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Artemisia argyi (A. argyi), a plant with a longstanding history as a raw material for traditional medicine and functional diets in Asia, has been used traditionally to bathe and soak feet for its disinfectant and itch-relieving properties. Despite its widespread use, scientific evidence validating the antifungal efficacy of A. argyi water extract (AAWE) against dermatophytes, particularly Trichophyton rubrum, Trichophyton mentagrophytes, and Microsporum gypseum, remains limited. This study aimed to substantiate the scientific basis of the folkloric use of A. argyi by evaluating the antifungal effects and the underlying molecular mechanisms of its active subfraction against dermatophytes. The results indicated that AAWE exhibited excellent antifungal effects against the three aforementioned dermatophyte species. The subfraction AAWE6, isolated using D101 macroporous resin, emerged as the most potent subfraction. The minimum inhibitory concentrations (MICs) of AAWE6 against T. rubrum, M. gypseum, and T. mentagrophytes were 312.5, 312.5, and 625 μg·mL-1, respectively. Transmission electron microscopy (TEM) results and assays of enzymes linked to cell wall integrity and cell membrane function indicated that AAWE6 could penetrate the external protective barrier of T. rubrum, creating breaches ("small holes"), and disrupt the internal mitochondrial structure ("granary"). Furthermore, transcriptome data, quantitative real-time PCR (RT-qPCR), and biochemical assays corroborated the severe disruption of mitochondrial function, evidenced by inhibited tricarboxylic acid (TCA) cycle and energy metabolism. Additionally, chemical characterization and molecular docking analyses identified flavonoids, primarily eupatilin (131.16 ± 4.52 mg·g-1) and jaceosidin (4.17 ± 0.18 mg·g-1), as the active components of AAWE6. In conclusion, the subfraction AAWE6 from A. argyi exerts antifungal effects against dermatophytes by disrupting mitochondrial morphology and function. This research validates the traditional use of A. argyi and provides scientific support for its anti-dermatophytic applications, as recognized in the Chinese patent (No. ZL202111161301.9).
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Antifúngicos/química , Arthrodermataceae , Artemisia/química , Simulación del Acoplamiento Molecular , Mitocondrias , Pruebas de Sensibilidad MicrobianaRESUMEN
Proficient mismatch repair or microsatellite stable (pMMR/MSS) colorectal cancers (CRCs) are vastly outnumbered by deficient mismatch repair or microsatellite instability-high (dMMR/MSI-H) tumors and lack a response to immune checkpoint inhibitors (ICIs). In this study, we reported two distinct expression patterns of ASCL2 in pMMR/MSS and dMMR/MSI-H CRCs. ASCL2 is overexpressed in pMMR/MSS CRCs and maintains a stemness phenotype, accompanied by a lower density of tumor-infiltrating lymphocytes (TILs) than those in dMMR/MSI CRCs. In addition, coadministration of anti-PD-L1 antibodies facilitated T cell infiltration and provoked strong antitumor immunity and tumor regression in the MC38/shASCL2 mouse CRC model. Furthermore, overexpression of ASCL2 was associated with increased TGFB levels, which stimulate local Cancer-associated fibroblasts (CAFs) activation, inducing an immune-excluded microenvironment. Consistently, mice with deletion of Ascl2 specifically in the intestine (Villin-Cre+, Ascl2 flox/flox, named Ascl2 CKO) revealed fewer activated CAFs and higher proportions of infiltrating CD8+ T cells; We further intercrossed Ascl2 CKO with ApcMin/+ model suggesting that Ascl2-deficient expression in intestinal represented an immune infiltrating environment associated with a good prognosis. Together, our findings indicated ASCL2 induces an immune excluded microenvironment by activating CAFs through transcriptionally activating TGFB, and targeting ASCL2 combined with ICIs could present a therapeutic opportunity for MSS CRCs.
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Fibroblastos Asociados al Cáncer , Neoplasias del Colon , Neoplasias Colorrectales , Animales , Ratones , Linfocitos T CD8-positivos , Neoplasias Colorrectales/genética , Modelos Animales de Enfermedad , Inestabilidad de Microsatélites , Repeticiones de MicrosatéliteRESUMEN
Atmospheric simulation chambers continue to be indispensable tools for research in the atmospheric sciences. Insights from chamber studies are integrated into atmospheric chemical transport models, which are used for science-informed policy decisions. However, a centralized data management and access infrastructure for their scientific products had not been available in the United States and many parts of the world. ICARUS (Integrated Chamber Atmospheric data Repository for Unified Science) is an open access, searchable, web-based infrastructure for storing, sharing, discovering, and utilizing atmospheric chamber data [https://icarus.ucdavis.edu]. ICARUS has two parts: a data intake portal and a search and discovery portal. Data in ICARUS are curated, uniform, interactive, indexed on popular search engines, mirrored by other repositories, version-tracked, vocabulary-controlled, and citable. ICARUS hosts both legacy data and new data in compliance with open access data mandates. Targeted data discovery is available based on key experimental parameters, including organic reactants and mixtures that are managed using the PubChem chemical database, oxidant information, nitrogen oxide (NOx) content, alkylperoxy radical (RO2) fate, seed particle information, environmental conditions, and reaction categories. A discipline-specific repository such as ICARUS with high amounts of metadata works to support the evaluation and revision of atmospheric model mechanisms, intercomparison of data and models, and the development of new model frameworks that can have more predictive power in the current and future atmosphere. The open accessibility and interactive nature of ICARUS data may also be useful for teaching, data mining, and training machine learning models.
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OBJECTIVE: To study the efficacy of Xiaoyao capsule in improving the clinical symptoms of sleep and mood disorders during recovery from coronavirus disease 2019 (COVID-19). METHODS: The study cohort comprised 200 patients with sleep and mood disorders during recovery from COVID-19. Patients were randomized into the control group and the experimental group in a 1:1 ratio by blocked randomization. The patients received either Xiaoyao capsule (experimental group) or a placebo Xiaoyao capsule (control group) for 2 weeks. The improvements in the Traditional Chinese Medicine (TCM) syndrome scales, total effective rates, and disappearance rates of irritability, anxiety, and poor sleep were compared between the two groups. RESULTS: The TCM syndrome pattern scales, total effective rates, and disappearance rates of irritability, anxiety, and poor sleep did not significantly differ between the experimental group versus the control group in the full analysis set and the per protocol set after 1 and 2 weeks of treatment ( > 0.05). CONCLUSIONS: Xiaoyao capsule do not significantly improve the clinical symptoms of sleep and mood disorders in patients in recovery from COVID-19.
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COVID-19 , Medicamentos Herbarios Chinos , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Medicamentos Herbarios Chinos/uso terapéutico , Trastornos del Humor/tratamiento farmacológico , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico , Resultado del TratamientoRESUMEN
【Objective】 To analyze the commonality and characteristics between voluntary blood donors and hematopoietic stem cell donors in this region, and explore the potential for integration and development between China Marrow Donors Program (CMDP) and voluntary blood donors, especially platelet donor databases, so as to improve recruitment success rate and inventory rate. 【Methods】 The database modeling and comparison methods were used to screen and stratify the matching and integration degree between the voluntary blood donors in recent 10 years and the marrow donors in the Shaanxi Branch of CMDP. The frequencies of HLA-A,-B alleles, HPA alleles and haplotypes were calculated with Arlequin 3. 5. 2. 2 software, and the matching probability of different platelet donor reserve pools was conducted according to the phenotypic frequencies. 【Results】 Among the voluntary donors with known HLA genotypes in this region, according to their blood donation behavior,the active blood donors excavated were divided into the first, second, third and fourth echelons of platelet donor reserve pools, with 696, 2 752, 9 092 and 12 028 donors, respectively. The first echelon had the highest proportion of 10-50 times of platelet donations and 10-20 times of whole blood donations, with 13.65% and 26.01%, respectively. The second echelon had 10-20 times of whole blood donations and 10-50 times of platelet donations, accounted for 15.04% and 1.38%, respectively, which were significantly different from other echelons' blood donation characteristics (P<0.05). With a database size of the existing platelet donor bank adding the first and second echelons (n=4 955), there was a 69.02% probability of matching at least one donor with matching HLA-A-B phenotype. When considering the matching ABO and HPA phenotypes, the probability of finding at least one donor with fully matching HLA, HPA and ABO isotype (type B as an example) was 48. 73%. 【Conclusion】 The three groups of whole blood donation, apheresis platelet donation and marrow donation in Xi'an area have a large cross-distribution. Compared with expanding the storage capacity from scratch, the active blood donors in CMDP database are the largest back-up force of platelet donors. While expanding the effective storage capacity, it can minimize the cost of building platelet donor bank and the demand for resources.
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The peeled stems of Syringa pinnatifolia(SP) is a representative Mongolian folk medicine with the effects of anti-depression, heat clearance, pain relief, and respiration improvement. It has been clinically used for the treatment of coronary heart disease, insomnia, asthma, and other cardiopulmonary diseases. As part of the systematic study on pharmacological substances of SP, 11 new sesquiterpenoids were isolated from the terpene-containing fractions of the ethanol extract of SP by liquid chromatography-mass spectrometry(LC-MS) and proton nuclear magnetic resonance(~1H-NMR) guided isolation methods. The planar structures of the sesquiterpenoids were identified by MS, 1D NMR, and 2D NMR data analysis, and were named pinnatanoids C and D(1 and 2), and alashanoids T-ZI(3-11), respectively. The structure types of the sesquiterpenoids included pinnatane, humulane, seco-humulane, guaiane, carryophyllane, seco-erimolphane, isodaucane, and other types. However, limited to the low content of compounds, the existence of multiple chiral centers, the flexibility of the structure, or lack of ultraviolet absorption, the stereoscopic configuration remained unresolved. The discovery of various sesquiterpenoids enriches the understanding of the chemical composition of the genus and species and provides references for further analysis of pharmacological substances of SP.
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Syringa , Sesquiterpenos , Terpenos , Asma , Cromatografía LiquidaRESUMEN
This study explores the effect of apigenin(APG), oxymatrine(OMT), and APG+OMT on the proliferation of non-small cell lung cancer cell lines and the underlying mechanisms. Cell counting kit-8(CCK-8) assay was used to detect the vitality of A549 and NCI-H1975 cells, and colony formation assay to evaluate the colony formation ability of the cells. EdU assay was employed to examine the proliferation of NCI-H1975 cells. RT-qPCR and Western blot were performed to detect the mRNA and protein expression of PLOD2. Molecular docking was carried out to explore the direct action ability and action sites between APG/OMT and PLOD2/EGFR. Western blot was used to study the expression of related proteins in EGFR pathway. The viability of A549 and NCI-H1975 cells was inhibited by APG and APG+OMT at 20, 40, and 80 μmol·L~(-1) in a dose-dependent manner. The colony formation ability of NCI-H1975 cells was significantly suppressed by APG and APG+OMT. The mRNA and protein expression of PLOD2 was significantly inhibited by APG and APG+OMT. In addition, APG and OMT had strong binding activity with PLOD2 and EGFR. In APG and APG+OMT groups, the expression of EGFR and proteins in its downstream signaling pathways was significantly down-regulated. It is concluded that APG in combination with OMT could inhibit non-small lung cancer, and the mechanism may be related to EGFR and its downstream signaling pathways. This study lays a new theoretical basis for the clinical treatment of non-small cell lung cancer with APG in combination with OMT and provides a reference for further research on the anti-tumor mechanism of APG in combination with OMT.
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Humanos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Apigenina , Simulación del Acoplamiento Molecular , Alcaloides , Quinolizinas , ARN Mensajero , Receptores ErbBRESUMEN
Chromodomain-helicase-DNA-binding protein 1 (CHD1) deletion is among the most common mutations in prostate cancer (PCa), but its role remains unclear. In this study, RNA sequencing was conducted in PCa cells after clustered regularly interspaced palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9)-based CHD1 knockout. Gene set enrichment analysis (GSEA) indicated upregulation of hypoxia-related pathways. A subsequent study confirmed that CHD1 deletion significantly upregulated hypoxia-inducible factor 1α (HIF1α) expression. Mechanistic investigation revealed that CHD1 deletion upregulated HIF1α by transcriptionally downregulating prolyl hydroxylase domain protein 2 (PHD2), a prolyl hydroxylase catalyzing the hydroxylation of HIF1α and thus promoting its degradation by the E3 ligase von Hippel-Lindau tumor suppressor (VHL). Functional analysis showed that CHD1 deletion promoted angiogenesis and glycolysis, possibly through HIF1α target genes. Taken together, these findings indicate that CHD1 deletion enhances HIF1α expression through PHD2 downregulation and therefore promotes angiogenesis and metabolic reprogramming in PCa.
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Masculino , Humanos , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/metabolismo , Proteínas de Unión al ADN/metabolismo , Prolil Hidroxilasas/metabolismo , Hipoxia , Neoplasias de la Próstata/patología , Glucólisis , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Línea Celular Tumoral , ADN Helicasas/metabolismoRESUMEN
This study aimed to explore the anti-inflammatory material basis and molecular mechanism of Artemisia stolonifera based on the analysis of the chemical components in different extracted fractions of A. stolonifera and their antioxidant and anti-inflammatory effects in combination with network pharmacology and molecular docking. Thirty-two chemical components were identified from A. stolonifera by ultra-performance liquid chromatography coupled to tandem quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS). Among them, there were 7, 21 and 22 compounds in water, n-butanol and ethyl acetate fractions, respectively. The antio-xidant capacity of different extracted fractions was evaluated by measuring their scavenging ability against 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl(DPPH) and 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonic acid)(ABTS) free radicals and total antioxidant capacity [ferric reducing antioxidant power(FRAP) assay]. The inflammatory model of RAW264.7 cells was induced by lipopolysaccharide(LPS), and the levels of nitrite oxide(NO), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) in the supernatant and the mRNA expression of related inflammatory factors in cells were used to evaluate the anti-inflammatory effects. The results revealed that ethyl acetate fraction of A. stolonifera was the optimal antioxidant and anti-inflammatory fraction. By network pharmacology, it was found that flavonoids such as rhamnazin, eupatilin, jaceosidin, luteolin and nepetin could act on key targets such as TNF, serine/threonine protein kinase 1(AKT1), tumor protein p53(TP53), caspase-3(CASP3) and epidermal growth factor receptor(EGFR), and regulate the phosphatidylinositol-3-kinase-protein kinase B(PI3K-AKT) and mitogen-activated protein kinase(MAPK) signaling pathways to exert the anti-inflammatory effects. Molecular docking further indicated excellent binding properties between the above core components and core targets. This study preliminarily clarified the anti-inflammatory material basis and mechanism of ethyl acetate fraction of A. stolonifera, providing a basis for the follow-up clinical application of A. stolonifera and drug development.
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Antioxidantes/química , Simulación del Acoplamiento Molecular , Artemisia , Farmacología en Red , Fosfatidilinositol 3-Quinasas , Antiinflamatorios/química , Medicamentos Herbarios Chinos/farmacología , Interleucina-6RESUMEN
Objective: To observe the antipruritic effect and mechanism of the volatile oil of Zanthoxylum bungeanum and Zanthoxylum schinifolium on chronic eczema to provide data support for clinical application and new drug development of Zanthoxylum bungeanum and Zanthoxylum schinifolium. Methods: The model of chronic eczema was established by using 2-dinitrochlorobenzene (DNCB), and the composition and content of volatile oil in Zanthoxylum schinifolium and Zanthoxylum bungeanum was determined by gas chromatography-mass spectrometry (GC-MS). The antipruritic effect by (EASI) score of eczema area and severity index and scratching times was then evaluated. Then, the contents of histamine, gastrin-releasing peptide (GRP), interleukin-4 (IL-4), and immunoglobulin E (IgE) in serum of rats was determined by enzyme-linked immunosorbent assay (ELISA). The tissue morphology was observed by HE staining. The expressions of H1R, PAR-2, TRPV1, TRPA1, and GRPR was then detected by immunohistochem-istry, Western blot, and QRT-PCR.Results: The results revealed that there were differences in the composition of volatile oil between Zanthoxylum bungeanum and Zanthoxylum schinifolium. Compared to the model group, the medium-dose group of Zanthoxylum bungeanum and Zanthoxylum schinifolium group significantly increased the difference of EASI score and scratching times, significantly decreased the concentrations of IL-4, IgE, GRP, and histamine, and significantly decreased the expression levels of H1R, PAR-2, TRPV1, and GRPR. The degree of inhibition on the patho-logical manifestations of chronic eczema was evident. There was no significant difference in antipruritic effect between the two groups. The expression of TRPA1 was inconsistent at the protein and gene level, which needs to be further researched (AU)
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Animales , Masculino , Ratas , Antipruriginosos/administración & dosificación , Eccema/tratamiento farmacológico , Histamínicos/administración & dosificación , Aceites Volátiles/administración & dosificación , Zanthoxylum/química , Modelos Animales de Enfermedad , Inmunoglobulina E , Interleucina-4 , Ratas Wistar , Enfermedad CrónicaRESUMEN
Tumor penetration and the accumulation of nanomedicines are crucial challenges in solid tumor therapy. By taking advantage of the MSC tumor-tropic property, we developed a mesenchymal stem cell (MSC)-based drug delivery system in which paclitaxel (PTX)-encapsulating hyaluronic acid-poly (D,L-lactide-co-glycolide) polymeric micelles (PTX/HA-PLGA micelles) were loaded for glioma therapy. The results indicated that CD44 overexpressed on the surface of both MSCs and tumor cells not only improved PTX/HA-PLGA micelle loading in MSCs, but also promoted the drug transfer between MSCs and adjacent cancer cells. It was hypothesized that CD44-mediated transcytosis played a crucial role and allowed deep glioma penetration depending on sequential intra-intercellular delivery via endocytosis-exocytosis. MSC-micelles were able to infiltrate from normal brain parenchyma towards contralateral tumors and led to the eradication of glioma. The survival of orthotopic glioma-bearing rats was significantly extended. In conclusion, the MSC-based delivery of HA-PLGA micelles is a potential strategy for tumor-targeting drug delivery.
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Glioma , Células Madre Mesenquimatosas , Animales , Línea Celular Tumoral , Dioxanos , Portadores de Fármacos/uso terapéutico , Sistemas de Liberación de Medicamentos/métodos , Glioma/tratamiento farmacológico , Ácido Hialurónico/uso terapéutico , Micelas , Paclitaxel , Polímeros/uso terapéutico , RatasRESUMEN
Inflammation is a common disease involved in the pathogenesis, complications, and sequelae of a large number of related diseases, and therefore considerable research has been directed toward developing anti-inflammatory drugs for the prevention and treatment of these diseases. Traditional Chinese medicine (TCM) has been used to treat inflammatory and related diseases since ancient times. According to the review of abundant modern scientific researches, it is suggested that TCM exhibit anti-inflammatory effects at different levels, and via multiple pathways with various targets, and recently a series of in vitro and in vivo anti-inflammatory models have been developed for anti-inflammation research in TCM. Currently, the reported classic mechanisms of TCM and experimental models of its anti-inflammatory effects provide reference points and guidance for further research and development of TCM. Importantly, the research clearly confirms that TCM is now and will continue to be an effective form of treatment for many types of inflammation and inflammation-related diseases.
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Medicamentos Herbarios Chinos , Medicina Tradicional China , Antiinflamatorios/farmacología , Medicamentos Herbarios Chinos/farmacología , Humanos , Inflamación/tratamiento farmacológico , Modelos TeóricosRESUMEN
Current chemical transport models generally use a constant secondary organic aerosol (SOA) yield to represent SOA formation from aromatic compounds under low NOx conditions. However, a wide range of SOA yields (10 to 42%) from m-xylene under low NOx conditions is observed in this study. The chamber HO2/RO2 ratio is identified as a key factor explaining SOA yield variability: higher SOA yields are observed for runs with a higher HO2/RO2 ratio. The RO2 + RO2 pathway, which can be increasingly significant under low NOx and HO2/RO2 conditions, shows a lower SOA-forming potential compared to the RO2 + HO2 pathway. While the traditional low-NOx chamber experiments are commonly used to represent the RO2 + HO2 pathway, this study finds that the impacts of the RO2 + RO2 pathway cannot be ignored under certain conditions. We provide guidance on how to best control for these two pathways in conducting chamber experiments to best obtain SOA yield curves and quantify the contributions from each pathway. On the global scale, the chemical transport model GEOS-Chem is used to identify regions characterized by lower surface HO2/RO2 ratios, suggesting that the RO2 + RO2 pathway is more likely to prove significant to overall SOA yields in those regions. Current models generally do not consider the RO2 + RO2 impacts on aromatic SOA formation, but preliminary sensitivity tests with updated SOA yield parameters based on such a pathway suggest that without this consideration, some types of SOA may be overestimated in regions with lower HO2/RO2 ratios.
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Contaminantes Atmosféricos , Aerosoles/química , Contaminantes Atmosféricos/análisis , Modelos Químicos , Compuestos Orgánicos/químicaRESUMEN
Objective:To explore the serum tenascin-C levels in patients with acute ST-segment elevation myocardial infarction (STEMI) and its impact on the long-term prognosis.Methods:One hundred and thirteen STEMI patients who were admitted to the Department of Cardiology of the First Affiliated Hospital of Dalian Medical University and successfully underwent emergency PCI from June 2015 to June 2016 were included in this prospective study. The serum tenascin-C levels were measured during hospitalization, and the patients were divided into tenascin-C ≥ 120 μg/L group and tenascin-C<120 μg/L group according to the serum tenascin-C level. Major adverse cardiovascular events (MACE) were observed during the 5 years follow up in all patients. According to the incidence of MACE, the patients were divided into MACE group and non-MACE group, and the predictive factors of MACE were analyzed. Continuous variables were presented as the mean±standard deviation and compared with the Student′s t-test. Categorical variables were presented as percentages and compared with the Chi-square test or Fisher′s exact test. Receiver operating characteristic (ROC) curve was used to analyze the value of serum tenascin-C level in predicting MACE in STEMI patients. Kaplan Meier survival analysis was used to compare the incidence of MACE between two groups. Cox proportional hazards regression model was used to analyze the risk factors of MACE during the 5 years follow up.Results:The serum tenascin-C levels in the STEMI patients increased on the first day after the onset of disease (46.5±24.8 μg/L), peaked on the third day (97.5±41.2 μg/L), and then gradually decreased. All patients were followed up for 5 years. There were 37 cases of MACE, including 4 cases of cardiac death (3.5%), 14 cases of heart failure (12.4%), 14 cases of recurrent myocardial infarction or revascularization (12.4%), and 5 cases of stroke (4.4%). For prediction of MACE, the area under the curve of the serum TN-C level was 0.953 (95% CI 0.918-0.988, P<0.05), which was thus a valuable biomarker in predicting MACE for STEMI patients. The incidence of MACE in the group of tenascin-C≥120 μg/L group was higher than that in the group of tenascin-C<120 μg/L group (86.4% [19/22] vs 19.8% [18/91]), and Kaplan-Meier survival analysis showed that the difference was statistically significant ( P<0.05). Cox proportional hazards model analysis showed that serum tenascin-C level was an independent predictor of MACE for STEMI patients during the 5 years follow-up ( HR=1.007, 95% CI 1.001-1.012, P<0.05). In addition, other variables including high sensitivity C-reactive protein ( HR=1.028, 95% CI 1.007-1.049, P<0.05), and cardiac troponin Ⅰ ( HR=1.004, 95% CI 1.000-1.008, P<0.05) were also found to be the independent predictors of MACE. Conclusions:The serum tenascin-C levels in STEMI patients increased significantly during the acute disease phase. Detecting the serum tenascin-C levels is valuable for predicting MACE in STEMI patients, and serum tenascin-C is an independent predictor of MACE in STEMI patients during the long-term follow-up period after acute myocardial infarction.
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Objective To explore the risk factors for vascular invasion and its influence on prognosis of resectable gastric cancer patients by analyzing the clinicopathological features. Methods We retrospectively analyzed the data of 1077 patients with stage Ⅰ-Ⅲ gastric cancer who underwent surgical resection. According to whether vascular invasion occurred, they were divided into LVI positive group (n=672) and LVI negative group (n=405). Logistic univariate and multivariate analyses were used for the relation between clinical pathological features and LVI. Survival analysis was used to study the relation between vascular invasion and survival rate in patients with stage Ⅰ gastric cancer. Results Univariate analysis showed that tumor size, type of differentiation, depth of invasion, lymph node metastasis, TNM stage, Lauren classification, nerve invasion and the increase of CEA, CA125 and CA199 were risk factors for vascular invasion (P < 0.05). Multivariate analysis showed that poor differentiation, deep invasion, lymph node metastasis, nerve invasion and elevated CA724 were independent risk factors for vascular invasion. The 5-year survival rate of stage Ⅰ gastric cancer patients with vascular invasion was significantly lower than that without vascular invasion (P < 0.01). Conclusion Gastric cancer patients with poor differentiation, deep invasion, lymph node metastasis, nerve invasion and elevated CA724 are more prone to vascular invasion. Patients with stage I gastric cancer at risk of vascular invasion should be treated more aggressively.
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【Objective】 To evaluate the appropriate optimal capacity and matching probability of the platelet donor database with known HLA/HPA genotype in Shaanxi aera, and provide data support for subsequent construction, maintenance and application of the local platelet donor database. 【Methods】 A total of 11 755 individuals from the Shaanxi Branch of China Marrow Donor Program, 401 and 249 unrelated random platelet donors in Shaanxi aera were enrolled to the population study of HLA-A, -B polymorphisms, HPA genotyping and CD36 antigen expression, respectively. The frequencies of HLA-A, -B alleles, HPA alleles and haplotypes were calculated with Arlequin 3. 5. 2. 2 software; matching probability and capacity evaluation of platelet donor database was conducted according to the phenotypic frequencies. 【Results】 The population genetic and phenotypic polymorphisms data of HLA-A, -B and HPA1-6, 10, 15, 21 in Shaanxi aera were obtained. The frequency of CD36 type Ⅰ or Ⅱ deficiency was 0.40%(1/249). According to the subsequent calculating and deriving, with a database size of 194 donors, the patient having approximate 95% probability could achieve matching of HPA1-6, 10, 15, 21 genotype. With a database size of 1500 donors, there is a 95% probability of matching at least one donor with HLA-A-B phenotype frequency >0.002 or haplotype frequency >0.001; meanwhile, the probability of matching a cross-reactive group donor should be 44.95%-97.57%. Based on database size of 8 856 and 15 033, the probabilities of matching HLA-A, -B phenotype were about 80% and 90%, respectively. 【Conclusion】 The differences in the distribution of HLA/HPA polymorphism in different regions make the establishment mode and optimal capacity of platelet donor database different. It is necessary to apply a variety of platelet matching transfusion strategies to expand the range of donor selection, thereby effectively reducing the database construction cost and resource requirements.
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ObjectiveTo investigate the effects and mechanism of baicalin (BA) on lipopolysaccharide (LPS)-induced acute lung injury in rats. MethodEighty healthy male SD rats were randomly divided into the control group, model group, low-dose BA (BA-L) group, medium-dose BA (BA-M) group, high-dose BA (BA-H) group, dexamethasone (DEX) group, SB203580 group, and BA + SB203580 group, with 10 rats in each group. The rats in the BA-L, BA-M, and BA-H groups were injected intraperitoneally with different doses (10, 50, 100 mg·kg-1) of BA solution, the ones in the DEX group with 5 mg·kg-1 DEX solution, the ones in the SB203580 group with 0.5 mg·kg-1 SB203580 solution, the ones in the BA + SB203580 group with 100 mg·kg-1 BA solution and 0.5 mg·kg-1 SB203580, and those in both the control group and model group with the same volume of normal saline, once per day, for seven successive days. One hour after the last administration, rats in all groups except for the control group were given 5 mg·kg-1 LPS via intratracheal instillation for inducing the acute lung injury, whereas those in the control group received the same volume of normal saline solution. Twelve hours later, the lung tissues were sampled and stained with htoxylin-eosin (HE) for observing the pathological changes, followed by the counting of the total number of cells and neutrophils in bronchoalveolar lavage fluid (BALF). The wet/dry weight ratio of the lung tissue and the contents of serum superoxide dismutase (SOD) and malondialdehyde (MDA) were measured. The activity of reactive oxygen species (ROS) in the lung tissue was detected by immunofluorescence and the levels of interleukin-1β (IL-1β), interleukin-18 (IL-18), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in BALF by enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry (IHC) was conducted to determine the relative expression of p-p38 mitogen-activated protein kinase (MAPK) and Western blotting was carried out to detect the protein expression levels of p-p38 MAPK, thioredoxin interacting protein (TXNIP), NOD-like receptor protein 3 (NLRP3), and cysteinyl aspartate specific protease-1 (Caspase-1) in the lung tissue. ResultCompared with the control group, the model group displayed inflammatory pathological changes in lung tissue, elevated wet/dry weight ratio, total number of cells and neutrophils in BALF, and ROS and MDA levels (P<0.01), decreased SOD activity (P<0.01), and up-regulated IL-1, IL-18, IL-6, TNF-α, p-p38 MAPK, NLRP3, and Caspase-1 expression (P<0.01). Compared with the model group, BA at different doses, SB203580, and BA + SB203580 all effectively alleviated the pathological changes in lung tissue induced by LPS, reduce the lung wet/dry weight ratio, the total number of cells and neutrophils in BALF, and ROS and MDA levels (P<0.05,P<0.01), enhanced the activity of SOD (P<0.05,P<0.01), and down-regulated the expression of IL-1β, IL-18, IL-6,TNF-α, p-p38 MAPK, NLRP3, and Caspase-1 in lung tissue (P<0.05,P<0.01). ConclusionBA has a protective effect against LPS-induced acute lung injury, which may be related to its inhibition of p38MAPK/NLRP3 signaling pathway and the improvement of inflammatory response.
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Atopic dermatitis is a chronic, refractory and inflammatory skin disease with the clinical manifestations of severe pruritus and recurrent attacks. It has a high incidence and is closely correlated with other allergic, autoimmune or infectious diseases, which can cause a variety of secondary diseases and mental and psychological disorders, seriously affecting the life quality of patients. Chinese herbal medicines have been used for the prevention and treatment of atopic dermatitis for thousands of years, and many Chinese herbal medicines (including compound prescriptions) effective for this disease have been recorded. These medicines generally have little adverse reactions and the treated patients have low recurrence rate of atopic dermatitis. According to the evidence of modern medicine, the onset of atopic dermatitis is related to the impairment of skin barrier function, abnormal immune response, and abnormal differentiation of mast cells, antigen-presenting cells, and eosinophils. Additionally, it is associated with mental, endocrine, metabolic and other factors. The defect of skin barrier function and the dysfunction of immune system are the main pathogenesis of atopic dermatitis. In recent years, scientists have achieved certain progress in improving skin barrier function with Chinese herbal medicines. This paper systematically summarizes the studies about the application of Chinese herbal medicines in regulating the expression of epidermal proteins, epidermal lipids, aquaporins, tight junction proteins, and antimicrobial peptides in recent 10 years, aiming to clarify the pathological mechanism and provide reference for the clinical research and application of Chinese herbal medicines in the treatment of atopic dermatitis.
RESUMEN
Objective: To analyzed perioperative safety of cytoreductive surgery (CRS) for patients with colorectal cancer peritoneal metastasis (CRPM) and to construct a predictive model for serious advese events (SAE). Methods: A descriptive case-series study was conducted to retrospectively collect the clinicopathological data and treatment status (operation time, number of organ resection, number of peritoneal resection, and blood loss, etc.) of 100 patients with peritoneal metastases from colorectal cancer or appendix mucinous adenocarcinoma who underwent CRS at the Sixth Affiliated Hospital of Sun Yat-sen University from January 2019 to August 2021. There were 53 males and 47 females. The median age was 52.0 (39.0-61.8) years old. Fifty-two patients had synchronous peritoneal metastasis and 48 had metachronous peritoneal metastasis. Fifty-two patients received preoperative neoadjuvant therapy. Primary tumor was located in the left colon, the right colon and the rectum in 43, 28 and 14 cases, respectively. Fifteen patients had appendix mucinous adenocarcinoma. Measures of skewed distribution are expressed as M (range). Perioperative safety was analyzed, perioperative grade III or higher was defined as SAE. Risk factors associated with the occurrence of SAEs were analyzed using multivariate logistic regression. A nomogram was plotted by R software to predict SAE, the efficacy of which was evaluated using the area under the ROC curve (AUC) and correction curves. Results: The median peritoneal cancer index (PCI) score was 16 (1-39). Sixty-eight (68.0%) patients achieved complete tumor reduction (tumor reduction score: 0-1). Sixty-two patients were treated with intraperitoneal hyperthermic perfusion chemotherapy (HIPEC). Twenty-one (21.0%) patients developed 37 SAEs of grade III-IV, including 2 cases of ureteral injury, 6 cases of perioperative massive hemorrhage or anemia, 7 cases of digestive system, 15 cases of respiratory system, 4 cases of cardiovascular system, 1 case of skin incision dehiscence, and 2 cases of abdominal infection. No grade V SAE was found. Multivariate logistic regression analysis showed that CEA (OR: 8.980, 95%CI: 1.428-56.457, P=0.019), PCI score (OR: 7.924, 95%CI: 1.486-42.259, P=0.015), intraoperative albumin infusion (OR: 48.959, 95%CI: 2.115-1133.289, P=0.015) and total volume of infusion (OR: 24.729, 95%CI: 3.956-154.562, P=0.001) were independent risk factors for perioperative SAE in CRS (all P<0.05). Based on the result of multivariate regression models, a predictive nomogram was constructed. Internal verification showed that the AUC of the nomogram was 0.926 (95%CI: 0.872-0.980), indicating good prediction accuracy and consistency. Conclusions: CRS is a safe and effective method to treat CRPM. Strict screening of patients and perioperative fluid management are important guarantees for reducing the morbidity of SAE.
Asunto(s)
Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adenocarcinoma Mucinoso/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Apéndice/cirugía , Neoplasias Colorrectales/patología , Terapia Combinada , Procedimientos Quirúrgicos de Citorreducción/métodos , Hipertermia Inducida/métodos , Neoplasias Peritoneales/secundario , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
The slab-coupled optical fiber sensor (SCOS) is an innovative electric field detector with an ultrawide measuring range and a millimeter-level package size. The core sensing part of the SCOS is a fiber-waveguide evanescent coupler (FWEC) that directly determines the device's main performance specifications. This paper presents an investigation of the spectrum characteristics of FWECs with various structural and curing parameters. Methods for fabricating an FWEC with higher resonant depth, narrower free spectral range, and sharper spectrum slope are determined based on the experimental results. Z-cut lithium-niobate FWEC and Z-cut lithium-tantalate FWEC of about ${{1}} \times {0.5} \times {0.3}\;{\rm{mm}}^3$ are fabricated on this basis. Excellent coupling characteristics are achieved in both, according to the relevant spectra. Electric field tests indicate that the peak wavelengths shift linearly with the external AC field amplitude by 0.11 nm/(kV/cm) and 0.24 nm/(kV/cm), respectively. Three optimization methods are proposed to enhance performance: optimizing material selection, adding an antenna structure, and adjusting the calibration method. The results of this work may provide workable guidance for developing miniature, all-dielectric electric field sensors.