Swimming training promotes angiogenesis of endothelial progenitor cells by upregulating IGF1 expression and activating the PI3K/AKT pathway in type 2 diabetic rats.

The present study aimed to investigate the effect of swimming training on the angiogenesis of endothelial progenitor cells (EPCs) in type 2 diabetes mellitus (T2DM) rats by upregulating the insulin­like growth factor 1 (IGF1) expression and to reveal its potential mechanism of action. Male Sprague­Dawley rats were divided into the Control, Model, Model train, Model train + short interfering (si)­NC and Model train + si­IGF1 groups. Serum glucose levels were measured using the oral glucose tolerance test. EPCs were isolated from the bone marrow cavity and identified through morphological observation and immunofluorescence staining. The expression of IGF­1 mRNA in rat serum and EPCs was analyzed by reverse transcription­quantitative PCR. The fasting insulin levels in serum were assessed by ELISA. Cell Counting Kit­8, scratch assay and tube formation assay were used to determine the cell viability, migration and tube formation of rat EPCs, and western blotting was employed to measure the expression levels of IGF1, phosphoinositide 3­kinase (PI3K), phosphorylated­PI3K, protein kinase B (AKT) and phosphorylated­AKT. The present study demonstrated that swimming training significantly decreased the glucose levels and homeostatic model assessment of insulin resistance scores, but increased the fasting insulin levels and IGF1 mRNA expression. Microscopic observation and immunofluorescence identification suggested that EPCs were successfully isolated. In addition, swimming training markedly elevated the levels of IGF1 and promoted cell viability, migration and tube formation in rat EPCs. Furthermore, IGF1 knockdown experiments indicated that swimming training might play a regulatory role by elevating the IGF1 expression to activate the PI3K/AKT pathway. Overall, swimming training promoted the angiogenesis of EPCs in T2DM rats and its potential mechanism may be related to the upregulation of IGF1 expression and the activation of the PI3K/AKT pathway.

Conformal thyroidectomy is a feasible option in papillary thyroid microcarcinoma: a retrospective cohort study with 10-year follow-up results.

BACKGROUND: In recent years, there has been an increasing prevalence of patients with papillary thyroid microcarcinoma (PTMC) without lymph node involvement in medical centers worldwide. For patients who are unable to undergo active surveillance (AS) and are afraid of postoperative complications, conformal thyroidectomy may be a suitable option to ensure both preservation of function and complete removal of the tumor. METHODS: The patients in the cohort during 2010 to 2015 were retrospectively enrolled strictly following the inclusion and exclusion criteria. The observation and control groups were defined based on the surgical approach, with patients in the observation group undergoing conformal thyroidectomy and patients in the control group undergoing lobectomy. Event-free survival (EFS), the interval from initial surgery to the detection of recurrent or metastatic disease, was defined as the primary observation endpoint. RESULTS: A total of 319 patients were included in the study, with 124 patients undergoing conformal thyroidectomy and 195 patients undergoing lobectomy. When compared to lobectomy, conformal thyroidectomy demonstrated reduced hospital stays, shorter operative times, and lower rates of vocal cord paralysis and hypoparathyroidism. Furthermore, the mean bleeding volume during the operation and the rate of permanent hypothyroidism were also lower in the conformal thyroidectomy group than in the lobectomy group. However, there was no statistically significant difference observed in the 5- and 10-year EFS between the two groups. CONCLUSIONS: Conformal thyroidectomy had advantages in perioperative management and short-term complication rates, with an EFS that was not inferior to that of lobectomy. Thus, conformal thyroidectomy is a feasible option for low-risk PTMC patients.

Transcriptomic and genomic profiling of multiple primary colorectal cancers reveals intratumor heterogeneity and a distinct immune microenvironment.

This study reported on the intratumor genomic and immunological heterogeneity of different tumor lesions from a single patient with multiple primary colorectal cancer (MPCC). The goal of this study was to explore the molecular and microenvironment characteristics of tumor lesions from different primary sites in a patient with MPCC. A total of three tumor lesions located in the hepatic flexure of the transverse colon, sigmoid colon, and rectum were collected from a 72-year-old male patient with MPCC. All three tumor samples were examined by using whole-exome sequencing (WES) and single-cell RNA sequencing (scRNA-seq). The transcriptome data of The Cancer Genome Atlas (TCGA) colon cancer (COAD) dataset were explored to characterize the biological impacts of certain immune cells. Only three nonsynonymous mutations were shared by all of the tumor lesions, whereas a number of single nucleotide variant (SNV) and copy number variation (CNV) mutations were shared by tumor samples from the sigmoid colon and rectum. Transcriptomic analysis showed that tumor lesions derived from the transverse colon had decreased levels of RTK, ERK, and AKT pathway activity, thus suggesting lower oncogenic properties in the transverse lesion compared to the other two samples. Further immune landscape evaluation by using single-cell transcriptomic analysis displayed significant intratumor heterogeneity in MPCC. Specifically, more abundant mucosal-associated invariant T (MAIT) cell infiltration was found in transverse colon tumor lesions. Afterwards, we found that higher MAIT cell infiltration may correlate with a better prognosis of patients with colon cancer (immunohistochemical status was MSI-L/pMMR) by using a publicly available TCGA dataset.

Hallmarks and novel insights for gastrointestinal stromal tumors: A bibliometric analysis.

BACKGROUND: Due to the increasing recognition of gastrointestinal stromal tumor (GIST), novel insights have appeared in both preclinical and clinical research and begun to reshape the field. This study aims to map the research landscape through bibliometric analysis and provide a brief overview for the future of the GIST field. METHODS: We searched the Web of Science Core Collection without publication data restrictions for GISTs and performed a bibliometric analysis with CiteSpace and VOSviewer software. RESULTS: In sum, 5,911 of 13,776 records were included, and these studies were published in 948 journals and written by 24,965 authors from 4,633 institutions in 100 countries. Referring to published reviews and bibliometric analysis, we classified the future trends in four groups. In epidemiological study, precise incidence and clinicopathological features in different regions and races might become potential hotspots. Novel therapy, such as drugs, modified strategies, radioligand therapy, was persistent hotspots in GIST fields, and ctDNA-guided diagnosis, monitoring, and treatment might meet future clinical needs. The debate over serosa surgery vs. mucosa surgery will remain active for a long time in GIST surgery, and function reserve surgery, biology-based surgery will play an important role in future. Moreover, rare GIST type, like NF-1-associated GIST, Carney triads and SDH mutant GIST, need more studies in pathogenesis and genetic mutation to provide appropriate treatment for this orphan GIST patients. CONCLUSIONS: Potential hotspots in future GIST trends might involve epidemiology, agents, resection therapy and rare type GIST, moreover, researchers could pay more attention in these four fields.

[Exploration and consideration on establishing a core outcome set of Traditional Chinese Medicine clinical trials in distal radius fracture].

There are inconsistencies in treatment outcomes, measurement instruments, and criteria for assessing clinical effectiveness in studies related to distal radius fractures (DRF), resulting in potential biases and failing to provide high-quality clinical evidence. To address these challenges, international researchers have reached a consensus on developing the core outcome indicator set for distal radius fractures(COS-DRF). However, it's important to note that the existing COS-DRF framework could not reflect the unique characteristics of Traditional Chinese Medicine (TCM) treatment. Currently, there are no established standards for treatment outcomes and measurement instruments specific to TCM clinical research, nor has a COS-DRF been established for TCM clinical studies in China. In light of these gaps, our research team aims to construct a core set of treatment outcomes for TCM clinical research on distal radius fractures. This involves compiling a comprehensive list of treatment outcomes and measurement instruments, initially derived from a thorough literature review and expert consensus, which will then undergo further refinement and updates based on real-world clinical experiences, incorporating feedback from 2 to 3 rounds of expert consensus or Delphi questionnaire surveys. Our goal is to establish a COS-DRF or CMS-DRF that aligns with the principles and practices of TCM, and provide high-quality evidence for clinical practice.

Consistency assessment and visualization of recommendations on gastroesophageal reflux disease: a scoping review of clinical practice guidelines.

INTRODUCTION: Gastroesophageal reflux disease (GERD) is a highly prevalent gastrointestinal disorder that causes diverse esophageal and extraesophageal symptoms. Many clinical practice guidelines (CPGs) have been issued around the world to provide practical evidence regarding GERD management. However, some of the recommendations discussed in various CPGs are inconsistent across individual documents. OBJECTIVES: We aimed to summarize the evidence from CPGs on GERD and assess the consistency of the recommendations. PATIENTS AND METHODS: In this scoping review, we identified current CPGs on the clinical management of GERD, which were comprehensively searched for in electronic databases and on relevant scientific websites. The recommendations were extracted using the population­intervention­comparison framework and were subsequently categorized into tables. RESULTS: Ultimately, 24 CPGs were identified. They included 86 recommendations, which were classified into 5 categories: definition, epidemiology, diagnosis, treatment, and complications. Among the identified recommendations, 68 were proposed in at least 2 CPGs, and they were assessed for the consistency of direction and strength. Overall, 32.4% of the recommendations (22/68) were consistent in direction and strength, whereas 60.3% (41/68) were consistent in direction but inconsistent in strength. Moreover, 7.4% (5/68) were inconsistent in direction. These referred to the relationship between GERD and tobacco consumption, Helicobacter pylori infection, diagnostic utility of the 2­week proton pump inhibitor test, cessation of special food, and antireflux surgery for GERD with extraesophageal symptoms. CONCLUSIONS: Most CPG recommendations regarding GERD were consistent in direction, except for 5 discrepancies, for which further well­designed, large­scale research is required to explain the inconsistency.

Can Dietary Nutrients Prevent Cancer Chemotherapy-Induced Cardiotoxicity? An Evidence Mapping of Human Studies and Animal Models.

Introduction: Chemotherapy has significantly improved cancer survival rates at the cost of irreversible and frequent cardiovascular toxicity. As the main dose-dependent adverse effect, cardiotoxic effects not only limit the usage of chemotherapeutic agents, but also cause the high risk of severe poor prognoses for cancer survivors. Therefore, it is of great significance to seek more effective cardioprotective strategies. Some nutrients have been reported to diminish cardiac oxidative damage associated with chemotherapy. However, the currently available evidence is unclear, which requires a rigorous summary. As such, we conducted a systematic review of all available evidence and demonstrated whether nutrients derived from food could prevent cardiotoxicity caused by chemotherapy. Methods: We searched Medline (via PubMed), Embase and the Cochrane Library from inception to Nov 9, 2021 to identify studies reporting dietary nutrients against cancer chemotherapy-related cardiotoxicity. We performed descriptive summaries on the included studies, and used forest plots to demonstrate the effects of various dietary nutrients. Results: Fifty-seven eligible studies were identified, involving 53 animal studies carried on rats or mice and four human studies in cancer patients. Seven types of dietary nutrients were recognized including polyphenols (mainly extracted from grapes, grape seeds, and tea), allicin (mainly extracted form garlic), lycopene (mainly extracted from tomatoes), polyunsaturated fatty acids, amino acids (mainly referring to glutamine), coenzyme Q10, and trace elements (mainly referring to zinc and selenium). Dietary nutrients ameliorated left ventricular dysfunctions and myocardial oxidative stress at varying degrees, which were caused by chemotherapy. The overall risk of bias of included studies was at moderate to high risk. Conclusion: The results indicated that dietary nutrients might be a potential strategy to protect cardiovascular system exposed to the chemotherapeutic agents, but more human studies are urged in this field.Systematic Review Registration: https://inplasy.com/inplasy-2022-3-0015/.

Analysis of Differential Diagnosis of Benign and Malignant Partially Cystic Thyroid Nodules Based on Ultrasound Characterization With a TIRADS Grade-4a or Higher Nodules.

Partially cystic thyroid nodules (PCTNs) are a kind of thyroid nodule with both solid and cystic components, and are usually misdiagnosed as benign nodules. The objective of this study was to determine the ultrasound (US) characterizations with a TIRADS Grade-4a or higher partially cystic thyroid nodules (PCTNs) which are associated with being malignant or benign. In this study, 133 PCTNs with a TIRADS Grade-4a or higher were enrolled; 83 were malignant and 50 were benign. TI-RADS classification can detect malignant PCTNs, and its sensitivity, specificity, positive predictive value, negative predictive value, and accuracy are 39.8%, 96.0%, 94.3%, 49.0%, and 60.9%, respectively. Univariate analyses revealed that nodule shape, margin, and structure were related to PCTNs' being benign and malignant, among which nodules taller-than-wide, with an irregular shape, non-smooth margin, eccentric sharp angle, or edge sharp angle were significantly associated with malignancy while ovoid to round nodules, smooth margins, multiple separation, and eccentric obtuse angle structures were significantly associated with a benign nature. For the solid part of PCTNs, its free margin, echo, and calcification are related to benign and malignant PCTNs. Among them, the free margin of the solid part is non-smooth, hypoechoic, and microcalcification, which are related to malignant PCTNs, while the free margin of the solid part is smooth, isoechoic, macrocalcification, non-calcification and are related to benign PCTNs. Calcification of solid part and free margin are important factors for predicting malignant PCTNs. In addition, nodules' composition, blood flow signal, and other factors had nothing to do with PCTNs' being benign or malignant. In the multivariate Logistic regression analysis, solid part calcification (OR: 17.28; 95%CI: 5.14~58.08) and free margin (OR: 3.18; 95%CI: 1.01~10.00) were revealed to be the strongest independent predictors for malignancy (P<0.05). Our study indicated that understanding the ultrasound characteristics of malignant PCTNs, to avoid misdiagnosed PCTNs patients, is important to make a precise diagnosis and prognosis of PCTNs.

Uncut Roux-en-Y might reduce the rate of reflux gastritis after radical distal gastrectomy: An evidence mapping from a systematic review.

BACKGROUND: To evaluate the efficacy, safety, technical feasibility, and effect of reducing the incidence of reflux gastritis from uncut Roux-en-Y (URY) reconstruction after radical distal gastrectomy (RDG) for gastric cancer. METHODS: A literature search was conducted in PubMed, EMBASE, Web of Science, the Cochrane Library, Chinese National Knowledge Infrastructure, and WanFang databases until June 30, 2020, to identify studies comparing URY reconstruction with other gastrointestinal tract reconstruction methods after RDG. The Newcastle-Ottawa Scale (NOS) and the Cochrane Collaboration's risk for bias assessment tool were used to assess the risk of bias. The study was performed using review manager RevMan 5.3.0 software. RESULTS: A total of 35 original studies (six randomized clinical trials (RCTs) and 29 cohort studies) were included in this analysis with a total of 4100 patients. For reflux gastritis, URY anastomosis was significantly superior to the other four types of anastomoses (Billroth-I (odds ratio (OR) = 0.16 [0.10, 0.27], P < 0.00001); Billroth-II (OR = 0.32 [0.20, 0.51], P < 0.00001); Billroth-II with Braun (OR = 0.14 [0.007, 0.26], P < 0.00001), and Roux-en-Y (OR = 0.59 [0.38, 0.91], P = 0.02)). Furthermore, URY anastomosis was better than Billroth-II with Braun (OR = 0.07, 95%confidence interval (CI): [0.02, 0.28], P = 0.0001) and Billroth-II (OR = 0.14, 95%CI: [0.09, 0.24], P < 0.00001) anastomoses for preventing bile reflux. In addition, for anastomotic leakage, URY anastomosis was significantly superior to Roux-en-Y (OR = 0.34, 95%CI: [0.13, 0.87], P = 0.02) anastomosis, and no statistically significant difference between URY and the other three reconstruction methods was found. The postoperative hospital stay of patients receiving URY anastomosis was substantially shorter than those receiving Billroth-II with Braun (MD: 2.84, 95%CI: [-3.16, -1.80], P < 0.00001), Bollroth-II (MD: 1.23, 95%CI: [-2.10, -0.37], P = 0.005) and Roux-en-Y (MD: 1.98, 95%CI: [-2.17, -1.78], P < 0.00001) anastomoses. CONCLUSION: URY reconstruction significantly reduce the rate of reflux gastritis after RDG, and it was a more favorable reconstruction method after RDG for its operative simplicity, safety, and reduced postoperative complications especially in Roux-en-Y stasis syndrome. Large sample size cohort studies and well-designed RCTs are needed for further confirmation of our findings. OTHER: This work was supported by the National Nature Science Foundation of China (No.81871962), Industry-University-Research Innovation Fund in the Ministry of Education of the People's Republic of China (No. 2018A01013) and the Autonomous Intelligent Unmanned System (No. 62088101). This study was registered with PROSPERO (CRD42020200906).

Clinicopathological characteristics and longterm survival of patients with synchronous multiple primary gastrointestinal stromal tumors: A propensity score matching analysis.

BACKGROUND: Multiple gastrointestinal stromal tumors (MGISTs) are specific and rare. Little is known about the impact of MGISTs on the survival of patients with gastrointestinal stromal tumors (GIST). The diagnosis, treatment and follow-up strategies of MGISTs is not specifically described in guidelines. AIM: To compare the clinicopathological characteristics and prognosis of MGISTs and solitary GISTs (SGISTs). METHODS: Patients diagnosed with primary GISTs from March 2010 to January 2020 were included. Due to the inhomogeneous distribution of several baseline characteristics and uneven MGIST and SGIST group sizes, propensity score matching was performed according to comorbidities, body mass index, tumor location, mitotic index, sex, age and American Society of Anesthesiologists score. Differences in clinicopathological characteristics and prognosis between patients with MGISTs and patients with SGISTs were compared. RESULTS: Among the entire cohort of 983 patients, the incidence of MGISTs was 4.17%. Before matching, patients with MGISTs and those with SGISTs had disparities in body mass index, surgical approach, tumor size and mitotic index. After 1:4 ratio matching, the clinical baseline data were comparable. The 5-year progression-free survival rate was 52.17% in the MGIST group and 75.00% in the SGIST group (P = 0.031). On multivariate analysis, tumor location, tumor size, mitotic index, imatinib treatment and MGISTs (hazard ratio = 2.431, 95% confidence interval = 1.097-5.386, P = 0.029) were identified as independent prognostic factors of progression-free survival. However, overall survival was similar between the SGIST and MGIST groups. CONCLUSION: Patients with MGISTs had poorer progression-free survival than patients with SGISTs. Risk criteria and diagnostic and treatment strategies should be developed to achieve personalized precision therapy and maximize the survival benefit.

Genetic mutations associated with sensitivity to neoadjuvant chemotherapy in metastatic colon cancer: A case report and review of literature.

BACKGROUND: Colorectal liver metastases (CLM) occur in 15%-30% of patients with colorectal cancer (CRC). Advancements in next generation sequencing (NGS) can provide more precise prognoses for cancer patients and help guide clinical treatment. However, the genetic variants that predict high sensitivity to neoadjuvant chemotherapy remain unclear, especially in patients with CLM. The aim of this study was to identify the relevant genetic variants in a single CLM patient and to summarize the current evidence on mutations and single nucleotide polymorphisms (SNPs) that objectively predict sensitivity to neoadjuvant chemotherapy. CASE SUMMARY: A 76-year-old male patient, who was diagnosed as stage IV colon cancer with liver metastases, was found to have APC/TP53/KRAS mutations. He showed a good therapeutic response to 12 courses of oxaliplatin regimens combined with Bevacizumab. Genetic analysis of the patient identified 5 genes with 7 detected SNPs that may be related to a better response to chemotherapy drugs. In addition, a critical literature review was performed based on a standardized appraisal form after selecting the articles. Ultimately, 21 eligible studies were appraised to assess the association between gene mutations and good prognosis. Mutations in KRAS, TP53, SMAD4, and APC were identified as being associated with a poor response to chemotherapy drugs, whereas mutations of CREBBP and POLD1 were associated with longer overall survival. CONCLUSION: NGS can identify precise predictors of response to neoadjuvant chemotherapy, leading to improved outcomes for CRC patients.

Current Trends and Research Topics Regarding Intestinal Organoids: An Overview Based on Bibliometrics.

Currently, research on intestinal diseases is mainly based on animal models and cell lines in monolayers. However, these models have drawbacks that limit scientific advances in this field. Three-dimensional (3D) culture systems named organoids are emerging as a reliable research tool for recapitulating the human intestinal epithelium and represent a unique platform for patient-specific drug testing. Intestinal organoids (IOs) are crypt-villus structures that can be derived from adult intestinal stem cells (ISCs), embryonic stem cells (ESCs), or induced pluripotent stem cells (iPSCs) and have the potential to serve as a platform for individualized medicine and research. However, this emerging field has not been bibliometric summarized to date. Here, we performed a bibliometric analysis of the Web of Science Core Collection (WoSCC) database to evaluate 5,379 publications concerning the use of organoids; the studies were divided into four clusters associated with the current situation and future directions for the application of IOs. Based on the results of our bibliometric analysis of IO applications, we systematically summarized the latest advances and analyzed the limitations and prospects.

Clinical features of gastric duplications: evidence from primary case reports and published data.

BACKGROUND: Alimentary tract duplications are rare congenital lesions, and only 2-8% of them are located in the stomach. Gastric duplications (GD) can lead to severe adverse events. Thus, surgical resection is required once the disease is diagnosed. The main purpose of this study is to describe the clinical features of gastric duplications and to provide evidence for the diagnosis and treatment. METHODS: A retrospective review of eight gastric duplications at two medical centers Peking University People's Hospital (PKUPH) and Shandong Provincial Hospital from 2010 to 2020 was conducted. Furthermore, the literature search was also conducted by retrieving data from PubMed, EMBASE and Cochrane Library databases from the date of the database inception to January 15, 2021. RESULTS: Eight patients who were diagnosed as gastric duplications and 311 published records were included in this study. In all, 319 patients were identified: Vomiting and abdominal pain were the most frequent clinical presentations among juveniles and adults respectively. There was no difference in gender distribution (F: 53.16% vs M: 46.84%), and the cystic gastric duplications were the most common type of the gastric duplications (87.04%). More than half (53.30%) of included cases were located in the greater curvature of stomach. CONCLUSIONS: Gastric duplications could present with a wide spectrum of symptomatology, which might be misdiagnosed easily as other diseases. For cystic gastric duplications, the optimal treatment was a complete surgical removal. But conservative treatment might be an alternative strategy for tubular gastric duplications.

What is the best surgical procedure of transverse colon cancer? An evidence map and minireview.

Colorectal cancers comprise a large percentage of tumors worldwide, and transverse colon cancer (TCC) is defined as tumors located between hepatic and splenic flexures. Due to the anatomy and embryology complexity, and lack of large randomized controlled trials, it is a challenge to standardize TCC surgery. In this study, the current situation of transverse/extended colectomy, robotic/ laparoscopic/open surgery and complete mesocolic excision (CME) concept in TCC operations is discussed and a heatmap is conducted to show the evidence level and gap. In summary, transverse colectomy challenges the dogma of traditional extended colectomy, with similar oncological and prognostic outcomes. Compared with conventional open resection, laparoscopic and robotic surgery plays a more important role in both transverse colectomy and extended colectomy. The CME concept may contribute to the radical resection of TCC and adequate harvested lymph nodes. According to published studies, laparoscopic or robotic transverse colectomy based on the CME concept was the appropriate surgical procedure for TCC patients.

Characterization of Global Research Trends and Prospects on Single-Cell Sequencing Technology: Bibliometric Analysis.

BACKGROUND: As single-cell sequencing technology has been gradually introduced, it is essential to characterize global collaboration networks and map development trends over the past 20 years. OBJECTIVE: The aim of this paper was to illustrate collaboration in the field of single-cell sequencing methods and explore key topics and future directions. METHODS: Bibliometric analyses were conducted with CiteSpace and VOSviewer software on publications prior to November 2019 from the Web of Science Core Collection about single-cell sequencing methods. RESULTS: Ultimately, we identified 2489 records, which were published in 495 journals by 14,202 authors from 1970 institutes in 61 countries. There was a noticeable increase in publications in 2014. The United States and high-income countries in Europe contributed to most of the records included. Harvard University, Stanford University, Karolinska Institutes, Peking University, and the University of Washington were the biggest nodes in every cluster of the collaboration network, and SA Teichmann, JC Marioni, A Regev, and FC Tang were the top-producing authors. Keywords co-occurrence analysis suggested applications in immunology as a developing research trend. CONCLUSIONS: We concluded that the global collaboration network was unformed and that high-income countries contributed more to the rapidly growth of publications of single-cell sequencing technology. Furthermore, the application in immunology might be the next research hotspot and developmental direction.

Different Medical Features and Strategies of Large Rectal Gastrointestinal Stromal Tumor: A Multi-Central Pooling Analysis.

PURPOSE: The rectum is a rare site for gastrointestinal stromal tumors (GISTs). Tumors in this critical anatomical site are prone to develop local recurrence, and this occurs at a high level even in low-risk tumors. Previous studies found that high-risk was the most common category in rectal gastrointestinal stromal tumors (RGISTs), and size was the most important factor affecting the long-term prognosis. We aimed to find out the most influential factor on clinical outcomes, and describe demographics, oncological differences, and surgical procedures in patients with poor prognosis. PATIENTS AND METHODS: Data on consecutive patients with RGIST, who were diagnosed at Peking University People's Hospital, Shandong Province Hospital, and The First Affiliated Hospital of Shandong First Medical University from 2010 to 2020, were retrospectively evaluated. Further, a literature search was conducted by retrieving data from PubMed, EMBASE, and the Cochrane Library databases from inception up to March 20, 2020. RESULTS: In all, 50 patients were diagnosed with RGIST at three medical centers, and 86 published records were finally included in the literature review. Combined analysis of the whole individual patient data showed that 5.5 cm was deemed an appropriate cut-off value for L-RGIST, and that patients usually showed a male predominance (67.59%), younger age at onset (56.61 years), higher operative difficulty, and poorer prognosis. CONCLUSION: Separation of patients with large RGIST from general patients may contribute to the recognition of the oncological characteristics and clinical management of this rare type of tumor.

N6-methyladenosine Regulator-Mediated Immune Genes Identify Breast Cancer Immune Subtypes and Predict Immunotherapy Efficacy.

Breast cancer (BRCA) is a heterogeneous malignancy closely related to the tumor microenvironment (TME) cell infiltration. N6-methyladenosine (m6A) modification of mRNA plays a crucial regulator in regulating the immune microenvironment of BRCA. Immunotherapy represents a paradigm shift in BRCA treatment; however, lack of an appropriate approach for treatment evaluation is a significant issue in this field. In this study, we attempted to establish a prognostic signature of BRCA based on m6A-related immune genes and to investigate the potential association between prognosis and immunotherapy. We comprehensively evaluated the m6A modification patterns of BRCA tissues and non-tumor tissues from The Cancer Genome Atlas and the modification patterns with TME cell-infiltrating characteristics. Overall, 1,977 TME-related genes were identified in the literature. Based on LASSO and Cox regression analyses, the m6A-related immune score (m6A-IS) was established to characterize the TME of BRCA and predict prognosis and efficacy associated with immunotherapy. We developed an m6A-IS to effectively predict immune infiltration and the prognosis of patients with BRCA. The prognostic score model represented robust predictive performance in both the training and validation cohorts. The low-m6A-IS group was characterized by enhanced antigen presentation and improved immune checkpoint expression, further indicating sensitivity to immunotherapy. Compared with the patients in the high-score group, the overall survival rate after treatment in the low-score group was significantly higher in the testing and validation cohorts. We constructed an m6A-IS system to examine the ability of the m6A signature to predict the infiltration of immune cells of the TME in BRCA, and the m6A-IS system acted as an independent prognostic biomarker that predicts the response of patients with BRCA in immunotherapy.

Clinical features of multiple gastrointestinal stromal tumors: A pooling analysis combined with evidence and gap map.

BACKGROUND: Multiple gastrointestinal stromal tumors (MGISTs) are a very rare type of gastrointestinal stromal tumor (GIST) and are usually observed in syndrome. AIM: The paper aimed to describe the clinical and oncological features of MGISTs and to offer evidence for the diagnosis and treatment. METHODS: Data of consecutive patients with MGISTs who were diagnosed at Peking University People's Hospital (PKUPH) from 2008 to 2019 were retrospectively evaluated. Further, a literature search was conducted by retrieving data from PubMed, EMBASE, and the Cochrane library databases from inception up to November 30, 2019. RESULTS: In all, 12 patients were diagnosed with MGISTs at PKUPH, and 43 published records were ultimately included following the literature review. Combined analysis of the whole individual patient data showed that female (59.30%), young (14.45%), and syndromic GIST (63.95%) patients comprised a large proportion of the total patient population. Tumors were mainly located in the small intestine (58.92%), and both CD117 and CD34 were generally positive. After a mean 78.32-mo follow-up, the estimated median overall survival duration (11.5 years) was similar to single GISTs, but recurrence-free survival was relatively poorer. CONCLUSION: The clinical and oncological features are potentially different between MGISTs and single GIST. Further studies are needed to explore appropriate surgical approach and adjuvant therapy.

Long noncoding RNA HIT000218960 promotes papillary thyroid cancer oncogenesis and tumor progression by upregulating the expression of high mobility group AT-hook 2 (HMGA2) gene.

Accumulating evidence suggests that long noncoding RNAs (lncRNAs) play an important role in oncogenesis and tumor progression. However, our knowledge of lncRNAs in thyroid cancer is still limited. To explore the crucial lncRNAs involved in oncogenesis of papillary thyroid cancer (PTC), we acquired data of differentially expressed lncRNAs between PTC tissues and paired adjacent noncancerous thyroid tissues through lncRNA microarray. In the microarray data, we observed that a newly identified lncRNA, HIT000218960, was significantly upregulated in PTC tissues and associated with a well-known oncogene, high mobility group AT-hook 2 (HMGA2) gene. Both in normal thyroid tissues and PTC tissues, the expression of HIT000218960 was significantly positively correlated with that of HMGA2 mRNA. Knockdown of HIT000218960 in PTC cells resulted in downregulation of HMGA2. In addition, functional assays indicated that inhibition of HIT000218960 in PTC cells suppressed cell proliferation, colony formation, migration and invasion in vitro. Increased HIT000218960 expression in PTC tissues was obviously correlated with lymph node metastasis and multifocality, as well as TNM stage. Those findings suggest that HIT000218960 might acts as a tumor promoter through regulating the expression of HMGA2.