This article explores the interaction between aspirin and safflower yellow injection from the perspective of pharmacokinetics, combined with pharmacological indicators such as anticoagulation. Quantitative HPLC analysis was performed for the detection of salicylic acid in plasma samples, and the pharmacokinetic effects of aspirin in combination with safflower yellow injection on aspirin’s hydrolyzed product salicylic acid was evaluated. Thromboxane B2 (TXB2) and 6-keto prostaglandin F1 in plasma were determined using enzyme-linked immunosorbent assay and fully automated biochemical analyzer α (6-keto-PGF1) α）, and the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and serum creatinine (Scr) were tested to evaluate the anticoagulant effect and safety indicators after long-term combined use of the two drugs, including liver and kidney function and cardiac pathological examination. The results showed that, compared with the aspirin group, there was no significant difference (P>0.05) in the plasma pharmacokinetic parameters of rats with combined use of safflower yellow injection. In addition, the plasma TXB2 in the combination group was significantly reduced compared to the aspirin group (P<0.01), yet with no significant difference for 6-keto-PGF1 α (P>0.05). There was no statistically significant difference in the levels of serum BUN, Scr, AST, and ALT between the two groups before and after treatment (P>0.05). These results suggest that the combination of aspirin and safflower yellow injection does not cause significant change in the blood concentration of salicylic acid. It does not affect the antiplatelet effect of aspirin.

Objective To study the influence of ANGPTL8 in lipopolysaccharide(LPS)-induced hepatic lipid deposition.Methods Male wild-type(WT)and ANGPTL8 knockout mice at 6-8 weeks were used to induce sepsis models by intrabitoneal injection of LPS(10 mg/kg).qPCR and immunofluorescence were used to detected the mRNA and protein expression of ANGPTL8 in liver tissue and HepG2 cells respectively;The contents of alanine aminotransferase(ALT),aspartate aminotransferase(AST)in serum and the triglyceride(TG)and malondialdehyde(MDA)in liver homogenate were detected by kits;the histopathological changes of liver tissue were analyzed through HE staining.Lipids accumulation in liver were detected by oil red O staining.The apoptosis of liver was determinated by TUNEL staining.RNA-seq was used to analyzing the differentially expressed genes in the liver tissue of WT and ANGPTL8 KO mice,and the qPCR and Western Blot were used to verify the differential expressed genes.Results The expression of ANGPTL8 in the liver was significantly upregulated at 48 hours after LPS stimulation.Compared with WT mice,the hepatic lipid deposition,steatosis,and apoptosis were significantly alleviated in liver of ANGPTL8 KO mice,the ALT and AST levels in serum and the TG and MDA content in liver homogenate of ANGPTL8 KO mice were also reduced significantly.The expression of caveolin-1(CAV1)in liver of ANGPTL8 KO mice was significantly higher than that of WT mice.Conclusions LPS promoted the expression and secretion of ANGPTL8 in liver tissue,and ANGPTL8 increased hepatic lipid deposition and peroxidation by inhibiting the expression of CAV1.

Objective:To investigate the effect of Qideng Mingmu capsule on the formation and remodeling of retinal neovascularization in mice with oxygen-induced retinopathy (OIR).Methods:Thirty-six postnatal day 7 (P7)SPF grade C57BL/6J pups were divided into normal group, OIR group, Qideng Mingmu capsule group and apatinib group by random number table method, with 9 mice in each group.The mice in the normal group were raised in normal environment.The mice in the other three groups were fed in hyperoxic environment of (75±2)% oxygen concentration for 5 days from P7 to P12 and then were fed in normal environment for 5 days from P12 to P17 to establish the OIR model.From P12, mice in Qideng Mingmu capsule group and apatinib group were given intragastric administration of Qideng Mingmu capsule (900 mg/kg) and vascular endothelial growth factor receptor 2 inhibitor apatinib (70 mg/kg) respectively, once a day for 5 consecutive days.On P17, paraffin sections of mouse eyeballs were made and stained with hematoxylin-eosin to count the number of vascular endothelial cells that broke through the internal limiting membrane.The retinal slices were prepared and stained with FITC-dextran to quantify the retinal non-perfusion area, neovascularization density and total vascular density.The distribution and fluorescence intensity of retinal vascular endothelial cell marker CD31 and pericyte marker α-smooth muscle actin (α-SMA) were observed by double immunofluorescence staining.Immunohistochemical staining was used to detect the expression and distribution of retinal hypoxia inducible factor-1α (HIF-1α) and vascular endothelial cadherin (VE-cadherin).The use and care of animals were in accordance with the Regulations on the Management of Laboratory Animals issued by the Ministry of Science and Technology.This study was approved by the Animal Ethics Committee of Chengdu University of Traditional Chinese Medicine (No.2019-30).Results:The number of vascular endothelial cells breaking through the internal limiting membrane in normal group, OIR group, Qideng Mingmu capsule group and apatinib group were (2.83±4.40), (37.33±5.43), (23.83±6.79) and (14.00±9.34), respectively, with a statistically significant overall difference ( F=28.313, P<0.001).There were more vascular endothelial cells breaking through internal limiting membrane in OIR group than in normal group, Qideng Mingmu capsule group and apatinib group, showing statistically significant differences (all at P<0.05).In the observation of mouse retinal slices, there were large non-perfusion areas, neovascularization buds and disordered distribution of blood vessels in OIR group.The distribution of blood vessels was more uniform and the areas of non-perfusion and neovascularization were smaller in Qideng Mingmu capsule group and apatinib group than in OIR group.The relative area of central retinal non-perfusion area and neovascularization density were significantly lower in normal group, Qideng Mingmu capsule group and apatinib group than in OIR group (all at P<0.05).The immunofluorescence intensity of CD31 and the absorbance value of HIF-1α were significantly lower, and the immunofluorescence intensity of α-SMA and the absorbance value of VE-cadherin were significantly higher in normal group, Qideng Mingmu capsule group and apatinib group than in OIR group (all at P<0.05). Conclusions:Qideng Mingmu capsule can inhibit retinal neovascularization formation, increase vascular pericyte coverage, relieve retinal hypoxia and increase vascular integrity in OIR mice.It can protect the retinal vessels of OIR mice.

Purpose: This study examined the diagnostic value of high-frequency ultrasound (HFUS) features in differentiating between benign and malignant skin lesions. Methods: A total of 1,392 patients with 1,422 skin lesions who underwent HFUS examinations were included in an initial dataset (cohort 1) to identify features indicative of malignancy. Qualitative clinical and HFUS characteristics were recorded for all lesions. To determine which HFUS and clinical features were suggestive of malignancy, univariable and multivariable logistic regression analyses were employed. The diagnostic performance of HFUS features combined with clinical information was evaluated. This assessment was validated using internal data (cohort 2) and multicenter external data (cohort 3). Results: Features significantly associated with malignancy included age above 60 years; lesion location in the head, face, and neck or genital regions; changes in macroscopic appearance; crawling or irregular growth pattern; convex or irregular base; punctate hyperechogenicity; blood flow signals; and feeding arteries. The area under the receiver operating characteristic curve, sensitivity, and specificity of HFUS features combined with clinical information were 0.946, 92.5%, and 86.9% in cohort 1; 0.870, 93.1%, and 80.8% in cohort 2 (610 lesions); and 0.864, 86.2%, and 86.6% in cohort 3 (170 lesions), respectively. However, HFUS is not suitable for evaluating lesions less than 0.1 mm in thickness or lesions exhibiting surface hyperkeratosis. Conclusion In a clinical setting, the integration of HFUS with clinical information exhibited good diagnostic performance in differentiating malignant and benign skin lesions. However, its utility was limited in evaluating extremely thin lesions and those exhibiting hyperkeratosis.

Purpose: This study examined the diagnostic value of high-frequency ultrasound (HFUS) features in differentiating between benign and malignant skin lesions. Methods: A total of 1,392 patients with 1,422 skin lesions who underwent HFUS examinations were included in an initial dataset (cohort 1) to identify features indicative of malignancy. Qualitative clinical and HFUS characteristics were recorded for all lesions. To determine which HFUS and clinical features were suggestive of malignancy, univariable and multivariable logistic regression analyses were employed. The diagnostic performance of HFUS features combined with clinical information was evaluated. This assessment was validated using internal data (cohort 2) and multicenter external data (cohort 3). Results: Features significantly associated with malignancy included age above 60 years; lesion location in the head, face, and neck or genital regions; changes in macroscopic appearance; crawling or irregular growth pattern; convex or irregular base; punctate hyperechogenicity; blood flow signals; and feeding arteries. The area under the receiver operating characteristic curve, sensitivity, and specificity of HFUS features combined with clinical information were 0.946, 92.5%, and 86.9% in cohort 1; 0.870, 93.1%, and 80.8% in cohort 2 (610 lesions); and 0.864, 86.2%, and 86.6% in cohort 3 (170 lesions), respectively. However, HFUS is not suitable for evaluating lesions less than 0.1 mm in thickness or lesions exhibiting surface hyperkeratosis. Conclusion In a clinical setting, the integration of HFUS with clinical information exhibited good diagnostic performance in differentiating malignant and benign skin lesions. However, its utility was limited in evaluating extremely thin lesions and those exhibiting hyperkeratosis.

Purpose: This study examined the diagnostic value of high-frequency ultrasound (HFUS) features in differentiating between benign and malignant skin lesions. Methods: A total of 1,392 patients with 1,422 skin lesions who underwent HFUS examinations were included in an initial dataset (cohort 1) to identify features indicative of malignancy. Qualitative clinical and HFUS characteristics were recorded for all lesions. To determine which HFUS and clinical features were suggestive of malignancy, univariable and multivariable logistic regression analyses were employed. The diagnostic performance of HFUS features combined with clinical information was evaluated. This assessment was validated using internal data (cohort 2) and multicenter external data (cohort 3). Results: Features significantly associated with malignancy included age above 60 years; lesion location in the head, face, and neck or genital regions; changes in macroscopic appearance; crawling or irregular growth pattern; convex or irregular base; punctate hyperechogenicity; blood flow signals; and feeding arteries. The area under the receiver operating characteristic curve, sensitivity, and specificity of HFUS features combined with clinical information were 0.946, 92.5%, and 86.9% in cohort 1; 0.870, 93.1%, and 80.8% in cohort 2 (610 lesions); and 0.864, 86.2%, and 86.6% in cohort 3 (170 lesions), respectively. However, HFUS is not suitable for evaluating lesions less than 0.1 mm in thickness or lesions exhibiting surface hyperkeratosis. Conclusion In a clinical setting, the integration of HFUS with clinical information exhibited good diagnostic performance in differentiating malignant and benign skin lesions. However, its utility was limited in evaluating extremely thin lesions and those exhibiting hyperkeratosis.

Purpose: This study examined the diagnostic value of high-frequency ultrasound (HFUS) features in differentiating between benign and malignant skin lesions. Methods: A total of 1,392 patients with 1,422 skin lesions who underwent HFUS examinations were included in an initial dataset (cohort 1) to identify features indicative of malignancy. Qualitative clinical and HFUS characteristics were recorded for all lesions. To determine which HFUS and clinical features were suggestive of malignancy, univariable and multivariable logistic regression analyses were employed. The diagnostic performance of HFUS features combined with clinical information was evaluated. This assessment was validated using internal data (cohort 2) and multicenter external data (cohort 3). Results: Features significantly associated with malignancy included age above 60 years; lesion location in the head, face, and neck or genital regions; changes in macroscopic appearance; crawling or irregular growth pattern; convex or irregular base; punctate hyperechogenicity; blood flow signals; and feeding arteries. The area under the receiver operating characteristic curve, sensitivity, and specificity of HFUS features combined with clinical information were 0.946, 92.5%, and 86.9% in cohort 1; 0.870, 93.1%, and 80.8% in cohort 2 (610 lesions); and 0.864, 86.2%, and 86.6% in cohort 3 (170 lesions), respectively. However, HFUS is not suitable for evaluating lesions less than 0.1 mm in thickness or lesions exhibiting surface hyperkeratosis. Conclusion In a clinical setting, the integration of HFUS with clinical information exhibited good diagnostic performance in differentiating malignant and benign skin lesions. However, its utility was limited in evaluating extremely thin lesions and those exhibiting hyperkeratosis.

Purpose: This study examined the diagnostic value of high-frequency ultrasound (HFUS) features in differentiating between benign and malignant skin lesions. Methods: A total of 1,392 patients with 1,422 skin lesions who underwent HFUS examinations were included in an initial dataset (cohort 1) to identify features indicative of malignancy. Qualitative clinical and HFUS characteristics were recorded for all lesions. To determine which HFUS and clinical features were suggestive of malignancy, univariable and multivariable logistic regression analyses were employed. The diagnostic performance of HFUS features combined with clinical information was evaluated. This assessment was validated using internal data (cohort 2) and multicenter external data (cohort 3). Results: Features significantly associated with malignancy included age above 60 years; lesion location in the head, face, and neck or genital regions; changes in macroscopic appearance; crawling or irregular growth pattern; convex or irregular base; punctate hyperechogenicity; blood flow signals; and feeding arteries. The area under the receiver operating characteristic curve, sensitivity, and specificity of HFUS features combined with clinical information were 0.946, 92.5%, and 86.9% in cohort 1; 0.870, 93.1%, and 80.8% in cohort 2 (610 lesions); and 0.864, 86.2%, and 86.6% in cohort 3 (170 lesions), respectively. However, HFUS is not suitable for evaluating lesions less than 0.1 mm in thickness or lesions exhibiting surface hyperkeratosis. Conclusion In a clinical setting, the integration of HFUS with clinical information exhibited good diagnostic performance in differentiating malignant and benign skin lesions. However, its utility was limited in evaluating extremely thin lesions and those exhibiting hyperkeratosis.

ObjectiveTo evaluate the effect of Astragali Radix （AR）-Angelicae Sinensis Radix （ASR） drug pair on supplementing Qi and activating blood circulation in rats with Qi deficiency and blood stasis and provide a theoretical basis for clinical rational medication and identification and quality control of compound pharmacodynamic substances from the three aspects of characteristic map， identification of pharmacodynamic substances， and comparison of blood components. MethodHigh-performance liquid chromatography （HPLC） was employed to establish the fingerprint of AR∶ASR （3∶1）， and ultra-high performance liquid chromatography-Q-Exactive Orbitrap-mass spectrometry （UPLC-Q-Exactive Orbitrap-MS） was employed to analyze the ingredients of the decoction. Adult male Wistar rats with SPF grades were selected and randomly divided into a blank group， a model group， a 3∶1 group， and a 5∶1 group. The rat model of Qi deficiency and blood stasis syndrome was prepared by controlling food intake and swimming in cold water every day. In parallel， each group was given medicine （or water） once a day. The dose of drug groups was 10.2 g∙kg^-1， and the model group and blank group were given the same amount of distilled water for 15 d. Animal behavior， body weight， whole blood and plasma viscosity， thymus index， spleen index， the levels of adenosine triphosphate （ATP）， adenosine diphosphate（ADP）， von willebrand factor （vWF）， and ATP/ADP value in serum of rats were recorded. The morphology of vascular endothelium was observed by hematoxylin-eosin （HE） staining and scanning electron microscopy. UPLC-Q-Exactive Orbitrap-MS was used to analyze prototype and metabolic components in serum. ResultThe fingerprint of AR-ASR drug pair （AR-ASR 3∶1） was established. UPLC-Q-Exactive Orbitrap MS identified 49 chemical components in vitro and preliminarily identified 11 prototype components absorbed into blood in vivo. As compared with the blank group， the body mass decreased significantly （P<0.01）， the whole blood （high shear， middle shear， and low shear） viscosity and plasma viscosity were significantly increased （P<0.05， P<0.01）， the thymus index and spleen index decreased significantly （P<0.05， P<0.01）， serum ATP content decreased significantly （P<0.01）， ADP content increased significantly （P<0.01）， ATP/ADP value decreased significantly （P<0.01）， and vWF content increased significantly （P<0.01）. The results of HE staining and scanning electron microscopy showed that the vessels were partially damaged， showing the structural disorder of the intima， the bulge， defect， and roughness of the endothelium， and the obvious cell adhesion and migration in the model group. As compared with the model group， the body mass also increased significantly （P<0.01）. The results of whole blood and plasma viscosity showed that the whole blood low shear viscosity was significantly decreased in the 3∶1 group （P<0.05）. The results of thymus index and spleen index showed that 5∶1 group significantly increased the thymus index of rats （P<0.05）. The results of serum ATP and ADP levels showed that the 5∶1 group had more significant effects on ATP and ADP levels （P<0.05）， and both groups significantly reduced ATP/ADP values （P<0.01）. The results of serum vWF level showed that the vWF content in the 3∶1 group decreased significantly （P<0.05）. The results of HE staining and scanning electronic microscopy showed that the damage of vascular endothelium was improved in the treatment group and the structure of intima was neat. ConclusionAR-ASR drug pair can improve the macro and micro indexes of rats with qi deficiency and blood stasis in the 3∶1 and 5∶1 groups. Overall， the 5∶1 ratio has a better effect on supplementing Qi but 3∶1 ratio has a better effect on promoting blood circulation.

Objective:To analyze the changes in plasma endothelin-1 (ET-1) concentrations in the patients with acute respiratory distress syndrome (ARDS).Methods:Fourteen patients with ARDS induced by trauma, 8 males and 6 females, aged 19-80 yr, were studied. The severity of ARDS was graded according to the Berlin definition of ARDS after admission to intensive care unit (ICU). Venous blood samples were obtained on 1st, 3rd and 5th days after admission to ICU, the plasma ET-1 concentrations were measured by radioimmunoassay, the pulmonary vascular permeability index (PVPI) was determined by PiCCO technique, and multiple organ dysfunction (MOD) score and lung injury score (LIS) were assessed. Spearman correlation of plasma ET-1 concentrations with MOD score, LIS and PVPI was analyzed.Results:MOD score, LIS, PVPI and plasma ET-1 concentrations were significantly decreased in mild ARDS patients ( n=5) as compared with moderate ARDS patients ( n=9, P<0.05). The plasma ET-1 concentration was positively correlated with MOD score, LIS and PVPI ( r=0.69, 0.76, 0.62, P<0.001). Conclusions:Plasma ET-1 concentrations can reflect the pulmonary vascular permeability and even the severity of the disease in the early stage of ARDS, so it is necessary to carry out dynamic monitoring in the patients.