Main Infection Control Measures for Respiratory Infectious Diseases in Medical Institutions and Public Places in China / 中国医学科学院学报

Respiratory infectious diseases (RID) are the major public health problems threatening the people's lives and health.Infection control (IC) is one of the effective tools to contain the occurrence and spread of RID.We collected the articles and data on IC published since January 1,2018 and summarized the achievements,problems,and challenges of IC from administrative control,management control,environment and engineering control,and personal protection in the medical institutions and public places in China.The efforts for IC vary in different regions and medical institutions of different levels.There are still links to be improved for IC from administrative control,management control,environment and engineering control,and personal protection,especially in community-level medical institutions and public areas.It is urgent to strengthen the implementation of IC policies and conduct IC precisely according to local situations.We proposed the following suggestions.First,the existing IC products and tools should be applied to precisely implement the IC measures;second,modern high technology should be employed to develop efficient and convenient IC products and tools;finally,a digital or intelligent IC platform should be built for monitoring infections,so as to contain the occurrence and spread of RID.

Immunogenicity of Whole / 生物医学与环境科学（英文）

Objectives@#To evaluate the immunogenicity of @*Methods@#Protein extracts from @*Results@#Immunization with @*Conclusion@#This is the advanced study to investigate the immunogenicity of

A comparative study of cerebellar development between appropriate-for-gestational age infants and small-for-gestational-age infants / 中国当代儿科杂志

OBJECTIVE@#To investigate whether there is a difference in cerebellar development between appropriate -for-gestational-age (AGA) infants and small-for-gestational-age (SGA) infants.@*METHODS@#A total of 165 AGA infants and 105 SGA infants, with a gestational age of 26-40 weeks, were enrolled in this study. Within 24-48 hours after birth, ultrasound examination was performed to measure the transverse diameter of the cerebellum, the height of the vermis, the area of the vermis, the perimeter of the vermis, and the area and perimeter of the cerebellum on transverse section. A Pearson correlation analysis was used to investigate the correlation between cerebellar measurements and gestational age.@*RESULTS@#In both AGA and SGA infants, all cerebellar measurements were positively correlated with gestational age (r=0.50-0.81, P0.05), while in the 34-36 weeks and 37-40 weeks subgroups, the SGA infants had significantly lower measurements than the AGA infants (P<0.05).@*CONCLUSIONS@#The SGA infants with a gestational age of <34 weeks have intrauterine cerebellar development similar to AGA infants, but those with a gestational age of ≥34 weeks have poorer intrauterine cerebellar development than AGA infants.

Immunological Evaluation of a Novel Mycobacterium tuberculosis Antigen Rv0674 / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to characterize the diagnostic and vaccine potential of a novel Mycobacterium tuberculosis antigen Rv0674.@*METHODS@#To evaluate the diagnostic potential and antigenicity of Rv0674, IgG was evaluated using ELISA and interferon (IFN)-γ was done by using ELISpot assay among TB patients and healthy donors. For immunogenicity evaluation, BALB/c mice were immunized with Rv0674. Cytokine production was determined by cytokine release assay using an ELISA kit, and the antibodies were tested using ELISA.@*RESULTS@#The results of serum Elisa tests showed that Rv0674 specific immunoglobulin G (IgG) response was higher in TB patients than negative controls. And Rv0674 had good performance in serological test with sensitivity and specificity of 77.1% and 81.1%, respectively. While it shows poor sensitivity and specificity of 26.23% and 79.69% for IFN-γ tests. In BALB/c mice, Rv0674 adjuvant by DDA/Poly I:C could also induce a high level of IFN-γ, interleukin-2 and interleukin-6 as well as a high IgG titer in both high- and low-dose groups indicating that Rv0674 is essential in humoral and cellular immunity. Moreover, the cytokine profile and IgG isotype characterized Rv0674 as a Th1/Th2-mixed-type protective immunity with the predominance of Th1 cytokines.@*CONCLUSION@#Rv0674 may be a good potential candidate for the development of TB serological diagnosis and a new TB vaccine.

Preliminary Study on Drug Susceptibility Profile and Resistance Mechanisms to Macrolides of Clinical Isolates of Non-tuberculous Mycobacteria from China / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>Macrolide susceptibility and drug resistance mechanisms of clinical non-tuberculous mycobacteria (NTM) isolates were preliminarily investigated for more accurate diagnosis and treatment of the infection in China.</p><p><b>METHODS</b>Four macrolides, including clarithromycin (CLAR), azithromycin (AZM), roxithromycin (ROX), and erythromycin (ERY), were used to test the drug susceptibility of 310 clinical NTM isolates from six provinces of China with the broth microdilution method. Two resistance mechanisms, 23S rRNA and erm, were analyzed with nucleotide sequence analysis.</p><p><b>RESULTS</b>Varied effectiveness of macrolides and species-specific resistance patterns were observed. Most Mycobacterium abscessus subsp. massiliense were susceptible and all M. fortuitum were highly resistant to macrolides. All the drugs, except for erythromycin, exhibited excellent activities against slow-growing mycobacteria, and drug resistance rates were below 22.2%. Only four highly resistant strains harbored 2,058/2,059 substitutions on rrl and none of other mutations were related to macrolide resistance. G2191A and T2221C on rrl were specific for the M. abscessus complex (MABC). Seven sites, G2140A, G2210C, C2217G, T2238C, T2322C, T2404C, and A2406G, were specifically carried by M. avium and M. intracellulare. Three sites, A2192G, T2358G, and A2636G, were observed only in M. fortuitum and one site G2152A was specific for M. gordonae. The genes erm(39) and erm(41) were detected in M. fortuitum and M. abscessus and inducible resistance was observed in relevant sequevar.</p><p><b>CONCLUSION</b>The susceptibility profile of macrolides against NTM was demonstrated. The well-known macrolide resistance mechanisms, 23S rRNA and erm, failed to account for all resistant NTM isolates, and further studies are warranted to investigate macrolide resistance mechanisms in various NTM species.</p>

First Report in China on the Identification and Drug Sensitivity of Mycobacterium elephantis Isolated from the Milk of a Cow with Mastitis / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>In this study, milk from a cow with mastitis was analyzed to determine the presence of mycobacterial infection. Milk quality and security problems pertaining to the safe consumption of dairy products were also discussed in this study.</p><p><b>METHODS</b>Milk was preprocessed with 4% NaOH. Then, mycobacteria were isolated from the milk sample on L-J medium. The isolate was identified using multiple loci Polymerase Chain Reaction (PCR) and multi-locus sequence analysis with 16S rRNA, sodA, hsp65, and ITS genes. The drug sensitivity of the isolate to 27 antibiotics was tested through alamar blue assay.</p><p><b>RESULTS</b>Smooth, moist, pale yellow colonies appeared on the L-J medium within a week after inoculation. Based on the results of multiple loci PCR analysis, the isolate was preliminarily identified as non-tuberculous mycobacteria. The 16S rRNA, SodA, hsp65, and ITS gene sequences of the isolate exhibited 99%, 99%, 99%, and 100% similarities, respectively, with those of the published reference strains of Mycobacterium elephantis (M. elephantis). The drug sensitivity results showed that the strain is resistant to isoniazid, p-aminosalicylic acid, and trimesulf but is sensitive to ofloxacin, rifampicin, amikacin, capreomycin, moxifloxacin, kanamycin, levofloxacin, cycloserine, ethambutol, streptomycin, tobramycin, rifabutin, ciprofloxacin, linezolid, cefoxitin, clarithromycin, and minocycline.</p><p><b>CONCLUSION</b>To the best of our knowledge, this study is initially to report the isolation of M. elephantis from the milk of a cow with mastitis in China.</p>

Rapid detection of rifampin-resistant clinical isolates of Mycobacterium tuberculosis by reverse dot blot hybridization / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>A PCR-reverse dot blot hybridization (RDBH) assay was developed for rapid detection of rpoB gene mutations in 'hot mutation region' of Mycobacterium tuberculosis (M. tuberculosis).</p><p><b>METHODS</b>12 oligonucleotide probes based on the wild-type and mutant genotype rpoB sequences of M. tuberculosis were designed to screen the most frequent wild-type and mutant genotypes for diagnosing RIF resistance. 300 M. tuberculosis clinical isolates were detected by RDBH, conventional drug-susceptibility testing (DST) and DNA sequencing to evaluate the RDBH assay.</p><p><b>RESULTS</b>The sensitivity and specificity of the RDBH assay were 91.2% (165/181) and 98.3% (117/119), respectively, as compared to DST. When compared with DNA sequencing, the accuracy, positive predictive value (PPV) and negative predictive value (NPV) of the RDBH assay were 97.7% (293/300), 98.2% (164/167), and 97.0% (129/133), respectively. Furthermore, the results indicated that the most common mutations were in codons 531 (48.6%), 526 (25.4%), 516 (8.8%), and 511 (6.6%), and the combinative mutation rate was 15 (8.3%). One and two strains of insertion and deletion were found among all strains, respectively.</p><p><b>CONCLUSION</b>Our findings demonstrate that the RDBH assay is a rapid, simple and sensitive method for diagnosing RIF-resistant tuberculosis.</p>

A primary investigation on the isoniazid-induced alterations in efflux gene expression among the isoniazid resistant Mycobacterium tuberculosis clinical isolates / 中华流行病学杂志

Objective To detect the changes on the expression of putative drug effiux genes caused by isoniazid-inducement in single resistance to the isoniazid Mycobacterium tuberculosis (M.tuberculosis) clinical isolates,for exploring the putative effiux genes which causing M.tuberculosis isoniazid resistance as well as the mechanism related to high expression of the putative effiux genes.Methods We selected 35 M.tuberculosis clinical isolates which were only resistant to isoniazid as well as 10 sensitive M.tuberculosis clinical isolates and using H37Rv as control.Each strain was cultured in 7H9 liquid medium without isoniazid and with subinhibitory isoniazid concentration (1/4 MIC) induction.After RNA extraction and reverse transcription,real-time PCR was conducted to assess the expression changes of 27 putative drug effiux pump genes with formula 2-△△CT to calculate the expression of each putative drug efflux pump genes.Results Of the 27 putative genes,13 of them were expressed at high level.High expression of Rv1258c gene had the maximum number of 6strains,followed by high expression of Rv0849 and Rv2265 which both had 5 strains.Fourteen strains (40.00％) out of the 35 strains had high expression pump genes.Six strains (17.14％) had only one highly expressed putative efflux pump gene.Eight strains (22.86％) had two or more highly expressed putative effiux pump genes,including two,four,five,seven genes that highly expressed in 4,2,1,1strains respectively.For the 27 putative genes,ten sensitive strains and H37Rv did not show highly expressed genes.Conclusion Rv1258c,Rv2265,Rv0849,etc.genes might be the putative effiux pumps genes of M.tuberculosis resistant to isoniazid.Isoniazid might serve as the inducer of M.tuberculosis part putative effiux pump genes,inducing activation and causing high expression of these putative effiux pump genes.

Characteristics of Mycobacterium tuberculosis genotype and the relationship between Beijing genotype and drug-resistant phenotypes in Tianjin / 中华流行病学杂志

Objective To explore the distribution and characteristics on genotype of Mycobacterium tuberculosis and the relationship between Beijing genotype and drug-resistant phenotypes in Tianjin city. Methods 656 clinical strains were collected from Tianjin Center for Tuberculosis Control and ten other Tuberculosis Institute in Tianjin from January 2008 to June 2009.Information regarding administration, clinical as well as laboratory findings of patients were collected.Proportion method was adopted to detect the susceptibility on four anti-tuberculosis drugs, namely streptomycin (SM), isoniazid (INH), rifampicin (RFP) and ehambutol (EMB). Both Beijing and non-Beijing genotypes were differentiated by multiplex PCR. The relationship between Beijing genotype and drug-resistant phenotypes was analyzed. Results In this study, the overall resistance rate of MTB was 26.98%, with multidrug-resistant rate was 6.25%. Among 656 MTB strains, 600isolates (91.46% ) belonged to Beijing genotype. There was significant difference between Beijing and non-Beijing genotype (x2=4.26, P=0.039) among the Tianjin household registered population.Concerning the drug resistance, there was no significant difference between the two groups.Conclusion Beijing genotype strains were the predominant one in Tianjin. The proportion of people infected with the Beijing genotype strains in Tianjin household registration of patients was significantly higher than the proportion of patients in the floating population in the same region.Results from the statistical analysis did not reveal any statistically significant association between Beijing genotype and drug resistance.

Molecular characterization of drug-resistant Beijing family isolates of Mycobacterium tuberculosis from Tianjin, China / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>Tuberculosis remains a severe public health issue, and the Beijing family of mycobacterium tuberculosis (M. tuberculosis) is widespread in East Asia, especially in some areas in China, like Beijing and Tianjin. This study aimed at determining the mutation patterns of drug-resistant Beijing strains of M. tuberculosis isolated from Tianjin, China.</p><p><b>METHODS</b>A total of 822 M. tuberculosis isolates were screened for drug resistance by an absolute concentration method and the genotype was identified by PCR. 169 drug-resistant isolates of the Beijing family were analyzed for the potential mutations in the rpoB, katG, inhA promoter region and in rpsL, rrs and embB genes, which are associated with resistance to rifampin (RFP), isoniazid (INH), streptomycin (SM) and ethambutol (EMB) respectively by PCR and DNA sequencing.</p><p><b>RESULTS</b>Fifty-eight out of 63 RFP-resistant isolates were found to carry the mutations within the 81-bp RFP resistance determining region (RRDR) of the rpoB gene and the most frequent mutations occurred at codon 531 (44.4%), 526 (28.6%), and 516 (7.9%) respectively. 16 mutation patterns affecting 12 different codons around the RRDR of rpoB were found. Of 116 INH-resistant isolates, 56 (48.3%) had the mutation of katG 315 (AGC-->ACC) (Ser-->Thr), 3 (2.6%) carried S315N (AGC-->AAC) and 27 (16.0%) had the mutation of inhA-15A-->T. 84 out of 122 SM-resistant isolates (68.9%) displayed mutations at the codons 43 or 88 with AAG-->AGG (Lys-->Arg) of the rpsL gene and 22 (18.0%) with the mutations at positions 513A-->C, 516C-->T or 905 A-->G in the rrs gene. Of 34 EMB-resistant isolates, 6 had mutation with M306V (ATG-->GTG), 3 with M306I (ATG-->ATT), 1 with M306I (ATG-->ATA), 1 with D328Y (GAT-->TAT), 1 with V348L (GTC-->CTC), and 1 with G406S (GGC-->AGC) in the embB gene.</p><p><b>CONCLUSION</b>These novel findings extended our understanding of resistance-related mutations in the Beijing strains of M. tuberculosis and may provide a scientific basis for development of new strategies for diagnosis and control of tuberculosis in China and other countries where Beijing strains are prevalent.</p>