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1.
Heli Gao Jia Dong Wuhu Zhang Huaxiang Xu Longyun Ye Hao Li Quanxing Ni Wenquan Wang Liang Liu 《Endocrine practice》2022,28(3):292-297
ObjectiveThe role of alternate sequential administration of sunitinib and capecitabine/temozolomide (CAPTEM) in metastatic pancreatic neuroendocrine tumors (PanNETs) remains unexplored. We thus aimed to analyze the efficacy and tolerability of this strategy in advanced grade 1/grade 2 PanNETs.MethodsIn total, data of 43 patients with metastatic PanNET were collected from a real-world database of a cancer center. Twenty-four patients were treated with sunitinib followed by CAPTEM (group 1), and 19 patients were treated with CAPTEM followed by sunitinib (group 2).ResultsTwenty-three patients were treated with first-line sunitinib or CAPTEM, and 20 patients were pretreated with somatostatin analog (SSA) or SSA in combination with transcatheter arterial chemoembolization. The objective response rate with first-line treatment was similar in both groups, whereas that with second-line treatment was higher in group 1 than in group 2, albeit with no significant differences (21.1% vs 5.3%, respectively; P = .205). Median progression-free survival (mPFS) for first-line and second-line treatments did not differ between the 2 groups (11 and 12 months vs 12 and 8 months, respectively). Following subgroup analyses, treatment with first-line sunitinib and sunitinib after pretreated SSA had a longer mPFS than that with second-line sunitinib after CAPTEM (11 months vs 8 months, respectively; P = .046), whereas treatment with first-line CAPTEM and CAPTEM after pretreated SSA had an mPFS similar to that of second-line CAPTEM after sunitinib treatment. CAPTEM and sunitinib had similar tolerability.ConclusionAlternating sunitinib and CAPTEM were well tolerated and associated with similar mPFS in grade 1/grade 2 PanNETs. However, larger prospective studies are required to investigate the efficacy of alternate sequential therapies for metastatic PanNET. 相似文献
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An imbalance in the gut microbiome is linked to immune disorders, such as autoimmune, allergic, and chronic inflammatory disorders. Elucidation of disease mechanisms is a matter of urgency. It requires precise elucidation of the structure-based mechanisms of protein interactions involved in disease onset. In addition, an understanding of the protein dynamics is vital because these fluctuations affect the function and interaction of disease-associated proteins. Experimental evaluation of not only protein interactions, functions, and structures but also the dynamics are time-consuming; therefore, computational predictions are necessary to elucidate disease mechanisms. Here, we introduce recent studies on structure-based analyses of proteins using computational approaches, particularly artificial intelligence (AI) and molecular dynamics (MD) simulations. 相似文献
5.
《Journal of lipid research》2023,64(9):100419
Oxidation of PUFAs in LDLs trapped in the arterial intima plays a critical role in atherosclerosis. Though there have been many studies on the atherogenicity of oxidized derivatives of PUFA-esters of cholesterol, the effects of cholesteryl hemiesters (ChEs), the oxidation end products of these esters, have not been studied. Through lipidomics analyses, we identified and quantified two ChE types in the plasma of CVD patients and identified four ChE types in human endarterectomy specimens. Cholesteryl hemiazelate (ChA), the ChE of azelaic acid (n-nonane-1,9-dioic acid), was the most prevalent ChE identified in both cases. Importantly, human monocytes, monocyte-derived macrophages, and neutrophils exhibit inflammatory features when exposed to subtoxic concentrations of ChA in vitro. ChA increases the secretion of proinflammatory cytokines such as interleukin-1β and interleukin-6 and modulates the surface-marker profile of monocytes and monocyte-derived macrophage. In vivo, when zebrafish larvae were fed with a ChA-enriched diet, they exhibited neutrophil and macrophage accumulation in the vasculature in a caspase 1- and cathepsin B-dependent manner. ChA also triggered lipid accumulation at the bifurcation sites of the vasculature of the zebrafish larvae and negatively impacted their life expectancy. We conclude that ChA behaves as an endogenous damage-associated molecular pattern with inflammatory and proatherogenic properties. 相似文献
6.
In order to investigate the effects of dietary ginger extract (GE) enriched in gingerols on broilers under heat stress (HS) from 21 to 42 days of age, a total of 144 Ross 308 male broilers were randomly allocated to three groups with six replicates of eight broilers per replicate. Broilers in the control group were raised at 22 °C and fed a basal diet, and broilers in the other two groups were raised under cyclic HS (34 °C from 9:00 to 17:00 and at 22 °C for the rest of the time) and fed the basal diet with or without 1000 mg/kg GE. Supplementation of GE improved (P < 0.05) final body weight, average daily gain and feed conversion ratio of broilers under HS, and tended (P < 0.1) to increase breast muscle yield. The alterations of serum total protein, albumin, total cholesterol levels and aspartate aminotransferase activity under HS were reversed (P < 0.05) by GE, which also decreased (P < 0.05) serum triglyceride level and alanine aminotransferase activity. The decreased redness (a* value) and increased drip loss of breast muscle induced by HS were restored (P < 0.05) by GE. Moreover, GE supplementation increased (P < 0.05) total antioxidant capacity and decreased (P < 0.05) malondialdehyde content in liver and breast muscle, and increased (P < 0.05) glutathione peroxidase activity in serum and breast muscle. In conclusion, dietary GE supplementation restored growth performance, serum metabolites and meat quality of broilers under HS possibly by improving antioxidant activity. 相似文献
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《Endocrine practice》2021,27(11):1165-1174
ObjectiveHereditary endocrine tumors (HET) were among the first group of tumors where predisposition syndromes were recognized. The utility of genetic awareness is having the capacity to treat at an earlier stage, screen for other manifestations and initiate family cascade testing. The aim of this narrative review is to describe the most common hereditary syndromes associated with frequently encountered endocrine tumors, with an emphasis on screening and surveillance.MethodsA MEDLINE search of articles for relevance to endocrine tumors and hereditary syndromes was performed.ResultsThe most common hereditary syndromes associated with frequently encountered endocrine tumors are described in terms of prevalence, genotype, phenotype, penetrance of malignancy, surgical management, screening, and surveillance.ConclusionMedical practitioners involved in the care of patients with endocrine tumors should have an index of suspicion for an underlying hereditary syndrome. Interdisciplinary care is integral to successful, long-term management of such patients and affected family members. 相似文献
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《Endocrine practice》2021,27(3):236-240
ObjectiveTo evaluate the prevalence of euthyroid hypertriiodothyroninemia and/or hyperthyroxinemia and its clinical characteristics in multiple myeloma (MM) patients.MethodsPreviously untreated, newly diagnosed patients with MM were enrolled at the Beijing Chao-yang Hospital between January 2016 and December 2019. Thyroid function and clinical characteristics were analyzed.ResultsA total of 105 patients were enrolled in this study. Thirteen (12.38%) patients exhibited euthyroid hypertriiodothyroninemia with strikingly elevated total triiodothyronine (TT3) levels (>8 ng/mL). Among these 13 patients, 12 patients were immunoglobulin (Ig) G type (92.31%), and 1 patient was light-chain κ type (7.69%). Compared with other patients with MM, patients with hypertriiodothyroninemia were more likely to be IgG type and had higher serum globulin and lower albumin levels and more advanced International Staging System stage (all P < .05). Among the 13 euthyroid hypertriiodothyroninemia patients, 8 patients have been followed up and checked for thyroid function. The TT3 levels in all 8 patients were normalized to the reference range after antimyeloma chemotherapy.ConclusionAbout 12% of patients with MM had euthyroid hypertriiodothyroninemia. Their strikingly elevated TT3 was normalized after chemotherapy. Clinicians should be aware of the possibility of high TT3 levels in euthyroid patients with MM and the potential risk of MM in patients with strikingly elevated TT3. 相似文献
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《Endocrine practice》2022,28(10):1100-1106
ObjectiveSince January 2020, the highly contagious novel coronavirus SARS-CoV-2 has caused a global pandemic. Severe COVID-19 leads to a massive release of proinflammatory mediators, leading to diffuse damage to the lung parenchyma, and the development of acute respiratory distress syndrome. Treatment with the highly potent glucocorticoid (GC) dexamethasone was found to be effective in reducing mortality in severely affected patients.MethodsTo review the effects of glucocorticoids in the context of COVID-19 we performed a literature search in the PubMed database using the terms COVID-19 and glucocorticoid treatment. We identified 1429 article publications related to COVID-19 and glucocorticoid published from 1.1.2020 to the present including 238 review articles and 36 Randomized Controlled Trials. From these studies, we retrieved 13 Randomized Controlled Trials and 86 review articles that were relevant to our review topics. We focused on the recent literature dealing with glucocorticoid metabolism in critically ill patients and investigating the effects of glucocorticoid therapy on the immune system in COVID-19 patients with severe lung injury.ResultsIn our review, we have discussed the regulation of the hypothalamic-pituitary-adrenal axis in patients with critical illness, selection of a specific GC for critical illness-related GC insufficiency, and recent studies that investigated hypothalamic-pituitary-adrenal dysfunction in patients with COVID-19. We have also addressed the specific activation of the immune system with chronic endogenous glucocorticoid excess, as seen in patients with Cushing syndrome, and, finally, we have discussed immune activation due to coronavirus infection and the possible mechanisms leading to improved outcomes in patients with COVID-19 treated with GCs.ConclusionFor clinical endocrinologists prescribing GCs for their patients, a precise understanding of both the molecular- and cellular-level mechanisms of endogenous and exogenous GCs is imperative, including timing of administration, dosage, duration of treatment, and specific formulations of GCs. 相似文献
11.
《Matrix biology》2020
We report here that Glypican-6 (GPC6)-null mice display at birth small intestines that are 75% shorter than those of normal littermates. Notably, we demonstrate that the role of GPC6 in intestinal elongation is mediated by both Hedgehog (Hh) and non-canonical Wnt signaling. Based on results from in vitro experiments, we had previously proposed that GPC6 stimulates Hh signaling by interacting with Hh and Patched1 (Ptc1), and facilitating/stabilizing their interaction. Here we provide strong support to this hypothesis by showing that GPC6 binds to Ptc1 in the mesenchymal layer of embryonic intestines. This study also provides experimental evidence that strongly suggests that GPC6 inhibits the activity of Wnt5a on the intestinal epithelium by binding to this growth factor, and reducing its release from the surrounding mesenchymal cells. Finally, we show that whereas the mesenchymal layer of GPC6-null intestines displays reduced cell proliferation and a thinner smooth muscle layer, epithelial cell differentiation is not altered in the mutant gut. 相似文献
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《Fungal biology》2020,124(9):814-820
Green mould disease of mushroom, Agaricus bisporus,is caused by Trichodermaspecies and can result in substantial crop losses.Label free proteomic analysis of changes in the abundance of A. bisporusproteins following exposure to T. aggressivumsupernatantin vitroindicated increased abundance of proteins associated with an oxidative stress response (zinc ion binding (+6.6 fold); peroxidase activity (5.3-fold); carboxylic ester hydrolase (+2.4 fold); dipeptidase (+3.2 fold); [2Fe-2S] cluster assembly (+3.3 fold)). Proteins that decreased in relative abundance were associated with growth: structural constituent of ribosome, translation (-12 fold), deadenylation-dependent decapping of nuclear-transcribed mRNA (-3.4 fold), and small GTPase mediated signal transduction (-2.6 fold). In vivoanalysis revealed that 10-4 T. aggressivuminoculum decreased the mushroom yield by 29% to 56% and 10-3 T. aggressivuminoculum decreased the mushroom yield by 68% to 100%. Proteins that increased in abundance in A. bisporusin vivofollowing exposure to T. aggressivumindicated an oxidative stress response and included proteins with pyruvate kinase activity (+2.6 fold) and hydrolase activity (+2.1 fold)). The results indicate that exposure of A. bisporusmycelium to T. aggressivum in vitroand in vivoresulted in an oxidative stress response and reduction in growth. 相似文献
13.
《Endocrine practice》2022,28(12):1203-1209
ObjectiveTo evaluate the 2016 Cincinnati International Turner syndrome (TS) consensus guideline adherence within our pediatric tertiary referral center and determine if patients managed in our single-day, coordinated multidisciplinary clinic (MDC) format showed superior adherence rates when compared with those managed outside our MDC format.MethodsWe retrospectively reviewed the charts of patients with TS followed at our center from January 1, 2018, to April 30, 2020. The individual and overall adherence rates of 9 age-appropriate screening recommendations were evaluated along with rates of TS comorbidities within our cohort.ResultsA total of 111 girls met the study criteria. Sixty-eight were managed in the MDC and 43 were managed outside the MDC. Only 42% of all the girls met all 9 evaluated age-appropriate screening recommendations, of 47 girls, 33 (70%) were managed in MDC compared with 14 (30%) who were managed in the non-MDC. Girls managed in the MDC had higher screening adherence rates versus non-MDC girls for 7 of the 9 evaluated screenings with especially large differences noted for thyroid stimulating hormone (95% vs 78%, P = .034), auditory evaluation (97% vs 65%, P < .001), and HgA1c levels (82% vs 54%, P = .014).ConclusionGirls managed in the MDC format showed higher rates of screening guideline adherence, both overall and with multiple specific screening tests, than those managed outside the MDC format. Overall guideline adherence remained low (42%), highlighting the need for continued optimization and improvement in guideline adherence in this unique subset of the population. 相似文献
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《Endocrine practice》2021,27(5):449-454
ObjectiveTo determine whether the use of an inhaled insulin would improve HbA1c.MethodsThis study was performed in 20 type 2 diabetes mellitus (T2DM) participants with HbA1c values ≥7.5 (58) to ≤11.5% (102 mmol/mol) on a variety of glucose-lowering regimens. Prandial Technosphere insulin (TI) was rapidly titrated based on a treatment algorithm using postprandial blood glucose to calculate premeal doses. A 2-week baseline period was followed by 12 weeks of active treatment with TI. The primary outcome was change in HbA1c. Secondary outcomes included glucose time in range (time in range: 70-180 mg/dL) obtained by a blinded continuous glucose monitoring during the baseline period and at the end of 12 weeks. Goals were to assess how to rapidly and safely initiate TI intensification, determine dosing requirements, and establish an effective dose range in uncontrolled T2DM.ResultsMean HbA1c decreased by −1.6% (−17 mmol/mol) from 9.0% (75 mmol/mol) at baseline to 7.4% (57 mmol/mol) at 12 weeks (P < .0001). Mean time in range increased from 42.2% to 65.7% (P < .0002). Mean prandial doses of TI were 18 or 19 units for all meals. Time below range was 1.1% baseline and 2.6% post treatment (P = .01).ConclusionTreatment with inhaled TI dosed using a simple algorithm improved glycemic control measured by both HbA1c and time in range, with low rates of hypoglycemia. These data add significantly to understanding TI in the management of T2DM patients for whom prandial insulin is a consideration. 相似文献
15.
《Endocrine practice》2021,27(6):621-625
ObjectiveTo review he impact of estrogen-containing feminizing hormone regimens on transgender individuals’ risk for VTE.MethodsWe evaluated VTE risk by screening 1170 relevant studies published from 1994 to 2020, focusing on meta-analysis data.ResultsThe type of oral estrogen, route of administration, patient demographics, and comorbidities may affect the risk of VTE. Venous thrombosis is the most common vascular complication associated with HT.ConclusionConjugated equine estrogens and 17-β estradiol appear to be safer than oral ethinyl estradiol. Transdermal estrogen formulations appear to be the least thrombogenic estrogens. Estrogens used concomitantly with progestins increase the risk of VTE compared to estrogens alone.To date, there are no data to demonstrate the benefit of holding HT prior to vaginoplasty or other gender affirming surgeries. For most young, healthy transgender women, there is little risk of VTE with HT, while older patients with risk factors should be discussed case by case. 相似文献
16.
《Indian pacing and electrophysiology journal》2022,22(2):61-67
BackgroundFurther in-vivo evidence is needed to support the usefulness of ablation index (AI) in guiding atrial fibrillation (AF) ablation. We aimed at evaluating the relationship between AI and other lesion indicators and the release of myocardial-specific biomarkers following radiofrequency AF ablation.MethodsForty-six patients underwent a first-time radiofrequency AF ablation and were prospectively enrolled in this study. Pulmonary vein isolation was performed by six experienced electrophysiologists with a point-by-point approach, guided by strict Visitag criteria and consistent AI target values. Myocardial-specific biomarkers troponin T and creatine kinase myocardial band were measured after 6 (TnT6 and CKMB6) and 20 h (TnT20 and CKMB20) following sheath removal. Ablation duration, impedance drop (ID), force-time integral (FTI) and AI were registered automatically and analyzed offline.ResultsTnT release was 985 ± 495 ng/L and 1038 ± 461 ng/L (p = ns) while CKMB release was 7.3 ± 2.7 μg/L and 6.5 ± 2.1 μg/L (p < 0.001) at 6 and 20 h respectively. Ablation duration, ID, FTI and AI were all significantly correlated with the release of myocardial-specific biomarkers both at 6 and 20 h. Ablation index showed the highest degree of correlation with TnT6, TnT20, CKMB6 and CKMB20 (Pearson's R 0.69, 0.69, 0.61, 0.64 respectively, p < 0.001). Multiple regression analysis demonstrated that AI had the strongest association with TnT6, TnT20, CKMB6 and CKMB20 (β 0.43, β 0.71, β 0.44 and β 0.43 respectively).ConclusionAblation index appears as the strongest lesion indicator as measured by the release of myocardial-specific biomarkers following radiofrequency catheter ablation for AF. 相似文献
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To mitigate the impacts of heat exposure, animals can take some actions to maintain their core body temperature, such as heat acclimation; however, the effect of heat acclimation on anxiety-like behavior in an open field is still not understood. The purpose of this study was to examine the anxiety-like behavior of heat acclimated rats in a temperate or heated open field. After being raised in a 23 °C environment for one week, male Wistar rats were exposed to a heated environment (32 °C) for 3 h (3H), 14 days (14D), or 28 days (28D), with free access to food and water, and compared with rats reared in a temperate environment (23 °C; Cont). After heat exposure, behavioral changes were monitored using an open field test (OFT) in a heated (32 °C) or temperate environment (23 °C). Compared with those in the Cont group, the body weights of rats in the 14D and 28D groups were lower. The OFT in the heated environment showed that grooming time was longer in 3H and 14D rats. In the temperate environment, grooming time was longer in all the heated groups. Rats from the 3H and 28D groups spent longer time in the center square when tested in the temperate environment. Rearing activity increased in 28D rats in the temperate environment, while the number of line crossings did not differ significantly between the heated groups and the two open fields. These results suggest that heat acclimation affected not only the physiological index such as core body temperature but also the anxiety-like behavior, mainly in the temperate open field. These changes might be beneficial when rats are faced with an open field. 相似文献
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《Arthropod Structure & Development》2015,44(5):455-467
Sternal pores are important features for identification of male thrips, especially within the subfamily Thripinae. They vary in shape, size and distribution even between species of one genus. Their functional role is speculated to be that of sex- and/or aggregation pheromone production. Yet, sexual aggregations are not reported in Echinothrips americanus, known to have sternal pores, while we observed aggregations in Megalurothrips sjostedti, previously reported to lack them.We examined the sternal glands and pores of the thripine species E. americanus and M. sjostedti males, in comparison with those of Frankliniella occidentalis using light microscopy, as well as scanning and transmission electron microscopy. Pore plates of F. occidentalis were ellipsoid and medial on sternites III–VII, while in E. americanus they were distributed as multiple micro pore plates on sternites III–VIII. In M. sjostedti they appeared as an extremely small pore in front of the posterior margin of each of sternites IV–VII. Pore plate and pore plate area were distributed similarly on sternites III–VII in F. occidentalis. However, in E. americanus the total pore plate area increased significantly from sternites III to VIII. Ultrastructure of cells associated with sternal glands showed typical characteristics of gland cells that differ in size, shape and number. The function of sternal glands is further discussed on the basis of morphological comparisons with other thrips species. 相似文献
19.
《Indian pacing and electrophysiology journal》2020,20(4):160-163
IntroductionAblating the slow pathway (SP) is the superior treatment for atrioventricular nodal reentrant tachycardia (AVNRT) with a low complication rate. However, the ablation of the SP could result in either complete elimination or modification of the SP. We aimed to investigate whether the duration of AH jump pre-ablation associated with the outcome of elimination of SP.MethodsWe included 56 patients with typical AVNRT (slow-fast), 20 males and 36 females, aged 44.2 ± 15.1 years. Slow pathway ablation was performed using classical approach. Univariate and multivariate analysis was performed for potential predictors of SP elimination.ResultsTypical AVNRT was inducible in all patients. Post-ablation, non-inducibility of AVNRT was obtained in all 56 (100%) patients, with SP elimination in 33 (61%) patients and SP modification in 23 (39%) patients. Patients with SP elimination had significantly longer AH jump than patients with SP modification. Cox regression analysis showed that AH jump duration was the independent predictor of SP elimination, in which every 20 ms increase in AH jump duration was associated with 1.30 higher rate of SP elimination. Furthermore, ROC curve analysis indicated that the AH jump duration of ≥100 ms had 6.14 times higher probability for complete elimination of the SP with a sensitivity of 79%, specificity of 70%, PPV of 79% and NPV of 70%.ConclusionsAH jump duration pre-ablation is associated with complete elimination of slow pathway during AVNRT ablation. 相似文献
20.
《Microbes and infection / Institut Pasteur》2022,24(1):104878
Influenza is an acute respiratory disease and a global health problem. Although influenza vaccines are commercially available, frequent antigenic changes in hemagglutinin might render them less effective or unavailable. We previously reported that modified outer membrane vesicle (fmOMV) provided immediate and robust protective immunity against various subtypes of influenza virus. However, the effect was transient because it was innate immunity-dependent. In this study, we investigated the effects of consecutive administration of fmOMV and influenza virus on the adaptive immune response and long-term protective immunity against influenza virus. When the mice were pretreated with fmOMV and subsequently infected with influenza virus, strong influenza-specific antibody and T cell responses were induced in both systemic and lung mucosal compartments without pathogenic symptoms. Upon the secondary viral challenge at week 4, the mice given fmOMV and influenza virus exhibited almost complete protection against homologous and heterologous viral challenge. More importantly, this strong protective immunity lasted up to 18 weeks after the first infection. These results show that pretreatment with fmOMV and subsequent infection with influenza virus efficiently induces broad and long-lasting protective immunity against various virus subtypes, suggesting a novel antiviral strategy against newly-emerging viral diseases without suitable vaccines or therapeutics. 相似文献