Immunoinflammation mediates the development of hypertensive nephropathy,and aberrant activation of the complement system,an important component of the innate immune system,plays an important role in the development of hypertensive nephropathy.Complement inhibition is expected to be a potential strategy for the treatment of hypertensive nephropathy.In this article,we summarized and reviewed relevant studies on the complement system in the development of hypertensive nephropathy,and complement-targeted drug therapy,aiming to provide new ideas for clinicians on the clinical diagnosis and treatment of hypertensive nephropathy.

Immunoinflammation mediates the development of hypertensive nephropathy,and aberrant activation of the complement system,an important component of the innate immune system,plays an important role in the development of hypertensive nephropathy.Complement inhibition is expected to be a potential strategy for the treatment of hypertensive nephropathy.In this article,we summarized and reviewed relevant studies on the complement system in the development of hypertensive nephropathy,and complement-targeted drug therapy,aiming to provide new ideas for clinicians on the clinical diagnosis and treatment of hypertensive nephropathy.

Objective:To explore the effects of canagliflozin on cardiac function and its regulation of ferroptosis in rats with heart failure with preserved ejection fraction (HFpEF).Methods:Thirty-two 7-week-old Dahl salt-sensitive rats were selected and randomly divided into four groups: the control group (fed with low-salt diet), the HFpEF group (fed with high-salt diet), the canagliflozin 20 group (fed with high-salt diet and 20 mg·kg -1·d -1 canagliflozin), and the canagliflozin 30 group (fed with high-salt diet and 30 mg·kg -1·day -1 canagliflozin). Body weight and blood pressure of the rats in each group were monitored. Metabolic cage tests were conducted at the10 th week of the experiment, and echocardiography was performed at the 12 th week, after which the rats were killed. Blood and left ventricular samples were collected. HE staining, Masson staining, Prussian blue iron staining, and reactive oxygen species staining were performed to observe the cardiomyocyte size and shape, degree of interstitial fibrosis, iron staining, reactive oxygen species production under optical microscope. The ultrastructure of cardiomyocytes was observed under electron microscope. Western blotting and real-time fluorescent quantitative reverse transcription polymerase chain reaction (RT-qPCR) were used to detect the expression levels of proteins and mRNA related to ferroptosis in left ventricular myocardial tissue of rats in each group. Results:After 1 week of adaptive feeding, all rats survived. Metabolic cage results showed that compared with control group, rats in the HFpEF group, canagliflozin 20 group and canagliflozin 30 group had more food intake, water intake and urine output, and lower body weight (all P<0.05). These changes were more pronounced in canagliflozin 20 group and canagliflozin 30 group than in HFPEF group, and only the body weight at the 12 th week showed a statistically significant difference between canagliflozin 20 group and canagliflozin 30 group ( P<0.05). The blood pressure of 6 th week and 12 th week, heart weight and left ventricular corrected mass of 12 th week of rats in HFpEF group were higher than those in control group, canagliflozin 20 group and canagliflozin 30 group, while the ratio of early mitral valve peak velocity to late mitral valve peak velocity of 12 th week was lower (all P<0.05). HE and Masson staining showed that compared to control group, the myocardial fibers in the left ventricular myocardial tissue of rats in HFpEF group were disordered, with larger cell diameter ((0.032±0.004) mm vs. (0.023±0.003) mm, P<0.05), irregular shape, obvious proliferation of interstitial collagen fibers, and higher collagen volume fraction (0.168±0.028 vs. 0.118±0.013, P<0.05). Compared with HFpEF group, rats in the canagliflozin 20 group and canagliflozin 30 had more orderly arranged myocardial fibers, more regular cardiomyocyte shape, smaller cell diameter, and lower collagen volume fraction ( P<0.05). It was observed under electron microscopy that, compared to control group, most of the striated muscles in myocardial tissue of HFpEF group were broken, and the Z line and M line could not be clearly distinguished, some changes such as mitochondrial swelling, membrane thickening, cristae reduction or even disappearance occurred. In the canagliflozin 20 group and canagliflozin 30 group, the arrangement of striated muscles in the myocardial tissue of rats tended to be more regular, and the morphological changes of mitochondria were milder. Prussian blue iron staining results showed that the iron content in myocardial tissue of rats in HFpEF group was higher than that in control group, canagliflozin 20 group and canagliflozin 30 group. Reactive oxygen species staining results showed that the reactive oxygen species content in the myocardial tissue of rats in HFpEF group was higher than that of control group, canagliflozin 20 group and canagliflozin 30 group. Biochemical analysis of myocardial tissue showed that Fe 2+ and malondialdehyde content in myocardial tissue of rats in HFpEF group were higher than those in control group, canagliflozin 20 group and canagliflozin 30 group, while glutathione content was lower (all P<0.05). Western blot and RT-qPCR detection results showed that compared to control group, rats in HFpEF group had higher expression levels of transferrin receptor 1 (protein relative expression level: 1.37±0.16 vs. 0.31±0.12), acyl-CoA synthetase long-chain family member 4 (protein relative expression level: 1.31±0.15 vs. 0.63±0.09) protein and mRNA, and lower expression levels of ferritin heavy chain 1 (protein relative expression level: 0.45±0.08 vs. 1.41±0.15) protein and mRNA (all P<0.05). There was no statistically significant difference in these indicators between canagliflozin 20 group and the canagliflozin 30 group (all P>0.05). There was no significant difference in levels of glutathione peroxidase 4 protein and mRNA expression in myocardial tissue of rats in four groups( P>0.05). Conclusion:Canagliflozin improves cardiac function in HFpEF rats by regulating the ferroptosis mechanism.

Objective:To evaluate the effectiveness and safety of the home-made umbrella-shaped Octoparms inferior vena cava filter in the prevention of pulmonary embolism.Methods:A multicenter, randomized, positive parallel controlled, non-inferiority clinical trial was conducted in ten hospitals in China from October 2017 to March 2019. A total of 188 subjects were enrolled according to the same inclusion and exclusion criteria in different institutes. The 188 subjects were randomly divided into the trial group or the control group according to 1∶1 by the central randomization system, with 94 cases in each group. Octoparms inferior vena cava filter was used in the trial group, and the Celect inferior vena cava filter in the control group. The primary effective index was clinical success rate,including the clinical success rate of filter placement and filter retrieval. The secondary index included the rate of manual success of the delivery sheath system,incidence of pulmonary embolism(within 6 months), incidence of filter fracture,migration (>20 mm),tilt(>15°) on insertion/retrieval,and the situation of inferior vena cava flow(within 6 months). Safety evaluation included the incidence of filter related complications and device-related adverse events immediately after surgery and during follow-up.Results:The success rate of implantation was 100% in 188 subjects. Filter retrieval was performed in 87 cases (92.55%) in the trial group and 91 cases (96.81%) in the control group. The clinical success rate of the trial group was 97.87%(92/94) and that of the control group 98.94%(93/94). There was no significant difference between the two groups (χ 2=0.77, P=0.380). The success rate of delivery sheath system was 96.81%(91/94) and 98.94%(93/94) in the trail group and the control group,respectively. There was no significant difference between the two groups( P=0.621). There was 1 case (1.22%) of new asymptomatic pulmonary embolism in the trial group after filter placement and 2 cases (2.44%) in the control group. There was no significant difference between the two groups ( P>0.05). No filter fracture or migration (>20 mm) occurred in either group. The tilting of filter (>15°) was found in 1 case (1.06%) in the test group and 1 case (1.06%) in the control group when the filter was placed. The tilting of filter (>15°) was found in 0 case in the test group and 2 cases (2.44%) in the control group when the filter was retrieved. There was no significant difference between the two groups ( P>0.05). Inferior vena cava thrombosis before filter retrieval was found in 5 cases (5.75%) in trial group and 3 cases (3.30%) in control group. There was no significant difference between the two groups ( P=0.489). There were no immediate serious complications during filter placement/removal in either group. No filter obstruction,migration,deformation,penetration and occlusion of inferior vena cava. The incidence of device-related adverse events was low in both group. There was no significant difference between the two groups ( P>0.05). Conclusion:The home-made umbrella-shaped Octoparms inferior vena cava filter is effective and safe in preventing pulmonary embolism, and is not worse than Celect filter.

Objective:By comparing the clinical data and follow-up data of patients with coronary heart disease combined with chronic kidney disease who choose different ways of revascularization for the first time when do PCI revascularization therapy again. To investigate the effect of coronary artery bypass grafting on revascularization for the first time in patients.Methods:A retrospective analysis of clinical data of 358 patients with coronary heart disease combined with chronic kidney disease who received revascularization PCI from January 2008 to December 2017 was made. All the patients were divided into CABG group(75 cases) and PCI group(283 cases) for clinical characteristics and prognosis comparison. According to the occurrence of major adverse cardiovascular events, Cox regression was carried out to establish a risk prediction model. Results:Compared with the patients in the two groups, the ratio of current smoking(17.33% vs. 33.57%, P=0.006) and hospitalized patients with recurrent acute myocardial infarction(28.00% vs. 40.64%, P=0.045) were decreased in CABG group, the ratio of triple-vessel disease(82.67% vs. 55.12%, P<0.001) and road via femoral artery(49.33% vs. 24.03%, P<0.001) were significantly increased in the CABG group, the Gensini score[136.00(100.75, 164.00) vs. 53.00(39.00, 74.00), P<0.001] and contrast agent dosage [300(200, 400)ml vs. 200(200, 300)ml, P<0.001] were significantly higher in CABG group, but the incidence of MACCE was significantly lower in CABG group than in PCI group (40.00% vs. 57.60%, χ2=7.571, P=0.0059). According to the Cox regression of MACCE events, it was found that CABG ( RR=0.586, 95% CI: 0.396-0.867, P=0.007) and higher glomerular filtration rate( RR=0.988, 95% CI: 0.980-0.997, P=0.007) were the protective factors, white blood cell elevation( RR=1.100, 95% CI: 1.020-1.187, P=0.013) and the application of renin-angiotensin-aldosterone system inhibitor( RR=1.380, 95% CI: 1.016-1.875, P=0.039) were independent risk factors. Conclusion:Patients with coronary heart disease combined with chronic kidney disease can benefit from CABG for the first time in revascularization, when they were confronted with PCI revascularization again.

Objective:The anti-FⅩa assay can be used to monitor the blood concentration of Rivaroxaban. The aim is to evaluate the critical value and diagnostic performance of this test on bleeding risk assessment.Methods:From September 2017 to June 2019, 368 patients were enrolled for retrospective cohort study, including 201 males and 167 females, aged (62.8±15.7) years old. They were divided into groups by age:≤60 years old group 105 cases,61-70 years old group 135 cases,≥71 years old group 128 cases. Anti-FⅩa was detected on ACL TOP 700 coagulation analyzer using chromogenic substrate method to quantitatively determine the plasma concentration of rivaroxaban. Anti-FⅩa data were expressed as M ( P25- P75);Kruskal-Wallis H test was used for comparison among groups; Mann-Whitney U test was for data comparison between two groups; positive rate comparison was performed by χ 2 test; the diagnostic performance of anti-FⅩa to assess bleeding risk was evaluated by ROC curve;Kaplan-Meier curve was used for the survival analysis;the risk ratio (HR) was obtained by Cox proportional hazard regression model. Results:Both the peak and trough plasma concentrations were higher in patients aged 61-70 years old than ≤60 years old ( U values were 5 618 and 5 725,respectively, P values were 0.006 and 0.011, respectively); higher in patients ≥71 years old than 61-70 years old ( U values were 6 438 and 6 317, respectively, P values were<0.001).The incidence of bleeding events was higher in the 61-70 years old group than ≤60 years old group (χ 2=3.06, P<0.05),while not significantly different in the ≥71 years old group from 61-70 years old group (χ 2=0.35, P>0.05).Both peak and trough blood concentrations were higher in patients with bleeding than without bleeding(U values were 1 429 and 2 185, respectively, P<0.001 and 0.001, respectively).ROC showed that the cut-off values of peak blood concentration in evaluation of the overall and the ≥61 year-old population′s bleeding risk were 200.8 ng/ml and 209.9 ng/ml,respectively, corresponding respectively with the sensitivity of 90.9% and 95.0%; the trough cut-off values were 35.1 ng/ml and 39.1 ng/ml, respectively, corresponding respectively with the sensitivity of 72.7% and 70.0%. However, all the above cut-off values gave a low diagnostic specificity. Survival analysis showed with 35.1 ng/ml as the trough cut-off value, the cumulative risk of bleeding significantly increased in patients above the cut-off value (Log-rank χ 2=4.513, P=0.034). The Cox proportional regression model demonstrated that the hazard ratios for peak and trough blood concentration predictions of bleeding risk were 1.023 (95% CI: 0.834-1.256) and 0.948 (95% CI: 0.773-1.164). respectively. Conclusions:Both the peak and trough values of blood concentration in bleeding patients are higher than non-bleeding patients. The peak blood concentration is highly sensitive to the risk of bleeding, and the elevated trough blood concentration levels indicate that the probability of bleeding risk increases in the short term. However, the specificity of both peak and trough values is relatively low in bleeding risk assessment. When used alone, the prediction of bleeding events does not have direct guiding significance. Dynamic monitoring and joint evaluation are recommended.

Venous thromboembolism (VTE) is a common multifactorial disease that results from hypercoagulable action of genetic factors and environmental exposures. VTE associated genetic factors include anticoagulant gene loss of function (LOF), procoagulant gene gain of function (GOF), the fibrinolytic system genes dysfunction, variants and epigenetic changes that cause hypercoagulability indirectly. Some VTE follows the pattern of Mendelian inheritance; also, genetic polymorphism is an important aspect of genetic susceptibility to VTE. For patients with suspected VTE associated genetic dysfunctions, polymorphisms test should be performed to those who is supposed to have obvious known polymorphisms genetic susceptibility. In contrast, the individuals who suffer from Mendelian disease or other types of disease with unknown gene variants, NGS test should be a good choice. Further, genetic polygenic risk score (PRS) or epigenetic biomarkers are suitable for VTE recurrence risk assessment.

Objective: Evaluate the diagnostic performance of three methods in testingheparin induced thrombocytopenia antibodies the clinical diagnosis performance of the three heparin induced thrombocytopenia(HIT) antibody testing. Methods: 143 patients were collected from the Tianjin Medical university general hospital and China-Japan friendship hospital from the 2017 Sep to 2018 Dec, 67 males and 76 females, with a mean age of (56.1±11.4) years, the pretest probability is estimated to be low (1-3 points) with 24 patients, intermediate (4-5 points) with 79 patients and high(6-8 points) with 40 patients. According to therapeutic regimen, the intermediate and high probability patients were divided into two groups: 31 cases in the heparin discontinuing group and 88 cases in the continuing heparin group. The three methods including:the particle immunofiltration assay to detect the plasma whole HIT antibody; the particle gel immunoassayto detect the plasma whole HIT antibody by ACL TOP 700 coagulation analyzer,; the chemiluminescent immunoassay to detect the plasma IgG-specific HIT antibody by ACL AcuStar chemiluminescent analyzer. Results: There was no significant difference between the high and intermediate probability patients for particle immunofiltration assay, particle gel immunoassay and chemiluminescent immunoassay(χ² was 3.15, 2.89 and 1.31 respectively, P>0.05). The positive rate with three assays were higher in the heparin discontinuing group than the continuing heparin group(χ² was 16.09, 43.37 and 26.94 respectively, P<0.01), the positive results of the chemiluminescent immunoassay only in the heparin discontinuing group. All of the patients with three assays positive simultaneousin the heparin discontinuing group(χ²=26.94, P<0.01); more patients in heparin discontinuing group with positive resultsby two assays (particle immunofiltration assay and particle gel immunoassay) than in the continuing heparin group(χ²=10.95, P<0.01); there was no obvious difference(χ²=1.80, P>0.05) between the continuing heparin group and the heparin discontinuing group for positive results with particle immunofiltration assay; all of the patients with there assays negative simultaneous in the continuing heparin group with a significant difference between the two groups(χ²=14.27, P<0.01). Conclusions Whole HIT antibodies had high sensitivity, and was especially suitable for excluding diagnosis, andthe diagnositic performance withtheparticle gel immunoassay precede the particle immunofiltration assay.For the patients with intermediate or high pretest probability and whole antibodies positive, even if they had been treated with alternative anticoagulant therapy, the IgG specific antibodies(chemiluminescent immunoassay) should be detected for definite diagnosis(if the conditions was appropriate), to verify the rationality of alternative anticoagulant therapy and to avoid overtreatment.

Rivaroxaban is an oral direct factor FXa inhibitor with predictable pharmacokinetics and no routine monitoring, but the laboratory tests can help to assess the safety and effectiveness of rivaroxaban. The laboratory tests for rivaroxaban include liquid chromatography tandem mass spectrometry (LC-MS / MS), prothrombin time(PT), anti factor Xa activity(anti-Xa), thromboelastography(TEG) and rotational thromboelastography(ROTEM). LC-MS / MS can be used to quantitatively detect the blood concentration of rivaroxaban with good specificity and sensitivity, but the instrument is expensive,technologically complex, and lack standardization, so it belongs to the laboratory developed tests(LDTs).Because of insufficient data of TEG and ROTEM, their clinical performance still needs to be verified. PT can detect "treatment concentration" of rivaroxaban, which can be used as a primary screening method to identify the overdose and the risk of severe bleeding, but the sensitivity of different reagents is different;anti-FXa test can sensitively reflect the change of blood concentration of rivaroxaban, and its clinical efficacy is similar to LC-MS/MS, and therefore it can be used as an effective method to guide doctors to use drugs rationally.

The clinical application of the laboratory examination with thrombosis can be divided into four categories,including risk assessment,diagnosis by exclusion,auxiliary diagnosis and therapic monitoring.Theevidence based parameters which subsumed into the international guidelines of thrombosis related clinical management,included the prothrombin time,activited partial thomboplastin time,anti-factor X a activity,D-dimer,coagulation factor Ⅷ,naturally occurring anticoagulants,antiphospholipid syndromeassociative parameters,heparin induced thrombocytopenia antibodies and platelet aggregation test,which provided the important evidence for clinical intervention and establishment of antithrombotic strategy.Theother thrombosis tests are still lack of sufficient evidence,therefore we need to participate in multicentric clinical randomized controlled study actively,and implementing the systematic review and meta-analysis forwardly,solving clinical questions based on PICO (Patients,Intervention,Comparision,Outcome),promoting the clinical application of laboratory parameters.