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Non-stimulant atomoxetine is recognized in various current clinical guidelines as an important alternative to stimulants for the pharmacological treatment of attention deficit/hyperactivity disorder (ADHD) in children. While its efficacy and tolerability for core symptoms are established, there is considerable inter-individual variability in response and exposure, highlighting the need for personalized dosing. In this review, we evaluated existing studies and summarized comprehensive evidence supporting the clinical implementation of therapeutic drug monitoring (TDM) and personalized dosing of atomoxetine, organized around a series of logically structured questions. Although there are notable gaps in achieving personalized dosing across multiple critical elements, the available evidence is helpful to endorse personalized dose adjustments based on TDM and CYP2D6 genotyping “whenever possible.” We advocate for ongoing improvement and enhancement in clinical practice. Future advancements will rely on a deeper understanding of ADHD, facilitating more precise diagnoses and personalized treatment strategies.

BackgroundIn recent years, the overall incidence of gastric cancer has decreased. However, the incidence of gastric signet ring cell carcinoma (SRCC) is still increasing year by year. Compared with other subtypes (non-SRCC) such as adenocarcinoma, SRCC usually exhibits a more aggressive biological behavior. Therefore, studying the prognostic differences and factors associated with SRCC is essential to improve the accuracy of diagnosis and prognosis. The purpose of this study was to investigate the prognostic factors influencing the prognosis of patients with SRCC and to develop personalized treatments for different subgroups of patients.MethodsThe data on gastric SRCC patients and gastric adenocarcinoma (AC) patients from 1992 to 2020 was obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The data of gastric SRCC as the external validation group was reviewed from the First Affiliated Hospital of Soochow University. The overall survival (OS) and cancer specific survival (CSS) at 1 and 2 years were predicted for SRCC patients by constructing prognostic nomograms. A series of validation methods, including Akaike information criterion (AIC), decision curve analysis (DCA), calibration curve analysis, the concordance index (C-index) and the area under the receiver operating characteristic (AUC) curve, were used to verify the accuracy and reliability of the models.ResultsIn all, 549 patients with SRCC were included after propensity score matching (PSM). Multivariate Cox regression analysis showed that T stage, N stage, M stage and surgical approach were independent risk factors affecting the prognosis of SRCC patients. A prognostic nomogram was constructed and validated as an accurate model for SRCC patients after scoring by receiver operating characteristic curve (ROC) curves and calibration plots. The patients were further divided into high-risk and low-risk groups, and the Kaplan-Meier curves showed that SRCC patients in the low-risk group could receive only surgery without chemotherapy, while chemotherapy plus surgery was a better option for SRCC patients in the high-risk group.ConclusionThe prognosis for SRCC was less favorable than that of AC in terms of CSS. The nomograms were developed and validated to predict OS and CSS in patients with SRCC, helping in developing appropriate individualized treatment schedules.

IntroductionLong-term use of chemical fertilizers (CFs) can cause soil compaction and acidification. In recent years, bio-organic fertilizers (BOFs) have begun to replace CFs in some vegetables and cash crops, but the application of CFs or BOFs has resulted in crop quality and disease occurrence.MethodsThis study aimed to analyze the microbial mechanism of differences between CFs and BOFs in root disease, quality, and yield of tuber Chinese herbal medicine. We studied the effects of CFs, organic fertilizers, commercial BOFs, biocontrol bacteria BOFs, and biocontrol fungi BOFs on rhizosphere microbial community structure and function, root rot, quality, and yield of Codonopsis pilosula at different periods after application and analyzed the correlation.Results and discussionCompared to CFs, the emergence rate and yield in BOF treatments were increased by 21.12 and 33.65%, respectively, and the ash content, water content, and disease index in the BOF treatments were decreased by 17.87, 8.19, and 76.60%, respectively. The structural equation model showed that CFs promoted the quality and yield of C. pilosula by influencing soil environmental factors, while BOFs directly drove soil bacterial community to reduce disease index and improve the quality and yield of C. pilosula. There was a stronger interaction and stability of soil microbial networks after BOF treatments. Microlunatus, Rubrobacter, Luteitalea, Nakamurella, and Pedomicrobium were identified as effector bacteria, which were related to disease prevention and yield and quality increase of C. pilosula. Microbial functional analysis indicated that the signal transduction and amino acid metabolism of soil bacteria might play a major role in improving the quality and yield of C. pilosula in the early and middle growth stages. In conclusion, compared to CFs, BOFs obtained a lower disease index of root rot and a higher quality and yield of C. pilosula by changing the structure and function of the rhizosphere bacterial community.

Over the past decade, the prevalence of inflammatory bowel disease (IBD) has significantly increased, making early detection crucial for improving patient survival rates. Medical research suggests that changes in the human gut microbiome are closely linked to IBD onset, playing a critical role in its prediction. However, the current gut microbiome data often exhibit missing values and high dimensionality, posing challenges to the accuracy of predictive algorithms. To address these issues, we proposed the comprehensive data optimization and risk prediction framework (CDORPF), an ensemble learning framework designed to predict IBD risk based on the human gut microbiome, aiding early diagnosis. The framework comprised two main components: data optimization and risk prediction. The data optimization module first employed triple optimization imputation (TOI) to impute missing data while preserving the biological characteristics of the microbiome. It then utilized importance-weighted variational autoencoder (IWVAE) to reduce redundant information from the high-dimensional microbiome data. This process resulted in a complete, low-dimensional representation of the data, laying the foundation for improved algorithm efficiency and accuracy. In the risk prediction module, the optimized data was classified using a random forest (RF) model, and hyperparameters were globally optimized using improved aquila optimizer (IAO), which incorporated multiple strategies. Experimental results on IBD-related gut microbiome datasets showed that the proposed framework achieved classification accuracy, recall, and F1 scores exceeding 0.9, outperforming comparison models and serving as a valuable tool for predicting IBD onset risk.

Plant growth, crop yield, and pest and disease control are enhanced by PGPR (Plant growth promoting rhizobacteria), which are beneficial microorganisms found in a close symbiosis with plant roots. Phytohormones are secreted, nutrient uptake is improved, and soil properties along with the microbiological environment are regulated by these microorganisms, making them a significant focus in agricultural research. In this study, the efficient PGPR strain T1 was isolated and screened from tobacco inter-root soil, and identified and confirmed by ITS sequencing technology. Tobacco growth indicators and soil property changes were observed and recorded through potting experiments. The activities of key enzymes (e.g., sucrase, catalase, urease) in soil were further determined. High-throughput sequencing technology was utilized to sequence the soil microbial community, and combined with macro-genomics analysis, the effects of T1 strain on soil microbial diversity and metabolic pathways were explored. Following the application of T1, significant improvements were observed in the height, leaf length, and width of tobacco plants. Furthermore, the physical and chemical properties of the soil were notably enhanced, including a 26.26% increase in phosphorus availability. Additionally, the activities of key soil enzymes such as sucrase, catalase, and urease were significantly increased, indicating improved soil health and fertility. Comprehensive joint microbiomics and macrogenomics analyses revealed a substantial rise in the populations of beneficial soil microorganisms and an enhancement in metabolic pathways, including amino acid metabolism, synthesis, and production of secondary metabolites. These increase in beneficial microorganisms and the enhancement of their metabolic functions are crucial for plant growth and soil fertility. This study provides valuable references for the development of innovative microbial fertilizers and offers programs for the sustainable development of modern agriculture.

BackgroundIntegrated traditional Chinese medicine and biomedicine is an effective method to treat tuberculosis (TB). In our previous research, traditional Chinese medicine preparation NiuBeiXiaoHe (NBXH) achieved obvious anti-TB effects in animal experiments and clinical practice. However, the action mechanism of NBXH has not been elucidated.MethodPeripheral blood mononuclear cells (PBMCs) were collected to extract mRNA and differentially expressed (DE) genes were obtained using gene microarray technology. Finally, GEO databases and RT-qPCR were used to verify the results of expression profile.ResultAfter MTB infection, most upregulated DE genes in mice were immune-related genes, including cxcl9, camp, cfb, c4b, serpina3g, and ngp. Downregulated DE genes included lrrc74b, sult1d1, cxxc4, and grip2. After treatment with NBXH, especially high-dose NBXH, the abnormal gene expression was significantly corrected. Some DE genes have been confirmed in multiple GEO datasets or in pulmonary TB patients through RT-qPCR.ConclusionMTB infection led to extensive changes in host gene expression and mainly caused the host’s anti-TB immune responses. The treatment using high-dose NBXH partially repaired the abnormal gene expression, further enhanced the anti-TB immunity included autophagy and NK cell-mediated cytotoxicity, and had a certain inhibitory effect on overactivated immune responses.

Prostate adenocarcinoma (PRAD) is a prevalent global malignancy which depends more on lipid metabolism for tumor progression compared to other cancer types. Although Stearoyl-coenzyme A desaturase (SCD) is documented to regulate lipid metabolism in multiple cancers, landscape analysis of its implications in PRAD are still missing at present. Here, we conducted an analysis of diverse cancer datasets revealing elevated SCD expression in the PRAD cohort at both mRNA and protein levels. Interestingly, the elevated expression was associated with SCD promoter hypermethylation and genetic alterations, notably the L134V mutation. Integration of comprehensive tumor immunological and genomic data revealed a robust positive correlation between SCD expression levels and the abundance of CD8+ T cells and macrophages. Further analyses identified significant associations between SCD expression and various immune markers in tumor microenvironment. Single-cell transcriptomic profiling unveiled differential SCD expression patterns across distinct cell types within the prostate tumor microenvironment. The Gene Ontology and Kyoto Encyclopedia of Genes and Genome analyses showed that SCD enriched pathways were primarily related to lipid biosynthesis, cholesterol biosynthesis, endoplasmic reticulum membrane functions, and various metabolic pathways. Gene Set Enrichment Analysis highlighted the involvement of elevated SCD expression in crucial cellular processes, including the cell cycle and biosynthesis of cofactors pathways. In functional studies, SCD overexpression promoted the proliferation, metastasis and invasion of prostate cancer cells, whereas downregulation inhibits these processes. This study provides comprehensive insights into the multifaceted roles of SCD in PRAD pathogenesis, underscoring its potential as both a therapeutic target and prognostic biomarker.

This article conducts experimental research on the influencing factors of the anti-skid performance testing system SCRIM for asphalt pavement. Studied the distribution pattern of anti-skid performance test results of the testing system under different testing speeds, test tires, temperature, water film thickness, test wheel position, tire wear degree, and other factors. Revealed the influence law of various influencing factors on the anti-skid performance of asphalt pavement. The test results indicate that the SFC test value decreases with the increase of vehicle speed. The test results of tires made of different materials vary greatly, and tires with wear exceeding 3 mm cannot be used for testing. The influence of water film thickness on the measured values varies depending on the SFC level. The SFC measurement value of the normal trajectory of the vehicle’s driving wheel track is the smallest, and the measurement value of the left trajectory is greater than that of the right trajectory. The SFC measurement decreases as the tire wear increases.

Climate change and intensified human activities have disrupted the natural hydrological regime and rhythm of river-connected lakes, extending the dry season, increasing water loss, and exposing previously submerged lake floors. This exposure has led to significant sediment hardening, which directly impacts submerged macrophytes. However, strategies to mitigate the negative effects of hardened sediments and promote the growth and development of submerged macrophytes remain largely unexplored. In this study, we selected typical hardened sediment from Dongting Lake to investigate the response of different growth forms of submerged macrophytes to multiple sediment remediation measures (loosening and litter addition) using a mesocosm experiment. The results indicated that loosening alone uniformly benefited all submerged macrophytes by increasing total biomass, relative growth rate (RGR), and the root/shoot ratio. Additionally, loosening altered the root traits of submerged macrophytes, promoting maximum root length (MRL) while reducing average root diameter (ARD). Moreover, different submerged macrophytes exhibited species-specific responses to the combination of loosening and litter addition. Notably, the combination of loosening and adding Miscanthus lutarioriparius litter had an antagonistic effect on the growth of Potamogeton wrightii and Myriophyllum spicatum. The response of functional traits of submerged macrophytes with similar growth forms to the same treatment was consistent. Our findings suggest that future sediment remediation efforts should consider matching specific treatments with the growth forms of submerged macrophytes to achieve optimal outcomes.

BackgroundChidamide is subtype-selective histone deacetylase (HDAC) inhibitor that showed promising result in clinical trials to improve prognosis of angioimmunoblastic T-cell lymphoma (AITL) patients. However, in real world settings, contradictory reports existed as to whether chidamide improve overall survival (OS). Therefore, we aimed to develop an interpretable machine learning (Machine learning)–based model to predict the 2-year overall survival of AITL patients based on chidamide usage and baseline features.MethodsA total of 183 patients with AITL were randomly divided into training set and testing set. We used 5 ML algorithms to build predictive models. Recursive feature elimination (RFE) method was used to filter for the most important features. The ML models were interpreted and the relevance of the selected features was determined using the Shapley additive explanations (SHAP) method and the local interpretable model–agnostic explanationalgorithm.ResultsA total of 183 patients with newly diagnosed AITL from 2012 to 2022 from 3 centers in China were enrolled in our study. Seventy-one patients were dead within 2 years after diagnosis. Five ML algorithms were built based on chidamide usage and 16 baseline features to predict 2-year OS. Catboost model presented to be the best predictive model. After RFE screening, 12 variables demonstrated the best performance (AUC = 0.8651). Using chidamide ranked third among all the variables that correlated with 2-year OS.ConclusionThis study demonstrated that the Catboost model with 12 variables could effectively predict the 2-year OS of AITL patients. Combining chidamide in the treatment therapy was positively correlated with longer OS of AITL patients.

Staphylococcus aureus (S. aureus) infection is a primary cause of otitis media (OM), the most common disease for which children are prescribed antibiotics. However, the abuse of antibiotics has led to a global increase in antimicrobial resistance (AMR). Nanozymes, as promising alternatives to traditional antibiotics, are being extensively utilized to combat AMR. Here, we synthesize a series of single-atom nanozymes (metal-C3N4 SANzymes) by loading four metals (Ag, Fe, Cu, Ru) with antibacterial properties onto a crystalline g-C3N4. These metal-C3N4 display a rob-like morphology and well-dispersed metal atoms. Among them, Ru-C3N4 demonstrates the optimal peroxidase-like activity (285.3 U mg–1), comparable to that of horseradish peroxidase (267.7 U mg–1). In vitro antibacterial assays reveal that Ru-C3N4 significantly inhibits S. aureus growth compared with other metal-C3N4 even at a low concentration (0.06 mg mL–1). Notably, Ru-C3N4 acts as a narrow-spectrum nanoantibiotic with relative specificity against Gram-positive bacteria. Biofilms formed by S. aureus are easily degraded by Ru-C3N4 due to its high peroxidase-like activity. In vivo, Ru-C3N4 effectively eliminates S. aureus and relieves ear inflammation in OM mouse models. However, untreated OM mice eventually develop hearing impairment. Due to its low metal load, Ru-C3N4 does not exhibit significant toxicity to blood, liver, or kidney. In conclusion, this study presents a novel SANzyme-based antibiotic that can effectively eliminate S. aureus and treat S. aureus-induced OM.

A well-connected network formed by multi-scale fractures is a key factor in the formation of high-quality reservoirs and the achievement of high and stable oil and gas production in tight sandstones. Taking the Upper Paleozoic of the Qingshimao gas field in the Ordos Basin, China, as an example, based on data from image logs, cores, and thin sections, fine quantitative characterization of multi-scale natural fractures in tight sandstone reservoirs was carried out. We also established a method for dividing network patterns of multi-scale fractures and discussed the effect of each fracture network pattern on the gas enrichment and production capacity. Results indicate regular changes in the length, density, aperture, porosity, permeability, and connectivity of natural fractures at different scales. Based on the spatial combination patterns and connectivity of fractures of different scales, four types of fracture network patterns were established: multi-scale fracture network with high density and multi-orientations, multi-scale fracture network with moderate-high density and dual orientations, small-scale fracture network with moderate density and dual orientations, small-scale fracture network with low density and single orientation. The first fracture network pattern can destroy the integrity of the cap layer, causing natural gas leakage. The second fracture network pattern is a favorable area for natural gas enrichment. The third fracture network pattern requires the use of hydraulic fracturing to obtain commercial airflow. The fourth fracture network pattern has little effect on reservoir control and storage. The study of natural fractures in tight sandstone reservoirs is usually based on a single-scale perspective. Understanding the development characteristics of multi-scale fractures and their controlling effects on the reservoir helps to comprehensively understand the spatial configuration relationship of multi-scale fracture network structure patterns and promotes the development of multi-scale fractures in tight reservoir research.

BackgroundThis study aimed to identify the predictive factors for prolonged length of stay (LOS) in elderly type 2 diabetes mellitus (T2DM) patients suffering from cerebral infarction (CI) and construct a predictive model to effectively utilize hospital resources.MethodsClinical data were retrospectively collected from T2DM patients suffering from CI aged ≥65 years who were admitted to five tertiary hospitals in Southwest China. The least absolute shrinkage and selection operator (LASSO) regression model and multivariable logistic regression analysis were conducted to identify the independent predictors of prolonged LOS. A nomogram was constructed to visualize the model. The discrimination, calibration, and clinical practicality of the model were evaluated according to the area under the receiver operating characteristic curve (AUROC), calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC).ResultsA total of 13,361 patients were included, comprising 6,023, 2,582, and 4,756 patients in the training, internal validation, and external validation sets, respectively. The results revealed that the ACCI score, OP, PI, analgesics use, antibiotics use, psychotropic drug use, insurance type, and ALB were independent predictors for prolonged LOS. The eight-predictor LASSO logistic regression displayed high prediction ability, with an AUROC of 0.725 (95% confidence interval [CI]: 0.710–0.739), a sensitivity of 0.662 (95% CI: 0.639–0.686), and a specificity of 0.675 (95% CI: 0.661–0.689). The calibration curve (bootstraps = 1,000) showed good calibration. In addition, the DCA and CIC also indicated good clinical practicality. An operation interface on a web page (https://xxmyyz.shinyapps.io/prolonged_los1/) was also established to facilitate clinical use.ConclusionThe developed model can predict the risk of prolonged LOS in elderly T2DM patients diagnosed with CI, enabling clinicians to optimize bed management.

Velocity pulse with strong energy input is the significant feature of near-fault ground motions. Bridges close to or passing across seismic faults may suffer from higher failure risk, which is inseparable from the influence of velocity pulse. This study aims to evaluate the nonlinear response characteristics of bridge structures under various near-fault ground motion conditions. A typical isolated continuous girder bridge is adopted, and two corresponding finite element models, i.e., considering and ignoring the heating effect of lead core bearings (LRBs), are established based on the OpenSees platform. Then, a total of 40 near-fault ground motion records are selected, and the pulses are extracted. Both the energy-based and deformation-based seismic responses are captured and compared to reveal the differences for the isolated bridge subjected to the original waves and the extracted pulses. The results highlight that the accuracy of the seismic evaluation based on the extracted pulses strongly depends on the precondition that the pulse period is close to the fundamental period of the isolated bridge. Hence, inputting the extracted pulses for predicting the in-elastic seismic response of isolated bridges locating at near-fault region is not an adequate replacement for those original waves of near-fault ground motions. In addition, the heating effect of LRBs will be magnified for the seismic response of isolated bridges subjected to the extracted pulses, and it will mainly affect the seismic responses of bearings and piers, i.e., the former increases and the latter decreases.

Background: Aging is characterized by a decline in the adaptability and resistance of the body. In this study, Bushen Kangshuai Granules (BKG), as a kind of Chinese herbal formula, was developed and shown to alleviate aging-related symptoms.Methods: Self-controlled study combined with RNA-seq and metabonomics were used to expound the efficacy and safety of BKG and revealed the regulation mechanism of BKG treating aging. In vitro experiments were used to confirm the analytical results. The aging cell model of AC16 cells were treated with D-galactose. The RT-qPCR was used to detect the impact of BKG on telomere length. The DCFH-DA staining was used for detecting intracellular ROS. The targeted signaling pathway was selected and verified using Western blot.Results: After 8 weeks of treatment, BKG significantly reduced SOD level (p = 0.046), TCM aging symptoms (p < 0.001) and TNF-α level (p = 0.044) in the elderly participants. High-throughput sequencing showed that BKG reversed the expression of 70 and 79 age-related genes and metabolites, respectively. Further enrichment analysis indicated that BKG downregulated the PI3K-AKT signaling pathway, extracellular matrix (ECM)-receptor interaction, and Rap1 signaling pathway, while up-regulating sphingolipid metabolism. The results of in vitro experiments show that, after D-gal treatment, the viability and telomere length of AC16 cells significantly decreased (p < 0.05), while the expression of ROS increased (p < 0.05), BKG significantly increased the telomere length of AC16 cells and reduced the level of ROS expression (p < 0.05). In addition, BKG decreased the expression of THBS1, PDGFRA, and EPS8L1(p < 0.05), consistent with the RNA-seq results. Our results also showed that BKG affects PI3K-AKT signaling pathway.Conclusion: BKG can significantly improve aging-related symptoms and increase SOD levels, which may be associated with the reversal of the expression of various aging-related genes. The PI3K-AKT signaling pathway and sphingolipid metabolism may be potential mechanisms underlying BKG anti-aging effects.

BackgroundPost-stroke depression (PSD) is a prevalent psychiatric disorder affecting about one-third of stroke survivors, significantly hindering recovery and quality of life. PSD also imposes a substantial burden on caregivers and healthcare systems. Aromatherapy has shown promise in alleviating depression, anxiety, and sleep disorders. This pilot randomized controlled trial aims to assess the feasibility and preliminary efficacy of mixed herb aromatherapy in treating PSD. Feasibility outcomes encompass recruitment, intervention adherence, assessment completion and safety assessment. Secondary outcomes include evaluations of depression, anxiety, cognitive function, sleep quality, quality of life, and brain function using EEG and fNIRS.MethodsThis single-blind pilot randomized controlled trial will be conducted at the Second Rehabilitation Hospital of Shanghai, enrolling ninety-nine post-stroke patients with PSD. Participants will be randomized into three groups: a Non-Active Control Group receiving standardized rehabilitation therapy, a CBT Group receiving conventional rehabilitation with bi-weekly CBT sessions, and an Aromatherapy Group receiving conventional rehabilitation with daily aromatic inhalation sessions. Interventions will last for four weeks, with efficacy assessed at baseline, post-intervention, and one month post-intervention. Rating scales will be used to measure changes in depression, sleep quality, cognitive function, and quality of life. EEG and fNIRS will specifically be used to measure changes in cerebral cortex activity and their correlations with depression. Feasibility will be evaluated through recruitment, intervention adherence, assessment completion and safety assessment.DiscussionThis pilot study highlights the potential of mixed herb aromatherapy inhalation for treating PSD, addressing limitations of CBT by promoting self-management. While demonstrating feasibility through recruitment, adherence, assessment completion and safety assessment, the study also acknowledges limitations such as unequal intervention times, the lack of physical function data. And the use of culturally relevant plant powders may enhance compliance but limits generalizability. Despite these constraints, the study provides valuable preliminary data and insights into the mechanisms of aromatherapy, encouraging further research and development of effective PSD treatments.

The Mammalian orthoreovirus (MRV) infects various mammals, including humans, and is linked to gastrointestinal, respiratory, and neurological diseases. A recent outbreak in Liuzhou, Guangxi, China, led to the isolation of a new MRV strain, GXLZ2301, from fecal samples. This strain replicates in multiple cell lines and forms lattice-like structures. Infected cells exhibit single-cell death and syncytia formation. The virus’s titers peaked at 107.2 TCID50/0.1 mL in PK-15 and BHK cells, with the lowest at 103.88 TCID50/0.1 mL in A549 cells. Electron microscopy showed no envelope with a diameter of about 70 nm. Genetic analysis revealed GXLZ2301 as a recombinant strain with gene segments from humans, cows, and pigs, similar to type 3 MRV strains from Italy (2015-2016). Pathogenicity tests indicated that while the bovine MRV strain did not cause clinical symptoms in mice, it caused significant damage to the gut, lungs, liver, kidneys, and brain. The emergence of this MRV strain may pose a threat to the health of animals and humans, and it is recommended that its epidemiology and recombination be closely monitored.

IntroductionBaloxavir Marboxil is a per oral small-molecule antiviral for the treatment of influenza. While the efficacy and safety of Baloxavir Marboxil have been thoroughly characterized across an extensive clinical trial, studies on the effectiveness of Baloxavir Marboxil in a real-world setting are still scarce.MethodsWe conducted an ambispective, observational, multi-center study that enrolled uncomplicated in-fluenza outpatients treated with Baloxavir Marboxil or Oseltamivir in East China. The primary endpoint was time from treatment to alleviation of all influenza symptoms (TTAIS). The secondary endpoints included time from treatment to alleviation of fever (TTAF) and household transmission during the duration of influenza.ResultsA total of 509 patients were enrolled. The median TTAIS in the Baloxavir Marboxil group and the Oseltamivir group was 28.0 h (IQR, 20.0 to 50.0) and 48.0 h (IQR, 30.0 to 67.0), respectively. The median TTAF in the Baloxavir Marboxil group and the Oseltamivir group was 18 h (IQR, 10.0–24.0) and 30.0 h (IQR, 19.0–48.0). In the COX multivariable analysis, Baloxavir Marboxil reduced the duration of influenza symptoms (HR = 1.36 [95%CI:1.12–1.64], p = 0.002) and the duration of fever (HR = 1.93 [95%CI:1.48–2.52], p

Musculoskeletal disorders, especially chronic muscle pain, have a significant impact on public health, affecting millions worldwide. This review examines recent advancements in the diagnosis and management of myofascial pain, with a focus on the refined application of trigger point theory. This theory now incorporates an intricate model that blends biomechanical and neurophysiological mechanisms, essential for understanding the initiation and persistence of pain, and necessitating targeted therapeutic interventions. Utilizing a methodical approach, this paper categorizes muscle pain into three types: Muscle Belly Pain, Origin-Insertion Pain, and Referred Pain, as delineated in the most recent edition of “Myofascial Pain and Dysfunction—The Trigger Point Manual.” Such classification enhances diagnostic precision and therapeutic effectiveness by establishing a specific treatment protocol for each type of pain. The paper discusses the implications of various treatments, such as dry needling and manual therapy, which are informed by empirically derived trigger point charts. These charts are instrumental in pinpointing the exact locations of pain sources and customizing treatment plans. Moreover, this review critically assesses the evolving nature of trigger point charts and champions a holistic approach to pain management. It underscores the necessity of integrating biomechanics, kinesiology, and compensatory mechanisms to provide a comprehensive understanding that allows practitioners to address not only symptomatic pain but also the root causes of musculoskeletal disorders, thereby enhancing long-term patient care outcomes in clinical environments.

SignificanceSince the advent of Optical Coherence Tomography (OCT) two decades ago, there has been substantial advancement in our understanding of intravascular biology. Identifying culprit lesion pathology through OCT could precipitate a paradigm shift in the treatment of patients with Acute Coronary Syndrome. Given the technical prowess of OCT in the realm of cardiology, bibliometric analysis can reveal trends and research focal points in the application of OCT for cardiovascular diseases. Concurrently, meta-analyses provide a more comprehensive evidentiary base, supporting the clinical efficacy of OCT-guided Percutaneous Coronary Intervention (PCI).DesignThis study employs a dual approach of Bibliometric and Meta-analysis.MethodsRelevant literature from 2003 to 2023 was extracted from the Web of Science Core Collection (WoSCC) and analyzed using VOSviewer, CiteSpace, and R for publication patterns, countries, institutions, authors, and research hotspots. The study compares OCT-guided and coronary angiography-guided PCI in treating adult coronary artery disease through randomized controlled trials (RCTs) and observational studies. The study has been reported in the line with PRISMA and AMSTAR Guidelines.ResultsAdhering to inclusion and exclusion criteria, 310 publications were incorporated, demonstrating a continual rise in annual output. Chinese researchers contributed the most studies, while American research wielded greater influence. Analysis of trends indicated that research on OCT and angiography-guided PCI has become a focal topic in recent cohort studies and RCTs. In 11 RCTs (n = 5,277), OCT-guided PCI was not significantly associated with a reduction in the risk of Major Adverse Cardiac Events (MACE) (Odds ratio 0.84, 95% CI 0.65–1.10), cardiac death (0.61, 0.36–1.02), all-cause death (0.7, 0.49–1.02), myocardial infarction (MI) (0.88, 0.69–1.13), target lesion revascularization (TLR) (0.94, 0.7–1.27), target vessel revascularization (TVR) (1.04, 0.76–1.43), or stent thrombosis (0.72, 0.38–1.38). However, in 7 observational studies (n = 4,514), OCT-guided PCI was associated with a reduced risk of MACE (0.66, 0.48–0.91) and TLR (0.39, 0.22–0.68).ConclusionOur comprehensive review of OCT in cardiovascular disease literature from 2004 to 2023, encompassing country and institutional origins, authors, and publishing journals, suggests that OCT-guided PCI does not demonstrate significant clinical benefits in RCTs. Nevertheless, pooled results from observational studies indicate a reduction in MACE and TLR.

PurposeThe purpose of study was to describe the association between ferritin and all-cause mortality of cases with stroke.MethodsClinical data derived from Multiparameter Intelligent Monitoring in Intensive Care were analyzed. The primary endpoint was 30-day mortality. The potential prognostic roles of Ferritin L were analyzed by Cox proportional hazard models. The independent prognostic roles of Ferritin L in the cases were analyzed by smooth curve fitting.ResultsConcerning 30-day mortality, the HR (95% CI) for a high Ferritin (≥373) was 1.925 (1.298, 2.854; p = 0.00113), compared to a low ferritin (< 373). After adjusting for multiple confounders, the HR (95% CI) for a high Ferritin (≥373) was 1.782 (1.126, 2.820; p = 0.01367), compared to a low Ferritin (< 373). A non-linear association between Ferritin and 30-day mortality was found. Using recursive algorithm and two-piecewise linear regression model, inflection point (IP) was calculated, which was 2,204. On the left side of the IP, there was a positive relationship between Ferritin and 30-day mortality, and the effect size, 95% CI and p value were 1.0006 (1.0004, 1.0009) p

Senecavirus A (SVA) is an emerging virus that causes the vesicular disease in pigs, clinically indistinguishable from other high consequence vesicular diseases. This virus belongs to the genus Senecavirus in the family Picornaviridae. Its genome is a positive-sense, single-stranded RNA, approximately 7,300 nt in length, with a 3′ poly(A) tail but without 5′-end capped structure. SVA can efficiently propagate in different cells, including some non-pig-derived cell lines. A wild-type SVA was previously rescued from its cDNA clone using reverse genetics in our laboratory. In the present study, the BSR-T7/5 cell line was inoculated with the passage-5 SVA. At 12 h post-inoculation, SVA-infected and non-infected cells were independently collected for the analysis on comparative transcriptomics. The results totally showed 628 differentially expressed genes, including 565 upregulated and 63 downregulated ones, suggesting that SVA infection significantly stimulated the transcription initiation in cells. GO and KEGG enrichment analyses demonstrated that SVA exerted multiple effects on immunity-related pathways in cells. Furthermore, the RNA sequencing data were subjected to other in-depth analyses, such as the single-nucleotide polymorphism, transcription factors, and protein–protein interactions. The present study, along with our previous proteomics and metabolomics researches, provides a multi-omics insight into the interaction between SVA and its hosts.

IntroductionThis study was conducted to evaluate the effects of dietary galacto-oligosaccharides (GOS) and hyocholic acids (HCA) during late gestation and lactation on reproductive performance, colostrum quality, antioxidant capacity and gut microbiota in multiparous sows.MethodsA total of 60 healthy multiparous cross-bred sows (Landrace × Yorkshire) were randomly fed 4 groups diets as follows: the basal diets (CTRL group), or the basal diets containing only 600 mg/kg GOS (GOS group), 600 mg/kg GOS + 100 mg/kg HCA (GOS + Low HCA group), and 600 mg/kg + 200 mg/kg HCA (GOS + High HCA group) from d 85 of gestation to weaning. Multiple parameters of sows were determined.ResultsThere was a trend of shortening the labor process of sows (p = 0.07) in the GOS group and GOS + Low/High HCA group. Compared with the CTRL group, the GOS + Low/High HCA group increased the average piglets weight at birth (p

BackgroundCoronary heart disease (CHD) is representative of cardiovascular disease and the leading cause of death in humans. Previous studies have shown that kidney disease is associated with CHD, and current treatment options that can improve both cardiac and renal functions still have some limitations. The traditional Chinese medicine Bu-Shen-Huo-Xue granule (BSHXG) can promote blood rheology, inhibit platelet agglutination, and improve heart and kidney functions.MethodsThis is a multicenter, randomized, double-blind, placebo-controlled clinical trial. A total of 210 participants will be randomized to the intervention group and the placebo group. The Guang’anmen Hospital of China Academy of Chinese Medical Sciences is the leading center, and the Affiliated Hospital of Shandong University of Chinese Medicine and the First Affiliated Hospital of Guangzhou University of Chinese Medicine are the participating units. In addition to conventional pharmacotherapy for angina, the intervention group will receive BSHXG while the placebo group will receive BSHXG placebo. All participants will receive 2 months of treatment with 6 months of follow-up. The primary outcome is the efficacy of angina pectoris symptoms in CHD. Secondary outcomes are nitroglycerin arrest, ECG efficacy, Seattle Angina Questionnaire score, serology indicators, assessment of safety, and cardiovascular endpoint events. The transcriptome and metabolome will be used to screen biomarkers for diagnosis and efficacy evaluation.DiscussionThis study aimed to evaluate the efficacy and safety of Bu-Shen-Huo-Xue granule in the treatment of coronary heart disease, and to evaluate the benefits to patients with coronary heart disease from both cardiac and renal indicators.Trial registrationThis trial is approved by the Ethical Review Committee of the Guang’anmen Hospital China Academy of Chinese Medical Sciences with the number 2022-224-KY-01, and has been registered on the Chinese Clinical Trials Registry with the number ChiCTR2300070977 on 27 April 2023.

BackgroundsPrunus mume in the Rosaceae and commonly referred to as mei or Chinese plum is widely used as a traditional ornamental flowering plant and fruit tree in China. Although some population and genetic analyses have been conducted for this species, no extensive comparisons of genetic variation from plastomes have yet been investigated.MethodsWe de novo assembled a total of 322 complete P. mume plastomes in this study and did a series of comparative analyses to better resolve pan-plastomic patterns of P. mume. To determine the phylogeny and domestication history of this species, we reconstructed the phylogenetic tree of Prunus genus, and resolved the population structure of P. mume. We also examined the nucleotide variation of P. mume to find potential DNA barcodes.ResultsThe assembled plastomes exhibited a typical quadripartite structure and ranged from 157,871 bp to 158,213 bp in total size with a GC content ranging from 36.73 to 36.75%. A total of 112 unique genes were identified. Single nucleotide variants (SNVs) were the most common variants found among the plastomes, followed by nucleotide insertions/deletions (InDels), and block substitutions with the intergenic spacer (IGS) regions containing the greatest number of variants. From the pan-plastome data six well-supported genetic clusters were resolved using multiple different population structure analyses. The different cultivars were unevenly distributed among multiple clades. We also reconstructed a phylogeny for multiple species of Prunus to better understand genus level diversity and history from which a complex introgressive relationship between mei and other apricots/plums was resolved.ConclusionThis study constructed the pan-plastome of P. mume, which indicated the domestication of P. mume involved multiple genetic origins and possible matrilineal introgression from other species. The phylogenetic analysis in Prunus and the population structure of P. mume provide an important maternal history for Prunus and the groundwork for future studies on intergenomic sequence transfers, cytonuclear incompatibility, and conservation genetics.

IntroductionTotal knee arthroplasty (TKA) is a widely-used treatment for end-stage knee osteoarthritis. However, it is common for patients to experience issues with knee joint function and abnormal gait following the surgery. Previous studies have primarily focused on concentric contraction of the quadriceps during TKA, neglecting the potential benefits of eccentric isokinetic training for the hamstrings. This protocol outlines a randomized, single-blind, controlled trial aimed at assessing the impact of eccentric isokinetic training for the hamstring muscles on pain, function, and gait in patients after TKA.Methods and analysisFifty participants between the ages of 50 and 80 with knee osteoarthritis undergo unilateral total knee arthroplasty (TKA) for the first time. They will be transferred to the rehabilitation department 10–14 days after the operation. The participants are randomly divided into two groups, with 25 participants in each group: the control group and the Hamstring training group. The Control group will receive routine rehabilitation treatment, while the Hamstring training group will receive a combination of routine rehabilitation treatment and isokinetic eccentric training of the hamstring. The intervention will last four consecutive weeks. Both groups will be assessed at three different times: before the intervention, after 4 weeks of intervention, and 4 weeks after the interventions (follow-up). The primary outcome will be functional capacity (TUGT) and Hospital for Special knee Score (HSS). Secondary outcomes will be knee-related health status (isokinetic knee position perception, Peak torque of hamstring strength), pain intensity (Visual analog scale, VAS) and 3D gait analysis.DiscussionThe study aims to provide relevant evidence on the effectiveness of eccentric hamstring muscle contraction training in improving knee joint function and walking function after TKA.Clinical trial registrationhttps://www.chictr.org.cn/showproj.html?proj=195544, Identifier ChiCTR2300073497.

IntroductionAnesthesia plays a critical role in modern surgical procedures by ensuring patient pain management and safety. This study aimed to investigate the knowledge and attitude of surgical patients and their families toward anesthesia.MethodsThis prospective, cross-sectional study included patients and their families in Wenzhou, China. Data collection and the measurement of knowledge and attitude scores were administered using a self-administered questionnaire.Results503 participants (69.98% patients, 30.02% families) were included. The mean knowledge and attitude scores were 7.93 ± 6.11 (possible range: 0–26), and 32.64 ± 2.59 (possible range: 8–40), respectively, indicating an inadequate knowledge and positive attitude. Moreover, a multivariable logistic regression analysis showed that age [odd ratio (OR) = 0.394, p = 0.018], residence (OR = 0.424, p = 0.002), household income per month (OR = 0.297 ~ 0.380, p

IntroductionThe association between mutations in susceptibility genes and the occurrence of ovarian cancer has been extensively studied. Previous research has primarily concentrated on genes involved in the homologous recombination repair pathway, particularly BRCA1 and BRCA2. However, a wider range of genes related to the DNA damage response pathways has not been fully explored.MethodsTo investigate the mutation characteristics of cancer susceptibility genes in the Chinese ovarian cancer population and the associations between gene mutations and clinical data, this study initially gathered a total of 1171 Chinese ovarian cancer samples and compiled a dataset of germline mutations in 171 genes.ResultsIn this study, it was determined that MC1R and PRKDC were high-frequency ovarian cancer susceptibility genes in the Chinese population, exhibiting notable distinctions from those in European and American populations; moreover high-frequency mutation genes, such as MC1R: c.359T>C and PRKDC: c.10681T>A, typically had high-frequency mutation sites. Furthermore, we identified c.8187G>T as a characteristic mutation of BRCA2 in the Chinese population, and the CHEK2 mutation was significantly associated with the early onset of ovarian cancer, while the CDH1 and FAM175A mutations were more prevalent in Northeast China. Additionally, Fanconi anemia pathway-related genes were significantly associated with ovarian carcinogenesis.ConclusionIn summary, this research provided fundamental data support for the optimization of ovarian cancer gene screening policies and the determination of treatment, and contributed to the precise intervention and management of patients.

The Period (PER) gene family is one of the core components of the circadian clock, with substantial correlations between the PER genes and cancers identified in extensive researches. Abnormal mutations in PER genes can influence cell function, metabolic activity, immunity, and therapy responses, thereby promoting the initiation and development of cancers. This ultimately results in unequal cancers progression and prognosis in patients. This leads to variable cancer progression and prognosis among patients. In-depth studies on the interactions between the PER genes and cancers can reveal novel strategies for cancer detection and treatment. In this review, we aim to provide a comprehensive overview of the latest research on the role of the PER gene family in cancer.

Objective: Bendamustine was approved for treating chronic lymphocytic leukemia and indolent B-cell non-Hodgkin lymphoma. Despite its therapeutic benefits, the long-term safety of bendamustine in a large population remains inadequately understood. This study evaluates the adverse events (AEs) associated with bendamustine, using a real-world pharmacovigilance database to support its clinical application.Methods: We conducted a post-marketing risk analysis to assess the association between bendamustine and its AEs. Data were extracted from the US FDA’s Adverse Event Reporting System (FAERS), covering the period from January 2017 to September 2023. The characteristics of bendamustine-associated AEs and the onset time were further analyzed. Statistical analysis was performed using MYSQL 8.0, Navicat Premium 15, Microsoft EXCEL 2016, and Minitab 21.0.Results: 9,461,874 reports were collected from the FAERS database, 9,131 identified bendamustine as the “primary suspected” drug. We identified 331 significant disproportionality preferred terms (PTs). Common AEs included pyrexia, neutropenia, infusion site reaction, progressive multifocal leukoencephalopathy (PML), injection site vasculitis, and pneumonia—all documented on bendamustine’s label. Notably, 16 unexpected and significant AEs were discovered, including hypogammaglobulinemia, which is concerning due to its potential to increase infection susceptibility following bendamustine treatment. Other significant findings were anaphylactic reactions, PML, and cutaneous malignancies, suggesting updates to the drug’s label may be necessary. Physicians should monitor for neurological and skin changes in patients and discontinue treatment if PML is suspected. Moreover, the median onset time for bendamustine-associated AEs was 13 days, with an interquartile range [IQR] of 0–59 days, predominantly occurring on the first day post-initiation. The β of bendamustine-related AEs suggested risk reduction over time.Conclusion: Our study uncovered some potential pharmacovigilance signals for bendamustine, providing important insights for its safe and effective clinical use.

BackgroundEsophageal cancer (EC) is a prevalent malignancy characterized by a low 5-year survival rate, primarily attributed to delayed diagnosis and limited therapeutic options. Currently, early detection of EC heavily relies on endoscopy and pathological examination, which pose challenges due to their invasiveness and high costs, leading to low patient compliance. The detection of DNA methylation offers a non-endoscopic, cost-effective, and secure approach that holds promising prospects for early EC detection.MethodsTo identify improved methylation markers for early EC detection, we conducted a comprehensive review of relevant literature, summarized the performance of DNA methylation markers based on different input samples and analytical methods in EC early detection and screening.FindingsThis review reveals that blood cell free DNA methylation-based method is an effective non-invasive method for early detection of EC, although there is still a need to improve its sensitivity and specificity. Another highly sensitive and specific non-endoscopic approach for early detection of EC is the esophageal exfoliated cells based-DNA methylation analysis. However, while there are substantial studies in esophageal adenocarcinoma, further more validation is required in esophageal squamous cell carcinoma.ConclusionIn conclusion, DNA methylation detection holds significant potential as an early detection and screening technology for EC.

The cultivation system requires that the approach providing biomass for all types of metabolic analysis is of excellent quality and reliability. This study was conducted to enhance the efficiency and yield of antifungal substance (AFS) production in Streptomyces yanglinensis 3–10 by optimizing operation conditions of aeration, agitation, carbon source, and incubation time in a fermenter. Dissolved oxygen (DO) and pH were found to play significant roles in AFS production. The optimum pH for the production of AFS in S. yanglinensis 3–10 was found to be 6.5. As the AFS synthesis is generally thought to be an aerobic process, DO plays a significant role. The synthesis of bioactive compounds can vary depending on how DO affects growth rate. This study validates that the high growth rate and antifungal activity required a minimum DO concentration of approximately 20% saturation. The DO supply in a fermenter can be raised once agitation and aeration have been adjusted. Consequently, DO can stimulate the development of bacteria and enzyme production. A large shearing effect could result from the extreme agitation, harming the cell and deactivating its products. The highest inhibition zone diameter (IZD) was obtained with 3% starch, making starch a more efficient carbon source than glucose. Temperature is another important factor affecting AFS production. The needed fermentation time would increase and AFS production would be reduced by the too-low operating temperature. Furthermore, large-scale fermenters are challenging to manage at temperatures that are far below from room temperature. According to this research, 28°C is the ideal temperature for the fermentation of S. yanglinensis 3–10. The current study deals with the optimization of submerged batch fermentation involving the modification of operation conditions to effectively enhance the efficiency and yield of AFS production in S. yanglinensis 3–10.

BackgroundObservational studies have shown that micronutrients can affect the occurrence of frailty. However, it is not clear whether there is a causal relationship between the two. This study aimed to explore the causal relationship between circulating micronutrient levels and frailty risk using a two-sample Mendelian randomization (TSMR) approach.MethodsWe gathered and screened instrumental variables (IVs) for six circulating micronutrients, including vitamin B12, vitamin B6, folate, vitamin C, vitamin D, and vitamin E, from published genome-wide association studies (GWAS) and the IEU OpenGWAS open database. Summary statistics for frailty were obtained from a GWAS meta-analysis, including the UK Biobank and TwinGene (N = 175,226). We performed two independent TSMR analyses and a meta-analysis based on the two independent MR estimates to assess the causal relationship between circulating micronutrientn and frailty.ResultsOur study found, no causal relationship between genetically predicted vitamin D (β = −0.059, p = 0.35), vitamin B6 (β = 0.006, p = 0.80), vitamin E (β = −0.011, p = 0.79), vitamin C (β = −0.044, p = 0.06), vitamin B12 (β = −0.027, p = 0.37), and folate (β = 0.029, p = 0.17), with frailty.ConclusionThis study showed that these six micronutrients did not reduce the risk of developing frailty. However, we think it is necessary further to investigate the relationship and mechanisms between micronutrients and frailty using methods such as randomized controlled trials.

BackgroundThe plant secondary metabolites (PSMs), as important plant resistance indicators, are important targets for screening plant insect resistance breeding. In this study, we aimed to investigate whether the population of Zeuzera coffeae (ZC) is affected by different varieties of Carya illinoinensis PSMs content. At the same time, the structure and function of the gut microbiome of ZC were also analyzed in relation to different pecan varieties.MethodsWe counted the populations of ZC larvae in four pecan varieties and determined the content of four types of PSMs. The structure and function of the larval gut microbiota were studied in connection to the number of larvae and the content of PSMs. The relationships were investigated between larval number, larval gut microbiota, and PSM content.ResultsWe found that the tannins, total phenolics, and total saponins of 4 various pecans PSMs stifled the development of the ZC larval population. The PSMs can significantly affect the diversity and abundance of the larval gut microbiota. Enrichment of ASV46 (Pararhizobium sp.), ASV994 (Olivibacter sp.), ASV743 (Rhizobium sp.), ASV709 (Rhizobium sp.), ASV671 (Luteolibacter sp.), ASV599 (Agrobacterium sp.), ASV575 (Microbacterium sp.), and ASV27 (Rhizobium sp.) in the gut of larvae fed on high-resistance cultivars was positively associated with their tannin, total saponin, and total phenolic content. The results of the gut microbiome functional prediction for larvae fed highly resistant pecan varieties showed that the enriched pathways in the gut were related to the breakdown of hazardous chemicals.ConclusionOur findings provide further evidence that pecan PSMs influence the structure and function of the gut microbiota, which in turn affects the population stability of ZC. The study’s findings can serve as a theoretical foundation for further work on selecting ZC-resistant cultivars and developing green management technology for ZC.

In order to realize the real-time processing and analysis of astronomical ultra-wide bandwidth signals, this study proposes a sub-band division algorithm based on RFSoC. The algorithm uses Kaiser window to design FIR prototype low-pass filter, adopts critical sampling polyphase filter bank to decompose ultra-wide bandwidth signal into several sub-bands, and encapsulates each sub-band into VDIF data frame and sends it to GPU server. The algorithm is implemented on RFSoC platform, and its effectiveness is verified by simulation and actual observation. The experimental results show that the algorithm can divide the astronomical ultra-wide bandwidth signal into multiple sub-bands in real time, packetize and transmit them to GPU. This research provides reproducible design and project for ultra-wide bandwidth signal sub-band division with low spectrum leakage and aliasing, high data accuracy, and fast processing speed.

Superoxide dismutase (SOD) protects plants from abiotic stress-induced reactive oxygen species (ROS) damage. Here, the effects of cadmium (Cd) exposure on ROS accumulation and SOD isozymes, as well as the identification of significant SOD isozyme genes, were investigated under different Cd stress treatments to Zhe-Maidong (Ophiopogon japonicus). The exposure to Cd stress resulted in a notable elevation in the SOD activity in roots. Cu/ZnSODa and Cu/ZnSODb were the most critical SOD isozymes in response to Cd stress, as indicated by the detection results for SOD isozymes. A total of 22 OjSOD genes were identified and classified into three subgroups, including 10 OjCu/ZnSODs, 6 OjMnSODs, and 6 OjFeSODs, based on the analysis of conserved motif and phylogenetic tree. Cu/ZnSOD-15, Cu/ZnSOD-18, Cu/ZnSOD-20, and Cu/ZnSOD-22 were the main genes that control the increase in SOD activity under Cd stress, as revealed via quantitative PCR and transcriptome analysis. Additionally, under various heavy metal stress (Cu2+, Fe2+, Zn2+, Mn2+), Cu/ZnSOD-15, Cu/ZnSOD-18, and Cu/ZnSOD-22 gene expression were significantly upregulated, indicating that these three genes play a critical part in resisting heavy metal stress. The molecular docking experiments performed on the interaction between oxygen ion (O2•−) and OjSOD protein have revealed that the critical amino acid residues involved in the binding of Cu/ZnSOD-22 to the substrate were Pro135, Ile136, Ile140, and Arg144. Our findings provide a solid foundation for additional functional investigations on the OjSOD genes, as well as suggestions for improving genetic breeding and agricultural management strategies to increase Cd resistance in O. japonicus.

IntroductionDanon disease is an X-linked disorder caused by pathogenic variants in lysosome-associated membrane protein 2 (LAMP2) gene, typically characterized by the triad of hypertrophic cardiomyopathy, myopathy, and intellectual disability. However, many patients may not present the typical presentation, especially in the early stage. Electrocardiogram (ECG) abnormalities can be found in almost all patients, with Wolff–Parkinson–White (WPW) syndrome being the most common. We reported the case of a 51-year-old woman who experienced multiple types of arrhythmias over three decades and was diagnosed with Danon disease late by genetic testing.Case summaryA 51-year-old woman with a 36-year history of intermittent palpitations was admitted due to hemodynamically stable ventricular tachycardia (VT). Her past medical history revealed multiple arrhythmias and ECG abnormalities in her 30s and 40s, including WPW syndrome with paroxysmal supraventricular tachycardia, paroxysmal atrial flutter, atrial fibrillation, ventricular tachycardia, and complete left bundle branch block. She denied any family history of cardiovascular disease or sudden death. Upon arrival, her vital signs were unremarkable. Cardiovascular magnetic resonance (CMR) imaging revealed left ventricular enlargement and late gadolinium enhancement (LGE) in the anterior, inferior, and lateral walls. Subsequent, whole-exome sequencing (WES) gene testing revealed a pathogenic heterozygous variant in LAMP2 gene (c.696T>A; p.Cys232Ter), which confirmed the diagnosis of Danon disease.ConclusionGenetic testing should be considered in patients who display multiple arrhythmias with LV structural abnormalities of unknown etiology for a possible Danon disease.

ObjectiveAccumulated evidence has suggested a relatively high recurrence rate in early-stage cervical cancer (CC) patients with risk factors. This study aimed to assess the efficacy and safety of consolidation chemotherapy following adjuvant therapy (concurrent chemoradiotherapy (CCRT) or radiotherapy (RT) alone) in stage IB-IIA CC patients with risk factors.MethodsA total of 237 stage IB-IIA CC patients who received radical surgery between January 2014 and December 2021 were included in the retrospective study. According to the types of adjuvant therapies, the patients were classified into the control group (CCRT or RT alone) and the study group (consolidation chemotherapy following CCRT or RT alone). The propensity score matching (PSM) was used to balance baseline characteristics between the two groups. The primary end points of the study were disease-free survival (DFS) and overall survival (OS).ResultsFor the entire cohort, no significant difference was observed in the DFS or OS between the study and control group, which was also confirmed in the PSM cohort (n=124). The multivariate analysis identified the high-risk factor type was an independent adverse prognostic factor for the patients. In patients with high risk factors, consolidation chemotherapy following adjuvant therapy was significantly associated with better clinical outcomes and identified as an independent prognostic favorable factor. Moreover, this association remained statistically significant in high-risk patients with ≥2 metastatic lymph nodes. In patients with intermediate risk factors, consolidation chemotherapy following adjuvant therapy was unrelated to DFS or OS. The safe assessment demonstrated consolidation chemotherapy following adjuvant therapy was significantly correlated with higher rates of ≥ grade 3 hematologic toxicities in both the global and subgroup analysis stratified by risk factor type.ConclusionConsolidation chemotherapy after adjuvant therapy provided survival benefits in stage IB-IIA CC patients with high risk factors, particularly those with ≥2 metastatic lymph nodes. However, related hematologic toxicities should be alerted in patient management. The actual efficacy and safety of consolidation chemotherapy still need to be investigated in more well-designed clinical trials.

Introduction: Ischemic stroke is the second most common chronic disease worldwide and is associated with high morbidity and mortality. Thromboembolism and platelet aggregation are the most characteristic features of stroke. Other than aspirin, no standard, accepted, or effective treatment for acute ischemic stroke has been established. Consequently, it is essential to identify novel therapeutic compounds for this condition.Methods: In this study, novel ozagrel/paeonol-containing codrugs were synthesized and characterized using 1H-NMR, 13C-NMR, and mass spectroscopy. Their antiplatelet aggregation activity was evaluated, with compound PNC3 found to exhibit the best effect. Subsequently, studies were conducted to assess its neuroprotective effect, pharmacokinetic properties and model its binding mode to P2Y12 and TXA2, two proteins critical for platelet aggregation.Results: The results indicated that PNC3 has good bioavailability and exerts protective effects against oxygen-glucose deprivation injury in PC12 cells. Molecular docking analysis further demonstrated that the compound interacts with residues located in the active binding sites of the target proteins.Conclusion: The codrugs synthesized in this study display promising pharmacological activities and have the potential for development as an oral formulation.

With the surge in astronomical data volume, modern astronomical research faces significant challenges in data storage, processing, and access. The I/O bottleneck issue in astronomical data processing is particularly prominent, limiting the efficiency of data processing. To address this issue, this paper proposes a tiered storage algorithm based on the access characteristics of astronomical data. The C4.5 decision tree algorithm is employed as the foundation to implement an astronomical data access correlation algorithm. Additionally, a data copy migration strategy is designed based on tiered storage technology to achieve efficient data access. Preprocessing tests were conducted on 418GB NSRT (Nanshan Radio Telescope) formaldehyde spectral line data, showcasing that tiered storage can potentially reduce data processing time by up to 38.15%. Similarly, utilizing 802.2 GB data from FAST (Five-hundred-meter Aperture Spherical radio Telescope) observations for pulsar search data processing tests, the tiered storage approach demonstrated a maximum reduction of 29.00% in data processing time. In concurrent testing of data processing workflows, the proposed astronomical data heat correlation algorithm in this paper achieved an average reduction of 17.78% in data processing time compared to centralized storage. Furthermore, in comparison to traditional heat algorithms, it reduced data processing time by 5.15%. The effectiveness of the proposed algorithm is positively correlated with the associativity between the algorithm and the processed data. The tiered storage algorithm based on the characteristics of astronomical data proposed in this paper is poised to provide algorithmic references for large-scale data processing in the field of astronomy in the future.

AimsTo evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of cetagliptin (CAS number:2243737-33-7) in Chinese patients with type 2 diabetes mellitus (T2DM). A population PK/PD model was developed to quantify the PK and PD characteristics of cetagliptin in patients.Materials and methods32 Chinese adults with T2DM were enrolled in this study. The subjects were randomly assigned to receive either cetagliptin (50 mg or 100 mg), placebo, or sitagliptin (100 mg) once daily for 14 days. Blood samples were collected for PK and PD analysis. Effects on glucose, insulin, C-peptide, and glucagon were evaluated following an oral glucose tolerance test (OGTT) (day15). Effects on HbA1c and glycated albumin (GA), and safety assessments were also conducted. Meanwhile, a population PK/PD model was developed by a sequential two-step analysis approach using Phoenix.ResultsFollowing multiple oral doses, cetagliptin was rapidly absorbed and the mean half-life were 34.9-41.9 h. Steady-state conditions were achieved after 1 week of daily dosing and the accumulation was modest. The intensity and duration of DPP-4 inhibition induced by 50 mg cetagliptin were comparable with those induced by sitagliptin, and 100 mg cetagliptin showed a much longer sustained DPP-4 inhibition (≥80%) than sitagliptin. Compared with placebo group, plasma active GLP-1 AUEC0-24h increased by 2.20- and 3.36-fold in the 50 mg and 100 mg cetagliptin groups. A decrease of plasma glucose and increase of insulin and C-peptide were observed following OGTT in cetagliptin groups. Meanwhile, a tendency of reduced GA was observed, whereas no decreasing trend was observed in HbA1c. All adverse events related to cetagliptin and sitagliptin were assessed as mild. A population PK/PD model was successfully established. The two-compartment model and Sigmoid-Emax model could fit the observed data well. Total bilirubin (TBIL) was a covariate of volume of peripheral compartment distribution (V2), and V2 increased with the increase of TBIL.ConclusionsCetagliptin was well tolerated, inhibited plasma DPP-4 activity, increased plasma active GLP-1 levels, and exhibited a certain trend of glucose-lowering effect in patients with T2DM. The established population PK/PD model adequately described the PK and PD characteristics of cetagliptin.

BackgroundParkinson’s disease (PD) is a prevalent neurodegenerative disorder that significantly benefits from early diagnosis for effective disease management and intervention. Despite advancements in medical technology, there remains a critical gap in the early and non-invasive detection of PD. Current diagnostic methods are often invasive, expensive, or late in identifying the disease, leading to missed opportunities for early intervention.ObjectiveThe goal of this study is to explore the efficiency and accuracy of combining fNIRS technology with machine learning algorithms in diagnosing early-stage PD patients and to evaluate the feasibility of this approach in clinical practice.MethodsUsing an ETG-4000 type near-infrared brain function imaging instrument, data was collected from 120 PD patients and 60 healthy controls. This cross-sectional study employed a multi-channel mode to monitor cerebral blood oxygen changes. The collected data were processed using a general linear model and β values were extracted. Subsequently, four types of machine learning models were developed for analysis: Support vector machine (SVM), K-nearest neighbors (K-NN), random forest (RF), and logistic regression (LR). Additionally, SHapley Additive exPlanations (SHAP) technology was applied to enhance model interpretability.ResultsThe SVM model demonstrated higher accuracy in differentiating between PD patients and control group (accuracy of 85%, f1 score of 0.85, and an area under the ROC curve of 0.95). SHAP analysis identified the four most contributory channels (CH) as CH01, CH04, CH05, and CH08.ConclusionThe model based on the SVM algorithm exhibited good diagnostic performance in the early detection of PD patients. Future early diagnosis of PD should focus on the Frontopolar Cortex (FPC) region.

With the continuous development of nuclear technology, the radiation exposure caused by radiation therapy is a serious health hazard. It is of great significance to further develop effective radiation countermeasures. B cells easily succumb to irradiation exposure along with immunosuppressive response. The approach to ameliorate radiation-induced B cell damage is rarely studied, implying that the underlying mechanisms of B cell damage after exposure are eager to be revealed. Recent studies suggest that Notch signaling plays an important role in B cell-mediated immune response. Notch signaling is a critical regulator for B cells to maintain immune function. Although accumulating studies reported that Notch signaling contributes to the functionality of hematopoietic stem cells and T cells, its role in B cells is scarcely appreciated. Presently, we discussed the regulation of Notch signaling on B cells under radiation exposure to provide a scientific basis to prevent radiation-induced B cell damage.

BackgroundA large number of literatures show that rhythmic auditory stimulation (RAS) can effectively improve Parkinson’s disease (PD) patients’ gait speed, frequency and speed. Its application and curative effect on upper limb motor function is relatively few.ObjectiveBy studying the immediate effect of RAS with different rhythms on the prefrontal cortex (PFC) blood oxygen response during upper limb movement in PD patients, this study discusses the potential neurophysiological mechanism of RAS on upper limb movement in PD patients, which is expected to provide guidance for patients with upper limb dysfunction such as Parkinson’s disease.MethodsIn this study, 31 PD patients with upper limb static tremors were recruited to complete the nail board task on the healthy upper limb under the baseline rhythm, slow rhythm and fast rhythm provided by the therapist. At the same time, fNIRS was used to observe the blood oxygen response of PFC.ResultsThere was no significant main effect onsidein all brain regions (p > 0.05), and there was no interaction between rhythm and side (p > 0.05); Except lPFC, the main effect of rhythm in other brain regions was significant (p

ObjectivesThe most frequent cause of kidney damage in systemic lupus erythematosus (SLE) is lupus nephritis (LN), which is also a significant risk factor for morbidity and mortality. Lactate metabolism and protein lactylation might be related to the development of LN. However, there is still a lack of relative research to prove the hypothesis. Hence, this study was conducted to screen the lactate-related biomarkers for LN and analyze the underlying mechanism.MethodsTo identify differentially expressed genes (DEGs) in the training set (GSE32591, GSE127797), we conducted a differential expression analysis (LN samples versus normal samples). Then, module genes were mined using WGCNA concerning LN. The overlapping of DEGs, critical module genes, and lactate-related genes (LRGs) was used to create the lactate-related differentially expressed genes (LR-DEGs). By using a machine-learning algorithm, ROC, and expression levels, biomarkers were discovered. We also carried out an immune infiltration study based on biomarkers and GSEA.ResultsA sum of 1259 DEGs was obtained between LN and normal groups. Then, 3800 module genes in reference to LN were procured. 19 LR-DEGs were screened out by the intersection of DEGs, key module genes, and LRGs. Moreover, 8 pivotal genes were acquired via two machine-learning algorithms. Subsequently, 3 biomarkers related to lactate metabolism were obtained, including COQ2, COQ4, and NDUFV1. And these three biomarkers were enriched in pathways ‘antigen processing and presentation’ and ‘NOD-like receptor signaling pathway’. We found that Macrophages M0 and T cells regulatory (Tregs) were associated with these three biomarkers as well.ConclusionOverall, the results indicated that lactate-related biomarkers COQ2, COQ4, and NDUFV1 were associated with LN, which laid a theoretical foundation for the diagnosis and treatment of LN.

This study investigates the clinical effects of the novel Traditional Chinese Medicine (TCM) topical wash used in combination with negative pressure irrigation and tadalafil for the treatment of vascular erectile dysfunction. Eighty-seven patients with vascular erectile dysfunction were divided into an observation group and a control group. The observation group was administered negative pressure irrigation (TCM) in combination with oral tadalafil for four weeks, and the control group was administered oral tadalafil for four weeks. The observation group included 21 patients with arterial erectile dysfunction and 22 with intravenous erectile dysfunction. After treatment, IIEF-5, EHS, GAD scores, PSV, EDV and RI in observation group were improved compared with those before treatment (P = 0.000, 0.000, 0.000, L0.000/R0.000, L0.000/R0.000, L0.003/R0.000). Erectile function (IIEF-5, EHS) was significantly improved compared with the control group (P = 0.008, 0.002). In the observation group, there were 21 cases of arterial erectile dysfunction and 22 cases of intravenous erectile dysfunction. After treatment, PSV of arterial ED improved significantly (P = L0.000/R0.000), but EDV did not decrease significantly (P = L0.084/R 0.098). In patients with venous ED, PSV increased (P = L0.026/R0.032) and EDV decreased significantly (P = L0.000/R0.000). These findings suggest that TCM negative pressure lavage combined with tadalafil improves the blood supply of the penile artery, relaxes smooth muscle, and improves the closing mechanism of venous vessels in patients with vascular erectile dysfunction, ultimately improving the erectile function.

Introduction: The application prospects of percutaneous endoscopic lumbar discectomy (PELD) as a minimally invasive spinal surgery method in the treatment of lumbar disc herniation are extensive. This study aims to find the optimal entry angle for the trephine at the L4/5 intervertebral space, which causes less lumbar damage and has greater postoperative stability. To achieve this, we conduct a three-dimensional simulated analysis of the degree of damage caused by targeted puncture-based trephine osteotomy on the lumbar spine.Methods: We gathered clinical CT data from patients to construct a lumbar model. This model was used to simulate and analyze the variations in trephine osteotomy volume resulting from targeted punctures at the L4/5 interspace. Furthermore, according to these variations in osteotomy volume, we created Finite Element Analysis (FEA) models specifically for the trephine osteotomy procedure. We then applied mechanical loads to conduct range of motion and von Mises stress analyses on the lumbar motion unit.Results: In percutaneous endoscopic interlaminar discectomy, the smallest osteotomy volume occurred with a 20° entry angle, close to the base of the spinous process. The volume increased at 30° and reached its largest at 40°. In percutaneous transforaminal endoscopic discectomy, the largest osteotomy volume was observed with a 50° entry angle, passing through the facet joints, with smaller volumes at 60° and the smallest at 70°. In FEA, M6 exhibited the most notable biomechanical decline, particularly during posterior extension and right rotation. M2 and M3 showed significant differences primarily in rotation, whereas the differences between M3 and M4 were most evident in posterior extension and right rotation. M5 displayed their highest stress levels primarily in posterior extension, with significant variations observed in right rotation alongside M4.Conclusion: The appropriate selection of entry sites can reduce lumbar damage and increase stability. We suggest employing targeted punctures at a 30° angle for PEID and at a 60° angle for PTED at the L4/5 intervertebral space. Additionally, reducing the degree of facet joint damage is crucial to enhance postoperative stability in lumbar vertebral motion units.

The principal pathogen responsible for chronic urinary tract infections, immunocompromised hosts, and cystic fibrosis patients is Pseudomonas aeruginosa, which is difficult to eradicate. Due to the extensive use of antibiotics, multidrug-resistant P. aeruginosa has evolved, complicating clinical therapy. Therefore, a rapid and efficient approach for detecting P. aeruginosa strains and their resistance genes is necessary for early clinical diagnosis and appropriate treatment. This study combines recombinase polymerase amplification (RPA) and clustered regularly interspaced short palindromic repeats-association protein 13a (CRISPR-Cas13a) to establish a one-tube and two-step reaction systems for detecting the mexX gene in P. aeruginosa. The test times for one-tube and two-step RPA-Cas13a methods were 5 and 40 min (including a 30 min RPA amplification reaction), respectively. Both methods outperform Quantitative Real-time Polymerase Chain Reactions (qRT-PCR) and traditional PCR. The limit of detection (LoD) of P. aeruginosa genome in one-tube and two-step RPA-Cas13a is 10 aM and 1 aM, respectively. Meanwhile, the designed primers have a high specificity for P. aeruginosa mexX gene. These two methods were also verified with actual samples isolated from industrial settings and demonstrated great accuracy. Furthermore, the results of the two-step RPA-Cas13a assay could also be visualized using a commercial lateral flow dipstick with a LoD of 10 fM, which is a useful adjunt to the gold-standard qRT-PCR assay in field detection. Taken together, the procedure developed in this study using RPA and CRISPR-Cas13a provides a simple and fast way for detecting resistance genes.

ObjectivesThis study aimed to evaluate the clinical performance of plasma cell-free DNA (cfDNA) next-generation sequencing (NGS) for pathogen detection in patients with sepsis.MethodsA total of 43 pairs of blood and plasma samples form 33 blood culture-positive patients were used as testing samples in metagenomic NGS (mNGS) and NGS of 16S ribosomal RNA gene amplicons (16S rRNA NGS). The results of routine tests, including microbial culture, complete blood count, and biochemical tests, were collected from electronic medical records.ResultsUsing blood as an mNGS testing sample, the proportion of host DNA was 99.9%, with only three bacteria and no fungi detected. When using plasma in mNGS, the proportion of host DNA was approximately 97%, with 84 bacteria and two fungi detected. Notably, 16S rRNA NGS detected 15 and 16 bacteria in 43 pairs of blood and plasma samples, respectively. Blood culture detected 49 bacteria (23 gram-negative bacilli and 26 gram-positive cocci) and four fungi, with 14 bacteria considered contaminants by clinical microbiologists. For all blood cultures, plasma cfDNA mNGS detected 78.26% (19/23) gram-negative rods, 17% (2/12) gram-positive cocci, and no fungi. Compared to blood cultures, the sensitivity and specificity of plasma cfDNA mNGS for detecting bacteria and fungi were 62.07% and 57.14%, respectively.ConclusionCompared to blood, plasma is more suitable for the detection of bloodstream infections using mNGS and is less affected by host DNA. The positive detection rate of plasma cfDNA mNGS for bloodstream infections caused by gram-negative bacteria was higher than that caused by gram-positive cocci.