[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 m⁶A-methylated RNA and chromatin modification remains largely unknown. We found that targeted inhibition of bromodomain-containing protein 4 (BRD4) by siRNA or its inhibitor (JQ1) significantly decreases mRNA m⁶A levels and suppresses the malignancy of breast cancer (BC) cells via increased expression of demethylase AlkB homolog 5 (ALKBH5). Mechanistically, inhibition of BRD4 increases the mRNA stability of ALKBH5 via enhanced binding between its 3' untranslated regions (3'UTRs) with RNA-binding protein RALY. Further, BRD4 serves as a scaffold for ubiquitin enzymes tripartite motif containing-21 (TRIM21) and ALKBH5, resulting in the ubiquitination and degradation of ALKBH5 protein. JQ1-increased ALKBH5 then demethylates mRNA of extra spindle pole bodies like 1 (ESPL1) and reduces binding between ESPL1 mRNA and m⁶A reader insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3), leading to decay of ESPL1 mRNA. Animal and clinical studies confirm a critical role of BRD4/ALKBH5/ESPL1 pathway in BC progression. Further, our study sheds light on the crosstalks between histone modification and RNA methylation.

In analytical techniques such as ion mobility spectrometry(IMS)and mass spectrometry(MS),the ionization efficiency of target analytes is primarily constrained by the type of ionization source and factors such as the species and number density of the reactant ions.Systematic investigation into the reactivity differences of various reactant ions under varying conditions can not only significantly enhance the detection sensitivity of target compound product ions but also provide a theoretical foundation for establishing efficient detection methods based on ion-molecule reaction mechanisms.In this study,the pressure of a pressure-tunable photoionization tandem ion mobility spectrometry(PI-tandem-IMS)was reduced from ambient pressure(100 kPa)to low pressure(20 kPa)to systematically examine the reactivity differences between two negative reactant ions,CO3-and CO4-,and methyl salicylate(MeSA)under varying pressures.When the pressure decreased,the increased relative signal intensity of CO4-significantly influenced the detection sensitivity of the characteristic product ion[MeSA·O2]-.Based on differences in ion mobility(k0),the delay time for the opening of TPG2 was adjusted to selectively inject CO-3 and CO-4 in the drift region 2.Independent characterization of the reactivity of these reactant ions with MeSA in the reaction region confirmed that CO4-exhibited superior reactivity toward MeSA.The theoretical model revealed an Arrhenius plot for the ion-molecule reaction between CO4-and MeSA,showing a positive correlation between the reaction rate coefficient(k)and temperature,the activation energy Ea was 62.45 kJ/mol.Furthermore,controlling parameters such as pressure or temperature significantly influenced the progression of this ion-molecule reaction,demonstrating the technical advantages of PI-tandem-IMS in mechanistic studies and regulation of ion-molecule reactions.

The resolving power and sensitivity are critical for on-site detection of hazardous chemicals using stand-alone ion mobility spectrometry(IMS).However,improving the sensitivity and resolving power of IMS has long been a prominent research hot spot.In the commonly used IMS based on the Bradbury-Nielsen gate(BNG),the gating voltage difference(GVD)applied between the two sets of grid wires affects the electric field distribution in the ionization region and the drift region.This,in turn,influences the spatial distribution and temporal width of the injected ion swarm,and has an impact on the ion mobility discrimination,sensitivity,and resolving power of the instrument.This study showed that increasing the GVD could induce an ion converging effect,boosting the ion number density in front of the BNG by nearly 300％.To simultaneously utilize temporal compression and ion converging effects,a novel BNG controlling mode was proposed by adding a chopping state to the conventional controlling mode.This chopping state reduced the mobility discrimination effects between ions with mobility differences up to about 0.90 cm2/(V·s)to 1/22 of their original value.When analyzing hazardous chemical mixtures using the novel BNG controlling mode,compared with conventional mode,the signal intensity of low-mobility methyl salicylate ions(MS·O2)-increased by 18-fold while the resolving power maintained around 100,and the detection limit for MS was improved from 3.75 μg/L to 97 ng/L.This novel BNG controlling mode only added a potential wave to the low voltage wires,with no requirement of changing the structure of the drift tube,and was easy to apply to existing commercial instruments.

A QuEChERS cleanup-ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method was established for simultaneous determination of traditional and emerging 71 kinds of per-and polyfluoroalkyl substances(PFAS)in Chinese herbal medicine Eckloniae Thallus.The extraction solvent employed here was 0.2%formic acid-acetonitrile with sodium chloride-anhydrous sodium sulfate(3:1,m/m)as salting-out agent,and the purification was carried out using graphitized carbon black and octadecyl-bonded silica as adsorbents.The sample separation was carried out on a Horizon C18 chromatographic column(150 mm×2.1 mm,1.6 μm)by gradient elution with 2.5 mmol/L ammonium acetate aqueous solution(containing 2.5 mmol/L acetic acid)and acetonitrile as the mobile phases.The flow rate was set at 0.4 mL/min,with an injection volume of 5 μL.The chromatographic separation of each target compound and internal standard substance could be achieved within 15 min.An electrospray ion source was utilized for simultaneous scanning of positive and negative ions under the scheduled multiple reaction monitoring(sMRM)mode,and the internal standard method was used for quantitative analysis.The results of method validations showed that the 71 kinds of PFAS had good linearity,with a correlation coefficient(r)greater than 0.997,spiked recoveries of 76.2%?122.0%and relative standard deviations(RSDs)of 5.5%?14.8%.The limits of detection were in the range of 0.3-60 ng/kg and the limits of quantification were in the range of 0.8-199 ng/kg.The developed method was used for detection of PFAS in 14 batches of Eckloniae Thallus samples,and a total of 19 kinds of PFAS were detected.The findings indicated that PFAS residues were commonly present in Eckloniae Thallus,with perfluorocarboxylic acids(PFCAs)exhibiting the highest concentrations.The method was simple,robust and efficient in preparation,sensitive in detection with high throughput,and suitable for monitoring residual PFAS compounds,including both ionic and neutral in food-medicine homology samples such as Eckloniae Thallus.

Objective To explore the application and effectiveness of the apprenticeship education model in Chinese herbal medicine teaching at Western medical college.Methods By comparing classic lecture-based teaching with a combined approach integrating apprenticeship education,the study assesses the impact on student learning outcomes.Participants included students from the 2018 cohort of the eight-year clinical medicine program and the 2022 cohort of the"4+4"pilot program at Peking Union Medical College,who received classic teaching methods and apprenticeship case-based teaching methods,respectively.Upon course completion,students completed a 14-item multiple-choice questionnaire covering essential theory of Chinese medicine,as well as specific categories such as qi-regulating,blood-activating herbs,among others.Results The overall accuracy rate in the apprenticeship case-based teaching group was significantly higher than that in the classic teaching group(P＜0.01).Conclusions The apprenticeship education model of Traditional Chinese Medicine has a positive effect on teaching of Chinese herbal medicine at West-ern medical college and warrants further promotion and application.

Objective To analyze the efficacy and safety of ustekinumab(UST)in patients with moderate-to-severe Crohn's disease(CD),and to identify factors influencing clinical outcomes.Methods Data were retrospectively collected from patients with moderate-to-severe CD treated with UST in the First Affiliated Hospital of Zhejiang Chinese Medical University and Hangzhou Hospital of Traditional Chinese Medicine between November 2020 and May 2023.Patients were categorized into first-line(not treated with biologic agents,n=68)and second-line(treated with biologic agents,n=66)treatment groups based on prior use of biologic agents.Baseline characteristics,including age,sex,smoking status,disease duration,age at diagnosis,lesion site,disease behavior,perianal disease,history of intestinal surgery,and CD-related drug use,were compared between the two groups.Crohn's disease activity indices(CDAI)were recorded at baseline,week 14,and week 52 to assess the clinical efficacy at weeks 14 and 52.Endoscopic evaluations were performed at baseline and week 52 to evaluate endoscopic efficacy at week 52.The 52-week drug persistence rate and safety profile were also analyzed.Influencing factors related to clinical outcomes were evaluated using univariate and multivariate logistic regression.Results A total of 134 patients with moderate-to-severe CD treated with UST were included.At week 14,clinical response and remission rates were 75.4%(101/134)and 33.6%(45/134),respectively,with no significant difference in clinical efficacy between first-line and second-line groups(clinical response rate:77.9%vs.72.7%,P=0.484;clinical remission rate:38.2%vs.28.8%,P=0.247).At week 52,clinical response and remission rates were 79.9%(107/134)and 56.0%(75/134),respectively.The rates of endoscopic response and remission were 70.9%(95/134)and 38.8%(52/134),respectively.There were no significant differences in clinical efficacy(clinical response rate:80.9%vs.78.8%,P=0.763;clinical remission rate:60.3%vs.51.5%,P=0.306)and endoscopic efficacy(endoscopic response rate:76.5%vs.65.2%,P=0.149;endoscopic remission rate:42.6%vs.34.8%,P=0.354)between the two groups.The 52-week drug persistence rate was 85.8%(115/134),and the adverse reaction rate was 4.5%(6/134).Compared with first-line treatment group,biologic-experienced patients had a significantly higher proportion of dose-optimized therapy in second-line treatment group(45.5%vs.22.1%,P=0.004).Multivariate logistic regression showed that the 14-week clinical response was a significant predictor of 52-week clinical remission,while perianal disease and intestinal surgery history were significant factors associated with treatment failure(P<0.05).Conclusions UST demonstrates significant efficacy in improving clinical and endoscopic outcomes for moderate-to-severe CD patients,with a favorable safety profile.Clinical response at 14 weeks is strongly predictive of clinical remission at 52 weeks.Patients with perianal disease or a history of intestinal surgery were at higher risk of treatment failure.

Objective: To investigate the mechanism of Anemoside B4 (AB4) on glutamine metabolism in oral li- chen planus (OLP) epithelial cells via the nitric oxide synthase 3 (NOS3)-dihydrofolate reductase (DHFR) axis . Methods: Bioinformatics analysis was performed to identify the intersection of molecular targets of OLP , AB4 , and genes related to glutamine metabolism . A lipopolysaccharide ( LPS)-induced HOK-16B model of OLP was estab- lished . HOK-16B were divided into Ctrl group , OLP group , AB4 group , OLP + oe-NOS3 group , OLP + sh-NOS3 group , OLP + sh-NOS3 + oe-DHFR group , and OLP + sh-NOS3 + AB4 group . Cell proliferation was detected by cell counting kit-8 (CCK-8) ; cell apoptosis was detected by TdT-mediated dUTP Nick-End Labeling ( TUNEL) ; inflammatory factors iInterleukin (IL)-1β, tumor necrosis factors-α ( TNF-α) concentrations in cell supernatants were measured using enzyme-linked immunosorbent assay (ELISA) kits; glutamine uptake and glutamate produc- tion were determined using kits; and the protein expression of alanine-serine-cysteine transporter2 ( ASCT2) and glutamine synthase (GLS) was assessed by Western blot. Results: Bioinformatics analysis of molecular targets of OLP , AB4 , and genes related to glutamine metabolism revealed three intersection targets : NFE2L2 , NOS1 , and NOS3 . Compared with the Ctrl group , the OLP group exhibited decreased HOK-16B cell viability (P < 0. 001) , increased apoptosis rate (P < 0. 01) , upregulated concentrations of IL-1βand TNF-α(P < 0. 001) , elevated glu- tamine uptake and glutamate production (P < 0. 01) , and enhanced expression of ASCPT2 and GLS proteins (P < 0. 001) . Compared with the OLP group , the AB4 group showed improved cell viability (P < 0. 05) , reduced apop- tosis rate and release of IL-1βand TNF-α(P < 0. 05) , decreased glutamine uptake and glutamate production (P < 0. 05) , and downregulated expression of ASCPT2 and GLS proteins ( P < 0. 001) . Compared with the OLP group , the OLP + oe-NOS3 group had increased HOK-16B cell viability (P < 0. 01) , reduced apoptosis rate (P < 0. 05) , decreased concentrations of IL-1βand TNF-α(P < 0. 05) , lowered glutamine uptake and glutamate pro- duction (P < 0. 05) , and weakened expression of ASCPT2 and GLS proteins (P < 0. 01) ; whereas the OLP + sh- NOS3 group had decreased HOK-16B cell viability ( P < 0. 05) , increased apoptosis rate ( P < 0. 05) , elevated concentrations of IL-1βand TNF-α ( P < 0. 01 ) , increased glutamine uptake and glutamate production ( P < 0. 05) , and enhanced expression of ASCPT2 and GLS proteins (P < 0. 001) . Compared with the OLP + sh-NOS3 group , both the OLP + sh-NOS3 + oe-DHFR group and the OLP + sh-NOS3 + AB4 group showed increased HOK- 16B cell viability (P < 0. 001) , reduced apoptosis rate (P < 0. 05) , decreased concentrations of IL-1βand TNF-α (P < 0. 01) , lowered glutamine uptake and glutamate production ( P < 0. 05) , and weakened expression of AS- CPT2 and GLS proteins ( P < 0. 05) . Conclusion AB4 inhibits the progression of OLP by mediating glutamine metabolism via the regulation of the NOS3-DHFR axis .

Nucleic acid-based molecular diagnostic methods are considered the gold standard for detecting infectious pathogens.However,when applied to portable or on-site rapid diagnostics,they still face various limitations and challenges,such as poor specificity,cumbersome operation,and portability difficulties.The CRISPR(Clustered regularly interspaced short palindromic repeats)/CRISPR-associated protein(Cas)-fluorescence detection method holds the potential to significantly enhance the specificity and signal-to-noise ratio of nucleic acid detection.In this study,we developed a portable grayscale reader detection system based on loop-mediated isothermal amplification(LAMP)-CRISPR/Cas.On one hand,in the presence of CRISPR RNA(crRNA),the CRISPR/Cas12a system was employed to achieve precise fluorescent detection of self-designed LAMP amplification reactions for influenza A and influenza B viruses.This further validated the high selectivity and versatility of the CRISPR/Cas system.On the other hand,the accompanying independently developed portable grayscale reader allowed for low-cost collection of fluorescence signals and high-reliability visual interpretation.At the end of the detection process,it directly provided positive or negative results.Practical sample analyses using this detection system have verified its reliability and utility,demonstrating that this system can achieve highly sensitive and highly specific portable analysis of influenza viruses.

The apprenticeship education of Traditional Chinese medicine(TCM)is an important pathway for the cultivation of talents in TCM education.The combination of institutional education and apprenticeship education is considered to be the most suitable educational model that aligns with the inherent characteristics of TCM education.The current status of TCM education in western medical institutions and the main challenges include the difficulty in transitioning between western and Chinese medical reasoning and limited clinical internship hours for TCM.The strengths and features of TCM apprenticeship education lie in cultural heritage,classical teachings,mentorship,practice orientation and personalized education.Therefore,integration of TCM apprenticeship education and clinical internships for western medical students represents a new educational model for medical undergraduates.