[Pathogenesis of benign prostatic hyperplasia from the perspective of syndrome differentiation of viscera based on the neuro-endocrine-immune network].

According to the theory of traditional Chinese medicine (TCM), benign prostatic hyperplasia (BPH) belongs to the category of "Jing Long". Clinical management of BPH in TCM is root-aimed and kidney-targeted, in combination with the treatment of other viscera based on the syndrome differentiation of zang-fu organs. The neuro-endocrine-immune network of modern medicine is similar to the holistic concept of TCM. Based on the study of the neuro-endocrine-immune network, with kidney deficiency as the root of pathogenesis, and starting from the classification of viscera, this review elucidates the etiologic mechanisms of BHP from the perspective of Chinese and Western medicine and provides some reference for medication.

Cross-talks between perivascular adipose tissue and neighbors: multifaceted nature of nereids.

Perivascular adipose tissue (PVAT) is a unique fat depot surrounding blood vessels and plays a vital role in the progression of vascular remodeling and dysfunction. PVAT exhibits remarkable differences in structure, phenotype, origin, and secretome across anatomical locations. The proximity of PVAT to neighboring vascular beds favors a niche for bidirectional communication between adipocytes and vascular smooth muscle cells, endothelial cells, and immune cells. In this review, we update our understanding of PVAT's regional differences and provide a comprehensive exploration of how these differences impact cross-talks between PVAT and the vascular wall. Different PVAT depots show different degrees of vasoprotective function and resilience to pathological changes such as obesity and vasculopathies, shaping multifaceted interactions between PVAT depots and adjacent vasculatures. The depot-specific resilience may lead to innovative strategies to manage cardiometabolic disorders.

Changes in gender disparities of depressive symptoms among middle-aged and older adults in China: an age-period-cohort analysis.

PURPOSE: Depression is one of the most common mental disorders and substantially decreases socioemotional well-being and health-related quality of life. Analyzing temporal patterns in depressive symptoms can reveal emerging risks that require attention and have implications for mental health promotion. The present study disentangled age, period, and cohort (APC) effects on trends in depressive symptoms and their gender disparities among China's nationally representative samples of middle-aged and older adults. METHODS: Using four-wave data (2011, 2013, 2015, and 2018) from the China Health and Retirement Longitudinal Study (N = 65455), APC effects were quantified based on the hierarchical APC model. The 10-item Center for Epidemiologic Studies Depression Scale (CES-D-10) was used to measure depressive symptoms. RESULTS: Depressive symptoms increased during late life and stabilized after reaching an advanced age. After further adjusting for individual characteristics, depressive symptoms exhibited a negative trend with advancing age. The mean levels of depressive symptoms remained stable during the study period. Depressive symptoms varied significantly across cohorts, with those born in 1949-1951 having the most severe depressive symptoms. Significant life-course and cohort variations existed in the gender gaps in depressive symptoms. Although women had higher mean scores on the CES-D-10 scale throughout the life course, the gender gaps in depressive symptoms gradually narrowed with age, as depressive symptoms decreased more rapidly among women. A widening trend in gender gaps in depressive symptoms was found among those born after the mid-1950s, mainly driven by a notable decline in depressive symptoms among men CONCLUSIONS: The convergence of living conditions between genders in late life, as a result of traditional Chinese culture, may have narrowed the gender gap in depressive symptoms. However, given the widening gender disparities in depressive symptoms among younger cohorts, more attention should be paid to women's mental health in the context of China's rapid socioeconomic development.

Plant-based diet indices and their interaction with ambient air pollution on the ovarian cancer survival: A prospective cohort study.

BACKGROUND: Ambient air pollution might serve as a prognostic factor for ovarian cancer (OC) survival, yet the relationships between plant-based diet indices (PDIs) and OC survival remain unclear. We aimed to investigate the associations of comprehensive air pollution and PDIs with OC survival and explored the effects of air pollution-diet interactions. METHODS: The present study encompassed 658 patients diagnosed with OC. The overall plant-based diet index (PDI), the healthful PDI (hPDI), and the unhealthful PDI (uPDI) were evaluated by a self-reported validated food frequency questionnaire. In addition, an air pollution score (APS) was formulated by summing the concentrations of particulate matter with a diameter of 2.5 microns or less, ozone, and nitrogen dioxide. Cox proportional hazard models were applied to calculate hazard ratios (HRs) and 95 % confidence intervals (CIs). The potential interactions of APS with PDIs in relation to overall survival (OS) were assessed on both multiplicative and additive scales. RESULTS: Throughout a median follow-up of 37.60 (interquartile: 24.77-50.70) months, 123 deaths were confirmed. Comparing to the lowest tertiles, highest uPDI was associated with lower OS of OC (HR = 2.06, 95 % CI = 1.30, 3.28; P-trend < 0.01), whereas no significant associations were found between either overall PDI or hPDI and OC survival. Higher APS (HR for per interquartile range = 1.27, 95 % CI = 1.01, 1.60) was significantly associated with worse OC survival, and the association was exacerbated by adherence to uPDI. Notably, an additive interaction was identified between combined air pollution and uPDI (P < 0.005 for high APS and high uPDI). We also found that adherence to overall PDI aggravated associations of air pollution with OC survival (P-interaction = 0.006). CONCLUSIONS: Joint exposure to various ambient air pollutants was significantly associated with lower survival among patients with OC, particularly for those who predominantly consumed unhealthy plant-based foods.

Cardioprotection of voluntary exercise against breast cancer-induced cardiac injury via STAT3.

Exercise is an effective way to alleviate breast cancer-induced cardiac injury to a certain extent. However, whether voluntary exercise (VE) activates cardiac signal transducer and activator of transcription 3 (STAT3) and the underlying mechanisms remain unclear. This study investigated the role of STAT3-microRNA(miRNA)-targeted protein axis in VE against breast cancer-induced cardiac injury.VE for 4 weeks not only improved cardiac function of transgenic breast cancer female mice [mouse mammary tumor virus-polyomavirus middle T antigen (MMTV-PyMT +)] compared with littermate mice with no cancer (MMTV-PyMT -), but also increased myocardial STAT3 tyrosine 705 phosphorylation. Significantly more obvious cardiac fibrosis, smaller cardiomyocyte size, lower cell viability, and higher serum tumor necrosis factor (TNF)-α were shown in MMTV-PyMT + mice compared with MMTV-PyMT - mice, which were ameliorated by VE. However, VE did not influence the tumor growth. MiRNA sequencing identified that miR-181a-5p was upregulated and miR-130b-3p was downregulated in VE induced-cardioprotection. Myocardial injection of Adeno-associated virus serotype 9 driving STAT3 tyrosine 705 mutations abolished cardioprotective effects above. Myocardial STAT3 was identified as the transcription factor binding the promoters of pri-miR-181a (the precursor of miR-181a-5p) and HOX transcript antisense RNA (HOTAIR, sponged miR-130b-3p) in isolated cardiomyocytes. Furthermore, miR-181a-5p targeting PTEN and miR-130b-3p targeting Zinc finger and BTB domain containing protein 20 (Zbtb20) were proved in AC-16 cells. These findings indicated that VE protects against breast cancer-induced cardiac injury via activating STAT3 to promote miR-181a-5p targeting PTEN and to promote HOTAIR to sponge miR-130b-3p targeting Zbtb20, helping to develop new targets in exercise therapy for breast cancer-induced cardiac injury.

Traceable Optical Physical Unclonable Functions Based on Germanium Vacancy in Diamonds.

Physical unclonable functions (PUFs) have emerged as an unprecedented solution for modern information security and anticounterfeiting by virtue of their inherent unclonable nature derived from distinctive, randomly generated physical patterns that defy replication. However, the creation of traceable optical PUF tags remains a formidable challenge. Here, we demonstrate a traceable PUF system whose unclonability arises from the random distribution of diamonds and the random intensity of the narrow emission from germanium vacancies (GeV) within the diamonds. Tamper-resistant PUF labels can be manufactured on diverse and intricate structural surfaces by blending diamond particles into polydimethylsiloxane (PDMS) and strategically depositing them onto the surface of objects. The resulting PUF codes exhibit essentially perfect uniformity, uniqueness, reproducibility, and substantial encoding capacity, making them applicable as a private key to fulfill the customization demands of circulating commodities. Through integration of a digitized "challenge-response" protocol, a traceable and highly secure PUF system can be established, which is seamlessly compatible with contemporary digital information technology. Thus, the GeV-PUF system holds significant promise for applications in data security and blockchain anticounterfeiting, providing robust and adaptive solutions to address the dynamic demands of these domains.

Vacancy Effect on the Luminescent and Water Responsive Properties of Vacancy-ordered Double Perovskite Derivatives.

Vacancy-ordered perovskites and derivatives represent an important subclass of hybrid metal halides with promise in applications including light emitting devices and photovoltaics. Understanding the vacancy-property relationship is crucial for designing related task-specific materials, yet research in this field remains sporadic. For the first time, we use the Connolly surface to quantitatively calculate the volume of vacancy (V□, □ = vacancy) in vacancy-ordered double perovskite derivatives (VDPDs). A relationship between void fraction and the structure, photoluminescent properties and humidity stability was established based on zero-dimensional (0-D) [N(alkyl)4]2Sb□Cl5□'-type VDPDs. Compared with the more commonly studied A2M(IV)X6□-type double perovskite (A = cation, M = metal ion, X = halide), [N(alkyl)4]2Sb□Cl5□' features double vacancy sites. Our results demonstrate an inverse relationship between the photoluminescent quantum yield and V□ in 0-D VDPDs. Additionally, structural transformation from A2SbCl5 to A3Sb2Cl9 was first reported, during which the novel 'gate-opening' gas adsorption phenomenon was observed in VDPDs for the first time, as evidenced by 'S'-shaped sorption isotherms for water vapor, indicating a cation-controlled water-vapor response behavior. A mixed-cation strategy was developed to modulate the humidity stability of VDPDs. Characterized by controllable water-responsive behavior and unique 'on-off-on' luminescent switching, A2M(III)□X5□'-type materials show great promise for multi-level information anti-counterfeiting applications.

Using bioactive compounds to mitigate the formation of typical chemical contaminants generated during the thermal processing of different food matrices.

With rising consumer awareness of health and wellness, the demand for enhanced food safety is rapidly increasing. The generation of chemical contaminants during the thermal processing of food materials, including polycyclic aromatic hydrocarbons, heterocyclic aromatic amines, and acrylamide happens every day in every kitchen all around the world. Unlike extraneous chemical contaminants (e.g., pesticides, herbicides, and chemical fertilizers), these endogenic chemical contaminants occur during the cooking process and cannot be removed before consumption. Therefore, much effort has been invested in searching for ways to reduce such thermally induced chemical contaminants. Recently, the addition of bioactive compounds has been found to be effective and promising. However, no systematic review of this practical science has been made yet. This review aims to summarize the latest applications of bioactive compounds for the control of chemical contaminants during food thermal processing. The underlying generation mechanisms and the toxic effects of these chemical contaminants are discussed in depth to reveal how and why they are suppressed by the addition of certain bioactive ingredients. Examples of specific bioactive compounds, such as phenolic compounds and organic acids, as well as their application scenarios, are outlined. In the end, outlooks and expectations for future development are provided based on a comprehensive summary and reflection of references.

Relevance and regulation of alternative splicing in plant secondary metabolism: current understanding and future directions.

The secondary metabolism of plants is an essential life process enabling organisms to navigate various stages of plant development and cope with ever-changing environmental stresses. Secondary metabolites, abundantly found in nature, possess significant medicinal value. Among the regulatory mechanisms governing these metabolic processes, alternative splicing stands out as a widely observed post-transcriptional mechanism present in multicellular organisms. It facilitates the generation of multiple mRNA transcripts from a single gene by selecting different splicing sites. Selective splicing events in plants are widely induced by various signals, including external environmental stress and hormone signals. These events ultimately regulate the secondary metabolic processes and the accumulation of essential secondary metabolites in plants by influencing the synthesis of primary metabolites, hormone metabolism, biomass accumulation, and capillary density. Simultaneously, alternative splicing plays a crucial role in enhancing protein diversity and the abundance of the transcriptome. This paper provides a summary of the factors inducing alternative splicing events in plants and systematically describes the progress in regulating alternative splicing with respect to different secondary metabolites, including terpenoid, phenolic compounds, and nitrogen-containing compounds. Such elucidation offers critical foundational insights for understanding the role of alternative splicing in regulating plant metabolism and presents novel avenues and perspectives for bioengineering.

RT-RPA-PfAgo detection platform for one-tube simultaneous typing diagnosis of human respiratory syncytial virus.

Human respiratory syncytial virus (HRSV) is the most prevalent pathogen contributing to acute respiratory tract infections (ARTI) in infants and young children and can lead to significant financial and medical costs. Here, we developed a simultaneous, dual-gene and ultrasensitive detection system for typing HRSV within 60 minutes that needs only minimum laboratory support. Briefly, multiplex integrating reverse transcription-recombinase polymerase amplification (RT-RPA) was performed with viral RNA extracted from nasopharyngeal swabs as a template for the amplification of the specific regions of subtypes A (HRSVA) and B (HRSVB) of HRSV. Next, the Pyrococcus furiosus Argonaute (PfAgo) protein utilizes small 5'-phosphorylated DNA guides to cleave target sequences and produce fluorophore signals (FAM and ROX). Compared with the traditional gold standard (RT-qPCR) and direct immunofluorescence assay (DFA), this method has the additional advantages of easy operation, efficiency and sensitivity, with a limit of detection (LOD) of 1 copy/µL. In terms of clinical sample validation, the diagnostic accuracy of the method for determining the HRSVA and HRSVB infection was greater than 95%. This technique provides a reliable point-of-care (POC) testing for the diagnosis of HRSV-induced ARTI in children and for outbreak management, especially in resource-limited settings.

Short-peptide-based enteral nutrition affects rats MDP translocation and protects against gut-lung injury via the PepT1-NOD2-beclin-1 pathway in vivo.

BACKGROUND: Peptide transporter 1 (PepT1) transports bacterial oligopeptide products and induces inflammation of the bowel. Nutritional peptides compete for the binding of intestinal bacterial products to PepT1. We investigated the mechanism of short-peptide-based enteral nutrition (SPEN) on the damage to the gut caused by the bacterial oligopeptide product muramyl dipeptide (MDP), which is transported by PepT1. The gut-lung axis is a shared mucosal immune system, and immune responses and disorders can affect the gut-respiratory relationship. METHODS AND RESULTS: Sprague-Dawley rats were gavaged with solutions containing MDP, MDP + SPEN, MDP + intact-protein-based enteral nutrition (IPEN), glucose as a control, or glucose with GSK669 (a NOD2 antagonist). Inflammation, mitochondrial damage, autophagy, and apoptosis were explored to determine the role of the PepT1-nucleotide-binding oligomerization domain-containing protein 2 (NOD2)-beclin-1 signaling pathway in the small intestinal mucosa. MDP and proinflammatory factors of lung tissue were explored to determine that MDP can migrate to lung tissue and cause inflammation. Induction of proinflammatory cell accumulation and intestinal damage in MDP gavage rats was associated with increased NOD2 and Beclin-1 mRNA expression. IL-6 and TNF-α expression and apoptosis were increased, and mitochondrial damage was severe, as indicated by increased mtDNA in the MDP group compared with controls. MDP levels and expression of proinflammatory factors in lung tissue increased in the MDP group compared with the control group. SPEN, but not IPEN, eliminated these impacts. CONCLUSIONS: Gavage of MDP to rats resulted in damage to the gut-lung axis. SPEN reverses the adverse effects of MDP. The PepT1-NOD2-beclin-1 pathway plays a role in small intestinal inflammation, mitochondrial damage, autophagy, and apoptosis.

Mycenabrunnescens (Basidiomycota, Mycenaceae), a new species of Mycena sect. Pterigenae from China.

Background: Mycena (Pers.) Roussel (1806) is a large genus of Mycenaceae known for having small to medium-sized basidiomata. It is typified by the species Mycenagalericulata (Scop.) Gray. For years, many mycologists have made important contributions to understanding Mycena and several monographs have been published. Three specimens were collected from China that belonged to the genus Mycena. On the basis of morphological analysis and phylogenetic analyses employing DNA sequences, a new species is described. New information: Mycenabrunnescens sp. nov. is described as a new species from subtropical areas of China. It is characterised by its brown pileus, whitish lamellae that turns brown when bruised, orange to brown lamellae edges, the absence of pleurocystidia and cheilocystidia with simple or branched excrescences at the apex containing yellowish-brown contents. We performed phylogenetic analyses on a concatenated dataset comprising the internal transcribed spacer and large subunit regions of nuclear ribosomal RNA using Bayesian Inference and Maximum Likelihood methods. The result showed that the new taxon clustered in an independent group and is closely related to M.albiceps and M.flosoides.

Neuronal double-stranded DNA accumulation induced by DNase II deficiency drives tau phosphorylation and neurodegeneration.

BACKGROUND: Deoxyribonuclease 2 (DNase II) plays a key role in clearing cytoplasmic double-stranded DNA (dsDNA). Deficiency of DNase II leads to DNA accumulation in the cytoplasm. Persistent dsDNA in neurons is an early pathological hallmark of senescence and neurodegenerative diseases including Alzheimer's disease (AD). However, it is not clear how DNase II and neuronal cytoplasmic dsDNA influence neuropathogenesis. Tau hyperphosphorylation is a key factor for the pathogenesis of AD. The effect of DNase II and neuronal cytoplasmic dsDNA on neuronal tau hyperphosphorylation remains unclarified. METHODS: The levels of neuronal DNase II and dsDNA in WT and Tau-P301S mice of different ages were measured by immunohistochemistry and immunolabeling, and the levels of DNase II in the plasma of AD patients were measured by ELISA. To investigate the impact of DNase II on tauopathy, the levels of phosphorylated tau, phosphokinase, phosphatase, synaptic proteins, gliosis and proinflammatory cytokines in the brains of neuronal DNase II-deficient WT mice, neuronal DNase II-deficient Tau-P301S mice and neuronal DNase II-overexpressing Tau-P301S mice were evaluated by immunolabeling, immunoblotting or ELISA. Cognitive performance was determined using the Morris water maze test, Y-maze test, novel object recognition test and open field test. RESULTS: The levels of DNase II were significantly decreased in the brains and the plasma of AD patients. DNase II also decreased age-dependently in the neurons of WT and Tau-P301S mice, along with increased dsDNA accumulation in the cytoplasm. The DNA accumulation induced by neuronal DNase II deficiency drove tau phosphorylation by upregulating cyclin-dependent-like kinase-5 (CDK5) and calcium/calmodulin activated protein kinase II (CaMKII) and downregulating phosphatase protein phosphatase 2A (PP2A). Moreover, DNase II knockdown induced and significantly exacerbated neuron loss, neuroinflammation and cognitive deficits in WT and Tau-P301S mice, respectively, while overexpression of neuronal DNase II exhibited therapeutic benefits. CONCLUSIONS: DNase II deficiency and cytoplasmic dsDNA accumulation can initiate tau phosphorylation, suggesting DNase II as a potential therapeutic target for tau-associated disorders.

[Effect of Peitu Yifei Granules on autophagy mechanism in rats with idiopathic pulmonary fibrosis based on PI3K/Akt/mTOR signaling pathway].

To investigate the mechanism by which Peitu Yifei Granules inhibit idiopathic pulmonary fibrosis(IPF) in rats, fifty specific-pathogen-free(SPF) grade male Wistar rats were randomly divided into blank group and modeling group. IPF was induced in the modeling group rats by tracheal infusion of 5 mg·kg~(-1) bleomycin(BLM) and then randomly divided into model group, pirfenidone group, and high-dose, medium-dose, and low-dose groups treated with Peitu Yifei Granules. After 24 hours of modeling, the treatment groups received intragastric administration of either Peitu Yifei Granules or pirfenidone as a positive control drug; meanwhile, the model group received an equal volume of normal saline. After 21 days of treatment administration, lung tissue samples were collected for analysis. Pathological changes in lung tissues were assessed using hematoxylin-eosin(HE) staining and Masson's trichrome staining. The expression levels of protein kinase B(Akt), mammalian target of rapamycin(mTOR), their phosphorylated forms, and sequestosome 1(p62) were determined through Western blot(WB). Fluorescent quantitative real-time polymerase chain reaction(RT-qPCR) was used to measure messenger ribonucleic acid(mRNA) expression levels of Beclin-1, microtubule-associated proteins 1A/1B light chain 3B(LC3B), and p62. Immunohistochemistry was performed to assess protein expression levels of Beclin-1 and LC3B in lung tissue samples. RESULTS:: demonstrated that lung tissue structure appeared normal without significant collagen deposition in the blank group rats. In contrast, rats from the model group exhibited thickened alveolar septa along with evident inflammatory changes and collagen deposition. Compared to the model group rats, those treated with Peitu Yifei Granules or pirfenidone showed significantly improved lung tissue structure with reduced inflammation and collagen deposition observed histologically. Furthermore, compared with those of the blank group, the expressions of p62 and its mRNA, p-Akt and p-mTOR protein in lung tissues of the model group were significantly increased, while Beclin-1, LC3B and their mRNA levels were significantly decreased. Compared with those of the model group, the expressions of p62 and its mRNA, p-Akt and p-mTOR in lung tissues of the pirfenidone group and Peitu Yifei Granules high-dose and medium-dose groups were significantly decreased, while Beclin-1, LC3B and their mRNA expressions were significantly increased. The above results indicate that Peitu Yifei Granules can improve autophagy levels in lung tissues by inhibiting the phosphoinositide 3-kinase(PI3K)/Akt/mTOR signaling pathway and delay the development of IPF disease.

Based on 3D-PDU and clinical characteristics nomogram for prediction of lymph node metastasis and lymph-vascular space invasion of early cervical cancer preoperatively.

PURPOSE: To develop and validate a nomogram based on 3D-PDU parameters and clinical characteristics to predict LNM and LVSI in early-stage cervical cancer preoperatively. MATERIALS AND METHODS: A total of first diagnosis 138 patients with cervical cancer who had undergone 3D-PDU examination before radical hysterectomy plus lymph dissection between 2014 and 2019 were enrolled for this study. Multivariate logistic regression analyses were performed to analyze the 3D-PDU parameters and selected clinicopathologic features and develop a nomogram to predict the probability of LNM and LVSI in the early stage. ROC curve was used to evaluate model differentiation, calibration curve and Hosmer-Lemeshow test were used to evaluate calibration, and DCA was used to evaluate clinical practicability. RESULTS: Menopause status, FIGO stage and VI were independent predictors of LNM. BMI and maximum tumor diameter were independent predictors of LVSI. The predicted AUC of the LNM and LSVI models were 0.845 (95%CI,0.765-0.926) and 0.714 (95%CI,0.615-0.813). Calibration curve and H-L test (LNM groups P = 0.478; LVSI P = 0.783) all showed that the predicted value of the model had a good fit with the actual observed value, and DCA indicated that the model had a good clinical net benefit. CONCLUSION: The proposed nomogram based on 3D-PDU parameters and clinical characteristics has been proposed to predict LNM and LVSI with high accuracy, demonstrating for the first time the potential of non-invasive prediction. The probability derived from this nomogram may have the potential to provide valuable guidance for physicians to develop clinical individualized treatment plans of FIGO patients with early cervical cancer.

Integrating serum pharmacochemistry, network pharmacology and untargeted metabolomics strategies to reveal the material basis and mechanism of action of Feining keli in the treatment of chronic bronchitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Feining keli (FNKL) is herbal preparation mainly made from Senecio cannabifolius Less., In recent years, more and more studies have found that FNKL has excellent therapeutic effects on chronic bronchitis (CB). Nevertheless, its pharmacodynamic material basis and mechanism of action are still unknown. AIM OF THE STUDY: This study aimed to explore the pharmacodynamic material basis and mechanism of action of FNKL in treating CB. MATERIALS AND METHODS: The CB rat model was induced using nasal drops of lipopolysaccharide (LPS) in combination with smoking. Various assessments including behavioral and body mass examination, lung index measurement, enzyme linked immunosorbent assay (ELISA), as well as histological analyses using hematoxylin and eosin (H&E) and Masson staining were conducted to validate the reliability of the CB model. The serum components of FNKL in CB rats were identified using ultra-high-performance liquid chromatography Orbitrap Exploris mass spectrometer (UHPLC-OE-MS). Network pharmacology was used to predict the network of action of the active ingredients in FNKL based on these serum components. Signaling pathways were enriched and analyzed, and molecular docking was conducted for key targets. Molecular dynamics simulations were performed using GROMACS software. The mechanism was confirmed through a series of experiments including Western blot (WB), immunofluorescence (IF), and reverse transcription (RT)-PCR. Additionally, untargeted metabolomics was employed to identify biomarkers and relevant metabolic pathways associated with the treatment of CB with FNKL. RESULTS: In CB rats, FNKL improved body mass, lung index, and pathological damage of lung tissues. It also decreased interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), malonaldehyde (MDA) levels, and percentage of lung collagen fiber area. Furthermore, FNKL increased IL-10 and superoxide dismutase (SOD) levels, which helped alleviate bronchial inflammation in the lungs. A total of 70 FNKL chemical components were identified in CB rat serum. Through network pharmacology analysis, 5 targets, such as PI3K, AKT, NF-κB, HIF-1α, and MYD88, were identified as key targets of FNKL in the treatment of CB. Additionally, the key signaling pathways identified were PI3K/AKT pathway、NF-κB/MyD88 pathway、HIF-1α pathway. WB, IF, and RT-PCR experiments were conducted to confirm the findings. Molecular docking studies demonstrated successful docking of 16 potential active components with 5 key targets. Additionally, molecular dynamics simulations indicated the stability of quercetin-3-galactoside and HIF-1α. Metabolomics analysis revealed that FNKL primarily regulated pathways related to alpha-linolenic acid metabolism, primary bile acid biosynthesis, bile secretion, arachidonic acid metabolism, neuroactive ligand-receptor interaction, and folate biosynthesis. Furthermore, the expression levels of traumatic acid, traumatin, alpha linolenic acid, cholic acid, 2-arachidonoylglycerol, deoxycholic acid, 7,8-dihydroneopterin, and other metabolites were found to be regulated. CONCLUSION: FNKL exhibits positive therapeutic effects on CB, with quercetin-3-galactoside identified as a key active component. The mechanism of FNKL's therapeutic action on CB involves reducing inflammatory response, oxidative stress, and regulating metabolism, and its molecular mechanism was better elucidated in a holistic manner. This study serves as a reference for understanding the pharmacodynamic material basis and mechanism of action of FNKL in treating CB, and provides avenues for exploring the effects of compounded herbal medicines on CB.

Depressive symptom mediates the association between the number of chronic diseases and cognitive impairment: a multi-center cross-sectional study based on community older adults.

Objective: The purpose of this study was to understand the relationship between the multiple chronic conditions (MCC), mental health and cognitive function of older adults in the community, and to propose a hypothesis that depressive symptom mediate the number of chronic diseases and cognitive impairment in older adults. Method: Participants aged 65 years and older from 35 communities in 14 cities in Guangxi, China were recruited. The residents' depressive symptom (PHQ-9) and cognitive status (AD-8) were evaluated, Chi-square test was used to explore the effects of different socio-demographic characteristics on depressive symptom and cognitive impairment. Pearson correlation analysis and the process model 4 were used to explore the relationship between the number of chronic diseases, depressive symptom and cognitive impairment. Result: A total of 11,582 older adults were included in our analysis. The rate of MCC reaching 26.53%. Hypertension combined with diabetes accounts for the highest proportion of two chronic diseases (13.2%). Among the combination of three chronic diseases, the highest incidence of coexisting hypertension combined with cervical/lumbar spondylosis, and rheumatoid arthritis (7.1%). In this study, depression symptoms accounted for 12.9% of older adults aged 65 and above, and cognitive impairment accounted for 27.4%. Female, older age, reside in urban areas, lower educational levels, no spouse, live alone, and MCC were risk factors for depressive symptom and cognitive impairment in older adults (P<0.05). Depressive symptom had a mediating effect in the number of chronic diseases and cognitive impairment, and the mediating effect (1.109) accounted for 44.13% of the total effect (0.247). Conclusion: The mental health of the older adult needs to be taken seriously, and improving depressive symptom can reduce the occurrence of cognitive impairment in older patients with MCC to a certain extent.

Network pharmacology-based exploration of molecular mechanisms underlying therapeutic effects of Jianpi Huatan Quyu recipe on chronic heart failure with spleen Qi deficiency syndrome.

BACKGROUND: Chronic heart failure is a complex clinical syndrome. The Chinese herbal compound preparation Jianpi Huatan Quyu recipe has been used to treat chronic heart failure; however, the underlying molecular mechanism is still not clear. AIM: To identify the effective active ingredients of Jianpi Huatan Quyu recipe and explore its molecular mechanism in the treatment of chronic heart failure. METHODS: The effective active ingredients of eight herbs composing Jianpi Huatan Quyu recipe were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The target genes of chronic heart failure were searched in the Genecards database. The target proteins of active ingredients were mapped to chronic heart failure target genes to obtain the common drug-disease targets, which were then used to construct a key chemical component-target network using Cytoscape 3.7.2 software. The protein-protein interaction network was constructed using the String database. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed through the Metascape database. Finally, our previously published relevant articles were searched to verify the results obtained via network pharmacology. RESULTS: A total of 227 effective active ingredients for Jianpi Huatan Quyu recipe were identified, of which quercetin, kaempferol, 7-methoxy-2-methyl isoflavone, formononetin, and isorhamnetin may be key active ingredients and involved in the therapeutic effects of TCM by acting on STAT3, MAPK3, AKT1, JUN, MAPK1, TP53, TNF, HSP90AA1, p65, MAPK8, MAPK14, IL6, EGFR, EDN1, FOS, and other proteins. The pathways identified by KEGG enrichment analysis include pathways in cancer, IL-17 signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, calcium signaling pathway, cAMP signaling pathway, NF-kappaB signaling pathway, AMPK signaling pathway, etc. Previous studies on Jianpi Huatan Quyu recipe suggested that this Chinese compound preparation can regulate the TNF-α, IL-6, MAPK, cAMP, and AMPK pathways to affect the mitochondrial structure of myocardial cells, oxidative stress, and energy metabolism, thus achieving the therapeutic effects on chronic heart failure. CONCLUSION: The Chinese medicine compound preparation Jianpi Huatan Quyu recipe exerts therapeutic effects on chronic heart failure possibly by influencing the mitochondrial structure of cardiomyocytes, oxidative stress, energy metabolism, and other processes. Future studies are warranted to investigate the role of the IL-17 signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, and other pathways in mediating the therapeutic effects of Jianpi Huatan Quyu recipe on chronic heart failure.

Pathologic and Molecular Features of Perihilar Cholangiocarcinoma Based on U-P Point Division.

CONTEXT.­: The Japanese Society of Hepato-Biliary-Pancreatic Surgery guidelines propose a classification scheme that differs from the Union for International Cancer Control (UICC) system, in which the anatomic U-P point is the boundary between intrahepatic cholangiocarcinoma and perihilar cholangiocarcinoma (PCC). OBJECTIVE.­: To investigate whether this classification system improves clinicopathologic and genomic differentiation. DESIGN.­: Fifty-eight PCC cases defined by the UICC system were collected and classified into intrahepatic PCC (IPCC) and extrahepatic PCC (EPCC) categories using U-P point division. They were analyzed by next-generation sequencing using a panel that targeted 425 cancer-related genes. RESULTS.­: The IPCC group exhibited a significant larger tumor size compared with the EPCC group (4.67 ± 2.44 cm versus 2.50 ± 0.91 cm, P = .002). The mutation frequency of KRAS proto-oncogene, GTPase (KRAS) Q61 was also significantly higher in the IPCC group than in the EPCC group (16.7% versus 0.0%, P = .03). There were no statistically significant differences in other pathologic features or genomic characteristics, including tumor mutation burden and microsatellite instability. Significant differences in gene mutation rates, such as phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA; 0.0% versus 15.8%, P = .01) and tumor protein p53 (TP53; 34.5% versus 63.2%, P = .04), were observed between PCC and adjacent biliary tract cancers. CONCLUSIONS.­: This study offers valuable insight into the clinicopathologic and genomic features of PCC. It is proposed that the U-P point division may have limited potential to refine the characterization of PCC regarding these features, and that the UICC classification system can readily demonstrate the molecular specificity of PCC.

Pulsatilla decoction alleviates DSS-induced UC by activating FXR-ASBT pathways to ameliorate disordered bile acids homeostasis.

Ethnopharmacological relevance: Pulsatilla decoction (PD) is a classical prescription for the treatment of ulcerative colitis. Previous studies have demonstrated that the therapeutic efficacy of PD is closely associated with the activation of Farnesoid X receptor (FXR). The activity of FXR is regulated by apical sodium-dependent bile acid transporter (ASBT), and the FXR-ASBT cascade reaction, centered around bile acid receptor FXR, plays a pivotal role in maintaining bile acid metabolic homeostasis to prevent the occurrence and progression of ulcerative colitis (UC). Aim of the study: To elucidate the underlying mechanism by which PD exerts its proteactive effects against Dextran Sulfate Sodium Salt (DSS)-induced ulcerative colitis, focusing on the modulation of FXR and ASBT. Materials and methods: To establish a model of acute ulcerative colitis, BALB/C mice were administered 3.5% DSS in their drinking water for consecutive 7 days. The disease activity index (DAI) was employed to evaluate the clinical symptoms exhibited by each group of mice. Goblet cell expression in colon tissue was assessed using glycogen schiff periodic acid-Schiff (PAS) and alcian blue staining techniques. Inflammatory cytokine expression in serum and colonic tissues was examined through enzyme-linked immunosorbent assay (ELISA). A PCR Array chip was utilized to screen 88 differential genes associated with the FXR-ASBT pathway in UC treatment with PD. Western blotting (WB) analysis was performed to detect protein expression levels of differentially expressed genes in mouse colon tissue. Results: The PD treatment effectively reduced the Disease Activity Index (DAI) score and mitigated colon histopathological damage, while also restoring weight and colon length. Furthermore, it significantly alleviated the severity of ulcerative colitis (UC), regulated inflammation, modulated goblet cell numbers, and restored bile acid balance. Additionally, a PCR Array analysis identified 21 differentially expressed genes involved in the FXR-ASBT pathway. Western blot results demonstrated significant restoration of FXR, GPBAR1, CYP7A1, and FGF15 protein expression levels following PD treatment; moreover, there was an observed tendency towards increased expression levels of ABCB11 and RXRα. Conclusion: The therapeutic efficacy of PD in UC mice is notable, potentially attributed to its modulation of bile acid homeostasis, enhancement of gut barrier function, and attenuation of intestinal inflammation.