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Haplogroups and single-nucleotide polymorphisms (SNP) of mitochondrial DNA (mtDNA) were associated with the prognosis of many types of cancer patients. However, whether mtDNA haplogroups contribute to clinical outcomes of colorectal cancer (CRC) in Chinese population remains to be determined. In this study, mtDNA of tissue samples from 445 CRC patients from Northwestern China was sequenced to evaluate the association between haplogroup and prognosis. The mtDNA sequencing data of 1015 CRC patients from Southern China were collected for validation. We found patients with mtDNA haplogroup M7 had a significantly higher death risk when compared with patients with other haplogroups in both Northwestern (Hazard ratio [HR] = 3.093, 95% CI = 1.768-5.411, p 0.001) and Southern (HR = 1.607, 95% CI = 1.050-2.459, p = 0.029) China. Then, a haplogroup M7-based mtSNP classifier was selected by using LASSO Cox regression analysis. A nomogram comprising the mtSNP classifier and clinicopathological variables was developed to predict the prognosis of CRC patients (area under the curve [AUC] 0.735, 95% CI = 0.679-0.791). Furthermore, patients with high- and low-risk scores calculated by the haplogroup M7-based mtSNP classifier exhibited significantly different overall survival (OS) and recurrence-free survival (RFS) (all p 0.001). Finally, RNA-seq and immunohistochemical analyses indicated the poor prognosis of patients with haplogroup M7 may be related to mitochondrial dysfunction and immune abnormalities in CRC tissues. In conclusion, the haplogroup M7 and haplogroup M7-based mtSNP classifier seems to be a practical and reliable prognostic predictor for CRC patients, which provides a potential tool of clinical decision-making for patients with haplogroup M7 in Chinese population.

Background: Cumulative data have shown that microRNAs (miRNA) are involved in the etiology and prognosis of colorectal cancer (CRC). Genetic polymorphisms in pre-miRNA genes may influence the biogenesis and functions of their host miRNAs. However, whether these polymorphisms are associated with CRC prognosis remains unknown.Methods: We analyzed the effects of seven single-nucleotide polymorphisms (SNP) in pre-miRNA genes on the prognosis of a Chinese population with 408 CRC patients with surgically-resected adenocarcinoma.Results: Two SNPs were identified to be significantly associated with recurrence-free survival and overall survival of the patients. The most significant SNP was rs6505162 in pre-miR-423. Compared with the homozygous wild-type genotype, the variant-containing genotypes of this SNP were significantly associated with both the overall survival (HR = 2.12, 95% CI = 1.34–3.34, P = 0.001) and the recurrence-free survival (HR = 1.59, 95% CI = 1.08–2.36, P = 0.019). Another SNP, rs4919510 in pre-miR-608, was also associated with altered recurrence-free survival (HR = 0.61, 95% CI = 0.41–0.92, P = 0.017). These effects were evident only in patients receiving chemotherapy but not in those without chemotherapy. In addition, the combined analysis of the two SNPs conferred a 2.84-fold (95% CI = 1.50–5.37, P = 0.001) increased risk of recurrence and/or death. Similarly, this effect was only prominent in those receiving chemotherapy (P < 0.001) but not in those without chemotherapy (P = 0.999).Conclusions: Our data suggest that genetic polymorphisms in pre-miRNA genes may impact CRC prognosis especially in patients receiving chemotherapy, a finding that warrants further independent validation.Impact: This is one of the first studies showing a prognostic role of pre-miRNA gene SNPs in CRC. Cancer Epidemiol Biomarkers Prev; 21(1); 217–27. ©2011 AACR.

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Background: Alterations in the genetic landscape of papillary thyroid carcinoma (PTC) compared with coincidental benign thyroid nodules, especially adenomatoid nodules, remain to be demonstrated. Methods: Multi-omics profiling of whole-exome sequencing, assay for transposase-accessible chromatin using sequencing (ATAC-seq), and transcriptome sequencing were used for analysis. Results: Chromatin accessibility in the PTC was lower than that in the benign nodules around the transcription start sites (distance Conclusions: This compendium of multi-omics data provides valuable insights and a resource for understanding the landscape of open chromatin features and regulatory networks in PTC and benign nodule pathogeneses.

Emphysematous splenic infection is a rare disease. In this case, a 33-year-old woman presented to the emergency department with a 10-day history of left-upper-quadrant abdominal pain and intermittent fever. She positively denied any previous history of illness or trauma. On admission to the hospital, her white-cell count, neutrophil percentage, C-reactive protein level, blood glucose, and urine glucose were higher than normal. Computed tomography (CT) revealed gas-fluid levels and infection in the spleen. After multidisciplinary consultation and discussions, the patient was diagnosed with emphysema spleen infection and diabetes, and the infection was most likely related to the diabetes. The patient was treated with antibiotics, hypoglycemic therapy, and transabdominal spleen infection puncture and drainage. Finally, the patient's infection and blood sugar were controlled, and the drainage fluid was unobstructed. To the best of our knowledge, emphysematous spleen infection has only been reported once previously in a super obese female patient in 2007. Interestingly, the patient in the present case was also an obese and diabetic middle-aged woman. Similar to other documented emphysematous infection cases, the disease onset of our patient was indistinct and insidious. Due to advances in imaging tools and knowledge of emphysematous nephritis, the patient was successfully diagnosed and treated in time.

Hepatocellular carcinoma (HCC) is the leading cause of cancer-related death worldwide. Enhanced mitochondrial fragmentation (MF) is associated with poor prognosis in HCC patients. However, its molecular mechanism in HCC remains elusive. Although enhanced MF activates effector T cells and dendritic cells, it induces immunoescape by decreasing the number and cytotoxicity of natural killer cells in the HCC immune microenvironment. Therefore, the influence of MF on the activity of different immune cells is a great challenge. Enhanced MF contributes to maintaining stemness by promoting the asymmetric division of liver cancer stem cells (LCSCs), suggesting that MF may become a potential target for HCC recurrence, metastasis, and chemotherapy resistance. Moreover, mechanistic studies suggest that MF may promote tumour progression through autophagy, oxidative stress, and metabolic reprogramming. Human-induced hepatocyte organoids are a recently developed system that can be genetically manipulated to mimic cancer initiation and identify potential preventive treatments. We can use it to screen MF-related candidate inhibitors of HCC progression and further explore the role of MF in hepatocarcinogenesis. We herein describe the mechanisms by which MF contributes to HCC development, discuss potential therapeutic approaches, and highlight the possibility that MF modulation has a synergistic effect with immunotherapy.

Background Mitochondria are key regulators in cell proliferation and apoptosis. Alterations in mitochondrial function are closely associated with inflammation and tumorigenesis. This study aimed to investigate whether mitochondrial transcription factor A (TFAM), a key regulator of mitochondrial DNA transcription and replication, is involved in the initiation and progression of colitis‐associated cancer (CAC). Methods TFAM expression was examined in tissue samples of inflammatory bowel diseases (IBD) and CAC by immunohistochemistry. Intestinal epithelial cell (IEC)‐specific TFAM‐knockout mice (TFAM △IEC) and colorectal cancer (CRC) cells with TFAM knockdown or overexpression were used to evaluate the role of TFAM in colitis and the initiation and progression of CAC. The underlying mechanisms of TFAM were also explored by analyzing mitochondrial respiration function and biogenesis. Results The expression of TFAM was downregulated in active IBD and negatively associated with the disease activity. The downregulation of TFAM in IECs was induced by interleukin‐6 in a signal transducer and activator of transcription 3 (STAT3)/miR‐23b‐dependent manner. In addition, TFAM knockout impaired IEC turnover to promote dextran sulfate sodium (DSS)‐induced colitis in mice. Of note, TFAM knockout increased the susceptibility of mice to azoxymethane/DSS‐induced CAC and TFAM overexpression protected mice from intestinal inflammation and colitis‐associated tumorigenesis. By contrast, TFAM expression was upregulated in CAC tissues and contributed to cell growth. Furthermore, it was demonstrated that β‐catenin induced the upregulation of TFAM through c‐Myc in CRC cells. Mechanistically, TFAM promoted the proliferation of both IECs and CRC cells by increasing mitochondrial biogenesis and activity. Conclusions TFAM plays a dual role in the initiation and progression of CAC, providing a novel understanding of CAC pathogenesis., Our study uncover the opposite roles of TFAM in the initiation and progression of CAC, indicating that TFAM switches from tumor suppressor in the premalignant stages of tumorigenesis to oncogene at later stages of disease. Our data suggest that measuring TFAM status may serve as a clinically useful tool to identify patients at risk for colon dysplasia or cancer. In contrast, TFAM might also be a prognostic biomarker and pharmacological target for advanced CAC.

Image-based separation of coal and gangue is susceptible to the external environment. This paper studies the effects of illuminance and external moisture on grayscale and texture features of coal a...

Purpose Surgical workflow recognition has emerged an important part of computer-assisted intervention systems for the modern operating room, and at the same time a very challenging problem. For sequence data, modelling of temporal information is essential for accurate identification. However, current phase recognition methods based on the CNN framework are not very adequate for the extraction of long-range dependencies. Methods Therefore, to better capture long-range dependencies, we propose a Temporal-based Swin Transformer Network (TSTNet) for the surgical video workflow recognition task. TSTNet contains two main parts: the Swin Transformer and the LSTM. The Swin Transformer incorporates the attention mechanism to encode remote dependencies and learn highly expressive representations. The LSTM is capable of learning longrange dependencies and is used to extract temporal information. The TSTNet organically combines the two components to extract spatiotemporal features that contain more contextual information. In particular, based on a full understanding of the natural features of the surgical video, we propose a priori revision algorithm (PRA) using a priori information about the sequence of the surgical phase. This strategy optimises the output of TSTNet and further improves the recognition performance. Results We have conducted extensive experiments using the Cholec80 dataset to validate the effectiveness of the TSTNet-PRA method. Our method achieves excellent performance on the Cholec80 dataset and can achieve an accuracy of 93.5%. This greatly exceeds the state-of-the-art methods. Conclusion By modelling remote temporal information and multi-scale visual information, we proposed the TSTNet-PRA method. It was evaluated on a large public dataset, showing high recognition capability superior to other spatiotemporal networks.

Studies comparing the incidence of reflux esophagitis (RE) and patients' quality of life (QoL) when using circular stapler (CS) and linear stapler (LS) in esophagojejunostomy (EJS) after laparoscopic total gastrectomy (LTG) are rare, and certainly there are not enough to make a definitive decision on best practice. Presented herein is a study on the comparison of the short-term outcomes, QoL of the patients with the focus on the incidence of RE after both linear and circular stapling in LTG.From January 2014 to October 2018, 120 patients were analyzed; of these, 42 patients underwent laparoscopy-assisted total gastrectomy (LATG) with CS (CS group) and 78 patients who underwent totally laparoscopic total gastrectomy (TLTG) with LS (LS group). We examined the results obtained in terms of perioperative outcomes, reflux-related assessments (GerdQ questionnaire and endoscopy findings with all cases; 24-h pH monitoring with limited cases), and EORTC QLQ-C30 and QLQ-STO22. In addition, questionnaires were also supplied to patients and the results were recorded.The incidence of anastomotic stenosis (7.1% vs. 0; P 0.05) and the median intraoperative blood loss (180.0 vs. 100.0 mL; P 0.05) of the CS group were higher than the LS group. The factor aside, no significant differences were observed between the two groups with regard to the incidence of RE assessed by the QLQ-STO22 reflux scale, the GerdQ scores, endoscopy (in all cases), or the percent time of pH 7 (in limited cases) (P 0.05). In the EORTC QLQ-C30 and QLQ-STO22, it was noted that the score of constipation [0 (0, 0) vs. 0 (0, 33.3); P = 0.028] and postoperative dysphagia [0 (0, 0) vs. 0 (0, 22.2); P = 0.046] of the LS group in a 1-year follow-up were lower than the CS group.TLTG with LS generated better results than LATG with CS in terms of the incidence of anastomotic stenosis, intraoperative blood loss, and postoperative constipation and dysphagia. Furthermore, when compared with circular stapling, linear stapling in EJS did not increase the incidence of RE assessed by the QLQ-STO22 reflux scale, the GerdQ scores, endoscopy (in all cases), or the percent time of pH 7 (in limited cases).

Accurately positioning and identifying coal and gangue under the heterogeneous and complex scenarios of coal production is a key and difficult problem for coal and gangue sorting robot. This paper ...

Primary liver cancer (PLC) may be mainly classified as the following four types: hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), hepatoblastoma (HB), and combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma (cHCC-ICC). The majority of PLC develops in the background of tumor microenvironment, such as inflammatory microenvironments caused by viral hepatitis, alcoholic or nonalcoholic steatohepatitis, carbon tetrachloride (CCl4), 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), and necroptosis-associated hepatic cytokine microenvironment caused by necroptosis of hepatocytes. However, the impact of different types of microenvironments on the phenotypes of PLC generated by distinct oncogenes is still unclear. In addition, the cell origin of different liver cancers have not been clarified, as far as we know. Recent researches show that mature hepatocytes retain phenotypic plasticity to differentiate into cholangiocytes. More importantly, our results initially demonstrated that HCC, ICC, and cHCC-ICC could originate from mature hepatocytes rather than liver progenitor cells (LPCs), hepatic stellate cells (HSCs) and cholangiocytes in AKT-driven, AKT/NICD-driven and AKT/CAT-driven mouse PLC models respectively by using hydrodynamic transfection methodology. Therefore, liver tumors originated from mature hepatocytes embody a wide spectrum of phenotypes from HCC to CC, possibly including cHCC-ICC and HB. However, the underlying mechanism determining the cancer phenotype of liver tumors has yet to be delineated. In this review, we will provide a summary of the possible mechanisms for directing the cancer phenotype of liver tumors (i.e., ICC, HCC, and cHCC-ICC) in terms of oncogenic driver genes and tumor microenvironment. Moreover, this study initially revealed the cell origin of different types of liver cancer.

Influence of folate metabolism has long been studied in cancer and copies evidences have suggested that the key genes involved were correlated with GC risk and prognosis. However, their genetically association and contribution for GC prognosis are still elusive. To evaluate the effect of folate metabolism related genes polymorphisms on the prognosis of gastric cancer (GC), the genotype of seven single nucleotide polymorphisms (SNPs) of three genes were selected and genotyped in a cohort of 664 GC patients, including genes of Methylenetetrahydrofolate reductase (MTHFR), Methionine synthase reductase (MTRR), and Methionine synthase (MTR). Kaplan-Meier Curve, long-rank tests and multivariate Cox proportional hazard model were used for prognosis analysis. The results demonstrated that TT or CT/TT genotypes of SNP rs1532268 in MTRR gene coding region are significantly associated with a poorer overall survival (OS) when compared with CC genotype (HR=2.340, 95% CI: 1.240-4.414, p=0.009; or HR=1.502, 95% CI: 1.083-2.085, p=0.015, respectively). Furthermore, comparing to that of the CC genotype, the detrimental effect of rs1532268 TT genotype was also evident in the special subgroups of GC patients, especially in patients with BMI

As emerging tumor components, intratumoral bacteria have been found in many solid tumors. Several studies have demonstrated that different cancer subtypes have distinct microbial compositions, and mechanistic studies have shown that intratumoral bacteria may promote cancer initiation and progression through DNA damage, epigenetic modification, inflammatory responses, modulation of host immunity and activation of oncogenes or oncogenic pathways. Moreover, intratumoral bacteria have been shown to modulate tumor metastasis and chemotherapy response. A better understanding of the tumor microenvironment and its associated microbiota will facilitate the design of new metabolically engineered species, opening up a new era of intratumoral bacteria-based cancer therapy. However, many questions remain to be resolved, such as where intratumoral bacteria originate and whether there is a direct causal relationship between intratumoral bacteria and tumor susceptibility. In addition, suitable preclinical models and more advanced detection techniques are crucial for studying the biological functions of intratumoral bacteria. In this review, we summarize the complicated role of intratumoral bacteria in the regulation of cancer development and metastasis and discuss their carcinogenic mechanisms and potential therapeutic aspects.

BACKGROUND: In recent years, rectal foreign bodies have become a common proctological emergency in the male population, especially older Chinese men, often requiring surgical intervention due to associated complications. This review aimed to describe the epidemiology and clinical characteristics of rectal foreign bodies in older men and examine the possible challenges presented by the condition to clinicians and society. METHODS: A comprehensive search was conducted in English-language databases and Chinese databases from January 2000 to December 2020. Studies concerning rectal foreign bodies were considered for this review if they reported the reason for a foreign body being in the rectum and related treatment measures. Contemporaneous rectal foreign bodies case data from General Surgery Department of Tangdu Hospital were also analyzed. According to differences in ethnicity, the older male patients were divided into a Chinese group and a non-Chinese group, and the parameters of the two groups were analyzed using statistical methods. RESULTS: A total of 159 studies were retrieved in an initial database search using “rectal foreign body” as the search term. These included 86 Chinese studies and 73 English-language studies. Collectively, these studies included 582 older male patients, 276 of whom were Chinese, and 307 who were non-Chinese. According to their source, the rectal foreign bodies were classified into 3 categories. The most common reason for a foreign body in the rectum was insertion for erotic purposes, with everyday articles accounting for most foreign body types. Sexual articles were mainly found to have been used in the pursuit of pleasure. There were no significant differences in foreign body sources, sizes, types, treatment selections, and outcomes between the two groups. DISCUSSION: Emergency hospital visits by older men with rectal foreign bodies due to erotic and sexual needs and practices are increasing. Although the sources, sizes, and types of foreign bodies were different, and patients recovered well after active and appropriate clinical treatment, the sexual needs of older men are a social issue that requires attention. Acknowledging and dealing with sexual issues is a multidimensional task that requires a collaborative effort to ensure a more humanistic approach to older patients.

BACKGROUND: Gastric cancer (GC) is one of the most malignant diseases and threatens the health of individuals across the globe. Hitherto, the identification of prognosis risk stratification on GC has mainly depended on the TNM staging, but owing to its inaccuracy and incompleteness, the prognostic value it offers remains controversial in the current clinical setting. Thus, an effective prognostic model for GC after radical gastrectomy is still needed. METHODS: Patients with pathologically confirmed GC who underwent radical gastrectomy from 2 different centers were retrospectively enrolled into a training and the validation cohort, respectively. The least absolute shrinkage and selection operator (LASSO) algorithm was applied to select variables among multiple factors, including clinical characteristics, pathological parameters, and surgery- and treatment-related indicators. The multivariate Cox regression method was used to establish the model to predict 1-, 2-, and 3-year survival. Both internal and external validations of the nomogram were then completed in terms of discrimination, calibration, and clinical utility. Finally, prognostic risk stratification of GC was conducted with X-tile software. RESULTS: A total of 1,424 patients with GC were eligible in this study, including 1,010 in the training cohort and 414 in the validation cohort. Seven indicators were selected by LASSO to develop the nomogram, including the number of positive lymph nodes, tumor size, adjacent organ invasion, vascular invasion, the level of carbohydrate antigen 125 (CA 125), depth of invasion, and human epidermal growth factor receptor 2 (HER2) status. The nomogram demonstrated a robust predictive capacity with favorable accuracy, discrimination, and clinical utility both in the internal and external validations. Moreover, we divided the population into 3 risk groups of survival according to the cutoff points generated by X-tile, and in this way, the nomogram was further improved into a risk-stratified prognosis model. CONCLUSIONS: We have developed a prognostic risk stratification nomogram for GC patients after radical gastrectomy with 7 available indicators that may guide clinical practice and help facilitate tailored decision-making, thus avoiding overtreatment or undertreatment and improving communication between clinicians and patients.

Background: Several recent studies have suggested that the long non-coding RNA (lncRNA) DSCAM-AS1 (Down syndrome cell adhesion molecule - anti-sense 1) is aberrantly expressed in many malignancies. Purpose: In this study, we aimed to explore the the role of DSCAM-AS1 in gastric carcinoma. Research Design: Expression of DSCAM-AS1 mRNA, miR-204, and TPT1 (Tumor Protein, Translationally-Controlled 1) were detected using quantitative real-time polymerase chain reaction (qRT-PCR). Proliferation and apoptosis of GC cells were determined using the CCK-8 cell counting assay and flow cytometry. The rate of cell migration and invasion was determined using a transwell assay. The relationships between DSCAM-AS1, miR-204, and TPT1 were predicted and confirmed using a dual-luciferase reporter assay. Expression of TPT1 protein was quantified by Western blot. Results: In this study, we found that DSCAM-AS1 was significantly overexpressed in GC tissues and cell lines. Functional experiments indicated that GC cells with DSCAM-AS1 silencing exhibited a dynamic reduction in proliferation and migration. We identified miR-204 as a target of DSCAM-AS1 and found that it targeted TPT1 in GC cells, which further led to decreased expression of miR-204 in GC tissues and cell lines. A rescue assay revealed that knocked-down DSCAM-AS1 hindered GC progression, which was reversed upon miR-204 downregulation or TPT1 overexpression. Conclusion: We conclude that DSCAM-AS1 is expressed as a tumor oncogene in GC progression, modulated via the miR-204/TPT1 axis. These findings indicate the potential of DSCAM-AS1 as a therapeutic target for GC prevention.

Background: In recent years, rectal foreign bodies are a common proctological emergency in the male population, especially in Chinese elderly men that often requires the intervention of the surgeon due to its complications. The aim of this review is to describe the epidemiology and clinical characteristics of rectal foreign bodies in elderly men and its possible challenge to clinicians and society. Methods: A comprehensive literature search was conducted in English databases (PubMed, Embase, Web of Science, the Cochrane Library) and Chinese databases (CNKI, Wan Fang, VIP, Chinese biomedical database) from January 2000 to December 2020. All rectal foreign bodies relevant studies were considered, if they reported the purpose for a foreign body in the rectum and related treatment measures. Contemporaneous rectal foreign bodies cases data from our center were also analyzed. Two authors independently extracted the data and reviewed the quality of the included research. According to the differences in population background, we divided the elderly Chinese male group and the elderly non-Chinese male group, the parameters of the two groups were analyzed by statistical methods.Results: A total of 159 literatures were preliminarily retrieved in initial literature search with rectal foreign body as the search term, including 86 Chinese literatures and 73 English literatures. A total of 582 patients were the elderly male patients, included 276 Chinese patients and 307 non-Chinese patients. In older men, the sources of foreign bodies can be divided into three categories: the ones that are inserted from the anus, the ones that are swallowed and thereafter become stuck in the rectum, the other that are caused by improper medical practices. The most common purpose for a foreign body in the rectum was insertion for erotic purposes. In the foreign body type, the daily articles account for the majority. Sexual articles are mainly found in pleasure seekers. There was no significant difference in foreign body sources, size, type, treatment selection and outcome between the two groups.Conclusions: In older men, there is an increasing number of cases of rectal foreign body emergency visits for erotic purposes and sexual needs. Although the source, size and type of foreign body are different, and patients can get a better recovery after active and appropriate clinical treatment, the sexual needs are social problem we should pay attention to in older men. Treatment of sexual issues is a multidimensional task that should be implemented as a collaborative effort and older people should get more humanistic care in this regard.

Aims: To assess the feasibility, safety, 1-year postoperative quality of life, and 2-year postoperative local recurrence of b-shaped laparoscopic dual anastomosis (bSLDA) technique in lapa...

This article has been retracted, and the online PDF has been watermarked “RETRACTION”. The retraction notice is available at http://doi.org/10.3233/MGC-220954.

In order to explore the application of deep learning based intelligent imaging technology in the diagnosis of colorectal cancer, Tangdu Hospital patients are selected as the research object in this study. By scanning the cancer sites, then distinguishing and extracting the features of the tumors, the collected data are input into the designed in-depth learning intelligent assistant diagnosis system for comparison. The results show that in the analysis of image prediction accuracy, the best prediction accuracy of T1-weighted image method is matrix GLCM (gray level co-occurrence matrix) algorithm, the best prediction accuracy of adding T1-weighted image method is matrix MGLSZM (multi-gray area size matrix) algorithm, and the best prediction accuracy of T2-weighted image method is ALL combination of all texture features, and the best prediction accuracy of three imaging sequences is not more than 0.8. In the AUC analysis of the area under the curve of different texture features, it is found that T2-weighted imaging method has obvious advantages in differentiating colorectal cancer from other methods. Therefore, through this study, it is found that in the use of deep learning intelligent assistant diagnosis system for the diagnosis of colorectal cancer, it can provide useful information for the clinical diagnosis of colorectal cancer to a certain extent. Although there are some deficiencies in the research process, it still provides experimental basis for the diagnosis and treatment of colorectal cancer in later clinical stage.

BACKGROUND: A sentinel lymph node biopsy (SLNB) is a routine procedure for axillary staging in cN0 breast cancer (BC) patients. Indocyanine green (ICG) fluorescence can detect sentinel lymph nodes with higher sensitivity than carbon nanoparticle suspension (CNS). The present study investigated the availability and benefits of a near-infrared (NIR) laparoscopy-assisted SLNB using ICG and carbon nanoparticle suspension as tracers. METHODS: Forty patients with invasive BC, who had clinically negative axillary lymph nodes, participated in this observational study. ICG and CNS tracers were injected into the periareolar region simultaneously or sequentially. In the endoscopy-assisted group (n=20), the patients were given NIR laparoscopic SLNB based on ICG fluorescence and CNS staining. In the open-surgery group, the patients were given traditional SLNB using an open incision, and CNS tracers were injected into the same region as that in the endoscopy-assisted group. RESULTS: In the endoscopy-assisted group, lymphatic vessels and sentinel lymph nodes (SLNs) were successfully identified using ICG fluorescence imaging in most patients (19/20). The average number of SLNs removed was 2.85 (range, 1–4) in the endoscopy-assisted group, and 3.40 (range, 1–7) in the open-surgery group. There was no significant difference between the number of detected nodes (P=0.30). The patients who underwent endoscopy-assisted SLNBs had similar operating times, blood loss and hospital-stay lengths, but lower postoperative drainage volumes and higher satisfaction scores, as they did not have axillary incisions. CONCLUSIONS: The NIR laparoscopy-assisted ICG-guided technique is a feasible and surgeon-friendly method for SLNB with good efficacy and acceptable safety. When combined with CNS, more SLNs can be detected and dissected.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer with higher incidence, the difficulty considered in PTC therapeutic process could be the property. Therefore, it is so important to know the factors that may indicate the progression course of cancer. In this study, we dissect the PTC intra-tumor microbiota and its role in influencing the tumor progression by 16S RNA sequences. The role of the PTC intra-tumor microbiome composition in 80 PTC patients was explored in this study. Overall substantial abundance of microbiome in PTC tumors from all patients were detected. We found that PTC patients with advanced lesion (T3 or T4) had significantly higher tumor bacteria diversity than the patients with relative mild lesion (T1/T2). Importantly, we identified a signature of three tumor bacterial taxa (Pseudomonas, Rhodococcus, Sphingomonas) highly predictive of PTC tumor invasion status. These data suggest that microbial host factors, independent of the genomic composition of the tumor, may determine tumor behaviors and patients’ outcomes. Furthermore, the correlation between specific bacterial genus and thyroid hormones or autoimmune thyroid disease-related antibodies may also indicate the potential contribution of microbiome in the relation between autoimmune thyroid disease or the irregular thyroid function and PTC progression.

BACKGROUND Although combination of cyclin-dependent kinase 4 and 6(CDK4/6) inhibitors with endocrine therapy for advanced breast cancer (ABC) prolongs PFS in patients, but also has associated toxic side effects. However, few previous studies have summarized the toxic and side effects of CDK4/6 inhibitors. Therefore, this study summarized the corresponding toxic and side effects of CDK/6 inhibitors, which is of great importance for doctors and patients to understand how to balance the high survival rate brought by drugs with the decreased quality of life and improve the management of BC. METHODS PubMed, Embase, The Cochrane Library, and VIP databases were systematically searched to collect randomized controlled trials (RCTs) of CDK4/6 inhibitors combined with endocrine therapy for advanced breast cancer from January 2010 to December 2019.Two investigators independently reviewed the literatures. Before using the RevMan 5.3 software for a meta-analysis, date were extracted and the risk of bias with the include studies were assessed. RESULTS A total of 64 RCTs involving 3685 patients were included. Compared with placebo combined with endocrine therapy, CDK4/6 inhibitors combined with endocrine therapy could improve the median progression free survival rate (hazard ratio 0.54, 95% confidence interval (CI):0.50-0.60, P

BACKGROUND: This study aimed to assess the safety and efficacy of laparoscopic distal gastrectomy (LDG) with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced gastric cancer (AGC). METHODS: In this case-matched study, we retrospectively reviewed the database of 223 patients with AGC who underwent LDG in Tangdu Hospital from April 2016 to February 2019. Among all participants, 177 patients underwent LDG alone and 46 underwent LDG with HIPEC. We matched total of 138 (1:2) patients from the LDG + HIPEC group (n 46) and the LDG group (n 92) for gender, age, date of operation, and tumor-node-metastasis (TNM) stage of tumor. RESULTS: There was no significant difference in the Clavien-Dindo classification of complications between LDG alone and LDG + HIPEC patients. Further analysis showed the morbidity of gastroparesis to be significantly increased in LDG + HIPEC patients. At the same time, we found that the operation time, the time to 1st flatus, and hospital stay were longer in LDG + HIPEC patients and the incidence of abdominal recurrence 2 years after operation was significantly higher in the LDG group than the LDG + HIPEC group. CONCLUSIONS: The combination of LDG with intraoperative HIPEC is a safe and feasible method for AGC and HIPEC will limit the recovery of gastrointestinal functions. In addition, during the follow-up of our study, although there was no statistical difference between the two groups in abdominal recurrence at 2 years after surgery, a decreasing trend of abdominal recurrence in LDG + HIPEC patients could be seen in comparison to LDG patients.

Background & Aims Hepatoblastoma (HB) and hepatocellular carcinoma (HCC) both exhibit notable cancer stem cell (CSC) features. Moreover, the development of both diseases is closely associated with the presence of CSCs. We investigated the role of brain-expressed X-linked protein 1 (BEX1) in regulating the CSC properties of HB and a subtype of HCC with high CSC features (CSC-HCC). Methods Stemness scores were analyzed in 5 murine HCC models. A subpopulation of BEX1-positive cells and BEX1-negative cells were sorted from HCC cell lines, and subjected to transcriptome analysis. The expression and function of BEX1 was examined via western blotting, sphere formation assays, and xenograft tumor models. Results We identified BEX1 as a novel CSC marker that was required for the self-renewal of liver CSCs. Furthermore, zebularine, a potent DNMT1 inhibitor, can induce the reactivation of BEX1 by removing epigenetic inhibition. Notably, BEX1 was highly expressed in patients with HB and CSC-HCC, but not in patients with non-CSC HCC. Moreover, DNMT1-mediated methylation of the BEX1 promoter resulted in differential BEX1 expression patterns in patients with HB, CSC-HCC, and non-CSC-HCC. Mechanistically, BEX1 interacted with RUNX3 to block its inhibition of β-catenin transcription, which led to the activation of Wnt/β-catenin signaling, and stemness maintenance in both HB and CSC-HCC. In contrast, downregulated BEX1 expression released RUNX3 and inhibited the activation of Wnt/β-catenin signaling in non-CSC-HCC. Conclusion BEX1, under the regulation of DNMT1, is necessary for the self-renewal and maintenance of liver CSCs through activation of Wnt/β-catenin signaling, rendering BEX1 a potentially valuable therapeutic target in both HB and CSC-HCC. Lay summary Cancer stem cells (CSCs) contribute to a high rate of cancer recurrence, as well as resistance to conventional therapies. However, the regulatory mechanisms underlying their self-renewal remains elusive. Herein, we have reported that BEX1 plays a key role in regulating CSC properties in different types of liver cancer. Targeting BEX1-mediated Wnt/β-catenin signaling may help to address the high rate of recurrence, and heterogeneity of liver cancer.

Background: Gastric cancer (GC) is one of the most common malignancies and its incidence rates vary widely between men and women. Previous studies have suggested that Cx43 and SCAMP1 are key functional proteins in tumors. Herein, the association between GJA1 and SCAMP1 polymorphisms and GC susceptibility and prognosis was evaluated.Methods: A total of three SNPs among 681 GC patients and 756 controls were tested using the Agena Mass ARRAY RS1000 system including GJA1 rs2071165, SCAMP1 rs4530741, and rs6874309. The strength of the association with cancer risk was assessed by the odds ratios and 95% confidence intervals generated from the logistic regression model. Kaplan-Meier Curve, long-rank tests, and a multivariate Cox proportional hazard model were used for prognosis analysis. The expression of GJA1 was assessed by immunohistochemistry.Results: The GJA1 rs2071165 AA/AG genotype significantly increased the risk of GC in the female Chinese population (odds ratio [OR] =1.55, 95% confidence interval, 95%CI] = 1.03–2.32, p = 0.034). Furthermore, the risk effect of rs2071165 was more evident in the subgroups of female patients with GC, stratified by age, clinical stage, tumor size, and recurrence/metastasis. However, no obvious differences in Cx43 expression in GC tissues were observed between males and females. Furthermore, no significant association between rs4530741 and rs6874309 polymorphisms in SCAMP1 and GC risk or prognosis was observed. Conclusion: In conclusion, this study suggests that GJA1 rs2071165 polymorphisms are associated with increased GC risk in females for the first time, which showed a potential new clinical marker for assessing GC risk in females.

Recently, increasing literature has been reported on optimal therapies in patients with advanced hepatocellular carcinoma (HCC) and many therapeutic modalities have been proposed to improve the survival rate. However, the results are not consistent due to different research protocols, small sample sizes and different study endpoints and there is no standard treatment protocol has been defined. Therefore, it is very important to explore the optimal bonding mode and to evaluate the efficacy and safety of the optimal sequential therapy for those patients.We searched available databases through January 2020 for relevant studies. The main outcome measure was 1-year overall survival (OS) and overall response rate (ORR); the secondary outcome measure was a composite of toxic effects retrieved grade 3 or 4 adverse events (AEs) from all included studies. Statistical analyses were conducted using STATA version 15 and GeMTC package in the R statistical software.After a detailed review, 8 randomized controlled trials (RCTs) and 20 retrospective studies involving 3,675 advanced HCC patients were included for network meta-analysis. Indirect comparisons showed that hepatic arterial infusion chemotherapy (HAIC) plus radiofrequency ablation (RFA) was highest probability of obtaining the best OS rate of 1 year [surface under the cumulative ranking (SUCRA), 0.95] and ORR (SUCRA, 0.86) when compared with other potential optimal therapies and which had ranked the first in all treatment regimens, followed by HAIC (SUCRA, 0.75). Direct and indirect comparison of 1-year OS and ORR with all treatment regimens each other showed that for all treatment regimens, patients showed significant clinical benefit when compared with transcatheter arterial chemoembolization (TACE) or sorafenib alone. However, the incidence of treatment-related AEs of grade 3 or 4 occurred in patients who have received targeted drug sorafenib therapy (SUCRA, 0.51) compared with other interesting regimens.HAIC may be a valuable therapeutic strategy for advanced HCC patients to prevent recurrence and metastasis after RFA, as well as in improving patient prognosis and quality of life. Meanwhile, HAIC combined with RFA is a safe and effective treatment in patients with advanced HCC, and this combination therapy can significantly prolong 1-year survival rate when compared with other optimal sequential therapies.This study is registered with PROSPERO, number CRD42020176149.

BACKGROUND: It is not clear whether laparoscopic and open distal gastrectomy produce similar outcomes in patients with locally advanced gastric cancer. Data from a multicenter, randomized, controlled trial (CLASS-01) showed that laparoscopic distal gastrectomy did not result in inferior disease-free survival at 3 years compared with open distal gastrectomy. Here, we present 5-year overall survival data from this trial. METHODS: From September 2012 through December 2014, we randomly assigned 1056 patients with clinical stage T2, T3, or T4a gastric cancer (without bulky nodes or distant metastases) to undergo either laparoscopic distal gastrectomy or open distal gastrectomy with D2 lymphadenectomy in a 1:1 ratio. We compared 5-year overall survival between groups in the intent to treat population. RESULTS: We analyzed data from 1039 patients who received curative therapy. At 5 years, the overall survival rates were 72.6% in the laparoscopic distal gastrectomy group and 76.3% in the open distal gastrectomy group (log-rank P =0.19; hazard ratio [HR], 1.17; 95% CI, 0.93–1.48; P =0.187). After we compared for competing risk events, gastric cancer-related deaths (HR, 1.14; 95% CI, 0.87–1.49; P =0.34) and deaths from other causes (HR, 1.23; 95% CI, 0.74–2.05; P =0.42) did not differ significantly between groups. Overall rates of survival did not differ significantly between groups with each tumor stage. CONCLUSIONS: Laparoscopic distal gastrectomy with D2 lymphadenectomy results in similar 5-year overall survival compared to open distal gastrectomy in patients with locally advanced gastric cancer by experienced surgeons in high-volume specialized institutions. TRIAL REGISTRATION: ClinicalTrials.gov. number, NCT01609309 FUNDING STATEMENT: This work was supported by the National Natural Science of China, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, the Key Clinical Specialty Discipline Construction Program from the National Health and Family Planning Commission of China, and the Program of Global Medical Affairs Department of Johnson & Johnson Medical Ltd. DECLARATION OF INTERESTS: None. ETHICS APPROVAL STATEMENT: Each participating center obtained institutional review board approval, according to local regulations. Patients provided written informed consent.

Importance It is not clear whether laparoscopic and open distal gastrectomy produce similar outcomes among patients with locally advanced gastric cancer. Data from a multicenter, randomized clinical trial (Chinese Laparoscopic Gastrointestinal Surgical Study [CLASS]-01) showed that laparoscopic distal gastrectomy did not result in inferior disease-free survival at 3 years compared with open distal gastrectomy. Objective To report 5-year overall survival data from the CLASS-01 trial of laparoscopic vs open distal gastrectomy among patients with locally advanced gastric cancer. Design, setting, and patients This was a noninferiority, open-label, randomized clinical trial conducted at 14 centers in China. A total of 1056 eligible patients with clinical stage T2, T3, or T4a gastric cancer without bulky nodes or distant metastases were enrolled from September 12, 2012, to December 3, 2014. Final follow-up was on December 31, 2019. Interventions Participants were randomized in a 1:1 ratio after stratification by site, age, cancer stage, and histologic features to undergo either laparoscopic distal gastrectomy (n = 528) or open distal gastrectomy (n = 528) with D2 lymphadenectomy. Main outcomes and measures The 5-year overall survival rates were updated to compare laparoscopic distal gastrectomy with open distal gastrectomy. All analyses were performed on an intention-to-treat basis. In addition, per-protocol and as-treated analyses were performed for overall survival. Results Data from 1039 patients (726 men [69.9%]; mean [SD] age, 56.2 [10.7] years) who received curative therapy were analyzed. At 5 years, the overall survival rates were 72.6% in the laparoscopic distal gastrectomy group and 76.3% in the open distal gastrectomy group (log-rank P = .19; hazard ratio, 1.17; 95% CI, 0.93-1.48; P = .19). After comparison for competing risk events, gastric cancer-related deaths (hazard ratio, 1.14; 95% CI, 0.87-1.49; P = .34) and deaths from other causes (hazard ratio, 1.23; 95% CI, 0.74-2.05; P = .42) did not differ significantly between groups. Overall rates of survival did not differ significantly between groups with each tumor stage. Conclusions and relevance This study found that laparoscopic distal gastrectomy with D2 lymphadenectomy performed by experienced surgeons in high-volume specialized institutions resulted in similar 5-year overall survival compared with open distal gastrectomy among patients with locally advanced gastric cancer. Trial registration ClinicalTrials.gov Identifier: NCT01609309.

It is now widely accepted that mitochondrial biogenesis is inhibited in most cancer cells. Interestingly, one of the possible exceptions is colorectal cancer (CRC), in which the content of mitochondria has been found to be higher than in normal colon mucosa. However, to date, the causes and effects of this phenomenon are still unclear. In the present study, we systematically investigated the functional role of mitochondrial single-strand DNA binding protein (mtSSB), a key molecule in the regulation of mitochondrial DNA (mtDNA) replication, in the mitochondrial biogenesis and CRC cell growth. Our results demonstrated that mtSSB was frequently upregulated in CRC tissues and that upregulated mtSSB was associated with poor prognosis in CRC patients. Furthermore, overexpression of mtSSB promoted CRC cell growth in vitro by regulating cell proliferation. The in vivo assay confirmed these results, indicating that the forced expression of mtSSB significantly increases the growth capacity of xenograft tumors. Mechanistically, the survival advantage conferred by mtSSB was primarily caused by increased mitochondrial biogenesis and subsequent ROS production, which induced telomerase reverse transcriptase (TERT) expression and telomere elongation via Akt/mTOR pathway in CRC cells. In addition, FOXP1, a member of the forkhead box family, was identified as a new transcription factor for mtSSB. Moreover, our results also demonstrate that proinflammatory IL-6/STAT3 signaling facilitates mtSSB expression and CRC cell proliferation via inducing FOXP1 expression. Collectively, our findings demonstrate that mtSSB induced by inflammation plays a critical role in the regulation of mitochondrial biogenesis, telomerase activation, and subsequent CRC proliferation, providing a strong evidence for mtSSB as drug target in CRC treatment.