[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。

Esophageal cancer is a prevalent malignant tumor of the digestive tract in China, and radical surgery remains the cornerstone of its comprehensive treatment. However, multifactorial challenges such as postoperative gastrointestinal tract reconstruction, traumatic stress, and tumor-related metabolic disturbances render esophageal cancer patients highly susceptible to malnutrition. Perioperative nutritional support therapy plays a crucial role in enhancing surgical safety, improving clinical outcomes, and elevating patients' quality of life by regulating metabolic homeostasis, preserving organ function, and optimizing the immune microenvironment. This article reviews the mechanisms underlying malnutrition in esophageal cancer, methods for nutritional status assessment, and precision intervention pathways based on multi-omics evaluations. The aim is to strengthen clinicians' awareness of standardized perioperative nutritional management for esophageal cancer patients and promote its clinical implementation, thereby facilitating postoperative recovery and improving long-term quality of life.

ObjectiveTo investigate whether Huanglian Jiedutang （HLJD） and its major active constituents （geniposide， baicalin， and berberine） can inhibit the inflammatory response of BV2 cells under lipopolysaccharide （LPS） stimulation via the high-mobility group protein B1 （HMGB1）/Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） signaling pathway， and to explore differences in therapeutic efficacy among the three monomers， their combined formula， and HLJD under equal content ratios. MethodsBV2 microglial cells were used as the primary experimental model. Cell viability was assessed using the cell counting kit-8 （CCK-8） method to examine the effects of different concentrations of dimethyl sulfoxide （DMSO， 0.8%， 0.4%， 0.2%， 0.1%， and 0.05%） on cell viability. IncuCyte was employed to monitor the growth of cells under different concentrations of HLJD （200， 100， 50， 25， 12.5， 6.25 mg·L^-1）. Nitric oxide （NO） assay was used to screen the optimal HLJD concentration. High-performance liquid chromatography （HPLC） determined the content of geniposide， baicalin， and berberine in HLJD， and experimental groups were subsequently established according to the relative proportions of these constituents. CCK-8 assay evaluated cell viability under different treatments. Enzyme-linked immunosorbent assay （ELISA） measured levels of inflammatory factors （TNF-α， IL-1β， IL-6， IL-10） in the supernatant. Flow cytometry assessed the effects of treatments on M1-type polarization of BV2 cells. Western blot determined the expression levels of HMGB1， TLR4， and NF-κB-related proteins. ResultsCompared with the blank group， DMSO at concentrations ≤0.2% did not affect cell viability within 48 h. BV2 cell growth plateaued at 24 h after treatment with 200 mg·L^-1 HLJD. Under stimulation with 2 mg·L^-1 LPS， this concentration of HLJD effectively reduced NO release， and 6 h pre-treatment had a stronger inhibitory effect on NO than direct administration. HPLC results showed that 1 mg of HLJD freeze-dried powder contained approximately 24 μg of geniposide， 15 μg of baicalin， and 30 μg of berberine. Based on these ratios， experimental groups were blank， LPS （2 mg·L^-1）， HLJD （200 mg·L^-1）， monomer combination， geniposide （4.8 mg·L^-1）， baicalin （3 mg·L^-1）， and berberine （6 mg·L^-1）. The monomer combination group consisted of all three active constituents dissolved together. LPS and HLJD or its active constituents did not affect cell viability compared with the blank group. LPS significantly increased TNF-α， IL-1β， IL-6， and IL-10 in the supernatant （P<0.01）. HLJD and its active constituents significantly reduced pro-inflammatory factors TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01） while upregulating anti-inflammatory IL-10 （P<0.01）， with the monomer combination showing the strongest effect （P<0.05， P<0.01）. Compared with the blank group， LPS significantly increased the proportion of CD80⁺CD86⁺ （M1-type） BV2 cells （P<0.01）. HLJD and its constituents partially inhibited M1 polarization （P<0.05， P<0.01）， with the monomer combination exhibiting the most pronounced effect （P<0.05， P<0.01）. Compared with the blank group， LPS upregulated HMGB1， TLR4， and NF-κB-related proteins （P<0.01）， whereas HLJD and its active constituents significantly reduced their expression （P<0.05， P<0.01）， with the monomer combination having the strongest regulatory effect （P<0.05， P<0.01）. ConclusionHLJD and its major active constituents （geniposide， baicalin， berberine） can inhibit LPS-induced inflammatory responses in BV2 cells. The combination of the three active constituents demonstrates the most potent anti-inflammatory effect， significantly attenuating M1-type polarization of BV2 cells via the HMGB1/TLR4/NF-κB signaling pathway.

Alzheimer’s disease (AD) is characterized by progressive cognitive deterioration and significant depression. However, the mechanisms linking depression to AD pathology remain unclear. Here, we investigated whether Notch2 signaling mediates depressionlike behaviors in presenilin-2 (PS2) N141I mutant mice, an early-onset AD model. PS2 wild-type (WT) and mutant (MT) mice aged 12-15 months were subjected to unpredictable chronic mild stress (UCMS) for 4 weeks, followed by sucrose preference, tail-hanging, and forced swimming tests. Behavioral assessments showed that UCMS exacerbated anhedonia and immobility only in PS2 MT mice. Molecular analysis revealed concomitant increases in plasma corticosterone, hippocampal γ-secretase activity, and Notch2 expression, and elevated total and phosphorylated glucocorticoid receptor levels in PS2 MT-UCMS mice. Gene expression profiling of human hippocampal datasets confirmed upregulation of NOTCH2 in Alzheimer’s disease and depression.Pharmacological inhibition of γ-secretase and Notch signaling with DAPT normalizes depressive behavior, reduces corticosterone release, attenuates GR phosphorylation, and inhibits Notch2 signaling in PS2 MT mice. These findings identify Notch2 as a pivotal mediator linking chronic stress to molecular changes associated with depression and AD, and suggest that targeting Notch2 signaling may provide therapeutic benefits for comorbid mood and neurodegenerative disorders.

In addition to well-known side effects such as rash, redness, and bone resorption, unexpected facial complications may occasionally occur several years after certain medical procedures. This report presents rare cases of orofacialsymptoms that developed as delayed responses to cosmetic filler injections. Three separate patients presented to theauthors’ institution with varying severities of orofacial symptoms. These symptoms, initially diagnosed clinically asinflammation or neoplasms of the parotid gland, were later identified through magnetic resonance imaging as diseases potentially associated with filler materials injected approximately 4-8 years earlier. The primary goal of this report was to inform specialists in the oral and maxillofacial field about the possibility of such complications, enabling them tomanage patient symptoms effectively and develop appropriate treatment strategies.

Objective: To address the relation among pelvic inflammatory disease (PID), genetic vulnerability and ovarian cancer (OC) risk, we assessed the association between PID and OC risk, alongside the interplay with germline homologous recombination repair (gHR) mutation, utilizing the UK Biobank. Methods: We conducted a prospective cohort study in the UK Biobank by tracking OC incidences between individuals with and without a PID history. Identification of gHR mutations (BRCA1, BRCA2, RAD51C, RAD51D, BRIP1) carriers were accomplished through paired whole-exome sequencing data. We used Cox’s regression models to evaluate the hazard ratios (HRs) for OC risks under PID. Results: In the large prospective cohort study, the adjusted HR for OC in patients with PID was 1.45 (95% confidence interval [CI]=0.90, 2.32) compared with those with non-PID.Intriguingly, age-stratified analysis unveiled a positive association between PID history and OC risk in those aged under 55 years (HR=1.92; 95% CI=1.02, 3.63). Moreover, individuals aged younger than 55 years harboring both a history of PID and gHR mutations exhibited the highest risk of OC (HR=7.40; 95% CI=1.03, 53.10). Conclusion An association between PID and OC risk emerged, notably in the subgroup aged younger than 55 years old. Individuals with both a PID history and gHR mutations exhibited the highest risk of OC. These findings imply PID as a potential precursor for OC, underscoring the importance of early intervention, particularly in the younger population with gHR mutations.

Objective:To explore the predictive value of platelet aggregation function for acute kidney injury (AKI) in sepsis patients based on decision curve.Methods:A retrospective study was conducted to collect and analyze the clinical data of 120 sepsis patients admitted to the Affiliated Hospital of Jiangnan University from January 2021 to December 2023. According to the incidence of AKI during hospitalization, they were divided into AKI group (37 cases) and non-AKI group (83 cases). The general data, platelet aggregation function index (platelet aggregation rate) and other laboratory indexes of the two groups were collected and compared. Logistic regression model was used to analyze the relationship between AKI and main indexes of platelet aggregation function in patients with sepsis. The area under the curve (AUC) was obtained by drawing the receiver operating characteristic (ROC) curve, and the predictive value of platelet aggregation function on AKI in patients with sepsis was analyzed. R language software was used to construct a nomogram model of platelet aggregation function combined with other main indicators to predict AKI in patients with sepsis. Based on the decision curve, the predictive efficacy of the model on AKI in patients with sepsis was analyzed.Results:The platelet aggregation rate in the AKI group was lower than that in the non-AKI group: (56.23 ± 7.86)% vs. (68.79 ± 8.54)%, and the thrombin time was longer than that in the non-AKI group: 17.00 (16.50, 18.00) s vs. 16.00 (15.00, 17.00) s. The levels of D-dimer, C-reactive protein and procalcitonin were higher than those in the non-AKI group: (1.55 ± 0.45) mg/L vs. (1.32 ± 0.41) mg/L, (107.53 ± 18.41) mg/L vs. (99.86 ± 17.25) mg/L, (3.10 ± 0.46) μg/L vs. (2.88 ± 0.42) μg/L, and the differences were statistically significant ( P<0.05). The results of constructing a Logistic regression model showed that AKI in sepsis patients may be related to abnormal levels of platelet aggregation rate, thrombin time, C-reactive protein and procalcitonin ( P<0.05). The ROC curve was drawn to obtain the corresponding AUC: the AUC of platelet aggregation rate predicting sepsis complicated with AKI was 0.860 (95% CI 0.789 to 0.931), which had certain predictive value. When the platelet aggregation rate was set to 62.84%, the best predictive value can be obtained, with sensitivity, specificity, and Jorden index of 83.80%, 80.70%, and 0.645, respectively. The nomogram model of platelet aggregation function assisting other major indicators in predicting AKI in sepsis patients had a C-index of 0.904 (95% CI 0.851 to 0.957), indicating good discrimination of the model. Through decision curve analysis of the clinical net benefit of the model, the results showed that the clinical net benefit of the model was higher than that of platelet aggregation rate and other major indicators when applied alone. When the risk threshold was within the range of 0 to 0.81 and 0.97 to 1.00, the model could provide a significant increase in clinical net benefit rate. Conclusions:Platelet aggregation function (platelet aggregation rate) can serve as an early auxiliary predictive indicator for the risk of AKI in sepsis patients, and can assist other major indicators to improve the predictive value of AKI in sepsis patients.

Objective:To explore the clinical efficacy of Shexiang Baoxin pill in patients with unstable angina pectoris(UAP)and type 2 diabetes mellitus(T2DM)using meta-analysis.Methods:We searched the databases including Pubmed,Web of Science,EMbase,EBSCO,Cochrane,CBM,CNKI and Wanfang for randomized controlled trials(RCTs)about the therapeutic effect of Shexiang Baoxin pill on patients with UAP and T2DM from the establish-ment to January 20th,2023.RevMan 5.3 software was used to perform meta-analysis to investigate the effect of Shexiang Baoxin pill on angina improvement and blood glucose fluctuation in patients with UAP and T2DM.Results:Six eligible literatures were included,including 346 patients in Shexiang Baoxin pill group and control group respec-tively.The results of meta-analysis showed that compared to participants in control group,those in Shexiang Baox-in pill group had significantly higher clinical overall efficiency(OR=3.13,95％CI 2.01～4.89,P＜0.001),and significantly lower angina attack frequency(MD=-0.66,95％CI-0.79～-0.52,P＜0.001),duration of angi-na(MD=-3.10,95％CI-4.11～-2.09,P＜0.001),and 2-hour postprandial blood glucose(MD=-1.79,95％CI-2.00～-1.57,P＜0.001).Conclusion:Shexiang Baoxin pill could improve clinical overall efficiency,an-gina attack frequency and duration,and reduce 2-hour postprandial blood glucose in patients with unstable angina pectoris and type 2 diabetes mellitus.

Objective To analyze the impact of the interval time(IT)between prostate biopsy(PB)and radical prostatectomy(RP)on the perioperative safety and prognostic efficacy of prostate cancer patients.Methods A retrospective analysis was performed on 87 patients who underwent extraperitoneal laparoscopic RP at our hospitals during Jun.2022 to Nov.2024.The patients were divided into the IT ≤2 weeks group(n=42)and the IT ≥4 weeks group(n=45)according to the interval between PB and RP.Baseline data,perioperative indicators,postoperative inflammatory factors,postoperative pathological results,urinary continence,and complication rates were compared between the two groups.Results No statistically significant differences were observed between the two groups in baseline information,operation time,intraoperative blood loss,intraoperative transfusion rate,postoperative hospital stay,catheter removal time,inflammatory factors and complications(P＞0.05).Pathological results showed no significant differences in cancer tissue proportion,positive rate of lymph node,positive rate of surgical margins,and postoperative Gleason scores(P＞0.05).However,the IT ≤2 weeks group exhibited significantly fewer cases of perineural invasion(25 vs.36,59.52％vs.80.00％)and vascular invasion(5 vs.12,11.90％vs.26.67％)compared to the IT≥4 weeks group(P＜0.05).There were no significant differences in postoperative urinary control rate and prostate-specific antigen(PSA)level between the two groups(P＞0.05).Conclusion Radical prostatectomy performed ≤2 weeks after prostate biopsy demonstrates better safety and prognosis.