Objective:To establish a rapid detection method based on matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF MS)for drug resistance of Carbapenem-resistant Enterobacteriaceae(CRE),so as to provide basis for enhancing clinically diagnostic effect.Methods:A total of 120 suspected CRE strains that were isolated from the clinical laboratory of Jiading District Central Hospital Affiliated to Shanghai University of Medicine&Health Sciences during October 2023 and September 2024 were collected,and the experimental detection of 44 strains was finally completed.The 44 suspected CRE bacterial strains were all from hospitalized patients.A rapid detection protocol based on the MALDI-TOF MS platform was initially established and improved,and experimental detection was carried out using the fully automatic rapid microbial mass spectrometry detection system(VITEK MS).The results of identification review and antimicrobial susceptibility test(AST)for VitEK-2 Compact strain was used as the reference standard.The screening results and detection efficacy of two kinds of detection methods were compared.Results:In the 44 suspected CRE strains,31 CRE strains were screened out by MALDI-TOF MS detection,and 31 CRE stains were screened out by VITEK-2 Compact recheck detection.In them,one strain of Enterobacter cloacae was confirmed as negativity by the MALDI-TOF MS test,but it was confirmed as CRE by the VITEK-2 Compact test.One strain of Klebsiella pneumoniae was confirmed as positivity by the MALDI-TOF MS test,but it was confirmed as mediator for carbapenem drugs by the VITEK-2 Compact test.The tested results of VITEK-2 Compact was used as standard,the results of four-grid table(2×2 contingency table)statistical method indicated that the sensitivity,specificity,accuracy rate and Youden index(R)of MALDI-TOF MS were respectively 96.7%,92.3%,100%and 89.1%.Conclusion:The rapid detection method based on the MALDI-TOF MS platform for CRE drug resistance has simple operation process and high accuracy rate,which can provide a basis for the application of targeted antibacterial drugs at early stage.

Objective:To establish a rapid detection method based on matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF MS)for drug resistance of Carbapenem-resistant Enterobacteriaceae(CRE),so as to provide basis for enhancing clinically diagnostic effect.Methods:A total of 120 suspected CRE strains that were isolated from the clinical laboratory of Jiading District Central Hospital Affiliated to Shanghai University of Medicine&Health Sciences during October 2023 and September 2024 were collected,and the experimental detection of 44 strains was finally completed.The 44 suspected CRE bacterial strains were all from hospitalized patients.A rapid detection protocol based on the MALDI-TOF MS platform was initially established and improved,and experimental detection was carried out using the fully automatic rapid microbial mass spectrometry detection system(VITEK MS).The results of identification review and antimicrobial susceptibility test(AST)for VitEK-2 Compact strain was used as the reference standard.The screening results and detection efficacy of two kinds of detection methods were compared.Results:In the 44 suspected CRE strains,31 CRE strains were screened out by MALDI-TOF MS detection,and 31 CRE stains were screened out by VITEK-2 Compact recheck detection.In them,one strain of Enterobacter cloacae was confirmed as negativity by the MALDI-TOF MS test,but it was confirmed as CRE by the VITEK-2 Compact test.One strain of Klebsiella pneumoniae was confirmed as positivity by the MALDI-TOF MS test,but it was confirmed as mediator for carbapenem drugs by the VITEK-2 Compact test.The tested results of VITEK-2 Compact was used as standard,the results of four-grid table(2×2 contingency table)statistical method indicated that the sensitivity,specificity,accuracy rate and Youden index(R)of MALDI-TOF MS were respectively 96.7%,92.3%,100%and 89.1%.Conclusion:The rapid detection method based on the MALDI-TOF MS platform for CRE drug resistance has simple operation process and high accuracy rate,which can provide a basis for the application of targeted antibacterial drugs at early stage.

Objective:To investigate the clinical features and prognosis of hypertrophic cardiomyopathy（HCM）in children.Methods:The clinical data of 184 children diagnosed as HCM,who visited Beijing Children's Hospital of Capital Medical University from January 1，2006 to August 31，2022 were retrospectively analyzed.The children were divided into primary HCM group and secondary HCM group according to the etiology of HCM，and their clinical characteristics and prognosis were compared.Results:A total of 184 children[115（62.50%）males and 69(37.50%) females] with HCM were included.The median age at first diagnosis was 4.54（0.50，10.25）years.Among the participants，141（76.63%）cases had primary HCM，and 43（23.37%）cases had secondary HCM.Compared with the patients in primary HCM group，the patients in secondary HCM group had lower age of onset，with a higher proportion of the children under 1 year of age.Most cases had atypical symptoms，including a higher proportion of first-onset heart failure，higher proportion of enlarged cardiac shadow on chest radiograph，and lower left ventricular ejection fraction in the secondary HCM group（ P<0.05）.The proportion of older children，ratio of ventricular septal thickness to left ventricular posterior wall thickness，and the detection rate of left ventricular outflow tract obstruction in the primary HCM group was higher than those in patients with secondary HCM group（ P<0.05）.The survival curve for two groups showed that the secondary HCM group had significantly lower 1-year，2-year，3-year，5-year，and 10-year survival rates than those in the primary HCM group（ P<0.05）. Conclusion:The clinical manifestations of HCM in children are heterogenous due to different etiology，and it is necessary to actively clarify the etiology，improve risk assessment，and provide personalized management and treatment method.

Objective To explore the early predictors of macrolide-unresponsive Mycoplasma pneumoniae pneumonia(MUMPP)and construct a nomogram prediction model.Methods The clinical data of 159 chil-dren with Mycoplasma pneumoniae pneumonia(MPP)admitted to the hospital from January 2023 to Februar-y 2024 were retrospectively collected.According to the time of admission,they were divided into modeling group(112 cases)and validation group(47 cases).The modeling group was further divided into MUMPP group(51 cases)and MPP group(61 cases)according to the drug response.The clinical data and laboratory indexes of each group were compared.The independent predictors of MUMPP were analyzed by univariate and multivariate analysis,and a nomogram prediction model was constructed.Receiver operating characteristic(ROC)curve,area under the curve(AUC),decision curve,calibration curve and Hosmer-Lemeshow goodness of fit test were used to evaluate the discrimination,clinical practicability and calibration of the model.Results The systemic immune inflammation index(SII),C-reactive protein(CRP)/albumin(ALB)and D-dimer were independent influencing factors of MUMPP(P＜0.05).The AUC was 0.938(95％CI 0.890-0.986)in the modeling group and 0.912(95％CI 0.832-0.992)in the validation group.x2 was 3.768 and P was 0.877 in Hosmer-Lemeshow goodness-of-fit test,threshold probability between 5％and 99％had high net clinical benefit.Conclusion The nomogram prediction model established by SII,CRP/ALB and D-dimer has good prediction accuracy and high clinical application value for children with MUMPP.

Hepatitis E is a globally distributed infection that varies in seroprevalence between developed and developing regions.In the less developed regions of Asia and Africa,a high seropositivity rate has been reported for hepatitis E virus(HEV)antibodies.Although acute hepatitis E is often self-limited and has a favorable prognosis,some populations experience severe manifestations,which may progress to liver failure.Moreover,some immunocompromised patients are at risk of developing chronic HEV infection and cirrhosis.Proactive screening,reducing misdiagnosis,improving patient management,timely anti-viral therapy for severe and chronic cases,and vaccination of high-risk groups are important measures to reduce the morbidity of hepatitis E.This review focused on the clinical presentation,management,and prevention of hepatitis E.

Background and aim:Few studies have reported hepatitis B surface antigen(HBsAg)kinetics after nucleos(t)ide analog(NA)discontinuation in patients with noncirrhotic chronic hepatitis B(CHB).The study specifically investigated long-term HBsAg kinetics after NA discontinuation. Methods:Between January 2014 to January 2024,this study prospectively enrolled 106 outpatients with noncirrhotic CHB who met the discontinuation criteria after NA consolidation treatment.Demographic,clinical,and laboratory data were collected and analyzed after NA discontinuation. Results:Ninety-six patients who finished 5 years of follow-up were included.HBsAg remained unde-tectable in 29 patients with end of treatment(EOT)HBsAg negativity.Among 67 patients with EOT HBsAg positivity,HBsAg seroclearance occurred in 12(17.9％)patients with an estimated annual inci-dence of HBsAg seroclearance of 3.6％.Patients with EOT HBsAg levels of ≤1000 IU/mL had a higher HBsAg seroclearance rate than those with EOT HBsAg levels of＞1000 IU/mL(33.3％vs.5.4％).The pro-portion of patients with HBsAg ≤1000 IU/mL increased during follow-up.Logistic regression analysis indicated that the EOT HBsAg level was an independent factor for HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/mL.The optimal EOT HBsAg cutoff for both HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/mL was 359 IU/mL. Conclusions:Patients with EOT HBsAg negativity experienced no relapse and maintained HBsAg sero-clearance during 5 years of follow-up after NA discontinuation.A higher HBsAg seroclearance rate can be obtained in patients with EOT HBsAg levels of ≤1000 IU/mL during 5 years of follow-up after NA discontinuation.Close monitoring and proper NA retreatment are recommended to guarantee the safety of NA discontinuation.

Background and aims:Antiviral therapy is essential for hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF).No data are available on the long-term prognosis or safety of tenofovir alafenamide(TAF),tenofovir disoproxil fumarate(TDF),or entecavir(ETV)in treating HBV-ACLF globally.This study was conducted to investigate the long-term efficacy and safety of the three nucleos(t)ide analogs in the treatment of HBV-ACLF.Methods:In this prospective,real-world cohort study,patients with HBV-ACLF were assigned to the TAF,TDF,and ETV groups.A total of 199 patients completed the 144-week follow-up.After propensity score matching(PSM),44 patients remained in each group for further analysis of survival status,incidence of hepatocellular carcinoma(HCC),virological response,and liver and renal function indicators.Results:In the original cohort,HCC developed in one patient in each group.No serious drug-related adverse events were observed.In the PSM cohort,the 144-week survival rates were 56.82％,75.00％,and 59.09％in the TAF,TDF,and ETV groups,respectively(P=0.118).When stratified into noncirrhosis and cirrhosis subgroups at baseline,the survival rate of the ETV group was slightly lower than that of the TAF and TDF group in noncirrhosis patients(P=0.338),and the survival rate of the TAF group was slightly lower than that of the TDF and ETV group in cirrhosis patients(P=0.052),but the differences were not statistically significant.The long-term overall survival rates in the TAF,TDF,and ETV groups were comparable.After 144 weeks,no significant difference in the virological response rate or liver or renal function indicators was found among the three groups,except for the level of aspartate amino-transferase,which was significantly higher in the TDF group than in the ETV group at week 144(P=0.001).Conclusions:There were no significant differences in the survival rate,incidence of HCC,efficacy or safety associated with the use of these three nucleos(t)ide analogs in treating HBV-ACLF.Trial registration:ClinicalTrials.gov NCT03920618.

Objective:To investigate the risk factors affecting the occurrence of sudden cardiac death（SCD）of hypertrophic cardiomyopathy（HCM）in children.Methods:This was a retrospective study.A total of 184 children with HCM who admitted to Beijing Children's Hospital，Capital Medical University from 1 January，2006 to 31 August，2022 were collected for clinical data and follow-up information.Risk factors affecting the occurrence of SCD in children with HCM were analyzed by Cox regression.Results:A total of 184 children with HCM were included in this study，including 69（37.50%）female cases and 115（62.50%）male cases.Cox regression showed that age less than one year（ HR=6.232，95% CI 2.858-13.591），female gender（ HR=2.547，95% CI 1.460-4.444），family history（ HR=2.622，95% CI 1.468-4.683），pathological Q waves in the electrocardiogram（ HR=2.290，95% CI 1.285-4.082），QRS fragmentation waves（ HR=3.526，95% CI 1.786-6.963），combined multiple arrhythmias（ HR=2.218，95% CI 1.136-4.333），high interventricular septal thickness on echocardiography（ HR=1.055，95% CI 1.008-1.105）,and high left ventricular posterior wall thickness（ HR=1.060，95% CI 1.026 -1.096）were risk factors for endpoint events in children. Conclusion:Age，sex，family history，electrocardiogram changes（pathological Q wave，QRS fragmentation wave，combined multiple arrhythmia），interventricular septum thickness and left ventricular posterior wall thickness are independent risk factors affecting the occurrence of SCD of HCM in children.

Objective:To investigate the risk factors affecting the occurrence of sudden cardiac death（SCD）of hypertrophic cardiomyopathy（HCM）in children.Methods:This was a retrospective study.A total of 184 children with HCM who admitted to Beijing Children's Hospital，Capital Medical University from 1 January，2006 to 31 August，2022 were collected for clinical data and follow-up information.Risk factors affecting the occurrence of SCD in children with HCM were analyzed by Cox regression.Results:A total of 184 children with HCM were included in this study，including 69（37.50%）female cases and 115（62.50%）male cases.Cox regression showed that age less than one year（ HR=6.232，95% CI 2.858-13.591），female gender（ HR=2.547，95% CI 1.460-4.444），family history（ HR=2.622，95% CI 1.468-4.683），pathological Q waves in the electrocardiogram（ HR=2.290，95% CI 1.285-4.082），QRS fragmentation waves（ HR=3.526，95% CI 1.786-6.963），combined multiple arrhythmias（ HR=2.218，95% CI 1.136-4.333），high interventricular septal thickness on echocardiography（ HR=1.055，95% CI 1.008-1.105）,and high left ventricular posterior wall thickness（ HR=1.060，95% CI 1.026 -1.096）were risk factors for endpoint events in children. Conclusion:Age，sex，family history，electrocardiogram changes（pathological Q wave，QRS fragmentation wave，combined multiple arrhythmia），interventricular septum thickness and left ventricular posterior wall thickness are independent risk factors affecting the occurrence of SCD of HCM in children.

Objective:To investigate effects of capecitabine metronomic chemotherapy combined with exemestane on the proliferation of breast cancer MCF-7 cells and PI3-K/AKT signaling pathway.Methods:MCF-7 cells cultured in vitro were divided into the control group (adding DMEM without drugs), 30 μmol/L exemestane group, capecitabine metronomic chemotherapy combined drugs group [30 μmol/L exemestane combined with different concentrations (50, 33, 17 μmol/L) of capecitabine]. CCK-8 assay was used to detect the cell proliferation inhibition rate, the half-maximal inhibitory concentration ( IC50) was calculated, and the changes of cell cycle and apoptosis rate of MCF-7 in different drug groups were assessed by using flow cytometry. The related-protein expression of PI3K-AKT signaling pathway of MCF-7 cells was detected by using Western blot. Results:The IC50 of capecitabine and exemestane on MCF-7 cells for 72 h was 101.2 μmol/L and 60.6 μmol/L, respectively. The proliferation inhibition rate of MCF-7 cells in 30 μmol/L exemestane for 24 h and 48 h combined with 50, 33 and 17 μmol/L capecitabine group was higher than that in 30 μmol/L exemestane group (all P<0.01). The apoptosis rates were (18.1±2.6)%, (34.6±3.0)%, (27.6±1.3)%, (23.1±1.6)%, respectively in 30 μmol/L exemestane group, 30 μmol/L exemestane + 50 μmol/L capecitabine group, 30 μmol/L exemestane + 33 μmol/L capecitabine group, 30 μmol/L exemestane + 17 μmol/L capecitabine group, and the difference was statistically significant ( F = 23.652, P<0.01). Compared with the control group, the proportion of MCF-7 cells in phase G 2 of 30 μmol/L exemestane group was increased [(16.7±2.6)% vs. (10.6±2.2)%], while that in phase G 1 was decreased [(53.3±4.0)% vs. (56.3±3.2)%]. The proportion of MCF-7 cells in phase S of 30 μmol/L exemestane + 50 μmol/L capecitabine group was increased [(39.0±3.6)% vs. (33.1±2.0)%]. MCF-7 cells of 30 μmol/L of exemestane + 33 μmol/L capecitabine group were more blocked in phase S [(51.7±4.1)%], and cells in phase G 2 were nearly disappeared [(1.2±0.5)%]; the cell proportion MCF-7 cells in phase G 2 of 30 μmol/L exemestane plus 17 μmol/L capecitabine group was increased [(26.2±3.1)%]. Western blot analysis showed that low dose capecitabine metronomic chemotherapy promoted exemestane to inhibit the expression of PI3K, motivated AKT serine phosphorylated at protein 473 [the increased expression of p-AKT (473)], promoted S6 protein expression at downstream of signaling pathway and increased its phosphorylation level (the increased expression of p-S6), thereby activating apoptosis signal. Conclusion:Capecitabine metronomic chemotherapy combined with exemestane can synergistically inhibit the proliferation of breast cancer MCF-7 cells and activate apoptosis mechanisms of MCF-7 cells through affecting PI3K-AKT signaling pathway.