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C3-functionalized dihydroquinolinones represent a class of important biologically active compounds. Although methods for synthesizing C2/4-functionalized dihydroquinolinones have been extensively reported, research on the synthesis of C3-functionalized dihydroquinolinone is extremely rare. Herein, we report for the first time a method for C3-alkenylated dihydroquinolinones via iron(III)-catalyzed amine-release triple condensation of enaminones. These reactions exhibit broad substrate scope and offer operationally simple, low-cost catalyzed procedures in a single step. Subsequent intramolecular and intermolecular additions to the alkene moiety provide diverse C3-functionalized dihydroquinolinone derivatives.
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BACKGROUND: Immune checkpoint inhibitors, such as anti-programmed cell death-1 (PD-1) and PD-1 ligand-1 (PD-L1) antibodies, have achieved breakthrough results in improving long-term survival rates in lung cancer. Although high levels of PD-L1 expression and tumor mutational burden have emerged as pivotal biomarkers, not all patients derive lasting benefits, and resistance to immune checkpoint blockade remains a prevalent issue. Comprehending the immunological intricacies of lung cancer is crucial for uncovering the mechanisms that govern responses and resistance to immunomodulatory treatments. This study aimed to explore the potential of peripheral immune markers in predicting treatment efficiency among lung cancer patients undergoing PD-1/PD-L1 checkpoint inhibitors. METHODS: This study enrolled 71 lung cancer patients undergoing PD-1/PD-L1 inhibitor therapy and 20 healthy controls. Immune cell subsets (CD4 + T cells, CD8 + T cells, B cells, NK cells, and NKT cells), phenotypic analysis of T cells and B cells, and PMA/Ionomycin-stimulated lymphocyte function assay were conducted. RESULTS: Lung cancer patients exhibited significant alterations in immune cell subsets, notably an increased percentage of Treg cells. Post-treatment, there were substantial increases in absolute numbers of CD3 + T cells, CD8 + T cells, and NKT cells, along with heightened HLA-DR expression on CD3 + T and CD8 + T cells. Comparison between complete remission and non-complete remission (NCR) groups showed higher Treg cell percentages and HLA-DR + CD4 + T cells in the NCR group. CONCLUSION: The study findings suggest potential predictive roles for immune cell subsets and phenotypes, particularly Treg cells, HLA-DR + CD4 + T cells, and naïve CD4 + T cells, in evaluating short-term PD-1/PD-L1 therapy efficacy for lung cancer patients. These insights offer valuable prospects for personalized treatment strategies and underscore the importance of immune profiling in lung cancer immunotherapy.
Subject(s)
B7-H1 Antigen , Immune Checkpoint Inhibitors , Lung Neoplasms , Programmed Cell Death 1 Receptor , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/immunology , Male , Female , Middle Aged , Immune Checkpoint Inhibitors/therapeutic use , Aged , B7-H1 Antigen/antagonists & inhibitors , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Biomarkers, Tumor , AdultABSTRACT
BACKGROUND: Lung cancer poses a global health threat necessitating early detection and precise staging for improved patient outcomes. This study focuses on developing and validating a machine learning-based risk model for early lung cancer screening and staging, using routine clinical data. METHODS: Two medical center, observational, retrospective studies were conducted, involving 2312 lung cancer patients and 653 patients with benign nodules. Machine learning techniques, including differential analysis and feature selection, were employed to identify key factors for modeling. The study focused on variables such as nodule density, carcinoembryonic antigen (CEA), age, and lifestyle habits. The Logistic Regression model was utilized for early diagnoses, and the XGBoost model was utilized for staging based on selected features. RESULTS: For early diagnoses, the Logistic Regression model achieved an area under the curve (AUC) of 0.716 (95% confidence interval [CI] 0.607-0.826), with 0.703 sensitivity and 0.654 specificity. The XGBoost model excelled in distinguishing late-stage from early-stage lung cancer, exhibiting an AUC of 0.913 (95% CI 0.862-0.963), with 0.909 sensitivity and 0.814 specificity. These findings highlight the model's potential for enhancing diagnostic accuracy and staging in lung cancer. CONCLUSION: This study introduces a novel machine learning-based risk model for early lung cancer screening and staging, leveraging routine clinical information and laboratory data. The model shows promise in enhancing accuracy, mitigating overdiagnosis, and improving patient outcomes.
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Hierarchical supramolecular systems, characterized by nanoscale sensitivity and macroscopic tangible changes, offer promising perspectives for the design of remotely controllable, rapid, and precise actuation materials, serving as a potential substitution for non-intelligent and complex actuation switches. Herein, we reported on the disassembly of orderly and rigid starch helical covalent structures, and their subsequent reassembly into a hierarchical supramolecular gel composed of nanocluster aggregates, integrating supramolecular interactions of three different scales. The incorporation of photo-sensitive FeIIITA, a complex of trivalent iron ions and tannic acid, significantly enhances the photo-responsive strain capacity of the hierarchical supramolecular gel. The supramolecular gel exhibits its features in a rapid light-responsive rate of hardness and viscosity, enabling the actuation of objects within 22 s under light exposure when employed as a remote actuation switch. Meanwhile, this actuation mechanism of the hierarchical supramolecular gel also has a promising perspective in precise control, identifying and actuating one of the two objects in distances of 0.8 mm even smaller scales. Our work provides a reliable reference for replacing complex actuation switches with intelligent materials for remote, rapid, and accurate actuation, and offers valuable insights for actuation in harsh and vacuum outdoor environments.
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BACKGROUND: Esophageal cancer (EC) metastasized to the kidney is extremely rare clinically. Here, we present a case of metachronous renal metastasis of esophageal squamous cell carcinoma (ESCC) through epithelial-mesenchymal transition (EMT). CASE PRESENTATION: A 60-year-old patient, male, complained of left waist pain for 5 days, 11 months after radical esophagectomy. Laboratory tests revealed haematuria. Both CT and PET-CT scan showed retroperitoneal lymph nodes and left renal masses. Subsequently the patient received a left nephrectomy and lymph nodes resection, and squamous cell carcinoma of kidney and renal hilar lymph nodes was diagnosed, combined with morphology, medical history and immunophenotype, it was presumed to be metastasis of ESCC through the EMT pathway. CONCLUSIONS: The renal metastasis of squamous cell carcinoma should be considered in patients with history of EC, although this is very rare. Histopathological examination combined with immunochemical detection is helpful in differential diagnosis.
Subject(s)
Antioxidants , Carbon Tetrachloride , Chemical and Drug Induced Liver Injury , Liver , Plant Oils , Rosa , Seeds , Animals , Antioxidants/pharmacology , Mice , Rosa/chemistry , Chemical and Drug Induced Liver Injury/prevention & control , Seeds/chemistry , Carbon Tetrachloride/adverse effects , Male , Plant Oils/pharmacology , Plant Oils/chemistry , Liver/drug effects , Liver/metabolism , Protective Agents/pharmacology , Humans , Plant Extracts/pharmacologyABSTRACT
BACKGROUND: Fusarium graminearum is a devastating fungal pathogen that poses a significant threat to global wheat production and quality. Control of this toxin-producing pathogen remains a major challenge. This study aimed to isolate strains with antagonistic activity against F. graminearum and at the same time to analyze the synthesis of deoxynivalenol (DON), in order to provide a new basis for the biological control of FHB. RESULTS: Total of 69 microorganisms were isolated from the soil of a wheat-corn crop rotation field, and an antagonistic bacterial strain F12 was identified as Burkholderia pyrrocinia by molecular biology and carbon source utilization. F. graminearum control by strain F12 showed excellent biological activities under laboratory conditions (95.8%) and field testing (63.09%). Meanwhile, the DON content of field-treated wheat grains was detected the results showed that F12 have significantly inhibited of DON, which was further verified by qPCR that F12 produces secondary metabolites that inhibit the expression of DON and pigment-related genes. In addition, the sterile fermentation broth of F12 not only inhibited mycelial growth and spore germination, but also prevented mycelia from producing spores. CONCLUSION: In this study B. pyrrocinia was reported to have good control of FHB and inhibition of DON synthesis. This novel B. pyrrocinia F12 is a promising biological inoculant, providing possibilities for controlling FHB, and a theoretical basis for the development of potential biocontrol agents and biofertilizers for agricultural use. © 2024 Society of Chemical Industry.
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Host immune dysfunction plays a crucial role in the onset, progression, and outcome of hemophagocytic lymphohistiocytosis (HLH). This study aimed to comprehensively evaluate the peripheral immune profiles in patients with newly diagnosed secondary hemophagocytic lymphohistiocytosis (sHLH), and explore their predictive value for patient prognosis. A total of 77 patients with sHLH were enrolled in this study, with 31 of them experiencing mortality. Flow cytometry was used to assess the percentages, absolute numbers, and phenotypes of lymphocyte subsets. Simultaneously, cytokine levels and routine laboratory indicators were also collected. In sHLH patients, lymphocyte subset absolute numbers were significantly impaired, accompanied by T cell hyperactivation, B cell hyperactivation, and increased plasmablast proliferation. Prognostic analysis revealed that lower CD8+ T cell percentages, elevated APTT, IL-6, IL-10 levels, and increased CD4+CD28null T cell proportions were associated with poor patient outcomes. The study demonstrates dysregulation in the counts and phenotypes of lymphocyte subsets in sHLH patients. Several key factors, including IL-6, IL-10, APTT, and various T cell percentages, have potential as prognostic markers and therapeutic targets in sHLH.
Subject(s)
Lymphohistiocytosis, Hemophagocytic , Humans , Lymphohistiocytosis, Hemophagocytic/complications , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/genetics , Interleukin-10 , Interleukin-6 , CD8-Positive T-Lymphocytes , CytokinesABSTRACT
The "schisandra-evodia" herb pair (S-E) is a herbal preparation to treat Alzheimer's disease (AD). This study aims to investigate the therapeutic efficacy and potential mechanism of S-E in AD rats, utilizing pharmacodynamic assessments and serum- and urine-based metabolomic analyses. Pharmacodynamic assessments included Morris water maze test, hematoxylin-eosin staining and immunohistochemistry experiments. The results of the study showed that the AD model was successful; the S-E significantly enhanced long-term memory and spatial learning in AD rats. Meanwhile, S-E notably ameliorated Aß25-35-induced cognitive impairment, improved hippocampal neuron morphology, decreased Aß deposition in the hippocampus and mitigated inflammatory damage. We then analyzed serum and urine samples using UPLC-MS/MS to identify potential biomarkers and metabolic pathways. Metabolomic analysis revealed alterations in 40 serum metabolites and 38 urine metabolites following S-E treatment, predominantly affecting pathways related to taurine and hypotaurine metabolism, linoleic acid metabolism, α-linolenic acid metabolism, glycerophospholipid metabolism and arachidonic acid metabolism. This study elucidates the biochemical mechanism underlying AD and the metabolic pathway influenced by S-E, laying the groundwork for future clinical applications.
Subject(s)
Alzheimer Disease , Metabolome , Metabolomics , Rats, Sprague-Dawley , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Animals , Metabolomics/methods , Rats , Chromatography, High Pressure Liquid/methods , Male , Metabolome/drug effects , Metabolome/physiology , Tandem Mass Spectrometry/methods , Disease Models, Animal , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/administration & dosage , Biomarkers/blood , Biomarkers/urine , Hippocampus/metabolism , Hippocampus/drug effects , Amyloid beta-Peptides/metabolismABSTRACT
Background/Objective: In the post-epidemic era, an increasing number of individuals were accustomed to learning sports and physical activity knowledge online for fitness and health demands. However, most previous studies have examined the influence of e-learning materials and resources on learners and have neglected intrinsic factors such as experience and physiological characteristics. Therefore, we conducted a study to investigate the effect of exercise habits and gender on sports e-learning behavior via eye-tracking technology. Methods: We recruited a sample of 60 undergraduate students (mean age = 19.6) from a university in Nanjing, China. They were randomly assigned into 4 groups based on 2 genders × 2 exercise habits. Their gaze behavior was collected by an eye-tracking device during the experiment. The cognitive Load Test and Learning Effect Test were conducted at the end of the individual experiment. Results: (1) Compared to the non-exercise habit group, the exercise habit group had a higher fixation count (P<0.05), a shorter average fixation duration (P<0.05), a smaller average pupil diameter (P<0.05), and a lower subjective cognitive load (P<0.05) and better learning outcome (P<0.05). (2) Male participants showed a greater tendency to process information from the video area of interest (AOIs), and had lower subjective cognitive load (P < 0.05) and better learning outcomes (P < 0.05). (3) There was no interaction effect between exercise habits and gender for any of the indicators (P > 0.05). Conclusion: Our results indicate that exercise habits effectively enhance sports e-learning outcomes and reduce cognitive load. The exercise habits group showed significant improvements in fixation counts, average fixation duration, and average pupil diameter. Furthermore, male subjects exhibited superior learning outcomes, experienced lower cognitive load, and demonstrated greater attentiveness to dynamic visual information. These conclusions are expected to improve sports e-learning success and address educational inequality.
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Despite remarkable successes in unimodal learning tasks, backdoor attacks against cross-modal learning are still underexplored due to the limited generalization and inferior stealthiness when involving multiple modalities. Notably, since works in this area mainly inherit ideas from unimodal visual attacks, they struggle with dealing with diverse cross-modal attack circumstances and manipulating imperceptible trigger samples, which hinders their practicability in real-world applications. In this paper, we introduce a novel bilateral backdoor to fill in the missing pieces of the puzzle in the cross-modal backdoor and propose a generalized invisible backdoor framework against cross-modal learning (BadCM). Specifically, a cross-modal mining scheme is developed to capture the modality-invariant components as target poisoning areas, where well-designed trigger patterns injected into these regions can be efficiently recognized by the victim models. This strategy is adapted to different image-text cross-modal models, making our framework available to various attack scenarios. Furthermore, for generating poisoned samples of high stealthiness, we conceive modality-specific generators for visual and linguistic modalities that facilitate hiding explicit trigger patterns in modality-invariant regions. To the best of our knowledge, BadCM is the first invisible backdoor method deliberately designed for diverse cross-modal attacks within one unified framework. Comprehensive experimental evaluations on two typical applications, i.e., cross-modal retrieval and VQA, demonstrate the effectiveness and generalization of our method under multiple kinds of attack scenarios. Moreover, we show that BadCM can robustly evade existing backdoor defenses. Our code is available at https://github.com/xandery-geek/BadCM.
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OBJECTIVE: Systemic autoimmune rheumatic diseases (SARDs) encompass a diverse group of complex conditions with overlapping clinical features, making accurate diagnosis challenging. This study aims to develop a multiclass machine learning (ML) model for early-stage SARDs classification using accessible laboratory indicators. METHODS: A total of 925 SARDs patients were included, categorised into SLE, Sjögren's syndrome (SS) and inflammatory myositis (IM). Clinical characteristics and laboratory markers were collected and nine key indicators, including anti-dsDNA, anti-SS-A60, anti-Sm/nRNP, antichromatin, anti-dsDNA (indirect immunofluorescence assay), haemoglobin (Hb), platelet, neutrophil percentage and cytoplasmic patterns (AC-19, AC-20), were selected for model building. Various ML algorithms were used to construct a tripartite classification ML model. RESULTS: Patients were divided into two cohorts, cohort 1 was used to construct a tripartite classification model. Among models assessed, the random forest (RF) model demonstrated superior performance in distinguishing SLE, IM and SS (with area under curve=0.953, 0.903 and 0.836; accuracy= 0.892, 0.869 and 0.857; sensitivity= 0.890, 0.868 and 0.795; specificity= 0.910, 0.836 and 0.748; positive predictive value=0.922, 0.727 and 0.663; and negative predictive value= 0.854, 0.915 and 0.879). The RF model excelled in classifying SLE (precision=0.930, recall=0.985, F1 score=0.957). For IM and SS, RF model outcomes were (precision=0.793, 0.950; recall=0.920, 0.679; F1 score=0.852, 0.792). Cohort 2 served as an external validation set, achieving an overall accuracy of 87.3%. Individual classification performances for SLE, SS and IM were excellent, with precision, recall and F1 scores specified. SHAP analysis highlighted significant contributions from antibody profiles. CONCLUSION: This pioneering multiclass ML model, using basic laboratory indicators, enhances clinical feasibility and demonstrates promising potential for SARDs classification. The collaboration of clinical expertise and ML offers a nuanced approach to SARDs classification, with potential for enhanced patient care.
Subject(s)
Lupus Erythematosus, Systemic , Rheumatic Diseases , Sjogren's Syndrome , Humans , Lupus Erythematosus, Systemic/diagnosis , Sjogren's Syndrome/diagnosis , Antibodies, Antinuclear , Rheumatic Diseases/diagnosis , Predictive Value of TestsABSTRACT
Musculoskeletal ultrasound (MSUS) is characterized as the dynamic, real-time and continuous visualization, the quantitative and qualitative localization,the simple operation and the absence of use contraindication. As a tool for auxiliary examination, treatment, evaluation and research, in acupuncture and moxibustion, MSUS may improve the accuracy of acupoint location, guide the direction and depth of needle insertion, monitor the reactions of deqi, guarantee the safety of operation and quantify the effect evaluation. Hence, it may provide an objective basis for acupuncture and moxibustion research and be conductive to display the operation techniques of acupuncture and moxibustion by means of objective approaches such as imaging and data.
Subject(s)
Acupuncture Therapy , Moxibustion , Musculoskeletal Diseases , Humans , Ultrasonography , Contraindications , Musculoskeletal Diseases/diagnostic imaging , Musculoskeletal Diseases/therapyABSTRACT
Liver cancer is the fourth most lethal cancer, but the treatment options for liver cancer are usually limited. Metabolic reprogramming is a hallmark of malignancy, ensuring activated cell glycolysis and increased macromolecular precursors required for the proliferation and migration of exuberant cancer cells. MicroRNAs (miRNAs) have been reported to participate in cancer metabolic shifts mainly by directly silencing the expression of specific genes. Here, we identified miR-148a-3p as a negative regulator for glycometabolism and cell proliferation in liver cancer. miR-148a-3p directly targets the 3'UTR of transmembrane protein 54 (TMEM54), leading to the significant inhibition of lactate production, glucose consumption, intracellular ATP level and extracellular acidification rate (ECAR), as well as the repression of the proliferation and colony formation ability of liver cancer cells. miR-148a-3p expression is often down-regulated in liver cancer tissues. In addition, there was a negative correlation between the expression levels of miR-148a-3p and TMEM54 in liver cancer tissues. Moreover, the low miR-148a-3p expression levels or high TMEM54 expression levels were associated with poorer prognosis in hepatocellular carcinoma (HCC) patients. Together, these findings support that the miR-148a-3p/TMEM54 regulatory pathway regulates the glycometabolism and cell proliferation in liver cancer, which is a possible target for the diagnosis and treatment of liver cancer.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , MicroRNAs , Humans , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Liver Neoplasms/genetics , MicroRNAs/genetics , MicroRNAs/metabolismABSTRACT
Thousands of years ago, humans started to use propolis because of its medicinal properties, and modern science has successfully identified several bioactive molecules within this resinous bee product. However, a natural propolis extract which has been removed the adhesive glue and preserved propolis bioactive compounds is urgently needed to maximise the therapeutic opportunities. In this study, a novel ultrafiltrate fraction from Brazilian green propolis, termed P30K, was demonstrated with anti-inflammatory properties, both inâ vitro and inâ vivo. Total flavonoids and total phenolic acids content in P30K were 244.6â mg/g and 275.8â mg/g respectively, while the IC50 value of inhibition of cyclooxygenase-2 (COX-2) was 8.30â µg/mL. The anti-inflammatory activity of P30K was furtherly corroborated in experimental models of lipopolysaccharides (LPS)-induced acute liver and lung injury. Mechanistically, integrated GC-MS and LC-MS based serum metabolomics analysis revealed that P30K modulated citrate cycle (TCA), pyruvate, glyoxylate and dicarboxylate metabolism pathways to inhibit secretion of pro-inflammatory cytokines. Results of network pharmacology and molecular docking suggested that P30K targeted catechol-O-methyltransferases (COMT), 11ß-hydroxysteroid dehydrogenases (HSD11B1), and monoamine oxidases (MAOA and MAOB) to promote cellular metabolomic rewiring. Collectively, our work reveals P30K as an efficient therapeutic agent against inflammatory conditions and its efficacy is related to metabolic rewiring.
Subject(s)
Propolis , Humans , Propolis/pharmacology , Molecular Docking Simulation , Flavonoids/pharmacology , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , BrazilABSTRACT
BACKGROUND: This research depicts the linkage of public leadership on public health delivery (PHD) and collaborative administration. The research is also focused to examine the effect of public leadership on public health delivery through the intervening variable of collaborative administration by using both social information processing theory and collaboration theory. METHODS: This research is based on quantitative method. Data was collected from 464 public hospital administration in the context of Pakistan. This study evaluated data using SPSS, AMOS, and PROCESS Macro. RESULTS: Public leadership has a positive profound effect on public health delivery and collaborative administration, and that collaborative administration significantly promotes public health delivery. The outcomes also exposed that public leadership has substantial influence on public health delivery through intervening collaborative administration. CONCLUSIONS: Whilst public leadership demonstrated positive outcomes on public health delivery and collaborative administration, there is a need for more rigor studies on collaborative governance leadership, collaborative ethics and collaborative norms in the public health service.
Subject(s)
Leadership , Public Health , Humans , Cognition , Pakistan , Social TheoryABSTRACT
Background: Mild cognitive impairment (MCI), an intermediate stage between normal aging and dementia, has emerged as a prominent research area in geriatric care due to its heightened propensity for progressing toward dementia. Sleep plays a pivotal role in cognitive function, with dyssomnias not only exacerbating cognitive and affective symptoms associated with neurodegenerative diseases but also contributing to disease progression. Aim: This bibliometric analysis investigates the global research on MCI with dyssomnias over the past two decades, aiming to discern key findings, research domains, and emerging trends in this field. Methods: In this study, a bibliometric analysis was conducted using the search terms "MCI" and "sleep". Data were extracted from the Web of Science Core Collection database, and visualization and collaborative analysis were performed using CiteSpace and VOSviewer. Results: This study encompassed 546 publications from 2003 to 2023. The publication volume and citation rate consistently increased over time. Neurosciences, Clinical Neurology, and Geriatrics Gerontology emerged as the top three research fields. The Journal of Alzheimer's Disease had the highest publication count, while Sleep Medicine received the most citations. USA, China, and Italy led in publication output. Collaborative clusters among authors and institutions were identified, but cooperation between clusters was limited. Active cocited reference clusters included "obstructive sleep apnea", "possible mediating pathways", and "isolated rapid eye movement sleep behaviour disorder". The top frequently mentioned keywords, besides "MCI", were "Alzheimer's disease", "dementia", "risk factor", and "Parkinson's Disease". Notable keyword clusters spanned circadian rhythm, Parkinson's disease, MCI, dementia with Lewy body, subjective cognitive impairment, Lewy body disease, Alzheimer's disease, and dietary patterns. Conclusion: The field of MCI with dyssomnias is rapidly expanding, encompassing a wide range of neurodegenerative disorders and sleep disturbances. Current research endeavors are primarily focused on elucidating the underlying pathogenesis, predicting disease progression, and developing innovative treatment strategies for individuals affected by MCI with dyssomnias.
Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Dyssomnias , Humans , Aged , Alzheimer Disease/diagnosis , Cognitive Dysfunction/complications , Disease Progression , Bibliometrics , Dyssomnias/complicationsABSTRACT
The incidence of type 2 diabetes is high, and the existing metformin hydrochloride (MH) tablets of 250 mg cannot meet the demands of the Chinese drug market. This study aimed to evaluate the bioequivalence and safety of generic formulations of MH tablets (test formulation [T], 250 mg/tablet) and innovative products (reference formulation [R], 250 mg/tablet) under fasting conditions. This was an open-label, single-dose, 2-period, 2-sequence crossover, single-center, randomized phase I clinical trial. T and R were considered bioequivalent if the adjusted geometric mean ratios (GMRs) and 90% confidence intervals of the area under the curve (AUC) and maximum concentration (Cmax ) were within the range of 0.8-1.25. Thirty-five participants completed the trial. The T/R adjusted GMRs (95.7% for Cmax , 98.7% for AUC0ât , 98.8% for AUC0â∞ ) were within the acceptable bioequivalence range of 80%-125%. No serious adverse events or suspected or unexpected serious adverse reactions occurred during this trial. The study findings confirmed that generic MH is a well-tolerated and bioequivalent alternative to innovative products under fasting conditions in healthy Chinese participants. (www.chinadrugtrials.org.cn; registration no. CTR20190356).
Subject(s)
Diabetes Mellitus, Type 2 , Metformin , Humans , Therapeutic Equivalency , Metformin/adverse effects , Diabetes Mellitus, Type 2/drug therapy , Fasting , Tablets , ChinaABSTRACT
Due to the advancement of 16S rRNA sequencing technology, the lower respiratory tract microbiota, which was considered non-existent, has been revealed. The correlation between these microorganisms and diseases such as tumor has been a hot topic in recent years. As the bacteria in the surrounding can infiltrate the tumors, researchers have also begun to pay attention to the biological behavior of tumor bacteria and their interaction with tumors. In this review, we present the characteristic of the lower respiratory tract bacteria and summarize recent research findings on the relationship between these microbiota and lung cancer. On top of that, we also summarize the basic feature of bacteria in tumors and focus on the characteristic of the bacteria in lung cancer. The relationship between bacteria in lung cancer and tumor development is also been discussed. Finally, we review the potential clinical applications of bacterial communities in the lower respiratory tract and lung cancer, and summarize key points of sample collection, sequencing, and contamination control, hoping to provide new ideas for the screening and treatment of tumors. .
Subject(s)
Humans , Lung Neoplasms , RNA, Ribosomal, 16S/genetics , Bacteria/genetics , Microbiota , Respiratory System , Lung/microbiologyABSTRACT
The policy of long-term prescription for chronic diseases in China is gradually being improved and implemented, and external long-term prescription dispensing is being encouraged. The long-term prescription policy runs through the links of drug supply, equipment, use and policy, involving government departments such as medical security and health, as well as stakeholders such as patients, medical institutions and designated detail pharmacies. There are still some problems in the external dispensing of long-term prescriptions, such as the disunity of drug catalogue and the need for coordination among regulatory parties in the policy link; the need to improve the participation enthusiasm and service ability in the equipment link; the increased difficulty of prescription management, the need to improve the circulation platform in the use link. The promotion of external long-term prescription policy requires health insurance, medical service, and the medicine industry co-development, multi-party participation, and policy coordination. Among them, the “dual channel” policy, the policy of centralized medicine procurement, and the pharmacy included in outpatient overall management policy have all played a positive role in promoting the implementation of external long-term prescription dispensing for chronic diseases. It is necessary to improve supporting policies and implement regulatory responsibilities in the policy link, promote drug classification and service capabilities in the equipment link, improve the electronic prescription circulation platform, and strengthen prescription management in use link, so as to promote the implementation of external long-term prescription dispensing.