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ObjectiveTo observe the effect of Scutellariae Radix-Coptidis Rhizoma on plaque stability in atherosclerotic (AS) mice and to explore its possible mechanism of action based on the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor kappa B (NF-κB) signaling pathway. MethodTen normal C57BL/6J mice were used as the normal group, and the same strain of ApoE knockout (ApoE-/-) mice were fed with a high-fat diet for 12 weeks to construct an atherosclerosis model. Mice were randomly divided into five groups, namely the model group, the atorvastatin group, and the Scutellariae Radix-Coptidis Rhizoma low-, medium-, and high-dose groups, with ten mice in each group. Then normal and model groups were given equal volume of saline gavage, and the low-, medium-, high-dose Scutellariae Radix-Coptidis Rhizoma groups were given 1.95, 3.9, 7.8 g·kg-1 of the drug by gavage for 8 weeks, respectively. The general state of mice was observed. Hematoxylin-eosin staining was utilized to observe the pathology of aortic root plaques and calculate the percentage of plaque area. Masson staining and oil red O staining combined with immunohistochemistry of F4/80 and α-SMA were used to detect the plaque components of aortic root plaques and calculate the plaque vulnerability index. Enzyme-linked immunosorbent assay was adopted to detect the expression levels of serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Western blot was applied to detect the protein expression levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), TLR4, MyD88, NF-κB p65, and phosphorylation (p) -NF-κB p65 in the aortic tissues of mice in each group. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) assay was employed to detect the expression levels of MMP-2, MMP-9, TLR4, and MyD88, NF-κB p65 mRNA. ResultCompared with the model group, the general state of the mice in each medication group was improved, and no obvious side effects were observed. Compared with the model group, the percentage of plaque area in the aortic root of AS mice was significantly reduced in the medium- and high-dose Scutellariae Radix-Coptidis Rhizoma groups (P<0.05). The content of collagen fibers and smooth muscle cells in the plaques of the high-dose Scutellariae Radix-Coptidis Rhizoma group was significantly increased (P<0.01), and the content of lipids and macrophages was significantly reduced (P<0.05), the plaque vulnerability index of each dose group of Scutellariae Radix-Coptidis Rhizoma was significantly reduced, with significant reduction of the medium- and high-dose groups (P<0.01). MMP-2 and MMP-9 protein and mRNA expression levels in aortic tissues were significantly reduced in medium- and high-dose Scutellariae Radix-Coptidis Rhizoma groups (P<0.05). The serum levels of TNF-α and IL-6 were significantly reduced in AS mice in medium- and high-dose Scutellariae Radix-Coptidis Rhizoma groups (P<0.05). In the medium- and high-dose Scutellariae Radix-Coptidis Rhizoma groups, the levels of TLR4, MyD88 protein, and mRNA expression in aortic tissues were significantly reduced (P<0.05), and the level of NF-κB p65 phosphorylation in aortic tissues was significantly reduced (P<0.05). ConclusionScutellariae Radix-Coptidis Rhizoma may play an anti-inflammatory and stabilizing role by inhibiting the TLR4/MyD88/NF-κB signaling pathway.
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ObjectiveTo investigate the therapeutic effect of Scutellariae Radix-Coptidis Rhizoma (SRCR) on atherosclerosis (AS) in mice and the effect of SRCR on macrophage pyroptosis in plaques via NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasomes. MethodApoE-/- mice were fed with a high-fat diet for the modeling of AS and randomized into model, atorvastatin (5 mg·kg-1), and low-, medium-, and high-dose (1.95, 3.9, 7.8 g·kg-1, respectively) SRCR groups. Normal C57BL/6J mice were selected as the control group. After 8 weeks of administration, hematoxylin-eosin staining was used to observe the pathological status of the aortic plaque. The lipid accumulation in aortic plaque was observed by oil red O staining. The serum levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in mice were measured. Immunofluorescence double staining was employed to detect the co-localized expression of EGF-like module-containing mucin-like hormone receptor-like 1 (EMR1)/NLRP3 and EMR1/gasdermin D (GSDMD). The serum levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) were determined by enzyme-linked immunosorbent assay (ELISA). The protein levels of NLRP3, apoptosis-associated speck-like protein (ASC), Caspase-1, cleaved Caspase-1, GSDMD, N-terminus of GSDMD (GSDMD-NT), pro-IL-1β, IL-1β, and IL-18 were determined by Western blot, and the mRNA levels of NLRP3, ASC, Caspase-1, GSDMD, IL-1β, and IL-18 were determined by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultCompared with the control group, the model group showed obvious plaques, elevated serum levels of TG, TC, LDL-C, IL-1β, and IL-18 (P<0.01), lowered serum level of HDL-C (P<0.01), and up-regulated expression of NLRP3 inflammasomes and molecules related to pyroptosis in the aortic plaques (P<0.01). Compared with the model group, SRCR, especially at the medium and high doses, alleviated the plaque pathology, reduced the lipid content in plaques (P<0.05, P<0.01), recovered the serum lipid levels (P<0.05), reduced the macrophage recruitment (P<0.01), activation of NLRP3 inflammasomes, and pyroptosis in aortic root plaques (P<0.05), lowered the serum IL-1β and IL-18 levels (P<0.01), and down-regulated the protein levels of NLRP3, ASC, Caspase-1, cleaved Caspase-1, GSDMD, GSDMD-NT, pro-IL-1β, IL-1β, and IL-18 (P<0.05) and the mRNA levels of NLRP3, ASC, Caspase-1, GSDMD, IL-1β, and IL-18 in the aortic tissue (P<0.05). ConclusionSRCR exerts a therapeutic effect on high-fat diet-induced AS in mice by inhibiting the activation NLRP3 inflammasomes and reducing the pyroptosis of macrophages in plaques.
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Three different preclinical evaluation methods of MTF through-frequency response, MTF through-focus-response and expected visual acuity were used to compare and analyze the imaging differences of IOLs with four different optical designs. The research work could be used in the simultaneous vision IOLs in the optical design stage and verify the optical quality of the IOLs, the results can predict the visual representation of the patients better. The evaluation results can provide reference for IOL manufacturers and users in product design, development, validation and application selection.
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Humanos , Diseño de Prótesis , Lentes Intraoculares , Visión Ocular , Agudeza VisualRESUMEN
To assess the reliability, validity and responsiveness of the Chinese version of the atopic dermatitis control tool (ADCT). After this study obtained authorization for the Chinese version of the ADCT scale. 114 patients with atopic dermatitis were enrolled from the Department of Dermatology, Peking University First Hospital using convenience sampling from October 2022. Patients were surveyed using the General Information Questionnaire, Chinese version of ADCT, patient-oriented eczema measure (POEM),peak pruritus numerical rating scale (PP-NRS),dermatology life quality index (DLQI) and the global patient self-assessment for disease severity. Mann-Whitney rank sum test and Spearman correlation analysis were used for item analysis; content validity was assessed using content validity index (CVI); exploratory factor analysis was used to assess structural validity; Cronbach' alpha coefficient was used to assess internal consistency; Spearman correlation analysis was used to assess the correlation of ADCT with other scales to assess external responsiveness. The results showed that all items were retained by item analysis. I-CVI was 0.9-1, and S-CVI/Average was 0.983; the scale extracted one common factor by factor analysis, the cumulative variance explanation rate was 77.927%; the Cronbach' alpha coefficient of the scale was 0.937; the correlation coefficients of the Chinese version of ADCT with POEM, PP-NRS, and DLQI were 0.805, 0.861, and 0.709 respectively. In conclusion, the Chinese version of the ADCT has adequate reliability, validity and responsiveness, and is suitable for measuring disease control in Chinese patients with atopic dermatitis.
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Humanos , Dermatitis Atópica , Calidad de Vida , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
OBJECTIVE@#To observe the clinical efficacy of acupuncture for prevention of moderate to severe seasonal allergic rhinitis.@*METHODS@#A total of 105 patients with moderate to severe seasonal allergic rhinitis were randomly divided into an observation group (53 cases, 3 cases dropped off) and a control group (52 cases, 4 cases dropped off). The patients in the observation group were treated with acupuncture at Yintang (GV 24+), Yingxiang (LI 20), Hegu (LI 4), Zusanli (ST 36), Fengchi (GB 20), Feishu (BL 13), etc. 4 weeks before the seizure period, once every other day, 3 times a week for 4 weeks. The patients in the control group were not given any intervention before the seizure period. Emergency drugs can be given appropriately during the seizure period in both groups. After seizure period, the seizure rate was recorded in the two groups; before treatment and on week 1, 2, 4, 6 of seizure period after treatment, the rhinoconjunctivitis quality of life questionnaire (RQLQ) score and total nasal symptom score (TNSS) were observed in the two groups; the rescue medication score (RMS) was recorded on week 1-6 of seizure period in the two groups.@*RESULTS@#The seizure rate of the observation group was 84.0% (42/50), which was lower than 100.0% (48/48) in the control group (P<0.05). After treatment, the scores of RQLQ and TNSS at each time point of seizure period were decreased compared with before treatment in the observation group (P<0.01), which were lower than the control group (P<0.01). The RMS score at each time point of seizure period in the observation group was lower than the control group (P<0.05, P<0.01).@*CONCLUSION@#Acupuncture can reduce the incidence of moderate to severe seasonal allergic rhinitis, relieve the symptoms, improve the quality of life and reduce the use of emergency drugs.
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Humanos , Rinitis Alérgica Estacional , Rinitis Alérgica/terapia , Calidad de Vida , Terapia por Acupuntura , Puntos de Acupuntura , Resultado del Tratamiento , ConvulsionesRESUMEN
Objective:To investigate the role of three-dimensional dose distribution-based deep learning model in predicting distant metastasis of head and neck cancer.Methods:Radiotherapy and clinical follow-up data of 237 patients with head and neck cancer undergoing intensity-modulated radiotherapy (IMRT) from 4 different institutions were collected. Among them, 131 patients from HGJ and CHUS institutions were used as the training set, 65 patients from CHUM institution as the validation set, and 41 patients from HMR institution as the test set. Three-dimensional dose distribution and GTV contours of 131 patients in the training set were input into the DM-DOSE model for training and then validated with validation set data. Finally, the independent test set data were used for evaluation. The evaluation content included the area under receiver operating characteristic curve (AUC), balanced accuracy, sensitivity, specificity, concordance index and Kaplan-Meier survival curve analysis.Results:In terms of prognostic prediction of distant metastasis of head and neck cancer, the DM-DOSE model based on three-dimensional dose distribution and GTV contours achieved the optimal prognostic prediction performance, with an AUC of 0.924, and could significantly distinguish patients with high and low risk of distant metastasis (log-rank test, P<0.001). Conclusion:Three-dimensional dose distribution has good predictive value for distant metastasis in head and neck cancer patients treated with IMRT, and the constructed prediction model can effectively predict distant metastasis.
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This study aims to investigate the effects of baicalein(BAI) on lipopolysaccharide(LPS)-induced human microglial clone 3(HMC3) cells, with a focus on suppressing inflammatory responses and elucidating the potential mechanism underlying the therapeutic effects of BAI on ischemic stroke via modulating the cAMP-PKA-NF-κB/CREB pathway. The findings have significant implications for the application of traditional Chinese medicine in treating cerebral ischemic diseases. First, the safe dosage of BAI was screened, and then an inflammation model was established with HMC3 cells by induction with LPS for 24 h. The cells were assigned into a control group, a model group, and high-, medium-, and low-dose(5, 2.5, and 1.25 μmol·L~(-1), respectively) BAI groups. The levels of superoxide dismutase(SOD) and malondialdehyde(MDA) in cell extracts, as well as the levels of interleukin-1β(IL-1β), IL-6, tumor necrosis factor-α(TNF-α), and cyclic adenosine monophosphate(cAMP) in the cell supernatant, were measured. Western blot was performed to determine the expression of protein kinase A(PKA), phosphorylated cAMP-response element binding protein(p-CREB), and nuclear factor-kappa B p65(NF-κB p65). Hoechst 33342/PI staining was employed to assess cell apoptosis. High and low doses of BAI were used for treatment in the research on the mechanism. The results revealed that BAI at the concentrations of 10 μmol·L~(-1) and below had no impact on normally cultured HMC3 cells. LPS induction at 200 ng·mL~(-1) for 24 h reduced the SOD activity and increased the MDA content in HMC3 cells. However, 5, 2.5, and 1.25 μmol·L~(-1) BAI significantly increased the SOD activity and 5 μmol·L~(-1) BAI significantly decreased the MDA content. In addition, BAI ameliorated the M1 polarization of HMC3 cells induced by LPS, as indicated by cellular morphology. The results of ELISA demonstrated that BAI significantly lowered the levels of TNF-α, IL-1β, IL-6, and cAMP in the cell supernatant. Western blot revealed that BAI up-regulated the protein levels of PKA and p-CREB while down-regulating the expression of NF-κB p65. Hoechst 33342/PI staining results indicated that BAI mitigated the apoptosis of HMC3 cells. Overall, the results indicated that BAI had protective effects on the HMC3 cells induced by LPS, and could inhi-bit inflammatory response and improve cell apoptosis, which might be related to the regulation of the cAMP-PKA-NF-κB/CREB pathway.
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Humanos , FN-kappa B/metabolismo , Microglía , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Lipopolisacáridos/farmacología , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
Objective: To understand the harm degree of underground noise and provide basis for noise control. Methods: In November 2019, 13 typical coal mines in Sichuan Province were selected as the research objects, and a total of 1203 sites and 609 jobs of noise exposure were investigated. Results: The noise intensity P75 >80 dB (A) was measured. The noise intensity of the inspection place of the air compressor is >86 dB (A) , the noise intensity of the inspection place of the gas drainage and the operation place of the main fan is between 80-85 dB (A) . Conclusion: Besides the harm of dust, noise exposure should also be paid attention to, and the measures of sound absorption and sound insulation should be taken or personal protection should be strengthened.
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Carbón Mineral , Minas de Carbón , Polvo/análisis , Ruido , Exposición ProfesionalRESUMEN
Objective: To study the effect of microRNA-126 (miR-126) on the polarization of human monocyte-derived macrophages stimulated by Porphyromonas gingivalis (Pg) lipopolysaccharide (LPS). Methods: Macrophages derived from human myeloid leukemia mononuclear cells were stimulated by Pg-LPS (5 mg/L) and by Pg-LPS (5 mg/L) after 24 h-transfection of miR-126 mimic or negative control RNA for 48 h, respectively. Real-time quantitative-PCR (qRT-PCR), enzyme-linked immunosorbent assay (ELISA) and Western blotting were conducted to detect the changes in miR-126, pro-inflammatory factor tumor necrosis factor-α (TNF-α), anti-inflammatory factors interleukin-10 (IL-10), inducible nitric oxide synthase (iNOS), arginase-1 (Arg-1) and M1 polarization-related pathways such as nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Results: Compared with non-LPS stimulation group (TNF-α: 1.000±0.020, iNOS: 1.125±0.064, miR-126: 1.004±0.113, IL-10: 1.003±0.053, Arg-1: 1.130±0.061), the mRNA levels of TNF-α (3.105±0.278) and iNOS (4.296±0.003) increased significantly (t=6.53, P=0.003; t=42.63, P<0.001, respectively), while miR-126, IL-10 and Arg-1 expressions (0.451±0.038, 0.545±0.004 and 0.253±0.017) decreased significantly (t=7.95, P=0.001; t=7.36, P=0.002; t=11.94, P<0.001, respectively) after Pg-LPS stimulated by human-derived macrophages for 48 h. The protein expression of iNOS, TNF-α, Arg-1 and IL-10 were consistent at mRNA levels. Meanwhile, the expressions of phospho-NF-κB p65 (p-p65), phospho-extracellular signal-regulated kinase (p-ERK) and phospho-p38 MAPK (p-p38) increased significantly, while the expression of Arg-1 decreased significantly. Compared with the negative controls (scramble RNA) (TNF-α: 1.141±0.197, iNOS: 1.173±0.115, IL-10: 1.032±0.138, Arg-1: 0.933±0.044), the mRNA levels of TNF-α (0.342±0.022) and iNOS (0.588±0.085) expressions significantly decreased (t=5.35, P=0.006; t=5.05, P=0.007), while IL-10 (1.786±0.221) and Arg-1 expressions (2.152±0.229) significantly increased (t=3.71, P=0.021; t=6.21, P=0.003) after Pg-LPS stimulation with miR-126 mimic transfection. The relative protein expressions of iNOS, p-p65, p-ERK and p-p38 significantly decreased (t=13.00, P<0.001; t=6.98, P=0.002; t=10.86, P<0.001; t=8.32, P=0.001), while the protein level of Arg-1 significantly increased (t=12.08, P<0.001). Conclusions: Pg-LPS could promote M1 polarization of macrophages. miR-126 might inhibit the effect of Pg-LPS on the M1 polarization of macrophages through down-regulating NF-κB and MAPK signaling pathways.
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Humanos , Polaridad Celular , Interleucina-10/metabolismo , Lipopolisacáridos/farmacología , Activación de Macrófagos , Macrófagos/efectos de los fármacos , MicroARNs/metabolismo , FN-kappa B/metabolismo , Porphyromonas gingivalis , ARN Mensajero/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVE@#To investigate the influence of positioning accuracy of the multi-leaf collimators (MLC) on the passing rate of the plan dose verification for volumetric modulation arc therapy (VMAT) of cervical cancer using an Elekta linear accelerator.@*METHODS@#The dose distributions were measured using Sun Nuclear's Mapcheck and Arccheck semiconductors matrix before and after MLC calibration in30 cervical cancer patients undergoing VMAT. Dosimetric comparisons were performed with 2D and 3D gamma passing rates of 3%, 3 mm and 2%, and 2 mm. The 3D gamma distribution was reconstructed with respect to the patient's anatomy using 3DVH software to evaluate the possible influence of MLC positioning accuracy.@*RESULTS@#Before and after MLC calibration, the gamma passing rates of Mapcheck were (88.80±1.81)% and (99.25 ± 0.53)% under 3% and 3 mm standard, respectively, with an average increase of 10.45%. The corresponding gamma passing rates of Arccheck were (87.61±1.98)% and (98.13±0.99)%, respectively, with an average increase of 10.52%. The gamma passing rates of 3DVH were (89.87±2.28)% and (98.3±1.15)%, respectively, with an average increase of 8.43%.@*CONCLUSION@#The MLC positioning accuracy is one of the main factors influencing dosimetric accuracy of VMAT for cervical cancer. The application of Autocal software facilitates MLC calibration and improves the accuracy and safety of VMAT delivery for cervical cancer.
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Femenino , Humanos , Aceleradores de Partículas , Control de Calidad , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada/métodos , Neoplasias del Cuello Uterino/radioterapiaRESUMEN
This study aims to explore the pharmacodynamic effect of baicalin on rat brain edema induced by cerebral ischemia reperfusion injury and discuss the mechanism from the perspective of inhibiting astrocyte swelling, which is expected to serve as a refe-rence for the treatment of cerebral ischemia with Chinese medicine. To be specific, middle cerebral artery occlusion(suture method) was used to induce cerebral ischemia in rats. Rats were randomized into normal group, model group, high-dose baicalin(20 mg·kg~(-1)) group, and low-dose baicalin(10 mg·kg~(-1)) group. The neurobehavior, brain index, brain water content, and cerebral infarction area of rats were measured 6 h and 24 h after cerebral ischemia. Brain slices were stained with hematoxylin and eosin(HE) for the observation of pathological morphology of cerebral cortex after baicalin treatment. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the content of total L-glutathione(GSH) and glutamic acid(Glu) in brain tissue, Western blot to measure the content of glial fibrillary acidic protein(GFAP), aquaporin-4(AQP4), and transient receptor potential vanilloid type 4(TRPV4), and immunohistochemical staining to observe the expression of GFAP. The low-dose baicalin was used for exploring the mechanism. The experimental results showed that the neurobehavioral scores(6 h and 24 h of cerebral ischemia), brain water content, and cerebral infarction area of the model group were increased, and both high-dose and low-dose baicalin can lower the above three indexes. The content of GSH dropped but the content of Glu raised in brain tissue of rats in the model group. Low-dose baicalin can elevate the content of GSH and lower the content of Glu. According to the immunohistochemical staining result, the model group demonstrated the increase in GFAP expression, and swelling and proliferation of astrocytes, and the low-dose baicalin can significantly improve this situation. The results of Western blot showed that the expression of GFAP, TRPV4, and AQP4 in the cerebral cortex of the model group increased, and the low-dose baicalin reduce their expression. The cerebral cortex of rats in the model group was severely damaged, and the low-dose baicalin can significantly alleviate the damage. The above results indicate that baicalin can effectively relieve the brain edema caused by cerebral ischemia reperfusion injury in rats, possibly by suppressing astrocyte swelling and TRPV4 and AQP4.
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Animales , Ratas , Acuaporina 4/genética , Astrocitos , Edema Encefálico/tratamiento farmacológico , Isquemia Encefálica/metabolismo , Flavonoides , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Ratas Sprague-Dawley , Reperfusión , Canales Catiónicos TRPV/uso terapéuticoRESUMEN
Aim To develop an LC-MS/MS method for the determination of prucalopride(PCP)in human plasma.Methods Prucalopride -13CD3(dPCP)was used as the internal standard.The analytes were extracted from human plasma through liquid-liquid extraction method using ethyl acetate, followed by being dried, and then the reconstitution was injected into LC-MS/MS systems.Agilent ZORBAX SB C18(3.0×100 mm, 3.5 μm)column and isocratic elution system composing of methanol and 1 mmol·L-1 ammonium acetate(80:20, V/V)provided chromatographic separation of PCP and dPCP.AB Sciex API4000 mass spectrometer equipped with an electrospray ionization source in positive ion mode was employed for mass detection, and data acquisition was carried out in multiple reaction monitoring(MRM)mode.The mass transition ion-pair was followed as m/z 368.4/196.0 for PCP and m/z 374.4/198.0 for dPCP.Results PCP and dPCP were eluted at 3.6 min, with no interference in human blank plasma.PCP in human plasma showed good linearity over the concentration range of 0.058 96-7.547 μg·L-1 with the correlation coefficient of 0.996 3-0.999 6.The lower limit of quantitation of this method was 0.058 96 μg·L-1.The intra-batch and inter-batch accuracy ranged from 98.29% to 108.2%, with good precision(CV<5.2%).The average matrix factors of normal, haemolysed and lipaemic matrix human samples all ranged from 96.48% to 106.3% with CV less than 8.39%.The average extraction recoveries of PCP at low, medium and high concentrations were 89.88%, 95.27% and 94.52% respectively, with CV less than 7.21%.PCP was stable in human samples after 6 h at room temperature, 60 h at -20 ℃, 56 days or three freeze-thaw cycles at -80 ℃; meanwhile, the processed plasma samples remained stable after being stored for 24 hours in autosampler at 8 ℃.Furthermore, PCP in human blood samples was proved to be stable after 4 h at room temperature.Conclusions The present LC-MS/MS method for the determination of PCP in human plasma was convenient, accurate, sensitive, stable, specific and reproducible and was proved to be suitable for the clinical pharmacokinetics and bioequivalence studies of PCP preparations.
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Objective:To investigate the effect and mechanism of Yiqi Fuzheng Jiedu decoction (YQFZJDD) on autophagy and growth of A549 cells. Method:A549 cells were intervened with YQFZJDD-containing serum prepared in advance. The levels of microtubule-associated protein 1 light chain 3 (LC3), homologue of yeast autophagy-related gene 6 (Beclin1), p62, p53, adenosine 5'-monophosphate-activated protein kinase (AMPK), phosphorylated AMPK (p-AMPK), mammalian target of rapamycin (mTOR), and phosphorylated mTOR (p-mTOR) were detected by Western blot assay, and microtubule-associated protein 1A/1B light chain 3B (MAP1LC3B) by immunofluorescence (IF) assay. The proliferation, invasion, and senescence of A549 cells were separately measured by 5-ethynyl-2'-deoxyuridine (EDU) staining, Transwell assay, and <italic>β</italic>-galactosidase staining. In the presence of autophagy inhibitor 3-methyladenine (3-MA, 5 mmol·L<sup>-1</sup>), the cells were divided into the 10% fetal bovine serum (blank) group, 10% control serum (control) group, low-, medium-, and high-dose 10% YQFZJDD-containing serum groups, and high-dose 10% YQFZJDD-containing serum + 3-MA group, followed by the measurement of A549 cell proliferation, invasion, and senescence. In the adoption of p53 inhibitor Pifithrin-<italic>α</italic> (PFT-<italic>α</italic>, 10 μmol·L<sup>-1</sup>), the cells were divided into the control group, PFT-<italic>α</italic> group, high-dose YQFZJDD-containing serum group, and high-dose YQFZJDD-containing serum + PFT-<italic>α</italic> group. Then the LC3-Ⅱ and Beclin1 expression, MAP1LC3B fluorescence intensity, as well as A549 cell proliferation, invasion and senescence were determined. Result:Compared with the blank group and control group, YQFZJDD-containing serum at the medium and high doses up-regulated the protein expression levels of LC3-Ⅱ and Beclin1 in A549 cells after 48-h intervention in a dose-dependent manner (<italic>P</italic><0.01). Besides, YQFZJDD-containing serum at the low-, medium-, and high-doses down-regulated p62 and p-mTOR/mTOR expression (<italic>P</italic><0.05, <italic>P</italic><0.01), elevated p53 and p-AMPK/AMPK (<italic>P</italic><0.01), decreased the number of proliferative and invasive cells, increased the number of senescent cells (<italic>P</italic><0.01), and enhanced the IF intensity of MAP1LC3B, with the optimal effect observed in the high-dose YQFZJDD-containing serum group (<italic>P</italic><0.01). Compared with the high-dose YQFZJDD-containing serum group, the high-dose YQFZJDD-containing serum + 3-MA group and high-dose YQFZJDD-containing serum + PFT-<italic>α</italic> group exhibited significantly increased proliferative and invasive cells but decreased senescent cells (<italic>P</italic><0.05, <italic>P<</italic>0.01). Meanwhile, the IF intensity of MAP1LC3B in the high-dose YQFZJDD-containing serum + PFT-<italic>α</italic> group was weakened and the LC3-Ⅱ and Beclin1 protein expression levels declined (<italic>P</italic><0.05, <italic>P<</italic>0.01). Conclusion:YQFZJDD promotes the autophagy of A549 cells through the p53/AMPK signaling pathway to inhibit their proliferation, invasion and migration but accelerate senescence, thus playing a crucial role in inhibiting the progression of lung cancer.
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Objective:To explore the antidepressant mechanism of Yinxing Mihuan oral solution (YMO) by investigating its effect on depression model rats. Method:The depression rats were induced by isolation combined with chronic unpredictable mild stress (CUMS) and then randomly divided into model group, fluoxetine group (10 mg·kg<sup>-1</sup>) and high-dose (618 mg·kg<sup>-1</sup>) and low-dose (309 mg·kg<sup>-1</sup>) YMO groups. A blank control group was also set up and ten rats were included in each group. Modeling lasted for 21 consecutive days, and rats were administered the 8th day after stimulation at a dose of 10 mL·kg<sup>-1</sup> for 14 days, except those in the blank control and model groups which were given distilled water. Afterward, the sucrose preference test, open field test, tail suspension test were carried out. The pathological changes of hippocampus in depression rats were observed after hematoxylin-eosin (HE) staining. The content of interleukin-1<italic>β </italic>(IL-1<italic>β</italic>), interleukin-6 (IL-6) and tumor necrosis factor-<italic>α </italic>(TNF-<italic>α</italic>) in the hippocampus of rats in each group and the expression of NOD-like receptor 3 (NLRP3) and other proteins in its related activation signaling pathways were detected with multi-factor detection (Luminex) and Western blot. Result:After 14 days of continuous administration, compared with the blank control group, the model group witnessed significantly reduced sugar water consumption rate and the times of rearing and significantly prolonged cumulative time of immobility during tail suspension (<italic>P</italic><0.05, <italic>P</italic><0.01). Compared with the model group, the fluoxetine group and the high-dose YMO group saw increases in the times of rearing, times of crossing and sugar water consumption rate and a significant decrease in the cumulative time of immobility during tail suspension (<italic>P</italic><0.05, <italic>P</italic><0.01). The results of HE staining showed that the neurons in the hippocampus of rats in the high-dose YMO group were arranged in order and slightly loosened, without obvious microglia infiltration observed. The levels of IL-1<italic>β</italic>, IL-6 and TNF-<italic>α</italic> in the hippocampus of the model group increased significantly as compared with the blank control group (<italic>P</italic><0.05, <italic>P</italic><0.01), and their content in the high-dose YMO group was significantly lowered in the comparison with the model group (<italic>P</italic><0.05, <italic>P</italic><0.01). Molecular biology experiments demonstrated that compared with the results of blank group, the expression of purinergic receptor P2X7 (P2RX7), NLRP3, apoptosis-associated speck-like protein (ASC), Caspase-1 and IL-1<italic>β</italic> remarkably increased in the model group (<italic>P</italic><0.05, <italic>P</italic><0.01). Additionally, the expression of P2RX7, NLRP3, ASC, Caspase-1 and IL-1<italic>β </italic>was significantly inhibited in the fluoxetine group and the high-dose YMO group compared with the model group (<italic>P</italic><0.05, <italic>P</italic><0.01). Conclusion:YMO can improve the depression-like behaviors of rats induced by isolation combined with CUMS, and its mechanism of action is related to the regulation of the P2RX7/NLRP3 signaling pathway.
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OBJECTIVE@#Herbal medicine is an important therapeutic option for benign prostatic hyperplasia (BPH), a common disease in older men that can seriously affect their quality of life. Currently, it is crucial to develop agents with strong efficacy and few side effects. Herein we investigated the effects of the extract of Rauwolfia vomitoria, a shrub grown in West Africa, on BPH.@*METHODS@#Rats with testosterone-induced BPH were treated with R. vomitoria. Prostates were histologically analyzed by Hematoxylin and eosin staining. Proliferation index and the expression levels of androgen receptor and its associated proteins were quantified through immunohistochemistry and immunoblotting. Androgen receptor target genes were examined by quantitative real-time polymerase chain reaction. The sperm count and body weight of rats were also measured.@*RESULTS@#The oral administration of R. vomitoria extract significantly reduced the prostate weight and prostate weight index in BPH rats, supported by the decreased thickness of the prostate epithelial layer and increased lumen size. Similar effects were observed in the BPH rats treated with the reference drug, finasteride. R. vomitoria extract significantly reduced the testosterone-induced proliferation markers, including proliferating cell nuclear antigen and cyclin D1, in the prostate glands of BPH rats; it also reduced levels of androgen receptor, its associated protein steroid 5α-reductase 1 and its downstream target genes (FK506-binding protein 5 and matrix metalloproteinase 2). Notably, compared with the finasteride group, R. vomitoria extract did not significantly reduce sperm count.@*CONCLUSION@#R. vomitoria suppresses testosterone-induced BPH development. Due to its milder side effects, R. vomitoria could be a promising therapeutic agent for BPH.
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Objective:To investigate the concentration level of chloroform in the water of swimming pool in Baoan District of Shenzhen City,and determine the risk factors. Methods:During May and July,2019,a total of 110 water samples from 40 swimming pools were collected in Xin’an subdistrict of Bao’an District for the examination of chloroform routine indicators. In addition, 38 pipe water samples were collected for the examination of chloroform and free residual chlorine. Results:The concentration of chloroform in the swimming pools was determined to be (43.400±27.802) μg/L with the median of 37.343 μg/L. Chloroform was correlated positively with total bacterial count(P<0.05),turbidity, free chlorine residual, and PH value(P<0.01). Conclusion:The disinfection quality of swimming pool water in Bao’an District remains low. It is necessary to determine the risk factors associated with chloroform in the swimming pool and further reduce the concentration level of disinfection by-products.
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Objective:To translate the Anticoagulation Knowledge Tool(AKT) into Chinese,and to test its reliability and validity in patients with atrial fibrillation.Methods:After obtaining the authorization of the original author, the Brislin cross-cultural translation method was used to translate from the original, back translate and cross-cultural adaptation of AKT to form the Chinese version of AKT. The reliability and validity were tested in 147 patients with atrial fibrillation from January to June in 2020 in Ruijin Hospital, Shanghai Jiaotong University School of Medicine.Results:The Chinese version retained 20 items of the original questionnaire,with the item content validity index of 0.857-1.000 and the average scale content validity index of 0.85. The Cronbach alpha coefficient was 0.812 and test-retest coefficient was 0.781.Conclusions:The Chinese version of AKT has been proved to be valid and reliable, which can be used to assess anticoagulation knowledge of patients with atrial fibrillation.
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Objective:To establish an automatic segmentation network based on different receptive fields for gross target volume (GTV) and organs at risk in patients with nasopharyngeal carcinoma.Methods:Radiotherapy data of 100 cases of nasopharyngeal carcinoma including CT images and GTV and organs at risk delineated by the physicians were collected. Ninety plans were randomly selected as the training dataset, and the other 10 plans as the validation dataset. Firstly, the images were subject to three data augmentation methods including center cropping, vertical flipping and rotation (-30°to 30°), and then input into MA_net networks proposed in this study for training. The model performance of networks was assessed by the number of network parameters (NP), floating-point number (FPN), the running memory (RM) and Dice index (DI), and eventually compared with DeeplabV3+ , PSP_net, UNet+ + and U_Net networks.Results:When the input image was in the size of 240×240, MA_net had a NP of 23.20%, 20.10%, 25.55% and 27.11% of these 4 networks, 50.02%, 19.86%, 6.37% and 13.44% for the FPN, 40.63%, 23.60%, 11.58% and 14.99% for the RM, respectively. For the DI of GTV, MA_net was 1.16%, 2.28%, 1.27% and 3.59% higher than these 4 networks. For the average DI of GTV and OAR, MA_net was 0.16%, 1.37%, 0.30% and 0.97% higher than these 4 networks.Conclusion:Compared with those four networks, the proposed MA_net network has slightly higher Dice index with fewer parameters, lower FPN and smaller RM.
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Buyang Huanwu Decoction, a representative prescription in traditional Chinese medicine(TCM) for tonifying Qi and activating blood, has been proved to be effective in preventing and treating acute cerebral infarction(ACI). It consists of Astragali Radix, Angelicae Sinensis Radix, Paeoniae Radix Rubra, Pheretima, Chuanxiong Rhizoma, Carthami Flos, and Persicae Semen, possessing multiple active ingredients. The neurovascular unit is a functionally and structurally interdependent multicellular complex composed of neurons-glial cells-blood vessels. It plays an important role in the pathological changes of cerebral ischemia and the permeability variation of the blood-brain barrier. In recent years, Buyang Huanwu Decoction has been found to protect the integrity of neurovascular units and improve the permeability of the blood-brain barrier, thereby alleviating stroke and other diseases caused by cerebral ischemia. This paper collated and summarized the protective effects of Buyang Huanwu Decoction on neurovascular units.
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Humanos , Isquemia Encefálica/tratamiento farmacológico , Infarto Cerebral , Medicamentos Herbarios Chinos , Medicina Tradicional ChinaRESUMEN
Objective:To investigate the normal range of fetal ventricles and posterior cranial fossa development in the second and third trimesters and their variations with gestational age using quantitative MRI analysis.Methods:This retrospective study enrolled 675 pregnant women who underwent prenatal MRI examination with an average gestational week of 29.0±8.5 in the Third Affiliated Hospital of Guangzhou Medical University from January 2016 to January 2020. MRI data of all the subjects were collected and analyzed, including left lateral ventricle trigonometric width (LLVTW) and right lateral ventricle trigonometric width (RLVTW), third ventricle width (TVW), fourth ventricle width (FVW), the anterior-posterior diameter of the fourth ventricle (APDFV), cavum septum pellucidum width (CSPW), cisterna magna width (CMW), etc. Spearman, Pearson correlation analysis, and t-test were used for the statistical analysis. Results:(1) Totally 675 fetuses were recruited, including 392 female and 283 male fetuses. No statistical difference of gestational weeks at MRI was found between male and female fetuses. (2)The mean value of TVW and CMW of the female fetuses were significantly higher than those of male fetuses [(0.60±0.05) vs (0.63±0.04) cm, t=-5.059; (0.57±0.14) vs (0.67±0.15) cm, t=-7.445; both P<0.001]. Spearman correlation analysis showed that TVW and CMW were negatively correlated with fetal gender ( r=-0.179 and-0.312, both P<0.001). (3)Pearson correlation analysis showed that LLVTW, RLVTW, TVW, FVW, APDFV, CSPW, and CMW were all positively correlated with gestational weeks ( r=0.310, 0.267, 0.205, 0.801, 0.829, 0.216 and 0.284, all P<0.001). FVW and APDFV were significantly linearly correlated with gestational weeks (r=0.801 and 0.829, both P<0.001). (4) There was no significant change in LLVTW and RLVTW in the second trimester, but a slight increase was found in the third trimester. TVW showed a scattered distribution in the second and third trimesters and increased slightly with the gestational week at 26 to 27 +6 gestational weeks. FVW and APDFV increased linearly while. CSPW increased slowly with gestational weeks in the second and third trimesters. CMW increased slightly with gestational weeks in the second and third trimesters but showed little change in the third trimester. Conclusions:The development of fetal ventricles and posterior cranial fossa in the second and third trimesters show a growth trend of varying degrees with the increase of gestational weeks. TVW and CMW are significantly negatively correlated with the fetal gender.