Back cover image: Highly biocompatible and self-illuminating carbon nanogels (CNGs) with dual ability of ROS imaging and PDT have been designed with self-assembled chemiluminescent carbonized polymer dots (CPDs). Different CPDs have been derived from biomass materials and exhibit polymer-like property, enabling their ability of self-assembling into CNGs through the hydrophilic and hydrophobic interaction. With efficient deep-red/near-infrared (NIR) CL emission and distinctive PDT capacity, H2O2-driven water-soluble chemiluminescent carbon nanogels are further designed by assembling the polymeric conjugate and CL donors. Mechanistically, ROS generated in the inflammatory sites can trigger the chemically initiated electron exchange luminescence between the CPDs and intermediate, enabling in vitro and in vivo CL imaging. Meanwhile, the production of such as 1O2, •OH and •–O2 from the chemiluminescent CNGs under the self-illumination can efficiently induce the apoptosis of tumor cell thus inhibit the tumor growth, resulting in cancer therapy. (DOI: 10.1002/smm2.1099)

Carbon dots (CDs), as one new class of carbon nanomaterials with various structure and extraordinary physicochemical properties, have attracted tremendous interest for their potential applications in tumor theranostics, especially in targeted bioimaging and therapy. In these areas, CDs and its derivatives have been employed as highly efficient imaging agent for photoluminescence bioimaging of tumors cells. With unique structure, optical and/or dose attention properties, CDs have been harnessed in various nanotheranostic strategies for diverse tumors through integrating with other functional nanoparticles or utilizing their inherent physical properties. Up to now, CDs have been approved as novel biomaterials by their excellent performances in precise targeted bioimaging and therapy for tumors. Herein, the latest progress in the development of CDs in targeted bioimaging and tumor therapy are reviewed. Meanwhile, the challenges and future prospects of the application of CDs in promising nanotheranostic strategies are discussed and proposed.

Abstract Carbon nanogels (CNGs) with dual ability of reactive oxygen species (ROS) imaging and photodynamic therapy have been designed with self‐assembled chemiluminescent carbonized polymer dots (CPDs). With efficient deep‐red/near‐infrared chemiluminescence (CL) emission and distinctive photodynamic capacity, the H2O2‐driven chemiluminescent CNGs are further designed by assembling the polymeric conjugate and CL donors, enabling an in vitro and in vivo ROS bioimaging capability in animal inflammation models and a high‐performance therapy for xenograft tumors. Mechanistically, ROS generated in inflammatory sites or tumor microenvironment can trigger the chemically initiated electron exchange luminescence in the chemical reaction of peroxalate and H2O2, enabling in vivo CL imaging. Meanwhile, part of the excited‐state electrons will transfer to the ambient H2O or dissolved oxygen and in turn lead to the type I and type II photochemical ROS production of hydroxyl radicals or singlet oxygen, endowing the apoptosis of tumor cells and thus enabling cancer therapy. These results open up a new avenue for the design of multifunctional nanomaterials for bioimaging and antienoplastic agents.

Abstract The benefit of systemic treatment in esophageal squamous cell carcinoma (ESCC) which has progressed after chemotherapy is still uncertain. Anlotinib (AL3818) is a novel multi-target TKI, inhibiting tumor angiogenesis and proliferation. A phase II trial (NCT02649361) has demonstrated that anlotinib has a durable antitumor activity with a manageable adverse event profile in refractory metastatic ESCC. This study (NCT03387904) aimed at comparing the effects and safety of Anlotinib Plus Irinotecan versus Irinotecan in patients with ESCC. Methods We conducted a prospective randomized, multicenter, phase II trial to compare the efficacy of Anlotinib Plus Irinotecan with Irinotecan in recurrent ESCC patients who had resistance to platinum or taxane-based chemotherapy. Eligible patients were adults with pathologically confirmed recurrent ESCC, and 82 patients were randomized 1:1 to Irinotecan (65 mg/m2/day 1 and day 8) with or without anlotinib (12 mg qd day 1 to 14) of a 21-day cycle till progression or intolerable. The primary endpoint is the disease control rate (DCR) and progression-free survival (PFS) and the secondary end points are objective response rate (ORR) and overall survival (OS). Results Between 13/1 2019 and 20/1 2020, a total of 43 patients were enrolled and randomly assigned to either the anlotinib plus irinotecan (n = 22) or the irinotecan group (n = 21).The mPFS was longer in trial group than in control group (89 days vs 66 days, HR = 0.447, P = 0.055). The Disease control rate (DCR) was 54.5% in trial group and 38.1% in the control group. The treatment-related adverse events (>10%) were fatigue (59.1%), nausea (50.0%), decreased appetite (36.4%), hoarseness (27.3%), thyroid-stimulating hormone elevation (22.7%), diarrhea (9.1%), and decreased lymphocytes count(9.1%) in trial group. Grade 3 AEs included fatigue (4.5% vs 4.8%), nausea (4.5% vs 0%) and diarrhea (4.5% vs 0%) in two groups. Conclusion Anlotinib plus irinotecan was similarly tolerable but prolonged PFS compared to irinotecan monotherapy as a second-line treatment in patients with recurrent ESCC.

Objective:Clinicopathological features, treatment and prognosis of urinary and male reproductive system soft tissue sarcoma (STS) and sarcomatoid carcinoma in adults were compared.Methods:A retrospective analysis was performed on the clinical data of 73 patients with STS and 15 patients with sarcomatoid carcinoma in adult urinary and male reproductive system in the First Affiliated Hospital of Zhengzhou University. There were 59 males and 14 females in STS group, with a median age of 41 (18-78)years old. The maximum tumor diameter ranged from 0.5 to 19.0 cm. The primary tumors were located in testis and peritesticular (23 cases), kidney (23 cases), prostate (15 cases), bladder (8 cases), ureter(3 cases), other parts(1 case). There were 18 cases of lymph node metastasis and 8 cases of distant metastasis. Among 73 patients with STS, 66 patients underwent surgical resection, of which 31 patients underwent radical resection. Among the 66 patients who underwent surgery, 3 patients received neoadjuvant chemotherapy; 22 patients received adjuvant chemotherapy; 5 patients were treated with adjuvant radiotherapy. Among 7 patients with STS did not receive surgical treatment, 2 patients received radiotherapy combined with chemotherapy, 2 patients received chemotherapy alone, and 3 patients received symptomatic support treatment.There were 11 males and 4 females in sarcomatoid carcinoma group, with a median age of 65 (23 - 84)years old. The measurable tumor diameter ranged from 0.4 to 16.9 cm. The primary tumors were located in kidney (6 cases), bladder (5 cases), ureter(2 cases) and prostate(2 cases). There were 2 patients of lymph node metastasis and 4 patients of distant metastasis. Of the 15 patients with sarcomatoid carcinoma, 12 patients underwent surgical resection, of which 5 patients underwent radical resection. 2 patients were treated with adjuvant therapy after operation. Among the 12 patients who received surgical treatment, 2 patients had distant metastasis before operation, all of which originated from the kidney. Among the 3 patients without surgical treatment, 1 patients received systemic chemotherapy and 2 patients received symptomatic supportive treatment. There was no significant difference in gender, tumor maximum diameter, distant metastasis and operation, chemotherapy, radiotherapy and operation combined with chemotherapy ( P>0.05) and there were significant differences in age, tumor primary location and lymph node metastasis ( P<0.05) between STS and sarcomatoid carcinoma patients.The categorical variables of the two groups were compared by χ2.With Kaplan-Meier method for univariate survival analysis, the Cox was used for multivariate analysis. Results:The median follow-up time was 18.3(0.3-90.4) months.In STS group, there were 14 patients of synovial sarcoma, 11 patients of liposarcoma, 15 patients of rhabdomyosarcoma, 16 patients of leiomyosarcoma, 10 patients of other types, and 7 patients of spindle cell sarcoma without specific classification. Among 66 patients with STS, 8 patients recurred, 14 patients metastasized after operation, 4 patients recurred and metastasized after operation. The 7 patients without surgical treatment all progressed. Among the 10 patients of sarcomatoid carcinoma without distant metastasis before operation, 3 patients recurred and 3 patients metastasized after operation. Two patients of renal sarcomatoid carcinoma with distant metastasis were treated with nephrectomy and chemotherapy. One of them had overall survival (OS) up to 2 years, and one recurred 2 months after operation. The 3 patients without surgical treatment all progressed without remission. The median OS of STS patients were 59.3 (95% CI 24.1-94.5) months and that of sarcomatoid carcinoma patients were 8.7 (95% CI 6.1-11.2) months. The OS of STS patients were better than those of sarcomatoid carcinoma patients ( HR=2.874, 95% CI 1.118-7.386, P=0.022). Conclusions:The onset age of STS in adult urinary and male reproductive system was lower than that in sarcomatoid carcinoma. The primary lesions of STS were mainly in testis, peritesticular and kidney. The primary lesions of sarcomatoid carcinoma were mainly in kidney. Among STS, leiomyosarcoma was the most common type.STS and sarcomatoid carcinoma should be diagnosed and treated with surgery quickly, and systemic therapy should be performed for patients who cannot be treated with surgery.

Objective: To find the biomarkers that accurately predict the survival of patients with esophageal squamous cell carcinoma (ESCC). Methods: The immune related genes that were significantly related to the overall survival (OS) of patients with ESCC were screened from The Cancer Genome Atlas (TCGA) database to construct a prognostic risk score model. The prognoses of the high-risk and low-risk groups were compared by Kaplan-Meier method. The accuracy of the model was evaluated by the receiver operating characteristic (ROC) curve. Tumor tissue samples of 83 patients with pathological diagnosis of ESCC were collected from Anyang Cancer Hospital for external verification. Cox regression analysis was used to comprehensively evaluate the effects of prognostic risk score and various clinical characteristics on OS of patients with ESCC. Results: Seven immune-related genes that were significantly related to survival prognosis were selected from the TCGA database and included in the prognostic risk score model, which were S100A12, SLC40A1, FABP9, TNFSF10, IGHA2, IL1F10, and STC2. The 1- and 2-year survival rates of the low-risk group (40 cases) were 94.3% and 82.5%, respectively, while those of the high-risk group (40 cases) were 75.9% and 32.9%, respectively.The prognosis of the high-risk group was worse than that of the low-risk group (P<0.001). The 83 external validation samples obtained consistent results by using the prognostic risk score model. The prognostic risk score was positively correlated with the content of CD4(+) T lymphocytes in ESCC (r(s)=0.259, P=0.020), but not correlated with the content of B lymphocytes, CD8(+) T lymphocytes, neutrophils, macrophages or dendritic cells (P>0.05). Conclusions: S100A12, SLC40A1, FABP9, TNFSF10, IGHA2, IL1F10, and STC2 were risk genes significantly associated with OS of patients with ESCC. The prognostic risk score was an independent prognostic factor for the OS of patients with ESCC, and it was correlated with the content of CD4(+) T lymphocytes in ESCC tissue.

目的 探讨基于免疫相关基因构建食管腺癌预后评分模型的方法和临床价值.方法 从癌症基因组图谱计划数据库下载获得食管腺癌样本及正常食管组织样本的基因表达谱以及性别、年龄、分化程度、TNM分期、生存时间、生存状态信息.使用Wilcox检验对食管腺癌样本与正常食管组织样本的免疫相关基因表达进行差异分析,继续使用Cox回归分析模型分析筛选出与患者预后显著相关的免疫相关基因构建预后评分模型,使用受试者工作特征(ROC)曲线评估所建模型预测能力.使用Cox回归分析模型分析评估预后评分与临床病理特征对患者总生存期的影响.结果 筛选出HSPA6、ULBP1、MAPT、CACYBP、DLL4、CCL26、RAC2、BMP8B、CSF2、OSM、OXTR等11个免疫相关基因构建食管腺癌预后评分模型,该模型是独立预后因素,1 a、3 a的ROC曲线的曲线下面积分别为0.859、0.919.结论 基于免疫相关基因构建的食管腺癌预后评分模型具有较好准确性,有助于临床决策的制定.

Objective:To investigate the influencing factors of second primary carcinoma (SPM) in patients with transitional cell carcinoma of bladder without distant metastasis.Methods:Patients diagnosed with transitional cell carcinoma of the bladder without distant metastasis were selected from the Surveillance, Epidemiology, and End Results (SEER) database from 1988 to 2016. The single factor analysis was conducted to select the factors influencing the occurrence of second primary cancer by using the cumulative incidence function (CIF) in the competitive risk model. Multivariate analysis was conducted by using the Fine-Gray model.Results:In total, 154 725 patients with transitional cell carcinoma of bladder without distant metastasis were identified. Multivariate analysis showed that marital status, age, race, gender, tumor invasion, radiotherapy, surgery and chemotherapy were the influencing factors of SPM ( P<0.05). Conclusions:Transitional cell carcinoma of bladder patients without distant metastasis should undergo risk screening for SPM to guide treatment, testing and follow-up plans.

目的 评价国产吉非替尼对晚期转移性肺腺癌患者的疗效和不良反应,并探讨其疗效的影响因素.方法 选取2017年9月至2018年10月就诊于郑州大学第一附属医院的103例晚期转移性肺腺癌患者为研究对象,患者连续口服国产吉非替尼片250 mg·d-1,直至出现疾病进展或因严重不良反应不能耐受而停止给药.治疗过程中,每1～2个月复查,根据美国国家肿瘤研究所实体瘤疗效客观评价标准每1～2个月评价疗效,并统计患者的疾病无进展生存期,分析患者年龄、性别、吸烟史、美国东部肿瘤协作组评分、淋巴结转移、脑转移、骨转移、肝转移、肾上腺转移、肿瘤分期、联合化疗等与患者疾病无进展生存期的关系,评估治疗期间不良反应发生情况.结果 103例晚期转移性肺腺癌患者的疾病无进展生存期为22～667 d,中位疾病无进展生存期为320 d.单因素分析结果显示,患者有无肾上腺转移、肿瘤分期早晚、有无联合化疗与国产吉非替尼治疗晚期转移性肺腺癌的疾病无进展生存期有关(P均＜0.05);多因素分析结果显示,肿瘤分期为Ⅳb期及未联合化疗是国产吉非替尼治疗晚期转移性肺腺癌患者疾病无进展生存期短的独立危险因素(P均＜0.05).治疗期间26例(25.2％)患者出现Ⅰ、Ⅱ级皮疹,1例(1.0％)患者出现Ⅲ级皮疹;6例(5.8％)患者出现Ⅰ、Ⅱ级腹泻;15例(14.6％)患者出现Ⅰ、Ⅱ级恶心;11例(10.7％)患者出现Ⅰ、Ⅱ级骨髓抑制;9例(8.7％)患者出现Ⅰ、Ⅱ级肝损伤.结论 患者有无肾上腺转移、肿瘤分期早晚、有无联合化疗可影响国产吉非替尼治疗晚期转移性肺腺癌患者的疾病无进展生存期,肿瘤分期为Ⅳb期和未联合化疗是导致国产吉非替尼治疗晚期转移性肺腺癌患者疾病无进展生存期缩短的独立危险因素.

目的 基于大样本量,筛选食管癌患者独立预测因子,构建个体化预测模型.方法 从监测、流行病学和最终结果(Surveillance,Epidemiology and End Results,SEER)临床数据库中确定了5 936例食管癌患者.随机选择纳入患者中70％ (n=4 156)作为训练队列,其余患者(n=1 780)作为外部验证队列.由训练队列构建预测模型,并使用验证队列进行验证.经过单因素与多因素Cox回归,筛选出独立预后指标,并全部纳入用于构建列线图预测模型,并通过计算C指数(C-index)及绘制校准曲线,检验模型的准确性.结果 根据多因素分析结果,诊断年龄、婚姻状况、肿瘤大小、肿瘤分级、肿瘤分期和区域淋巴结状况与食管癌患者的特异性生存(cancer specific survival,CSS)相关.将所有这些因素综合起来,构建nomogram.预测模型C指数显著高于第七版AJCC分期系统[(0.751,95％CI,0.737～0.764) VS (0.697,95％CI,0.684～ 0.711),P＜0.001].校准曲线显示,模型预测效果与实际生存相吻合,进一步验证了模型的区分能力及校准能力.结论 该列线图预测模型能够较准确预测食管癌患者预后状态,并较传统TNM分期系统有所改善,能够更好地区分高危患者,并指导临床治疗措施的选择.

目的:基于大样本量,构建个体化预测模型及危险分层系统.方法:从美国SEER临床数据库中,筛选结肠癌术后患者,进行模型构建,并筛选一组独立的中国人群,用于外部验证.经过单因素与多因素Cox回归分析,筛选出独立预后指标,并全部纳入用于构建列线图预测模型.通过计算一致性指数(C-index)及绘制校准曲线,检验模型准确性.结果:列线图模型共纳入11个独立预后因子,C-index在训练组、内部验证组及外部验证组分别为0.768,0.761和0.759,均>0.7,且优于第7版美国癌症联合委员会(AJCC)-TNM分期系统(0.729,0.720,0.735).校准曲线显示,模型预测效果与实际生存相吻合,进一步验证了模型的区分及校准能力.通过决策树分析,依据模型预测个体风险评分,进行危险分层,模型的实际应用价值得到确定.结论:该列线图预测模型能够较准确预测结肠癌术后患者预后状态,并较传统TNM分期系统有所改善,基于预测模型的危险分层系统,能够更好地区分高危患者,并指导选择临床治疗措施.