Objective:To investigate the prevalence of norovirus and the correlation between norovirus infection and stool traits and clinical symptoms in children with acute gastroenteritis during 2021-2022.Method:A total of 2 195 anal swab samples were collected from cases of acute gastroenteritis in Beijing Children 's Hospital Affiliated to Capital Medical University from January 2021 to December 2022. PCR fluorescent probe assay was performed to detect norovirus，the clinical information and test results were performed by statistical analysis. Results:The detection rate of norovirus was 19.09%（419/2 195）in 2 195 children. The detection rates of male and female were 17.80%（244/1 371）and 21.24%（175/824），respectively，with statistically significant differences between genders（ χ2=3.945, P<0.05）. The positivity rate of noroviruses was higher in aged 1 month to 3 years［29.09%（64/220）~40.69%（94/231）］，especially in 1 year［40.69%（94/231）］. The norovirus detection rate ranged from 2.44%（2/82）to 35.84%（62/173）in different months，with a high detection rate between January and March，higher in the winter and spring［28.36%（150/529），21.07%（146/693）］，showing a clear seasonal distribution.Clinical symptoms of both vomiting and diarrhea were significantly more common among norovirus positive than negative children，the difference was statistically significant（ χ2=57.29, P<0.05）. Conclusion:In the high incidence season of winter and spring，for infants and young children aged 1 month to 3 years with diarrhea accompanied by vomiting symptoms，especially those aged 1 year，it is recommended to undergo norovirus related testing in time. Early treatment and isolation measures should be taken for diagnosed children to reduce cross infection and prevent outbreaks.

Objective To detect the serum levels of CC chemokine receptor 2(CCR2)and C-reactive pro-tein(CRP)in stroke patients,and analyze their relationship with the severity of stroke associated pneumonia and their clinical significance.Methods A total of 78 patients with stroke associated pneumonia who were di-agnosed and treated in the hospital from October 2022 to February 2023 were collected as the study group,ac-cording to the severity of pneumonia,the study group was divided into mild group(31 cases),moderate group(29 cases),and severe group(18 cases),78 stroke patients who did not develop pneumonia were included into control group.Pearson method was applied to analyze the correlation between serum CCR2 and CRP levels in stroke associated pneumonia patients.Multivariate Logistic regression was applied to analyze the factors influ-encing the occurrence of stroke associated pneumonia.Receiver operating characteristic(ROC)curve was ap-plied to analyze the diagnostic value of serum CCR2 and CRP for stroke associated pneumonia.Results The National Institute of Health stroke scale(NIHSS)score,serum CCR2,and CRP levels in the study group were obviously higher than those in the control group(P<0.05).The levels of serum CCR2 and CRP increased with the aggravation of pneumonia(P<0.05).The levels of serum CCR2 and CRP in the study group were positively correlated(r=0.799,P<0.05).NIHSS score,CCR2,and CRP levels were risk factors for stroke associated pneumonia in stroke patients(P<0.05).The area under the curve(AUC)for the diagnosis of stroke associated pneumonia using serum CCR2 and CRP alone was 0.873 and 0.888,respectively,and the AUC for the combined detection of the two was 0.936,the combined detection of the two was superior to the individual detection of serum CCR2 and CRP(Zcombination-CCR2=1.987,Zcombination-CRP=1.832,P=0.041,0.047).Conclusion Serum CCR2 and CRP are closely related to the severity of stroke associated pneumonia,and their combined detection has high diagnostic value for stroke associated pneumonia.

Objective To investigate the diagnostic value of serum soluble fms-like tyrosine kinase 1(sFlt-1)and soluble differentiation cluster 14(sCD14)in stroke-associated pneumonia(SAP).Methods A total of 67 SAP patients admitted to the hospital from March 2022 to January 2023 were selected as the study group,and 50 stroke patients without pneumonia during the same period were selected as the control group.Enzyme-linked immunosorbent assay was used to measure serum sFlt-1 and sCD14 levels.Pearson correlation analysis was used to analyze the correlation between serum sFlt-1,sCD14 levels and clinical data.Multivariate Logistic regression was used to analyze the influencing factors of SAP in patients with stroke.Receiver operating char-acteristic(ROC)curve was used to analyze the diagnostic value of serum sFlt-1 and sCD14 levels in predicting SAP in patients with stroke.Results The serum levels of sFlt-1 and sCD14 in SAP patients were higher than those in stroke patients without pneumonia and stroke patients with pneumonia alone(P＜0.05).SAP in stroke patients was associated with age,atrial fibrillation,heart failure,aspiration,dysphagia,brain stem stroke,proton pump inhibitor use,fever,cough,dyspnea,low-density lipoprotein cholesterol,procalcitonin(PCT),C-reactive protein,white blood cell count,national institutes of health stroke scale(NIHSS)score,clinical pulmonary infection(CPIS)score(P＜0.05).Correlation analysis showed that serum sFlt-1 level was positively correlated with sCD14(r=0.439,P＜0.001),and serum sFlt-1 and sCD14 levels were positively correlated with NIHSS score and CPIS score(P＜0.05).Multivariate Logistic regression analysis showed that sFlt-1,sCD14,proton pump inhibitor use,PCT,dysphagia,and age were the influencing factors of SAP in stroke patients(P＜0.05).ROC curve results showed that the area under the curve of serum sFlt-1 and sCD14 combined to evaluate SAP in stroke patients was higher than that of single detection(ZsFlt-1-combined=2.194,P=0.028,ZscD14-combined=2.310,P=0.002).Conclusion The serum levels of sFlt-1 and sCD14 are in-creased in SAP patients,and the combination of the two has a good diagnostic value for predicting the occur-rence of SAP.

Background Cadmium (Cd) is a ubiquitous and toxic heavy metal that can accumulate in human body. Previous studies have shown that Cd exposure can induce neurotoxicity, but the underlying mechanism remains unclear. Objective To investigate the metabolic impacts of multiple doses of Cd on mouse neural stem cells (NSCs), and to explore the potential mechanism and biomarkers of its neurotoxicity. Methods The NSCs were obtained from the subventricular zone (SVZ) of 1-day-old neonatal C57BL/6 mice. The passage 3 (P3) NSCs were exposed to CdCl₂ at designed doses (0, 0.5, 1.0, and 1.5 μmol·L⁻¹). The cells were treated with seven replicates, of which one plate was for cell counting. After 24 h of exposure, the intracellular and extracellular metabolites were extracted respectively and then detected by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS). The orthogonal partial least-squares discriminant analysis (OPLS-DA) was applied to visualize the alterations of metabolomic profiles and to identify the differential metabolites (DMs) based on their variable importance for the projection (VIP) value >1 and P<0.05. The metabolite set enrichment analysis (MSEA) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed to recognize the significantly altered metabolite sets and pathways. The dose-response relationships were established and the potential biomarkers of Cd exposure were identified by 10% up-regulated or 10% down-regulated effective concentration (EC) of target metabolites. Results A total of 1201 metabolites were identified in the intracellular metabolomic samples and 1207 for the extracellular metabolomic samples. The intracellular and extracellular metabolome of Cd-treated NSCs were distinct from that of the control group, and the difference grew more distant as the Cd dosage increased. At 0.5, 1.0, and 1.5 μmol·L⁻¹ dosage of Cd, 87, 83, and 185 intracellular DMs and 161, 176, and 166 extracellular DMs were identified, respectively. Within the significantly changed metabolites among the four groups, 176 intracellular DMs and 167 extracellular DMs were identified. Both intracellular and extracellular DMs were enriched in multiple lipid metabolite sets. Intracellular DMs were mainly enriched in taurine and hypotaurine metabolism, glycerophospholipid metabolism, and glycerolipid metabolism pathways. Extracellular DMs changed by Cd were mainly enriched in glycerophospholipid metabolism, steroid hormone biosynthesis, and cysteine and methionine metabolism pathways. Among intracellular DMs, 125 metabolites were fitted with dose-response relationships, of which 108 metabolites showed linear changes with the increase of Cd dosage. And 134 metabolites were fitted with dose-response relationships among extracellular DMs, of which 86 metabolites showed linear changes. The intracellular DMs with low EC values were hypotaurine, ethanolamine, phosphatidylethanolamine, and galactose, while the extracellular DMs with low EC values were acetylcholine and 1,5-anhydrosorbitol. Conclusion Cd treatment can significantly alter the intracellular and extracellular metabolome of mouse NSCs in a dose-dependent manner. The neurotoxicity of Cd may be related to glycerophospholipid metabolism. Acetylcholine, ethanolamine, and phosphatidylethanolamine involved in glycerophospholipid metabolism pathway might be potential biomarkers of Cd-induced neurotoxicity.

Objective:To investigate the changes in epidemiological characteristics of common respiratory pathogens in children in Beijing during COVID-19 epidemic.Methods:A total of 9 728 serum samples were collected from cases of acute respiratory infections in Beijing Children′s Hospital from January 2020 to December 2020. Indirect immunofluorescence antibody test was performed to detect IgM antibodies against eight common respiratory pathogens and the test results were statistically analyzed. The eight common respiratory pathogens were influenza virus A (FluA), influenza virus B (FluB), respiratory syncytial virus (RSV), adenovirus (ADV), parainfluenza virus (PIV), Mycoplasma pneumoniae ( Mp), Chlamydia pneumoniae ( Cp) and Legionella pneumophila ( Lp). Results:The detection rate of respiratory pathogens in 9 728 cases was 41.71% (4 058/9 728) and respiratory viruses (FluA, FluB, RSV, ADV and PIV) accounted for 46.18%(2 343/5 074)of all detected pathogens. Mp, FluB and FluA accounted for 84.73%(4 299/5 074)of all detected pathogens, and the detection rates were 24.27% (2 361/9 728), 11.49% (1 118/9 728) and 8.43% (820/9 728), respectively. There were 846 cases positive for two kinds of pathogens, and the most common co-infection was Mp and FluB. The detection rates in male and female were 37.56% (2 089/5 562) and 47.26% (1 969/4 166), respectively. There were significant differences in the total detection rate and the positive rates of PIV and Mp between different sexes ( P<0.05). The detection rate in school-age children (6-12 years old) was the highest (52.26%, 1 535/2 937). The detection rates of respiratory pathogens in different months ranged from 30.12% (203/674) to 49.81% (268/538) with higher rates in autumn and winter [42.45% (1 304/3 072) and 43.29% (1 618/3 738)]. The detection rates of FluA and FluB were higher in summer [11.46% (195/1 701)] and winter [14.63% (547/3738)], respectively. Most of RSV infection occurred in summer [1.35% (23/1 701)], and Mp could be detected all year round, especially in winter and spring [27.21% (1 017/3 738) and 25.64% (312/1 217)]. The detection rate of respiratory pathogens in outpatient group was higher than that in inpatient group [46.48% (1 583/3 406) vs 39.15% (2 475/6 322)]. The detection rate in severe cases was 26.10% (71/272). The detection rates of total pathogens, FluB and Mp were higher in outpatients than in inpatients and the differences were statistically significant ( P<0.05). The detection rates of FluA, PIV and ADV were higher in inpatients than in outpatients and the differences were statistically significant ( P<0.05). The detection rates of total pathogens, FluB and Mp in mild cases were significantly higher than those in severe cases and the differences were statistically significant ( P<0.05). The detection rate of RSV in severe cases was significantly higher than that in mild cases and the difference was statistically significant ( P<0.05). Conclusions:The protective measures taken during the period of regular prevention and control of COVID-19 epidemic could better prevent the spread of respiratory viruses, having a certain impact on the population susceptible to respiratory pathogens and typical seasonal patterns, but had little effect on the prevention and control of Mp. New protective measures needed to be studied to prevent Mp infection in children during epidemical season.

Objective:To evaluate the effects of patient-controlled intravenous analgesia (PCIA) with esketamine on postpartum depression (PPD) in puerpera undergoing cesarean section.Methods:A total of 300 American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients, aged 25-35 yr, with body mass index≤35 kg/m 2, scheduled for elective cesarean section under spinal anesthesia, were divided into 2 groups ( n=150 each) by a random number table method: control group (group C) and esketamine group (group E). PCIA was performed at the end of surgery.In group C, the PCIA solution contained sufentanil citrate 50 μg, butorphanol tartrate 12 mg and metoclopramide injection 20 mg in 200 ml of 0.9% normal saline.In group E, the PCIA solution contained esketamine 1 mg/kg, sufentanil citrate 50 μg, butorphanol tartrate 12 mg and metoclopramide injection 20 mg in 200 ml of 0.9% normal saline.The PCA pump was set to deliver a background infusion of 4 ml/h and a bolus dose of 4 ml at 30 min lockout interval.The analgesia lasted for 48 h after surgery, and the visual analog scale (VAS) score was maintained<4 points.Acetaminophen 0.5 g was administered orally as a rescue analgesic when VAS score≥4 points and pain was still unrelieved after PCA pump was pressed twice in a row.The Edinburgh Postnatal Depression Scale (EPDS) was performed at 1 day before and at 3, 7 and 42 days after surgery.Depression was classified on EPDS as mild (score≥10) and severe (score≥13). The patients with preoperative depression were excluded from the study.The occurrence and degree of depression were recorded.The requirement for rescue analgesia within 0-6 h, 6-12 h, 12-24 h and 24-48 h after surgery and development of adverse effects within 3 days after surgery were recorded. Results:Compared with group C, the incidence of PPD was significantly decreased and degree was reduced at 3 and 7 days after surgery, incidence of rescue analgesia was decreased in different time periods ( P<0.05), and no significant change was found in the incidence of adverse effects in group E ( P>0.05). Conclusion:Esketamine can not only provide good postoperative analgesia but also improve PPD in puerpera when it is used for PCIA after cesarean section.

Multi-modal therapeutics are emerging for simultaneous diagnosis and treatment of cancer. Polymeric carriers are often employed for loading multiple drugs due to their versatility and controlled release of these drugs in response to a tumor specific microenvironment. A theranostic nanomedicine was designed and prepared by complexing a small gadolinium chelate, conjugating a chemotherapeutic drug PTX through a cathepsin B-responsive linker and covalently bonding a fluorescent probe pheophorbide a (Ppa) with a branched glycopolymer. The branched prodrug-based nanosystem was degradable in the tumor microenvironment with overexpressed cathepsin B, and PTX was simultaneously released to exert its therapeutic effect. The theranostic nanomedicine, branched glycopolymer-PTX-DOTA-Gd, had an extended circulation time, enhanced accumulation in tumors, and excellent biocompatibility with significantly reduced gadolinium ion (Gd

Objective To investigate the characteristics of neonatal methylmalonic aciduria (MMA)regarding clinical manifestations,laboratory findings,gene mutations,treatments and prognosis.Methods Acylcamitine levels in blood samples of 207 308 neonates born from January 2016 to December 2017 in Xuzhou were detected by liquid chromatography tandem mass spectrometry and the abnormal results were further confirmed by detecting organic acids in urine samples with gas chromatography-mass spectrometry and gene sequencing analysis.Patients with isolated MMA were treated with dietary control and levocarnitine,while those complicated by homocysteinemia were treated with vitamin B12,levocarnitine,glycine betaine and calcium folinate.Clinical manifestations,laboratory findings,imaging features,genotypes,treatments and prognosis of patients with MMA were retrospectively analyzed.Paired sample t-test was applied for statistical analysis.Results MMA was eventually diagnosed in 12 patients,among which three were isolated MMA and nine were complicated by homocysteinemia.The three isolated MMA cases failed to response to vitamin B12 treatment without any symptoms on diagnosis.However,vitamin B12 was effective for the other nine patients,among which four had no clinical symptoms on diagnosis and five had manifestations such as slow response,recurrent vomiting,poor feeding,dyspnea,anemia and jaundice.Abnormal results of cranial MRI included bilateral basal ganglia damage,enlarged extracranial space,ventriculomegaly and changes in white matter.All patients underwent genetic analysis and three were found with MUT gene mutations and nine with MMACHC gene mutations.MUT gene mutations were classified into five types,including c.I106G＞A,c.1880A＞G,c.441T＞A,c.581C＞T and c.1741C＞T.Eight types of MMACHC gene mutations were identified,including c.609G＞A,c.658_660delAAG,c.482G＞A,c.1A＞G,c.567dupT,c.80A＞G,c.276+1G＞A and c.228_23 l delTGAC.Two mutations,c.276+lG＞A and c.228 23 ldelTGAC,were novel mutations.The most common mutation in MMACHC gene was c.609G＞A,followed by c.658_660delAAG and c.482G＞A.One of the isolated MMA patients died after refusing treatments and the other two showed significant decrease in serum propionylcarnitine,propionylcarnitine to acetylcarnitine ratio,serum homocysteine and methylmalonic acid and methylcitric acid in urine after treatment.Moreover,of the two patients who were alive at follow-up,one experienced normal growth and development and the other suffered from growth retardation.The ratio of propionylcamitine to acetylcarnitine and the levels of serum propionylcarnitine,serum homocysteine and methylmalonic acid and methylcitric acid in urine were significantly decreased in the nine patients with MMA complicated by homocystinuria after one month of treatment [0.88±0.35 vs 0.13±0.05,(7.12±1.90) μ mol/L vs (3.18±1.08) μ mol/L,(136.48±38.14) μ mol/L vs (34.41±17.33) μmol/L,103.51±69.62vs 5.35±2.15 and 7.95±6.88 vs 1.02±0.48,t=-6.166,-6.687,-12.941,-4.208 and-3.015,respectively,all P＜0.05].Two deaths,three asymptomatic and four psychomotor retardation patients were reported during follow-up.Conclusions Newborn screening with liquid chromatography tandem mass spectrometry is important for early diagnosis of MMA.MMACHC gene defects are the main causes of MMA in Xuzhou area and the predominant one is c.609G＞A mutation.Prognosis of MMA might be related to disease type,age of onset and patient's reactivity to vitamin B12.

Objective To investigate the clinical features and SLC22A5 gene mutation types in patients with primary carnitine deficiency(PCD).Methods The free carnitine(CO) and acylcarnitine levels in the blood of 210 908 neonates from newborn screening program and 576 children with suspected clinical inherited metabolic diseases were measured by using liquid chromatography tandem mass spectrometry method during September 2015 to December 2017,after that the SLC22A5 gene mutations were analyzed in the children with low CO level and the diagnosis was made.The clinical characteristics,laboratory findings,genotypes,treatment and prognosis were retrospectively analyzed in patients.Paired sample t test was used to compare the biochemical indexes of patients before and after the treatments.Results Ten children were diagnosed with PCD(9 cases from newborn screening program,1 case from clinical patients),and 7 children were diagnosed with maternal carnitine deficiency.After treatment with oral Levocarnitine,the free carnitine and acylcarnitine of the patients returned to the normal levels.The clinical symptoms disappeared in 1 patient out of clinical patients,and the other 16 patients from newborn screening program were asymptomatic and showed normal growth and development.Seventeen patients got genetic analysis,and 10 types of mutations were found,including c.1400C ＞ G,c.1462C ＞ T,c.797C ＞ T,c.95A ＞ G,c.92C ＞ T,c.1093A ＞ C,c.761G ＞ A,c.865C ＞ T,c.428C ＞ T,c.1195C ＞ T,among which two of them (c.1093A ＞ C and c.92C ＞ T) were novel mutations.The most common mutation of SLC22A5 gene was c.1400C ＞ G.Conclusions Liquid chromatography tandem mass spectrometry technology is sufficient to screen newborns and maternal carnitine deficiency,and the c.1400C ＞ G mutation is found at the highest frequency in Xuzhou area.If patients receive early treatment,they may have a good prognosis.

Objective To explore the relationship between blood pressure variability and different types of stroke.Methods One hundred and twenty-five ischemic stroke subjects,78 hemorrhagic stroke patients and 66 non-stroke individuals,collected in our hospital from January 1,2013 to December 31,2015,were enrolled according to the inclusion and exclusion criteria.All indicators of blood pressure variability were calculated from 24 h ambulatory blood pressure,including nighttime blood pressure fall (BPF),moming surge in blood pressure (MBPS),standard deviation (SD),weighted SD (wSD),and coefficient of variation (CV).Results As compared with non-stroke subjects,ischemic and hemorrhagic stroke individuals had significantly increased systolic MBPS (P＜0.05),and the systolic MBPS of ischemic stroke group was significantly lower than those of hemorrhagic stroke group (P＜0.05).CV,wSD and BPF of systolic blood pressure (SBP) in the ischemic and hemorrhagic groups were significantly higher than those in the non-stroke subjects (P＜0.05);CV and SBPF of diastolic blood pressure in hemorrhagic group were significantly different as compared those in the non-stroke subjects (P＜0.05).The factors which were significantly associated with ischemic stroke in Logistic regression,included high-density lipoprotein,nighttime SBP,wSD of SBP,CV of SBP,while smoking,nighttime SBP,wSD of SBP,MBPS,and CV of SBP were observed as important influence factors for hemorrhagic stoke patients.Conclusion Whether ischemic stroke,or hemorrhagic stroke are associated with short-term blood pressure variability.