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Abstract This study aimed to investigate the knowledge, attitude, and practice (KAP) of non-emergency surgical patients toward anesthesia. This cross-sectional study was conducted between May and October 2023 at Zibo Central Hospital among non-emergency surgical patients. A total of 429 valid questionnaires were enrolled (mean age: 42.81 ± 13.17 years old; 227 (52.91%) females). The mean KAP scores were 7.79 ± 3.95 (possible range: 0–18), 32.35 ± 2.80 (possible range: 8–40), and 18.14 ± 3.96 (possible range: 6–24), respectively. Multivariate logistic regression analysis showed that knowledge (OR = 1.095, 95% CI 1.036–1.158, P = 0.001) and previous poor anesthesia experience (OR = 0.081, 95% CI 0.017–0.386, P = 0.002) were independently associated with practice. Non-emergency surgical patients had inadequate knowledge, positive attitude, and proactive practice towards anesthesia. It is crucial for healthcare professionals to implement targeted educational interventions to inform patients about the anesthesia process, potential risks, and benefits.

Abstract Previous studies have reported associations between newly diagnosed diabetes and poor outcomes after percutaneous coronary intervention (PCI), but there is limited data focusing on elderly patients (age ≥ 65). This study aimed to analyze the prevalence and clinical implications of newly diagnosed diabetes in elderly patients who underwent PCI. From 2004 to 2021, a total of 2456 elderly patients who underwent invasive PCI at Korea University Guro Hospital were prospectively enrolled and followed up for a median of five years. The primary endpoint was five-year major adverse cardiovascular events (MACE). Cox regression was used to evaluate whether newly diagnosed diabetes impacted on long-term clinical outcomes. Newly diagnosed diabetes was presented in approximately 8.1% to 10.9% of elderly patients who underwent PCI. Those who had a new diagnosis of diabetes had a higher risk of MACE than previously known diabetes (25.28% vs. 19.15%, p = 0.039). After adjusting for significant factors, newly diagnosed diabetes remained an independent predictor of MACE (HR [hazard ratio] 1.64, 95% confidence interval [CI] 1.24–2.17, p

Abstract Multiple sevoflurane exposures may damage the developing brain. The neuroprotective function of dexmedetomidine has been widely confirmed in animal experiments and human studies. However, the effect of dexmedetomidine on the glymphatic system has not been clearly studied. We hypothesized that dexmedetomidine could alleviate sevoflurane-induced circulatory dysfunction of the glymphatic system in young mice. Six-day-old C57BL/6 mice were exposed to 3% sevoflurane for 2 h daily, continuously for 3 days. Intraperitoneal injection of either normal saline or dexmedetomidine was administered before every anaesthesia. Meanwhile the circulatory function of glymphatic system was detected by tracer injection at P8 and P32. On P30-P32, behavior tests including open field test, novel object recognition test, and Y-maze test were conducted. Primary astrocyte cultures were established and treated with the PI3K activator 740Y-P, dexmedetomidine, and small interfering RNA (siRNA) to silence ΔFosB. We propose for the first time that multiple exposure to sevoflurane induces circulatory dysfunction of the glymphatic system in young mice. Dexmedetomidine improves the circulatory capacity of the glymphatic system in young mice following repeated exposure to sevoflurane through the PI3K/AKT/ΔFosB/AQP4 signaling pathway, and enhances their long-term learning and working memory abilities.

Abstract Background Triple-negative breast cancer (TNBC) is recognized as the most aggressive and immunologically infiltrated subtype of breast cancer. A high circulating neutrophil-to-lymphocyte ratio (NLR) is strongly linked to a poor prognosis among patients with breast cancer, emphasizing the critical role of neutrophils. Although the involvement of neutrophils in tumor metastasis is well documented, their interactions with primary tumors and tumor cells are not yet fully understood. Methods Clinical data were analyzed to investigate the role of neutrophils in breast cancer. In vivo mouse model and in vitro co-culture system were used for mechanism researches. Blocking experiments were further performed to identify therapeutic agents against TNBC. Results TNBC cells secreted GM-CSF to sustain the survival of mature neutrophils and upregulated CD11b expression. Through CD11b, neutrophils specifically binded to ICAM1 on TNBC cells, facilitating adhesion. Transcriptomic sequencing combined with human and murine functional experiments revealed that neutrophils, through direct CD11b-ICAM1 interactions, activated the MAPK signaling pathway in TNBC cells, thereby enhancing tumor cell invasion and migration. Atorvastatin effectively inhibited ICAM1 expression in tumor cells, and tumor cells with ICAM1 knockout or treated with atorvastatin were unresponsive to neutrophil activation. The MAPK pathway and MMP9 expression were significantly inhibited in the tumor tissues of TNBC patients treated with atorvastatin. Conclusions Targeting CD11b-ICAM1 with atorvastatin represented a potential clinical approach to reduce the malignant characteristics of TNBC. Graphical Abstract

Abstract Fetal adenocarcinoma of the lung (FLAC) is a rare form of lung adenocarcinoma and was divided into high-grade (H-FLAC) and low-grade (L-FLAC) subtypes. Despite the existence of some small case series studies, a comprehensive multi-omics study of FLAC has yet to be undertaken. In this study, we depicted the multi-omics landscapes of this rare lung cancer type by performing multi-regional sampling on 20 FLAC cases. A comparison of multi-omics profiles revealed significant differences between H-FLAC and L-FLAC in a multi-omic landscape. Two subtypes also showed distinct relationships between multi-layer intratumor heterogeneity (ITH). We discovered that a lower genetic ITH was significantly associated with worse recurrence-free survival and overall survival in FLAC patients, whereas higher methylation ITH in H-FLAC patients suggested a short survival. Our findings highlight the complex interplay between genetic and transcriptional heterogeneity in FLAC and suggest that different types of ITH may have distinct implications for patient prognosis.

Abstract Background Gastric cancer is the fifth most common cancer type. Most patients are diagnosed at advanced stages with poor prognosis. A non-invasive assay for the detection of early-stage gastric cancer is highly desirable for reducing associated mortality. Methods We collected a prospective study cohort of 110 stage I–II gastric cancer patients and 139 non-cancer individuals. We performed whole-genome sequencing with plasma samples and profiled four types of cell-free DNA (cfDNA) characteristics, fragment size pattern, copy number variation, nucleosome coverage pattern, and single nucleotide substitution. With these differential profiles, we developed an ensemble model to detect gastric cancer signals. Further, we validated the assay in an in-house first validation cohort of 73 gastric cancer patients and 94 non-cancer individuals and an independent second validation cohort of 47 gastric cancer patients and 49 non-cancer individuals. Additionally, we evaluated the assay in a hypothetical 100,000 screening population by Monte Carlo simulation. Results Our cfDNA-based assay could distinguish early-stage gastric cancer from non-cancer at an AUROC of 0.962 (95% CI: 0.942–0.982) in the study cohort, 0.972 (95% CI: 0.953–0.992) in the first validation cohort and 0.937 (95% CI: 0.890–0.983) in the second validation cohort. The model reached a specificity of 92.1% (128/139) and a sensitivity of 88.2% (97/110) in the study cohort. In the first validation cohort, 91.5% (86/94) of non-cancer individuals and 91.8% (67/73) of gastric cancer patients were correctly identified. In the second validation cohort, 89.8% (44/49) of non-cancer individuals and 87.2% (41/47) of gastric cancer patients were accurately classified. Conclusions We introduced a liquid biopsy assay using multiple dimensions of cfDNA characteristics that could accurately identify early-stage gastric cancer from non-cancerous conditions. As a cost-effective non-invasive approach, it may provide population-wide benefits for the early detection of gastric cancer. Trial registration This study was registered on ClinicalTrials.gov under the identifier NCT05269056 on March 7, 2022.

Genetic factors play significant roles in the tumorigenicity of lung cancer; however, there is lack of systematic and large‐scale characterization of pathogenic germline variants for lung cancer. In this study, germline variants in 146 preselected cancer‐susceptibility genes were detected in 17 904 Chinese lung cancer patients by clinical next‐generation sequencing. Among 17 904 patients, 1738 patients (9.7%) carried 1840 pathogenic/likely pathogenic (P/LP) variants from 87 cancer‐susceptibility genes. SBDS (SBDS ribosome maturation factor) (1.37%), TSHR (thyroid stimulating hormone receptor) (1.20%), BLM (BLM RecQ like helicase) (0.62%), BRCA2 (BRCA2 DNA repair associated) (0.62%), and ATM (ATM serine/threonine kinase) (0.45%) were the top five genes with the highest overall prevalence. The top mutated pathways were all involved in DNA damage repair (DDR). Case–control analysis showed SBDS c.184A>T(p.K62*), TSHR c.1574T>C(p.F525S), BRIP1 (BRCA1 interacting helicase 1) c.1018C>T(p.L340F), and MUTYH (mutY DNA glycosylase) c.55C>T(p.R19*) were significantly associated with increased lung cancer risk (q value

Continued population growth and limited land availability will facilitate the utilization of plant growth regulators (PGRs) in sustainable agriculture to enhance crop yields. The PGRs industry has progressed significantly from 2003 to 2022, resulting in a surge of research activities in the field of PGRs. However, the existing studies lack the exploration of the industry trends, as well as the challenges and opportunities for innovation in PGR development. Here, we analyze the dynamic trends within the PGR industry by examining key factors such as the PGR market, patent applications, scientific papers, and PGRs registrations from 2003 to 2022. Additionally, we investigate the specific effects of major agrochemicals on plants. These data will provide essential insights into the ongoing evolution and future trends of PGRs. Importantly, it is crucial to actively pursue research and development (R&D) of a broader range of PGRs to respond to the current needs of the PGR market and drive further growth therein.

Objectives: Thromboembolism is a recognized complication of nephrotic syndrome (NS). Evidence supporting the use of rivaroxaban to prevent NS-related thrombosis is limited and controversial. This study aimed to explore the impact of NS on rivaroxaban pharmacokinetics and to collect observational data on the efficacy and safety of rivaroxaban as primary thromboprophylaxis in patients with NS. Methods: This prospective study analyzed 141 patients with NS who received rivaroxaban (10 mg/day) for thromboprophylaxis. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to measure the trough and peak plasma concentrations (Ctrough and Cmax) of rivaroxaban. The influence of clinical and genetic factors on these concentrations was examined using multivariate logistic regression. Results: The median Cmax and Ctrough were 68.5 ng/mL (IQR, 31.7-105.5 ng/mL) and 4.4 ng/mL (IQR, 1.2-11.9 ng/mL), respectively. The incidence of thromboembolic events (TEs) was 12.8%, while that of bleeding events was 14.2%, although all were classified as minor. Albumin level was the most significant factor affecting Cmax (ρ = 0.55; P < 0.001) and was also significantly associated with TEs (0.81; 0.71-0.91 per 1.0 g/dL increase; P = 0.001) and bleeding risks (1.11; 1.03-1.19 per 1.0 g/dL increase; P = 0.008). Single nucleotide polymorphisms (SNPs) in the ABCB1 gene significantly influenced Ctrough but were not associated with clinical outcomes. Conclusion: Hypoalbuminemia significantly affects the pharmacokinetics of rivaroxaban in NS patients. A dose-adjustment strategy based on rivaroxaban concentrations, accounting for variable albumin levels, may improve the safety and efficacy of thromboprophylaxis in this population.

Introduction: Gouty nephropathy (GN) arises from factors like excessive purine intake, metabolic disorders or abnormal synthesis, and uric acid hypersaturation in the blood, leading to urate crystal deposition in kidney tissue. DaiTongXiao (DTX) is a remedy used by the Dai people of China. It shows efficacy in lowering uric acid levels and exhibits anti-inflammatory and kidney-protective properties.Methods: A GN rat model was induced using adenine and potassium oxonate. Following DTX administration, various parameters were assessed in urine, serum, and kidney tissue. Western blot analysis evaluated TLR4/MyD88/NF-κB signaling proteins, while immunofluorescence examined NF-κB nuclear expression.Results: DTX treatment improved kidney morphology, increased body weight, and kidney index and enhanced urinary levels of blood urea nitrogen (Bun), 24-h urinary protein, uric acid (UA), and allantoin in GN rats, reducing UA, Bun, creatinine (Cre), cystatin C (CysC), serum amyloid A (SAA), α1-microglobulin (MG), and β2-MG in serum analysis. Renal tissue assessments showed decreased xanthine oxidase (XOD), hydroxyproline (Hyp), α-smooth muscle actin (α-SMA), and collage type Ⅳ (COL-Ⅳ). Kidney damage severity was notably reduced. DTX lowered serum inflammatory factors like interleukin (IL) −18, tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), transforming growth factor-β1 (TGF-β1), and IL-1β in the rat serum, reducing chemokine monocyte chemoattractant protein-1 (MCP-1) and adhesion factor vascular cell adhesion molecule-1(VCAM-1). Western blotting demonstrated the downregulation of TLR4/MyD88/NF-κB pathway proteins, and immunofluorescence revealed reduced NF-κB expression in renal tissue.Discussion: DTX exhibits significant anti-GN effects by modulating TLR4/MyD88/ NF-κB pathway protein expression, reducing inflammatory factor release, and inhibiting GN progression.

Accurate haplotyping facilitates distinguishing allele-specific expression, identifying cis-regulatory elements, and characterizing genomic variations, which enables more precise investigations into the relationship between genotype and phenotype. Recent advances in third-generation single-molecule long read and synthetic co-barcoded read sequencing techniques have harnessed long-range information to simplify the assembly graph and improve assembly genomic sequence. However, it remains methodologically challenging to reconstruct the complete haplotypes due to high sequencing error rates of long reads and limited capturing efficiency of co-barcoded reads. We here present a pipeline, AsmMix, for generating both contiguous and accurate diploid genomes. It first assembles co-barcoded reads to generate accurate haplotype-resolved assemblies that may contain many gaps, while the long-read assembly is contiguous but susceptible to errors. Then two assembly sets are integrated into haplotype-resolved assemblies with reduced misassembles. Through extensive evaluation on multiple synthetic datasets, AsmMix consistently demonstrates high precision and recall rates for haplotyping across diverse sequencing platforms, coverage depths, read lengths, and read accuracies, significantly outperforming other existing tools in the field. Furthermore, we validate the effectiveness of our pipeline using a human whole genome dataset (HG002), and produce highly contiguous, accurate, and haplotype-resolved assemblies. These assemblies are evaluated using the GIAB benchmarks, confirming the accuracy of variant calling. Our results demonstrate that AsmMix offers a straightforward yet highly efficient approach that effectively leverages both long reads and co-barcoded reads for haplotype-resolved assembly.

Abstract Objective We analyzed the influence of the location of the upper and lower cement on the sandwich vertebrae (SV) by computer finite element analysis. Materials and Methods A finite element model of the spinal segment of T11‐L1 was constructed and 6 mL of cement was built into T11 and L1 simultaneously. According to the various distributions of bone cement at T11 and L1, the following four groups were formed: (i) Group B‐B: bilateral bone cement reinforcement in both T11 and L1 vertebral bodies; (ii) Group L‐B: left unilateral reinforcement in T11 and bilateral reinforcement in L1; (iii) Group L‐R: unilateral cement reinforcement in both T11 and L1 (cross); (iv) Group L‐L: unilateral cement reinforcement in both T11 and L1 (ipsilateral side). The maximum von Mises stress (VMS) and maximum displacement of the SV and intervertebral discs were compared and analyzed. Results The maximum VMS of T12 was in the order of size: group B‐B

Summary: Increased cases of sepsis during COVID-19 in the absence of known bacterial pathogens highlighted role of viruses as causative agents of sepsis. In this study, we investigated clinical, laboratory, proteomic, and metabolomic characteristics of viral sepsis patients (n = 45) and compared them to non-sepsis patients with COVID-19 (n = 186) to identify molecular mechanisms underlying the pathology of viral sepsis in COVID-19. We identified unique metabolomic and proteomic signatures that suggest a substantial perturbation in the coagulation, complement, and platelet activation pathways in viral sepsis. Our proteomic data indicated elevated coagulation pathway protein (fibrinogen), whereas a decrease in many of the complement proteins was observed. These alterations were associated with the functional consequences such as susceptibility to secondary bacterial infections and potentially contributing to both local and systemic disease phenotypes. Our data provide novel aspect of COVID-19 pathology that is centered around presence of sepsis phenotype in COVID-19.

Background: Ketamine, as a non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, was originally used in general anesthesia. Epidemiological data show that ketamine has become one of the most commonly abused drugs in China. Ketamine administration might cause cognitive impairment; however, its molecular mechanism remains unclear. The glymphatic system is a lymphoid system that plays a key role in metabolic waste removal and cognitive regulation in the central nervous system. Methods: Focusing on the glymphatic system, this study evaluated the behavioral performance and circulatory function of the glymphatic system by building a short-term ketamine administration model in mice, and detected the expression levels of the 5-HT2c receptor, ΔFosb, Pten, Akt, and Aqp4 in the hippocampus. Primary astrocytes were cultured to verify the regulatory relationships among related indexes using a 5-HT2c receptor antagonist, a 5-HT2c receptor short interfering RNA (siRNA), and a ΔFosb siRNA. Results: Ketamine administration induced ΔFosb accumulation by increasing 5-HT2c receptor expression in mouse hippocampal astrocytes and primary astrocytes. ΔFosb acted as a transcription factor to recognize the AATGATTAAT bases in the 5′ regulatory region of the Aqp4 gene (−1096 bp to −1087 bp), which inhibited Aqp4 expression, thus causing the circulatory dysfunction of the glymphatic system, leading to cognitive impairment. Conclusions: Although this regulatory mechanism does not involve the Pten/Akt pathway, this study revealed a new mechanism of ketamine-induced cognitive impairment in non-neuronal systems, and provided a theoretical basis for the safety of clinical treatment and the effectiveness of withdrawal.

This paper reports a mini-resonant photoacoustic sensor for high-sensitivity trace gas sensing. The sensor primarily contains a sphere-cylinder coupled acoustic resonator, a cylindrical buffer chamber, and a fiber-optic acoustic sensor. The acoustic field distributions of this mini-resonant photoacoustic sensor and the conventional T-type resonant photoacoustic sensor have been carefully evaluated, showing that the first-order resonance frequency of the present mini-resonant photoacoustic sensor is reduced by nearly a half compared to that of the T-type resonant photoacoustic sensor. The volume of the developed photoacoustic cavity is only about 0.8 cm3. Trace methane is selected as the target analytical gas and a detection limit of 101 parts-per-billion at 100-s integration time has been achieved, corresponding to a normalized noise equivalent absorption (NNEA) coefficient of 1.04 × 10−8 W·cm−1·Hz−1/2. The developed mini-resonant photoacoustic sensor provides potential for high-sensitivity trace gas sensing in narrow spaces.

Auxin is an important phytohormone that regulates a string of vital rapid responses, and its signaling perception mechanism has been one of the hot spots of research. It has been shown that the ABP1/TMKs module is involved in regulating extracellular auxin signaling, however, the role of ABP1 as an auxin receptor is highly controversial. Therefore, the mechanism of quintessential TMKs sense extracellular auxin remains unresolved. Recently, a study identified two new auxin-binding proteins, ABL1 and ABL2, which directly interact with TMKs to perceive apoplast auxin. This groundbreaking research unravels the mystery surrounding how plants perceive extracellular auxin signals.

Particulate matter (PM), usually formed as aerosols suspended in atmosphere, is becoming a carrier of viruses and bacteria, accelerating the spread of respiratory diseases. Hence, air filtration devices are widely utilized for removing PM. In this study, a regenerated cellulose (RC) film was prepared with the properties of good mechanical strength, antibacterial, and highly efficient filtration (EF) properties, through cellulose dissolution and further crosslinking with P(AGE-DMDAAC)/ZnO. Results exhibited that the Young's modulus of the composite membrane was nearly 4.3 GPa. Additionally, the antibacterial performance against Escherichia coli and Staphylococcus aureus, was up to 99.89% and 99.67%, respectively. Meanwhile, RC composite filter exhibited a high PM 2.5 capture efficiency (over 99.91%). This study introduces an interesting approach to produce antibacterial films with the characteristics of notably good mechanical performance and high fine particle EF that can be utilized in a high humidity environment.

Abstract Objectives In the current study, for the first time, we reported a novel HCV molecular diagnostic approach termed reverse transcription loop-mediated isothermal amplification integrated with a gold nanoparticles-based lateral flow biosensor (RT-LAMP-AuNPs-LFB), which we developed for rapid, sensitive, specific, simple, and visual identification of HCV. Methods A set of LAMP primer was designed according to 5’untranslated region (5’UTR) gene from the major HCV genotypes 1b, 2a, 3b, 6a, and 3a, which are prevalent in China. The HCV-RT-LAMP-AuNPs-LFB assay conditions, including HCV-RT-LAMP reaction temperature and time were optimized. The sensitivity, specificity, and selectivity of our assay were evaluated in the current study. The feasibility of HCV-RT-LAMP-AuNPs-LFB was confirmed through clinical serum samples from patients with suspected HCV infections. Results An unique set of HCV-RT-LAMP primers were successfully designed targeting on the 5’UTR gene. The optimal detection process, including crude nucleic acid extraction (approximately 5 min), RT-LAMP reaction (67℃, 30 min), and visual interpretation of AuNPs-LFB results (~ 2 min), could be performed within 40 min without specific instruments. The limit of detection was determined to be 20 copies per test. The HCV-RT-LAMP-AuNPs-LFB assay exhibited high specificity and anti-interference. Conclusions These preliminary results confirmed that the HCV-RT-LAMP-AuNPs-LFB assay is a sensitive, specific, rapid, visual, and cost-saving assay for identification of HCV. This diagnostic approach has great potential value for point-of-care (POC) diagnostic of HCV, especially in resource-challenged regions.

Abstract The present study provides a systematic review of prosody research in linguistic journals through a bibliometric analysis. Using the bibliographic data from 2001 to 2021 in key linguistic journals that publish prosody-related research, this study adopted co-citation analysis and keyword analysis to investigate the state of the intellectual structure and the emerging trends of research on prosody in linguistics over the past 21 years. Additionally, this study identified the highly cited authors, articles and journals in the field of prosody. The results offer a better understanding of how research in this area has evolved and where the boundaries of prosody research might be pushed in the future.

Objective The aim of this study was to investigate the effect of geriatric training integrated with ideological and political education on the processing ability of standardized training for resident physicians to cultivate the physician-patient relationship. Methods From September 2019 to June 2022,a total of 40 cases at Geriatrics Training Base of the First Hospital of Jilin University were selected,including 19 males and 21 females.Before and after training,DDPQR-10 questionnaire was used to investigate,and then to evaluate the effect of standardized training of geriatrics integrating ideological education on the processing ability of the physician-patient relationship of geriatrics. Results After standardized training,the bed management ability of standardized training students and the proportion of standardized training students who obtained the qualification certificate of doctors were significantly increased,all P

Abstract Background ATM and ATR are two critical factors to regulate DNA damage response (DDR), and their mutations were frequently observed in different types of cancer, including non-small cell lung cancer (NSCLC). Given that the majority of identified ATM/ATR mutations were variants of uncertain significance, the clinical/molecular features of pathogenic ATM/ATR aberrations have not been comprehensively investigated in NSCLC. Methods Next-generation sequencing (NGS) analyses were conducted to investigate the molecular features in 191 NSCLC patients who harbored pathogenic/likely pathogenic ATM/ATR mutations and 308 NSCLC patients who did not have any types of ATM/ATR variants. The results were validated using an external cohort of 2727 NSCLC patients (including 48 with ATM/ATR pathogenic mutations). Results Most pathogenic ATM/ATR genetic alterations were frameshift and nonsense mutations that disrupt critical domains of the two proteins. ATM/ATR-mutated patients had significantly higher tumor mutational burdens (TMB; P

Objectives To investigate the effectiveness of belimumab on active lupus nephritis (LN) and explore the predictors, including serological biomarkers, of renal response to belimumab in a real-world setting.Methods This multicentre, real-world observational study enrolled patients with active LN receiving intravenous belimumab as an add-on therapy with 24-hour urine protein≥1 g and estimated glomerular filtration rate≥30 mL/min/1.73 m2 at baseline. Complete renal response (CRR), partial renal response (PRR), no renal response (NRR) and primary efficacy renal response (PERR) were evaluated. Multivariable logistic regression was used to identify risk factors for NRR to belimumab at 6 months.Results Among the 122 patients enrolled, the proportions of patients achieving CRR, PRR, NRR and PERR were 35.9%, 17.1%, 47.0% and 44.4% at 6 months (n=117) and 55.6%, 19.4%, 26.4% and 58.3% at 12 months (n=72), respectively. Proteinuria, daily prednisone dosage and Systemic Lupus Erythematosus Disease Activity Index 2000 scores significantly decreased at 6 and 12 months (p

BackgroundLower respiratory tract infections represent prevalent ailments. Nonetheless, current comprehension of the microbial ecosystems within the lower respiratory tract remains incomplete and necessitates further comprehensive assessment. Leveraging the advancements in metagenomic next-generation sequencing (mNGS) technology alongside the emergence of machine learning, it is now viable to compare the attributes of lower respiratory tract microbial communities among patients across diverse age groups, diseases, and infection types.MethodWe collected bronchoalveolar lavage fluid samples from 138 patients diagnosed with lower respiratory tract infections and conducted mNGS to characterize the lung microbiota. Employing various machine learning algorithms, we investigated the correlation of key bacteria in patients with concurrent bronchiectasis and developed a predictive model for hospitalization duration based on these identified key bacteria.ResultWe observed variations in microbial communities across different age groups, diseases, and infection types. In the elderly group, Pseudomonas aeruginosa exhibited the highest relative abundance, followed by Corynebacterium striatum and Acinetobacter baumannii. Methylobacterium and Prevotella emerged as the dominant genera at the genus level in the younger group, while Mycobacterium tuberculosis and Haemophilus influenzae were prevalent species. Within the bronchiectasis group, dominant bacteria included Pseudomonas aeruginosa, Haemophilus influenzae, and Klebsiella pneumoniae. Significant differences in the presence of Pseudomonas phage JBD93 were noted between the bronchiectasis group and the control group. In the group with concomitant fungal infections, the most abundant genera were Acinetobacter and Pseudomonas, with Acinetobacter baumannii and Pseudomonas aeruginosa as the predominant species. Notable differences were observed in the presence of Human gammaherpesvirus 4, Human betaherpesvirus 5, Candida albicans, Aspergillus oryzae, and Aspergillus fumigatus between the group with concomitant fungal infections and the bacterial group. Machine learning algorithms were utilized to select bacteria and clinical indicators associated with hospitalization duration, confirming the excellent performance of bacteria in predicting hospitalization time.ConclusionOur study provided a comprehensive description of the microbial characteristics among patients with lower respiratory tract infections, offering insights from various perspectives. Additionally, we investigated the advanced predictive capability of microbial community features in determining the hospitalization duration of these patients.

Our recent multi-omics studies have revealed rich sources of novel bioactive proteins and polypeptides from marine organisms including cnidarians. In the present study, we initially conducted a transcriptomic analysis to review the composition profile of polypeptides from Zoanthus sociatus. Then, a newly discovered NPY-like polypeptide-ZoaNPY was selected for further in silico structural, binding and virtually pharmacological studies. To evaluate the pro-angiogenic effects of ZoaNPY, we employed an in vitro HUVECs model and an in vivo zebrafish model. Our results indicate that ZoaNPY, at 1–100 pmol, enhances cell survival, migration and tube formation in the endothelial cells. Besides, treatment with ZoaNPY could restore a chemically-induced vascular insufficiency in zebrafish embryos. Western blot results demonstrated the application of ZoaNPY could increase the phosphorylation of proteins related to angiogenesis signaling including PKC, PLC, FAK, Src, Akt, mTOR, MEK, and ERK1/2. Furthermore, through molecular docking and surface plasmon resonance (SPR) verification, ZoaNPY was shown to directly and physically interact with NPY Y2 receptor. In view of this, all evidence showed that the pro-angiogenic effects of ZoaNPY involve the activation of NPY Y2 receptor, thereby activating the Akt/mTOR, PLC/PKC, ERK/MEK and Src- FAK-dependent signaling pathways. Furthermore, in an excision wound model, the treatment with ZoaNPY was shown to accelerate the wound healing process in mice. Our findings provide new insights into the discovery and development of novel pro-angiogenic drugs derived from NPY-like polypeptides in the future.

Fibrosis-related diseases (FRD) include conditions like myocardial fibrosis, pulmonary fibrosis, hepatic fibrosis, renal fibrosis, and others. The impact of fibrosis can be severe, causing organ dysfunction, reduced functionality, and even organ failure, leading to significant health issues. Currently, there is a lack of effective modern anti-fibrosis drugs in clinical practice. However, Chinese medicine has a certain beneficial effect on the treatment of such diseases. Angelica sinensis, with its considerable medicinal value, has garnered attention for its anti-fibrosis properties in recent investigations. In the past few years, there has been a growing number of experimental inquiries into the impact of angelica polysaccharide (ASP), angelica water extract, angelica injection, and angelica compound preparation on fibrosis-associated ailments, piquing the interest of researchers. This paper aims to consolidate recent advances in the study of Angelica sinensis for the treatment of fibrosis-related disorders, offering insights for prospective investigations. Literature retrieval included core electronic databases, including Baidu Literature, CNKI, Google-Scholar, PubMed, and Web of Science. The applied search utilized specified keywords to extract relevant information on the pharmacological and phytochemical attributes of plants. The investigation revealed that Angelica sinensis has the potential to impede the advancement of fibrotic diseases by modulating inflammation, oxidative stress, immune responses, and metabolism. ASP, Angelica sinensis extract, Angelica sinensis injection, and Angelica sinensis compound preparation were extensively examined and discussed. These constituents demonstrated significant anti-fibrosis activity. In essence, this review seeks to gain a profound understanding of the role of Angelica sinensis in treating fiber-related diseases. Organ fibrosis manifests in nearly all tissues and organs, posing a critical challenge to global public health due to its widespread occurrence, challenging early diagnosis, and unfavorable prognosis. Despite its prevalence, therapeutic options are limited, and their efficacy is constrained. Over the past few years, numerous studies have explored the protective effects of traditional Chinese medicine on organ fibrosis, with Angelica sinensis standing out as a multifunctional natural remedy. This paper provides a review of organ fibrosis pathogenesis and summarizes the recent two decades’ progress in treating fibrosis in various organs such as the liver, lung, kidney, and heart. The review highlights the modulation of relevant signaling pathways through multiple targets and channels by the effective components of Angelica sinensis, whether used as a single medicine or in compound prescriptions.

Introduction As malaria declines, low-density malaria infections (LMIs) represent an increasing proportion of infections and may have negative impacts on child health and cognition, necessitating development of targeted and effective solutions. This trial assesses the health, cognitive and socioeconomic impact of two strategies for detecting and treating LMI in a low transmission setting.Methods and analysis The study is a 3-arm open-label individually randomised controlled trial enrolling 600 children aged 6 months to 10 years in Bagamoyo district, Tanzania. Children are randomised to one of three arms: active case detection with molecular (ACDm) testing by high volume quantitative PCR (qPCR), passive case detection also with molecular testing (PCDm) and a control of standard PCD using rapid diagnostics tests (RDTs). Over the 2-year trial, ACDm participants receive malaria testing using RDT and qPCR three times annually, and malaria testing by RDT only when presenting with fever. PCDm and PCD participants receive malaria testing by RDT and qPCR or RDT only, respectively, when presenting with fever. RDT or qPCR positive participants with uncomplicated malaria are treated with artemether lumefantrine. The primary outcome is cumulative incidence of all-cause sick visits. Secondary outcomes include fever episodes, clinical failure after fever episodes, adverse events, malaria, non-malarial infection, antibiotic use, anaemia, growth faltering, cognition and attention, school outcomes, immune responses, and socioeconomic effects. Outcomes are assessed through monthly clinical assessments and testing, and baseline and endline neurodevelopmental testing. The trial is expected to provide key evidence and inform policy on health, cognitive and socioeconomic impact of interventions targeting LMI in children.Ethics and dissemination Study is approved by Tanzania NatHREC and institutional review boards at University of California San Francisco and Ifakara Health Institute. Findings will be reported on ClinicalTrials.gov, in peer-reviewed journals and through stakeholder meetings.Trial registration number NCT05567016.

Abstract Background Patients frequently die from cardiac causes after radiotherapy for esophageal cancer. Early detection of cardiac death risk in these patients is crucial to improve clinical decision‐making and prognosis. Thus, we modeled the risk of cardiac death after irradiation for esophageal cancer. Methods A retrospective analysis of 37,599 esophageal cancer cases treated with radiotherapy in the SEER database between 2000 and 2018 was performed. The selected cases were randomly assigned to the model development group (n = 26,320) and model validation group (n = 11,279) at a ratio of 7:3. We identified the risk factors most commonly associated with cardiac death by least absolute shrinkage and selection operator regression analysis (LASSO). The endpoints for model development and validation were 5‐ and 10‐year survival rates. The net clinical benefit of the models was evaluated by decision curve analysis (DCA) and concordance index (C‐index). The performance of the models was further assessed by creating a receiver operating characteristic curve (ROC) and calculating the area under the curve (AUC). Kaplan‐Meier (K‐M) survival analysis was performed on the probability of death. Patients were classified according to death probability thresholds. Five‐ and ten‐year survival rates for the two groups were shown using K‐M curves. Results The major risk factors for cardiac death were age, surgery, year of diagnosis, sequence of surgery and radiotherapy, chemotherapy and a number of tumors, which were used to create the nomogram. The C‐indexes of the nomograms were 0.708 and 0.679 for the development and validation groups, respectively. DCA showed the good net clinical benefit of nomograms in predicting 5‐ and 10‐year risk of cardiac death. The model exhibited moderate predictive power for 5‐ and 10‐year cardiac mortality (AUC: 0.833 and 0.854, respectively), and for the development and validation cohorts (AUC: 0.76 and 0.813, respectively). Conclusions Our nomogram may assist clinicians in making clinical decisions about patients undergoing radiotherapy for esophageal cancer based on early detection of cardiac death risk.

Abstract Background Gout is the most common inflammatory arthritis and closely related to metabolic syndrome, leading to excruciating pain and the decline in quality of patients’ life. However, the pathogenesis of gout is still unclear, and novel biomarkers are demanded for the early prediction and diagnosis of gout. Objective This study aimed at profiling the dysregulated metabolic pathways in asymptomatic hyperuricemia (AHU) and gout and elucidating the associations between AHU, gout and metabolomics, which may aid in performing gout screening. Methods A total of 300 participants, including 114 healthy controls, 92 patients with AHU, and 94 patients with gout, were analyzed by using a combination of dried blood spot (DBS) sampling and mass spectrometry (MS) technology. Multiple algorithms were applied to characterize altered metabolic profiles in AHU and gout. The mainly altered metabolites were identified by random forest analysis. Results There were significant differences in AHU and gout compared with control group. The altered metabolites were involved in oxidation of fatty acids, carnitine synthesis, urea cycle, and amino acid metabolism in AHU and gout. Random forest classification of 16 metabolites yielded 3 important features to distinguish gout from AHU. Conclusions Distinct metabolomic signatures were observed in AHU and gout. The selected metabolites may have the potential to improve the early detection of gout.

Abstract Purpose Critically ill patients with sepsis account for significant disease morbidity and healthcare costs. Low muscle mass has been proposed as an independent risk factor for poor short-term outcomes, although its effect on long-term outcomes remains unclear. Methods Retrospective cohort analysis of patients treated at a quaternary care medical center over 6 years (09/2014 - 12/2020). Critically ill patients meeting Sepsis-3 criteria were included, with low muscle mass defined by $$\le$$ ≤ 5th percentile skeletal muscle index, measured at the L3 lumbar level (L3SMI) on Computed-Tomography (CT) scan ( $$\le$$ ≤ 41.6 cm2/m2 for males and $$\le$$ ≤ 32.0 cm2/m2 for females). L3SMI was calculated by normalizing the CT-measured skeletal muscle area to the square of the patient’s height (in meters). Measurements were taken from abdominal/pelvic CT scan obtained within 7 days of sepsis onset. The prevalence of low muscle mass and its association with clinical outcomes, including in-hospital and one-year mortality, and post-hospitalization discharge disposition in survivors, was analyzed. Unfavorable post-hospitalization disposition was defined as discharge to a location other than the patient’s home. Results Low muscle mass was present in 34 (23%) of 150 patients, with mean skeletal muscle indices of 28.0 ± 2.9 cm2/m2 and 36.8 ± 3.3 cm2/m2 in females and males, respectively. While low muscle mass was not a significant risk factor for in-hospital mortality (hazard ratio 1.33; 95% CI 0.64 – 2.76; p = 0.437), it significantly increased one-year mortality after adjusting for age and illness severity using Cox multivariate regression (hazard ratio 1.9; 95% CI 1.1 – 3.2; p = 0.014). Unfavorable post-hospitalization discharge disposition was not associated with low muscle mass, after adjusting for age and illness severity in a single, multivariate model. Conclusion Low muscle mass independently predicts one-year mortality but is not associated with in-hospital mortality or unfavorable hospital discharge disposition in critically ill patients with sepsis.

The presence of large genomic rearrangements (LGRs) has been heavily investigated in breast and ovarian cancer. However, correlations between LGRs and cancer types beyond these two have not been extensively profiled, likely due to the highly inefficient methods of detecting these types of alterations. This study utilized next‐generation sequencing (NGS) to analyze and classify the germline LGR profile in 17 025 cancer patients across 22 cancer types. We characterized newly identified LGRs based on predicted pathogenicity and took a closer look at genes that acquire both germline and somatic mutations within our samples. The detection method for LGRs was validated using droplet digital polymerase chain reaction (ddPCR) assay of commonly investigated LGR genes. In total, 15 659 samples from across 22 cancer types were retained for analysis after filtering. We observed that, in our cohort, the cancer types with the highest proportion of germline LGRs were ovarian cancer (4.7%), renal cell carcinoma (2.5%), breast cancer (2%), glioma (1.8%) and thyroid carcinoma (1.8%). Annotation of detected germline variants revealed several genes—MSH2, FANCA and PMS2—that contain novel LGRs. We observed co‐occurrences between germline LGRs in MSH2 and somatic single nucleotide variants/insertion and deletions (SNVs/InDels) in BRCA2, KTM2B, KDM5A, CHD8, and HNF1A. Furthermore, our analysis showed that samples with pathogenic and likely pathogenic germline LGRs tended to also have higher mutational burden, chromosomal instability, and microsatellite instability ratio compared to samples with pathogenic germline SNVs/InDels. In this study, we demonstrated the prevalence of pathogenic germline LGRs beyond breast and ovarian cancer. The profiles of these pathogenic or likely pathogenic alterations will fuel further investigations and highlight new understanding of LGRs across multiple cancer types.

Exosomes are small membrane vesicles in a cell culture. They are secreted by most cells and originate from the endosomal pathway. A variety of proteins, lipids, and genetic materials have been shown to be carried by exosomes. Once taken up by neighboring or distant cells, the bioactive compounds in exosomes can regulate the condition of recipient cells. Typically, producing exosomes in large quantities requires cell culture, resulting in high production costs. However, exosomes are abundant in milk and can be isolated on a large scale at a low cost. In our study, we found that milk exosomes can promote the synthesis and reconstruction of stratum corneum lipids, enhance skin barrier function, and provide greater protection for the skin. Furthermore, milk exosomes have anti-inflammatory properties that can reduce skin irritation, redness, and other symptoms, giving immediate relief. They also exhibit antioxidant activity, which helps neutralize free radicals and slows down the skin aging process. Additionally, milk exosomes inhibit melanin production, aiding in skin whitening. Ongoing research has uncovered the benefits of milk exosomes for skin improvement and their application in cosmetics, skin healthcare, and other fields, and these applications are continuing to expand.

Abstract Introduction Whether airway‐compromised airway–esophageal fistula (AEF) patients should undergo combined airway and esophageal stenting is controversial. This study was designed to evaluate the survival prognosis and poststent interventions in AEF patients with airways compromised by advanced malignancy with or without airway stents. Methods A retrospective analysis of the medical records, survival times, and poststent interventions of 17 patients with or without airway stents was performed. Results The causes of AEF were esophageal cancer (11/17, 64.7%), lung cancer (6/17, 29.4%), and thyroid cancer (1/17, 5.9%). All patients received a nasogastric tube (n = 12) or underwent gastrostomy (n = 5) to resume enteral nutrition. Thirteen patients underwent airway stent insertion (13/17, 76.5%), whereas four patients did not. Four patients with a high risk of stent migration received external stent fixation to the trachea. Three of the patients with stents suffered severe granulation tissue formation and needed repeated bronchoscopy interventions. In the stented group, none of the patients developed stent migration, and the overall median survival time was 9 months, compared with 1.25 months in the nonstented group (P = 0.04). Cox proportional hazards regression revealed that stent insertion, nasogastric tube insertion, and transcatheter bronchial artery chemoembolization were protective factors against death, whereas surgery‐related fistula, fistula larger than 2 cm, continued chemotherapy, and age were risk factors for poor survival (P

Abstract Aims To map the themes and methods of nursing researches involving eye‐tracking as a measurement, and offer suggestion for future nursing research using eye‐tracking. Design We conducted a scoping review following the methodology outlined in the JBI Manual for Evidence Synthesis on scoping reviews. Methods Eligibility criteria were established based on Population (involving nursing or nursing students), Concept (utilizing eye‐tracking as a research method), and Context (in any setting). Articles were retrieved from the PubMed, Web of Science, Embase, CINAHL, APA PsycInfo, and Scopus databases, spanning from database inception to November 17, 2023. The included studies were analysed using descriptive statistics and content analysis. Results After duplicates were removed, 815 citations were identified from searches of electronic databases and other resources, and 66 met the inclusion criteria finally. Thirty‐eight studies were conducted in a simulated environment. Five application domains were identified, and most of the studies (N = 50) were observational. The domains found in our review did not cover all topics of nursing research in the same depth. Additionally, 39 studies did not solely explicate eye‐tracking data but instead integrated behavioural measures, scales/questionnaires, or other physiological data. Conclusions Eye‐tracking emerges as a significant research tool in uncovering visual behaviour, particularly in nursing research focused on nursing education. This study not only summarized the application and interpretation of eye‐tracking data but also recognized its potential in advancing clinical nursing research and practice. To effectively harness the capabilities of eye‐tracking in elucidating cognitive processes, future research should aim for a clearer grasp of the theoretical underpinnings of the addressed research problems and methodological choices. It is crucial to emphasize the standardization of eye‐tracking method reporting and ensuring data quality. No Patient or Public Contribution.

Background. Gastric cancer (GC) is the most common malignant tumor and ranks third in the world. LncRNA H19 (H19), one of the members of lncRNA, is overexpressed in various tumors. However, many undetermined molecular mechanisms by which H19 promotes GC progression still need to be further investigated. Methodology. A series of experiments was used to confirm the undetermined molecular mechanism including wound healing and transwell assays. Key Results. In this study, a significant upregulation of H19 expression was detected in GC cells and tissues. The poor overall survival was observed in GC patient with high H19 expression. Overexpression of H19 promoted the migration of GC cells, while knockdown of H19 significantly inhibited cell migration. Moreover, miR-148a-3p had a certain negative correlation with H19. Luciferase reporter assay confirmed that H19 could directly bind to miR-148a-3p. As expected, miR-148a mimics inhibited cell migration and invasion induced by H19 overexpression. The above findings proved that H19 functions as a miRNA sponge and verified that miR-148a-3p is the H19-associated miRNA in GC. We also confirmed that SOX-12 expression was upregulated in GC patient’s samples. SOX-12 expression was positively correlated with expression of H19 and was able to directly bind to miR-148a-3p. Importantly, in vitro wound healing assay showed that knockout of SOX-12 could reverse the promoting effect of H19 overexpression on cell migration. Conclusion. In conclusion, H19 has certain application value in the diagnosis and prognosis of GC. Specifically, H19 accelerates GCs to migration and metastasis by miR-138a-3p/SOX-12 axis.

For a multi-dimensional measure of positive youth development (PYD), its factor structure should be invariant across groups and over time. This study examined the factorial validity of the 44-item short form of the "Chinese Positive Youth Development Scale" (CPYDS-SF) that assesses 15 dimensions of PYD attributes. Using two waves of longitudinal data with a one-year interval in between, this study examined the factor structure of the scale and whether the structure is invariant between gender groups and across time. The data were collected from 3,328 adolescents at Wave 1 and 3,638 adolescents at Wave 2, with a matched sample of 2,905 adolescents (mean age = 12.57 ± 0.72 at Wave 1; 49.54% girls). Confirmatory factor analysis revealed that the 15-factor structure fitted the data well. The findings of invariance tests further supported this structure's invariance across gender and time, indicating a stable factor structure of CPYDS-SF among Chinese adolescents. These findings suggest that CPYDS-SF can be used to examine gender differences and the longitudinal development of PYD qualities among Chinese adolescents.

IntroduceAnkylosing spondylitis (AS), rheumatoid arthritis (RA), and osteoarthritis (OA) are three rheumatic immune diseases with many common characteristics. If left untreated, they can lead to joint destruction and functional limitation, and in severe cases, they can cause lifelong disability and even death. Studies have shown that early diagnosis and treatment are key to improving patient outcomes. Therefore, a rapid and accurate method for rapid diagnosis of diseases has been established, which is of great clinical significance for realizing early diagnosis of diseases and improving patient prognosis.MethodsThis study was based on Fourier transform infrared spectroscopy (FTIR) combined with a deep learning model to achieve non-invasive, rapid, and accurate differentiation of AS, RA, OA, and healthy control group. In the experiment, 320 serum samples were collected, 80 in each group. AlexNet, ResNet, MSCNN, and MSResNet diagnostic models were established by using a machine learning algorithm.ResultThe range of spectral wave number measured by four sets of Fourier transform infrared spectroscopy is 700-4000 cm-1. Serum spectral characteristic peaks were mainly at 1641 cm-1(amide I), 1542 cm-1(amide II), 3280 cm-1(amide A), 1420 cm-1(proline and tryptophan), 1245 cm-1(amide III), 1078 cm-1(carbohydrate region). And 2940 cm-1 (mainly fatty acids and cholesterol). At the same time, AlexNet, ResNet, MSCNN, and MSResNet diagnostic models are established by using machine learning algorithms. The multi-scale MSResNet classification model combined with residual blocks can use convolution modules of different scales to extract different scale features and use resblocks to solve the problem of network degradation, reduce the interference of spectral measurement noise, and enhance the generalization ability of the network model. By comparing the experimental results of the other three models AlexNet, ResNet, and MSCNN, it is found that the MSResNet model has the best diagnostic performance and the accuracy rate is 0.87.ConclusionThe results prove the feasibility of serum Fourier transform infrared spectroscopy combined with a deep learning algorithm to distinguish AS, RA, OA, and healthy control group, which can be used as an effective auxiliary diagnostic method for these rheumatic immune diseases.

Background: Ischemic stroke, caused neurological dysfunction due to inadequate blood supply to brain, has a high morbidity and mortality. Ethyl pyruvate (EP), a simple aliphatic ester derived from pyruvic acid, has the advantages of safety and stability. Studies have confirmed that EP has anti-oxidative, anti-inflammation, anti-tumor, and other pharmacological effects, and it demonstrates significant therapeutic effects on multiple diseases. GAS6 and its high affinity Axl receptor play an important role in cell adhesion, anti-apoptosis, proliferation and migration by activating downstream signal transduction pathways. Previous studies have demonstrated the neuroprotective effects of the GAS6/Axl axis. Methods: A series of experimental methods were employed to confirm the effect of EP against cerebral hypoxia/reoxygenation (HR) injury. Results: In this study, the protective effect and mechanism of EP on HR injury in N2a cells was explored. The results found that treatment with EP could increase HR-injured neuronal viability, improve cell morphology, and reduce LDH release and ROS accumulation, thereby exhibiting a neuroprotective effect. Furthermore, EP treatment restored the down-regulated expression of GAS6, Axl, NQO1, PGC-1α, NRF1, and UCP2 caused by HR injury. Specifically, it was observed that the neuroprotective effect of EP was partially inhibited by GAS6 siRNA. Conclusion: In conclusion, these results suggest that EP treatment attenuates HR-induced oxidative stress injury in neuroblastoma cells via activating GAS6/Axl signaling.

Lacto-N-fucopentaoses (LNFPs) of type I to V are representative components of human milk oligosaccharides (HMOs) and have garnered increasing attention due to their multi-functional activities. These activities include regulating intestinal flora, resisting pathogen adhesion, and promoting the development and repair of the nervous system. Due to the limited resource of HMOs, artificial synthesis of HMOs can provide an alternative pathway to circumvent this limitation. Currently, LNFPs can be produced using various methods, including biosynthesis, chemical synthesis, and enzymatic synthesis. Currently, emphasis is placed on the last two methods. Chemical synthesis-based methods typically involve strict reaction conditions, cumbersome steps, and low yields. On the other hand, enzymatic synthesis offers several advantages, including mild reaction conditions, high yield, and good selectivity. However, only a few reports have focused on in vivo fermentation as a means to produce LNFPs, despite its cost advantage. In vivo fermentation presents an opportunity to supply the key substrates for fucosyl transfer reactions, namely LNnT and GDP-Fuc, along with the required biosynthesis enzymes. Further exploration of this approach is warranted.This paper aims to review the synthesis methods of LNFPs, their functional activities, and emerging trends in their development. By evaluating the different synthesis approaches, this review seeks to contribute to the advancement of LNFPs production and utilization.

Abstract Background Angiogenesis is regarded as a critical role in bone repair and regeneration, involving in pathological bone disorders such as osteoporosis. Aucubin, an iridoid glycoside primarily derived from Eucommia ulmoides, is reported to inhibit osteoclast activity, enhance bone formation and promote angiogenesis in osteoporosis models. Our study is to further investigate the anti-osteoporosis effect of aucubin in transgenic medaka, and the pro-angiogenic effect of aucubin and its mechanism of action both in vivo and in vitro. Methods The anti-osteoporosis effect of aucubin was confirmed by using RANKL-stimulated bone resorption transgenic medaka. The pro-angiogenic effect of aucubin in vivo was investigated using vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor II (VRI)-induced vascular insufficient transgenic zebrafish model. Furthermore, endothelial cell proliferation, migration, tube formation and the mechanisms were evaluated to identify the pro-angiogenic effect of aucubin in normal and su5416-injured human umbilical vein endothelial cells (HUVECs). Results Aucubin decreased the resorption of the mineralized bone matrix and centra degradation in heat-shocked transgenic col10α1:nlGFP/rankl:HSE:CFP medaka. Moreover, aucubin reversed VRI-induced vascular insufficiency in zebrafish through regulating flt1, kdr, kdrl, vegfaa, ang-1, ang-2, tie1 and tie2 mRNA expressions in Tg(fli1a:EGFP)y1 or AB wild type zebrafish. Aucubin promoted cell proliferation by upregulating p-mTOR, p-Src, p-MEK, p-Erk1/2, p-Akt and p-FAK in HUVECs. Furthermore, aucubin exhibited a pro-angiogenic effect on su5416-injured HUVECs by promoting their proliferation, migration, and tube formation through regulating the phosphorylation of VEGFR2, MEK, ERK and the ratio of Bcl2-Bax. Conclusion Aucubin could reduce bone resorption in RANKL-induced osteoporosis medaka by live imaging. Meanwhile, aucubin exhibited a protective effect in VRI-induced vascular insufficient zebrafish by regulating VEGF-VEGFR and Ang-Tie signaling pathways. Additionally, aucubin promoted the proliferation, migration and tube formation of HUVECs probably by mediating VEGFR2/MEK/ERK, Akt/mTOR and Src/FAK signalling pathways. This study further indicated the dual effect of aucubin on angiogenesis and osteogenesis which may be beneficial to its treatment of osteoporosis.

Abstract Early diagnosis of cancer treatment‐related cardiac dysfunction (CTRCD) is important as cancer therapy increases the risk of cardiac dysfunction. High‐sensitivity cardiac troponin T (hs‐cTnT) is a highly specific marker of myocardial injury. However, its diagnostic value for CTRCD has not been systematically evaluated. This meta‐analysis aimed to evaluate whether hs‐cTnT could be used as an early diagnostic biomarker for CTRCD. We systematically surveyed PubMed, Embase, Cochrane Library, and Web of Science databases for studies of hs‐cTnT for the diagnosis of CTRCD before 1 April 2022. Patients of all ages and all cancer types who underwent echocardiographic left ventricular ejection fraction assessment and blood hs‐cTnT and received anticancer therapy (including chemotherapy, radiotherapy, targeted therapy, immune checkpoint inhibitors, and other treatments) were included in this study, resulting in a total of eight studies with 1294 patients. The occurrence of CTRCD was associated with elevated hs‐cTnT [sensitivity: 0.78, 95% confidence interval (CI): 0.64–0.88; specificity: 0.75, 95% CI: 0.59–0.86; area under the curve (AUC): 0.83, 95% CI: 0.80–0.86]. We further performed subgroup analysis and found that the AUC of hs‐cTnT elevation for the diagnosis of CTRCD increased from 0.83 to 0.90 (95% CI: 0.87–0.92) at 3–6 months, suggesting a higher early diagnostic value of hs‐cTnT compared with echocardiography for CTRCD. In terms of clinical applicability, the Fagan plot showed pre‐test and post‐test probabilities of 51% and 9%, respectively, indicating that hs‐cTnT testing can improve the accuracy of clinical diagnosis of CTRCD. However, it was not possible to determine the optimal cut‐off value for early diagnosis of CTRCD with hs‐cTnT. The Deeks funnel plot was largely symmetrical (P = 0.74); hence, publication bias was not observed. Hs‐cTnT allowed early CTRCD diagnosis at 3–6 months. However, further high‐quality research is needed to determine the optimal cut‐off value for early CTRCD diagnosis with this biomarker.

Abstract Background Locoregional recurrence is of high risk and is associated with a poor prognosis in terms of OS for non‐small cell lung cancer (NSCLC). Local control is essential for radical cure of NSCLC. Previous studies have investigated the clinicopathological risk factors for locoregional recurrence, but the genomic biomarkers associated with locoregional recurrence have been inadequately studied. Methods A total of 118 patients who underwent tumor resection with mutation‐detected tumor specimens were included. Tumor samples at surgery and pretreatment/postoperative blood samples were collected for mutational profiling. Results Among 48 patients with disease recurrence, 46% developed locoregional recurrence (LR) and 75% developed distant metastasis (DM). The 3‐year actuarial risk of LR and DM was 25% and 43%, respectively. The first sites of failure were locoregional only (29%), locoregional and distant (10%), and distant only (61%). Patients with LR showed significantly higher ctDNA level than those with only DM at the time of initial recurrence. On multivariate analysis of baseline risk factors, the presence of allele frequency heterogeneity and baseline ctDNA shedding were found to be independently associated with a higher risk of LR. Patients with disruptive TP53 mutations had significantly lower LR‐free survival as compared to patients with wild‐type TP53 or nondisruptive mutations. EGFR mutations showed a favorable prognostic value for LR and is not induced by EGFR tyrosine kinase inhibitor therapy. Both disruptive TP53 mutation and EGFR mutation remained the significant prognostic factor after adjustment for histological type, pathologic nodal stage and adjuvant therapy. Conclusions Nearly half of disease recurrences after surgery for NSCC involved locoregional sites. We identified genomic biomarkers from baseline tumor and ctDNA samples which showed promising prognostic value for LR only. This can help identify patients who had a higher risk of locoregional recurrence regardless of the risk of distant metastasis.

Abstract ACT001 is a novel sesquiterpene lactone derivative that has been shown to have significant antitumor and anti-inflammatory effects. However, the effect of ACT001 on nonalcoholic steatohepatitis (NASH) is unknown. Methionine and choline deficient (MCD) diet induced NASH model in C57BL/6J mice. Steatosis, inflammation and fibrosis-related indices of serum and liver tissues were detected by fully automated biochemical analyzer, enzyme-linked immunosorbent assay (ELISA) kit, flow cytometry, hematoxylin and eosin (H&E), Masson and immunohistochemical staining. The results showed that ACT001 reduced serum lipid and inflammatory factor levels, attenuated hepatic steatosis, inflammation and fibrosis, and inhibited hepatic oxidative stress and activation of NOD-like receptor protein 3 (NLRP3) inflammatory vesicles in NASH mice. In addition, 381 differentially expressed proteins (DEPs), including 162 up-regulated and 219 down-regulated proteins, were identified in the MCD group and ACT001 high-dose group using isotope labeling relative and absolute quantification (iTRAQ) technique analysis. Among these DEPs, five proteins associated with NAFLD were selected for real-time fluorescence quantitative PCR (RT-qPCR) validation, and the results were consistent with proteomics. In conclusion, ACT001 has a therapeutic effect on NASH, and the results of proteomic analysis will provide new ideas for the mechanism study of ACT001 for NASH treatment.

Objective: To rapidly assess the effectiveness, safety, economy, and applicability of Shaoma Zhijing granule (SZG) for the treatment of children with tic disorders (TD), and provide currently available best evidence for decision-makers of health policies. Methods: We conducted a rapid health technology assessment (RHTA) to explore the value of SZG. A systematic literature search in eight literature databases and on three clinical trial registration platforms was performed. The literature was screened according to eligibility criteria. The screening process and data extraction were conducted by two reviewers, and the quality of the literature was also assessed. The results were summarized, analyzed, and presented in tables or figures. Results: A total of five randomized controlled trials (RCTs) were included in this study, of which one was published in English (in the Journal of Child Psychology and Psychiatry) and four in Chinese journals. The overall risk of bias for the five RCTs was evaluated as “some concerns.” SZG monotherapy or in combination with tiapride was better than tiapride alone in improving traditional Chinese medicine (TCM) syndromes and tic symptoms, with a daily cost of ¥67.50–107.22. Adverse events were mainly related to the digestive, respiratory, and neurological systems, but all were mild. Conclusion: Overall, the current RHTA of published, peer-reviewed literature has located a small body of evidence evaluating the use of SZG for the treatment of TD in children. SZG has effects on improving TCM syndromes and tic symptoms; the daily cost is ¥67.50–107.22; and all adverse events are mild. High-quality studies with long-term follow-up should be conducted, so as to provide local evidence and consistently guide and improve scientific decision-making.

Abstract Background Large fragment deletion (LFD) of EGFR was associated with carcinogenesis in many types of cancers. However, the molecular features of EGFR‐LFD have not been studied in the Asian cancer population. Method Here we retrospectively analyzed the targeted sequencing data from a large cancer database. Results EGFR‐LFD was detected at a frequency of 0.03% with EGFRvIII being the most frequently observed LFD. TERTp variants were identified in 60% of the cases. TP53 alterations (33%) were mutually exclusive with TERTp variants and coexisted with EGFR‐LFD in lung cancer and colorectal cancer. EGFR amplification (67%) and chromosome 10p deletion (53%) were the most focal‐level and arm‐level CNV in this cohort. EGFR exon2–17 skipping was found in the tumor tissue of one patient after progressing on osimertinib. Conclusion Our study provided valuable insights into the distribution and molecular characteristics of EGFR‐LFD, hoping to shed light on the treatment management for EGFR‐LFD carriers.

Abstract HER2-positive gastric cancer (GC) makes up 15–20% of all GC incidences, and targeted therapy with trastuzumab is the standard of treatment. However, the mechanisms of resistance to trastuzumab are still not fully understood and presents a significant challenge in clinical practice. In this study, whole exome sequencing (WES) was performed on paired tumor tissues before trastuzumab treatment (at baseline) and at progressive disease (PD) in 23 GC patients. Clinicopathological and molecular features that may be associated with primary and/or acquired resistance to trastuzumab were identified. Lauren classification of intestinal type was associated with a more prolonged progression-free survival (PFS) than diffuse type (HR = 0.29, P = 0.019). Patients with low tumor mutation burden (TMB) showed significantly worse PFS, while high chromosome instability (CIN) was correlated with prolonged OS (HR = 0.27; P = 0.044). Patients who responded to treatment had a higher CIN than nonresponders, and a positive trend towards increasing CIN was observed as response improved (P = 0.019). In our cohort, the most common genes to acquire mutations are AURKA, MYC, STK11, and LRP6 with four patients each. We also discovered an association between clonal branching pattern and survival, with an extensive clonal branching pattern being more closely related to a shorter PFS than other branching patterns (HR = 4.71; P = 0.008). We identified potential molecular and clinical factors that provide insight regarding potential association to trastuzumab resistance in advanced HER2-positive GC patients.

Abstract The aim of this study was to explore the feasibility of Raman spectroscopy combined with computer algorithms in the diagnosis of primary Sjögren syndrome (pSS). In this study, Raman spectra of 60 serum samples were acquired from 30 patients with pSS and 30 healthy controls (HCs). The means and standard deviations of the raw spectra of patients with pSS and HCs were calculated. Spectral features were assigned based on the literature. Principal component analysis (PCA) was used to extract the spectral features. Then, a particle swarm optimization (PSO)-support vector machine (SVM) was selected as the method of parameter optimization to rapidly classify patients with pSS and HCs. In this study, the SVM algorithm was used as the classification model, and the radial basis kernel function was selected as the kernel function. In addition, the PSO algorithm was used to establish a model for the parameter optimization method. The training set and test set were randomly divided at a ratio of 7:3. After PCA dimension reduction, the specificity, sensitivity and accuracy of the PSO-SVM model were obtained, and the results were 88.89%, 100% and 94.44%, respectively. This study showed that the combination of Raman spectroscopy and a support vector machine algorithm could be used as an effective pSS diagnosis method with broad application value.

Abstract Background Kinase domain duplications (KDDs) have recently been recognized as oncogenic mutations and possible association with drug resistance in cancers. Method Here, targeted sequencing was performed with the tumor tissue and/or plasma from 65 cancer patients with KDDs. Result Intact KDDs were identified in approximately 0.1% of the total population across multiple cancer types. EGFR KDD was first identified in colorectal cancer and breast cancer, whereas FGFR2 KDD was first identified in gastric cancer. Tumors with EGFR KDD displayed lower concurrent TP53 gene alterations (p = 0.03) and slightly higher chromosome instability (p = 0.27) compared to tumors with non‐EGFR‐KDDs. Immune pathway analysis further revealed the enrichment of the cytokine receptors pathway (93%) in the KDD carriers. Hyperprogression‐related gene mutations were identified in four cases. Conclusion Collectively, our data revealed the genomic features of KDD alterations in a multi‐cancer cohort, providing more information for the potential treatment application in the KDD carriers.

AIM: To illustrate clinicopathological features of orbital non-rhabdomyosarcoma soft tissue sarcoma (NRSTS), and to compare the treatment outcome between postoperative radiotherapy (RT) and chemotherapy in a retrospective analysis nearly 20y. METHODS: A retrospective cohort study of 56 patients with orbital NRSTS were reviewed, 34 of whom received postoperative RT, and 22 received postoperative chemotherapy. The clinicopathological features, local recurrence, metastases, and survival data were recorded. Survival analysis was performed using the Kaplan-Meier method. RESULTS: During follow-up (111.8mo, ranged 8-233mo) for 56 patients, 19 patients of them developed local recurrence, and 7 patients developed distant metastases. Fifteen patients died during follow-up period. Overall survival rates considering the whole study group was 78.57% at 5y, and 72.16% at 10y after the initial diagnosis. Compared with chemotherapy, RT was associated with lower risk of local recurrence [hazard ratio for RT vs chemotherapy, 0.263, 95% confidence interval (CI), 0.095-0.728, P=0.0015]; with lower risk of distant metastasis (hazard ratio for RT vs chemotherapy, 0.073, 95%CI, 0.015-0.364, P=0.0014); and with lower risk of death from disease (hazard ratio for RT vs chemotherapy, 0.066, 95%CI, 0.022-0.200, P