[摘 要] 目的：探讨环状RNA CEMIP（circCEMIP）对膀胱癌UMUC-3细胞增殖、迁移和侵袭的影响及其分子机制。方法：通过TCGA数据库分析circCEMIP在膀胱癌组织中的表达水平，分析其表达与膀胱癌患者临床分期及生存期的关系。采用qPCR法检测circCEMIP在膀胱癌细胞5637、UMUC-3、MGH-U3、J82和T24中的表达。利用RNA干扰技术，分别将si-circCEMIP及其阴性对照（si-NC）、anti-miR-335及其阴性对照（anti-miR-NC）转染UMUC-3细胞，记为si-circCEMIP组、si-NC组、si-circCEMIP + anti-miR-335组和si-circCEMIP + anti-miR-NC组。采用克隆形成实验、划痕愈合实验和Transwell实验分别检测circCEMIP和miR-335表达对UMUC-3细胞增殖、迁移和侵袭能力的影响，双萤光素酶报告基因实验验证circCEMIP与miR-335的靶向关系，WB法检测细胞中VEGF-C信号通路相关蛋白的表达。构建UMUC-3细胞裸鼠皮下移植瘤模型，观察敲低circCEMIP对移植瘤生长的影响。结果：膀胱癌组织中circCEMIP呈高表达（P < 0.01），其表达水平与膀胱癌的临床分期正相关（P < 0.01），circCEMIP高表达患者生存率较低（P < 0.01）。circCEMIP在膀胱癌5637、UMUC-3、MGH-U3、J82和T24细胞中呈高表达（均P < 0.01）。敲低circCEMIP显著降低UMUC-3细胞的增殖、迁移和侵袭能力（均P < 0.01）。circCEMIP可靶向结合miR-335（P < 0.01），敲低circCEMIP能显著上调miR-335表达（P < 0.01）。抑制miR-335表达能逆转敲低circCEMIP对UMUC-3细胞增殖、迁移和侵袭的抑制作用（均P < 0.01）。敲低circCEMIP能明显下调VEGF-C信号通路相关蛋白VEGF-C、MMP-2、MMP-9和β-catenin表达（均P < 0.01），抑制miR-335表达能部分逆转敲低circCEMIP对该通路相关蛋白表达的抑制作用（均P < 0.01）。体内实验证实，敲低circCEMIP能够抑制裸鼠膀胱癌移植瘤的生长（P < 0.01）。结论：敲低circCEMIP通过上调miR-335表达抑制膀胱癌UMUC-3细胞的增殖、迁移和侵袭。

Objective To explore the impact of number of positive regional lymph nodes (nPRLN) in N1 stage on the prognosis of non-small cell lung cancer (NSCLC) patients. Methods Patients with TxN1M0 stage NSCLC who underwent lobectomy and mediastinal lymph node dissection from 2010 to 2015 were screened from SEER database (17 Regs, 2022nov sub). The optimal cutoff value of nPRLN was determined using X-tile software, and patients were divided into 2 groups according to the cutoff value: a nPRLN≤optimal cutoff group and a nPRLN>optimal cutoff group. The influence of confounding factors was minimized by propensity score matching (PSM) at a ratio of 1 : 1. Kaplan-Meier curves and Cox proportional hazards models were used to evaluate overall survival (OS) and lung cancer-specific survival (LCSS) of patients. Results A total of 1316 patients with TxN1M0 stage NSCLC were included, including 662 males and 654 females, with a median age of 67 (60, 73) years. The optimal cutoff value of nPRLN was 3, with 1165 patients in the nPRLN≤3 group and 151 patients in the nPRLN>3 group. After PSM, there were 138 patients in each group. Regardless of before or after PSM, OS and LCSS of patients in the nPRLN≤3 group were superior to those in the nPRLN>3 group (P<0.001). N1 stage nPRLN>3 was an independent prognostic risk factor for OS [HR=1.52, 95%CI (1.22, 1.89), P<0.001] and LCSS [HR=1.72, 95%CI (1.36, 2.18), P<0.001]. Conclusion N1 stage nPRLN>3 is an independent prognostic risk factor for NSCLC patients in TxN1M0 stage, which may provide new evidence for future revision of TNM staging N1 stage subclassification.

[摘 要] 目的：探究环状核酸适配体-药物偶联物（ApDC）联合抗CD19嵌合抗原受体T/NK（CAR19-T/NK）细胞对Nalm6白血病细胞杀伤效果的增强作用。方法： 用数据库分析寻找白血病细胞的标志物蛋白酪氨酸激酶7（PTK7），设计合成靶向PTK7的核酸适配体sgc8，进一步合成两种ApDC：核酸适配体偶联吉西他滨（sgc8-GEM）和环状核酸适配体偶联吉西他滨（C-sgc8-GEM），琼脂糖凝胶电泳分析其稳定性。用CD19-CAR过表达慢病毒转染人外周血T/NK细胞构建CAR19-T和CAR19-NK细胞，流式细胞术检测sgc8与Nalm6细胞的结合力，CCK-8法和流式细胞术检测sgc8-GEM、C-sgc8-GEM，以及其分别与CAR19-T和CAR19-NK细胞联合应用对Nalm6细胞的杀伤能力。结果： PTK7 mRNA在白血病细胞中呈高表达（P < 0. 01）；C-sgc8-GEM比sgc8-GEM稳定性更高，与GEM比较，sgc8-GEM更能有效杀伤Nalm6细胞（P < 0.001）；C-sgc8-GEM或sgc8-GEM分别与CAR19-T/NK细胞联合应用比单独用C-sgc8-GEM、sgc8-GEM、CAR19-T/NK细胞对Nalm6细胞的毒性均更强（P < 0.001）。结论：成功建立环状ApDC与CAR19-T/NK细胞联合应用法，通过双靶点有效提高了对Nalm6细胞的毒性，为急性淋巴细胞白血病提供了新的治疗思路。

Objective The study aimed to elucidate the population composition and seasonal distribution characteristics of mosquitoes in Laoshan District, Qingdao City, providing a scientific basis for the prevention and control of mosquito-borne infectious diseases. Methods Mosquito surveillance was conducted in Laoshan District in Qingdao City using light traps from April to November 2020-2022. Dominant mosquito species were identified using the Berger-Parker dominance index(I)and mosquito density was compared using the Kruskal-Wallis H test. The seasonal distribution characteristics of adult mosquitoes were analyzed using concentration and circular distribution method. Spearman rank correlation analysis was used to study the relationship between mosquito populations and meteorological factors with mean monthly temperature, mean monthly relative humidity, and mean monthly rainfall. Results The mean mosquito density for the trapping period was 9.771 females/(trap·night)in 2020,9.771 in 2021, and 9.427 in 2022. There was no statistically significant difference in mosquito density between different years(H = 0.095, P = 0.954). In total, 2 781 adult female mosquitoes comprising five species from four genera were captured over three years. Culex pipiens(I = 0.654), Aedes albopictus(I = 0.202), and Aedes aegypti(I = 0.118)were identified as dominant species. Seasonal fluctuations in the adult mosquitoes were unimodal, and primarily concentrated from June to September. The peak period of adult mosquito varied between years with statistical significance. (F = 3.838, P ＜ 0.05). Mosquito density was highly correlated with mean monthly temperature, mean monthly relative humidity and mean monthly precipitation(P＜ 0.05). Conclusions Cx. pipiens pallens, Ae. albopictus, and Ar. inamoratus are the dominant mosquito species in the Laoshan District of Qingdao City. The activity of adult mosquitoes is seasonal, and primarily concentrated in summer and autumn, during which the risk of mosquito-borne diseases such as dengue fever is increased.

Objective To investigate the current status of sleep disorders in patients with Alzheimer’s disease (AD) and its relationship with physical activity, and analyze the intervention effect of light therapy. Methods A total of 345 patients with AD admitted to the First Affiliated Hospital of Air Force Medical University from June 2020 to June 2025 were included. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the sleep disorders, and the Physical Activity Scale for the Elderly (PASE) was applied to evaluate the physical activity. Pearson correlation analysis model was adopted to analyze the correlation between PSQI and PASE in patients with AD. 345 patients with AD were treated with light therapy intervention for 4 weeks. The changes of PSQI and PASE scores were compared before and after intervention. Results Among the 345 patients with AD, 251 cases had sleep disorders, accounting for 72.75% (251/345), and the PSQI score was (9.87±2.95) points. The scores of leisure activity, housework and occupation-related activity of PASE were (25.81±6.12) points, (78.15±12.93) points, and (45.31±8.74) points, respectively. Pearson correlation analysis model revealed that the leisure activity score of PASE was negatively correlated with the PSQI score (P<0.05), and the scores of housework and occupation-related activity were not significantly correlated with the PSQI score (P>0.05). After 4 weeks of light therapy intervention, the score of leisure activity of patients was increased significantly (P<0.05), while the scores of housework and occupation-related activity did not change significantly (P>0.05), and the PSQI scores were decreased significantly (P<0.05). Conclusion There is a correlation between sleep disorders and leisure time and physical activity in patients with Alzheimer&#39;s disease. The implementation of light therapy intervention can effectively improve sleep disorders in AD patients.

Objective The present study aimed to evaluate the clinical efficacy of hydraulic sinus floor elevation for the treatment of insufficient bone height in the posterior maxilla through a systematic review and Meta-analysis, so as to provide evidence for clinical practice. Methods Databases including PubMed, Embase, Cochrane Library, and Clinical Trials.gov were searched up to May 2025. Randomized controlled trials, non-randomized controlled trials, cohort studies, cross-sectional studies, and case-control studies that involved patients receiving hydraulic sinus floor elevation with simultaneous or delayed implant placement were included. Exclusion criteria comprised in vitro studies, animal experiments, narrative reviews, unpublished data, commentaries or expert opinions, studies with unclear sample sizes, and publications without full-text access or unavailable outcome data. Three investigators independently performed literature screening and quality assessment. A single-arm Meta-analysis was conducted using Stata 18.0 for studies meeting the inclusion criteria. The outcome measures were the incidence of sinus membrane perforation, implant survival rate, and endo-sinus bone gain. The Cochrane Risk of Bias 2 (RoB2) tool and the Joanna Briggs Institute (JBI) critical appraisal checklist were used to assess the methodological quality of randomized controlled trials and non-randomized controlled trials, respectively. The overall certainty of evidence was assessed using the GRADE（Grading of Recommendations Assessment, Development and Evaluation）system. Results Nineteen studies with 982 patients, 1 151 elevated sites, and 1 263 implants were finally included. The Meta-analysis showed that the intraoperative sinus membrane perforation rate of hydraulic sinus floor elevation was 2.0% [ES = 0.02, 95% CI (0.00, 0.04)] (18 studies, 1 061 sites); the implant survival rate was 99.0% [ES = 0.99, 95% CI (0.97, 1.00)] (17 studies, 1 253 implants); and the mean vertical bone gain was 7.80 mm. For this outcome, heterogeneity among studies was extremely high (I2 = 98.6%), thus only descriptive analysis was performed. Egger&#39;s test revealed no significant publication bias for the three outcomes. GRADE grading indicated very low certainty of evidence for mucosal perforation, implant survival rate, and endo sinus bone gain. Conclusion Current preliminary evidence suggests that hydraulic sinus lift may be a safe minimally invasive technique, but the evidence is very low, and more high quality, long term follow up randomized controlled clinical trials are still needed for further verification.

Objective To explore the mediating role of activities of daily living (ADL) in pain and depressive symptoms in the elderly in China. Methods Utilizing the data from 2020 China Health and Retirement Longitudinal Study, 4403 Chinese elderly individuals aged ≥ 60 years old were selected as the research subjects. Depression Scale (CES-D 10) of the Center for Epidemiological Survey and ADL scale were used in the study. The PROCESS4.1 macro was used to test the mediating effect of daily living activities between pain and depressive symptoms, and the Bootstrap method was applied for verification of the mediating variables. Results A total of 2368 cases of depressive symptoms were detected in the elderly in China, with a detection rate of 53.78%. Pain was positively correlated with depressive symptoms (r=0.27, P<0.01), and activities of daily living were negatively correlated with pain and depressive symptoms (r=-0.27, -0.337, P<0.01). The results showed that the total effect value of pain on depressive symptoms was 0.33, the direct effect value was 0.24, and the mediating effect value of daily living activities was 0.09, accounting for 27.27%. Conclusion Pain and activities of daily living are important factors influencing depressive symptoms in the elderly, and activities of daily living play a partial mediating role in the relationship between pain and depressive symptoms in the elderly.

Objective To evaluate the value of postoperative radiotherapy (PORT) in patients with stage ⅢA-N2 non-small cell lung cancer who received complete resection and chemotherapy. Methods Patients with stage ⅢA-N2 non-small cell lung cancer who received complete resection and chemotherapy were chosen from the SEER Research Plus Database [17 Registries, November 2012 Submission (2000-2019)]. The patients were divided into a PORT group and a non-PORT group according to whether the PORT was used. To balance baseline characteristics between non-PORT and PORT groups, R software was used to conduct a propensity score matching (PSM) with a ratio of 1 : 1 and a matching tolerance of 0.01. Both the Cox regression analysis and Kaplan-Meier survival analysis were conducted to evaluate the value of PORT in terms of overall survival (OS) and disease-specific survival (DSS). Results In total, 2468 patients with stage ⅢA-N2 non-small cell lung cancer were enrolled, including 1078 males and 1390 females with a median age of 65 (58-71) years. There were 1336 patients in the PORT group, and 1132 patients in the non-PORT group. Cox regression analysis showed that PORT was not significantly associated with OS (multivariate analysis: HR=1.051, 95%CI 0.949-1.164, P=0.338) and DSS (multivariate analysis: HR=1.094, 95%CI 0.976-1.225, P=0.123). No statistical difference was found in the OS or DSS between non-PORT group and PORT group after PSM analysis (P＞0.05). Conclusion PORT does not have a survival benefit for patients with stage ⅢA-N2 non-small cell lung cancer who received complete resection and chemotherapy.

As an important strategy in antiviral drug development, nucleoside analogs (NAs) have attracted considerable attention due to their unique mechanisms of action and favorable safety profile. This review systematically summarizes recent advances in the mechanisms of action of NAs, focusing on the following four aspects: (1) Targeting viral polymerases, inhibiting viral replication through mechanisms such as non-absolute termination, delayed chain termination and induction of viral RNA mutations in addition to classical chain termination, which has been newly discovered; (2) Regulating RNA methylation modifications—for instance, competitively inhibiting methyltransferases, which significantly reduces viral replication efficiency; (3) Depleting nucleotide pools—by affecting host cell purine nucleotide synthesis pathways, thereby indirectly inhibiting viral replication; and (4) Immunomodulatory functions—including activation of the STING pathway to promote interferon production. Furthermore, this review systematically discusses the breakthrough progress in prodrug technologies for addressing key clinical challenges such as drug resistance and off-target toxicity of NAs. These advances provide crucial technical support for the clinical translation of NAs. These advances provide key technical support for the clinical translation of NAs. This review clarifies the multi-target action rules of NAs and provides a theoretical framework for the design of next-generation broad-spectrum antiviral agents.