ObjectiveTo investigate serum β2-MG, sCHE, and PSGL-1 expression in patients with esophageal cancer and their relationship to lung infection after mediastinoscopy. MethodsA total of 118 patients with esophageal cancer were selected and divided into infected and uninfected groups according to whether they developed lung infection after surgery. An automatic microbiological identification system was used to detect the pathogenic bacteria of lung infection. ELISA was used to detect the levels of β2-MG, sCHE, and PSGL-1. Multivariate logistic regression was used to analyze the influencing factors of postoperative lung infection in patients with esophageal cancer. ROC curves were plotted to analyze the assessment value of serum β2-MG, sCHE, and PSGL-1 on postoperative lung infection. ResultsFifty-two strains of bacteria were isolated from the sputum of 38 patients with postoperative lung infections, and these included 35 (67.31%) Gram-negative, 14 (26.92%) Gram-positive, and 3 (5.77%) fungal strains. The difference in long-term smoking history between the infected and uninfected groups was statistically significant (P<0.05). Serum β2-MG and PSGL-1 levels were significantly higher and sCHE levels were significantly lower in the infected group than in the uninfected group (P<0.05). Serum β2-MG and PSGL-1 levels were sequentially higher (P<0.05) and sCHE levels were sequentially lower (P<0.05) in the mild, moderate, and severe lung infection groups. Long-term smoking history, β2-MG, and PSGL-1 were risk factors affecting postoperative lung infection in patients with esophageal cancer (P<0.05), and sCHE was a protective factor (P<0.05). The AUCs of serum β2-MG, sCHE, and PSGL-1 for assessing postoperative lung infections were 0.807, 0.845, and 0.800, respectively, and the AUC of the three combined factors for assessing postoperative lung infections was 0.954, which was superior to that assessed individually (Zcombination vs. β2-MG=2.576, Zcombination vs. sCHE=2.623, Zcombination vs. PSGL-1=2.574, all P<0.05). ConclusionThe serum levels of β2-MG and PSGL-1 increase and the sCHE level decreases in patients with esophageal cancer and postoperative pulmonary infection, which are also related with lung infection. Combined testing can improve the evaluation value of postoperative pulmonary infection in patients.

Targeted therapies have markedly improved the prognosis of lung cancer patients; nevertheless, challenges persist, including limited beneficiary populations and the emergence of drug resistance. This study investigates the molecular mechanisms of mutant TP53 in lung cancer, aiming to contribute to novel strategies for targeted therapy. The TCGA database was employed to delineate the mutational landscape of TP53 in lung cancer patients. Differential gene expression between TP53-mutant and wild-type patients was analyzed, followed by functional enrichment. DSG3 protein expression in lung cancer patients was assessed using IHC, and its impact on prognosis was analyzed in the TCGA database. The influence of TP53 on the downstream gene DSG3 was investigated using qPCR, ChIP-qPCR, and luciferase reporter gene assays. Protein enrichment in the DSG3 promoter region was examined through IP-MS, and the regulatory role of the HIF1-α/TP53 complex on DSG3 was explored using Co-IP, luciferase assays, and ChIP-qPCR. Molecular interactions between TP53 (R273H) and HIF1-α were detected through immunoprecipitation and molecular docking. The effects and mechanisms of DSG3 on lung cancer phenotypes were assessed through WB, transwell, and wound healing assays. TP53 mutations were present in 47.44

BackgroundAt present, minimally invasive radical esophagectomy is the main surgical method for esophageal cancer treatment, but it has inherent limitations. We have developed a novel method of radical esophagectomy without thoracotomy to improve this situation, namely, by using EMLE. We evaluated the feasibility and safety of expandable mediastinoscopic and laparoscopic radical esophagectomy (EMLE) through a retrospective analysis.MethodsFrom January 2019 to June 2022, we successfully performed 106 cases of radical resection of esophageal cancer with this new surgical technique, gradually improved the surgical path, and recorded the perioperative data and postoperative complications of all patients.ResultsThe operation was successfully performed in all patients except for two patients who required a switch to open surgery. The mean operation time was 171.11 ± 33.29 min and the mean intraoperative blood loss was 93.53 ± 56.32 ml. The mean number of removed lymph nodes was 23.59 ± 5.42. The postoperative complications included pneumonia (3.77%), recurrent laryngeal nerve palsy (1.89%), anastomotic leak (14.15%), pleural effusion (5.66%), chylothorax (2.83%), and reoperation (4.72%). All complications were graded I–III per the Clavien–Dindo classification. No perioperative death was recorded.ConclusionExpandable mediastinoscopic and laparoscopic radical esophagectomy is feasible for radical resection of esophageal cancer, with good therapeutic effect and safety. Because of its minimal impact on patients and convenient operation, it is a novel surgical option for patients with esophageal cancer and is expected to become a standard surgical method for radical esophagectomy in the future.

Objective:To analyze the clinical characteristics of patients with malignant pulmonary sclerosing pneumocytoma (PSP) with metastasis, recurrence, and growth and to improve clinicians' understanding of PSP in patients with malignant tumor characteristics.Methods:A total of 46 PSP patients with malignant tumor characteristics were identified in the literature search and compared with 38 patients with benign PSP diagnosed and treated in our hospital in the past 5 years. We explored the pathogenesis, clinical symptoms, diagnostic methods, treatment strategies and prognosis of PSP patients with malignant tumor.Results:The characteristics of young age (≤41 years old), larger tumor (≥36mm), lymph node metastasis and distribution in East Asians are indicative of PSP with malignant potential. Such patients should undergo segmental resection or lobectomy, combined with necessary lymph node dissection or biopsy. All patients with PSP should have an entire course of follow-up management, because they may have an adverse prognosis such as recurrence, growth, metastasis, and even death.Conclusion:PSP has the potential for malignancy. Anatomical lobectomy or segmental resection combined with lymph node dissection should be performed in PSP with some specific characteristics. Inappropriate diagnosis and treatment may lead to poor prognosis in PSP patients.

Jianxing He, Hengrui Liang, Wei Wang, Andrey Akopov, Alberto Aiolfi, Keng-Leong Ang, Luca Bertolaccini, Kaican Cai, Qingdong Cao, Baojun Chen, Chang Chen, Chun Chen, Donglai Chen, Fengxia Chen, Jun Chen, Lei Chen, Mingwu Chen, Yongbing Chen, Zhuxing Chen, Chao Cheng, Dong Cui, Fei Cui, Tianyang Dai, Qinglong Dong, Paolo A. Ferrari, Raja M. Flores, Junke Fu, Soichiro Funaki, Marios E. Froudarakis, Xiangfeng Gan, Mingfei Geng, Jialong Guo, Qiang Guo, Yongtao Han, Jintao He, Kaiming He, Kyoji Hirai, Jian Hu, Shuqiao Hu, Jian Huang, Jun Huang, Wenfa Jiang, Kyung Soo Kim, Gabor Kiss, Fanyi Kong, Lan Lan, Xuefeng Leng, Bin Li, Gaofeng Li, Hecheng Li, Hefei Li, Heng Li, Jiwei Li, Xiaoqiang Li, Shuben Li, Yinfen Li, Zhuoyi Li, Yi Liang, Lixia Liang, Wenhua Liang, Yongde Liao, Wanli Lin, Xu Lin, Hongxu Liu, Hui Liu, Jixian Liu, Jun Liu, Xiang Liu, Zihao Liu, Xingzhao Lu, Qingquan Luo, Naiquan Mao, Qi Pan, Dazhi Pang, Jun Peng, Jun Peng, Eugenio Pompeo, Rulin Qian, Kun Qiao, Bassam Redwan, Zi Sang, Wenlong Shao, Jianfei Shen, Weiyu Shen, Sook-Whan Sung, Wenfang Tang, Tianhu Wang, Guangsuo Wang, Haitao Wang, Huien Wang, Jiyong Wang, Wen Wang, Yongyong Wang, Zhenyuan Wang, Li Wei, Wei Wei, Hao Wu, Jie Wu, Zhaohua Xia, Chenyang Xu, Enwu Xu, Hai Xu, Ning Xu, Quan Xu, Rongyu Xu, Shun Xu, Chaokun Yang, Hanyu Yang, Shengli Yang, Jun Yi, Guangjian Zhang, Hao Zhang, Jia Zhang, Man Zhang, Xiao Zhang, Yajie Zhang, Zhe Zhang, Zhifeng Zhang, Honglin Zhao, Jian Zhao, Xiaodong Zhao, Jianping Zhou, Yanran Zhou, Chengchu Zhu, Shaojin Zhu, Xinhai Zhu, Jian Cui, Yubo Yan, Ke-Neng Chen

The emergence of drug resistance hinders the treatment of malignant tumors, and autophagy plays an important role in tumor chemotherapy resistance. However, its mechanism in non-small cell lung cancer (NSCLC) has not been well-researched. We aim to investigate the role of miR-101-3p in cisplatin-resistant via regulation of autophagy-related protein 4D (ATG4D) and autophagy. Cell viability, apoptosis, fluorescence intensity of GFP-LC3 and RFP-GFP-LC3 were determined using Cell Counting Kit-8 (CCK-8) assay, flow cytometry, and Laser scanning confocal microscope analysis, respectively. The levels of LC3II/LC3I, P62 and ATG4D were detected by Western blot. The results showed that the sensitivity to cisplatin in NSCLC cells was up-regulated by miR-101-3p mimics treatment, inducing promoting cell apoptosis and inhibiting autophagy. Further mechanistic study identified that ATG4D was a direct target of miR-101-3p. Moreover, ATG4D siRNA also could reverse miR-101-3p inhibitor-induced the up-regulation of ATG4D and the ration of LC3II/LC3I, the down-regulation of p62 expression. Our findings indicated that miR-101-3p could regulate sensitivity to cisplatin of NSNCC cells by regulating autophagy mediated by ATG4D. Therefore, miR-101-3p may act as a potential therapeutic target for the treatment of NSCLC.

Background: This article aims to analyze the correlation between microvessel density (MVD) and multi-spiral CT(MSCT) perfusion parameters of esophageal cancer lesions, and the diagnostic value of combining C-terminal binding protein 2 (CtBP2) and P16 inhibitor of cyclin-dependent kinase 4a (P16(INK4A)). Methods: A total of 42 cases of normal esophageal mucosa tissues >5 cm from the cancer tissue were selected as the control group. The expression levels of CtBP2 and P16(INK4A) and the values of MSCT perfusion parameters and MVD were compared in the control group and esophageal cancer group. SP immunohistochemical staining was used to detect protein expression levels of CtBP2 and P16(INK4A). The Pearson method was used to analyze the differences and pertinence of MSCT perfusion parameters and MVD in the control group and esophageal cancer group. The receiver operating characteristic (ROC) curve was used to calculate the diagnostic value of CtBP2 and P16(INK4A) combined with MVD and MSCT perfusion parameters in esophageal cancer. Results: The positive expression rate of P16(INK4A) in the esophageal cancer group was significantly lower than that in the control group. The positive expression rates of CtBP2, blood volume (BV), mean transit time (MTT), surface permeability (permeability surface, PS), and MVD values were significantly higher than those of the control group (P<0.05). There was no significant difference in blood flow (BF) value between the 2 groups (P>0.05). The BF value of the tumor invading the fibrous membrane was significantly higher than that of the non-invading fibrous membrane (P<0.05), and the PS and MVD values of the patients with lymph node metastasis were higher than those without lymph node metastasis (P<0.05). The MSCT perfusion parameters BF and BV were significantly positively correlated with MVD (P<0.05), while MTT, PS, and MVD were not significantly correlated (P>0.05). ROC results showed that the areas under curve (AUC) of CtBP2, P16INK4A, and MSCT were 0.625, 0.747, and 0.812, respectively. However, the area under the combined detection curve was larger, at 0.869. Conclusions: MSCT perfusion imaging of esophageal cancer lesions can indirectly reflect the angiogenesis of esophageal cancer, and the combination of CtBP2 and P16(INK4A) can effectively improve the diagnostic efficiency of the disease.

Mediastinoscopy was originally applied for lymph node biopsy and mediastinal tumor resection. Improved video imaging with spreadable working channels enabled mediastinoscopy for inspection and tissue biopsy in the superior mediastinum but it is rarely used in minimally invasive esophageal cancer surgery. In this prospective trial, the practicability and security of spreadable video-assisted mediastinoscopic combined with laparoscopic transhiatal esophagectomy (VAME) with video-assisted thoracoscopic esophagectomy (VATE) were compared. A total of 200 eligible patients with esophageal squamous cell carcinoma were randomly divided into VAME or VATE groups. Early postoperative outcomes and lymph node dissection between the two groups were compared. The operation time was significantly shorter (164.3 ± 47.0 min vs. 265.4 ± 47.2 min, P < 0.001), the number of dissected lymph nodes was less (15.8 ± 4.5 vs. 20.3 ± 6.5, P < 0.001), and the intraoperative blood loss was also significantly reduced (94.7 ± 56.7 mL vs. 184.4 ± 65.2 mL, P < 0.001) in the VAME compared to the VATE group, respectively. The incidence of pneumonia was lower (7% vs. 29%; P < 0.001) and the length of hospital stay was shorter in the VAME group compared to the VATE group (18.0 ± 7.6 days vs. 23.2 ± 7.2, P < 0.001, respectively). The chyle leak incidence appeared to be lower in the VAME group but statistical significance was not reached (1% vs. 4%; P = 0.369). There were no differences in the incidence of anastomotic leakages and recurrent laryngeal nerve paralysis between the groups. No 30-day mortality occurred in any of the cases. VAME appears to be a practicable and secure method for esophagectomy but needs further proof of concept. Clinical registration number: Registered at Chinese Clinical Trial Registry, ChiCTR1900022797.

BACKGROUND:Long non-coding RNAs (lncRNAs) can play pivotal roles in tumor progression by acting as microRNA (miRNA) sponges. This study aimed to investigate the association of a novel lncRNA, TRPM2-AS, with the miR-138-5p/EGFR axis in the development of non-small cell lung cancer (NSCLC).METHODS:Sixty NSCLC tissues and paired adjacent non-tumor tissues were analyzed. The relative expression levels of TRPM2-AS, miR138-5p, and epidermal growth factor receptor (EGFR) and the interactions between them were analyzed. The NSCLC cell lines NCI-H1299 and A549 were transfected with TRPM2-AS shRNA/pcDNA, and miR-138-5p mimics. Cell proliferation, migration, invasion, and apoptosis were examined in response to different transfection conditions. Dual-luciferase reporter assay was performed to identify the target interactions between TRPM2-AS, miR-138-5p, and EGFR. A549 cells stably transfected with shRNA were injected into BALB/c null nude mice to establish a tumor xenograft model.RESULTS:TRPM2-AS was up-regulated in NSCLC tumors and cell lines. Cell proliferation, migration, and invasion were inhibited in NSCLC cells treated with sh-TRPM2-AS, while apoptosis was induced. The targeting of TRPM2-AS by miR138-5p and miR138-5p by EGFR were validated with dual-luciferase reporter assay. TRPM2-AS was found to be negatively correlated with miR138-5p but positively correlated with EGFR. PI3K/AKT/mTOR was activated by pcDNA-EGFR but inactivated by miR-138-5p mimics. In the tumor xenograft mouse model, sh-TRPM2-AS suppressed tumor formation, reduced the expression of EGFR and Ki67, and promoted tumor cell apoptosis.CONCLUSIONS:Our results suggested that TRPM2-AS can increase the levels of EGFR via sponging miR-138-3p; this promoted NSCLC cell proliferation, migration, and invasion in vitro, and exacerbated tumors in vivo. These findings highlight TRPM2-AS/miR-138-5p as a potential target for reducing drug resistance in patients with NSCLC.

Circular RNA mediator of cell motility 1 (circ-MEMO1) was identified as an oncogene in non-small cell lung cancer (NSCLC). Nevertheless, the working mechanism behind circ-MEMO1-mediated progression of NSCLC is barely known. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect the expression of circ-MEMO1, microRNA-101-3p (miR-101-3p), and KRAS proto-oncogene, GTPase (KRAS). Cell proliferation and aerobic glycolysis were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and glycolysis detection kits. Flow cytometry was used to evaluate cell cycle progression and apoptosis of NSCLC cells. Western blot assay was used to measure the protein expression of hexokinase 2 (HK2), lactate dehydrogenase A (LDHA), KRAS, CD9, CD81, tumor susceptibility 101 (TSG101), and Golgi matrix protein 130 kDa (GM130). The target relationship between miR-101-3p and circ-MEMO1 or KRAS was predicted by StarBase software and confirmed by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and RNA-pull down assay.In vivotumor growth assay was conducted to assess the effect of circ-MEMO1in vivo. Exosomes were isolated using the ExoQuick precipitation kit. Circ-MEMO1 was up-regulated in NSCLC, and high expression of circ-MEMO1 predicted poor prognosis in NSCLC patients. Circ-MEMO1 accelerated the proliferation, cell cycle progression, and glycolytic metabolism and inhibited the apoptosis of NSCLC cells. Circ-MEMO1 negatively regulated the expression of miR-101-3p through direct interaction, and si-circ-MEMO1-induced biological effects were attenuated by the introduction of anti-miR-101-3p. MiR-101-3p directly interacted with the 3 ' untranslated region (3 ' UTR) of KRAS messenger RNA (mRNA), and KRAS level was regulated by circ-MEMO1/miR-101-3p axis. Circ-MEMO1 silencing suppressed the NSCLC tumor growthin vivo. ROC curve analysis revealed that high expression of serum exosomal circ-MEMO1 (exo-circ-MEMO1) might be a valuable diagnostic marker for NSCLC. Circ-MEMO1 facilitated the progression and glycolysis of NSCLC through regulating miR-101-3p/KRAS axis.

PURPOSE To investigate the expression and significance of the expression of nucleostemin (NS) and proliferating cell nuclear antigen (PCNA) protein in non-small cell lung cancer (NSCLC). METHODS Immunohistochemistry (streptavidin-peroxidase method) was used to detect NS and PCNA expression in 53 NSCLC samples and 15 normal lung samples. RESULTS NS protein expression was detected in 54.7% (29/53) of the NSCLC samples and 0% (0/15) of the normal lung samples (p<0.01). Furthermore, the positive expression rate of PCNA was 6.67% (1/15) in normal lung samples and 71.7% (38/53) in NSCLC samples (p<0.05). Also, the NS protein expression rate was 65.2% (15/23) in adenocarcinoma tissue samples, significantly higher than that in squamous tissues, where the NS expression rate was 46.7% (14/30) (p<0.05). In addition, the NS expression rate of 42.9% (15/35) in well or moderately differentiated tumor tissues was lower than the rate of 77.8% (14/18) in poorly differentiated tumor tissues (p<0.05). The grade of differentiation had no correlation with tumor-node-metastasis (TNM) stage and lymph node metastasis (p>0.05). Also, the positive expression rate of PCNA was significantly higher in NSCLC samples than in normal lung samples (p<0.05). In addition, a positive correlation was found between NS and PCNA expression in NSCLC (p<0.05). CONCLUSION The highly valuable tumor molecular markers, NS and PCNA, had higher expression levels in NSCLC samples. Combined detection of NS and PCNA may be important for the early diagnosis of lung cancer and individualized therapy, having also an important role in predicting tumor prognosis.