Abstract BackgroundBased on previous meta-analyses and comparative evidence, robotic approach might lead to a higher or at least similar spleen-preservation rates when comparing with laparoscopic approach in spleen preserving distal pancreatectomy (SPDP) for benign or low-grade malignant pancreatic tumors 1–3 . But high-quality evidence lacks and controversy exists. Therefore, we planned to initiate a prospective, patient-blinded, randomized, controlled trial (RCT) to compare robotic assisted spleen preserving distal pancreatectomy (RSPDP) with laparoscopic spleen preserving distal pancreatectomy (LSPDP), with special consideration to the success rate of splenic vessel-preserving (Kimura) approach, as well as perioperative variables, and cost analysis.MethodsPatients with benign or low-grade malignant pancreatic tumors are potential candidates for this RCT. Enrolled participants are randomized into RSPDP (observational arm) or LSPDP (control arm) groups as a ratio of 1:1. The primary outcome is the success rate of splenic vessel-preserving (Kimura) approach. The secondary outcomes include total success rate of spleen preserving (Kimura and Warshaw approaches), intraoperative variables, time to functional recovery, postoperative complications, mortality, and cost/efficacy analysis.DiscussionWe plan to conduct a randomized controlled trial to detect the potential advantages of robotic approach in spleen vessels preservation compared with traditional laparoscopic approach. RSPDP may improve spleen vessels preservation rate in selected patients.Trial registrationChinese Clinical Trial Registry, No: ChiCTR2000029177. Registered on 18 January, 2020.
Flourine-18-flortaucipir tau positron emission tomography (PET) was developed for the detection for Alzheimer's disease. Human imaging studies have begun to investigate its use in chronic traumatic encephalopathy (CTE). Flortaucipir-PET to autopsy correlation studies in CTE are needed for diagnostic validation. We examined the association between end-of-life flortaucipir PET and postmortem neuropathological measurements of CTE-related tau in six former American football players.Three former National Football League players and three former college football players who were part of the DIAGNOSE CTE Research Project died and agreed to have their brains donated. The six players had flortaucipir (tau) and florbetapir (amyloid) PET prior to death. All brains from the deceased participants were neuropathologically evaluated for the presence of CTE. On average, the participants were 59.0 (SD = 9.32) years of age at time of PET. PET scans were acquired 20.33 (SD = 13.08) months before their death. Using Spearman correlation analyses, we compared flortaucipir standard uptake value ratios (SUVRs) to digital slide-based AT8 phosphorylated tau (p-tau) density in a priori selected composite cortical, composite limbic, and thalamic regions-of-interest (ROIs).Four brain donors had autopsy-confirmed CTE, all with high stage disease (n = 3 stage III, n = 1 stage IV). Three of these four met criteria for the clinical syndrome of CTE, known as traumatic encephalopathy syndrome (TES). Two did not have CTE at autopsy and one of these met criteria for TES. Concomitant pathology was only present in one of the non-CTE cases (Lewy body) and one of the CTE cases (motor neuron disease). There was a strong association between flortaucipir SUVRs and p-tau density in the composite cortical (ρ = 0.71) and limbic (ρ = 0.77) ROIs. Although there was a strong association in the thalamic ROI (ρ = 0.83), this is a region with known off-target binding. SUVRs were modest and CTE and non-CTE cases had overlapping SUVRs and discordant p-tau density for some regions.Flortaucipir-PET could be useful for detecting high stage CTE neuropathology, but specificity to CTE p-tau is uncertain. Off-target flortaucipir binding in the hippocampus and thalamus complicates interpretation of these associations. In vivo biomarkers that can detect the specific p-tau of CTE across the disease continuum are needed.
Abstract Tiaogan Yunpi Decoction (TGYPD) is a clinical experience commonly used by tutors to treat diarrhea-irritable bowel syndrome (D-IBS); it has been commonly employed to treat ulcerative colitis and chemotherapy-induced intestinal mucositis. However, the mechanism of TGYPD in D-IBS treatment remains unclear. In the present study, the potential mechanism of TGYPD for irritable bowel syndrome was tested by network pharmacology combined with the IBS rat model. On the whole, 56 active ingredients were screened out, and 238 assessed targets were identified; 1934 known disease targets regarding the occurrence and development of irritable bowel syndrome were successfully searched from the disease database. GO biological processes primarily impact cytokine receptor binding, transcription factor activity, cytokine activity, antioxidant activity, biosynthesis regulation, cell cycle regulation and other cellular active sites of irritable bowel syndrome. Besides, the mentioned processes are involved in AGE- RAGE signaling pathway, TNF and IL-17 signaling pathway, Toll-like receptor (TLRs) signaling pathway, multiple cancer signaling pathways, and viral key signaling pathways of infection, hepatitis and endocrine resistance. As reported by the protein interaction network (PPI), IL-6, CXCL8, VEGFR, JUN, MAPK3 and AKT1 are likely to act as the critical targets for TGYPD to treat IBS. Moreover, in the model of IBS-D rats, TGYPD is capable of significantly reducing stool Bristol type and AWR scores, as well as effectively decreasing TNF-αand IFN-γ. As revealed from colon pathological section, TGYPD can relieve intestinal damage and mitigate intestinal mucosal immune inflammation. As suggested from the results of the Western blotting assay, TGYPD is capable of suppressing the expression of TLR4-MYD88-NF-kB signaling pathway in intestines. In brief, the results achieved in this study suggest that TGYPD can significantly mitigate immune inflammation and protect against intestinal mucosal barrier in the intestines of the IBS-D rat model. This study provides novel insights that can be referenced by other TCM studies.
Excessive postoperative blood loss after cardiopulmonary bypass is a common problem, especially in patients suffering from congenital heart diseases. The efficacy of epsilon aminocaproic acid (EACA) as a prophylactic treatment for postoperative bleeding after pediatric open-heart surgery has not been determined. This meta-analysis investigates the efficacy of EACA in the minimization of bleeding and blood transfusion and the maintenance of coagulation tests after pediatric open-heart surgery.A comprehensive literature search was performed to identify all randomized clinical trials on the subject. PubMed, Embase, the Cochrane Library, and the Chinese Medical Journal Network were screened. The primary outcome used for the analysis was postoperative blood loss. Secondary outcomes included postoperative blood transfusion, re-exploration rate and postoperative coagulation tests. The mean difference (MD) and risk ratio (RR) with 95% confidence intervals (CI) were used as summary statistics.Five trials were included in this meta-analysis of 515 patients. Prophylactic EACA was associated with a reduction in postoperative blood loss, but this difference did not reach statistical significance (MD: -7.08; 95% CI: -16.11 to 1.95; P = 0.12). Patients treated with EACA received fewer postoperative blood transfusions, including packed red blood cells (MD: -8.36; 95% CI: -12.63 to -4.09; P = 0.0001), fresh frozen plasma (MD: -3.85; 95% CI: -5.63 to -2.08; P < 0.0001), and platelet concentrate (MD: -10.66; 95% CI: -18.45 to -2.87; P = 0.007), and had a lower re-exploration rate (RR: 0.46; 95% CI: 0.23 to 0.92; P = 0.03). Prophylactic EACA also improved coagulation tests 6 hours after open-heart surgery.Prophylactic EACA minimizes postoperative blood transfusion and helps maintain coagulation in pediatric patients undergoing open-heart surgery. Therefore, the results of this study indicate that adjunctive EACA is a good choice for the prevention of postoperative blood transfusion following pediatric cardiac surgery.
Background: Immune function is recognized as an important prognostic indicator in gastric cancer (GC). The relationship between the lymphocyte-monocyte ratio (LMR) and tumor-associated macrophage (TAM) has received far less attention. Methods: A total of 401 patients from a prospective trial (NCT02327481) were enrolled in this study. The relationships between the LMR, TAM, and clinicopathologic variables were analyzed using a Kaplan-Meier log-rank survival analysis, and multivariate Cox regression models were used to identify associations with recurrence-free survival (RFS) and overall survival (OS). The discriminatory power of the prognostic models for both RFS and OS were compared. The decision curve analysis was performed to compare the clinical utility of the prognostic models. Results: High LMR was observed in 81.5% of the 401 GC patients, and high TAM infiltration was observed in 45.9% of the patients. In a multivariate Cox analysis of all patients, LMR and TAM were both independent prognostic factors for RFS and OS. Patients with high TAM expression had similar mean LMR levels than patients with low TAM expression. Moreover, LMR appeared to lose its prognostic significance in patients with high TAM expression levels. Finally, the model that included the TAM had better predictive capability and clinical utility for both RFS and OS. Conclusions: Although LMR and TAM are both independent predictors of RFS and OS in resectable GC patients, LMR seem to attenuate its prognostic significance in patients with high TAM expression. This information may be helpful in the clinical management of patients with GC. Further external studies are warranted to confirm this hypothesis.
To investigate the role of alteplase, a widely-used thrombolytic drug, in platelet function.Human platelets were incubated with different concentrations of alteplase followed by analysis of platelet aggregation in response to adenosine diphosphate (ADP), collagen, ristocetin, arachidonic acid or epinephrine using light transmittance aggregometry. Platelet activation and surface levels of platelet receptors GPIbα, GPVI and αIIbβ3 were analysed using flow cytometry. The effect of alteplase on clot retraction was also examined.This study demonstrated that alteplase significantly inhibited platelet aggregation in response to ADP, collagen and epinephrine in a dose-dependent manner, but it did not affect ristocetin- or arachidonic acid-induced platelet aggregation. Alteplase did not affect platelet activation as demonstrated by no differences in P-selectin levels and PAC-1 binding being observed in collagen-stimulated platelets after alteplase treatment compared with vehicle. There were no changes in the surface levels of the platelet receptors GPIbα, GPVI and αIIbβ3 in alteplase-treated platelets. Alteplase treatment reduced thrombin-mediated clot retraction.Alteplase inhibits platelet aggregation and clot retraction without affecting platelet activation and surface receptor levels.
Recent studies demonstrated high expression of lysosome-associated membrane protein 3 (LAMP3) in a variety of malignancies including esophageal squamous cell carcinoma, gastrointestinal cancer, breast cancer, and cervical cancer and its involvement in several biological activities of tumor cells. However, the expression of LAMP3 and its value in oral squamous cell carcinoma (OSCC) remain unclear. In this study, we examined the expression of LAMP3 in OSCC tissue samples and investigated the relationship between LAMP3 and clinical characteristics of patients with OSCC. We examined mRNA and protein levels of LAMP3 in OSCC tissues and neighboring normal tissues using quantitative real-time polymerase chain reaction and immunohistochemistry analyses, respectively. Both the mRNA and protein levels of LAMP3 were significantly higher in OSCC tissues than in adjacent normal tissues. Chi-square analysis showed that the high LAMP3 expression was notably linked to the degree of tumor differentiation and advanced TNM stage. Univariate and multivariate analyses showed that the high LAMP3 expression was an independent prognostic marker in OSCC. Our results suggest that LAMP3 might act as a potential anticancer target and a prognostic marker in patients with OSCC.
Background: Cystic lesions of the pancreas are common and increasingly detected in Grade A hospitals. Majority of patients have accepted the limited local surgery due to a low risk for developing a malignancy. However, duodenal obstruction contributed to duodenum ischemia origin postoperatively is quite rare and difficult to treat. Objective: The potential causes of duodenal obstruction after surgery were analysised, and value of pharmacological treatments including Erythromycin was emphasized. Results: The upper digestive tract contrast radiography (UDCR) and enhanced-CT scan of abdomen revealed a narrow luminal cavity of duodenum especially its third part, and a remarkable thickened wall. The presentations removed completely after pharmacological treatments. No any complications including tumor recurrence and intestinal obstruction were found after 3-year follow-up. Conclusions: Erythromycin and Procaine allow for the therapy of ischemic duodenal obstruction.
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