[摘 要] 目的：探讨lncRNA DLEU2通过EZH2/H3K27me3途径调控IKKα介导甲状腺癌（TC）放射性碘抵抗的作用机制。方法：利用TCGA数据库分析TC中DLEU2的表达及其与EZH2的相关性。构建放射性碘抵抗的TPC-1细胞（RR-TPC-1细胞）模型及裸鼠移植瘤模型，通过敲低或过表达DLEU2（si-DLEU2/OE-DLEU2）、抑制EZH2（UNC1999）、过表达IKKα（OE-IKKα）进行干预，采用qPCR、WB、RIP、ChIP、CCK-8、流式细胞术、TUNEL染色及体内成瘤实验检测基因与蛋白表达、表观修饰、细胞增殖、凋亡及肿瘤生长。结果：TCGA分析显示，DLEU2在TC组织中显著上调（P < 0.001），与患者不良预后相关（P = 0.008 4），且与EZH2表达呈正相关（r = 0.390, P < 0.001）；RIP证实EZH2与DLEU2存在相互作用/结合（P < 0.05）。体外实验表明，敲低DLEU2可显著下调RR-TPC-1细胞中EZH2、IKKα表达及H3K27me3修饰水平，抑制NF-κB通路活化（P < 0.05或P < 0.01），抑制细胞增殖、促进凋亡（均P < 0.05）。联合敲低DLEU2与抑制EZH2进一步增强上述效应，而过表达IKKα则可部分逆转上述效应（P < 0.05或P < 0.01）。体内实验进一步证实，敲低DLEU2联合抑制EZH2可显著抑制移植瘤生长，增加肿瘤细胞凋亡（均P < 0.01）；IKKα过表达则部分逆转上述抗肿瘤效应（P < 0.05或P < 0.01）。结论：lncRNA DLEU2通过招募EZH2催化H3K27me3修饰，间接激活IKKα/NF-κB信号并形成正反馈环路，介导TPC-1细胞131I抵抗。

ObjectivePancreatic ductal adenocarcinoma (PDAC) exhibits a limited response to current treatments due to its dense fibrotic stroma and highly immunosuppressive tumor microenvironment. In recent years, advancements in cellular immunotherapy, particularly chimeric antigen receptor macrophage (CAR-M) therapy, have offered new hope for pancreatic cancer treatment. Although CAR-M therapy demonstrates dual potential in directly killing tumor cells and remodeling the immune microenvironment, it still faces challenges such as complex in vitro preparation processes and low in vivo targeting and delivery efficiency. Therefore, developing strategies for efficient and targeted in vivo delivery of CAR genes has become crucial for overcoming current therapeutic limitations. This study aims to develop an orally administrable nano-gene delivery system for the targeted delivery of CAR genes to pancreatic tumor sites. MethodsCore nano-gene particles (PNP/pCAR) were constructed by loading plasmid DNA encoding CAR (pCAR) with cationic polypeptides (PNP). Subsequently, PNP/pCAR was surface-modified with β-glucan to prepare the targeted nanoparticles (βGlus-PNP/pCAR). The loading efficiency of PNP for pCAR was quantitatively assessed by gel retardation assay. The particle size, Zeta potential, morphology, and storage stability of PNP/pCAR were characterized using a Malvern particle size analyzer and transmission electron microscopy. At the cellular level, RAW 264.7 macrophages were selected. The cytotoxicity of PNP/pCAR was evaluated using the CCK-8 assay. The cellular uptake efficiency and lysosomal escape ability of the nanoparticles were assessed via flow cytometry and confocal microscopy. Transfection efficiency was quantitatively evaluated by detecting the expression of the reporter gene GFP using flow cytometry. At the in vivo level, an orthotopic pancreatic cancer mouse model was established. Cy7-labeled βGlus-PNP/pCAR nanoparticles were administered orally, and the fluorescence distribution in mice was dynamically monitored at 1, 2, 4, 8, and 16 h post-administration using a small animal in vivo imaging system. Forty-eight hours after oral gavage, the mice were euthanized, and pancreatic tumor tissues were collected for further analysis of intratumoral fluorescence signals using the imaging system. Additionally, βGlus-PNP/pCAR-GFP nanoparticles loaded with the reporter gene (GFP) were administered orally. Forty-eight hours post-administration, pancreatic tumor tissues were harvested to prepare frozen sections, and GFP expression was observed and analyzed under a fluorescence microscope. ResultsThe PNP carrier exhibited a high loading capacity for pCAR. The successfully prepared PNP/pCAR nanoparticles were regular spheres with a hydrodynamic diameter of approximately (120±10) nm and a Zeta potential of about +(6±1) mV. They maintained good structural stability after incubation in PBS buffer for 7 d. Cell experiments demonstrated that PNP/pCAR exhibited no significant cytotoxicity in RAW 264.7 cells while being efficiently internalized and effectively escaping lysosomal degradation. The transfection positive rate of PNP/pCAR-GFP in RAW 264.7 cells reached (25±3)%, surpassing that of Lipofectamine 2000-loaded pCAR-GFP (Lipo/pCAR-GFP), which was (20±1)%.In vivo experiments revealed that, compared to unmodified PNP/pCAR, βGlus-PNP/pCAR exhibited strongerin situ pancreatic tumor targeting ability after oral administration. Furthermore, oral administration of βGlus-PNP/pCAR-GFP resulted in significant GFP protein expression detectable within pancreatic tumor tissues. ConclusionThis study successfully constructed and validated an orally administrable, pancreatic cancer-targeting polypeptide-based nano-gene delivery system. It provides an important technological foundation in delivery systems and experimental basis for the subsequent development of in situ CAR-M-based therapeutic strategies for pancreatic cancer.

ObjectivePancreatic ductal adenocarcinoma (PDAC) exhibits a limited response to current treatments due to its dense fibrotic stroma and highly immunosuppressive tumor microenvironment. In recent years, advancements in cellular immunotherapy, particularly chimeric antigen receptor macrophage (CAR-M) therapy, have offered new hope for pancreatic cancer treatment. Although CAR-M therapy demonstrates dual potential in directly killing tumor cells and remodeling the immune microenvironment, it still faces challenges such as complex in vitro preparation processes and low in vivo targeting and delivery efficiency. Therefore, developing strategies for efficient and targeted in vivo delivery of CAR genes has become crucial for overcoming current therapeutic limitations. This study aims to develop an orally administrable nano-gene delivery system for the targeted delivery of CAR genes to pancreatic tumor sites. MethodsCore nano-gene particles (PNP/pCAR) were constructed by loading plasmid DNA encoding CAR (pCAR) with cationic polypeptides (PNP). Subsequently, PNP/pCAR was surface-modified with β-glucan to prepare the targeted nanoparticles (βGlus-PNP/pCAR). The loading efficiency of PNP for pCAR was quantitatively assessed by gel retardation assay. The particle size, Zeta potential, morphology, and storage stability of PNP/pCAR were characterized using a Malvern particle size analyzer and transmission electron microscopy. At the cellular level, RAW 264.7 macrophages were selected. The cytotoxicity of PNP/pCAR was evaluated using the CCK-8 assay. The cellular uptake efficiency and lysosomal escape ability of the nanoparticles were assessed via flow cytometry and confocal microscopy. Transfection efficiency was quantitatively evaluated by detecting the expression of the reporter gene GFP using flow cytometry. At the in vivo level, an orthotopic pancreatic cancer mouse model was established. Cy7-labeled βGlus-PNP/pCAR nanoparticles were administered orally, and the fluorescence distribution in mice was dynamically monitored at 1, 2, 4, 8, and 16 h post-administration using a small animal in vivo imaging system. Forty-eight hours after oral gavage, the mice were euthanized, and pancreatic tumor tissues were collected for further analysis of intratumoral fluorescence signals using the imaging system. Additionally, βGlus-PNP/pCAR-GFP nanoparticles loaded with the reporter gene (GFP) were administered orally. Forty-eight hours post-administration, pancreatic tumor tissues were harvested to prepare frozen sections, and GFP expression was observed and analyzed under a fluorescence microscope. ResultsThe PNP carrier exhibited a high loading capacity for pCAR. The successfully prepared PNP/pCAR nanoparticles were regular spheres with a hydrodynamic diameter of approximately (120±10) nm and a Zeta potential of about +(6±1) mV. They maintained good structural stability after incubation in PBS buffer for 7 d. Cell experiments demonstrated that PNP/pCAR exhibited no significant cytotoxicity in RAW 264.7 cells while being efficiently internalized and effectively escaping lysosomal degradation. The transfection positive rate of PNP/pCAR-GFP in RAW 264.7 cells reached (25±3)%, surpassing that of Lipofectamine 2000-loaded pCAR-GFP (Lipo/pCAR-GFP), which was (20±1)%.In vivo experiments revealed that, compared to unmodified PNP/pCAR, βGlus-PNP/pCAR exhibited strongerin situ pancreatic tumor targeting ability after oral administration. Furthermore, oral administration of βGlus-PNP/pCAR-GFP resulted in significant GFP protein expression detectable within pancreatic tumor tissues. ConclusionThis study successfully constructed and validated an orally administrable, pancreatic cancer-targeting polypeptide-based nano-gene delivery system. It provides an important technological foundation in delivery systems and experimental basis for the subsequent development of in situ CAR-M-based therapeutic strategies for pancreatic cancer.

Objective: To investigate the trend in disease burden of asthma attributable to tobacco in China from 1990 to 2021, so as to provide the basis for improving intervention measures of asthma. Methods: Data on asthma-related mortality and disability-adjusted life years (DALY) attributable to tobacco among adults aged ≥30 years in China from 1990 to 2021 were collected from the Global Burden of Disease (GBD) 2021 database. Age-standardized mortality and age-standardized DALY rate were calculated using the GBD world standard population structure to analyze the tobacco-attributable asthma burden. The average annual percent change (AAPC) was employed to evaluate temporal trends in the age-standardized mortality and DALY rate from 1990 to 2021. Results: In China, the age-standardized mortality and age-standardized DALY rate of asthma attributable to tobacco decreased from 0.73/100 000 and 22.20/100 000 in 1990 to 0.17/100 000 and 6.64/100 000 in 2021, showing downward trends (AAPC=-4.603% and -3.888%, both P<0.05). Among males, the tobacco-attributable age-standardized mortality and age-standardized DALY rate declined from 1.44/100 000 and 41.05/100 000 in 1990 to 0.36/100 000 and 12.79/100 000 in 2021 (AAPC=-4.369% and -3.810%, both P<0.05). Among females, the corresponding rates decreased from 0.21/105 and 5.37/105 to 0.03/105 and 1.08/105 (AAPC=-6.074% and -5.074%, both P<0.05). In 2021, males had higher tobacco-attributable age-standardized mortality and age-standardized DALY rate for asthma than females. Both the mortality and DALY rate of asthma attributable to tobacco increased with age, peaking in the age group ≥80 years at 7.84/100 000 and 112.07/100 000, respectively. Conclusion From 1990 to 2021, the disease burden of asthma attributable to tobacco showed a declining trend in China, with males and elderly population aged ≥80 years bearing a relatively heavier disease burden.

Diabetic tendinopathy is a common and disabling musculoskeletal complication of diabetes, clinically characterized by tendon thickening, pain, impaired healing capacity and compromised biomechanical performance, collectively undermining joint function and quality of life. Its pathogenesis is multifactorial. On the one hand, chronic hyperglycaemia promotes the abnormal accumulation of advanced glycation end products (AGEs) within tendon collagen, leading to non-enzymatic crosslinking and engagement of the receptor for AGEs (RAGE), which in turn triggers inflammasome activation and sustains inflammatory responses. On the other hand, the diabetic milieu disrupts collagen metabolic homeostasis, impairs microvascular function and induces peripheral neuropathy; together, these alterations drive extracellular matrix degeneration and weaken the mechanical properties of tendon. Exercise, as a non-pharmacological intervention, can ameliorate these pathological changes through multiple integrated mechanisms. First, exercise attenuates tendon inflammation and restores microenvironmental homeostasis. Regular physical activity reduces AGE-RAGE signalling, thereby suppressing downstream expression of tumour necrosis factor (TNF) and interleukin-1β (IL-1β), while upregulating the anti-inflammatory cytokine interleukin-10 (IL-10). This shift from a pro-inflammatory to a pro-resolving milieu not only restrains chronic inflammation but may also limit excessive inflammasome activation in tenocytes and tissue-resident immune cells. Second, exercise enhances local expression of insulin-like growth factor 1 (IGF-1), thereby activating the phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt) signalling pathway. This axis stimulates tenocyte proliferation, augments synthesis of type I collagen —— the principal load-bearing component of tendon —— and thereby promotes tissue repair, preserves tensile strength and supports matrix synthesis and structural integrity. In addition, exercise improves blood supply and nutrient delivery to tendon by increasing the expression of vascular endothelial growth factor (VEGF), connective tissue growth factor (CTGF) and the small leucine-rich proteoglycan decorin (DCN), thereby enhancing capillary growth, coordinating collagen fibrillogenesis and actively suppressing pathological vascular calcification. Exercise also increases the expression of angiopoietin-like 4 (ANGPTL4), fibroblast growth factor 2 (FGF-2) and CD34. Through the concerted actions of these factors, exercise promotes angiogenesis, restores the microvascular network and ensures adequate oxygen and nutrient supply to relatively ischaemic tendon tissue. Finally, exercise elevates levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), supporting neuronal survival, axonal growth and the function of sensory and sympathetic nerve endings within tendon, thereby exerting neurotrophic and neuromodulatory effects and improving tendon innervation and neuromuscular control. Moreover, exercise upregulates collapsin response mediator protein 2 (CRMP-2), a molecule involved in axonal guidance and regeneration, and moderately increases the activity of substance P (SP), thereby helping to regulate neurogenic inflammation, pain perception and trophic support for tenocytes. Drawing together current evidence, this review systematically summarizes the mechanisms underlying diabetic tendinopathy and examines the mechanistic basis of exercise intervention, with the aim of providing a theoretical framework for the development of precise exercise strategies for affected individuals. However, several key issues remain unresolved: the therapeutic efficacy and mechanistic specificity of different exercise modalities in diabetic tendinopathy have yet to be defined, and early diagnostic biomarkers remain insufficiently characterized. Future studies should apply multi-omics approaches to profile AGE subtypes, miRNA signatures and collagen metabolic products, and should also clarify the adverse effects and underlying mechanisms of excessive exercise or mechanical overloading in diabetic tendinopathy. Such efforts will further elucidate the therapeutic effects and mechanisms of exercise in diabetic tendinopathy and provide a stronger basis for precision exercise prescription and fitness guidance in patients with diabetes.

ObjectiveTo explore the key genes influencing diacylglycerol metabolism in neuroblastoma （NB）， clarify the expression and clinical significance of diacylglycerol acyltransferase 2 （DGAT2） in NB， and provide a theoretical basis for the diagnosis and targeted therapy of NB. MethodsNB transcriptome data were obtained from GEO （GSE49710） and TCGA （TARGET-NBL） databases. Differentially expressed genes （DEGs） commonly upregulated in MYCN-amplified groups were screened， and the key gene DGAT2 was identified by intersecting the screened DEGs with the diacylglycerol metabolism-related gene set followed by prognostic analysis and comparison. The expression of DGAT2 was analyzed via the R2 database. The potential impact of DGAT2 on the immune microenvironment was explored by combining the single-cell dataset GSE137804. Immunohistochemistry （IHC） was used to detect the expression level of DGAT2 and its correlation with MYCN expression in 55 clinical NB tissues and mouse xenograft tumor tissues. ResultsA total of 907 DEGs commonly upregulated in the MYCN-amplified groups were screened， among which three DEGs were highly expressed in the diacylglycerol metabolism-related gene set （P＜0.05）. After comparison， DGAT2 was found to have the most significant impact on prognosis （HR=1.4， 95% CI：1.2，1.7； P=5.41×10^-7）. Survival analysis showed that patients with high DGAT2 expression had a significantly shorter overall survival. Single-cell analysis revealed that high expression of DGAT2 led to an immunosuppressive microenvironment in NB. IHC results showed that the expression of DGAT2 in NB tissues was significantly positively correlated with MYCN expression in the tumor tissue microarrays of clinical NB patients and the tissues of mouse ectopic xenograft tumors （r_s=0.369 4，P＜0.01）. ConclusionsDGAT2 is highly expressed in MYCN-amplified NB， and may independently predict poor prognosis in NB patients. It is expected to become a diagnostic marker for NB and a potential therapeutic target for MYCN-amplified NB.

AIM: To evaluate the effects of the myopia prevention and control guidance station(MPCGS)on axial elongation in school-age children.METHODS:This was a prospective cohort study.Students enrolled in Grades 1 to 3 of primary schools in Qingyang District, Chengdu, in the first half of 2022 who completed continuous follow-up from 2022 to 2025 were included in this study. Among them, three schools that implemented the MPCGS in 2023 were assigned to the intervention group, and another three schools in the same district without MPCGS served as the control group. The intervention group received the school-hospital-family integrated model for myopia prevention and control,while the control group only received routine vision screening without such intervention measures.Students were categorized into three groups based on their grade in 2022: Group A(Grade 1), Group B(Grade 2), and Group C(Grade 3). Comparisons were stratified by grade, with independent samples t-tests used for intergroup analyses of annual axial elongation(ΔAL)between the intervention and control groups, and repeated-measures ANOVA(Bonferroni-corrected post-hoc test)used for intervention group comparisons across different time points.RESULTS:Totally 3 404 students were enrolled in this study, including 1 709 in the intervention group(897 males and 812 females, aged 7.64±0.88 y)and 1 695 in the control group(902 males and 793 females, aged 7.75±0.97 y). In the intervention group, there were 537 students in subgroup A(293 males and 244 females, aged 7.08±0.28 y), 721 in subgroup B(369 males and 352 females, aged 8.03±0.29 y), and 451 in subgroup C(235 males and 216 females, aged 9.07±0.30 y). In the control group, there were 559 students in subgroup A(295 males and 264 females, aged 7.05±0.28 y), 497 in subgroup B(269 males and 228 females, aged 8.04±0.30 y), and 639 in subgroup C(338 males and 301 females, aged 9.08±0.30 y). No significant differences were observed between the intervention and control groups within each grade(A, B, and C)at baseline age, sex, SE, AL, ΔSE(2022-2023), and ΔAL(2022-2023)(all P>0.05). During the first intervention year(2023-2024), intergroup comparisons revealed no significant differences in ΔAL between the intervention and control groups within Groups A, B, and C(all P>0.05). During the second intervention year(2024-2025), the intervention group showed significantly lower ΔAL than the control group within Groups A and B(PSymbol|@@0.001 and P=0.017, respectively), while no significant difference in ΔAL was detected in Group C(P=0.419). In the intervention group, there were significant differences in ΔAL at different time points among Groups A, B and C(all P<0.001). Compared with the first year before intervention, the ΔAL of each subgroup significantly decreased in the second year of intervention(all P<0.0167).CONCLUSION:The implementation of the school-hospital-family integrated MPCGS model was associated with slowed axial elongation. This association exhibited a time-dependent cumulative effect and was more pronounced in lower-grade children(grades 1-2).

Objective To evaluate the effect of laparoscopic surgery on incarcerated inguinal hernia(IIH)in children.Methods A total of 81 IIH children treated at Jinhua Maternal & Child Health Hospital from September 2018 to December 2023 were selected as subjects.The children were divided into laparoscopic surgery group(n=45)and open surgery group(n=36).Comparative analysis was conducted on admission age,gender,duration of incarceration,surgical timing,intraoperative hernia contents,and postoperative complications between two groups.Results Operative duration,intraoperative blood loss,postoperative bowel function recovery time,number of occult hernias,and hospitalization duration in laparoscopic surgery group were statistically better than those in open surgery group(P＜0.05).There were fewer postoperative complications in laparoscopic group compared to open surgery group,there was significant difference between two groups(P＜0.05).Conclusion Compared with traditional open surgery,laparoscopic surgery for IIH in children has the advantages of less trauma,shorter operation time and hospitalization time,and less intraoperative bleeding.

The new quality productive forces of medical and health provides a new impetus for the high-quality development of hospitals. Based on a systematic analysis of the development connotation of hospitals′ new quality productive forces and the innovation of hospital service mode, this study found that hospitals at all levels were actively attempting to expand their service boundaries and service delivery paths due to the innovation of the medical mode and the change of the public health concept. However, constrained by such bottlenecks as the lagging construction of modern hospital management system and the consolidation of organizational management system, hospitals generally encountered problems such as the weak transformation of service concept and the insufficient endogenous impetus for reform. Additionally, the poor repeatability of some medical innovation practices and the delayed social promotion resulted in a lag in the iterative upgrading of hospital service modes, which was difficult to meet the escalating health needs of the people. Therefore, the authors proposed to construct the innovation path of hospital service mode oriented to new quality productive forces with the support of the dynamic capacity theory, build the hospital innovation environment with the assistance of innovation policies, strengthen the building of the hospital′s multidisciplinary and interprofessional innovation team guided by clinical needs and the provision of special disease services, improve the system construction to realize the full life cycle management of hospital service model innovation activities. To enhance the collaborative creation of multi-institution medical and health service models and promote multi-point application and promotion, thereby further enriching the supply of medical and health services and facilitating the in-depth implementation of the Healthy China strategy.

AIM To investigate the clinical effects of Jinhua Qinggan Granules combined with azithromycin on patients with Mycoplasma pneumoniae pneumonia.METHODS One hundred and three patients were randomly assigned into control group(51 cases)for 1-week intervention of both azithromycin and conventional treatment,and observation group(52 cases)for 1-wee intervention of Jinhua Qinggan Granules,azithromycin and conventional treatment.The changes in clinical effects,remission time for local symptoms(cough,wheezing,fever,pulmonary wet rales),pulmonary function indices(PEF,FEV1,FEV1/FVC),immune function indices(CD4+,CD8+,CD4+/CD8+),NLRP3 inflammatory pathway factors(Caspase-1,IL-1β,IL-18)and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05),along with shorter remission time for local symptoms(P＜0.05).After the treatment,the two groups displayed increased pulmonary function indices,CD4+,CD4+/CD8+(P＜0.05),and decreased CD8+,NLRP3 inflammatory pathway factors(P＜0.05),especially for the observation group(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with Mycoplasma pneumoniae pneumonia,Jinhua Qinggan Granules combined with azithromycin can safely and effectively improve clinical symptoms,pulmonary functions and immune functions,whose mechanism may contribute to the regulation of NLRP3 inflammasome pathway expressions.