Hepatic arterial infusion chemotherapy (HAIC) delivers high local drug concentrations for hepatoma treatment but faces challenges such as catheter-related complications and systemic toxicity. To address these, we developed Mel-gel, an ultrasound-driven hydrogel system formed entirely by the chemotherapeutic agent Melphalan (Mel) without chemical modifications. Under ultrasound, Mel transitions from spherical to worm-like aggregates, rapidly forming a nanofiber-based hydrogel through non-covalent interactions. This innovative system offers sustained drug release, excellent bioavailability, and improved biosafety profiles. Mel-gel enables expedited catheter removal, reduces systemic toxicity, enhances local drug concentration, and prolongs drug-cell interaction time. Compared to conventional HAIC systems, Mel-gel’s unique in situ formation maximizes drug delivery and achieves superior targeting within complex vascular structures. In a rat orthotopic hepatoma model, Mel-gel-assisted HAIC demonstrated remarkable therapeutic efficacy, achieving a tumor inhibition rate of 98.09%, activating anti-tumor immune responses, and curing 60% of treated rats. This novel ultrasound-responsive hydrogel represents a promising advancement in hepatoma treatment, offering enhanced precision, efficacy, and safety. Additionally, Mel-gel’s versatile drug delivery capabilities may enhance the pharmacokinetics of various drugs and support synergistic therapies. This novel hydrogel system offers a promising advancement in hepatoma treatment, aiming to optimize outcomes and expand its application to other therapeutic agents.

Malignant melanoma is a highly aggressive and metastatic skin cancer characterized by tyrosinase overexpression. Therefore, harnessing the activation of tyrosinase-catalyzed toxicity enables targeted tumor-specific therapy while sparing surrounding healthy tissues. Herein, an AND logic-gated, cyanobacteria (Cyan)-driven, living therapeutic alginate hydrogel is proposed that activates the tyrosinase-catalyzed ferroptotic phenolic prodrug N-(4-hydroxyphenyl) acetamide (APhH), triggering cascaded reactive oxygen species (ROS) generation and glutathione (GSH) depletion for melanoma-specific ferroptosis. The therapeutic mechanism operates through a sequential dual-input procedure: microorganism-driven photosynthetic oxygenation and endogenous tyrosinase catalysis. Light-activated Cyan performs photosynthetic oxygen production, alleviating tumor hypoxia while acting as the essential cofactor for tyrosinase. Once activated, tyrosinase catalyzes the conversion of APhH into the cytotoxic benzoquinone derivative, 4-acetamido-o-benzoquinone (APhQ). Concurrently, oxygen is transformed into ROS, synergizing with APhQ to deplete GSH for glutathione peroxidase 4 inactivation, thereby promoting lipid peroxide generation. The combined effects of ROS generation, GSH depletion, and lipid peroxide accumulation culminate in a potent ferroptotic response, selectively targeting melanoma cells while sparing healthy tissue. This study highlights the potential of an AND logic-gated approach for achieving highly specific, targeted prodrug activation, enhancing precision in melanoma treatment.

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The benefit of rivaroxaban in thromboprophylaxis after oncologic lung surgery remains unknown. To evaluate the efficacy and safety of rivaroxaban, patients who underwent thoracic surgery for lung cancer were enrolled, and randomly assigned to rivaroxaban or nadroparin groups in a 1:1 ratio; anticoagulants were initiated 12-24 h after surgery and continued until discharge. Four hundred participants were required according to a noninferiority margin of 2%, assuming venous thromboembolism (VTE) occurrence rates of 6.0% and 12.6% for patients in the rivaroxaban and nadroparin groups, respectively. The primary efficacy outcome was any VTE during the treatment and 30-day follow-up periods. The safety outcome was any on-treatment bleeding event. Finally, 403 patients were randomized (intention-to-treat [ITT] population), with 381 included in per-protocol (PP) population. The primary efficacy outcomes occurred in 12.5% (25/200) of the rivaroxaban group and 17.7% (36/203) of the nadroparin group (absolute risk reduction, -5.2%; 95% confidence interval [CI], [-12.2-1.7]), indicating the noninferiority of rivaroxaban in ITT population. Sensitivity analysis was performed in the PP population and yielded similar results, confirming the noninferiority of rivaroxaban. In the safety analysis population, the incidence of any on-treatment bleeding events did not differ significantly between the groups (12.2% for rivaroxaban vs. 7.0% for nadroparin; relative risk [RR], 1.9; 95% CI, [0.9-3.7]; p = .08), including major bleeding (9.7% vs. 6.5%; RR, 1.6 [95% CI, 0.9-3.7]; p = .24), and nonmajor bleeding (2.6% vs. 0.5%; RR, 5.2 [95% CI, 0.6-45.2]; p = .13). Rivaroxaban for thromboprophylaxis after oncologic lung surgery was shown to be noninferior to nadroparin.

Hollow structures have demonstrated great potential in drug delivery owing to their privileged structure, such as high surface-to-volume ratio, low density, large cavities, and hierarchical pores. In this review, we provide a comprehensive overview of hollow structured materials applied in targeting recognition, smart response, and drug release, and we have addressed the possible chemical factors and reactions in these three processes. The advantages of hollow nanostructures are summarized as follows: hollow cavity contributes to large loading capacity; a tailored structure helps controllable drug release; variable compounds adapt to flexible application; surface modification facilitates smart responsive release. Especially, because the multiple physical barriers and chemical interactions can be induced by multishells, hollow multishelled structure is considered as a promising material with unique loading and releasing properties. Finally, we conclude this review with some perspectives on the future research and development of the hollow structures as drug carriers.

Background: Our study investigates treatment profiles in octogenarian patients with small cell lung cancer (SCLC) and assesses each treatment’s role in a stage-specific manner. Methods: Patient data from individuals with SCLC aged 80 years and older between 1988 and 2015 in the Surveillance, Epidemiology, and End Results Program (SEER) database were extracted. Cancer-specific survival (CSS) between patients with no treatment and different treatment groups were compared by the Kaplan-Meier method, with stratifications by stage. Cox Proportional Hazard model further identified independent prognostic factors. Results: A total of 7,290 patients were included in this study. Notably, 3,358 (46.1%) patients did not receive active treatment. Compared with the no active treatment group, the CSS of patients who received treatment was significantly improved (median 6 vs. 0 months, P<0.001) and further validated in stage subgroups. Chemotherapy combined with local therapy was associated with the best CSS in regional and distant disease stages, with the hazard ratios (HR) and 95% confidence intervals (CI) being 0.30 (0.26–0.34) and 0.27 (0.25–0.30), respectively. Local therapy only appeared to confer better oncological outcomes (HR =0.33; 95% CI: 0.25–0.42) than chemotherapy only (HR =0.37; 95% CI: 0.29–0.47) in the localized disease stage. Conclusions: Although nearly half of octogenarians with SCLC did not receive active treatment in the real clinical setting, these patients may benefit from treatment. Chemotherapy combined with local therapy may provide the best treatment choice in octogenarians with advanced SCLC, while local therapy appears to play a more critical role in treating those with early-stage disease.

目的 对某三甲医院国临库、国标库及医保库的疾病、形态学及手术编码库进行比较分析,找出编码应用上存在差异,为管理层面充分整合编码库提供建议.方法 应用Microsoft Office Excel 2010对疾病编码库、手术编码库、形态学编码库中的编码和名称进行VLOOKUP函数分析,对实际需要映射的条目数,组织临床专家和编码专家,对每条需要映射的条目数进行审核.结果 国临版以国标版为基础,疾病、形态学及手术相同条目分别为21 253、1106及8738条;新增编码占39.3％、11.2％及34.5％;实际需要映射:疾病库583条、形态学库294条及手术库146条.国临版以医保版为基础,疾病、形态学及手术相同条目分别为31 129、1422及12 435条;新增编码占9.7％、0％及6.4％;实际需要映射:疾病库1756条、形态学库68条及手术库125条.结论 通过国临版对国标版的三种编码库条目以及国临版对医保版的三种编码库条目的比对分析,找出少数实际需要映射编码的明细,并组织专家的建议、审核映射编码库,从而使本院现有各个版本编码库达到高度统一,为管理层面充分整合编码库提供建议,同时减小支付技术障碍,节省行政和服务管理成本.

Noninvasive assessments of the risk of lymph node metastasis (LNM) in patients with lung adenocarcinoma (LAD) are of great value for selecting individualized treatment options. However, the diagnostic accuracies of different preoperative LN evaluation methods in routine clinical practice are not satisfactory. Here, an assessment to detect folate receptor (FR)-positive circulating tumor cells (CTCs) based on ligand-targeted enzyme-linked polymerization is established. FR-positive CTCs have the potential to improve the specificity and sensitivity of diagnosing LNM in lung cancer patients. The addition of CTC level improved the diagnostic efficiency of the initial prediction model that comprises other clinical parameters. A nomogram for predicting preoperative LNM is established, which showed good prediction and calibration capacities and achieved an average area under the curve of 0.786. Good correlations are observed between the CTC level and nodal classifications, such as the number of positive LNs and the ratio of the number of positive LNs to removed LNs (LN ratio or LNR). The ligand-targeted enzyme-linked polymerization-assisted assessment of CTCs enables noninvasive detection and has a useful predictive value for the preoperative diagnosis of LNM in patients with LAD.

目的 比较肺段切除术和肺叶切除术在直径≤2 cm且术中冰冻证实微乳头和实性亚型阴性肺腺癌中的治疗效果。方法 纳入2020年6月至2021年3月多中心行肺段切除术或肺叶切除术的234例肺腺癌患者。根据随机数字表法将患者分为两组：肺段切除组（段切组）119例，男44例、女75例，年龄（56.6±8.9）岁；肺叶切除组（叶切组）115例，男43例、女72例，年龄（56.2±9.5）岁。比较两组患者临床资料。结果 两组患者术前基线资料差异无统计学意义（P＞0.05）。两组患者均无围术期死亡病例。两组患者在手术时间[（111.2±30.0）min vs.（107.3±34.3）min]、术中失血量[（54.2±83.5）mL vs.（40.0±16.4）mL]、引流管拔管时间[（2.8±0.6）d vs.（2.6±0.6）d]、住院时间[（3.9±2.3）d vs.（3.7±1.1）d]和病理分期方面差异均无统计学意义（P＞0.05）。叶切组患者术后半年用力肺活量（2.9 L vs. 3.1 L,P=0.014）和一秒用力呼气容积占预计值的百分比（79.2%vs. 82.0%,P=0.034）均比术前差，差异有统计学意义；段切组患者术前术后差异无统计学意义（3.1 L vs. 2.9L,P=0.131;81.8%vs. 81.4%,P=0.689）。结论 肺段切除术可有效保护患者肺功能，有望改善患者术后生活质量。

目的 探讨中国胆囊癌病人的外科治疗模式、病理学特征和预后.方法 收集中国13个省市的26家医院自2010年1月至2017年12月收治的4345例胆囊癌病人临床资料,分析中国胆囊癌病人的地区、性别、年龄分布;基于病人的诊疗记录与检查结果对手术病人肿瘤的可切除性进行评估,分析可切除性肿瘤病人的外科治疗模式,参照术前检查、手术记录和术后病理学检查结果评估可切除性肿瘤手术治疗是否达到根治标准,分析行根治性手术胆囊癌病人的病理学特征.结果 4345例胆囊癌病人中,男性1664例(38.23％),女性2681例(61.77％).行外科手术治疗的病人3129例(71.01％),其中可切除性肿瘤2074例(66.28％).在可切除性肿瘤2074例病人中,仅1133例(54.63％)在术前即诊断为胆囊恶性肿瘤,1002例(48.31％)行根治性切除,1072例(51.69％)未达根治标准.胆囊癌根治性切除病人的病理学检查结果中,736例(73.45％)为腺癌,348例(34.73％)为低分化癌,376例(37.52％)伴肝侵犯,152例(15.17％)伴神经浸润,96例(9.58％)伴血管内癌栓,78例(7.78％)伴周围脂肪组织浸润,89例(8.88％)伴周围器官受累,328例(32.73％)活体组织病理学检查淋巴结阳性.获得生存随访资料的2357例手术治疗病人术后中位生存期为16.17个月,多因素Cox回归生存分析结果显示肿瘤TNM分期(P＜O.001)、肿瘤分化程度(P＜0.001)、肝脏侵犯(P＜0.001)、RO切除(P=0.003)均为术后生存期的独立预后因素.结论 中国胆囊癌术前诊断率有待提高;胆囊癌外科治疗模式亟待规范;病理学检查报告中反映的多个因素与胆囊癌病人预后密切相关,其描述的规范化对指导胆囊癌病人的精准治疗有重要意义.

Feature Editor's Note—Global enthusiasm for a uniportal approach to video-assisted thoracoscopic (VATS) resection of thoracic neoplasms has seen a surge during the past decade subsequent to the first reported case in 2010. Proponents of the approach argue for diminished postoperative pain, reduced hospital length of stay, and more rapid recovery compared with a 3-hole VATS technique. Of note, in the only published randomized study that compared uniportal with other VATS techniques for lobectomy, there was no difference in postoperative outcomes including pain, length of stay, or complications (Perna et al.

Double sleeve, bronchial and vascular reconstructions are challenging procedures indicated for centrally located tumours to avoid pneumonectomy. Traditionally, these resections have been performed by thoracotomy, but thanks to advances in imaging systems, better surgical instruments and the gained experience in video-assisted thoracic surgery (VATS), the scenario now is different. During the last decade, we have seen a rapid evolution of the uniportal VATS technique from simple lobectomies to advanced double sleeve bronchovascular procedures and carinal resections. The advantages of VATS over open surgery for major lung resections in terms of postoperative pain and morbidity, length of hospital stay and quality of life have prompted experienced surgeons to adopt uniportal VATS for cases requiring a sleeve resection. However, when a double bronchial and vascular sleeve resection is required, the adoption rate of minimally invasive surgery is still very low even for very experienced VATS surgeons. The difficulty of tumour mobilization, complexity of the suturing technique and the concern about possible uncontrolled massive bleeding during VATS are the main reasons for this low rate of adoption. In this article, we describe the technical aspects and tricks of this procedure when it is done by the uniportal VATS approach.

外科手术是治疗肺部疾病的重要手段,但临床工作中时常遇到合并受损肺功能状态的患者。肺通气或弥散功能的下降,增加患者围术期并发症风险,并影响远期生存率。术前需要根据患者的疾病分期,拟定切除范围,结合患者肺功能状况,评估并预测患者围术期并发症风险以及远期生活质量,综合利弊,以决定是否行外科手术,以及手术切除的范围。

Objective:To explore the incidence and treatment of lung cancer after lung transplantation.Methods:Between January 2003 and July 2016, 80 patients were retrospectively reviewed after lung transplantation. And the incidence, treatment and prognosis of lung cancer were analyzed after lung transplantation.Results:Twelve cases (15%) of malignancies occurred after lung transplantation, including lung cancer ( n=10, 12.5%), renal carcinoma ( n=1, 1.25%) and larynx cancer ( n=1, 1.25%). One lung cancer patient became lost to follow-ups. Among 9 other cases, 5 patients of stage I lung cancer had a median survival of >24 months while another 4 patients with stage II/III lung cancer had a median survival of 2.5(2-5) months. All tumors occurred at the preserved side. Pathological types included squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma and small cell lung cancer. Age(61.8±6.6 vs. 54.0±11.0 years, P=0.03) and smoking (20.4% vs. 2.7%, P=0.02)were two important risk factors for lung cancer. The differences were statistically significant. Conclusions:Lung cancer is a major late complication after lung transplantation. Age and smoking are two important risk factors for lung cancer. The pathological types of lung cancer are diverse and the overall prognosis is poor.

肺移植手术质量控制涉及肺移植人员团队建设、受体的选择、受体术前诊断评估、脑死亡供体的维护、供体的评估与获取、外科手术、术后管理以及术后随访等诸多环节。精细化管理是手术质量控制的核心理念,唯有将肺移植手术质量控制常态化,为今后开展肺移植管理的多团队协作以及共同发展提供基础保障;构建完备的肺移植数据库以挖掘数据资源,提升移植质量;全面构建多团队参与协作下的中国肺移植质量控制体系,方可切实提高我国肺移植外科诊疗的整体水平。

An accurate genotyping analysis is one of the critical prerequisites for lung cancer targeted therapy. Here, a quantitative polymerase chain reaction (qPCR)-based mutation detection system, mutation-selected amplification-specific system PCR (MASS-PCR), is developed. The specific primers and probes used in MASS-PCR exactly match with the mutant sequence that only allows mutant gene to emit the fluorescence peak. To determine the sensitivity of MASS-PCR, 717 lung cancer specimens, 61 formalin-fixed paraffin-embedded (FFPE) tissues, and 656 fresh reaction tissues are collected and undergo mutation detection of lung cancer driver genes (EGFR, KRAS, BRAF, HER2, MET, ALK, and ROS1). These samples are divided into two groups. Mutations in Group I, which has 631 fresh reaction tissues, are analyzed by MASS-PCR and the amplification refractory mutation system PCR (ARMS-PCR). While group II samples, 25 fresh reaction tissues and 61 FFPE tissues, are screened through MASS-PCR and next-generation sequencing (NGS). All results are verified by direct sequencing. MASS-PCR shows high consistency with ARMS-PCR (kappa value > 0.733) and NGS (kappa value = 0.79) (P < 0.001). For the samples with inconsistent MASS-PCR and ARMS-PCR results, DS results more likely support the MASS-PCR results. These data suggest that MASS-PCR is a convenient, accurate, and economical method for the detection of lung cancer driver gene mutations in clinical practice.

OBJECTIVE:To determine the optimal number of lymph nodes (LNs) examined and the role of adjuvant chemotherapy in stage I lung cancer. METHODS:The National Cancer Database was queried for surgically treated patients with pathologic stage I lung cancer between 2006 and 2014 (N = 65,438). The optimal LN numbers were determined in the multivariate Cox model and were further validated in the cohort with clinical stage I disease (N = 117,112) in terms of nodal upstaging and prognostic stratification. The role of adjuvant chemotherapy in patients with suboptimal staging (number of LNs examined was less than than the optimum) was evaluated in each T stage. RESULTS:The number of LNs examined correlated with tumor size (p < 0.001). There were increasing survival benefits with each additional LN examined-up to eight, nine, 10, and 11 nodes for patients with T1a, T1b, T1c, and T2a, respectively. Validation from the cohort with clinically staged disease showed that the threshold of eight to 11 LNs was an independent predictor of nodal upstaging (OR = 1.706, 95% confidence interval [CI] 1.608-1.779) and survival outcome (hazard ratio = 0.890, 95% CI: 0.865-0.916). After propensity matching, adjuvant chemotherapy was associated with improved survival in patients with stage T2a disease having suboptimal staging (hazard ratio = 0.841, 95% CI: 0.714-0.990), but not in patients with stage T1a to T1c disease. CONCLUSION:LN evaluation was important for accurate staging and adequate treatment, and examinations of an increasing number of nodes for progressively higher T components (i.e., eight, nine, 10, and 11 nodes for T1a, T1b, T1c, and T2a tumors, respectively) seemed crucial to predict upstaging and survival outcomes. Adjuvant chemotherapy might be beneficial to patients with stage T2a disease who have suboptimal nodal staging.

The performance of next generation sequencing in profiling somatic mutations from plasma samples, especially in early-stage cancer, is limited by its sensitivity due to the extremely low amount of cell-free DNA (cfDNA). Polymerase-chain reaction amplification of limited amounts of DNA often results in product redundancy and the amplification of contaminant DNA. Numerous methods have been developed to detect and quantify ultralow frequency mutations. In this study, the potential of tagging each DNA molecule with a unique molecular identifier (UMI) is explored to detect ultralow frequency mutations in early-stage lung cancer patients. Paired tissue and blood samples from 32 patients with early-stage (stage IA-IIB) nonsmall cell lung cancer are sequenced using a panel consisting of 168 cancer-related genes. Collectively, 93.8% of tissue samples and 59.4% of plasma samples have mutations detected. The concordance rates are acceptable for all patients except for stage IA. Notably, mutations at an alleleic frequency as low as 0.1% are detected in UMI-tagged cfDNA samples. Moreover, patients with nonadenocarcinoma histology have a significantly higher detection rate than patients with adenocarcinoma (92.9% vs 33.3%, P = 0.002). The study demonstrates the potential of UMI in early detection of lung cancer from plasma samples.

OBJECTIVES:A retrospective study was performed to investigate the association between EGFR mutations and visceral pleural invasion (VPI), and evaluate the prognostic value of EGFR in resected non-small-cell lung cancer (NSCLC) patients with VPI. MATERIALS AND METHODS:Clinicopathological characteristics and follow-up information were collected from 508 consecutive patients with surgically resected stage I-III NSCLC, and EGFR mutations were detected based on real-time PCR technology. Significant results (P<0.05) from univariate logistic regression analysis were involved as covariates to adjust confounding factors in the analysis of independent factors. RESULTS:VPI and EGFR mutations were detected in 229 (45.1%) and 243 (47.8%) cases in NSCLC, respectively. There was a significant association between EGFR mutations and VPI development. Both 19-del (adjusted OR =2.13, 95%CI =1.13-3.99, P=0.019) and L858R (adjusted OR =2.89, 95%CI =1.59-5.29, P=0.001) could significantly increase the risk of VPI development compared with EGFR wild-type. Higher frequency of L858R (adjusted OR =2.63, 95%CI =1.42-4.88, P=0.002) was detected in VPI patients compared with non-VPI patients. 19-del (adjusted HR =0.31, 95%CI =0.12-0.80, P=0.015) was an independent prognostic factor for a better disease-free survival (DFS) in non-VPI patients. No significant association was shown between EGFR mutations and DFS in VPI patients. CONCLUSION:EGFR mutations were significantly associated with VPI development in NSCLC, but no significant association was observed between EGFR mutations and DFS in the patients with VPI. 19-del was a favorable prognostic factor for DFS in non-VPI patients.

In response to infection, polymorphonuclear neutrophils (PMN) are recruited in the infectious sites, and employ three major strategies to fight against the microbes including phagocytosis, degranulation, and neutrophil extracellular traps (NETs). NETs are a meshwork of chromatin fibers mixed with granule-derived antimicrobial peptides and enzymes, which trap and kill the bacteria extracellularly. In this study, by using a mouse sepsis model, we identified a novel mechanism by which NETs induce macrophage (Mϕ) pyroptosis, a caspase-1-dependent regulated cell death. We show that NET-derived HMGB1, acting through RAGE and dynamin-dependent signaling, triggers an intra-Mϕ cascade of molecular events including cathepsin B (CatB) release from the ruptured lysosomes, followed by pyroptosome formation and caspase-1 activation, and subsequent Mϕ pyroptosis. The study further demonstrates that Mϕ pyroptosis augments inflammatory responses following sepsis. These findings shed light on the proinflammatory role of NETs in mediating PMN–Mϕ interaction, which therefore influences the progress of inflammation following infection.