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As a commonly used traditional Chinese medicine in clinical practice, Tripterygium wilfordii has the functions of dispelling wind and removing dampness, detoxicating and destroying parasites, detumescence, pain relief, promoting blood circulation, and dredging collateral. Modern pharmacological studies show that it also has other functions such as anticancer, anti-inflammation, and immunosuppression. It has been widely used to treat autoimmune diseases, renal diseases, and tumors. T. wilfordii contains a variety of chemical components, among which triptolide (TP) can cause varying degrees of damage to human digestive, circulatory, reproductive, and other systems, with liver injury being the most common one, which greatly limits the development of TP in new drug research and industrial application. Therefore, the authors focused on the research hotspot of TP-induced liver injury and summarized relevant Chinese and international literature regarding the clinical manifestations, injury mechanisms, and detoxification strategies of TP-induced liver injury. This helps to provide a scientific basis for the clinical drug safety and scientific drug supervision of TP. The clinical manifestations of TP-induced liver injury are mostly abnormal transaminases, loss of appetite, nausea and vomiting, anorexia, yellow staining of skin and sclera, and yellow urine. The mechanisms of the above clinical manifestations involve apoptosis, oxidative stress, influence on cytochrome P450 superfamily, macrophage polarization, regulation of biological clock gene Clock, etc. Among them, cell apoptosis is related to neurogenic locus notch homolog protein 1 (Notch1), dynamin-related protein 1 (Drp1)-cytochrome C (Cyt C), phosphatidylinositide 3-kinases (PI3K)/protein kinase B (Akt), mitogen-activated protein kinase (MAPK), tumor suppressor protein 53 (p53), Fas cell surface death receptor (Fas)/Caspase-8, and other signaling pathways. Oxidative stress is related to inhibition of nuclear factor-erythroid 2-related factor 2 (NRF2) signaling pathway, promotion of cytochrome P450 2E1 (CYP2E1) expression, and excessive accumulation of reactive oxygen (ROS). The influence of the cytochrome P450 superfamily is manifested as reducing the substrate affinity, activity, and expression of cytochrome P450 3A (CYP3A), cytochrome P450 2C9 (CYP2C9), cytochrome P450 2C19 (CYP2C19), and cytochrome P450 1A2 (CYP1A2). Promoting the transformation of macrophages into the M1 type is related to the secretion of inflammatory factors and the accumulation of endotoxin, and the internal rhythmic regulation of the biological clock gene Clock, is related to the expression of cytochrome P450 3A11 (CYP3A11) metabolic enzyme. The detoxification strategies in the clinical application include herbs-processing detoxification strategy and drug-pairing detoxification. The traditional Chinese medicines and monomers that are helpful for detoxification include Glycyrrhiza uralensis, Paeonia lactiflora, Lysimachia christinae, Rehmannia glutinosa, saffron, and paeoniflorin. The reviews and discussion about these topics can help to provide more references for related research and clinical application of TP.
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Objective To establish an HPLC-based method for the determination of α-obscurine,ferulic acid,hydroxysafflower yellow A,benzoylneaconitine,benzoylaconitine,periplosin,4-methoxysalicylsalicylate,kaempferol and oleanolic acid simultaneously in Shujin Tongluo Black Plaster.Methods HPLC method was used to determine the 9 components in Shujin Tongluo Black Plaster simultaneously.The 70%methanol extracts were analyzed using Waters SunFire C18 chromatography column(4.6 mm×250 mm,5 μm),in mobile phase containing acetonitrile-0.2%phosphoric acid solution for gradient elution with volume flow rate of 1.0 mL/min;column temperature was set at 25℃;detection wavelength was set at 230 nm.Results The 9 components had good linear relationship in their respective ranges(r≥0.999 7).The average recoveries were between 98.06%-100.56%and RSD was between 0.48%-2.56%,respectively.Conclusion The method has the advantage of repeatability,simple and fast,and can be used as the quality control of Shujin Tongluo Black Plaster.
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Objective:To investigate the effect and mechanism of ionizing radiation on ferroptosis in mouse hepatocytes.Methods:Twenty-four C57BL/6J mice were divided into two groups by random number table method: healthy control group (control group, n=6) and irradiation group (whole liver was irradiated with a single dose of 30 Gy X-ray, n=18). Mice were sacrificed at 6, 24 and 72 h (6 mice per time point) after irradiation to obtain liver tissue and plasma samples. The contents of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in plasma were measured by automatic biochemical analyzer. The prothrombin time (PT) and activated partial thromboplastin time (APTT) were measured by automatic biochemical analyzer. Pathological changes of liver tissues were observed by hematoxylin-eosin (HE) staining. The iron deposition in liver tissues was detected by Prussian blue staining. The expression levels of 4-Hydroxynonenal (4HNE) and hepcidin in the liver were determined by immunohistochemical staining, and quantitative analysis was performed. Plasma malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, total antioxidant capacity (T-AOC) and glutathione (GSH) content were determined by microplate reader analysis according to the kit instructions. The expression levels of transferrin receptor 1 (TfR1), p53, solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in the liver were measured by Western blot. Results:Compared with the control group, the plasma contents of ALT ( t=5.15, 5.47, both P<0.001) , AST at 6 and 24 h after irradiation were increased ( t=8.42, 2.50, both P<0.001), the plasma PT was prolonged ( t=3.12, P=0.011) and the APTT was shortened ( t=3.26, P=0.009) at 72 h after radiation in the irradiation group. Histopathological results showed that evident liver edema was observed at 6, 24 and 72 h after irradiation ( t=9.58, 10.09, 18.70, all P<0.001). Different degrees of iron deposition were observed ( t=8.57, 15.31, 32.11, all P<0.001). The infiltration of hepcidin positive cells was significantly increased after irradiation ( t=5.36, 13.17, 17.11, all P<0.001). The number of 4HNE positive cells was significantly increased ( t=18.86, 22.67, 9.12, all P<0.001). At the same time, ionizing radiation induced a significant increase in plasma MDA content ( t=4.36, 7.47, 8.22, all P<0.001), and a decrease in SOD ( t=4.52, 5.80, 7.60, all P<0.001), T-AOC ( t=13.24, 20.49, 24.96, all P<0.001) and GSH ( t=2.78, 6.07, 11.25, P=0.020, <0.001, <0.001), respectively. The expression level of TfR1 protein was significantly up-regulated ( t=3.46, 5.40, P=0.026, 0.006), whereas that of GPX4 protein was significantly down-regulated ( t=11.88, 30.63, both P<0.001) at 24 and 72 h after irradiation. At 6, 24 and 72 h after irradiation, the expression level of p53 protein was significantly up-regulated and maintained at a high level ( t=7.84, 4.25, 8.22, P=0.001, 0.013, 0.001), while that of SLC7A11 protein was significantly down-regulated ( t=9.29, 19.96, 9.09, all P<0.001). Conclusion:Ionizing radiation induces the ferroptosis in hepatocytes, and its mechanism may be related to the activation of p53-SLC7A11-GPX4 pathway.
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ObjectiveTo explore the mechanism of Shaoyaotang (SYT) in the treatment of ulcerative colitis (UC) based on network pharmacology and experimental verification. MethodThe core components, target genes, and main pathways of SYT were predicted based on network pharmacology, and UC-related components, target genes, and pathways were screened. Dextran sodium sulfate (DSS) was used to induce the UC model in mice, and the effect of SYT on UC mice was observed, followed by mechanism verification. ResultNetwork pharmacology indicated that 174 active components and corresponding 159 target genes of SYT were screened, and the related pathways were those mediated by 5-hydroxytryptamine (5-HT) degredation and 5-HT receptor 3. The results of animal experiments showed that compared with the model group, the SYT group showed increased body weight and colon length(P<0.01), reduced disease activity index (DAI) score (P<0.01), improved histopathological manifestations, reduced concentrations of 5-HT in the colonic tissues and serum (P<0.05, P<0.01), and increased mRNA expression of monoamine oxidase A (MAOA), monoamine oxidase B (MAOB), sodium-dependent serotonin transporter (SLC6A4), and 5-HT receptor 3A (5-HTR3A) related to 5-HT metabolism in the colon (P<0.01). ConclusionSYT can alleviate the local inflammatory response of the intestinal tract in UC by regulating 5-HT degredation pathways.
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Objective:To study the protective effect of recombinant human ADAMTS13 (rhADAMTS13) on radiation-induced intestinal injury.Methods:Thirty C57BL/6 J mice were randomly divided into healthy control group, 12 Gy abdominal irradiation group (simple irradiation group) and rhADAMTS13 combined with 12 Gy irradiation group (combined group) with 6, 12 and 12 mice per group. The combined group was given 2.5 μg/kg rhADAMTS13 via tail vein injection 3 d before irradiation. 12 Gy X-ray abdominal irradiation was given to the simple irradiation group.The mice were executed at 1 and 3 d after irradiation, and plasma vWF, ADAMTS13 and CRP concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Intestinal histopathological changes were observed by hematoxylin-eosin (HE) staining.Intestinal Ki67, TNF- α and MPO expression levels were detected by immunohistochemical staining.Plasma malondialdehyde (MDA), superoxide dismutase (SOD) activity and total antioxidant capacity (T-AOC) were measured by biochemical kits.Results:Compared with the healthy control group, the plasma vWF level was increased( t=6.20、12.29, P<0.05) and ADAMTS13 level was decreased( t=9.82、22.83, P<0.05)in mice at 1(1.38±0.11)and 3 (1.70±0.10)after irradiation.Compared with the simple irradiation group, the plasma vWF level was reduced ( t=2.93, 3.96, P<0.05) and ADAMTS13 level was increased ( t=5.09, 9.82, P<0.05) in mice at 1 (1.23±0.12) and 3 d (1.48±0.09) after irradiation in the combined group. Immunohistochemical staining showed that the number of Ki67 + cells in the crypt of the combined group increased significantly ( t=9.82, P<0.05) and the degree of TNF-α and MPO infiltration decreased significantly ( t=15.44, 14.33, P<0.05) compared with the simple irradiation group.In addition, rhADAMTS13 intervention significantly reduced plasma CRP ( t=5.02, 2.96, P<0.05) and MDA ( t=2.47, 2.55, P<0.05), but increased SOD activity ( t=2.64, 5.64, P<0.05) and T-AOC ( t=3.05, 5.07, P<0.05). Conclusions:rhADAMTS13 attenuates radiation-induced intestinal injury in mice by reducing the levels of inflammation and oxidative stress, providing a new strategy for the protection of radiation-induced intestinal injury.
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OBJECTIVES@#Fluorouracil chemotherapeutic drugs are the classic treatment drugs of gastric cancer. But the problem of drug resistance severely limits their clinical application. This study aims to investigate whether hypoxia microenvironment affects gastric cancer resistance to 5-fluorouracil (5-FU) and discuss the changes of gene and proteins directly related to drug resistance under hypoxia condition.@*METHODS@#Gastric cancer cells were treated with 5-FU in hypoxia/normoxic environment, and were divided into a Normoxic+5-FU group and a Hypoxia+5-FU group. The apoptosis assay was conducted by flow cytometry Annexin V/PI double staining. The real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were used to detect the expression level of hypoxia inducible factor-1α (HIF-1α), multidrug resistance (MDR1) gene, P-glycoprotein (P-gp), and vascular endothelial growth factor (VEGF) which were related to 5-FU drug-resistance. We analyzed the effect of hypoxia on the treatment of gastric cancer with 5-FU.@*RESULTS@#Compared with the Normoxic+5-FU group, the apoptosis of gastric cancer cells treated with 5-FU in the Hypoxia+5-FU group was significantly reduced (P<0.05), and the expression of apoptosis promoter protein caspase 8 was also decreased. Compared with the the Normoxic+5-FU group, HIF-1α mRNA expression in the Hypoxia+5-FU group was significantly increased (P<0.05), and the mRNA and protein expression levels of MDR1, P-gp and VEGF were also significantly increased (all P<0.05). The increased expression of MDR1, P-gp and VEGF had the same trend with the expression of HIF-1α.@*CONCLUSIONS@#Hypoxia is a direct influencing factor in gastric cancer resistance to 5-FU chemotherapy. Improvement of the local hypoxia microenvironment of gastric cancer may be a new idea for overcoming the resistance to 5-FU in gastric cancer.
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Humanos , Fluoruracila/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Resistência a Múltiplos Medicamentos , Fatores de Crescimento do Endotélio Vascular/metabolismo , Hipóxia , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Linhagem Celular Tumoral , Hipóxia Celular , RNA Mensageiro/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Microambiente TumoralRESUMO
Objective:To explore high-frequency color Doppler ultrasound characteristics of extramammary Paget′s disease (EMPD) .Methods:From January 2015 to October 2019, 32 patients with pathologically confirmed EMPD were collected from the Affiliated Hospital of Jining Medical University, and characteristics of their high-frequency color Doppler ultrasound images were retrospectively analyzed.Results:Of the 32 lesions, 25 were located on the external genitalia (21 on the scrotum, 4 on the perineum) , 4 on the medial thigh, 1 on the lower abdominal wall, 1 in the perianal region, and 1 on the neck. Ipsilateral inguinal lymph node metastasis occurred in 3 patients, and bilateral inguinal lymph node metastasis in 1 patient. High-frequency ultrasonography showed no obvious abnormal ultrasound manifestations in 6 cases, and thickened skin lesions in 26 cases. According to the morphological and high-frequency ultrasound manifestations, 26 skin lesions were classified into 2 types: 21 diffuse-type lesions with unclear borders and irregular shapes, and 5 mass-type lesions with clear borders and irregular shapes. Solid and homogeneously hypoechoic areas were observed in 18 cases, and solid and heterogeneously hypoechoic areas in 8. According to the Adler blood flow classification, the 26 lesions were classified into 4 grades: 2 of grade 0, 5 of grade 1, 8 of grade 2, and 11 of grade 3.Conclusion:EMPD shows characteristic high-frequency color Doppler ultrasound manifestations, which can facilitate its clinical diagnosis.
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Objective:To analyze the epidemiological features of geriatric humeral surgical neck fractures from 2010 through 2019 in The Third Hospital of Hebei Medical University.Methods:A retrospective study was conducted of the data of the inpatients aged ≥60 years who had been treated for humeral surgical neck fractures in The Third Hospital of Hebei Medical University from 2010 through 2019. The patients were divided into 2 groups by the year of admission: the former five-year group (group A from January 1, 2010 to December 31, 2014) and latter five-year group (group B from January 1, 2015 to December 31, 2019). The data of the patients were compared between the 2 groups to find the epidemiological characteristics and trends of the humeral surgical neck fractures in the 10-year period.Results:A total of 312 geriatric humeral surgical neck fractures were included, accounting for 1.2%(312/25, 764) of the upper limb fractures and 0.4% (312/88, 886) of all the fractures in the same period. There were 64 males and 248 females, giving a male/female ratio of 0.26∶1. Their ages ranged from 60 to 93 years. The peak age of the fractures was from 60 to 69 years for both males and females. Falls and indoor activity injuries accounted for the largest proportion (71.2%, 222/312). The common fracture types were 11-A2 and 11-A3. The proportion of overweight and obese patients by the body mass index (BMI) was the largest (58.7%, 183/312). There were no statistically significant differences between groups A and B in male/female ratio (0.37:1 versus 0.22:1) or in proportion of peak age patients [42.7% (38/89) versus 55.2% (123/223)] ( P>0.05). There were statistically significant differences between the 2 groups in injury causes, fracture types and BMI distribution ( P<0.05). Conclusions:The geriatric humeral surgical neck fractures accounted for 1.2% of the upper limb fractures and 0.4% of all the fractures in the same period. There were more female patients than male ones. Falls and indoor activity injuries were the most common causes. The proportions of complex fractures and overweight and obese patients increased.
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Objective:To analyze the epidemiological characteristics of all the patients with intertrochanteric fracture admitted to the Third Hospital of Heibei Medical University in the past 10 years.Methods:Data of patients with intertrochanteric fracture admitted to our hospital from January 1, 2010 to December 31, 2019 were retrospectively analyzed. According to the year of admission, all the patients were divided into two groups: the first five years (group A) and the last five years (group B). Gender, age, injury cause, Evans classification, complicated diseases, length of hospital stay and whether surgical treatment or not were compared.Results:A total of 6,125 patients with intertrochanteric fracture were included in the study, including 2,664 males and 3,461 females with a male to female ratio of 0.77∶1. The peak age was 70-79 for males and 80-89 for females. There were 2,314 cases in group A (male to female ratio was 0.91∶1) and 3,811 cases in group B (0.70∶1), showing significant differences between the 2 groups in the male to female ratio ( χ2=25.265, P< 0.05). The peak age ranged from 70 to 80 years (31.9%,739/2,314) in group A and from 80 to 90 years (34.5%, 1,313/3,811) in group B. There were significant differences between the 2 groups in the sex ratios of age groups from 70 to 79 years ( χ2=0.024, P< 0.05). In all the 6,152 patients with a definite injury cause, the fall and indoor activity accounted for the highest proportion (83.9%, 5,140/6,125), and the proportion of group A was 75.4% (1,745/2,314) while the proportion of group B was 89.1%(3,395/3,811) showing a significant differences between the 2 groups in injury cause ( χ2=14.363, P< 0.05). Based on X-ray films or computer tomography (CT) of 3,560 patients, the Evans type II and III were the most common types. Type II accounted for the highest proportion in group A (38.1%, 239/628) while type III did in group B (39.5%, 1,159/2,932) . There were significant differences between the 2 groups in the proportion of Evans classification ( χ2=183.569, P< 0.05). Of all the 6,125 fracture cases, 4,846 fracture patients (79.1%) were complicated with medical diseases. There was a statistically significant difference between the 2 group of the patients who were complicated with medical diseases ( χ2=8.916, P< 0.05). A total of 5,148 patients were treated by operation and 1,925 patients were in group A while the other 3,259 cases were in group B. In group A, the median hospitalization was 14 days and the quartile interval was 8 days. In group B, the median hospitalization and the quartile interval was 12 days and 8 days respectively. There were significant differences between the 2 groups in length of hospital stay for patients treated by surgery ( Z=-9.909, P<0.001). Conclusion:The intertrochanteric fractures admitted to the Third Hospital of Heibei Medical University in the past 10 years were more common in females than in males. Fall and indoor activity was the most common injury cause. Evans types II and III prevailed. The fractures showed an aging trend by comparing the former 5 years and latter 5 years. The number of intertrochanteric fracture patients complicated with medical diseases increased significantly, but the total days of hospitalization was on the decline.
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Objective To study the role of alternative complement pathway overactivation in malignant nephrosclerosis.Methods (1) Fifty patients with confirmed malignant nephrosclerosis by renal needle biopsy were enrolled.Meanwhile,twenty-five cases of time-zero renal needle biopsy were enrolled as control subjects.Enzyme linked immunosorbent assay (ELISA) was used to detect alternative complement pathway of the complement initiation factor B,positive regulation factor P,negative regulation factor H,and the complement end products C3a and C5a in the plasma and urine.(2) Immunohistochemistry was used to detect the deposition of the complement end product C5b-9,C4d and mannan binding lectin (MBL) of lectin pathway in the renal biopsies.Double immunofluorescence labeling method was used to assay the deposition of C5b-9 and CD34 (endothelial cell marker) in the arteriolar endothelium and glomerular capillary endothelium.Results (1) The plasma and urine levels of complement factor B,factor P,C3a and C5a in malignant nephrosclerosis patients were significantly higher than those in control subjects (all P < 0.05),while the plasma and urine levels of complement factor H in malignant nephrosclerosis patients were lower than those in control subjects (all P < 0.05).(2) The plasma level of factor P was positively correlated with 24 h urine protein (rs=0.465,P=0.001).Urinary factor B/urinary creatinine,urinary factor P/urinary creatinine and urinary C3a/urinary creatinine were positively correlated with serum creatinine in malignant nephrosclerosis patients (rs=0.483,P < 0.001;rs=0.352,P=0.012;rs=0.319,P=0.024),while urinary factor H/urinary creatinine was negatively correlated with serum creatinine and 24 h urine protein (rs=-0.299,P=0.035;rs=-0.342,P=0.015).Urinary C5a/urinary creatinine was positively correlated with serum creatinine and 24 h urine protein (rs=0.525,P < 0.001;rs=0.496,P < 0.001).(3) Immunohistochemical results showed that there were C5b-9 deposited in the arterioles and glomerular capillary wall in malignant nephrosclerosis patients,and no deposition in control renal tissues.Meanwhile,the semi-quantitative scores showed that C5b-9 deposition intensity was positively correlated with serum creatinine and 24 h urine protein (rs=0.791,P< 0.001;rs=0.345,P=0.014).The double immunofluorescence labeling analysis showed that the C5b-9 and CD34 deposited in the arteriolar endothelium and glomerular capillary endothelium.(4) Plasma level of factor B in malignant nephrosclerosis patients was positively correlated with plasma C3a level (r=0.331,P=0.022).Plasma level of factor P was positively correlated with C5b-9 score (rs=0.300,P=0.034).Urinary B was positively correlated with urinary C3a,C5a and C5b-9 score (rs=0.311,P=0.028;rs=0.465,P=0.001;rs=0.428,P=0.002).Urinary factor P was also positively correlated with urinary C3a and C5a (rs=0.307,P=0.030;rs=0.442,P=0.001).Immunohistochemical result showed that there were C4d deposited in the arterioles and glomerular,and no deposition of MBL.Conclusion Complement activation via the alternative pathway may be involved in malignant nephrosclerosis and related to the severity of the disease.
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Objective:To compare the effect of various antigen retrieval methods in paraffin sections of renal biopsy tissue, and explore the best antigen retrieval method.Methods:Forty-five renal biopsy specimens were collected from the First Affiliated Hospital of Zhengzhou University, including lupus nephritis ( n=10), membranous nephropathy ( n=10), IgA nephropathy ( n=10) and amyloidosis glomerulopathy ( n=15). Five retrieval methods (including high pressure thermal retrieval combined with trypsin retrieval, microwave thermal retrieval combined with trypsin retrieval, high pressure thermal retrieval, microwave thermal retrieval and gastroprotease retrieval) were used for immunofluorescence staining of paraffin sections. Renal tissue specimens were divided into six groups according to different antigen retrieval methods, frozen section specimens used as a control group. The immunofluorescence semi-quantitative scores of paraffin sections of the five heat-repairing antigen methods and frozen sections were compared. Results:Immunofluorescence staining of hyperbaric thermal retrieval combined with trypsin retrieval group and microwave thermal retrieval combined with trypsin retrieval group were similar with those of frozen sections. Compared with the control group, there were no significant difference in the semi-quantitative immunofluorescence scores between the two groups (all P>0.05). However, Immunofluorescence staining of hyperbaric thermal retrieval, microwave thermal retrieval, pepsin digestion had significantly higher false negative rate than those of frozen sections. Compared with the control group, the difference in semi-quantitative immunofluorescence score was statistically significant (all P<0.05). Conclusion:High pressure heat retrieval combined with trypsin retrieval or microwave heat retrieval combined with trypsin retrieval is the first choice of antigen retrieval methods.
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Objective:To explore the association between urinary stone disease (USD) and peripheral arterial disease (PAD).Methods:The study was based on the cross-sectional chronic diseases survey performed in Pinggu district, Beijing from March to May, 2014. All subjects completed a questionnaire, physical examination, renal ultrasound examination to detect USD, ankle-brachial index (ABI) examination to detect PAD (defined as ABI<0.9 on either side of the body), and brachial-ankle pulse wave velocity (baPWV) measurement to estimate arterial stiffness. Blood and first morning urine sample were detected for serum creatinine, blood glucose and so on.Results:There were 10 281 participants included in this study. Among these participants, the prevalences of USD and PAD were 5.66% and 3.95%, respectively. Compared with non-stone participants, the persistent USD formers had a higher prevalence of PAD (8.26% vs 3.90%, P<0.001) and baPWV [(16.3±3.5) m/s vs (15.5±3.2) m/s, P<0.001]. Even after adjusting the confounding factors, the persistent USD formers also had a 2.066-fold increased risk of PAD ( OR=2.066, 95% CI 1.276-3.343, P=0.003). In the subgroup analysis, persistent USD patients in older participants who were≥60 years old, women, chronic kidney disease, and central obesity had a significantly increased risk of PAD. Conclusions:In the present population, persistent USD is positively associated with a high risk of PAD and increased arterial stiffness. Patients with persistent USD should be screened for vascular diseases.
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Objective@#To study the role of alternative complement pathway overactivation in malignant nephrosclerosis.@*Methods@#(1) Fifty patients with confirmed malignant nephrosclerosis by renal needle biopsy were enrolled. Meanwhile, twenty-five cases of time-zero renal needle biopsy were enrolled as control subjects. Enzyme linked immunosorbent assay (ELISA) was used to detect alternative complement pathway of the complement initiation factor B, positive regulation factor P, negative regulation factor H, and the complement end products C3a and C5a in the plasma and urine. (2) Immunohistochemistry was used to detect the deposition of the complement end product C5b-9, C4d and mannan binding lectin (MBL) of lectin pathway in the renal biopsies. Double immunofluorescence labeling method was used to assay the deposition of C5b-9 and CD34 (endothelial cell marker) in the arteriolar endothelium and glomerular capillary endothelium.@*Results@#(1) The plasma and urine levels of complement factor B, factor P, C3a and C5a in malignant nephrosclerosis patients were significantly higher than those in control subjects (all P<0.05), while the plasma and urine levels of complement factor H in malignant nephrosclerosis patients were lower than those in control subjects (all P<0.05). (2) The plasma level of factor P was positively correlated with 24 h urine protein (rs=0.465, P=0.001). Urinary factor B/urinary creatinine, urinary factor P/urinary creatinine and urinary C3a/urinary creatinine were positively correlated with serum creatinine in malignant nephrosclerosis patients (rs=0.483, P<0.001; rs=0.352, P=0.012; rs=0.319, P=0.024), while urinary factor H/urinary creatinine was negatively correlated with serum creatinine and 24 h urine protein (rs=-0.299, P=0.035; rs=-0.342, P=0.015). Urinary C5a/urinary creatinine was positively correlated with serum creatinine and 24 h urine protein (rs=0.525, P<0.001; rs=0.496, P<0.001). (3) Immunohistochemical results showed that there were C5b-9 deposited in the arterioles and glomerular capillary wall in malignant nephrosclerosis patients, and no deposition in control renal tissues. Meanwhile, the semi-quantitative scores showed that C5b-9 deposition intensity was positively correlated with serum creatinine and 24 h urine protein (rs=0.791, P<0.001; rs=0.345, P=0.014). The double immunofluorescence labeling analysis showed that the C5b-9 and CD34 deposited in the arteriolar endothelium and glomerular capillary endothelium. (4) Plasma level of factor B in malignant nephrosclerosis patients was positively correlated with plasma C3a level (r=0.331, P=0.022). Plasma level of factor P was positively correlated with C5b-9 score (rs=0.300, P=0.034). Urinary B was positively correlated with urinary C3a, C5a and C5b-9 score (rs=0.311, P=0.028; rs=0.465, P=0.001; rs=0.428, P=0.002). Urinary factor P was also positively correlated with urinary C3a and C5a (rs=0.307, P=0.030; rs=0.442, P=0.001). Immunohistochemical result showed that there were C4d deposited in the arterioles and glomerular, and no deposition of MBL.@*Conclusion@#Complement activation via the alternative pathway may be involved in malignant nephrosclerosis and related to the severity of the disease.
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Objective To explore the correlation between ultrasound features and tumor biological variation with calcification morphological types in differentiated thyroid carcinoma ( DTC) . Methods T he clinical data of 598 patients with DTC calcification diagnosed by ultrasound ,surgery and clinicopathology were retrospectively analyzed . According to the 2017 edition of the American College of Radiology ( ACR) T hyroid Imaging Report and Data System ( T I‐RADS ) classification system standard ,DTC ultrasonic calcification morphological characteristics were divided into 5 types , and the correlation between DTC ultrasonic calcification morphological types and tumor biological characteristics and their variations were analyzed by Spearman correlation analysis . Results Of the 598 patients ,527 cases ( 88 .13% ) were typical papillary thyroid cancer( PTC) ,27 cases ( 4 .52% ) were typical follicular thyroid cancer( FTC) ,and 44 cases ( 7 .36% ) were variant subtype ( including 25 cases of follicular type ,9 cases of high cell type ,6 cases of clear cell type and 4 cases of eosinophilic type) . T I‐RADS diagnosis :44 cases ( 7 .36% ) were Ⅰ ~ Ⅲ class , 179 cases ( 29 .93% ) were Ⅳ class performing fine needle aspiration cytology( FNAC) ,375 cases ( 62 .71% ) were Ⅴ class . T he coincidence rate between ultrasound and clinicopathological diagnosis was 92 .64% ( 554/598) . Morphological types of ultrasonic calcification in 554 cases of DTC :type Ⅰ microcalcification in 416 cases ( 75 .09% ) ;type Ⅱ calcification in 71 cases ( 12 .82% ) ;type Ⅲ calcification in 41 cases ( 7 .40% ) ;typeⅣ calcification in 20 cases ( 3 .61% ) ;type Ⅴ calcification in 6 cases ( 1 .08% ) . T here were correlations between type Ⅰ ,Ⅱ ,Ⅲ ultrasonic calcification morphological types and the tumor biological characteristics and its variant subtypes of DTC ( r =0 .634 ,0 .592 ,0 .479 ;all P =0 .01 ) . Conclusions T I‐RADS Ⅳ - Ⅴclass level+ Adler Ⅱ - Ⅲ blood flow has a high practical value for the ultrasonic diagnosis of DTC ,and FNAC can be performed in suspicious type Ⅳ DTC . Type Ⅰ - Ⅲ ultrasonic calcification morphological types and the main types of tumor biological characteristics and its variant of DTC ,and has an important clinical value for the diagnosis of DTC by ultrasound ,which provides an important reference basis for guiding FNAC ,selecting surgical procedure ,postoperative follow‐up and prognosis judgment .
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Objective@#To explore the correlation between ultrasound features and tumor biological variation with calcification morphological types in differentiated thyroid carcinoma (DTC).@*Methods@#The clinical data of 598 patients with DTC calcification diagnosed by ultrasound, surgery and clinicopathology were retrospectively analyzed. According to the 2017 edition of the American College of Radiology (ACR) Thyroid Imaging Report and Data System (TI-RADS) classification system standard, DTC ultrasonic calcification morphological characteristics were divided into 5 types, and the correlation between DTC ultrasonic calcification morphological types and tumor biological characteristics and their variations were analyzed by Spearman correlation analysis.@*Results@#Of the 598 patients, 527 cases (88.13%) were typical papillary thyroid cancer(PTC), 27 cases (4.52%) were typical follicular thyroid cancer(FTC), and 44 cases (7.36%) were variant subtype (including 25 cases of follicular type, 9 cases of high cell type, 6 cases of clear cell type and 4 cases of eosinophilic type). TI-RADS diagnosis: 44 cases (7.36%) were Ⅰ~Ⅲ class, 179 cases (29.93%) were Ⅳ class performing fine needle aspiration cytology(FNAC), 375 cases (62.71%) were Ⅴ class. The coincidence rate between ultrasound and clinicopathological diagnosis was 92.64% (554/598). Morphological types of ultrasonic calcification in 554 cases of DTC: type Ⅰ microcalcification in 416 cases (75.09%); type Ⅱ calcification in 71 cases (12.82%); type Ⅲ calcification in 41 cases (7.40%); type Ⅳ calcification in 20 cases (3.61%); type Ⅴ calcification in 6 cases (1.08%). There were correlations between type Ⅰ, Ⅱ, Ⅲ ultrasonic calcification morphological types and the tumor biological characteristics and its variant subtypes of DTC(r=0.634, 0.592, 0.479; all P=0.01).@*Conclusions@#TI-RADS Ⅳ-Ⅴ class level+ Adler Ⅱ-Ⅲ blood flow has a high practical value for the ultrasonic diagnosis of DTC, and FNAC can be performed in suspicious type Ⅳ DTC. Type Ⅰ-Ⅲ ultrasonic calcification morphological types and the main types of tumor biological characteristics and its variant of DTC, and has an important clinical value for the diagnosis of DTC by ultrasound, which provides an important reference basis for guiding FNAC, selecting surgical procedure, postoperative follow-up and prognosis judgment.
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Objective To investigate the correlation between ultrasound findings and clinical pathological types of adrenal cortical tumors(ACT).Methods The clinical data and ultrasonographic finding of 138 ACT patients undergoing surgical treatment in Affiliated Hospital of Qingdao University from January 2006 to December 2015 were retrospectively reviewed.The correlation between ultrasonic signs and pathological types of ACT was analyzed with Spearman method.Results There were 65 males and 73 females aged 18-71 years old.Among 138 cases,90 patients were characterized by hypertension,Cushing signs,Coon signs and abnormal sexual character, with the clinical diagnosis of adrenal cortical hyperplasia or adenoma;while 48 asymptomatic patients were first detected by ultrasonography.The coincidence rate of ultrasound and clinical pathological diagnosis was 92.0%(127/138),and 11 cases were misdiagnosed.The coincidence rate of ultrasound and surgical diagnosis was 94.2%(130/138), and 8 cases were misdiagnosed.The coincidence rate for no functional adenoma was 95.8%(46/48), for cortisol cortical adenoma was 94.1%(32/34),for aldosterone cortical adenoma was 93.6%(29/31),for cortical cysts was 9/10,for no functional adenocarcinoma was 5/6,for sexual abnormal cortical adenocarcinoma was 3/4,for cortisol cortical adenocarcinoma was 2/3,for mucous cortical adenoma was 1/2.The diameter of ACT was 0.6-11.5 cm.The low echo nodules of the adrenal region with a diameter <2.0 cm were associated with aldosterone cortical adenomas(r=0.485, P=0.01); the low echo or isoechoic nodules with a diameter 2.0-5.0 cm were associated with cortical adenomas or non-functional adenomas(r=0.567,0.452,P=0.01),and the circular non-echo nodules were associated with cortical cysts(r=0.483, P=0.01); the irregular nodules with a diameter >5.0 cm were associated with cortical adenocarcinoma(r=0.595, P=0.01).Conclusion The ultrasound image of ACT is related to different clinical pathological types,which can provide important information for clinical diagnosis and selection of surgical modalities.
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Objective To investigate the relationship between dyslipidemia and nephrolithiasis in a population-based study.Methods All participants were investigated by questionnaires,physical examinations and laboratory tests including liver and renal function,lipid profile,serum fasting glucose,glycosylated hemoglobin.Nephrolithiasis was diagnosed by kidney Bultrasonography.Subjects with estimated glomerular filtration rate (eGFR) < 60 ml · min-1 · (1.73 m2)-1were excluded.Results 10 316 individuals were enrolled with an average age of (54.88 ± 10.27) years (range 17-88 years) and the ratio of male to female 1:1.12.The prevalence of nephrolithiasis was 5.6%,3.7% and 7.8% for whole population,women and men,respectively.In women,only eGFR in stone group was significantly lower than that in non-stone group (P < 0.05).However,participants in stone group were significantly older (P < 0.05),of higher blood pressure (P < 0.01),higher serum uric acid (P < 0.01),worse renal function (serum creatinine,P < 0.05;eGFR,P < 0.01),and higher low-density lipoprotein (LDL) (P < 0.05),compared with those in non-stone group in men.Logistic regression analysis showed that only eGFR (P < 0.05) was the independent influential factor for kidney stones in women;In men,LDL was an independent influential factor for nephrolithiasis with a hazard ratio of 1.149 (95%CI 1.003-1.317,P < 0.05),except for mean blood pressure and eGFR.After being divided into normal group,borderline high group and high LDL group according to the LDL level,with the increase of LDL,the prevalence of nephrolithiasis was significantly increased by 7.3%,8.3% and 10.6% in men respectively.There was no significant relationship between total cholesterol,triglyceride,high-density lipoprotein and nephrolithiasis.Conclusions Dyslipidemia is associated with nephrolithiasis in men,and high LDL cholesterol is an independent risk factor for nephrolithiasis.Clinical lipid testing not only helps to reduce the risk of atherosclerotic disease,but also reduces the risk of kidney stones.
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Objective:To explore clinical application value of color Doppler ultrasound (CDU) assigned to diagnose triple-negative breast cancer (TNBC) and axillary lymph node metastasis (ALNM).Methods:A retrospectively analyzed of proved of clinical data on the 863 patients breast cancer in women by CDU inspection,operation and pathology.According results will be divided into TNBC group and non negative breast cancer (NTNBC) group via clinical pathological and immunohistochemical detection.Using multi-factor unconditioned Logistic regression analysis the CDU supposed the diagnosis and the correlation of TNBC.Results:The coincidence rate of CDU and pathological diagnosis was 90.96% (785/863),78 cases (9.04%) remove breast masses,105 patients TNBC group and NTNBC group 680 patients.The mass circular or elliptic (48.57% vsl0.70 %),the tumor maximum diameter 5.0 cm (21.90% vs 15.30 %),micro calcifications (87.62% vs 74.12 %),state clearly (56.19% vs 41.47 %),no burr edge character (74.29% vs 41.62 %),peripheral hyperechoic halo ring (74.29% vs46.76 %),rear echo attenuation (72.38% vs 46.76 %),no ALNM (61.90% vs 37.35%) comparing the two groups exists significant difference (P< 0.05),while the mass number,and vertical and horizontal diameter ratio,degree of echo,echo distribution and blood flow classification comparing the two groups were no significant difference (P> 0.05).The CDU fu points > 10 divided into NTNBC and pathological coincidence rate 93.93% (680/724),8 ~ 10 points TNBC suspected diagnosis coincidence rate 11.51% (16/139),< 8 points TNBC tendency diagnosis coincidence rate 64.03% (89/139),TNBC total diagnostic coincidence rate was 75.54% (105/139).In CDU diagnosed 785 cases of breast cancer,the ALN enlargement in 319 cases (40.64%),with TNBC group was 61.90% (65/105),NTNBC group was 37.35% (254/680).Logistic regression analysis results:tumor assumes the circular or elliptic,edge without burr,peripheral hyperechoic halo ring,rear echo attenuation and ALNM with TNBC has certain correlation (P<0.05).Conclusion:The seemingly benign breast diseases and axillary lymph node enlargement,the CDU,supposed less than 8 points,age 50 or less or not at the same time,menopause or having a history of breast cancer susceptibility to family,important reference index,clinical value has high of CDU diagnostic of TNBC and ALNM.
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Objective To investigate the effects of c?myc promoter binding protein 1(MBP?1)gene on the proliferation of human Saos?2 osteo?sarcoma cells in vitro. Methods Saos?2 cells were divided into three groups:blank control group(untransfected cells),negative group(cells transfected with missense sequence)and experimental group(cells transfected with MBP?1 shRNA). Two MBP?1 shRNA sequences and one neg?ative control shRNA sequence were designed ,synthesized and cloned into pSIREN?retroQ plasma. Then the recombinant plasmids were construct?ed and transfected into human Saos?2 osteosarcoma cells by Lipofectamine 2000. The expressions of MBP?1 mRNA and protein in Saos?2 cells were detected by real?time PCR and Western blot ,respectively. The effects of altered expression of MBP?1 on cell proliferation were measured by CCK?8 cell proliferation assay. The expressions of cyclin D1 and cyclin E in Saos?2 were determined by Western blot. Results PCR and sequenc?ing results indicated that the recombinant plasmids pSIREN?retroQ was constructed. The relative expression level of MBP?1 mRNA in the MBP?1 siRNA transfection group was significantly decreased than that in blank control group(P<0.05). Compared with the blank control group,the ex?pression levels of MBP?1 protein in the experimental group also significantly decreased. The proliferation abilities of Saos?2 cells at 48,72,and 96 hours after MBP?1 siRNA transfection were significantly increased than those in the blank control group(P<0.05). Compared with the blank con?trol group,the expression levels of cyclin D1 and cyclin E protein in the experimental group also significantly increased(P<0.05). Conclusion Knockdown of the expression of MBP?1 gene promotes the proliferation of human Saos?2 osteosarcoma cells. MBP?1 gene may become the new tar?get of gene therapy for osteosarcoma.
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Objective:To investigate the role of C3a,C5a and their receptors in the pathogenesis of IgA nephropathy (IgAN). Methods:A total of twenty-eight 6-8 weeks old female BALB/c mice were investigated.And they were negative control group , WT group,C3aR-/-group,C5aR-/-group(the latter three groups were named as experimental groups ),seven mice in each group.All the mice were infected through respiratory tract with infectious SV (experimental groups) or PBS(negative control group),combined with tail vein challenge to make IgAN animal model.Testing 24 h total urinary protein , serum urea nitrogen ( BUN ) and creatinine ( Cr ) , using direct immunofluorescence to test the renal deposition of IgA and C 3,observing renal pathologic lesion under PAS staining with light microscopy.RT-qPCR was used to test the relative mRNA expression of TNF-α,TGF-β,IL-1β,IL-6,MCP-1.Results: After 15 weeks,the level of UTP in experimental group was significantly higher than negative control group ,and the same results as WT group than C3aR-/-group and C5aR-/-group.There was no significant difference among groups for BUN and Cr.Combined with negative control group , experimental groups had significant renal pathological lesions , and the changes of WT group was more severe than C3aR-/-group and C5aR-/-group.The results of relative mRNA expression of TNF-α,TGF-β,IL-1β,IL-6,MCP-1 was the same as the level of 24 h UTP,at the same time,the relative mRNA expression of IL-1β,IL-6,MCP-1 in C3aR-/-group was significantly less than C5aR-/-group.Conclusion:The deficiency of C3a/C5a receptors can protect kidney from injury in IgAN ,and C3a receptor has more significant role in protect kidney from injury in IgAN.