Non-alcoholic fatty liver disease (NAFLD) has emerged as a public health challenge, yet the available therapeutic options remain limited. Evidence suggests that NAFLD may advance to more serious conditions, including steatohepatitis or cirrhosis, which are associated with poor outcomes. Current drug therapies exhibit insufficient therapeutic efficacy due to short half-life and premature clearance. In this work, we elucidate the critical impact of endoplasmic reticulum stress (ERS) on inflammatory process associated with NAFLD using bioinformatics tools. By analysing single-cell RNA sequencing data from an animal model of NAFLD, we identified hepatocytes as the primary cell type implicated in ERS. Melatonin (Mel), a compound known for its antioxidative properties, also modulates the ERS pathway, suggesting its potential to slow NAFLD progression. To exploit this therapeutic potential, we developed a nanoparticle (NP), GalNAc-MM@PLGA/Mel, which incorporates engineered macrophage membranes to specifically target hepatocytes and mitigate ERS. The addition of GalNAc moieties on the membrane significantly enhanced the ability of NPs to specifically bind to hepatocytes. Moreover, Mel, delivered through this platform, effectively reduced inflammation and lipid accumulation by inhibiting both the ERS pathway and its downstream NF-κB signaling cascade. Consequently, this engineered NP-based strategy offers a promising, safe and cost-efficient approach to managing NAFLD.

Lung cancer remains the leading cause of cancer-related mortality worldwide, and immune checkpoint blockade is often limited by an immunosuppressive tumor microenvironment (TME). To address these challenges, we developed a novel multifunctional nanoplatform, based on a mesoporous Fe3O4 core and silica shell, co-loading pemetrexed and an anti-PD-L1 antibody (PD-L1&Pem@msNPs). The construct enables checkpoint-targeted delivery, alternating magnetic field (AMF)-triggered hyperthermia and controlled drug release, enabling a singlesystem chemo-immuno-magnetothermal regimen. We comprehensively investigated the physicochemical properties, magnetothermal performance, loading/conjugation, and release behavior, and validated cellular uptake and cytotoxicity in vitro. In subcutaneous and orthotopic lung tumor models, PD-L1&Pem@msNPs achieved superior tumor suppression and extended survival compared with control formulations. Mechanistically, transcriptomic profiling together with immunophenotyping demonstrated marked TME remodeling, with increased intratumoral T-cell representation accompanied by coordinated rewiring of macrophages status. Notably, longitudinal flow cytometry revealed a shift in T-cell states from an exhausted-intermediate (Tex-int) toward a progenitor-like (Tex-prog) phenotype, consistent with restoration of T-cell functionality under treatment. Collectively, PD-L1&Pem@msNPs provides an externally activatable, modular platform to remodel the TME and improve the therapeutic impact of PD-L1 blockade in lung cancer.

Stimulus-responsive nanomaterials, particularly with targeting capabilities, have garnered significant attention in the cancer therapy. However, the biological safety of these innovative materials in vivo remains unknown, posing a hurdle to their clinical application. Here, a pH/H 2 O 2 dual-responsive and targeting nano carrier system (NCS) was developed using core shell structure of Fe 3 O 4 mesoporous silicon (MSN@Fe 3 O 4 ) as main body, scutellarin (SCU) as antitumor drug and polymer cyclodextrin (PCD) as molecular switch (denoted as PCD@SCU@MSN@Fe 3 O 4 , abbreviated as NCS). The NCS, with an average particle size of 100 nm, displayed exceptional SCU loading capacity, a result of its uniform radial channel structure. The in vitro investigation under condition of pH and H 2 O 2 indicated that NCS performed excellent pH/H 2 O 2 -triggered SCU release behavior. The NCS displayed a higher cytotoxicity against tumor cells (Huh7 and HCT116) due to its pH/H 2 O 2 dual-triggered responsiveness, while the PCD@MSN@Fe 3 O 4 demonstrated lower cytotoxicity for both Huh7 and HCT116 cells. In vivo therapeutic evaluation of NCS indicates significant inhibition of tumor growth in mouse subcutaneous tumor models, with no apparent side-effects detected. The NCS not only enhances the bioavailability of SCU, but also utilizes magnetic targeting technology to deliver SCU accurately to tumor sites. These findings underscore the substantial clinical application potential of NCS.

Letters to the Editors Anti-TIF1-γ antibody-positive dermatomyositis caused by camrelizumab in a patient with oesophageal cancer

肿瘤科涉及的疾病广泛、病情复杂多变、肿瘤相关知识更新快,这些特征对临床实践提出了更高的要求及更大的挑战.因此,在肿瘤教学工作中,培养缜密的临床思维对于肿瘤专业研究生胜任临床肿瘤工作具有重要的现实意义.以问题为基础的教学法(PBL)目前得到大家的一致认可.然而,如何在PBL教学中培养肿瘤专业学生良好的临床思维值得探索.考虑不同肿瘤、不同个体导致患者的诊治存在本质性差别,因此,该文将从器官功能和形态的差异化表现、肿瘤进程时间节点的临床差异化表现、肿瘤患者治疗方式差异化表现、肿瘤患者合并基础疾病的差异化表现4个方面,探讨以肿瘤差异化表现为导向的PBL教学法在肿瘤科专业型研究生临床思维培养的应用价值.

Aim:To compare the efficacy and safety of radiotherapy in combination with immunotherapy after achieving disease control from the first-line combination therapy of platinum-based chemotherapy and immunotherapy for advanced lung squamous cell carcinoma (LUSC).Methods:This study retrospectively evaluated the patients with advanced LUSC treated with the combination of radiotherapy with immunotherapy and chemotherapy (ICRT group, n = 52) or immunotherapy and chemotherapy (ICT group, n = 63) as the first-line treatment from April 2018 to April 2022. Using propensity score matching (PSM), 50 pairs were created, while the confounders and bias were controlled. The objective response rate (ORR), duration of overall response (DOR), progression-free survival (PFS), overall survival (OS), and adverse events were analyzed in the two groups. The PFS and OS were re-analyzed separately for patients treated with thoracic radiotherapy.Results:After PSM, the median PFS (12.23 vs. 7.43 months; P <0.001) and median OS (19.7 vs. 12.9 months; P <0.001) were significantly longer in the ICRT group than those in the ICT group. Both the PFS and OS rates were also significantly higher in the ICRT group than those in the ICT group, except for the OS rates in the 6th and 12th months. The mDOR of the ICRT group patients (17.10 vs. 8.27 months; P <0.001) was significantly higher than that of the ICT group patients. The median PFS, median OS, and local control rate were significantly longer in the thoracic radiotherapy group than in the control group. Radiation pneumonia was the most common adverse effect after radiotherapy; however, no treatment-related deaths occurred. The Cox regression analysis showed that ECOG scores 0-1, presence of necrosis in the tumor, radiotherapy, and optimal efficacy better than the stable disease (SD) were independent factors, affecting the PFS, while the patients with recurrent post-operative, pre-treatment NLR, radiotherapy, and optimal efficacy better than SD were the independent factors, affecting the OS.Conclusions:The combination of radiotherapy with systematic immunotherapy and chemotherapy for the advanced LUSC was effective with tolerable adverse effects.

In the past few years, drug delivery systems have been used extensively to improve solubility, stability, and pharmacokinetics of chemotherapeutic drugs. However, traditional delivery systems fail to fulfill the required standard of effectiveness, primarily owing to issues of drug resistance exhibited by cancer cells and inherent differences among the patients. In this regard, combination therapy offers advantages of synergistic mechanism, reduced drug dosage, and enhanced therapeutic effect, which can be effectively utilized for the treatment of cancer. However, different types of therapeutic agents exhibit different pharmacokinetic properties and action targets in vivo, which lead to uncontrollable concentration ratio of therapeutic agents at the lesion site. This in turn causes serious side effects and affects synergistic anticancer effect. Importantly, multifunctional co-delivery systems are characterized by good pharmacokinetic properties, ability to provide targeted delivery, and controlled release in response to tumor microenvironment. Such delivery systems are widely used for co-delivery of therapeutic agents, which further assist in obtaining better synergistic anticancer effect, and can be potentially used for clinical application. Multifunctional co-delivery systems often exhibit complex structures and construction process. Since cyclodextrin is characterized by self-assembly property, it is possible to quickly construct cyclodextrin-based multifunctional co-delivery systems, with convenience and flexibility. The application of cyclodextrin in the construction of multifunctional co-delivery systems for cancer therapy has gained immense attention in the past few years. The present study provided overview of latest progress in the field of cyclodextrin-based multifunctional co-delivery systems for cancer synergistic therapy.

Aim The aim of the study is to compare the efficacy and safety of monotherapy with a sequential immune checkpoint inhibitor (ICI) programmed cell death protein-1 (PD-1) and its combination with multi-target drug sorafenib after transcatheter arterial chemoembolization (TACE) for advanced hepatocellular carcinoma (HCC). Methods We conducted a retrospective evaluation of patients with advanced HCC who had received sequential PD-1 sorafenib (duplex group, n = 25) or monotherapy PD-1 alone (PD-1 group, n = 41) after TACE during April 2018–September 2021. Propensity score matching (PSM) was applied to correct the selection bias, and 22 pairs were created. The objective response rate (ORR), duration of the overall response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events were analyzed for both groups. Results After PSM, the median PFS (7.63 vs. 2.9 months; p = 0.0335) was significantly longer for the duplex group than for the PD-1 group. The median OS (21.63 vs. 16.43 months; p = 0.103) was longer for the duplex group than for the PD-1 group, albeit without any statistical difference. The CR rate, ORR, DCR, and PFS rates at the first, third, and sixth months were higher for the duplex group than for the PD-1 group, wherein the PFS rate of the third and sixth months were statistically different. The OS rates at the sixth, 12th, and 18th months were better for the duplex group than for the PD-1 group, while the 18th-month OS rate (54.5% vs. 33.9%, p = 0.030) were statistically different between them. The most common adverse events after TACE included liver function injury, leukocytopenia, and thrombocytopenia, albeit without any statistical differences between the groups. Cox regression analysis showed that sorafenib combined immunotherapy after TACE and the achieving of CR or PR during the treatment were independent factors affecting PFS. Moreover, CNLC stage-IIIa, TACE frequency ≤2, and achievement of CR or PR were independent influencing factors of OS. Conclusions Sequential PD-1 combined with sorafenib therapy after TACE for advanced HCC treatment is safe and effective, especially for patients with good initial treatment response, to further improve the disease prognosis.

随着近年来医学院校不断扩招,医学生的管理难度增加,为了保证教育质量,兼职班主任制度氤氲而生,班主任们重点关注学生的思想动态、心理素质,帮助学生树立正确的价值观.本文从兼职班主任的实践工作经历出发,探讨了目前兼职班主任制度在影像医学专业的局限性及应对措施,希望对高等医学院校建立健全兼职班主任制度起到积极作用.

目的 探讨CT引导下经皮肺穿刺活检结合快速现场细胞学评价(C-ROSE)在肺周围型肿物诊治中的临床价值.方法 选取2018年8月至2019年11月该院肿瘤中心收治的107例胸部CT检查提示周围型肺肿物的患者,随机分为试验组(n=53)和对照组(n=54),行CT引导下经皮肺肿物穿刺活检.试验组将穿刺组织行抹片后再行C-ROSE,对照组穿刺组织不做任何处理.术后对两组组织均行常规组织学病理检测,必要时辅以免疫组织化学协助诊断.结果 试验组中C-ROSE灵敏度为97.96％、特异度为100％,与组织学诊断高度一致.试验组与对照组穿刺时间分别为(18.79±3.39)min,(18.09±3.49)min;穿刺次数分别为(3.15±0.89)次,(2.87±0.75)次;穿刺气胸发生率分别为7.55％、5.56％,出血发生率分别为1.89％、1.85％.试验组中无因诊断及基因检测需要二次取材患者.对照组中因诊断需重新取材1例,因基因检测需重新取材3例.结论 C-ROSE指导CT引导下经皮肺穿刺活检具有较高临床应用价值.

目的 探讨芪鹿补血颗粒在宫颈癌同步放化疗中的作用.方法 选取2019年4月1至9月1日在该中心行宫颈癌同步放化疗患者40例,根据是否口服芪鹿补血颗粒分为观察组和对照组,各20例.观察两组患者血红蛋白(Hb)及生活质量(QOL)情况.结果 同步放化疗后,观察组患者Hb水平及QOL评分均高于对照组,差异均有统计学意义(P<0.05).结论 芪鹿补血颗粒在宫颈癌同步放化疗中具有显著辅助治疗作用,可升高Hb水平,改善贫血,提高患者QOL,值得临床推广使用并进一步观察其应用的远期疗效.

Objective To evaluate the clinical efficacy of oral ulcer protective agent in the prevention and treatment of oral mucositis in nasopharyngeal carcinoma (NPC) radiotherapy and its effect upon serum inflammatory factors.Methods A total of 90 patients diagnosed with nasopharyngeal carcinoma presenting with grade I oral mucositis caused by radiotherapy in our hospital were selected and randomly divided into two groups.In the experimental group,oral ulcer protective agent was given,and Kangfuxin gargle was administered in the control group.The incidence time and degree of radioactive oral mucositis,visual analogue scale (VAS) pain score,serum levels of CRP,TGF-β1,IL-6 and T lymphocyte subsets were statistically compared between two groups by independent-sample t-test.Results At 4 and 6 weeks after corresponding treatment,the incidence of grade Ⅱ and Ⅲ oral mucositis in the experimental group was significantly lower than that in the control group (P=0.018,0.021,0.027,0.014)).In the experimental group,the incidence of moderate and severe pain assessed by VAS was significantly lower compared with that in the control group (P=0.019,0.025);After corresponding treatment,the CRP levels in both groups were down-regulated and the CRP level in the experimental group was considerably lower than that in the control group (P=0.013).The levels of TGF-β1 and IL-6 in the control group were significantly increased (P=0.015、0.021),whereas dramatically declined in the experimental group (P=0.012,0.019).CD3(+),CD4 (+),CD8(+) and CD4(+)/CD8(+) were remarkably elevated in two groups,and more significant increase was observed in the experimental group (P=0.024,0.036,0.029,0.017).Conclusions Oral ulcer protective agent can effectively inhibit the progression of oral mucosal injury,shorten the healing time and relieve the pain of oral mucosal injury in patients with NPC.,which is worthy of clinical application.

With the development of materials science and pharmaceutics, the application of mesoporous silica nanoparticles with a gated switch in the field of drug delivery has attracted much attention in the past decades. Cyclodextrins (CD) as promising gated materials have become a new area of interest in recent years due to their properties of self-assembly and function of host-guest interaction. CD is one kind of extensively studied host molecules and the host-guest interactions with different guest molecules can respond to different signals, and thus can be applied as intelligent gated switches for smart drug carriers. Switchable gatekeepers based on CD hosts with different guest molecules (such as benzimidazole, azobenzene, and ferrocene) respond to different stimuli modes (such as pH, light, and redox) that change the host-guest interactions and trigger drug release. The different structural features, mechanisms of action, and potent applications of these switchable gatekeepers are discussed. In addition, some personal perspectives and challenge on this field are presented.

A series of novel pendant polymers, composed of a poly(epsilon-lysine) (epsilon-PL) ((M) over barw: 4,000gmol(-1)) main chain and three kinds of amino acid beta-cyclodextrin (CD) derivatives, were prepared by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide-assisted synthesis and characterized by nuclear magnetic resonance, Fourier transform infrared spectroscopy, thermal gravimetric analysis, X-ray power diffraction, and scanning electron microscopy. Cytotoxicity and moisture absorption of the pendant polymers were also tested. Compared with epsilon-PL, all the pendant polymers exhibited lower moisture absorption and cytotoxicity. The synthesis method of the pendant polymers is simple, feasible, and has good practicability. We suggest these polymers have potential applications in many fields, especially in gene delivery vector and drug delivery systems.

Specificity protein1 (Sp1) is required for TGF-β-induced epithelial-to-mesenchymal transition (EMT) which has been demonstrated to aggravate the progression of cancer including lung cancer. microRNA-29c (miR-29c) is identified to inhibit EMT, but the correlation between miR-29c and Sp1 in human lung cancer remain incompletely clarified. Here, we confirmed decreased expression of miR-29c and enhanced expression of Sp1 in lung cancer tissues (n = 20) and found that Sp1 could be targeted and inhibited by miR-29c. Besides, the expression of miR-29c was down-regulated in high-metastatic lung cancer cell lines and TGF-β1-treated cells. The inhibition of miR-29c or overexpression of Sp1 in 95C and A549 cells dramatically enhanced the cell migration and invasion, and also induced the decrease in the expression of epithelial markers, e.g. thyroid transcription factor 1 (TTF-1) and E-cadherin, together with an increase in mesenchymal markers including vimentin, α-smooth muscle actin (α-SMA), which could be restored by overexpression of miR-29c mimics during the TGF-β-induced EMT. Moreover, dual-luciferase reporter assay was performed and the results indicated that miR-29c/Sp1 could form an auto-regulatory loop with TGF-β1, which impaired TGFB1 transcription. Furthermore, miR-29c overexpression could abrogate the tumor progression and inhibit the Sp1/TGF-β expressions in vivo, indicating that miR-29c could be a tumor suppressor and repress the Sp1/TGF-β axis-induced EMT in lung cancer.

目的:观察MUC1对人结肠癌细胞HCT116增殖、侵袭及化疗敏感性的影响.方法:采用MUC1表达阴性的结肠癌细胞株HCT116,通过慢病毒转染、嘌呤霉素筛选、半定量RT-PCR和Western blot鉴定构建稳定表达MUC1的HCT116细胞株;实验分空病毒组和MUC1病毒组;CCK实验和软琼脂克隆形成实验检测两组细胞的增殖能力,Transwell侵袭实验检测两组细胞的侵袭能力;MTT法和流式细胞仪检测两组细胞对奥沙利铂的敏感性,酶底物法检测Caspase-3活性.结果:获得稳定表达MUC1的HCT116细胞株;两组细胞贴壁生长无差异;与空病毒组相比,MUC1病毒组细胞软克隆形成数增加,穿过小室的细胞数增加(P＜0.05);MUC1病毒组细胞对奥沙利铂的敏感性降低,MUC1病毒组Caspase-3活性水平低于空病毒组(P＜0.05).结论:MUC1与结肠癌的非锚定依赖生长、侵袭和化疗敏感性有关.

A targeting gene carrier for cancer-specific delivery was successfully developed through a "multilayer bricks-mortar" strategy. The gene carrier was composed of adamantane-functionalized folic acid (FA-AD), an adamantane-functionalized poly(ethylene glycol) derivative (PEG-AD), and β-cyclodextrin-grafted low-molecular-weight branched polyethylenimine (PEI-CD). Carriers produced by two different self-assembly schemes, involving either precomplexation of the PEI-CD with the FA-AD and PEG-AD before pDNA condensation (Method A) or pDNA condensation with the PEI-CD prior to addition of the FA-AD and PEG-AD to engage host-guest complexation (Method B) were investigated for their ability to compact pDNA into nanoparticles. Cell viability studies show that the material produced by the Method A assembly scheme has lower cytotoxicity than branched PEI 25 kDa (PEI-25KD) and that the transfection efficiency is maintained. These findings suggest that the gene carrier, based on multivalent host-guest interactions, could be an effective, targeted, and low-toxicity carrier for delivering nucleic acid to target cells.

MUC1是一种异源二聚体跨膜糖蛋白,由氮端亚单位(MUC1-N)和碳端亚单位(MUC1-C)组成.MUC1在多种上皮来源的肿瘤组织中异常表达,其与肿瘤的发生发展密切相关.MUC1-N可与细胞间黏附分子-1、E-选择素和半乳凝素-3相互作用并且通过MUC1-C调节信号传导,MUC 1-C可与表皮生长因子受体家族和其他酪氨酸激酶受体相互作用并且参与PI3K→AKT、MAP、NF-κB、Wnt、STAT、P53和Erα信号通路,因此MUC1与肿瘤的增殖、侵袭转移和化疗耐药密切相关.本研究阐述了MUC1-N和MUC1-C与其他分子相互作用以及在激活肿瘤相关信号通路中的作用,最后回顾了MUC1-N单抗、MUC1-C小分子肽和MUC1疫苗在临床试验阶段的研究情况.

目的:研究MUC1胞内段(MUC1-CT)抑制剂GO-201对人肺腺癌A549细胞放射敏感性影响.方法:MTT检测不同剂量以及不同时间GO-201对肺腺癌A549细胞的增殖抑制率;克隆形成实验检测GO-201对A549细胞放射增敏作用,单击多靶模型拟合细胞存活曲线并计算Dq、D0、SF2值和放疗增敏比(sensitizing enhancing vatio,SER);流式细胞术检测各实验组细胞活性氧水平,Western blot法检测锰超氧化物歧化酶(manganese superoxide dismutase,MnSOD)表达变化.结果:MUC 1-CT抑制剂GO-201可抑制肺腺癌A549细胞的增殖,其作用24、48、72 h IC50值分别是30.79、23.32、13.60 μmol/L.并且对肺腺癌A549细胞具有放射增敏作用,其放疗增敏比SER为1.14;联合照射组中,A549细胞活性氧水平明显升高(F=12.019,P=0.008),Mn-SOD蛋白表达量明显下降(F=5.465,P=0.048),与对照组比较差异具有统计学意义.结论:MUC1-CT抑制剂GO-201可增加人肺腺癌A549细胞的放射敏感性.