RÉSUMÉ
In order to construct a prognostic evaluation model of TLS features in COAD and better realize personalized precision medicine in COAD. Colon adenocarcinoma (COAD) is a common malignant tumor of the digestive system. At present, there is no effective prognostic marker to predict the prognosis of patients. Tertiary lymphoid structure (TLS) affects cancer progression by regulating immune microenvironment. Mining COAD biomarkers based on TLS-related genes helps to improve the prognosis of patients. In order to construct a prognostic evaluation model of TLS features in COAD and better realize personalized precision medicine in COAD. The mRNA expression data and clinical information of COAD and adjacent tissues were downloaded from the Cancer Genome Atlas database. The differentially expressed TLS-related genes of COAD relative to adjacent tissues were obtained by differential analysis. TLS gene co-expression analysis was used to mine genes highly related to TLS, and the intersection of the two was used to obtain candidate genes. Univariate, LASSO, and multivariate Cox regression analysis were performed on candidate genes to screen prognostic markers to construct a risk assessment model. The differences of immune characteristics were evaluated by ESTIMATE, ssGSEA and CIBERSORT in high and low risk groups of prognostic model. The difference of genomic mutation between groups was evaluated by tumor mutation burden score. Screening small molecule drugs through the GDSC library. Finally, a nomogram was drawn to evaluate the clinical value of the prognostic model. Seven TLS-related genes ADAM8, SLC6A1, PAXX, RIMKLB, PTH1R, CD1B, and MMP10 were screened to construct a prognostic model. Survival analysis showed that patients in the high-risk group had significantly lower overall survival rates. Immune microenvironment analysis showed that patients in the high-risk group had higher immune indicators, indicating higher immunity. The genomic mutation patterns of the high-risk and low-risk groups were significantly different, especially the KRAS mutation frequency was significantly higher in the high-risk group. Drug sensitivity analysis showed that the low-risk group was more sensitive to Erlotinib, Savolitinib and VE _ 822, which may be used as a potential drug for COAD treatment. Finally, the nomogram constructed by pathological features combined with RiskScore can accurately evaluate the prognosis of COAD patients. This study constructed and verified a TLS model that can predict COAD. More importantly, it provides a reference standard for guiding the prognosis and immunotherapy of COAD patients.
Sujet(s)
Marqueurs biologiques tumoraux , Tumeurs du côlon , Structures lymphoïdes tertiaires , Microenvironnement tumoral , Humains , Microenvironnement tumoral/génétique , Microenvironnement tumoral/immunologie , Tumeurs du côlon/génétique , Tumeurs du côlon/traitement médicamenteux , Tumeurs du côlon/anatomopathologie , Tumeurs du côlon/mortalité , Structures lymphoïdes tertiaires/génétique , Structures lymphoïdes tertiaires/anatomopathologie , Pronostic , Marqueurs biologiques tumoraux/génétique , Régulation de l'expression des gènes tumoraux , Femelle , Mâle , Mutation , Adénocarcinome/génétique , Adénocarcinome/traitement médicamenteux , Adénocarcinome/anatomopathologie , Adénocarcinome/mortalité , Adulte d'âge moyen , Analyse de profil d'expression de gènes , Antinéoplasiques/usage thérapeutiqueRÉSUMÉ
Introduction. Contamination of specimens and overuse of broad spectrum antibiotics contribute to false positives and false negatives, respectively. Therefore, useful and applicable biomarkers of bacteremia are still required.Hypothesis/Gap Statement. IL-6 can be used as a serum biomarker to discriminate among bacterial infections and fungal infections in febrile patients with a bloodstream infection.Aim. We aimed to evaluate the diagnostic efficiency of neutrophil/lymphocyte ratio (NLR), procalcitonin (PCT) and interleukin-6 (IL-6) in discriminating Gram-negative (G-) bacteria from Gram-positive (G+) bacteria and fungi in febrile patients.Methodology. A total of 567 patients with fever were evaluated. Serum levels of IL-6, PCT, NLR and CRP were compared among a G- group (n=188), a G+ group (n=168), a fungal group (n=38) and a culture negative group (n=173). Sensitivity, specificity, Yuden's index and area under the Receiver operating characteristic (ROC) curve (AUC) were obtained to analyse the diagnostic abilities of these biomarkers in discriminating bloodstream infection caused by different pathogens.Results. Serum IL-6 and PCT in the G- group increased significantly when compared with both the G+ group and fungal group (P <0.05). AUC of IL-6 (0.767, 95â% CI:0.725-0.805) is higher than AUC of PCT (0.751, 95â% CI:0.708-0.796) in discriminating the G- group from G+ group. When discriminating the G- group from fungal group, the AUC of IL-6 (0.695, 95â% CI:0.651-0.747) with a cut-off value of 464.3 pg ml-1 was also higher than the AUC of PCT (0.630, 95â% CI:0.585-0.688) with a cut-off value of 0.68 ng ml-1. Additionally, AUC of NLR (0.685, 95â% CI:0.646-0.727) in discriminating the fungal group from G+ group at the cut-off value of 9.03, was higher than AUC of IL-6, PCT and CRP.Conclusion. This study suggests that IL-6 could be used as a serum biomarker to discriminate among bacterial infections and fungal infections in febrile patients with a bloodstream infection. In addition, NLR is valuable to discriminate fungal infections from Gram-positive infections in febrile patients with a bloodstream infection.
Sujet(s)
Marqueurs biologiques/sang , Fièvre/sang , Infections bactériennes à Gram négatif/sang , Infections bactériennes à Gram positif/sang , Mycoses/sang , Adolescent , Adulte , Sujet âgé , Hémogramme , Protéine C-réactive/analyse , Calcitonine/sang , Analyse discriminante , Fièvre/diagnostic , Infections bactériennes à Gram négatif/diagnostic , Infections bactériennes à Gram positif/diagnostic , Humains , Interleukine-6/sang , Lymphocytes/cytologie , Mâle , Adulte d'âge moyen , Mycoses/diagnostic , Granulocytes neutrophiles/cytologie , Courbe ROC , Études rétrospectives , Jeune adulteRÉSUMÉ
Glucose oxidase (GOx) is regarded as an ideal endogenous natural enzyme for tumor starvation therapy and photothermal therapy (PTT) is a promising strategy for the ablation of primary tumor. In this work, Cu-doped cobalt oxide and porous carbon nanocomposites (CuCo(O)@PCNs) were synthesized from double-layered ZIF-8@ZIF-67 and GOx was loaded in the porous carbon to form a CuCo(O)/GOx@PCNs hybrid nanozyme. CuCo(O) was characterized as the Cu0.3Co2.7O4 phase through X-ray diffraction analysis and it can react with H2O2 to generate O2 and alleviate tumor hypoxia, resulting in the recovered enzymatic activity of GOx and the enhanced starvation therapy. The porous nanocarbon can ablate the primary tumor because of its high photothermal conversion efficiency of 40.04%. The three-in-one functions of oxygen supply, glucose consumption, and photothermal conversion were realized in the ZIFs-derived CuCo(O)/GOx@PCNs nanozyme and the starvation therapy effect was improved by PTT and oxygen supplement. Furthermore, the inhibition effect of CuCo(O)/GOx@PCNs on metastatic tumor is similar to combined therapy of the nanozyme and the immune checkpoint-blocking antibody, α-PD-1. The related antitumor immune mechanism was studied through the analysis of immune-related proinflammatory cytokines and the activated T cells. This work may provide new ideas for the development and application of the ZIFs-derived hybrid nanozyme in tumor therapy and the CuCo(O)/GOx@PCNs nanozyme may be a promising alternative to immune checkpoint inhibitors.
Sujet(s)
Carbone/usage thérapeutique , Cobalt/usage thérapeutique , Cuivre/usage thérapeutique , Glucose oxidase/usage thérapeutique , Imidazoles/usage thérapeutique , Réseaux organométalliques/usage thérapeutique , Tumeurs/thérapie , Oxydes/usage thérapeutique , Animaux , Lignée cellulaire tumorale , Humains , Immunothérapie , Souris , Thérapie photothermique , Hypoxie tumoraleRÉSUMÉ
OBJECTIVE: Gastric cancer (GC) is a gastrointestinal tumor. This study is aimed to explore the regulatory mechanism of long non-coding RNA BLACAT1 (BLACAT1)/microRNA-149-5p (miR-149-5p)/KIF2A cascade on GC. METHODS: The expression of BLACAT1, miR-149-5p and KIF2A in GC was detected by qRT-PCR. The proliferation, migration and invasion of GC cells in vitro were analyzed by MTT, wound-healing and transwell assay, respectively. The xenograft tumor model was constructed in nude mice to confirm the inhibition effect of BLACAT1 knockdown on GC in vivo. Then, dual-luciferase reporter assay was used to detect the interactions among BLACAT1, miR-149-5p and KIF2A. Western blot assay was performed to determine the protein expression of KIF2A. RESULTS: The expression of BLACAT1 and KIF2A was up-regulated in GC, but miR-149-5p expression was down-regulated. Silencing of BLACAT1 retarded the proliferation, migration and invasion of GC cells in vitro and the growth of tumor xenograft in vivo. Moreover, BLACAT1 acted as the molecular sponge of miR-149-5p to up-regulate KIF2A expression. At last, feedback experiments suggested that BLACAT1 accelerated the proliferation, migration and invasion of GC cells by regulating miR-149-5p/KIF2A axis. CONCLUSION: BLACAT1 facilitated the tumorigenesis of GC through regulating miR-149-5p/KIF2A axis, which indicated BLACAT1/miR-149-5p/KIF2A cascade may be a new therapeutic target.
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BACKGROUND: To evaluate an innovative open necrosectomy strategy with continuous positive drainage and prophylactic diverting loop ileostomy for the management of late infected pancreatic necrosis (LIPN). METHODS: Consecutive patients were divided into open necrosectomy (ON) group (n = 23), open necrosectomy with colonic segment resection (ON+CSR) group (n = 8) and open necrosectomy with prophylactic diverting loop ileostomy (ON+PDLI) group (n = 11). Continuous positive drainage (CPD) via double-lumen irrigation-suction tube (DLIST) was performed in ON+PDLI group. The primary endpoints were duration of organ failure after surgery, postoperative complication, the rate of re-surgery and mortality. The secondary endpoints were duration of hospitalization, cost, time interval between open surgery and total enteral nutrition (TEN). RESULTS: The recovery time of organ function in ON+PDLI group was shorter than that in other two groups. Colonic complications occurred in 13 patients (56.5%) in the ON group and 3 patients (27.3%) in the ON+PDLI group (p = 0.11). The length of stay in the ON+PDLI group was shorter than the ON group (p = 0.001). The hospitalization cost in the ON+PDLI group was less than the ON group (p = 0.0052). CONCLUSION: ON+PDLI can avoid the intestinal dysfunction, re-ileostomy, the resection of innocent colon and reduce the intraoperative trauma. Despite being of colonic complications before or during operation, CPD + PDLI may show superior effectiveness, safety, and convenience in LIPN.
Sujet(s)
Infections intra-abdominales , Pancréatite aigüe nécrotique , Drainage , Humains , Iléostomie/effets indésirables , Pancréatite aigüe nécrotique/chirurgie , Complications postopératoires/étiologie , Complications postopératoires/prévention et contrôle , Études rétrospectives , Résultat thérapeutiqueRÉSUMÉ
To establish a continuous reinfusion of succus entericus and enteral nutrition (EN) in complex high-output fistula (HOF). Percutaneous puncture and catheterization technique was used to establish continuous reinfusion of succus entericus and EN in complex HOF. From May 2010 to June 2018, 21 patients with complex HOF used continuous reinfusion of succus entericus and EN. Six of them were completely cured, and 15 cases were cured after definitive surgery. Percutaneous puncture and catheterization technique was shown to be a useful and effective method for establishing continuous reinfusion of succus entericus and EN in patients with complex HOF. This method can prevent succus entericus loss and remove the barrier to implementing EN in HOF.
Sujet(s)
Colostomie , Nutrition entérale/méthodes , Fistule intestinale/thérapie , Sécrétions intestinales , Adulte , Femelle , Humains , Fistule intestinale/imagerie diagnostique , Fistule intestinale/étiologie , Mâle , Adulte d'âge moyen , Nutrition parentérale , Études rétrospectivesRÉSUMÉ
This study aimed to assess the efficacy of double-lumen irrigation-suction tube (DLIST) in treating severe intra-abdominal infection (SIAI) induced by endoscopic sphincterotomy-related perforation (EST-rP). We enrolled 34 consecutive patients who had been transferred to our hospital with SIAI induced by EST-rP from January 2000 to June 2018. Then they were assigned into two groups based on whether or not rescue surgery had been performed: failed nonoperative treatment group (n = 9) and failed rescue surgery treatment group (n = 25). All 34 patients received DLIST for positive draining by surgery in our hospital. Data collection included demographics, indication for endoscopic retrograde cholangiopancreatography, time to rescue surgery, surgical procedure, surgical success rate, complications, hospital stay, and postoperative outcome. The research enrolled 34 patients (ages 27-79 years, mean of 57.8 ± 12.1 years). There were no significant differences in age and gender between two groups (P > 0.05). After being admitted, they were diagnosed with sepsis induced by SIAI (Sequential Organ Failure Assessment score range of 2-6, mean of 3.6 ± 0.95). The time from endoscopic retrograde cholangiopancreatography to rescue surgery was 12 to 336 hours (mean of 73.7 ± 72.2 hours); overall hospital stay was 15 to 405 (mean of 127.5 ± 81.5) days. The hospital stay was significantly longer in the failed rescue surgery group than that of the failed nonoperative treatment group (P < 0.05). The overall mortality rate was 11.8 per cent (4/34). The mortality rate was 16 per cent (4/25) and 0 per cent (0/9), respectively. As a modified suction technology, DLIST placement can effectively treat SIAI induced by EST-rP and lower the mortality rate of rescue surgery treatment.
Sujet(s)
Infections intra-abdominales/thérapie , Complications postopératoires/thérapie , Sphinctérotomie endoscopique/effets indésirables , Aspiration (technique)/instrumentation , Adulte , Sujet âgé , Cholangiopancréatographie rétrograde endoscopique , Femelle , Humains , Infections intra-abdominales/étiologie , Mâle , Adulte d'âge moyen , Études rétrospectives , Aspiration (technique)/méthodes , Résultat thérapeutiqueRÉSUMÉ
Background: Coupled plasma filtration adsorption (CPFA) is an extracorporeal treatment based on plasma filtration associated with an adsorbent cartridge and hemofiltration. CPFA is able to remove inflammatory mediators and it has been used to treat severe sepsis and multiple organ dysfunction. Limited experience exists on the use of CPFA in treating intra-abdominal infection (IAI). Methods: In this study, the efficacy of CPFA in treating patients with severe IAI and liver failure was evaluated in a retrospective analysis of 76 cases. Results: The survival rate of patients treated with CPFA was 82.6%, with effective removal of endotoxin and inflammatory mediators. Conclusion: Our data suggest that CPFA can be safely and effectively used to lower morbidity and mortality rates of patients with severe IAI and liver failure.
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Endotoxines/composition chimique , Hémofiltration , Infections intra-abdominales/thérapie , Plasma sanguin , Adsorption , Adulte , Sujet âgé , Femelle , Humains , Infections intra-abdominales/complications , Défaillance hépatique/complications , Mâle , Adulte d'âge moyen , Études rétrospectives , Taux de survieRÉSUMÉ
RATIONALE: Currently, fistucolysis helps to establish intestinal nutrition and succus entericus reinfusion in the case of controllable mature high-output enterocutaneous fistula. However, if the tube cannot reach the distal limb of a fistula, fistuloclysis is not achieved. We proposed a strategy to establish succus entericus reinfusion for intractable intestinal fistula through percutaneous enterostomy. PATIENT CONCERNS: A 43-year-old man was transferred to our facility for postoperative enterocutaneous fistulae, sepsis, malnutrition, and electrolyte and fluid imbalance. The contrast X-ray demonstrated the breakdown of the primary anastomosis, with fistula output ranging from 1500 to 2000âmL/d, despite the administration of medications to reduce gastrointestinal secretions. DIAGNOSES: The patient was diagnosed with high-output anastomosis fistula by gastrointestinal radiography. INTERVENTIONS: We used percutaneous enterostomy to establish fistuloclysis. OUTCOMES: Fistuloclysis was established by percutaneous enterostomy successfully. No complications were found during the past 4-month follow-up after percutaneous enterostomy. He is waiting for reconstruction surgery after 6 months' enteral nutrition (EN). LESSONS: Fistuloclysis-assisted EN, if used appropriately, avoids the complications of long-term parenteral nutrition (PN) and may promote faster fistula healing.
Sujet(s)
Nutrition entérale/méthodes , Entérostomie/méthodes , Traitement par apport liquidien/méthodes , Fistule intestinale , Complications postopératoires/thérapie , Sepsie , Troubles de l'équilibre hydroélectrolytique , Adulte , Humains , Fistule intestinale/diagnostic , Fistule intestinale/étiologie , Fistule intestinale/physiopathologie , Fistule intestinale/chirurgie , Intestins/imagerie diagnostique , Intestins/physiopathologie , Mâle , État nutritionnel , Radiographie abdominale/méthodes , Sepsie/étiologie , Sepsie/thérapie , Stomies chirurgicales , Résultat thérapeutique , Troubles de l'équilibre hydroélectrolytique/étiologie , Troubles de l'équilibre hydroélectrolytique/thérapieRÉSUMÉ
INTRODUCTION: Hepatic Portal Venous Gas (HPVG) is a rare pathological condition that may be caused by iatrogenic factors. CASE REPORT: A 66-year-old Chinese male patient with HPVG underwent laparotomy for chronic bowel ischemia. Transcathete cardiac defibrillator was implanted via left subclavian vein for ventricular tachycardia. DISCUSSION: There are many hypotheses about how gas runs through the intestine into the mesenteric portal venous system. HPVG patients can be improved through comprehensive management. Patients with mesenteric ischemia should be observed in hospital and after discharge, and need surgical intervention if chronic bowel ischemia recurs. CONCLUSION: This case proves the usefulness of comprehensive management in treating HPVG. Prognosis of HPVG should consider the pathological changes contributing to HPVG.
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BACKGROUND: An optimal alimentary tract reconstruction technique after laparoscopic total gastrectomy (LTG) remains controversial. The authors developed a new simple technique for intracorporeal esophagojejunal anastomosis that employs a conventional purse-string suture instrument (PSI) and circular stapler. METHODS: From May 2014 to April 2016, 41 consecutive patients with gastric cancer underwent LTG in the author's institution. Intracorporeal esophagojejunal anastomosis using the following method was attempted for all patients. After total gastrectomy was completed laparoscopically, a small vertical incision (about 40 mm) was created at the left midclavicular line and retracted by a wound retractor. An anvil of a 25 mm circular stapler was introduced into the abdominal cavity. Then a previously prepared surgical glove, which was cut open at the thumb and the little finger through which the two hand shafts of the PSI were passed separately and sealed by ties, was attached to the wound retractor to maintain airtightness, and the PSI was introduced into the abdominal cavity. The following procedure was similar to conventional open surgery except that it was performed under laparoscopic vision. RESULTS: Intracorporeal esophagojejunal anastomosis was performed successfully for all 41 patients. No case required extension of the initial incision for difficulties during anastomosis. The mean operation time was 245 minutes, and the mean time for the purse-string suture and anvil placement was 15 minutes. Tumor-free margins were achieved in all 41 patients. There were no anastomosis-related complications or other major surgical complications. CONCLUSIONS: With the described method, intracorporeal esophagojejunal anastomosis can be performed easily and safely.
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Anastomose chirurgicale/méthodes , Gastrectomie/méthodes , Laparoscopie/méthodes , Tumeurs de l'estomac/chirurgie , Agrafage chirurgical/méthodes , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Anastomose chirurgicale/effets indésirables , Oesophage/chirurgie , Femelle , Gastrectomie/effets indésirables , Humains , Jéjunum/chirurgie , Laparoscopie/effets indésirables , Mâle , Adulte d'âge moyen , Durée opératoire , Études rétrospectives , Agrafage chirurgical/effets indésirables , Techniques de suture/effets indésirables , Matériaux de sutureRÉSUMÉ
BACKGROUND: Mobilization of the thyroid during an endoscopic thyroidectomy (ET) via a breast approach was originally carried out from the lower pole to the upper pole (upward approach). Here, we applied a modified circular approach to achieve better exposure of the surgical field, in which the path of thyroid mobilization started from the isthmus and resembled a circle. The purpose of this study is to evaluate the safety and feasibility of the circular approach compared with the upward approach. PATIENTS AND METHODS: From December 2008 to June 2013, 144 patients who underwent attempted ET via a breast approach were enrolled in this study, and their clinical outcomes were evaluated. RESULTS: In total, 141 of 144 procedures were successfully performed under endoscopy, including 60 (42.6%) via the upward approach and 81 (57.4%) via the circular approach. The mean operating time was significantly shorter in the circular approach group than in the upward approach group (90.6 minutes versus 112.5 minutes for hemithyroidectomy; 109.5 minutes versus 133.2 minutes for subtotal thyroidectomy; P<.05). Furthermore, the incidence of the transient recurrent laryngeal nerve palsy decreased in the circular approach group compared with the upward approach group (2.5% versus 13.3%; P<.05). CONCLUSIONS: These results seem to indicate that the circular approach is a better method of mobilizing the thyroid, especially for large nodules located in the lower pole of the thyroid. This approach may provide a better view of the surgical field, reduced operating times, and fewer postoperative complications.