[摘 要] 目的：系统评价CD19 CAR-T细胞免疫疗法对比标准治疗在复发/难治性弥漫性大B细胞淋巴瘤（R/R DLBCL）患者中疗效与安全性，通过探索性分析探索不同CAR-T细胞产品对疗效的潜在影响，为临床治疗决策提供循证参考。方法：计算机检索中国知网、万方数据库、维普期刊数据库、中国生物医学文献数据库、PubMed、Embase和Cochrane Library数据库，搜集CD19 CAR-T细胞疗法对比标准治疗用于R/R DLBCL的随机对照试验（RCT），检索时限均为建库至2025年10月25日。由2位研究者独立进行文献筛选、数据提取和质量评价，采用R4.2.2软件进行Meta分析。结果：共纳入2项Ⅲ期RCT研究（ZUMA-7、TRANSFORM），各结局指标均根据异质性检验结果选择固定效应模型合并数据。疗效方面，CD19 CAR-T细胞疗法可显著改善患者无事件生存期（HR=0.455，95%CI：0.363~0.570，P < 0.001）和降低死亡风险（HR = 0.738，95%CI：0.575~0.947，P = 0.017）；同时可显著提高完全缓解率（RR = 1.879，95%CI：1.574~2.242，P < 0.001）。按产品类型的探索性分析显示，liso-cel和axi-cel均优于标准治疗（liso-cel：HR = 0.380，95%CI：0.260~0.540，P < 0.001；axi-cel：HR = 0.510，95%CI：0.380~0.680，P < 0.001），但该分析为不同试验间的对比，证据等级有限。安全性结局显示：CAR-T细胞疗法的免疫效应细胞相关神经毒性综合征（ICANS）发生率显著升高（RR = 22.387，95%CI：4.353~115.132，P < 0.001）；≥3级细胞因子释放综合征（CRS）发生率数值升高（RR = 8.181，95%CI：0.935~71.574，P = 0.058），差异无统计学意义。纳入研究的偏倚风险整体为低；敏感性分析证实结果稳健。结论：基于2项RCT的Meta分析结果，CD19 CAR-T细胞（liso-cel/axi-cel）可作为R/R DLBCL二线治疗的选择之一，其疗效优于标准治疗，且特征性不良反应（CRS/ICANS）经规范管理后可控，可根据患者基线状态个体化选择CAR-T细胞产品。本研究证据基础薄弱，上述结论尚需更多高质量、大样本RCT验证。

Background/Aims: Recent advances in computer-aided diagnosis (CADx) systems have demonstrated expert-level accuracy in the optical diagnosis of colorectal polyps. High-confidence (HC) diagnoses have been defined as those made within 3 seconds without hesitation, and these systems have been shown to improve diagnostic accuracy. We aimed to evaluate the performance of endoscopists with varying levels of experience in diagnosing colorectal polyps with the assistance of a new CADx system applying the 3-second rule and without artificial intelligence assistance. Methods: In this multicenter ex vivo study, 35 endoscopists assessed 100 polyps (51 adenomas, 39 hyperplastic polyps, 10 sessile serrated lesions) using narrow-band imaging video clips on an online platform. Assessments consisted of individual endoscopist diagnosis and CADx-assisted diagnosis. HC assignments followed the 3-second rule in both phases. Performance metrics included HC accuracy, HC rate, and adherence to the Preservation and Incorporation of Valuable Endoscopic Innovations (PIVI) and Simple Optical Diagnosis Accuracy (SODA) thresholds. Results: HC diagnostic accuracy improved from 78.3% (95% confidence interval [CI], 76.6% to 80.0%) to 89.8% (95% CI, 88.6% to 90.9%) with CADx assistance (p<0.001). The proportion of HC predictions increased from 64.2% to 75.4% (p<0.001). Novice endoscopists showed marked improvement with CADx (74.1% vs 88.8%; p<0.001). CADx-assisted diagnoses nearly met SODA and PIVI thresholds under the 3-second rule. Additional analysis demonstrated that CADx assistance significantly improved interobserver agreement and ground truth, particularly for novices (κ=0.37 to κ=0.65; p<0.001). Conclusions Integrating CADx with the 3-second rule significantly enhances the performance of endoscopists in the optical diagnosis of colorectal polyps, with the greatest benefit observed among novice endoscopists.

Purpose: We aimed to investigate the prevalence and genotype distribution of human papillomavirus (HPV) among Korean males and explore implications for targeted vaccination strategies. Materials and Methods: A total of 44,065 males underwent HPV testing between March 2014 and February 2022 using the Anyplex™ II HPV 28 system, detecting 19 high-risk (HR) and 9 low-risk (LR) HPV types. Additionally, data from 507 male patients at local clinic (2017–2022) were analyzed to compare genotype prevalence between those with (WAT group) and without (WAT X group) genital warts. Results: Overall HPV positivity was 59.1%. HPV 6 (33.3%) and HPV 11 (11.0%) were the most prevalent LR genotypes, while HPV 16 (5.2%) dominated HR infection. Multiple HPV genotype co-infection occurred in 49.3% of positive cases, with 11.3% involving multiple HR types. Younger males (teens, 20s) exhibited higher HR-HPV positivity, although total HPV positivity peaked in the 40s (60.1%). Non–9-valent HR genotypes (HPV 53, 51, 39, 66) accounted for 27.6%–35.0% of infections annually. At local clinic, HPV 43 was significantly associated with genital warts (p=0.017). Conclusions These data support including males in national HPV vaccination strategies using the current 9-valent vaccine and underscore the need for ongoing genotype surveillance to monitor non‑vaccine high‑risk types and inform public health policy, and support inclusion of males in national HPV vaccination strategies using the current 9‑valent vaccine.

Background: and Purpose Induced hypertension therapy (IHT) is effective for treating early neurological deterioration (END) in patients with single subcortical infarction (SSI). However, the underlying pathophysiology of SSI is diverse and may affect the efficacy of IHT. Methods: We reviewed patients with SSI who experienced END and received IHT were enrolled. END was defined as ≥2-point increase in the National Institutes of Health Stroke Scale (NIHSS) score, ≥1 motor point increase. IHT was performed by using phenylephrine infusion to raise systolic blood pressure by 10%–20% over baseline. SSI was classified into three subtypes: distal (dSSI), proximal (pSSI), and SSI with parental artery disease (SSIPAD; with stenosis at parental artery disease <50%). Responders were defined as patients who showed neurological improvement (decrease of ≥2 points in NIHSS, ≥1 motor point decrease) within one day after IHT initiation. Multivariable analysis identified factors associated with responders. Results: Characteristics were compared between responders and non-responders, and factors associated with response to IHT were investigated. Among 96 patients (mean age, 64.7± 12.9 years; 61.5% male), 49 (51.0%) patients were categorized as responders. Multivariable analysis showed that pSSI (adjusted odds ratio [aOR]=18.10, 95% confidence interval [CI] 5.04–80.60, p<0.001) and SSIPAD (aOR=4.56, 95% CI 1.31–19.00, p=0.024) were associated with a positive response to IHT compared to dSSI. Additionally, less white matter changes (Fazekas scale 0–1) were associated with a better response to IHT (aOR=0.15, 95% CI 0.03–0.67,p=0.019). Conclusions Response to IHT varied according to SSI subtypes and the severity of small vessel changes.

OBJECTIVE To investigate the effects of Mitoxantrone liposomes （Lipo-MIT） on the proliferation， migration and cancer stem cell （CSCs） stemness of ovarian cancer cells， as well as to explore its mechanism of action based on the phosphoinositide 3-kinase （PI3K）/protein kinase B （AKT） pathway. METHODS The effects of Lipo-MIT on cell proliferation， migration and the stemness characteristics of CSCs were investigated through in vitro experiments. A human ovarian cancer A2780 cells xenograft tumor model of nude mouse was established to explore the effects of Lipo-MIT at doses of 2 and 5 mg/kg on the safety of tumor-bearing mice， as well as in vivo tumor growth and the pathological characteristics of tumor tissues. The influence of Lipo-MIT on the expression levels of PI3K/AKT pathway-related proteins， epithelial-mesenchymal transition related proteins， and stemness related proteins in both cells and tumor tissues was also investigated. RESULTS The half maximal inhibitory concentrations of Lipo-MIT against A2780， SK-OV3， and OV-CAR5 cells were 0.72， 5.41， and 2.77 μmol/L， respectively. Compared with solvent control （0.1% dimethyl sulfoxide）， 0.5-2.5 μmol/L Lipo-MIT significantly reduced the cell colony formation rate， shortened the cell migration distance， decreased the number of migrated cells， down-regulated the protein expression of N-cadherin， up-regulated the protein expression of E-cadherin （P＜0.05）， and also decreased the stem cell sphere formation frequency and down-regulated the protein expression of aldehyde dehydrogenase 1A1 （ALDH1A1） （P＜0.05）. Additionally， 1.0 and 2.5 μmol/L Lipo-MIT significantly reduced the stem cell sphere formation probability and down-regulated the protein expression of sex determining region Y box protein 2 in cells （P＜0.05）. In vivo experimental results demonstrated that 2， 5 mg/kg Lipo-MIT had no significant effects on the body weight， food intake， water intake， and organ （heart， liver， spleen， lung， and kidney） indices of tumor-bearing nude mice （P＞0.05）， but could significantly improve the pathological changes of tumor tissues and remarkably inhibit the protein expressions of N-cadherin， CD133 and ALDH1A1（ only at 5 mg/kg Lipo-MIT）， up-regulate the expression of E- cadherin （only at 5 mg/kg Lipo-MIT） in tumor tissues （P＜0.05）. Lipo-MIT at different concentrations/doses significantly reduced the phosphorylation levels of PI3K and AKT proteins in cells/tumor tissues （P＜0.05）. CONCLUSIONS Lipo-MIT can inhibit the proliferation and migration of ovarian cancer cells and the stemness by suppressing the activity of the PI3K/AKT pathway.

OBJECTIVE To explore the transformation of the dispensing and drug pickup process in traditional Chinese medicine pharmacy （TCM Pharmacy） in our hospital based on data-intelligence-driven， aiming to improve pharmacists’ work efficiency and patients’ drug pickup experience. METHODS Value stream mapping and journey mapping were used to systematically identify non-value-added links in pharmacists’ dispensing process and key pain points in patients’ drug pickup under the traditional process. An intelligent dispensing and drug pickup system for the TCM Pharmacy was developed based on the C# and Android television platforms， and a machine-learning model was adopted to predict patients’ drug pickup waiting time. A comprehensive evaluation was performed from three perspectives： system performance， prediction accuracy， and satisfaction of pharmacists and patients. RESULTS The system successfully streamlined non-value-added links such as “waiting for writing on the board” and “searching for drugs”， and realized multimodal dynamic prompts of dispensing status through auditory （number calling） and visual （television terminal） channels. The constructed model for predicting drug pickup waiting time exhibited good fitting degree and generalization ability （mean absolute error＝4.28 min， R 2 ＝0.882）. The comprehensive satisfaction scores of pharmacists and patients in the traditional mode were significantly increased from （70.99±1.74） and （73.58±1.98） to （90.02±1.30） and （88.61±2.08） in the new system， respectively （ P ＜0.01）. CONCLUSIONS The transformation of the intelligent drug dispensing and pickup system for TCM pharmacy based on data-intelligence-driven effectively improves the efficiency of pharmacists’ dispensing work， realizes process transparency and waiting time predictability， and significantly enhances patients’ drug pickup experience.

The integrated medical and elderly care model is a new type of elderly care model designed to address the demands of the elderly in terms of physical health， daily care， and spiritual comfort. It has significant practical significance for actively responding to the problems of population aging. However， this model still faces a series of ethical dilemmas in practical. By analyzing the ethical issues that may arise during the integration of medical and elderly care services， including conflicts between medical care and elderly autonomy， the challenges faced by informed consent， conflicts of interest between medical and elderly care services， and blurred boundaries between family care and social care， this paper proposed corresponding strategies， such as improving the construction of personalized care mechanisms， optimizing multi-level protection systems for informed consent， establishing a unified interest coordination mechanism and resource sharing platform， and strengthening the synergy between family support and social care. These strategies aimed to promote the healthy development of the integrated medical and elderly care model， ensure the protection of the basic rights and interests and well-being of the elderly to the greatest extent， and ultimately achieve a fairer and more sustainable aging social governance system.

LIU Wansu， as the foremost of the four great masters of the Jin-Yuan period， established the "theory of fire-heat'' and extended the fire-heat pathogenesis framework to the field of stroke， thereby forming the theory of ''fire-heat inducing stroke''. This achieved a paradigmatic shift in stroke etiology from ''exogenous wind inducing stroke'' to ''fire-heat inducing stroke''. This paper systematically reviews the developmental trajectory of LIU Wansu's ''fire-heat inducing stroke'' theory and explores the social background， academic origins， and core connotations of its theoretical construction. The study found that， based on the ''Nineteen Pathomechanisms'' in the Huangdi's Internal Classic （Huang Di Nei Jing） and combined with clinical practice， LIU Wansu proposed that fire-heat is the fundamental cause of stroke， and that the Six Climatic Factors and the Five Zhi-Emotions can all transform into fire. He further constructed a stratified syndrome differentiation and therapeutic system centered on clearing heat and purging fire， emphasizing differentiated treatment of exterior and interior syndromes， Six Meridians syndrome differentiation， and seasonally adjusted medication. This theory not only resolved the diagnostic and therapeutic dilemmas of febrile epidemic diseases during the Jin-Yuan period， but also exerted a profound influence on later physicians such as ZHANG Zihe and ZHU Danxi， thereby promoting the pluralistic development of stroke theory in traditional Chinese medicine （TCM）. Modern pharmacological research provides solid scientific evidence， confirming that the ''fire-heat'' pathological state is highly associated with key mechanisms such as excessive inflammatory responses， oxidative stress， and excitatory amino acid toxicity following cerebral ischemia. Heat-clearing and fire-purging prescriptions and agents， such as Huanglian Jiedu Tang and baicalin， can exert multi-target neuroprotective effects by regulating inflammatory signaling， enhancing antioxidant enzyme activity， and balancing neurotransmitters. This not only verifies the scientific basis of the ''fire-heat inducing stroke'' theory from a modern biological perspective but also provides conclusive evidence for the clinical application of heat-clearing and fire-purging therapy. LIU Wansu's ''fire-heat inducing stroke'' theory represents a major milestone in the historical understanding of stroke pathogenesis， and its academically transitional insights continue to hold core guiding value for the pattern identification and treatment of ischemic stroke today.

ObjectiveTo investigate whether Huanglian Jiedutang can inhibit neutrophil infiltration in the brains of middle cerebral artery occlusion （MCAO） mice by regulating the expression of neutrophil-related chemokines in exosomes， thereby achieving therapeutic effects. MethodsA total of 130 male specific pathogen-free （SPF） C57BL/6J mice were randomly divided into four groups： Sham-operated group， MCAO model group， Huanglian Jiedutang group （6 g·kg^-1）， and Ginaton group （21.6 mg·kg^-1）， with 10 mice in the Ginaton group and 40 mice in each of the remaining three groups. Mice in the Huanglian Jiedutang group and the Ginaton group were administered the corresponding drugs by oral gavage once daily at a volume of 0.15 mL·（10 g）^-1 for 7 consecutive days， while the sham-operated and model groups received an equal volume of saline via the same route. After 7 days， MCAO surgery was performed. The distal and proximal ends of the right common carotid artery （CCA） were ligated， a small incision was made between the two ligatures， and a silicone rubber-coated monofilament with a rounded tip was inserted into the lumen to occlude the CCA. The filament was left in place for 1 h to establish a focal cerebral ischemia model. At 24 h after modeling， mice were evaluated. Neurological function was assessed using the Longa score. Cerebral infarct volume was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Cerebral blood flow was observed by laser speckle imaging. Hematoxylin and eosin （HE） staining and Nissl staining were used to observe pathological changes in brain tissues. Exosomes were isolated from mouse plasma and brain tissues by ultracentrifugation and molecular size exclusion and identified by electron microscopy， particle size analysis， and protein blotting. Long-chain RNA libraries of exosomes were constructed and sequenced. Real-time quantitative reverse transcription polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of inflammatory factors and neutrophil-related chemokines in exosomes from plasma and brain tissues of each group. Enzyme-linked immunosorbent assay （ELISA） was used to detect the protein expression of inflammatory factors and neutrophil-related chemokines in exosomes from brain tissues of each group. Immunohistochemistry was used to detect the expression of the neutrophil-specific protein myeloperoxidase （MPO） in the brains of mice in each group. ResultsCompared with the sham-operated group， the model group showed decreased neurological function scores （P<0.01）， obvious cerebral infarction （P<0.01）， reduced cerebral blood flow （P<0.01）， neuronal necrosis in the brain， and decreased numbers of Nissl bodies （P<0.01）. The mRNA expression levels of IL-1β， MPO， CXCL1， CXCL2， CXCL3， CXCL10， CCL2， and CCL3 in exosomes from plasma and brain tissues were significantly increased （P<0.05， P<0.01）. The protein expression levels of IL-1β， MPO， CXCL2， and CXCL10 in exosomes from brain tissues were increased （P<0.05， P<0.01）， and MPO-positive rates and mean optical density values in brain tissues were elevated （P<0.01）. Compared with the model group， the Huanglian Jiedutang group and the Ginaton group showed increased neurological function scores （P<0.05）， reduced cerebral infarct volume （P<0.01）， restored cerebral blood flow （P<0.01）， reduced necrotic cells in the brain， and increased numbers of Nissl bodies （P<0.01）. In the Huanglian Jiedutang group， the mRNA expression levels of IL-1β， MPO， CXCL1， CXCL2， CXCL3， CXCL10， CCL2， and CCL3 in exosomes from plasma and brain tissues were decreased （P<0.05， P<0.01）. The protein expression levels of IL-1β， MPO， CXCL2， and CXCL10 in exosomes from brain tissues were reduced （P<0.05， P<0.01）， and MPO-positive rates and mean optical density values in brain tissues were decreased （P<0.01）. ConclusionHuanglian Jiedutang can effectively regulate the expression of neutrophil-related chemokines in exosomes from plasma and brain tissues of MCAO mice， thereby reducing neutrophil infiltration in the brain and achieving therapeutic effects.