Exploration of leech therapy in treating gouty rats and its uric acid lowering mechanism.

BACKGROUND: Gout is a hyperuricemia (HUA)-related inflammatory reaction in the joints. Leech therapy has been effective in the gout, but the exact mechanism is unclear. OBJECTIVES: In this study, an exploration of the therapeutic mechanism of leech therapy in HUA and gouty arthritis (GA) rats was done. MATERIAL AND METHODS: HUA and GA construction utilizing sodium urate crystal, the potassium form of oxygen oxazine acid, and adenine. Serum and tissues were collected to measure uric acid (UA), creatinine (Cr), and urea nitrogen (UN). Enzyme linked immunosorbent assay was executed to evaluate the levels of xanthine oxidase (XOD), interleukin-6 (IL-6)and tumor necrosis factor α (TNF-α). The expression of glucose transporter 9 (GLUT9), organic anion transporter 3 (OAT3), adenosine triphosphate (ATP)-binding cassette efflux transporter G2 (ABCG2) and the nuclear factor kappa B (NF-kB), interleukin-1ß (IL-1ß), Toll-like Receptor 2 (TLR2) were assessed by Western blot and visualized in immunohistochemistry staining. RESULTS: Leech therapy reduces the levels of UA, Cr, and UN as well as the liver and serum levels of XOD activity, increasing the expressions of GLUT9, ABCG2, and OAT3 in the kidney. Meanwhile, it reduces joint swelling and lowers the levels of TNF-α, IL-6, IL-1ß, TLR2, and NF-kB. CONCLUSIONS: Leech therapy regulates the metabolism of uric acid and treats gouty arthritis with an anti-inflammatory effect.

Development and validation of a prognostic immunoinflammatory index for patients with gastric cancer.

BACKGROUND: Studies have demonstrated the influence of immunity and inflammation on the development of tumors. Although single biomarkers of immunity and inflammation have been shown to be clinically predictive, the use of biomarkers integrating both to predict prognosis in patients with gastric cancer remains to be investigated. AIM: To investigate the prognostic and clinical significance of inflammatory biomarkers and lymphocytes in patients undergoing surgical treatment for gastric cancer. METHODS: Univariate COX regression analysis was performed to identify potential prognostic factors for patients with gastric cancer undergoing surgical treatment. Least absolute shrinkage and selection operator-COX (LASSO-COX) regression analysis was performed to integrate these factors and formulate a new prognostic immunoinflammatory index (PII). The correlation between PII and clinical characteristics was statistically analyzed. Nomograms incorporating the PII score were devised and validated based on the time-dependent area under the curve and decision curve analysis. RESULTS: Patients exhibiting elevated neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and systemic immune inflammatory index displayed inferior progression-free survival (PFS) and overall survival (OS). Conversely, low levels of CD3(+), CD3(+) CD8(+), CD4(+)CD8(+), and CD3(+)CD16(+)CD56(+) T lymphocytes were associated with improved PFS and OS, while high CD19(+) T lymphocyte levels were linked to worse PFS and OS. The PII score demonstrated associations with tumor characteristics (primary tumor site and tumor size), establishing itself as an independent prognostic factor for both PFS and OS. Time-dependent area under the curve and decision curve analysis affirmed the effectiveness of the PII-based nomogram as a robust prognostic predictive model. CONCLUSION: PII may be a reliable predictor of prognosis in patients with gastric cancer undergoing surgical treatment, and it offers insights into cancer-related immune-inflammatory responses, with potential significance in clinical practice.

Comparison of linear energy transfer measurement for therapeutic carbon beam using CR-39 and TLD.

The measurement of linear energy transfer (LET) is crucial for the evaluation of the radiation effect in heavy ion therapy. As two detectors which are convenient to implant into the phantom, the performance of CR-39 and thermoluminescence detector (TLD) for LET measurement was compared by experiment and simulation in this study. The results confirmed the applicability of both detectors for LET measurements, but also revealed that the CR-39 detector would lead to potential overestimation of dose-averaged LET compared with the simulation by PHITS, while the TLD would have a large uncertainty measuring ions with LET larger than 20 keVµm-1. The results of this study were expected to improve the detection method of LET for therapeutic carbon beam and would finally be benefit to the quality assurance of heavy ion radiotherapy.

Evaluating the influence of sarcopenia and myosteatosis on clinical outcomes in gastric cancer patients undergoing immune checkpoint inhibitor.

BACKGROUND: The development and progression of gastric cancer (GC) are closely linked to the nutritional status of patients. Although immunotherapy has been demonstrated to be clinically effective, the relationships of sarcopenia and myosteatosis with the use of immune checkpoint inhibitors (ICIs) in patients with gastric cancer remain to be characterized. AIM: To assess the effects of sarcopenia and myosteatosis on the clinical outcomes of patients with GC undergoing treatment with an ICI. METHODS: We performed a retrospective study of patients who were undergoing immunotherapy for GC. For the evaluation of sarcopenia, the optimal cut-off value for the skeletal muscle index was established using receiver operating characteristic analysis of data obtained from pre-treatment computed tomography images at the L3 vertebral level. Myosteatosis was defined using the mean skeletal muscle density (SMD), with a threshold value of < 41 Hounsfield units (HU) for patients with a body mass index (BMI) < 25 kg/m² and < 33 HU for those with a BMI ≥ 25 kg/m². The log-rank test was used to compare progression-free survival (PFS) and overall survival (OS), and a Cox proportional hazard model was used to identify prognostic factors. Nomograms were developed to predict the PFS and OS of patients on the basis of the results of multivariate analyses. RESULTS: We studied 115 patients who were undergoing ICI therapy for GC, of whom 27.4% had sarcopenia and 29.8% had myosteatosis. Patients with sarcopenia or myosteatosis had significantly shorter PFS and OS than those without these conditions. Furthermore, both sarcopenia and myosteatosis were found to be independent predictors of PFS and OS in patients with GC administering an ICI. The prediction models created for PFS and OS were associated with C-indexes of 0.758 and 0.781, respectively. CONCLUSION: The presence of sarcopenia or myosteatosis is a reliable predictor of the clinical outcomes of patients with GC who are undergoing treatment with an ICI.

Preoperative glucose-to-lymphocyte ratio predicts survival in cancer.

Background: Systemic inflammation and glucose metabolism have been closely related to the survival of cancer patients. Therefore, we aimed to evaluate whether preoperative glucose-to-lymphocyte ratio (GLR) can be used to predict the survival of cancer patients. Methods: We retrospectively examined 2172 cancer patients who underwent surgery from January 1, 2014, to December 31, 2016. There were 240 patients with non-small cell lung cancer (NSCLC), 378 patients with colorectal cancer (CRC), 221 patients with breast cancer (BC), 335 patients with gastric cancer (GC), 270 patients with liver cancer, 233 patients with esophageal cancer (EC), 295 patients with renal cancer, and 200 patients with melanoma. The formula for preoperative GLR calculation was as follows: GLR=glucose/lymphocyte count. The overall survival (OS) was estimated using the Kaplan-Meier method. The predictive factors for OS were determined using multivariate analysis. Results: The Kaplan-Meier analysis showed that the median survival time in the high-GLR group was much shorter than that of those in the low-GLR group for different cancers. Cox multivariate regression analysis reveals that preoperative GLR was an independent factor for predicting overall survival in different tumor types. Conclusion: Elevated preoperative GLR was remarkably associated with a poorer prognosis in patients with NSCLC, CRC, breast cancer, gastric cancer, kidney cancer, liver cancer, esophageal cancer, and melanoma. Preoperative GLR promises to be an essential predictor of survival for cancer patients.

CircATP13A1 (hsa_circ_0000919) promotes cell proliferation and metastasis and inhibits cell apoptosis in pancreatic ductal adenocarcinoma via the miR-186/miR-326/HMGA2 axis: implications for novel therapeutic targets.

Pancreatic ductal adenocarcinoma (PDAC) is a notoriously aggressive malignancy with a survival rate of merely 9%. The prognosis in patients with PDAC is relatively poor, particularly in patients with advanced distant metastases. However, the mechanisms of PDAC progression remain elusive. Circular RNAs (circRNAs) have been implicated in the development of various malignancies, including PDAC. Therefore, this study aimed to investigate how a novel circRNA, circATP13A1, regulates PDAC progression. We used the GEO database to determine circATP13A1 expression levels in cancer and adjacent cells and employed the limma package of R software to identify differentially expressed circRNAs. We detected the expression of circATP13A1, miR-186, and miR-326 using qRT-PCR and investigated the effect of circATP13A1 on cell proliferation, migration, invasion, and apoptosis in vitro using the Cell Counting Kit-8 (CCK-8), the transwell migration assay, and the flow cytometry assay. We then performed RNA pull-down assay, RNA immunoprecipitation (RIP), and Western blot to verify the interaction between circATP13A1, miR-186, miR-326, and HMGA2. Moreover, we used a naked mice model to determine how circATP13A1 affects tumor growth and progression in vivo. Loss and gain of function analyses revealed that circATP13A1 upregulation promotes cell proliferation, migration, invasion and tumor growth both in vitro and in vivo, which results in PDAC progression and poor prognosis in patients. CircATP13A1 knockdown significantly impaired cell proliferation and migration of PDAC cell lines. Additionally, circATP13A1 knockdown significantly increased the expression of miR-186 and miR-326, while reducing the expression of HMGA2 (P < 0.05), indicating that miR-186 and miR-326 are downstream targets of circATP13A1. Rescue experiments support the interactions between circATP13A1, miR-186, miR-326, and HMGA2. In conclusion, we demonstrated that circATP13A1 sponges the miR-186/miR-326/HMGA2/axis, acting as an oncogene to promote PDAC development.

DeepPhe-CR: Natural Language Processing Software Services for Cancer Registrar Case Abstraction.

PURPOSE: Manual extraction of case details from patient records for cancer surveillance is a resource-intensive task. Natural Language Processing (NLP) techniques have been proposed for automating the identification of key details in clinical notes. Our goal was to develop NLP application programming interfaces (APIs) for integration into cancer registry data abstraction tools in a computer-assisted abstraction setting. METHODS: We used cancer registry manual abstraction processes to guide the design of DeepPhe-CR, a web-based NLP service API. The coding of key variables was performed through NLP methods validated using established workflows. A container-based implementation of the NLP methods and the supporting infrastructure was developed. Existing registry data abstraction software was modified to include results from DeepPhe-CR. An initial usability study with data registrars provided early validation of the feasibility of the DeepPhe-CR tools. RESULTS: API calls support submission of single documents and summarization of cases across one or more documents. The container-based implementation uses a REST router to handle requests and support a graph database for storing results. NLP modules extract topography, histology, behavior, laterality, and grade at 0.79-1.00 F1 across multiple cancer types (breast, prostate, lung, colorectal, ovary, and pediatric brain) from data of two population-based cancer registries. Usability study participants were able to use the tool effectively and expressed interest in the tool. CONCLUSION: The DeepPhe-CR system provides an architecture for building cancer-specific NLP tools directly into registrar workflows in a computer-assisted abstraction setting. Improved user interactions in client tools may be needed to realize the potential of these approaches.

Cellular and molecular imaging of CAR-T cell-based immunotherapy.

Chimeric Antigen Receptor T cell (CAR-T) therapy has emerged as a transformative therapeutic strategy for hematological malignancies. However, its efficacy in treating solid tumors remains limited. An in-depth and comprehensive understanding of CAR-T cell signaling pathways and the ability to track CAR-T cell biodistribution and activation in real-time within the tumor microenvironment will be instrumental in designing the next generation of CAR-T cells for solid tumor therapy. This review summarizes the signaling network and the cellular and molecular imaging tools and platforms that are utilized in CAR-T cell-based immune therapies, covering both in vitro and in vivo studies. Firstly, we provide an overview of the existing understanding of the activation and cytotoxic mechanisms of CAR-T cells, compared to the mechanism of T cell receptor (TCR) signaling pathways. We further describe the commonly employed tools for live cell imaging, coupled with recent research progress, with a focus on genetically encoded fluorescent proteins (FPs) and biosensors. We then discuss the utility of diverse in vivo imaging modalities, including fluorescence and bioluminescence imaging, Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET), and photoacoustic (PA) imaging, for noninvasive monitoring of CAR-T cell dynamics within tumor tissues, thereby providing critical insights into therapy's strengths and weaknesses. Lastly, we discuss the current challenges and future directions of CAR-T cell therapy from the imaging perspective. We foresee that a comprehensive and integrative approach to CAR-T cell imaging will enable the development of more effective treatments for solid tumors in the future.

Mechanical force regulates ligand binding and function of PD-1.

Immune checkpoint blockade targeting PD-1 shows great success in cancer therapy. However, the mechanism of how ligand binding initiates PD-1 signaling remains unclear. As prognosis markers of multiple cancers, soluble PD-L1 is found in patient sera and can bind PD-1, but fails to suppress T cell function. This and our previous observations that T cells exert endogenous forces on PD-1-PD-L2 bonds prompt the hypothesis that mechanical force might be critical to PD-1 triggering, which is missing in the soluble ligand case due to the lack of mechanical support afforded by surface-anchored ligand. Here we show that PD-1 function is eliminated or reduced when mechanical support on ligand is removed or dampened, respectively. Force spectroscopic analysis reveals that PD-1 forms catch bonds with both PD-Ligands <7 pN where force prolongs bond lifetime, but slip bonds >8 pN where force accelerates dissociation. Steered molecular dynamics finds PD-1-PD-L2 complex very sensitive to force due to the two molecules' "side-to-side" binding via ß sheets. Pulling causes relative rotation and translation between the two molecules by stretching and aligning the complex along the force direction, yielding new atomic contacts not observed in the crystal structure. Compared to wild-type, PD-1 mutants targeting the force-induced new interactions maintain the same binding affinity but display lower rupture force, shorter bond lifetime, reduced tension, and most importantly, impaired capacity to suppress T cell activation. Our results uncover a mechanism for cells to probe the mechanical support of PD-1-PD-Ligand bonds using endogenous forces to regulate PD-1 triggering.

An EMT-Related Gene Signature to Predict the Prognosis of Triple-Negative Breast Cancer.

INTRODUCTION: Epithelial-mesenchymal transition (EMT) is an important biological process in tumor invasion and metastasis, and thus a potential indicator of the progression and drug resistance of breast cancer. This study comprehensively analyzed EMT-related genes in triple-negative breast cancer (TNBC) to develop an EMT-related prognostic gene signature. METHODS: With the application of The Cancer Genome Atlas (TCGA) database, Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), and the Genotype-Tissue Expression (GTEx) database, we identified EMT-related signature genes (EMGs) by Cox univariate regression and LASSO regression analysis. Risk scores were calculated and used to divide patients with TNBC into high-risk group and low-risk groups by the median value. Kaplan-Meier (K-M) and receiver operating characteristic (ROC) curve analyses were applied for model validation. Independent prognostic predictors were used to develop nomograms. Then, we assessed the risk model in terms of the immune microenvironment, genetic alteration and DNA methylation effects on prognosis, the probability of response to immunotherapy and chemotherapy, and small molecule drugs predicted by The Connectivity Map (Cmap) database. RESULTS: Thirteen EMT-related genes with independent prognostic value were identified and used to stratify the patients with TNBC into high- and low-risk groups. The survival analysis revealed that patients in the high-risk group had significantly poorer overall survival than patients in the low-risk group. Populations of immune cells, including CD4 memory resting T cells, CD4 memory activated T cells, and activated dendritic cells, significantly differed between the high- and low-risk groups. Moreover, some therapeutic drugs to which the high-risk group might show sensitivity were identified. CONCLUSIONS: Our research identified the significant impact of EMGs on prognosis in TNBC, providing new strategies for personalizing TNBC treatment and improving clinical outcomes.

DeepPhe-CR: Natural Language Processing Software Services for Cancer Registrar Case Abstraction.

Objective: The manual extraction of case details from patient records for cancer surveillance efforts is a resource-intensive task. Natural Language Processing (NLP) techniques have been proposed for automating the identification of key details in clinical notes. Our goal was to develop NLP application programming interfaces (APIs) for integration into cancer registry data abstraction tools in a computer-assisted abstraction setting. Methods: We used cancer registry manual abstraction processes to guide the design of DeepPhe-CR, a web-based NLP service API. The coding of key variables was done through NLP methods validated using established workflows. A container-based implementation including the NLP wasdeveloped. Existing registry data abstraction software was modified to include results from DeepPhe-CR. An initial usability study with data registrars provided early validation of the feasibility of the DeepPhe-CR tools. Results: API calls support submission of single documents and summarization of cases across multiple documents. The container-based implementation uses a REST router to handle requests and support a graph database for storing results. NLP modules extract topography, histology, behavior, laterality, and grade at 0.79-1.00 F1 across common and rare cancer types (breast, prostate, lung, colorectal, ovary and pediatric brain) on data from two cancer registries. Usability study participants were able to use the tool effectively and expressed interest in adopting the tool. Discussion: Our DeepPhe-CR system provides a flexible architecture for building cancer-specific NLP tools directly into registrar workflows in a computer-assisted abstraction setting. Improving user interactions in client tools, may be needed to realize the potential of these approaches. DeepPhe-CR: https://deepphe.github.io/.

The role of main pancreatic duct stent in the enucleation of benign/borderline pancreatic head tumors: a cohort study.

PURPOSE: This study aimed to reveal the role of preoperative main pancreatic duct (MPD) stent placement in reducing the intraoperative main pancreatic duct injury rate and the incidence of postoperative pancreatic leakage following pancreatic tumor enucleation. METHODS: A retrospective cohort analysis was performed for all patients with benign/borderline pancreatic head tumors who were treated with enucleation. The patients were divided into two groups (standard vs. stent) depending on whether they underwent main pancreatic duct stent placement prior to surgery. RESULTS: Thirty-three patients were finally included in the analytical cohort. Compared with the standard group, patients in the stent group had a shorter distance between tumors and main pancreatic duct (p=0.01) and presented with larger tumors (p<0.01). The rates of POPF (grade B&C) were 39.1% (9/23) and 20% (2/10) in the standard and stent groups, respectively (p<0.01). Major postoperative complications occurred more frequently in the standard group than in the stent group (14 versus 2; p<0.01). No significant differences in mortality, in-hospital stay or medical cost were observed between the two groups (p>0.05). CONCLUSIONS: MPD stent placement prior to surgery may facilitate pancreatic tumor enucleation, minimize MPD injury and decrease the occurrence of postoperative fistula.

Natural discoidal lipoproteins with tiny modification for tumor extracellular dissociation in antitumor chemoimmunotherapy.

Appealing cancer immunotherapy requires synchronous presentation of tumor antigens and immunoadjuvant. Herein, a "one-step" modification strategy is proposed to tinily remould endogenous discoidal high density lipoprotein (dHDL) for tumor-homing and site-specific chemoimmunotherapy. For molecular targeting therapy, lipophilic immunoadjuvant CpG oligodeoxynucleotides is conjugated to facilitate HDL-surface anchoring; and GC nucleotides provide enough reservoir for completion of doxorubicin (Dox) "sandwich". After administration, the tiny size (~30 nm) of disc nanodrug can maneuver deeply into tumors for receptor binding and in situ structural collapse. The intracellular concentrated CpG-Dox induce potent immunogenic cell death from burst Dox liberation at acidic pH. In turn, the released antigens and CpG motifs are simultaneously recognized by dendritic cells for antigen presentation and antitumor T cell responses. Combination chemoimmunotherapy with discoidal nanodrugs performed highest tumor weight inhibitory of 93.2% and extend the median survival time at a safe level. Collectively, this study suggests that the minimalist revolution of natural dHDL particulates may provide a biomimicry nanoplatform for site-specific amplified chemoimmunotherapy.

PD-1 suppresses TCR-CD8 cooperativity during T-cell antigen recognition.

Despite the clinical success of blocking its interactions, how PD-1 inhibits T-cell activation is incompletely understood, as exemplified by its potency far exceeding what might be predicted from its affinity for PD-1 ligand-1 (PD-L1). This may be partially attributed to PD-1's targeting the proximal signaling of the T-cell receptor (TCR) and co-stimulatory receptor CD28 via activating Src homology region 2 domain-containing phosphatases (SHPs). Here, we report PD-1 signaling regulates the initial TCR antigen recognition manifested in a smaller spreading area, fewer molecular bonds formed, and shorter bond lifetime of T cell interaction with peptide-major histocompatibility complex (pMHC) in the presence than absence of PD-L1 in a manner dependent on SHPs and Leukocyte C-terminal Src kinase. Our results identify a PD-1 inhibitory mechanism that disrupts the cooperative TCR-pMHC-CD8 trimolecular interaction, which prevents CD8 from augmenting antigen recognition, explaining PD-1's potent inhibitory function and its value as a target for clinical intervention.

Transfer characteristic of fluorine from atmospheric dry deposition, fertilizers, pesticides, and phosphogypsum into soil.

Fluorine (F) is widely dispersed in the environment and frequently used in industry and agriculture with a high migration ability. Thus, it is essential to understand the leaching characteristic of F in soil from industry and agriculture sources. Several sources of F pollutants in soil, including fertilizers, pesticides, phosphogypsum, and atmospheric deposition, were selected to investigate leaching characteristics of F in soil by leaching experiments. The addition of phosphate fertilizer and compound fertilizer (N:P:K = 20:10:15) enhanced the leachability of F in soil and the proportion of F leached out from soil treated by these fertilizers were 0.25% and 0.24%, respectively. However, unanticipated lower leachability of F appeared in compound fertilizer (N:P:K = 17:17:17), nitrogen fertilizer, dipterex, fluoroglycofen, fluopimomide, simulative dry deposition (YF3), and phosphogypsum loaded soils compared with additive-absent treatment. Although phosphogysum had a high F concentration, minimum proportion of F released (0.18%) was observed in phosphogypsum-coverd soil. The amounts of F leaching-out from surface soils (0-25 cm) treated with nitrogen fertilizer decreased 1.03 kg ha-1 comparing with blank control. Soil with phosphate fertilizer leached 5.47 kg F ha-1 a year, having the highest environment risk to deeper soil and groundwater. However, phosphogypsum and dry deposition of airbone F chemical had few effects on F leaching in soil. F-containing materials from agricultural process may leach more F from surface soils than industrial sources.

[Molecular mechanism of Puerariae Lobatae Radix in treatment of hepatocellular carcinoma based on network pharmacology].

To investigate the potential mechanism of Puerariae Lobatae Radix in the treatment of hepatocellular carcinoma by network pharmacology and in vitro cell experiment. The main active components of Puerariae Lobatae Radix and their predicted targets were obtained from TCMSP, and the disease targets were obtained from GeneCards database. The disease and drug prediction targets were intersected to select the common potential therapeutic targets. The "compound-target-disease" network diagram was constructed in Cytoscape 3.7.1, and the common targets were input into the STRING database to build the PPI network of proteins interaction. GO function and KEGG pathway enrichment analysis on effective targets were performed by using R software. Autodock vina 1.1.2 was used for molecular docking. Finally, the core targets and pathways were preliminarily verified by in vitro experiments. The proliferation of human hepatocellular carcinoma cells was detected by CCK-8 and EDU enzyme staining, and the expressions of PTEN, PDK1, Akt and GSK3 were detected by Western blot. In this study, 10 components of Puerariae Lobatae Radix(9 components involved in hepatocellular carcinoma-related targets and signaling pathways), and 149 hepatocellular carcinoma-related targets and 156 signaling pathways were screened out. The results of network analysis indicated that Puerariae Lobatae Radix may play an anti-hepatocellular carcinoma effect on key targets, such as Akt, IL6, MAPK3, EGFR, and key pathways, such as PI3 K-Akt. The results of molecular docking indicated that puerarin, genistein and daidzein had a good binding ability with the key targets such as AKT1, MAPK3, MAPK1 and CASP3, and puerarin had the lowest Vina score with AKT1 and MAPK3 and also similar to them. In vitro cell experiments confirmed that puerarin has a significantly inhibitory effect on the proliferation of human hepatocellular carcinoma cells. Western blot results showed that puerarin could increase the phosphorylation of PTEN in human hepatocellular carcinoma cells through the PTEN/Akt/GSK3ß signaling pathway, and the phosphorylation level of its downstream Akt decreased. This series of studies confirm that puerarin can treat hepatocellular carcinoma by blocking PTEN/Akt/GSK3ß cellular signaling pathway, so as to provide ideas for subsequent studies for the molecular mechanism of puerarin in the treatment of liver cancer.

Blood-based Genomic Profiling of Circulating Tumor DNA from Patients with Advanced Pancreatic Cancer and its Value to Guide Clinical Treatment.

Objective: Pancreatic cancer (PC) is a malignant tumor with limited therapeutic choices and extremely poor prognosis. Personalized therapy based on gene alternations is a promising choice. Considering tumor heterogeneity, the practice of ctDNA analysis has drawn the attention. Here, we try to assess the applicability of ctDNA in PC. Methods and materials: Next generation sequencing (NGS) was performed from blood samples of 223 PC patients and tissue sample of 564 PC patients. Genomic data from the TCGA database were also utilized. In addition, two cases received personalized treatment based on ctDNA sequencing results were reported. Results: Based on ctDNA sequencing, the genomic features of PC was revealed. Totally, 68.2% of patients detected at least one reportable genomic alteration (GA) from ctDNA. The frequently altered genes were KRAS (53.5%), followed by TP53 (52.8%), and CDKN2A (15.1%). Cell cycle control (8%) and DNA damage response (8%) pathways enriched the most mutated genes. Compared with mutations from tissue samples and a tissue-genomic database, similar frequencies of GAs were detected from ctDNA. The first two highest frequent mutation of genes were the same, but some of mutated genes were inclined to be observed in ctDNA, like AR. And two cases who received personalized therapy achieved better clinical benefit. Conclusion: Blood-source ctDNA sequencing could be regarded as a meaningful complement to tissue testing, and might guide clinically therapeutic regimen.

Interactive Exploration of Longitudinal Cancer Patient Histories Extracted From Clinical Text.

PURPOSE: Retrospective cancer research requires identification of patients matching both categorical and temporal inclusion criteria, often on the basis of factors exclusively available in clinical notes. Although natural language processing approaches for inferring higher-level concepts have shown promise for bringing structure to clinical texts, interpreting results is often challenging, involving the need to move between abstracted representations and constituent text elements. Our goal was to build interactive visual tools to support the process of interpreting rich representations of histories of patients with cancer. METHODS: Qualitative inquiry into user tasks and goals, a structured data model, and an innovative natural language processing pipeline were used to guide design. RESULTS: The resulting information visualization tool provides cohort- and patient-level views with linked interactions between components. CONCLUSION: Interactive tools hold promise for facilitating the interpretation of patient summaries and identification of cohorts for retrospective research.

[Effects of minimally invasive versus open esophagectomy on circulating tumor cells in patients with esophageal cancer].

OBJECTIVE: To investigate the effects of minimally invasive esophagectomy (MIE) and open esophagectomy (OE) on the level of circulating tumor cells (CTCs) in patients with esophageal cancer (EC). METHODS: A total of 73 patients with EC undergoing MIE (n=38) or OE (n=35) in our department between October, 2015 and October, 2017 were enrolled, with 10 patients with benign esophagus disease and 10 healthy volunteers as controls. The levels of CTCs in the peripheral blood of the participants were detected using CanPatrolTM technique and analyzed for their association with the operation methods and perioperative complications. RESULTS: CTCs were detected in 60.3% (44/73) of the EC patients but in none of the control subjects. CTC level after the surgery was significantly higher than that during the surgery, and CTC level during the surgery was significantly higher than that before surgery (P<0.001). The preoperative and intra-operative CTC levels were not significantly different between MIE and OE groups (P>0.05), but the postoperative CTC level was significantly lower in MIE group than in OE group, and postoperative increment of CTC level (from the preoperative level) was significantly lower in MIE group than in OE group (P<0.001). The total incidence of postoperative complications was significantly lower in MIE group than in OE group (28.9% vs 54.3%, P=0.023), and in both groups, CTC levels in patients with complications were significantly higher than those in patients without complications (P=0.001 and P=0.005 in MIE and OE groups, respectively). CONCLUSION: MIE may help to reduce the number of peripheral blood CTCs early after the operation, and dynamic monitoring CTCs level assists in evaluation of the prognosis of EC patients. CTC level may serve as an indicator for monitoring the prognosis of EC.

[Effects of geranylgeranyltransferaseâ silencing on the proliferation of tongue squamous cancer cells].

Objective This study aims to investigate the effect of geranylgeranyltransferaseⅠ (GGTase-Ⅰ) on the proliferation and growth of tongue squamous cancer cells. Methods Three small interfering RNAs (siRNAs) were designed on the basis of the GGTase-Ⅰ sequence in GeneBank. These siRNAs were then transfected into tongue squamous cancer cells Cal-27. The mRNA and protein expression of GGTase-Ⅰ and RhoA were examined by real-time quantitative polymerase chain reaction and Western blotting, respectively. The expression of Cyclin D1 and p21 were examined by Western blotting. The proliferation and growth ability were analyzed by cell counting kit-8 assay and flow cytometry. Results The mRNA and protein expression of GGTase-Ⅰ in Cal-27 was reduced significantly after the GGTase-Ⅰ siRNAs were transfected (P<0.05). No significant difference in RhoA mRNA and protein expression was detected (P>0.05). Cyclin D1 expression decreased, whereas p21 expression increased significantly. The cell cycle was altered, and the growth-proliferative activity was inhibited (P<0.05). Conclusion GGTase-Ⅰ siRNA can inhibit the expression of GGTase-Ⅰ and the proliferative activity of tongue squamous cancer cells. GGTase-Ⅰ may be a potential target for gene therapy in tongue squamous cell cancer.