Objective To observe the effects of Yiqi Huoxue Prescription in regulating METTL3/HAND2/TGF-β1 signaling axis on rats with qi deficiency and blood stasis syndrome of coronary heart disease.Methods Totally 48 male SD rats were randomly divided into sham-operation group,model group,Yiqi Huoxue Prescription group and Western medicine(isosorbide mononitrate)group,with 12 rats in each group.Except for the sham-operation group,the animal models of coronary heart disease with qi deficiency and blood stasis syndrome were prepared by the method of ligation of the left anterior descending branch of coronary artery combined with swimming exhaustion.After modeling,Yiqi Huoxue Prescription group and the Western medicine group were gavaged for 28 d.The general conditions of the rats were observed,and electrocardiograms and echocardiograms were collected to detect the cardiac function of the rats,blood rheology was used to detect the degree of blood stasis,HE staining was used to observe the morphology of myocardial tissue,immunohistochemistry was used to detect the expression of METTL3,TGF-β1,Smad2 and Smad3 in myocardial tissue,RT-PCR and Western blot were used to detect the expression of METTL3,HAND2,TGF-β1,Smad2 and Smad3 mRNA and protein in myocardial tissue.Results Compared with the sham-operation group,the model group rats showed symptoms of qi deficiency such as mental lethargy,slow movement,drowsiness,and decreased body mass,significant elevation of ST segment on electrocardiogram,the left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)decreased(P＜0.01),the left ventricular end diastolic volume(LVEDV),left ventricular end systolic volume(LVESV),left ventricular end diastolic diameter(LVEDd)and left ventricular end systolic diameter(LVEDs)increased(P＜0.01),the red blood cell aggregation index,Carcasson viscosity and whole blood viscosity increased(P＜0.01);with enlargement and necrosis of myocardial cells,disordered arrangement of myocardial fibers,and infiltration of inflammatory cells into myocardial tissue,the mRNA and protein expressions of METTL3,TGF-β1,Smad2 and Smad3 in myocardial tissue increased(P＜0.05,P＜0.01),while the mRNA and protein expression of HAND2 decreased(P＜0.01).Compared with the model group,the Yiqi Huoxue Prescription group and the Western medicine group showed significant improvement in the mental state of rats,significant ST segment regression on electrocardiogram,LVEF and LVFS increased(P＜0.01),LVEDV,LVESV,LVEDd and LVEDs decreased(P＜0.05,P＜0.01),with red blood cell aggregation index,Carcasson viscosity and whole blood viscosity decreased(P＜0.01);the arrangement of myocardial fibers was neat,the structure and morphology of myocardial cells were improved,the infiltration of inflammatory cells was reduced,the mRNA and protein expressions of METTL3,TGF-β1,Smad2 and Smad3 in myocardial tissue decreased(P＜0.05,P＜0.01),and the mRNA and protein expression of HAND2 increased(P＜0.05,P＜0.01).Conclusion Yiqi Huoxue Prescription can alleviate the pathological damage of myocardial tissue in rats with coronary heart disease of qi deficiency and blood stasis syndrome,improve heart function and inhibit inflammatory response.Its mechanism may be related to the regulation of the METTL3/HAND2/TGF-β1 signaling axis.

Objective To observe the effects of Yiqi Huoxue Prescription in regulating METTL3/HAND2/TGF-β1 signaling axis on rats with qi deficiency and blood stasis syndrome of coronary heart disease.Methods Totally 48 male SD rats were randomly divided into sham-operation group,model group,Yiqi Huoxue Prescription group and Western medicine(isosorbide mononitrate)group,with 12 rats in each group.Except for the sham-operation group,the animal models of coronary heart disease with qi deficiency and blood stasis syndrome were prepared by the method of ligation of the left anterior descending branch of coronary artery combined with swimming exhaustion.After modeling,Yiqi Huoxue Prescription group and the Western medicine group were gavaged for 28 d.The general conditions of the rats were observed,and electrocardiograms and echocardiograms were collected to detect the cardiac function of the rats,blood rheology was used to detect the degree of blood stasis,HE staining was used to observe the morphology of myocardial tissue,immunohistochemistry was used to detect the expression of METTL3,TGF-β1,Smad2 and Smad3 in myocardial tissue,RT-PCR and Western blot were used to detect the expression of METTL3,HAND2,TGF-β1,Smad2 and Smad3 mRNA and protein in myocardial tissue.Results Compared with the sham-operation group,the model group rats showed symptoms of qi deficiency such as mental lethargy,slow movement,drowsiness,and decreased body mass,significant elevation of ST segment on electrocardiogram,the left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)decreased(P＜0.01),the left ventricular end diastolic volume(LVEDV),left ventricular end systolic volume(LVESV),left ventricular end diastolic diameter(LVEDd)and left ventricular end systolic diameter(LVEDs)increased(P＜0.01),the red blood cell aggregation index,Carcasson viscosity and whole blood viscosity increased(P＜0.01);with enlargement and necrosis of myocardial cells,disordered arrangement of myocardial fibers,and infiltration of inflammatory cells into myocardial tissue,the mRNA and protein expressions of METTL3,TGF-β1,Smad2 and Smad3 in myocardial tissue increased(P＜0.05,P＜0.01),while the mRNA and protein expression of HAND2 decreased(P＜0.01).Compared with the model group,the Yiqi Huoxue Prescription group and the Western medicine group showed significant improvement in the mental state of rats,significant ST segment regression on electrocardiogram,LVEF and LVFS increased(P＜0.01),LVEDV,LVESV,LVEDd and LVEDs decreased(P＜0.05,P＜0.01),with red blood cell aggregation index,Carcasson viscosity and whole blood viscosity decreased(P＜0.01);the arrangement of myocardial fibers was neat,the structure and morphology of myocardial cells were improved,the infiltration of inflammatory cells was reduced,the mRNA and protein expressions of METTL3,TGF-β1,Smad2 and Smad3 in myocardial tissue decreased(P＜0.05,P＜0.01),and the mRNA and protein expression of HAND2 increased(P＜0.05,P＜0.01).Conclusion Yiqi Huoxue Prescription can alleviate the pathological damage of myocardial tissue in rats with coronary heart disease of qi deficiency and blood stasis syndrome,improve heart function and inhibit inflammatory response.Its mechanism may be related to the regulation of the METTL3/HAND2/TGF-β1 signaling axis.

Background It is projected that the frequency, density, and duration of compound hot extreme may increase in the 21st century in the context of global warming. Objective To explore the association between compound hot extreme and blood pressure, and identify sensitive populations. Methods This was a cross-sectional study. The study subjects were from six Guangdong Province Chronic Disease and Nutrition Surveys during 2002 through 2015. A questionnaire was administered to the participants with questions about demographic information, drinking and smoking status, and measurements on their height, weight, and blood pressure were also collected. We chose the data of May, September, and October to explore the association between compound hot extreme and blood pressure. Compound hot extreme means a hot day with a proceeding hot night. Daily meteorological data were obtained from China Meteorological Data Service Centre. We employed inverse distance weighting to interpolate the temperature and relative humidity values for each participant. A distributed lag non-linear model was used to estimate the association between compound hot extreme and blood pressure. Stratified analyses by sex, age, area, body mass index (BMI), smoking status, and drinking status were also performed to identify sensitive populations. A sensitivity analysis was conducted by adjusting the degrees of freedom for lag spline and removing relative humidity. Result A total of 10967 participants without history of hypertension were included in this study. The average systolic blood pressure (SBP) was 120.8 mmHg and the average diastolic blood pressure (DBP) was 74.5 mmHg. The proportion of participants who experienced hot day, hot night, or compound hot extreme were 9.34%, 17.95% and 2.90%, respectively. Compared to hot day, hot night and compound hot extreme were related with decreased blood pressure, and the effect of compound hot extreme was stronger: the changes and 95%CI for SBP was −6.2 (−10.3-−2.1) mmHg, and for DBP was −2.7 (−5.2-−0.2) mmHg. Compound hot extreme induced decreased SBP among male, population ≥ 65 years, and those whose BMI < 24 kg·m^-2, and their ORs (95%CIs) were −6.2 (−10.7-−1.6). −19.1 (−33.0-−5.1), and −6.7 (−11.8~−1.6) mmHg, respectively, and also decreased DBP among population ≥ 65 years, and its OR (95%CI) was −8.4 (−15.6-−1.1) mmHg. During compound hot extremes, participants living in rural areas showed decreased SBP and DBP, and the ORs (95%CIs) were −10.5 (−16.6-−4.5) and −4.4 (−7.7-−1.1) mmHg respectively, while those living in urban areas showed increased SBP, and the OR (95%CI) was 9.7 (2.9-16.5) mmHg. A significant decrease in blood pressure [OR (95%CI)] was also found in non-smokers [DBP, −3.7 (−6.6-−0.8) mmHg] and non-drinkers [SBP, −4.8 (−9.4-−0.2) mmHg; DBP, −3.4 (−6.0-−0.9) mmHg]. Conclusion Compound hot extreme is negatively associated with SBP, and being male, aged 65 years and over, and having BMI < 24 kg·m⁻² may be more sensitive to compound hot extreme.

Objectives To access the bacteriology in patients with sepsis due to biliary tract infection to provide a basis for empirical selection of proper antibiotic treatment.Methods This is a single-center retrospective study on 214 patients with biliary tract infection admitted from August 2014 to July 2016 to the surgical intensive care units (ICU) of The First Affiliated Hospital of Sun Yat-sen University.To study the demographic information,sequential organ failure assessment (SOFA),usage of antibiotics before ICU and duration of ICU were analyzed.Bile,peritoneal drainage and blood samples were collected.Results 47 septic shock patients and 25 septic patients due to biliary tract infection were enrolled in the trial.The two groups (the shock group vs.the sepsis group) had a significant difference in the duration of ICU stay [(6.4 ± 4.6) d vs.(2.3 ± 1.8) d,P ＜ 0.05].48 strains of pathogens were isolated from the bile samples.The major pathogens were Escherichia coli (E.coli) (n =23,47.9％),Enterococcus faecalis (n =8,16.7％) and Enterococcus faecium (n =2,4.2％).80 strains of pathogens were isolated from the peritoneal drainage culture samples.E.coli,pseudomonas aeruginosa,and Klebsiella pneumoniae ranked the top 3 species,accounting for 26.3％,11.3％ and 7.5％,respectively.The sensitivity of E.coli isolated from bile to amikacin,imipenem and panipenem were all over 90.0％.Conclusions E.coli was the principal gram-negative bacterium in biliary infection induced sepsis.Early administration of carbapenemes may reduce the occurrence of septic shock in these patients.

Objective Sodium-bile acid cotransporter plays an important role in the development of Echinococcus.The present study aimed to clone sodium bile acid cotransporter gene in Echinococcus multilocularis (EmSBACT5) and to analyze the bioinformatics of its coding protein.Methods EmSBACT5 gene was amplified by reverse transcription RCR (RT-PCR) technology and its nucleotide sequence was sequenced.Bioinformatics softwares were used to predict and analyze the physical and chemical properties, hydrophilicity/hydrophobicity, transmembrane domain, post-translational modification sites, structural domain, secondary structure, tertiary structure, subcellular localization and biological functions of the coding protein.Results The complete open reading frame was amplified with 654 bp in length, encoding 217 amino acids.The homology of the nucleic acid sequence and amino acid sequence of EmSBACT5 gene were 98% and 96% with the published SBACT5 in Echinococcus granulosus (EgSBACT5) respectively.Protein analysis results showed that the molecular formula of EmSBACT5 protein was C1141H1797N273O284S11.Its relative molecular mass was 24240 and isoelectric point was 8.99.There were 9 post-translational modification sites and 4 typical domains.Alpha helical, β-sheet, β-turn and random coil accounted for 29.95%, 31.80%, 7.83% and 30.41%, respectively.This protein was a hydrophobic membrane protein and was mainly located in the cytoplasmic membrane, and it might play a role in the processes of material transport and signal transmission.Conclusion The EmSBACT5 gene was cloned successfully and the informatics characteristics of its coding protein were obtained, which provides basic information for prevention and control of echinococcosis.

At present,corresponding cell-free parasite DNA molecules (CFPD) has been detected in serum,plasma,urine,saliva and other bodily fluids of a variety of the patients with parasitic diseases.Due to its high specificity and sensitivity,the CFPD shows a strong advantage of noninvasive diagnosis and continuous monitoring,etc.in parasitic diseases.This article namely reviews the current research of CFPD in the patients with parasitic disease at home and abroad in recent years,so as to provide new ideas for the development direction of parasitic disease diagnosis in the future.The current related problems are discussed in the mean time.

ObjectiveTo assess the value of passive leg raising (PLR) test in predicting fluid responsiveness in patients with sepsis-induced cardiac dysfunction.Methods A prospective observational cohort study was conducted. Thirty-eight patients under mechanical ventilation suffering from sepsis-induced cardiac dysfunction admitted to Department of Surgical Intensive Care Unit of First Affiliated Hospital of Sun Yat-Sen University from September 2013 to July 2014 were enrolled. The patients were studied in four phases: before PLR (semi-recumbent position with the trunk in 45°), PLR (the lower limbs were raised to a 45° angle while the trunk was in a supine position), before volume expansion (VE, return to the semi-recumbent position), and VE with infusing of 250 mL 5% albumin within 30 minutes. Hemodynamic parameters were recorded in every phase. The patients were classified into two groups according to their response to VE: responders (at least a 15% increase in stroke volume,ΔSVVE≥15%), and non-responders. The correlations among all changes in hemodynamic parameters were analyzed by linear correlation analysis, and the receiver operating characteristic curve (ROC) was plotted to assess the value of hemodynamic parameters before and after PLR in predicting fluid responsiveness.Results Of 38 patients, 25 patients were responders, and 13 non-responders. There was no significant difference in the baseline and hemodynamic parameters at semi-recumbent position between the two groups. The changes in SV and cardiac output (CO) after PLR (ΔSVPLR andΔCOPLR) were significantly higher in responders than those of non-responders [ΔSVPLR: (14.7±5.7)%vs. (6.4±5.3)%,t = 4.304,P = 0.000;ΔCOPLR: (11.2±7.5)% vs. (3.4±2.3)%,t = 3.454,P = 0.001], but there was no significant difference in the changes in systolic blood pressure, mean arterial pressure, pulse pressure, and heart rate after PLR (ΔSBPPLR,ΔMAPPLR,ΔPPPLR andΔHRPLR) between two groups.ΔSVVE in responders was significantly higher than that of the non-responders [(20.8±5.5) % vs. (5.0±3.7) %,t = 8.347,P = 0.000]. It was shown by correlation analysis thatΔSVPLR was positively correlated withΔSVVE (r = 0.593,P = 0.000),ΔCOPLR was positively correlated withΔSVVE (r = 0.494,P = 0.002). The area under ROC curve (AUC) ofΔSVPLR≥8.1% for predicting fluid responsiveness was 0.860±0.062 (P = 0.000), with sensitivity of 92.0% and specificity of 70.0%; the AUC ofΔCOPLR≥5.6% for predicting fluid responsiveness was 0.840±0.070 (P = 0.000), with sensitivity of 84.0%and specificity of 76.9%; the AUC ofΔMAPPLR≥6.9% for predicting fluid responsiveness was 0.662±0.089, with sensitivity of 68.0% and specificity of 76.9%; the AUC ofΔSBPPLR≥6.4% for predicting fluid responsiveness was 0.628±0.098, with sensitivity of 76.0% and specificity of 61.5%; the AUC ofΔPPPLR≥6.2% for predicting fluid responsiveness was 0.502±0.094, with sensitivity of 56.0% and specificity of 53.8%; the AUC ofΔHRPLR≥-1.7%for predicting fluid responsiveness was 0.457±0.100, with sensitivity of 56.0% and specificity of 46.2%.Conclusion In patients with sepsis-induced cardiac dysfunction, changes in SV and CO induced by PLR are accurate indices for predicting fluid responsiveness, but the changes in HR, MAP, SBP and PP cannot predict the fluid responsiveness.

BACKGROUNDMany studies have shown that continuous renal replacement therapy (CRRT) could clean lactate and treat the hyper-lactatemia. On the contrary, some other studies found that filter lactate clearance only accounted for a very small part of total lactate clearance and the hemofilter's contribution to the overall lactate clearance was negligible. The objective of this study was to evaluate the effects of various doses of continuous veno-venous hemofiltration (CVVH) on plasma lactate elimination in critically ill patients.

METHODSPatients were divided into three groups according to their incipient plasma lactate concentration. Group A: lactate ≤ 2 mmol/L, group B: lactate 2-5 mmol/L, group C: lactate ≥ 5 mmol/L. Three different doses (20 ml × kg(-1)× h(-1), 35 ml × kg(-1)× h(-1) and 45 ml × kg(-1)× h(-1)) of CVVH were applied to critically ill patients who experiencing CVVH. The concentrations of plasma lactate in pre-(A), post-dialyzer (V) sites and ultrafiltrate were measured after each dosage of CVVH was carried out for 30 minutes. Rate of lactate clearance by the filter (RLC) and filter lactate clearance (FLC) and Lactate-Sieving Coefficient (LSC) were calculated under different circumstances, including different doses of CVVH and different incipient lactate levels.

RESULTSFifteen patients were enrolled and 104 blood samples were drawn and lactate concentrations were measured in this study. RLC was found increased ((9.36 ± 9.73) mmol/h, (13.92 ± 12.56) mmol/h and (16.52 ± 12.71) mmol/h, P < 0.05 respectively) with the dose of CVVH increased. RLC was also increased ((3.46 ± 1.46), (10.38 ± 5.50) and (24.53 ± 14.69) mmol/h, P < 0.05 respectively) with the incipient lactate increased. FLC was increased ((1.95 ± 0.63), (2.95 ± 0.74) and (3.45 ± 0.54) L/h, P < 0.05 respectively) with the dose of CVVH increased. There was no significant difference of LSC in different doses of CVVH and different incipient lactate levels.

CONCLUSIONSPlasma lactate can be eliminated by CVVH and different doses of CVVH affect the rate of lactate clearance in critically ill patients.

Adult ; Aged ; Aged, 80 and over ; Critical Illness ; Female ; Hemofiltration ; Humans ; Lactic Acid ; blood ; Male ; Middle Aged

Objective To assess the efficacy and safety of dl-3-butylphthalide on the treatment of acute ischemic stroke. Methods A total of 197 patients who were in the period of 72 hours of first attack of ischemic stroke of internal carotid artery with NIHSS from 5 to 25 scores were enrolled in this multi-center, randomized, double-blind and aspirin-control study. Compound " Dan Shen" was used as a baseline therapy. Results Basical recovery plus significant improvement was seen in 74.7% of the patients in dl-3-butylphthalide group and 60.9% in aspirin group (CMH value 4.0,P=0.047);There was a significant improvement for dl-3-butylphthalide group regarding NIHSS total score, total score difference value and Barthel index on the day 11th and 21st after treatment compared with control group. The main adverse reaction of dl-3-butylphthalide was increased aminotransferase and mainly the slight increase of aspartate aminotransferase, by 4.34% and 0 respectively. Conclusion dl-3-butyiphthalide should be regarded as an effective and safe treatment for ischemic stroke and a treatment without severe side effects.

Objective To evaluate the early effect of hypoxemia on central executive function of working memory.Methods 24 patients with obstructive sleep apnea syndrome (OSAS) and 20 healthy matching controls were studied in probe retrieval task.Results In control group,both the low and high conflict identification tasks elicited the N270 component with right prefrontal [F4,(2.2?2.7) ?V]and posterior [P3,(7.0?3.0) ?V; P4,(6.9 ? 3.1) ?V] distribution. N430 was elicited in high conflict condition with right hemispheric lateralization. The positive component,P300( 300～400 ms) distributed remarkably at parietal scalp[P3,(7.0?3.0) ?V; P4,(6.9?3.1) ?V]was elicited only in identity identification task. The N270 was significantly decreased in the frontal regions in mild OSAS patients [F4,(5.0 ? 4.5) ?V]; F3,(6.0?4.5) ?V] in comparison with the controls( P