ObjectiveTo provide technical support for the molecular surveillance of pathogenic bacteria strains carrying mobile colistin resistance-1 （mcr⁃1） gene isolate from inlet of wastewater treatment plants （WWTP）. MethodsThe Enterobacteriaceae strains carrying mcr⁃1 resistance gene isolate from inlet of WWTP during April 1 to June 30， 2023 in Shanghai were cultured on blood-rich and SS culture medium and were identified using a mass spectrometry analyzer. The mcr⁃1 gene and copy number were detected by real-time fluorescence quantitative PCR. Drug susceptibility test was performed by microbroth dilution method. The copy numbers of Escherichia coli carrying mcr⁃1 gene isolated from wastewater and human fecel were statistically analyzed by SPSS 25.0. ResultsA total of 14 strains carrying the mcr⁃1 gene were isolated from 49 WWTP samples， and the positive isolation rate was 28.6%， including 12 non-diarrheal E. coli strains and 2 Klebsiella pneumoniae strains. The drug susceptibility results showed that all 14 strains were multi-drug resistant bacteria. They were all sensitive to imipenem and tigecycline， but were ampicillin- and cefazolin-resistant. There was no significant difference in the copy number between human-sourced diarrheal E. coli and wastewater-sourced non-diarrheal E. coli （t=0.647， P>0.05）. ConclusionThe isolation and identification of strains carrying the mcr⁃1 gene from inlet of WWTP samples were firstly established in Shanghai. The multi-drug resistance among the isolated strains is severe. To effectively prevent and control the spread of colistin-resistant bacteria， more attention should be paid to the surveillance of mcr⁃1 gene.

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*

China has classified the Corona Virus Disease 2019(COVID-19) as a statutory category B infectious disease and managed it according to Category B since January 8, 2023.In view that Omicron variant is currently the main epidemic strain in China, in order to guide the treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection in children with the times, refer to the Diagnosis and Treatment Protocol for Novel Coronavirus Infection (Trial 10 th Edition), Expert Consensus on Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fourth Edition) and the Diagnosis and Treatment Strategy for Pediatric Related Viral Infections.The Expert Consensus on the Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fifth Edition) has been formulated and updated accordingly on related etiology, epidemiology, pathogenic mechanism, clinical manifestations, auxiliary examination, diagnosis and treatment, and added key points for the treatment of COVID-19 related encephalopathy, fulminating myocarditis and other serious complications for clinical reference.

Objective:Early death (ED) characteristics and predictive factors analysis in patients with severe/very severe aplastic anemia (SAA/VSAA) treated with intensive immunosuppression therapy and establish an ED prediction model.Methods:The clinical data of 232 patients with SAA/VSAA treated with Antithymocyte immunoglobulin (ATG) at the Peking Union Medical College Hospital from August 2003 to August 2021 were collected. The characteristics and causes of ED within 90 days were analyzed retrospectively. Cox proportional hazards model was used to screen the ED risk factors and build a prediction model.Results:Only 19 patients (8.2% ) developed ED with a median time of 24 (3-85) days among the 232 patients with SAA/VSAA who received ATG treatment. The main cause of ED was infection (84.2% ) , followed by cerebral hemorrhage (10.5% ) . Multivariate analysis showed that VSAA ( HR=15.359, 95% CI 1.935-121.899, P=0.010) , fungal infection prevention by posaconazole ( HR=0.147, 95% CI 0.019-1.133, P=0.066) , lymphocyte count (LYM) ≤ 0.5×10 9/L ( HR=3.386, 95% CI 1.123-10.206, P=0.030) , and PLT ≤ 5×10 9/L ( HR=8.939, 95% CI 1.948-41.019, P=0.005) were ED’s independent influencing factors. To build a clinical prediction model, VSAA, fungal infection prevention by posaconazole, LYM ≤ 0.5×10 9/L, and PLT ≤ 5×10 9/L were scored with 3, -2, 1, and 2, respectively. The integral model AUC=89.324 (95% CI 80.859-97.789) . The ED risk in patients with a score ≥ 3 was 23.1 (95% CI 5.3-100.2) times that in patients with a score<3. Conclusion:ED caused by infection and cerebral hemorrhage is an important challenge for SAA/VSAA to be treated with ATG. VSAA, LYM ≤ 0.5×10 9/L, and PLT ≤ 5×10 9/L patients who did not use posaconazole to prevent fungal infection had a high ED risk.

Monkeypox is a zoonotic disease.Previous studies have shown that children are vulnerable to monkeypox and are also at high risk for severe disease or complications.In order to improve pediatricians′ understanding of monkeypox and achieve early detection, early diagnosis, early treatment and early disposal, the committee composed of more than 40 experts in the related fields of infectious diseases, pediatrics, infection control and public health formulate this expert consensus, on the basis of the latest clinical management and infection prevention and control for monkeypox released by the World Health Organization (WHO), the guidelines for diagnosis and treatment of monkeypox (version 2022) issued by National Health Commission of the People′s Republic of China and other relevant documents.During the development of this consensus, multidisciplinary experts have repeatedly demonstrated the etiology, epidemiology, transmission, clinical manifestations, laboratory examinations, diagnosis and differential diagnosis, treatment, discharge criteria, prevention, case management process and key points of prevention and control about monkeypox.

Since December 2019, severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infections have raged globally for more than 2 years.China has always adopted scientific and effective prevention and control measures to achieved some success.However, with the continuous variation of SARS-CoV-2 cases and imported cases from abroad, the prevention and control work has become more difficult and complex.With the variation of the mutant strain, the number of cases in children changed, and some new special symptoms and complications were found, which proposed a new topic for the prevention and treatment of SARS-CoV-2 infection in children in China.Based on the third edition, the present consensus according to the characteristics of the new strain, expounded the etiology, pathology, pathogenesis, and according to the clinical characteristics and experience of children′s cases, and puts forward recommendations on the diagnostic criteria, laboratory examination, treatment, prevention and control of children′s cases for providing reference for further guidance of effective prevention and treatment of SARS-CoV-2 infection in children in China.

At present, severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection is still rampant worldwide.As of September 10, 2021, there were about 222 million confirmed cases of corona virus disease 2019(COVID-19)and more than 4.6 million deaths worldwide.With the development of COVID-19 vaccines and the gradual vaccination worldwide, the increasing number of cases in children and unvaccinated young people has drawn attention.According to World Health Organization surveillance data, the proportion of COVID-19 infection cases in children gradually increased, and the proportion of cases in the age groups of under 5 years and 5-14 years increased from 1.0% and 2.5% in January 2020 to 2.0% and 8.7% in July 2021, respectively.At present, billions of adults have been vaccinated with various COVID-19 vaccines worldwide, and their protective effects including reducing infection and transmission, reducing severe disease and hospitalization, and reducing death, as well as high safety have been confirmed.Canada, the United States, Europe and other countries have approved the emergency COVID-19 vaccination in children and adolescents aged 12 to 17 years, and China has also approved the phased vaccination of COVID-19 vaccination in children and adolescents aged 3 to 17 years. For smooth advancement and implementation of COVID-19 vaccination in children, academic institutions, including National Clinical Research Center for Respiratory Diseases, National Center for Children′s Health, and The Society of Pediatrics, Chinese Medical Association organized relevant experts to reach this consensus on COVID-19 vaccination in children.

Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection is still worldwide.As a vulnerable group, severe and dead pediatric cases are also reported.Under this severe epidemic situation, children should be well protected.With the widespread vaccination of SARS-CoV-2 vaccine in adults, the infection rate have decreased.Therefore, SARS-CoV-2 vaccine inoculation for children groups step by step is of great significance to the protection of children and the prevention and control of corona virus disease 2019(COVID-19) as a whole.But the safety of children vaccinated with SARS-CoV-2 vaccine is a main concern of parents.Therefore, in order to ensure the safety of vaccination and the implementation of vaccination work, National Clinical Research Center for Respiratory Diseases, National Center for Children′s Health and the Society of Pediatrics, Chinese Medical Association organized experts to interpret the main issue of parents about SARS-CoV-2 vaccine for children, in order to answer the doubts of parents.

OBJECTIVE: To detect the ectodysplasin A (EDA) gene mutation in patients with hypohidro-tic ectodermal dysplasia (HED), and to analyze the distribution pattern of missing permanent teeth and the systemic manifestation of HED patients with EDA gene mutation. METHODS: Twelve HED families were enrolled from clinic for genetic history collection, systemic physical examination and oral examination. Peripheral blood or saliva samples were collected from the probands and the family members to extract genomic DNA. PCR amplification and Sanger sequencing were utilized to detect the EDA gene variations, which were compared with the normal sequence (NM_001399.5). The functional impact of EDA gene variants was then evaluated by functional prediction of mutation, conservation analysis and protein structure prediction. The pathogenicity of each EDA gene variation was assessed according to the stan-dards and guidelines of the American College of Medical Genetics and Genomics (ACMG). The systemic phenotype and missing permanent tooth sites of HED patients with EDA gene mutations were summarized, and the missing rate of each tooth position was analyzed and compared. RESULTS: Eight out of twelve HED families were identified to carry EDA gene mutations, including: c.164T>C(p.Leu55Pro); c.457C>T (p.Arg153Cys); c.466C>T(p.Arg156Cys); c. 584G>A(p.Gly195Glu); c.619delG(p.Gly207Profs*73); c.673C>T(p.Pro225Ser); c.676C>T(p.Gln226*) and c.905T>G(p.Phe302Cys). Among them, c.164T>C(p.Leu55Pro); c.619delG(p.Gly207Profs*73); c.673C>T(p.Pro225Ser); c.676C>T(p.Gln226*) and c.905T>G(p.Phe302Cys) were novel mutations. The HED patients with EDA gene mutations in this study were all male. Our results showed that the average number of missing permanent teeth was 13.86±4.49, the average number of missing permanent teeth in the upper jaw was 13.14±5.76, the missing rate was 73.02%. And in the lower jaw, the average number of missing permanent teeth was 14.57±3.05, the missing rate was 80.95%. There was no significant difference in the number of missing teeth between the left and right sides of the permanent dentition (P>0.05). Specifi-cally, the maxillary lateral incisors, the maxillary second premolars and the mandibular lateral incisors were more likely to be missing, while the maxillary central incisors, the maxillary and mandibular first molars had higher possibility of persistence. CONCLUSION This study detected novel EDA gene pathogenic variants and summarized the distribution pattern of missing permanent teeth of HED patients, thus enriched the variation and phenotype spectrum of EDA gene, and provided new clinical evidence for genetic diagnosis and prenatal consultation.
Ectodermal Dysplasia ; Ectodermal Dysplasia 1, Anhidrotic/genetics* ; Ectodysplasins/genetics* ; Humans ; Male ; Mutation ; Pedigree ; Phenotype

Objective To evaluate the safety and efficacy of lenalidomide plus rituximab in treatment of the patients with relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL). Methods The clinical data of the patients with relapsed/refractory B-NHL after the varieties of treatment methods in Peking Union Medical College Hospital between January 2015 and December 2017 were retrospectively analyzed. All the patients were treated with R2 regimen: oral lenalidomide (25 mg/d for day 1-day 21) and rituximab (375 mg/m2 of intravenous infusion on day 1, 28-day of each cycle); the efficacy was evaluated after three cycles. After this induction phase, the patients achieving complete response (CR), partial response (PR), or stable disease (SD) were given R2 regimen until the end of 8 cycles. The major end point was overall response rate (ORR) defined as CR + PR. Secondary end point included 1-year progression free survival (PFS), 1-year overall survival (OS) and grade 3-4 adverse events. T cell and B cell subsets of 7 patients at baseline were measured, and T cell and B cell subsets of 13 patients with good efficacy were dynamically observed. Results A total of 49 patients who received 1-4 chemotherapy regimens were included. The ORR after the R2 treatment for 3 courses was 65% (32/49). Thirty-six patients (9 cases of CR, 22 cases of PR, 5 cases of SD) were enrolled in R2 maintenance treatment. The median follow-up time was 13 months, 1-year PFS rate was 61% and 1-year OS rate was 84% . The most common adverse event was bone marrow suppression, including grade 3-4 neutropenia (27% ), grade 3-4 thrombocytopenia (6% ) and grade 4 anemia (4% ), most of which could be controlled by prolonging interval cycles or reduced lenalidomide dosage. The decreased number of CD19+B cell after treatment could be seen in 13 patients who obtained good efficacy under the dynamic observation. Conclusion Lenalidomide plus rituximab is well tolerated and highly active in the treatment of relapsed/refractory B-NHL.