[Analysis of the clinical predictive value of lactate on the prognosis of patients with acute-on-chronic liver failure combined with infection].

Objective: To explore the predictive value of lactic acid for the adverse prognostic outcomes in patients with acute-on-chronic liver failure combined with infection. Methods: A retrospective analysis was conducted on the clinical data of 208 cases of ACLF combined with infection who were hospitalized from January 2014 to March 2016. Patients were divided into a survival group (n = 83) and a mortality group (n = 125) according to the results of a 90-day follow-up. The clinical data were statistically analyzed between the two groups. Multivariate logistic regression with two categorical variables was used to analyze the independent risk factors for 90-day disease mortality and establish a new prediction model. The receiver operating characteristic curve (ROC curve) was used to evaluate the predictive value of lactic acid, the MELD score, the MELD-Na score, lactic acid combined with the MELD score, lactic acid combined with the MELD-Na score, and the new model. Results: The 90-day mortality rate of 208 cases of ACLF combined with infection was 60.1%. There were statistically significant differences in white blood cell count, neutrophil count, total bilirubin (TBil), serum creatinine (Cr), blood urea nitrogen (BUN), blood ammonia, the international normalized ratio (INR), lactic acid (LAC), procalcitonin, the MELD score, the MELD-Na score, hepatic encephalopathy (HE), acute kidney injury (AKI), and bleeding between the two groups. Multivariate logistic regression analysis showed that TBil, INR, LAC, HE, and bleeding were independent risk factors for 90-day mortality in patients with ACLF combined with infection. After the establishment of MELD-LAC, MELD-Na-LAC, and a new prediction model, the ROC curve revealed that the AUC (95% confidence interval) of MELD-LAC and MELD-Na LAC were 0.819 (0.759 ~ 0.870) and 0.838 (0.780 ~ 0.886), respectively, and was superior than the MELD score [0.766 (0.702 ~ 0.823)] and MELD-Na score [0.788 (0.726 ~ 0.843)], with P < 0.05, while the new model had an AUC of 0.924, the sensitivity of 83.9%, specificity of 89.9%, and accuracy of 87.8%, which was higher than LAC, MELD score, MELD-Na score, MELD-LAC, and MELD-Na-LAC (P < 0.01). Conclusion: Lactic acid is an independent risk factor for mortality in patients with ACLF combined with infection, and it improves the clinical predictive value of MELD and MELD-Na for the prognosis of mortality.

[Five-year clinical outcomes of patients with in-stent chronic total occlusion undergoing percutaneous coronary intervention].

Objective: To evaluate the safety and long-term clinical efficacy of percutaneous coronary intervention (PCI) in patients with in-stent chronic total occlusion (IS-CTO) lesions. Metheds: This is a retrospective analysis. Patients with IS-CTO who underwent PCI in Fuwai hospital from January 2010 to December 2013 were enrolled. A total of 212 patients who met the inclusion criteria were included in the IS-CTO group, 212 matched patients with primary CTO lesions were included in the de novo CTO group. The incidence of complications and the success rate of PCI were compared between the two groups. Successful PCI was defined as successfully implantation of stent(s) at target CTO lesions. The primary endpoint was defined as a composite event of cardiac death and myocardial infarction (MI). Secondary endpoints including PCI success, all-cause death, cardiac death, MI, target vessel related MI, revascularization, target vessel revascularization, heart failure for rehospitalization. The patients were followed up for 5 years after PCI. Results: A total of 424 cases were included. The mean age was (57.8±10.5) years, there were 364 males in this cohort. The left ventricular ejection fraction was significantly lower ((58.7±9.2)% vs. (61.0±7.7)%, P=0.01) and the SYNTAX scores was significantly higher (19.4±8.3 vs. 15.3±10.0, P<0.01) in IS-CTO group than that in de novo CTO group. The proportion of patients with target CTO lesions in left anterior descending artery was significantly higher (42.9% (50/212) vs. 23.6% (91/212), P<0.01) in IS-CTO group than that in de novo CTO group. The rate of successful PCI (71.7% (152/212) vs. 69.8% (148/212), P=0.70) and complication (40.6% (86/212) vs. 36.3% (77/212), P=0.37) was similar between the two groups. The incidence of primary endpoint at 5 years was significantly higher in IS-CTO group (10.8% (23/212) vs. 4.7% (10/212), P=0.02), which was driven by higher incidence of MI (9.0% (19/212) vs. 4.2% (9/212), P=0.05). There were a trend of higher secondary endpoints in IS-CTO group (all P>0.05). Conclusion: The safety and effectiveness of PCI are acceptable in patients with IS-CTO, but the risk of long-term cardiac death and MI is higher among patients with IS-CTO as compared to patients with primary CTO lesions.

[The safety and efficacy of Firesorb bioresorbable scaffold in first-in-man study for coronary artery disease: the four-year outcomes].

Objective: To evaluate the 4-year clinical outcomes of patients following Firesorb bioresorbable scaffold (BRS) implantation. Methods: The study reported the 4-year follow-up results of the FUTURE I study. FUTURE I was a prospective, single-center, open-label, first-in-man study which evaluated the feasibility, preliminary safety, and efficacy of Firesorb stent in the treatment of coronary artery stenosis. A total of 45 patients with single de novo lesions in native coronary arteries ,who hospitalized in Fuwai Hospital from January to March 2016 were enrolled. After successfully stent implantation these patients were randomized in a 2∶1 ratio into cohort 1 (n=30) or cohort 2 (n=15). The patients in cohort 1 underwent angiographic, IVUS or OCT examination at 6 months and 2 years; and cohort 2 underwent angiographic, IVUS or OCT at 1 and 3 years. All patients underwent clinical follow-up at 1, 6 months and 1 year and annually thereafter up to 5 years. The primary endpoint was target lesion failure (TLF, including cardiac death, target vessel myocardial infarction, and ischemia-driven target lesion revascularization). Secondary endpoints included patient-oriented composite endpoint (PoCE, defined as composite of all death, all miocardial infarction, or any revascularization). Results: A total of 45 patients were enrolled and implanted with Firesorb BRS, including 35 males (77.8%), and the age was (54.4±9.3) years. At 4 years, 10 patients in cohort 1 were reexamined by coronary angiography and OCT examination. Among them, 2 patients' stents were completely degraded and absorbed. Compared with the OCT images of the other 8 patients in cohort 2 at 3 years, the degree of stent degradation was increased, and no stent adherence was found. The 4-year clinical follow-up rate was 100%. In 4-year clinical following up, 2 patients suffered PoCE (4.4%): 1 patient underwent non-target vessel revascularization the day after index procedure and target vessel revascularization (Non-target lesion revascularization) at 2-year imaging follow-up; the other patient underwent target lesion revascularization during imaging follow-up at 4 years but not due to ischemic driven. There was no scaffold thrombosis or TLF events through 4 years. Conclusions: Four years after the implantation, complete degradation and absorption of the Firsorb stent are evidenced in some patients. Firesorb stent is feasible and effective in the treatment of patients with non-complex coronary lesions.

[Clinical characteristics of infection-induced acute renal injury in acute-on-chronic liver failure].

Objective: To investigate the incidence rate, influencing factors and prognosis of infection-induced acute renal injury (AKI) in patients with acute-on-chronic liver failure (ACLF). Methods: 516 cases with acute-on-chronic liver failure complicated with infection that were hospitalized in our hospital during 2014 to 2016 were retrospectively studied. General conditions and clinical characteristics of the patients were collected, and grouped according to the presence or absence of incidence and severity of AKI. General conditions, laboratory results, occurrence of complications and survival were compared and analyzed. Results: The main causes were HBV infection (67.8%) and alcoholic liver disease (20.0%). The most common sites of infection were abdominal cavity, lung and blood. Multivariate analysis showed that neutrophil count, TBIL, lactate and septic shock were independent risk factors for infection-induced AKI in ACLF patients. The cumulative mortality in patients with AKI after infection at 28, 90 and 360 days was significantly higher than those without AKI (51.6% and 20.5%, 70.2% and 40.3%, 73.4% and 45.9%; P < 0.01). In both groups, deaths had occurred mainly in the early (0 ~ 28 d) and middle (29 ~ 90 d) stage of follow-up period. In the late follow-up period (91-360 d), there was no statistically significant difference in mortality rate between the two groups. Conclusion: Infection is an important inducing cause of AKI in ACLF patients. The underlying liver disease and the severity of infection are significantly related to the infection-induced AKI in ACLF patients, and once AKI occurs after infection, the mortality rate of the patients is significantly increased.

[Long-term outcomes of patients with ST-elevation myocardial infarction undergoing early versus late delayed percutaneous coronary intervention using drug-eluting stents].

Objective: To compare the long-term outcomes in ST-elevation myocardial infarction (STEMI) patients who underwent early or late delayed percutaneous coronary intervention (PCI) using drug-eluting stents (DES). Methods: This study was a retrospective, observational and single-center study. Consecutive STEMI patients (n=977), who admitted to Fuwai Hospital in 2013 and underwent successful selective PCI using drug-eluting stents (DES) within 3 to 35 days after symptom onset were enrolled and divided into the early delayed PCI (3-14 d) group (n=495) and the late delayed PCI (15-35 d) group (n=482). General clinical data of the patients and related data of coronary angiography and interventional therapy were collected, and the endpoint events were followed up. The primary endpoint was 2-year major adverse cardiac and cerebrovascular events (MACCE) including cardiac death, recurrent myocardial infarction, definite or probable stent thrombosis and ischemic stroke. The secondary endpoint was 2-year ischemia-driven target vessel revascularization. The incidence of endpoint events of the two groups was compared, and it was compared again after the primary baseline characteristics such as age and gender were matched by the propensity scoring method at a 1∶1 ratio. Results: A total of 910 (93.1%) patients who underwent delayed PCI were transferred from other hospitals, and 292 (29.9%) patients received thrombolysis before PCI. The time interval before PCI was 14 (10, 20) days. The incidence of 2-year MACCE (3.0%(15/495) vs. 2.3%(11/482), P=0.468) and ischemia-driven target vessel revascularization (3.8%(19/495) vs. 5.0%(24/482), P=0.385) were similar between the two groups. The incidence of 2-year MACCE (3.3%(15/453 vs. 2.4%(11/453), P=0.426) and ischemia-driven target vessel revascularization (4.2% (19/453) vs. 4.9%(22/453), P=0.632) were also similar between the two groups after matching propensity score. Conclusion: The long-term clinical outcomes after early delayed PCI using DES is statistically equivalent to those of late delayed PCI using DES for STEMI patients who missed the time window for emergency PCI.

[Prognostic value of SYNTAX score on 1 year outcome in patients underwent percutaneous coronary intervention].

Objective: To investigate the prognostic value of SYNTAX score on 1 year outcome in coronary heart disease patients underwent percutaneous coronary intervention(PCI). Methods: The present study (PANDA Ⅲ trial) was a perspective, multi-center, randomized controlled trial. Between December 2013 and August 2014, 2 348 patients who underwent PCI from 46 centers were enrolled. SYNTAX score was calculated from all patients. Patients were divided into 3 groups based on SYNTAX score: lower risk group (SYNTAX score≤22, 1 777 patients), intermediate risk group (SYNTAX score 23-32, 412 patients), and higher risk group (SYNTAX score≥33, 159 patients). The patients were followed up after the procedure for one year.Primary endpoint was target lesion failure (TLF), including cardiac death, target vessel myocardial infarction,and ischemia driven target lesion revascularization. Secondary endpoints included stent thrombosis and major adverse cardiac events were defined as a composite of all-cause death, myocardial infarction and any revascularization. Results: (1) A total of 1 766 (99.2%), 411 (99.8%),and 159 (100%) patients in the lower risk group, intermediate risk and higher risk group completed the 1 year follow up. (2) Incidence of TLF were 5.6%(99/1 763) in lower risk group, 8.8%(36/411) in intermediate risk group,and 8.8%(14/159) in higher risk group(P=0.03). The incidence of target vessel myocardial infarction in lower risk group was 3.9%(68/1 763), 6.6%(27/411) in intermediate risk group,and 7.5% (12/159) in higher risk group(P=0.01).Prevalence of cardiac death and ischemia driven target lesion revascularization was similar among the 3 groups(P>0.05).(3) The probable stent thrombosis events rate was 0.1% (1/1 763), 0.7% (3/411), and 0.6% (1/159) in the lower, intermediate,and higher risk groups respectively (P=0.02). The incidence of major adverse cardiac events was 8.1% (142/1 763) in lower-risk group, 11.7% (48/411) in intermediate risk group, and 14.5% (23/159) in higher risk group (P<0.01). The incidence of all-cause death was 1.7%(30/1 763) in lower-risk group, 1.7%(7/411) in intermediate risk group, and 6.3%(10/159)in higher risk group (P<0.01). The incidence of myocardial infarction was 4.2% (74/1 763) in lower-risk group, 6.6% (27/411) in intermediate risk group, and 8.2% (13/159) in higher risk group(P=0.02).Incidence of any revascularization was similar among groups(P=0.59). (4) The multivariable Cox analysis showed that age (HR=1.04, 95%CI 1.02-1.06, P<0.01), total implanted stent length (HR=1.01, 95%CI 1.00-1.02, P=0.03), and baseline SYNTAX score (HR=1.02, 95%CI 1.02-1.04, P=0.02) were independent risk factors of TLF after PCI in this patient cohort. Conclusion: The SYNTAX score is a valuable tool for predicting prognosis on 1 year in coronary heart disease patients underwent PCI. Trial Registration www.clinicaltrials.gov, NCT02017275.

[Long term safety and efficacy of a novel abluminal groove-filled biodegradable polymer sirolimus-eluting stent for the treatment of coronary de novo lesions].

Objective: To compare the long term safety and efficacy of the novel abluminal groove-filled biodegradable polymer sirolimus-eluting stent(Firehawk stent) and permanent polymer coating everolimus eluting stent(Xience V stent) for the treatment of coronary de novo lesions. Methods: This prospective, multi-center, non-inferiority, randomized control trial(TARGETⅠ trial) was performed between August 2010 and April 2011, a total of 460 patients with primary, de novo, single vessel and single coronary lesion from 16 medical centers were enrolled. The diameter stenosis of target lesion was ≥70%, and lesion length was≤24 mm. The patients were randomly assigned to treatment with Firehawk stent (Firehawk stent group) or Xience V stent (Xience V stent group) groups by a web-based allocation system and was stratified by center. The late lumen loss after 9 months, target lesion failure (TLF) which was a composite of cardiac death, target vessel myocardial infarction, or ischemia driven target lesion revascularization, patient-oriented composite endpoint (PoCE) which was a composite of all cause death, all cause myocardial infarction, or any revascularization, and stent thrombosis after 5 years were compared between the two groups. Results: (1) There were 2 patients without stent implantation dropped out of this trial. There were 227 patients in Firehawk stent group, and 231 patients in Xience V stent group. The baseline characteristics were similar between the two groups(all P>0.05). (2) The 9 months late lumen loss in Firehawk stent group was non-inferior to that in Xience V stent group ((0.13±0.24)mm vs. (0.13±0.18)mm, P=0.94). (3) A total of 442 (96.5%) patients completed 5 years clinical follow-up. There were no significant differences on 5-year TLF rate (6.0%(13/217) vs. 6.7% (15/225), P=0.77) and PoCE rate (12.0%(26/217) vs. 17.8% (40/225), P=0.09) between the Firehawk stent group and Xience V stent group. (4) Kaplan-Meier analysis showed that TLF rates between 1-5 years were similar in Firehawk stent group and Xience V stent group (5.7% and 6.6% respectively, HR=0.88, 95%CI 0.42-1.84, P=0.72). Land-Mark analysis showed that TLF rates bewteen 1-5 years were similar in Firehawk stent group and Xience V stent group (3.6% and 4.4% respectively, HR=0.83, 95%CI 0.34-2.00, P=0.67). Kaplan-Meier analysis showed that PoCE rates between 1-5 years were also similar in Firehawk stent group and Xience V stent group (11.4% and 17.3% respectively, HR=0.64, 95%CI 0.39-1.04, P=0.07). Land-Mark analysis showed that PoCE rates after 5 years were similar in Firehawk stent group and Xience V stent group (8.4% and 10.0% respectively, HR=0.66, 95%CI 0.40-1.10, P=0.11). (5) No stent thrombosis was documented in Firehawk stent group during the 5 years follow-up period, and there was 1 case of stent thrombosis in Xience V stent group after 3 years of stent implantation. Conclusion: TARGETⅠ trial results of 5 years follow up indicate the novel Firehawk stent have a durable safety and efficacy profile which is comparable to the Xience V stent in treating patients with single de novo coronary lesion. Clinical Trial Registration North American Clinical Trial Registration Center, NCT01196819.

An Escherichia coli vector to express and purify foreign proteins by fusion to and separation from maltose-binding protein.

A plasmid vector has been constructed that directs the synthesis of high levels (approximately 2% of total cellular protein) of fusions between a target protein and maltose-binding protein (MBP) in Escherichia coli. The MBP domain is used to purify the fusion protein in a one step procedure by affinity chromatography to crosslinked amylose resin. The fusion protein contains the recognition sequence (Ile-Glu-Gly-Arg) for blood coagulation factor Xa protease between the two domains. Cleavage by factor Xa separates the two domains and the target protein domain can then be purified away from the MBP domain by repeating the affinity chromatography step. A prokaryotic (beta-galactosidase) and a eukaryotic (paramyosin) protein have been successfully purified by this method.

Analysis of regulation of phoB expression using a phoB-cat fusion.

The phoB gene, which encodes a positive control factor for a number of phosphate-regulated genes in Escherichia coli, was cloned into multicopy plasmid pBR322. A phoB-cat fusion that expressed chloramphenicol transacetylase from the phoB promoter was constructed. Studies of the expression of the phoB-cat fusion showed that the pattern of regulation of the phoB gene was similar to that of the phoA gene, the structural gene for alkaline phosphatase. The phoB gene was derepressed under conditions of phosphate starvation, was constitutively expressed in a phoR background, and required the phoM gene product for expression in a phoR strain. Finally, a functional phoB product was required for its own synthesis. Our results indicate either that phoA gene expression responds directly to the concentration of the phoB gene product in cells or that the phoA and phoB controlling elements are quite similar.