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Abstract Aims To construct a quality evaluation index system for clinical drug trials nursing management and obtain the weight of all indicators. Design A mixed‐method research design with a quantitative component was used, primarily qualitative. Methods Through a literature review and semi‐structured interview, an expert consultation questionnaire on the quality of nursing evaluation indicators for clinical drug trials was developed in April 2021. Eighteen experts in clinical drug trial nursing, medical, and pharmacy conducted 2 rounds of consultation according to the Delphi method to determine the indicators for evaluating the quality of clinical drug trial nursing. The weights of each indicator were determined using analytic hierarchical analysis. Results The established quality evaluation system of clinical drug trial nursing mainly includes 3 first‐level indicators, 12 second‐level indicators, and 59 third‐level indicators. The positive coefficients of the two rounds of expert consultation were 90%–100%, and the authority coefficients were 0.831 and 0.885, respectively; the coordination coefficients were 0.189 and 0.214, respectively. The consulting results and weight settings are reliable. The evaluation index system we constructed is in line with the characteristics of the clinical drug trial nursing profession, with clear index levels and strong clinical operability, which can provide a reference for the assessment, monitoring and improvement of nursing quality in clinical drug trials. It will also clarify how nurses contribute to subjects' safety.

Abstract Background Ischemic strokes are primarily caused by intracranial and extracranial atherosclerotic stenosis. Nontraditional lipid parameters broaden traditional lipid profiles, better reflect the metabolism and interaction between different lipid components, and optimize the predictive ability of lipid profiles for atherosclerotic diseases. This research was carried out to investigate the predictive value of nontraditional lipid parameters for intracranial or extracranial atherosclerotic stenosis. Methods The investigation collected data from inpatients who underwent cervical vascular ultrasonography, carotid CTA, cerebral artery CTA or MRA, and brain MRI or CT from December 2014 to December 2021. The nontraditional lipid parameters were calculated by collecting traditional lipid parameters. To evaluate the predictive power of nontraditional lipid parameters, logistic regression and receiver operating characteristic curve (ROC) analyses were performed. Results Based on the inclusion and exclusion criteria, 545 patients were included. According to the imaging results, inpatients were divided into two groups, including no intracranial or extracranial atherosclerotic stenosis (n = 250) and intracranial or extracranial atherosclerotic stenosis (AS, n = 295). Among them, AS was further divided into three subgroups: intracranial atherosclerotic stenosis (ICAS), extracranial atherosclerotic stenosis (ECAS) and combined intracranial and extracranial atherosclerotic stenosis (IECAS). Logistic regression analysis showed that nontraditional lipid parameters, including the atherogenic index of plasma (AIP), remnant cholesterol (RC), nonhigh-density lipoprotein cholesterol (non-HDL-C), lipoprotein combine index (LCI), atherogenic coefficient (AC), Castelli’s index-I (CRI-I) and Castelli’s index-II (CRI-II), were significantly correlated with intracranial or extracranial atherosclerotic stenosis (P

Chinese sweet lily (Lilium davidii var. unicolor), the only edible lily in the world, has high nutritional value. At present, the application of preservation technology is relatively backward, resulting in a large loss of lily. Therefore, the preservation has become one of the key factors limiting the development of the edible lily bulbs industry. This paper reviews the various application of pretreatment and storage technologies for the preservation of lily bulbs. It is considered that irradiation and proper preservative can be used for pretreatment. Vacuum packaging can be used for short-term storage and transportation. Phase temperature storage could be as a long-term storage mode of lily bulbs.

Adversity stress is the main environmental factor limiting plant growth and development, including salt and other stress factors. This study delves into the adaptability and salt tolerance mechanisms of Machilus faberi Hemsl, a species with potential for cultivation in salinized areas. We subjected the plants to various salt concentrations to observe their growth responses and to assess key physiological and biochemical indicators. The results revealed that under high salt concentrations (500 and 700 mmol−1/L), symptoms such as leaf yellowing, wilting, and eventual death were observed. Notably, plant height and shoot growth ceased on the 14th day of exposure. Chlorophyll content (a, b, total a + b, and the a/b ratio) initially increased but subsequently decreased under varying levels of salt stress. Similarly, the net photosynthetic rate, stomatal conductance, leaf water content, and root activity significantly declined under these conditions. Moreover, we observed an increase in malondialdehyde levels and relative conductivity, indicative of cellular damage and stress. The activity of superoxide dismutase and ascorbate peroxidase initially increased and then diminished with prolonged stress, whereas peroxidase activity consistently increased. Levels of proline and soluble protein exhibited an upward trend, contrasting with the fluctuating pattern of soluble sugars, which decreased initially but increased subsequently. In conclusion, M. faberi exhibits a degree of tolerance to salt stress, albeit with growth limitations when concentrations exceed 300 mmol−1/L. These results shed light on the plant’s mechanisms of responding to salt stress and provide a theoretical foundation for its cultivation and application in salt-affected regions.

In order to improve the efficiency of urban planning and design and reduce the construction waste caused by inefficient design schemes, this paper proposes an application method of environmental protection building elements based on artificial intelligence technology in the field of urban planning and design. This model enables agents to learn how to interact with the environment with appropriate strategies, so as to generate the road network design scheme required by users. In order to better control the generation of the result scheme, this paper designs the rules and feedback of the agent. Among them, rules restrict the behavior of agents to avoid design schemes that do not meet the road design specifications. Feedback determines the values followed by agents, that is, the direction of agent strategy optimization. The experimental results show that after 4×105 iterations of the training process, the model is derived and used to generate 10000 plot road network schemes, the mean and variance of key indicators are calculated, and the scores of 153 plots with similar area and shape and the same land function in the same indicators from the real case base are calculated. From the performance of these indicators, it can be seen that the performance of the road network generated by the model is similar to that of the real road network in terms of traffic performance. Conclusion. the model completely retains the structural geographic information inside the plot, and the generated results can be directly applied to mainstream urban design software through data format conversion.

Objective This study was performed to evaluate the efficacy and feasibility of percutaneous mechanical thrombectomy (PMT) combined with catheter-directed thrombolysis (CDT) in patients with acute pulmonary embolism (APE) and lower extremity deep venous thrombosis (LEDVT). Methods In total, 20 consecutive patients with APE and LEDVT were prospectively selected for PMT combined with CDT. Mechanical thrombus fragmentation and aspiration using a pigtail rotation catheter followed by CDT was performed in each patient. Details regarding the patients’ clinical presentation and outcome, pulmonary status parameters (pulmonary arterial pressure, partial pressure of oxygen in arterial blood, Miller score, thigh and calf circumference, and shock index), and lower extremity parameters (thrombus-lysis grade and Villalta scale score) were recorded. Results All 20 patients’ clinical manifestations significantly improved. Both the clinical success rate and technical success rate were 100%. No major adverse events occurred during hospitalization. Four patients developed iliac vein compression syndrome and underwent stent implantation in the iliac vein. No pulmonary embolism recurred within 16.5±6.8 months of follow-up. Conclusions The combination of PMT and CDT is a safe and effective treatment for APE and LEDVT with good short- and intermediate-term clinical outcomes.

The paper investigated general function projective finite-time lag synchronization(GFPFTLS) between two coupled networks with different dimensions and unknown outer disturbances via Razumikhin approach. Basing on finite-time stabilization theorem of time delay system, the decentralized feedback control strategy and properties of norm for irregular matrices, some useful time-delay independent general function finite-time projective lag synchronization criteria have been obtained. Numerical simulations showed the effectiveness and feasibility of the proposed approaches. [ABSTRACT FROM AUTHOR]

In this study, a novel methodology for the fabrication of gradient porous structures is introduced, predicated upon the phase evolution characteristics of immiscible polymer blends. Initially, a comprehensive flow-phase field dynamics model is developed. This model couples the principles of phase field theory and the dynamics of fluid flow to the two-phase evolution process, facilitating a numerical simulation of the phase evolution. Subsequently, the phase field parameters of model are determined and combined with the temperature field, thereby enabling a targeted and controlled fabrication of gradient porous structures. Finally, the efficacy and practical applicability of the proposed methodology are substantiated through the construction of illustrative examples. This approach, as delineated herein, provides a robust framework for the efficient design and realization of intricate, interconnected gradient porous structures with potential applications in various scientific and engineering domains.

Abstract Background Factor XI (FXI) deficiency is an autosomal hemorrhagic disorder characterized by reduced plasma FXI levels. Multiple ancestral variants in the F11 gene have been identified in Ashkenazi Jews and other selected European populations. However, there are few reports of predominant variants in Chinese and/or East Asian populations. The aim of this study is to characterize the genotypes and phenotypes of FXI deficiency and identify the predominant variants. Results Of the 41 FXI-deficient patients, 39 exhibited severe FXI defects, considerably more than those with partial defects. The APTT levels showed a negative correlation with FXI activity levels (coefficient=-0.584, P

Erythropoietin-producing hepatocellular carcinoma A3 (EphA3) is a member of the largest subfamily of tyrosine kinase receptors-Eph receptors. Previous studies have shown that EphA3 is associated with tissue development. Recently, we have found that the expression of EphA3 is elevated in the hypothalamus of mice with diet-induced obesity (DIO). However, the role of EphA3 in hypothalamic-controlled energy metabolism remains unclear. In the current study, we demonstrated that the deletion of EphA3 in the hypothalamus by CRISPR/Cas9-mediated gene editing promotes obesity in male mice with high-fat diet feeding rather than those with normal chow diet feeding. Moreover, the deletion of hypothalamic EphA3 promotes high-fat DIO by increasing food intake and reducing energy expenditure. Knockdown of EphA3 leads to smaller intracellular vesicles in GT1-7 cells. The current study reveals that hypothalamic EphA3 plays important roles in promoting DIO. [ABSTRACT FROM AUTHOR]

Vaccinium dunalianum, a medicinal plant, is utilized for Quezui Tea production from its leaf buds and young leaves. Despite prior research on V. dunalianum revealing several medicinal compounds, the comprehensive variations in metabolites during its growth and development, along with the molecular mechanisms underlying high chlorogenic acid (CGA) yield, remain unclear. Through a joint analysis of transcriptomics and proteomics, our study first identified 15 key structural genes and 3 transcription factors influencing CGA biosynthesis in V. dunalianum, offering new evidence to understand its regulatory network. Furthermore, non-targeted metabolomics analysis provides the first extensive report on the metabolic profile of V. dunalianum, furnishing a valuable dataset for deeper exploration of its nutritional and medicinal value, and the development of a quality evaluation system for its product Quezui Tea. This study offers the most comprehensive molecular information on V. dunalianum, marking a significant step toward understanding and enhancing the plant’s potential for medicinal and nutritional applications. Additionally, this study also reveals V. dunalianum holds promise as a natural antioxidant source for functional foods, providing data support for network pharmacology.

Background Psoriasis is a chronic inflammatory skin disease. A strong association between the AhR/ NFκB axis and the inflammatory response in psoriasis. Indigo (IDG) has demonstrated significant anti-inflammatory properties. This study aimed to assess the anti-psoriatic efficacy of IDG while investigating the underlying mechanisms involved. Methods In the in vitro experiments, cell viability was assessed using the CCK-8. qRT-PCR was employed to measure the mRNA levels of NF-κB, TNF-α, IL-1β, AhR, and CYP1A1. Western blotting was conducted to examine alterations in cytoplasmic and nuclear AhR protein levels. Additionally, an IDG nanoemulsion (NE) cream was prepared for the in vivo experiments. A psoriasis-like skin lesion mice model was induced using IMQ (62.5 mg/day for 7 days). The severity of psoriasis was evaluated using PASI, and skin lesions were scored while epidermal thickness was assessed via HE staining. The expression of inflammatory markers, including IL-6, IL-13, IL-17A, MCP-1, and TNF-α, was detected in skin lesions using Luminex. The levels of CYP1A1, p65, and p-p65 proteins were determined by Western blotting. Results LPS stimulation significantly elevated TNF-α, IL-6, and NF-κB mRNA levels, which were notably reduced by IDG treatment. Additionally, IDG significantly enhanced the expression of AhR and CYP1A1 mRNA. Further investigation revealed that IDG facilitated AhR translocation from the cytoplasm to the nucleus. In the IMQ-induced psoriasis-like mouse model, IDG NE substantially ameliorated the severity of skin lesions. Moreover, IDG NE treatment reduced the upregulation of inflammatory cytokines such as IL-6, IL-17A, MCP-1, and TNF-α in IMQ-induced skin lesions. It was also observed that IDG NE treatment increased CYP1A1 protein expression while inhibiting p65 and p-p65 protein expression. Conclusion IDG emerges as a promising treatment for psoriasis, demonstrating effective therapeutic outcomes. Its mechanism of action is likely linked to the modulation of the AhR/NFκB signaling pathway.

ObjectiveThis study aimed to assess and visually depict the clinical evidence landscape of traditional Chinese exercises and identify any research gaps and future research needs.MethodsWe comprehensively searched seven Chinese and English databases to identify randomized controlled trials (RCTs) and systematic reviews (SRs) evaluating the effects of traditional Chinese exercises from their inception until May 2023. The quality of evidence was assessed via the GRADE approach, and the research topics, intervention effects, and strength of evidence were graphically displayed.ResultsThis evidence map includes 2,017 studies, comprising 1,822 RCTs and 195 SRs. These studies were conducted globally in various countries. Among the traditional Chinese exercises, Tai Chi and Baduanjin have received the most research attention, with a growing number of publications. When traditional Chinese exercises were compared with the control groups, 88.2% of the included SRs reported significantly positive effects, 4.1% reported unclear effects, and 7.7% reported no significant differences. The findings suggested that traditional Chinese exercises could benefit patients with osteoarthritis, osteoporosis, hypertension, coronary heart disease, diabetes, chronic obstructive pulmonary disease, stroke, Parkinson’s disease, anxiety, and depression. However, the overall quality of the evidence was suboptimal, with 11.3% rated as moderate, 45.6% as low, and 43.1% as critically low.ConclusionThis evidence map visually represents valuable information on traditional Chinese exercises. While most studies have reported significant benefits, the overall quality of evidence is low.

Abstract Prostate cancer (PCa) ranks as the second most prevalent cancer among males globally. However, the exact mechanisms underlying its progression remain inadequately elucidated. The present study sought to investigate the role and underlying molecular mechanism of hsa_circ_0001671 (circ_0001671) in the pathogenic behavior of PCa cells. Guided by the ceRNA theory, miR-27b-3p was employed to identify circRNAs that could potentially regulate Bloom Syndrome Protein (BLM). A series of experimental approaches including bioinformatics, luciferase assays, Fluorescent In Situ Hybridization (FISH), RNA-pulldown, and RNA Immunoprecipitation (RIP) were utilized to validate the miRNA sponge function of circ_0001671. Divergent primer PCR, RNase R treatments, and Sanger sequencing were conducted for the identification of circ_0001671. Quantitative RT-PCR and Western blot analyses were performed to validate gene expression levels. Both in vitro and in vivo experiments were conducted to assess the functional role of circ_0001671 in PCa cells.It was observed that the expression levels of circ_0001671 and BLM were significantly elevated in PCa tissues and cell lines, whereas miR-27b-3p showed decreased expression. Circ_0001671 was found to promote cellular proliferation, migration, and invasion, while inhibiting apoptosis. In vivo assays confirmed that circ_0001671 facilitated tumor growth. Further mechanistic studies revealed that circ_0001671 acted as a competing endogenous RNA (ceRNA) for BLM by sponging miR-27b-3p. The oncogenic role of circ_0001671 in PCa was shown to be modulated through the miR-27b-3p/BLM axis. In conclusion, circ_0001671 exerts an oncogenic effect in prostate cancer through the regulation of BLM by sponging miR-27b-3p, thus suggesting a novel molecular target for the treatment of PCa.

Abstract Background This study aimed to investigate the potential association between the circadian rhythm of blood pressure and deceleration capacity (DC)/acceleration capacity (AC) in patients with essential hypertension. Methods This study included 318 patients with essential hypertension, whether or not they were being treated with anti-hypertensive drugs, who underwent 24-hour ambulatory blood pressure monitoring (ABPM). Patients were categorized into three groups based on the percentage of nocturnal systolic blood pressure (SBP) dipping: the dipper, non-dipper and reverse dipper groups. Baseline demographic characteristics, ambulatory blood pressure monitoring parameters, Holter recordings (including DC and AC), and echocardiographic parameters were collected. Results In this study, the lowest DC values were observed in the reverse dipper group, followed by the non-dipper and dipper groups (6.46 ± 2.06 vs. 6.65 ± 1.95 vs. 8.07 ± 1.79 ms, P

Abstract In recent years, there has been an increase in the incidence and mortality rates of prostate cancer (PCa). However, the specific molecular mechanisms underlying its occurrence and development remain unclear, necessitating the identification of new therapeutic targets. Through bioinformatics analysis, we discovered a previously unstudied differential gene called HIST3H2A in prostate cancer. Our study revealed that HIST3H2A is highly expressed in PCa tissues, as confirmed by analysis of both the GEO and UALCAN databases. Further analysis using the KEGG database demonstrated that HIST3H2A regulates the pathway of programmed necroptosis in cells. Additionally, we observed significant up-regulation of HIST3H2A in PCa tissues and cell lines. HIST3H2A was found to regulate cell proliferation, migration, invasion, and the epithelial-mesenchymal transition (EMT) process in tumors. Notably, HIST3H2A’s role in regulating programmed necroptosis in prostate cancer cells differs from its role in apoptosis. In vitro and in vivo experiments collectively support the key role of HIST3H2A in promoting the development of prostate cancer, highlighting its potential as a therapeutic target for patients with PCa.

Abstract Aims Left ventricular aneurysm (LVA) is an important complication of acute myocardial infarction. The aim of this study was to investigate the possible predictive value of blood urea nitrogen‐to‐albumin ratio (BAR) for the LVA formation in acute ST‐segment elevation myocardial infarction (STEMI) patients who underwent primary percutaneous coronary intervention (PCI). Methods and results A total of 1123 consecutive patients with STEMI were prospectively enrolled. The clinical and laboratory data were compared between LVA group and non‐LVA group. Multivariable logistic regression analysis was performed to assess the independent risk factors of LVA formation. Predictive power of BAR and composite variable for LVA formation were assessed using receiver operating characteristic curve. LVA was detected in 162 patients (14.4%). The BAR was significantly higher in patients with LVA [0.16 (0.13–0.19) vs. 0.13 (0.10–0.17), P

AbstractCarcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) restricts platelet activation via platelet collagen receptor GPVI/FcRγ-chain. In this study, screening against collagen-induced platelet aggregation was performed to identify functional CEACAM1 extracellular domain fragments. CEACAM1 fragments, including Ala-substituted peptides, were synthesized. Platelet assays were conducted on healthy donor samples for aggregation, cytotoxicity, adhesion, spreading, and secretion. Mice were used for tail bleeding and FeCl3-induced thrombosis experiments. Clot retraction was assessed using platelet-rich plasma. Extracellular segments of CEACAM1 and A1 domain-derived peptide QDTT were identified, while N, A2, and B domains showed no involvement. QDTT inhibited platelet aggregation. Ala substitution for essential amino acids (Asp139, Thr141, Tyr142, Trp144, and Trp145) in the QDTT sequence abrogated collagen-induced aggregation inhibition. QDTT also suppressed platelet secretion and “inside-out” GP IIb/IIIa activation by convulxin, along with inhibiting PI3K/Akt pathways. QDTT curtailed FeCl3-induced mesenteric thrombosis without significantly prolonging bleeding time, implying the potential of CEACAM1 A1 domain against platelet activation without raising bleeding risk, thus paving the way for novel antiplatelet drugs.

Lithium-ion batteries (LIBs) have been widely applied in electronic communication, transportation, aerospace, and other fields, among which separators are vital for their electrochemical stability and safety. Electrospun polyvinylidene fluoride (PVDF)-based separators have a large specific surface area, high porosity, and remarkable thermal stability, which significantly enhances the electrochemistry and safety of LIBs. First, this paper reviewed recent research hotspots and processes of electrospun PVDF-based LIB separators; then, their pivotal parameters influencing morphology, structures, and properties of separators, especially in the process of electrospinning solution preparation, electrospinning process, and post-treatment methods were summarized. Finally, the challenges of PVDF-based LIB separators were proposed and discussed, which paved the way for the application of electrospun PVDF-based separators in LIBs and the development of LIBs with high electrochemistry and security.

The polyketide griseofulvin is a natural antifungal compound and research in griseofulvin has been key in establishing our current understanding of polyketide biosynthesis. Nevertheless, the griseofulvin gsf biosynthetic gene cluster (BGC) remains poorly understood in most fungal species, including Penicillium griseofulvum where griseofulvin was first isolated. To elucidate essential genes involved in griseofulvin biosynthesis, we performed third-generation sequencing to obtain the genome of P. griseofulvum strain D-756. Furthermore, we gathered publicly available genome of 11 other fungal species in which gsf gene cluster was identified. In a comparative genome analysis, we annotated and compared the gsf BGC of all 12 fungal genomes. Our findings show no gene rearrangements at the gsf BGC. Furthermore, seven gsf genes are conserved by most genomes surveyed whereas the remaining six were poorly conserved. This study provides new insights into differences between gsf BGC and suggests that seven gsf genes are essential in griseofulvin production. [ABSTRACT FROM AUTHOR]

Abstract Background DNA methylation played a crucial role in the pathogenesis of immune thrombocytopenia (ITP). However, genome-wide DNA methylation analysis has not been applied thus far. The present study aimed to provide the first DNA methylation profiling for ITP. Methods Peripheral blood CD4+ T lymphocytes samples were collected from 4 primary refractory ITP cases and 4 age-matched healthy controls, and DNA methylome profiling was performed using Infinium MethylationEPIC BeadChip. Differentially methylated CpG sites were further validated in another independent cohort of 10 ITP patients and 10 healthy controls using qRT-PCR. Results The DNA methylome profiling identified a total of 260 differentially methylated CpG sites mapping to 72 hypermethylated and 64 hypomethylated genes. These genes were mainly enriched in the actin nucleation of the Arp2/3 complex, vesicle transport, histone H3-K36 demethylation, Th1 and Th2 cell differentiation, and Notch signaling pathway according to the GO and KEGG databases. The mRNA expression of CASP9, C1orf109, and AMD1 were significantly different. Conclusions Given the altered DNA methylation profiling of ITP, our study provides new insights into its genetic mechanism and suggests candidate biomarkers for the diagnosis and treatment of ITP.

Abstract Objective Cuproptosis‐related genes are closely related to lung adenocarcinoma (LUAD), which can be analyzed via the analysis of long noncoding RNA (lncRNA). To date, the clinical significance and function of cuproptosis‐related lncRNAs are still not well elucidated. Further analysis of cuproptosis‐related prognostic lncRNAs is of great significance for the treatment, diagnosis, and prognosis of LUAD. Methods In this study, a multiple machine learning (ML)‐based computational approach was proposed for the identification of the cuproptosis‐related lncRNAs signature (CRlncSig) via comprehensive analysis of cuproptosis, lncRNAs, and clinical characteristics. The proposed approach integrated multiple ML algorithms (least absolute shrinkage and selection operator regression analysis, univariate and multivariate Cox regression) to effectively identify the CRlncSig. Results Based on the proposed approach, the CRlncSig was identified from the 3450 cuproptosis‐related lncRNAs, which consist of 13 lncRNAs (CDKN2A‐DT, FAM66C, FAM83A‐AS1, AL359232.1, FRMD6‐AS1, AC027237.4, AC023090.1, AL157888.1, AL627443.3, AC026355.2, AC008957.1, AP000346.1, and GLIS2‐AS1). Conclusions The CRlncSig could well predict the prognosis of different LUAD patients, which is different from other clinical features. Moreover, the CRlncSig was proved to be an effective indicator of patient survival via functional characterization analysis, which is relevant to cancer progression and immune infiltration. Furthermore, the results of RT‐PCR assay indicated that the expression level of FAM83A‐AS1 and AC026355.2 in A549 and H1975 cells (LUAD) was significantly higher than that in BEAS‐2B cells (normal lung epithelial).

BackgroundDiabetic kidney disease (DKD) has become the leading cause of kidney failure, causing a significant socioeconomic burden worldwide. The usual care for DKD fails to achieve satisfactory effects in delaying the persistent loss of renal function. A Chinese herbal medicine, Tangshen Qushi Formula (TQF), showed preliminary clinical benefits with a sound safety profile for people with stage 2-4 DKD. We present the protocol of an ongoing clinical trial investigating the feasibility, efficacy, and safety of TQF compared to placebo in delaying the progressive decline of renal function for people with stage 2-4 DKD.MethodsA mixed methods research design will be used in this study. A randomized, double-blind, placebo-controlled pilot trial will evaluate the feasibility, efficacy, and safety of TQF compared to placebo on kidney function for people with stage 2-4 DKD. An embedded semi-structured interview will explore the acceptability of TQF granules and trial procedures from the participant’s perspective. Sixty eligible participants with stage 2-4 DKD will be randomly allocated to the treatment group (TQF plus usual care) or the control group (TQF placebo plus usual care) at a 1:1 ratio for 48-week treatment and 12-week follow-up. Participants will be assessed every 12 weeks. The feasibility will be assessed as the primary outcome. The changes in the estimated glomerular filtration rate, urinary protein/albumin, renal function, glycemic and lipid markers, renal composite endpoint events, and dampness syndrome of Chinese medicine will be assessed as the efficacy outcomes. Safety outcomes such as liver function, serum potassium, and adverse events will also be evaluated. The data and safety monitoring board will be responsible for the participants’ benefits, the data’s credibility, and the results’ validity. The intent-to-treat and per-protocol analysis will be performed as the primary statistical strategy.DiscussionConducting a rigorously designed pilot trial will be a significant step toward establishing the feasibility and acceptability of TQF and trial design. The study will also provide critical information for future full-scale trial design to further generate new evidence supporting clinical practice for people with stage 2-4 DKD.Trial registration numberhttps://www.chictr.org.cn/, identifier ChiCTR2200062786.

ABSTRACT The monkeypox virus, which was declared as a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO), continues to cause infection cases worldwide. Given the risk of virus evolution, it is essential to identify monkeypox virus infection in a timely manner and isolate patients to prevent outbreaks so that the vulnerable population is protected and the emergence of dangerous monkeypox variants is restrained. In this study, a novel one-pot recombinase polymerase amplification-Clustered Regularly Interspaced Short Palindromic Repeats (RPA-CRISPR) assay for monkeypox based on a sucrose-aided multiphase aqueous system has been established with an ultra-high sensitivity of a single copy, which is 10 times higher than the existing RPA-CRISPR one-pot method. The entire reaction was completed within 60 min at 37°C. The detection method exhibited good specificity, effectively distinguishing monkeypox from other orthopoxviruses. The detection results could be observed by the naked eye under ultraviolet or blue light, making it highly suitable for home or limited healthcare settings. The assay has solved the incompatibility between the Cas12a cleavage reaction and the RPA reaction and shows good specificity, accuracy, and the rapidness and convenience important for point-of-care testing. It provides an effective tool for the early diagnosis of monkeypox and sets a technical example of using a multiphase aqueous system to establish one-pot RPA-CRISPR detection. IMPORTANCE The monkeypox virus was declared as a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO) and continues to cause infection cases worldwide. Given the risk of virus evolution, it is essential to identify monkeypox virus infection in a timely manner to prevent outbreaks. This study establishes a novel one-pot recombinase polymerase amplification-Clustered Regularly Interspaced Short Palindromic Repeats (RPA-CRISPR) assay for monkeypox virus with an ultra-high sensitivity. The assay shows good specificity, accuracy, and the rapidness and convenience important for point-of-care testing. It provides an effective tool for the early diagnosis of monkeypox, which is useful for the prevention of an epidemic.

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can mutate frequently and many new strains have emerged thus far. The clinical and epidemiological characteristics differ with each dominant strain. OBJECTIVES: Obtain an understanding of the clinical characteristics of patients infected with the Omicron variants of the SARS CoV-2. DESIGN: Retrospective cohort SETTINGS: Teaching hospital in China. PATIENTS AND METHODS: Data on sociodemography, signs/symptoms, hospital stay, viral shedding period, comorbidities, treatment options and final outcome were retrieved from hospital electronic medical record. We collected nasopharyngeal samples, laboratory data, and clinical data from patients admitted to the hospital with SARS CoV-2. MAIN OUTCOME MEASURES: Clinical characteristics of the patients infected with Omicron variant of SARS CoV-2. SAMPLE SIZE: 445 patients RESULTS: The median age was 43.0 years with a range from 2 to 75 years. Two-thirds of the participants were male and one-third were female. Almost half of the participants (51.9%) had no symptoms, whereas 48.1% had at least one symptom. Of symptomatic patients, 26.7% had mild symptoms and 21.3% had moderate symptoms. No patients were admitted with severe or critical symptoms. All patients discharged from the hospital after complete recovery without any serious complications or death. The most common symptom was cough followed by sore throat and fever. Less common symptoms were having sputum, stuffy nose, and muscle pain. Rare symptoms were weakness, headache, diarrhea, hemoptysis and nausea/vomiting. CONCLUSIONS: All patients had mild to moderate symptoms. Shortness of breath was not a common symptom among the study group. No patients needed invasive oxygen therapy in this cohort. LIMITATIONS: Single center and retrospective design. CONFLICT OF INTEREST: None.

Introduction: Luteolin inhibits platelet activation and thrombus formation, but the mechanisms are unclear. This study investigated the effects of luteolin on GPVI-mediated platelet activation in vitro and explored the effect of luteolin on thrombosis, coagulation, and platelet production in vivo.Methods: Washed human platelets were used for aggregation, membrane protein expression, ATP, Ca2+, and LDH release, platelet adhesion/spreading, and clot retraction experiments. Washed human platelets were used to detect collagen and convulxin-induced reactive oxygen species production and endogenous antioxidant effects. C57BL/6 male mice were used for ferric chloride-induced mesenteric thrombosis, collagen-epinephrine induced acute pulmonary embolism, tail bleeding, coagulation function, and luteolin toxicity experiments. The interaction between luteolin and GPVI was analyzed using solid phase binding assay and surface plasmon resonance (SPR).Results: Luteolin inhibited collagen- and convulxin-mediated platelet aggregation, adhesion, and release. Luteolin inhibited collagen- and convulxin-induced platelet ROS production and increased platelet endogenous antioxidant capacity. Luteolin reduced convulxin-induced activation of ITAM and MAPK signaling molecules. Molecular docking simulation showed that luteolin forms hydrogen bonds with GPVI. The solid phase binding assay showed that luteolin inhibited the interaction between collagen and GPVI. Surface plasmon resonance showed that luteolin bonded GPVI. Luteolin inhibited integrin αIIbβ3-mediated platelet activation. Luteolin inhibited mesenteric artery thrombosis and collagen- adrenergic-induced pulmonary thrombosis in mice. Luteolin decreased oxidative stress in vivo. Luteolin did not affect coagulation, hemostasis, or platelet production in mice.Discussion: Luteolin may be an effective and safe antiplatelet agent target for GPVI. A new mechanism (decreased oxidative stress) for the anti-platelet activity of luteolin has been identified.

Sepsis is a syndrome of dysregulated host response caused by infection, which leads to life-threatening organ dysfunction. It is a familiar reason of death in critically ill patients. Liver injury frequently occurs in septic patients, yet the development of targeted and effective treatment strategies remains a pressing challenge. Macrophages are essential parts of immunity system. M1 macrophages drive inflammation, whereas M2 macrophages possess anti-inflammatory properties and contribute to tissue repair processes. Mesenchymal stem cells (MSCs), known for their remarkable attributes including homing capabilities, immunomodulation, anti-inflammatory effects, and tissue regeneration potential, hold promise in enhancing the prognosis of sepsis-induced liver injury by harmonizing the delicate balance of M1/M2 macrophage polarization. This review discusses the mechanisms by which MSCs regulate macrophage polarization, alongside the signaling pathways involved, providing an idea for innovative directions in the treatment of sepsis-induced liver injury.

Abstract Background The middle turbinate axilla (MTA) has always been used as a stable anatomic landmark for endoscopic surgeons to locate the lacrimal sac on the lateral nasal wall. Yet, little is known about whether the lacrimal sac size will affect the positioning effect of MTA on lacrimal sac. The aim of this study was to investigate the regularity of lacrimal sac size and lacrimal sac localization through the reference position of the MTA on computed tomographic dacryocystography (CT-DCG) images. Methods A series of 192 endoscopic dacryocystorhinostomy (DCR) surgeries were performed. All the patients had been diagnosed as unilateral nasolacrimal duct obstruction and received CT-DCG examinations. According to the maximum transverse diameter of the lacrimal sac on CT-DCG, the patients were classified into three groups. Measurements were taken on CT-DCG parasagittal images. Results The average distance from the sac superior fundus (SSF) to the MTA was 7.52 mm ± 3.23 mm, and it increased with the increase of the maximum transverse diameter of the sac among groups (p

The efficacy of many coronavirus disease 2019 (COVID-19) vaccines has been shown to decrease to varying extents against new severe acute respiratory syndrome coronavirus 2 variants, which are responsible for the continuing COVID-19 pandemic. Combining intramuscular and intranasal vaccination routes is a promising approach for achieving more potent immune responses. We evaluated the immunogenicity of prime-boost protocols with a chimpanzee adenovirus serotype 68 vector-based vaccine, ChAdTS-S, administered via both intranasal and intramuscular routes in BALB/c mice. Intramuscular priming followed by an intranasal booster elicited the highest levels of IgG, IgA, and pseudovirus neutralizing antibody titres among all the protocols tested at day 42 after prime immunization compared with the intranasal priming/intramuscular booster and prime-boost protocols using only one route. In addition, intramuscular priming followed by an intranasal booster induced high T-cell responses, measured using the IFN-γ ELISpot assay, that were similar to those observed upon intramuscular vaccination. All ChAdTS-S vaccination groups induced Th1-skewing of the T-cell response according to intracellular cytokine staining and Meso Scale Discovery cytokine profiling assays on day 56 after priming. This study provides reference data for assessing vaccination schemes of adenovirus-based COVID-19 vaccines with high immune efficacy.

The C2 domain containing protein extended synaptotagmin (E-Syt) plays important roles in both lipid homeostasis and the intracellular signaling; however, its role in physiology remains largely unknown. Here, we show that hypothalamic E-Syt3 plays a critical role in diet-induced obesity (DIO). E-Syt3 is characteristically expressed in the hypothalamic nuclei. Whole-body or proopiomelanocortin (POMC) neuron-specific ablation of E-Syt3 ameliorated DIO and related comorbidities, including glucose intolerance and dyslipidemia. Conversely, overexpression of E-Syt3 in the arcuate nucleus moderately promoted food intake and impaired energy expenditure, leading to increased weight gain. Mechanistically, E-Syt3 ablation led to increased processing of POMC to α-melanocyte-stimulating hormone (α-MSH), increased activities of protein kinase C and activator protein-1, and enhanced expression of prohormone convertases. These findings reveal a previously unappreciated role for hypothalamic E-Syt3 in DIO and related metabolic disorders. [ABSTRACT FROM AUTHOR]

Highlights Yield, N content, and specific surface area of biochar predicted by machine learning Gradient boosting regression outperformed random forest, with test R2 of 0.81–0.95 Temperature, nitrogen, and ash were top features for predicting the three targets The yield and properties of biochar were engineered and experimentally verified

Abstract Background Obesity in children has become one of the key concerns of the World Health Organization, and the incidence of related non-communicable diseases is also rising. This study evaluates the effect of family sports participation on the treatment and prevention of obesity in children aged 0–14 years by systematic analysis. Method A literature review from 2000 to 2020 was conducted. According to PRISMA-IPD (Preferred Reporting Items for MetaAnalyses of individual participant data) guidelines. The two researchers independently assessed the risk and bias of the articles, obtained a comprehensive, high-quality result, and extracted the data based on the Cochrane intervention system review manual. Randomized controlled trials (RCTs) were selected from the searches that used family sports interventions or family sports combined with dietary adjustments and behavioral habits change. Only studies targeting overweight or obese children aged 0–14 years were included. Results The search resulted in a total of 16 studies. Across all 16 studies, there were a total of 1680 participants in the experimental groups and 1701 participants in the control groups. The results are as follows: body mass index (BMI) (SMD-RE = − 4.10, 95% CI (− 0.84 to 0.02), Z = 1.88, p = 0.06); Body weight (SMD-RE = − 0.77, 95% CI (− 1.53 to − 0.01), Z = 2.00, p = 0.05); Waist circumference (SMD-RE = − 0.45, 95% CI (− 1.36 to 0.47), Z = 0.96, p = 0.34); and Body fat rate (SMD-FE = − 0.06, 95% CI (− 0.22 to 0.11), Z = 0.69, p = 0.49). Hence, through family sports intervention among obese children, juvenile and obese body composition—BMI, body weight, waist circumference, and body fat rate—are all reduced. But only body weight was statistically significant. Conclusions Compared with the samples without family sports, the weight of obese children participating in family sports decreased, but there were no significant differences in other relevant physical indicators. Follow-up research should examine large-scale clinical trials with family sports as a single factor intervention, which are needed to provide stronger evidence of the intervention effect. However, family activities can help obese children grow and develop by improving their exercise capacity, enhancing their lifestyles, and facilitating communication and relationships with their parents. In the future, long-term sports training plans for children with obesity should be implemented.

Immune thrombocytopenia (ITP) is one of the most prevalent acquired bleeding disorders in children, which is primarily characterized by a decrease in platelet count. It can be classified into two subtypes: primary ITP and secondary ITP. The underlying mechanisms causing ITP are complex and not fully comprehended. Helicobacter pylori (H. pylori) infections can lead to ITP and potentially trigger various autoimmune diseases. Furthermore, there is evidence of a correlation between thyroid disease and ITP. In this case report, we describe the case of an 11-year-old patient who presented with ITP, Hashimoto's thyroiditis (HT), and H. pylori infection. Following anti-H. pylori treatment and thyroxine supplementation, the child's platelet count increased compared to the previous count. The limitation of this report is that the platelet count of this child returned to normal after anti-H. pylori and thyroxine supplementation, so we cannot distinguish the effect of anti-H. pylori and thyroxine supplementation on the platelet count in this child. Despite this limitation, we still believe that early screening for thyroid function and H. pylori, as well as prompt eradication of H. pylori, along with thyroxine supplementation, may be beneficial in treating and improving the prognosis of children diagnosed with ITP.