Activation of non-classical Wnt signaling pathway effectively enhances HLA-A presentation in acute myeloid leukemia.

Objective: The escape from T cell-mediated immune surveillance is an important cause of death for patients with acute myeloid leukemia (AML). This study aims to identify clonal heterogeneity in leukemia progenitor cells and explore molecular or signaling pathways associated with AML immune escape. Methods: Single-cell RNA sequencing (scRNA-seq) was performed to identified AML-related cellular subsets, and intercellular communication was analyzed to investigate molecular mechanisms associated with AML immune escape. Bulk RNA sequencing (RNA-seq) was performed to screen differentially expressed genes (DEGs) related to hematopoietic stem cell progenitors (HSC-Prog) in AML, and critical ore signaling pathways and hub genes were found by Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The mRNA level of the hub gene was verified using quantitative real-time PCR (qRT-PCR) and the protein level of human leukocyte antigen A (HLA-A) using enzyme-linked immuno sorbent assay (ELISA). Results: scRNA-seq analysis revealed a large heterogeneity of HSC-Prog across samples, and the intercellular communication analysis indicated a strong association between HSC-Prog and CD8+-T cells, and HSC-Prog also had an association with HLA-A. Transcriptome analysis identified 1748 DEGs, enrichment analysis results showed that non-classical wnt signaling pathway was associated with AML, and 4 pathway-related genes (RHOA, RYK, CSNK1D, NLK) were obtained. After qRT-PCR and ELISA validation, hub genes and HLA-A were found to be down-regulated in AML and up-regulated after activation of the non-classical Wnt signaling pathway. Conclusion: In this study, clonal heterogeneity of HSC-Prog cells in AML was identified, non-classical wnt signaling pathways associated with AML were identified, and it was verified that HLA-A could be upregulated by activation of non-classical wnt signaling, thereby increasing antigen presentation.

A new tau dephosphorylation-targeting chimera for the treatment of tauopathies.

Abnormal accumulation of hyperphosphorylated tau protein plays a pivotal role in a collection of neurodegenerative diseases named tauopathies, including Alzheimer's disease (AD). We have recently conceptualized the design of hetero-bifunctional chimeras for selectively promoting the proximity between tau and phosphatase, thus specifically facilitating tau dephosphorylation and removal. Here, we sought to optimize the construction of tau dephosphorylating-targeting chimera (DEPTAC) and obtained a new chimera D14, which had high efficiency in reducing tau phosphorylation both in cell and tauopathy mouse models, while showing limited cytotoxicity. Moreover, D14 ameliorated neurodegeneration in primary cultured hippocampal neurons treated with toxic tau-K18 fragments, and improved cognitive functions of tauopathy mice. These results suggested D14 as a cost-effective drug candidate for the treatment of tauopathies.

Effectiveness of different intrusion modes of maxillary anterior teeth with mini-implants in clear aligner treatment: a three-dimensional finite element analysis.

BACKGROUND: The intrusion of maxillary anterior teeth is often required and there are various intrusion modes with mini-implants in clear aligner treatment. The objective of this study was to evaluate the effectiveness of maxillary anterior teeth intrusion with different intrusion modes, aiming to provide references for precise and safe intrusion movements in clinical practice. METHODS: Cone-beam computed tomography and intraoral optical scanning data of a patient were collected. Finite element models of the maxilla, maxillary dentition, periodontal ligaments (PDLs), clear aligner (CA), attachments, and mini-implants were established. Different intrusion modes of the maxillary anterior teeth were simulated by changing the mini-implant site (between central incisors, between central and lateral incisor, between lateral incisor and canine), loading site (between central incisors, on central incisor, between central and lateral incisor, between lateral incisor and canine), and loading mode (labial loading and labiolingual loading). Ten conditions were generated and intrusive forces of 100 g were applied totally. Then displacement tendency of the maxillary anterior teeth and CA, and stress of the PDLs were analyzed. RESULTS: For the central incisor under condition L14 and for the canine under conditions L11, L13, L23, and L33, the intrusion amount was negative. Under other conditions, the intrusion amount was positive. The labiolingual angulation of maxillary anterior teeth exhibited positive changes under all conditions, with greater changes under linguoincisal loading. The mesiodistal angulation of canine exhibited positive changes under labial loading, while negative changes under linguoincisal loading except for condition L14. CONCLUSIONS: The intrusion amount, labiolingual and mesiodistal angulations of the maxillary anterior teeth were affected by the mini-implant site, loading site, and loading mode. Labial and linguoincisal loading may have opposite effects on the intrusion amount of maxillary anterior teeth and the mesiodistal angulation of canine. The labiolingual angulation of the maxillary incisors would increase under all intrusion modes, with greater increases under linguoincisal loading.

Introduction and impact of routine whole genome sequencing in the diagnosis and management of sarcoma.

BACKGROUND: Sarcomas are diverse neoplasms with highly variable histological appearances in which diagnosis is often challenging and management options for metastatic/unresectable disease limited. Many sarcomas have distinctive molecular alterations, but the range of alterations is large, variable in type and rapidly increasing, meaning that testing by limited panels is unable to capture the broad spectrum of clinically pertinent genomic drivers required. Paired whole genome sequencing (WGS) in contrast allows comprehensive assessment of small variants, copy number and structural variants along with mutational signature analysis and germline testing. METHODS: Introduction of WGS as a diagnostic standard for all eligible patients with known or suspected soft tissue sarcoma over a 2-year period at a soft tissue sarcoma treatment centre. RESULTS: WGS resulted in a refinement in the diagnosis in 37% of cases, identification of a target for personalised therapy in 33% of cases, and a germline alteration in 4% of cases. CONCLUSION: Introduction of WGS poses logistical and training challenges, but offers significant benefits to this group of patients.

PCCA variant rs16957301 is a novel AKI risk genotype-specific for patients who receive ICI treatment: Real-world evidence from All of Us cohort.

Background: Immune checkpoint inhibitors (ICIs) enhance the immune system's ability to target and destroy cancer cells by blocking inhibitory pathways. Despite their efficacy, these treatments can trigger immune-related adverse events (irAEs), such as acute kidney injury (ICI-AKI), complicating patient management. The genetic predispositions to ICI-AKI are not well understood, necessitating comprehensive genomic studies to identify risk factors and improve therapeutic strategies. Objective: To identify genetic predispositions for ICI-AKI using large-scale real-world data. Methods: A systematic literature search led to 14 candidate variants related to irAEs. We performed a candidate variant association study with these 14 variants using the All of Us cohort (AoU, v7, cutoff date: 7/1/2022). A cohort for cancer patients receiving ICI and a general cohort were established to evaluate ICI-AKI risk. Logistic regression, adjusted for sex, was used to evaluate the impact of each candidate genotype, separately for self-reported and ancestry-estimated race. Kaplan-Meier survival analysis assessed the genetic effects on AKI-free survival. Results: The ICI cohort (n=414) showed a one-year AKI incidence rate of 23.2%, significantly higher than the general cohort (6.5%, n=213,282). The rs16957301 variant (chr13:100324308, T>C) in the PCCA gene was a significant risk genotype for ICI-AKI among self-reported Caucasians (Beta=0.93, Bonferroni-corrected P-value=0.047) and ancestry estimated Caucasians (Beta = 0.94, Bonferroni-corrected P-value=0.044). Self-reported Caucasians with the rs16957301 risk genotypes (TC/CC) developed AKI significantly earlier (3.6 months) compared to the reference genotype (TT, 7.0 months, log-rank P=0.04). Consistent results were found in ancestry-estimated Caucasians. This variant did not present significant AKI risks in the general cohort (Beta: -0.008-0.035, FDR: 0.75-0.99). Conclusion: Real-world evidence from the All of Us cohort suggests that, in Caucasians, PCCA variant rs16957301 is a novel AKI risk genotype specific to ICI treatment. Additional studies are warranted to validate rs16957301 as risk marker for AKI in Caucasian patients treated with ICIs and to assess its risk in other ancestral populations.

Unique urine and serum metabolomic signature in patients with excessive alcohol use: An exploratory study.

BACKGROUND: Excessive alcohol consumption has a multifaceted impact on the body's metabolic pathways and organ systems. The objectives of this study were to characterize global metabolomic changes and identify specific pathways that are altered in individuals with excessive alcohol use. METHODS: This exploratory study included 22 healthy controls with no known history of excessive alcohol use and 38 patients identified as using alcohol excessively. A Fibrosis-4 score was used to determine the risk of underlying alcohol-associated liver disease among the excessive drinkers. RESULTS: We found significantly altered urinary and serum metabolites among excessive drinkers, affecting various metabolic pathways including the metabolism of lipids, amino acids and peptides, cofactors and vitamins, carbohydrates, and nucleotides. Levels of two steroid hormones-5alpha-androstan-3beta,17beta-diol disulfate and androstenediol (3beta,17beta) disulfate-were significantly higher in both the serum and urine samples of excessive drinkers. These elevated levels may be associated with a higher risk of liver fibrosis in individuals with excessive alcohol use. CONCLUSION: Alcohol consumption leads to marked alterations in multiple metabolic pathways, highlighting the systemic impact of alcohol on various tissues and organ systems. These findings provide a foundation for future mechanistic studies aimed at elucidating alcohol-induced changes in these metabolic pathways and their implications.

Chromomycins from soil-derived Streptomyces sp. inhibit the growth of human non-small cell lung cancer cells by targeting c-FLIP.

Three chromomycin derivatives, chromomycins A3 (1, CA3), A5 (2, CA5), and monodeacetylchromomycin A3 (3, MDA-CA3), were identified from the soil-derived Streptomyces sp. CGMCC 26516. A reinvestigation of the structure of CA5 is reported, of which the absolute configuration was unambiguously determined for the first time to be identical with that of CA3 based on nuclear magnetic resonance (NMR) data analysis as well as NMR and electronic circular dichroism calculations. Compounds 1-3 showed potent cytotoxicity against the non-small-cell lung cancer (NSCLC) cells (A549, H460, H157-c-FLIP, and H157-LacZ) and down-regulated the protein expression of c-FLIP in A549 cells. The IC50 values of chromomycins in H157-c-FLIP were higher than that in H157-LacZ. Furthermore, si-c-FLIP promoted anti-proliferation effect of chromomycins in NSCLC cells. In nude mice xenograft model, 1 and 2 both showed more potent inhibition on the growth of H157-lacZ xenografts than that of H157-c-FLIP xenografts. These results verify that c-FLIP mediates the anticancer effects of chromomycins in NSCLC.

Noviherbaspirillum album sp. nov., an airborne bacteria isolated from an urban area of Beijing, China.

A Gram-negative, ellipsoidal to short-rod-shaped, motile bacterium was isolated from Beijing's urban air. The isolate exhibited the closest kinship with Noviherbaspirillum aerium 122213-3T, exhibiting 98.4 % 16S rRNA gene sequence similarity. Phylogenetic analyses based on 16S rRNA gene sequences and genomes showed that it clustered closely with N. aerium 122213-3T, thus forming a distinct phylogenetic lineage within the genus Noviherbaspirillum. The average nucleotide identity and digital DNA-DNA hybridization values between strain I16B-00201T and N. aerium 122213-3T were 84.6 and 29.4 %, respectively. The respiratory ubiquinone was ubiquinone 8. The major fatty acids (>10 %) were summed feature 3 (C16:1ω6c/C16:1ω7c, 43.3 %), summed feature 8 (C18:1ω7c/C18:1ω6c, 15.9 %) and C12:0 (11.0 %). The polyamine profile showed putrescine as the predominant compound. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, unknown lipids and unknown phosphatidylaminolipids. The phenotypic, phylogenetic and chemotaxonomic results consistently supported that strain I16B-00201T represented a novel species of the genus Noviherbaspirillum, for which the name Noviherbaspirillum album sp. nov. is proposed, with I16B-00201T (=CPCC 100848T=KCTC 52095T) designated as the type strain. Its DNA G+C content is 59.4 mol%. Pan-genome analysis indicated that some Noviherbaspirillum species possess diverse nitrogen and aromatic compound metabolism pathways, suggesting their potential value in pollutant treatment.

High-power single-frequency continuous-wave 355 nm UV laser via a frequency-correlated dual-wavelength laser.

An all-solid-state single-frequency continuous-wave (CW) 355 nm ultraviolet (UV) laser based on a dispersion-compensated doubly resonant resonator is presented in this Letter that is achieved by employing homemade high-stability all-solid-state frequency-correlated dual-wavelength lasers at 1064 and 532 nm and a temperature-controlled type-I critical-phase-matching LiB3O5 (LBO) to act as the fundamental laser source and the nonlinear medium, respectively. The frequency-correlated dual-wavelength single-frequency CW laser supplies the fundamental frequency 1064 and 532 nm lasers with good frequency synchronization. And the temperature-controlled LBO acts as the dispersion-compensation element to realize double resonance of the 1064 and 532 nm laser. Finally, a 4.2 W high-stability 355 nm UV laser is experimentally obtained, and the corresponding total conversion efficiency is up to 20.5%. To the best of our knowledge, this is the highest power reported about single-frequency CW 355 nm UV laser. The presented method can pave a way to develop a compact single-frequency 355 nm UV laser with high output power.

Bacillus amyloliquefaciens LM-1 Affects Multiple Cell Biological Processes in Magnaporthe oryzae to Suppress Rice Blast.

Magnaporthe oryzae, one of the most destructive rice pathogens, causes significant losses during the rice harvest every year. Bacillus amyloliquefaciens has been explored in many crops as a potential biocontrol agent. However, the mechanisms of B. amyloliquefaciens controled rice blast are not fully understood. Here, a biocontrol strain LM-1, isolated from a contaminated medium, was identified as B. amyloliquefaciens using morphological observation, physiological and biochemical tests, and 16S rDNA sequencing. LM-1 inhibited the growth and pathogenicity of M. oryzae and Bipolaris oryzae (Breda de Haan) Shoem. The mycelia of M. oryzae co-cultured with LM-1 were enlarged and broken by fluorescence microscopy using calcofluor white. LM-1 inhibited the mycelia of M. oryzae from producing conidia. Genes itu, srf, and fenB were detected in LM-1. Furthermore, the supernatant of LM-1 interfered with the appressorium formation of M. oryzae, blocked conidial cell death, and reduced autophagy degradation but did not affect the normal germination of rice seeds and seeding growth. Additionally, we observed hypersensitivity reactions, reactive oxygen species, and iron accumulation reduction in rice cells inoculated with supernatant. Our study reveals that LM-1 has a control effect on rice blast and affects cell wall integrity, sporulation, appressorium formation, cell death, and autophagy.

Maximizing arsenic trioxide's anticancer potential: Targeted nanocarriers for solid tumor therapy.

Arsenic trioxide (ATO) has gained significant attention due to its promising therapeutic effects in treating different diseases, particularly acute promyelocytic leukemia (APL). Its potent anticancer mechanisms have been extensively studied. Despite the great efficacy ATO shows in fighting cancers, drawbacks in the clinical use are obvious, especially for solid tumors, which include rapid renal clearance and short half-life, severe adverse effects, and high toxicity to normal cells. Recently, the emergence of nanomedicine offers a potential solution to these limitations. The enhanced biocompatibility, excellent targeting capability, and desirable effectiveness have attracted much interest. Therefore, we summarized various nanocarriers for targeted delivery of ATO to solid tumors. We also provided detailed anticancer mechanisms of ATO in treating cancers, its clinical trials and shortcomings as well as the combination therapy of ATO and other chemotherapeutic agents for reduced drug resistance and synergistic effects. Finally, the future study direction and prospects were also presented.

Effects of early nutritional intervention on oral mucositis and basic conditions in patients receiving radiotherapy for head and neck cancer: Randomized controlled trial (ChiCTR2000031418).

BACKGROUND & AIMS: This study aims to observe the effects of early nutritional intervention on radiation-induced oral mucositis (OM) and the nutritional status of patients with head and neck cancer (HNC) receiving radiotherapy. METHODS: Eligible patients receiving radiotherapy for HNC were randomly divided into an early nutritional intervention group (enteral nutritional intervention was administered at the beginning of radiotherapy) and a late nutritional intervention group (enteral nutritional intervention was administered at the beginning of eating restriction) in a 1:1 ratio. The primary endpoint was radiation-induced OM. Secondary endpoints included nutrition-related indicators, immune function, overall survival (OS), progression-free survival (PFS), quality of life, and other radiotherapy-induced adverse effects. RESULTS: A total of 100 patients were enrolled between 2020 and 2021, including 50 each in the early nutritional intervention group and in the late group. The incidence of Grade-III/IV OM was lower in the early treatment group than in the late treatment group (2% vs 14%, P = 0.059). By week 7 weight loss was significantly lower in the early group than in the late group (1.08 kg, 95% CI: 0.08-2.09, P = 0.035). Regarding the PG-SGA scores after receiving radiotherapy, the early group comprised more well-nourished and fewer malnourished patients than those in the late group (P = 0.002). The scores of the immune function indices of T cell CD3+, CD4+/CD8+, and B cell CD19+ were slightly higher in the early group than in the late group; however, the difference was not statistically significant (all P > 0.05). PFS and OS were better in the early group than in the late group; however, the differences were not statistically significant (P > 0.05). CONCLUSIONS: Early nutritional intervention can effectively improve the nutritional status and reduce the incidence of high-grade OM in patients with HNC receiving radiotherapy. TRIAL REGISTRATION: Chinese Clinical Trials Registry (http://www.chictr.org.cn). CHICTR-ID: ChiCTR2000031418.

Polydopamine bridging encapsulated laccase on MOF-based mixed-matrix membrane for selective dye/salt separation.

Mixed-matrix membranes (MMMs) exhibit significant potential for dye/salt separation. However, overcoming the "trade-off" between permeability and selectivity, as well as membrane fouling, remains a formidable task. In this work, a biocatalytic membrane was prepared using polydopamine (PDA) as a "bridge" connecting the metal-organic framework (MOF)-based MMM and immobilized laccase. The MOF-based MMM featured an interconnected MOF anchoring on the polyvinylidene fluoride (PVDF) skeleton structure, effectively mitigating the "trade-off" phenomenon and enabling efficient separation of dyes and salts. Enzyme-MOF was in situ grown on the MOF-based MMM via coordination reactions between PDA and metal ion, effectively degrading the adhesion of organic pollutants and fouling, ensuring the long-term stable operation of the membrane. The Lac-MOF@PDA MMM exhibited excellent water permeability of 142.4 L·m-2·h-1, 100 % rejection for dye, and less than 10 % rejection for NaCl. Furthermore, the separation mechanism of Lac-MOF@PDA MMM was systematically investigated, and the results suggested a synergistic combination of rejection, adsorption and catalysis processes. This biocatalytic membrane with multiple sieving and biological catalysis is expected to pave a promising way for efficient wastewater treatment applications.

TrajVis: a visual clinical decision support system to translate artificial intelligence trajectory models in the precision management of chronic kidney disease.

OBJECTIVE: Our objective is to develop and validate TrajVis, an interactive tool that assists clinicians in using artificial intelligence (AI) models to leverage patients' longitudinal electronic medical records (EMRs) for personalized precision management of chronic disease progression. MATERIALS AND METHODS: We first perform requirement analysis with clinicians and data scientists to determine the visual analytics tasks of the TrajVis system as well as its design and functionalities. A graph AI model for chronic kidney disease (CKD) trajectory inference named DisEase PrOgression Trajectory (DEPOT) is used for system development and demonstration. TrajVis is implemented as a full-stack web application with synthetic EMR data derived from the Atrium Health Wake Forest Baptist Translational Data Warehouse and the Indiana Network for Patient Care research database. A case study with a nephrologist and a user experience survey of clinicians and data scientists are conducted to evaluate the TrajVis system. RESULTS: The TrajVis clinical information system is composed of 4 panels: the Patient View for demographic and clinical information, the Trajectory View to visualize the DEPOT-derived CKD trajectories in latent space, the Clinical Indicator View to elucidate longitudinal patterns of clinical features and interpret DEPOT predictions, and the Analysis View to demonstrate personal CKD progression trajectories. System evaluations suggest that TrajVis supports clinicians in summarizing clinical data, identifying individualized risk predictors, and visualizing patient disease progression trajectories, overcoming the barriers of AI implementation in healthcare. DISCUSSION: The TrajVis system provides a novel visualization solution which is complimentary to other risk estimators such as the Kidney Failure Risk Equations. CONCLUSION: TrajVis bridges the gap between the fast-growing AI/ML modeling and the clinical use of such models for personalized and precision management of chronic diseases.

Factors affecting meibomian gland area loss in symptomatic adults.

AIM: To characterize the distribution of meibomian gland (MG) area loss (MGL) and its relationship with demographic characteristics, mites, and symptoms. METHODS: This retrospective observational study included patients who visited the Dry Eye Clinic of Shenzhen Eye Hospital between June 2020 and August 2021. General patient characteristics, ocular symptoms, Demodex test results of the eyelid edges, and the results of a comprehensive ocular surface analysis were collected. MGL was analyzed using Image J software. RESULTS: This study enrolled 1204 outpatients aged 20-80 (40.70±13.44)y, including 357 males (29.65%) and 847 females (70.35%). The patients were classified into mild (n=155; 12.87%), moderate (n=795; 66.03%), severe (n=206; 17.11%), and extremely severe (n=48; 3.99%) MGL groups. MGL was significantly larger in female than in male (P=0.006). The degree of MGL also significantly differed in age (P<0.001) and the more numbers of mites with severity (P<0.001). Multivariate disordered multinomial logistic regression analysis identified that female sex, older age, secretory symptoms, and a large number of mites were risk factors for MGL (P<0.05). CONCLUSION: Patients with MGL are more likely to be older, female, more numbers of mites, and increased secretion.

Unlocking the potential of surface modification with phosphate on ball milled zero-valent iron reactivity:Implications for radioactive metal ions removal.

Numerous investigations have illuminated the profound impact of phosphate on the adsorption of uranium, however, the effect of phosphate-mediated surface modification on the reactivity of zero-valent iron (ZVI) remained enigmatic. In this study, a phosphate-modified ZVI (P-ZVIbm) was prepared with a facile ball milling strategy, and compared with ZVIbm, the U(VI) removal amount (435.2 mg/g) and efficiency (3.52×10-3 g·mg-1·min-1) of P-ZVIbm were disclosed nearly 2.0 and 54 times larger than those of ZVIbm respectively. The identification of products revealed that the adsorption mechanism dominated the removal process for ZVIbm, while the reactive modified layer strengthened both the adsorption pattern and reduction performance on P-ZVIbm. DFT calculation result demonstrated that the binding configuration shifted from bidentate binuclear to multidentate configuration, further shortening the Fe-U atomic distance. More importantly, the electron transferred is more accessible through the surface phosphate layer, and selectively donated to U(VI), accounting for the elevated reduction performance of P-ZVIbm. This investigation explicitly underscores the critical role of ZVI's surface microenvironment in the domain of radioactive metal ion mitigation and introduces a novel methodology to amplify the sequestration of U(VI) from aqueous environments.

Risk of mortality among patients with alcohol-associated hepatitis in the US from 2007 to 2021.

BACKGROUND: /Aims: Alcohol-associated hepatitis (AH) mortality and risk factors have not been carefully studied in real-world settings. We examined the rate, temporal trend, and risk factors of mortality in AH. METHODS: We conducted a cohort study of individuals with AH diagnoses using medical claims data from Optum's Clinformatics® Data Mart (CDM). Participants were individuals covered by Medicare Advantage and commercial insurance policies. Cases were identified using diagnostic codes. Cox regressions were used to estimate 90 and 180-day mortality rates by hospitalization status. RESULTS: The cohort included 32,001 patients (72% men) who had at least one year of continuous insurance coverage prior to AH diagnoses. Of these, 20,912 were hospitalized within seven days of diagnosis. Ninety and 180-day mortality rates were 12.0% (95% CI [11.6%, 12.5%]) and 16.0% (95% CI [15.4%, 16.5%]), respectively, for the hospitalized patients and 3.1% (95% CI [2.8%, 3.4%]) and 5.1% (95% CI [4.6%, 5.5%]) for the non-hospitalized patients. Pre-existing liver disease, even in a mild form, was associated with an increased risk of death. In hospitalized patients, a history of mild liver disease was associated with a 24% increase in 180-day mortality risk (HR= 1.24, 95% CI: [1.14, 1.36]). Moderate-to-severe liver disease was associated with a more than doubled risk (HR= 2.33, 95% CI: [2.12, 2.56]). CONCLUSIONS: History of liver disease was associated with significantly increased AH mortality. The finding highlights the chronic disease context of AH and suggests that prior diagnosis of liver disease should be considered for prognosis and targeted prevention.

Clerodendranthus Spicatus: A review of its active compounds, mechanisms of action, and clinical studies in urinary diseases.

Clerodendranthus spicatus (Thunb.) C.Y.Wu (CS) is a widely studied plant that shows potential in treating urinary diseases. Previous studies have focused on its chemical composition, pharmacological effects, and clinical applications. This review aims to provide a comprehensive summary and evaluation of the existing literature on CS. It also suggests future research directions to increase our understanding of its medicinal value. 129 pieces of literature were selected from several databases, including PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), Wan-fang Database, and Google Scholar, and were analyzed. Forty-five active compounds of CS have pharmacological effects such as lowering uric acid, anti-inflammation, anti-oxidation, and kidney protection. The potential mechanisms of these effects may be related to inhibiting transforming growth factor ß1 (TGF-ß1) activation, reducing inflammatory factors such as IL-8, IL-1ß, TNF-α, PGE2, IFN-γ, and IL-6 levels, suppressing the activation of NF-κB, JAK/STAT pathway, enhancing the clearance of ROS, MDA DPPH·, and O2 ̇ -, and regulating the expression of apoptosis-related pathways and proteins. This paper also discusses the quality control of CS and its efficacy and safety in treating urinary diseases. The study concludes that CS has a high potential for treating urinary diseases. Future studies should focus on observing the metabolic changes of CS active compounds in vivo and investigating the effects of CS on key signaling pathways. Additionally, more standardized and reasonable clinical studies and safety evaluation experiments should be conducted to obtain more clinical data.

The prognostic value of prognostic nutritional index in postoperative onset of PAH in children with isolated VSD: a prospective cohort study based on propensity score matching analysis.

Background: The mechanism of pulmonary arterial hypertension (PAH) after surgery/intervention for isolated venticlular septal defect (VSD) in children is unknown. Reliable prognostic indicators for predicting postoperative PAH are urgently needed. Prognostic nutration index (PNI) is widely used to predict postoperative complications and survival in adults, but it is unclear whether it can be used as an indicator of prognosis in children. Methods: A total of 251 children underwent VSD repair surgery or interventional closure in Hunan Children's Hospital from 2020 to 2023 were collected. A 1:1 propensity score matching (PSM) analysis was performed using the nearest neighbor method with a caliper size of 0.2 Logistics regression analysis is used to examine factors associated with the development of PAH. Results: The cut-off value for PNI was determined as 58.0. After 1:1 PSM analysis, 49 patients in the low PNI group were matched with high PNI group. Children in the low PNI group had higher risk of postoperative PAH (P = 0.002) than those in the high PNI group. Multivariate logistics regression analysis showed that PNI (RR: 0.903, 95% CI: 0.816-0.999, P = 0.049) and tricuspid regurgitation velocity (RR: 4.743, 95% CI: 1.131-19.897, P = 0.033) were independent prognostic factors for the development of PAH. Conclusion: PNI can be used as a prognostic indicator for PAH development after surgery/intervention in children with isolated VSD.