR-T cells, ET019003, had a good safety profile and could induce rapid responses and durable CR in patients with relapsed or refractory DLBCL, even primary CNS lymphoma, presenting a novel and potent therapeutic option for these patients. Trial registration: NCT04014894.

Deoxynivalenol (DON), as a widespread Fusarium mycotoxin in cereals, food products, and animal feed, is detrimental to both human and animal health. The liver is not only the primary organ responsible for DON metabolism but also the principal organ affected by DON toxicity. Taurine is well known to display various physiological and pharmacological functions due to its antioxidant and anti-inflammatory properties. However, the information regarding taurine supplementation counteracting DON-induced liver injury in piglets is still unclear. In our work, twenty-four weaned piglets were subjected to four groups for a 24-day period, including the BD group (a basal diet), the DON group (3 mg/kg DON-contaminated diet), the DON+LT group (3 mg/kg DON-contaminated diet + 0.3% taurine), and the DON+HT group (3 mg/kg DON-contaminated diet + 0.6% taurine). Our findings indicated that taurine supplementation improved growth performance and alleviated DON-induced liver injury, as evidenced by the reduced pathological and serum biochemical changes (ALT, AST, ALP, and LDH), especially in the group with the 0.3% taurine. Taurine could counteract hepatic oxidative stress in piglets exposed to DON, as it reduced ROS, 8-OHdG, and MDA concentrations and improved the activity of antioxidant enzymes. Concurrently, taurine was observed to upregulate the expression of key factors involved in mitochondrial function and the Nrf2 signaling pathway. Furthermore, taurine treatment effectively attenuated DON-induced hepatocyte apoptosis, as verified through the decreased proportion of TUNEL-positive cells and regulation of the mitochondria-mediated apoptosis pathway. Finally, the administration of taurine was able to reduce liver inflammation due to DON, by inactivating the NF-κB signaling pathway and declining the production of pro-inflammatory cytokines. In summary, our results implied that taurine effectively improved DON-induced liver injury. The underlying mechanism should be that taurine restored mitochondrial normal function and antagonized oxidative stress, thereby reducing apoptosis and inflammatory responses in the liver of weaned piglets.

To improve patient survival in sepsis, it is necessary to curtail exaggerated inflammatory responses. Fucoxanthin (FX), a carotenoid derived from brown algae, efficiently suppresses pro-inflammatory cytokine expression via IRF3 activation, thereby reducing mortality in a mouse model of sepsis. However, the effects of FX-targeted IRF3 on the bacterial flora (which is disrupted in sepsis) and the mechanisms by which it impacts sepsis development remain unclear. This study aims to elucidate how FX-targeted IRF3 modulates intestinal microbiota compositions, influencing sepsis development. FX significantly reduced the bacterial load in the abdominal cavity of mice with cecal ligation and puncture (CLP)-induced sepsis via IRF3 activation and increased short-chain fatty acids, like acetic and propionic acids, with respect to their intestines. FX also altered the structure of the intestinal flora, notably elevating beneficial Verrucomicrobiota and Akkermansia spp. while reducing harmful Morganella spp. Investigating the inflammation–flora link, we found positive correlations between the abundances of Morganella spp., Proteus spp., Escherichia spp., and Klebsiella spp. and pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) induced by CLP. These bacteria were negatively correlated with acetic and propionic acid production. FX alters microbial diversity and promotes short-chain fatty acid production in mice with CLP-induced sepsis, reshaping gut homeostasis. These findings support the value of FX for the treatment of sepsis.

Objective: The objective of this study is to explore the current situation, clinical research hot spots, and trends of traditional Chinese medicine (TCM) nursing technology in rheumatoid arthritis (RA), to draw a panorama of clinical research, to provide the basis and clues for subsequent high-level evidence integration and further in-depth research. Materials and Methods: Seven databases including China National Knowledge Infrastructure, Chinese Scientific Journal Database (VIP), Wanfang Database, Chinese Biomedical Literature Database (Sino-Med), PubMed, Embase, and the Cochrane Library were searched. The bibliometric method and visualization software CiteSpace were used to conduct a multi-dimensional analysis of the included literature. Results: A total of 805 pieces of literature were included (of them, one was written in German and four in English), and the number of published literature showed an increasing trend year by year. There were only 30 (3.73%) pieces of literature published in nursing journals. The hot spots of the co-occurrence map were concentrated in: (1) the nursing of fumigation in RA; (2) the efficacy evaluation of TCM nursing technology on pain, joint malformation, and joint dysfunction caused by RA. The included literature themes focused on five TCM technologies: fumigation, moxibustion, acupoint patching, acupoint injection, and Chinese herbal soaking. The beginning year and strength in TCM fumigation were 2012 and 5.2, and those in moxibustion were 2011 and 3.38. Conclusion: The related studies are on the rise. It has entered the field of international readers with clear research hot spots. However, there are still shortcomings such as little literature published in Chinese nursing core journals, few non-Chinese-related documents, and a lack of international exchanges and cooperation. The current research hot spots in this field are TCM fumigation, and the cutting-edge trend of future research may be fumigation and moxibustion technology. It is suggested that further research can focus on evidence integration and original research on the self-optimization of these two techniques.

Competences for conducting research is vitally important for college EFL teachers’ career development, but many college English teachers are demotivated in academic research. To investigate teachers’ motivation on academic activities, this study firstly explored motivational changes of college EFL teachers (mean age 37.39, SD 9.77) for conducting research in their teaching career, and then delved into the factors underlying their demotivation by sending questionnaires. In the end, several English teachers and officers managing research projects were interviewed to elicit solutions to overcome EFL teachers’ demotivation to conduct research. This study found that college EFL teachers had large possibilities to suffer from demotivation to conduct research. Exploratory factor analysis indicated five factors causing their demotivation, including weak research ability, negative emotions and attitudes, poor research surroundings, research management problems and insufficient resources. Thematic analysis demonstrated that ecological solutions should be taken by different stakeholders in EFL teachers’ working ecology, including universities, research communities, government, and publishers. This study problematized the static view on teachers’ demotivation to conduct research and provided some insights and implications for reasons and solutions for demotivation.

PURPOSESurvivors of childhood cancer often experience treatment-related chronic health conditions. Given its vast population, China shares a large proportion of the global childhood cancer burden. Yet, screening and treatment of late effects in survivors of childhood cancer remain underaddressed in most regions of China. This study aimed to identify high-priority late effects for harmonizing screening guidelines within the Chinese Children's Cancer Group (CCCG), as well as barriers and enablers of the implementation of surveillance recommendations in local practice.METHODSTo establish clinical consensus, 12 expert panelists who represent major institutions within the CCCG completed a Delphi survey and participated in a focus group discussion. The survey solicited ratings of the prevalence, severity, and priority for screening of 45 late effects. Major themes identified from the focus group were analyzed using thematic analysis.RESULTSThe Delphi survey identified eight high-priority late effects for harmonization within CCCG: osteonecrosis, osteoporosis, left ventricular dysfunction, secondary brain tumors, treatment-related myeloid leukemia, gonadal dysfunction, growth hormone deficiency, and neurocognitive deficits. The common barriers to implementing survivorship programs include lack of support and resources for clinicians to provide follow-up care. Patients were also concerned about privacy issues and lacked awareness of late effects. Many institutions also lacked rehabilitation expertise and referral pathways.CONCLUSIONBy identifying obstacles related to the professional setting, patient behavior, and organization of care, our study identified resources and a framework for establishing collaborative strategies to facilitate follow-up care of childhood cancer survivors in China.

IntroductionWhether steroid response is an independent risk factor for acute lymphoblastic leukemia (ALL) is controversial. This study aimed to investigate the relationship between response to dexamethasone and prognosis in children with ALL.MethodsWe analyzed the data of 5,161 children with ALL who received treatment in accordance with the Chinese Children’s Cancer Group ALL-2015 protocol between January 1, 2015, and December 31, 2018, in China. All patients received dexamethasone for 4 days as upfront window therapy. Based on the peripheral lymphoblast count on day 5, these patients were classified into the dexamethasone good response (DGR) and dexamethasone poor response (DPR) groups. A peripheral lymphoblast count ≥1× 109/L indicated poor response to dexamethasone.ResultsThe age, white blood cell counts, prevalence of the BCR/ABL1 and TCF3/PBX1 fusion genes, and rates of recurrence in the central nervous system were higher in the DPR than in the DGR group (P

Children with hematological malignancies are at increased risk of hepatitis B virus infection. This study assessed the immunogenicity and safety profile of HBV vaccination in pediatric hemato-oncological children. A nonrandomized interventional study was conducted from January 2017 to February 2020 in Shanghai, China. Seventy-three pediatric hemato-oncological children with hepatitis B surface antibody (anti-HBs) titers

The coronavirus disease 2019 (COVID-19) pandemic has illustrated the critical need for effective prophylactic vaccination to prevent the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Intranasal vaccination is an attractive approach for preventing COVID-19 as the nasal mucosa is the site of initial SARS-CoV-2 entry and viral replication prior to aspiration into the lungs. We previously demonstrated that a single intranasal administration of a candidate adenovirus type 5-vectored vaccine encoding the receptor-binding domain of the SARS-CoV-2 spike protein (AdCOVID) induced robust immunity in both the airway mucosa and periphery, and completely protected K18-hACE2 mice from lethal SARS-CoV-2 challenge. Here we show that a single intranasal administration of AdCOVID limits viral replication in the nasal cavity of K18-hACE2 mice. AdCOVID also induces sterilizing immunity in the lungs of mice as reflected by the absence of infectious virus. Finally, AdCOVID prevents SARS-CoV-2 induced pathological damage in the lungs of mice. These data show that AdCOVID not only limits viral replication in the respiratory tract, but it also prevents virus-induced inflammation and immunopathology following SARS-CoV-2 infection.

Rosiglitazone (Avandia) and pioglitazone (Actos) belong to the class of thiazolidinediones (TZDs) drugs that act by increasing insulin sensitivity and are widely used for treating diabetic patients with insulin resistance. TZDs exhibit anti-inflammatory and antioxidant properties, then may play an active role in inhibiting plaque formation and coronary atherosclerosis. But the results of evidence-based medicine suggest that TZDs may increase the risk of cardiovascular adverse events. To explore the dispute in depth, our meta-analysis aimed to evaluate the changes in vascular endothelial and plaque-related indicators following treatment with TZDs in diabetic patients with coronary atherosclerosis. According to our meta-analysis, TZDs showed an inhibiting effect on plaque progression and a protective effect on the vascular endothelium in patients with diabetes and coronary atherosclerosis. Interestingly, these effects may not depend on the regulation of inflammation and lipid metabolism. By this token, TZDs may develop a potential protective effect on myocardial infarction.Systematic review registration[https://www.crd.york.ac.uk/prospero/], identifier [CRD42021231663].

Background and methodsThe study evaluated prognostic factors associated with varicella-zoster virus (VZV) infection and mortality in children with acute lymphoblastic leukemia (ALL) using data from the multicenter Chinese Children’s Cancer Group ALL-2015 trial.ResultsIn total, 7,640 patients were recruited, and 138 cases of VZV infection were identified. The incidence of VZV infection was higher in patients aged ≥ 10 years (22.5%) and in patients with the E2A/PBX1 fusion gene (11.6%) compared to those aged

ObjectiveThe aim of this study was to retrospectively explore the relationship between serum sodium and in-hospital mortality and related factors in critically ill patients with spontaneous subarachnoid hemorrhage (SAH).MethodsData were collected from the Medical Information Mart for Intensive Care IV database. Restricted cubic splines were used to explore the relationship between serum sodium and in-hospital mortality. Receiver operating characteristic analysis was used to calculate the optimal cutoff value of sodium fluctuation, and decision curve analysis was plotted to show the net benefit of different models containing serum sodium.ResultsA total of 295 patients with spontaneous SAH were included in the retrospective analysis. The level of sodium on ICU admission and minimum sodium in the ICU had a statistically significant non-linear relationship with in-hospital mortality (non-linear P-value < 0.05, total P-value < 0.001). Serum sodium on ICU admission, minimum serum sodium during ICU, and sodium fluctuation were independently associated with in-hospital mortality with odds ratios being 1.23 (95% confidence interval (CI): 1.04–1.45, P = 0.013), 1.35 (95% CI: 1.18-1.55, P < 0.001), and 1.07 (95% CI: 1.00–1.14, P = 0.047), respectively. The optimal cutoff point was 8.5 mmol/L to identify in-hospital death of patients with spontaneous SAH with sodium fluctuation, with an AUC of 0.659 (95% CI 0.573-0.744).ConclusionAmong patients with spontaneous SAH, we found a J-shaped association between serum sodium on ICU admission and minimum sodium values during ICU with in-hospital mortality. Sodium fluctuation above 8.5 mmol/L was independently associated with in-hospital mortality. These results require being tested in prospective trials.

Summary: Mammarenavirus are a large family of enveloped negative-strand RNA viruses that include several agents responsible for severe hemorrhagic fevers. Until now, no FDA-licensed drug has been admitted for treating an arenavirus infection, and only few effective anti-arenavirus drugs have been tested in vivo. In this work, we designed a recombinant reporter arenavirus lymphocytic choriomeningitis virus that stably expressed nanoluciferase (LCMV-Nluc). The LCMV-Nluc was proved to share similar biological properties with wild-type LCMV and the Nluc intensity reliably reflected viral replication both in vitro and in vivo. Replication of the Nluc-encoding virus in living mice can be visualized by real-time bioluminescent imaging, and bioluminescence can be detected in a variety of organs of infected mice. This work provides a novel approach that enables real-time study of the arenavirus infection and is a convenient and valuable tool for screening of compounds that are active against arenaviruses in vitro and in living mice.

Sepsis is a serious disease with high mortality and has been a hot research topic in medical research in recent years. With the continuous reporting of in-depth research on the pathological mechanisms of sepsis, various compounds have been developed to prevent and treat sepsis. Natural small-molecule compounds play vital roles in the prevention and treatment of sepsis; for example, compounds such as resveratrol, emodin, salidroside, ginsenoside, and others can modulate signaling through the NF-κB, STAT3, STAT1, PI3K, and other pathways to relieve the inflammatory response, immunosuppression, and organ failure caused by sepsis. Here, we discuss the functions and mechanisms of natural small-molecule compounds in preventing and treating sepsis. This review will lay the theoretical foundation for discovering new natural small-molecule compounds that can potentially prevent and treat sepsis.

Decoy receptor 3 (DcR3), a soluble glycosylated protein in the tumor necrosis factor receptor superfamily, plays a role in tumor and inflammatory diseases. Sepsis is a life-threatening organ dysfunction caused by the dysregulation of the response to infection. Currently, no specific drug that can alleviate or even cure sepsis in a comprehensive and multi-level manner has been found. DcR3 is closely related to sepsis and considerably upregulated in the serum of those patients, and its upregulation is positively correlated with the severity of sepsis and can be a potential biomarker for diagnosis. DcR3 alone or in combination with other markers has shown promising results in the early diagnosis of sepsis. Furthermore, DcR3 is a multipotent immunomodulator that can bind FasL, LIGHT, and TL1A through decoy action, and block downstream apoptosis and inflammatory signaling. It also regulates T-cell and macrophage differentiation and modulates immune status through non-decoy action; therefore, DcR3 could be a potential drug for the treatment of sepsis. The application of DcR3 in the treatment of a mouse model of sepsis also achieved good efficacy. Here, we introduce and discuss the progress in, and suggest novel ideas for, research regarding DcR3 in the diagnosis and treatment of sepsis.

Sepsis is associated with high rates of mortality in the intensive care unit and accompanied by systemic inflammatory reactions, secondary infections, and multiple organ failure. Biological macromolecules are drugs produced using modern biotechnology to prevent or treat diseases. Indeed, antithrombin, antimicrobial peptides, interleukins, antibodies, nucleic acids, and lentinan have been used to prevent and treat sepsis. In vitro, biological macromolecules can significantly ameliorate the inflammatory response, apoptosis, and multiple organ failure caused by sepsis. Several biological macromolecules have entered clinical trials. This review summarizes the sources, efficacy, mechanism of action, and research progress of macromolecular drugs used in the prevention and treatment of sepsis.

Monthly Precipitation Forecasts (MPF) play a critical role in drought monitoring, hydrological forecasting and water resources management. In this study, we applied two advanced Machine Learning Models (MLM) and latest General Circulation Models (GCM) to generate deterministic MPFs with a resolution of 0.5° across China. Then the Bayesian Joint Probability (BJP) modeling approach is employed to calibrate and generate corresponding ensemble MPFs. Raw and post-processing MPFs were put against gridded observations over the period of 1981–2015. The results indicated that: (1) for deterministic evaluation, the forecasting performance of MLMs was more inclined to generate random forecasts around the mean value, while the GCMs could reflect the increasing or decreasing trend of precipitation to some degree; (2) for probabilistic evaluation, the four BJP calibrated ensemble MPFs were unbiased and reliable. Compared to climatology, reliability and sharpness were all significantly improved. However, in terms of overall accuracy metric, the ensemble MPFs generated from MLMs were similar to climatology. In contrast, the ensemble MPFs generated from GCMs achieved better forecasting skill and were not dependent on forecasting regions and months. Moreover, the post-processing method is necessary to achieve not only bias-free but also reliable as well as skillful ensemble MPFs. HIGHLIGHTS Two advanced Machine Learning Models are employed to generate monthly precipitation forecasts with a resolution of 0.5 degree.; The latest seasonal forecasts of ECMWF are evaluated with the same forecasting grid cells and lead time.; The BJP modeling approach is used to calibrate above four raw forecasts.; A comprehensive comparison is achieved for the raw and post-processing forecasts.;

Background: Postmenopausal osteoporosis (PMOP) is a common disease that has decreased bone strength as its main symptom after menopause. Effective treatment for PMOP remains lacking, but traditional Chinese medicine has some advantages in delaying bone loss. Jiangu granule is a traditional Chinese medicine prescription commonly used to treat PMOP. Previous studies have demonstrated its efficacy, but the mechanism of action remains uncharacterized. Purpose: This study aims to observe and discuss the mechanism of Jiangu granule to ameliorate bone loss in OVX rats by regulating the gut microbiota (GM)-short-chain fatty acids (SCFAs)- Treg/Th17 axis. Methods: Female SD rats were divided into the sham operation (S), Jiangu granule (J), and model group (M). Bilateral ovaries were surgically removed from the rats in the J and M groups. After 6 and 12 weeks, rats were sacrificed, and femur, tibia, vertebrae, serum, spleen, colon, and feces samples were collected. We detected the strength of bones, gut microbiota structure, and SCFAs in feces, the Treg and Th17 cell levels in the spleen, and cytokine levels in the serum. Result: Jiangu granule restored the abundance of gut microbiota, increased the content of SCFAs, reduced the permeability of colon epithelium, increased the proportion of Treg cells in the spleen, changed the osteoimmunomodulation-related cytokines, effectively prevented bone loss, and enhanced bone strength. Conclusion: Jiangu granule can effectively improve bone loss in OVX rats, possibly by regulating the “GM-SCFAs-Treg/Th17″ axis.

Chimeric antigen receptor T (CAR-T) cells targeting CD19 have achieved great clinical responses in patients with relapsed or refractory (R/R) acute B lymphoblastic leukemia. However, severe adverse events such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome restrict it to further application. Tocilizumab is the corner stone for the treatment of severe CRS. It has been used to treat mild CRS in recent years, whereas some statistical supports clarifying the suitable timing of its administration are lacking. Sixty-seven patients with B-cell acute lymphoblastic leukemia (B-ALL) were treated with CD19-CART and enrolled in the study, of which 33 patients received Tocilizumab. Application of Tocilizumab in patients with grade 2 CRS in American Society for Transplantation and Cellular Therapy (ASTCT) criteria can significantly shorten the duration of CRS without affecting side effects and long-term efficacy. However, a number of patients still developed severe CRS with early use of Tocilizumab, indicating the significance of the introduction of clinical laboratories to assist medications. Statistically, patients with less than fourfold increase in IL-6 levels had a higher incidence of severe CRS after receiving Tocilizumab (37.5% versus. 0%, p=0.0125), which provided a basis for refining CRS intervention strategies under the guidance of IL-6.Clinical Trial Registrationwww.clinicaltrials.gov, NCT02965092 and NCT04008251

We are concerned with the qualitative and asymptotic analysis of solutions to the nonlocal equation $$ (-\Delta)^su+V(|z|)u=Q(|z|)u^p\quad \text{in} \ \mathbb{R}^{N},$$ where $N\geq 3,\ 0\frac{N+2s}{N+2s+1}$, and $\theta_1,\ \theta_2>0,\ V_0,\ Q_0>0$. Under various hypotheses on $a_1,\, a_2,\, \alpha,\, \beta$, we establish the existence of infinitely many radial solutions. A key role in our arguments is played by the Lyapunov–Schmidt reduction method.

Background: Pediatric palliative care (PPC) does not meet current needs, particularly in low- and middle-income countries. Objective: We evaluated the first PPC team to serve patients with cancer in a tertiary children's hospital in China. Design: Single-center retrospective study. Setting/Participants: The core team members included oncologists, nurses, and a social worker. The team delivered palliative care through the outpatient clinic, consultations, a 24/7 hotline, and a hospice room located in the observation ward. Patients were referred by pediatric oncologists. We analyzed data for 92 children (54 boys and 38 girls; aged 7 months to 16 years) who required palliative care from August 2012 to August 2018. The most common primary diseases were leukemia and neuroblastoma. Measurements: We investigated the time from referral to death, symptoms during the prior month, the effects of informing children above eight years, and family satisfaction. Results: Among 88 deaths, the median time from referral to death was 17 (range 1?218) days. Most children had multiple symptoms (mean???standard deviation 4.2???3.2 per child). The most common symptoms in the last month of life were pain, loss of appetite, fatigue, fever, and dyspnea. Children above eight years who were not informed about their condition experienced more anxiety or depression. All families were satisfied with the services. Conclusions: The palliative care counseling team is feasible and could be complementary to conventional medicine in caring for children with life-limiting illnesses. This model has an important role in PPC in China or developing countries with scarce medical resources.

BackgroundCardiovascular autonomic neuropathy (CAN) is common in patients with type 2 diabetes mellitus (T2DM), mainly presented as decreased heart rate variability (HRV) which often leads to cardiac death. However, HRV measurement is not convenient in most clinics. Therefore, identifying high-risk patients for CAN in diabetes with easier measurements is crucial for the early intervention and prevention of catastrophic consequences.MethodsIn this cross-sectional study, 675 T2DM patients with normocalcemia were selected. Of these, they were divided into two groups: normal HRV group (n = 425, 100 ms≤ SDNN ≤180 ms) vs. declined HRV group (n = 250, SDNN

Summary: Background: Diabetic retinopathy (DR) is a leading cause of blindness in the working-age population, which is characterized by retinal neurodegeneration and vascular dysfunction. Long non-coding RNAs (LncRNAs) have emerged as critical regulators in several biological processes and disease progression. Here we investigated the role of lncRNA AQP4-AS1 in retinal neurovascular dysfunction induced by diabetes. Methods: Quantitative RT-PCR was used to detect the AQP4-AS1 expression pattern upon diabetes mellitus-related stresses. Visual electrophysiology examination, TUNEL staining, Evans blue staining, retinal trypsin digestion and immunofluorescent staining were conducted to detect the role of AQP4-AS1 in retinal neurovascular dysfunction in vivo. MTT assays, TUNEL staining, PI/Calcein-AM staining, EdU incorporation assay transwell assay and tube formation were conducted to detect the role of AQP4-AS1 in retinal cells function in vitro. qRT-PCR, western blot and in vivo studies were conducted to reveal the mechanism of AQP4-AS1-mediated retinal neurovascular dysfunction. Findings: AQP4-AS1 was significantly increased in the clinical samples of diabetic retinopathy patients, high glucose-treated Müller cells, and diabetic retinas of a murine model. AQP4-AS1 silencing in vivo alleviated retinal neurodegeneration and vascular dysfunction as shown by improved retinal capillary degeneration, decreased reactive gliosis, and reduced RGC loss. AQP4-AS1 directly regulated Müller cell function and indirectly affected endothelial cell and RGC function in vitro. Mechanistically, AQP4-AS1 regulated retinal neurovascular dysfunction through affecting AQP4 levels. Interpretation: This study reveals AQP4-AS1 is involved in retinal neurovascular dysfunction and expected to become a promising target for the treatment of neurovascular dysfunction in DR. Funding: This work was generously supported by the grants from the National Natural Science Foundation of China (Grant No. 81800858, 82070983, 81870679 and 81970823), grants from the Medical Science and Technology Development Project Fund of Nanjing (Grant No ZKX17053 and YKK19158), grants from Innovation Team Project Fund of Jiangsu Province (No. CXTDB2017010), and the Science and Technology Development Plan Project Fund of Nanjing (Grant No 201716007, 201805007 and 201803058).

Black zirconia ceramics has many problems, such as uneven color and poor phase stability. The reason for this phenomenon is that the colorant uses a colorant with a complex black spinel structure, and also the application of a dyeing method. To improve the color uniformity and phase stability of black ceramics, TiO2 was introduced to replace the traditional complex black spinel, a high-temperature reduction method (HTR) was employed to prepare a black Ti-doped zirconia ceramic, stead of the conventional dyeing method. After the HTR at 1400 °C, the concentration of Ti3+ and oxygen vacancies increased, and the lightness of the ceramic samples decreased from 93.48 to 44.17. The black ceramic is uniform in color and stable in phase, avoiding the disordered phase of the spinel doped multiphase zirconia ceramic. The results indicate that the overall color of the samples depends on the development mechanism of the color center. The formation of color centers (F+ centers) in this work was related to the electronic transition of Ti 3d states and oxygen vacancies generated during the HTR. F+ centers cause a strong light absorbance over the entire visible light range (400–750 nm), so that the color of the ceramics is black. Based on their good color attributes, black ceramics have great potential in industry, for example as the back plate of mobile phones.

Generally, the unit cell in a proton exchange membrane fuel cell (PEMFC) stack is divided into different zones according to the characteristics of the bipolar plate. There is a zone that has been neglected, which we define as the “neck zone” for the first time in this work. Uneven stress and deformation are prone to appearing in the neck zone due to its unique structure. A three-dimensional finite element model was applied to study the influence of the membrane electrode assembly (MEA) frame materials on the mechanical characteristics of the neck zone. In addition, the sealing and the water–gas transport performances of the neck zone were evaluated via the stress fluctuation and deformation. It was found that even with the commercial polyethylene naphthalate (PEN) frame, a leak point would be generated at the region with the lowest stress, reducing the performance and even causing safety hazards. The invasion rate was proposed to assess the water–gas transport ability. When an inappropriate frame material was adopted, the invasion rate went up to 32.4%, severely hindering the water and the air transport. It was concluded that MEA frames with a higher elastic modulus and thickness are preferred for the neck zone to obtain a high property of sealing and water–gas transport.

Recently, the focus of fuel cell technologies has shifted from light-duty automotive to heavy-duty vehicle applications, which require improving the stability of membrane electrode assemblies (MEAs) at high constant potential. The hydrophilicity of Pt makes it easy to combine with water molecules and then oxidize at high potential, resulting in poor durability of the catalyst. In this work, an ionic liquid [BMIM][NTF2] was used to modify the Pt catalyst (Pt/C + IL) to create a hydrophobic, antioxidant micro-environment in the catalyst layer (CL). The effect of [BMIM][NTF2] on the decay of the CL performance at high constant potential (0.85 V) for a long time was investigated. It was found that the performance attenuation of Pt/C + IL in the high-potential range (OCV 0.75 V) was less than that of commercial Pt/C after 10 h. The Pt-oxide coverage test showed that the hydrophobic micro-environment of the CL enhanced the stability by inhibiting Pt oxidation. In addition, the electrochemical recovery of Pt oxides showed that the content of recoverable oxides in Pt/C + IL was higher than that in commercial Pt/C. Overall, modifying the Pt catalyst with hydrophobic ionic liquid is an effective strategy to improve the catalyst stability and reduce the irreversible voltage loss caused by the oxide at high constant potential.

Anthracycline-associated cardiotoxicity is frequently seen in cancer survivors years after treatment, but it is rare in patients on chemotherapy. This study aimed to investigate the clinical characteristics of cardiac disorders in children with acute lymphoblastic leukemia (ALL) during chemotherapy. A retrospective case study was conducted in children with ALL, for whom electrocardiogram (ECG) and echocardiography (Echo) were regularly assessed before each course of chemotherapy. The cardiac disorders were diagnosed according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Binary logistic regression analysis was used to identify risk factors associated with cardiac disorders. There were 171 children eligible for the study, and 78 patients (45.61%) were confirmed as having cardiac disorders. The incidence of cardiac disorders was dependent upon the cumulative dose of daunorubicin (DNR) (p = 0.030, OR = 1.553, 95% CI: 1.005–3.108). Four patients (2.34%) presented with palpitation, chest pain, and persistent tachycardia, and they were cured or improved after medical intervention. A total of 74 patients (43.27%) had subclinical cardiac disorders confirmed by ECG or Echo. ECG abnormalities were commonly seen in the induction and continuation treatments, including arrhythmias (26, 15.20%), ST changes (24, 14.04%) and conduction disorders (4, 2.34%). Pericardial effusion (14, 8.19%), left ventricular hypertrophy (11, 6.43%), a widened pulmonary artery (5, 2.92%) and valvular insufficiency (5, 2.92%) suggested by Echo occurred after induction chemotherapy. Therefore, cardiac disorders with clinical manifestations are rare and need early intervention. Subclinical cardiac disorders are common but very hidden in children during ALL chemotherapy. Regular ECG and Echo could help paediatricians to identify and monitor patients with asymptomatic cardiac disorders earlier.

This article aims to study the dynamic change of teachers’ beliefs among pre-service teachers. A longitudinal design was adopted to investigate English language teaching (ELT) pre-service teachers’ belief change after a 3-month teaching practicum by administering pretest and posttest questionnaires, semistructured interviews, and reflective journals. Repeated measures and paired sample t -test analyses showed significant differences across different aspects of beliefs in all the participants, but belief changes were significant after the practicum only within the experimental group, particularly in the aspects of student management, teaching evaluation, and student learning. In contrast, belief changes were not significant within the control group. Further inductive content analyses of semistructured interviews and reflective journals from the experimental group confirmed these changes and conclusively revealed some potential factors contributing to the changes. The results shed light on how pre-service teachers evolve in their career development and help educators adjust appropriate education policies to improve the quality of English teacher education, particularly in the Chinese context.

Radio frequency (RF) tempering has been proposed as a new alternative method for tempering frozen products because of its advantages of rapid and volumetric heating. In this study, the texture of RF-tempered frozen tilapia fillets was determined under different RF conditions, the effects of related factors on the texture were analyzed, and the mechanisms by which RF tempering affected the texture of the tempered fillets were evaluated. The results show that the springiness (from 0.84 mm to 0.79 mm), cohesiveness (from 0.64 mm to 0.57 mm), and resilience (from 0.33 mm to 0.25 mm) decreased as the electrode gap was increased and the power remained at 600 W, while the shear force increased as the power was increased for the 12 cm electrode gap (from 15.18 N to 16.98 N), and the myofibril fragmentation index (MFI) values were markedly higher at 600 W than at 300 W or 900 W (p < 0.05). In addition, the tempering uniformity had a positive effect on hardness and chewiness. The statistical analysis showed that the texture after RF tempering under different RF conditions correlated relatively strongly with the free water content, cooking loss, and migration of bound water to immobilized water. The decrease in free water and bound water migration to immobilized water resulted in a significant increase in cohesiveness and resilience.

The coronavirus disease 2019 (COVID-19) pandemic has highlighted the urgent need for effective prophylactic vaccination to prevent the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Intranasal vaccination is an attractive strategy to prevent COVID-19 as the nasal mucosa represents the first-line barrier to SARS-CoV-2 entry. The current intramuscular vaccines elicit systemic immunity but not necessarily high-level mucosal immunity. Here, we tested a single intranasal dose of our candidate adenovirus type 5-vectored vaccine encoding the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein (AdCOVID) in inbred, outbred, and transgenic mice. A single intranasal vaccination with AdCOVID elicited a strong and focused immune response against RBD through the induction of mucosal IgA in the respiratory tract, serum neutralizing antibodies, and CD4+ and CD8+ T cells with a Th1-like cytokine expression profile. A single AdCOVID dose resulted in immunity that was sustained for over six months. Moreover, a single intranasal dose completely protected K18-hACE2 mice from lethal SARS-CoV-2 challenge, preventing weight loss and mortality. These data show that AdCOVID promotes concomitant systemic and mucosal immunity and represents a promising vaccine candidate.

Abstract Background Chronic myelogenous leukemia (CML) is a pluripotent hematopoietic stem cell disorder caused by the fusion of the BCR and ABL1 genes. Quantitative RT-PCR (qRT-PCR) is a routinely performed screening technique to identify BCR-ABL1 fusion genes, but a limitation of this method is its inability to recognize novel fusions that have not been previously characterized. Next-generation sequencing (NGS) is an effective and sensitive detection method for the determination of novel BCR-ABL1 fusion genes as well as previously characterized ones. The oncoprotein tyrosine kinase BCR-ABL1 is a constitutively active kinase involved in the activation of a number of signaling pathways, and it has been the therapeutic target for tyrosine kinase inhibitors (TKIs) such as imatinib. Reports have presented opposing viewpoints about the effect of the disrupted Src homology 3 (SH3) domain on TKI efficacy. Findings We here report that using NGS we identified a novel BCR-ABL1 fusion gene with breakpoints in the BCR intron 14 and the ABL1 intron 2, leading to partial deletion of its SH3 domain. In the present case, the patient received targeted therapy with the TKI imatinib at 400 mg/day and no adverse reaction was reported. The patient eventually entered remission with decreased proliferation of karyocytes and granulocytes. We also identified mutations in genes, including TP53, FLT3, ASXL1, SETBP1, CEBPA and CBL, that seemed to have an influence on the outcome of TKI therapy targeting the BCR-ABL1 protein. Conclusions Together with previously reported results, it is clear that the genetic heterogeneity of CML patients significantly affects the presentation of the disease and its progression and therefore should inform the design of the therapeutic strategy.

Background: Recent studies have demonstrated that pterygium has a close relationship with dry eye disease. This study is to determine abnormalities in meibomian gland and tear function in patients with pterygium and to assess the relationship between the variables. Materials and Methods: Forty eyes from forty patients with primary nasal pterygium and forty eyes from forty volunteers without ocular pathologies were enrolled in this study. Ocular surface disease index scores, meibomian gland expression scores, lid margin abnormality scores, meiboscore, tear film breakup time (BUT), Schirmer test (SIT) value, and the lower tear meniscus height (TMH), tear meniscus depth (TMD), and tear meniscus area (TMA) using Fourier domain optical coherence were performed. Analysis of variance was applied for intergroup comparisons. A statistical significance level of P < 0.05 was considered. Results: Ocular symptom scores, BUT scores, lid margin abnormality, meibomian gland expression, and meiboscore were significantly higher in pterygium patients than in controls (P < 0.01 for all scores). However, the SIT scores, the lower TMH, TMD, and TMA values did not revealed a significant difference between two groups (all P > 0.05). Multivariate regression analysis demonstrated that meiboscore significantly correlated with ocular symptom scores, BUT, lid margin abnormality scores, and meibomian gland expression scores. Conclusions: Meibomian gland function may be altered in pterygium patients, which is associated with uncomfortable ocular symptoms. Being aware of meibomian gland changes seems essential to understand the complex relationship among pterygium, tear film functions, and ocular surface changes.

Philadelphia chromosome-positive (Ph+) is considered as a high risk of acute lymphoblastic leukemia (ALL). Tyrosine kinase inhibitors (TKIs) are tailored drug for Ph+ ALL, but Ik6 is associated with TKI resistance and poor outcome of Ph+ ALL. In the present study, we investigated the potential benefit of combination therapy with imatinib and Huaier extract, a traditional Chinese medicine, in Ik6+ Ph+ ALL. The Ik6+ Ph+ -ALL cell lines Sup-B15 or BV173 were treated with Huaier extract, imatinib or the combination of the two. Analysis of cell proliferation showed that the combined treatment of imatinib and Huaier extract exhibited a greater effect on cell inhibition. Using flow cytometry and Western blot, enhanced effects on the induction of cell apoptosis were observed. The combination of the two drugs also exhibited a significant effect in decreasing the protein and enzymatic activity levels of BCR-ABL. The molecular mechanisms may be involved in BCR-ABL related pathways, including the inactivation of p-AKT, p-STAT5, p-mTOR and p-Lyn. Consistent with the in vitro results, the combination of Huaier extract and imatinib inhibit the growth and infiltration of xenografted tumors. Taken together, our findings show that Huaier extract enhances the anticancer efficacy of imatinib in Ik6+ Ph+ ALL Further, it also provides a potential clinical application in the treatment of refractory Ph+ ALL.

Background: Traditional Chinese medicine nursing (TCM nursing) is one of the highlights of nursing profession in China, which plays a significant role in Chinese healthcare system. However, bottlenecks exist in TCM nursing development. It’s necessary to explore the discipline connotation and advantages of TCM nursing in nursing education and clinical practice and introduce modern nursing concepts. Methods: We analysis the connotations of TCM nursing, the bottlenecks it faces, and strategies to facilitate TCM nursing development. Results: Qualitative research method and evidence-based nursing concepts are key strategies to solve the dilemma TCM nursing confronts with and are quite essential in TCM nursing development. Conclusion: We should embed qualitative research method and evidence-based nursing concepts into TCM nursing advancement so as to facilitate the advancement of TCM nursing and promote its globalization.