1.β-lactamase genotyping of multi-drug resistant Acinetobacter baumannii in a neonatal intensive care unit
Gangfeng YAN ; Yun CAO ; Di QU ; Chuanqing WANG ; Chao CHEN
Chinese Journal of Perinatal Medicine 2011;14(5):257-260
Objective To investigate the correlation between drug resistance and β-actamase genes of multi-drug resistance Acinetobacter baumannii (MDR-AB) in neonatal intensive care unit to provide evidence for rational antibiotics administration and nosocomial infection control.Methods Twenty-six MDR-AB strains were separated and collected from clinical specimens.The minimum inhibitory concentrations of 13 antimicrobial agents were determined by agar dilution method.Genotypes of β-lactamase were detected by polymerase chain reaction.Results The resistant rates of the 26 strains to Ceftazidime,Cefoxitin,Piperacillin-tazobactam and Ciprofloxacin were 100.0%.About 80.8% to 96.2% of these strains were resistant to the other antimicrobial drugs.Among the 26 MDR-AB strains,100% (26/26) strains possessed oxa-51,77% (20/26) possessed oxa-23 gene,54% (14/26) carried arnpC gene,both oxa-23 and ampC were identified in 42% (11/26) strains,while oxa-24,oxa-58,imp-1,imp-4 and vim-2 gene were not identified.Conclusions The drug resistance of Acinetobacter baumannii is serious,oxa-23 and ampC are the major plactamase genes carried by MDR-AB in neonatal intensive care unit.
2. Comparison on pharmacokinetics and tissue distribution of tanshinone IIA lipid microsphere and sodium tanshinone IIA silate injection
Chinese Traditional and Herbal Drugs 2013;44(15):2105-2111
Objective: To compare the pharmacokinetics in rats and tissue distribution in mice of tanshinone IIA (TNS) lipid microsphere and sodium tanshinone IIA silate (STS) injection after iv injection. Methods: A sensitive and specific RP-HPLC method was established to determine the concentration of TSN and STS in rat plasma and mice tissue. The TSN and STS levels in plasma of rats and tissues of mice were compared after iv single dose administration of TSN lipid microsphere (5.40 mg/kg) and STS injection (7.27 mg/kg), and the results were fitted by pharmacokinetic and statistic analyses. Results: The bioavailability (AUC0-∞) and peak concentration (Cmax) values of TSN were 2.14 and 2.22 folds as those of STS, the clearance (CL), apparent volume of distribution (V), and mean repair time (MRT) values of TSN were lower (P < 0.01), and other pharmacokinetic parameters had no significant deviation. The results on the tissue distribution of TSN and STS in mice showed that the contents of TSN in heart, liver, spleen, lung, and kidney tissues were 1.94, 0.11, 0.98, 1.65, and 0.28 folds as those of STS with the same molar dose, and the content of TSN in brain tissue increased more significantly than that of STS which has not been detected. Conclusion: The pharmacokinetics and tissue distribution of TSN and STS at the same molar dose have significant differences, the AUC and Cmax values of TSN are higher, and the concentration of TSN could be increased in heart, brain, and lung tissues significantly, compared with those of STS.
3.Large-scale expansion of clinical-grade human adipose-derived stem cells using the extracellular matrix
Yuehan SU ; Chao WEI ; Pinlei LV ; Yun CAO ; Yun QIU ; Qing ZHENG ; Shudong XIAO ; Zheng WANG
Chinese Journal of Tissue Engineering Research 2014;(10):1521-1531
BACKGROUND:Large-scale expansion of undifferentiated and multipotential adipose-derived stem cells using serum-free culture system is a difficult issue to be resolved. OBJECTIVE:To establish an in vitro culture system combined with the extracellular matrix in order to investigate the efficiency, effectiveness and security of extracellular matrix on expanding adipose-derived stem cells. METHODS:In vitro isolated adipose-derived stem cells were seeded in traditional two-dimensional plastic plates and extracellular matrix-coated plates supplemented with serum-free medium respectively. After in vitro expansion, total cellnumber, expression of cellsurface markers, cellsenescence degree and multipotent differentiation ability (adipogenic, osteoblastic and chondrogenic differentiation) of adipose-derived stem cells cultured under both conditions were detected and compared. Moreover, the clinical safety of adipose-derived stem cells expanded in extracellular matrix-coated plates was investigated. RESULTS AND CONCLUSION:Total cellnumber of passage 5 adipose-derived stem cells cultured in extracellular matrix-coated plates was 10 times more than that in traditional two-dimensional plastic plates. Flow-cytometric analysis showed that adipose-derived stem cells cultured with extracellular matrix expressed stem cellsurface markers. cellular senescence examination showed that almost al of passage 15 adipose-derived stem cells cultured with extracellular matrix showed no aging, while most passage 5 adipose-derived stem cells cultured by the two-dimensional system aged and lost their proliferation ability. Multidirectional induction of adipose-derived stem cells showed that passage 15 adipose-derived stem cells cultured with extracellular matrix could stil differentiate into adipocytes, osteoblasts and chondrocytes as passage 5 adipose-derived stem cells did, which performed much better than the induced differentiations of passage 5 adipose-derived stem cells cultured by the two-dimensional system. Karyotype analysis and in vivo invasion experiment insured the clinical safety of adipose-derived stem cells expanded with extracellular matrix. Al above results suggest a safe and more efficient expansion system of extracellular matrix for clinical application using the serum-free culture system combined with extracellular matrix.
4.Investigation of peripherally inserted central catheter-associated infection in neonates
Gangfeng YAN ; Yun CAO ; Xiaojing HU ; Chao CHEN ; Siyuan JIANG ; Chuanqing WANG
Chinese Pediatric Emergency Medicine 2011;18(1):44-46,49
Objective To analyze the incidence,bacterial spectrum and clinical features of peripherally inserted central catheter-associated bloodstream infection in neonates, and to investigate the effect of infection control strategies on the occurrence of infection,by which it is helpful in choosing effective strategies for clinical practice. Methods Clinical data, results of blood culture and culture of the catheter tip were collected from 72 infants (66 of them were very low birth weight) admitted to NICU from July, 2007 to August, 2008. The incidence of PICC-associated bloodstream infection (PICC-BSI) in the old hospital was compared with that of the new hospital. Results Bacterial colonization was not found. PICC-BSI was found in 15 cases (18. 1%), including 11 cases (13.2%) with definite sepsis and 4 cases (4. 8 %) with clinical sepsis.The incidence of PICC-BSI was 10. 2/1 000 PICC-days as a whole,with 16. 1/1 000 PICC-days in the old hospital and,7. 7/1 000 PICC-days in the new hospital respectively. Eleven organisms were isolated including Coagulase negative staphylococcus (CoNS) (4 strains), Acinetobacter baumannii (3 strains), Klebsiella pneumonia (2 strains), Enterococcus(1 strain), and Candida parapsilosis (1 strain). The incidence of PICC-BSI in the new hospital was lower compared with that of the old hospital. Conclusion Most of the isolated organisms of PICC-BSI are opportunistic and multi-drug resistant pathogen. PICC-BSI can be reduced by the effective infection control strategies in NICU.
5.Respiratory burst function of neutrophils in very low birth weight infants
Jie CHENG ; Xiaochuan WANG ; Yun CAO ; Chao CHEN ; Siyuan JIANG ; Yeheng YU ; Jingyi WANG
Chinese Journal of Perinatal Medicine 2014;17(10):667-671
Objective To investigate the respiratory burst function of neutrophils in very low birth weight infants (VLBWI).Methods Twenty two VLBWI was divided into two groups:neonatal respiratory distress syndrome (NRDS) and non NRDS (11 in each).The respiratory burst function of neutrophils in the peripheral blood of VLBWI within 48 hours after birth was determined using the flow cytometrydihydrorhodamine 1,2,3 method before and after the chemical stimulation of phorbol-12-myrismte 14 acetate (PMA),and the gp91Phox was also measured in resting neutrophils by flow cytometry.Twenty healthy term neonates served as controls.Mann-Whitney U test was used for statistical analysis.Results Before the stimulation of PMA,the percentage of activated neutrophils of VLBWI [(49.10±20.19) %] producing a respiratory burst was higher than that of term neonates [(18.73 ±6.81) %] (Z--4.911,P=0.000),however,after the stimulation of PMA,the percentage of activated neutrophils of VLBWI [(96.58 ± 3.44) %] was lower than that of term neonates [(99.20±0.62) %] (Z--3.186,P=0.001),and the stimulation index (SI) of VLBWI (171.40 ± 103.35) was lower than that of term neonates (306.30 ± 138.47),with significant difference (Z=-3.413,P=0.001).The geometric mean of gp91Phox in VLBWI (21.66± 19.87) was higher compared with term neonates (19.60±8.03),however,the difference was not significant (P=0.350).The percentage of neutrophils that expressed gp91Phox [(56.11 ± 29.40) %] was lower in VLBWI than that in term neonates [(80.14± 14.87) %],with significant difference (Z=-2.374,P=0.018).Before the stimulation of PMA,the percentage of activated neutrophils of VLBWI with NRDS (63.40± 16.45) %] was higher than that of VLBWI without NRDS [(34.80± 11.65) %],with significant difference (Z=-3.382,P=0.001),the SI of VLBWI with NRDS (129.46 ± 75.36) was significantly lower than that of VLBWI without NRDS (213.35 ± 113.49) (Z=-2.331,P=0.020).Conclusions Neutrophils producing a respiratory burst in both VLBWI and term neonates are active without stimulation of PMA,while the phenomenon is more obvious in VLBWI.Neutrophils in VLBWI and term infants can be activated by the stimulation of PMA,and express gp91Phox.The activation and gp91Phox expression of neutrophils in VLBWI with NRDS tend to be lower than those in VLBWI without NRDS.
6.Retrospective analysis of 76 neonates with invasive fungal infection in 2004-2014
Junyan HAN ; Yun CAO ; Siyuan JIANG ; Chao CHEN ; Qi ZHOU ; Na CHEN
Chinese Journal of Perinatal Medicine 2016;19(8):586-591
Objective To investigate the clinical features of neonatal invasive fungal infection(IFI) so as to guide diagnosis,prevention and treatment of IFI.Methods Seventy-six neonates with IFI admitted to the Neonatal Intensive Care Unit (NICU) at Children's Hospital of Fudan University from 2004 to 2014 were included in the study.Pathogens,clinical manifestation,risk factor exposure,laboratory findings,complications,and clinical outcome of neonatal IFI were analyzed.Results Seventy-six cases were diagnosed as IFI between 2004 and 2014,with an yearly increasing trend.Sixty-eight patients were premature infants (89.5%).Of the 76 cases,except one with unknown birth weight,11(14.7%),34(45.3%),20(26.7%)and 10 (13.3%) cases had birth weight < 1 000 g,(≥ 1 000-<1 500) g,(≥ 1 500-<2 500) g and ≥ 2 500 g,respectively.The pathogens were mainly Candida (74/76,97.4%),including 26 cases of Candida albicans (34.2%).However,the incidence of non-Candida albicans infection was increasing.Candida guilliermondii was the most common in nonCandida albicans,accounting for 29.2% (14/48).All Candida albicans were sensitive to fluconazole.One strain of Candida glabrata was resistant to fluconazole.The most common risk factors included use of broad-spectrum antibiotics(93.3%,56/60),parenteral nutrition(70.0%,42/60),central vein catheterization(53.3%,32/60),invasive ventilation(40.0%,24/60) and history of abdominal surgery(21.7%,13/60).Clinical manifestations of IFI included temperature instability,frequent apnea,increased requirement of respiratory support and feeding intolerance.Among all cases,six were diagnosed as central nervous system infection.Of the patients who received cranial MRI,46.8%(22/47) showed multiple abnormal signals in cerebral parenchyma.Fiftytwo patients were cured and seven patients died before discharge,including one death due to fungal infection.Conclusions There is an increasing trend of IFI cases in NICU,especially in premature infants.Non-Candida albicans has become the main pathogenic fungus.There are no specific clinical manifestations in neonatal IFI.Use of broad-spectrum antibiotics,parenteral nutrition and central venous catheterization are common risk factors,and preventive measures should be taken in high-risk infants.In addition,IFI in neonates may affect important organs such as central nervous system,thus early treatment is necessary in suspected patients.
7.Neonatal lupus erythematosus: analysis of 8 cases
Qun YANG ; Xiao-Mei SHAO ; Yun CAO ; Chao CHEN ; Guo-Qiang CHENG ; Yi-Yun SHI ; Li-Jun ZHOU
Chinese Journal of Pediatrics 2008;46(z1):56-60
Objective Neonatal lupus erythematosus (NLE) is an uncommon" passive autoimmune disease, which is associated with transplacental passage of maternal antibodies. It is often misdiagnosed as intrauterine infection or sepsis. The main purpose of this retrospective study was to summarize its clinical manifestations related with pathogenesis.Methods Data of all the NLE neonates, including clinical manifestations, immunochemical evidence of serum antinuclear antibodies (ANA), antibody to Ro/Sjogren's syndrome A ( anti-Ro/SSA), antibody to La/Sjogren' s syndrome B (anti-La/SSB) and anti-dsDNA antibodies in both infants and mothers, and images from head ultrasound and CT scans were analyzed. Follow-up was performed until one and half years of age or when all the clinical abnormalities had been resolved.Results Totally 8 cases (3 males and 5 females ) seen between September 2003 and February 2006 met the diagnostic criteria of NLE, in whom 4 were small for gestational age and one was born prematurely. Mean gestational age was (38.1 ± 1.9 ) weeks, mean birth weight (2605 ± 420) g, mean admission age (22.4 ± 27.7 ) days (2 hours-72 days) and mean age of onset (9.4 ± 12. 1)days (0-28 days). The common clinical manifestations included cutaneous lupus lesions (8 infants ), neural system abnormalities (2 infants ) and congenital heart block (2 infants). Annular, erythematous or desquamative lesions were seen in skin and all disappeared before 6 months of age. One patient presented with third degree atrio-ventricular block and was delivered by cesarean section because of " fetal distress" He did not recover by the end of one and half years follow-up. One infant was hypotonic with delayed neuro-motor development initially and during follow-up with both abnormal neonatal behavioral neurological assessment (NBNA) and imaging findings. Brain CT scan showed generalized low density involving periventricular and deep white matter at one week of age. At the age of one and a half years, he presented with normal mental development index determined by Child Development Center of China (CDCC) infant intelligence mensuration. Other abnormal clinical findings such as hepatosplenomegaly, anemia, thrombocytopenia, cholestasis and elevated liver enzyme activities were all resolved before 6 months of age. Only 3 mothers of the NLE infants were diagnosed as systemic lupus erythematosus (SLE) before parturition and only one received partial therapy. At least anti-Ro/SSA antibody or anti-La/SSB antibody or ANA was found in the affected patients. Seven cases had circulating anti-Ro and/or anti-La antibodies in the mothers and in the newborns, while ANA was positive in seven newborns and in all mothers. All the clinical symptoms disappeared before 18 months ot age except for congenital heart block. No special intervention was applied.Conclusions Serum auto-antibodies should be investigated to rule out NLE when a newborn infant has congenital heart block or rashes or thrombocytopenia, although there is no maternal history of SLE. Central nervous system abnormalities in NLE are likely to be a transient phenomenon and whether it will cause long-term sequelae is uncertain.
8.Clinical research on cake-separated moxibustion for impaired glucose regulation.
Li WANG ; Sheng-Chao CAI ; Xiao-Feng QIN ; Wei-Hua YUAN ; Cheng-Gong HE ; Yun-Yan CAO
Chinese Acupuncture & Moxibustion 2013;33(12):1081-1084
OBJECTIVETo observe clinical curative effect of cake-separated moxibustion on impaired glucose regulation (IGR) and explore its action mechanism.
METHODSSixty cases were randomly divided into a simple lifestyle intervention group (control group) and a cake-separated moxibustion combined with lifestyle intervention group (observation group), 30 cases in each one. The control group was treated with lifestyle intervention. Based on lifestyle intervention, cake-separated moxibustion at Pishu (BL 20), Weishu (BL 21) and Yishu (EX-B 3) was applied to the observation group. Fast plasma glucose (FPG), two hours plasma glucose after oral glucose tolerance test (OGTT2hPG), fasting insulin (FINS), homa insulin resistance index (HOMA-IR), blood lipid, body mass index (BMI) and waist circumference (WC) were observed in the two groups before and after treatment.
RESULTSAfter treatment, the OGTT2hPG and FPG were both decreased significantly (both P<0.05) in the two groups, compared between the two groups, the differences of FPG [(0.41 +/- 0.42) mmol/L vs (0.05 +/- 0.08)mmol/L] and OGTT2hPG [(0.85 +/- 0.53)mmol/L vs (0.17 +/- 0.19)mmol/L] were both statistically significant. There were no significant changes in FINS, HOMA-IR, blood lipid, BMI and WC in the control group before and after treatment (all P>0.05), but FINS, HOMA-IR levels, triglycerides (TG), total cholest-erol (TC), low density lipoprotein (LDL-C), BMI and WC in the observation group were decreased obviously after treatment (all P<0.05), which had statistical differences between the two groups (all P<0.05).
CONCLUSIONThe cake-separated moxibustion combined with lifestyle intervention can obviously control blood glucose levels, improve insulin resistance and blood lipid levels, decrease BMI and WC.
Adult ; Aged ; Female ; Glucose ; metabolism ; Glucose Intolerance ; metabolism ; physiopathology ; therapy ; Humans ; Insulin ; Male ; Middle Aged ; Moxibustion ; Waist Circumference
9.Design, synthesis and evaluation of 5-aminobenzimidazolone derivatives as acetylcholinesterase inhibitors.
Zheng-yue MA ; Jun-jie LI ; Jun-tao CHEN ; Yun-feng TIAN ; Ying-chao ZHANG ; Yu-qing CAO
Acta Pharmaceutica Sinica 2015;50(1):64-69
The target compounds were prepared from 5-aminobenzimidazolone by two steps reaction, and their AChE inhibitory activities were measured by Ellman method in vitro. The AChE inhibitory activity of compound 4d is the best of them, and its IC50 value is equal to 7.2 μmol·L(-1), which is better than that of rivastigmine; moreover the 4d had no inhibitory activities to BuChE. Therefore, the inhibitory activities of 5-aminobenzimidazolone derivatives to acetylcholinesterase are worth further researching.
Acetylcholinesterase
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metabolism
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Benzimidazoles
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chemical synthesis
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chemistry
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Cholinesterase Inhibitors
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chemical synthesis
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chemistry
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Drug Design
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Phenylcarbamates
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chemistry
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Rivastigmine
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Structure-Activity Relationship
10.Design, synthesis and evaluation of new L-proline derivatives as acetylcholinesterase inhibitors.
Yun-feng TIAN ; Jun-tao CHEN ; Jun-jie LI ; Ying-chao ZHANG ; Ting-ting CAO ; Zheng-yue MA
Acta Pharmaceutica Sinica 2015;50(6):719-724
In this paper, fourteen new L-proline derivatives were designed and synthesized, and their acetlcholinesterase (AChE) inhibitory activities were also investigated in vitro. New L-proline derivatives were prepared from substituted 2-bromo-1-acetophenones through four-step reaction; and their bioactivities as AChE inhibitors were measured by Ellman spectrophotometry. The results showed that the target compounds had a certain AChE inhibitory activity to in vitro. The bioactivity of compound 8b was the best of them, and its IC50 value was 5.45 µmol.L-1, which was better than that of rivastigmine. So the acetylcholinesterase inhibitory activities of new L-proline derivatives were worth to be further studied.
Acetylcholinesterase
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Cholinesterase Inhibitors
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chemical synthesis
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chemistry
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Drug Design
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Proline
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analogs & derivatives
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Rivastigmine
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chemistry
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Structure-Activity Relationship