[摘 要] 目的：探讨复发/转移性鼻咽癌（NPC）接受含PD-1单抗免疫治疗的临床特征和预后影响因素。方法：回顾性分析2019年3月至2024年7月期间南部战区总医院确诊的95例NPC患者的临床资料和外周血生化及免疫学指标。预后分析采用Kaplan-Meier曲线，组间比较使用Log-rank检验，采用Cox比例风险模型进行单因素和多因素分析。结果：95例患者中男性81例，女性14例，中位年龄49.72岁（16~74岁），Ⅳ期91例（95.79%），所有患者均采用免疫治疗，联合或不联合化疗方案治疗，中位无进展生存期（mPFS）为10.5个月，客观缓解率（ORR）70.53%，疾病控制率（DCR）89.47%，接受含铂治疗方案患者PFS相对更长，且差异有统计学意义。紫杉醇 + 顺铂 + 氟尿嘧啶（TPF）对比吉西他滨 + 顺铂（GP）和紫杉醇 + 顺铂（TP）显示出更长的PFS，但差异无统计学意义。不同PD-1单抗治疗组间的PFS未显示出有统计学意义的差异。单因素及多因素Cox回归分析结果显示，肿瘤复发状态、初始血浆EBV感染状态、治疗周期数、基线外周血SII是复发/转移性NPC患者接受PD-1抑制剂治疗疗效预测的独立相关因素（均P < 0.05），并且非复发患者、初始血浆EBV DNA阳性、接受 ≥ 4治疗周期、基线外周血SII < 772.81的患者接受PD-1抑制剂治疗预后相对更好。结论：在接受PD-1抑制剂治疗的复发/转移性NPC患者中，非复发患者、初始血浆EBV DNA阳性、≥ 4治疗周期且外周血SII < 772.81者PFS相对更长，可早期识别免疫治疗效果不佳患者并精准干预。

Stroke is the leading cause of death and disability among adults in China， and its common complications include digestive system abnormalities， cognitive impairment， depression， stroke-associated pneumonia， and hemiplegia. The combination of traditional Chinese and Western medicine has great potential in treating post-stroke complications. Xinglou Chengqitang （XLCQT） is a representative prescription of alleviating the disease in the upper part by treating the lower part. It has definite therapeutic effect and high safety. Clinically， XLCQT is often used to treat stroke and its complications. However， the quantity and quality of clinical trials of XLCQT in treating post-stroke complications need to be improved. Additionally， since the basic research is weak， the material basis and multi-target mechanism for the efficacy of this prescription are unknown. This article reviews XLCQT in terms of the pharmacodynamic basis， medicinal properties， safety evaluation， and progress in clinical research and mechanisms in treating post-stroke complications. This article summarizes 22 key active ingredients of XLCQT in treating acute stroke complicated with syndrome of phlegm heat and fu-organ excess. Among these key active ingredients， resveratrol， kaempferol， luteolin， chrysoeriol， apigenin， （+）-catechin， and adenosine have good pharmacokinetic properties and high bioavailability. The mechanisms of XLCQT in treating post-stroke complications are complex， including inflammatory response， brain-gut axis， hypothalamic-pituitary-adrenal （HPA） axis， intestinal flora， neurotrophic factors， autophagy， oxidative stress， and free radical damage. This review helps to deeply understand the pharmacodynamic basis and mechanisms of XLCQT in treating post-stroke complications and provides a theoretical basis for the clinical application of XLCQT against post-stroke complications and the development of drugs.

OBJECTIVE To assess the bleeding risk signals associated with the concomitant use of direct oral anticoagulants （DOACs） and triazole antifungals， and to provide pharmacovigilance evidence for the safety evaluation and monitoring of combined clinical use. METHODS Adverse event reports involving the concomitant use of DOACs and triazole antifungals were extracted from the US FDA Adverse Event Reporting System （FAERS） from the first quarter of 2004 to the third quarter of 2025. Nine bleeding-related preferred terms （PTs） were selected. The Ω shrinkage measure， additive model， multiplicative model， and combined risk ratio method were employed to detect drug-drug interaction signals. The strength of positive signals was further analyzed based on the Ω shrinkage measure. RESULTS A total of 790 adverse event reports involving the concomitant use of DOACs and triazole antifungals were included， among which 229 reports involved nine bleeding-related PTs. A total of 13 signals were consistently identified as posit ive by all four methods. These signals involved six drug combinations： apixaban-fluconazole， apixaban-posaconazole， rivaroxaban-itraconazole， dabigatran etexilate-fluconazole， apixaban-voriconazole， and dabigatran etexilate-itraconazole. The Ω shrinkage measure showed that the apixaban-posaconazole combination exhibited stronger signals for bleeding （ Ω ＝2.73， Ω 025 ＝2.05） and hemoptysis （ Ω ＝2.17， Ω 025 ＝0.83）； the apixaban-fluconazole combination exhibited stronger signals for hematoma （ Ω ＝2.30， Ω 025 ＝1.47） and hematuria （ Ω ＝1.71， Ω 025 ＝0.74）； the rivaroxaban-itraconazole combination exhibited stronger signals for epistaxis （ Ω ＝2.01， Ω 025 ＝0.90） and hematoma （ Ω ＝1.93， Ω 025 ＝0.42）； no positive Ω signals were observed for intracranial hemorrhage or upper gastrointestinal hemorrhage. CONCLUSION S This study suggests that the concomitant use of DOACs and triazole antifungals may increase the risk of bleeding-related events， with differences in signal strength and signal distribution across various drug combinations. In clinical practice， particular attention should be paid to the concomitant use of apixaban or rivaroxaban with strong cytochrome P450 3A4 or P-glycoprotein inhibitors such as posaconazole and itraconazole. For other DOAC-triazole antifungal combinations， close monitoring for bleeding-related manifestations and timely adjustment of anticoagulation or antifungal regimens are also warranted.

[摘 要] 目的：探究环状RNA（circRNA）调控舌鳞状细胞癌（TSCC）顺铂（CDDP）耐药的机制。方法：本研究以TSCC化疗敏感CAL27细胞与耐药CAL27-res细胞为研究对象，RT-qPCR检测两种细胞内hsa_circ_0034762的表达量差异，流式细胞术检测细胞凋亡率，Western blotting检测自噬相关蛋白p62及LC3-Ⅱ/LC3-Ⅰ比值，透射电镜观察自噬小体的数量，双萤光素酶报告实验检测hsa_circ_0034762与miR-17-3p的结合关系，荧光原位杂交实验检测二者在细胞中的共定位，敲低hsa_circ_0034762联合抑制miR-17-3p进行功能回复实验。结果：相比亲本化疗敏感细胞，TSCC耐药细胞CAL27-res自噬水平显著提升，表现为自噬小体数量增加、LC3-Ⅱ/LC3-Ⅰ比值升高及p62蛋白表达降低。hsa_circ_0034762在TSCC耐药组织及CAL27-res细胞中高表达。敲低hsa_circ_0034762后，CAL27-res细胞凋亡率升高，自噬小体数量减少，p62蛋白表达增加，LC3-Ⅱ/LC3-Ⅰ比值降低（均P < 0.05）。双萤光素酶报告实验与荧光原位杂交实验发现hsa_circ_0034762与miR-17-3p存在靶向结合作用。抑制miR-17-3p可部分逆转hsa_circ_0034762敲低所致的促凋亡及抑制自噬效应。结论：hsa_circ_0034762在TSCC耐药细胞及组织中高表达。敲低hsa_circ_0034762可能通过miR-17-3p抑制细胞自噬并促进细胞凋亡，从而降低TSCC细胞的化疗耐药性。

This studyobtained the proteins of virulence factors EsxA and EsxB from Mycobacterium haemophilum and explored their interactions both in vitro and in vivo.The aim was to lay a foundation for further analysis of the functional mechanisms of EsxA and EsxB,and to further the development of drugs targeting Mycobacterium haemophilum.On the basis of bioinformatics analysis of the virulence factors EsxA and EsxB from Mycobacterium haemophilum,we performed molecular cloning,using Mycobacterium haemophi-lum as a template to construct recombinant plasmids EsxA-pGl01,EsxB-pGl01,and EsxB-pET-29b.The proteins of EsxA,EsxB,and their complex were expressed with a prokaryotic system,then purified through nickel-affinity chromatography and gel filtration chromatography.Intracellular colocalization was determined through fluorescence colocalization.Prokaryotic expression systems for EsxA,EsxB,and their complex were successfully constructed,and purified proteins were obtained.Fluorescence colocalization indi-cated that EsxA and EsxB interacted in vivo.In vivo fluorescence colocalization and in vitro complex formation suggested that EsxA and EsxB interacted both intracellularly and extracellularly.Our findings lay a foundation for studying the pathogenic mechanisms of the virulence factors EsxA and EsxB in Mycobacterium haemophilum,and performing structural analysis of their complex.

This study investigated the influence of Leptospira interrogans infection on the expression of the autophagy-related proteinsmyosin-like BCL2 interacting protein(Beclin-1),microtubule-associated proteinlight chain 3B(LC3B),and sequestosome 1(P62).C3H/HeJ mice were infected with L.interrogansserovar stain Lai for construction of an animal model of leptospirosis.Silver strain-ing was used to detect leptospires in lung,liver,and kidney tissues of L.interrogans-infected mice.Histological changes in these tis-sues were detected with hematoxylin and eosin(HE)staining.The morphology of autophagosomes and leptospires in the lung,liver,and kidney tissues of L.interrogans-infected micewere determined through transmission electron microscopy.Expression of the autophagy-related proteins Beclin-1,LC3B,and P62 in the lung,liver,and kidney tissues of L.interrogans-infected C3H/HeJ mice was measured with immunohistochemistry.In these tissues,silver straining examination revealed leptospires.These tissues also showed histopathological changes typical of leptospirosis,such as pulmonary hemorrhage,extensive hepatocyte necrosis,both glomerular and tubular necrosis,and inflammatory cell infiltration;moreover,the leptospires were surrounded by autophagosomes.Immunohistochemi-cal examination indicated elevated expression of both Beclin-1 and LC3B in the lung,liver and kidney tissues of L.interrogans-infected mice(P<0.05),whereas the P62 level was significantly diminished in every tissue sample during L.interrogans infection(P<0.05).These results indicated that autophagy is activated during L.interrogans infection in the lung,liver,and kidney tissues of C3H/HeJ mice.

Objective To investigate the expression changes of serum circRNA membrane bound O-acyltransferase 2(circRNA MBOAT2)and circRNA recombinant actinin 4(circRNA ACTN4)in patients with cholangiocarcinoma and their relationship with prognosis.Methods 96 patients with cholangiocarcinoma treated at the First Hospital of Handan City from January 2020 to January 2022 in Department of Hepatobiliary Surgery were regarded as as the cholangiocarcinoma group.Additionally,85 patients with intraductal stones and 90 healthy volunteers were collected as the stone group and control group,respectively.Quantitative real-time reverse transcription PCR(qRT-PCR)was applied to detect the expression levels of circRNA MBOAT2 and circRNA ACTN4.χ2 test was applied to analyze the relationship between circRNA MBOAT2 and circRNA ACTN4 and clinical pathological features.Pearson was applied to analyze the correlation between circRNA MBOAT2 and circRNA ACTN4 in patients with cholangiocarcinoma.ROC was applied to analyze the diagnostic value of circRNA MBOAT2 and circRNA ACTN4 in the occurrence of cholangiocarcinoma.COX was applied to analyze the influencing factors of poor prognosis in patients with cholangiocarcinoma.Kaplan-Meier method was applied for survival analysis.Results circRNA MBOAT2(1.24±0.38)and circRNA ACTN4(1.27±0.42)in cholangiocarcinoma group were higher than those in stone group(1.02±0.31,1.05±0.34)and control group(0.83±0.24,0.78±0.21),and the stone group was higher than that in control group,with statistically significance(t=5.016～14.025,all P<0.05).There was a positive correlation between circRNA MBOAT2 and circRNA ACTN4 in patients with cholangiocarcinoma group(r=0.428,P<0.05).Combined diagnosis of MBOAT2 and ACTN4 was better than single diagnosis of cholangiocarcinoma(Z=4.063,4.004,all P<0.05);circRNA MBOAT2 and circRNA ACTN4 were correlated with clinical staging and lymph node status(t=5.091～5.984,all P<0.05).Positive lymph node status and elevated levels of circRNA MBOAT2 and circRNA ACTN4 were independent risk factors for mortality(HR=1.527,1.582,1.727,all P<0.05).The cumulative survival rate of patients with high expression of circRNA MBOAT2(23.40%vs 46.94%)and circRNA ACTN4(24.00%vs 47.83%)was lower than that of patients with low expression(χ2=5.809,5.946,all P<0.05).Conclusion The serum levels of circRNA MBOAT2 and circRNA ACTN4 increase with the progression of the disease,and the combination of the two has certain value in diagnosing the occurrence of cholangiocarcinoma.

Objective To investigate the occurrence of liver function abnormalities in patients with follicular lymphoma(FL)treated with the G-CDOP regimen in the real world.Methods Using the hospital information system,a retrospective collection of clinical data was conducted on inpatients diagnosed with FL and treated with at least four courses of the G-CDOP regimen in the Department of Hematology,the First Affiliated Hospital of Soochow University from September 2021 to August 2023.The analysis focused on the incidence,severity,and types of liver function abnormalities,as well as the timing of these occurrences in relation to medication use and other relevant clinical characteristics.Results The study encompassed a total of 55 patients with FL,out of which 30 patients encountered liver function abnormalities during the G-CDOP regimen treatment,yielding an incidence rate of 54.5%.There were 23 cases(41.8%)of grade 1,3 cases(5.5%)of grade 2,and 4 cases(7.3%)of grade 3 liver function abnormalities.Among them,12 cases(21.8%)were hepatocellular injury type,while the cholestasis type was observed in 4 cases(7.3%),and the mixed type was found in 14 cases(25.5%).Liver function abnormalities appeared in 21 patients(38.2%)during the first cycle of the G-CDOP regimen treatment,5 patients(9.1%)in the second cycle,and 1 patient(1.8%),2 patients(3.6%),and 1 patient(1.8%)in the third,fourth,and fifth cycles.Conclusion The G-CDOP regimen has the potential to impact liver function indicators in FL patients,but most are mild and reversible.However,there are also cases of severe liver injury that need to attract clinical attention.

Purpose To analyze the value of a deep learning(DL)radiomics model based on dynamic contrast-enhanced MRI images in predicting the expression of Ki-67 status in breast cancer.Materials and Methods A retrospective analysis of 152 breast cancer patients confirmed by pathological results at Guangdong Women and Children Hospital,MRI images and clinical pathological data were reviewed,and based on postoperative immunohistochemistry results,the images of the high and low expression groups of Ki-67 were randomly sampled in a ratio of 8∶2 to form a training set of 122 cases and a validation set of 30 cases.Single-factor and multi-factor Logistic regression analyses of clinical data were performed to select independent predictors of breast cancer expressing Ki-67 status.The ResNet-18 model was used as the basic model for DL feature extraction.Hand-crafted radiomic features and DL features were extracted.Eight machine learning models were constructed based on clinical features,hand-crafted radiomic features,DL features,and their combinations.The area under the receiver operating characteristic curve was used to evaluate the predictive performance of the models,and the best model was determined as the output model.Results The progesterone receptor status(OR=0.764,P=0.040)and human epidermal growth factor receptor-2 status(OR=1.187,P=0.046)were independent clinical predictors of breast cancer expressing Ki-67 status.The combined feature models demonstrated superior performance over the individual feature models,and the support vector machine algorithm had the highest prediction performance in the validation set,with an area under the curve of 0.847.Conclusion The DL radiomics model based on dynamic contrast-enhanced MRI images can effectively predict the expression of Ki-67 status in breast cancer.The support vector machine algorithm combined with feature model is the best,which can help the clinical diagnosis and treatment of breast cancer and prognosis evaluation.

Objective To explore the potential mechanism of Gegen qinlian decoction(GGQLD)containing serum in ameliorating nonalcoholic fatty liver disease(NAFLD)in human hepatocellular carcinoma HepG2 cells based on transcriptomics.Methods An in vitro model of NAFLD was constructed by free fatty acid(FFA)-induced fat accumulation in HepG2 cells,and cells were treated with different proportions of GGQLD and pioglitazone-containing serum.The lipid deposition in each group was detected by oil red O staining,and the lipid content in each group was evaluated by triglyceride level.Transcriptome technology was used to detect the differentially expressed genes between the intervention groups,and GO annotation analysis,KEGG enrichment analysis and protein interaction(PPI)network analysis were performed to verify the differentially expressed genes by RT-PCR.Results Compared with normal control group,the number of red lipid droplets in the model control group increased,and the triglyceride content increased significantly(P＜0.01).Compared with model control group,the content of red lipid droplets in the GGQLD medium dose group showed a decreasing trend,and the intracellular triglyceride content decreased significantly(P＜0.05).A total of 608 differentially expressed genes were identified by transcriptome analysis,of which 163 differentially expressed genes were up-regulated and 445 differentially expressed genes were down-regulated.GO enrichment analysis showed that the differentially expressed genes were mainly involved in the regulation of MAP kinase phosphatase activity.KEGG analysis showed that the differentially expressed genes were mainly involved in MAPK signaling pathway.RT-PCR results showed that GGQLD up-regulated the expression level of MAP2K6 mRNA and down-regulated the expression levels of FOSL1,CTSL,DUSP5,DUSP1,JUN,HSPA6,IL1A,IL11 and RELB mRNA,which may be mainly involved in MAPK signaling pathway.Conclusion GGQLD has the effect of improving NAFLD,which may be related to MAPK signaling pathway.