ABSTRACT
BACKGROUND AND AIMS: Succinate dehydrogenase enzyme (SDH) is frequently diminished in samples from patients with hepatocellular carcinoma (HCC), and SDH reduction is associated with elevated succinate level and poor prognosis in patients with HCC. However, the underlying mechanisms of how impaired SDH activity promotes HCC remain unclear. APPROACH AND RESULTS: In this study, we observed remarkable downregulations of SDH subunits A and B (SDHA/B) in chronic liver injury-induced murine HCC models and patient samples. Subsequent RNA sequencing, hematoxylin and eosin staining, and immunohistochemistry analyses of HCC samples revealed that Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) were significantly upregulated in HCC, with their levels inversely correlating with that of SDHA/B. YAP/TAZ stability was greatly enhanced in SDHA/B-depleted HCC cells along with accumulation of succinate. Further mechanistic analyses demonstrated that impaired activity of SDHA/B resulted in succinate accumulation, which facilitated the deNEDDylation of cullin1 and therefore disrupted the E3 ubiquitin ligase SCF ß-TrCP complex, consequently leading to YAP/TAZ stabilization and activation in HCC cells. The accelerated in vitro cell proliferation and in vivo tumor growth caused by SDHA/B reduction or succinate exposure were largely dependent on the aberrant activation of YAP/TAZ. CONCLUSIONS: Our study demonstrated that SDHA/B reduction promotes HCC proliferation by preventing the proteasomal degradation of YAP/TAZ through modulating cullin1 NEDDylation, thus binding SDH-deficient HCC cells to YAP/TAZ pathway and rendering these cells vulnerable to YAP/TAZ inhibition. Our findings warrant further investigation on the therapeutic effects of targeting YAP/TAZ in patients with HCC displaying reduced SDHA/B or elevated succinate levels.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Animals , Mice , Carcinoma, Hepatocellular/pathology , Adaptor Proteins, Signal Transducing/metabolism , Liver Neoplasms/pathology , Trans-Activators/metabolism , YAP-Signaling Proteins , Succinates , Electron Transport Complex II/metabolismABSTRACT
The explosive growth of China's express delivery industry has greatly increased plastic waste, with low-value plastics not effectively utilized, such as PE packaging bags, which are often not recycled and end up in landfills or incinerators, causing significant resource waste and severe plastic pollution. A gate -to- grave life cycle assessment was adopted to assess the impacts of express delivery plastic waste (EDPW) management models (S1, landfill; S2, incineration; S3, mechanical pelletization), with Suzhou, China as a case. Results showed that mechanical pelletization, was the most environmentally advantageous, exhibiting a comprehensive environmental impact potential of -215.54 Pt, significantly lower than that of landfill (S1, 78.45 Pt) and incineration (S2, -121.77 Pt). The analysis identified that the end-of-life disposal and sorting stages were the principal contributors to environmental impacts in all three models, with transportation and transfer stages of residual waste having minimal effects. In terms of all environmental impact categories, human carcinogenic toxicity (HTc) emerged as the most significant contributor in all three scenarios. Specifically, S1 exhibited the most detrimental effect on human health, while S2 and S3 showed positive environmental impacts. Based on these findings, it is recommended that the application and innovation in mechanical recycling technologies be enhanced, the promotion of the eco-friendly transformation of packaging materials be pursued, and a sustainable express delivery packaging recycling management system be established. These strategies are essential for achieving more eco-friendly management of EDPW, reducing its environmental pollution, and moving towards more sustainable express delivery management practices.
Subject(s)
Incineration , Plastics , Recycling , Waste Disposal Facilities , Waste Management , China , Waste Management/methods , Refuse Disposal/methods , HumansABSTRACT
Islet transplantation is a potential treatment option for certain patients with type 1 diabetes; however, it still faces barriers to widespread use, including the lack of tools to monitor islet grafts post-transplantation. This study investigates whether labeling neonatal porcine islets (NPI) with polyvinylpyrrolidone-coated superparamagnetic iron oxide nanoparticles (PVP-SPIO) affects their function, and whether this nanoparticle can be utilized to monitor NPI xenografts with magnetic resonance imaging (MRI) in a mouse model. In vitro, PVP-SPIO-labeled NPI in an agarose gel was visualized clearly by MRI. PVP-SPIO-labeled islets were then transplanted under the kidney capsules of immunodeficient nondiabetic and diabetic mice. All diabetic mice that received transplantation of PVP-SPIO-labeled islets reached normoglycemia. Grafts appeared as hypo-intense areas on MRI and were distinguishable from the surrounding tissues. Following injection of spleen cells from immunocompetent mice, normoglycemic recipient mice became diabetic and islet grafts showed an increase in volume, accompanied by a mixed signal on MRI. Overall, this study demonstrates that PVP-SPIO did not affect the function of NPI that PVP-SPIO-labeled islets were easily seen on MRI, and changes in MRI signals following rejection suggest a potential use of PVP-SPIO-labeled islets to monitor graft viability.
Subject(s)
Diabetes Mellitus, Experimental , Islets of Langerhans Transplantation , Islets of Langerhans , Animals , Humans , Islets of Langerhans Transplantation/methods , Magnetic Iron Oxide Nanoparticles , Magnetic Resonance Imaging/methods , Mice , Povidone , Swine , Transplantation, Heterologous/methodsABSTRACT
Amounting evidence suggested that long non coding RNAs (lncRNAs) played vital roles in the progression of various cancers. The aim of this study is to examine the biological roles and underlying mechanisms of lncRNA MAFG-AS1 in the tumorigenesis of breast cancer (BC) cells. Here we showed that downregulation of MAFG-AS1 inhibited the viability, migration, and invasion of BC cells. Mechanism investigation showed that inhibition of MAFG-AS1 induced apoptosis via the intrinsic apoptotic pathway and overexpression of Bcl-2 could inhibited it. Further, MAFG-AS1 acts as a sponge of miR-574-5p which directly binds to SOD2 mRNA. Re-expression of SOD2 using a 3'-UTR mutant SOD2 reversed the effects of silencing of MAFG-AS1 on BC cells. Finally, downregulation of MAFG-AS1 inhibited the growth of tumour in vivo. Together, MAFG-AS1 acts as an oncogene via regulation of miR-574-5p/SOD2 axis in BC cells.
Subject(s)
Breast Neoplasms/genetics , Gene Expression Regulation, Neoplastic , MicroRNAs/metabolism , RNA, Long Noncoding/metabolism , Superoxide Dismutase/genetics , Animals , Apoptosis , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Carcinogenesis , Caspases/metabolism , Cell Line, Tumor , Cell Movement , Cell Survival , Female , Humans , Mice, SCID , Neoplasm Invasiveness , Superoxide Dismutase/metabolismABSTRACT
BACKGROUND: Surgical resection is the only potentially curative treatment for pancreatic ductal adenocarcinoma (PDAC) and the survival of patients after radical resection is closely related to relapse. We aimed to develop models to predict the risk of relapse using machine learning methods based on multiple clinical parameters. METHODS: Data were collected and analysed of 262 PDAC patients who underwent radical resection at 3 institutions between 2013 and 2017, with 183 from one institution as a training set, 79 from the other 2 institution as a validation set. We developed and compared several predictive models to predict 1- and 2-year relapse risk using machine learning approaches. RESULTS: Machine learning techniques were superior to conventional regression-based analyses in predicting risk of relapse of PDAC after radical resection. Among them, the random forest (RF) outperformed other methods in the training set. The highest accuracy and area under the receiver operating characteristic curve (AUROC) for predicting 1-year relapse risk with RF were 78.4% and 0.834, respectively, and for 2-year relapse risk were 95.1% and 0.998. However, the support vector machine (SVM) model showed better performance than the others for predicting 1-year relapse risk in the validation set. And the k neighbor algorithm (KNN) model achieved the highest accuracy and AUROC for predicting 2-year relapse risk. CONCLUSIONS: By machine learning, this study has developed and validated comprehensive models integrating clinicopathological characteristics to predict the relapse risk of PDAC after radical resection which will guide the development of personalized surveillance programs after surgery.
Subject(s)
Adenocarcinoma , Machine Learning , Humans , ROC Curve , Recurrence , Support Vector MachineABSTRACT
To investigate whether chemotherapy could prolong the postoperative survival time in patients with early stages pancreatic ductal adenocarcinoma (PDAC). A total of 5280 stage â A -â ¡B PDAC patients diagnosed from 2010 to 2015 were selected from surveillanceï¼epidemiologyï¼and end results (SEER) database. Propensity score matching (PSM) analysis was adopted to reduce the baseline differences between the groups. Univariate survival analysis was conducted with the Kaplan-Meier method. Multivariate survival analysis was performed with the Cox proportional hazards model. Univariate and multivariate survival analyses showed that age, differentiation, stage, chemotherapy were independent risk factors for the survival of PDAC patients. After PSM, it is found that adjuvant chemotherapy could prolong the median overall survival time (mOS) for stage â B, â ¡A and â ¡B patients. However, for stage â A patients, there were no significant differences in 3-year survival rate and mOS between patients with chemotherapy (=283) and without chemotherapy (=229) (57.4% vs 55.6%, vs all >0.05). Further analyses show that among 101 patients with well differentiated PDAC and 294 patients with moderately differentiated PDAC, there were no significant differences in survival rate and mOS between patients with and without chemotherapy (all >0.05). Among 117 patients with low-differentiated + undifferentiated PDAC, 3-year survival rate and mOS in patients with chemotherapy were significantly better than those without chemotherapy (48.5% vs 34.1%, vs all <0.05). Chemotherapy regimen used currently is not beneficial for patients with moderately and well differentiated stage â A PDAC, but it is an independent prognostic factor for low-differentiated + undifferentiated PDAC patients.
Subject(s)
Adenocarcinoma , Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Adenocarcinoma/pathology , Carcinoma, Pancreatic Ductal/drug therapy , Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Pancreatic Ductal/surgery , Chemotherapy, Adjuvant , Humans , Neoplasm Staging , Pancreatic Neoplasms/drug therapy , Prognosis , Propensity ScoreABSTRACT
BACKGROUND: The aim of this study is to assess the validity of the measurement of pepsinogen as a screening test for chronic atrophic gastritis (AG) in health check-up populations in China. METHODS: Patients from consecutive regular health check-up were enrolled from January 2014 to June 2015. Endoscopy, combined with monitoring the Helicobacter pylori (Hp) infections, and measuring the serum pepsinogen (PG) were used to determine the diagnostic accuracy of PG for the screening of atrophic gastritis. Histopathology was assessed by the Operative Link on Gastritis Assessment (OLGA) system. Statistical analysis was performed using SPSS statistical software. RESULTS: The total Hp infection rate was 40%. Based on pathology, the 996 participants were divided into three groups: non-atrophic (NAG), mild-moderate atrophic (MAG): stage I and II of the OLGA classification, and severe atrophic (SAG): stage III and IV of the OLGA classification. Compared with NAG and MAG groups, PGR decreased significantly in SAG group (p < 0.05). PGI and PGII levels were significantly elevated in Hp-positive group, while the PGR was markedly decreased (p < 0.01). When MAG and SAG groups were combined and compared with NAG group, the best cutoff value for atrophy diagnosis was PGI ≤50.3 ng/ml; the cutoff value in Hp-negative group was absolutely higher than in Hp-positive group. When NAG and MAG groups were combined and compared with the SAG group, the best cutoff value for diagnosis of severe atrophy was at PGR ≤4.28. The cutoff values in Hp-negative and Hp-positive groups were calculated at PGR ≤6.28 and ≤4.28, respectively. CONCLUSIONS: Pepsinogens play an important role in the identification of patients with atrophic gastritis and severe AG. Use of different cutoff values of PG for Hp-negative and Hp-positive groups may offer greater efficacy in the diagnosis of AG.
Subject(s)
Gastritis, Atrophic/diagnosis , Helicobacter Infections/blood , Helicobacter pylori , Mass Screening/methods , Pepsinogen A/blood , Adult , China , Female , Gastritis, Atrophic/microbiology , Gastritis, Atrophic/pathology , Helicobacter Infections/complications , Humans , Male , Middle Aged , Reference ValuesABSTRACT
OBJECTIVE: To investigate the effects of siRNAs targeting CD97 immune epitopes on proliferation, infiltration, apoptosis and cell cycle of breast cancer cells. METHODS: siRNA sequences targeting CD97EGF and CD97Stalk immune epitopes were designed according to Gene Bank NM_001025160.2 with smart siCatchTM siRNA design software. CD97siRNAs were transfected into MDA-MB231 cells in which CD97 was highly expressed. Highest sensitive CD97EGF and CD97Stalk siRNA were screened by Western blotting. Inverted microscope was used to observe the growth of CD97siRNAs-transfected MDA-MB231 cells; the proliferation activity of MDA-MB231 cells was detected by MTT method; the wound healing assay and Transwell migration test were performed to examine the migration and infiltration ability of CD97EGF and CD97Stalk siRNA-transfected MDA-MB231 cells; the effects of CD97EGF siRNA and CD97Stalk siRNA on cell apoptosis and cell cycle of MDA-MB231 cells were detected by TUNEL and flow cytometry. RESULTS: The growth and proliferation activity of CD97siRNAs-transfected MDA-MB231 cells were significantly lower than those in the control groups, and such differences were more significant in CD97Stalk siRNA-transfected group (all P<0.05); scratch test showed that the wound healing rate was lower in CD97siRNAs-transfected groups, especially in CD97Stalk siRNA-transfected group (all P<0.05); Transwell migration showed that the number of MDA-MB231 cells crossing through chambers were less in CD97siRNAs-transfected groups, especially in CD97Stalk siRNA-transfected group (all P<0.05); no significant difference in cell apoptosis was observed between CD97siRNAs-transfected groups and control groups; cell cycle detection showed that CD97siRNAs-transfected groups had less cells in G0/G1 phase and more cells in S phase compared with the control groups, and such effect on cell cycle was more marked in CD97Stalk siRNA-transfected group (all P<0.05). CONCLUSIONS: CD97 plays an important role in the cell growth, proliferation, migration and invasion of breast cancer MDA-MB231 cells, and compared with CD97EGF, CD97Stalk may have more effective inhibitory effects on cellular malignant behaviors.
Subject(s)
Antigens, CD , Epitopes , RNA, Small Interfering , Antigens, CD/genetics , Antigens, CD/immunology , Apoptosis/drug effects , Breast Neoplasms , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Epitopes/genetics , Humans , Neoplasm Invasiveness , RNA, Small Interfering/pharmacology , Receptors, G-Protein-CoupledABSTRACT
BACKGROUND: We systematically reviewed and performed a meta-analysis of the available data regarding neoadjuvant chemo- and/or radiotherapy with special emphasis on tumor response/progression rates, toxicities, and clinical benefit, i.e. resection probabilities and survival estimates. METHODS AND FINDINGS: Trials were identified by searching PUBMED, MEDLINE, and the Cochrane Central Register of Controlled Trials from 1966 to Feb 2015. A total of 18 studies (n = 959) were analyzed. the estimated fraction of patients with complete response was 2.8% (CI 0.8-4.7%) and with partial response 28.7% (CI 18.9%-38.5%). Stable disease was averaged to 45.9% (CI 32.9%-58.9%) in all patients and tumor progression under therapy occurred by estimation in 16.9% (CI 10.2%-23.6%) of the patients. The weighted frequency of those who underwent resection was 65.3% (CI 54.2%-76.5%), and the proportion of R0 resection amounted to 57.4% (CI 48.2%-66.5%). The weighted mean of median survival amounted to 17.9 months (range: 14.7-21.2 months) for the overall cohort of patients, 25.9 months (range: 21.1-30.7 months) for those who were resected, and 11.9 months (range: 10.4-13.5 months) for unresected patients. CONCLUSIONS: The resection and R0 resection rates in the group of borderline resectable tumor patients after neoadjuvant therapy are similar to the resectable tumor patients, much higher than those in unresectable tumor patients. The survival estimates of borderline resectable tumor patients after neoadjuvant therapy were similar to resectable tumor patients. Patients with borderline resectable pancreatic cancer should be included in neoadjuvant protocols and subsequently be reevaluated for resection. How to find chemo-responsiveness before neoadjuvant chemotherapy so as to give individualized treatment is still an important issue.
Subject(s)
Antineoplastic Agents/therapeutic use , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/surgery , Radiotherapy , Antineoplastic Agents/administration & dosage , Chemotherapy, Adjuvant , Humans , Radiotherapy, AdjuvantABSTRACT
RNA interference (RNAi)-mediated gene therapy is a promising approach to cure various diseases. However, developing an effective, safe, specific RNAi delivery system remains a major challenge. In this study, a novel redox-responsive polyetherimide (PEI)-based nanovector, mPEG-SeSe-PEI, was developed and its efficacy evaluated. We prepared three mPEG-SeSe-PEI vector candidates for small interfering glyceraldehyde-3-phosphate dehydrogenase (siGADPH) and determined their physiochemical properties and transfection efficiency using flow cytometry and PEG11.6-SeSe-PEI polymer. We investigated the silencing efficacy of GADPH mRNA expression in PANC-1 cells and observed that PEG11.6-SeSe-PEI/siGADPH (N/P ratio=10) polyplexes possessed the appropriate size and zeta-potential and exhibited excellent in vitro gene silencing effects with the least cytotoxicity in PANC-1 cells. In conclusion, we present PEG11.6-SeSe-PEI as a potential therapeutic gene delivery system for small interfering RNA (siRNA).
Subject(s)
Gene Transfer Techniques , Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+)/genetics , Polyethylene Glycols/administration & dosage , Polymers/administration & dosage , RNA, Small Interfering/administration & dosage , Cell Line, Tumor , Gene Silencing , Humans , Polyethylene Glycols/chemistry , Polymers/chemistry , RNA Interference , RNA, Messenger/antagonists & inhibitorsABSTRACT
BACKGROUND: TGFß-induced (TGFBI/ßig-H3) is a protein inducible by TGFß1 and secreted by many types of cells. It binds to collagen, forms part of the extracellular matrix (ECM), and interacts with integrins on cell surfaces. In this study, we investigated the role of TGFBI in tumorigenesis and the underlying mechanisms. METHODS: Patient serum TGFBI levels were determined by ELISA. TGFBI transgenic and gene knockout mice and TGFBI-overexpressing liver cells were used for mechanistic studies. RESULTS: We demonstrated that patients with cholangiocarcinomas, hepatic carcinomas or gastric carcinomas presented significantly elevated serum TGFBI levels, and the excess TGFBI was derived from the tumor masses. TGFBI overexpression in mice resulted in increased incidence of spontaneous tumors and N,N-diethylnitrosamine (DEN)-induced liver tumor nodules, compared to that in wild type (WT) mice, while TGFBI knockout mice were comparable to WT controls in these 2 aspects. TGFBI promoted the survival of Aml-12 liver cells with DNA damage after irradiation, and augmented their post-irradiation proliferation. It activated the FAK/AKT/AKT1S1/PRS6/EIF4EBP pathway, which is known to modulate cell survival and proliferation. CONCLUSIONS: Our data suggest that TGFBI functions as a promoter of certain gastrointestinal tract cancers. It provides a survival advantage to cells with DNA damage. Over a long time span, this advantage could translate into increased tumor risks.
Subject(s)
Carcinogenesis/metabolism , Extracellular Matrix Proteins/metabolism , Gastrointestinal Neoplasms/metabolism , Gastrointestinal Neoplasms/pathology , Gastrointestinal Tract/pathology , Transforming Growth Factor beta/metabolism , Animals , Apoptosis , Carcinogens , Cell Proliferation , Cell Survival , DNA Damage , Extracellular Matrix Proteins/blood , Gastrointestinal Neoplasms/blood , Humans , Liver Neoplasms/pathology , Mice, Inbred C57BL , Mice, Knockout , Phosphorylation , Signal Transduction , Transforming Growth Factor beta/bloodABSTRACT
OBJECTIVE: To study 3 different strategies of urine drainage following hypospadias urethroplasty, the clinical nursing in their application, and their effects. METHODS: We retrospectively analyzed the clinical data of 595 cases of hypospadias treated by urethroplasty. After surgery, 133 of the patients underwent urine drainage by suprapubic cystostomy (group A), 202 by urethral stent- tube indwelling (group B), and 260 by early initiative micturition with the urethral stent-tube (group C). All the patients received routine postoperative nursing care required for hypospadias repair. RESULTS: Operations were successfully completed in all the cases. Group C showed a remarkably shorter hospital stay and lower incidence rates of urinary fistula and urethral stricture than groups A and B (P<0.05), but there were no significant differences in the three indexes between A and B (P<0.05). CONCLUSION: For urine drainage following hypospadias repair, early initiative micturition with the urethral stent-tube can significantly reduce postoperative complications, decrease difficulties and workload of nursing care, and shorten the hospital stay of the patient.
Subject(s)
Drainage/methods , Hypospadias/surgery , Urethra/surgery , Urine , Cystostomy , Humans , Length of Stay , Male , Postoperative Complications/prevention & control , Plastic Surgery Procedures , Retrospective Studies , Stents , Urethral Stricture/prevention & control , Urinary Fistula/prevention & control , Urologic Surgical Procedures, MaleABSTRACT
Congenital diaphragmatic hernias are primarily found in infants and have a high mortality rate due to neonatal respiratory distress. The most common type of congenital diaphragmatic hernia is Bochdalek hernia, which occurs in the posterolateral diaphragm, with the left side being the most commonly affected. However, congenital diaphragmatic hernias are extremely rare in adults and are often misdiagnosed due to their subtle symptoms. Therefore, we suggest that a contrast-enhanced CT scan should be used for early screening and diagnosis in all patients with sudden severe pain or recurrent ambiguous symptoms in the chest and abdomen. This case report presents a rare occurrence of Bochdalek hernia in an adult male. The patient experienced nonspecific abdominal symptoms after eating. The hernia resulted in the displacement of the left kidney, the transverse colon of the splenic flexure, and most of the stomach into the thoracic cavity. This displacement led to atelectasis of the left lung, which reached three-fifths of its capacity. The patient underwent successful treatment using a combination of laparoscopy and open surgery. Follow-up CT scans conducted two weeks, three months, and one year later revealed a stable condition with no complications.
ABSTRACT
Gastrointestinal stromal tumors (GISTs) are soft tissue sarcomas that originate from the mesenchymal cells of the gastrointestinal tract. Extra-GISTs (EGISTs) are caused by sites outside the gastrointestinal tract. We reported a case of EGIST of the pancreas in a 51-year-old woman. Enhanced CT scan showed a rounded, slightly hypointense focus in the head of the pancreas and the right pars compacta of the descending duodenum. Routine laboratory and endocrine tests were unremarkable. The patient underwent laparoscopic surgery. The diagnosis of EGIST was confirmed through histopathological and immunohistochemical examination. The tumor was found to be CD117+, CD34+, and DOG+ with a high risk of malignancy. No recurrence was observed during the nine-month postoperative follow-up.
ABSTRACT
Precise prognostication is vital for guiding treatment decisions in people diagnosed with pancreatic cancer. Existing models depend on predetermined variables, constraining their effectiveness. Our objective was to explore a novel machine learning approach to enhance a prognostic model for predicting pancreatic cancer-specific mortality and, subsequently, to assess its performance against Cox regression models. Datasets were retrospectively collected and analyzed for 9,752 patients diagnosed with pancreatic cancer and with surgery performed. The primary outcomes were the mortality of patients with pancreatic carcinoma at one year, three years, and five years. Model discrimination was assessed using the concordance index (C-index), and calibration was assessed using Brier scores. The Survival Quilts model was compared with Cox regression models in clinical use, and decision curve analysis was done. The Survival Quilts model demonstrated robust discrimination for one-year (C-index 0.729), three-year (C-index 0.693), and five-year (C-index 0.672) pancreatic cancer-specific mortality. In comparison to Cox models, the Survival Quilts models exhibited a higher C-index up to 32 months but displayed inferior performance after 33 months. A subgroup analysis was conducted, revealing that within the subset of individuals without metastasis, the Survival Quilts models showcased a significant advantage over the Cox models. In the cohort with metastatic pancreatic cancer, Survival Quilts outperformed the Cox model before 24 months but exhibited a weaker performance after 25 months. This study has developed and validated a novel machine learning-based Survival Quilts model to predict pancreatic cancer-specific mortality that outperforms the Cox regression model.
ABSTRACT
The traditional recognition of extracellular matrix (ECM) at tissue sections relies on the time-consuming immunofluorescence that could not meet the demand of rapid diagnosis. Herein, we introduce a thickness-resolved electrochemiluminescence (ECL) microscopy to image thin-layer ECM at tissue sections for fast histopathological analysis. The unique surface-confined ECL mechanism enables to unveil the diversity and complexity of multiple tissue structures with varying thicknesses. Notably, the short lifetimes and the limited diffusion of electrogenerated coreactant radicals combined with their chemical reactivity result in a 2-fold increase in ECL intensity on ECM structures compared to the remaining tissue, enabling ECM visualization without specific labeling. The further quantitation of the ECM localization within tissue sections furnishes crucial insights into tumor progression and, more importantly, differentiates carcinoma and paracancerous tissues from patients in less than 30 min. Moreover, the reported electrochemistry-based microscopy is a dynamic approach allowing to investigate the transport, tortuosity, and trafficking properties through the tissues. This thickness-resolved recognition strategy not only opens new avenues for imaging complex samples but also holds promise for expediting tissue pathologic diagnosis, offering a more automated protocol with enhanced quantitative data compared to current intraoperative pathology methods.
Subject(s)
Electrochemical Techniques , Extracellular Matrix , Neoplasms , Humans , Extracellular Matrix/chemistry , Extracellular Matrix/metabolism , Electrochemical Techniques/methods , Neoplasms/diagnosis , Neoplasms/pathology , Neoplasms/diagnostic imaging , Neoplasms/metabolism , Luminescent Measurements/methods , Microscopy/methodsABSTRACT
Modern machine learning models toward various tasks with omic data analysis give rise to threats of privacy leakage of patients involved in those datasets. Here, we proposed a secure and privacy-preserving machine learning method (PPML-Omics) by designing a decentralized differential private federated learning algorithm. We applied PPML-Omics to analyze data from three sequencing technologies and addressed the privacy concern in three major tasks of omic data under three representative deep learning models. We examined privacy breaches in depth through privacy attack experiments and demonstrated that PPML-Omics could protect patients' privacy. In each of these applications, PPML-Omics was able to outperform methods of comparison under the same level of privacy guarantee, demonstrating the versatility of the method in simultaneously balancing the privacy-preserving capability and utility in omic data analysis. Furthermore, we gave the theoretical proof of the privacy-preserving capability of PPML-Omics, suggesting the first mathematically guaranteed method with robust and generalizable empirical performance in protecting patients' privacy in omic data.
Subject(s)
Algorithms , Privacy , Humans , Data Analysis , Machine Learning , TechnologyABSTRACT
BACKGROUND/AIMS: Open approach was the conventional ways for surgical treatment of pancreatic islet cell tumor. The study was to report the outcome of open approach with pancreatic islet cell tumor in a single institution in China. METHODOLOGY: Forty-four consecutive pancreatic islet cell tumor patients who underwent surgical treatment were retrospectively analyzed. RESULTS: There were 16 pancreatic nonfunctioning islet cell tumor (PNIT) patients and 28 functioning islet cell tumor patients which were insulinoma. Seventeen PNIT were found and larger than media size of thirty-nine insulinoma (4.53 +/- 2.67 vs. 1.87 +/- 0.86, p < 0.05) in diameter. The size of malignant and benign PNIT has a significant difference (6.33 +/- 2.06 vs. 3.45 +/- 2.51, p < 0.05 ), but not in insulinoma. Among PNIT, distal pancreatectomy plus splenectomy were required in 8 patients, while segmental pancreatectomy was performed in 3 cases. In addition, 1 and 4 patients received pancreatoduodenectomy and tumor enucleation respectively. Seventeen insulinomas patients (60.7%) underwent enucleation, and 2 patients (7.1%) underwent distal pancreatectomy with splenectomy. Segmental pancreatectomy, pancreatoduodenectomy and distal pancreatectomy preserving spleen was performed in 2, 4 and 3 cases respectively. The percentage was zero in-hospital death. The morbidity was 6.2% (1/16) for PNIT and 28.6% (8/28) for insulinomas. CONCLUSIONS: Open surgery remains a nice way in the management of pancreatic islet cell tumor at least in our institution.
Subject(s)
Insulinoma/surgery , Neuroendocrine Tumors/surgery , Pancreatectomy , Pancreatic Neoplasms/surgery , Pancreaticoduodenectomy , Adenoma, Islet Cell , Adult , Aged , China , Female , Humans , Insulinoma/pathology , Male , Middle Aged , Neuroendocrine Tumors/pathology , Pancreatectomy/adverse effects , Pancreatic Neoplasms/pathology , Pancreaticoduodenectomy/adverse effects , Postoperative Complications/etiology , Retrospective Studies , Splenectomy , Treatment Outcome , Tumor Burden , Young AdultABSTRACT
BACKGROUND/AIMS: Identification of biomarkers for pancreatic cancer may help diagnosis and treatment of patients. METHODOLOGY: This pilot study evaluated potential markers for pancreatic adenocarcinoma (PAC) in peripheral blood mononuclear cells (PBMC). RNA samples were isolated from PBMCs and hybridized to oligonucleotide arrays. RESULTS: Twenty five-fold leave-two-out analysis identified 10 cancer-associated genes (CAGs). The PAC patients could be identified by the expression profiles of their PBMC with a specificity of 96% and a sensitivity of 80%. CONCLUSIONS: Ten CAGs were potential new markers in PBMC for patients with PAC.
Subject(s)
Adenocarcinoma/genetics , Gene Expression Profiling , Pancreatic Neoplasms/genetics , Adenocarcinoma/blood , Aged , Female , Humans , Leukocytes, Mononuclear , Male , Middle Aged , Oligonucleotide Array Sequence Analysis , Pancreatic Neoplasms/blood , Pilot Projects , Sensitivity and Specificity , Tissue Array AnalysisABSTRACT
OBJECTIVE: To assess the application value of a new radiofrequency device Habib 4X in liver resection. METHODS: A retrospective study was performed during March 2010 to July 2011.Forty-four patients underwent liver resection with radiofrequency device Habib 4X and another 54 patients traditional liver resection.Intraoperative blood loss, blood transfusion, Pringle's maneuver requirement, liver parenchyma transaction time, liver function recovery, complications, mortality and recurrence were recorded. RESULTS: The mean resection time was (67 ± 22) min for Habib 4X group versus (93 ± 23) min for traditional group (P = 0.000). Pringle's maneuver was required in 10 patients (22.7%) for Habib 4X group and 31 (57.4%) for traditional group (P = 0.001). The mean blocking time was (7 ± 2) vs (18 ± 6) min (P = 0.001), mean blood loss volume (243 ± 132) vs (500 ± 421) ml (P = 0.002). Postoperative recovery of liver function was better in Habib 4X group than traditional group. None developed mortality in Habib 4X group. And no resection margin recurred during a 18-month follow-up. CONCLUSIONS: Bipolar radiofrequency device Habib 4X is recommended for pre-coagulation in hepatectomy. And the advantages of minimized blood loss and reduced resection time result in its lower rates of morbidity and mortality.