[摘 要] 目的：探索外周免疫功能状态与肺癌转移的关联，筛选可用于肺癌转移“正虚”评估的外周血免疫标志物。方法：回顾性分析2023年3月至2025年4月期间上海中医药大学附属市中医医院收治的肺癌患者治疗前的外周血免疫标志物，根据是否存在远处转移，将患者分为无转移组与转移组，比较两组间免疫细胞和细胞因子的表达差异。将单因素分析P < 0.05的外周血免疫指标纳入多因素二元Logistic回归模型，以识别肺癌转移的独立预测因素。结果：共纳入193例肺癌患者（无转移组101例，转移组92例），两组在性别、年龄、吸烟史、饮酒史、病理类型间的差异均无统计学意义（均P > 0.05）。单因素分析显示，无转移组与转移组间有多项免疫指标存在显著差异（均P < 0.05），包括：淋巴细胞计数，CD3+、CD4+、CD8+ T、CD19+ B细胞及CD3-CD16+56+ NK细胞绝对计数，Treg细胞、CD8+CD28+ Treg细胞、G-MDSC和CD3-CD16+CD56+dim NK细胞百分率，以及细胞因子IL-1β、IL-6和IL-10水平。将差异性指标行二元Logistic回归分析，提示外周血中Treg细胞和CD8+CD28+ Treg细胞百分率是肺癌发生远处转移的独立预测因素[OR = 1.193, 95% CI（1.047, 1.36）, P < 0.01; OR = 0.978, 95% CI（0.957, 0.999）, P < 0.05]。结论：外周血免疫功能紊乱是肺癌转移“正虚”的生物学基础，本研究以量化指标证实外周免疫功能状态与肺癌转移的相关性，为“正虚伏毒”和“肿瘤转移态”理论提供了实证。

Objective To investigate the clinical efficacy of percutaneous closure of foramen ovale guided by transthoracic echocardio-graphy with simply delivery sheath.Methods The clinical data of patients with patent foramen ovale underwent interventional closure and percutaneous closure guided by transthoracic echocardiography with simply delivery sheath in our hospital from January 2020 to December 2022 were analyzed retrospectively,the patients were divided into interventional closure group(40 cases)and simply delivery sheath group(39 cases).The operation time,incidence of surgical complications,and surgical success rates of patients in the two groups were compared.The closure effect were evaluated by ultrasound immediately after surgery.All the patients were followed up for 6 months after surgery to evaluate remission of the symptoms.Results The surgical success rate of simply delivery sheath group(100%)was higher than that of interventional closure group(90.0%),with statistically significant difference(P<0.05).The operation time of simply delivery sheath group was longer than that of interventional closure group,with statistically significant difference(P<0.05).One patient in the interventional closure group had small amount of pericardial effusion during the operation.Two patients had decreased blood pressure and slowed heart rate in simply delivery sheath group,and symptoms disappeared after treatment.There was no significant difference in the incidence of complications between the two groups(P>0.05).After 6-month follow-up,all occluders were in good position and no residual leakage was found.The symptoms of headache or dizziness disappeared in 28 patients in interventional closure group,significantly relieved in 8 patients;the symptoms of headache or dizziness disappeared in 30 patients in simply delivery sheath group,and significantly relieved in 9 patients.Conclusion Percutaneous closure for patent foramen ovale under the guidence of transthoracic echocardiography with simply delivery sheath is safe and feasible with satisfactory efficacy and higher successful rate without radiation hazard.It is worthy of clinical promotion.

Objective To investigate the therapeutic mechanism of Tujia medicine Toddalia asiatica alcohol extract(TAAE)for synovial pannus formation in rats with college-induced arthritis(CIA).Methods Sixty male SD rats were randomized into normal control group,CIA model group,TGT group,3 TAAE treatment groups at low,medium and high doses(n=10).Except for those in the normal control group,all the rats were subjected to CIA modeling using a secondary immunization method and treatment with saline,TGT or TAAE by gavage once daily for 35 days.The severity of arthritis was assessed using arthritis index(AI)score,and knee joint synovium pathologies were examined with HE staining.Serum levels of TNF-α,IL-6,and IL-1β were detected with ELISA;the protein expressions of PI3K,Akt,p-PI3K,p-Akt,VEGF,endostatin,HIF-1α,MMP1,MMP3,and MMP9 in knee joint synovial tissues were determined using Western blotting,and the mRNA expressions of TNF-α,IL-6,IL-1β,VEGF,HIF-1α,PI3K,and Akt were detected with RT-PCR.Results Treatment of CIA rat models with TAAE and TGT significantly alleviated paw swelling,lowered AI scores,and reduced knee joint pathology,neoangiogenesis,and serum levels of inflammatory factors.TAAE treatment obviously increased endostatin protein expression,downregulated p-PI3K,p-Akt,MMP1,MMP3,MMP9,VEGF,and HIF-1α proteins,and reduced TNF-α,IL-6,IL-1β,PI3K,Akt,VEGF,and HIF-1α mRNA levels in the synovial tissues,and these changes were comparable between high-dose TAAE group and TGT group.Conclusion TAAE can improve joint symptoms and inhibit synovial pannus formation in CIA rats by regulating the expressions of HIF-1α,VEGF,endostatin,MMP1,MMP3,and MMP9 via the PI3K/Akt signalling pathway.

Objective:To explore the effect and mechanism of c-Myc on regulating the expression of immune-related ligands in Y subtype small-cell lung cancer (SCLC) characterized by high expression of immune-related molecules.Methods:The Y subtype SCLC cell line H196 was randomly divided into the control group, c-Myc inhibitor 10058-F4 group, histone deacetylase 1 (HDAC1) inhibitor pyroxamide group, and 10058-F4 plus pyroxamide group. The co-culture system with NK-92MI cells was used to determine the effect of H196 cells on the function of natural killer (NK) cells. Western Blotting and co-immunoprecipitation assays were used to detect the effect of c-Myc on class Ⅰ HDAC, and flow cytometry was used to detect the regulatory effect of c-Mycon CD47, programmed cell death ligand 1 (PD-L1), and CD155, which are highly expressed immune checkpoints in Y subtype SCLC, and major histocompatibility complex classⅠ-related chains A and (MICA/B), which is a poorly expressed immune-activating ligand in SCLC, and the role of HDAC. Chromatin immunoprecipitation (ChIP) assay and real-time quantitative polymerase chain reaction (RT-qPCR) were used to determine the regulatory mechanism of c-Myc-HDAC1 on MICA/B expression.Results:Inhibition of c-Myc decreased the mortality of H196 cells in the co-culture system and down-regulated the expression of MICA/B. Compared with the NK+H196 group [(42.54±2.47)%], the proportion of cells killed by NK-92MI cells in the NK+H196+10058-F4 group was lower [(28.48±3.38)%, P＜0.001]. The mean fluorescence intensity (MFI) of MICA/B on the cells in the 10058-F4 group (36.40±0.82) was lower than that in the control group (91.23±8.60, P＜0.001). And c-Myc could bind to HDAC1, whose protein level was up-regulated by 10058-F4 while the mRNA level was not. Compared with the cells in the control group (90.10±4.91), the MFI of MICA/B on the cells in the pyroxamide group was significantly increased (145.70±5.86, P＜0.001), and the MFI of MICA/B on the cells in the 10058-F4+pyroxamide group (54.60±2.88) was significantly increased compared with the cells in the 10058-F4 group (35.97±1.60, P＜0.001). The percentage of MICA promoter gene fragments in the c-Myc antibody precipitation group (0.125±0.037) was significantly higher than that in the IgG group (0.000 8±0.000 3, P=0.004). MICB had a similar trend, suggesting that the c-Myc-HDAC1 complex could bind to the promoter region of MICA/B. The MFI of CD47 on the cells in the 10058-F4 group (60.07±0.21) was significantly lower than cells in the control group (70.27±1.37, P＜0.001), but the MFIs of PD-L1 (13.50±0.61) and CD155 (829.70±41.19) were significantly higher than those on the cells in the control group (9.23±0.94, P＜0.01; 496.00±4.36, P＜0.001, respectively). Conclusions:c-Myc may promote the expression of MICA/B and CD47 in Y subtype SCLC cells by binding and inhibiting HDAC1, while it may also be involved in inhibiting the expression of PD-L1 and CD155 in SCLC cells.

Objective:To explore the effect and mechanism of c-Myc on regulating the expression of immune-related ligands in Y subtype small-cell lung cancer (SCLC) characterized by high expression of immune-related molecules.Methods:The Y subtype SCLC cell line H196 was randomly divided into the control group, c-Myc inhibitor 10058-F4 group, histone deacetylase 1 (HDAC1) inhibitor pyroxamide group, and 10058-F4 plus pyroxamide group. The co-culture system with NK-92MI cells was used to determine the effect of H196 cells on the function of natural killer (NK) cells. Western Blotting and co-immunoprecipitation assays were used to detect the effect of c-Myc on class Ⅰ HDAC, and flow cytometry was used to detect the regulatory effect of c-Mycon CD47, programmed cell death ligand 1 (PD-L1), and CD155, which are highly expressed immune checkpoints in Y subtype SCLC, and major histocompatibility complex classⅠ-related chains A and (MICA/B), which is a poorly expressed immune-activating ligand in SCLC, and the role of HDAC. Chromatin immunoprecipitation (ChIP) assay and real-time quantitative polymerase chain reaction (RT-qPCR) were used to determine the regulatory mechanism of c-Myc-HDAC1 on MICA/B expression.Results:Inhibition of c-Myc decreased the mortality of H196 cells in the co-culture system and down-regulated the expression of MICA/B. Compared with the NK+H196 group [(42.54±2.47)%], the proportion of cells killed by NK-92MI cells in the NK+H196+10058-F4 group was lower [(28.48±3.38)%, P＜0.001]. The mean fluorescence intensity (MFI) of MICA/B on the cells in the 10058-F4 group (36.40±0.82) was lower than that in the control group (91.23±8.60, P＜0.001). And c-Myc could bind to HDAC1, whose protein level was up-regulated by 10058-F4 while the mRNA level was not. Compared with the cells in the control group (90.10±4.91), the MFI of MICA/B on the cells in the pyroxamide group was significantly increased (145.70±5.86, P＜0.001), and the MFI of MICA/B on the cells in the 10058-F4+pyroxamide group (54.60±2.88) was significantly increased compared with the cells in the 10058-F4 group (35.97±1.60, P＜0.001). The percentage of MICA promoter gene fragments in the c-Myc antibody precipitation group (0.125±0.037) was significantly higher than that in the IgG group (0.000 8±0.000 3, P=0.004). MICB had a similar trend, suggesting that the c-Myc-HDAC1 complex could bind to the promoter region of MICA/B. The MFI of CD47 on the cells in the 10058-F4 group (60.07±0.21) was significantly lower than cells in the control group (70.27±1.37, P＜0.001), but the MFIs of PD-L1 (13.50±0.61) and CD155 (829.70±41.19) were significantly higher than those on the cells in the control group (9.23±0.94, P＜0.01; 496.00±4.36, P＜0.001, respectively). Conclusions:c-Myc may promote the expression of MICA/B and CD47 in Y subtype SCLC cells by binding and inhibiting HDAC1, while it may also be involved in inhibiting the expression of PD-L1 and CD155 in SCLC cells.

Healthy lifestyles and good living habits are effective strategies and important approaches to prevent chronic non-communicable diseases. With the development of evidence-based medicine, the evidence translation system has made some achievements in clinical practice. There is, however, no comprehensive, professional and efficient system for translating lifestyle evidence globally. Therefore, the Health Lifestyle Evidence (HLSE) Group of Lanzhou University constructed the HLSE Evidence Translation System (https://hlse.cn/), with the aim of synthesizing, evaluating, translating, and applying lifestyle-related evidence resources. This paper aims to introduce the functional module design of the evidence translation system, the system development process and testing, introduce the interface design and function demonstration, and explain the significance of constructing the HLSE.

To systematically construct a guideline to provide a methodological guide for researchers to develop patient decision aids.

Healthy lifestyles and good living habits are effective strategies and important approaches to prevent chronic non-communicable diseases. With the development of evidence-based medicine, the evidence translation system has made some achievements in clinical practice. There is, however, no comprehensive, professional and efficient system for translating lifestyle evidence globally. Therefore, the Health Lifestyle Evidence (HLSE) Group of Lanzhou University constructed the HLSE Evidence Translation System (https://hlse.cn/), with the aim of synthesizing, evaluating, translating, and applying lifestyle-related evidence resources. This paper aims to introduce the functional module design of the evidence translation system, the system development process and testing, introduce the interface design and function demonstration, and explain the significance of constructing the HLSE.

To systematically construct a guideline to provide a methodological guide for researchers to develop patient decision aids.

Objective To investigate the therapeutic mechanism of Tujia medicine Toddalia asiatica alcohol extract(TAAE)for synovial pannus formation in rats with college-induced arthritis(CIA).Methods Sixty male SD rats were randomized into normal control group,CIA model group,TGT group,3 TAAE treatment groups at low,medium and high doses(n=10).Except for those in the normal control group,all the rats were subjected to CIA modeling using a secondary immunization method and treatment with saline,TGT or TAAE by gavage once daily for 35 days.The severity of arthritis was assessed using arthritis index(AI)score,and knee joint synovium pathologies were examined with HE staining.Serum levels of TNF-α,IL-6,and IL-1β were detected with ELISA;the protein expressions of PI3K,Akt,p-PI3K,p-Akt,VEGF,endostatin,HIF-1α,MMP1,MMP3,and MMP9 in knee joint synovial tissues were determined using Western blotting,and the mRNA expressions of TNF-α,IL-6,IL-1β,VEGF,HIF-1α,PI3K,and Akt were detected with RT-PCR.Results Treatment of CIA rat models with TAAE and TGT significantly alleviated paw swelling,lowered AI scores,and reduced knee joint pathology,neoangiogenesis,and serum levels of inflammatory factors.TAAE treatment obviously increased endostatin protein expression,downregulated p-PI3K,p-Akt,MMP1,MMP3,MMP9,VEGF,and HIF-1α proteins,and reduced TNF-α,IL-6,IL-1β,PI3K,Akt,VEGF,and HIF-1α mRNA levels in the synovial tissues,and these changes were comparable between high-dose TAAE group and TGT group.Conclusion TAAE can improve joint symptoms and inhibit synovial pannus formation in CIA rats by regulating the expressions of HIF-1α,VEGF,endostatin,MMP1,MMP3,and MMP9 via the PI3K/Akt signalling pathway.