BACKGROUND: Statins can block many intracellular signal transductive pathways and suppress the proliferation of various cells by affecting the synthesis of mevalonic acid and the translation following modification of some membrane-connecting proteins.OBJETCIVE: To investigate the influence of simvastatin on the proliferation of lung fibroblasts, the synthesis of collagen and the secretion of matrix metalproteinase-2 (MMP-2).DESIGN:Completely randomized controlled study.SETTING: At Organ Transplanting Research Institute of Fuwai Cardiovasular Diseases Hospital, Peking Union Medical College.MATERIALS: This study was carried out at the Laboratory of Cardiology of Beijing Union Medical College hospital, Peking Union Medical College from June 2004 to October 2004. Lung fibroblasts derived from neonatal SD rats were co-cultured in vitro with different dosage of simvastatin of 0, 1, 5, 10,50 μmol/L, and 50 μmol/L simvastatin + 200 μmol/L mevalonic acid.METHODS: Lung fibroblasts deriving from neonatal SD rat were co-cultured with different dosage of simvastatine in vitro. Methyl thiazolyl tetrazolium colorinetry was used to detect the cell proliferation, and cell immunohistochemical assay was used to determine the collagen synthesis and meanwhile,MMP-2 content in supernatant was examined with enzyme-linked immunosorbent assay.MAIN OUTCOME MEASURES: The proliferation of fibroblasts, the synthesis of collagen and the secretion of MMP-2 due to different dosage of simvastatin intervention and simvastatin combined with mevalonic acid.presenting the expression of type Ⅰ, Ⅲ of collagen in lung fibroblasts and the level of MMP-2 in 5, 10, 50 μmol/L simvastatin group were obviously lower than those of 0 μmol/L simvastatin group (0. 520 ± 0.010, 0. 334 ± 0.011,0.260±0.012, 0.111±0.011; 0.508±0.011, 0.324±0.014, 0.232±0.015, 0. 083 ±0. 015; 0.445 ±0. 017, 0. 305 ±0. 015, 0.216 ±0. 015,0.068±0.012; 0.561±0.013, 0.361 ±0.012, 0.289±0.012, 0.140value, the mean absorbency( A value) in lung fibroblasts and the level of MMP-2 in 50 μmol/L simvastatin + 200 μmol/L mevalonic acid group were obviously higher than that of the 50 μmol/L simvastatin group(0. 567±0.015, 0.354±0.014, 0.283±0.012, 0.138±0.011, t=4.715-10.950, P ＜ 0.01).CONCLUSION: Simvastatin could suppress the fibroblast proliferation and collagen synthesis, attenuate the secretion of MMP-2 and suppress consequently the adhesion and migration of lung fibroblasts; moreover, it has the capability of anti-cell proliferation by affecting the mevalonic acid pathway.

Objective:To study the effects of recombinant human vascular endothelial growth factor on proliferation and differentiation of rat osteoblasts. Methods: Cell culturing, light microscop, MTT assay and PNPP assay were performed to observe the effects of rhVEGF on proliferation and differentiation of the cells. Results: rhVEGF could stimulate osteoblasts proliferation and differentiation. The maximal effect on proliferation was observed at a concentration of 3.125 ng/ml on the third day. ALP activities in osteoblasts were increased most significantly at a concentration of 12.5 ng/ml. Conclusion: rhVEGF may not only induce angiogenesis to facilitate bone formation, but also stimulate this process in a direct way by inducing proliferation and differentiation of osteoblasts.

Objective:To assess the efficacy and safety of acupuncture compound anesthesia(ACA)for traditional thyroidectomy. Methods:Randomized controlled trials(RCTs)studying the use of ACA for traditional thyroidectomy were retrieved from PubMed,Excerpta Medica Database(EMBASE),Cochrane Library,Web of Science,China National Knowledge Infrastructure(CNKI),Chongqing VIP Database(CQVIP),Wanfang Academic Journal Full-text Database(Wanfang),and China Biology Medicine Disc(CBM)from inception to September 30,2021.Two investigators independently extracted data and assessed the risk of bias and quality of the studies.Anesthesia effectiveness was the primary outcome,while the secondary outcomes included various pain scales,vital signs,analgesic consumption,and adverse events.Review Manager 5.3 was used for meta-analysis.Weighted mean difference(WMD),standardized mean difference(SMD),and confidence interval(CI)were used for statistical descriptions. Results:A total of 16 papers were included,involving 1228 patients.Meta-analysis showed that anesthesia effectiveness was significantly improved after adding acupuncture as an adjunct[SMD=0.62,95%CI(0.40,0.83),P<0.0001,I2=36%].Besides,ACA can also moderate vital signs and reduce the feeling of pain[SMD=-1.61,95%CI(-2.61,-0.61),P<0.00001,I2=95%],analgesic consumption,and adverse events.Subgroup analysis of the electroacupuncture(EA)group further revealed that the effectiveness of low-frequency EA[WMD=0.43,95%CI(0.30,0.55),P<0.00001,I2=15%]and the entire operative stimulation of EA[WMD=0.55,95%CI(0.33,0.77),P<0.00001,I2=0%]was significantly better than high-frequency EA and short-time stimulation of EA during the operation.Further,no significant difference existed between conventional analgesia and acupuncture analgesia. Conclusion:ACA is beneficial to traditional thyroidectomy regarding efficacy and safety when acupuncture is applied as an adjunct.However,additional high-quality studies with larger sample sizes are needed to verify the findings.

Objective To investigate de-escalation of empiric broad-spectrum antibiotics treatment for patients in intensive care unit (ICU).Methods Data of the patients discharged from ICU in the Second Affiliated Hospital of Zhejiang University from July 1 to December 31 of 2012 and from July 1 to December 31 of 2013 were retrospectively reviewed.Patients with initial use of empirical broad-spectrum antibiotics within 3 d after ICU admission were included in the study.Clinical data including status of infection,the initial empiric antimicrobial therapy,pathogens culture and adjustment of antibiotics in 5 days were analyzed.Results A total of 841 patients were discharged from ICU during the study periods and antibiotics were used in 786 (93.5％) patients.Among 786 patients,389 (49.5％) were treated empirically with broad-spectrum antibiotics,but only 269 (69.2％) had evidences of bacterial infections.Of the 389 patients with empiric antibiotics use,de-escalation of antibiotics was applied only in 6 (1.54％) patients within 5 days after the initiation of treatment.In 269 patients with evidence of infection,specimen sampling and culture were performed in 248 (92.2％) patients within 3 days,among which 165 samples were positive,and the clinical isolates were mainly multi-drug resistant gram negative bacilli and colonized bacteria in oropharyngeal cavity.De-escalation was applied only in 4 (1.49％,4/269) patients with evidences of bacterial infections.Conclusion Broad-spectrum antibiotics as initial empiric therapy is common for patients in ICU,however de-escalation of empiric therapy is rarely applied even in patients with positive results in pathogen isolation and culture.

Objective To construct a new replicating adenovirus vector CNHK600-p53 carrying anti-tumor gene p53 and investigate its effect on hepatocarcinoma cell line PLC/PRF5. Methods The methylthiazolyl tetrazolium assay (MTT) was used to observe the killing effect of Fluorouracil, Mitomycin and Epirubicin alone or in combination with adenovirus CNHK600-p53 on PLC/PRF5. Results When 5-Fu at concentration of 400?g/ml, the inhibition rate was (65?4. 2) % ; with MMC at 1?g/ml, the rate was (41?1.9)%; and it was (65?1.8)% when EPI at concentration of 10?g/ml. With PLC/PRF5 infected by adenovirus CNHK600-p53 ( MOI = 0. 625) , the inhibition rate was significantly increased to (89?5. 3)%,(60?2.3)% and (75?1.5)% respectively; When MOI was 0.3125, 0.625, 1.25, the inhibition rate in CNHK600-p53 group and Ad-p53 group was (27?2. 5)% , (30?3. 7)% , (61?4. 3)% and(4?2.7)%, (5?3.5)%, (16?4.5)% respectively. Conclusion For hepatocarcinoma cell line PLC/PRF5 the effect of CNHK600-p53 is stronger than Ad-p53.

Objective To investigate the effect of bone marrow derived endothelial progenitor cells (EPC)transplantation on microenvironments in a murine model of chronic vein thrombosis.EPCs transplantation was evaluated whether it can up-regulate thrombus organization and recanalization associated cytokines(VEGF,ANG-1 and MCP-1). Method EPCs from immature Wister rats' bone marrow were isolated using a Ficoll density gradient centrifugation,and cultured in fibronectin-coated plate in EGM-2M Vmedium.EPCs were harvested on the 10th day,then were transplanted into chronic inferior vens cava thrombus of adult Wister rat through the femoral vein.Rats were divided into three groups:blank control group(group A,sham operation),the control group(group B,the medium injected)and the experimental group(group C,EPCs injected).The rats were sacrificed after 28 days.VEGF,ANG-1 and MCP-1 mRNA was measured by real-time quantitative PCR and protein expression change by Western blotting from IVC and thrombus tissue. Results EPCs were identificated successfullv by immunohistochemistry,immunofluorescence and function,then were transplanted into chronic inferior vena cava thrombus of adult rats.After EPCs transplantation,the VEGF,ANG-1 and MCP-1 mRNA expression in group C expression was significantly up-regulated with statistical significance(P＜0.01)compared with group A and group B in IVC and thrombus tissue by real-time PCR.There was no significant difference between group A and group B (P＞0.05).VEGF,ANG-1 and MCP-1 protein expression were similar to mRNA expression.There was significant increase in group C compared to group A and group B(P＜0.01)and no statistical significance between group A and group B(P＞0.05).Conclusion EPCs deriving from bone marrow may change the microenvimnment of chronic vein thrombus through up-regulating thrombus organization and recanalization associated cytokines(VEGF,ANG-1 and MCP-1).

Objective To summarize and analyze the surgical therapies for liver and gastric multiple primary cancers. Methods The clinical data of 14 patients with liver and gastric carcinomas surgically treated in our hospital from January 2004 to January 2008 were retrospectively analyzed.Results Of the 14 patients, 12 underwent simultaneous resection of liver and gastric carcinomas,1 resection of the gastric carcinoma 2 months after the liver surgery and 1 removal of liver cancer found 2 years after the surgery for antral adenocarcinoma. The median survival time of these patients was 23 months. The 1-and 3-year survival rate was 78.6% and 35.7%, respectively. Conclusion Due to different pathological characteristics, the therapies of liver and gastric multiple primary cancers are completely different from that of the recurring and metastatic carcinoma. Both tumors can be treated by radical resection and the effect is similar to single cancer. Positive treatment is crucial for long-term survival of the patients.

Objective To develop an overall health risk model and to evaluate its convergent validity and reliability.Methods Health examination results of 230 adults from a public institution were collected by using Chinese Health Risk Appraisal Questionnaire V1.0 (CHRAQ V1.0).An CHRAQ V1.0-based overall health risk model was then developed,which included 34 items.Kolmogorov-Smirnov was used to test normal distribution of the data.Pearson correlation coefficient and Spearman correlation coefficient were used to evaluate parallel validity of the model.Crane Bach coefficient,Spearman-Brown coefficient and test-retest reliability were calculated to evaluated the reliability of the model.Results In this study,212 valid questionnaires (92.17％) were received.The average score of the newly developed overall health risk model was 41.96 ± 9.69,and its kurtosis coefficient and coefficient of skewness were 2.105 and 0.862,respectively.In Kolmogorov-Smirnov,the data were normally distributed (Z =1.073,P =0.199).The correlation coefficient of positive rate of all objective examinations with model scores was 0.774 (P ＜ 0.05).The Cronbach's alpha coefficient,Spearman-Brown coefficient and test-retest reliability of the model were 0.652,0.784 and 0.841,respectively (P ＜ 0.05).Conclusion In this investigation,our newly developed overall health risk model shows good validity and reliability and application prospect in the field of health management.

Objective To evaluate the the protectice effect of dexmedetomidine combined limb remote ischemic postcondition on alleviating focal cerebral ischemic reperfusion injury in rats .Methods 48 healthy adult male SD rats were randomly divided into 4 groups(n= 12) :control group(C) ,limb remote ischemic postcondition group(R) and dexmedetomidine postconditioning group(D) and combination group(R/D) .The rat model of focal cerebral ischemic reperfusion injury was induced by middle cerebral artery oc‐clusion(MCAO) .The group C only received MCAO ,the left femoral artery was isolated without blocking ;the group R received 120 min brain ischemia ,the left femoral artery was occluded by 3 cycles of 10 min occlusion/10 min reperfusion before brain reperfu‐sion ;the group D received dexmedetomidine 3 μg/kg by intraperitoneal injection before brain reperfusion .The group R/D combined the above two kinds of processing method .The neurologic function was evaluated at 24 h of reperfusion and then the rats were sac‐rificed at 48 h of reperfusion .The brain was removed for determining the cerebral infarct volume .Results The neurologic function scores after 24 h reperfusion in the group D ,R and R/D were superior to those in the group C (P< 0 .01) .The rat cerebral infarct volume percentages after 48 h reperfusion in the group D ,R and R/D were significantly lower than those in the group C ( P <0 .01) .The infarct area volume percentage in the group R/D was significantly lower than that in the group R ,the difference showed statitistical significance(P< 0 .01) .The infarct volume percentage in group R/D was significantly decreased compared with the group D(P< 0 .05) .Conclusion Both dexmedetomidine and limb remote ischemic postcondition can attenuate the focal cerebral is‐chemic reperfusion injury in rats .Their combination can significantly reduce the cerebral infarction volume and has synergic protec‐tion effect .

Objective To establish and validate an ultra performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS)method for quantification of MRX-I,a new oxazolidinone antibacterial agent,in human plasma and urine.Methods Chromatographic separation was performed on a Waters ACQUITY UPLC BEH C8 column using an isocratic elution.The mo-bile phase consisted of acetonitrile and water (40∶60,v/v).Quantitative analysis was conducted in the multiple reaction moni-toring mode.Linezolid was used as an internal standard.Liquid-liquid extraction with ethyl acetate was used to remove impuri-ties in the plasma and urine samples.The method was validated in terms of matrix effect,recovery,precision,accuracy and stability.Results The calibration curves were linear within the range of 0.005 00-1 .00 mg/L.The lower limit of quantification was 0.005 00 mg/L for both plasma and urine samples.Retention time was less than 1 .5 min for both MRX-I and internal standard in plasma and urine.The ma-trix effect factors of plasma and urine for MRX-I was 90.4%±8.2% and 82.7%±7.9%,respectively.The recovery of MRX-I was 112.8% ± 13.4% from plasma and 105.6% ± 13.4% from urine samples,respectively.The inter- and intra-day accuracy of MRX-I was 98.9%-105.0% and 96.5%-102.6% in plasma samples,and 92.7%-98.6% and 95.1 %-105.7% in urine samples.MRX-I was stable for 24 h at room tem-perature,48 h in automatic sampler after pretreatment,and stable after 3 freeze-thaw cycles in plasma and urine.MRX-I was also stable at-40℃for eight months in plasma and six months in urine,respectively.Conclusions The UPLC-MS/MS method established in this study shows high sensitivity and specificity for determination of MRX-I in human plasma and urine.The re-sults of validation are consistent with the requirement of bioanalytical method validation.