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1.
Artigo em Inglês | MEDLINE | ID: mdl-32601815

RESUMO

PURPOSE: The incidence of pancreatic neuroendocrine tumors (pNETs) has continued to increase, but for pNETs, there is still no distinction between treatments based on anatomical location. We aim to determine whether NETs located at the head and body/tail of the pancreas are different. PATIENTS AND METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2016), we focused on pNETs patients with comprehensive information. The patients were divided into two groups based on tumors' location. We compared the characteristics of the two groups and assessed the risk factors for lymphatic metastasis. Survival analysis was performed based on the biological characteristics of the tumor. RESULTS: In all 3011 patients, pNETs were more common in the body/tail (62.94%) than in the head (37.06%) of the pancreas. The risk factors for lymph node metastasis in the two groups were different. Nonmetastatic, low-grade pancreatic body/tail NETs had the best prognosis (p < 0.001). For low-grade tumors (G1-G2), lymphatic metastasis did not significantly affect the prognosis of patients with pancreatic head NETs (p = 0.098) but affected the overall survival of patients with pancreatic body/tail NETs (p < 0.001). The tumors at the pancreatic head were larger (p = 0.001), more likely to have positive lymph nodes (p < 0.001) and more prone to locally advanced and distant invasion (p < 0.001). The prognosis of pancreatic head NETs 21-40 mm was worse than that of body/tail pNETs (p < 0.001). For non-functional NETs, the overall survival of pancreatic body/tail tumors was better (p < 0.001). CONCLUSION: The pancreatic head and pancreatic body/tail NETs have different biological characteristics and clinical outcomes and they should be treated differently.

2.
World J Gastroenterol ; 26(22): 3087-3097, 2020 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-32587450

RESUMO

BACKGROUND: In recent decades, an increasing number of patients have received minimally invasive intervention for infected pancreatic necrosis (IPN) because of the benefits in reducing postoperative multiple organ failure and mortality. However, there are limited published data regarding infection recurrence after treatment of this patient population. AIM: To investigate the incidence and prediction of infection recurrence following successful minimally invasive treatment in IPN patients. METHODS: Medical records for 193 IPN patients, who underwent minimally invasive treatment between February 2014 and October 2018, were retrospectively reviewed. Patients, who survived after the treatment, were divided into two groups: one group with infection after drainage catheter removal and another group without infection. The morphological and clinical data were compared between the two groups. Significantly different variables were introduced into the correlation and multivariate logistic analysis to identify independent predictors for infection recurrence. Sensitivity and specificity for diagnostic performance were determined. RESULTS: Of the 193 IPN patients, 178 were recruited into the study. Of them, 9 (5.06%) patients died and 169 patients survived but infection recurred in 13 of 178 patients (7.30%) at 7 (4-10) d after drainage catheters were removed. White blood cell (WBC) count, serum C-reactive protein (CRP), interleukin-6, and procalcitonin levels measured at the time of catheter removal were significantly higher in patients with infection than in those without (all P < 0.05). In addition, drainage duration and length of the catheter measured by computerized tomography scan were significantly longer in patients with infection (P = 0.025 and P < 0.0001, respectively). Although these parameters all correlated positively with the incidence of infection (all P < 0.05), only WBC, CRP, procalcitonin levels, and catheter length were identified as independent predictors for infection recurrence. The sensitivity and specificity for infection prediction were high in WBC count (≥ 9.95 × 109/L) and serum procalcitonin level (≥ 0.05 ng/mL) but moderate in serum CRP level (cut-off point ≥ 7.37 mg/L). The catheter length (cut-off value ≥ 8.05 cm) had a high sensitivity but low specificity to predict the infection recurrence. CONCLUSION: WBC count, serum procalcitonin, and CRP levels may be valuable for predicting infection recurrence following minimally invasive intervention in IPN patients. These biomarkers should be considered before removing the drainage catheters.

3.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 51(3): 365-370, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32543144

RESUMO

Objective: To investigate the effect of down-regulation of SND1 expression on senescence of human diploid fibroblasts. Methods: Western blot and immunohistochemistry were used to detect the expression of SND1 in young or senescent 2BS cells and aged tissues. Immunofluorescence was conducted to detect the localization of SND1 in young 2BS cells. CCK8 and EDU were performed to detect the proliferation of 2BS. Colony formation analysis was used to evaluate the capacity of colony formation of 2BS. Expression chip and RT-qPCR analysis were performed to detect the change of SASP expression level. ß-galactosidase staining was employed to indicate the senescent 2BS cells. Results: The expression of SND1 in the senescent 2BS cells was significantly down-regulated compared with in the younger 2BS cells, and in human colon adenomas, its expression was also significantly down-regulated compared with in non-lesion colon tissues. In young 2BS, knockdown of SND1 inhibited the proliferation and colony formation of 2BS, and led to stronger senescence-associated beta-galactosidase staining (SA-ß-gal). Expression chip and RT-qPCR analysis indicated that knockdown of SND1 up-regulated the expression of senescence-associated secretory phenotype components (SASP). Conclusions: Our data indicated that down-regulation of SND1 regulated human diploid cell senescence by up-regulating the expression of SASP components.

4.
Stem Cell Res Ther ; 11(1): 228, 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32522253

RESUMO

BACKGROUND: The beneficial functions of bone marrow mesenchymal stem cells (BM-MSCs) decline with decreased cell survival, limiting their therapeutic efficacy for myocardial infarction (MI). Irisin, a novel myokine which is cleaved from its precursor fibronectin type III domain-containing protein 5 (FNDC5), is believed to be involved in a cardioprotective effect, but little was known on injured BM-MSCs and MI repair yet. Here, we investigated whether FNDC5 or irisin could improve the low viability of transplanted BM-MSCs and increase their therapeutic efficacy after MI. METHODS: BM-MSCs, isolated from dual-reporter firefly luciferase and enhanced green fluorescent protein positive (Fluc+-eGFP+) transgenic mice, were exposed to normoxic condition and hypoxic stress for 12 h, 24 h, and 48 h, respectively. In addition, BM-MSCs were treated with irisin (20 nmol/L) and overexpression of FNDC5 (FNDC5-OV) in serum deprivation (H/SD) injury. Furthermore, BM-MSCs were engrafted into infarcted hearts with or without FNDC5-OV. RESULTS: Hypoxic stress contributed to increased apoptosis, decreased cell viability, and paracrine effects of BM-MSCs while irisin or FNDC5-OV alleviated these injuries. Longitudinal in vivo bioluminescence imaging and immunofluorescence results illustrated that BM-MSCs with overexpression of FNDC5 treatment (FNDC5-MSCs) improved the survival of transplanted BM-MSCs, which ameliorated the increased apoptosis and decreased angiogenesis of BM-MSCs in vivo. Interestingly, FNDC5-OV elevated the secretion of exosomes in BM-MSCs. Furthermore, FNDC5-MSC therapy significantly reduced fibrosis and alleviated injured heart function. CONCLUSIONS: The present study indicated that irisin or FNDC5 improved BM-MSC engraftment and paracrine effects in infarcted hearts, which might provide a potential therapeutic target for MI.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32488454

RESUMO

To explore the superiority of radiomics analysis in the diagnostic performance of coronary computed tomography angiography (CCTA) for identifying myocardial ischaemia and predicting major adverse cardiovascular events (MACE). A total of 105 lesions from 88 patients who underwent CCTA and invasive fractional flow reserve measurement were collected as the training set, and another 31 patients with CCTA and clinical outcome information were used as the validation set. Conventional CCTA features included the stenosis diameter, length, Agatston score and high-risk plaque characteristics. After extracting and selecting radiomics features, the robustness of the radiomics features was examined, and then conventional and radiomics models were established using logistic regressions. The area under the receiver operating characteristic (ROC) curve (AUC) and Net Reclassification Index (NRI) were analysed to compare the discrimination and classification abilities between the two models in both the training and validation sets. A total of 1409 radiomics features were extracted, and three wavelet features were finally screened out. The robustness test showed good stability for the refined radiomics features. Compared with the conventional model, the radiomics model displayed a significantly improved diagnostic performance in the training set (AUC 0.762 vs. 0.631, 95% confidence interval [CI] 0.671-0.853 vs. 0.519-0.742, P = 0.058) but a slightly improved diagnostic performance in the validation set (AUC 0.671 vs. 0.592, 95% CI 0.466-0.875 vs. 0.519-0.742, P = 0.448). The NRI of the radiomics model was increased in both the training and validation sets (NRI 0.198 and 0.238, respectively). Quantitative radiomics analysis was feasible and might help to improve the diagnostic performance of CCTA but is still controversial for predicting MACE.

6.
Circ Res ; 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32392088

RESUMO

Rationale: Doxorubicin (DOX) is one of the most potent antitumor agents available; however, its clinical use is restricted because it poses a risk of severe cardiotoxicity. Previous work has established that CircITCH is a broad-spectrum tumor-suppressive circular RNA and that its host gene, ITCH, is involved in doxorubicin-induced cardiotoxicity (DOXIC). Whether CircITCH plays a role in DOXIC remains unknown. Objective: We aimed to dissect the role of CircITCH in DOXIC and further decipher its potential mechanisms. Methods and Results: Circular RNA sequencing was performed to screen the potentially involved circRNAs in doxorubicin-induced cardiotoxicity pathogenesis. Quantitative PCR (qPCR) and RNA ISH (in situ hybridization) revealed that CircITCH was downregulated in DOX-treated human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as well as in the autopsy specimens from cancer patients who suffered from DOX-induced cardiomyopathy. Cell death/viability assays, detection of cardiomyocyte necrosis markers, microelectrode array, and cardiomyocyte functional assays revealed that CircITCH ameliorated DOX-induced cardiomyocyte injury and dysfunction. Detection of cellular/mitochondrial oxidative stress and DNA damage markers verified that CircITCH alleviated cellular/mitochondrial oxidative stress and DNA damage induced by DOX. RNA pull-down assays, Ago2 immunoprecipitation and double fluorescent ISH (FISH) identified miR-330-5p as a direct target of CircITCH. Moreover, CircITCH was found to function by acting as an endogenous sponge that sequestered miR-330-5p. Bioinformatic analysis, luciferase reporter assays and qPCR showed that SIRT6, BIRC5 (Survivin) and ATP2A2 (SERCA2a) were direct targets of miR-330-5p and that they were regulated by the CircITCH/miR-330-5p axis in DOXIC. Further experiments demonstrated that CircITCH-mediated alleviation of DOXIC was dependent on the interactions between miR-330-5p and the 3´-UTRs of SIRT6, BIRC5 and ATP2A2 mRNA. Finally, AAV9 vector-based overexpression of the well-conserved CircITCH partly prevented DOXIC in mice. Conclusions: CircITCH represents a novel therapeutic target for DOXIC because it acts as a natural sponge of miR-330-5p, thereby upregulating SIRT6, Survivin and SERCA2a to alleviate DOX-induced cardiomyocyte injury and dysfunction.

7.
Can J Cardiol ; 36(6): 915-930, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32439306

RESUMO

With more than 1,800,000 cases and 110,000 deaths globally, COVID-19 is one of worst infectious disease outbreaks in history. This paper provides a critical review of the available evidence regarding the lessons learned from the Chinese experience with COVID-19 prevention and management. The steps that have led to a near disappearance of new cases in China included rapid sequencing of the virus to establish testing kits, which allowed tracking of infected persons in and out of Wuhan. In addition, aggressive quarantine measures included the complete isolation of Wuhan and then later Hubei Province and the rest of the country, as well as closure of all schools and nonessential businesses. Other measures included the rapid construction of two new hospitals and the establishment of "Fangcang" shelter hospitals. In the absence of a vaccine, the management of COVID-19 included antivirals, high-flow oxygen, mechanical ventilation, corticosteroids, hydroxychloroquine, tocilizumab, interferons, intravenous immunoglobulin, and convalescent plasma infusions. These measures appeared to provide only moderate success. Although some measures have been supported by weak descriptive data, their effectiveness is still unclear pending well controlled clinical trials. In the end, it was the enforcement of drastic quarantine measures that stopped SARS-CoV-2 from spreading. The earlier the implementation, the less likely resources will be depleted. The most critical factors in stopping a pandemic are early recognition of infected individuals, carriers, and contacts and early implementation of quarantine measures with an organised, proactive, and unified strategy at a national level. Delays result in significantly higher death tolls.


Assuntos
Betacoronavirus , Controle de Doenças Transmissíveis , Infecções por Coronavirus , Pandemias , Administração dos Cuidados ao Paciente , Pneumonia Viral , Betacoronavirus/isolamento & purificação , Betacoronavirus/patogenicidade , China/epidemiologia , Controle de Doenças Transmissíveis/métodos , Controle de Doenças Transmissíveis/organização & administração , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Infecções por Coronavirus/transmissão , Humanos , Pandemias/prevenção & controle , Administração dos Cuidados ao Paciente/métodos , Administração dos Cuidados ao Paciente/organização & administração , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Pneumonia Viral/terapia , Pneumonia Viral/transmissão
8.
J Pineal Res ; : e12666, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32369647

RESUMO

Calcific aortic valve disease (CAVD) is highly prevalent with marked morbidity and mortality rates and a lack of pharmaceutical treatment options because its mechanisms are unknown. Melatonin is reported to exert atheroprotective effects. However, whether melatonin protects against aortic valve calcification, a disease whose pathogenesis shares many similarities to that of atherosclerosis, and the underlying molecular mechanisms remain unknown. In this study, we found that the intragastric administration of melatonin for 24 weeks markedly ameliorated aortic valve calcification in high cholesterol diet (HCD)-treated ApoE-/- mice, as evidenced by reduced thickness and calcium deposition in the aortic valve leaflets, improved echocardiographic parameters (decreased transvalvular peak jet velocity and increased aortic valve area), and decreased osteogenic differentiation marker (Runx2, osteocalcin, and osterix) expression in the aortic valves. Consistent with these in vivo data, we also confirmed the suppression of in vitro calcification by melatonin in hVICs. Mechanistically, melatonin reduced the level of CircRIC3, a procalcification circular RNA, which functions by acting as a miR-204-5p sponge to positively regulate the expression of the procalcification gene dipeptidyl peptidase-4 (DPP4). Furthermore, CircRIC3 overexpression abolished the inhibitory effects of melatonin on hVIC osteogenic differentiation. Taken together, our results suggest that melatonin ameliorates aortic valve calcification via the regulation of CircRIC3/miR-204-5p/DPP4 signaling in hVICs; therefore, melatonin medication might be considered a novel pharmaceutical strategy for CAVD treatment.

9.
Biochim Biophys Acta Mol Basis Dis ; 1866(8): 165799, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32304741

RESUMO

Microgravity exposure results in vascular remodeling and cardiovascular dysfunction. Here, the effects of mitochondrial oxidative stress on vascular smooth muscle cells (VSMCs) in rat cerebral arteries under microgravity simulated by hindlimb unweighting (HU) was studied. Endoplasmic reticulum (ER)-resident transmembrane sensor proteins and phenotypic markers of rat cerebral VSMCs were examined. In HU rats, CHOP expression was increased gradually, and the upregulation of the PERK-eIF2α-ATF4 pathway was the most pronounced in cerebral arteries. Furthermore, PERK/p-PERK signaling, CHOP, GRP78 and reactive oxygen species were augmented by PERK overexpression but attenuated by the mitochondria-targeting antioxidant MitoTEMPO. Meanwhile, p-PI3K, p-Akt and p-mTOR protein levels in VSMCs were increased in HU rat cerebral arteries. Compared with the control, HU rats exhibited lower α-SMA, calponin, SM-MHC and caldesmon protein levels but higher OPN and elastin levels in cerebral VSMCs. The cerebral VSMC phenotype transition from a contractile to synthetic phenotype in HU rats was augmented by PERK overexpression and 740Y-P but reversed by MitoTEMPO and the ER stress inhibitors tauroursodeoxycholic acid (TUDCA) and 4-phenylbutyric acid (4-PBA). In summary, mitochondrial oxidative stress and ER stress induced by simulated microgravity contribute to phenotype transition of cerebral VSMCs through the PERK-eIF2a-ATF4-CHOP pathway in a rat model.

10.
Am J Respir Crit Care Med ; 201(11): 1372-1379, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32242738

RESUMO

Rationale: The global death toll from coronavirus disease (COVID-19) virus as of May 12, 2020, exceeds 286,000. The risk factors for death were attributed to advanced age and comorbidities but have not been accurately defined.Objectives: To report the clinical features of 85 fatal cases of COVID-19 in two hospitals in Wuhan.Methods: Medical records were collected of 85 fatal cases of COVID-19 between January 9, 2020, and February 15, 2020. Information recorded included medical history, exposure history, comorbidities, symptoms, signs, laboratory findings, computed tomographic scans, and clinical management.Measurements and Main Results: The median age of the patients was 65.8 years, and 72.9% were male. Common symptoms were fever (78 [91.8%]), shortness of breath (50 [58.8%]), fatigue (50 [58.8%]), and dyspnea (60 [70.6%]). Hypertension, diabetes, and coronary heart disease were the most common comorbidities. Notably, 81.2% of patients had very low eosinophil counts on admission. Complications included respiratory failure (80 [94.1%]), shock (69 [81.2%]), acute respiratory distress syndrome (63 [74.1%]), and arrhythmia (51 [60%]), among others. Most patients received antibiotic (77 [90.6%]), antiviral (78 [91.8%]), and glucocorticoid (65 [76.5%]) treatments. A total of 38 (44.7%) and 33 (38.8%) patients received intravenous immunoglobulin and IFN-α2b, respectively.Conclusions: In this depictive study of 85 fatal cases of COVID-19, most cases were males aged over 50 years with noncommunicable chronic diseases. The majority of the patients died of multiple organ failure. Early onset of shortness of breath may be used as an observational symptom for COVID-19 exacerbations. Eosinophilopenia may indicate a poor prognosis. A combination of antimicrobial drugs did not offer considerable benefit to the outcome of this group of patients.


Assuntos
Infecções por Coronavirus/mortalidade , Pneumonia Viral/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , China/epidemiologia , Comorbidade , Doença das Coronárias/epidemiologia , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/virologia , Pandemias , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto Jovem
11.
Artigo em Inglês | MEDLINE | ID: mdl-32284883

RESUMO

The increased incidence of systemic lupus erythematosus (SLE) in recent decades might be related to changes in modern dietary habits. Since sodium chloride (NaCl) promotes pathogenic T cell responses, we hypothesize that excessive salt intake contributes to the increased incidence of autoimmune diseases, including SLE. Given the importance of dendritic cells (DCs) in the pathogenesis of SLE, we explored the influence of an excessive sodium chloride diet on DCs in a murine SLE model. We used an induced lupus model in which bone marrow-derived dendritic cells (BMDCs) were incubated with activated lymphocyte-derived DNA (ALD-DNA) and transferred into C57BL/6 recipient mice. We observed that a high-salt diet (HSD) markedly exacerbated lupus progression, which was accompanied by increased DC activation. NaCl treatment also stimulated the maturation, activation and antigen-presenting ability of DCs in vitro. Pretreatment of BMDCs with NaCl also exacerbated BMDC-ALD-DNA-induced lupus. These mice had increased production of autoantibodies and proinflammatory cytokines, more pronounced splenomegaly and lymphadenopathy, and enhanced pathological renal lesions. The p38 MAPK-STAT1 pathway played an important role in NaCl-induced DC immune activities. Taken together, our results demonstrate that HSD intake promotes immune activation of DCs through the p38 MAPK-STAT1 signaling pathway and exacerbates the features of SLE. Thus, changes in diet may provide a novel strategy for the prevention or amelioration of lupus or other autoimmune diseases.

12.
Signal Transduct Target Ther ; 5(1): 34, 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32296043

RESUMO

The increased incidence of systemic lupus erythematosus (SLE) in recent decades might be related to changes in modern dietary habits. Since sodium chloride (NaCl) promotes pathogenic T cell responses, we hypothesize that excessive salt intake contributes to the increased incidence of autoimmune diseases, including SLE. Given the importance of dendritic cells (DCs) in the pathogenesis of SLE, we explored the influence of an excessive sodium chloride diet on DCs in a murine SLE model. We used an induced lupus model in which bone marrow-derived dendritic cells (BMDCs) were incubated with activated lymphocyte-derived DNA (ALD-DNA) and transferred into C57BL/6 recipient mice. We observed that a high-salt diet (HSD) markedly exacerbated lupus progression, which was accompanied by increased DC activation. NaCl treatment also stimulated the maturation, activation and antigen-presenting ability of DCs in vitro. Pretreatment of BMDCs with NaCl also exacerbated BMDC-ALD-DNA-induced lupus. These mice had increased production of autoantibodies and proinflammatory cytokines, more pronounced splenomegaly and lymphadenopathy, and enhanced pathological renal lesions. The p38 MAPK-STAT1 pathway played an important role in NaCl-induced DC immune activities. Taken together, our results demonstrate that HSD intake promotes immune activation of DCs through the p38 MAPK-STAT1 signaling pathway and exacerbates the features of SLE. Thus, changes in diet may provide a novel strategy for the prevention or amelioration of lupus or other autoimmune diseases.

13.
Perit Dial Int ; : 896860820915022, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32223521

RESUMO

A simple, noninvasive method for removing peritoneal dialysis (PD) catheters, called the "pull technique," has become popular in recent years. Physicians still worry, however, about the range of its application and possible complications such as infection of the retained cuff and breakage. We, therefore, applied this technique in patients and enriched its administration for removing PD catheters. Altogether, 24 PD catheter removals in 24 patients were reviewed during the period from July 2018 to October 2019 in our hospital. Using the pull technique, the PD catheter's superficial cuff was dissected using an electronic knife, and the deep cuff was retained. All patients' catheters were successfully removed with no breakage. No incision or retained cuff was infected during the follow-up period (1.1-15.6 months). The appropriate peak force of pull traction was approximately 12-13 pounds, not very different from the mean maximum tensile force of 21.48 pounds for silicone tube breakage. The use of intermittent (rather than sustained) traction may reduce the breakage risk of the silicone tube. This method is a safe, practical, minimally invasive method for removing PD catheters, and it is suitable for application on special patients with peritonitis or who are on an immunosuppressant.

14.
BMC Gastroenterol ; 20(1): 94, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32252649

RESUMO

BACKGROUND: Agenesis of the dorsal pancreas (ADP) is a very rare disease with no specific symptoms, and the pathogenesis is not clear. Some patients will be accompanied by other diseases, such as pancreatic tumor or pancreatitis. But most cases are very atypical and difficult to distinguish. Some syndromes of pancreatic exocrine insufficiency are common in patients with ADP. Here, we report two cases of ADP and summarize the clinical features, diagnosis, and treatment of ADP. CASE PRESENTATION: Case A is a 65-year-old Chinese woman who presented with abdominal pain accompanied by nausea, bloating and acid reflux. The enhanced abdominal CT scan found nothing meaningful except the absence of the body and tail of the pancreas. The diagnosis was considered as gastrointestinal dysfunction cause by exocrine pancreatic insufficiency and recovered after symptomatic treatment. Case B is a 61-year-old Chinese woman who presented with abdominal pain accompanied by fever, vomiting and bloating. The abdominal CT showed multiple stones in the gallbladder, and the body and tail of the patient's pancreas were absent. She was diagnosed with cholelithiasis and recovered after laparoscopic cholecystectomy. CONCLUSION: Agenesis of the dorsal pancreas (ADP) is a rare congenital disease with an unclear pathogenesis that presents multiple symptoms. It should be considered when the patients have non-specific, persistent and unexplained symptoms such as bloating or uncontrolled blood sugar. Imaging examination is helpful for diagnosis. And it does not require surgical intervention unless it accompanies other diseases, EPI need to be considered when the non-specific gastrointestinal symptoms appear.

15.
Oncol Rep ; 43(5): 1606-1618, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32323798

RESUMO

Accumulating evidence suggests that lncRNAs are involved in almost all normal physiological processes and that aberrant expression of lncRNAs may be involved in the development of diseases, including non­small cell lung cancer (NSCLC). However, the roles of lncRNA­TPTE pseudogene 1 (TPTEP1) in lung cancer and the underlying molecular mechanisms have remained elusive. In the present study, significant downregulation of TPTEP1 in tumors compared with normal tissues from patients with NSCLC was observed. Overexpression of TPTEP1 inhibited cell proliferation and induced apoptosis in NSCLC cells. A bioinformatics analysis based on miRDB predicted microRNA (miR)­328­5p as a potential binding miRNA for TPTEP1. Using a dual­luciferase reporter assay and western blot analysis, it was further validated that TPTEP1 sponged miR­328­5p to upregulate Src kinase signaling inhibitor 1 (SRCIN1) in NSCLC cells. Through regulation of SRCIN1, TPTEP1 was indicated to inactivate the Src and STAT3 pathways in NSCLC cells. Notably, silencing of SRCIN1 reversed the TPTEP1 overexpression­induced inhibition of cell proliferation and increase of the apoptotic rate in NSCLC cells. Pearson correlation analysis revealed a significant positive correlation between TPTEP1 and SRCIN1 mRNA levels in NSCLC tumors. The present results provided insight into the roles of TPTEP1 in NSCLC and the underlying mechanisms.

16.
J Cell Mol Med ; 24(10): 5476-5490, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32286000

RESUMO

Diabetes mellitus causes endothelial dysfunction, which further exacerbates peripheral arterial disease (PAD). Improving endothelial function via reducing endothelial oxidative stress (OS) may be a promising therapy for diabetic PAD. Activation of liver X receptor (LXR) inhibits excessive OS and provides protective effects on endothelial cells in diabetic individuals. Therefore, we investigated the effects of LXR agonist treatment on diabetic PAD with a focus on modulating endothelial OS. We used a streptozotocin-induced diabetes mouse model combined with a hindlimb ischaemia (HLI) injury to mimic diabetic PAD, which was followed by LXR agonist treatment. In our study, the LXR agonist T0901317 protected against HLI injury in diabetic mice by attenuating endothelial OS and stimulating angiogenesis. However, a deficiency in endothelial Sirtuin1 (SIRT1) largely inhibited the therapeutic effects of T0901317. Furthermore, we found that the underlying therapeutic mechanisms of T0901317 were related to SIRT1 and non-SIRT1 signalling, and the isoform LXRß was involved in LXR agonist-elicited SIRT1 regulation. In conclusion, LXR agonist treatment protected against HLI injury in diabetic mice via mitigating endothelial OS and stimulating cellular viability and angiogenesis by LXRß, which elicited both SIRT1-mediated and non-SIRT1-mediated signalling pathways. Therefore, LXR agonist treatment may be a promising therapeutic strategy for diabetic PAD.

17.
Antiviral Res ; 177: 104777, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32217151

RESUMO

The Hepatitis B Virus (HBV) ribonuclease H (RNaseH) is a promising but unexploited drug target. Here, we synthesized and analyzed a library of 57 amide-containing α-hydroxytropolones (αHTs) as potential leads for HBV drug development. Fifty percent effective concentrations ranged from 0.31 to 54 µM, with selectivity indexes in cell culture of up to 80. Activity against the HBV RNaseH was confirmed in semi-quantitative enzymatic assays with recombinant HBV RNaseH. The compounds were overall poorly active against human ribonuclease H1, with 50% inhibitory concentrations of 5.1 to >1,000 µM. The αHTs had modest activity against growth of the fungal pathogen Cryptococcus neoformans, but had very limited activity against growth of the Gram - bacterium Escherichia coli and the Gram + bacterium Staphylococcus aureus, indicating substantial selectivity for HBV. A molecular model of the HBV RNaseH templated against the Ty3 RNaseH was generated. Docking the compounds to the RNaseH revealed the anticipated binding pose with the divalent cation coordinating motif on the compounds chelating the two Mn++ ions modeled into the active site. These studies reveal that that amide αHTs can be strong, specific HBV inhibitors that merit further assessment toward becoming anti-HBV drugs.

18.
ANZ J Surg ; 90(4): 514-520, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32115876

RESUMO

BACKGROUND: To investigate the clinical efficacy and mechanism of laparoscopic sleeve gastrectomy (LSG) in improving renal function in obese patients. METHODS: We retrospectively reviewed the anthropometric indices (waist circumference, hip circumference and body mass index (BMI)), renal function indices (serum creatinine, urea and urinary albumin:creatinine ratio (UACR)), serum inflammatory indices (C-reactive protein, interleukin-6 and tumour necrosis factor-α) and an adipose factor (leptin) in 50 patients with obesity (BMI ≥32.5 kg/m2 ) who underwent LSG in our hospital from January 2018 to January 2019. RESULTS: Patients constituted 23 men and 27 women, with an average age of 32.5 ± 8.7 years and BMI of 43.99 ± 8.29 kg/m2 . Body weight and BMI 1 month post-operatively were significantly lower than preoperatively (P < 0.05), and the renal function indices serum creatinine, urea and UACR, improved significantly 3 months post-operatively (P < 0.05). C-reactive protein, interleukin-6 and tumour necrosis factor-α levels improved significantly 3 months post-operatively (P < 0.05), while leptin levels decreased significantly 1 month post-operatively (P < 0.05). Six months post-operatively, the remission rates for type 2 diabetes mellitus, sleep apnoea syndrome and hypertension were 83.8%, 92.9% and 88.6%, respectively. CONCLUSIONS: LSG led to body weight loss and significantly improved serum creatinine, urea and UACR values in patients with obesity, which may be related to changes in adipocytokines and inflammatory factors, post-operatively. LSG is expected to become a new treatment to prevent or treat renal insufficiency caused by obesity.

19.
Int J Nanomedicine ; 15: 1321-1333, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32161461

RESUMO

Introduction: Currently, the unsatisfactory treatment of cardiac hypertrophy is due to the unbridled myocardial fibrosis. Melatonin has been demonstrated to ameliorate cardiac hypertrophy and its accompanied fibrosis in previous studies. But it is not clinically appealing due to its short-lasting time against the hostile microenvironment when administered orally. Methods: Herein, to address this, poly (lactide) polycarboxybetaine (PLGA-COOH) accompanied by cardiac homing peptide (CHP) and superparamagnetic iron oxide nanoparticles (SPIONs) were used to establish a novel drug delivery and transportation strategy for melatonin via a facile two-step emulsion method. This study characterized these nanoparticles (CHP-mel@SPIONs) and tested their delivery to the hypertrophied heart and their effect on myocardial hypertrophy and fibrosis in an animal model of pressure overload-induced cardiac hypertrophy. Results: The engineered magnetic nanoparticles of CHP-mel@SPIONs were spherical (diameter = 221 ± 13 nm) and had a negative zeta potential of -19.18 ± 3.27 mV. The CHP-mel@SPIONs displayed excellent drug encapsulation capacities of SPIONs (75.27 ± 3.1%) and melatonin (77.69 ± 6.04%) separately, and their magnetic properties were characterized by constructing magnetic hysteresis curves and exhibited no remnant magnetization or coercivity. The animal experiments showed that compared with mel@SPIONs, CHP-mel@SPIONs accumulated more in the heart, especially in the presence of an external magnetic field, with in vivo echocardiography and RT-PCR and histological assessments confirming the amelioration of the myocardial hypertrophy and fibrosis with low drug doses. Conclusion: This simple biocompatible dual-targeting nanoagent may be a potential candidate for the guided clinical therapy of heart disease.


Assuntos
Cardiomegalia/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas de Magnetita/química , Melatonina/administração & dosagem , Miocárdio/patologia , Animais , Cardiomegalia/patologia , Modelos Animais de Doenças , Óxido Ferroso-Férrico/química , Fibrose , Coração/efeitos dos fármacos , Campos Magnéticos , Melatonina/farmacologia , Nanoestruturas , Peptídeos/química , Pressão , Ratos Sprague-Dawley
20.
Asian J Surg ; 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32169516

RESUMO

BACKGROUND: Postoperative pancreatic fistula (POPF) remains the main cause of surgery related mortality after pancreaticoduodenectomy. Various pancreatoenteric anastomosis methods have been developed to reduce the POPF rate. However, the optimum choice has not been clarified. METHODS: A literature search is performed in electronic databases, including PubMed, Medline, Embase, CNKI and the Cochrane Library. Studies comparing modified Blumgart anastomosis with interrupted transpancreatic suture are included in this meta-analysis. Grade B/C POPF, overall POPF rate and overall sever complication rate (Clavien-Dindo classification IIIa or more) are measured as primary outcomes. Revman 5.3 was used to perform the analysis. RESULTS: Five retrospective comparative studies and 1 randomized controlled trial with a total number of 1409 patients are included in our analysis. Meta-analysis revealed that modified Blumgart anastomosis is associated with lower rate of grade B/C POPF [Odds Ratio (OR) 95% confidence interval (CI),0.32 (0.12-0.84); P = 0.02] and intra-abdominal abscess [OR 95%CI, 0.43 (0.29-0.65); P < 0.01] comparing with interrupted transpancreatic suture. However, this procedure could not reduce overall POPF [OR 95%CI,0.70 (0.34-1.44); P = 0.34] and overall sever complication rate [OR 95%CI,0.91 (0.48-1.72); P = 0.77]. CONCLUSION: At current level of evidence, modified Blumgart anastomosis is superior to interrupted transpancreatic suture in terms of grade B/C POPF and intra-abdominal abscess. However, high-grade evidence will be necessary to confirm these results.

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