[The variation of serum uric acid levels among patients with myocardial infarction treated with ticagrelor and the association between serum uric acid and platelet reactivity].

Objectives: To compare the impact of ticagrelor or clopidogrel on serum uric acid levels among patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI) and further evaluate the effects of variation of serum uric acid levels on platelet reactivity. Methods: STEMI patients who admitted to Fuwai Hospital from April 2017 to January 2020, and underwent primary PCI and discharged alive with aspirin and ticagrelor or clopidogrel were included in this study. Patients were divided into ticagrelor group and clopidogrel group. The baseline clinical data were collected. Serum uric acid and creatinine levels at baseline and 30 days post-PCI were measured. Light transmittance aggregometry was used to assess maximum aggregation rate induced by adenosine diphosphate and arachidonic acid. The changes of serum uric acid and creatinine were compared between the two groups. Multivariate logistic regression was performed to evaluate independent related factors for rise in the uric acid levels, and the effect of variation of serum uric acid level on platelet reactivity was analyzed. Results: A total of 967 patients were included, the age was (59.4±12.1) years, and 163 case were female. There were 550 cases in ticagrelor group (56.9%) and 417 cases in clopidogrel group (43.1%). Baseline serum uric acid and creatinine levels were similar between the 2 groups. At 30 days, the serum uric acid level [(347.2±96.5) mmol/L vs. (341.2±105.3) mmol/L, P=0.009] and absolute [46.4 (-2.4, 88.1) mmol/L vs. 25.0 (-21.9, 73.0) mmol/L, P=0.001] and percentage [13.2 (-0.01, 29.0) % vs. 7.9 (-5.7, 25.0) %, P=0.007] increase in the serum uric acid levels were significantly higher in ticagrelor group than in clopidogrel group. The level of serum creatinine at 30 days was significantly lower in ticagrelor group than in clopidogrel group [(89.7±21.3) µmol/L vs. (94.4±43.9) µmol/L, P<0.05], whereas there were no differences in absolute [8.0 (-1.4, 16.6) µmol/L vs. 7.8 (-2.0, 16.6) µmol/L] and percentage [10.5 (-1.7%, 22.6%) vs. 9.8 (-2.4%, 22.1%)] change in the serum creatinine between the 2 groups (all P>0.05). Logistic regression analysis showed that, after adjusting for confounding factors, ticagrelor therapy was an independent related factor of serum uric acid elevation (OR=1.582, 95% CI:1.023-2.447, P=0.039). The variation of the serum uric acid levels did not affect platelet aggregation and the percentage of high platelet reactivity in both groups. Conclusions: Ticagrelor use is related to a significant increase in the serum uric acid levels at 30 days post-PCI in this patient cohort. The variations in the uric acid levels do not increase the percentage of high platelet reactivity in STEMI patients treated with ticagrelor or clopidogrel.

[Associations between postprocedural D-dimer, hs-CRP, LDL-C levels and prognosis of acute myocardial infarction patients treated by percutaneous coronary intervention].

Objective: To investigate the association between postprocedural D-dimer, high sensitivity C-reactive protein(hs-CRP) and low-density lipoprotein-cholesterol(LDL-C) and outcomes of acute myocardial infarction (AMI) patients treated by percutaneous coronary intervention(PCI), in order to clarify the impacts of thrombotic, inflammatory and cholesterol risks on long-term prognosis. Methods: Patients with AMI who underwent emergency PCI from January 2010 to June 2017 in Fuwai Hospital with complete baseline data were enrolled. Patients were stratified into four groups according to quartiles of D-dimer, hs-CRP and LCL-C. Cox regression was used to analyze the relationship between these biomarkers and prognosis. Restricted cubic spline (RCS) was used to characterize the continuous association between risk of all-cause death and biomarkers. The primary outcome was all-cause death. Results: A total of 3 614 patients were included in the analysis. The age was (59.2±12.0) years old, and 2 845 (78.7%) were male and 3 161 (87.5%) patients were diagnosed as ST-segment elevation myocardial infarction. The follow-up time was 652 (414, 1 880) days. Survival analysis showed that postprocedural D-dimer and hs-CRP were significantly associated with all-cause mortality (all P<0.05). Cox regression with multiple adjustments showed that patients with D-dimer≥580 µg/L presented higher risk of all-cause death (HR=2.03, 95%CI 1.22-3.38, P=0.006), compared to patients with D-dimer<220 µg/L. RCS analysis showed that risk of all-cause death was stably high when D-dimer reached 500 µg/L. Multivariable Cox regression also showed that patients with hs-CRP<2.74 mg/L (HR=1.86, 95%CI 1.10-3.15, P=0.020)or hs-CRP≥11.99 mg/L (HR=2.14, 95%CI 1.35-3.40, P=0.001) presented higher mortality compared to patients whose hs-CRP was 2.74-7.18 mg/L. RCS analysis indicated a J-shaped relation between hs-CRP and mortality, as greater risk of death was observed when hs-CRP was lower than 2 mg/L or higher than 10 mg/L. LDL-C was not associated with outcomes (all P>0.05). Conclusions: Postprocedural D-dimer is significantly associated with long-term prognosis of AMI patients treated by PCI. Patients with extremely high or low levels of hs-CRP presents worse outcomes. Intensive and tailored antithrombotic or anti-inflammatory therapies should be considered for patients with increased thrombotic risk and those with extremely high or low inflammatory risk.

[Comparison of six-month follow-up results of primary percutaneous coronary intervention guided by optical coherence tomography or coronary angiography].

Objective: To compare the 6-month follow-up results of primary percutaneous coronary intervention (PPCI) guided by optical coherence tomography (OCT) or coronary angiography (CAG) alone in a larger ST-segment elevation myocardial infarction (STEMI) cohort. Methods: We enrolled 275 STEMI patients undergoing OCT-guided PPCI from March 2017 through December 2018. Two hundred and seventy-five propensity score matched STEMI patients undergoing CAG-guided PPCI served as control group. The 6-month clinical follow-up results were compared between the two groups. The demographic data, complications, coronary angiography and OCT characteristics were evaluated. Results: OCT evaluation showed that there were 151 patients (54.9%) with plaque prolapse and 113 patients (41.1%) with stent malposition. Proximal and/or distal dissection of stents occurred in 38 patients (13.8%), of which 3 patients (1.1%) had both proximal and distal dissection. Of the 38 patients, 2 patients received rescue stent implantation. Results of clinical follow-up at 6 months showed that there was no significant difference in cardiovascular death, repeat myocardial infarction, target vessel revascularization, stroke and hemorrhage endpoint events between OCT-guided PPCI patients and CAG-guided PPCI patients (P=0.682). Conclusion: Clinical events at 6 months are similar between OCT-guided PPCI and CAG-guided PPCI for STEMI patients.

[Trend of clinical features in patients with acute coronary syndrome undergoing emergent percutaneous coronary intervention].

Objective: To investigate the clinical features and change trend of patients with acute coronary syndrome(ACS) undergoing emergent percutaneous coronary intervention(PCI). Methods: In this retrospective study, we retrieved all medical records of 4 907 ACS patients who underwent emergent PCI in Fuwai hospital from January 1,2010 to December 31,2016. We analyzed the clinical features and change trend in these patients. According to clinical diagnosis, patients were grouped as ST-elevated myocardial infarction(STEMI) group (3 719 cases) and NSTE-ACS group (patients with non-STEMI and unstable angina, 1 188 cases). Results: The ACS patients were aged (59.5±11.8) years old. There were 3 772 males and 1 135 females. The annual number of ACS patients underwent emergent PCI increased from 412 patients in 2010 to 1 067 patients in 2016. The number of NSTE-ACS patients increased from 11.4% (47/412) in 2010 to 26.5% (283/1 067) in 2016. Compared with STEMI group, patients in NSTE-ACS group were significantly older ((61.2±10.9) years old vs. (58.9±12.1) years old,P<0.01).The percent of female patients (30.1% (358/1 188) vs. 20.9% (777/3 719), P < 0.01), history of hypertension (69.1% (821/1 188) vs. 60.4% (2 248/3 719,P <0.01), previous PCI (25.8% (307/1 188) vs. 12.4% (461/3 719), P <0.01), and previous coronary artery bypass grafting (3.0% (36/1 188) vs. 1.0% (37/3 719), P <0.01) were all significantly higher in NSTE-ACS group than in STEMI group. On the other hand, NSTE-ACS patients presented less chronic renal failure (2.9% (35/1 188) vs. 4.3% (173/3 719), P <0.05) and hepatic dysfunction (8.5% (101/1 188) vs. 13.3% (495/3 719), P<0.01) as compared to ACS patients. In coronary angiography, NSTE-ACS patients had a higher prevalence of left-main disease (14.0% (166/1 188) vs. 7.8% (291/3 719), P<0.012 5) and triple vessel disease (47.8% (568/1 188) vs. 43.5% (1 619/3 719), P<0.012 5). There were no differences in prevalence of diabetes mellitus (31.9% (1 187/3 719) vs. 34.8% (414/1 188),P>0.05) and acute renal failure (0.1% (38/3 719) vs. 0.6% (7/1 188),P>0.05) between STEMI group and NSTE-ACS group. Conclusions: This single center retrospective analysis reveals that there is an increasing trend of NSTE-ACS patients from 2010 to 2016. Furthermore, there are more high-risk clinical characteristics in NSTE-ACS patients than in STEMI patients.

The role of miR-146b-5p in TLR4 pathway of glomerular mesangial cells with lupus nephritis.

OBJECTIVE: MicroRNAs (miRNAs) are now recognized as important regulators of gene expression. The aim of the study was to investigate the role of miR-146b-5p in the TLR4 pathway and provide the basis for the treatment of lupus nephritis. MATERIALS AND METHODS: The glomerular mesangial cells were cultured in vitro and divided into 3 groups: control group, a group of miR-146b-5p mimic added, and a group of miR-146b-5p inhibitor added. The levels of IL-6 and IL-8 in the cell culture supernatant of the three groups were detected by ELISA. The cell proliferation was detected by MTT. The expressions of MiR-146b-5p and TLR4 pathway-associated factor TRAF6 were detected by RT- PCR. The expression of TRAF6 and IRAK1 protein was detected by Western blot. RESULTS: The overexpression of miR-146b-5p could reduce the level of IL6 and IL8 in cell culture and inhibit glomerular mesangial cell proliferation in some degree. Also, the overexpression of miR-146b-5p could inhibit the expressions of TLR4 pathway-associated factor TRAF6 and IRAK1mRNA, and the expressions of TRAF6 and IRAK1 protein. CONCLUSIONS: MiR-146b-5p attenuated the inflammatory response of glomerular mesangial cells by inhibiting the expressions levels of TRAF6 and IRAK1 in lupus nephritis.

NAC attenuates adriamycin-induced nephrotic syndrome in rats through regulating TLR4 signaling pathway.

OBJECTIVE: Nephrotic syndrome (NS) is a detrimental renal disease that affects a large population. It is suggested that Toll-like Receptor 4 (TLR4) signaling pathway plays an important role in NS. The aim of this study was to evaluate the immunosuppressive effect of N-acetylcysteine (NAC) in the treatment of NS elucidate its interaction with TLR4 pathway in a rat model. MATERIALS AND METHODS: Rat NS model was constructed using the Bertain method by injecting adriamycin (4.5 mg/kg) intravenously at day 1, and injecting 2 mg/kg adriamycin (ADR) at day 7. NS rats were treatment with NAC of 150 mg/kg daily through gavage. Control rats received equivalent amounts of saline daily. Quantitative Real-time PCR was used to evaluate TLR4 expression in kidney tissues after treatments. Western blot analysis was used to evaluate NF-κBp65 expression. ELISA was used to evaluate the expression of immunological factors, including TNF-α, IL-6, and IL-1ß. RESULTS: Rat NS models demonstrated higher protein levels in urine, accompanied by an increased in the TLR4 level. After NAC treatment, TLR4 level was reduced. NAC treatment also attenuated the NF-κBp65 overexpression in NS rats. Concomitantly, TNF-α, IL-6, and IL-1ß levels, which are indicators of immunological and informatory responses, were also decreased after NAC treatment. CONCLUSIONS: NAC treatment ameliorated nephrotic syndrome in NS rat models by suppressing TLR4 signaling, as well as immunological and inflammatory responses.

Pachymic acid ameliorates sepsis-induced acute kidney injury by suppressing inflammation and activating the Nrf2/HO-1 pathway in rats.

OBJECTIVE: To investigate the protective effects and underlying mechanisms of pachymic acid (PA) on sepsis-induced acute kidney injury (AKI). MATERIALS AND METHODS: Sepsis-induced AKI model was made by cecal ligation and puncture (CLP) surgery in SD rats. Animals were randomly divided into 5 groups: a sham group, a CLP group, and three PA-treated groups, which received intraperitoneal injection of PA at the dosage of 5, 20 and 50 mg/kg.bw, respectively. Kidney index, Cre and BUN contents were determined to evaluate the renal function. Pathological changes of kidney tissue were observed by HE staining. Levels of inflammatory mediators (TNF-α, IL-6) were measured to assess the inflammation in renal tissue. Moreover, the expression levels of iNOS, Nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were studied by Real-time PCR and Western blot. RESULTS: PA treatment can significantly decrease the kidney index, and notably drop the contents of Cre and BUN. Renal pathological damage was also found to be effectively improved by PA in a dose-dependent manner. PA treatment was observed to inhibit the renal inflammation by reducing the TNF-α and IL-6 levels. Besides, PA treatment significantly decreased the expression levels of iNOS, and enhanced the expression of Nrf2 and HO-1 in the kidney. CONCLUSIONS: PA had potential therapeutic effects on sepsis-induced AKI in rats, and the activity may be associated with the anti-inflammatory function and antioxidant effect via activating Nrf2/ HO-1 pathway.

Gefitinib compared with systemic chemotherapy as first-line treatment for chemotherapy-naive patients with advanced non-small cell lung cancer: a meta-analysis of randomised controlled trials.

To define the efficacy of gefitinib in chemotherapy-naive patients with advanced non-small cell lung cancer, we carried out a meta-analysis of randomised controlled trials. Medline, Embase, the Cochrane controlled trials register and the Science Citation Index were searched. Seven trials were identified, covering a total of 4656 subjects. As compared with chemotherapy, gefitinib was effective in the selected patients: the corresponding summary hazard ratios (gefitinib versus chemotherapy) for progression-free survival were 0.43 (0.32, 0.58) (P < 0.001) for the subgroup of patients with epidermal growth factor receptor (EGFR) mutant treated with gefitinib monotherapy, 0.71 (0.60, 0.83) (P < 0.001) for the subgroup of patients with lung adenocarcinoma; but was detrimental for the patients without EGFR mutant treated by gefitinib monotherapy [hazard ratio = 2.16 (1.17, 3.99), P = 0.01]. Significantly improved survival was found in the gefitinib group compared with the control in the subgroup of patients with lung adenocarcinoma [hazard ratio = 0.89 (0.81, 0.99); P = 0.03], but not found in the subgroup of patients with EGFR mutant [hazard ratio = 0.87 (0.68, 1.12); P = 0.28]. In conclusion, first-line treatment with gefitinib conferred prolonged progression-free survival than treatment with systemic chemotherapy in a molecularly or histologically defined population of patients with non-small cell lung cancer, and improved survival in the subgroup of patients with lung adenocarcinoma.

Effects of berberine on intracellular free calcium in smooth muscle cells of Guinea pig colon.

AIM: To investigate the effects and mechanism of berberine (Ber) on the intracellular free calcium concentration ([Ca(2+)](i)) in the smooth muscle cells of guinea pig colon. METHODS: The changes of [Ca(2+)](i) were assayed by the biwavelength spectrophotometry with Fura 2-AM in the cell suspension of the smooth muscle cells, which were freshly isolated from guinea pig colon. RESULTS: In the resting state, [Ca(2+)](i) in the HEPES-Ringer solution (CaCl(2) 1.5 mmol.l(-1)) was (108 +/- 9.4) nmol.l(-1) (n = 7). Ber had no significant effects on the resting [Ca(2+)](i), but markedly inhibited the increase in [Ca(2+)](i )induced by 60 mmol.l(-1) KCl in a concentration-dependent manner. The value of IC(50 )was 34.09 micromol.l(-1). 30 and 100 micromol.l(-1) Ber also inhibited the elevation of [Ca(2+)](i) evoked by 10 micromol.l(-1) Ach in a dose-dependent fashion in the presence or absence of extracellular Ca(2+). In addition, Ber inhibited the elevation of [Ca(2+)](i) stimulated by cyclopiazonic acid (CPA) in a dose-dependent manner. This effect was more potent in the HEPES-Ringer solution (IC(50) = 37.79 micromol.l(-1)) than Ca(2+)-free medium (IC(50) = 49.70 micromol.l(-1)). CONCLUSIONS: Ber possessed an inhibitory effect on the influx of extracellular Ca(2+) and Ca(2+)-release from intracellular stores in the smooth muscle cells of colon. That is to say Ber may be a blocker of Ca(2+) channels.

[Effects of berberine on intracellular calcium concentration in smooth muscle cells of guinea pig colon].

The purpose of the present investigation is to study how berberine (Ber) affect the intracellular free calcium concentration ( Ca(2+) (i)) of the smooth muscle cells of guinea pig colon by means of biwavelength spectrophotometry with Fura 2 AM in a cell suspension specimen. In the resting state, Ca(2+) (i) in HEPES Ringer solution (CaCl2 1.5 mmol/L) was 108 9.4 nmol/L (n=7), which was not significantly affected by Ber. On the other hand, Ber inhibited the increased Ca(2+) (i) induced by 60 mmol/L KCl in a dose dependent manner, with a value of IC(50) being 34.09 micromol/L. 30, 100 micromol/L Ber also inhibited 10 micromol/L ACh evoked Ca(2+) (i) elevation in a dose dependent manner either in the presence or absence of extracellular Ca(2+). In addition, Ber inhibited cyclopiazonic acid (CPA) stimulated Ca(2+) (i) elevation dose dependently. This effect was more potent in HEPES Ringer solution (IC(50)=37.79 micromol/L) than in Ca(2+) free medium (IC(50)=49.70 micromol/L). The above results suggest that Ber exerts an inhibitory effect on the extracellular Ca(2+) influx and the Ca(2+) release from intracellular stores.