Endothelial dysfunction plays a crucial role in the development of arteriosclerosis (AS). Accumulating evidence suggests that endothelial dysfunction is an initiating event in the etiology of arteriosclerosis. This article reviewed the relationship between endothelial dysfunction and atherosclerosis, and the effects of therapeutic drugs especially statins on endothelial dysfunction.

High-fat diet has led to rapid increase in population withdyslipidemia due to the improvement of living standard, which has seriously endangished people′s health.Blood lipid examination is the an important method to diagnose and monitordyslipidemia.Precision detection and proper management can effectively help doctor to diagnose and treat dyslipidemia.This article mainly introduced international and domestic guidelines about dyslipidemia and related progress as well as highlightin this field.Meanwhile, we provided several advices on dyslipidemia from various perspectives.Clinical laboratory related personnel should analyze the influenced factors on blood lipid test examination at pre-test, on-test and post-test and providebetter detection and managementfor blood lipid.

Objective To observe the month age distribution of peroxisome proliferators activated receptor gamma (PPARγ) expression in rat kedney. Methods Wistar rats aged 3 months,12 months and 24 months were made as models who represented young, middle-aged and old group respectively. Western blotting, immunohistochemical (IHC) and in-situ hybridization (ISH) were used to detect the expression and location of protein and mRNA of PPARγ in rat kidney. Results Western blotting results showed that the expression of PPARγ protein was higher in 3 months group than in 24 months group (0.94±0.05 vs. 0.78±0.02, P＜0.01) and 12 months group (0.87±0.04, P＞0.05), and it reduced in 24 months group than in 12 months group (P＞0.05). By IHC,the PPARγ protein was localized predominantly in the nuclear of tubular epithelia and collecting duct cells in each group. In old age group, PPARγ protein was also detected little in the mesangial and Bowman's capsule epithelial cells. Meanwhile, the distribution of PPARγ mRNA with ISH was consistent with above findings. Additional, semi-quantitative analysis of ISH results verified that the level of PPARγ mRNA decreased with ageing. Conclusions As a nuclear transcription factor,PPARγ participates in the regulation of rat kidney aging.

Objective To investigate the effect of rosiglitazone (RGTZ) on anti-oxidation in aging rat kidney. Methods Twenty-four-month-old male Sprague-Dawley rats were randomly divided into three groups (n=10): control group (CON), rosiglitazone group (RGTZ) and caloric restriction group (CR). The CON rats were allowed ad libitum access to feed and tap water.The RGTZ rats received intragastric administration of RGTZ (4 mg·kg-1·d-1),and the CR rats were provided with a vitamin and mineral fortified version of the same diet at a level of 40% less food (by weight) than the CON rats. After 12 weeks all the animals were sacrificed by decapitation, and both the body weight and the percentage of kidney and heart in each group were measured.Western blot was performed to analyze the expression of PPARγ protein. The content of MDA and the activity of SOD and GSH-PX in kidney tissue were detected. Besides, frozen sections of kidney tissue were stained for senescence-associated-13 galactosidase (SA-β-Gal). Results The body weight of CR rats decreased obviously, in contrast, which did not change in CON and RGTZ group. Percentage of kidney and heart to body weight was normal in CR or RGTZ group after intervention. Western blot result showed that PPARγ protein expression in rat kidney was significantly higher in RGTZ and CR group as compared to CON group (P<0.05). Compared with RGTZ and CR rats, obviously lower activities of SOD and GSH-Px were noted in CON rats, however, the content of MDA was higher in CON rats. Additionally, the positive staining area of [3-Gal in CR and RGTZ group was significantly smaller than that in CON rats (P<0.05, P<0.01 ). Conclusion RGTZ can defer the kidney aging in senescence SD rat, and the mechanism may be related to amelioration of oxidative damage and enhancement of antioxidation.

Pulmonary fibrosis is the late stage of many lung diseases. It′s a pathological process with excessive deposition of extracellular matrix, tissue scar formation and lung tissue remodeling. Recently, DNA methylation has been demonstrated to involve in organ fibrosis, includingpulmonary, liver, renal fibrosis and so on. DNA methylation plays an important role in clinical diagnosis and treatment. This article reviews the role of DNA methylation in the development of pulmonary fibrosis and discusses thepathogenic mechanism of pulmonary fibrosis and new anti-fibrotic strategy.

Objective To determine the pharmacokinetic interaction between cefalor and bromhexine in healthy Chinese volunteers. Methods Twelve subjects received a cefaclor (CEF) treatment, a bromhexine (BHX) treatment, and a co-treatment of CEF and BHX with a 3 × 3 Latin square design. The wash-out time between periods was 14 days. The plasma and urine drug concentrations of CEF and BHX were detected by HPLC-UV and LC/MS, respectively. Results All the 12 volunteers completed the study. There were no significant differences in AUC0-t and Cmax of CEF in logarithm between the single administration group of CEF and the co-administration group of CEF with BHX. Two one sided t-test showed that CEF was bioequivalent in the 2 groups. There were no significant differences in tmax, MRT, t1/2, and Clr between the 2 groups. Vd/F was significantly lower in the single CEF group than in the co-administration group of CEF and BHX. There were no significant differences of AUC0-t and Cmax of BHX in logarithm between the single administration group of BHX and the co-administration group of BHX with CEF. Two one sided t-test showed that BHX was bioequivalent in the 2 groups. There were no significant differences in tmax, MRT, t1/2, Vd/F, and Clr between the 2 groups. Conclusion There is no significant pharmacokinetic parameter change in the drug absorption, metabolism, and excretion, but Va/F of CEF significant increases in the co-administration of CEF with BHX. The co-administration of CEF and BHX has no adverse drug interaction. The increase of Vd/F may be a favorable drug interaction, which may be the mechanism of the synergistic effect of the 2 drugs.

0.05)in the main pharmacokinetic parameters between the domestic preparation and the imported preparation,which suggests they are bioequivalent.

OBJECTIVE:To study the pharmacokinetics of prulifloxacin capsules in Chinese healthy volunteers after single and multiple oral administration of prulifloxacin capsules.METHODS:A total of 12 healthy adult subjects were randomly grouped by 3? 3 Latin square,who were assigned to receive oral single dose of 132,264 and 528mg prulifloxacin capsules and multiple doses of 264mg prulifloxacin capsule for 6 days in succession.The blood concentration of NM394-the metabolite of Prulifloxacin was determined by HPLC at different time after oral administration of Prulifloxacin.The simulation and fitting,and computation of parameters were performed using DAS ver1.0 software.RESULTS:All 12 subjects had completed single oral administration test,with no adverse drug reactions appeared during the test.No prulifloxacin but its metabolite-NM394 was identified in the blood sample of subjects.The high,medium and low dosage groups were all fitted two-compartment model.The pharmacokinetics fitted first order kinetics process without gender difference.There was no accumulation and pharmacokinetic parameters change after multiple oral administration of prulifloxacin,suggesting prulifloxacin had no self-enzyme inhibition or induction.CONCLUSION:The established method is sensitive,accurate,reliable and specific,and it can meet the requirement of clinical pharmacokinetic trial.Its parameters are in line with literature reported abroad,with no gender difference among Chinese adults.

Objective:To investigate the correlation between serum C3 and glomerular microthrombosis in patients with lupus nephritis (LN).Methods:Patients who were diagnosed as LN by renal biopsy hospitalized in Department of Nephrology, the First Affiliated Hospital of Shenzhen University from January 2010 to February 2019 were retrospectively analyzed and they were divided into glomerular microthrombosis group (GMT group) and non-glomerular microthrombosis group (non-GMT group). The demographic data, clinical characteristics, pathology and prognosis of the two groups were compared. Logistic regression and smooth curve fitting of generalized additive mixed model analysis were used to explore the correlation between serum C3 and glomerular microthrombosis. Renal prognosis of the two groups were compared by the Kaplan-Meier survival curve.Results:A total of 116 patients were enrolled, aged (32.79±11.43) years old, in which 108 cases (93.10%) were female. Thirty-seven patients (31.90%) were confirmed to be combined with GMT (GMT group) and 79 cases were not (non-GMT group). Compared with the non-GMT group, patients in the GMT group were relatively older ( t=-2.876, P=0.002), with higher proportion of hypertension ( χ2=7.492, P=0.006), higher urine protein quantitation ( Z=-2.115, P=0.003), lower levels of eGFR and serum complement C3 ( Z=3.469, P<0.001; t=1.744, P<0.001), higher systemic lupus erythematosus disease activity index ( t=-2.758, P=0.007). As to the pathological characteristics, type IV LN patients were the majority (72.97%). Proportion of crescents and pathological activity indicators of the GMT group were higher ( Z=-1.866, P=0.002; t=-5.005, P<0.001), nuclear fragmentation, endothelial hyperplasia and renal tubular atrophy were more serious ( χ2=14.987, P<0.001; χ2=15.695, P<0.001; χ2=4.130, P=0.042). Multivariate logistic regression analysis indicated that serum complement C3 was a relational factor of the formation of GMT in LN patients ( OR=0.966, 95% CI 0.938-0.995, P=0.023). Smooth curve fitting of generalized additive mixed model analysis indicated that level of complement C3 had a linear relationship with the changing trend of GMT. The Kaplan-Meier curve showed that there were statistical differences between the two groups in terms of complete remission of urine protein (Log-rank χ2=5.858, P=0.016) and doubled serum creatinine/end-stage renal disease (Log-rank χ2=3.945, P=0.047). Conclusions:Serum C3 is closely related to the formation of GMT in LN patients, and statistical differences were demonstrated in the renal prognosis of GMT group and non-GMT group.

Objective:To establish a diagnostic model for glomerular micro thrombosis (GMT) in lupus nephritis through clinical indicators.Methods:A continuous collection of patients diagnosed with lupus nephritis (LN) by renal biopsy in the Department of Nephrology, Shenzhen Second People's Hospital, from January 2010 to March 2021. All patients were admitted and discharged through the inclusion and exclusion criteria. Demographic data, clinical characteristics, biochemical indicators, and immune indicators were collected. A GMT diagnosis model was established from the most important variables among the abovementioned variables through machine learning and Logistic stepwise regression analysis. The model was presented through a nomogram. The receiver operating characteristic curve (ROC), the clinical decision curve and the calibration curve were used to evaluate the model discrimination, clinical use and accuracy, respectively. The internal verification of the model was carried out by repeated sampling 500 times by the Bootstrap method.Results:There were a total of 129 patients with lupus nephritis including the study, including 117 females (90.7%); the average age was (34±11) years. There were 39 patients with GMT (30.2%). Using machine learning to screen out the top 10 important variables from 47 candidate variables, then through logistic stepwise regression analysis, five variables were further screened to establish the diagnostic model of GMT, namely hemoglobin [ OR(95% CI)=0.966(0.943, 0.990), P=0.005], serum C3 [ OR(95% CI)=0.133(0.022, 0.819), P=0.030], systolic blood pressure [ OR(95% CI)=1.027(1.005, 1.049), P=0.017], lymphocyte count [ OR(95% CI)=0.462(0.213, 0.999), P=0.049], and TT [ OR(95% CI)=1.260(0.993, 1.597), P=0.057]. Draw up the equation of the GMT diagnosis model of lupus nephritis and establish a nomogram to present the model. The area under curve (AUC) of the diagnostic model was 0.823, 95% CI(0.753, 0.893), indicating that the model had a reasonable degree of discrimin-ation. The Hosmer-Lemeshow test showed a perfect fit between the predicted GMT risk and the observed GMT risk ( χ2= 14.62, P=0.067). The clinical decision curve and clinical impact curve reflect that the model had a good clinical application value, especially when the threshold probability is between 0.4 and 0.6, the application value is more significant. In addition, after 500 repeated samplings by the Bootstrap method, the average AUC was 0.825, 95% CI(0.753, 0.893), which is basically the same as the AUC obtained by the original model. Conclusion:We established a diagnostic model of GMT inLN based on clinical indicators through machine learning and logistic stepwise regression analysis. It is used for early diagnosis of the risk of GMT before the renal biopsy.