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While studying time fractional fluid flow problems it is typical to consider the Caputo derivative, however, these models have limitations including a singular kernel and an infinite waiting time from a random walk perspective. To help remedy this problem, this paper considers a tempered Caputo derivative, giving the system a finite waiting time. Initially, a fast approximation to a generalised tempered diffusion problem is developed using a sum of exponential approximation. The scheme is then proven to be unconditionally stable and convergent. The convergence properties are also tested on a sample solution. The fast scheme is then applied to a system of coupled tempered equations which describes the concentration, temperature and velocity of a nanofluid under the Boussinesq approximation. The most notable finding is that increasing both the fractional and tempering parameters reduces the heat transfer ability of the nanofluid system.
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OBJECTIVE: To analyze protein profiles in septic patients, and to find potential new targets for the diagnosis and treatment of sepsis. METHODS: A cross sectional observational study was conducted. From January to December 2019, 12 septic patients and 9 healthy volunteers were recruited in the emergency intensive care unit (EICU) of the emergency department of the Affiliated Hospital of Southwest Medical University. The peripheral blood of the two groups was collected for protein mass spectrometry analysis, and the data-independent acquisition technology was used to obtain the expression data of each protein. The obtained data was imported into the online network tool Integrated Differential Expression and Pathway analysis (IDEP2), the data underwent ID converted and were homogenized to verify their comparability, and then principal component analysis was used to eliminate outlier data. Then data with P < 0.05, log2fold change (FC) > 1 or log2FC < -1 were considered to have a statistically significant difference, and the differential proteins were screened out. On the DAVID website, the screened differential proteins would be analyzed by gene ontology (GO), and the biological process, cellular components, and molecular function of the proteins would be analyzed. Protein enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed. Protein-protein interaction (PPI) analysis was performed through the Search Tool for the Retrieval of Interacting Genes Database (STRING) website to find closely related proteins. RESULTS: The data in this study were shown to be comparable after normalization. A total of 125 differential proteins were screened, of which 99 were up-regulated and 26 were down-regulated. GO enrichment analysis discovered that these proteins were mainly extracellular, with cellular regulatory functions and catalytic functions involved in biological regulation, metabolic process and immune process. KEGG pathway analysis suggested that these proteins were involved in amino acid, carbohydrate metabolism and immune-related pathways. PPI analysis showed that key proteins included matrix metalloproteinase 14 (MMP14), fibulin 1 (FBLN1), plasma kallikrein 1 (KLKB1), etc., and finally screened out MMP14 and KLKB1, which were closely related to inflammation and immunity. Both might be potential new targets for early diagnosis and treatment of sepsis. CONCLUSIONS: MMP14 and KLKB1 may be potential biomarkers for the diagnosis, treatment and prognosis of sepsis.
Sujet(s)
Biologie informatique , Kallicréines/sang , Matrix metalloproteinase 14/métabolisme , Antigène spécifique de la prostate/sang , Sepsie , Marqueurs biologiques , Biologie informatique/méthodes , Études transversales , Analyse de profil d'expression de gènes , Réseaux de régulation génique , Humains , Matrix metalloproteinase 14/génétique , Kallicréine plasmatique/génétique , Cartes d'interactions protéiques/génétique , Protéomique , Sepsie/diagnostic , Sepsie/génétique , Sepsie/thérapie , Kallicréines tissulaires/génétiqueRÉSUMÉ
Based on relevant literature, this study adopted entrepreneurial learning theory to construct a relationship model between entrepreneurial learning and entrepreneurial intention. In this framework, entrepreneurial learning was divided into three dimensions: entrepreneurial education learning, experiential learning, and social network learning. A questionnaire survey was conducted among 1,399 undergraduate students in Zhejiang Province to investigate how entrepreneurial learning influenced entrepreneurial intention, while considering the mediating effect of entrepreneurial self-efficacy. This empirical research found that: (1) experiential learning and social network learning had significant positive impacts on entrepreneurial intention, but there was no significant relationship between entrepreneurial education learning and entrepreneurial intention; (2) entrepreneurship education learning and social network learning had significant positive relationships with entrepreneurial self-efficacy, but experiential learning had a significant negative relationship with entrepreneurial self-efficacy; and (3) entrepreneurial self-efficacy partially mediated the relationship between experiential learning, social network learning, and entrepreneurial intention, and fully mediated the relationship between entrepreneurial education learning and entrepreneurial intention. These findings suggest that colleges and universities in China could broaden entrepreneurial learning and strengthen social network learning.
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Tumor deposits (TD) of colorectal cancer (CRC) in the 8th edition of TNM classification (TNM 8th) were staged as N1c, but the number of TDs was ignored. The aim of this study was to analyze the association of TD with CRC and verify the rationale for TD staging in the TNM 8th. A total of 517 patients with CRC, surgically treated from Aug. 2013 to Dec. 2017, were retrospectively reviewed. Univariate and multivariate analyses were used to observe the correlations between clinicopathologic features and TD. The reasonability of TD staging in TNM 8th was validated by prognostic analysis. The occurrence of TD in CRC was 11.2% (154/1375). Multivariate analysis indicated that T stage (P<0.001, OR = 2.026 and 5.380, 95% CI: 0.917-4.474 and 2.229-12.981 for T3 and T4 respectively) and TNM stage (P<0.001, OR = 9.051 and 16.305, 95% CI: 2.055-39.857 and 3.780-70.323 for TNM II and TNM III respectively) were independent risk factors for TD status. Only degree of differentiation (P = 0.020, OR = 0.197, 95% CI: 0.050-0.774 for poorly differentiated) was an independent risk factor for number of TDs. Survival analysis showed that patients with TD exhibited a significantly worse prognosis compared to patients without TD (P<0.001), and a significant prognostic difference was found among groups TD = 1, TD = 2/3 and TD≥4 (all P<0.05). Patients in T3-4aN1a/1b had a worse prognosis than patients in T3-4aN1c did, although both groups were classified as TNM IIIB (P = 0.022). TD was an adverse indicator in CRC, and the varying number of TDs represented a classified prognostic factor in CRC. TD staging in the TNM 8th might not be reasonable as it ignores the status and the number of TDs.
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The aim of the present study was to evaluate the efficacy and safety of imatinib mesylate in unresectable gastrointestinal stromal tumor (GIST) and to discuss its therapeutic regimen. A patient with unresectable GIST is described, and several key clinical studies are reviewed, including the clinical trials B2222 and S0033, which contain recently reported results of the long-term clinical outcome of imatinib in patients with unresectable or metastatic GIST. The recent results of the two studies demonstrate the long-term efficacy and safety of imatinib for unresectable or metastatic GIST. A positive response to imatinib treatment was observed in the present patient, which is consistent with the data of the B2222 and S0033 trials. However, further long-term, large-scale, multicenter and controlled trials are required to determine the relative efficacy of combining imatinib agents with surgical procedures or administering imatinib alone.
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Hepatolithiasis, originally as oriental cholangiohepatitis, especially prevails in Asia, but globalization and intercontinental migration have also converted the endemic disease dynamics around the world. Characterized by its high incidence of ineffective treatment and recurrence, hepatolithiasis, always, poses a therapeutic challenge to global doctors. Although the improved surgical and non-surgical techniques have evolved over the past decade, incomplete clearance and recurrence of calculi are always so common and disease-related mortality from liver failure and concurrent cholangiocarcinoma still exists in the treatment of hepatolithiasis. In the late stage of hepatolithiasis, is it suitable for liver transplantation (LT)? Herein, we propose a comprehensive review and analysis of the LTx currently in potential use to treat hepatolithiasis. In our subjective opinion, and as is objective from the literatures so far, also given the strict indications, LT remains one of the definitive treatments for terminal hepatolithiasis.
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Lithiase/chirurgie , Maladies du foie/chirurgie , Transplantation hépatique , HumainsRÉSUMÉ
OBJECTIVE: To observe the impact of intraoperative peritoneal chemotherapy with Lobaplatin on the safety of postoperative bowel function and complications in patients with advanced colorectal cancer. METHODS: A total of 103 colorectal cancer patients undergoing surgical operations in our department between October 2013 and October 2014 were prospectively enrolled in this study and were randomly divided into peritoneal chemotherapy group(55 cases) and control group(48 cases) according to the random table. In therapy group, patients were treated with peritoneal implantation of 40 mg Lobaplatin intraoperatively and followed by intravenous chemotherapy using FOLFOX regimen with Oxaliplatin, Fluorouracil and Leucovorin. In control group, only FOLFOX regimen was fulfilled. Then the recovery time of bowel function, the incidence of adverse reactions and complications, and the pre- and post-chemotherapy routine blood tests and hepatorenal functions were compared. RESULTS: The recovery time of bowel function in peritoneal chemotherapy group and control group was(72.1±11.8) h and(68.7±13.4) h respectively without significant difference(P>0.05). Each group had 6 cases with incisional fat liquefaction(10.9% vs. 12.5%, P>0.05). There was no serious infection in both groups. During intravenous chemotherapy, in peritoneal chemotherapy group and control group, the incidence of nausea and vomit(42 cases, 76.4% vs. 40 cases, 83.3%), constipation(38 cases, 69.1% vs. 29 cases, 60.4%), and diarrhea(4 cases, 7.3% vs. 5 cases, 10.4%) were observed and there were no significant differences(all P>0.05). It was noted that all these side effects vanished after chemotherapy or cured by symptomatic treatment. There were no significant differences between two groups in indexes of white blood cell, platelet, alanine aminotransferase, aspartate transaminase, and creatinine(all P>0.05), neither after operation nor after chemotherapy. CONCLUSION: Peritoneal implantation of Lobaplatin as intraoperative chemotherapy for advanced colorectal cancer is safe and tolerable.
Sujet(s)
Antinéoplasiques/administration et posologie , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Tumeurs colorectales/traitement médicamenteux , Cyclobutanes/administration et posologie , Composés organiques du platine/administration et posologie , Antinéoplasiques/effets indésirables , Protocoles de polychimiothérapie antinéoplasique/administration et posologie , Cyclobutanes/effets indésirables , Fluorouracil/administration et posologie , Humains , Perfusions parentérales , Soins peropératoires , Leucovorine/administration et posologie , Composés organiques du platine/effets indésirables , Résultat thérapeutiqueRÉSUMÉ
When gene therapy is performed for the treatment of malignant tumors, gene transfer efficiency and selectivity are highly important. Polymer vehicle microspheres are a novel type of therapy, which have been developed rapidly in recent years and are able to control drug release, prolong the biological half-life of drugs, decrease side effects and achieve targeted delivery. The present study was designed to construct a polymer microsphere-encapsulated recombinant adenovirus with human tissue inhibitors of the matrix metalloproteinase-1 (TIMP-1) gene, and to discuss its characterization for the purpose of liver cancer gene therapy. The microsphere was prepared from biodegradable poly-DL-lactide-poly(ethylene glycol) (PELA) encapsulating rAdTIMP-1, the recombinant adenovirus carrying TIMP-1, by a modified double-emulsion method. The particle morphology, diameter, virus encapsulation, loading rate and release kinetics of the rAd-microspheres were determined in vitro. Hepatocellular carcinoma (HCC) HepG2 cells were transfected with the rAd-microsphere and the efficiency of transfection was assessed by fluorescent microscopy. The production and expression of TIMP-1 was identified by gelatin zymography and western blot analysis, and the invasiveness was detected by a matrigel matrix invasion assay. The microsphere encapsulating rAdTIMP-1 was successfully constructed with a diameter of 1.965 µm, encapsulation efficiency of 60.0%, a viral load of 10.5 x 10(8)/mg, a virus release of ~60% within 120 h and a total release time of >240 h. The resultant rAd-microspheres were able to efficiently transfect HepG2 cells with the transfection efficiency enhanced by ~90%. As a result, the transfected HepG2 cells had significantly increased TIMP-1 enzyme activity and the expression of TIMP-1 was detected by western blot analysis. In addition, the proliferation and invasion ability of the HCC cells was markedly inhibited by the rAd-microspheres. The resultant rAd-microspheres, PELA-encapsulated recombinant TIMP-1 adenovirus, had enhanced transfection efficiency and were able to markedly inhibit the in vitro biological behavior of HepG2 cells. This provides an experimental basis for this polymer application and may pave the way for prospective in vivo clinical trials and further comprehensive therapy for liver cancer.