Despite advances in chimeric antigen receptor T cell (CAR T cell) therapy for leukemia and lymphoma, solid tumors remain challenging because of limited target specificity and safety concerns. Neoantigens like KRASG12V, a highly prevalent yet undruggable mutation in solid tumors, offer tumor-exclusive specificity. This study developed CAR T cells targeting KRASG12V/HLA-A*02:01 using phage antibody display to identify high-affinity single-chain variable fragments. Engineered B9 CAR T cells specifically lysed tumor cells and patient-derived cancer organoids expressing KRASG12V/HLA-A*02:01, demonstrating potent antitumor activity. Animal studies showed that B9 CAR T cells effectively controlled tumor growth in subcutaneous pancreatic ductal adenocarcinoma (PDAC) xenografts, as well as in metastatic and peritoneal PDAC models. Safety assessments in NCG-HLA-A2.1 and C57BL/6 mice revealed no detectable in vivo toxicity, supporting the clinical applicability of B9 CAR T cells. Collectively, our neoantigen-targeted CAR T cell therapy against solid tumors shows great potential for future clinical trials in patients with KRASG12V/HLA-A*02:01, paving the way for clinical translation.

BACKGROUND:Lung Adenocarcinoma (LUAD), a common and aggressive form of lung cancer, poses significant treatment challenges due to its low survival rates. AIM:To better understand the role of ferroptosis driver genes in LUAD, this study aimed to explore their diagnostic and prognostic significance, as well as their impact on treatment approaches and tumor immune function in LUAD. METHODS:To accomplish the defined goals, a comprehensive methodology incorporating both in silico and wet lab experiments was employed. A comprehensive analysis was conducted on a total of 233 ferroptosis driver genes obtained from the FerrDB database. Utilizing various TCGA databases and the RT-qPCR technique, the expression profiles of 233 genes were examined. Among them, TP53, KRAS, PTEN, and HRAS were identified as hub genes with significant differential expression. Notably, TP53, KRAS, and HRAS exhibited substantial up-regulation, while PTEN demonstrated significant down-regulation at both the mRNA and protein levels in LUAD samples. The dysregulation of hub genes was further associated with poor overall survival in LUAD patients. Additionally, targeted bisulfite-sequencing (bisulfite-seq) analysis revealed aberrant promoter methylation patterns linked to the dysregulation of hub genes. RESULTS & DISCUSSION:Furthermore, hub genes were found to participate in diverse oncogenic pathways, highlighting their involvement in LUAD tumorigenesis. By leveraging the diagnostic and prognostic potential of ferroptosis driver hub genes (TP53, KRAS, PTEN, and HRAS), significant advancements can be made in the understanding and management of LUAD pathogenesis. CONCLUSION:Therapeutic targeting of these genes using specific drugs holds great promise for revolutionizing drug discovery and improving the overall survival of LUAD patients.

Glioma accounts for 80% of malignant central nervous system, with high incidence and extremely difficult to cure. However, for the role of ER stress apoptosis in tumor has caused great attention, the neuronal polarity molecule glycogen synthase kinase-3 beta(GSK-3 beta) endoplasmic network stress apoptosis pathway in tumor mechanism is a hot research in recent years, but for GSK-3 beta ER stress apoptosis pathway in different levels of glioma research is extremely rare. In this experiment, we jointly explored the significance of GSK-3 beta ER apoptosis pathway in different grades of glioma, which provided a strong basis for the precise treatment of glioma. 35 inpatients from December 2021 to December 2022 were enrolled into the different grades of glioma group and the normal control group. Tumor tissue was classified according to medical pathology. The other five normal brain tissues were obtained from the normal brain tissue of the fistula created in non-functional areas. One of the brain samples was stored for the apoptosis index (AI) of TUNEL (chromogenic method), and another part was stored in liquid nitrogen for the expression of GRP78, IRE 1, ATF 6, PERK, p-Tyr216-GSK-3 beta, p-Ser 9-GSK-3 beta, and Caspase-3. The AI values of different grades of glioma and normal control groups showed that the normal control, low-grade glioma and high-grade glioma groups were 8. 131 +/- 0.234, 68.523 +/- 1.392 and 22. 421 +/- 0.236, respectively. The AI value was higher in the glioma group than in the normal controls (P < 0.05), while the AI value in the glioma group was negatively correlated with its malignancy (r = -0.725, P = 0.000). Western blot showed: compared with the normal control group, apoptosis initiation protein GRP78 expression, IRE 1, ATF 6, PERK decreased (P < 0.05); pathway key protein p-Ser 9-GSK-3 beta increased, and p-Tyr216-GSK-3 beta decreased (P < 0.05); pathway executive protein Caspase-3 increased (P < 0.05). However, the apoptosis initiation protein GRP78, IRE 1, ATF 6, PERK increased (P < 0.05); pathway key protein p-Ser 9-GSK-3 beta decreased and p-Tyr216-GSK-3 beta was increased (P < 0.05); pathway execution protein Caspase-3 expression decreased (P < 0.05). Conclusion: the AI value of low-grade glioma is higher than that of high-grade glioma, indicating that the progression of brain glioma may inhibit cell apoptosis. The increased apoptosis index and the expression changes of GSK-3 beta ER stress cell apoptosis pathway in the glioma group indicate that the apoptosis pathway in GSK-3 beta ER stress cells was initiated and executed in glioma. In low-grade glioma cells, there may be a mechanism to inhibit IRE 1, ATF 6, PERK, and p-Tyr216-GSK-3 beta expression, which further promotes cell apoptosis and inhibited tumor progression. And with the progression of glioma, The expression of IRE 1, ATF 6, PERK, GRP78, and p-Tyr216-GSK-3 beta was gradually increased, The expression of P-Ser 9-GSK-3 beta, Caspase-3 was gradually decreased, It indicates that GRP78, IRE 1, ATF 6, PERK and p-Tyr216-GSK-3 beta may be involved in the progression of glioma; Meanwhile, brain glioma cells may, by inhibiting the expression of P-Ser 9-GSK-3 beta and the apoptosis executive protein Caspase-3, Further inhibited the apoptosis of brain glioma cells, promoted the progression of brain glioma. Inhibiting the expression of IRE 1, ATF 6, PERK, GRP78 and p-Tyr216-GSK-3 beta may be of great significance to inhibiting the progression of glioma, which provides a strong basis for guiding the precision treatment of clinical glioma.

BackgroundAngiomyolipoma with epithelial cysts (AMLEC) is an extremely rare subtype of kidney angiomyolipoma that contains epithelial-lined cysts. The most distinctive immunohistochemical feature of AMLEC is its immunoreactivity with melanocytic markers. AMLEC also has a distinct histological structure, which aids in its pathological diagnosis. To date 27 cases of AMLEC have been reported in 11 case series. However, the molecular biology underlying the pathogenesis of AMLEC remains unexplored.Case reportA 30-year-old female was diagnosed with AMLEC and underwent partial nephrectomy. Histologically, the cross-section of cystic tissue revealed a multilocular appearance, with some cysts containing thrombus-like material, and the wall thickness was approximately 0.2 ~ 0.3 cm. Additionally, the compact subepithelial cellular stroma showed strong and diffuse nuclear labeling for estrogen receptor, progesterone receptor, and CD10, as well as HMB45 and Melan A, which are markers of melanocytic differentiation. Furthermore, using a DNA targeted sequencing panel with next-generation sequencing, we identified a nonsense mutation in TSC Complex Subunit 2 (TSC2) gene, resulting in the formation of a premature termination codon. Moreover, the mutated genes found to be enriched in the PI3K-AKT pathway. The patient in this case had a favorable postoperative follow-up at 3 months.ConclusionTo the best of our knowledge, this study represents the first analysis of genotype mutations in AMLEC, providing valuable insights for future clinical practice. These findings have significant potential in guiding the understanding and management of AMLEC, paving the way for further research and advancements in the field.

目的:探讨多种方法联合检测在鉴别诊断猫抓病中的临床价值.方法:1例62岁女性,利用影像学检查、18F-FDG PET/CT、组织病理学检查和实时荧光定量PCR(RT-PCR)鉴别诊断猫抓病.结果:影像学和18F-FDG PET/CT检查结果提示,患者左乳房外上象限可见不规则、低密度的肿块,且左侧腋窝淋巴结呈高代谢.组织病理学检查提示乳腺良性增生及左腋窝淋巴结肉芽肿性改变,初步排除恶性可能.RT-PCR明确汉氏巴尔通体感染引起的猫抓病.结论:多种方法联合检测在鉴别诊断猫抓病中具有重要临床应用价值.

The early diagnosis of lung cancer is closely associated with the decline of mortality. A panel consisting of seven lung cancer-related autoantibodies (7-AABs) has been shown to be a reliable and specific indicator for the early detection of lung cancer, with a specificity of ~90% and a positive predictive value of ~85%. However, its low sensitivity and negative predictive value limit its wide application. To improve its diagnostic value, the diagnostic efficiencies of 7-AABs in combination with non-specific tumor markers were retrospectively investigated for the detection of early-stage lung cancer. A total of 217 patients with small lung nodules who presented with ground-glass opacity or solid nodules as well as 30 healthy controls were studied. The concentrations of 7-AABs and heat shock protein 90a (HSP90a) were assessed using ELISA. Automated flow fluorescence immune analysis was used for the assessment of CEA, CYFRA21-1, CA199 and CA125 levels. The results showed that 7-AABs + HSP90a possessed a remarkably improved diagnostic efficiency for patients with small pulmonary nodules or for patients with lung nodules of different types, which suggested that 7-AABs in combination with HSP90a could have a high clinical value for the improvement of the diagnostic efficiency of early-stage lung cancer.

目的 检测非特殊型浸润性乳腺癌(invasive breast carcinoma of no special type,IBC-NST)中miR-608和巨噬细胞移动抑制因子(macrophagemigration inhibitory factor,MIF)的表达,探讨两者在IBC-NST中表达的临床意义及相关性.方法 采用qRT-PCR技术检测25例IBC-NST和癌旁正常乳腺组织中miR-608和MIF的表达,分析两者表达与IBC-NST临床病理特征的关系,采用Pearson相关性分析两者之间表达的相关性;采用免疫组化法检测82例IBC-NST组织中MIF的表达,利用Graph-Pad Prism 6.0绘制生存曲线;运用细胞转染结合qRT-PCR和Western blot法检测人乳腺癌细胞株中miR-608对MIF表达的调控作用.结果 MIF基因和蛋白在IBC-NST组织中呈高表达(P<0.05),miR-608在IBC-NST组织中呈低表达(P<0.05);并且MIF蛋白表达与淋巴结转移、TNM分期、分子分型和p53突变相关(P<0.05).IBC-NST组织中miR-608和MIF基因表达呈负相关(r=-0.6695,P<0.001).与对照组相比,转染miR-608 mimics可下调MIF的mRNA和蛋白表达,转染miR-608 in-hibitor可上调MIF的mRNA和蛋白表达.结论 在IBC-NST组织中miR-608低表达,而MIF高表达;MIF蛋白表达与HER-2过表达型和三阴型分子亚型、p53突变及患者无进展生存期相关;miR-608与MIF的表达呈负相关,且miR-608负向调控MIF的表达.miR-608和MIF可能是IBC-NST的预后标志物和潜在治疗靶点.

目的:分析术中冰冻肺硬化性肺泡细胞瘤(pulmonary sclerosing pneumocytom,PSP)最常被误诊的原因及寻找对策.方法:回顾性分析27例PSP临床病理资料,复习冰冻和石蜡切片,结合免疫组化染色综合分析.结果:术中冰冻PSP的确诊率为70.4％(19/27),边界清楚及出现2种以上组织结构(尤其是乳头和硬化伴钙化的结构)容易被确诊;冰冻表现为单一血管瘤样或实体结构容易被误诊;免疫组化显示,PSP表面上皮细胞和间质细胞均表达EMA(18/18,100％)、TTF1(18/18,100％)和Vim(3/3,100％),且表面上皮细胞表达AE1/AE3(16/16,100％)、CK7(19/19,100％)和NapsinA(15/16,93.8％),间质细胞表达ER(7/10,70％)和PR(9/10,90％),间质细胞Ki-67指数≤3％.结论:冰冻中PSP有一定误诊率,存在5个陷阱:肿瘤边界不清、单一组织结构、血管瘤样腔内蛋白水肿液、间质细胞胞质透明或呈梭形、瘤周复杂的炎症背景.增加冰冻取材块数寻找其他几种结构及2类细胞有利于提高冰冻确诊率.

目的 探讨FAM83D在胰腺腺癌(PAAD)组织中的表达及临床意义.方法 基因表达谱动态分析(GEPIA)工具在线分析FAM83D基因表达及预后,KMplot数据库进行验证;选择2018年1月至2019年12月皖南医学院附属弋矶山医院病理科PAAD术后组织蜡块60对,包括癌组织和癌旁组织,使用免疫组织化学染色(IHC)检测FAM83D蛋白的表达;FAM83D作用机制使用基因集富集分析.结果 与正常组织比较,肿瘤组织中FAM83D mRNA表达明显升高(P＜0.01).与癌旁组织比较,癌组织IHC评分显著增高(P＜0.01).PAAD患者FAM83D蛋白高表达与淋巴结转移有关(P＜0.05).与FAM83D mRNA低表达组比较,FAM83D mRNA高表达组总生存期、无进展生存期明显缩短(P＜0.01).FAM83D上调与多个基因集呈正相关(P＜0.05).结论 FAM83D在PAAD发生发展中具有重要作用,可望成为潜在治疗靶点和新型分子标志物.

The chemokine ligand C-X-C motif chemokine ligand 11 (CXCL11) is involved in the progression of various cancers, but its biological roles in colorectal cancer (CRC) remain confused. Therefore, the prognostic value and underlying mechanism of CXCL11 in CRC were preliminarily evaluated. Three independent datasets were used for mRNA-related analysis: one dataset from the Cancer Genome Atlas (TCGA, n = 451) and two single-cell RNA sequencing (scRNA-seq) datasets from Gene Expression Omnibus (GEO): GSE146771 and GSE132465. In addition, a colon adenocarcinoma (COAD) patient cohort (the Yijishan Hospital cohort, YJSHC, n = 108) was utilized for analysis of cell infiltration by immunohistochemistry. We determined the distribution of CXCL11 in tumor tissue across all TCGA cancers and found that CXCL11 expression was significantly upregulated in both COAD and rectal adenocarcinoma (READ). However, the upregulation of CXCL11 mRNA was associated with a better prognosis in COAD, but not in READ. Within the YJSHC, the patients with a high abundance of intratumoral CXCL11+ cells had prolonged survival (p = 0.001). Furthermore, we found that the high CXCL11 expression group had a higher proportion of antitumor immune cells, and a lower proportion of protumor immune cells. Additionally, we discovered the changes of gene expression and enriched immune pathway network mediated by CXCL11. Interestingly, both cytotoxic genes (IFNG, GZMA, GZMB, GZMK, GZMM, and PRF1) and immunosuppressive molecules, including PD-L1, were positively correlated with CXCL11 expression. CXCL11, which promoted antitumor immunity to benefit survival, was identified as an independent prognostic biomarker in patients with COAD.

目的 探讨颅内去分化孤立性纤维性肿瘤(solitary fi-brous tumor,SFT)的临床病理特征、免疫表型及鉴别诊断.方法 回顾性分析1例颅内去分化SFT的临床病理特征、影像学表现及免疫表型,并复习相关文献.结果 患者男性,54岁,右侧颞叶SFT术后1年,MRI提示原颅内占位术后右侧颞叶占位,考虑复发.镜检:瘤细胞短梭形,异型明显,呈血管外皮瘤样排列,可见出血、坏死,部分区域胞质红染,核偏位,核分裂象10～15个/10 HPF;免疫表型:瘤细胞弥漫表达 BCL-2、STAT6,局灶表达 CK(AE1/AE3)、EMA、CD34、CD99、desmin、MyoD1、Myogenin、Myoglobin、SMA,Ki-67增殖指数约50％.结论 颅内去分化SFT与发生于脑膜部的梭形细胞肿瘤的临床特点及影像学表现相似,需结合病理检查及免疫表型进行鉴别.单一手术难以完整切除,易复发恶变,预后差.

目的 探讨斯钙素(STC)基因在食管癌组织中的表达及临床意义.方法 采用GEPIA在线工具分析TCGA数据库食管癌组织中STC-1、STC-2的表达及其与临床预后的关系;免疫组织化学法检测食管癌组织和癌旁组织中STC-2蛋白的表达并分析其临床意义.结果 TCGA数据显示,食管癌组织(n=182)中STC-1、STC-2的mRNA表达水平均显著高于正常组织(n=286),仅STC-2 mRNA的表达与患者总生存期(OS)密切相关(P=0.035).免疫组化结果显示,80.0％(60/75)的食管癌组织中STC-2蛋白表达水平显著高于配对正常组织(P<0.001),且STC-2蛋白表达与患者18F-氟代脱氧葡萄糖(18F-FDG)的标准化摄取值(SUV)(P<0.001)、临床分期(P=0.033)和OS(P=0.0429)显著相关.结论 STC-2高表达可能在食管癌的发生发展中发挥重要作用,是食管癌预后判断的潜在分子标志物.

BACKGROUND:Circular RNAs (circRNAs) are key regulators in the progression of various cancers. Abnormal DNA methylation patterns feature prominently in the regulation of the expression of tumor-related genes. This study is aimed at investigating the molecular mechanism of circ_0040809 affecting colorectal cancer (CRC) progression by regulating DNA methyltransferase 1 (DNMT1).METHODS:circ_0040809 was selected from the circRNA microarray datasets (GSE142837 and GSE138589). Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to examine the expression of circ_0040809, miR-515-5p, and DNMT1 mRNA in paired cancerous and paracancerous tissues of 40 CRC patients, as well as in cell lines. Western blotting was conducted for detecting DNMT1 protein expression in CRC cells. Cell proliferation, migration, and apoptosis were assessed through CCK-8, Transwell, and flow cytometry assays. Bioinformatics and dual-luciferase gene assay were conducted to predict and verify, respectively, the targeted relationships between circ_0040809 and miR-515-5p, as well as between miR-515-5p and DNMT1 mRNA.RESULTS:In CRC tissues and cells, circ_0040809 and DNMT1 expression are markedly increased, whereas miR-515-5p expression is decreased. Also, high circ_0040809 expression is significantly linked to shorter overall survival. Cell function compensation experiments reveal that circ_0040809 silencing inhibits CRC cell proliferation and migration and promotes apoptosis, while circ_0040809 overexpression has the opposite effects. Mechanistically, circ_0040809 competitively binds to miR-515-5p to elevate DNMT1 expression. Rescue assay reveals that overexpressed miR-515-5p partly counteracts the tumor-facilitating impact of circ_0040809.CONCLUSIONS:circ_0040809 facilitates CRC cell proliferation and migration, and inhibits apoptosis, through modulating miR-515-5p/DNMT1 axis. Our study implies that targeting circ_0040809 may be a therapy strategy for CRC treatment.

目的 探讨单羧酸转运蛋白(MCTs)在结直肠癌(CRC)中的表达及临床意义.方法 GEPIA2在线工具分析MCT1～4在CRC组织的表达及临床意义.选择江苏省徐州市中心医院2019年CRC组织标本存档蜡块53例,免疫组化检测MCT4蛋白的表达,正电子发射计算机断层成像(PET/CT)结果由患者术前检查获得.结果 癌症和肿瘤基因图谱(TCGA)数据库中,仅有MCT4 mRNA在结肠腺癌(COAD)组织(275例)和直肠腺癌(READ)组织(92例)中的表达显著高于正常组织,差异有统计学意义(P＜0.05).MCT4高表达与CRC患者较差的无病生存期(DFS)有关(P＜0.05).此外,MCT4蛋白表达在CRC组织明显高于正常组织,差异有高度统计学意义(P＜0.01).对于MCT4高表达患者,PET/CT检查的18氟脱氧葡萄糖(18F-FDG)的标准化摄取值(SUV)高于MCT4低表达患者,差异有高度统计学意义(P＜0.01).结论 MCT4在CRC发生发展中具有重要作用,可望成为新的治疗靶点.

目的 探讨谷胱甘肽过氧化物酶2(GPX2)在肺腺癌中的表达及临床意义.方法 收集皖南医学院弋矶山医院病理科和徐州市中心医院病理科2010年1月至2013年12月存档的152例原发性肺腺癌及其癌旁正常组织标本蜡块.标本行免疫组织化学检测GPX2与ATP结合盒转运蛋白(ABCB6)在肺腺癌组织中的表达.正电子发射计算机断层成像(PET/CT)结果由患者术前检查获得.利用在线工具GEPIA、cBioPortal分析GPX2 mRNA在肺腺癌组织的表达.采用采取t检验比较GPX2表达量和18F-FDG的最大化标准摄取值在肺癌组织和正常组织的差异,采用Pearson相关性分析分析GPX2与ABCB6蛋白表达的相关性,采取χ2检验比较GPX2蛋白表达在不同临床病理特征之间的差异,同时应用Kaplan-Meier法分析肺腺癌患者的生存预后.结果 基于TCGA和GTEx数据,GPX2 mRNA在肺腺癌组织(483例)的表达较正常组织(347例)明显升高,且与ABCB6表达水平呈正相关(r=0.57,P<0.001).在本研究的样本中,89例(58.6％)肺腺癌组织的GPX2蛋白表达较正常组织升高(P<0.001),同样,GPX2与ABCB6蛋白表达水平正相关(r=0.697,P<0.001);其中,GPX2高表达患者(29例)的18F-FDG的最大化标准摄取值也高于GPX2低表达患者(26例),差异具有统计学意义(t=4.262,P<0.001).虽然GPX2蛋白表达在不同临床病理特征之间的差异均无统计学意义(P>0.05),但是GPX2表达升高的患者较GPX2低表达患者无进展生存期减少[平均34.75个月(95％CI:29.746～39.747)vs 48.91个月(95％CI:41.033～56.779),P=0.009].结论 GPX2在肺腺癌发挥癌基因作用,其作用机制可能与ABCB6介导的糖酵解有关.

A pneumonia outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was first identified in Wuhan, present a major threat to public health since December 2019.1 There are more than 50 000 confirmed cases and 1300 dead cases worldwide for the past month or more, because of the occurrence of a highly contagious performance.2 Patients had clinical manifestations of fever, cough, shortness of breath, diarrhea, vomiting, and so on.3, 4 We herein report a case of SARS-CoV-2, describe the epidemic history, clinical diagnosis, and the changes of clinical parameters during the combination therapy. A 47-year-old man came to the People's Hospital in Wuwei with a 7-day history of unexplained fever, cough and bosom frowsty on 21 January 2020. The patient had a chief complaint that he had a fever (up to a maximum of 39.3°C), cough productive of white phlegm, stuffy and runny noses, vertigo, fatigue, chest tightness, and nausea, while he had no chest pain, sore throat or breathing problems. He disclosed that he had returned to Wuwei city on January 18 from Wuhan city by car. The patient with a history of hypertension grade 2 and type 2 diabetes has been smoking since he was 27 years old and reported no alcohol abuse. Nasopharyngeal swab specimens were collected on January 23, 29, and 30 according to the CDC guidelines.5 After putting nasopharynx swab into the nasal cavity, twist it on the nasopharynx mucosa, keep it for 10 to 15 seconds, and then remove it, and finally, insert it into a sterile tube containing viral transport medium. The specimens were examined by RT-PCR. Three gene targets including RdRP, E and N genes were detected. The positive expression (CT value ≤ 43) of the three genes, or RdRP and E genes, or RdRP and N genes indicates SARS-CoV-2 is positive.6 Other examinations were also performed as well. The study was approved by the Ethics Review Committee of the First Affiliated Hospital of Wanan Medical College, and adhered to the tenets of the Declaration of Helsinki. Written informed consent was obtained from the patient for using clinical records in this study. Based on his primary laboratory report, chest radiograph, clinical and epidemiologic information, the patient received the treatment of interferon-alpha and methylprednisolone. However, he was transferred to the First Affiliated Hospital of Wannan Medical College, Wuhu, China on January 23, because of acute exacerbation of clinical symptoms including expiratory dyspnea, poor diet, and lethargy. The laboratory tests were shown in Table 1 (day 0). The results indicated the patient with stable vital signs, significantly decreased lymphocytes and increased c-reactive protein but slightly elevated fibrinogen, neutrophil, lactic dehydrogenase, and fibrinogen. A computed tomography (CT) lung imaging was reported as showing the multiple patchy high-density shadows scattered mainly in the border regions of lungs which were solid changes in which the air bronchogram sign was seen or ground-glass opacifications changes, as well as slightly thickened pleura (Figure S1a). Combination therapy was initiated with lopinavir and ritonavir tablets (800/200 mg daily), methylprednisolone (40 mg daily), recombinant human interferon alfa-2b (10 million IU daily), ambroxol hydrochloride (60 mg daily) and moxifloxacin hydrochloride (0.4 g daily), to inhibit the virus replication, relieve asthma, resolve phlegm, and implement the empirical antibiotic treatment. In addition, the high flow humidification oxygen inhalation therapy was used for preventing acute hypoxic respiratory failure. The treatment of blood glucose, blood pressure, and rehydration therapy was performed. On the second day of treatment, the patient's temperature had low-grade intermittent fevers (range from 36.0°C to 37.2°C). With the exception of occasional chest tightness and shortness of breath, the other symptoms including cough productive of white phlegm, stuffy and runny noses, vertigo, and fatigue were improved. On day 3 of treatment, methylprednisolone was reduced to 20 mg daily and withdraw on day 5. In addition, the high flow humidification oxygen inhalation therapy was removed until the 8th day of treatment, based on the markedly improved respiratory function. According to the persistent negative results of SARS-CoV-2 on days 6 and 7, as well as the lung lesions partially absorbed (Figure S1b), the patient was discharged on day 10. During treatment, the patient's body temperature, pulse, and respiratory rate had slight fluctuation (Figure S1c), and the laboratory results got better improvement, especially lymphocyte count (Table 1; day 8). In our patients, laboratory tests are necessary, especially the total lymphocyte count (TLC) which shows a significant decline. After recovery, the TLC reaches the normal level. Chest CT examination combined with the detection of SARS-CoV-2 RNA is helpful for the diagnosis.7 Moreover, the patient, who failed to respond to methylprednisolone and interferon therapy in other hospitals, received additional lopinavir and ritonavir tablets therapy in our hospital and got a quick improvement of the clinical symptoms. The authors declare that there are no conflict of interests. This work was supported by the Natural Science Foundation of Anhui Province (no. 1908085QH325) and the Natural science research project of universities in Anhui Province (no. KJ2017A260). The authors thank the patient for participation in this study. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

The aim of this study was to explore the roles of GPX2, a member of the glutathione peroxidase family (GPXs, GSH-Px), in cisplatin (DDP) resistance in lung adenocarcinoma (LUAD). GPX2 was found to be the most significantly upregulated gene in a DDP-resistant A549/DDP cell line compared with the parental A549 cell line by RNA sequencing. The knockdown of GPX2 expression in A549/DDP cells inhibited cell proliferation in vitro and in vivo, decreased the IC50 values of DDP, induced apoptosis, inhibited the activities of GSH-Px and superoxide dismutase (SOD), inhibited ATP production and glucose uptake, and increased malondialdehyde (MDA) and reactive oxygen species (ROS) production; while GPX2 overexpression in A549 cells resulted in the opposite effects. Using gene set enrichment analysis (GSEA), we found that GPX2 may be involved in DDP resistance through mediating drug metabolism, the cell cycle, DNA repair and energy metabolism, and the regulation of an ATP-binding cassette (ABC) transporters member ABCB6, which is one of the hallmark genes in glycolysis. Moreover, immunohistochemistry revealed that GPX2 was upregulated in 58.6% (89/152) of LUAD cases, and elevated GPX2 expression was correlated with high expression of ABCB6, high 18-fluorodeoxyglucose (18F-FDG) uptake, and adverse disease-free survival (DFS) in our cohort. The Cancer Genome Atlas (TCGA) data also indicated that GPX2 expression was higher in LUAD than it was in normal lung tissues, and the mRNA expression levels of GPX2 and ABCB6 were positively correlated. In conclusion, our study demonstrates that GPX2 acts as oncogene in LUAD and promotes DDP resistance by regulating oxidative stress and energy metabolism.

AIMSThe homeobox (HOX) genes function as transcriptional factors that can promote tumorigenesis. However, the expression profile of HOXA10 and the role this protein plays in solid tumors are unclear. Here we examined HOXA10 protein expression in samples from colorectal cancer (CRC) patients to address the clinical significance of this protein.MATERIALS AND METHODSSeven independent investigations from the Oncomine database were retrieved. A total of 85 patients who underwent radical excision followed by 5-fluorouracil (5-FU)-based adjuvant chemotherapy were enrolled. Immunohistochemistry was performed on pairs of cancerous and normal tissues to detect the expression of both HOXA10, and the phosphatase and tensin homolog deleted on chromosome ten (PTEN). Lentivirus-mediated RNA interference was used to knock down HOXA10 expression in LoVo and HT-29 cell lines, then cells' proliferation, apoptosis, and tumor growth in vivo were detected.RESULTSOncomine data showed that HOXA10 expression was significantly upregulated in CRC tissues compared with relevant normal controls. In our study, 58 cases (68.2%) showed positive HOXA10 protein expression in tumor tissue and negative expression in normal tissues. HOXA10 protein upregulation was consistent with PTEN downregulation. Although not related to clinicopathological parameters, a significant correlation was found between HOXA10 upregulation and a decreased 5-year disease-free survival (DFS). A Cox proportional hazards model further suggested that HOXA10 overexpression was an independent factor to predict DFS of CRC patients. Furthermore, HOXA10 knockdown significantly increased sensitivity to 5-FU chemotherapy in vitro and in vivo.CONCLUSIONSSignificant HOXA10 overexpression in CRC may be a potential biomarker indicating poor prognosis and 5-FU resistance.

目的 探讨肝激酶(LK)B1基因表达水平与非小细胞肺癌(NSCLC)患者的临床病理特征及与预后的相关性.方法 应用实时荧光定量-聚合酶链式反应(RT-PCR)和Western印迹法检测LKB1基因mRNA和蛋白表达,并结合23例NSCLC临床资料进行分析.结果 LKB1基因在癌组织和癌旁正常组织均有表达,癌组织表达明显低于癌旁正常组织(P<0.05).LKB1基因在鳞癌和腺癌表达无统计学差异(P>0.05).LKB1表达水平与分化程度相关(P<0.05),与患者年龄、临床分期、肿瘤大小不相关(P>0.05).LKB1基因mRNA低表达组中位无进展生存期(PFS)〔8.20(95％CI:6.29～10.11)个月〕显著低于高表达组〔16.57(95％CI:11.20～21.94)个月〕(P<0.05).LKB1基因蛋白低表达组PFS〔9.07(95％CI:5.80～12.34)个月〕显著低于高表达组〔15.36(95％CI:12.52～18.20)个月〕(P<0.05).结论 LKB1基因表达水平与NSCLC组织分化程度相关,且LKB1低表达可能提示预后不良.