Objective To study the effects of esmolol on fluid responsiveness and hemodynamic parameters in patients with septic shock.Methods A prospective self-control study was conducted.Fifteen septic shock patients undergoing mechanical ventilation admitted to Department of Critical Care Medicine of Yijishan Hospital from January 2015 to August 2015 were enrolled.All patients enrolled in this study were given the treatment based on American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM) Consensus 2012.Esmolol was intravenously injected at a beginning rate of 6 mg·kg-1·h-1, and then the dose was adjusted to reduce heart rate by 10％ from baseline.The changes in hemodynamic and systemic oxygen metabolism indexes were monitored by pulse indicator continuous cardiac output (PiCCO) before and 2 hours after the esmolol administration, and the fluid responsiveness was evaluated by stroke volume variation (SVV).SVV ≥ 10％ was considered to be a positive fluid responsiveness.Results In 15 patients, 9 were male and 6 female, with an age of 65 ± 16.Among them 10 patients suffered from pulmonary infection, and 5 patients with abdominal infection.Acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score was 21 ±9;sequential organ failure score (SOFA) was 8 ±4.28-day mortality was 40.0％.SVV was significantly decreased after esmolol infusion as compared with baseline [(14 ± 5)％ vs.(17 ±7)％, t =2.400, P =0.031].Heart rate [HR (bpm): 100±4 vs.112±8, t =8.161, P =0.000], cardiac output [CO (L/min):6.13 ± 1.45 vs.7.88 ± 1.82, t =4.046, P =0.001], cardiac index [CI (mL·s-1·m-2): 51.51 ± 11.00 vs.66.18 ± 11.48, t =4.131, P =0.001], stroke volume index [SVI (mL/m2): 31.0 ± 6.4 vs.35.4 ± 6.5, t =2.577, P =0.020], the maximum rate of left ventricular pressure rise [dp/dt max (mmHg/s): 927±231 vs.1 194±294, t =3.775, P =0.002], global ejection fraction (GEF: 0.21 ±0.05 vs.0.24±0.06, t =3.091, P =0.008), cardiac function index (CFI: 5.03 ± 1.37 vs.6.59 ± 1.92, t =4.769, P =0.000) showed significant decrease during esmolol infusion.On the other hand, central venous pressure [CVP (mmHg, 1 mmHg =0.133 kPa): 9±3 vs.8±3, t =-3.617, P =0.003], diastolic blood pressure (DBP, mmHg: 69± 15 vs.66± 13, t =-2.656, P =0.019), systemic vascular resistance index (SVRI, kPa·s·L-1·m-2:206.8±69.8 vs.206.8±69.8, t =-3.255, P =0.006) were significantly increased during esmolol infusion.No significant difference was found in systolic blood pressure [SBP (mmHg): 120 ± 25 vs.123 ± 18, t =0.678, P =0.509],mean arterial pressure [MAP (mmHg): 86 ± 18 vs.85 ± 14, t =-0.693, P =0.500], global end diastolic volume index [GEDVI (mL/m2): 614 ± 84 vs.618 ± 64, t =0.218, P =0.830], extravascular lung water index [EVLWI (mL/kg):5.99±1.50 vs.5.73±1.14, t =-1.329, P =0.205], central venous oxygen saturation (ScvO2: 0.711±0.035 vs.0.704 ± 0.048, t =-0.298, P =0.773), arterial blood lactate [Lac (mmol/L): 3.1± 0.3 vs.3.0 ± 0.4, t =-0.997, P =0.345],and difference of central venous-arterial carbon dioxide partial pressure [Pcv-aCO2 (mmHg): 4.1 ± 0.9 vs.4.7 ± 0.5,t =1.445, P =0.182] as compared with those before esmolol treatment.Conclusion Heart rate control with esmolol infusion may reduce fluid responsiveness, cardiac function, heart rate and cardiac output without adverse effect on systemic perfusion in septic shock patients.

Objective To evaluate the effect of cell-penetrating peptide (protein transduction domain 4,PTD4) mediated copper-zinc superoxide dismutase (Cu/Zn SOD) on hypoxia/reoxygenation injury (HRI) in rat myocardial cells.Methods Rat myocardial cell H9C2 HRI model was prepared by using the anaerobic incubator (85% N2,10% H2,5% CO2).The HRI group (without adding any treating factor in HRI cell culture fluid),HRI+Cu/Zn SOD group (adding 10 μmol/L Cu/Zn SOD) and HRI+PTD4-Cu/Zn SOD group (10 μmol/L PTD4-Cu/Zn SOD) were set up.In addition,normally cultured myocardial cells served as the normal control group.After incubating for 30 min,the ultra microstructure of mitochondria was observed under transmission electron microscope.The mitochondrial membrane potential was detected by JC-1 kit.The myocardial cell apoptosis was detected by TdT mediated dUTP nick end labeling TUNEL technique.Results The mitochondria injury degree after 30 min incubation in the PTD4-Cu/Zn SOD group was significantly improved compared with the HRI group.Compared with the normal control group,the mitochondrial membrane potential in the HRI group was significantly decreased,while the mitochondrial membrane potential in the PTD4-Cu/Zn SOD group was lower than that in the normal control group,but compared with the HRI group,which was obviously recovered.The cardiomyocyte apoptosis in the HRI+PTD4-Cu/Zn SOD group was (10.20±2.77)%,which was significantly decreased compared with (28.40±2.41)% in the HRI group,the difference was statistically significant (P<0.05).Conclusion PTD4 mediated Cu/Zn SOD can attenuate HRI in rat myocardial cells.

Objective:To evaluate the efficacy and safety of micronised fenofibrate on lipid and uric acid metabolism in patients with hyperlipidemia.Methods: A total of 116 patients with hypertriglyceridemia and hyperuricemia received 200 mg micronised fenofibrate for 4 weeks.Physical and laboratory investigations of lipid profiles,serum uric acid,and 24 h urine uric acid,for adverse effects were assessed.Results:(1) Serum triglyceride(TG) was significantly reduced by 51%,whilst high density lipoprotein cholesterol(HDL-C) increased 24% after 4-week fenofibrate treatment.Moreover,serum total cholesterol(TC) and low density lipoprotein cholesterol(LDL-C) were reduced by 10% and 12%,respectively.(2) Serum uric acid levels were significantly reduced by 28.3% [from(462.8?73.5) ?mol/L to(320.1?83.0) ?mol/L] after fenofibrate treatment,independent of baseline uric acid le-vels.There was no difference in serum uric acid changes between male gender and female gender(29.8% and 25.1%,respectively).(3) Urine uric acid levels were increased by 36.0% [from(2 874.2?503.4) ?mol/L to(3 604.2?769.7) ?mol/L].The urine uric acid changes were 41.1% in male gender group and 33.4% in female gender group.The uric acid clearance/creatinin clearance ratio was increased in all cases after treatment.Conclusion: Micronised fenofibrate treatment could significantly improve lipid and uric acid metabolism in patients with hypertriglyceridemia and hyperuricemia,and is ge-nerally safe and well tolerated.The anti-hyperuricemic effect of fenofibrate is a result of increasing the urinary excertion of uric acid,independent of baseline level and gender.

Objective: To investigate the current situation and influencing factors of knowledge, attitude and practice (KAP) of fall prevention among the elderly in Huzhou City, Zhejiang Province, so as to provide the evidence for the development of fall intervention for the elderly. Methods: The permanent residents aged 60 years and over in Huzhou City were selected using multi-stratified cluster sampling method from March to April 2023. Demographic information, activity of daily living (ADL), fall risk, and KAP of fall prevention was collected using questionnaire surveys. Factors affecting KAP of fall prevention were identified using a multivariable logistic regression model. Results: Totally 2 160 questionnaires were allocated, and 2 104 valid questionnaires were recovered, with an effective recovery rate of 97.41%. There were 1 063 males (50.52%) and 1 041 females (49.48%), and 861 residents aged 60 to <70 years (40.92%). The awareness of fall prevention knowledge was 84.13%, the percentage of attitude towards fall prevention was 85.88%, and the percentage of practice of fall prevention was 14.59%. Multivariable logistic regression analysis showed that age, educational level, exercise duration and fall risk were associated with the awareness of fall prevention knowledge; age, educational level, marital status, exercise duration, ADL and fall risk were associated with the attitude towards fall prevention; gender, age, educational level, marital status, exercise duration, chronic diseases, ADL and fall risk were associated with the practice of fall prevention (all P<0.05). The desired access to fall prevention knowledge was mainly dominated by medical personnel, accounting for 75.51% (589/780). Conclusions The practice towards fall prevention among the elderly is relatively low in Huzhou City. The KAP of fall prevention is related to age, educational level, exercise duration and fall risk.

Objective To explore the impact of metabolic syndrome (MS)in bone mineral density (BMD) in elderly male type 2 diabetics (T2DM). Methods One hundred and fourty cases were divided into MS group and non-MS(NMS)group according to with or without MS. Height,weight were measured, body mass index(BMI) were calculated and the total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), glycated hemoglobin (HbA1c)were tested. The bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DEXA). The differences among these groups were compared and the risk factors for MS were analyzed. Results The MD, BMI, TC,TG in MS group was higher than that in NMS group (P < 0.05 vs. P < 0.01),and HDL-C was lower than NMS group (P < 0.05). Correlation analysis showed that BMD was negatively correlated with age , TG , HDL-C , and was positively correlated with BMI.The results of multiple stepwise regression analysis showed that age ,HDL-C,BMI were independent risk factors for BMD. Conclusion The BMD significantly increases in T2DM with MS.Obesity and low HDL-C have positive effects in bone mass.

AIM:Toinvestigatetheeffectofnicotinicacidamide(NAA)ontheinfusiondamageofhuman umbilical cord mesenchymal stem cells ( hUC-MSCs) under the condition of instant blood-mediated inflammatory reaction ( IBMIR) .METHODS:Normal peripheral blood without anticoagulant at volume of 2.7 mL was mixed with 0.3 mL phys-iological saline (as blank group), CFSE labeled hUC-MSCs (1 ×106 cells in 0.3 mL as MSC group) and CFSE labeled hUC-MSCs (1 ×106 cells in 0.3 mL) preprocessed with NAA at concentration of 10 mmol/L for 24 h ( as MSC+NAA group) , respectively.The mixture was immediately injected into the improved Chandler Loop model, placed in 37℃water bath, and then started the peristaltic pump at the speed of 20 mL/min for 1 h.The number of CFSE labeled hUC-MSCs, platelets, white blood cells were counted and the concentration of complement C3a was measured before and after cycling, respectively.RESULTS: After 1 h circulation, the platelet dissipation rate were ( 29.96 ±10.88 )% in blank group, (77.76 ±19.29)% in MSC group all and (50.13 ±18.10)% in MSC +NAA group; and the leukocyte counts were (37.82 ±13.81)%in blank group, (64.57 ±17.08)% in MSC group and (41.52 ±17.26)% in MSC+NAA group. Compared with blank group, the differences of the dissipation rates in MSC group and MSC+NAA group all had statistical significance.The hUC-MSCs relative survival rate in MSC+NAA group was higher than that in MSC group.C3a concentra-tions in blank group, MSC group and MSC+NAA group were (206.27 ±58.10), (230.47 ±39.61) and (208.37 ± 40.66) μg/L, respectively.CONCLUSION:Co-circulating the mixture of hUC-MSCs with normal peripheral blood with-out anticoagulant in the improved Chandler Loop for 1 h depletes a large number of hUC-MSCs and blood components, and increases C3a, suggesting that this model can induce IBMIR.NAA has a protective effect on the hUC-MSCs in the infusion damage by inhibiting IBMIR, reducing the wastage of the blood components and enhancing the survival rate of the hUC-MSCs.

Objective To investigate the potential role of soluble triggering receptor expressed on ayeloid cells-1(sTREM-1) expression in serum,endotracheal aspiration (ETA),bronchoalveolar lavage fluid (BALF) and exhaled breath condensate (EBC) as early biomarkers for the diagnosis of ventilator-associated pneumonia (VAP) in patients with acute ischemic stroke.Methods One hundred and thirty-two patients with clinically suspected VAP were prospectively included in this multicenter study.The levels of sTREM-1 in serum,ETA,BALF and EBC were analyzed for diagnostic evaluation at the time of VAP clinically suspected.The bacterial count over 104/CFU as a gold standard for VAP,and the receiver operating characteristic curves were used to identify the ideal cutoff values.Results VAP was confirmed in 76 patients (57.58％).In VAP patients (VAP group) and non-VAP patients (non-VAP group),the level of sTREM-1 in BALF was 32.35 (30.08-41.72) and 18.92(11.89-31.72) ng/L,and the level of sTREM-1 in EBC was 1.57 (1.02-2.61) and 0.41(0.19-1.61)ng/L respectively.The level of sTREM-1 in BALF and in EBC in VAP group was significantly higher than that in non-VAP group (P ＜0.05).The optimum cutoff value for sTREM-1 in BALF according to the maximum Youden index was 23.61 ng/L.This cutoff value had 85.5％ sensitivity and 73.1％ specificity,with 0.813 area under the curve.sTREM-1 in BALF had excellent correlation with that in EBC (R2 =0.78,P ＜ 0.05).Conclusions The results of this prospective study suggest that sTREM-1 levels in BALF and EBC have better roles in facilitating the diagnosis of VAP and thus may be practically recommended to guide the administration of antibiotics when VAP is suspected.

The validity of HbA1C and fasting plasma glucose(FPG)for screening of diabetes in community population was investigated.A total of 1 794 subjects from two sub-districts of Yangpu District,Shanghai,underwent a 75 goral glucose tolerance test(OGTT)and HbA1C determination.Based on 1999 World Health Organization criteria,there were 1 411 subjects with normal glucose tolerance(NGT),111 impaired fasting glucose(IFG),73 impaired glucose tolerance(IGT),33 IFG+IGT,and 166 diabetes.According to the receiver operating characteristic curve,the optimal cut-point of FPG for diagnosing diabetes was 6.15 mmol/L with sensitivity of 89.0%,specificity of 92.8%,and area under the curve of 0.959.The cut-point of HbA1C for diagnosing diabetes was 6.5% with a sensitivity and specificity of 71.1% and 80.2%.The area under the curve was 0.822.The screening model using FPG ≥6.1mmol/L and HbA1C≥6.5% had sensitivity of 66.9% and specificity of 97.0%.When the model was FPG ≥6.1 mmol/L or HbA1C ≥6.5%,the sensitivity and specificity was 96.3% and 76.7% respectively.The results suggest that both FPG and HbA1C have good value for screening diabetes in community,and FPG combined with HbA1C may further promote diagnostic efficacy.

Objective To investigate the value of percutaneous transhepatic cholangioscopy (PTCS) for diagnosis and treatment of biliary cast after liver transplantation. Methods Data of 11 patients with biliary cast after liver transplantation, who underwent PTCS from April 2008 to November 2010, were retrospectively analyzed. Results In 11 patients , one had biliary cast in common bile duct, 3 in right intra-hepatic bile duct, 4 in left intra-hepatic bile duct, and 3 distributed in intra- and extra-hepatic bile ducts. A total of 68 times of PTCS were performed in 11 patients, achieving significant decrease in levels of serum transaminase and bilirubin in 10. Occasional fever occurred in 1 patient after closure of drainage tube,which was managed by replacement with a thinner one. There were no severe complications such as biliary fistula or uncontrollable bleeding. Partial rupture of fistula occurred in 1 case. All patients were followed up for 10-30 months and were all in good condition except one patient died from other disease during the followup. Conclusion PTCS is a safe, effective and applicable method to treat the biliary cast after liver transplantation.

Ranolazine hydrochloride sustained-release tablet (RH-ST) was prepared and its release behavior in vitro was studied. The pharmacokinetic characteristics and bioavailability in six Beagle dogs after oral administration of RH-ST and ranolazine hydrochloride common tablets (RH-CT) as reference were compared. Three kinds of matrix, hydroxypropylmethylcellulose (HPMC K4M), ethylcellulose (EC 100cp) and acrylic resins (Eudragit RL100) were selected as functional excipients to keep ranolazine hydrochloride (RH) release for 12 hours. Through orthogonal designs, the polymers were quantified and the optimized cumulative release profile was obtained. The single oral dose of RH-ST 500 mg and RH-CT 333.3 mg was given to six dogs using a two way crossover design. Plasma levels were determined by LC-MS and the absorption fractions were calculated according to Loo-Riegelman formula. The steady-state concentration of RH in plasma of six dogs and its pharmacokinetics behaviors after continuous oral administration of RH-ST and RH-CT at different time intervals were studied by LC-MS. The steady-state pharmacokinetic parameters were computed by software program BAPP2.0. With the increase of the amount of the matrix, the drug release was decreased. The most important factor influencing drug release is the quantity of HPMC K4M. Drug release within the period (from 0 h to 12 h) fitted well into Higuchi model. The correlation coefficient (r) between the dissolution in vitro in release media of the distilled water and the absorptin fraction in vivo was 0.9550. To compare with RH-CT, RH-ST in vivo has a steady and slow release behavior, Tmax was obviously delayed (3.00 +/- 0.50) h and the relative bioavailability was over 80 percentage. The combined use of multiple polymers can decrease the tablet weight effectively, and the drug release rate can be decreased both in vitro and in vivo.