Study on the cost-control effect of diagnosis-related groups based on meta-analysis.

OBJECTIVE: To evaluate the effect of diagnosis-related group (DRG) payment method systematically before and after implementation in terms of average hospitalization day, cost and care quality. METHOD: Restricted the period from 2019 to May 31, 2023, we use 6 databases from CNKI, Wipu, Wanfang, PubMed, ScienceDirect, and web of science. With the related study, we extract the data about DRG, then we conducted meta-analysis of the data about length of stay (LOS) and cost by RevMan 5.4 and Stata 12.0 software. Care quality is in conjunction with literature reports. RESULT: About 24 articles were included, covering 2 indicators: average hospitalization expenses and days. Meta-analysis shows that implementing DRG payment method has an advantage in terms of average hospital stay (pooled effect: -1.13%, 95% CI: -1.42 to -0.84, P = .00), and the difference is statistically significant. There is also an advantage in average hospitalization expenses (pooled effect: -2.58, 95% CI: -3.38 to -1.79, P = .00), and the difference is statistically significant. CONCLUSION: The use of DRG payment method can effectively reduce LOS and average hospitalization expenses. However, quality of care may decline with DRG adoption.

aChIP is an efficient and sensitive ChIP-seq technique for economically important plant organs.

Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is crucial for profiling histone modifications and transcription factor binding throughout the genome. However, its application in economically important plant organs (EIPOs) such as seeds, fruits and flowers is challenging due to their sturdy cell walls and complex constituents. Here we present advanced ChIP (aChIP), an optimized method that efficiently isolates chromatin from plant tissues while simultaneously removing cell walls and cellular constituents. aChIP precisely profiles histone modifications in all 14 tested EIPOs and identifies transcription factor and chromatin-modifying enzyme binding sites. In addition, aChIP enhances ChIP efficiency, revealing numerous novel modified sites compared with previous methods in vegetative tissues. aChIP reveals the histone modification landscape for rapeseed dry seeds, highlighting the intricate roles of chromatin dynamics during seed dormancy and germination. Altogether, aChIP is a powerful, efficient and sensitive approach for comprehensive chromatin profiling in virtually all plant tissues, especially in EIPOs.

Abnormalities of brain structure and function in cervical spondylosis: a multi-modal voxel-based meta-analysis.

Background: Previous neuroimaging studies have revealed structural and functional brain abnormalities in patients with cervical spondylosis (CS). However, the results are divergent and inconsistent. Therefore, the present study conducted a multi-modal meta-analysis to investigate the consistent structural and functional brain alterations in CS patients. Methods: A comprehensive literature search was conducted in five databases to retrieve relevant resting-state functional magnetic resonance imaging (rs-fMRI), structural MRI and diffusion tensor imaging (DTI) studies that measured brain functional and structural differences between CS patients and healthy controls (HCs). Separate and multimodal meta-analyses were implemented, respectively, by employing Anisotropic Effect-size Signed Differential Mapping software. Results: 13 rs-fMRI studies that used regional homogeneity, amplitude of low-frequency fluctuations (ALFF) and fractional ALFF, seven voxel-based morphometry (VBM) studies and one DTI study were finally included in the present research. However, no studies on surface-based morphometry (SBM) analysis were included in this research. Due to the insufficient number of SBM and DTI studies, only rs-fMRI and VBM meta-analyses were conducted. The results of rs-fMRI meta-analysis showed that compared to HCs, CS patients demonstrated decreased regional spontaneous brain activities in the right lingual gyrus, right middle temporal gyrus (MTG), left inferior parietal gyrus and right postcentral gyrus (PoCG), while increased activities in the right medial superior frontal gyrus, bilateral middle frontal gyrus and right precuneus. VBM meta-analysis detected increased GMV in the right superior temporal gyrus (STG) and right paracentral lobule (PCL), while decreased GMV in the left supplementary motor area and left MTG in CS patients. The multi-modal meta-analysis revealed increased GMV together with decreased regional spontaneous brain activity in the left PoCG, right STG and PCL among CS patients. Conclusion: This meta-analysis revealed that compared to HCs, CS patients had significant alterations in GMV and regional spontaneous brain activity. The altered brain regions mainly included the primary visual cortex, the default mode network and the sensorimotor area, which may be associated with CS patients' symptoms of sensory deficits, blurred vision, cognitive impairment and motor dysfunction. The findings may contribute to understanding the underlying pathophysiology of brain dysfunction and provide references for early diagnosis and treatment of CS. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, CRD42022370967.

Association between cardiometabolic index and hepatic steatosis and liver fibrosis: a population-based study.

BACKGROUND: The cardiometabolic index (CMI) is a new type of obesity index that is based on a combination of lipid levels and abdominal obesity indicators. It is closely correlated with the occurrence of diabetes mellitus, atherosclerosis, hypertension, and other diseases, thus playing an important role in the screening of metabolic diseases. This is coupled with hepatic steatosis and fibrosis which are characterized by excessive liver fat deposition. The aim of this study was to investigate the possible association between CMI and hepatic steatosis and liver fibrosis. METHODS: A cross-sectional investigation was conducted using the 2017-2020 National Health and Nutrition Examination Survey (NHANES) dataset to probe the relationship between CMI and hepatic steatosis and liver fibrosis, while multiple linear regression models were used to test the linear association between CMI and controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). Smooth-fit curves and threshold effects analysis were used to describe the nonlinear relationships. Subgroup analyses were performed according to gender, age, body mass index (BMI), hypertension, diabetes, cardiovascular disease, and smoking status. RESULTS: A total of 3084 adults aged 18-80 years were included in this analysis, and after controlling for a variety of variables, there was a significant positive correlation between CMI and CAP [20.38 (16.27,24.49)]. When subgroups were analyzed, this positive correlation was found to be stronger in the female population than in the male (P for interaction = 0.0303). Furthermore, the association between CMI and CAP was nonlinear. Using multiple regression analysis, it was shown that the linear relationship between CMI and liver fibrosis was not significant [-0.09 (-0.47,0.29)]. CONCLUSIONS: The findings suggest that elevated CMI levels are associated with hepatic steatosis, but that CMI is not linked to liver fibrosis. Larger prospective investigations are needed to confirm our findings.

LAMC2 regulates the proliferation, invasion, and metastasis of gastric cancer via PI3K/Akt signaling pathway.

OBJECTIVES: Gastric cancer (GC) is a prevalent malignant tumor widely distributed globally, exhibiting elevated incidence and fatality rates. The gene LAMC2 encodes the laminin subunit gamma-2 chain and is found specifically in the basement membrane of epithelial cells. Its expression is aberrant in multiple types of malignant tumors. This research elucidated a link between LAMC2 and the clinical characteristics of GC and investigated the potential involvement of LAMC2 in GC proliferation and advancement. MATERIALS AND METHODS: LAMC2 expressions were detected in GC cell lines and normal gastric epithelial cell lines via qRT-PCR. Silencing and overexpression of the LAMC2 were conducted by lentiviral transfection. A xenograft mouse model was also developed for in vivo analysis. Cell functional assays were conducted to elucidate the involvement of LAMC2 in cell growth, migration, and penetration. Further, immunoblotting was conducted to investigate the impact of LAMC2 on the activation of signal pathways after lentiviral transfection. RESULTS: In the findings, LAMC2 expression was markedly upregulated in GC cell lines as opposed to normal gastric epithelial cells. In vitro analysis showed that sh-LAMC2 substantially inhibited GC cell growth, migration, and invasion, while oe-LAMC2 displayed a contrasting effect. Xenograft tumor models demonstrated that oe-LAMC2 accelerated tumor growth via high expression of Ki-67. Immunoblotting analysis revealed a substantial decrease in various signaling pathway proteins, PI3K, p-Akt, and Vimentin levels upon LAMC2 knockdown, followed by increased E-cadherin expression. Conversely, its overexpression exhibited contrasting effects. Besides, epithelial-mesenchymal transition (EMT) was accelerated by LAMC2. CONCLUSION: This study provides evidence indicating that LAMC2, by stimulating signaling pathways, facilitated EMT and stimulated the progression of GC cells in laboratory settings and mouse models. Research also explored that the abnormal LAMC2 expression acts as a biomarker for GC.

Ideal cardiovascular health index and high-normal blood pressure in elderly people: evidence based on real-world data.

Limited information is available on the cardiovascular health (CVH) index and risk of high-normal blood pressure (HNBP) in elderly people. Randomized cluster sampling, multivariate logistic regression, and mediating effects analysis were used in this study analyze the relationship between CVH index and HNBP in the elderly. 1089 non-hypertensive residents aged 65 years or older completed the study. The positive rate of HNBP was 75.85% (male vs. female: 76.13% vs. 75.64%, P = 0.852); The ideal rate of CVH (ideal CVH index ≥ 5 items) was 14.51% (male vs. female: 15.91% vs. 13.46%, P = 0.256). Compared with people with 0-2 ideal CVH index, the risk of HNBP in people with 4 ideal indexes and ≥ 5 ideal indexes decreased by 50% and 63%, respectively, and their OR (95% CI) were 0.50 (0.31, 0.81) and 0.37 (0.21, 0.66), respectively. The results of the trend test showed that the risk of HNBP decreased by 32% for every increase in the ideal CVH index (trend P < 0.001) and TyG index does not play a mediating role in this relationship. That is, increasing the number of ideal CVH index may effectively reduce the risk of HNBP in elderly by one-third.

Platelet-rich plasma (PRP) in nerve repair.

Platelet-rich plasma (PRP) has the capability of assisting in the recovery of damaged tissues by releasing a variety of biologically active factors to initiate a hemostatic cascade reaction and promote the synthesis of new connective tissue and revascularization. It is now widely used for tissue engineering repair. In addition, PRP has demonstrated nerve repair and pain relief, and has been studied and applied to the facial nerve, median nerve, sciatic nerve, and central nerve. These suggest that PRP injection therapy has a positive effect on nerve repair. This indicates that PRP has high clinical value and potential application in nerve repair. It is worthwhile for scientists and medical workers to further explore and study PRP to expand its application in nerve repair, and to provide a more reliable scientific basis for the opening of a new approach to nerve repair.

Alterations in degree centrality and functional connectivity in tension-type headache: a resting-state fMRI study.

Previous studies have provided evidence of structural and functional changes in the brains of patients with tension-type headache (TTH). However, investigations of functional connectivity alterations in TTH have been inconclusive. The present study aimed to investigate abnormal intrinsic functional connectivity patterns in patients with TTH through the voxel-wise degree centrality (DC) method as well as functional connectivity (FC) analysis. A total of 33 patients with TTH and 30 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning and were enrolled in the final study. The voxel-wise DC method was performed to quantify abnormalities in the local functional connectivity hubs. Nodes with abnormal DC were used as seeds for further FC analysis to evaluate alterations in functional connectivity patterns. In addition, correlational analyses were performed between abnormal DC and FC values and clinical features. Compared with HCs, patients with TTH had higher DC values in the left middle temporal gyrus (MTG.L) and lower DC values in the left anterior cingulate and paracingulate gyri (ACG.L) (GRF, voxel-wise p < 0.05, cluster-wise p < 0.05, two-tailed). Seed-based FC analyses revealed that patients with TTH showed greater connections between ACG.L and the right cerebellum lobule IX (CR-IX.R), and smaller connections between ACG.L and ACG.L. The MTG.L showed increased FC with the ACG.L, and decreased FC with the right caudate nucleus (CAU.R) and left precuneus (PCUN.L) (GRF, voxel-wise p < 0.05, cluster-wise p < 0.05, two-tailed). Additionally, the DC value of the MTG.L was negatively correlated with the DASS-depression score (p = 0.046, r=-0.350). This preliminary study provides important insights into the pathophysiological mechanisms of TTH.

Identification and validation of a novel glycolysis-related ceRNA network for sepsis-induced cardiomyopathy.

Purpose: Sepsis-induced cardiomyopathy (SIC) is a major life-threatening condition in critically infected patients. Early diagnosis and intervention are important to improve patient prognosis. Recognizing the pivotal involvement of the glycolytic pathway in SIC, this study aims to establish a glycolysis-related ceRNA network and explore novel diagnostic avenues. Materials and methods: SIC-related datasets were carefully filtered from the GEO database. CytoHubba was used to identify differentially expressed genes (DEGs) associated with glycolysis. A predictive method was then used to construct an lncRNA-miRNA-mRNA network. Dual-luciferase reporter assays validated gene interactions, and the specificity of this ceRNA network was confirmed in peripheral blood mononuclear cells (PBMCs) from SIC patients. Logistic analysis was used to examine the correlation between the ceRNA network and SIC. Diagnostic potential was assessed using receiver operating characteristic (ROC) curves, and correlation analysis investigated any associations between gene expression and clinical indicators. Results: IER3 was identified as glycolysis-related DEG in SIC, and a ceRNA network (SNHG17/miR-214-3p/IER3) was established by prediction. Dual luciferase reporter gene assay confirmed the presence of mutual binding between IER3, miR-214-3p and SNHG17. RT-qPCR verified the specific expression of this ceRNA network in SIC patients. Multivariate logistic analysis established the correlation between the ceRNA network and SIC. ROC analysis demonstrated its high diagnostic specificity (AUC > 0.8). Correlation analysis revealed a negative association between IER3 expression and oxygenation index in SIC patients (p < 0.05). Furthermore, miR-214-3p expression showed a negative correlation with NT-proBNP (p < 0.05). Conclusion: In this study, we identified and validated a ceRNA network associated with glycolysis in SIC: SNHG17/miR-214-3p/IER3. This ceRNA network may play a critical role in the onset and development of SIC. This finding is important to further our understanding of the pathophysiological mechanisms underlying SIC and to explore potential diagnostic and therapeutic targets for SIC.

RAE1 promotes gastric carcinogenesis and epithelial-mesenchymal transition.

AIMS: The purpose of this study was to explore the role of RAE1 in the invasion and metastasis of gastric cancer (GC) cells. MATERIALS AND METHODS: RAE1 expression in GC cells was determined by reverse-transcription polymerase chain reaction (qRT-PCR) and Western blotting (WB). Cell models featuring RAE1 gene silencing and overexpression were constructed by lentiviral transfection; The proliferation, migration, and invasion ability of cells were detected by cell counting, colony formation assay, would healing assay, and transwell invasion and migration test. WB analysis of ERK/MAPK signaling pathway (ERK1/2, p-ERK1/2, c-Myc) and EMT-related molecules (ZEB1, E-cadherin, N-cadherin, and Vimentin). RESULTS: The expression level of RAE1 in GC was notably higher than in adjacent tissues. Elevated RAE1 expression correlated with an unfavorable prognosis for GC patients. Knockdown of RAE1, as compared to the control group, resulted in a significant inhibition of proliferation, migration, and invasion abilities in GC cell lines. Furthermore, RAE1 knockdown led to a substantial decrease in the expression of N-cadherin, vimentin, ZEB1, p-ERK1/2, and c-Myc proteins, coupled with a marked increase in E-cadherin expression. The biological effects of RAE1 in GC cells were effectively reversed by the inhibition of the ERK/MAPK signaling pathway using SCH772984. Additionally, RAE1 knockdown demonstrated a suppressive effect on GC tumor size in vivo. Immunohistochemistry (IHC) results revealed significantly lower expression of Ki-67 in RAE1 knockout mice compared to the control group. CONCLUSIONS: RAE1 promotes GC cell migration and invasion through the ERK/MAPK pathway and is a potential therapeutic target for GC therapy.

Brain functional connectivity alterations of Wernicke's area in individuals with autism spectrum conditions in multi-frequency bands: A mega-analysis.

Characterized by severe deficits in communication, most individuals with autism spectrum conditions (ASC) experience significant language dysfunctions, thereby impacting their overall quality of life. Wernicke's area, a classical and traditional brain region associated with language processing, plays a substantial role in the manifestation of language impairments. The current study carried out a mega-analysis to attain a comprehensive understanding of the neural mechanisms underpinning ASC, particularly in the context of language processing. The study employed the Autism Brain Image Data Exchange (ABIDE) dataset, which encompasses data from 443 typically developing (TD) individuals and 362 individuals with ASC. The objective was to detect abnormal functional connectivity (FC) between Wernicke's area and other language-related functional regions, and identify frequency-specific altered FC using Wernicke's area as the seed region in ASC. The findings revealed that increased FC in individuals with ASC has frequency-specific characteristics. Further, in the conventional frequency band (0.01-0.08 Hz), individuals with ASC exhibited increased FC between Wernicke's area and the right thalamus compared with TD individuals. In the slow-5 frequency band (0.01-0.027 Hz), increased FC values were observed in the left cerebellum Crus II and the right lenticular nucleus, pallidum. These results provide novel insights into the potential neural mechanisms underlying communication deficits in ASC from the perspective of language impairments.

"Two-Stage Rocket-Propelled" Strategy Boosting Theranostic Efficacy with Mitochondria-Specific Type I-II Photosensitizers.

Imaging-guided photodynamic therapy (PDT) holds great potential for tumor therapy. However, achieving the synergistic enhancement of the reactive oxygen species (ROS) generation efficiency and fluorescence emission of photosensitizers (PSs) remains a challenge, resulting in suboptimal image guidance and theranostic efficacy. The hypoxic tumor microenvironment also hinders the efficacy of PDT. Herein, we propose a "two-stage rocket-propelled" photosensitive system for tumor cell ablation. This system utilizes MitoS, a mitochondria-targeted PS, to ablate tumor cells. Importantly, MitoS can react with HClO to generate a more efficient PS, MitoSO, with a significantly improved fluorescence quantum yield. Both MitoS and MitoSO exhibit less O2-dependent type I ROS generation capability, inducing apoptosis and ferroptosis. In vivo PDT results confirm that this mitochondrial-specific type I-II cascade phototherapeutic strategy is a potent intervention for tumor downstaging. This study not only sheds light on the correlation between the PS structure and the ROS generation pathway but also proposes a novel and effective strategy for tumor downstaging intervention.

Aggregation-induced emission-active iridium (III)-based mitochondria-targeting nanoparticle for two-photon imaging-guided photodynamic therapy.

The efficacy of imaging-guided photodynamic therapy (PDT) is compromised by the attenuation of fluorescence and decline in reactive oxygen species (ROS) generation efficiency in the physiological environment of conventional photosensitizers, limited near-infrared (NIR) absorption, and high systemic cytotoxicity. This paper presents the synthesis of two cyclometalated Ir (III) complexes (Ir-thpy and Ir-ppy) by using a triphenylamine derivative (DPTPA) as the primary ligand and their encapsulation into an amphiphilic phospholipid to form nanoparticles (NPs). These complexes exhibit aggregation-induced emission features and remarkably enhanced ROS generation compared to Chlorin e6 (Ce6). Moreover, Ir-thpy NPs possess the unique ability to selectively target mitochondria, leading to depolarization of the mitochondrial membrane potential and ultimately triggering apoptosis. Notably, Ir-thpy NPs exhibit exceptional photocytotoxicity even towards cisplatin-resistant A549/DDP tumor cells. In vivo two-photon imaging verified the robust tumor-targeting efficacy of Ir-thpy NPs. The in vivo results unequivocally demonstrate that Ir-thpy NPs exhibit excellent tumor ablation along with remarkable biocompatibility. This study presents a promising approach for the development of multifunctional Ir-NPs for two-photon imaging-guided PDT and provides novel insights for potential clinical applications in oncology.

Cardiometabolic index is associated with increased depression: A population-based study.

BACKGROUND AND AIM: Depression is a common and complex psychiatric disorder, and lipid metabolism plays an important role in the development of psychiatric disorders such as depression. Cardiometabolic index (CMI) is a novel index that synthesizes two quantitative indicators of blood lipids (triglyceride(TG)/high-density lipoprotein cholesterol (HDL-C)) and human obesity-related parameters (waist height ratio (WHtR)). This study used NHANES data to explore the correlation between CMI and the incidence of depression. METHODS AND RESULTS: Based on the data of the National Health and Nutrition Examination Survey (NHANES) 2011-2018, multivariate logistic regression, sensitivity analysis, and smooth curve fitting were used to study the relationship between CMI and depression. Subgroup analysis and interaction tests were used to investigate whether the association was stable in different populations. CMI was positively associated with depression in 7229 participants aged >20 years. In the fully adjusted model, each unit increase in CMI was associated with 36 % higher likelihood of depression symptoms [1.36(1.16,1.59)]. Participants in the highest quartile of CMI had a 62 % higher risk of depression than participants in the lowest quartile [1.62(1.17,2.23)]. This positive correlation was more pronounced in those with hypertension. CONCLUSIONS: CMI was associated with a higher PHQ-9 score and an increased likelihood of depression among US adults. Further large-scale prospective studies are still need to analyze the role of CMI in depression.

Lower serum testosterone is associated with increased likelihood of arthritis.

Studies have suggested that serum testosterone levels may be strongly correlated with the pathogenesis of arthritis. Therefore, the aim of this study was to assess the relationship between serum testosterone levels and arthritis in US adults using the National Health and Nutrition Examination Survey (NHANES). We used the database from NHANES, 2013-2016 to perform a cross-sectional study. This study investigated the relationship between serum testosterone and arthritis using multivariate logistic regression models and also used smoothed curve fitting and generalized additivity models. A total of 10,439 adults were included in this analysis. A significant negative association between serum testosterone and arthritis was found in a linear regression analysis. The study showed that the arthritis group had lower testosterone levels than the non-arthritis group. The univariate multivariate analyses of Q4, using Q1 as a reference, all showed a significantly lower risk of developing arthritis. In subgroup analyses, the negative correlation between serum testosterone levels and arthritis was more significant in women and those with a body mass index (BMI) ≥ 30 kg/m2. After controlling for various variables, we found a significant association between serum testosterone and arthritis in this analysis. Further study of the relationship between testosterone and arthritis is necessary to clarify the specific mechanism of serum testosterone action on arthritis.

Stochastic scheduling of autonomous mobile robots at hospitals.

This paper studies the scheduling of autonomous mobile robots (AMRs) at hospitals where the stochastic travel times and service times of AMRs are affected by the surrounding environment. The routes of AMRs are planned to minimize the daily cost of the hospital (including the AMR fixed cost, penalty cost of violating the time window, and transportation cost). To efficiently generate high-quality solutions, some properties are identified and incorporated into an improved tabu search (I-TS) algorithm for problem-solving. Experimental evaluations demonstrate that the I-TS algorithm outperforms existing methods by producing high-quality solutions. Based on the characteristics of healthcare requests and the AMR working environment, scheduling AMRs reasonably can effectively provide medical services, improve the utilization of medical resources, and reduce hospital costs.

Molecular mechanism of Danshenol C in reversing peritoneal fibrosis: novel network pharmacological analysis and biological validation.

OBJECTIVE: The primary objective of this study is to elucidate the molecular mechanism underlying the reversal of peritoneal fibrosis (PF) by Danshenol C, a natural compound derived from the traditional Chinese medicine Salvia miltiorrhiza. By comprehensively investigating the intricate interactions and signaling pathways involved in Danshenol C's therapeutic effects on PF, we aim to unveil novel insights into its pharmacological actions. This investigation holds the potential to revolutionize the clinical application of Salvia miltiorrhiza in traditional Chinese medicine, offering promising new avenues for the treatment of PF and paving the way for evidence-based therapeutic interventions. METHODS: Firstly, we utilized the YaTCM database to retrieve the structural formula of Danshenol C, while the SwissTargetPrediction platform facilitated the prediction of its potential drug targets. To gain insights into the genetic basis of PF, we acquired the GSE92453 dataset and GPL6480-9577 expression profile from the GEO database, followed by obtaining disease-related genes of PF from major disease databases. R software was then employed to screen for DEG associated with PF. To explore the intricate interactions between Danshenol C's active component targets, we utilized the String database and Cytoscape3.7.2 software to construct a PPI network. Further analysis in Cytoscape3.7.2 enabled the identification of core modules within the PPI network, elucidating key targets and molecular pathways critical to Danshenol C's therapeutic actions. Subsequently, we employed R to perform GO and KEGG pathway enrichment analyses, providing valuable insights into the functional implications and potential biological mechanisms of Danshenol C in the context of PF. To investigate the binding interactions between the core active components and key targets, we conducted docking studies using Chem3D, autoDock1.5.6, SYBYL2.0, and PYMOL2.4 software. We applied in vivo and in vitro experiments to prove that Danshenol C can improve PF. In order to verify the potential gene and molecular mechanism of Danshenol C to reverse PF, we used quantitative PCR, western blot, and apoptosis, ensuring robust and reliable verification of the results. RESULTS: ① Wogonin, sitosterol, and Signal Transducer and Activator of Transcription 5 (STAT5) emerged as the most significant constituents among the small-molecule active compounds and gene targets investigated. ②38 targets intersected with the disease, among which MAPK14, CASP3, MAPK8 and STAT3 may be the key targets; The results of GO and KEGG analysis showed that there was a correlation between inflammatory pathway and Apoptosis. ④Real-time PCR showed that the mRNA expressions of MAPK8 (JNK1), MAPK14 (P38) and STAT3 were significantly decreased after Danshenol C treatment (P < 0.05), while the mRNA expression of CASP3 was significantly increased (P < 0.05)⑤Western blot showed that protein expressions of CASP3 and MAPK14 were significantly increased (P < 0.05), while the expression of STAT3 and MAPK8 was decreased after Danshenol C treatment (P < 0.05). ⑥There was no significant difference in flow analysis of apoptosis among groups. CONCLUSION: The findings suggest that Danshenol C may modulate crucial molecular pathways, including the MAPK, Apoptosis, Calcium signaling, JAK-STAT signaling, and TNF signaling pathways. This regulation is mediated through the modulation of core targets such as STAT3, MAPK14, MAPK8, CASP3, and others. By targeting these key molecular players, Danshenol C exhibits the potential to regulate cellular responses to chemical stress and inflammatory stimuli. The identification of these molecular targets and pathways represents a significant step forward in understanding the molecular basis of Danshenol C's therapeutic effects in PF. This preliminary exploration provides novel avenues for the development of anti-PF treatment strategies and the discovery of potential therapeutic agents. By targeting specific core targets and pathways, Danshenol C opens up new possibilities for the development of more effective and targeted drugs to combat PF. These findings have the potential to transform the landscape of PF treatment and offer valuable insights for future research and drug development endeavors.

Correlation between bone mineral density and sarcopenia in US adults: a population-based study.

INTRODUCTION: In the aging process of the body, in addition to changes in fat and muscle content, there is also bone loss, implying the possibility of a strong muscle-bone-lipid link. In this study, we initially investigated the relationship between lumbar BMD and low muscle mass and the relationship between "muscle-bone-lipid." METHODS: The datasets from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 were used in a cross-sectional investigation. BMD and appendicular skeletal muscle (ASM) were measured by dual-energy X-ray absorptiometry (DXA), and appendicular skeletal muscle was adjusted by body mass index (BMI) as a marker of sarcopenia. Weighted multivariate regression and logistic regression analysis were used to explore the independent relationship between lumbar BMD and sarcopenia. Fitted smoothing curves and threshold effect analysis were used to describe the nonlinear relationship. RESULT: In 8386 participants with ages 20-59 years, there was a negative association between lumbar BMD and sarcopenia. In the fully adjusted model, the risk of developing sarcopenia decreased by 93% for each 1-unit increase in lumbar BMD (OR = 0.07, 95%CI 0.03-0.20). The risk of sarcopenia was 58% lower in participants in the highest quartile of lumbar BMD than in those in the lowest quartile (OR = 0.42, 95%CI 0.27-0.64). This negative association was more pronounced in the population of women with BMI ≥ 25. CONCLUSION: Our findings suggest that lumbar BMD is negatively associated with sarcopenia in US adults. The dynamic balance between "muscle-bone-lipid" is likely to be related to the pathogenesis of bone loss.

3D organization of regulatory elements for transcriptional regulation in Arabidopsis.

BACKGROUND: Although spatial organization of compartments and topologically associating domains at large scale is relatively well studied, the spatial organization of regulatory elements at fine scale is poorly understood in plants. RESULTS: Here we perform high-resolution chromatin interaction analysis using paired-end tag sequencing approach. We map chromatin interactions tethered with RNA polymerase II and associated with heterochromatic, transcriptionally active, and Polycomb-repressive histone modifications in Arabidopsis. Analysis of the regulatory repertoire shows that distal active cis-regulatory elements are linked to their target genes through long-range chromatin interactions with increased expression of the target genes, while poised cis-regulatory elements are linked to their target genes through long-range chromatin interactions with depressed expression of the target genes. Furthermore, we demonstrate that transcription factor MYC2 is critical for chromatin spatial organization, and propose that MYC2 occupancy and MYC2-mediated chromatin interactions coordinately facilitate transcription within the framework of 3D chromatin architecture. Analysis of functionally related gene-defined chromatin connectivity networks reveals that genes implicated in flowering-time control are functionally compartmentalized into separate subdomains via their spatial activity in the leaf or shoot apical meristem, linking active mark- or Polycomb-repressive mark-associated chromatin conformation to coordinated gene expression. CONCLUSION: The results reveal that the regulation of gene transcription in Arabidopsis is not only by linear juxtaposition, but also by long-range chromatin interactions. Our study uncovers the fine scale genome organization of Arabidopsis and the potential roles of such organization in orchestrating transcription and development.

Type 2 diabetes mellitus plays a protective role against osteoporosis --mendelian randomization analysis.

BACKGROUND: Type 2 diabetes mellitus (DM2) and osteoporosis (OP) are currently the two most significant causes of mortality and morbidity in older adults, according to clinical evidence. The intrinsic link between them is yet unknown, despite reports of their coexistence. By utilizing the two-sample Mendelian randomization (MR) approach, we sought to evaluate the causal impact of DM2 on OP. METHODS: The aggregate data of the whole gene-wide association study (GWAS) were analyzed. A two-sample MR analysis was performed using single-nucleotide polymorphisms (SNPs), which are strongly associated with DM2, as instrumental variables (IVs) to evaluate the causal analysis of DM2 on OP risk with OR values, using inverse variance weighting, MR-egger regression, and weighted median methods, respectively. RESULT: A total of 38 single nucleotide polymorphisms were included as tool variables. According to the results of inverse variance-weighted (IVW), we found that there was a causal relationship between DM2 and OP, in which DM2 had a protective effect on OP. For each additional case of DM2, there is a 0.15% decrease in the odds of developing OP (OR = 0.9985;95%confidence interval:0.9974,0.9995; P value = 0.0056). There was no evidence that the observed causal effect between DM2 and the risk of OP was affected by genetic pleiotropy (P = 0.299). Using Cochran Q statistics and MR-Egger regression in the IVW approach, the heterogeneity was calculated; P > 0.05 shows that there is a significant amount of heterogeneity. CONCLUSION: A causal link between DM2 and OP was established by MR analysis, which also revealed that DM2 decreased the occurrence of OP.