Objective To investigate the relationship between serum cystatin C(CysC)level and the risk of Parkinson's disease(PD)in middle-aged and elderly people in China.Methods Based on the baseline survey data from the China Health and Retirement Longitudinal Study(CHARLS)in 2011,participants who were not diagnosed with PD at the time of the baseline survey were recruited.The onset of PD was tracked and followed up until 2020,and the participants were divided into PD group and non-PD group according to whether they were newly diagnosed with PD in 2020.Multivariable Logistic regression analysis was performed to assess the association between serum CysC level and the risk of PD.Subgroup and interaction analyses were performed to assess effect modifications by age,gender and depression.Additionally,restricted cubic spline(RCS)was used to explore the linear or non-linear relationship between serum CysC level and the risk of PD in different subgroups.Results We included a total of 3 339 subjects in this study,who consisted of 1 495 males(44.77％)and 1 844 females(55.23％).While baseline participants were followed until 2020,32 subjects had a new PD,and the incidence of PD was 0.96％.The median age of PD group was 63.00 years.Multivariable Logistic regression analysis found that CysC was an independent risk factor for the risk of PD,and CysC was positive significantly associated with the risk of PD(OR=2.34,95％ CI:1.14-4.82,P=0.021).Subgroup analysis showed that CysC was positively associated with PD in females(OR=2.70,95％ CI:1.30-5.58,P=0.007)and subjects aged 60 years or older(OR=5.29,95％ CI:1.69-16.53,P=0.004).RCS model indicated a linear relationship between serum CysC level and the risk of PD in females(Ptotal=0.018,Pnon-linear=0.062)and subjects aged 60 years or older(Ptotal=0.024,Pnon-linear=0.379).Conclusion High level of CysC may increase the risk of PD in middle-aged and elderly people,especially in females and those aged 60 years or older.

Objective To investigate the relationship between serum cystatin C(CysC)level and the risk of Parkinson's disease(PD)in middle-aged and elderly people in China.Methods Based on the baseline survey data from the China Health and Retirement Longitudinal Study(CHARLS)in 2011,participants who were not diagnosed with PD at the time of the baseline survey were recruited.The onset of PD was tracked and followed up until 2020,and the participants were divided into PD group and non-PD group according to whether they were newly diagnosed with PD in 2020.Multivariable Logistic regression analysis was performed to assess the association between serum CysC level and the risk of PD.Subgroup and interaction analyses were performed to assess effect modifications by age,gender and depression.Additionally,restricted cubic spline(RCS)was used to explore the linear or non-linear relationship between serum CysC level and the risk of PD in different subgroups.Results We included a total of 3 339 subjects in this study,who consisted of 1 495 males(44.77％)and 1 844 females(55.23％).While baseline participants were followed until 2020,32 subjects had a new PD,and the incidence of PD was 0.96％.The median age of PD group was 63.00 years.Multivariable Logistic regression analysis found that CysC was an independent risk factor for the risk of PD,and CysC was positive significantly associated with the risk of PD(OR=2.34,95％ CI:1.14-4.82,P=0.021).Subgroup analysis showed that CysC was positively associated with PD in females(OR=2.70,95％ CI:1.30-5.58,P=0.007)and subjects aged 60 years or older(OR=5.29,95％ CI:1.69-16.53,P=0.004).RCS model indicated a linear relationship between serum CysC level and the risk of PD in females(Ptotal=0.018,Pnon-linear=0.062)and subjects aged 60 years or older(Ptotal=0.024,Pnon-linear=0.379).Conclusion High level of CysC may increase the risk of PD in middle-aged and elderly people,especially in females and those aged 60 years or older.

Objective To analyze the changes in the expression levels of serum Dickkopf-related protein 1(DKK-1)and latent transforming growth factor binding protein 2(LTBP2)in patients with connective tissue disease(CTD)related interstitial pneumonia(IP)of different disease activity levels before and after treatment.Methods A total of 121 CTD patients who visited the First Affiliated Hospital of Hebei North University from January 2022 to October 2023 were collected and separated into an observation group(CTD-related IP patients,n=62)and a reference group(CTD without IP patients,n=59)based on the incidence of IP.The observation group was separated into a stable phase group(n=26)and an acute exacerbation phase group(n=36)based on disease activity.Enzyme-linked immunosorbent assay(ELISA)detected DKK-1 and LTBP2 levels.Pearson or Spearman were used to analyze correlations between DKK-1 and LTBP2 levels with clinical data.Logistic regression was applied to analyze influencing factors of acute exacerbation in CTD-related IP patients.Results The serum levels of DKK-1(14.98±3.32 ng/ml)and LTBP2(32.64±4.01 ng/ml)in the observation group were higher than those in the reference group(2.21±0.67 ng/ml,8.73±2.15 ng/ml),the differences were statistically significant(t=28.983,57.518,all P＜0.05).The proportions of patients with ground glass opacity(66.67%)and honeycomb opacity(52.78%),serum DKK-1(19.67±4.10 ng/ml),LTBP2(38.76±4.92 ng/ml)and C-reactive protein(CRP)(32.46±3.12 mg/L)in the acute exacerbation group were higher than those in the stable phase group(30.77%,23.08%,8.48±1.37 ng/ml,24.17±3.65 ng/ml,22.05±2.80 mg/L),the differences were statistically significant(t/x2=7.790,5.534,13.362,12.781,13.524,all P<0.05).The serum levels of DKK-1 and LTBP2 in patients with acute exacerbation of CTD-related IP after treatment were positively correlated with ground glass opacities,honeycomb opacities,CRP and different disease activity(r=0.526,0.518,0.513,0.548;0.499,0.514,0.520,0.561,all P<0.05).As the treatment time extended,the serum levels of DKK-1 and LTBP2 in CTD-related IP patients in the stable and acute exacerbation groups decreased,and the serum levels of DKK-1 and LTBP2 in the acute exacerbation group were higher than those in the stable group before treatment,1 month after treatment,and 3 months after treatment,the differences were statistically significant(t=13.355,13.206,15.913;12.781,12.263,11.161,all P<0.05).DKK-1[OR(95%CI):2.458(1.297～4.657)],LTBP2[OR(95%CI):2.739(1.567～4.789)]were independent risk factors for acute exacerbation of CTD related IP patients(all P<0.05).Conclusion The serum levels of DKK-1 and LTBP2 in CTD-related IP patients are increased,and closely related to disease activity.Both decrease after 3 months of treatment and can monitor the treatment efficacy of patients to a certain extent.

Enterotoxigenic Escherichia coli（ETEC）infection can induce watery diarrhea，leading to dehydration，electrolyte disturbance，and even death in severe cases. Recombinant B subunit/inactivated whole-cell cholera（rBS/WC）vaccine is effective in preventing ETEC infectious diarrhea. On the basis of the latest evidence on etiology and epidemiology of ETEC，as well as the effectiveness，safety，and health economics of rBS/WC vaccine，National Clinical Research Center for Child Health（The Children’s Hospital，Zhejiang University School of Medicine）and Zhejiang Provincial Center for Disease Control and Prevention invited experts to develop expert consensus on rBS/WC vaccine in prevention of ETEC infectious diarrhea. It aims to provide the clinicians and vaccination professionals with guidelines on using rBS/WC vaccine to reduce the incidence of ETEC infectious diarrhea.

Objective To explore the efficacy and prognosis of haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HSCT) for severe aplastic anemia (SAA).Methods The clinical data were retrospectively analyzed for 40 SAA cases undergoing haplo-HSCT from September 2013 to February 2018.The conditioning regimen contained cyclophosphamide,fludarabine and antithymocyte globulin with or without busulfan or low-dose total body irradiation.Cyclosporin A,short-term methotrexate and mycophenolate mofetil were dosed for preventing graft versus host disease (GVHD).The median counts of mononuclear cell and CD34+ stem cell were 5.3(2.0～13.5) × 108/kg and 5.6 (1.6 ～ 15.9) × 106/kg respectively.Results Among them,hematopoietic reconstitution was achieved (n =36,90.0 ％).The median times for myeloid engraftment and platelet engraftment were 15(10-25) and 17(10～58) days respectively.The incidence of acute graft-versushost disease(aGVHD)was (35.0± 6.8) ％.The incidence of chronic GVHD (cGVHD) was (23.0 ±7.4) ％.And 28 SAA cases (70.0 ％) survived during a median follow-up period of 353(30～1226)days,The cumulative overall survival (OS) was (67.8 ± 7.8) ％,the average survival time (883 ± 82)days and transplantation-related death (TRM) within 100 days (10.0 ± 3.1) ％.Conclusions Haplo-HSCT is an effective treatment for SAA patients.And a larger number of cases are required for enhancing OS.

The persistence of covalently closed circular DNA (cccDNA) in the nucleus of liver cells is a key factor that hinders the cure of chronic hepatitis B. However,it is difficult to eliminate cccDNA with existing anti-HBV therapy. Recent studies have found that serum HBV RNA may be a new indicator reflecting the activity of cccDNA in hepatocytes and evaluating the clinical efficacy of CHB patients . This article reviews recent advances in the properties,detection methods,and clinical significance of HBV RNA, particularly the application of antiviral therapy in CHB patients.

Objective To summarize the clinical characteristics and treatment of 17 children with Listeria monocytogenes(LM) meningitis (LMM).Methods Case histories (including clinical features,laboratory examination,treatment,prognosis) of 17 LMM children who were hospitalized at the Department of Infectious Disease of Beijing Children's Hospital from January 1,2013 to December 31,2017 were analyzed retrospectively.The age ranged from 7 months to 10 years,with an average of 3 years and 5 months.Among them,1 case ＜ 1 year old,1-3 years old was most common(10 cases,accounted for 59％),2 cases ＞3-＜6 years old,and 4 cases≥6 years old.Related literatures were summarized.Results All of 17 patients were diagnosed by a positive cerebrospinal fluid culture of LM.All patients had fever.Other symptoms included seizures,headache and vomiting were found during the course of disease;infectious symptoms were relatively mild.The symptoms presented 7 to 50 days before admission.None of the patients was known to have immune deficiencies or any other underlying diseases.Five cases underwent strain typing,all resulting from strain type l/2a.All patients used cephalosporin antibiotics before the diagnosis.After the diagnosis was confirmed,sensitive antibiotics were used according to the drug sensitivity test,including Penicillin,Meropenem,Vancomycin,Linezolid,and Sulfamethoxazole-trimethoprim (SMZ),etc.Out of the 17 patients,2 case had hydrocephalus,of which 1 cases had clinical symptoms,and underwent surgery for a ventriculoperitoneal shunt.All patients were followed up for 1 year,with good prognosis and no neurological sequela.Conclusions LMM is rare in children,especially in children with no immune deficiencies.LMM in children can present with hydrocephalus.Ampicillin remains the first choice of treatment,while meropenem,SMZ and Linezolid can be used as substitution drugs.

Objective To analyze the clinical characteristics and prognosis of disseminated cryptococcosis in children.Methods The data of disseminated cryptococcosis inpatients were reviewed retrospectively at Beijing Children's Hospital,Capital Medical University,from January 2002 to September 2014.The demographic data,clinical manifestations,laboratory findings,imaging,antifungal treatments and outcomes of all the patients were analyzed.Results Overall 25 children with disseminated cryptococcosis were enrolled including 17 boys(68.0％).The average age was 7 years old.Four cases (16.0％) had underlying conditions,among them 1 case had human immunodeficiency virus(HIV)-positive.The median time to diagnosis was 32 (23-47) days,44.0％ of the patients (11 cases) were misdiagnosed,and 8 cases misdiagnosed as tuberculosis.All patients had fever.Other common clinical manifestations included cough (16 cases),headache (10 cases),vomiting (10 cases),altered mental status (6 cases) and stomachache (6 cases).Respiratory system involvement was seen in all cases,central nervous system was involved in 18 cases,other organ involvement included lymph nodes,spleen,liver,kidney,skin,skeleton and costicartilage.Amphotericin B (AmB) + Fluconazole (Flu) ± 5-flucytosine (5-FC) was the most common therapy (15 cases),Flu ± 5-FC for 6 cases,AmB ± 5-FC for 2 cases,Voricanazole (VOR) for 1 case.Sixteen cases (66.7％) got recovery/improved on discharge,8 cases (33.3％) rejected to the advise and discharged with treatment failure,and the HIV-infected patient transferred to a special hospital.Fifteen patients (60.0％) were followed up,and 13 cases (87.0％) showed recovery,but 2 died in the long-term prognosis.Conclusions Disseminated cryptococcosis in children is more common in school-age boys.Most patients are without underlying conditions.Disseminated cryptococcosis can cause multiple organ damage.Patients with prolonged fever,cough,headache,with or without underlying diseases,can be suspected as disseminated cryptococcosis.Blood and cerebrospinal fluid culture for fungus,cryptococcal antigen should be performed for early diagnosis and treatment.

OBJECTIVETo analyze risk factors, clinical features, outcomes and antibiotic resistance of Escherichia coli(E.coli) causing bloodstream infections in children.

METHODAll inpatients with E. coli positive blood culture in Beijing Children's Hospital from January 2012 to May 2014 were enrolled; 112 cases were included, 66 cases (58.9%) were male, and 46 cases(41.1%) were female. Age range was 2 days to 16 years. Among them, 43 cases (38.4%) were neonates, 19 cases (17.0%) aged from 1 month to 1 year, 14 cases (12.5%) were 1-3 years old, and 36 cases (32.1%) were over three years old. We analyzed the divisions to which the patients were admitted, source of infection, underlying diseases, clinical characteristics, antibiotic resistance, and treatment outcomes, etc.

RESULTForty-six cases (41.1%) were treated in division of hematology, 42 (37.5%) in neonatology, 9 (8.0%) in internal medicine, 8 (7.1%) in surgery, and 7 (6.3%) in pediatric intensive care unit. Sixty-five cases(58.0%) had underlying diseases. Fever was the most frequently presented symptom, as it was seen in 91 cases (81.3%); 52 cases(46.4%) had respiratory symptoms. Among these, 43 cases had pneumonia, 3 cases had respiratory failure, 3 cases were diagnosed as upper respiratory tract infection, 2 had pulmonary hemorrhage and 1 case had bronchitis. Twenty-six cases (23.2%)were diagnosed as severe sepsis and purulent meningitis separately, 14 cases(12.5%) had urinary tract infection. There were 73 (65.2%) strains inducing extended spectrum β-lactamases (ESBLs), of which 6 (8.2%) and 10 (13.7%) strains were resistant to amikacin and carbapenems respectively. Resistance rate against other antimicrobial agents varied from 64.6% to 100%.

OUTCOMES92 (82.1%) cases were cured or had improvement while 20 patients (17.9%) died or could not be cured at the end of treatment. Positive ESBLs (χ(2) = 6.609, P = 0.010), being complicated with severe sepsis (χ(2) = 40.253, P = 0.000) and requiring mechanical ventilation (χ(2) = 34.441, P = 0.000) indicate poor prognosis.

CONCLUSIONPatients with underlying diseases and newborns are susceptible to E. coli bloodstream infection. ESBLs infection, severe sepsis and mechanical ventilation indicate poor prognosis in E. coli blood stream infection. Clinicians may use carbapenems as empirical treatment for ESBLs infection. There may be carbapenem-resistant enterobacteriaceae strains infection if patients receiving treatment with carbapenems have no response.

Adolescent ; Bacteremia ; Carbapenems ; therapeutic use ; Child ; Child, Preschool ; Drug Resistance, Bacterial ; Escherichia coli ; drug effects ; Escherichia coli Infections ; blood ; drug therapy ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial ; Microbial Sensitivity Tests ; Pneumonia ; Urinary Tract Infections ; beta-Lactamases

Objective To summarize the clinical features of histiocytic necrotizing lymphadenitis (HNL) and the lesion of central neural system in children.Methods Data of the 4 cases in Beijing Children's Hospital from January 2009 to December 2014 were reviewed and analyzed,as well as other files of 12 patients from PubMed,CNKI,etc.Results All 4 patients mentioned above started from fever and lymphadenopathy,3 cases had headache,2 cases of them experienced altered mental status,and 1 case had cclampsia.The findings of cerebrospinal fluid (CSF) test was similar to viral encephalitis;2 cases had normal magnetic resonance imaging (MRI) result;1 case with MRI test indicated brain white matter diseases with extensive intracerebral hemorrhage,and 1 case had small range of encephalomalacia in left cerebral hemisphere and cerebral dura mater.Through CSF examination,2 cases were positive to Epstein-Barr viral capsid antigen (EBV-VCA)-IgM,while the 2 other cases had no positive trace of EBV-VCA-IgM.Lymph node biopsy was in accordance with HNL typical changes,1 case was positive for Epstein-Barr virus encoded RNA (EBER).Twelve cases in previous literatures were diagnosed as HNL by lymph node biopsy,and their clinical features of central nervous system were headache and altered mental status.There was no change in pathogen.It is also found that the cases in which CSF was performed had shown being negative.CT/MRI image descriptions involved in temporosphenoid lobe,hippocampus,caudate lobe,leptomeninges,etc.Conclusions HNL can be complicated with lesions of the central nervous system,characterized by aseptic meningitis,encephalitis,etc.The prognosis of most cases is good,a few can have neurological sequelae.HNL may relapse,so long-term follow-up is ne-cessary.Epstein-Barr virus in HNL and lesion of central nervous system mechanism still needs further research.