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OBJECTIVE@#To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS).@*METHODS@#In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4.@*RESULTS@#Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group.@*CONCLUSIONS@#In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable.
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XueBiJing is an intravenous five-herb injection used to treat sepsis in China.The study aimed to develop a liquid chromatography-tandem mass spectrometry(LC-MS/MS)-or liquid chromatography-ultraviolet(LC-UV)-based assay for quality evaluation of XueBiJing.Assay development involved identifying marker constituents to make the assay therapeutically relevant and building a reliable one-point cali-brator for monitoring the various analytes in parallel.Nine marker constituents from the five herbs were selected based on XueBiJing's chemical composition,pharmacokinetics,and pharmacodynamics.A selectivity test(for"similarity of response")was developed to identify and minimize interference by non-target constituents.Then,an intercept test was developed to fulfill"linearity through zero"for each analyte(absolute ratio of intercept to C response,＜2％).Using the newly developed assays,we analyzed samples from 33 batches of XueBiJing,manufactured over three years,and found small batch-to-batch variability in contents of the marker constituents(4.1％-14.8％),except for senkyunolide I(26.5％).
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BACKGROUND@#New definitions for sepsis and septic shock (Sepsis-3) were published, but the strategy to adjust vasopressors after the initial guidelines is still unclear. We conducted a retrospective observational study to explore dosing strategy of norepinephrine (NE).@*METHODS@#A retrospective observational study in the 15-bed mixed intensive care unit of a tertiary care university hospital. The study was performed on septic shock patients after 30 mL/kg fluid resuscitation and mean arterial pressure (MAP) levels reached >65 mmHg requiring NE. We divided patients into NE dosage increase and decrease groups, and collected hemodynamic and tissue perfusion parameters before (T1) and after (T2) adjusting NE dosage.@*RESULTS@#In both NE increase and decrease groups, central venous pressure (CVP) and pressure difference between usual MAP and MAP (dMAP) at the T1 time point were associated with lactate clearance. In groups LC HM (CVP 0 mmHg) and HC HM (CVP ≥ 10 mmHg, dMAP > 0 mmHg), decrease in NE dosage decreased lactate level, while in group HC LM (CVP ≥ 10 mmHg, dMAP ≤ 0 mmHg), both increase and decrease in NE dosage led to increase lactate level.@*CONCLUSIONS@#After patients with septic shock (Sepsis-3) resuscitated to reach the initial recovery target goals, combination of CVP and MAP refer to usual levels can help doctors make the next decision to make the correct choice of increase NE dosage or decrease NE dosage.
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Background:@#New definitions for sepsis and septic shock (Sepsis-3) were published, but the strategy to adjust vasopressors after the initial guidelines is still unclear. We conducted a retrospective observational study to explore dosing strategy of norepinephrine (NE).@*Methods:@#A retrospective observational study in the 15-bed mixed intensive care unit of a tertiary care university hospital. The study was performed on septic shock patients after 30 mL/kg fluid resuscitation and mean arterial pressure (MAP) levels reached >65 mmHg requiring NE. We divided patients into NE dosage increase and decrease groups, and collected hemodynamic and tissue perfusion parameters before (T1) and after (T2) adjusting NE dosage.@*Results:@#In both NE increase and decrease groups, central venous pressure (CVP) and pressure difference between usual MAP and MAP (dMAP) at the T1 time point were associated with lactate clearance. In groups LC HM (CVP <10 mmHg, dMAP > 0 mmHg) and HC HM (CVP ≥ 10 mmHg, dMAP > 0 mmHg), decrease in NE dosage decreased lactate level, while in group HC LM (CVP ≥ 10 mmHg, dMAP≤0 mmHg), both increase and decrease in NE dosage led to increase lactate level.@*Conclusions:@#After patients with septic shock (Sepsis-3) resuscitated to reach the initial recovery target goals, combination of CVP and MAP refer to usual levels can help doctors make the next decision to make the correct choice of increase NE dosage or decrease NE dosage.
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<p><b>OBJECTIVE</b>To observe the alteration of QT dispersion (QTd) and QTc dispersion (QTcd) in hemodialysis patients after oral administration of Zhigancao Decoction (, Roasted Licorice Decoction, RLD).</p><p><b>METHODS</b>To investigate the alteration of QTd and QTcd in 68 routine hemodialysis patients before and after hemodialysis with 12-lead electrocardiogram (ECG) after orally administrated RLD for 4 weeks. Blood was also taken for measurement of plasma electrolytes, liver function, renal function, hemoglobin (Hgb) and hematocrit (HCT).</p><p><b>RESULTS</b>After hemodialysis, QTd and QTcd were prolonged evidently; the difference was significant between before and after hemodialysis (P<0.05). After RLD orally administrated for 4 weeks, QTd and QTcd only slightly increased after dialysis compared with pre-dialysis (P>0.05). The QTd and QTcd of the post-therapy-post-dialysis decreased significantly compared with the pre-therapy-post-dialysis (P<0.05). There were no other significant changes in other variables (post-therapy-pre-dialysis vs. pre-therapy-pre-dialysis, or post-therapy-post-dialysis vs. pre-therapy-post-dialysis;P>0.05). After therapy, the number of patients with supraventricular arrhythmia, occasional ventricular premature beat and multiple ventricular premature beat were decreased from 15 to 4, 10 to 2 and 7 to 1, respectively.</p><p><b>CONCLUSION</b>RLD therapy not only lowered the increased QTd and QTcd after hemodialysis, but also displayed a safety profile.</p>
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Adult , Aged , Female , Humans , Male , Middle Aged , Demography , Drugs, Chinese Herbal , Therapeutic Uses , Electrocardiography , Kidney Failure, Chronic , Drug Therapy , Renal DialysisABSTRACT
Objective To evaluate the diagnostic performance of noninvasive fractional flow reserve (FFR) derived from coronary computed tomographic angiography (CTA) (FFRCT) for functional myocardial ischemia.Methods Thirty-nine patients undergone coronary CTA and FFR examination from Aug.2012 to Jul.2015 in PLA General Hospital were retrospectively included in present study.Measurements of invasive FFR value was used as reference standard,and FFRCT based on coronary CTA image was performed in either per-patient or per-vessel level to assess the accuracy,specificity,sensitivity,the positive predictive value and negative predictive value for functional myocardial ischemia.Results In per-patient level,the accuracy of FFRCT was 82.05％,sensitivity was 83.33％,specificity was 80.95％,positive predictive value was 78.95％ and negative predictive value was 85.00％.In per-vessel level,the accuracy of FFRCT was 76.79％,sensitivity was 69.57％,specificity was 81.82％,positive predictive value was 72.73％ and negative predictive value was 79.41％.The area under ROC was 0.826 in per-patient level,and 0.786 in per-vessel level.For per-vessel,FFRCT was positively correlated with FFR value significantly (r=0.644;95％CI:0.458-0.775).Conclusion With FFR as reference standard,domestic noninvasive FFRCT can be used for the diagnosis of functional myocardial ischemia with high diagnostic performance and clinical application prospect.
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The anti-tumor activity of folate receptor targeting docetaxel-loaded membrane-modified liposomes (FA-PDCT-L) was investigated in vitro and in vivo. FA-PDCT-L was prepared by organic solvent injection method. Transmission electron microscope, dynamic light scattering and electrophoretic light scattering were employed to study the physicochemical parameters of FA-PDCT-L. The inhibitory effects of docetaxel injection (DCT-I), non-modified DCT liposomes (DCT-L) and FA-PDCT-L on the growth of MCF-7 and A-549 cells at different incubation times were detected by CCK-8 assay; and the hemolytic test was employed in vitro. Tumor mice were randomized into 4 groups: DCT-I, DCT-L, FA-PDCT-L and control group (normal saline), and given drugs at 10 mg x kg(-1) x d(-1) through tail vein. The tumor volume, mice weight, inhibition rate of tumor and life span were measured at the end of experiments. The IC50 of the FA-PDCT-L for MCF-7 and A549 cell lines were significantly lower than that of DCT-I and DCT-L, without hemolysis reaction observed. Compared with control group, the weights of tumor in DCT-I, DCT-L and FA-PDCT-L were decreased, especially for FA-PDCT-L, with inhibitory rates at 79.03 % (P < 0.05). The life span and median survival time of FA-PDCT-L treated mice were significantly higher than that of DCT-I and DCT-L. In conclusion, FA-PDCT-L shows a good anti-tumor activity, indicating that it is potential carriers for DCT in the treatment of tumor.
Subject(s)
Animals , Female , Humans , Mice , Rabbits , Antineoplastic Agents , Pharmacology , Cell Line, Tumor , Cell Proliferation , Cyanoacrylates , Chemistry , Drug Carriers , Folate Receptors, GPI-Anchored , Chemistry , Inhibitory Concentration 50 , Liposomes , Chemistry , Lung Neoplasms , Pathology , MCF-7 Cells , Neoplasm Transplantation , Particle Size , Polyethylene Glycols , Chemistry , Random Allocation , Sarcoma 180 , Pathology , Taxoids , Pharmacology , Tumor BurdenABSTRACT
A novel amphiphilic copolymer, folate-poly (PEG-cyanoacrylate-co-cholesteryl cyanoacrylate) (FA-PEG-PCHL) was synthesized as liposomal modifying material with folate receptor targeting and long circulating property. FA-PEG-PCHL-modified docetaxel-loaded liposomes (FA-PDCT-L) were prepared by organic solvent injection method, and the system was optimized using central composite design-response surface methodology. The structure of the FA-PEG-PCHL copolymer was confirmed by FT-IR and 1H NMR. Ultrafiltration technique, transmission electron microscope, dynamic light scattering and electrophoretic light scattering, and fluorescence polarization method were used to study the physicochemical parameters of FA-PDCT-L. FA-PDCT-L showed spherical or ellipsoid shape. The mean particle sizes were in the range of 111.6-126.9 nm, zeta potentials were from -6.54 mV to -14.13 mV and the drug encapsulation efficiency achieved 97.8%. The observed values agreed well with model predicted values. The membrane fluidity increased with the increment of the molecular weight of PEG and the decrement of the amount of FA-PEG-PCHL. The in vitro release test showed that the drug could be sustained-released from liposomes without a burst release and with stability for 6 months. After 24 h only 31.1%, 27.2% and 19.5% of encapsulated docetaxel were released for FA-PDCT10000-L, FA-PDCT4000-L and FA-PDCT2000-L, respectively. This work is useful for further research on the application of the synthesized copolymer-modified long circulating liposomes for cancer therapy.
Subject(s)
Antineoplastic Agents , Cholesterol Esters , Chemistry , Cyanoacrylates , Chemistry , Delayed-Action Preparations , Drug Carriers , Chemistry , Drug Delivery Systems , Folate Receptors, GPI-Anchored , Chemistry , Liposomes , Chemistry , Molecular Weight , Particle Size , Polyethylene Glycols , Chemistry , Polymers , Chemistry , TaxoidsABSTRACT
Oxaliplatin-loaded nanostuctured lipid carriers (OP-NLC) were prepared by ultrasonic emulsification method. And its optimal prescription was selected by orthogonal design. The laser light scattering technique, zeta potential analyzer, TEM, DSC, XRD and HPLC were employed to study the physicochemical parameters of OP-NLC, which displayed in terms of particle size, zeta potential, crystalline, drug loading and encapsulation efficiency. The results showed that OP-NLC had an average diameter of (111 +/- 20) nm, zeta potential of (-27.4 +/- 13.1) mV, encapsulation efficiency of (77.4 +/- 2.5) % and drug content of (0.8 +/- 1.5) mg mL(-1). TEM, DSC and XRD indicated that OP-NLC was spherical and the drug was dispersed as nanoparticles by means of non-crystalline. The in vitro release test showed that the drug could be sustained-released from NLC in buffer solution (pH 4.5) after a burst release in initial phase.