Traditional Chinese medicine (TCM) formula extraction optimization is vital for clinical efficacy and standardization. This study targeted an anti-hepatocarcinoma formula, combining orthogonal experimental design (OED) with machine learning (ML) to optimize extraction-focused on extraction yield and paeoniflorin content. OED revealed extraction time as the key factor influencing both metrics, while ML modeling identified optimal parameters. Experimental validation achieved a 43.21% extraction yield and 74.2 mg total paeoniflorin, confirming ML's utility in process refinement. The OED-ML integration proves a powerful tool for TCM preparation optimization, accelerating cost-effective, eco-friendly technology development and advancing formula standardization. This work highlights AI's role in modernizing TCM R&D, offering a replicable framework to balance efficacy, affordability, and sustainability.

Triple-negative breast cancer (TNBC) remains a formidable clinical challenge owing to its aggressive phenotype and limited treatment options. To address this, we employed ligand-based rational drug design coupled with scaffold hybridization to develop a series of novel procaspase-3 activators. From 28 designed compounds, F17 and F21 emerged as lead candidates, exhibiting superior in vitro procaspase-3 activation. Density functional theory calculations confirmed their enhanced zinc-binding affinity, with adsorption energies (Eads) of -14.8332 eV (F17) and -14.8797 eV (F21), compared to -12.7474 eV for PAC-1, along with stronger electrostatic potential minima (-67.20 and -66.99 kcal/mol, respectively). In silico ADMET profiling indicated favorable drug-like properties, including good aqueous solubility, low blood-brain barrier penetration, and moderate intestinal absorption. In TNBC MDA-MB-231 models, both compounds demonstrated potent anti-proliferative activity, with IC50 values of 25.82 μM (F17) and 25.03 μM (F21) after 48 h, outperforming PAC-1 (33.81 μM). They also significantly inhibited cell migration, reducing wound closure to 11.19% (F21) compared with 20.60% in controls, and induced caspase-3-dependent apoptosis. Importantly, in vivo neurotoxicity assessments revealed no significant neuronal damage at doses up to 50 mg/kg, underscoring their improved safety profile over earlier activators. These results establish F21 as a particularly promising preclinical candidate and provide a rational framework for developing target-specific, neurotoxicity-sparing procaspase-3 activators for TNBC therapy.

Sophora flavescens is a widely used medicinal plant in traditional Chinese medicine, particularly known for its rich flavonoid content. Historically used in traditional medicine, this herb has been documented in the Shennong’s Classic of Materia Medica (Shennong Bencao Jing) for its effects in clearing heat, eliminating dampness, and serving as an anthelmintic and diuretic, for treating various conditions, including dysentery, jaundice, and skin diseases. Recent research on S. flavescens has expanded, particularly concerning its flavonoid compounds, which exhibit significant pharmacological activities, including antimicrobial, antioxidant, hepatoprotective, hypoglycemic, and antitumor effects. This review systematically summarizes the chemical constituents of S. flavescens, identifying over 130 flavonoid compounds, primarily isoprenylflavonoids, with a specific focus on their antitumor activities. Studies have shown that representative compounds, such as kurarinone and kushenol G, selectively exhibit cytotoxic effects against various cancer cell lines (e.g., HepG2, A549, MCF-7) while sparing normal cells. The antitumor mechanisms are primarily attributed to apoptosis induction, modulation of oxidative stress, and regulation of multiple signaling pathways, including the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway and the cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) pathway. Furthermore, safety assessments indicate that while the overall toxicity of flavonoids from S. flavescens is relatively low, certain compounds may pose hepatotoxic risks at high doses, warranting further attention in clinical applications. This review aims to provide an in-depth analysis and discussion of the chemical diversity, antitumor efficacy, and mechanisms of action of S. flavescens flavonoids, establishing a theoretical foundation and research direction for the development of novel anticancer drugs.

AMPA receptors (AMPARs) mediate most of the fast excitatory synaptic transmission in the mammalian brain. Their efficacy in responding to presynaptic glutamate release depends on their kinetics, which are determined by AMPARs and their auxiliary subunit composition. α/β-Hydrolase domain-containing 6 (ABHD6) is an AMPAR auxiliary subunit that has been shown to negatively regulate the surface delivery of AMPARs and AMPAR-mediated currents. Overexpression of ABHD6 has been shown to decrease the rising slope and increase the decay τ of mEPSCs. However, whether ABHD6 is involved in regulating AMPAR kinetics remains unclear. Here, we found that ABHD6 itself had no effect on the gating kinetics of GluA1 and GluA2(Q) containing homomeric receptors. However, in the presence of the auxiliary subunit TARP γ-2, ABHD6 accelerated the deactivation and desensitization of both GluA1 and GluA2(Q) containing homomeric receptors independent of their splicing isoforms (flip and flop) and the editing isoforms of GluA2 (R or G at position 764), except for the deactivation of GluA2(Q)i-G isoform. Besides, the recovery from desensitization of GluA1 with flip splicing isoform was slowed by the co-expression of ABHD6 in the presence of TARP γ-2. Furthermore, ABHD6 accelerated the deactivation and desensitization of GluA1i/GluA2(R)i-G and GluA2(R)i-G/GluA3(R)i heteromeric receptors in the presence of TARP γ-2. We also found that ABHD6-knockout neurons displayed slower deactivation and desensitization. Therefore, these results demonstrate that ABHD6 regulates AMPAR gating kinetics in a TARP γ-2-dependent manner.

Wilson's disease (WD) is an autosomal recessive disorder associated with impaired copper metabolism that results in hepatic manifestations. However, as a rare disease, the underlying pathogenic mechanism and drug development have lagged behind. Studies have reported that copper accumulation is associated with potential increases in iron levels, which can lead to further exacerbation of oxidative damage and has been observed in WD patients. Therefore, removing excess copper from the body and enhancing antioxidant capacity are crucial in treatment. Melatonin (MLT) is an endogenous hormone with anti-oxidative stress, anti-inflammatory, and anti-ferroptosis properties, and can chelate transition metals. Thus, the study aimed to investigated the relationship between WD and ferroptosis, and the therapeutic efficacy and mechanism of MLT using copper-laden rats and HepG2 cell models. Our results suggested that copper overload significantly increased oxidative stress and altering ferroptosis-related metabolites of the liver in copper-laden rats. In vivo and in vitro experiments showed that copper overload disrupts the ceruloplasmin-ferroportin (Cp-Fpn) iron transport system, leading to increased iron levels and promoting ferroptosis, as indicated by the decreased levels of ferroptosis-related proteins GPX4, with these findings further supported by RSL3 and Ferrostatin-1. Further, we found that MLT could improve liver function, iron levels and enhance its antioxidant capacity. In addition, MLT was also able to inhibit ferroptosis by activating the Nrf2/SLC7A11/GPX4 pathway. The effect is more effective than penicillamine, the current therapeutic drugs.Key Policy HighlightsCopper overload induces hepatic ferroptosis in Wilson's disease via iron accumulation, glutathione depletion, and lipid peroxidation.Reduced ceruloplasmin disrupts the ferroportin-mediated iron efflux system, aggravating ferroptosis.Melatonin alleviates liver injury and copper accumulation by inhibiting ferroptosis via activation of the Nrf2/SCL7A11/Gpx4 pathway.

The widespread use of QDs raises health and environmental concerns, and the ROS induced oxidative stress is reported as the main mechanism of QDs toxicity. Cytochrome P450 (CYP450) superfamily, the primary enzyme system for metabolizing external compounds in the liver, also generates reactive oxygen species (ROS), making it crucial for detoxification and ROS production. Therefore, we investigated whether QDs could cause liver tissue damage by affecting the activity of CYP450 isoenzymes (CYP1A2, CYP2E1, CYP2D2, and CYP3A1) in liver microsomes, thereby altering ROS generation. This mechanism has not been previously reported. Our experiments indicate that CdTe QDs exhibit a dose/time-dependent relationship with the enzymatic activities of CYP1A2 and CYP2E1, which are closely related to ROS generation. However, an inconsistency was observed between the data for CYP2E1 activity in vivo and in vitro due to the complexity of in vivo regulatory factors. More importantly, in vitro experiments have shown that CdTe QDs can significantly promote the enzymatic activity of CYP1A2. Therefore, we speculate that CdTe QDs may induce ROS generation by enhancing CYP450 enzyme activities. In addition, molecular docking experiments were conducted to illustrate the impact of CdTe QDs on the structure of CYP1A2, leading to functional change (i.e., enzyme activity). These findings suggest a novel mechanism by which CdTe QDs regulate CYP450 activities in liver microsomes, particularly CYP1A2. This may represent a crucial pathway through which CdTe QDs induce excessive ROS generation, leading to oxidative stress and liver damage.

Wearable biosensors represent a significant advancement in preventive health monitoring by enabling early disease detection through real-time bioanalysis. This review examines the evolution of point-of-care testing (POCT), with a focus on materials, fabrication techniques, and real-world applications. These biosensors utilize advanced materials, such as supramolecular hydrogels, and innovative manufacturing methods, providing high sensitivity, specificity, and portability. They enable continuous monitoring of biomolecules─including proteins, nucleic acids, and pathogens─in peripheral body fluids, thereby supporting the early diagnosis of diseases such as infections, cardiovascular disorders, diabetes, and cancer. The integration of wireless data transmission and artificial intelligence further enhances the applicability of these devices in both clinical and remote healthcare settings. The implementation of such technologies shows potential for reducing healthcare expenditures and improving therapeutic outcomes. However, challenges remain in standardizing POCT protocols, ensuring cost-effectiveness, and safeguarding patient data privacy. This review underscores the potential of wearable biosensors in global healthcare while emphasizing the necessity for continued research to address current limitations.

Caspase-3 is an essential intracellular protein mediating cell apoptosis and a key target in the apoptosis pathway of cancer cell. Activating its existing inactive proenzyme, Procaspase-3, induces apoptosis in various tumor cells and has emerged as a promising cancer therapy strategy. In this study, a novel series of hybrid caffeic acid benzylidene hydrazide derivatives were rationally designed and evaluated as potent procaspase-3 activators. Caffeic acid was first identified as a privileged scaffold for procaspase-3 activation through structure-based pharmacophore modeling. By hybridizing this natural product scaffold with optimized structural elements from PAC-1, a reference procaspase-3 activator, 28 target compounds (K-01 ∼ K-28) were successfully synthesized. Molecular modeling studies revealed that these hybrid compounds possess enhanced zinc chelation capacity, a crucial mechanism for procaspase-3 activation. The antiproliferative activity of these compounds was systematically evaluated against A549 (non-small cell lung cancer) and A375 (melanoma) cell lines. Among the synthesized derivatives, 23 compounds (82.1 %) demonstrated superior potency compared to PAC-1 (positive control). Notably, compounds K-15 and K-22 exhibited significant activity against A549 cells (IC50 = 3.96 ± 1.07 μM and 5.60 ± 2.20 μM, respectively) while maintaining minimal cytotoxicity toward human lung epithelial cells (BEAS-2B), as evidenced by high cell viability rates of 91.99 % and 95.37 %. Direct procaspase-3 activation by these lead compounds was further confirmed through mechanistic studies. In silico ADMET profiling demonstrated that the lead compound K-15 exhibits optimal pharmacokinetic properties, including moderate aqueous solubility (Level 2), negligible blood-brain barrier penetration (Level 4), absence of hepatotoxicity risk, and favorable intestinal absorption (Level 1). All compounds were confirmed to be non-inhibitors of CYP2D6, indicating minimal potential for drug-drug interactions. These results demonstrate that the hybrid molecular design strategy effectively combines the pharmacophoric advantages of both natural products and synthetic activators. The developed procaspase-3 activators exhibit improved therapeutic potential and represent promising candidates for further development as targeted anticancer agents modulating the caspase-3 activation pathway.

Cancer, particularly lung, liver, and other malignancies, remains a major global health challenge due to their high incidence, complex etiology, and resistance to conventional therapies. Flavonoids derived from Sophora flavescens (Kushen) have gained attention for their potential in cancer prevention and treatment. This study uses network pharmacology, based on Traditional Chinese Medicine's holistic approach, and molecular simulation techniques to explore the anticancer mechanisms of Sophora flavescens flavonoids, aiming to provide a theoretical basis for developing plant-based anticancer agents. Active compounds and their targets were identified through literature screening and target identification methods. A cancer-related protein–protein interaction (PPI) network was constructed to identify key therapeutic targets, helping to understand how these flavonoids exert multitarget anticancer effects. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses elucidated mechanisms related to cancer cell proliferation inhibition, apoptosis induction, and signaling pathway regulation. Network pharmacology analysis identified TP53, ESR1, SRC, AKT1, and MAPK1 as key anticancer targets, involved in essential biological processes like phosphorylation and protein kinase activity. KEGG analysis showed that these flavonoids modulate critical pathways, particularly PI3K-Akt and RAS/RAF/MEK/ERK. Molecular docking revealed that rutin and luteolin-7-O-gentiobioside strongly bind to MAPK1, with interaction energies of 77.1466 kcal/mol and 79.2011 kcal/mol, respectively, indicating promising anticancer effects. Additionally, compounds with different substitution positions, such as those with glycosylation at the 7-OH position or isoprenyl groups at the C-8 positions, exhibited significantly higher interaction energies. Non-covalent interaction analysis further clarified how these flavonoids enhance anticancer effects through stable binding, with hydrogen bonds and hydrophobic contacts stabilizing interactions with MAPK1. Molecular dynamics simulations also confirmed the stability of these interactions, and binding free energy calculations revealed that luteolin-7-O-gentiobioside and rutin exhibited the lowest binding free energies (− 153.7841 kcal/mol and − 132.7434 kcal/mol, respectively), significantly outperforming the original ligand (− 57.7209 kcal/mol), further supporting the therapeutic potential of these compounds. To complement these findings, in silico ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) predictions were employed to evaluate the pharmacokinetic and safety profiles of rutin and luteolin-7-O-gentiobioside. The systematic analysis revealed critical issues in solubility, blood–brain barrier penetration, and hepatotoxicity, providing strategic guidance for structural optimization and formulation design. This study provides valuable insights into the multitarget anticancer mechanisms of Sophora flavescens flavonoids and supports their potential as plant-derived anticancer agents. However, further experimental and clinical studies, especially integrating TCM practice, are needed to validate these findings.

This study aims to elucidate the potential targets and molecular mechanisms underlying the anticancer effects of Red fermented rice extract using molecular simulation techniques. The inhibitory effects of different elution fractions of Red fermented rice extract on A549 and MCF-7 cell proliferation were evaluated through CCK-8 assays. Liquid chromatography-mass spectrometry (LC-MS) was employed to elucidate the structural information of active components, while molecular simulation techniques aided in identifying target proteins based on small molecule structures. Protein immunoblotting was utilized to investigate the mechanisms of action of relevant targets. The study found that the petroleum ether-ethyl acetate and ethyl acetate elution fractions of Red fermented rice extract significantly inhibited A549 and MCF-7 cell proliferation, with stronger effects observed on A549 cells. LC-MS structural analysis identified 25 small molecule structures. Molecular simulations successfully revealed interaction between active elution fractions of Red fermented rice extract and the cancer-related protein FGFR1. Further investigation into the phosphorylation of FGFR1 and its downstream pathway targets PI3K/AKT demonstrated that the active elution fractions exerted their anticancer activity by inhibiting the phosphorylation of FGFR1, PI3K, and AKT proteins. This comprehensive study, integrating CCK-8 assays, LC-MS, molecular simulation techniques, and protein immunoblotting, provides a deep understanding of the anticancer mechanisms of Red fermented rice extract, guiding its further development and clinical application.

Copper serves as an indispensable cofactor for all living organisms, and its excessive accumulation has been associated with a variety of diseases. Wilson’s disease (WD) serves as an illustrative example of copper toxicity in humans, frequently presenting with liver and/or neuropsychiatric symptoms. The current therapeutic drugs, penicillamine (PA) and zinc gluconate (ZnG), have constraints, and research on their combination efficacy remains insufficient. It has been reported that melatonin (MLT) plays a vital role in binding to transition metals and exhibits strong antioxidant capacity. To investigate the therapeutic efficacy of MLT and combined treatment, rats were randomly divided into the following seven groups: the control (Con) group, copper-laden model rat (Mod) group, PA-treated group, ZnG-treated group, MLT- treated group, PA-ZnG-treated group, and PA-MLT-treated group. Then potential mechanisms and targets were investigated using a combination of metabolomics and network pharmacology and verified by molecular docking and qPCR. The findings revealed that MLT and the combination significantly improved behavior, pathology and copper levels in copper-laden rats. The results of the metabolomics study showed that profoundly altered metabolites were identified, and alanine, aspartate and glutamate metabolism, pyruvate metabolism, citrate cycle (TCA cycle), and glycolysis/gluconeogenesis were explored. In addition, molecular docking showed that MLT had high binding affinity with key targets, and qPCR results revealed that MLT could reverse the mRNA expression of targets GOT2 and PKM2. It was concluded that MLT effectively improves brain injury in copper-laden rats, and this effect was linked with the altered features of the metabolite profiles

The mechanisms through which aging increases heart injury remain partially understood. Protein phosphorylation plays a critical regulatory role in cell survival and death. Using an unbiased phosphoproteomics approach, we aimed to identify the proteins whose phosphorylation could be causatively related to aging-related cardiomyocyte apoptosis and elucidate the underlying mechanisms. Comparative phosphoproteomics was conducted on cardiac tissues obtained from young (8 weeks) and aged (24 months) mice. Our findings revealed that the Mammalian Target of Rapamycin phosphorylation at T1262 (mTORT1262) was reduced in the aging heart. Immunohistochemical and Western blot analyses confirmed these findings in aging myocardia and D-galactose-induced senescent AC16 cardiomyocytes. In hypoxia/reoxygenation cardiomyocytes, mTORT1262 phosphorylation deficiency (mTORT1262A, lentivirus-mediated transfection) inhibited AKT1, suppressed NF-κB, activated FOXO1/3a signaling, and ultimately exacerbated apoptosis. Conversely, mTORT1262 pseudophosphorylation (mTORT1262E) exhibited opposite effects. Through bioinformatics and CO-IP, purinergic receptor P2X4 (P2X4R) was found to be the possible receptor responsible for mTORT1262 phosphorylation. Knockdown of P2X4R increased apoptosis, whereas its overexpression decreased it. In senescent cardiomyocytes, P2X4R expression and mTORT1262 and AKT1S473 phosphorylation were reduced, NF-κB signaling was suppressed, and FOXO1/3a signaling was activated. We demonstrated that P2X4R downregulation and the subsequent reduction of mTORT1262 phosphorylation is a novel mechanism contributing to cardiomyocyte apoptosis in aging hearts. The P2X4R-mTOR-AKT1 signaling pathway represents a potential therapeutic target against accelerated cardiac injury in aging.

Epidemiological evidence has indicated a closely link between PM0.1 exposure and the incidence rate of cardiovascular diseases. This study explores the underlying communication roles of platelet-derived extracellular vesicles (PEVs) heterogeneous subpopulations in cardiovascular injury. PEVs and PMEVs which were extracted from platelet-rich plasma (PRP) un-exposure or exposure to PM0.1 by TIM4 affinity beads. By optimizing separation conditions, replacing pipelines, and resetting injection procedures, Asymmetric flow field-flow fractionation (AF4) was employed to separate, purify, characterize, and enrich PEVs and PMEVs heterogeneous subpopulations (small PEVs, PEVs-S/PMEVs-S: <100 nm; medium PEVs, PEVs-M/PMEVs-M: 100-200 nm; and large PEVs, PEVs-L/PMEVs-L: >200 nm). The results showed that the cargoes of PMEVs heterogeneous subpopulations which were released by PRP stimulated by PM0.1 were changed obviously. Moreover, compared with PEVs, PMEVs can lead to a decrease in the survival rate of Human Umbilical Vein Endothelial Cells (HUVECs). In PMEVs-S subpopulations, the alterations of lipids associated with membrane fusion and cell signaling transport (such as PC, Cer), as well as miRNAs related to inflammation, angiogenesis, and migration (miR-223, miR-22, miR-126, and miR-150), are similar to those in PMEVs-M subpopulations but distinct from PMEVs-L subpopulations. This study revealed the diverse communication mechanisms underlying PM0.1-induced cardiovascular injury, thereby offering potential avenues for the development of new biomarkers and therapeutic targets.

UV irradiation significantly alters nanoplastics (NPs) physicochemical properties, thus affecting their biological toxicity. This study is the first to assess the influence of virgin and UV-aged polystyrene NPs (v-PS NPs, a-PS NPs) on the intestinal barrier of ICR mice. We found that a-PS NPs can cause more severe intestinal barrier damage compared with v-PS NPs. The reason may be attributed to that a-PS NPs produced more ROS in intestinal tissue. Moreover, the strong oxidizing property of hydroxyl radicals (·OH) generated from the a-PS NPs can damage cell membranes through lipid peroxidation, thereby leading to a low clearance rate of ·OH due to the impaired intestinal tissue function, in turn, causing more ROS to accumulate and inducing severe oxidative damage. This research underscores the crucial role of ·OH in mediating oxidative damage from UV-aged nanoparticles, emphasizing the need to consider environmental factors in assessing NPs toxicity.

分析信息管理与信息系统(卫生信息管理方向)专业发展现状,结合首都医科大学信息管理与信息系统专业(卫生信息管理方向)人才培养实践,从人才培养、教育教学和课程设置等方面详细阐述其模式创新探索路径.

目的:对围术期不同水化治疗方案预防支架置入术后患者对比剂肾损伤疗效进行Meta分析,系统评价多种水化治疗方案预防支架置入术后患者对比剂肾损伤发生的效果并给出最优的干预方案.方法:计算机检索PubMed、EMbase、Cochrane Library、中国知网、万方、维普和中国生物医学数据库,纳入国内外有关水化治疗的不同干预方法对于支架置入术后患者对比剂肾损伤疗效的临床研究文献,检索时限均从建库至2021 年12 月31 日,收集符合要求的随机对照试验(RCT)文献,运用Cochrane系统评价的方法,使用RevMen5.4软件对研究结果进行Meta分析.结果:最终共纳入5篇文献,总计988例支架置入病例,结果显示围术期静脉水化治疗对于预防对比剂肾损伤的效果优于围术期口服水化治疗,总有效率(RR=0.59,0.95％CI:0.40～0.87,Z=2.70,P=0.007)差异有统计学意义.结论:相对于围术期单纯口服水化治疗,围术期静脉水化治疗可更好地减少支架置入术后患者对比剂肾损伤的发生率.

Nanostructured lipid carriers is a new dosage form in food industry. As a delivery system for functional foods, it has a high drug loading and encapsulation rate, which can effectively increase the bioavailability and stability of fat-soluble bioactive substances, improve the nutritional value and safety of food, and control the release of encapsulating materials, so it has a broad application prospect. In this paper, the classification of structural characteristics (imperfect type, amorphous type and multiple type) and several common preparation methods of nanostructured lipid carriers are reviewed, including the process flow as well as the advantages and drawbacks of hot high-pressure homogenization, cold high-pressure homogenization, solvent emulsification diffusion method, solvent emulsification evaporation method, solvent injection/solvent displacement method, microemulsion technique, emulsification ultrasonic method, membrane contractor, phase inversion techniques and super critical fluid method. The protection and delivery of nanostructured lipid carriers for essential fatty acids, carotenoids, phytosterols, fat-soluble vitamins, polyphenols and other bioactive substances in functional food field are summarized. The limitations and future research trends of nanostructured lipid carriers delivery system in food industry are summarized and discussed, which would provide a theoretical basis for subsequent research.

目的 了解北京市卫生系统≥60岁老年人新型冠状病毒肺炎疫苗(以下简称"新冠疫苗")接种情况及影响因素.方法 采用多阶段分层抽样方法,从北京市卫生系统21家医院中选择7家为调查点,在知情同意的原则下对其中≥60岁的老年人(离退休职工)按照年龄构成比开展问卷调查.收集数据以例(％)描述,比较不同项目类别受调查对象疫苗接种情况,采用Logistic回归方法分析影响疫苗接种的因素.结果 回收有效问卷617份.调查对象的新冠疫苗接种率为63.9％(394/617),60～69岁、70～79岁、≥80岁年龄段的接种率分别为75.8％(257/339)、65.5％(97/148)、30.8％(40/130).接种疫苗者轻微不良反应发生率为23.1％(91/394),严重不良反应发生率为0.3％(1/394).Logistic回归分析结果显示年龄、基础病数量、居住区域是否组织了集中接种、是否有流感疫苗接种史对≥60岁老年人接种新冠疫苗具有显著影响(均P＜0.05).60～79岁年龄段和≥80岁年龄段老年人未接种新冠疫苗的首位原因不同,分别是有接种禁忌和很少出门感染可能性小.结论 不同年龄段老年人新冠疫苗接种率差异较大;要提高≥60岁老年人对新冠疫苗的接种率,需针对老年人基础疾病多以及不同年龄段老年人未接种的主要原因,采取针对性的宣传动员及接种策略.

Graphene oxide (GO) has emerged as a potential drug delivery vector. For siRNA delivery, GO should be modified to endow it with gene delivery ability and targeting effect. However, the cationic materials used previously usually had greater toxicity. In this study, GO was modified with a non-toxicity cationic material (chitosan) and a tumor specific monoclonal antibody (anti-EpCAM) for the delivery of survivin-siRNA (GCE/siRNA). And the vector (GCE) prepared was proved with excellent biosafety and tumor targeting effect. The GCE exhibited superior performance in loading siRNA, maintained stability in different solutions and showed excellent protection effect for survivin-siRNA in vitro. The gene silencing results in vitro showed that the mRNA level and protein level were down-regulated by 48.24% ± 2.50% and 44.12% ± 3.03%, respectively, which was equal with positive control (P > 0.05). It was also demonstrated that GCE/siRNA had a strong antitumor effect in vitro, which was attributed to the efficient antiproliferation, and migration and invasion inhibition effect of GCE/siRNA. The results in vivo indicated that GCE could accumulate siRNA in tumor tissues. The tumor inhibition rate of GCE/siRNA 54.74% ± 5.51% was significantly higher than control 4.87% ± 8.49%. Moreover, GCE/siRNA showed no toxicity for blood and main organs, suggesting that it is a biosafety carrier for gene delivery. Taken together, this study provides a novel design strategy for gene delivery system and siRNA formulation.