OBJECTIVE To investigate the effect of plasma trough concentration of venetoclax and its influencing factors in patients with acute myeloid leukemia （AML）. METHODS After 5 days of venetoclax administration， venous blood samples were collected from AML patients before the next dose. Plasma trough concentrations of venetoclax were determined using high-performance liquid chromatography-tandem mass spectrometry. Spearman correlation was used to assess the correlations between venetoclax plasma trough concentration and various parameters （including patients’ general information， venetoclax-related indicators， liver function indicators， kidney function indicators， and blood routine indicators）. Multiple linear regression analysis was performed to identify independent factors influencing plasma trough concentration of venetoclax. Using efficacy as dependent variable [complete remission （CR）+partial remission （PR） vs. no remission （NR）]， univariate and multivariate binary Logistic regression analyses were conducted to identify factors affecting efficacy. The receiver operating characteristic （ROC） curve was used to evaluate the predictive value of venetoclax plasma trough concentration for clinical efficacy （assessed as CR）. RESULTS A total of 172 venetoclax plasma trough concentration measurements from 101 patients were included in this study. The median plasma trough concentration of venetoclax was 2.38 （1.18， 3.85） μg/mL； the median sampling time for plasma trough concentration of venetoclax was 10 （7， 15） d； the duration of venetoclax use was （34±12） d. Multiple linear regression analysis showed that alkaline phosphatase （ B ＝14.65， 95%CI： 5.35-23.95， P ＝0.002）， total bilirubin （ B ＝－101.71， 95%CI： －197.16 to －6.25， P ＝0.037）， and white blood cell count （ B ＝－106.84， 95%CI： －187.61 to －26.07， P ＝0.010） were independent factors influencing plasma trough concentration of venetoclax. Due to patient attrition during treatment， 114 venetoclax plasma trough concentration measurements from 69 patients were included for efficacy evaluation. The results showed that 46 patients （66.7%） achieved CR， 11 patients （15.9%） achieved PR， and 12 patients （17.4%） were NR. Multivariate binary Logistic regression analysis showed that age， hemoglobin， venetoclax plasma trough concentration， hematocrit， and mean corpuscular hemoglobin were independent factors affecting patient efficacy （ P ＜0.05）. ROC curve analysis showed that the cut-off value of plasma trough concentration of venetoclax for predicting patient efficacy （assessed as CR） was 1.68 μg/mL （AUC＝0.66， 95%CI： 0.54-0.78， P ＝0.014）. CONCLUSIONS There is considerable inter-individual variability in plasma trough concentration of venetoclax among AML patients. Plasma trough concentration of venetoclax is significantly correlated with alkaline phosphatase， total bilirubin， and white blood cell count. Plasma trough concentration of venetoclax is an independent factor affecting patient’s efficacy， and when the cut-off value for predicting CR is above 1.68 μg/mL， better effects may be achieved.

OBJECTIVE To improve the research capacity and research enthusiasm of dispensing pharmacists in pharmacy intravenous admixture services （PIVAS）， facilitate their career development， and further promote the sustainable development of hospital pharmacy disciplines. METHODS A full-chain pharmacy practice research path covering topic orientation， topic evaluation， and implementation was explored and constructed for PIVAS. Multiple approaches including framework condensation for topic selection， department empowerment and improved incentive mechanisms were adopted to systematically boost the research competence and enthusiasm of PIVAS dispensing pharmacists. Four dimensions of indicators， including PIVAS research output， operational level， career development of staff and external influence， were compared between the pre-implementation period （2020- 2022） and post-implementation period （2023-2025） to evaluate the implementation effect of the path. RESULTS After the application of the PIVAS pharmacy practice research path， the number of published papers and comprehensive quality score of papers increased by 150.00% and 161.90% respectively compared with those before implementation. The number of approved research projects and comprehensive quality score of projects rose by 166.67% and 225.00%， and the number of authorized patents increased by 100.00%. The monthly number of external errors decreased from （0.42±0.18） pieces/month pre-implementation to （0.28±0.23） pieces/month post-implementation （P＞0.05）. Dispensing efficiency was elevated from （121.83±2.48） bags/（hour· person） to （139.00±3.46） bags/（hour·person） （P＜0.05）. The research participation rate of PIVAS dispensing pharmacists grew from 15.00% to 50.00%， and the overall satisfaction rate of staff increased from 55.00% to 85.00% （P＜0.05）. Within the 3 years after path implementation， our hospital PIVAS received a total of 22 trainees from external medical institutions， and the number of external institutional visits increased by 374.07% versus the pre-implementation stage. CONCLUSIONS The constructed pharmacy practice research path for PIVAS can significantly improve PIVAS research output， operational efficiency and external influence， and effectively promote the career growth of dispensing pharmacists working in PIVAS.

Iron overload is strongly associated with heart disease. Ferroptosis is a new form of regulated cell death indicated in cardiac ischemia-reperfusion (I/R) injury. However, the specific molecular mechanism of myocardial injury caused by iron overload in the heart is still unclear, and the involvement of ferroptosis in iron overload-induced myocardial injury is not fully understood. In this study, we observed that ferroptosis participated in developing of iron overload and I/R-induced cardiomyopathy. Mechanistically, we discovered that Parkin inhibited iron overload-induced ferroptosis in cardiomyocytes by promoting the ubiquitination of long-chain acyl-CoA synthetase 4 (ACSL4), a crucial protein involved in ferroptosis-related lipid metabolism pathways. Additionally, we identified p53 as a transcription factor that transcriptionally suppressed Parkin expression in iron-overloaded cardiomyocytes, thereby regulating iron overload-induced ferroptosis. In animal studies, cardiac-specific Parkin knockout mice (Myh6-CreER ^T2 /Parkin ^fl/fl ) fed a high-iron diet presented more severe myocardial damage, and the high iron levels exacerbated myocardial I/R injury. However, the ferroptosis inhibitor Fer-1 significantly suppressed iron overload-induced ferroptosis and myocardial I/R injury. Moreover, Parkin effectively protected against impaired mitochondrial function and prevented iron overload-induced mitochondrial lipid peroxidation. These findings unveil a novel regulatory pathway involving p53-Parkin-ACSL4 in heart disease by inhibiting of ferroptosis.

ObjectivesTo investigate the molecular epidemiological characteristics of HIV-1 infection among men who had sex with men (MSM) in Taizhou City, Zhejiang Province, and to provide a scientific reference for acquired immune deficiency syndrome prevention and control efforts. MethodsThe research subjects were all newly reported MSM population in Taizhou City from 2020 to 2023. Blood samples without antiviral therapy were collected. The HIV-1 pol gene was amplified and sequenced, and the sequences were submitted to the Stanford University drug resistance database to identify the mutation sites and drug resistance. MEGA 11.0 software was used to analyze the nucleic acid sequences, construct phylogenetic tree, and calculate genetic distance of gene sequences. The molecular transmission network diagram of HIV-1 was constructed using Cytoscape_v3.10.1, and the influencing factors of network entry were analyzed by logistic regression. ResultsA total of 363 newly reported HIV-infected MSM patients were included, with a median age [M (P₂₅, P₇₅)] of 34 (26,47) years old. The majority had an educational level of junior high school or below (55.65%). A total of eight subtypes were found, mainly CRF07_BC and CRF01_AE. The primary drug resistance rate was 10.47% (38/363). The optimal molecular network gene distance was 0.019, with a network access rate of 42.70% (155/363), and a total of 47 molecular clusters were formed. Multivariate logistic analyses showed that compared with the CRF01_AE subtype, the clustering risk of CRF07_BC subtype was higher (OR=1.916, 95%CI: 1.191‒3.109), cases with drug resistance had a higher risk of cluster formation than those without drug resistance (OR=2.011, 95%CI: 1.006‒4.080), and recent infected patients had a lower risk of entering the largest molecular cluster than long-term infected patients (OR=0.376, 95%CI: 0.137‒0.928). ConclusionThe newly diagnosed infections among the MSM population are active in Taizhou City, Zhejiang Province, with a high level of primary drug resistance. Individuals carrying drug-resistant strains are more likely to cluster. Drug resistance monitoring should be strengthened to prevent further spread of drug-resistant strains in the network.

To promote the standardization and normalization of perioperative care for follicular unit extraction(FUE) hair transplantation, ensure treatment efficacy, and align with advancements in the specialty, the Nursing Branch of the Chinese Association of Plastic and Aesthetics organized a panel of domestic experts. By integrating evidence-based medicine with clinical practice experience, and following thorough discussions, these experts developed the Clinical Practice Expert Consensus on Perioperative Nursing Care for Follicular Unit Extraction (2025). This consensus provides a comprehensive overview of hair transplantation, covering preoperative preparation, surgical procedures, intraoperative coordination, postoperative management, and complication prevention and treatment. It serves as a key reference and guide for implementing standardized perioperative nursing care in FUE hair transplantation.

Objective To investigate the value of contrast-enhanced ultrasound(CEUS)liver imaging reporting and data system version 2017(LI-RADS v2017)in the differential diagnosis between hepatocellular carcinoma(HCC)and other hepatic malignancies(OM)less than or equal to 3 cm.Methods The clinical and imaging data of 163 liver lesions less than or equal to 3 cm in 126 patients with pathologically-confirmed liver malignancy were retrospectively analyzed.The patient underwent CEUS from Jan.2018 to Jun.2022 in our hospital,including 133 with HCC and 30 with OM.Nodules were classified based on the CEUS features according to the CEUS LI-RADS v2017.The evaluation of CEUS characteristics and CEUS LI-RADS v2017 in differential diagnosis of HCC and OM were calculated based on pathological findings.Results There were significant differences in the characteristics of arterial phase enhancement,timing of washout onset and washout degree between the HCC group and the OM group(all P＜0.001).The HCC group was mainly LR-3(20 lesions,15.04%),LR-4(25 lesions,18.80%)and LR-5(82 lesions,61.65%),and the OM group was mainly LR-M(28 lesions,93.33%).The specificity and positive predictive value of late washout for HCC were 93.33%(28/30)and 98.06%(101/103),respectively;and the sensitivity of early washout for OM was 93.33%(28/30).With LR-5 as the criterion to diagnose HCC,the sensitivity was 61.65%(82/133),the specificity was 93.33%(28/30),and the positive predictive value was 97.62%(82/84);with LR-4/5 as the criterion to diagnose HCC,the sensitivity was 80.45%(107/133),the specificity was 93.33%(28/30),and the positive predictive value was 98.17%(107/109),with the sensitivity of LR-4/5 being significantly higher than those of LR-5(P=0.001).With LR-M as the criterion to diagnose OM,the sensitivity was 93.33%(28/30)and the specificity was 95.49%(127/133).Conclusion The CEUS LI-RADS v2017 can effectively distinguish HCC from OM less than or equal to 3 cm.LR-5 has a low sensitivity for HCC,while LR-4/5 can improve the sensitivity for HCC.

Objective To assess the therapeutic efficacy of low-intensity focused ultrasound(LIFU)on knee arthrofibrosis in rats and explore its underlying mechanisms.Methods Fifteen male SD rats(8 weeks old,weighing 250～300 g)were randomly divided into a blank control group,a model group,and an ultrasound treatment group,with 5 animals in each group.Rat model of knee joint stiffness was established in the model and ultrasound treatment group.The rats in the ultrasound group received LIFU intervention(frequency:1 MHz,power:1.5 W,20 min per session,5 times/week)for 4 weeks.The knee ranges of motion(ROM,flexion and extension)were measured in all 3 groups at 0,14 and 28 d after intervention.Histological analysis was conducted for the morphological changes in the posterior capsular area of the knee.After the synovial fibroblasts were primary isolated from rat knee joints,the cells were divided into blank control,LIFU,TGF-β(10 ng/mL),and TGF-β+LIFU groups.Changes in fibrosis-related indicators and the TGF-β/Smad signaling pathway were assessed in each group.Results In the animal experiments,LIFU intervention for 14 d resulted in significantly improved flexion-extension ROM in knee joints when compared with the rats in the model group(P<0.05),and the improvement was more obvious at 28 d after intervention(P<0.05).After 28 d of LIFU intervention,the fibrosis of the posterior capsule of the knee joint was notably improved in the ultrasound group than the model group,and the expression levels of fibrosis-related indicators(α-SMA,TGF-β)were decreased(P<0.05).In the cellular experiments,the TGF-β group exhibited remarkable up-regulation of fibrosis-related molecules(α-SMA,COL1A1,COL3A1)at both protein and mRNA levels(P<0.05),and activation of the TGF-β/Smad signaling pathway when compared to the blank control group.While LIFU intervention inhibited the expression of TGF-β-induced upregulation of fibrotic indicators(α-SMA,COL1A1,COL3A1)and the activation of TGF-β/Smad signaling pathway(P<0.05).Conclusion LIFU can effectively improve knee arthrofibrosis in rats,which potentially through the inhibition of fibroblast activation and modulation of the TGF-β/Smad signaling pathway.

Objective To investigate the effects and mechanisms of anti-IL-13 monoclonal antibody in alle-viating goblet cell metaplasia and hyperplasia in the treatment of acute subglottic laryngitis.Methods Periph-eral blood samples of children with acute subglottic laryngitis were collected and the children were divided into Mild group and Moderate-Severe group.Normal bronchial epithelial cells(NHBE cells)were cultured in vitro at the gas/liquid interface(ALI).Cell experiment were grouped as follows:Group-1(NHBE cell maintenance cultured group),Group-2(ciliated cell differentiation induction group),Group-3(IL-13 treatment group),and Group-4(IL-13+anti-IL-13 monoclonal antibody treatment group).The levels of inflammatory cytokines IL-10,IFN-γ and IL-13 in peripheral blood or cell culture supernatant were measured by enzyme linked immu-nosorbent assay(ELISA).The expression levels of goblet cell differentiation marker WGA and ciliary cell dif-ferentiation marker AAT,and the levels of phosphorylated(p-)ERK 1/2 and ERK 1/2 were determined by Western blot.The Cells diameter were measured by optical microscope.In vivo experiment,30 female C57BL/6J mice were randomly divided into Control group,Model group[(ovalbumin(OVA)and lipopolysaccharide(LPS)induced ashma mice model],and Model+anti-IL-13 antibody group(mice were treated intranasal with anti-IL-13 monoclonal antibody),10 mice in each group.Results Compared with Mild group,serum levels of IL-10,IFN-γ and IL-13 in Moderate-Severe group were increased(P＜0.05).Compared with Group-1 cells,in Group-2 cells AAT expression was up-regulated(P＜0.05).Compared with Group-1 cells,in Group-3 cells WGA expression was up-regulated(P＜0.05),the levels of IL-10,IFN-γ,and IL-13 were increased(P＜0.05),goblet cells diameters increased(P＜0.05),and the levels of p-ERK 1/2 were up-regulated(P＜0.05).Compared with Group-3,in Group-4 cells WGA expression were down-regulated(P＜0.05).IL-10,IFN-γ,and IL-13 levels were decreased(P＜0.05),goblet cells diameters decreased(P＜0.05),and the levels of p-ERK 1/2 were down-regulated(P＜0.05).There was no significant difference in the expression levels of ERK 1/2 among the four groups(P＞0.05).In vivo animal experiment,compared with Control group,the bronchial inflammation score of the Model group mice was increased(P＜0.05).Compared with Model group,the bronchial inflammation score of the Model+anti-IL-13 antibody group was decreased(P＜0.05).Conclusion Anti-IL-13 monoclonal antibody can inhibit airway goblet cell metaplasia and hyperplasia,and may be used to relieve acute subglottic laryngitis.

Objective:To explore the medication law of TCM external therapy for the treatment of diabetic foot using data mining methods.Methods:Literature on TCM external treatment for diabetic foot was retrieved from CNKI, Wanfang Data, and Chongqing VIP from the establishment of the databases to June 30, 2024. Excel 2019 software was used to conduct frequency statistics on drug frequency, properties, tastes and meridian tropism, drug efficacy, and commonly used drug pairs. Ancient and Modern Medical Cases Cloud Platform V3.5 was used for association rules, and SPSS Statistics 27.0 was used for complex network analyses.Results:A total of 425 articles were included, involving 328 prescriptions and 232 drugs. The drugs with higher frequency were Carthami Flos, Angelicae Sinensis Radix, Cinnamomi Ramulus, Olibanum, etc. The main tastes were pungent, bitter, and sweet; the main properties were cold and warm; the main meridians were heart, spleen, and liver meridians. The main efficacy was promoting blood circulation and removing blood stasis, clearing heat, and tonifying deficiency; association rule analysis obtained 20 commonly used drug pairs; clustering analysis resulted in four core drug combinations; complex network analysis led to one core prescription.Conclusions:TCM external therapy for diabetic foot follows the guiding principles of "promoting blood circulation and unblocking collaterals, tonifying deficiency and clearing heat" with coordinated regulation of the "heart-liver-spleen meridians". The core prescription and stage-specific formulation strategies reflect a trinity diagnostic and therapeutic approach of "disease differentiation-syndrome differentiation-stage differentiation", providing valuable reference and insights for clinical prescription practices.

Objective Sleep is an important physiological process for maintaining normal cognitive functions,but with the accelerated pace and increased work pressure in modern society,sleep deprivation has become a common phenomenon.It has been shown that sleep deprivation interferes with higher cognitive functions such as working memory,but the specific mechanism of its effect is still not completely clear.The present study aimed to systematically investigate the effects of 36 hours of sleep deprivation on the stages of the working memory processing chain and its neural mechanisms through behavioral and event-related potential(ERP)techniques.Methods Using a randomized controlled experimental design,48 healthy adult subjects were recruited and randomly assigned to sleep deprivation and control groups.All subjects completed a 2-back phonological working memory task,and behavioral data(response time and correctness)and ERP data(P2,N2,and P3 component wave amplitudes)were collected at 0 and 36 hours,respectively.The effects of sleep deprivation on working memory behavioral performance and neurophysiological indices were assessed by ANOVA.Results Behavioral results showed that the sleep deprivation group had a significantly longer response time after 36 hours,but no significant decrease in correctness,indicating a decrease in response efficiency but stable accuracy.ERP results showed that P2 amplitude did not change significantly before and after sleep deprivation,indicating that the early perception and categorization stages were limitedly affected by sleep deprivation;whereas,N2 and P3 amplitudes decreased significantly after sleep deprivation,reflecting that later cognitive processing such as conflict monitoring and resource allocation and other late cognitive processing were significantly disturbed.Conclusion Through ERP technology,this study uncovers the phased impact of 36-hour sleep deprivation on the working memory processing chain.The study found that early perceptual and categorization stages may be less susceptible to the effects of sleep deprivation,likely due to their relatively automatic processing and lower demand for cognitive resources.In contrast,during later stages of cognitive processing,particularly in higher-order functions such as conflict monitoring and resource allocation,sleep deprivation significantly impaired task performance efficiency by disrupting prefrontal cortex function.This finding deepens the understanding of the mechanisms underlying the effects of sleep deprivation and provides a scientific basis for cognitive intervention and management strategies in high-stress occupational groups.Future studies can further explore the long-term effects of sleep deprivation and its neural mechanisms by combining multimodal techniques.