[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 assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

Objective To analyze the efficacy of sintilizumab combined with paclitaxel(albumin-bound)and nedaplatin(TN chemotherapy regimen)in patients with advanced non-small cell lung cancer(NSCLC)and its effects on serum tumor markers and immune cell levels.Methods The patients were divided into control group and treatment group according to random number table method.In the control group,80 mg·m-2 nedaplatin and 260 mg·m-2 paclitaxel(albumin-bound type)were injected intravenally on the 1st day for 21 days.The etreatment group was given sindilizumab 200 mg intravenously on the basis of the control group,21 days a cycle for 4 cycles.The anti-tumor efficacy,tumor markers,lung function,immune cytokines and adverse drug reactions of the two groups were compared after 4 cycles of treatment,and the 1-year survival of the two groups was statistically analyzed.Results A total of 7 cases fell off during treatment.Finally,98 patients in the treatment group and 96 patients in the control group were included in the analysis.After treatment,the objective response rate(ORR)of treatment group and control group were 43.88％(43 cases/98 cases)and 29.17％(28 cases/96 cases);the disease control rate(DCR)were 77.55％(76 cases/98 cases)and 60.42％(58 cases/96 cases),the difference was statistically significant(all P＜0.05).After treatment,carbohydrate antigen 125(CA125)in treatment group and control group were(39.03±5.97)and(42.15±6.35)U·mL-1;squamous cell carcinoma antigen(SCCA)were(4.58±0.63)and(5.29±0.84)ng·mL-1;forced vital capacity(FVC)were(2.96±0.52)and(2.71±0.49)L;forced expiratory volume in the first second(FEV1)/FVC were(68.47±11.39)％and(64.92±10.43)％;Th1/Th2 were 5.01±0.63 and 5.36±0.74;Th17/Treg were 1.04±0.15 and 1.20±0.19;CD4+/CD8+were 1.36±0.19 and 1.23±0.17,respectively.The differences were statistically significant(all P＜0.05).The total incidence of adverse drug reactions in treatment group and control group were 25.51％(25 cases/98 cases)and 22.92％(22 cases/96 cases),respectively,the difference was not statistically significant(P＞0.05).There was no significant difference in 1-year overall survival curves between the two groups(P＞0.05).Conclusion Sindilizumab combined with TN chemotherapy regimen in the treatment of advanced NSCLC can enhance the anti-tumor efficacy,reduce the level of tumor markers,improve lung function and immune function,and has good safety.

Objective To compare the efficacy and safety of empagliflozin and linagliptin in the treatment of patients with type 2 diabetes mellitus(T2DM)with heart failure(HF).Methods Patients with T2DM and HF were randomly into control group and treatment group.Both groups were treated with individualized anti-HF and metformin-based hypoglycemic therapy.On this basis,the control group was given linagliptin orally(5 mg each time,once a day),while the treatment group was given oral administration of empagliflozin 10 mg every day.Patients in both groups were treated continuously for 6 months.The clinical efficacy and blood glucose indicators[fasting blood glucose(FBG),2 h postprandial blood glucose(2 h PBG),hemoglobin A1c(HbA1c)],cardiac molecular markers[N-terminal pro-brain natriuretic peptide(NT-proBNP),fibroblast growth factor 23(FGF23),copeptin(CPP)]and caridac function indicators[left ventricular end-diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF),left ventricular remodeling index(LVRI)]before and after treatment were compared,and the adverse drug reactions were recorded.Results There were 40 cases in treatment group and 40 cases in control group.After treatment,the total effective rates in treatment group and control group were 97.50％(39 cases/40 cases)and 80.00％(32 cases/40 cases),with no significant difference(P＜0.05).The FBG levels in treatment group and control group were(7.64±1.18)and(7.83±1.24)mmol·L-1;2 h PBG levels were(8.97±1.46)and(9.04±1.35)mmol·L-1;HbA1c levels were(7.58±1.27)％and(7.65±1.42)％,all with no significant difference(all P＞0.05).The NT-proBNP levels in treatment group and control group were(612.53±204.62)and(1 045.24±316.75)pg·mL-1;FGF23 levels were(362.74±62.61)and(493.27±74.64)μg·L-1;CPP levels were(12.58±3.43)and(16.87±4.36)pmol·L-1;LVEDD values were(51.19±2.36)and(53.35±2.24)mm;LVEF values were(52.69±3.38)％and(50.28±3.75)％;LVRI values were(2.62±0.29)and(2.96±0.33)kg·L-1,all with significant difference(all P＜0.05).The incidence rates of adverse reactions in treatment group and control group were 5.00％(2 cases/40 cases)and 10.00％(4 cases/40 cases),with no significant difference(P＞0.05).Conclusion Both empagliflozin and linagliptin can effectively reduce the blood glucose in patients with T2DM complicated with HF.Empagliflozin can better promote the improvement of cardiac function in patients without significantly increase the incidence of adverse drug reactions.

Objective To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons(PAHs)during critical brain development and explore their potential link with the intestinal microbiota. Methods Liquid chromatography-tandem mass spectrometry was used to determine ten hydroxyl metabolites of PAHs(OH-PAHs)in 36-month-old children.Subsequently,37 children were categorized into low-and high-exposure groups based on the sum of the ten OH-PAHs.Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify non-targeted metabolites in the urine samples.Furthermore,fecal flora abundance was assessed by 16S rRNA gene sequencing using Illumina MiSeq. Results The concentrations of 21 metabolites were significantly higher in the high exposure group than in the low exposure group(variable importance for projection>1,P<0.05).Most of these metabolites were positively correlated with the hydroxyl metabolites of naphthalene,fluorine,and phenanthrene(r=0.336-0.531).The identified differential metabolites primarily belonged to pathways associated with inflammation or proinflammatory states,including amino acid,lipid,and nucleotide metabolism.Additionally,these distinct metabolites were significantly associated with specific intestinal flora abundances(r=0.34-0.55),which were mainly involved in neurodevelopment. Conclusion Higher PAH exposure in young children affected metabolic homeostasis,particularly that of certain gut microbiota-derived metabolites.Further investigation is needed to explore the potential influence of PAHs on the gut microbiota and their possible association with neurodevelopmental outcomes.

AIM To investigate the clinical effects of Dense Fire-Needling combined with Shentong Zhuyu Decoction on patients with knee osteoarthritis of Wind-Phlegm Blocking Collateral Pattern.METHODS Sixty-two patients were randomly assigned into control group(31 cases)for 2-week intervention of Shentong Zhuyu Decoction,and observation group(31 cases)for 2-week intervention of both Dense Fire-Needling and Shentong Zhuyu Decoction.The changes in clinical effects,TCM syndrome scores,VAS score,Lysholm score,WOMAC score,serological indices(MMP-3,IL-6,TNF-α)and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed decreased TCM syndrome scores,VAS score,WOMAC score,serological indices(P＜0.05),and increased Lysholm score(P＜0.05),especially for the observation group(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients of Wind-Phlegm Blocking Collateral Pattern,Dense Fire-Needling combined with Shentong Zhuyu Decoction can safely and effectively relieve clinical symptoms and pain,improve knee joint functions,enhance clinical effects,and regulate body inflammatory factor levels.

The compound (E)-1-(4-(3-(5-chloro-6-oxo-3,6-dihydropyridin-1(2H)-yl)-3-oxo-propyl-1-ene-1-yl) phenyl)-3-(4-fluorophenyl) urea (C12), a novel derivative of piperlongumine previously synthesized by our research group, was investigated in this study to examine its effects on human non-small cell lung cancer cell line H1299 in vitro and elucidate its potential mechanism of action. The impact of C12 on the proliferation, migration, and invasion abilities of H1299 cells were assessed using methyl thiazolyl tetrazolium (MTT) assay, wound healing assay, cloning formation assay, and Transwell assay. Flow cytometry was employed to evaluate the influence of C12 on cell cycle progression, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), and apoptosis induction in H1299 cells. Western blot analysis was conducted to investigate the expression levels of p21, Cyclin B1, CDK1, Bax, Bcl-2, JNK, p-JNK, Erk1/2, p-Erk1/2, p38 and p-p38 proteins for exploring the anti-tumor mechanism underlying C12's actions. The results demonstrated that C12 exerted inhibitory effects on the proliferation, migration, and invasion capacities of H1299 cells in a time-dependent and concentration-dependent manner. Moreover, C12 induced G2/M phase arrest in the cell cycle, reduced MMP levels, elevated ROS production, and triggered apoptotic processes. Flow cytometry analysis revealed that C12 downregulated Cyclin B1 and CDK1 protein expressions, resulting in G2/M phase arrest. C12 also upregulated Bax/Bcl-2 ratio, promoting apoptosis. Furthermore, C12 activated MAPK signaling pathway by enhancing phosphorylation levels of JNK, Erk1/2, and p38 proteins. In conclusion, C12 significantly suppressed proliferation, migration, and invasion capabilities while inducing cell cycle arrest and apoptosis in H1299 cells. These effects may be attributed to activation of the MAPK signaling pathway.

Kawasaki disease (KD) is an acute systemic vasculitis that primarily affects children. If left untreated in the early stages of the disease, it can lead to coronary artery aneurysms or the formation of arterial fistulae, and in severe cases, myocardial infarction. The pathogenesis of KD is related to the infiltration of immune cells into the walls of the coronary arteries. Macrophages play a crucial role in the development of KD by participating in inflammatory responses and neovascularization. Vascular endothelial growth factor (VEGF) is upregulated in the serum and coronary arteries of patients with KD, promoting inflammation and neovascularization, thereby increasing the risk of aneurysms. Aspirin is one of the standard treatment methods for KD. It exerts anti-inflammatory and anti-thrombotic effects by inhibiting platelet aggregation and reducing inflammatory mediators, thus controlling the acute symptoms of the disease. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of Children′s Hospital of Nanjing Medical University. Single-cell nuclear transcriptome sequencing (snRNA-seq) can provide profound insights into the cellular and molecular landscape of KD. Through snRNA-seq analysis, it was found that aspirin may improve endothelial dysfunction by downregulating VEGF levels in coronary endothelial cells and inhibiting macrophage-mediated proangiogenic signals to endothelial cells, thereby preventing arterial stenosis or aneurysm formation.

Objective:To explore the clinical characteristics,molecular characteristics,treatment and prognosis of pediatric Philadelphia chromosome-like acute lymphoblastic leukemia(Ph-like ALL)with a therapeutic target.Methods:A total of 27 patients of Ph-like ALL with targeted drug target were initially diagnosed in Children's Hospital of Soochow University from December 2017 to June 2021.The data of age,gender,white blood cell(WBC)count at initial diagnosis,genetic characteristics,molecular biological changes,chemotherapy regimen,different targeted drugs were given,and minimal residual disease(MRD)on day 19,MRD on day 46,whether hematopoietic stem cell transplantation(HSCT)were retrospective analyed,and the clinical characteristics and treatment effect were summarized.Survival analysis was performed by Kaplan-Meier method.Results:The intensity of chemotherapy was adjusted according to the MRD level during induced remission therapy in 27 patients,10 patients were treated with targeted drugs during treatment,and 3 patients were bridged with HSCT,1 patient died and 2 patients survived.Among the 24 patients who did not receive HSCT,1 patient developed relapse,and achieved complete remission(CR)after treatment with chimeric antigen receptors T cells(CAR-T).The 3-year overall survival,3-year relapse-free survival and 3-year event-free survival rate of 27 patients were(95.5±4.4)％,(95.0±4.9)％and(90.7±6.3)％respectively.Conclusion:Risk stratification chemotherapy based on MRD monitoring can improve the prognosis of Ph-like ALL in children,combined with targeted drugs can achieve complete remission as soon as possible in children whose chemotherapy response is poor,and sequential CAR-T and HSCT can significantly improve the therapeutic effect of Ph-like ALL in children whose MRD is continuously positive during induced remission therapy.

Aim To investigate the effects of L-argi-nine on spontaneous contraction of rat colon and the relative mechanisms.Methods An organ bath system was use to measure the spontaneous contraction of both longitudinal smooth muscle strips(LMS)and circular muscle strips(CMS).Whole-cell voltage-clamp tech-niques were applied to observe the alterations in cur-rents of L-type voltage-dependent Ca2+channels(VD-CCs),and voltage-gated K+channel(Kv)in single smooth muscle cells(SMCs)from rat colon.Results L-Arginine(1 mmol·L-1)significantly enhanced the spontaneous contraction of both LMS and CMS.The excitatory response to L-arginine was remarkably attenuated by tetrodotoxin(1 mmol·L-1)and atro-pine(1 mmol·L-1),antagonist of muscarinic ACh receptor(mAChR).However,the inhibitor of nitric oxide(NO)synthesis L-NNA(1 mmol·L-1)failed to block the action of L-Arginine.Furthermore,whole-cell patch-clamp recordings showed that L-arginine ac-tivated VDCCs and inhibited Kv channels on SMCs.Conclusions L-Arginine exerts an excitatory effect on colonic motility in a nitric oxide(NO)-independent manner and the stimulatory action of L-arginine is part-ly mediated by mAChR.In addition,VDCCs and Kv channels are both involved in L-arginine-induced exci-tation.