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Objective:To investigate the influencing factors for early recurrence after curative pancreaticoduodenectomy of pancreatic head cancer.Methods:The retrospective case-control study was conducted. The clinicopathological data of 104 patients with pancreatic head cancer who underwent radical resection in Fudan University Shanghai Cancer Center from May 2014 to May 2015 were collected. There were 62 males and 42 females, aged (61±10)years. Patients underwent carative pancreaticoduodenectomy. Observation indicators: (1) surgical situations; (2) follow-up; (3) influencing factors for early recurrence after curative pancreaticoduodenectomy of pancreatic head cancer. Follow-up was conducted using telephone interview to detect recurrence of patients up to postoperative 1 year. Measurement data with normal distribution were represented as Mean±SD. Count data were described as absolutes numbers, and comparison between groups was analyzed using the chi-square test. Multivariate analysis was analyzed using the Logistic regression model. Results:(1) Surgical situations: 104 patients underwent curative pancreaticoduodenec-tomy successfully. The volume of intraoperative blood loss was (474±280)mL and the number of lymph node dissection was 21±10. (2) Follow-up: 104 patients received postoperative follow-up, 44 of whom had early recurrence. Of the 44 patients with early recurrence, 42 cases had intraperitoneal recurrence including 23 cases with liver metastasis, 7 cases with metastasis in surgical site, 7 cases with retroperitoneal lymph node metastasis, 5 cases with omentum metastasis, 2 cases had extraperitoneal recurrence including 1 case with pleural metastasis and 1 case with pulmonary metastasis. (3) Influencing factors for early recurrence after curative pancreaticoduodenectomy of pancreatic head cancer: results of univariate analysis showed levels of preoperative CA19-9, levels of postoperative CA19-9, the number of lymph node dissection were related factors for early recurrence after curative pancreaticoduodenectomy of pancreatic head cancer ( χ2=5.833, 9.276, 4.261, P<0.05). Results of multivariate analysis showed that postoperative CA19-9 >37 U/mL was an independent risk factor for early recurrence after curative pancreaticoduodenectomy of pancreatic head cancer ( odd ratio=3.599,95% confidence interval as 1.551-8.347, P<0.05). Conclusion:Postoperative CA19-9>37 U/mL is an independent risk factor for early recurrence after curative pancreaticoduodenectomy of pancreatic head cancer.
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The clinical trial is a crucial part of the clinical study. High level medical evidence, getting from the clinical trial, can guide the clinical practice. Compared with pancreatic cancer, the number of clinical trials of pancreatitis is still less as it is a special and complicated disease. The ESCAPE study, initiated by the Dutch pancreatitis research group, was a prospective, multicenter, randomized clinical trial to find the best approach for patients with painful chronic pancreatitis. The results of ESCAPE study were published on the Journal of the American Medical Association in 2020. ESCAPE study is a paradigm for clinical trial of pancreatitis from trial design, study implementation and result analysis. This paper not only focuses on the latest results of ESCAPE study, but also summarizes the key points and problems of clinical trials of pancreatitis. It is extremely urgent to launch clinical trials of pancreatitis widely and canonically, which is helpful to increase the influence of China in the field of pancreas.
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Objective To evaluate the effect of tyrosol on myocardial ischemia-reperfusion (I/R) injury in diabetic rats and the role of silent mating-type information regulation 1 (SIRT1)/adenosine monophosphate-activated protein kinase (AMPK)/endothelial nitric oxide synthase (eNOS) signaling pathway.Methods SPF healthy adult male Sprague-Dawley rats,weighing 200-220 g,were intraperitoneally injected with streptozotocin 60 mg/kg to establish the model of diabetes mellitus.Fifty-six diabetic rats were divided into 4 groups (n =14 each) using a random number table method:sham operation group (S group),myocardial I/R group (I/R group),myocardial I/R plus tyrosol group (I/R+T group),and myocardial I/R plus tyrosol plus SIRT1 inhibitor EX527 group (I/R+T+E group).In I/R+T and I/R+T+E groups,tyrosol 20 mg · kg-1 · d-1 was given by gavage for 45 consecutive days,and the equal volume of normal saline was given in the other two groups.In I/R+T+E group,EX527 5 mg · kg-1 · d-1 was intraperitoneally injected for 3 consecutive days before ischemia,and EX527 5 mg/kg was intraperitoneally injected at 20 min before repeffusion.Myocardial I/R was induced by ligation of the left anterior descending branch of coronary artery for 30 min followed by 2-h reperfusion.The myocardial infarct volume was measured by TTC staining.The levels of creatine kinase-MB (CK-MB),lactic dehydrogenase (LDH) and 5-F2t-isoprostane in serum and superoxide dismutase (SOD) in myocardial tissues were detected by enzyme-linked immunosorbent assay.The expression of SIRT1,AMPK,phosphorylated AMPK (p-AMPK),eNOS and p-eNOS was detected by Western blot.Results Compared with S group,the levels of serum CK-MB,LDH and 15-F2t-Isoprostane and myocardial infarction volume were significantly increased,the SOD activity was decreased,and the SIRT1 expression was down-regulated in I/R group,and the levels of serum CKMB,LDH and 15-F2t-Isoprostane and myocardial infarction volume were significantly increased,the SOD activity was decreased,the SIRT1 expression was down-regulated,and the expression of p-AMPK and peNOS was up-regulated in I/R+T and I/R+T+E groups (P＜0.05).Compared with I/R group,the levels of serum CK-MB,LDH and 15-F2t-Isoprostane and myocardial infarction volume were significantly decreased,the SOD activity was increased,and the expression of SIRT1,p-AMPK and p-eNOS was up-regulated in I/R+T group (P＜0.05),and no significant change was found in the parameters mentioned above in I/R+ T+E group (P＞0.05).Compared with I/R+T group,the levels of CK-MB,LDH and 15-F2t-isoprostane in serum and myocardial infarct volume were significantly increased,the SOD activity was increased,and the expression of SIRT1,p-AMPK and p-eNOS was down-regulated in I/R+T+E group (P＜0.05).Conclusion Tyrosol can mitigate myocardial I/R injury,and the mechanism may be related to activating SIRT1/AMPK/eNOS signaling pathway and inhibiting oxidative stress response in diabetic rats.
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This study was designed to investigate the role of CD36 in palmitic acid (PA)-induced apoptosis of astrocytes and the potential mechanisms of the action. MTT assay was used to detect cell viability and TUNEL assay to detect cell apoptosis. It was found that PA significantly decreased astrocyte cell viability and increased cell apoptosis. The uptake of BODIPY FL C16 by astrocytes was measured by flow cytometry. The results showed that CD36 played a key role in the process of PA uptake by astrocytes. The changes of intracellular calcium concentration were detected by FLIPR real-time fluorescence recording system. It was found that IP3R mediated PA signal to induce intracellular calcium release and finally caused endoplasmic reticulum calcium depletion. The intracellular ROS level was detected with CM-H2DCFDA fluorescence staining. The ROS level was induced by PA in astrocytes. The effect was blocked by CD36 inhibitor SSO through inhibition of the uptake of PA. PA-induced calcium overload and ROS increase were prevented by IP3R inhibitor APB. SSO, APB and antioxidant NAC all had significant inhibitory effects on PA-induced astrocyte cell viability decrease. In conclusion, CD36 mediates the translocation of PA into astrocytes, which leads to calcium overload, oxidative stress and eventually cell apoptosis.
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Pancreatic cancer is a highly malignant, fast progressive digestive system neoplasm with poor prognosis, and the incidence has increased significantly in the recent years. The treatment mode of pancreatic cancer has been transformed from surgery-first approach to multidisciplinary approach including surgery, chemotherapy, radiotherapy and other comprehensive treatment modalities, accompanying with significant improvement in clinical efficacy. During the last decade, the molecular mechanism of pancreatic cancer has been explored in depth. Indeed, we had a clearer understanding of the disease, which provides clues for translation of basic research into clinical practice. This review summarized recent high quality studies on pancreatic cancer including pathogenic factor, advances in basic research, and clinical treatment.
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Pancreatic ductal adenocarcinoma (PDAC) is among the most devastating human malignancies. The poor clinical outcome in PDAC is partly attributed to a growth-permissive tumor microenvironment. In the PDAC microenvironment, the stroma is characterized by the development of extensive fibrosis, with stromal components outnumbering pancreatic cancer cells. Each of the components within the stroma has a distinct role in conferring chemoresistance to PDAC, and intrinsic chemoresistance has further worsened this pessimistic prognosis. The nucleoside analog gemcitabine (GEM) is usually the recommended first-line chemotherapeutic agent for PDAC patients and is given alone or in combination with other agents. The mechanisms of intrinsic resistance to GEM are an active area of ongoing research. This review highlights the important role the complex structure of stroma in PDAC plays in the intrinsic resistance to GEM and discusses whether antistroma therapy improves the efficacy of GEM. The addition of antistroma therapy combined with GEM is expected to be a novel therapeutic strategy with significant survival benefits for PDAC patients.
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Diabetes mellitus can cause central nervous system disorder that is summarized as diabetic encephalopathy, which manifests in cognitive dysfunction and other mental illnesses. Astrocyte ,with a huge number and extensive functions,is an im?portant part of the central nervous system. Morphological and functional changes in astrocyte have been observed in diabetes mellitus , which involve the quantity,the expression of neurotransmitters and relative transporters,the activity of enzyme,the storage of glyco?gen and the intercellular connection and communication.
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Diabetes mellitus can cause central nervous system disorder that is summarized as diabetic encephalopathy, which manifests in cognitive dysfunction and other mental illnesses. Astrocyte, with a huge number and extensive functions, is an important part of the central nervous system. Morphological and functional changes in astrocyte have been observed in diabetes mellitus, which involve the quantity, the expression of neurotransmitters and relative transporters, the activity of enzyme, the storage of glycogen and the intercellular connection and communication.
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With the increase of morbidity and mortality, pancreatic cancer will not only become one of the leading causes of death in China, but also a major public health problem in the world. New onset cases of pancreatic cancer all around the world are expected to increase year by year. The prognosis of patients with pancreatic cancer is poor. The 5-year survival rate is only about 6%. The major reason for the poor prognosis is the lack of typical clinical symptoms in the early stage of disease, which makes it difficult to detect and control its relevant recurrence and metastasis. Moreover, lack of effective chemotherapy drugs and resistance to existing chemotherapy drugs are also important reasons for its dismal status. Radical resection surgery is still the most effective treatment. However, even after radical resection surgery, early recurrence and distant metastasis are still the main problems that bother patients. This article reviews recent high quality studies on pancreatic cancer including epidemiological investigation, advances in basic research, and clinical treatment.
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Background and purpose:Lower expression of E-cadherin is associated with metastasis of cancer cells, however, the correlation between E-cadherin and glucose metabolism has seldom been reported. This article studied the correlation between E-cadherin and glycolysis effect in PANC-1 cells.Methods:Through treatment of transforming growth factor β (TGF-β) in PANC-1 cells to decrease E-cadherin expression, knock-down the gene of E-cadherin interaction protein β-catenin, and overexpressing of E-cadherin, the effects of E-cadherin on the glucose uptake and lactate production ability and on the expression of key glycolytic genes were assessed.Results:E-cadherin negatively regulated the glycolytic effect of PANC-1 cells by inhibiting glucose uptake and lactate production (P<0.05). Moreover, E-cadherin interacting partner β-catenin signiifcantly promoted glucose metabolism transformation in PANC-1 cells (P<0.05). Moreover, key glycolysis regulator sirtuin 3 (SIRT3) could lower E-cadherin expression.Conclusion:Lower expression of E-cadherin induced the transformation of glucose metabolism transformation in PANC-1 cells and manipulation of E-cadherin expression level could change the glycolysis effect. Moreover, through maneuver glycolysis process could inhibit high metastatic potential of pancreatic cancer cells.
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Background and purpose: Lysine specific demethylase 1(LSD1) is an important chromatin modifier. It epigenetically regulates gene expression pattern through chromatin modification and participates in maintenance of tumor malignant properties, such as oncogenesis, development, invasion, migration and metabolic transformation. SIRT3 (sirtuin 3) is a mitochondria localized tumor suppressor and regulates tumor metabolic transformation and oxidative stress. The correlation between LSD1 and SIRT3 has never been reported before. This study aimed to elucidate the correlation between LSD1 and SIRT3 with gene transcriptional regulation methods. Methods: RNA interference technique, co-immunoprecipitation assay(CoIP), chromatin immune-precipitation assay(ChIP) and ifrelfy luciferase activity assay were employed to elucidate the correlation between LSD1 and SIRT3 in pancreatic cancer. Results:mRNA and protein levels of SIRT3 were signiifcantly elevated in LSD1 knock-down PANC-1 cells. LSD1 interacts with PGC-1α, an important regulator of SIRT3 gene expression. LSD1 and PGC-1αoccupied the same region in SIRT3 promoter region through ChIP analysis. Luciferase activity assay validated LSD1 as a negative regulator of PGC-1αin SIRT3 gene transcriptional regulation. Conclusion:LSD1, as an important tumor promoter, negatively regulates the expression of tumor suppressor gene SIRT3, these results provide important clues for the role that LSD1 plays in aberrant metabolism and oxidative stress.
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[Objective]To establish a method to determine the contents of glucase and fructose in extracts of leaves of Lonicera hypoglauca Miq. using HPLC-ELSD, and apply this method to study the content change of glucose and fructose in different solvents extracts in leaves of Lonicera hypoglauca Miq. [Methods] The chromatographic separation was achieved on Lichrospher NH2 column using a mobile phase composed of a mixture of acetonitrile and water(90:10) at a flow rate of 0.8mL·min-1 and the column temperature was 25℃.The ELSD drift tube temperature was set at 70℃ and the carrying gas was N2 and the flow rate of the gas was 1.6L·min-1. [Results] Glucose and fructose from extracts of the leaves of Lonicera hypoglauca Miq. could be wel separated, and the linearity ranges of glucose and fructose were shown at the concentration of 0.5840~1.168mg·mL-1 and 0.8256~1.8576mg·mL-1, the average recovery rate of glucose and fructose were 96.88%(RSD=1.11%) and 97.55%(RSD=1.15%), the stability of glucose and fructose was 2.12%and 0.38%, and the repeatability was 1.31% and 0.24%. Among the water extract,50% alcohol extract and 95% alcohol extract,the content of the glucose and fructose in the water extract was highest,which was 2.19mg·mL and 4.10mg·mL-1, the 50% alcohol extract was second, which was 1.13mg·mL-1 and 2.12mg·mL-1, and the 95% alcohol extract was lowest, which was 0.45mg·mL-1 and 0.65mg·mL-1.[Conclusion] The method is simple, accurate and has good repeatability, and can be used to determine the contents of glucose and fructose in the extract of leaves of Lonicera hypoglauca Miq. In this batch of leaves of Lonicera hypoglauca Miq., the contents of fructose and glucose were of water extract>50%ethanol extract>95%ethanol extract.
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Objective To investigate expressions of the vascular endothelial growth factor (VEGF) family and their receptors in cardiac repair/remodeling after myocardial infarction (MI).Methods The infarcted rat heart model were constructed,real time PCR (RT-PCR) and Western blots (WB) were used.Results Compared to the normal myocardium,VEGF-A was significantly decreased in MI group during the 42 days observation period but decreased at day 1,which was 0.89 ±0.04 of control group in D1,0.25 ±0.03 of control in D14; VEGF-B was significantly suppressed in the infarcted heart,which level was 0.09 ± 0.04 of control; However,VEGF-C and VEGF-D were markedly increased in the infarcted heart in MI group,which was 5.31 ± 0.21 and 9.24 ± 0.47 times of control.Meanwhile,VEGFR-1 and 2 were 0.11 ± 0.02 and 0.14 ± 0.04 of control in the infarcted heart,but VEGFR-3 was significantly increased in blood vessels,6.81 ± 0.42 times of control group.Conclusions VEGF isoforms and VEGFR subtypes were differentially expressed in the infarcted heart.It suggests that these isoforms may regulate multiple responses during cardiac repair/remodeling.
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OBJECTIVE: To determine the features of earthquake-related pelvic crush fractures versus non-earthquake fractures with digital radiography and multidetector row computed tomography. METHODS: One hundred and sixty-seven survivors with pelvic crush fractures in the 2008 Sichuan earthquake were entered in our study as the earthquake-related group (139 underwent digital radiography, 28 underwent multidetector row computed tomography); 70 victims with non-earthquake pelvic fractures were enrolled into this study as the non-earthquake group (54 underwent digital radiography, 16 underwent multidetector row computed tomography). Data were reviewed retrospectively between groups, focusing on anatomic distributions, status of pelvic bone fractures, numbers of pelvic bones involved, and classification of pelvic ring fractures according to the Tile classification system. RESULTS: Pelvic fractures occurred more frequently in the pubis in the earthquake-related group than in the non-earthquake group (135/167, 81 percent vs. 48/70, 69 percent). In addition, comminuted fractures were more common in the earthquake-related group than in the non-earthquake group (55/167, 33 percent vs. 10/70, 14 percent). Multiple fractures were less common in the earthquake-related group than in the non-earthquake group (81/167, 49 percent vs. 46/70, 66 percent). Regarding the classification of pelvic ring fractures, Type C predominantly composed of subtype C3 occurred more frequently (64/167, 38 percent vs. 12/70, 17 percent), and Type A was less common in the earthquake-related group than in the non-earthquake group (31/167, 19 percent vs. 23/70, 32 percent). All differences were statistically significant (p<0.05). No difference was found in Type B fractures between the groups (72/167, 43 percent vs. 35/70, 50 percent). CONCLUSION: Earthquake-related pelvic crush fractures can be characterized by a high incidence of pelvic fractures occurring in the pubis, comminuted fractures, and Type C fractures predominantly composed by subtype C3, despite a low incidence of multiple fractures.
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Young Adult , Accidents , Disasters , Earthquakes , Fractures, Bone , Multidetector Computed Tomography , Pelvic Bones/injuries , Radiographic Image Enhancement , China/epidemiology , Fractures, Bone/classification , Fractures, Bone/epidemiology , Pelvic Bones , Retrospective StudiesABSTRACT
The aim of this study was to investigate features of abdominal earthquake-related crush traumas in comparison with non-earthquake injury. A cross sectional survey was conducted with 51 survivors with abdominal crush injury in the 2008 Sichuan earthquake, and 41 with abdominal non-earthquake injury, undergoing non-enhanced computed tomography (CT) scans, serving as earthquake trauma and control group, respectively. Data were analyzed between groups focusing on CT appearance. We found that injury of abdominal-wall soft tissue and fractures of lumbar vertebrae were more common in earthquake trauma group than in control group (28 vs 13 victims, and 24 vs 9, respectively; all P < 0.05); and fractures were predominantly in transverse process of 1-2 vertebrae among L1-3 vertebrae. Retroperitoneal injury in the kidney occurred more frequently in earthquake trauma group than in control group (29 vs 14 victims, P < 0.05). Abdominal injury in combination with thoracic and pelvic injury occurred more frequently in earthquake trauma group than in control group (43 vs 29 victims, P < 0.05). In conclusion, abdominal earthquake-related crush injury might be characteristic of high incidence in injury of abdominal-wall soft tissue, fractures of lumbar vertebrae in transverse process of 1-2 vertebrae among L1-3 vertebrae, retroperitoneal injury in the kidney, and in combination with injury in the thorax and pelvis.