OBJECTIVES: To investigate the genomic characteristics and prognostic factors of juvenile myelomonocytic leukemia (JMML) with RAS mutations. METHODS: A retrospective analysis was conducted on the clinical data of JMML children with RAS mutations treated at the Hematology Hospital of Chinese Academy of Medical Sciences, from January 2008 to November 2022. RESULTS: A total of 34 children were included, with 17 cases (50%) having isolated NRAS mutations, 9 cases (27%) having isolated KRAS mutations, and 8 cases (24%) having compound mutations. Compared to children with isolated NRAS mutations, those with NRAS compound mutations showed statistically significant differences in age at onset, platelet count, and fetal hemoglobin proportion (P<0.05). Cox proportional hazards regression model analysis revealed that hematopoietic stem cell transplantation (HSCT) and hepatomegaly (≥2 cm below the costal margin) were factors affecting the survival rate of JMML children with RAS mutations (P<0.05); hepatomegaly was a factor affecting survival in the non-HSCT group (P<0.05). CONCLUSIONS Children with NRAS compound mutations have a later onset age compared to those with isolated NRAS mutations. At initial diagnosis, children with NRAS compound mutations have poorer peripheral platelet and fetal hemoglobin levels than those with isolated NRAS mutations. Liver size at initial diagnosis is related to the prognosis of JMML children with RAS mutations. HSCT can improve the prognosis of JMML children with RAS mutations.
Humans ; Leukemia, Myelomonocytic, Juvenile/therapy* ; Mutation ; Male ; Female ; Child, Preschool ; Retrospective Studies ; Child ; Infant ; GTP Phosphohydrolases/genetics* ; Membrane Proteins/genetics* ; Adolescent ; Hematopoietic Stem Cell Transplantation ; Proportional Hazards Models ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis

Nitrofurazone(NFZ)is an antibiotic that is used as a veterinary drug in aquaculture.NFZ abuse can lead to a series of environmental and health issues,making it crucial to establish a rapid and highly sensitive method for NFZ detection.In this study,platinum nanoparticle(PtNPs)-loaded zeolitic imidazolate framework(ZIF-8)was used as a precursor,and PtNPs functionalized nitrogen doped porous carbon(NC)was obtained through pyrolysis.Pt@NC was combined with multi-walled carbon nanotubes(MWCNTs)and cast onto a glassy carbon electrode(GCE)surface to construct an electroch-emical sensor.Electrochemical tests revealed that Pt@NC/WCNT/GCE exhibited an electrochemical active area of 0.066 cm2 and a heterogeneous electron transfer rate constant(k0)of 2.03×10-3 cm/s,which were higher than other materials.Compared with the electrodes modified by other materials,the NFZ generated the highest peak current of irreversible reduction peak on the Pt@NC/WCNT/GCE electrode.In comparison with Pt@ZIF-8/WCNT/GCE,after pyrolysis and carbonization treatment,the reduction current of NFZ increased by 2.19 times,and the reduction peak potential shifted positively by 19 mV simultaneously.When compared with NC/WCNT/GCE,the PtNPs in the composite material enhanced the NFZ current by 4.25 times.Additionally,the experimental conditions for detecting NFZ using the sensor were optimized,including the carbonization temperature of Pt@ZIF-8,ratio of Pt@NC to CNT,loading amount of the modified material,and electrolyte pH.Under the optimized conditions,the sensor demonstrated a linear detection range for NFZ of 0.20-240 μmol/L,a sensitivity of 9.995 μA/((μmol/L)?cm2)and a limit of detection(LOD)of 0.06 μmol/L.The sensor exhibited excellent anti-interference capability,good reproducibility,and stability,with spiked recoveries for NFZ in water samples ranging from 94.6%to 105.6%.This study provided a novel electrochemical sensing approach for NFZ detection.

Objective To analyze the drug resistance and serotype of Group B Streptococcus(GBS)isolated from pediatric patients,provide reference for the prevention and treatment of GBS infection as well as vaccine develop-ment in children.Methods 163 non-repetitive GBS strains detected at Beijing Children's Hospital of Capital Medi-cal University from January 1,2016 to December 31,2023 were collected.Strains were conducted resistance analy-sis and serotype testing.Results Among the 163 GBS strains,121 and 42 were invasive and non-invasive infection isolates,respectively.No strains were found to be resistant to penicillin,ceftriaxone,cefepime,linezolid,and van-comycin,and resistance rates to erythromycin,clindamycin,and levofloxacin were 91.4％,90.8％,and 53.4％,re-spectively.Non-invasive infection isolates had a higher resistance rate to levofloxacin than invasive infection isolates.The distribution of bacterial serotypes from high to low was as follows:type Ⅰb(n=75,46.0％),type Ⅲ(n=65,39.9％),type Ⅴ(n=13,8.0％),type Ⅰa(n=6,3.7％),type Ⅱ(n=2,1.2％),type Ⅳ and Ⅵ(n=1,0.6％,each).There was a statistically significant difference in the distribution of serotypes between invasive and non-invasive infection isolates(P＜0.05).Serotype distributions of erythromycin-and clindamycin-resistant GBS strains were both statistically different between two groups(both P＜0.05),while serotype distribution of levoflo-xacin-resistant GBS strains was not statistically different between two groups(P＞0.05).Conclusion GBS strains in children in Beijing have high resistance rates to erythromycin and clindamycin,with serotypes Ⅰb and Ⅲ being more frequent.Serotypes with high prevalence have higher resistance.Continuously monitoring on the epidemiology of GBS infection is crucial for the clinical prevention and treatment of GBS infection in children as well as the devel-opment of vaccines.

Objective To analyze the status and gene subtype distribution of human papillomavirus(HPV)infec-tion in male patients in dermatology outpatient department,provide reference for the prevention and treatment of male HPV infection.Methods Male patients who visited and conducted HPV detection in the dermatology outpa-tient department of a hospital from January 2022 to March 2023 were retrospectively surveyed.Patients were divi-ded into five groups:viral warts group,dermatitis and rash group,urinary tract infection group,balanoposthitis group,and asymptomatic group.Relationship between genotype distribution and patient age,clinical diagnosis,and symptom types was statistically analyzed.Results A total of 1 035 male patients underwent HPV detection,out of which 567 were positive,with a positive detection rate of 54.78％.286,164,6,109,and 470 cases were from viral warts,dermatitis and rash,urinary tract infection,balanoposthitis,and asymptomatic group,respectively.21 sub-types of HPV were detected,with the top three subtypes being type 6(17.97％),11(12.37％),and 52(8.70％).The positive rate of single type HPV infection was 29.86％,accounting for 54.50％.Positive rates of infection,low-risk infection,and multiple mixed infection in different age groups were compared,differences were all statisti-cally significant(all P＜0.05).The positive infection rate in the age group of＜20 years old was higher than that in the age groups of 20-＜30,30-＜40,and 40-＜50 years old,differences were all statistically significant(all P＜0.05).Among the positive patients,199 cases(35.10％)had no clinical symptoms,while 368(64.90％)had clinical symptoms,mainly manifested as viral warts(40.74％,n=231).In viral warts group,HPV-positive pa-tients were mainly of low-risk type,accounting for 80.95％;In balanoposthitis group,HPV-positive patients were mainly of high-risk type,accounting for 84.78％;In asymptomatic group,HPV-positive patients were mainly infected with high-risk types,accounting for 86.43％.Conclusion HPV infection in male outpatient department of derma-tology is mainly single type infection.The clinical diagnosis of low-risk infection is mainly viral warts,while high-risk in-fection is mainly manifested as balanoposthitis.In asymptomatic group,positive infections are mainly of high-risk type.

Objective To observe the therapeutic effect and mechanism of polydatin on intrauterine adhesions(IUA)in rats.Methods Eight rats were randomly selected as the sham operation group from 40 fertile female SD rats,and the remaining 32 rats were given intrauterine mechanical injury combined with lipopolysaccharide infection to induce IUA model.The 32 model rats were randomly divided into model group,low-,medium-and high-dose groups of polydatin,with 8 rats in each group,and the corresponding intervention lasted for 14 days.The morphological structure of endometrium was observed by hematoxylin-eosin(HE)staining,the thickness of endometrium was measured and the number of endometrial glands was counted.Masson staining was used to observe endometrial fibrosis;enzyme-linked immunosorbent assay(ELISA)was used to detect the contents of tumor necrosis factor-α(TNF-α),interleukin(IL)-1β and IL-6 in endometrial tissue.Western Blot was used to detect the ptotein expressions of key proteins of Wnt/β-catenin signaling pathway,including β-catenin,glycogen synthase kinase 3β(GSK-3β),phosphorylated glycogen synthase kinase 3β(p-GSK-3β),Cyclin D1,and fibrosis-related proteins,including transforming growth factor β1(TGF-β1),α-smooth muscle actin(α-SMA),type I collagen(ColⅠ)and type Ⅲ collagen(Col Ⅲ).Results Compared with the sham operation group,the endometrial tissue of rats in the model group and the low-,medium-and high-dose groups of polydatin showed different degrees of pathological damage,the thickness of the endometrium and the number of glands decreased,and there were obvious different degrees of collagen fiber deposition.The levels of TNF-α,IL-1β,IL-6,the relative protein expressions of β-catenin,Cyclin D1 and the activation level of GSK-3β protein,the relative protein expressions of TGF-β1,α-SMA,ColⅠ and Col Ⅲ in endometrial tissue were increased(P＜0.05).Compared with the model group,the pathological damage of endometrial tissue in the low-,medium-and high-dose groups of polydatin was improved,the endometrial thickness and the number of glands were increased,and the endometrial fibrosis was alleviated.In addition,the levels of the above indicators in the endometrial tissue were decreased(P＜0.05)in a dose-dependent manner.Conclusion Polydatin can promote endometrial repair and inhibit excessive endometrial fibrosis in rats with IUA,and its mechanism may be related to the inhibition of Wnt/β-catenin signaling pathway activation.

Objective To investigate the infiltration of peripheral monocyte in the hippocampal CA3 area in neuralgia mice at different time points and explore the effects of the infiltration on neuralgia and the neuralgia-induced anxiety-like behavior in mice.Methods The healthy male C57 mice were randomly divided into four groups:sham,sciatic nerve branch selective injury(SNI)model(SNI),CCR2 inhibitor RS102895(SNI+RS102895)and microglial inhibitor minocycline(MC)(SNI+MC)groups.Both the sham and SNI groups were further divided into 7 days,14 days and 18 days groups,and the SNI+RS102895 and SNI+MC groups were sampled on the 18th day.Neuralgia was induced by SNI,and mechanical hyperalgesia was assessed by paw withdrawal threshold(PWTs)at different time points.Elevated plus maze(EPM)and open field test(OFT)were performed respectively two days and one day before sacrifice.Immunofluorescence was used to observe the expressions of leukocyte differentiation antigen 45(CD45)and the co-expression with microglial markers ionized calcium binding adaptor molecule-1(IBA-1),transmembrane protein 119(TMEM119),astrocyte marker glial fibrillary acidic protein(GFAP),and neuronal marker neuronal nuclei(NeuN)in the hippocampal CA3.The percentage of monocytes in the whole brain of 14 days SNI mice was determined by flow cytometry.Minocycline at 90 mg/(kg·d),RS 102895 at 5 mg/(kg·d)and saline were administered orally on the 5th to 16th day in the corresponding 18 days groups,and the effects of blocking monocyte infiltration on neuralgia and anxiety-like behavior and the expressions of CD45 and 1BA-1 in CA3 region of hippocampus were observed.Results On the first day after SNI,the PWTs of mice in the 7 days and 14 days groups decreased and continued until before sacrifice(P＜0.01).The CD45 expression did little in the 7 days sham group.Compared with the sham group at the same time point,the CD45 expression did not increase in 7 days SNI mice((P＞0.05)and increased significantly in 14 days SNI mice(P＜0.01),only slightly co-expressed with IBA-1 and TMEM119 and no co-expression with GFAP and NeuN,the percentage of monocytes in the whole brain increased significantly in 14 days SNI mice(P＜0.01).Inhibition of microglial activation or CCR2 expression reduced the expression of CD45 in the CA3 in SNI mice(P＜0.01),increased the PWTs(P＜0.01)and alleviated anxiety-like behavior in SNI mice(P＜0.01).Conclusion There was an infiltration of peripheral monocytes in the hippocampal CA3 region after 14 days of SNI-induced neuralgia,which might be involved in the maintenance of neuralgia and the development of neuralgia-induced anxiety-like behaviors.

Objective To investigate the attributable risk(AR)of Acinetobacter baumannii(AB)infection in criti-cally ill patients.Methods A multicenter retrospective cohort study was conducted among adult patients in inten-sive care unit(ICU).Patients with AB isolated from sterile body fluid and confirmed with AB infection in each cen-ter were selected as the infected group.According to the matching criteria that patients should be from the same pe-riod,in the same ICU,as well as with similar APACHE Ⅱ score(±5 points)and primary diagnosis,patients who did not infect with AB were selected as the non-infected group in a 1:2 ratio.The AR was calculated.Results The in-hospital mortality of patients with AB infection in sterile body fluid was 33.3％,and that of non-infected group was 23.1％,with no statistically significant difference between the two groups(P=0.069).The AR was 10.2％(95％CI:-2.3％-22.8％).There is no statistically significant difference in mortality between non-infected pa-tients and infected patients from whose blood,cerebrospinal fluid and other specimen sources AB were isolated(P＞0.05).After infected with AB,critically ill patients with the major diagnosis of pulmonary infection had the high-est AR.There was no statistically significant difference in mortality between patients in the infected and non-infec-ted groups(P＞0.05),or between other diagnostic classifications.Conclusion The prognosis of AB infection in critically ill patients is highly overestimated,but active healthcare-associated infection control for AB in the ICU should still be carried out.

ObjectiveTo analyze the surveillance status of acute respiratory tract infection pathogens in Fengxian District of Shanghai, and to determine the pathogen spectrum and epidemiological characteristics of acute respiratory tract infection in the district. MethodsCase surveillance data from Fengxian Central Hospital were collected through the Shanghai Integrated Surveillance System for Acute Respiratory Infections, and respiratory specimens were collected from the 50^th week of 2022 to the 49^th week of 2023 for nucleic acid detection of 25 pathogens and bacterial culture testing. Case surveillance data from Fengxian Central Hospital were collected through the National Influenza Sentinel Surveillance System, and respiratory specimens were collected for nucleic acid detection of 5 pathogens. ResultsThe percentage seeking for medical visits of influenza-like illness (ILI) and severe acute respiratory infection (SARI) were 4.74% and 0.81%, respectively, with epidemic peaks in winter and spring. A total of 1 610 samples were detected, among which 354 were SARI cases, whose age of P₂₅ and P₇₅ quartiles were 44 years and 71 years, respectively, with a positive detection rate of 48.31%. Among the 1 256 ILI cases, the age of P₂₅ and P₇₅ quartiles were 21 years and 39 years, respectively. The positive detection rate of pathogens was 65.04% in 123 ILI cases under comprehensive surveillance of respiratory tract infection and 66.11% in 1 133 ILI cases under influenza surveillance. The positive rates of influenza andSARS-CoV-2 in SARI samples were 12.99% and 29.66%, respectively. The positive rates of influenza and SARS-CoV-2 in ILI case samples were 33.20% and 31.53%, respectively. Influenza virus concentrated in the winter and spring. The ILI and SARI cases had the highest positivity rates in the 6‒14 years old group and 15‒24 years old group, respectively. ConclusionThe main pathogens of respiratory tract infection in Fengxian District of Shanghai were SARS-CoV-2 and influenza virus. Special efforts should be made to monitor respiratory disease pathogens in the population under 24 years old, and surveillance of SARI cases aged ≥60 years should be strengthened. The influenza virus and SARS-CoV-2 are alternating, which is different from the past and requires a change in the previous prevention and control strategies.

Objective Human papillomavirus(HPV)is a detriment virus to human health,because it can cause malignant tumors.HPV vaccine has been developed and plays an important role in preventing a range of diseases caused by HPV.HPV vaccine as a primary prevention measure,has demonstrated excellent protective efficacy and safety in preventing HPV-related infection and cervical cancer.This article summarizes the application of preventive HPV vaccine and its safety,and provides reference for the widespread vaccination of HPV vaccine in China.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.