Objective: To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer. Materials and Methods: A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs. Results: All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027). Conclusion The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.

Objective To conduct a multidimensional and multi-level evaluation of the comprehensive clinical value of empagliflozin in the treatment of type 2 diabetes mellitus.Methods Based on the National Essential Medicines List(2018 Edition),dapagliflozin was selected as the control.A comprehensive clinical evaluation index system was established through literature review,focus group interviews and in-depth expert interviews,encompassing six dimensions:safety,efficacy,economy,suitability,innovation,and accessibility.The Delphi method and hierarchical direct weighting method were used to screen indicators and determine their weights.Evidence for each indicator was collected and integrated both qualitatively and quantitatively through literature research,real-world studies,and pharmacoeconomic evaluations.Experts scored the indicators based on the collected evidence,and a total score for the comprehensive clinical evaluation of empagliflozin was calculated by combining these scores with indicator weights,followed by a comparative analysis with dapagliflozin.Results A comprehensive clinical evaluation of empagliflozin in the treatment of type 2 diabetes mellitus was successfully established,consisting of 6 primary indicators,14 secondary indicators,and 41 tertiary indicators.The overall evaluation score for empagliflozin was 90.35,and 89.47 for dapagliflozin.Conclusion The comprehensive clinical value of empagliflozin in the treatment of type 2 diabetes mellitus is slightly higher than that of dapagliflozin.This finding can serve as a reference for rational clinical drug use and related decision-making.

Aim To study the mechanism of salidro-side combined with rosavin in rats with ischemic stroke.Methods The MCAO rats was established by using thread-embolic method.The rats were divided into the sham group,MCAO group,salidroside com-bined with rosavin group,and positive control group;the drug was given continuously for seven days.Western blot was used to detect apoptosis indicators.Proteomics was used to analyse differential proteins(DEPs).STEP receptor inhibitor was injected into the lateral ventricles,the rats were administered for seven days,then the apoptosis indicators were detected.Re-sults Salidroside combined with rosavin could reduce neurological function scores in MCAO rats and inhibit cell apoptosis.Quantitative proteomics identified 496 DEPs in brain tissue and discovered core proteins STEP,p38,and CRTC1.Salidroside combined with rosavin could promote the STEP and CRTC1 while in-hibiting p38 protein.After treatment with STEP inhibi-tor,those effects were reversed.Conclusion Salidro-side combined with rosavin can inhibit cell apoptosis in MCAO rats,which is closely related to the regulation of the STEP/p38/CRTC1 signaling pathway.

Objective To introduce the concepts and principles of the win ratio method and to analyze it in the context of a case study of a clinical trial in cerebrovascular disease.Methods Based on the study of clopidogrel with aspirin in high risk patients with acute non disabling cerebrovascular events 2,and key prognostic factors,the outcome events were defined sequentially as ① time to death within 90 d,② time to recurrence of ischemic stroke within 90 d,③ time to moderate-to-severe hemorrhage within 90 d.Using clopidogrel combined with aspirin as the reference group,the winning ratio(Rw)of ticagrelor combined with aspirin was analyzed by the win ratio method,and the 95% confidence interval(CI)of Rw was estimated by the Bootstrap method and compared with the hazard ratio(HR)calculated by the competing risk model.Results When only fatal events were considered,the win ratio method suggested that the ticagrelor group was significantly better than the clopidogrel group,Rw=2.00(95% CI:1.52-2.47),and after stepwise inclusion of ischemic stroke and moderate-to-severe hemorrhage recurrence,the win ratio method yielded a value of 1.29(95% CI:1.25-1.57),and the HR value from Fine and Gray competing risk regression was 0.78(95% CI:0.65-0.95),both of which indicated that the efficacy of the ticagrelor group was superior to that of the clopidogrel group.Conclusion The win ratio method can be used to analyze clinical trials with composite endpoints after prioritizing multiple outcome variables,showing the advantages of win ratio and its promising application in cerebrovascular disease research.

Acute ischemic stroke(AIS)is associated with high mortality and disability rates,presenting a substantial challenge to global public health challenge.Intravenous thrombolysis(IVT)is recognized as a cornerstone of early AIS treatment and is recommended as the standard therapeutic approach by both national and international guidelines.However,the clinical efficacy of IVT remains suboptimal due to several limitations,including a narrow therapeutic time window and the inevitable activation of the coagulation system and platelet aggregagation during thrombolysis.These factors may contribute to adverse outcomes such as early neurological deterioration(END)and vascular re-occlusion.Antiplatelet therapy(APT),which inhibits platelet aggregations,reduces microthrombus formation,and stabilizes the vascular endothelium with multifaceted mechanisms,has emerged as a promising adjunctive strategy to IVT,offering potential synergistic effects.This review summarized the latest evidence from both domestic and international studies,focusing on the mechanisms of APT,recent clinical advancements in IVT combined with APT,and the safety and efficacy of APT administration at different time windows relative to IVT.Emphasis is placed on the influence of various antiplatelet agents,dosing regimens,and initiation timing on therapeutic outcomes,alongside a comprehensive evaluation in the context of current guideline recommendations and clinical practice.Current guidelines recommend initiating APT 24 h after IVT,following imaging confirmation to exclude the risk of intracranial hemorrhage.However,the efficacy and safety of earlier APT initiation remain inconclusive.Individualized treatment strategies,such as early administration of low-dose,short-acting APT or combination therapy in specific patient subgroups,may effectively balance therapeutic benefits and risks.The adjunctive use of APT in IVT holds promise for enhancing efficacy and improving clinical outcomes,but precise stratification of safety and efficacy is essential.Future research should focus on optimizing combination IVT and APT strategies through individualized patient profiling,appropriate drug selection,and dynamic imaging monitoring to achieve precision management in AIS treatment.

The"promising zone"is a method used to analyze interim data from adaptive design clinical trials in an unblinded state.It allows for the adjustment of sample size based on interim results to enhance the trial's probability of success or minimize investment in unnecessary sample size.Mehta and Pocock proposed rules for increasing sample size based on interim analysis results using the concept of the"promising zone"(MP design).Furthermore,combination of the MP design with group sequential design can set up early stopping boundaries in trials,allowing for a reduction in sample size under favorable or unfavorable zone.The combination test(CT)design further optimizes the framework of the"promising zone",by considering sample size and conditional power in combination to achieve the highest conditional power with the smallest sample size.This review summarizes the principles of the"promising zone",introduces the method of determining the"promising zone"and re-estimating sample size,and further illustrates the feasibility of this method in clinical trials with a practical case.

Aim To study the effect of p-benzoyl sali-droside(pOBz)on angiogenesis after ischemic stroke and to explore the underlying mechanism.Methods The MCAO model was prepared by suture method.Rats were divided into four groups:sham,MCAO,pOBz administration,and edaravone positive control,treated for seven days.The mNSS was used to assess the neurological impairment.Western blotting was em-ployed to detect CD31,NICD,and Hes-1 protein ex-pression,while immunofluorescence staining was ap-plies to quantify CD31-positive cells in ischemic brain tissue.In vitro an OGD/R model was established in HUVECs.Following treatment with varying pOBz con-centrations(0.01,0.1,1 μmol·L-1),the CCK-8 as-say was uses to measure cell viability,and in vitro tube formation assay was utilized to evaluate angiogenesis.Western blotting was employed again to assess CD31,NICD and Hes-1 protein levels.To further elucidate the mechanism,HUVEC were treated with the Notch inhibitor DAPT prior to grouping and pOBz administra-tion,and the same parameters were evaluated.Results pOBz significantly reduced the mNSS score of MCAO rats,increased CD31-positive cell counts,and upregu-lated CD31,NICD,and Hes-1 protein expression(P＜0.01).In vitro results further showed that pOBz could dose-dependently increase the survival rate and angio-genesis ability of HUVEC induced by OGD/R,and promote CD31,NICD and Hes-1 proteins(P＜0.01),and Notch inhibitor DAPT could reverse the above effects of pOBz.Conclusion pOBz promotes angio-genesis in HUVEC,and its mechanism involves activa-tion of the Notch signaling pathway.

Objective To investigate the feasibility of fluorescence analysis method for determining the encapsulation efficiency(EE)of PEGylated liposomes(PEG-L)and their application in studying the accelerated blood clearance(ABC)phenomenon.Meth-ods DiR-labeled PEGylated liposomes(PEG-DiR-L)were prepared via ethanol injection.Free DiR and total DiR samples were ob-tained using ultrafiltration centrifugation and ultrasonic demulsification,respectively.The EE of PEG-DiR-L was calculated by quantif-ying DiR levels in both samples using a multifunctional microplate reader.Male Sprague-Dawley(SD)rats were divided into two groups:the single injection group[first injected with phosphate-buffered saline(PBS),followed by PEG-DiR-L 7days later]and the repeated injection group(first injected with empty PEG-L,followed by PEG-DiR-L 7days later).Blood samples were collected from the eye canthus of rats,and the plasma concentrations of PEG-DiR-L were measured to construct pharmacokinetic profiles and calculate key pharmacokinetic parameters.Tissue distribution was assessed by ex vivo imaging of heart,liver,spleen,lung,and kidney samples u-sing the IVIS spectroscopy.Results The EE of PEG-DiR-L determined by ultrafiltration centrifugation was 97.68％±0.23％.Com-pared to the single-dose group,the repeated-dose group exhibited significantly accelerated plasma clearance,with reduced AUC(0→t)、AUC(0→∞)、MRT(0→t)、MRT(0→∞)and t1/2z,alongside increased CLz and Vz(P＜0.05).Hepatic accumulation of PEG-DiR-L was markedly enhanced in the repeated-dose group.Conclusion The results of plasma pharmacokinetics and tissue distribution indicated that the ABC phenomenon occurred in the repeated injection group,suggesting that the fluorescence analysis method is able to determine the encapsulation rate of PEG-L and be used to study the ABC phenomenon.

Depression is a highly heterogeneous psychiatric disorder with complex pathogenesis influenced by the interplay of biological,psychological,and social-environmental factors.Based on the 2021 edition of the Chinese Guidelines for the Prevention and Treatment of Depressive Disorders,which explicitly identify gender as a significant risk factor for depression onset,this paper systematically reviews the gender-differentiated pathogenesis and therapeutic advances in depression from both traditional Chinese medicine(TCM)and Western medical perspectives.In Western medicine,a large number of studies have demonstrated the sex-specific mechanism of estrogen/testosterone fluctuations and monoamine transmitter system regulation.While in TCM,although the constitution theory proposes that there are significant gender differences in congenital constitution and that qi depression and qi deficiency are associated with susceptibility to depression,current evidence primarily relies on cross-sectional surveys and lacks validation through high-quality RCTs.Compared with Western medicine,the direct research on gender-differentiated antidepressant effects in TCM remains relatively underdeveloped.In future study,it may be possible to deepen and improve the research on anti-depression in TCM from the biological markers of particular constitutions in the gender dimension.This paper advocates establishing a bio-psycho-social integrated intervention model,advancing mechanistic exploration through prospective cohort studies and multi-omics technologies,and promoting precision diagnosis and treatment systems based on gender differences,and to form a three-dimensional diagnosis and treatment and research system that covers biomarkers,social role assessment,and TCM constitution identification,in order to provide a new theoretical framework and a practical pathway for the precise medical treatment of depression.

Objective To conduct a multidimensional and multi-level evaluation of the comprehensive clinical value of empagliflozin in the treatment of type 2 diabetes mellitus.Methods Based on the National Essential Medicines List(2018 Edition),dapagliflozin was selected as the control.A comprehensive clinical evaluation index system was established through literature review,focus group interviews and in-depth expert interviews,encompassing six dimensions:safety,efficacy,economy,suitability,innovation,and accessibility.The Delphi method and hierarchical direct weighting method were used to screen indicators and determine their weights.Evidence for each indicator was collected and integrated both qualitatively and quantitatively through literature research,real-world studies,and pharmacoeconomic evaluations.Experts scored the indicators based on the collected evidence,and a total score for the comprehensive clinical evaluation of empagliflozin was calculated by combining these scores with indicator weights,followed by a comparative analysis with dapagliflozin.Results A comprehensive clinical evaluation of empagliflozin in the treatment of type 2 diabetes mellitus was successfully established,consisting of 6 primary indicators,14 secondary indicators,and 41 tertiary indicators.The overall evaluation score for empagliflozin was 90.35,and 89.47 for dapagliflozin.Conclusion The comprehensive clinical value of empagliflozin in the treatment of type 2 diabetes mellitus is slightly higher than that of dapagliflozin.This finding can serve as a reference for rational clinical drug use and related decision-making.