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The traditional intravenous infusion configuration in medical institutions has the shortcomings of long time and low efficiency， and it is difficult to ensure that the dispensed liquid medicine is not contaminated. At the same time， medical staff may be exposed to risks such as cytotoxic drugs due to lack of protection. To solve the defects and deficiencies in intravenous infusion configuration， the “Dolphin 7” pharmacy intravenous compounding robots are introduced in our hospital， cluster management platform is constructed based on data middle platform service exchange system； mini-intelligent PIVAS module is designed and constructed. The mode can reduce the workload of medical staff， save medical construction and labor costs， also help to promote and deepen the construction of intelligent hospitals.
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OBJECTIVE@#The study aimed to estimate the benchmark dose (BMD) of coke oven emissions (COEs) exposure based on mitochondrial damage with the mitochondrial DNA copy number (mtDNAcn) as a biomarker.@*METHODS@#A total of 782 subjects were recruited, including 238 controls and 544 exposed workers. The mtDNAcn of peripheral leukocytes was detected through the real-time fluorescence-based quantitative polymerase chain reaction. Three BMD approaches were used to calculate the BMD of COEs exposure based on the mitochondrial damage and its 95% confidence lower limit (BMDL).@*RESULTS@#The mtDNAcn of the exposure group was lower than that of the control group (0.60 ± 0.29 vs. 1.03 ± 0.31; P < 0.001). A dose-response relationship was shown between the mtDNAcn damage and COEs. Using the Benchmark Dose Software, the occupational exposure limits (OELs) for COEs exposure in males was 0.00190 mg/m 3. The OELs for COEs exposure using the BBMD were 0.00170 mg/m 3 for the total population, 0.00158 mg/m 3 for males, and 0.00174 mg/m 3 for females. In possible risk obtained from animal studies (PROAST), the OELs of the total population, males, and females were 0.00184, 0.00178, and 0.00192 mg/m 3, respectively.@*CONCLUSION@#Based on our conservative estimate, the BMDL of mitochondrial damage caused by COEs is 0.002 mg/m 3. This value will provide a benchmark for determining possible OELs.
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Male , Female , Animals , Coke , Polycyclic Aromatic Hydrocarbons , DNA Copy Number Variations , Benchmarking , Occupational Exposure/analysis , DNA, Mitochondrial/genetics , DNA DamageABSTRACT
Objective:To study the epidemic situation of Marmota himalayana plague and Yersinias infection in Yugur Autonomous County of Sunan (Sunan County) of Gansu Province, and to provide new ideas for prevention and control of plague. Methods:From 2014 to 2018, liver and spleen, cecum, throat swabs and blood samples of Marmota himalayana were collected on the spot in Sunan County, where Yersinia strains were isolated and identified, and plague F1 antigen and antibody were detected. Results:A total of 634 liver and spleen samples, 427 cecum samples and 426 throat swabs samples were collected from Marmota himalayana, and 23 strains of Yersinia pestis, 2 strains of Yersinia marcescens, and 1 strain of Yersinia flexneri were detected, with the detection rates of 3.63% (23/634), 0.47% (2/427) and 0.23% (1/426), respectively. The detection rate of Yersinia pestis in different years was statistically significantly different (χ 2 = 13.19, P = 0.010). A total of 1 822 serum samples of Marmota himalayana were detected, and 5 F1 antibody positive samples were detected, with a positive rate of 0.27%, the difference of positive rate between different years was statistically significant (χ 2 = 25.22, P < 0.001); 282 liver and spleen tissue homogenates of Marmota himalayana were detected, 22 F1 antigen positive samples were detected, the positive rate was 7.80%, and there was no statistically significant difference between different years (χ 2 = 7.85, P = 0.097). The 23 strains of Yersinia pestis detected were distributed in Mati Tibetan Township (12 strains), Dahe Township (6 strains) and Qifeng Tibetan Township (5 strains); 1 strain of Yersinia flexneri and 2 strains of Yersinia marcescens were both located in Dahe Township. Conclusion:There is an epidemic of plague among animals in Sunan County from 2014 to 2018, and the areas where Yersinia pestis and non pathogenic Yersinia are detected overlapped.
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Objective:To investigate the distribution and molecular characteristics of Yersinia isolated from diarrhea patients in Jiangsu Province. Methods:From 2017 to 2021, the stool samples of diarrhea patients were collected in Tongshan District of Xuzhou City and Dongtai City of Yancheng City, Jiangsu Province, where the national active monitoring sites of Yersinia enterocolitica, then Yersinia was isolated; meanwhile, suspected Yersinia strains were collected from sentinel hospitals in the province. The DNA of isolated strains was extracted for whole genome resequencing, and the data were uploaded to the EnteroBase database for Yersinia species identification; the original data were cleaned and processed for 16S ribosomal RNA (16S rRNA) gene polymorphism analysis. Five virulence genes (ail, ystA, ystB, yadA, virF) were scanned through the National Center for Biotechnology Information (NCBI) and Pathogen Virulence Factor Database (VFDB), and K-mer Tree was constructed and genomic characteristics were analyzed. Results:From 2017 to 2021, a total of 2 058 stool samples from diarrhea patients were collected, and 57 strains of Yersinia were isolated and identified; meanwhile, two Yersinia strains were collected from the sentinel hospital. Compared with EnteroBase database, 51 strains were identified as Yersinia enterocolitica, 4 strains as Yersinia proxima, 1 strain each as Yersinia aleksiciae, Yersinia massiliensis, Yersinia intermedia and Yersinia canariae. The 16S rRNA gene polymorphism analysis showed that all strains were clustered into 3 groups, which could distinguish Yersinia enterocolitica from other Yersinia. Among the 51 strains of Yersinia enterocolitica, 49 strains were virulence genotype Ⅲ(ail-, ystA-, ystB+, yadA-, virF-), two strains were virulence genotype Ⅱ(ail+, ystA+, ystB-, yadA-, virF-); and 8 other Yersinia strains were virulence genotype Ⅳ (ail-, ystA-, ystB-, yadA-, virF-). K-mer analysis could distinguish Yersinia enterocolitica from other Yersinia, JS-XZ-2020001 strain was far away from other Yersinia enterocolitica isolates, and serotype O8 strains were more concentrated. Conclusions:The clinical isolates of Yersinia enterocolitica from diarrhea patients are mainly Yersinia and other Yersinia co-exist in a small amount in Jiangsu Province, two new Yersinia species ( Yersinia proxima and Yersinia canariae) are discovered. The virulence genotype of Yersinia enterocolitica is mainly type Ⅲ. The 16S rRNA gene polymorphism analysis and K-mer analysis can effectively distinguish Yersinia enterocolitica from other Yersinia.
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The risk of plague epidemics and relapse of various types of plague foci persists in Inner Mongolia Autonomous Region. For Marmota sibirica plague foci, the animal plague has not been found but antibody has been detected positive. Nowadays, Marmota sibirica has been increasing in population and distribution in China. In bordering countries Mongolia and Russia, the animal plague has been continuously prevalent. For Spermophilus dauricus plague foci, the animal plague has been taken place now and then. Compared to the above foci, the animal plague is most prevalent in Meriones unguiculatus plague foci and frequently spread to humans. Due to higher strain virulence and historical disaster in Marmota sibirica plague foci and Spermophilus dauricus plague foci, plague prevention and control should be strengthened on these foci. In addition to routine surveillance, epidemic dynamics need to be further monitored in these two foci, in order to prevent their relapse and spread to humans.
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Animals , Humans , China/epidemiology , Epidemics , Plague/prevention & control , Prevalence , Sciuridae , Yersinia pestisABSTRACT
Objective To evaluate the effect and mechanism of cysteine rich protein 61, namely CCN family member 1(CCN1) on the survival of adipose tissues in rats after autologous fat grafting. Methods At 1 week after the establishment of autologous fat grafting rat models, all animals were randomly divided into the CCN1 group (n=20) and control group (n=20). The survival of fat grafts, the morphology of fat graft tissues, the proportion of active adipocytes and the number of new blood vessels of rats were statistically compared between two groups. The levels of differential expressed messenger ribonucleic acid (mRNA) in the fat graft tissues of rats were compared between two groups by high-throughput sequencing and subsequently subject to cluster analysis. The expression levels of related proinflammatory cytokines of fat graft tissues of rats were statistically compared between two groups. Results The weight retention rate of adipose tissues in the CCN1 group was significantly higher than that in the control group (P < 0.05). In the CCN1 group, the integrity of adipocytes was considerably higher, the degree of vesiculation and vacuolation, the degree of inflammatory cell aggregation and the degree of fibrosis were significantly lower than those in the control group (all P < 0.000 1). Immunofluorescence staining demonstrated that the proportion of active adipocytes with uniform morphology was higher in the CCN1 group, whereas the proportion of active adipocytes was lower and the cells were observed in different sizes accompanied by vesiculation in the control group. Compared with the control group, the quantity of new blood vessels was significantly higher, and the expression levels of platelet derived growth factor (PDGF) and fibroblast growth factor (FGF) mRNA were remarkably higher in the CCN1 group (all P < 0.05). High-throughput sequencing analysis showed that the data at the transcriptome levels significantly differed between two groups. In the CCN1 group, the gene expression levels of cell surface markers, inflammatory cytokines and chemokines related to M1 macrophages tended to decline. Real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) revealed that the mRNA expression levels of interleukin (IL)-8, IL-1 and Toll-like receptor (TLR) 2 in the CCN1 group were significantly lower than those in the control group (P < 0.01-0.05). Conclusions During autologous fat grafting, supplement of exogenous CCN1 may effectively promote the neovascularization of adipose tissues and improve the survival rate of fat graft probably by mediating the transformation of macrophages into M2 phenotype via down-regulating the TLR2 expression level.
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OBJECTIVE@#To investigate whether collagen peptides can improve the immune functions of mice under the condition of simulated weightlessness.@*METHODS@#Mouse tail-suspension model was used to simulate the effects of weightlessness. Tail-suspended mice were intraperitoneally injected with 600 mg collagen peptides per kilogram body weight once a day for 10 days. Then, the mice were killed, and white blood cells were counted and classified. Lymphocyte subsets and T lymphocyte proliferations in spleens were analyzed.@*RESULTS@#Compared with normal control group, total and differential count of leukocytes, lymphocytes, T cells，CD4 and CD8 T cells, B cells and NK cells, and splenic T lymphocyte proliferation all decreased in the weightlessness simulated mice (P＜0.05). Except for NK cells, the above-mentioned parameters were increased after administration of collagen peptides, and some of the parameters were recovered to the levels of normal control mice (P＜0.05).@*CONCLUSION@#Collagen peptides can effectively improve peripheral blood lymphocyte distributions and T lymphocyte proliferations of mice under the condition of simulated weightlessness. This study nay provid the experimental basis for improvement of immune functions of astronauts.
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Animals , Mice , CD8-Positive T-Lymphocytes , Cell Proliferation , Collagen , Lymphocyte Count , Peptides , Spleen , Weightlessness , Weightlessness SimulationABSTRACT
Objective@#To investigate the etiologic and epidemiologic features of an infectious diarrhea outbreak in a boarding school in Fuyang city, Anhui province.@*Methods@#Traceability hypothesis of this study was tested according to the epidemiological characteristics of the cases. Feces, anal swabs, water samples and food residues related to the patients and chefs were collected for pathogen isolation and detection. Biochemical identification, virulence gene detection, drug susceptibility test, PFGE and multilocus sequence typing were performed.@*Results@#The incidence rate (3.41%) of different dormitory buildings within the water supply area by shallow wells was higher than that (0.98%) of the deep wells, with statistical significance (χ2=17.215, P<0.001). Sixteen strains belonged to the Shigella Sonneri family were isolated from the patient’s samples, and all carrying the ipaH gene. Seven strains belonged to sen and ial genes. Set1 gene that did not appear in all the 16 strains were highly resistant to ampicillin, tetracycline, compound xinnomine, cefazoline, cefotaxime, gentamicin, naphthidinic acid and streptomycin, including 9 strains to doxycycline. The pulse field pattern of the 16 strains of Shigella sonneri appeared the same, with the ST type as ST152.@*Conclusion@#When combined data from the etiological and epidemiological investigation, it was confirmed that Shigella sonneri was the pathogen of this outbreak, and water from the shallow wells might be responsible for the source of infection.
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Yersiniosis is one of the "other infectious diarrhea" of the notifiable infectious diseases and also an important food-borne disease. However, it lacked the basis or standard for diagnosis. The Chinese Preventive Medicine Association coordinated experienced researchers from National Institute for Communicable Disease Control and Prevention, China CDC and other institutes to produce the group standard entitled "Diagnosis of Yersiniosis" (T/CPMA 005-2019). Based on the principle of "legality, scientificity, advancement, and feasibility" , the standard gives a clear definition for Yerisiniosis, stipulates diagnosis basis, principles and main differential diagnosis and provides two informative appendixes for epidemiological and clinical characteristics and a normative appendix for laboratory detection. The standard provides accurate basis and methods of Yersiniosis diagnosis for hospitals and CDCs at all levels in China. It will solve the problems that Yersiniosis cannot be clearly diagnosed for clinical cases and in the outbreaks.
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Objective@#To illuminate the epidemic characteristics of Yersiniosis among children in the central city of Beijing and the accuracy of current clinical diagnosis towards Yersiniosis.@*Methods@#Etiological surveillance of diarrheal patients, a total of 3 493 cases, was performed in a children hospital in central area of Beijing from 2011 to 2018 continuously. Collected the epidemiological and clinical information of the cases, analyzed the clinical and etiological diagnosis for Yersiniosis and bacterial dysentery and compared the distribution of Yersiniosis cases with the different symptoms.@*Results@#A total of 3 493 acute diarrhea cases distributed from the age of 6 months to 13 years old, M (P25, P75) was 1.50 (0.75, 3.17) years old. The 28 cases were isolated Yersinia enterocolitica (isolation rate of 0.80%) and they could be diagnosed as Yersiniosis by etiology. The isolation peaked in May and February. A total of 85.71% (24/28) of Yersiniosis cases were under 5-year old. The children of 3-4 age group had the highest isolation rate (1.52%) while the rate (0.18%) of 0-1 age group was the lowest (P=0.025). The Yersinia enteroclitica isolation rates of diarrheal patients with the symptoms including mucus feces, fever, white blood cell (WBC) and red blood cell (RBC) in feces were higher than the patients without these symptoms (P>0.05). The 9 of 28 Yersiniosis cases by etiology diagnosis were clinical diagnosed as bacillary dysentery.@*Conclusion@#The infants and young children under 5-year old were the main population of Yersiniosis adolescent patients under 14-year old. The typical symptoms characterized with mucus stool, fever, WBC and RBC by routine microscopic examination. The preliminary clinical diagnosis of Yersiniosis is easily confused with bacterial dysentery.
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Infants with fetal growth restriction (FGR) who did not achieve full in utero growth potential because of environmental factors are at increased risk of morbidity and mortality compared with those with normal in utero growth.Diagnosis and management of FGR are becoming more standardized as clinical guidelines sponsored by academic societies and governments are emerging.However,how to accurately identify FGR fetus and manage the pregnancies appropriately remain controversial.Early prevention of FGR and standardized administration of prenatal glucocorticoids and magnesium sulfate are urgently needed to be addressed with more evidences.
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Objective@#In this study, we analyze the regulation mechanisms of the expression of ampD in AmpC β-lactamase and the regulation mechanism of β-N-acetylglucosaminidase (NagZ) in Yersinia enterocolitica.@*Methods@#We construct the mutation strains of Yersinia enterocolitica AmpD (AmpD1-3) gene (ampD1-3), Low-Molecular-Mass Penicillin-Binding Proteins (LMM PBPs) gene (pbp4, pbp5a, pbp5b, pbp7), NagZ gene (nagZ), and ampR gene by deleting and complementing genes, and induce them by cefoxitin. We determined the activity of AmpC β-lactamase activity (U) of mutant strains (basal level and induce level) by using cephalothiophene hydrolysis method, the promoter activity of AmpC β-lactamase ((relative light unit (RLU)) was detected by the luxCDABEreporter system, and the activity of β-N-acetylglucosaminidase (nmol/L) was determined by by using 4-nitrophenyl N-acetyl-β-D-glucosaminide as the chromogenic substrate.@*Results@#AmpD1 (Basal level: (3.29±1.58) U; Induced level: (4.08±1.75) U) was the most potent one. The YEΔ5b, YEΔ4Δ5b, YEΔ5aΔ5b and YEΔ5bΔ7 of ampC promoter activity increase significantly, whichYEΔ4Δ5b is the highest one (Basal level: (106 903.16±61 910.61) RLU; Induced level: (205 427.45±45 352.17) RLU). The YEΔ4Δ5bΔ7 of ampC promoter activity is the highest among triple mutant strain (Basal level: (304 108.04±99 274.53) RLU; Induced level: (531 440.21±68 891.02) RLU). Quadruple deletion strain YEΔ4Δ5aΔ5bΔ7 have the highest ampC promoter activity (Basal level: (1 013 810.99±260 955.96) RLU; Induced level: (1 230 214.59±205 526.79) RLU). After the deletion of nagZ gene, there is no significant change in β-lactamase activity of YEΔD1D2D3ΔZ, while β-lactamase activity of YEΔ4Δ5aΔ5bΔ7ΔZ shows a significant decrease (Basal level: (0.30±0.20) U; Induced level: (0.29±0.21) U), which basically drops to the wild strain level.@*Conclusion@#This is the first report of ampC multi-step upregulation mechanism driven by three AmpD homologues in Yersinia enterocolitica. The AmpC regulation mode with the function of single PBP4, PBP5a or PBP7 is relatively low, which work in coordination with PBP5b. Yersinia enterocolitica have both NagZ-depend and NagZ-independent mechanisms for β-lactamase expression.
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Objective To understand the etiological characteristics of bacterial diarrhea in different areas,including large cities,mid-sized/small cities and rural area,in China.Methods A cross-sectional surveillance was conducted in 17 provinces of China from 2010 to 2014.The acute diarrhea outpatients were selected from clinics or hospitals in large cities,mid-sized/small cities,including rural-urban fringe zones,and rural areas.The demographical and clinical characteristics of the patients were collected by using questionnaire,and stool samples were taken from them for laboratory detection of 17 kinds of bacteria.The differences in pathogen positive rates (PPR) and pathogen spectrum across the cases from three-type areas were compared.The different infection risk in different cases were analyzed with unconditional logistic regression model.Results In our study,we enrolled 9 253 cases from large cities,5 138 cases from rural areas and 13 683 cases from midsized/small cites.The pathogen with largest differences in infection rate across the three-type areas was Shigella (S.)flexneri (rural area:5.81％,mid-sized/small city:2.78％,large city:0.46％),followed by Aeromonas (A.) hydrophila (rural area:2.14％,mid-sized/small city:0.96％,large city:0.48％).Compared with cases in large cities,the cases in mid-sized/small cities and rural areas had higher infection risks for S.flexneri (mid-sized/small city:OR =6.481,95％CI:4.666-9.002,rural area:OR =11.304,95％ CI:8.018-15.938) and A.hydrophila (mid-sized/small city:OR=1.992,95％ CI:1.401-2.832,rural area:OR=4.083,95％ CI:2.833-5.884).The constituent ratio of diarrheagenic Escherichia coli and Salmonella increased with the urbanization development,while the ratios of Shigella and A.hydrophila had an opposite trend.S.sonnei (60.00％) was the predominant serogroup of Shigella in urban infections,while S.flexneri (77.37％) was the predominant serogroup in rural infections.Conclusion The differences in pathogen spectrum of bacterial diarrhea were obvious across large cities,mid-sized/small cities and rural areas in China,especially the differences in the infection rates of S.flexneri and A.hydrophila.
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Objective To understand the etiological characteristics of bacterial diarrhea in different areas,including large cities,mid-sized/small cities and rural area,in China.Methods A cross-sectional surveillance was conducted in 17 provinces of China from 2010 to 2014.The acute diarrhea outpatients were selected from clinics or hospitals in large cities,mid-sized/small cities,including rural-urban fringe zones,and rural areas.The demographical and clinical characteristics of the patients were collected by using questionnaire,and stool samples were taken from them for laboratory detection of 17 kinds of bacteria.The differences in pathogen positive rates (PPR) and pathogen spectrum across the cases from three-type areas were compared.The different infection risk in different cases were analyzed with unconditional logistic regression model.Results In our study,we enrolled 9 253 cases from large cities,5 138 cases from rural areas and 13 683 cases from midsized/small cites.The pathogen with largest differences in infection rate across the three-type areas was Shigella (S.)flexneri (rural area:5.81％,mid-sized/small city:2.78％,large city:0.46％),followed by Aeromonas (A.) hydrophila (rural area:2.14％,mid-sized/small city:0.96％,large city:0.48％).Compared with cases in large cities,the cases in mid-sized/small cities and rural areas had higher infection risks for S.flexneri (mid-sized/small city:OR =6.481,95％CI:4.666-9.002,rural area:OR =11.304,95％ CI:8.018-15.938) and A.hydrophila (mid-sized/small city:OR=1.992,95％ CI:1.401-2.832,rural area:OR=4.083,95％ CI:2.833-5.884).The constituent ratio of diarrheagenic Escherichia coli and Salmonella increased with the urbanization development,while the ratios of Shigella and A.hydrophila had an opposite trend.S.sonnei (60.00％) was the predominant serogroup of Shigella in urban infections,while S.flexneri (77.37％) was the predominant serogroup in rural infections.Conclusion The differences in pathogen spectrum of bacterial diarrhea were obvious across large cities,mid-sized/small cities and rural areas in China,especially the differences in the infection rates of S.flexneri and A.hydrophila.
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AIM:To study the influence of bone marrow mesenchymol stem cell-drived exosomes(BMSC-exo-somes)on hindlimb activity,and the numbers of reactive astrocytes and residual neurons in spinal cord injury(SCI)rats. METHODS:BMSCs were cultured using the whole bone marrow adherent culture method and surface markers CD 90 and CD34 were verified by flow cytometry.Exosomes were isolated by ultracentrifugation and the morphology of exosomes was observed under transmission electron microscope.The protein markers CD63 and CD9 were verified by Western blot.After exosomes were applied to SCI rats,the Basso,Beattie and Bresnahan locomotor rating scale score,the Nissl staining of the lesion site,and the numbers of reactive astrocytes and residual neurons were assessed at various time points.RESULTS:Transmission electron microscopic observation revealed the presence of saucer -shaped vesicles.BMSC-exosomes were found to express high levels of CD63 and CD9.Compared with injury group,significant improvement of hindlimb activity scores from day 14 after injury in treatment group was observed(P<0.05),and less reactive astrocytes and more residual neu-rons from day 7 after injury were also observed(P<0.05).CONCLUSION:BMSC-exosomes inhibit reactive astrocytes and death of neurons,and improve hindlimb activity in the rats after SCI.
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Objective To establish an extensively drug-resistant Acinetobacter baumannii (XDR-AB) infection model using Caenorhabditis elegans (C.elegans),and evaluate the effect of efflux pump inhibitors(EPIs) on reversal of ciprofloxacin resistance in XDR-AB.Methods XDR-AB infection model of C.elegans was established,six EPIs(CCCP,PAβN,NMP,omeprazole,reserpine,and verapamil)combined with ciprofloxacin were used to treat the infected model,the survival rate of C.elegans was recorded to evaluate the in vivo activities of drugs,toxicity test and in vitro drug susceptibility test were also performed.Results Lethal effect of different concentrations of XDR-AB on C.elegans was varied,5 × 106 CFU/mL of XDR-AB was selected to infect C.elegans.C.elegans survival test showed that survival curves of C.elegans infected with XDR-AB for 3 hours and curves of control group (polymixin B was added) were not significantly different (x2 =3.154,P＞0.05);compared with control group,survival curves of C.elegans infected with XDR-AB for 6 hours or 9 hours were significantly different (both P＜0.001),but 6 hours and 9 hours were not significantly different(x2 =0.669,P＞0.05),6 hours was chosen as the duration of infection,36 hours was appropriate for the duration of antimicrobial therapy.Ciprofloxacin with EPIs for infection model revealed that low concentration of PAβN,NMP,omeprazole,and reserpine could improve the survival rate of C.elegans by 30％-40％,15％-20％,20％-30％,and 20％ respectively,high concentration of verapamil could improve the survival rate of infected C.elegans by about 30％.In vitro susceptibility test and toxicity test results showed that ciprofloxacin combined respectively with CCCP,omeprazole,and verapamil could reduce minimum inhibitory concentration(MIC) to the original 1/4,combined respectively with PAβN,NMP,and reserpine could reduce MIC to the original 1/2,CCCP had the best bacterial inhibitory effect in vitro,but the toxicity was large,and was not suitable for the study of pharmacodynamics in vivo.Conelusion The infection model of C.elegans XDR-AB is initially and successfully established,which is used to evaluate the efficiency of six EPIs for reversing ciprofloxacin resistance.
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<p><b>OBJECTIVE</b>To screen out differentially expressed microRNAs (miRNAs) in the plasma of children with methylmalonic acidemia (MMA), to determine the expression of miR-9-1 in plasma and to preliminarily evaluate the significance of miR-9-1 as a biomarker in MMA.</p><p><b>METHODS</b>Plasma was obtained from 17 MMA children, 10 hyperhomocysteinemia (HHcy) children without MMA (HHcy group), and 10 normal controls. Of 17 MMA children, 12 had HHcy (MMA+HHcy group), and 5 had no HHcy (MMA group). The differentially expressed miRNAs were screened out by miRNA microarray. Differentially expressed miR-9-1 was selected, and plasma miR-9-1 levels were determined by RT-PCR. Urine was collected from MMA patients who received vitamin B12 treatment, and plasma miR-9-1 levels were determined by RT-PCR after treatment.</p><p><b>RESULTS</b>The miRNA microarray analysis showed that 26 miRNAs were differentially expressed, among which 16 miRNAs (including miR-9-1) were down-regulated over 2 times, while 10 miRNAs were up-regulated over 2 times. The MMA+HHcy , MMA and HHcy groups had significantly down-regulated miR-9-1 compared with the normal control group (P<0.01). The patients who showed a good response to vitamin B12 treatment had significantly increased plasma miR-9-1 levels, without significant difference compared with the normal control group.</p><p><b>CONCLUSIONS</b>Plasma miR-9-1 is significantly down-regulated in MMA patients, but it is significantly up-regulated after vitamin B12 treatment, suggesting that miR-9-1 may act as a biomarker in monitoring the progression of MMA.</p>