Advance in the Research of Epidermal Growth Factor Receptor Inhibitors Related to Lung Cancer / 中国药学杂志

Epidermal growth factor receptor (EGFR), a member of the super family of protein tyrosine kinase receptors, plays a crucial role in proliferation, apoptosis, aggression and metastasis of tumor cells. The target-EGFR inhibitors have been a hotspot and tendency in the progress of anti-tumors. Currently, the target-EGFR inhibitors have made a steady progress and many valuable drugs in the clinical treatment have been developed. However, many patients will be resistance to the drugs due to the mutation of amino acid. Therefore, drugs which can be effective in the later treatment or long-term therapies will always be deficient. In this article, the research progress and mechanism of anti-tumor of small molecules EGFR inhibitors in detail are reviewed.

Detection and clinical analysis of acute lower respiratory tract infection with human coronaviruses in children in Beijing area 2007-2015 / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate human coronaviruses (HCoVs) infection in children with acute lower respiratory tract infection(ALRTI)and to explore the clinical features of ALRTI caused by HCoVs in children.</p><p><b>METHOD</b>Totally 4 371 children with clinical diagnosis of ALRTI during the period from March 2007 to February 2015 seen in Beijing Children's Hospital were recruited into this study. Patients were divided into 4 groups by age, including 1 890 cases in < 1 year group, 788 cases in 1-3 years group, 553 cases in 3-6 years group, 1140 cases in ≥6 years group. One nasopharyngeal aspirate specimen was collected from each patient. RT-PCR methods were applied to detect 9 common respiratory viruses including HCoVs (including HCoV-OC43, HCoV-229E, HCoV-NL63 and HCoV-HKU1), respiratory syncytial virus (RSV) and so on. Clinical features of ALRTI with single HCoVs infection were analyzed and compared with hospitalized ALRTI cases with single RSV infection in the same period.</p><p><b>RESULT</b>(1) Totally 2 895 cases were positive for at least one virus in this study in 4 371 ALRTI patients (positive rate 66.23%), in which 147 cases were positive for HCoVs infection (positive rate 3.36%). (2) Positive rates of HCoVs in each year from 2007 to 2014 were 6.11%, 3.79%, 4.69%, 4.31%, 2.38% 2.10%, 0.77% and 2.65%, respectively. The mean positive rates of HCoVs for each month from January to December were 2.53%, 2.12%, 3.63%, 6.68%, 1.53%, 3.77%, 3.92%, 3.00%, 2.15%, 5.26%, 3.01% and 2.80%. (3) Detection results of each subtypes of HCoVs in total 4 371 pediatric ALRTI patients were: 48 cases positive for HCoV-OC43(1.10%), 32 cases positive for HCoV-229E(0.73%), 25 cases positive for HCoV-NL63 (0.57%), 27 cases positive for HCoV-HKU1 (0.62%). (4) Positive rates of HCoVs infection in <1 year group, 1-3 years group, 3-6 years group and ≥ 6 years group were 4.13%, 5.08%, 2.71% and 1.23%, respectively. There were significant differences in positive rates of HCoV among groups (χ² = 27.218, P<0.01). (5) There were 16 hospitalized cases with single infection of HCoVs in this study, of which 12 cases were diagnosed as bronchopneumonia, 3 cases developed acute laryngeal obstruction, 2 cases had acute bronchial asthma attack. Common clinical manifestations included cough (14 cases), gasping (13 cases), dyspnea (9 cases), fever (6 cases), hoarseness (4 cases), laryngeal stridor (4 cases) and abnormality on chest X-ray (including fuzzy lung texture, patchy shadow and consolidation) (12 cases). (6) There were no significant differences in the incidence of clinical manifestations (including cough, gasping, dyspnea, fever and abnormality on chest X-ray), complications (including respiratory failure, myocardial damage, and acute bronchial asthma attack) and mechanical ventilation between hospitalized ALRTI patients with single HCoV infection and 193 patients with single RSV infection in the same period.</p><p><b>CONCLUSION</b>HCoVs are pathogens of ALRTI in children, The overall positive rate of HCoVs was 3.36% in this study. The clinical manifestations and severity of ALRTI caused by single HCoVs was comparable to that of ALRTI with single RSV infection in children.</p>

The significance of ultrasonic cardiac output monitor for monitoring cardiac function in the children with pneumonia complicated with heart failure / 中国小儿急救医学

Objective To explore the application of the ultrasonic cardiac output monitor(USCOM) in the children with pneumonia complicated with heart failure.Methods Fourteen children with pneumonia complicated with heart failure were enrolled in the experimental group and thirty-two children with common pneumonia were enrolled in the control group.We used the USCOM to measure the cardiac output indicators,including the aortic peak velocity,heart rate,stroke volume index,cardiac index,ejection time and correcting ejection time.Results The heart rate in the experimental group was faster than that of control group[(174 ±10) beats/min vs (133 ± 14) beats/min,P ＜0.05],the aortic peak velocity in the experimental group was lower than that of control group [(1.246 ±0.234) m/s vs (1.449 ±0.300) m/s,P ＜0.05],the stroke volume index in the experimental group was lower than that of control group [(29.357 ± 6.500) ml/m2 vs (40.188 ±5.337) ml/m2,P ＜0.05],and the correcting ejection time in the experimental group was shorter than that of control group [(342.560 ± 8.219) ms vs (354.430 ± 16.500) ms,P ＜ 0.05].Conclusion The cardiac function monitoring by USCOM is accurate and convenient,and USCOM can provide the accurate evidence for the clinical application.

Risk factors related to mortality of deep fungal infection in pediatric intensive care unit / 中国小儿急救医学

Objective To investigate the risk factors related to mortality of children with deep fungal infection in pediatric intensive care unit(PICU).Methods A retrospective case-control study was applied.Ninty-six patients admitted to PICU with clinical or definite diagnosis of deep fungal infection from Nov 2005 to Mar 2009 were included.The risk factors related to mortality wereanalyzed with the logistic regression analysis.The research factors included:sex,age,primary diseases,complications,invasive operations and therapeutic measures etc.Results Of all 96 children,28 died (28.2％).According to the analytical results of multivariate logistic regression,the variables significantly associated with mortality were immunosuppressive (OR =185.770,95 ％ CI 11.467 ～ 3 009.507),mechanical ventilation (OR =11.555,95 ％ CI 2.780 ～ 48.039),hypoproteinemia (OR =1.246,95％ CI 1.133 ～ 1.369) and low pediatric critical illness score (OR =1.086,95 ％ CI 1.008 ～ 1.169).Conclusion The risk factors related to mortality of children with deep fungal infection in PICU were immunosuppressive,mechanical ventilation,hypoproteinemia and low pediatric critical illness score.

Serological and molecular capsular typing, antibiotic susceptibility and multilocus sequence typing of Streptococcus pneumoniae isolates from invasive and non-invasive infections / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Streptococcus pneumoniae (S. pneumoniae) is a major causative agent of severe infections, including sepsis, pneumonia, meningitis, and otitis media, and has become a major public health concern. We report the pneumococcal serotype and sequence type (ST) distribution, and antimicrobial resistance of 39 S. pneumoniae strains from seven hospitals in China.</p><p><b>METHODS</b>Blood/cerebrospinal fluid (CSF) and sputum isolates from patients were analyzed to determine S. pneumoniae serotypes by polymerase chain reaction (PCR) and the Neufeld Quellung reaction, the multilocus sequence types (MLST) by PCR and sequencing, and susceptibility to antimicrobial agents by the VITEK Gram Positive Susceptibility Card.</p><p><b>RESULTS</b>A total of 39 isolates were collected including 21 blood/CSF and 18 sputum isolates. Conventional serotyping by the Quellung reaction required 749 reactions. In contrast, PCR based typing needed only 106 PCR reactions. The most frequent serotypes from the blood/CSF isolates were 14 (38.1%), 19A (14.3%), 23F (9.5%), and 18C (9.5%). In the sputum isolates the most frequent serotypes were 19F (33.3%), 23F (16.7%), 19A (11.1%), and 3 (11.1%). The incidence of penicillin resistance in the blood/CSF and sputum isolates was 66.7% and 55.6%, respectively. Statistical analysis showed that patients = 5 years old had a higher resistance to penicillin when they compared with the patients = 65 years old (P = 0.011). Serotypes 14, 19A and 19F were significantly associated with penicillin resistance (P < 0.001). ST320, ST271, and ST876 isolates showed high resistant rates to several antibiotics including penicillin (P = 0.006). All of the isolates of serotype 19A were resistant to both penicillin and erythromycin, and they were all multi-drug resistant (MDR) isolates.</p><p><b>CONCLUSIONS</b>The specificity and sensitivity of multiplex-PCR are good, and this method represents a substantial savings of time and money, and can be widely used in the laboratory and clinical practice. Data from this research showed an extremely high prevalence of penicillin resistance and an increasing prevalence of multi-drug resistant (MDR) rate in S. pneumoniae. A distinctive emergence of serotype 19A was observed which was also associated with the increasing prevalence of antimicrobial resistance. Therefore, nationwide surveillance of pneumococcal resistance and serotypes is strongly warranted.</p>

Three years surveillance of viral etiology of acute lower respiratory tract infection in children from 2007 to 2010 / 中华儿科杂志

<p><b>OBJECTIVE</b>Viruses are common pathogens of acute lower respiratory tract infection (ALRTI) in children. There are few studies on consecutive monitoring of viral pathogens of ALRTI in a larger cohort during the past several years. The aim of this study was to investigate the viral pathogens of ALRTI in children of different age groups and to outline the epidemic feature of different viruses.</p><p><b>METHOD</b>(1) Totally 1914 (1281 male and 709 female) children with clinical diagnosis of ALRTI during the period of March 2007 to March 2010 were recruited into this study. These patients were hospitalized patients in department of internal medicine or outpatients in emergency department in Beijing Children's Hospital. The patients were divided into four groups, including 1072 patients < 1 year old, 326 patients 1- < 3 years old, 158 patients 3- < 6 years old, 358 patients ≥ 6 years old. One nasopharyngeal aspirate specimen was collected from each patient. Reverse transcription (RT) PCR methods were applied to detect common respiratory viruses including respiratory syncytial virus (RSV), human rhinovirus (HRV), influenza virus type A, B and C (IFA, IFB, IFC), parainfluenza virus (PIV) type 1-4, adenovirus (ADV), enterovirus (EV), human coronavirus (HCOV), human metapneumovirus (HMPV) and human bocavirus (HBOV).</p><p><b>RESULT</b>(1) The total positive rate of viruses was 70.3%. The positive rate was 83.0% (890/1072) in the group of < 1 year old, and 80.1% (261/326) in group of 1- < 3 years old, 60.8% (96/158) in group of 3- < 6 years old and 27.7% (99/358) in group of ≥ 6 years old, respectively. There was a significant difference in the positive rate among different age groups (χ² = 2213.5, P = 0.000). The top three viruses were RSV, HRV and PIV; and the positive rates were 50.9%, 36.2% and 12.0% respectively in group of < 1 year old. (2) The epidemic seasons of RSV and HRV were winter and spring, and PIV infection was epidemic in spring and summer. (3) The detection rates of 2 or more viruses were 38.2%, 36.4%, 30.2% and 15.2% in groups of < 1 year old, 1- < 3 years old, 3- < 6 years old and ≥ 6 years old, respectively. There was a significant difference in the mixed infection rate among different age groups (χ² = 1346.00, P = 0.000).</p><p><b>CONCLUSION</b>RSV, HRV and PIV were the most predominant pathogens in younger children with ALRTI. Different viral infections had different seasonal features. Mixed infections with two or more viruses were detected in substantial proportion of patients with ALRTI, but further studies are needed to explore the clinical significance of mixed infection with viruses in patients with ALRTI.</p>

Preliminary molecular epidemiology of the Staphylococcus aureus in lower respiratory tract infections: a multicenter study in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Staphylococcus aureus (S. aureus) remains as an important microbial pathogen resulting in community and nosocomial acquired infections with significant morbidity and mortality. Few reports for S. aureus in lower respiratory tract infections (LRTIs) have been documented. The aim of this study was to explore the molecular epidemiology of S. aureus in LRTIs in China.</p><p><b>METHODS</b>A multicenter study of the molecular epidemiology of S. aureus in LRTIs was conducted in 21 hospitals in Beijing, Shanghai and twelve other provinces from November 2007 to February 2009. All the collected S. aureus strains were classified as minimum inhibitory concentration (MIC), mecA gene, virulence genes Panton-Valentine Leukocidin (PVL) and γ-hemolysin (hlg), staphylococcal cassette chromosome mec (SCCmec) type, agr type, and Multilocus Sequence Typing (MLST).</p><p><b>RESULTS</b>Totally, nine methicillin-sensitive S. aureus (MSSA) and 29 methicillin-resistant S. aureus (MRSA) strains were isolated after culture from a total of 2829 sputums or bronchoalveolar lavages. The majority of MRSA strains (22/29) had a MIC value of ≥ 512 µg/ml for cefoxitin. The mecA gene acting as the conservative gene was carried by all MRSA strains. PVL genes were detected in only one S. aureus strain (2.63%, 1/38). The hlg gene was detected in almost the all S. aureus (100% in MSSA and 96.56% in MRSA strains). About 75.86% of MRSA strains carried SCCmec III. Agr type 1 was predominant (78.95%) among the identified three agr types (agr types 1, 2, and 3). Totally, ten sequence type (ST) of S. aureus strains were detected. A new sequence type (ST1445) was found besides confirming ST239 as the major sequence type (60.53%). A dendrogram generated from our own MLST database showed all the bootstrap values ≤ 50%.</p><p><b>CONCLUSION</b>Our preliminary epidemiology data show SCCmec III, ST239 and agr type 1 of S. aureus as the predominant strains in LRTIs in Mainland of China.</p>

Drug-resistant genes carried by Acinetobacter baumanii isolated from patients with lower respiratory tract infection / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Acinetobacter baumanii (A. baumanii ) remains an important microbial pathogen resulting in nosocomial acquired infections with significant morbidity and mortality. The mechanism by which nosocomial bacteria, like A. baumanii, attain multidrug resistance to antibiotics is of considerable interest. The aim in this study was to investigate the spread status of antibiotic resistance genes, such as multiple β-lactamase genes and aminoglycoside-modifying enzyme genes, from A. baumanii strains isolated from patients with lower respiratory tract infections (LRTIs).</p><p><b>METHODS</b>Two thousand six hundred and ninety-eight sputum or the bronchoalveolar lavage samples from inpatients with LRTIs were collected in 21 hospitals in the mainland of China from November 2007 to February 2009. All samples were routinely inoculated. The isolated bacterial strains and their susceptibility were analyzed via VITEK-2 expert system. Several kinds of antibiotic resistant genes were further differentiated via polymerase chain reaction and sequencing methods.</p><p><b>RESULTS</b>Totally, 39 A. baumanii strains were isolated from 2698 sputum or bronchoalveolar lavage samples. There was not only a high resistant rate of the isolated A. baumanii strains to ampicillin and first- and second-generation cephalosporins (94.87%, 100% and 97.44%, respectively), but also to the third-generation cephalosporins (ceftriaxone at 92.31%, ceftazidine at 51.28%) and imipenem (43.59%) as well. The lowest antibiotic resistance rate of 20.51% was found to amikacin. The OXA-23 gene was identified in 17 strains of A. baumanii, and the AmpC gene in 23 strains. The TEM-1 gene was carried in 15 strains. PER-1 and SHV-2 genes were detected in two different strains. Aminoglycoside-modifying enzyme gene aac-3-Ia was found in 23 strains, and the aac-6'-Ib gene in 19 strains. aac-3-Ia and aac-6'-Ib genes hibernated in three A. baumanii strains that showed no drug-resistant phenotype.</p><p><b>CONCLUSIONS</b>A. baumanii can carry multiple drug-resistant genes at the same time and result in multi-drug resistance. Aminoglycoside-modifying enzyme genes could be hibernating in aminoglycoside sensitive strains without expressing their phenotype.</p>

Evaluation of ultrasonic technology for monitoring children's cardiac output / 中国小儿急救医学

Objective To explore the accuracy of the ultrasonic cardiac output monitor(USCOM) device for estimation of children's cardiac output.Methods We conducted a prospective study in Beijing Children's Hospital.Sixty healthy children were enrolled in this study.We evaluated the accuracy of USCOM monitor device in the measurement of cardiac output by comparing with the measurements obtained by the M-Teichholz formula and the Doppler aortic blood flow method.Results The data from the USCOM monitor device had better consistency with those from the M-Teichholz formula (r=0.88,P<0.05),and there was no significant difference (P>0.05) between the two methods.The similar results were found between the USCOM method and the Doppler aortic blood flow method (r=0.83,P<0.05).Conclusion This study shows that cardiac output monitoring by USCOM is accurate,and USCOM is a promising technique in cardiac output monitoring.

Effect of Nasal Continuous Positive Airway Pressure on Cardiac Function in Children with Pneumonia Complicated with Heart Failure / 实用儿科临床杂志

Objective To investigate the effect of nasal continuous positive airway pressure (NCPAP) on cardiac function in children with pneumonia complicated with heart failure.Methods Twenty-two children with pneumonia complicated with heart failure were selected in emergency room of Beijing Children′s Hospital Affiliated to Capital Medical University from Oct.2008 to Mar.2009,aged 1 month and 15 days to 2 years and 8 months,prospective clinical study.Cardiac function[including cardiac index(CI),heart rate(HR) and stroke volume index(SVI)] before and after NCPAP 0.04-0.05 kPa for 30 minutes were monitored by ultrasonic cardiac output monitoring(USCOM).Results After the application of 0.04-0.05 kPa NCPAP for 30 minutes,the heart rate decreased signi-ficantly [(173?10) beats/min vs (151?13) beats/min P0.05].Conclusions NCPAP might improve cardiac function by increasing stroke volume index and decreasing heart rate and respiratory rate in children with pneumonia complicated with heart failure.

Pathogenic anlysis of 44 cases with ventilator-associated pneumonia in PICU / 中国小儿急救医学

Objective　To find out the morbidity and main pathogens of ventilator-associated pneumonia(VAP) in PICU.Methods　44 VAP cases were reviewed.Results　44 VAP cases were diagnosed and analyzed from 1998, 2 to 2001,1,the morbidity of VAP was 69.8%.The predominant pathogen was Pseudomonas aeruginosa.Conclusion　It has reference value in consideri ng the possible pathogens of pneumonia.