Objective To evaluate the bioequivalence of the test preparation and reference preparation of azithromycin capsules in healthy Chinese subjects.Methods A total of 48 subjects were enrolled in this study using a randomized,open,two-sequence,cross design.Each subject received a single oral dose of azithromycin capsules test drug(T)or reference drug(R)for 250 mg.The concentrations of azithromycin in plasma were determined by Liquid Chromatograph Mass Spectrometer,and the pharmacokinetic parameters were calculated by WinNonlin 8.1 software to evaluate the bioequivalence.Results The main pharmacokinetic parameters of azithromycin after a single fasting dose of the test drug and the reference drug were as follows:the Cmax were respectively(319.89±127.35)and(330.41±122.11)ng·mL-1;AUC0-192h were respectively(2 423.04±587.15)and(2 489.97±685.73)ng·h·mL-1;AUC0-∞ were respectively(2 753.40±644.96)and(2 851.71±784.05)ng·h·mL-;tmax were respectively(2.60±1.11)and(2.62±1.13)h;t1/2 were respectively(76.76±15.14)and(79.83±17.14)h.The 90％confidence intervals for the geometric mean ratios of Cmax,AUC0-192h and AUC0-∞ of T and R were 87.52％-107.18％,91.46％-105.80％and 91.17％-105.06％,respectively.Conclusion The test preparation of azithromycin capsule was bioequivalent to the reference preparation under fasting condition.

Objective To design a novel oxygenator to solve the existing problems of extracorporeal membrane oxygenation(ECMO)machine in high transmembrane pressure difference,low efficiency of blood oxygen exchange and susceptibility to thrombosis.Methods The main body of the oxygenator vascular access flow field was gifted with a flat cylindrical shape.The topology of the vascular access was modeled in three dimensions,and the whole flow field was cut into a blood inlet section,an inlet buffer,a heat exchange zone,a blood oxygen exchange zone,an outlet buffer and a blood outlet section.The oxygenator was compared with Quadrox oxygenator by means of ANSYS FLUENT-based simulation and prototype experiments.Results Simulation calculations showed the oxygenator designed was comparable to the clinically used ones in general,and gained advantages in transmembrane pressure difference,blood oxygen exchange and flow uniformity.Experimental results indicated that the oxygenator behaved better than Quadrox oxygenator in transmembrane pressure difference and blood oxygen exchange.Conclusion The oxygenator has advantages in transmem-brane pressure difference,temperature change,blood oxygen ex-change and low probability of thrombosis.[Chinese Medical Equipment Journal,2024,45(3):23-28]

OBJECTIVETo investigate the differences of metabolic pathways of leucocyte-deplated RBCs prepared by using lipid whole blood and nomal blood during routine storage so as to provide some reference for clinical blood use.

METHODSTwenty U whole blood from 20 donors, including 10 U lipid blood and 10 U normal whole blood, were selected for preparing leukodepleted red blood cells, red blood cells were taken from storage bags on day 0, 14 and 35, respectively. Metabolites in the red blood cells were analyzed, red blood cell metabolic extracts were detected by UPLC-MS/MS. The metabolite data of RBC from 2 groups were analyzed by SIMCA-P 13.0 software using OPLS-DA and by SPSS 19.0 using Mann-Whitney U test. Difference of metabolic pathways was described according to different metabolites.

RESULTSThe glucose, adenine, pyruvic acid, GSH, GSSG and niacinamide levels on day 0 in lipid RBCs were higher than those in the control group(P<0.05). The glucose, pyruvic acid and GSH levels on day 14 in lipid RBCs were lower than those in the control group (P<0.05), and the levels of adenine, GSSG and niacinamide were higher than that in the control group (P<0.05). The glucose level on day 0 was lower than that in the control group (P<0.05), and the levels of adenine and niacinamide were higher than those in the control group (P<0.05). but the pyruvic acid, GSH and GSSG levels were not significantly different between 2 groups (P>0.05).

CONCLUSIONCompared with the normal red blood cells, the energy metabolism pathway decreases in lipid red blood cells within the storage period and pentose phosphate pathway increases.

Blood Preservation ; Erythrocytes ; Glucose ; Humans ; Lipids ; Tandem Mass Spectrometry

Objective To evaluate the cytotoxicity of natural killer(NK)-92 cell lines against various human hepatocellular carcinoma cells(HCCs)and to explore the potential mechanism.Methods We established a culture method of NK-92 cell lines in vitro.Lactate debydrogenase(LDH)cytotoxicity assays and cytokine release assays were performed to determine whether NK-92 cell lines could recognize and kill HCCs in vitro.At the same time,Nu/Nu mices were housed. Subcutaneous(sc)xenografts HepG2 models of human hepatocellular carcinoma were established.1×107NK-92 cells were intravenously(iv)injected through the tail vein on days 2,9,16,23 while the control group was injected with PBS in the same way.Tumor size, tumor volume, tumor mass and mouse survival status were closely observed in experimental and control groups.Mice were euthanized when tumor-bearing time reached 28 days.Xenograft tissues were taken for general observation.Sections were cut and processed for HE staining and immunofluorescence staining.The expression of glypican-3(GPC3)protein in xenografts tissue was clearly defined.Results NK-92 cell lines that were chronically cultured in vitro and maintained typical phenotypic characteristics of NK cells with good cellular activity.Enhanced cytotoxicity and IFN-γ production of NK-92 cell lines were identified by LDH and ELISA,indicating that NK-92 cell lines could recognize and kill different kinds of HCCs.In addition,NK-92 cell lines efficiently suppressed the growth of HCC xenografts in vivo.Tumor volume in experimental group was significantly reduced compared with control group and there was low a GPC 3 expression in experimental group through immunofluorescence and immunohistochemistry results, pointing to the possibility that the cytotoxicity of NK cells was correlated with GPC3 +HCCs.Conclusion NK cells provide a promising means of therapeutic intervention for HCCs.NK-92 cell lines could eliminate HCC cells in vitro and in vivo.The cytotoxicity of NK-92 cell lines may work by killing the GPC3-positive cells in the liver cancer tissue.In addition to the anti-tumor effect, NK cells also have cytotoxicity on pathogens such as bacteria and viruses.

Objective To study the clinical efficacy and safety of arthroscopic minimally invasive surgery applied in tibial plateau fracture. Method 50 patients with tibial plateau fracture from Jan 2014 to Jan 2016 were randomly divided into control group (traditional surgery) and observation group (arthroscopic minimally invasive surgery) according to the random number method, 25 patients in each. The surgery condition, postoperative complications and function recovery of knee joint were observed and compared. Results Compared with the control group, the operation time, intraoperative blood loss, ambulation time, weight-bearing ambulation time, and postoperative drainage volume were significantly decreased in observation group with statistical difference (P < 0.05); compared with the control group, the incidence of postoperative complications such as postoperative wound infection, malunion, traumatic arthritis, knee joint stiffness was obviously reduced in the observation group with statistical difference (P < 0.05); compared with the control group, the excellent rates of knee joint function score and radio-graphic score were significantly increased in the observation group with statistical difference (P < 0.05). Conclusion The arthroscopic minimally invasive surgery can significantly reduce the incidence of postoperative complications for patients with tibial plateau fracture and is beneficial to the recovery of knee joint function with higher clinical efficacy and treatment safety.

OBJECTIVETo investigate the clinical effect of fast-track surgery combined with Chinese medicine treatment in devascularization operation for cirrhotic esophageal varices.

METHODSSeventy-two patients with cirrhotic esophageal varices were selected from January 2009 to June 2013, and randomly assigned to a conventional group and a fast-track group (fast-track surgery combined with Chinese medicine treatment) using a randomized digital table, 36 cases in each group. Operation and anesthesia recovery time, postoperative hospitalization and quality of life were recorded and compared between groups during the perioperative period.

RESULTSCompared with the conventional group, the fast-track group had longer operation time (253.6±46.4 min vs. 220.6±51.0 min) and anesthesia recovery time (50.5±15.9 min vs. 23.5±9.6 min; P<0.01); less bleeding (311.3±46.8 mL vs. 356.2±57.5 mL; P<0.01) and less transfusion (1932.3±106.9 mL vs. 2045.6±115.4 mL; P<0.01); as well as faster recovery of gastrointestinal function, shorter postoperative hospitalization and higher quality of life. There were no serious postoperative complications and no further bleeding occurred.

CONCLUSIONFast-track surgery combined with Chinese medicine treatment is a safe and feasible approach to accelerate the recovery of patients with cirrhotic portal hypertension in perioperative period of devascularization operation.

Adult ; Aged ; Anesthesia Recovery Period ; Blood Loss, Surgical ; Blood Transfusion ; Chronic Disease ; Esophageal and Gastric Varices ; surgery ; therapy ; Female ; Humans ; Length of Stay ; Liver Cirrhosis ; complications ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Operative Time ; Postoperative Complications ; Postoperative Period ; Quality of Life ; Splenectomy

BACKGROUNDIn vivo quantification of choroidal neovascularization (CNV) based on noninvasive optical coherence tomography (OCT) examination and in vitro choroidal flatmount immunohistochemistry stained of CNV currently were used to evaluate the process and severity of age-related macular degeneration (AMD) both in human and animal studies. This study aimed to investigate the correlation between these two methods in murine CNV models induced by subretinal injection.

METHODSCNV was developed in 20 C57BL6/j mice by subretinal injection of adeno-associated viral delivery of a short hairpin RNA targeting sFLT-1 (AAV.shRNA.sFLT-1), as reported previously. After 4 weeks, CNV was imaged by OCT and fluorescence angiography. The scaling factors for each dimension, x, y, and z (μm/pixel) were recorded, and the corneal curvature standard was adjusted from human (7.7) to mice (1.4). The volume of each OCT image stack was calculated and then normalized by multiplying the number of voxels by the scaling factors for each dimension in Seg3D software (University of Utah Scientific Computing and Imaging Institute, available at http://www.sci.utah.edu/cibc-software/seg3d.html). Eighteen mice were prepared for choroidal flatmounts and stained by CD31. The CNV volumes were calculated using scanning laser confocal microscopy after immunohistochemistry staining. Two mice were stained by Hematoxylin and Eosin for observing the CNV morphology.

RESULTSThe CNV volume calculated using OCT was, on average, 2.6 times larger than the volume calculated using the laser confocal microscopy. The correlation statistical analysis showed OCT measuring of CNV correlated significantly with the in vitro method (R 2 =0.448, P = 0.001, n = 18). The correlation coefficient for CNV quantification using OCT and confocal microscopy was 0.693 (n = 18, P = 0.001).

CONCLUSIONSThere is a fair linear correlation on CNV volumes between in vivo and in vitro methods in CNV models induced by subretinal injection. The result might provide a useful evaluation of CNV both for the studies using CNV models induced by subretinal injection and human AMD studies.

Animals ; Choroidal Neovascularization ; pathology ; physiopathology ; Disease Models, Animal ; Fluorescein Angiography ; Humans ; Mice ; Mice, Inbred C57BL ; Tomography, Optical Coherence

OBJECTIVETo study the toxicity of methomyl to acetylcholinesterase (AChE) in different regions.

METHODSThe optimal temperature and time for measurement of AChE activity were determined in vitro. The dose- and time-response relationships of methomyl with AChE activity in human erythrocyte membrane, rat erythrocyte membrane, cortical synapses, cerebellar synapses, hippocampal synapses, and striatal synapses were evaluated. The half maximal inhibitory concentration (IC50) and bimolecular rate constant (K) of methomyl for AChE activity in different regions were calculated, and the type of inhibition of AChE activity by methomyl was determined.

RESULTSAChE achieved the maximum activity at 370 °C, and the optimal time to determine initial reaction velocity was 0-17 min. There were dose- and time-response relationships between methomyl and AChE activity in the erythrocyte membrane and various brain areas. The IC50 value of methomyl for AChE activity in human erythrocyte membrane was higher than that in rat erythrocyte membrane, while the Ki value of methomyl for AChE activity in rat erythrocyte membrane was higher than that in human erythrocyte membrane. Among synapses in various brain areas, the striatum had the highest IC50 value, followed by the cerebellum, cerebral cortex, and hippocampus, while the cerebral cortex had the highest Ki value, followed by the hippocampus, striatum, and cerebellum. Lineweaver-Burk diagram demonstrated that with increasing concentration of methomyl, the maximum reaction velocity (Vmax) of AChE decreased, and the Michaelis constant (Km) remained the same.

CONCLUSIONMethomyl is a reversible non-competitive inhibitor of AChE. AChE of rat erythrocyte membrane is more sensitive to methomyl than that of human erythrocyte membrane; the cerebral cortical synapses have the most sensitive AChE to methomyl among synapses in various brain areas.

Acetylcholinesterase ; metabolism ; Animals ; Cerebellum ; drug effects ; Cerebral Cortex ; drug effects ; Erythrocyte Membrane ; drug effects ; enzymology ; Hippocampus ; drug effects ; Humans ; Inhibitory Concentration 50 ; Methomyl ; toxicity ; Rats ; Synapses ; drug effects ; Toxicity Tests

Aged, 80 and over ; Animals ; Antiviral Agents ; therapeutic use ; Humans ; Influenza, Human ; diagnosis ; drug therapy ; virology ; Male