Objective:To investigate the clinical phenotype and prognosis among different genotypes of progressive familial intrahepatic cholestasis(PFIC) by cases analysis.Methods:The PFIC cases diagnosed at Beijing Children′s Hospital from 2015 to 2022 were collected, and the clinical phenotypic characteristics, treatment and prognosis were compared and analyzed.Results:A total of 628 cases of cholestatic liver disease were diagnosed, and 26 cases of PFIC were found, accounting for 4.1%.The number of PFIC 2 were the most, 14(53.8%)cases; three(11.5%) cases were PFIC 1; five(19.2%)cases were PFIC 3; while two(7.7%) cases were PFIC 4 and PFIC 6, respectively, and there was no case of PFIC 5.Type 1, 2, 4, and 6 had early onset ages(2 days to 21 months), while type 3 had a wide range of onset ages(8 to 145 months). The symptoms included jaundice(96.2%), pruritus(42.3%), and mucosal bleeding(15.4%). All three cases of type 1 had extrahepatic manifestations of diarrhea and malnutrition.Two cases of type 3 were found to have end-stage liver disease.Cases of PFIC 3 had increased serum γ-glutamyltransferase(97.2-439.5 U/L), while those of other types were normal.The bile acids were all increased(10.1-599.6 μmol/L). Abdominal ultrasound mainly showed liver enlargement(80.8%)and enhanced echogenicity of liver parenchyma(73.1%), enlargement of the spleen(61.5%). Ultrasound liver elastography ranged from 6.3 kPa to 23.1 kPa, there were 21(80.8%) cases ≥9 kPa.Among 26 cases, one case was lost to follow-up, and 11 cases were effective by oral medication alone.Fourteen children were still suffering from relapse or progress after drug treatment: four cases received liver transplantation (three cases had a good prognosis and one case died), two cases received biliary drainage, six cases were still taking drugs orally, and two cases died without active intervention in disease progress.Conclusion:Type 2 is the most common type in PFIC.The onset of most cases is in infancy.Jaundice, pruritus and hepatosplenomegaly are common clinical manifestations, and extrahepatic manifestations can be seen in type 1 cases.Type 3 cases can start with end-stage liver disease.Bile acid of all cases are increased.Except for type 3, the serum γ-glutamyltransferase of cases are normal.Oral medication has certain effects on some cases, but more than half progress, and some need biliary diversion or liver transplantation.

Objective:To clarify the M protein ( emm gene) types and drug susceptibility characteristic variations of Group A Streptococcus (GAS) in children in Beijing. Methods:The GAS strains isolated from throat swab samples of children diagnosed with scarlet fever and pharyngeal infection in scarlet fever etiology surveillance sentinel hospitals in 16 districts of Beijing in 2018, 2019 and 2021 were analyzed retrospectively.PCR amplification and sequencing were used for emm genotyping, and the minimum inhibitory concentrations (MIC) of 10 antibiotics were determined by the broth microdilution method.The data were analyzed using χ2 test and Fisher′ s exact method between groups. Results:A total of 557 GAS strains were collected, and 11 emm genotypes ( emm1, emm3, emm4, emm6, emm11, emm12, emm22, emm75, emm89, emm128, and emm212) were detected.Of 557 strains, 238 trains were of emm1 type (42.73%), 271 strains were of emm12 type (48.65%) and 48 strains were of other emm types (8.62%). The detection rates of emm1, emm12 and other emm type genes in 2018, 2019, and 2021 were [37.50% (105/280 strains), 57.14% (160/280 strains), 5.36% (15/280 strains)], [49.05% (129/263 strains), 39.54% (104/263 strains), 11.41% (30/263 strains)], and [28.57% (4/14 strains), 50.00% (7/14 strains), 21.43% (3/14 strains)], respectively.In children infected with emm12 in 2018 and 2019, there were more children under 6 years old than children over 6 years old (62.50% vs.46.88%, 46.36% vs.30.36%) (χ 2=7.182, 6.973; all P<0.05). Drug susceptibility testing results suggested that 225 randomly selected GAS strains were all 100.00% sensitive to 7 antibiotics including Penicillin, Levofloxacin, Meropenem, Linezolid, Cefotaxime, Cefepime and Vancomycin.The rates of resistance to Erythromycin, Tetracycline and Clindamycin were [88.57% (93/105 strains), 87.62% (92/105 strains), 86.67% (91/105 strains)], and [94.34% (100/106 strains), 94.34% (100/106 strains), 87.74% (93/106 strains)] in 2018 and 2019, respectively.The test strains were 100.00% (14/14 strains) resistant to the above 3 antibiotics in 2021.MIC 50 and MIC 90 values of Penicillin in 2018, 2019, and 2021 were (0.03 mg/L, 0.03 mg/L), (0.03 mg/L, 0.06 mg/L), and (0.06 mg/L, 0.06 mg/L), respectively.Among 225 GAS strains, 207 strains had drug resistance and were resistant to more than one drug.Specifically, 94.69% (196/207 strains) were resistant to Erythromycin, Tetracycline and Clindamycin.About 4.35% (9/207 strains) were resistant to both Erythromycin and Clindamycin.A total of 0.97% (2/207 strains) were resistant to Erythromycin and Tetracycline. Conclusions:The emm genotypes of GAS in children in Beijing are diverse in 2018, 2019 and 2021.The dominant genotypes are emm12 and emm1, and emm12 is the main epidemiological type.GAS strains maintain highly resistant to Erythromycin, Clindamycin and Tetracycline, and sensitive to Penicillin and other antibiotics.However, MIC 50 and MIC 90 of Penicillin shows an ascending trend.

COVID-19 ; China/epidemiology* ; Disease Outbreaks ; Humans ; SARS-CoV-2

Objective:To summarize and analyze the clinical features of food protein-induced enterocolitis syndrome (FPIES).Methods:The medical history and follow-up data of 5 children with FPIES diagnosed in Department of Gastroenterology, Beijing Children′s Hospital of Capital Medical University from July 2018 to September 2019 were collected, and their clinical characteristics were summarized and analyzed.Results:Five children with FPIES were all infants, including 3 females and 2 males.Before the onset of the disease, the cases visited multiple departments and the average number of visits before diagnosis was 3.There were 4 cases of milk protein allergy and 1 case of egg white allergy.The patients had acute vomiting [5 cases (100%)], diarrhea [4 cases (80%)], early shock symptoms [5 cases (100%)], transient fever [2 cases (40%)]. Hematogenous leukocytes were increased in 3 cases (60%), C-reactive protein was increased in 1 case (20%), faecal leukocytes(+ )[2 cases (40%)], occult blood (+ ) [1 case (20%)]. Four cases were tested for food allergen specific IgE, of which 2 cases (40%) were positive for milk protein.After avoiding allergens, 3 patients (60%) needed intravenous rehydration treatment and 2 cases (40%) received oral rehydration treatment.The above 5 cases recovered quickly.Three patients (60%) used antibiotics.Four cases (80%) of the first-degree relatives of FPIES had a clear history of allergy.Families of children with FPIES had low awareness of the disease before the diagnosis was made, and the allergens were strictly avoided according to the doctor′s instructions after the diagnosis was made.Similar allergic reactions did not occur again, and complementary foods were gradua-lly added under the guidance of the doctor.Two patients had multiple food allergies.The body weight and length of 2 children with growth retardation were catching up with each other.Conclusions:FPIES is a serious food allergy related gastrointestinal disease which is easy to be misdiagnosed clinically.The diagnosis requires a combination of the family and personal allergy history, diet records, the characteristic performance of disease onset, the effect of diet avoi-dance and the necessary differential diagnosis.The long-term management and monitoring after diagnosis is also very important.

Objective:To analyze epidemiological characteristics of influenza in Beijing during 2015—2020 influenza seasons.Methods:Weekly numbers of cases with influenza-like illness and weekly data of virologic surveillance was used to analyze epidemic trend and characteristics of influenza.Results:From June 26, 2015 to June 28, 2020, influenza-like illness (ILI) was 1.58%. A total of 49868 pharyngeal swab samples were collected from ILI cases, and positive rate of influenza virus nucleic acid was 16.32% by real-time PCR. Of these positive samples, 40.89% (6 474) were A(H3N2), 27.86% (4 410) were A (H3N2), 20.78% (3 290) were B/Victoria lineage, and 10.09%(1597) were B/Yamagata lineage. There were correlation between ILI and positive rate of influenza virus ( r=0.796, P<0.001), and ILI percentage and positive rate were also correlated ( r=0.808, P<0.001). The active duration in 2018—2018, 2018—2019 influenza seasons were longer. Weekly numbers of influenza-like illness cases of 2017—2018, 2018—2019 influenza seasons were higher (49 628 and 71 555), peak value of positive rate in the above seasons was higher (58.51% and 57.08%). Conclusions:The epidemic characteristics of influenza during 2015—2020 years was in accordance with the temperate regions of the northern hemisphere. There were longer active period and higher epidemic level in 2017—2018, 2018—2019 influenza seasons. The dominant influenza virus subtypes varied in the different seasons.

Objective:To analyze the relationship between the cycle threshold ( Ct) values of N gene of COVID-19 cases and the secondary attack risk in close contacts, and identify the relationship between respiratory viral load and infectivity in COVID-19 cases. Methods:The COVID-19 cases with records of Ct values of N gene within 0-7 days of onset were selected, and their close contacts were recruited as the subjects of study. We collected the information of close contacts, including name, gender, age, isolation mode, exposure mode and outcome (whether they were infected with SARS-CoV-2 or not) and other variables. Multivariate logistic regression models were used to identify the relationship between Ct values of N gene of COVID-19 cases and secondary attack risk in close contacts. Results:A total of 1 618 close contacts were recruited, in whom 77 were confirmed as symptomatic or asymptomatic COVID-19 patients with overall secondary attack rate of 4.8%. The multivariate logistic regression analysis indicated that eating together ( OR=2.741, P=0.054), living together ( OR=9.721, P<0.001), non-centralized isolation ( OR=18.437, P<0.001) and COVID-19 case's values of N gene within 0-7 days of onset being <20 ( OR=8.998, P=0.004) or 20-25 ( OR=3.547, P=0.032) were significantly associated with higher likelihood of being infected with SARS-CoV-2 in close contacts. Conclusion:The results indicated that positive relationship exists between respiratory viral load and infectivity in COVID-19 cases, suggesting that Ct values of N gene can be used as an early warning indicator for the management of close contacts of COVID-19 cases.

Objective To calculate both the epidemic and intensity thresholds for different levels in Beijing and to establish a tiered alert system in the 2018-2019 influenza season as well as to evaluate the performance of calculated thresholds.Method Weekly count of influenza-like illness and percentage of influenza-like illness (ILI％) of the last five influenza seasons were modeled by 'moving epidemic method'(MEM) to calculate the influenza epidemic and intensity thresholds at different levels.A cross-validation procedure was used to evaluate the performance.Indicators of Matthew correlation coefficient,Youden's index,sensitivity and specificity were calculated.Results For weekly count of influenza-like illness,data showed that the epidemic threshold for 2018-2019influenza season was 12 984 and the medium,high and very high intensity thresholds were 22 503,37 589,47 157,respectively.Matthew correlation coefficient of the epidemic threshold was 62％ and youden's index as 60％,sensitivity as 69％,specificity as 91％.Data on weekly ILI％,the epidemic threshold for 2018-2019 influenza season was 1.66％,with medium,high and very high intensity thresholds as 2.46％,3.84％ and 4.66％,respectively.The overall Matthew correlation coefficient of the epidemic threshold was 59％,with 54％ for the Youden's index,sensitivity as 60％ and specificity as 94％.Conclusions MEM produced a good specific signal for detecting the influenza epidemics and the accuracy of the method was acceptable.The early warning performance regarding the application of weekly count on influenza-like illness was slightly better than ILI％.This method could be applied in the practical influenza epidemic alert "work in Beijing".

Objective:To explore the infection rate and clinical characteristics of toxigenic Clostridium difficile in children with inflammatory bowel disease (IBD). Methods:From July 2015 to October 2016, the fecal samples and clinical data of 30 IBD children admitted to Department of Gastroenterology, Beijing Children′s Hospital, Capital Medical University, as well as the specimens and data of 30 healthy children were collected in the meantime. The toxin gene of Clostridium difficile was detected and clinical characteristics of children with positive toxin gene were analyzed retrospectively. χ 2 test was used to compare the variables between groups. Results:Among the 30 IBD patients, 15 were in ulcerative colitis (UC) group and 15 in Crohn′s disease (CD) group. In the IBD group, 6 (3 in UC and 3 in CD group) had positive result of toxigenic Clostridium difficile (20%), among whom 5 were toxin Clostridium difficile A (tcdA) +toxin Clostridium difficile B (tcdB) -, and 1 was tcdA+tcdB+. In the healthy group, only one had positive result of toxigenic Clostridium difficile (3%), which was tcdA+tcdB-. Binary toxin gene was negative in both groups. The infection rate of toxigenic Clostridium difficile in IBD group was significantly higher than that in healthy control group (χ 2=4.043, P=0.044). In UC group, no Clostridium difficile toxin gene was detected during the remission period (0/1), one case was positive for toxin gene (1/11) during mild active period, and 2 cases were (2/3) during moderately active period. There were significant differences in the infection rate of toxigenic Clostridium difficile between patients in different active period (χ 2=4.000, P=0.046). The main manifestations of the 6 cases were diarrhea, abdominal pain and bloody stool, and the relapsed case was characterized by sudden aggravation. TcdA was detected in all toxin gene positive samples, and 1 case combined with tcdB had more serious bloody mucopurulent stool. Five cases had colonoscopy, but there was no obvious characteristics of toxigenic Clostridium difficile colitis such as yellow white plaques or pseudomembranous spot. Three cases had antibiotic exposure history. All 6 cases were sensitive to metronidazole treatment, and stable without relapse during the 3-month follow-up. Conclusions:The infection rate of toxigenic Clostridium difficile in children with IBD is higher than that in healthy children. The patients with both tcdA and tcdB could have more serious clinical symptoms, although there may not be specific pathological changes of toxigenic Clostridium difficile colitis. The recognition of toxigenic Clostridium difficile infection in IBD children should be strengthened in clinical work.

Objective To investigate chromosomal abnormalities in fetuses with conotruncal defects(CTD).Methods From January 2013 to February 2017,107 fetuses (singleton pregnancy) prenatally diagnosed as CTD in Beijing Anzhen Hospital were enrolled.Umbilical cord specimens of these fetuses were collected after termination of pregnancy and analyzed by low coverage whole gene sequencing to detect chromosomal aneuploidy and copy number variations.Types of chromosomal abnormalities in these cases were analyzed.Chi-square test was used for statistical analysis.Results Twenty-two cases (21％,22/107) were identified with chromosomal abnormalities.The most common seen chromosomal abnormalities were found in those with interrupted aortic arch (2/2),followed by those with tetralogy of Fallot and pulmonary atresia/stenosis accompanied with ventricular septal defect (28％,12/43).No chromosomal abnormalities were detected in fetuses with aortopulmonary septal defect (0/2).Differences were shown in the detection rates of chromosomal abnormalities among different types of CTD (x2=12.744,P=0.026).Among the 22 fetuses with chromosomal abnormalities,there were seven with abnormal aneuploidy (three trisomy-13s,two trisomy-18s,one trisomy-21 and one 45,X) and 15 with pathogenic copy number variations [11 cases with 22q11.2 microdeletion syndrome,two with 17p12p11.2 microdeletion (Smith-Magenis syndrome),one with 8p23.3p21.3 microduplication and one with 2p23.1p25.2 microdeletion].Of the 15 cases with pathogenic copy number variations,12 segments of microdeletion/microduplications were de novo and one was paternally inherited,while the causes of the other two were not clear because their parents refused chromosomal testing.Conclusions Fetal CTD are likely to be accompanied with aneuploidy abnormalities and chromosome microdeletions/microduplications and the detection rate of chromosomal abnormalities varied with the type of CTD.Microdeletion and microduplication,especially de novo microdeletions/duplications,are the common chromosomal abnormalities.Chromosome analysis is recommended for fetuses prenatally diagnosed with CTD.

Aim To investigate the inhibitory effects of urocortin2 (UCN2) on ventral tegmental area (VTA) nervous activity of morphine addiction rats and the mechanism. Methods Morphine addiction rats and the microiontophoresis method were used to observe the effects of UCN2 on VTA neuron′s spontaneous dis-charge changing rule, as well as the inhibitory effects of UCN2 on DA neuron′s cluster spontaneous dis-charge, to identify UCN2 and DA on the same VTA neuron. Morever, the inhibitor of corticotropin-regula-ting factor′s receptor ( CRF-2 R ) and the blocker of protein kinase A ( PKA ) , AST-2 B and H89 , were used to investigate the effects of UCN2 on VTA neuron′s of morphine addiction rats. Results UCN2 could inhibit the firing rate 82% (31/38) of the tested VTA neuron ( P<0. 01 ) , the discharge frequency changed from (20. 89 ± 2. 86) Hz to (13. 66 ± 3. 93) Hz (P<0. 01). Further, the inhibitor of PKA, AST-2B and H89 could ablolish the inhibitory effects of UCN2 . Morever, the excitatory firing of VTA neurons was at-tenuated by addition of UCN2 , while AST application could inhibit the UCN2′s inhibitory effects. Conclu-sion UCN2 could regulate the effects of VTA via PKA pathway and may thereby contribute to the improvement of drug addiction.