[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。

The Type III Secretion System (T3SS) serves as a pivotal virulence apparatus for numerous Gram-negative bacterial pathogens, enabling them to infect both animal and plant hosts. Functioning as a molecular syringe, the T3SS directly translocates bacterial effector proteins from the bacterial cytoplasm into the interior of eukaryotic host cells. These effectors are central weapons that precisely manipulate a wide spectrum of host cellular physiological processes, ranging from cytoskeletal dynamics to immune signaling, to establish a favorable niche for bacterial survival and proliferation. Among the diverse arsenal of T3SS effectors, the YopJ family constitutes a critical group of virulence factors. Members of this family are characterized by a conserved catalytic triad structure—a hallmark of the CE clan of cysteine proteases that has been evolutionarily repurposed to confer acetyltransferase activity. A defining and intriguing feature of these enzymes is their stringent dependence on a host-derived eukaryotic cofactor, inositol hexakisphosphate (IP₆), for allosteric activation. This requirement acts as a sophisticated molecular safeguard, ensuring enzymatic activity only within the appropriate host environment, thereby preventing detrimental effects on the bacterium itself. While seminal studies on individual members such as Yersinia’s YopJ and Salmonella’s AvrA have provided deep mechanistic insights, a systematic and integrative understanding of the structure-function relationships across the entire family remains fragmented. Key questions persist regarding how a conserved catalytic core has diverged to recognize distinct host substrates in different kingdoms of life. To address this gap, this article provides a systematic review of the YopJ family, focusing on three interconnected aspects: their structural features, their catalytic mechanism, and their divergent immunosuppressive strategies in animal versus plant hosts. By conducting a comparative analysis of the sequences and resolved three-dimensional structures of three representative members (e.g., HopZ1a, PopP2, AvrA), we elucidate regions of significant variation embedded within the conserved core catalytic architecture. These variable regions, often involving surface loops and substrate-binding interfaces, are crucial determinants of target specificity and functional specialization. The functional divergence of this effector family is most apparent when comparing their modes of action in different hosts. In animal hosts, YopJ-family effectors primarily sabotage innate immune signaling pathways. They achieve this by acetylating key serine and threonine residues within the activation loops of critical kinases in the MAPK and NF‑κB pathways. This post-translational modification blocks the phosphorylation and subsequent activation of these kinases, leading to potent suppression of inflammatory cytokine production. Conversely, in plant hosts, the strategy broadens to dismantle the two-tiered plant immune system. YopJ homologs target a more diverse set of substrates, including immune-associated receptor-like cytoplasmic kinases (RLCKs), microtubule networks via tubulin acetylation (which disrupts cellular trafficking and signaling), and transcription factors central to defense gene regulation. This multi-target approach effectively suppresses both Pattern-Triggered Immunity (PTI) and Effector-Triggered Immunity (ETI). In conclusion, this synthesis aims to deepen the mechanistic understanding of YopJ family-mediated pathogenesis by integrating structural biology with cellular function across host kingdoms. Elucidating the precise molecular basis for substrate selection—how conserved platforms achieve target diversity—is a major frontier. Furthermore, this knowledge provides a vital theoretical foundation for developing novel anti-virulence strategies. Targeting the conserved IP₆-binding pocket or the catalytic acetyltransferase activity itself represents a promising avenue for designing broad-spectrum inhibitors that could disarm this critical family of bacterial effectors, potentially offering new therapeutic approaches against a range of pathogenic bacteria.

Objective To develop a diagnostic model combining the CT angiography(CCTA)-derived myocardial radiomics signatures with the CT-derived fractional flow reserve(CT-FFR)based on coronary CCTA and investigate the diagnostic accuracy of the hybrid model for hemodynamically significant coronary artery disease(CAD).Methods The patients presenting stable angina pectoris,diagnosed with CAD,and clinically referred for CCTA examination and invasive coronary angiography were prospectively recruited.Radiomics features of the left ventricular myocardium were extracted from the three main perfusion territories demarcated according to the coronary blood supply.The extracted features were first selected by the minimum redundancy maximum relevance feature ranking method.A least absolute shrinkage and selection operator Logistic regression algorithm with leave-one-out cross-validation was then employed to construct a radiomics model.The CT-FFR value was generated for each blood vessel.The area under the receiver operating characteristics curve(AUC_ROC),sensitivity,and specificity were adopted to evaluate the performance of each model against the reference standard invasive coronary angiography/FFR.Results A total of 70 patients[42 men and 28 women;(61±10) years old] were included in this study and complemented CCTA examination,with 175 vessels and the corresponding myocardial territories undergoing invasive coronary angiography/FFR.A total of 1 656 specific radiomics parameters were extracted,from which 14 features were selected to establish the radiomics model.The AUC_ROC,sensitivity,and specificity were 0.797(95%CI=0.732-0.861),77.1%,and 73.7%for the radiomics model,0.892(95%CI=0.841-0.943),81.4%,and 88.8%for the CT-FFR model,and 0.928(95%CI=0.890-0.965),83.3%,and 88.4%for the hybrid model,respectively.The hybrid model outperformed the radiomics model and CT-FFR alone(P=0.040).Conclusions The radiomics signatures of the vessel-related myocardium from CCTA could provide incremental value to the diagnostic performance of CT-FFR and improve vessel-specific ischemia detection.The hybrid model combining CT-FFR with radiomics signatures is potentially feasible for improving the diagnostic accuracy for hemodynamically significant CAD.
Coronary Angiography/methods* ; Tomography, X-Ray Computed ; Humans ; Hemodynamics ; Coronary Artery Disease/diagnostic imaging* ; Male ; Female ; Middle Aged ; Aged ; Radiomics ; Angina Pectoris/diagnostic imaging* ; China ; Image Processing, Computer-Assisted ; Coronary Vessels/diagnostic imaging*

Objective:To explore the risk factors of adverse events during the perioperative period of transurethral resection of bladder tumor(TURBT)in bladder cancer patients with coronary atherosclerotic heart disease(CAD).Methods:We retrospectively analyzed the clinical data of bladder cancer patients who underwent TURBT in Beijing Anzhen Hospital from June 2022 to September 2024.All patients with bladder cancer and CAD underwent coronary computed tomography angiography(CCTA)for diagnosis and assessment of CAD before surgery.Based on the CCTA results,the patients with bladder cancer and CAD were divided into two groups:those with mild to moderate coronary stenosis and those with severe coronary stenosis.The severe coronary stenosis group was further divided into two subgroups based on whether they received low-molecular-weight heparin(LMWH)bridging therapy or continued their anti-platelet treatment before surgery.Perioperative anticoagulation and antiplatelet strategies were adjusted according to the opinions of the specialists.The incidence of adverse events within 30 days postoperative-ly was followed up and analyzed.Results:A total of 80 bladder cancer patients with CAD who underwent TURBT were included in the study.Among the 80 patients with CAD,55(68.8％)had mild to moder-ate coronary stenosis,and 25(31.2％)had severe coronary stenosis.Compared with those had mild to moderate coronary stenosis,the patients who had severe coronary stenosis had a higher incidence of post-operative bleeding and pulmonary embolism,although the differences were not statistically significant(P＞0.05).However,the incidence of postoperative myocardial infarction was significantly higher in the patients who had severe coronary stenosis(P=0.034).Among the patients with severe coronary stenosis,8(32.0％)received LMWH bridging therapy before TURBT,and 17(68.0％)continued their previous antiplatelet treatment.Compared with those who continued antiplatelet treatment,the patients who re-ceived LMWH bridging therapy had a higher incidence of postoperative bleeding and pulmonary embo-lism,although the differences were not statistically significant(P＞0.05).However,the incidence of postoperative myocardial infarction was significantly higher in the LMWH bridging group(P=0.032).Conclusion:Patients with mild-to-moderate coronary stenosis demonstrate relatively low perioperative risk during TURBT procedures and may safely undergo TURBT following antiplatelet therapy discontinuation.Conversely,those with severe coronary stenosis exhibit significantly higher perioperative risk and require intensive monitoring.In bladder cancer patients with concomitant severe coronary stenosis,perioperative LMWH bridging therapy is associated with increased myocardial infarction risk,whereas continued anti-platelet therapy does not elevate postoperative bleeding risk.Current evidence therefore supports maintai-ning antiplatelet therapy in these patients,with appropriate bleeding risk assessment.

Aim To study the protective effect of the silibinin derivative Sil-1 on acute myocardial ischemia in SD rats and its mechanism of action.Methods Af-ter 18 hours of oxygen-glucose deprivation and treat-ment of H9c2 cells,the protective effect of Sil-1 on rat cardiomyocytes was examined.SD rats were treated 30 minutes before surgery,followed by 24 h ligation of the left anterior descending coronary artery.The cardiopro-tective effects of Sil-1 and its mechanisms for improving myocardial ischemic injury were investigated using pro-teomics technology.Results In vitro,compared with the control group,the activity of H9c2 cells in the mod-el group showed reduced cell viability,increased dead cells,elevated ROS and higher levels of LDH and in-flammatory cytokines TNF-α,IL-1β and IL-6 in the culture medium.Sil-1 could improve the above condi-tions to different degrees.In vivo,compared with the control group,rats in the model group showed signifi-cantly higher T waves on electrocardiogram,significant ischemic areas in the heart section,disorganized ar-rangement of cardiomyocytes,increased inflammatory factor infiltration and elevated CK,CK-MB,LDH and inflammatory factors TNF-α,IL-6 and IL-1β.Besides,NF-κB phosphorylation levels in myocardial tissue in-creased.Sil-1 improved the above conditions to varying degrees.The results of proteomics showed that 90 pro-teins were found between the control vs model group and the Sil-1 vs model group,and KEGG enrichment a-nalysis showed that MAPK,chemokines,VEGF and other signaling pathways were abundant.Western blot results showed that Sil-1 blocked the phosphorylation of ERK,JNK and p38 MAPK.Conclusions Sil-1 inhib-its the MAPK pathway by blocking the phosphorylation of JNK,ERK,and p38 MAPK,and achieves a protec-tive effect on rats with acute myocardial infarction.

Objective:To construct a structural equation model for neck work-related musculoskeletal disorders (WMSDs) in the footwear industry and analyze the mediating effect of fatigue in the model.Methods:From November 2018 to December 2019, stratified cluster sampling was adopted to select all the workers (3565 people) from 7 footwear enterprises in Fujian Province as the research subjects. The incidence of WMSDs, fatigue and work-related condition were investigated by using the Chinese version of the Musculoskeletal Disorders Questionnaire. A structural equation model of individual factors, work type, work posture, work organization factors, and fatigue on neck WMSDs was constructed to analyze the mediating effect of fatigue among them.Results:The incidence rate of WMSDs in the neck of footwear workers was 39.6% (1413/3565) , and the incidence rate of neck fatigue was 46.6% (1662/3565) .The final structural equation model was constructed with a χ2/ df of 9.927, a goodness-of-fit index of 0.961, an adjusted goodness-of-fit index of 0.946, and a root mean square error of approximation of 0.050. Except for the χ2/ df, all other fit indicators met the standard. Individual factors and work posture factors had a direct effect on neck WMSDs, with standardized path coefficients of 0.101 and 0.077, respectively ( P<0.05) . Individual factors, work type, work posture, and work organization had indirect effects on neck WMSDs through fatigue, the standardized path coefficients of indirect effects were 0.163, 0.090, 0.206, 0.105, respectively, and the standardized path coefficients of the total effect were 0.264, 0.090, 0.282, and 0.105 respectively ( P<0.05) . The indirect effects of individual factors and work posture factors on neck WMSDs through fatigue accounted for 61.74% and 73.05% of the total effects, respectively. The standardized path coefficient of fatigue on WMSDs was 0.689 ( P<0.001) , with the highest coefficient among all paths. Conclusion:Individual factors, work type, work posture, and work organization factors are important influencing factors in the occurrence and development of neck WMSDs in the footwear industry, and fatigue plays an important mediating role in them.

Non-small cell lung cancer (NSCLC), as the predominant histological subtype of lung cancer, accounts for approximately 85% of all lung cancer cases. In recent years, immune checkpoint inhibitors (ICIs), represented by programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors, have achieved breakthrough advancements in patients with driver gene-negative NSCLC. They have been established as a key component of first-line treatment regimens and have significantly improved clinical outcomes. However, limited clinical evidence has emerged showing the phenomenon of histological transformation from NSCLC to small cell lung cancer (SCLC) in patients experiencing disease progression after ICIs monotherapy or combination therapy. Systematic research data on the clinical characteristics, molecular biological basis, and subsequent treatment strategies for such transformation events are currently lacking. This article reports a case of SCLC transformation occurring in a patient with KRAS-mutated lung adenocarcinoma after 16 months of ICIs combination therapy and provides a systematic review of 22 similar published cases. The study demonstrates that small cell transformation is a critical mechanism of immunotherapy resistance, and transformed patients exhibit poor prognosis. The research emphasizes the importance of dynamic monitoring of neuron-specific enolase (NSE) and standardized repeat biopsies during treatment, providing a basis for clinical practice. This aids in enhancing the recognition and management capabilities for this rare histological transformation, ultimately improving patient outcomes.
Humans ; Immune Checkpoint Inhibitors/therapeutic use* ; Lung Neoplasms/immunology* ; Carcinoma, Non-Small-Cell Lung/immunology* ; Small Cell Lung Carcinoma/genetics* ; Male ; Middle Aged ; Female

Combined small cell lung cancer (CSCLC) is a cancer that mixes small cell lung cancer (SCLC) with non-small cell lung cancer (NSCLC) components according to the World Health Organization's 2015 New Pathologic Classification of Lung Cancer. Composed of a mixture of SCLC and NSCLC components, CSCLC is classified as a subtype of SCLC in neuroendocrine tumors. Currently, research on SCLC mainly focuses on single-component pure SCLC, with relatively few studies on CSCLC, which is clinically rare and has no standardized treatment protocols and lacks a unified perception of the clinicopathological features and prognostic predictive indexes of CSCLC. Further observation of efficacy and prognosis is needed. We report the treatment course of a case of CSCLC and provide a literature review of the current status of research on CSCLC.
.
Humans ; Small Cell Lung Carcinoma/diagnostic imaging* ; Lung Neoplasms/diagnostic imaging* ; Male ; Middle Aged

OBJECTIVE: To explore the mechanism of Dihuang Yinzi (DHYZ) in the treatment of Alzheimer's disease (AD) by integrating metabolomics and experimental verification. METHODS: Forty-eight male APP/PS1 mice were divided into model, high- (DHYZ-H), medium- (DHYZ-M), and low-dose DHYZ (DHYZ-L) groups (12 mice per group) according to a random number table. Mice in DHYZ groups were gavaged with DHYZ 6.34, 12.68, and 25.35 g/(kg·d), respectively. Twelve C57BL/6 mice were gavaged with distilled water as the blank group. Metabolomics was used to analyze differential metabolites in the brains of mice. Morris water maze test was used to detect the memory abilities of mice. The hematoxylin-eosin staining and transmission electron microscopy were used to observe the general morphology and ultrastructure of neurons. The enzyme-linked immunosorbent assay was used to detect the levels of superoxide dismutase (SOD), reactive oxygen species (ROS), and amyloid β -protein 1-42 (A β_1-42). The real-time quantitative polymerase chain reaction was used to detect the mRNA expressions of density-regulated protein 1 (DRP1), fission 1 (FIS1), mitofusin-1 (MFN1), and optic atrophy protein 1 (OPA1). Western blot was used to detect the protein expressions of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP response binding protein (CREB), brain-derived neurotrophic factor (BDNF), synapsin 1 (SYN1), synaptophysin (SYP), and postsynaptic density protein 95 (PSD95). RESULTS: A total of 82 differential metabolites were identified in the brains of APP/PS1 mice, among which 7 differential metabolites could be regulated by DHYZ. After DHYZ intervention, the memory abilities of mice significantly increased (P<0.05 or P<0.01), the number of synapses and neurons in the hippocampus increased, and the mitochondrial morphology and structure were relatively intact. The DHYZ groups exhibited a significant reduction in hippocampal ROS and A β_1-42 levels, along with a significant elevation in SOD level (P<0.05 or P<0.01). The mRNA expressions of DRP1 and FIS1 were reduced, while the mRNA expressions of MFN1 and OPA1 were increased after DHYZ treatment (P<0.05 or P<0.01). The cAMP/PKA/CREB-BDNF pathway was activated, and the expressions of SYN1, SYP and PSD95 proteins were significantly increased in the DHYZ-H group (P<0.05 or P<0.01). CONCLUSIONS DHYZ could improve mitochondrial dynamics and synaptic plasticity in APP/PS1 mice, inhibit oxidative stress, and thereby enhancing learning and memory abilities in APP/PS1 mice. Its mechanism might be related to activation of the cAMP/PKA/CREB-BDNF signaling pathway.
Animals ; Brain-Derived Neurotrophic Factor/metabolism* ; Male ; Cyclic AMP Response Element-Binding Protein/metabolism* ; Brain/drug effects* ; Metabolomics ; Mice, Inbred C57BL ; Neuronal Plasticity/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Cyclic AMP-Dependent Protein Kinases/metabolism* ; Cyclic AMP/metabolism* ; Reactive Oxygen Species/metabolism* ; Amyloid beta-Protein Precursor/metabolism* ; Mice, Transgenic ; Mice ; Amyloid beta-Peptides/metabolism* ; Signal Transduction/drug effects* ; Alzheimer Disease/drug therapy* ; Superoxide Dismutase/metabolism*

Objective:To analyze the efficacy, influencing factors, and risk warning of multi-plane low-temperature plasma radiofrequency ablation（MLT-RFA） in the treatment of obstructive sleep apnea hypopnea syndrome（OSAHS）. Methods:A total of 118 OSAHS patients admitted from October 2022 to June 2024 were selected as the research subjects. They were divided into mild group（n=46）, moderate group（n=52）, and severe group（n=20） according to the severity of their condition. MLT-RFA treatment was used for all patients. After surgery, the results of polysomnography（PSG） and the changes in the Calier Sleep Apnea Quality of Life Index（SAQLI） were observed before and after treatment. The incidence of complications after treatment was recorded, and the clinical efficacy of the patients was evaluated. At the same time, they were divided into a treatment effective group（n=106） and an ineffective group（n=12） according to their effects. The general clinical data of the two groups were compared, and binary logistics regression analysis was conducted to identify independent factors that affect treatment efficacy and construct a model. ROC curve analysis was used to evaluate the diagnostic efficacy of the model. Results:The treatment effectiveness rate of the mild group was 93.48%, the moderate group was 90.38%, and the severe group was 80.00%. There was no statistically significant difference in the treatment effectiveness rate among the three groups（P>0.05）. The AHI of the mild group, moderate group, and severe group increased sequentially, while the LSaO2and SAQLI scores decreased sequentially. After treatment, the AHI of all three groups decreased compared to before treatment, while the LSaO2and SAQLI scores increased compared to before treatment, and the differences were statistically significant（P<0.05）. The pre-treatment AHI of the effective group was lower than that of the ineffective group, and the pre-treatment LSaO2and SAQLI were higher than those of the ineffective group, with statistically significant differences（P<0.05）. Pre-treatment LSaO2and pre-treatment SAQLI are independent factors affecting the efficacy of MLT-RFA（P<0.05）. The AUC of pre-treatment LSaO2, pre-treatment SAQLI, and combined prediction were 0.907, 0.763, and 0.947, respectively, with sensitivities of 0.896, 0.840, and 0.917, and specificities of 0.833, 0.667, and 0.887, respectively. Conclusion:MLT-RFA has a significant effect on the treatment of OSAHS, and the AHI, LSaO2, and SAQLI of patients before treatment can predict the treatment effect, with LSaO2 and SAQLI being independent influencing factors. The combinerd prediction model exhibits high diagnostic efficiency, sensitivity, and specificity.
Radiofrequency Ablation/methods* ; Plasma Gases ; Sleep Apnea, Obstructive/surgery* ; Polysomnography ; Postoperative Complications/epidemiology* ; Quality of Life ; Severity of Illness Index ; Treatment Outcome ; Humans