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Background: To improve perioperative frailty status in patients undergoing laparoscopic colorectal cancer surgery (LCCS), we explored a new intensive prehabilitation program that combines prehabilitation exercises with standard enhanced recovery after surgery (ERAS) and explored its impact., Methods: We conducted a prospective randomized controlled trial. Between April 2021 to August 2021, patients undergoing elective LCCS were randomized into the standardized ERAS (S-ERAS) group or ERAS based on prehabilitation (group PR-ERAS). Patients in the PR-ERAS group undergoing prehabilitation exercises in the perioperative period in addition to standard enhanced recovery after surgery. We explored the effects of this prehabilitation protocol on frailty, short-term quality of recovery (QoR), psychological status, postoperative functional capacity, postoperative outcomes, and pain., Results: In total, 125 patients were evaluated, and 95 eligible patients were enrolled and randomly allocated to the S-ERAS (n = 45) and PR-ERAS (n = 50) groups. The Fried score was higher in the PR-ERAS group on postoperative day (7 (2(2,3) vs. 3(2,4), P = 0.012). The QoR-9 was higher in the PR-ERAS group than in the S-ERAS group on the 1st, 2nd, 3rd, and 7th postoperative days. The PR-ERAS group had an earlier time to first ambulation (P < 0.050) and time to first flatus (P < 0.050)., Conclusion: Prehabilitation exercises can improve postoperative frailty and accelerate recovery in patients undergoing LCCS but may not improve surgical safety. Therefore, better and more targeted prehabilitation recovery protocols should be explored., Clinical Trial Registration: www.clinicaltrials.org , identifier NCT04964856., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Yuan, Liu, Tang, He, Chen, Xiong, Huang and Qian.)

Background: Laparoscopic right hemicolectomy is a standard treatment modality for right colon cancer. However, performing intracorporeal anastomosis (IA) for totally laparoscopic right hemicolectomy (TLRH) remains a challenge for some surgeons. To simplify IA in TLRH we used self-pulling and latter transection (SPLT) reconstruction in TLRH, and compared this procedure with overlap IA and laparoscopy-assisted right hemicolectomy (LARH) in order to evaluate its safety and effectiveness., Methods: Patients with right colon cancer who underwent SPLT-TLRH, TLRH with overlap IA or LARH between July 2019 and June 2023 were evaluated retrospectively. Basic information, oncological features, perioperative outcomes, and postoperative complications were compared between groups., Results: In total, 188 patients with right colon cancer that underwent SPLT-TLRH (n = 60), TLRH(n=21) or LARH (n = 107) were included in the study. No patient required conversion to open surgery. The operation time in SPLT-TLRH group was significantly shorter than that in TLRH group (P<0.05). Compared with LARH group, SPLT-TLRH group had significantly longer distal margins, shorter skin incisions (P < 0.001), time to first flatus, time to first defecation, and postoperative hospital stays (P<0.05)., Conclusion: We introduced SPLT to TLRH. The SPLT-TLRH group demonstrated better short-term outcomes. Therefore, we believe that SPLT reconstruction is effective and safe in TLRH for right colon cancer, and can simplify reconstruction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, He, Tang, Chen, Xiong, Zou, Woraikat, Qian and Li.)

Background: Acute myeloid leukemia (AML) is a heterogeneous hematopoietic malignancy. Patient prognosis cannot be accurately assessed in National Comprehensive Cancer Network (NCCN) risk stratification subgroups based on the current criteria. This study aimed to develop a novel prognostic score model for the quantitative prediction of prognosis in AML., Results: We developed a prognostic risk scoring model of AML using differentially expressed genes to predict prognosis in patients with AML. Furthermore, we evaluated the effectiveness and clinical significance of this prognostic model in 4 AML cohorts and 905 patients with AML. A prognostic risk scoring model of AML containing eight prognosis-related genes was constructed using a multivariate Cox regression model. The model had a higher predictive value for the prognosis of AML in the training and validation sets. In addition, patients with lower scores had significantly better overall survival (OS) and even-free survival (EFS) than those with higher scores among patients with intermediate-risk AML according to the NCCN guidelines, indicating that the model could be used to further predict the prognosis of the intermediate-risk AML populations. Similarly, patients with high scores had remarkably poor OS and EFS in the normal-karyotype populations, indicating that the scoring model had an excellent predictive performance for patients with AML having normal karyotype., Conclusions: Our study provided an individualized prognostic risk score model that could predict the prognosis of patients with AML., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yu, Wang, Yang, Fang, Wen, Jiao, Qian, Le, Shan, Gao, Hua and Li.)

SET domain-containing 2 (SETD2) is a lysine methyltransferase that catalyzes histone H3 lysine36 trimethylation (H3K36me3) and has been revealed to play important roles in the regulation of transcriptional elongation, RNA splicing, and DNA damage repair. SETD2 mutations have been documented in several cancers, including clear cell renal cell carcinoma (ccRCC). SETD2 deficiency is associated with cancer occurrence and progression by regulating autophagy flux, general metabolic activity, and replication fork speed. Therefore, SETD2 is considered a potential epigenetic therapeutic target and is the subject of ongoing research on cancer-related diagnosis and treatment. This review presents an overview of the molecular functions of SETD2 in H3K36me3 regulation and its relationship with ccRCC, providing a theoretical basis for subsequent antitumor therapy based on SETD2 or H3K36me3 targets., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yu, Qian, Wang, Xiao, Zhu and Ju.)

Background: Self-pulling and latter transection (SPLT) reconstruction has been applied in total laparoscopic total gastrectomy and BI reconstruction (known as Delta SPLT) in total laparoscopic distal gastrectomy (TLDG) in some previous studies. This approach can reduce the technical difficulty of the surgery as well as the quantity of cartridges required, with manageable safety. Here, we used SPLT to complete Roux-en-Y reconstruction in TLDG and evaluated the safety and effectiveness of this novel method by comparing it with conventional Roux-en-Y reconstruction in laparoscopy-assisted distal gastrectomy (LADG)., Methods: Patients with gastric cancer who underwent SPLT-TLDG or LADG between June 2019 and September 2021 were retrospectively analyzed. Baseline information and postoperative short-term surgical outcomes of the two groups were compared., Results: A total of 114 patients with gastric cancer were included in the study. Patients underwent SPLT-TLDG (n = 73, 64.0%) or LADG (n = 41, 36.0%). No patient underwent open surgery. There were no differences in patient demographics or tumor characteristics between the two groups. The mean intraoperative blood loss was 47.1 ± 34.3 ml in the SPLT-TLDG group, which was significantly less than that in the LADG group (P = 0.022). There were no significant differences in operation time, harvested lymph nodes, time to first flatus, time to liquid intake, or postoperative hospital stay between the two groups. Nine and five patients had short-term postoperative complications in the SPLT-TLDG and LADG groups, respectively., Conclusion: We introduced a self-pulling and latter transected Roux-en-Y reconstruction (SPLT-RY) for use in TLDG. We showed that SPLT-RY reconstruction in TLDG is a safe and feasible surgical method in terms of short-term surgical outcomes and has the advantages of simplifying the reconstruction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential a conflict of interest., (Copyright © 2022 Chen, Yang, Woraikat, Tang and Qian.)

Background: Postoperative recurrence impedes the curability of early-stage hepatocellular carcinoma (E-HCC). We aimed to establish a novel recurrence-related pathological prognosticator with artificial intelligence, and investigate the relationship between pathological features and the local immunological microenvironment., Methods: A total of 576 whole-slide images (WSIs) were collected from 547 patients with E-HCC in the Zhongshan cohort, which was randomly divided into a training cohort and a validation cohort. The external validation cohort comprised 147 Tumor Node Metastasis (TNM) stage I patients from The Cancer Genome Atlas (TCGA) database. Six types of HCC tissues were identified by a weakly supervised convolutional neural network. A recurrence-related histological score (HS) was constructed and validated. The correlation between immune microenvironment and HS was evaluated through extensive immunohistochemical data., Results: The overall classification accuracy of HCC tissues was 94.17%. The C-indexes of HS in the training, validation and TCGA cohorts were 0.804, 0.739 and 0.708, respectively. Multivariate analysis showed that the HS (HR= 4.05, 95% CI: 3.40-4.84) was an independent predictor for recurrence-free survival. Patients in HS high-risk group had elevated preoperative alpha-fetoprotein levels, poorer tumor differentiation and a higher proportion of microvascular invasion. The immunohistochemistry data linked the HS to local immune cell infiltration. HS was positively correlated with the expression level of peritumoral CD14 + cells ( p = 0.013), and negatively with the intratumoral CD8 + cells ( p < 0.001)., Conclusions: The study established a novel histological score that predicted short-term and long-term recurrence for E-HCCs using deep learning, which could facilitate clinical decision making in recurrence prediction and management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Qu, Tian, Qiu, Guo, Tao, Liu, Tang, Qian, Wang, Li, Hu, Zhou, Fan, Zou, Hou and Shi.)

Microbes and microbiota dysbiosis are correlated with the development of lung cancer; however, the airway taxa characteristics and bacterial topography in synchronous multiple primary lung cancer (sMPLC) are not fully understood. The present study aimed to investigate the microbiota taxa distribution and characteristics in the airways of patients with sMPLC and clarify specimen acquisition modalities in these patients. Using the precise positioning of electromagnetic navigation bronchoscopy (ENB), we analyzed the characteristics of the respiratory microbiome, which were collected from different sites and using different sampling methods. Microbiome predictor variables were bacterial DNA burden and bacterial community composition based on 16sRNA. Eight non-smoking patients with sMPLC in the same pulmonary lobe were included in this study. Compared with other sampling methods, bacterial burden and diversity were higher in surface areas sampled by bronchoalveolar lavage (BAL). Bacterial topography data revealed that the segment with sMPLC lesions provided evidence of specific colonizing bacteria in segments with lesions. After taxonomic annotation, we identified 4863 phylotypes belonging to 185 genera and 10 different phyla. The four most abundant specific bacterial community members detected in the airway containing sMPLC lesions were Clostridium, Actinobacteria, Fusobacterium , and Rothia , which all peaked at the segments with sMPLC lesions. This study begins to define the bacterial topography of the respiratory tract in patients with sMPLC and provides an approach to specimen acquisition for sMPLC, namely BAL fluid obtained from segments where lesions are located., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Qian, Deng, Krimsky, Feng, Peng, Tai, Peng and Jiang.)

Purpose: To assess the impact of enhanced recovery after surgery (ERAS) protocols in laparoscopic radical nephrectomy (LRN)., Methods: The clinical data of 89 patients underwent LRN in Zhongnan Hospital of Wuhan University from February 2019 to September 2021 were collected (40 in the ERAS group and 49 in the pre-ERAS group). The clinical characteristics, prognosis, and length of hospital stay (LOS) were compared between the two groups using t test, Mann-Whitney test, and chi-square test., Results: Total LOS and postoperative LOS were significantly shorter in ERAS group than in pre-ERAS group [15.0 (13.5-19.5) vs . 12.0 (10.0-14.0), P < 0.001; 8.0 (7.0-10.0) vs . 7.0 (5.0-8.8), P = 0.001]. Compared with the pre-ERAS group, the hospitalization expenses of the ERAS group were also lower (P = 0.023). In addition, the incidence of postoperative complications in the ERAS group also decreased (P = 0.054)., Conclusions: ERAS protocol in LRN could help accelerate the recovery of patients and is worthy of clinical promotion., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, He, Yao, Xiong, Shi, Wang, Qian and Wang.)

Background: Hyaluronan-mediated motility receptor ( HMMR ) plays a pivotal role in cell proliferation in various cancers, including lung cancer. However, its function and biological mechanism in lung adenocarcinoma (LUAD) remain unclear., Methods: Data on HMMR expression from several public databases were extensively analyzed, including the prognosis of HMMR in the Gene Expression Profiling Interactive Analysis (GEPIA) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed using DAVID and gene set enrichment analysis (GSEA) software. The correlation between HMMR expression and immune cell infiltration was analyzed in the Tumor Immune Estimation Resource (TIMER) database, and the gene and protein networks were examined using the GeneMANIA and STRING databases. Experimentally, the expression of HMMR in LUAD and lung cancer cell lines was determined using immunohistochemistry and quantitative RT-PCR assays. Besides, the function of HMMR on cancer cell proliferation and migration was examined using cell growth curve and colony formation, Transwell, and wound healing assays., Results: In this study, we found that HMMR was elevated in LUAD and that its high expression was associated with poor clinicopathological features and adverse outcomes in LUAD patients. Furthermore, our results demonstrated that the expression of HMMR was positively correlated with immune cell infiltration and immune modulation. Interestingly, diverse immune cell infiltration affects the prognosis of LUAD. In the functional assay, depletion of HMMR significantly repressed the cancer cell growth and migration of LUAD. Mechanically, we found that that the DNA methylation/TMPO-AS1/let-7b-5p axis mediated the high expression of HMMR in LUAD. Depletion of TMPO-AS1 and overexpression of let-7b-5p could result in the decreased expression of HMMR in LUAD cells. Furthermore, we found that TMPO-AS1 was positively correlated with HMMR , yet negatively correlated with let-7b-5p expression in LUAD., Conclusions: Our findings elucidated that the DNA methylation/TMPO-AS1/let-7b-5p axis mediated the high expression of HMMR , which may be considered as a biomarker to predict prognosis in LUAD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jiang, Tang, Yuan, Wang, Zhang, Qian, Cho and Duan.)

Objective: YTH domain family 2 (YTHDF2) is an important N6-methyladenosine (m6A) reader, but its role in lung adenocarcinoma remains elusive. This study assessed its function in lung adenocarcinoma., Methods: YTHDF2 expression in lung adenocarcinoma was explored using public databases, such as The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumour Analysis Consortium (CPTAC). The effect of YTHDF2 on a lung adenocarcinoma cell line was explored by performing cytological and molecular experiments. Molecules downstream of YTHDF2 were identified using proteomics, and the related pathways were verified through cytological and molecular biology experiments., Results: YTHDF2 expression was upregulated in lung adenocarcinoma, and patients with high YTHDF2 expression experienced prolonged overall survival. In two lung cancer cell lines, YTHDF2 knockdown inhibited proliferation but promoted migration, invasion, and the epithelial-mesenchymal transition. The proteomic analysis identified 142 molecules downstream of YTHDF2, and 11 were closely related to survival. Further experiments revealed that YTHDF2 inhibited expression of the family with sequence similarity 83D (FAM83D)-TGFβ1-SMAD2/3 pathway components. This study is the first to show that YTHDF2 regulated the downstream TGFβ1-SMAD2/3 pathway through FAM83D in lung adenocarcinoma., Conclusion: YTHDF2 inhibits the migration and invasion of lung adenocarcinoma cells by regulating the FAM83D-TGFβ1-pSMAD2/3 pathway, which may play an important role in lung cancer metastasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhao, Wang, Zhao, Weng, Qian, Shi, Gu, Ying, Qian and Zhang.)

Head-and-neck squamous cell carcinoma (HNSCC) is characterized by a high frequency of neck lymph node metastasis (LNM), a key prognostic factor. Therefore, identifying the biological processes during LNM of HNSCC has significant clinical implications for risk stratification. This study performed Gene Ontology enrichment analysis of differentially expressed genes between tumors with LNM and those without LNM and identified the involvement of immune response in the lymphatic metastasis of HNSCC. We further identified greater infiltrations of CD8 + T cells in tumors than in adjacent normal tissues through immunochemistry in the patient cohort ( n  = 62), indicating the involvement of CD8 + T cells in the antitumor immunity. Hierarchical clustering analysis was conducted to initially identify the candidate genes relevant to lymphocyte-mediated antitumor response. The candidate genes were applied to construct a LASSO Cox regression analysis model. Three genes were eventually screened out as progression-related differentially expressed candidates in HNSCC and a risk scoring system was established based on LASSO Cox regression model to predict the outcome in patients with HNSCC. The score was calculated using the formula: 0.0636 × CXCL11 - 0.4619 × CXCR3 + 0.2398 × CCR5. Patients with high scores had significantly worse overall survival than those with low scores ( p  < 0.001). The risk score showed good performance in characterizing tumor-infiltrating lymphocytes and provided a theoretical basis for stratifying patients receiving immune therapies. Additionally, a nomogram including the risk score, age, and TNM stage was constructed. The prediction model displayed marginally better discrimination ability and higher agreement in predicting the survival of patients with HNSCC compared with the TNM stage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Luo, Yu, Qian and Zhu.)

Objectives: To discriminate viable tumors from benign periablational enhancement (BPE) in early stage after radiofrequency ablation (RFA) is a major confounding problem. The goal of this study is to evaluate quantitative assessment and diagnostic value of CT perfusion between viable tumors and BPE after RFA in the rabbit liver VX2 tumor model, with pathological results as the standard., Methods: Twenty-eight VX2 liver tumors were treated with RFA, on days 1, 3, 7, and 14, seven rabbits were randomly chosen for CT perfusion and performed pathology examinations immediately. The perfusion parameters along with the profile of time-density curves (TDCs) and pseudo-color images of the parameters were observed in both BPE and viable tumors, then compared with the pathology results. The perfusion parameters included blood flow (BF), blood volume (BV), time to peak (TTP), permeability (P), arterial liver perfusion (ALP), portal venous perfusion (PVP) and hepatic perfusion index (HPI)., Results: A total of 26/28 rabbits successfully underwent CT perfusion, while 6/26 lesions were confirmed to be viable tumors. The TDCs of BPE were mainly speed-up platform curves (15/26), while the viable tumors showed mainly speed-up speed-down (3/6) and speed-up platform (2/6) curves. The PVP values were significantly higher, and the HPI values were significantly lower for BPE at all time points than viable tumors (P < 0.05). Both of PVP value and HPI value have high efficiency for the differential diagnosis of the viable tumors and BPE at each time point. These characteristics of CT perfusion parameters were consistent with pathological changes., Conclusions: The TDCs, PVP and HPI have the potential to indicate BPE and viable tumors effectively early after RFA treatment, the results were highly consistent with pathology. CT perfusion has advantages with great efficacy in monitoring the therapeutic effect early after RFA treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yue, Dong, Huang, Yang, Qian, Yi, Alwalid, Ren, Han and Li.)

Objectives: To analyze the clinical outcomes of Transarterial chemoembolization (TACE) for unresectable or "ablation unsuitable" hepatocellular carcinoma (HCC) in the caudate lobe (CL) found at initial presentation in clinical practice., Methods: Fifty-eight patients with HCC-CL undergoing conventional TACE from January 2015 to January 2020 were enrolled in our medical center. Overall survival (OS), progression-free survival (PFS), tumor response rate and major complication rates were analyzed. Multivariate analyses for potential clinical and radiologic factors were performed by using the Cox proportional hazard model., Results: The median OS was 23 months (95%CI: 18.1-27.9), and the median PFS was 11 months (95%CI: 7.4-14.6). The 1-, 3-, and 5-years OS rates were 66.5%, 31.9% and 15.7%, respectively. The 0.5, 1-, and 3-years PFS rates were 60.3%, 44.5% and 6.3%, respectively. Objective response rate was 53.4% and disease control rate was 79.3%. The most serious complication was bile duct injury, with an incidence of 3.4%. Multivariable analysis revealed that total bilirubin, Barcelona Clinic Liver Cancer stage, nonselective chemoembolization and TACE session were four significant factors associated with OS., Conclusions: Superselective TACE treatment might be associated with better survival benefits in unresectable or "ablation unsuitable" HCC in the CL without macroscopic vascular invasion (MVI) and adequate liver function, compared with the non-selective TACE group, and should be considered as an important reliable therapy for surgeons and interventional radiologists., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yan, Ren, Qian, Kan, Zhang, Chen, Liang and Zheng.)

Lung cancer is the leading cause of cancer-related death in the world. Early diagnosis has great significance for the survival of patients with lung cancer. In this paper, attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy combined with chemometrics was used to study the serum samples from patients with lung cancer and healthy people. The results of spectral band area comparison showed that the concentrations of protein, lipid and nucleic acids molecules in serum of patients with lung cancer were increased compared with those in healthy people. The original spectra were preprocessed to improve the accuracy of principal component regression (PCR) and partial least squares-discriminant analysis (PLS-DA) models. PLS-DA results for first derivative spectral data in nucleic acids (1250-1000cm -1 ) band showed 80% sensitivity, 91.89% specificity and 87.10% accuracy with high R c 2 of 0.8949 and R v 2 of 0.8153, low RMSEC of 0.3136 and RMSEV of 0.4180. It is shown that ATR-FTIR spectroscopy combined with chemometrics might be developed as a simple method for clinical screening and diagnosis of lung cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yang, Ou, Qian, Yang, Bai, Yang, Shi and Liu.)

Background: The purpose of this study was to compare the efficacy and safety of transarterial chemoembolization (TACE) in combination with radiofrequency ablation (RFA) (TACE-RFA) and repeat hepatectomy in the treatment of recurrent hepatocellular carcinoma (HCC) after curative resection., Methods: This retrospective study evaluated consecutive medical records of patients who received either TACE-RFA or repeat hepatectomy between January 2010 and May 2021. Overall survival (OS), progression-free survival (PFS), and complications were compared., Results: Of the 2672 patients who received either TACE-RFA or repeat hepatectomy, 111 eligible patients were included in our study, 63 in the TACE-RFA group and 48 in the repeat hepatectomy group. The median OS was 38 months in the TACE-RFA group and 42 months in the repeat hepatectomy group, with no statistically difference between the two groups ( P =0.45). Meanwhile, there was also no statistically significant difference in PFS between the two groups ( P =0.634). Although both groups achieved similar outcomes, the rate of major complications was significantly higher in the repeat hepatectomy group ( P =0.003)., Conclusions: Patients with recurrent HCC in the TACE-RFA group and the repeat hepatectomy group had similar OS and PFS regardless of the patient's tumor diameter, but the TACE-RFA group was safer and more minimally invasive., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zheng, Ren, Hu and Qian.)

Purpose: To validate the feasibility of using peri-tumoral radiofrequency hyperthermia (RFH)-enhanced chemotherapy to obliterate hepatic tumor margins., Method and Materials: This study included in vitro experiments with VX2 tumor cells and in vivo validation experiments using rabbit models of liver VX2 tumors. Both in vitro and in vivo experiments received different treatments in four groups (n=6/group): (i) RFH-enhanced chemotherapy consisting of peri-tumoral injection of doxorubicin plus RFH at 42°C; (ii) RFH alone; (iii) doxorubicin alone; and (iv) saline. Therapeutic effect on cells was evaluated using different laboratory examinations. For in vivo experiments, orthotopic hepatic VX2 tumors in 24 rabbits were treated by using a multipolar radiofrequency ablation electrode, enabling simultaneous delivery of both doxorubicin and RFH within the tumor margins. Ultrasound imaging was used to follow tumor growth overtime, correlated with subsequent histopathological analysis., Results: In in vitro experiments, MTS assay demonstrated the lowest cell proliferation, and apoptosis analysis showed the highest apoptotic index with RFH-enhanced chemotherapy, compared with the other three groups (p<0.01). In in vivo experiments, ultrasound imaging detected the smallest relative tumor volume with RFH-enhanced chemotherapy (p<0.01). The TUNEL assay further confirmed the significantly increased apoptotic index and decreased cell proliferation in the RFH-enhanced therapy group (p<0.01)., Conclusion: This study demonstrates that peri-tumoral RFH can specifically enhance the destruction of tumor margins in combination with peri-tumoral injection of a chemotherapeutic agent. This new interventional oncology technique may address the critical clinical problem of frequent marginal tumor recurrence/persistence following thermal ablation of large (>3 cm) hepatic cancers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Zhang, Song, Weng, Li, Li, Qian, Ji, Pietrini, Ji and Yang.)

Kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP) are the most common RCC types. RCC has high immune infiltration levels, and immunotherapy is currently one of the most promising treatments for RCC. Collagen triple helix repeat containing 1 (CTHRC1) is an extracellular matrix protein that regulates tumor invasion and modulates the tumor microenvironment. However, the association of CTHRC1 with the prognosis and tumor-infiltrating lymphocytes of KIRP and KIRC has not been reported. We examined the CTHRC1 expression differences in multiple tumor tissues and normal tissues via exploring TIMER, Oncomine, and UALCAN databases. Then, we searched the Kaplan-Meier plotter database to evaluate the correlation of CTHRC1 mRNA level with clinical outcomes. Subsequently, the TIMER platform and TISIDB website were chosen to assess the correlation of CTHRC1 with tumor immune cell infiltration level. We further explored the causes of aberrant CTHRC1 expression in tumorigenesis. We found that CTHRC1 level was significantly elevated in KIRP and KIRC tissues relative to normal tissues. CTHRC1 expression associates with tumor stage, histology, lymph node metastasis, and poor clinical prognosis in KIRP. The CTHRC1 level correlates to tumor grade, stage, nodal metastasis, and worse survival prognosis. Additionally, CTHRC1 is positively related to different tumor-infiltrating immune cells in KIRP and KIRC. Moreover, CTHRC1 was closely correlated with the gene markers of diverse immune cells. Also, high CTHRC1 expression predicted a worse prognosis in KIRP and KIRC based on immune cells. Copy number variations (CNV) and DNA methylation might contribute to the abnormal upregulation of CTHRC1 in KIRP and KIRC. In conclusion, CTHRC1 can serve as a biomarker to predict the prognosis and immune infiltration in KIRP and KIRC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhou, Shen, Xiong, Cheng, Xu, Wang, Qian, Ju and Zhang.)

Purpose: To evaluate the treatment effect of radiofrequency-induced hyperthermia (RFH) combined with intra-tumoral chemotherapy for rabbit VX2 liver tumors and explore the underlying mechanism that drives local hyperthermia-enhanced chemotherapy., Materials and Methods: VX2 cell lines and rabbits with liver VX2 tumors were randomly allocated to four treatment groups including: (1) combination therapy of Doxorubicin (DOX) plus hyperthermia/RFH (n=6); (2) DOX only; (3) hyperthermia/RFH only (n=6); and (4) phosphate-buffered saline-treated control (n=6). Cell viability and doxorubicin uptake by VX2 tumor cells were assayed using flow cytometry and fluorescence microscopy 24 h after treatments. Western blot was used to evaluate the expression level of heat shock protein 70 (HSP70) in tumor cells and tissues. For the harvested VX2 tumors, fluorescence microscopy was used to evaluate the distribution and penetration of doxorubicin in tumor tissues and HSP70 expression was analyzed by Western blot and immunohistochemistry., Results: RFH enhanced the chemotherapeutic effect of doxorubicin in VX2 cells and rabbit liver VX2 tumors resulting in higher apoptosis and lower cell viability. Flowcytometry of VX2 cells showed more apoptotic cells in combination therapy of hyperthermia and DOX, compared with other three groups in-vitro experiments (45.80 ± 1.27% vs 20.66 ± 0.71%, vs 15.16 ± 0.81% and 0.62 ± 0.06%, respectively, p<0.01). The quantitative analysis by Western blot and immunohistochemistry showed increased expression of HSP70 in both VX2 tumor cells (1.28 ± 0.13 vs 0.64 ± 0.13 vs 0.83 ± 0.10 vs 0.15 ± 0.03, respectively, p<0.05) and tumors (1.47 ± 0.13 vs 0.51 ± 0.13 vs 0.74 ± 0.11 vs 0.16 ± 0.04, respectively, p <0.01). Fluorescence microscopy showed increased uptake of DOX in tumor cells in the combination therapy group., Conclusions: RFH/hyperthermia enhanced the chemotherapeutic effect of DOX in VX2 tumors by promoting the uptake of DOX and the expression HSP70 in tumors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Qian, Chen, Zhang, Chick, Ji, Zheng and Yang.)

Our study's goal was to screen novel biomarkers that could accurately predict the progression and prognosis of bladder cancer (BC). Firstly, we used the Gene Expression Omnibus (GEO) dataset GSE37815 to screen differentially expressed genes (DEGs). Secondly, we used the DEGs to construct a co-expression network by weighted gene co-expression network analysis (WGCNA) in GSE71576. We then screened the brown module, which was significantly correlated with the histologic grade ( r = 0.85, p = 1e-12) of BC. We conducted functional annotation on all genes of the brown module and found that the genes of the brown module were mainly significantly enriched in "cell cycle" correlation pathways. Next, we screened out two real hub genes (ANLN, HMMR) by combining WGCNA, protein-protein interaction (PPI) network and survival analysis. Finally, we combined the GEO datasets (GSE13507, GSE37815, GSE31684, GSE71576). Oncomine, Human Protein Atlas (HPA), and The Cancer Genome Atlas (TCGA) dataset to confirm the predict value of the real hub genes for BC progression and prognosis. A gene-set enrichment analysis (GSEA) revealed that the real hub genes were mainly enriched in "bladder cancer" and "cell cycle" pathways. A survival analysis showed that they were of great significance in predicting the prognosis of BC. In summary, our study screened and confirmed that two biomarkers could accurately predict the progression and prognosis of BC, which is of great significance for both stratification therapy and the mechanism study of BC., (Copyright © 2019 Wang, Chen, Ju, Qian, Liu, Wang and Xiao.)

Kidney cancer ranks as one of the top 10 causes of cancer death; this cancer is difficult to detect, difficult to treat, and poorly understood. The most common subtype of kidney cancer is clear cell renal cell carcinoma (ccRCC) and its progression is influenced by complex gene interactions. Few clinical studies have investigated the molecular markers associated with the progression of ccRCC. In this study, we collected microarray profiles of 72 ccRCCs and matched normal samples to identify differentially expressed genes (DEGs). Then a weighted gene co-expression network analysis (WGCNA) was conducted to identify co-expressed gene modules. By relating all co-expressed modules to clinical features, we found that the brown module and Fuhrman grade had the highest correlation ( r = -0.8, p = 1e-09). Thus, the brown module was regarded as a clinically significant module and subsequently analyzed. Functional annotation showed that the brown module focused on metabolism-related biological processes and pathways, such as fatty acid oxidation and amino acid metabolism. We then performed a protein-protein interaction (PPI) network to identify the hub nodes in the brown module. It is worth noting that only one candidate, acetyl-CoA acetyltransferase (ACAT1), was considered to be the final target most relevant to the Fuhrman grade of ccRCC, by applying the intersection of hub genes in the co-expressed network and the PPI network. ACAT1 was subsequently validated using another two external microarray datasets and the TCGA dataset. Intriguingly, validation results indicated that ACAT1 was negatively correlated with four grades of ccRCC, which was also consistent with our results from qRT-PCR analysis and immunohistochemistry staining of clinical samples. Overexpression of ACAT1 inhibited the proliferation and migration of human ccRCC cells in vitro . In addition, the Kaplan-Meier survival curve showed that patients with a lower expression of ACAT1 showed a significantly lower overall survival rate and disease-free survival rate, indicating that ACAT1 could act as a prognostic and recurrence/progression biomarker of ccRCC. In summary, we found and confirmed that ACAT1 might help to identify the progression of ccRCC, which might have important clinical implications for enhancing risk stratification, therapeutic decision, and prognosis prediction in ccRCC patients., (Copyright © 2019 Chen, Peng, Luo, Zhou, Wang, Qian, Xiao and Wang.)