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

OBJECTIVE: To explore and evaluate the efficacy and safety of a modified thiotepa-based conditioning regimen combined with autologous hematopoietic stem cell transplantation (ASCT) for the treatment of primary central nervous system lymphoma (PCNSL). METHODS: In a retrospective, single center, single arm study, we collected data of 28 patients with PCNSL who underwent high-dose chemotherapy followed by autologous stem cell transplantation (HDC-ASCT) at our center from March 2021 to December 2024. The clinical characteristics of the patients, the conditioning regimen details, treatment-related toxicities and adverse reactions, post-transplant disease remission status, and survival outcomes were analyzed. RESULTS: A total of 28 patients were included. Among them, 19 patients received ASCT as first-line consolidation therapy in complete response (CR) or partial response (PR) status, and 9 patients with relapsed/refractory disease underwent salvage ASCT. The median time to neutrophil engraftment was 9 days (range: 5-11 days), and the median time to platelet engraftment was 10 days (range: 6-13 days). All patients achieved CR at the initial efficacy evaluation post-ASCT. The main complications during the transplantation period were febrile neutropenia (26 cases) and grade 3 diarrhea (9 cases). No transplantation-related mortality occurred. Post-ASCT, 19 patients received maintenance therapy, which was demonstrated to be safe and effective. Three patients relapse, and one patient died. The median progression-free survival (PFS) and overall survival (OS) of patients were not reached. The estimated 1-year and 2-year cumulative PFS rates were 88.4% and 66.3%, respectively, while the 1-year and 2-year OS rates were both 94.1%. CONCLUSION The modified thiotepa-based conditioning regimen combined with ASCT is safe and effective for the treatment of PCNSL.
Humans ; Thiotepa/therapeutic use* ; Retrospective Studies ; Transplantation, Autologous ; Transplantation Conditioning/methods* ; Central Nervous System Neoplasms/therapy* ; Hematopoietic Stem Cell Transplantation ; Female ; Male ; Middle Aged ; Adult ; Lymphoma/therapy* ; Treatment Outcome ; Aged

Objective To investigate the impact of emodin(EM)on vascular endothelial cell injury in rats with diabetes macroangiopathy by regulating hypoxia inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)signaling pathway.Methods SD rats were divided into blank group and modeling group,the rats in the modeling group were fed with high fat and high sugar combined with N-nitro-L-arginine methyl ester to build the diabetes macroangiopathy model,and the blank group was fed with ordinary diet.The vascular endothelial cells successfully isolated from the thoracic aorta of rats in blank group and modeling group were named control group and model group,respectively.The vascular endothelial cells in the modeling group were divided into model group,dimethyloxallyl glycine(DMOG)group(10 μmol·L-1DMOG),combined group(80 mg·L-1EM+10 μmol·L-1 DMOG)and experimental-L,-M,-H groups(20,40,80 mg·L-1 EM).The apoptosis of rat vascular endothelial cells was detected by flow cytometry;Western blot was applied to detect the expression of HIF-1αand VEGF proteins in rat vascular endothelial cells.Results The apoptosis rates of vascular endothelial cells in experimental-M,-H groups,DMOG group,combined group,model group and control group were(10.18±0.36)％,(6.28±0.20)％,(24.96±1.18)％,(12.36±0.49)％,(18.76±0.68)％and(4.59±0.26)％;HIF-1α protein levels were 0.96±0.07,0.78±0.06,2.03±0.12,1.05±0.13,1.58±0.12 and 0.69±0.05;VEGF protein levels were 0.59±0.05,0.23±0.02,0.98±0.06,0.63±0.04,0.86±0.07 and 0.11±0.01.The above indexes in the model group were compared with the control,DMOG,experimental-M and experimental-H groups,and the above indexes in the combined group were compared with the experimental-H group,and the differences were statistically significant(all P＜0.05).Conclusion EM may inhibit HIF-1α/VEGF pathway to improve vascular endothelial cell injury in rats with diabetes macroangiopathy.

Two methods including gas chromatography tandem mass spectrometry (GC-MS/MS) and high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) were established to detect common alkyl sulfonates and aryl sulfonates genotoxic impurities. Four alkyl sulfonates and methyl benzenesulfonate were determined by GC-MS/MS using butyl methanesulfonate as the internal standard, the chromatographic column was HP-5MS UI (30 mm × 0.25 mm, 0.25 µm), the carrier gas was helium, the flow rate was 1.0 mL·min^-1 in a constant flow mode, the sample inlet temperature was set to 250 ℃, the split ratio was 10∶1, and the initial temperature of the heating program was 80 ℃, maintained for 1 minute, and then increased to 240 ℃ at a heating rate of 30 ℃·min^-1 for 2 minutes. The mass spectrometry detector was an electron bombardment ion source (EI source), the data collection condition was multi reaction monitoring mode (MRM), and method validation using the raw material of clinical drug citalopram hydrobromide as a sample. The results showed that the linear range of four alkyl sulfonates and methyl benzenesulfonate were good at 3-50 ng·mL^-1 and 9-150 ng·mL^-1, with a correlation coefficient of r > 0.999, The spiked recovery was 80%-120%. The detection limits were 1 and 3 ng·mL^-1; Ten aryl sulfonates determined by LC-MS/MS, the chromatographic column was CSH Fluoro phenyl (100 mm × 2.1 mm, 1.7 µm), the mobile phase was methanol (B)-5 mmol·L^-1 ammonium formate (D), with a flow rate of 0.2 mL·min^-1, and gradient elution was performed. The gradient program (T/% B) was set as 0/20, 25/90, 35/90, 42/20. The mass spectrometer detector was electro spray ionization with positive ionization mode (ESI⁺), the data collection was in dynamic multi reaction monitoring mode (dMRM), and the method was validated using the raw material of the clinical drug citalopram hydrobromide as a sample. The results showed that the linear range of aryl sulfonates were good at 9-2 000 ng·mL^-1, 3-100 ng·mL^-1 and 0.9-30 ng·mL^-1, respectively. The correlation coefficient r > 0.999, the spiked recovery was 80%-120%. The detection limits were 30, 1 and 0.3 ng·mL^-1. Two detection methods did not detect potential sulfonate genotoxicity impurities in the above APIs. The established analytical methods are reliable and effective, which can provide reference for drug quality control and detection.

Background::Differentiated thyroid cancer (DTC) is commonly diagnosed in women of child-bearing age, but whether pregnancy influences the prognosis of DTC remains controversial. This study aimed to summarize existing evidence regarding the association of pregnancy with recurrence risk in patients previously treated for DTC.Methods::We searched PubMed, Embase, Web of Science, Cochrane, and Scopus based on the prespecified protocol registered at PROSPERO (CRD42022367896). After study selection, two researchers independently extracted data from the included studies. For quantitative data synthesis, we used random-effects meta-analysis models to pool the proportion of recurrence (for pregnant women only) and odds ratio (OR; comparing the risk of recurrence between the pregnancy group and the nonpregnancy group), respectively. Then we conducted subgroup analyses to explore whether risk of recurrence differed by response to therapy status or duration of follow-up time. We also assessed quality of the included studies.Results::A total of ten studies were included. The sample size ranged from 8 to 235, with participants’ age at pregnancy or delivery ranging from 28 to 35 years. The follow-up time varied from 0.1 to 36.0 years. The pooled proportion of recurrence in all pregnant patients was 0.13 (95% confidence intervals [CI]: 0.06-0.25; I2: 0.58). Among six included studies reporting response to therapy status before pregnancy, we observed a trend for increasingly higher risk of recurrence from excellent, indeterminate, and biochemically incomplete to structurally incomplete response to therapy ( Ptrend <0.05). The pooled risk of recurrence in the pregnancy group showed no evidence of a significant difference from that in the nonpregnancy group (OR: 0.75; 95% CI: 0.45-1.23; I2: 0). The difference in follow-up time (below/above five years) was not associated with either the proportion of recurrence in all pregnant patients ( P >0.05) or the OR of recurrence in studies with a comparison group ( P >0.05). Two included studies that focused on patients with distant metastasis also did not show a significant difference in disease recurrence between pregnancy and nonpregnancy groups (OR: 0.51 [95% CI: 0.14-1.87; I2: 59%]). Conclusion::In general, pregnancy appears to have a minimal association with the disease recurrence of DTC with initial treatment. Clinicians should pay more attention to progression of DTC among pregnant women with biochemical and/or structural persistence.Registration::PROSPERO, https://www.crd.york.ac.uk/PROSPERO/; No. CRD42022367896.

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.

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.

This study was aimed at understanding the detection rate,drug resistance characteristics,virulence characteris-tics,multi-locus sequence typing,and other molecular epidemic and pathogenic characteristics of Campylobacter jejuni and Campylobacter coli in children in Guangdong Province from 2020 to 2022.Anal swabs or stool samples of suspected infection cases in children from 2020 to 2022 were collected from two hospitals in Guangzhou,Guangdong Province.Campylobacter was isolated and cultured through the filtration method,and identified with a microbial mass spectrometry system;antibiotic resist-ance was analyzed with the agar dilution method;bacterial genome nucleic acids were extracted,and whole-genome sequencing was conducted;and drug resistance genes,virulence genes,multi-locus sequence typing,and phylogenetic analysis based on whole-genome single nucleotide polymorphisms were analyzed from whole-genome sequencing results.First,53 strains of Campy-lobacter were detected through continuous routine monitoring in this study,with a positive detection rate of 2.94％.Among them,Campylobacter jejuni accounted for 81.13％(43/53)and Campylobacter coli accounted for 18.87％(10/53).In addition,16 strains of Campylobacter were screened through multi-pathogen surveillance,including 11 strains of Campylobacter jejuni and 5 strains of Campylobacter coli.Drug resistance ex-periments and whole genome sequencing were conducted on 46 Campylobacter isolates,including 33 isolates of Campylobacter jejuni and 13 isolates of Campylobacter coli.The resistance rate of Campylobacter to erythromycin,a widely used clinical treatment,was21.73％(10/46);that to tetracycline was 80.43％(37/46);those to the quinolone antibiotics nalidixic acid and ciprofloxacin were 76.08％(35/46)and 71.73％(33/46)respectively;and that to chloramphenicol was lowest,at 2.17％(1/46).The drug resistance rate was generally higher for Campylobacter coli than Campylobacter jejuni,and the differences in the indicators of erythromycin,gentamicin,streptomycin,telithromycin,and clindamycin were statistically significant.A total of 30 isolates of multidrug-resistant Campylobacter were detected,including nine multidrug-resistant phenotypes.Whole-ge-nome sequence analysis indicated that 46 Campylobacter isolates carried antibiotic resistance genes for antibiotics such as quino-lones,tetracyclines,β-lactams,and aminoglycosides,and carried 128 virulence factor genes in five categories.All 46 isolates of Campylobacter were identified as 35 ST type through MLST typing,and phylogenetic analysis indicated no obvious dominant ST type.Campylobacter coli had more SNPs than Campylobacter jejuni.In conclusion,the positive detection rate of Campy-lobacter in Guangzhou City,Guangdong Province stabilized from 2020 to 2022,and the detection rate of Campylobacter jejuni was higher than that of Campylobacter coli.Campylobacter isolates were resistant to tetracyclines and quinolone,and showed a wide spectrum of multi-drug resistance,which was relatively severe among Campylobacter coli.Resistance genes and drug-resistant phenotypes were correlated and had predictive significance.The virulence genes of Campylobacter jejuni were more a-bundant than those of Campylobacter coli,possibly because of the higher detection rate and pathogenicity of Campylobacter jejuni.The phylogenetic tree showed clear branches with high genetic diversity and no clearly dominant clonal group.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

Objective To reveal the spatial distribution patterns of key pollutants in the Huaihe River Basin and quantify the risks and burdens of non-gastrointestinal cancers by the grade of pollution,providing targets and data support for enhanced management of water pollution in the Huaihe River Basin. Methods Surface water quality data of the Huaihe River Basin were obtained from the National Surface Water Environmental Quality Monitoring Network(2021).Incidence data of seven cancers were extracted from the 2019 Annual Report of the China Cancer Registry.Random forest and SHapley Additive exPlanations were employed to select key pollutants,and pollution was graded based on the spatial analysis of the Huaihe River Basin.The cancer risks and population attributable fractions were calculated under pollution grades. Results Five key pollutants linked to cancers were identified,including total nitrogen,total phosphorus,chemical oxygen demand,biochemical oxygen demand after 5 days,and arsenic.Pollution was graded into three levels regarding the combined effects of pollutants.Compared with the low pollution areas,high pollution areas showed increased risks of lung cancer(RR=1.26,95%CI:1.06-1.50),breast cancer(female)(RR=1.46,95%CI:1.21-1.77),pancreatic cancer(RR=1.46,95%CI:1.06-2.01),brain cancer(RR=1.44,95%CI:1.05-1.98),and gallbladder cancer(RR=1.60,95%CI:1.03-2.50).The grade of pollution contributed to more than 5% of cases for most cancers above. Conclusions The potential cancer risks and burdens attributed to surface water pollution cannot be overlooked.Addressing this challenge necessitates close collaboration of various stakeholders to strengthen policy development,enhance environmental governance,and implement public health interventions.
Humans ; China/epidemiology* ; Rivers/chemistry* ; Neoplasms/etiology* ; Water Quality ; Environmental Monitoring ; Water Pollutants, Chemical/analysis* ; Phosphorus/analysis* ; Spatial Analysis ; Nitrogen/analysis* ; Arsenic/analysis* ; Water Pollution/adverse effects* ; Female