Objectives:To investigate clinical characteristics, outcomes and antimicrobial resistance of community-acquired Pseudomonas aeruginosa (CAPA) infections in Chinese pediatric patients. Methods:This retrospective study was conducted at 6 tertiary hospitals in China during January 2016 to December 2018. The clinical and microbiological data of CAPA infected hospitalized children in Hainan and in other regions were collected and compared, and the antimicrobial resistance patterns, clinical characteristics and antibiotic therapy were analyzed. Between different groups were compared using the Chi-square test and Mann-Whitney U test. Results:Among 91 patients, 63 cases were males, 28 cases were females, and 74 cases were from Hainan province, 17 cases were from other regians. The age of consultation was 22.5 (5.4, 44.0) months. Twenty-four cases (26%) had underlying diseases. Fever (79 cases (87%)) and cough (64 cases (70%)) were common initial symptoms. Other concomitant symptoms included wheezing 8 cases (9%), diarrhea 3 cases (3%) and vomiting 4 cases (4%). Twenty-eight cases (31%) had organ infections, including pneumonia 22 cases (24%), skin infection 5 cases (5%), meningitis, intra-abdominal infection and upper urinary tract infection each 1 case (1%). The resistance rate of CAPA isolates to cefepime (4% (4/90)), amikacin (1% (1/90)), ciprofloxacin (2% (2/90)) and levofloxacin (1% (1/89)) was low, and to ceftazidime, piperacillin, piperacillin-azobactam, carbapenem was 12% (11/90), 3/16, 18% (10/56) and 6% (5/90), respectively. Antimicrobial combination therapy accounted for 52% (47/91) of empirical therapy and 59% (52/88) of definite therapy. Two cases (2%) were hopeless discharged, and 3 cases (3%) died during hospitalization. The worse prognosis of CAPA infection is significantly different among children in other regions and in Hainan (4/17 vs. 1% (1/74), χ2=9.74, P<0.05). Conclusions:The invasive CAPA-infection has regional difference in incidence and prognosis in China. Clinical symptoms and signs are non-specific. CAPA strains isolated from pediatric patients display low level of resistance to most of the common antipseudomonal antibiotics. The proportion of poor prognostic outcome is lower in Hainan than in other regions.

Objective: To explore the direct⁃on⁃target micro⁃droplet growth assay (DOT⁃MGA) for rapid detection of the susceptibility of tigecycline and polymyxin. Methods: A total of 67 strains of Klebsiella pneumoniae were collected for DOT⁃MGA. 6 μl droplets with or without tigecycline or polymyxin (The final drug concentration is 2 μg/ml) were added in triplicate into the wells of the MALDI plate with four incubation time points (3 h ,4 h ,6 h , and 8 h) . The results were classified as susceptible (score < 1. 7) and non⁃susceptible (score≥1 . 7) according to the Bruker Biotype software Results: After incubation for 4 h , the growth efficiency, specificity and positive predictive value of tigecycline and polymyxin were both 100. 00% . The classification consistency rate was 98. 15% and 96. 15% , the sensitivity was 96. 30% and 92. 31% , and the negative predictive value was 96. 45% and 92. 86% , respectively. Conclusion DOT⁃MGA can provide rapid and reliable drug susceptibility diagnosis of tigecycline and polymyxin ,which is of great significance for the clinical anti⁃infective treatment.

Objective:To explore the clinical phenotype characteristics of early-onset epileptic encephalopathy (EOEE) caused by sodium channel mutations.Methods:A retrospective study was used.A total of 52 EOEE patients treated in the Department of Neurology, Children′s Hospital of Fudan University and Department of Neurology, Wuhan Children′s Hospital, Tongji Medical College, Huazhong University of Science & Technology from June 2016 to June 2019 were recruited.Peripheral blood samples of 52 patients and their parents were collected for analyzing pathogenic mutations by the next generation sequencing and copy number variations of whole exons in family. Chi- square test was used to compare seizure control data among different voltage-gated sodium channel α1 subunit ( SCN1A) mutation types. Results:A total of 35/52 cases (67.3%) were diagnosed as Dravet syndrome, 3/52 cases (5.8%) were West syndrome, and 14/52 cases (26.9%) were non-symptomatic EOEE.The electroencephalogram (EEG) findings showed a large number of multifocal spikes, spike-slow waves, sharp waves, and sharp-slow waves.A total of 45/52 cases (86.5%) showed normal brain magnetic resonance imaging(MRI), 1 case had slightly widened bilateral frontal sulcus, 1 case had widened bilateral temporal pole and frontal top subarachnoid space, and the remaining 5 cases had widened extracerebral space and slightly larger ventricles.Thirteen cases were re-examined with brain MRI, and 3 cases had mild brain atrophy.A total of 43/52 cases (82.7%) were examined with SCN1A gene mutations, of which 28/52 cases (53.8%) were missense mutations, 5/52 cases (9.6%) were nonsense mutations, 7/52 cases (13.5%) were frameshift mutations and 3/52 cases (5.8%) were splice site mutations.A total of 3/52 cases (5.8%) had SCN2A mutations, of which 2/52 cases (3.8%) were missense mutations, and 1/52 case (1.9%) was a frameshift mutation, 1/52 cases (1.9%) carrying the missense mutation of the SCN3A gene.A total of 5/52 cases (9.6%) had missense mutations of the SCN8A gene.After an average of 1-year follow-up, a total of 13/52 cases (25.0%) had more than 1-year control of seizure, of which 6/52 cases (11.5%) with seizure control for more than 2 years, and 4/52 cases (7.7%) with more than 3-year control.Children carrying SCN1A missense mutations were relatively easier to be controlled for seizures than those carrying SCN1A truncation mutations (nonsense mutations+ frameshift mutations) ( P<0.05). In 5 children carrying SCN8A mutations, 2 cases of them had seizures control for more than 1 year after adding Oxcarbazepine, but the improvement of mental motor function was not obvious. Conclusions:In children with EOEE associated with sodium channel gene mutations, SCN1A, SCN2A, SCN3A, and SCN8A mutations were pathogenic factors.Among them, SCN1A was the most common pathogenic gene for EOEE, with the mutation rate of 82.7%.Dravet syndrome was the most common clinical phenotype of EOEE associated with sodium channel gene mutations.Epileptic seizures in children carrying SCN1A missense mutations were easier to be controlled than those with truncated mutation (nonsense mutations + frameshift mutations), suggesting that the gene mutation type was related to the degree of seizures control.Oxcarbazepine was effective in the treatment of EOEE with SCN8A gene mutations, indicating that the combination therapy using anti-epilepsy drugs can be applied to EOEE patients according to the type of gene function.

Background: Helicobacter pylori (Hp) infection is related to the occurrence of many upper digestive tract diseases, and the eradication rate has been decreasing year by year. Aims: To investigate the risk factors affecting initial eradication rate of Hp infection. Methods: Clinical data of 428 patients with Hp infection were retrospectively analyzed. Four regimens (14-day esomeprazole 20 mg + amoxicillin 750 mg, qid; 10-day esomeprazole 20 mg + amoxicillin 750 mg, qid; 14-day esomeprazole 20 mg + amoxicillin 1 000 mg, tid; 14-day esomeprazole 20 mg + bismuth 220 mg + amoxicillin 1 000 mg + clarithromycin 500 mg, bid) were given, and effect of antibiotic resistance on Hp eradication was analyzed, the relevant risk factors affecting the eradication rate of Hp were investigated. Results: The eradication rate of ITT analysis was 86.4%, PP analysis was 87.6%. The eradication rates of 4 regimens for ITT analysis were 90.8%, 79.8%, 82.7%, 91.9%, respectively, and were 90.8%, 81.2%, 85.1%, 92.7% for PP analysis, respectively. The antibiotic resistance rate was 30.3%, 97.4% and 36.8% for clarithromycin, metronidazole and levofloxacin, respectively. The recurrence rate of 116 patients was 4.3% after one year of eradication. Smoking, poor compliance, CYP2C19 gene polymorphism were risk factors for eradication rate of Hp (P<0.05). Conclusions: Smoking, poor compliance and ultra-rapid metabolizers, extensive metabolizers of CYP2C19 gene polymorphism can reduce Hp eradication rate. In clinical practice, patient education should be strengthened to urge patients to quit smoking. The quality of follow-up should be improved and proton pump inhibitor that has less impact on CYP2C19 gene polymorphism should be used, thereby increase the Hp eradication rate.

Objective:To evaluate the role of adiponectin in sevoflurane pretreatment-induced improvement in cognitive function in mice with myocardial ischemia/reperfusion (I/R).Methods:Thirty SPF healthy adult male wild-type C57 mice, aged 8-10 weeks, weighing 20-25 g, were divided into 3 groups ( n=10 each) using a random number table method: sham operation group (group Sham), myocardial I/R group (group MI/R) and sevoflurane pretreatment group (group SP). Another 10 SPF healthy male adiponectin knockout SPF mice, aged 8-10 weeks, weighing 20-25 g, were selected and served as APNKO group.Myocardial I/R was induced by 30 min occlusion of anterior descending branch of left coronary artery followed by reperfusion.In SP and APNKO groups, sevoflurane pretreatment included 3 cycles of 10-minute inhalation of 2% sevoflurane-93% O 2-5% CO 2 interspersed with 15-minute inhalation of 95% O 2-5% CO 2, and then the model was established.At 1, 2 and 4 days of reperfusion, cognitive function was assessed by Morris water maze test. Results:There was no significant difference in swimming velocity at each time point between the 4 groups ( P>0.05). Compared with group Sham, the escape latency was significantly prolonged, and the frequency of crossing the original platform was decreased at each time point in group MI/R ( P<0.05). Compared with group MI/R, the escape latency was significantly shortened, and the frequency of crossing the original platform was increased at each time point in group SP ( P<0.05). Compared with group SP, the escape latency was significantly prolonged, and the frequency of crossing the original platform was decreased at each time point in group APNKO ( P<0.05). Conclusion:Adiponectin is involved in the process of sevoflurane pretreatment-induced improvement in cognitive function in mice with myocardial I/R.

Background & Objective: Nonsense mutations in SMC1A have been reported only in females with cluster seizures, all of whom have been described as drug-resistant epilepsy. Here, we aim to explore the use of ketogenic diet treatment. Methods: The clinical data of female patients with de novo nonsense mutations in SMC1A were collected and analyzed. The clinical data was recruited and analyzed. The peripheral blood of children and their parents was collected. The next generation sequencing was used to find suspected pathogenic mutations and all the confirmed mutations were verified by Sanger sequencing. Results: Three patients with heterozygous de novo mutations in SMC1A gene were reviewed. All patients were females, presenting with seizure onset at age between 2.5 to 11 months old. One patient had mild developmental delay. One had moderate developmental delay. Another had severe developmental retardation. None of the patients had a clinical diagnosis of Cornelia de Lange syndrome. All three patients had prominent clinical features of cluster seizures. All the nonsense mutations were predicted damaging SMC1A protein by PolyPhen-2 HVAR. All the patients were treated with multiple antiepileptic drugs but their seizures remained refractory. When initiated with ketogenic diet, they became seizure free within 3 to 4 weeks. Conclusion: SMC1A nonsense mutations can cause early onset epilepsy only in females with cluster seizures. These patients are characterized by drug-resistant epilepsy, but all our three patients have good effect on ketogenic diet add-on therapy.

Objective: To explore the clinical features, the serotype distribution and drug resistance of the isolates in patient with invasive pneumococcal disease (IPD). Methods: By retrieving the laboratory information system in 18 children′s hospitals from 2012 to 2017, the children with IPD were enrolled. Streptococcus pneumoniae (Spn) must be isolated from the sterile sites (blood, cerebrospinal fluid, hydrothorax and joint effusion etc.). The clinical characteristics, serotype, drug resistance, treatment and prognosis were reviewed and analyzed. According to the telephone follow up results, the patients were divided into death group and recovered group. The index as an independent risk factor of mortality was demonstrated by multivariate logistic regression analysis. Results: There were 1 138 children with IPD, including 684 male and 454 female. The proportion of male to female was 1.5∶1. The age ranged from one day to 16 years. The median age was 1 year 3 month. The majority was under 5 years of age (89.3%, n= 1 016), especially under 2 years of age (61.9%, n=704). In all cases, 88.2% (n=1 004) were community acquired infection. The infections included meningitis (n=446, 39.2%), pneumonia with bacteremia (n=339, 29.8%), and bacteremia without focus (n=232, 20.4%). Underlying diseases were found in 242 cases (21.3%). Co-infections were determined in 62 cases (5.4%) with mycoplasma, 27 cases (2.4%) with adenovirus and 34 cases with influenza virus (3.0%). The penicillin insensitivity (PNSP) rates in meningitis and non-meningitis isolates were 69.5% (276/397) and 35.9% (221/615), respectively. There were 81 strains serotyped, in which 93.8% (76/81) were covered by 13-valent protein-polysaccharide conjugate vaccine (PCV13). In the 965 patients who were followed up by phone call, 156 cases (16.2%) were confirmed dead. The independent risk factors for the death were under 2 years of age (OR=2.143, 95%CI 1.284-3.577, P=0.004), meningitis (OR=3.066, 95%CI 1.852-5.074, P<0.01), underlying disease (OR=4.801, 95%CI 2.953-7.804, P<0.01), septic shock(OR=3.542, 95%CI 1.829-6.859, P<0.01), disseminated intravascular coagulation (DIC) (OR=4.150, 95%CI 1.468-11.733, P=0.007), multiple organ failure (OR=12.693, 95%CI 6.623-24.325, P<0.01) and complications of central nervous system (OR=1.975, 95%CI 1.144-3.410, P=0.015). Conclusions Most children with IPD were under 5 years of age, having underlying diseases and acquired the infection in community. The independent risk factors for death were under two years old, meningitis, underlying diseases and multiple organ failure. The problem of drug resistance was severe. The universal immunization of PCV13 would be effective to prevent IPD in Chinese children.

Objective To explore the changes and their clinical significance of peripheral blood myeloid-derived suppressor cells (MDSC)and their subtypes in patients with inflammatory bowel disease (IBD).Methods From April 2016 to April 2017,99 hospitalized IBD patients in 2nd Xiangya Hospital of Central South University were enrolled as observation group one,which included 84 Crohn's disease (CD) (70 in active phase and 14 in remission phase)and 15 patients with ulcerative colitis(UC).At the same period,32 healthy controls were enrolled as healthy control group one.The proportion of peripheral blood MDSC and subtypes of CD patients,UC patients and healthy controls were examined.Observation group two including 62 IBD patients (47 CD and 15 UC)were selected from observation group one and 21 healthy individuals were selected from healthy control group one as healthy control.The serum levels of tumor necrosis factorα(TNF-α)and interleukin 8 (IL-8)were detected.Chi square test,t test and one-way analysis of variance were performed for statistical analysis.Pearson correlation was performed for correlation analysis.Results The proportion of MDSC in peripheral blood mononuclear cells of CD and UC patients of observation group one were both higher than that of healthy control group one ((6 .30 ± 3.97)% and (7.50±3.12)% vs.(3.94±2.25)%,respectively),and the differences were statistically significant (t＝-3.22 and -3.21,both P＜0.01).The proportion of granulocytic MDSC in peripheral blood mononuclear cells of CD patients was higher than that of UC patients and healthy control group one ((65.69±20.45)% vs.(50.93±13.56)% and (51.50±11.61)%,respectively),and the differences were statistically significant (t＝2 .93 and 3 .79 ,both P＜0 .01 ).The proportion of monocytic MDSC in peripheral blood mononuclear cells of UC patients was higher than that of CD patients and healthy control group one ((28.41±18.33)% vs.(18.38±17.43)% and (28.17±10.22)%,respectively),and the differences were statistically significant (t＝2.22 and 2.93,both P＜0.05 ).The proportion of granulocytic MDSC was higher and the proportion of monocytic MDSC was lower in peripheral blood mononuclear cells of CD patients in active phase than those of CD patients in remission phase ((67 .36 ± 2.27)% vs.(46.49±6.32)%,and (17.19±2.02)% vs.(34.33±6.12)%),and the differences were statistically significant (t＝3.60 and 3.26,both P＜0.01).The serum level of TNF-αof CD patients of observation group two was higher than that of UC patients and healthy control group two ((7.83± 6.54)ng/L vs.(4.77±2.12)ng/L and (4.40±2.05)ng/L),and the differences were statistically significant (t＝2.01 and 2.53,both P＜0.05).The serum level of IL-8 of UC patients of observation group two was higher than that of CD patients and healthy control group two ((65.80±45.14)ng/L vs. (25.80±22.32)ng/L and (26.40±22.37)ng/L),and the differences were statistically significant (t＝4.87 and 4.21,both P＜0.01).Granulocytic MDSC was positively correlated with TNF-α(r＝0.319, P＝0 .0 1 1 )and was negatively correlated with IL-8 (r＝-0 .2 9 6 ,P＝0 .0 1 9 ).Monocytic MDSC was negatively correlated with TNF-α(r＝-0.260,P＝0.040)and was positively correlated with IL-8 (r＝0.306,P＝0.016).Conclusions The proportion of granulocytic MDSC in peripheral blood mononuclear cells significantly increases in active CD patients,while the proportion of monocytic MDSC significantly increases in UC and CD patients in remission phase.Detection of MDSC and their subtypes maybe helpful in the differentiation of CD and UC as well as the diagnosis and treatment of CD.

Objective To investigate the biocompatibility and biodegradability of mini-implants of PLA-based composites in experimental animals by histomorphometry, and to study its clinical application in orthodontic treatment. Methods Six adult male Beagle dogs were randomly divided into 3 groups, a total of 72 mini-implants were implanted to the mandibular. Two Beagle dogs were sacrificed at 2 months、4 months and 6 months after surgery. Animals were intramuscularly injected with tetracycline on 14 and 4 days before sacrifice. Mandibular specimens and the surfaces of mini-implants were examined with Cone beam CT, CBCT and Scanning Electronic Microscopy and SEM respectively. Histopathologocal changes were observed with toluidine blue staining and HE staining. Results The results of CBCT assay showed that the mini-implants were gradually radiopacity with the extension of time. SEM assay showed that the morphology of mini-implants surface was significantly changed;micro-implants degradation occured gradually.New bone formation was observed around the micro-implants within 10 days.Toluidine blue staining showed the formation of new bone around the mini-implants. However, the inflamma-tion around the implants was not observed. Conclusion The biocompatibility of biodegradable mini-implant is good. This mini-implant is biodegradable in vivo and can promote the formation of the surrounding bone tissue.

Objective To explore the application value of respiratory syncytial virus RNA (RSV-RNA) and respiratory syncytial virus IgM (RSV-IgM) antibody in the diagnosis of children with respiratory infection .Methods From September 2015 to April 2017 ,56 cases of respiratory syncytial virus infection were selected ,and the specimens of pharyngeal secretions were collected ,and RSV-RNA was detected ,in addition ,fasting venous blood was taken from children ,and the RSV-IgM antibody was detected .The positive rate of detection and correlation with age and time of onset were statistically analyzed .Results The positive rates of RSV-RNA and RSV-IgM were 89 .29% and 32 .14% ,respectively .The detection rate of RSV-RNA was significantly higher than that of RSV-IgM ,and the difference was statistically significant (P<0 .05) .The two groups ,≤6 months and from >6 months to 1 year old ,the detection rates of RSV-RNA in children was higher than RSV-IgM (P<0 .05) ,and the detection rate of RSV-RNA in chil-dren with ≤7 days of onset was higher than that of RSV-IgM (P<0 .05) .Conclusion The detection of children with RSV infec-tion ,which the detection of RNA has higher accuracy than IgM ,especially for children ≤1 year old ,the onset time is shorter(≤7 days) ,plays an important guiding role for early diagnosis .