Extracting Pulmonary Nodules and Nodule Characteristics from Radiology Reports of Lung Cancer Screening Patients Using Transformer Models.

 Pulmonary nodules and nodule characteristics are important indicators of lung nodule malignancy. However, nodule information is often documented as free text in clinical narratives such as radiology reports in electronic health record systems. Natural language processing (NLP) is the key technology to extract and standardize patient information from radiology reports into structured data elements. This study aimed to develop an NLP system using state-of-the-art transformer models to extract pulmonary nodules and associated nodule characteristics from radiology reports. We identified a cohort of 3080 patients who underwent LDCT at the University of Florida health system and collected their radiology reports. We manually annotated 394 reports as the gold standard. We explored eight pretrained transformer models from three transformer architectures including bidirectional encoder representations from transformers (BERT), robustly optimized BERT approach (RoBERTa), and A Lite BERT (ALBERT), for clinical concept extraction, relation identification, and negation detection. We examined general transformer models pretrained using general English corpora, transformer models fine-tuned using a clinical corpus, and a large clinical transformer model, GatorTron, which was trained from scratch using 90 billion words of clinical text. We compared transformer models with two baseline models including a recurrent neural network implemented using bidirectional long short-term memory with a conditional random fields layer and support vector machines. RoBERTa-mimic achieved the best F1-score of 0.9279 for nodule concept and nodule characteristics extraction. ALBERT-base and GatorTron achieved the best F1-score of 0.9737 in linking nodule characteristics to pulmonary nodules. Seven out of eight transformers achieved the best F1-score of 1.0000 for negation detection. Our end-to-end system achieved an overall F1-score of 0.8869. This study demonstrated the advantage of state-of-the-art transformer models for pulmonary nodule information extraction from radiology reports. Supplementary Information: The online version contains supplementary material available at 10.1007/s41666-024-00166-5.

G20 roadmap for carbon neutrality: The role of Paris agreement, artificial intelligence, and energy transition in changing geopolitical landscape.

The rapid advancement of artificial intelligence (AI) in the 21st century is driving profound societal changes and playing a crucial role in optimizing energy systems to achieve carbon neutrality. Most G20 nations have developed national AI strategies and are advancing AI applications in energy, manufacturing, and agriculture sectors to meet this goal. However, disparities exist among these nations, creating an "AI divide" that needs to be addressed for regulatory consistency and fair distribution of AI benefits. Here, we look at the linear effects of AI and the Paris Agreement (AI), as well as their potential interaction on carbon neutrality. We also investigate whether geopolitical risk (GPR) can hinder or enhance efforts to attain carbon neutrality through energy transition (ET). To measure carbon neutrality of G20 countries, we employed a robust parametric Malmquist index combined with the fixed-effect panel stochastic frontier model to account for heterogeneity. Results indicate that from 1990 to 2022, carbon neutrality has improved primarily due to technological advancements. Developed G20 countries led in technological progress, while developing countries showed modest gains in carbon efficiency. Using the Driscoll-Kraay robust standard error method, we found that AI has a positive but insignificant linear effect on carbon neutrality. However, the interaction between PA and AI was positive and statistically significant, suggesting that PA augments AI's potential in accelerating carbon neutrality. Energy transition accelerates carbon neutrality in both developed and developing G20 countries. However, the role of energy transition in achieving carbon neutrality becomes negative when the interaction term between energy transition and geopolitical risk (ET × GRP) is incorporated. Regarding control variables, green innovation positively impacts carbon neutrality, whereas financial development has an insignificant effect. Industrial structure and foreign direct investment both negatively affect carbon neutrality, thereby supporting the pollution haven hypothesis. It is recommended that strategies to bridge the "AI divide" and uphold geopolitical stability are crucial to achieve carbon neutrality.

A Fixed-Time Proximal Gradient Neurodynamic Network With Time-Varying Coefficients for Composite Optimization Problems and Sparse Optimization Problems With Log-Sum Function.

This article presents a novel proximal gradient neurodynamic network (PGNN) for solving composite optimization problems (COPs). The proposed PGNN with time-varying coefficients can be flexibly chosen to accelerate the network convergence. Based on PGNN and sliding mode control technique, the proposed time-varying fixed-time proximal gradient neurodynamic network (TVFxPGNN) has fixed-time stability and a settling time independent of the initial value. It is further shown that fixed-time convergence can be achieved by relaxing the strict convexity condition via the Polyak-Lojasiewicz condition. In addition, the proposed TVFxPGNN is being applied to solve the sparse optimization problems with the log-sum function. Furthermore, the field-programmable gate array (FPGA) circuit framework for time-varying fixed-time PGNN is implemented, and the practicality of the proposed FPGA circuit is verified through an example simulation in Vivado 2019.1. Simulation and signal recovery experimental results demonstrate the effectiveness and superiority of the proposed PGNN.

New resorcylic acid derivatives of Lysimachia tengyuehensis against MRSA and VRE by interfering with bacterial metabolic imbalance.

The abuse of antibiotics leads to the rapid spread of bacterial resistance, which seriously threatens human life and health. Now, 8 resorcylic acid derivatives, including 4 new compounds (1-4) were isolated from Lysimachia tengyuehensis by bio-guided isolation, and they inhibited both methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) (MIC = 4-8 µg/mL). Notably, 1 and 2 rapidly killed MRSA and VRE within 40 min without drug resistance in 20 days. Mechanically, they potently disrupted biofilm and cell membrane by interfering with bacterial metabolic imbalance. The structure-activity relationship (SAR) revealed that the lipophilic long carbon chains (C-5/C-6) and hydrophilic hydroxyl/carboxyl groups were essential for the anti-MRSA and VRE bioactivity. Additionally, they effectively recovered MRSA-infected skin wounds and VRE-infected peritoneal in vivo. Resorcylic acid derivatives showed significant anti-MRSA and VRE bioactivity in vitro and in vivo with potential application for the first time.

Develop and validate a computable phenotype for the identification of Alzheimer's disease patients using electronic health record data.

INTRODUCTION: Alzheimer's disease (AD) is often misclassified in electronic health records (EHRs) when relying solely on diagnosis codes. This study aimed to develop a more accurate, computable phenotype (CP) for identifying AD patients using structured and unstructured EHR data. METHODS: We used EHRs from the University of Florida Health (UFHealth) system and created rule-based CPs iteratively through manual chart reviews. The CPs were then validated using data from the University of Texas Health Science Center at Houston (UTHealth) and the University of Minnesota (UMN). RESULTS: Our best-performing CP was "patient has at least 2 AD diagnoses and AD-related keywords in AD encounters," with an F1-score of 0.817 at UF, 0.961 at UTHealth, and 0.623 at UMN, respectively. DISCUSSION: We developed and validated rule-based CPs for AD identification with good performance, which will be crucial for studies that aim to use real-world data like EHRs. Highlights: Developed a computable phenotype (CP) to identify Alzheimer's disease (AD) patients using EHR data.Utilized both structured and unstructured EHR data to enhance CP accuracy.Achieved a high F1-score of 0.817 at UFHealth, and 0.961 and 0.623 at UTHealth and UMN.Validated the CP across different demographics, ensuring robustness and fairness.

Metal-Organic Framework Supported Low-Nuclearity Cluster Catalysts for Highly Selective Carbon Dioxide Electroreduction to Ethanol.

It is still a great challenge to achieve high selectivity of ethanol in CO2 electroreduction reactions (CO2RR) because of the similar reduction potentials and lower energy barrier of possible other C2+ products. Here, we report a MOF-based supported low-nuclearity cluster catalysts (LNCCs), synthesized by electrochemical reduction of three-dimensional (3D) microporous Cu-based MOF, that achieves a single-product Faradaic efficiency (FE) of 82.5 % at -1.0 V (versus the reversible hydrogen electrode) corresponding to the effective current density is 8.66 mA cm-2. By investigating the relationship between the species of reduction products and the types of catalytic sites, it is confirmed that the multi-site synergism of Cu LNCCs can increase the C-C coupling effect, and thus achieve high FE of CO2-to-ethanol. In addition, density functional theory (DFT) calculation and operando attenuated total reflectance surface-enhanced infrared absorption spectroscopy further confirmed the reaction path and mechanism of CO2-to-EtOH.

κ-Carrageenan masking bitterness perception in surimi gels containing potassium chloride-based salt substitutes: Gel properties, oral processing, and sensory evaluation.

κ-Carrageenan (CG) was employed to mask the bitterness induced by 50% KCl in surimi gels to achieve salt reduction and gel performance improvement. The combination of KCl and CG (KCl + CG) yielded the increased textural characteristics and water-holding capacity (WHC) of surimi gels and facilitated the transition of free water to immobilized water. In addition, the KCl + CG supplement increased the turbidity and particle size of myofibrillar protein (MP) sols but decreased the surface hydrophobicity in a dose-dependent manner. The hydrophobic interactions and disulfide bonds played crucial roles in maintaining the stability of MP gels. The specific binding of potassium ions to the sulfate groups of CG limited the release and diffusion of potassium ions from the surimi gels during oral processing, effectively masking the bitterness perception and maintaining the saltiness perception. This study provides a promising strategy to reduce the utilization of sodium salt in surimi products.

Washed microbiota transplantation promotes homing of group 3 innate lymphoid cells to the liver via the CXCL16/CXCR6 axis: a potential treatment for metabolic-associated fatty liver disease.

Despite the observed decrease in liver fat associated with metabolic-associated fatty liver disease (MAFLD) in mice following fecal microbiota transplantation, the clinical effects and underlying mechanisms of washed microbiota transplantation (WMT), a refined method of fecal microbiota transplantation, for the treatment of MAFLD remain unclear. In this study, both patients and mice with MAFLD exhibit an altered gut microbiota composition. WMT increases the levels of beneficial bacteria, decreases the abundance of pathogenic bacteria, and reduces hepatic steatosis in MAFLD-affected patients and mice. Downregulation of the liver-homing chemokine receptor CXCR6 on ILC3s results in an atypical distribution of ILC3s in patients and mice with MAFLD, characterized by a significant reduction in ILC3s in the liver and an increase in ILC3s outside the liver. Moreover, disease severity is negatively correlated with the proportion of hepatic ILC3s. These hepatic ILC3s demonstrate a mitigating effect on hepatic steatosis through the release of IL-22. Mechanistically, WMT upregulates CXCR6 expression on ILC3s, thereby facilitating their migration to the liver of MAFLD mice via the CXCL16/CXCR6 axis, ultimately contributing to the amelioration of MAFLD. Overall, these findings highlight that WMT and targeting of liver-homing ILC3s could be promising strategies for the treatment of MAFLD.

The effect of modified Qiyuan paste on mice with low immunity and sleep deprivation by regulating GABA nerve and immune system.

BACKGROUND: Low immunity and sleep disorders are prevalent suboptimal health conditions in contemporary populations, which render them susceptible to the infiltration of pathogenic factors. LJC, which has a long history in traditional Chinese medicine for nourishing the Yin and blood and calming the mind, is obtained by modifying Qiyuan paste. Dendrobium officinale Kimura et Migo has been shown to improve the immune function in sleep-deprived mice. In this study, based on the traditional Chinese medicine theory, LJC was prepared by adding D. officinale Kimura et Migo to Qiyuan paste decoction. METHODS: Indicators of Yin deficiency syndrome, such as back temperature and grip strength, were measured in each group of mice; furthermore, behavioral tests and pentobarbital sodium-induced sleep tests were performed. An automatic biochemical analyzer, enzyme-linked immunosorbent assay kit, and other methods were used to determine routine blood parameters, serum immunoglobulin (IgG, IgA, and IgM), cont (C3, C4), acid phosphatase (ACP) and lactate dehydrogenase (LDH) levels in the spleen, serum hemolysin, and delayed-type hypersensitivity (DTH) levels. In addition, serum levels of γ-aminobutyric acid (GABA) and glutamate (Glu) were detected using high-performance liquid chromatography (HPLC). Hematoxylin-eosin staining and Nissl staining were used to assess the histological alterations in the hypothalamus tissue. Western blot and immunohistochemistry were used to detect the expressions of the GABA pathway proteins GABRA1, GAD, GAT1, and GABAT1 and those of CD4+ and CD8+ proteins in the thymus and spleen tissues. RESULTS: The findings indicated that LJC prolonged the sleep duration, improved the pathological changes in the hippocampus, effectively upregulated the GABA content in the serum of mice, downregulated the Glu content and Glu/GABA ratio, enhanced the expressions of GABRA1, GAT1, and GAD, and decreased the expression of GABAT1 to assuage sleep disorders. Importantly, LJC alleviated the damage to the thymus and spleen tissues in the model mice and enhanced the activities of ACP and LDH in the spleen of the immunocompromised mice. Moreover, serum hemolysin levels and serum IgG, IgA, and IgM levels increased after LJC administration, which manifested as increased CD4+ content, decreased CD8+ content, and enhanced DTH response. In addition, LJC significantly increased the levels of complement C3 and C4, increased the number of white blood cells and lymphocytes, and decreased the percentage of neutrophils in the blood. CONCLUSIONS: LJC can lead to improvements in immunocompromised mice models with insufficient sleep. The underlying mechanism may involve regulation of the GABA/Glu content and the expression levels of GABA metabolism pathway-related proteins in the brain of mice, enhancing their specific and nonspecific immune functions.

Plastid phylogenomics contributes to the taxonomic revision of taxa within the genus Sanicula L. and acceptance of two new members of the genus.

Introduction: The genus Sanicula L. is a taxonomically complicated taxa within Apiaceae, as its high variability in morphology. Although taxonomists have performed several taxonomic revisions for this genus, the interspecific relationships and species boundaries have not been satisfactorily resolved, especially for those endemic to China. This study mainly focused on S. giraldii var. ovicalycina, S. tienmuensis var. pauciflora, and S. orthacantha var. stolonifera and also described two new members of the genus. Methods: We newly sequenced sixteen plastomes from nine Sanicula species. Combined with eleven plastomes previously reported by us and one plastome downloaded, we performed a comprehensively plastid phylogenomics analysis of 21 Sanicula taxa. Results and Discussion: The comparative results showed that 21 Sanicula plastomes in their structure and features were highly conserved and further justified that two new species were indeed members of Sanicula. Nevertheless, eleven mutation hotspot regions were still identified. Phylogenetic analyses based on plastome data and the ITS sequences strongly supported that these three varieties were clearly distant from three type varieties. The results implied that these three varieties should be considered as three independent species, which were further justified by their multiple morphological characters. Therefore, revising these three varieties into three independent species was reasonable and convincing. Moreover, we also identified and described two new Sanicula species (S. hanyuanensis and S. langaoensis) from Sichuan and Shanxi, China, respectively. Based on their distinct morphological characteristics and molecular phylogenetic analysis, two new species were included in Sanicula. In summary, our study impelled the revisions of Sanicula members and improved the taxonomic system of the genus.

The Concentration of Benzo[a]pyrene in Food Cooked by Air Fryer and Oven: A Comparison Study.

The air fryer utilizes heated air rather than hot oil to achieve frying, eliminating the need for cooking oil, rendering it a healthier cooking method than traditional frying and baking. However, there is limited evidence supporting that the air fryer could effectively reduce the level of food-derived carcinogen. In this study, we compared the concentration of Benzo[a]pyrene (BaP), a typical carcinogen, in beef patties cooked using an air fryer and an oven, under different cooking conditions, including temperatures (140 °C, 160 °C, 180 °C, and 200 °C), times (9, 14, and 19 min), and oil added or not. The adjusted linear regression analysis revealed that the BaP concentration in beef cooked in the air fryer was 22.667 (95% CI: 15.984, 29.349) ng/kg lower than that in beef cooked in the oven. Regarding the air fryer, the BaP concentration in beef cooked without oil brushing was below the detection limit, and it was significantly lower than in beef cooked with oil brushing (p < 0.001). Therefore, cooking beef in the air fryer can effectively reduce BaP concentration, particularly due to the advantage of oil-free cooking, suggesting that the air fryer represents a superior option for individuals preparing meat at high temperatures.

Impacts of hot electron diffusion, electron-phonon coupling, and surface atoms on metal surface dynamics revealed by reflection ultrafast electron diffraction.

Metals exhibit nonequilibrium electron and lattice subsystems at transient times following femtosecond laser excitation. In the past four decades, various optical spectroscopy and time-resolved diffraction methods have been used to study electron-phonon coupling and the effects of underlying dynamical processes. Here, we take advantage of the surface specificity of reflection ultrafast electron diffraction (UED) to examine the structural dynamics of photoexcited metal surfaces, which are apparently slower in recovery than predicted by thermal diffusion from the profile of absorbed energy. Fast diffusion of hot electrons is found to critically reduce surface excitation and affect the temporal dependence of the increased atomic motions on not only the ultrashort but also sub-nanosecond times. Whereas the two-temperature model with the accepted physical constants of platinum can reproduce the observed surface lattice dynamics, gold is found to exhibit appreciably larger-than-expected dynamic vibrational amplitudes of surface atoms while keeping the commonly used electron-phonon coupling constant. Such surface behavioral difference at transient times can be understood in the context of the different strengths of binding to surface atoms for the two metals. In addition, with the quantitative agreements between diffraction and theoretical results, we provide convincing evidence that surface structural dynamics can be reliably obtained by reflection UED even in the presence of laser-induced transient electric fields.

Evaluating site-of-care-related racial disparities in kidney graft failure using a novel federated learning framework.

OBJECTIVES: Racial disparities in kidney transplant access and posttransplant outcomes exist between non-Hispanic Black (NHB) and non-Hispanic White (NHW) patients in the United States, with the site of care being a key contributor. Using multi-site data to examine the effect of site of care on racial disparities, the key challenge is the dilemma in sharing patient-level data due to regulations for protecting patients' privacy. MATERIALS AND METHODS: We developed a federated learning framework, named dGEM-disparity (decentralized algorithm for Generalized linear mixed Effect Model for disparity quantification). Consisting of 2 modules, dGEM-disparity first provides accurately estimated common effects and calibrated hospital-specific effects by requiring only aggregated data from each center and then adopts a counterfactual modeling approach to assess whether the graft failure rates differ if NHB patients had been admitted at transplant centers in the same distribution as NHW patients were admitted. RESULTS: Utilizing United States Renal Data System data from 39 043 adult patients across 73 transplant centers over 10 years, we found that if NHB patients had followed the distribution of NHW patients in admissions, there would be 38 fewer deaths or graft failures per 10 000 NHB patients (95% CI, 35-40) within 1 year of receiving a kidney transplant on average. DISCUSSION: The proposed framework facilitates efficient collaborations in clinical research networks. Additionally, the framework, by using counterfactual modeling to calculate the event rate, allows us to investigate contributions to racial disparities that may occur at the level of site of care. CONCLUSIONS: Our framework is broadly applicable to other decentralized datasets and disparities research related to differential access to care. Ultimately, our proposed framework will advance equity in human health by identifying and addressing hospital-level racial disparities.

Frequency of periprocedural myocardial injury and infarction stratified by cardiac troponin I and cardiac troponin T.

BACKGROUND: There are different definitions of periprocedural myocardial infarction (PPMI) both in terms of thresholds for cardiac biomarkers and the ancillary criteria for myocardial ischemia. Cardiac Troponin I (cTnI) and cardiac Troponin T (cTnT) are used interchangeably to diagnose PPMI. OBJECTIVES: This study evaluated the frequency of periprocedural myocardial injury and infarction as defined by the Society of Cardiovascular Angiography & Interventions (SCAI), the Academic Research Consortium-2 (ARC-2), and the 4th Universal definition of MI (4UDMI) stratified using cTnT versus cTnI, among patients with chronic coronary syndrome (CCS) and unstable angina. RESULTS: Among 830 patients, PPMI rates according to the SCAI, ARC2 and 4UDMI criteria were 4.34 %, 2.05 %, and 4.94 % respectively, with higher rates seen for all definitions when using cTnI versus cTnT (SCAI: 9.84 % vs. 1.91 %, p < 0.001; ARC 2: 3.15 % vs. 1.56 %, p = 0.136; and 4UDMI 5.91 % vs. 4.51 %, p = 0.391). Minor and major periprocedural myocardial injury was respectively observed in 58.31 % and 27.10 % of patients, with rates of both significantly higher when using cTnI versus cTnT (Minor: 69.29 % vs. 53.47 %, p < 0.001, Major: 49.21 % vs. 17.36 %, p < 0.001). CONCLUSIONS: Among patients with CCS and unstable angina, PPMIs defined by SCAI occurred more frequently when using cTnI as opposed to cTnT, whereas the type of troponin had no impact on the incidence of PPMIs according to the ARC-2 and 4UDMI.

CYP1A2 Polymorphism and Drug Co-administration Affect the Blood Levels and Adverse Effects of Pirfenidone.

BACKGROUND: Mutations in metabolic enzymes and co-administration of drugs may affect the blood concentration of pirfenidone effective in pulmonary fibrosis. To provide a basis for the precise clinical use of pirfenidone, the authors analyzed the correlation between steady-state pirfenidone trough concentration and adverse drug reactions (ADRs) and examined the impact of CYP1A2*1C (rs2069514) and *1F (rs762551) variants and co-administration on pirfenidone blood concentrations and ADRs. METHODS: Forty-four patients were enrolled. The blood concentration of pirfenidone was determined using high-performance liquid chromatography. CYP1A2*1C and *1F genotypes were determined using direct SNP sequencing. Additional information related to drug associations was collected to screen factors affecting drug metabolism. RESULTS: The highest predictive value of ADRs was observed when the steady-state trough concentration of pirfenidone was 3.18 mcg·mL-1 and the area under the receiver operating characteristic curve was 0.701 (P = 0.024). The pirfenidone concentration-to-dose ratio (C/D) in CYP1A2*1F homozygous AA mutants was lower than that in C carriers (CC+AC) (1.28 ± 0.85 vs. 2.03 ± 1.28 mcg·mL-1; P = 0.036). Adverse drug reaction (ADR) incidence in the homozygous AA mutant group (28.0%) was significantly lower than that in the C carriers (CC+AC) (63.2%; P = 0.020), and ADR incidence in the A carriers (AC+AA) was considerably lower than that in the CC group (85.7%; P = 0.039). The C/D value of the combined lansoprazole/rabeprazole group was lower than that of the noncombination group (P < 0.05). CONCLUSIONS: The ADR incidence was positively correlated with pirfenidone blood concentration. The CYP1A2 (rs762551) AA genotype is associated with lower pirfenidone concentrations and fewer ADRs. Lansoprazole/rabeprazole co-administration reduced pirfenidone concentrations. Randomized controlled trials should further explore personalized dosing of pirfenidone and combination therapies.

A nanonewton force sensor using a U-shape tapered microfiber interferometer.

Nanomechanical measurements, especially the detection of weak contact forces, play a vital role in many fields, such as material science, micromanipulation, and mechanobiology. However, it remains a challenging task to realize the measurement of ultraweak force levels as low as nanonewtons with a simple sensing configuration. In this work, an ultrasensitive all-fiber nanonewton force sensor structure based on a single-mode-tapered U-shape multimode-single-mode fiber probe is proposed and experimentally demonstrated with a limit of detection of ~5.4 nanonewtons. The use of the sensor is demonstrated by force measurement on a human hair sample to determine the spring constant of the hair. The results agree well with measurements using an atomic force microscope for the spring constant of the hair. Compared with other force sensors based on optical fiber in the literature, the proposed all-fiber force sensor provides a substantial advancement in the minimum detectable force possible, with the advantages of a simple configuration, ease of fabrication, and low cost.

Comparison of the use of a spiral nasojejunal tube and transendoscopic enteral tubing in washed microbiota transplantation via the mid-gut route.

Background: Methods for washed microbiota transplantation (WMT) through the mid-gut include transendoscopic enteral tubing (TET) and manual spiral nasojejunal tube (SNT) placement have not been studied. Methods: This prospective interventional study was performed at a single centre. Patients were divided into the SNT and mid-gut TET groups based on their conditions and wishes. In the SNT group, an SNT was passively inserted into the stomach, and abdominal X-rays were taken within 24 h to confirm tube placement in the small intestine. In the mid-gut TET group, mid-gut TET was placed in the small intestine for gastroscopy. Data on the clinical efficacy of WMT, intubation time, cost, overall comfort score, adverse reactions, etc., were collected from the two groups. Results: Sixty-three patients were included in the study (SNT group (n = 40) and mid-gut TET group (n = 23)). The clinical efficacy of WMT in the SNT and mid-gut TET groups was 90 % and 95.7 %, respectively (P = 0.644). Compared with the mid-gut TET group, the SNT group showed a shorter operation time (120 s vs. 258 s, P = 0.001) and a lower average cost (641.7 yuan vs. 1702.1 yuan, P = 0.001). There was no significant difference in the overall comfort score or the incidence of common discomfort symptoms between the two groups. Conclusion: The different implantation methods have different advantages; compared with mid-gut TET placement, manual SNT placement provides some benefits.

Exploring the efficacy and mechanism of Bailing capsule to improve polycystic ovary syndrome in mice based on intestinal-derived LPS-TLR4 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with reproductive dysfunction and metabolic abnormalities, particularly characterized by insulin resistance and chronic low-grade inflammation. Multiple clinical studies have clearly demonstrated the significant efficacy and safety of the combination of Bailing capsules (BL) in the treatment of PCOS, but its pharmacological effects and mechanisms still require further study. AIM OF THE STUDY: To evaluate the effect of BL on improving PCOS in mice and explore the mechanism. METHODS: In this study, Dehydroepiandrosterone (DHEA) injection was administered alone and in combination with a high-fat and high-sugar diet to induce PCOS-like mouse. They were randomly divided into five groups: normal group (N), PCOS group (P), Bailing capsule low-dose group (BL-L), Bailing capsule high-dose group (BL-H) and Metformin + Daine-35 group (M + D). Firstly, the effects of BL on ovarian lesions, serum hormone levels, HOMA-IR, intestinal barrier function, inflammation levels, along with the expression of IRS1, PI3K, AKT, TLR4, Myd88, NF-κB p65, TNF-α, IL-6, and Occludin of the ovary, liver and colon were investigated. Finally, the composition of the gut microbiome of fecal was tested. RESULTS: The administration of BL significantly reduced body weight, improved hormone levels, improved IR, and attenuated pathological damage to ovarian tissues, up-regulated the expression of IRS1, PI3K, and AKT in liver. It also decreased serum LPS, TNF-α, and IL-6 levels, while downregulating the expression of Myd88, TLR4, and NF-κB p65. Additionally, BL improved intestinal barrier damage and upregulated the expression of Occludin. Interestingly, the abundance of norank_f__Muribaculacea and Lactobacillus was down-regulated, while the abundance of Akkermansia was significantly up-regulated. CONCLUSION: The results of the study showed that BL exerts a treatment PCOS effect, which may be related to the modulation of the gut microbiota, the improvement of insulin resistance and the intestinal-derived LPS-TLR4 inflammatory pathway. Our research will provide a theoretical basis for the clinical treatment of PCOS.

Celastrol inhibits mouse B16-F10 melanoma cell survival by regulating the PI3K/AKT/mTOR signaling pathway and repressing HIF-1α expression.

OBJECTIVE: Melanoma, with its high degree of malignancy, stands as one of the most dangerous skin cancers and remains the primary cause of death from skin cancer. With studies demonstrating the potential of traditional Chinese medicine to intervene and treat melanoma, we turned our attention to celastrol. Celastrol is a triterpene compound extracted from the traditional Chinese medicine derived from Tripterygium wilfordii. Previous studies have shown that celastrol exerts inhibitory effects on various malignant tumors, including melanoma. Hence, our goal was to clarify the impact of celastrol on cell viability, apoptosis, and cell cycle progression by elucidating its effects on the PI3K/AKT/mTOR pathway. METHODS: CCK-8 and wound healing assays were used to determine the effect of celastrol on the viability and migration of B16-F10 cells. Changes in cell apoptosis, cell cycle, reactive oxygen species (ROS), and mitochondrial membrane potential were detected by flow cytometry. PI3K/AKT/mTOR pathway proteins and HIF-α mRNA expression in B16-F10 cells were detected by western blotting and qPCR. Moreover, the addition of a PI3K activator demonstrated that celastrol could inhibit the function of B16-F10 cells via the PI3K/AKT/mTOR pathway. RESULTS: Celastrol inhibited the viability and migration of B16-F10 cells. Through the inhibition of the PI3K/AKT/mTOR pathway down-regulates the expression of HIF-α mRNA, thereby causing an increase of ROS in cells and a decrease in the mitochondrial membrane potential to promote cell apoptosis and cell cycle arrest. The inhibitory effect of celastrol on B16-F10 cells was further demonstrated by co-culturing with a PI3K activator. CONCLUSION: Celastrol inhibits the function of B16-F10 cells by inhibiting the PI3K/AKT/mTOR cellular pathway and regulating the expression of downstream HIF-α mRNA.

Anxiety and depression status in patients with idiopathic pulmonary fibrosis and outcomes of nintedanib treatment: an observational study.

BACKGROUND: Anxiety and depression are common comorbidities in idiopathic pulmonary fibrosis (IPF) that impair health-related quality of life. However, there is a lack of studies focusing on the mental disorder of IPF after antifibrotic treatment and their related predictive factors. METHODS: Patients with an initial diagnosis of IPF were enrolled. Data on demographics, lung function, Generalized Anxiety Disorder-7 (GAD-7) Scale, Patient Health Questionnaire 9 (PHQ-9), Patient Health Questionnaire-15 (PHQ-15), and St. George's Respiratory Questionnaire total score(SGRQ-T) were collected. Changes in anxiety, depression, somatic symptoms, and quality of life scores before and after nintedanib treatment were compared, and the related predictive factors were analyzed. RESULTS: A total of 56 patients with a first diagnosis of IPF were enrolled, with 42 and 35 patients suffering from anxiety and depression, respectively. The GAD-7, PHQ-9, PHQ-15, and SGRQ scores were higher in the anxiety and depression groups. SGRQ total score (SGRQ-T) [OR = 1.075, 95%CI= (1.011, 1.142)] was an independent predictor of IPF combined with anxiety (p < 0.05); SGRQ-T [OR = 1.080, 95%CI= (1.001, 1.167)] was also an independent predictor of IPF combined with depression (p < 0.05). After treatment, GAD-7, PHQ-9, PHQ-15, and SGRQ scores decreased (p < 0.05). ΔSGRQ-T significantly affected ΔGAD-7 (ß = 0.376, p = 0.009) and ΔPHQ-9 (ß = 0.329, p = 0.022). CONCLUSION: Anxiety and depression in IPF patients are closely related to somatic symptoms, pulmonary function, and quality of life. The SGRQ-T score is of great value for assessing anxiety and depression in patients with IPF. Short-term treatment with nintedanib antifibrotic therapy can alleviate anxiety and depression in IPF patients.