[Objective] To evaluate the feasibility of a novel outpatient infusion model for blinatumomab in two acute lymphoblastic leukemia (ALL) patients, aiming to address challenges of poor treatment tolerance, high healthcare costs, and compromised quality of life, thereby providing clinical insights for broader adoption of this approach. [Methods] Two post-allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients undergoing blinatumomab maintenance therapy were selected to evaluate the efficacy of the outpatient infusion model. Patient selection criteria, nursing protocols, standardized workflows, and advancements in infusion practices were systematically analyzed combined with a review of global developments in this field. [Results] Both patients completed outpatient blinatumomab infusion without severe adverse events, demonstrating preliminary feasibility and safety of this model. The novel approach enhanced treatment convenience, reduced hospitalization costs, and improved quality of life. [Conclusion] Despite the limited sample size, this pilot study highlights the potential of outpatient blinatumomab administration as a viable alternative to traditional inpatient regimens.

The interaction between organelles is the focus of re-search in neural development.The contact site of endoplasmic reticulum and mitochondria is the focus of Parkinson's disease(PD)in recent years.The research shows that mitochondria,endoplasmic reticulum(ER),lysosome and other organelles play an important role in neurogenesis.Specifically,metabolic turnover,reactive oxygen species production,mitochondrial dy-namics,mitochondrial autophagy,mitochondria-mediated apop-tosis,and interactions between mitochondria and the ER all play a role in neurogenesis.In PD,abnormal ER-mitochondrial inter-action can affect mitochondrial calcium overload,mitochondrial fission and fusion imbalance,and lipid homeostasis disorder.Therefore,here we review the recent progress in the main regu-latory mechanisms of ER-mitochondrial interaction and address the effects of abnormal ER-mitochondrial interactions on PD.

Aim To explore the effects of sirolimus on the growth and development of motor,vascular,nerv-ous,and immune systems through zebrafish models.Methods After 3 hours of fertilization of zebrafish embryos,different concentrations of sirolimus were add-ed to the growth environment,and the growth and de-velopment of the embryos was recorded.Transgenic ze-brafish models labeled with blood vessels,nerves or im-mune cells were used to compare the drug effects on the growth and development of those systems.Results At the concentration of 0.5 μmol·L-1,the hatching rate and the body length(P＜0.01)were significantly smaller than those of the control group,and movement was also significantly slowed down.Meanwhile,the length of axons of the nervous system,the development of intersegmental vessels,and the growth of immune cells were significantly delayed by drug treatment.But when the concentration was below 0.1 μmol·L-1,there was no statistically difference between the control group and the sirolimus group.Conclusions When the concentration of sirolimus exceeds a certain level,it can significantly slow down the growth and development of movement,blood vessels,nervous system and im-mune system of zebrafish.Therefore,in clinical prac-tice,it is important to monitor the blood concentration of sirolimus in children on time.

Objective:To screen interleukin(IL)-1β secretion-related membrane transporters by macrophage experiment in vitro and conventional knockout mice.Methods:THP-1 cell line was differentiated to obtain human THP-1-derived macrophages,and the primary macrophages were obtained from human peripheral blood.FVB wild-type mice with the same sex and age were used as the controls of MRP1 knockout mice.The macrophages in abdominal cavity and bone marrow of mice were cultivated.The cells were treated with ABCC1/MRP1,ABCG2/BCRP,ABCB1/P-gp,OATP1B1,and MATE transporter inhibitors,then stimulated by lipopolysaccharide and adenosine triphosphate.The secretion level of IL-iβ was detected by ELISA,Western blot,and immunofluorescence.Results:After inhibiting ABCC1/MRP1 transporter,the secretion of IL-1β decreased significantly,while inhibition of the other 4 transporters had no effect.In animal experiment,the level of IL-1 β secreted by macrophages in bone marrow of MRP1 knockout mice was significantly lower than control group(P＜0.05).Conclusion:ABCC1/MRP1 transporter is a newly discovered IL-1β secretion pathway,which is expected to become a new target for solving clinical problems such as cytokine release syndrome.

Objective:To detect the pharmacokinetic(PK)parameters of coagulation factor Ⅷ(FⅧ)in adult patients with severe hemophilia A,identify the potential factors influencing FⅧ PK,and optimize the use of FⅧ in individual prophylaxis regimens.Methods:PK characteristics of FⅧ were studied in a total of 23 severe hemophilia A adults.The correlation of patients'characteristics including age,von Willebrand factor antigen(vWF:Ag),blood group,weight,body mass index(BMI)and FⅧ genotype,with FⅧ PK were evaluated.Individual prophylaxis regimens were given based on FⅧ PK parameters.Results:The mean terminal half-life(t1/2)of FⅧ was 20.6±9.3 h,ranged from 11.47 h to 30.12 h.The age(r=0.580)and vWF:Ag(r=0.814)were significantly positively correlated with t1/2 of FⅧ.The mean area under the plasma concentration curve(AUC)of FⅧ was 913±399(328-1 878)IU h/dl,and the AUC of FⅧ was positively correlated with age(r=0.557)and vWF:Ag(r=0.784).The mean residence time(MRT)of FⅧ was 24.7±12.4(13.2-62.2)h,and the MRT of FⅧ was positively correlated with age(r=0.664)and vWF:Ag(r=0.868).The mean in vivo recovery(IVR)of FⅧ was 2.59±0.888(1.5-4.29)IU/dl per IU/kg,the mean clearance(CL)of FⅧ was 3±1.58(0.97-7.18)ml/(kg·h),and there was no significant correlation of IVR and CL with age and vWF:Ag.According to the individual PK parameters,ultra low-dose,low-dose and moderate-dose FⅧ were applied to 15,6,2 adults patients with severe hemophilia A for prophylaxis,respectively.Conclusion:There are significant individual differences in the FⅧ half-life of adult patients with severe hemophilia A.The older the patient,the higher the vWF:Ag level,and the longer the FⅧ half-life.Individual administration is required based on the FⅧ PK parameters to optimize prophylaxis treatment.

In November 2023, the seventh National Nucleic Acid Vaccine Conference was held to deeply discuss the immune mechanism, safety risks, advantages, and disadvantages of nucleic acid vaccines, and review the safety and effectiveness of COVID-19 vaccines developed by nucleic acid vaccine technology. Some prospectives were formed in the meeting that in the post-pandemic era, nucleic acid vaccine technology will play a role in the following areas: dealing with pathogens that are difficult to be prevented by traditional vaccines, promoting the upgrading of traditional live attenuated vaccines, contributing to the development of multivalent and combined vaccines, and rapid response to emerging and re-emerging infectious diseases. These views point out the direction for the future development of nucleic acid vaccine technology.

Objective:To further improve the understanding of paroxysmal nocturnal hemoglobinuria (PNH), we retrospectively analyzed and summarized the clinical characteristics, treatment status, and survival status of patients with PNH in Zhejiang Province.Methods:This study included 289 patients with PNH who visited 20 hospitals in Zhejiang Province. Their clinical characteristics, comorbidity, laboratory test results, and medications were analyzed and summarized.Results:Among the 289 patients with PNH, 148 males and 141 females, with a median onset age of 45 (16-87) years and a peak onset age of 20-49 years (57.8% ). The median lactic dehydrogenase (LDH) level was 1 142 (604-1 925) U/L. Classified by type, 70.9% (166/234) were classical, 24.4% (57/234) were PNH/bone marrow failure (BMF), and 4.7% (11/234) were subclinical. The main clinical manifestations included fatigue or weakness (80.8%, 235/289), dizziness (73.4%, 212/289), darkened urine color (66.2%, 179/272), and jaundice (46.2%, 126/270). Common comorbidities were hemoglobinuria (58.7% ), renal dysfunction (17.6% ), and thrombosis (15.0% ). Moreover, 82.3% of the patients received glucocorticoid therapy, 70.9% required blood transfusion, 30.7% used immunosuppressive agents, 13.8% received anticoagulant therapy, and 6.3% received allogeneic hematopoietic stem cell transplantation. The 10-year overall survival (OS) rate was 84.4% (95% CI 78.0% -91.3% ) . Conclusion:Patients with PNH are more common in young and middle-aged people, with a similar incidence rate between men and women. Common clinical manifestations include fatigue, hemoglobinuria, jaundice, renal dysfunction, and recurrent thrombosis. The 10-year OS of this group is similar to reports from other centers 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.

Objective To analyze the antimicrobial susceptibility,molecular types,serotypes,virulence factors and resistance mechanisms of Streptococcus agalactiae(S.agalactiae)isolated from pregnant women with ad-vanced maternal age in Tangshan City,and provide basic data for the treatment,prevention and control of S.aga-lactiae infection.Methods 42 strains of S.agalactiae isolated from pregnant women with advanced maternal age in North China University of Science and Technology Affiliated Hospital as well as Tangshan Maternal and Child Health Hospital were collected.Detection of antimicrobial susceptibility and whole genome sequencing of 13 antimi-crobial agents were performed.Results The percentage of tetracycline,erythromycin,levofloxacin,and chloram-phenicol concurrently resistant strains was 7.1％,35.7％of the strains presented multidrug resistance to erythro-mycin,clindamycin,and levofloxacin.The carriage rates of resistance genes ermB and tetM were 66.7％and 47.6％,respectively.29 strains(69.0％)exhibited mutations in both gyrA and parC fluoroquinolone resistance determi-nants.42 strains of S.agalactiae belonged to 4 serotypes,namely ⅠB(35.7％),Ⅲ(33.3％),Ⅴ(26.2％),andⅠA(4.8％);and 11 sequence types(STs),with the highest proportion being ST10(35.7％)and ST19(31.0％);as well as 6 clonal complexes(CCs),among which CC19(42.9％)and CC12(35.7％)had the highest proportion.All S.agalactiae carried virulence factor-encoding genes of cfb,cylE,and pavA.Conclusion The molecular types and serotypes of S.agalactiae carried by pregnant women with advanced maternal age in Tangshan City pre-sent polymorphism,with obvious multidrug resistance,and carry multiple types of drug resistance genes and viru-lence genes.

Objective To observe the value of shear wave elastography(SWE),superb microvascular imaging(SMI)and their combination with conventional ultrasound for diagnosing cervical cancer.Methods Data of 178 patients with cervical lesion confirmed by pathology were retrospectively analyzed.The patients were divided into malignant group(n=32)and benign group(n=146),and those in benign group were further divided into low-grade or high-grade cervical intraepithelial neoplasia subgroups,cervical leiomyosarcoma subgroup,cervical polyps subgroup and cervicitis subgroup.The manifestations of lesion on conventional ultrasound,SWE and SMI were observed,and the mean value of Young's modulus(Emean)and SMI flow index(Ratio)were collected.The optimal cut-off value of SWE Emean and SMI Ratio were obtained with receiver operating characteristic(ROC)curves,and the classification of benign or malignant lesions were predicted.The consistency of predictive results and pathology results were assessed with the Kappa test.The diagnostic efficacies of conventional ultrasound,SWE and SMI alone and their combination were compared.Results The age of patients in malignant group was higher than that in benign group(P＜0.05).SWE Emean and SMI Ratio were both higher in malignant group than those in each benign subgroup(all P＜0.05).Taken 44.35 kPa and 3.95％ as the best cut-off values,the consistency of SWE Emean classification results and pathological results was good(Kappa=0.818),while of SMI Ratio was moderate(Kappa=0.453).The efficacy of conventional ultrasound,SWE and SMI alone for classifying benign and malignant cervical lesions(AUC=0.845,0.914,0.892)were all higher than that of their combination(AUC=0.806,all adjusted P＜0.05).The sensitivity of SWE and SMI for diagnosing cervical cancer was 90.60％ and 93.78％ respectively,with specificity of 95.20％ and 72.60％,respectively.Conclusion SWE hag higher efficacy for diagnosing cervical cancer,while SMI had better sensitivity but lower specificity.Combination of conventional ultrasound,SWE and SWI did not increase the efficacy of ultrasound for diagnosing cervical cancer.