We fit various color–magnitude diagrams(CMDs) of the high-latitude Galactic globular clusters NGC 5024(M53),NGC 5053,NGC 5272(M3),NGC 5466,and NGC 7099(M30) by isochrones from the Dartmouth Stellar Evolution Database...We fit various color–magnitude diagrams(CMDs) of the high-latitude Galactic globular clusters NGC 5024(M53),NGC 5053,NGC 5272(M3),NGC 5466,and NGC 7099(M30) by isochrones from the Dartmouth Stellar Evolution Database and Bag of Stellar Tracks and Isochrones for α–enrichment [α/Fe] = +0.4.For the CMDs,we use data sets from Hubble Space Telescope,Gaia,and other sources utilizing,at least,25 photometric filters for each cluster.We obtain the following characteristics with their statistical uncertainties for NGC 5024,NGC 5053,NGC 5272,NGC 5466,and NGC 7099,respectively:metallicities [Fe/H] =-1.93 ± 0.02,-2.08 ± 0.03,-1.60 ± 0.02,-1.95 ± 0.02,and-2.07 ± 0.04 dex with their systematic uncertainty 0.1 dex;ages 13.00 ± 0.11,12.70 ± 0.11,11.63 ± 0.07,12.15 ± 0.11,and 12.80 ± 0.17 Gyr with their systematic uncertainty 0.8 Gyr;distances(systematic uncertainty added) 18.22 ± 0.06 ± 0.60,16.99 ± 0.06 ± 0.56,10.08 ± 0.04 ± 0.33,15.59 ±0.03 ± 0.51,and 8.29 ± 0.03 ± 0.27 kpc;reddenings E(B-V) = 0.023 ± 0.004,0.017 ± 0.004,0.023 ± 0.004,0.023 ± 0.003,and 0.045 ± 0.002 mag with their systematic uncertainty 0.01 mag;extinctions AV= 0.08 ± 0.01,0.06 ± 0.01,0.08 ± 0.01,0.08 ± 0.01,and 0.16 ± 0.01 mag with their systematic uncertainty 0.03 mag,which suggest the total Galactic extinction AV= 0.08 across the whole Galactic dust to extragalactic objects at the North Galactic Pole.The horizontal branch morphology difference of these clusters is explained by their different metallicity,age,mass-loss efficiency,and loss of low-mass members in the evolution of the core-collapse cluster NGC 7099 and loose clusters NGC 5053 and NGC 5466.展开更多
The first-line treatment for autoimmune hepatitis involves the use of prednisone or prednisolone either as monotherapy or in combination with azathioprine(AZA).Budesonide has shown promise in inducing a complete bioch...The first-line treatment for autoimmune hepatitis involves the use of prednisone or prednisolone either as monotherapy or in combination with azathioprine(AZA).Budesonide has shown promise in inducing a complete biochemical response(CBR)with fewer adverse effects and is considered an optional first-line treatment,particularly for patients without cirrhosis;however,it is worth noting that the design of that study favored budesonide.A recent real-life study revealed higher CBR rates with prednisone when equivalent initial doses were administered.Current guidelines recommend mycophenolate mofetil(MMF)for patients who are intolerant to AZA.It is important to mention that the evidence supporting this recommendation is weak,primarily consisting of case series.Nevertheless,MMF has demonstrated superiority to AZA in the context of renal transplant.Recent comparative studies have shown higher CBR rates,lower therapeutic failure rates,and reduced intolerance in the MMF group.These findings may influence future guidelines,potentially leading to a significant modification in the first-line treatment of autoimmune hepatitis.Until recently,the only alternative to corticosteroids was lifelong maintenance treatment with AZA,which comes with notable risks,such as skin cancer and lymphoma.Prospective trials are essential for a more comprehensive assessment of treatment suspension strategies,whether relying on histological criteria,strict biochemical criteria,or a combination of both.Single-center studies using chloroquine diphosphate have shown promising results in significantly reducing relapse rates compared to placebo.However,these interesting findings have yet to be replicated by other research groups.Additionally,second-line drugs,such as tacrolimus,rituximab,and infliximab,should be subjected to controlled trials for further evaluation.展开更多
Alcohol consumption accounts for 3.8% of annual global mortality worldwide, and the majority of these deaths are due to alcoholic liver disease(ALD), mainly alcoholic cirrhosis. ALD is one of the most common indicatio...Alcohol consumption accounts for 3.8% of annual global mortality worldwide, and the majority of these deaths are due to alcoholic liver disease(ALD), mainly alcoholic cirrhosis. ALD is one of the most common indications for liver transplantation(LT). However, it remains a complicated topic on both medical and ethical grounds, as it is seen by many as a "self-inflicted disease". One of the strongest ethical arguments against LT for ALD is the probability of relapse. However, ALD remains a common indication for LT worldwide. For a patient to be placed on an LT waiting list, 6 mo of abstinence must have been achieved for most LT centers. However, this "6-mo rule" is an arbitrary threshold and has never been shown to affect survival, sobriety, or other outcomes. Recent studies have shown similar survival rates among individuals who undergo LT for ALD and those who undergo LT for other chronic causes of end-stage liver disease. There are specific factors that should be addressed when evaluating LT patients with ALD because these patients commonly have a high prevalence of multisystem alcohol-related changes. Risk factors for relapse include the presence of anxiety or depressive disorders, short pre-LT duration of sobriety, and lack of social support. Identification of risk factors and strengthening of the social support system may decrease relapse among these patients. Family counseling for LT candidates is highly encouraged to prevent alcohol consumption relapse. Relapse has been associated with unique histopathological changes, graft damage, graft loss, and even decreased survival in some studies. Research has demonstrated the importance of a multidisciplinary evaluation of LT candidates. Complete abstinence should be attempted to overcome addiction issues and to allow spontaneous liver recovery. Abstinence is the cornerstone of ALD therapy. Psychotherapies, including 12-step facilitation therapy, cognitive-behavioral therapy, and motivational enhancement therapy, help support abstinence. Nutritional therapy helps to reverse muscle wasting, weight loss, vitamin deficiencies, and trace element deficiencies associated with ALD. For muscular recovery, supervised physical activity has been shown to lead to a gain in muscle mass and improvement of functional activity. Early LT for acute alcoholic hepatitis has been the subject of recent clinical studies, with encouraging results in highly selected patients. The survival rates after LT for ALD are comparable to those of patients who underwent LT for other indications. Patients that undergo LT for ALD and survive over 5 years have a higher risk of cardiorespiratory disease, cerebrovascular events, and de novo malignancy.展开更多
Inflammatory bowel diseases(IBD)are chronic inflammatory disorders of the gastrointestinal tract associated with multifactorial conditions such as ulcerative colitis and Crohn’s disease.Although the underlying mechan...Inflammatory bowel diseases(IBD)are chronic inflammatory disorders of the gastrointestinal tract associated with multifactorial conditions such as ulcerative colitis and Crohn’s disease.Although the underlying mechanisms of IBD remain unclear,growing evidence has shown that dysregulated immune system reactions in genetically susceptible individuals contribute to mucosal inflammation.However,conventional treatments have been effective in inducing remission of IBD but not in preventing the relapse of them.In this way,mesenchymal stromal cells(MSC)therapy has been recognized as a promising treatment for IBD due to their immunomodulatory properties,ability to differentiate into several tissues,and homing to inflammatory sites.Even so,literature is conflicted regarding the location and persistence of MSC in the body after transplantation.For this reason,recent studies have focused on the paracrine effect of the biofactors secreted by MSC,especially in relation to the immunomodulatory potential of soluble factors(cytokines,chemokines,and growth factors)and extracellular vehicles that are involved in cell communication and in the transfer of cellular material,such as proteins,lipids,and nucleic acids.Moreover,treatment with interferon-γ,tumor necrosis factor-α,and interleukin-1βcauses MSC to express immunomodulatory molecules that mediate the suppression via cell-contact dependent mechanisms.Taken together,we present an overview of the role of bioactive factors and cell membrane proteins derived from MSC as a cell-free therapy that can improve IBD treatment.展开更多
BACKGROUND Gastroenteropancreatic neuroendocrine tumours(GEP-NETs)are slow-growing cancers that arise from diffuse endocrine cells in the gastrointestinal tract(GINETs)or the pancreas(P-NETs).They are relatively uncom...BACKGROUND Gastroenteropancreatic neuroendocrine tumours(GEP-NETs)are slow-growing cancers that arise from diffuse endocrine cells in the gastrointestinal tract(GINETs)or the pancreas(P-NETs).They are relatively uncommon,accounting for 2%of all gastrointestinal malignancies.The usual treatment options in advanced GEP-NET patients with metastatic disease include chemotherapy,biological therapies,and peptide receptor radionuclide therapy.Understanding the impact of treatment on GEP-NET patients is paramount given the nature of the disease.Health-related quality of life(HRQoL)is increasingly important as a concept reflecting the patients’perspective in conjunction with the disease presentation,severity and treatment.AIM To conduct a systematic literature review to identify literature reporting HRQoL data in patients with GEP-NETs between January 1985 and November 2019.METHODS The PRISMA guiding principles were applied.MEDLINE,Embase and the Cochrane library were searched.Data extracted from the publications included type of study,patient population data(mid-gut/hind-gut/GI-NET/P-NET),sample size,intervention/comparators,HRQoL instruments,average and data spread of overall and sub-scores,and follow-up time for data collection.RESULTS Forty-three publications met the inclusion criteria.The heterogeneous nature of the different study populations was evident;the percentage of female participants ranged between 30%-60%,whilst average age ranged from 53.8 to 67.0 years.Eight studies investigated GI-NET patients only,six studies focused exclusively on P-NET patients and the remaining studies involved both patient populations or did not report the location of the primary tumour.The most commonly used instrument was the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30(n=28)with consistent results across studies;the GI-NET-specific module Quality of Life Questionnaire-GINET21 was used in six of these studies.A number of randomised trials demonstrated no HRQoL changes between active treatment and placebo arms.The Phase III NETTER-1 study provides the best data available for advanced GEP-NET patients;it shows that peptide receptor radionuclide therapy can significantly improve GEP-NET patients’HRQoL.CONCLUSION HRQoL instruments offer a means to monitor patients’general disease condition,disease progression and their physical and mental well-being.Instruments including the commonly used European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 and GINET21 lack,however,validation and a defined minimal clinical important difference specifically for GINET and P-NET patients.展开更多
Orthobiologics are biological materials that are intended for the regeneration or healing of bone,cartilage and soft tissues.In this review we discuss the use of orthobiologics for hip disorders providing an update.Th...Orthobiologics are biological materials that are intended for the regeneration or healing of bone,cartilage and soft tissues.In this review we discuss the use of orthobiologics for hip disorders providing an update.The orthobiologics included in this article are hyaluronic acid,platelet rich plasma,bone marrow,adipose tissue and expanded mesenchymal stem cells.We explain the concepts and definitions of each orthobiological product,and the literature regarding its use in the hip joint.The paucity of guidelines for the production and characterization of the biological products leads to uneven results across the literature.Each biologic therapy has indications and benefits;however,noteworthy are the characterization of the orthobiologics,the application method and outcome analysis for further improvement of each technique.展开更多
基金financial support from the Russian Science Foundation (grant No.20-72-10052)。
文摘We fit various color–magnitude diagrams(CMDs) of the high-latitude Galactic globular clusters NGC 5024(M53),NGC 5053,NGC 5272(M3),NGC 5466,and NGC 7099(M30) by isochrones from the Dartmouth Stellar Evolution Database and Bag of Stellar Tracks and Isochrones for α–enrichment [α/Fe] = +0.4.For the CMDs,we use data sets from Hubble Space Telescope,Gaia,and other sources utilizing,at least,25 photometric filters for each cluster.We obtain the following characteristics with their statistical uncertainties for NGC 5024,NGC 5053,NGC 5272,NGC 5466,and NGC 7099,respectively:metallicities [Fe/H] =-1.93 ± 0.02,-2.08 ± 0.03,-1.60 ± 0.02,-1.95 ± 0.02,and-2.07 ± 0.04 dex with their systematic uncertainty 0.1 dex;ages 13.00 ± 0.11,12.70 ± 0.11,11.63 ± 0.07,12.15 ± 0.11,and 12.80 ± 0.17 Gyr with their systematic uncertainty 0.8 Gyr;distances(systematic uncertainty added) 18.22 ± 0.06 ± 0.60,16.99 ± 0.06 ± 0.56,10.08 ± 0.04 ± 0.33,15.59 ±0.03 ± 0.51,and 8.29 ± 0.03 ± 0.27 kpc;reddenings E(B-V) = 0.023 ± 0.004,0.017 ± 0.004,0.023 ± 0.004,0.023 ± 0.003,and 0.045 ± 0.002 mag with their systematic uncertainty 0.01 mag;extinctions AV= 0.08 ± 0.01,0.06 ± 0.01,0.08 ± 0.01,0.08 ± 0.01,and 0.16 ± 0.01 mag with their systematic uncertainty 0.03 mag,which suggest the total Galactic extinction AV= 0.08 across the whole Galactic dust to extragalactic objects at the North Galactic Pole.The horizontal branch morphology difference of these clusters is explained by their different metallicity,age,mass-loss efficiency,and loss of low-mass members in the evolution of the core-collapse cluster NGC 7099 and loose clusters NGC 5053 and NGC 5466.
文摘The first-line treatment for autoimmune hepatitis involves the use of prednisone or prednisolone either as monotherapy or in combination with azathioprine(AZA).Budesonide has shown promise in inducing a complete biochemical response(CBR)with fewer adverse effects and is considered an optional first-line treatment,particularly for patients without cirrhosis;however,it is worth noting that the design of that study favored budesonide.A recent real-life study revealed higher CBR rates with prednisone when equivalent initial doses were administered.Current guidelines recommend mycophenolate mofetil(MMF)for patients who are intolerant to AZA.It is important to mention that the evidence supporting this recommendation is weak,primarily consisting of case series.Nevertheless,MMF has demonstrated superiority to AZA in the context of renal transplant.Recent comparative studies have shown higher CBR rates,lower therapeutic failure rates,and reduced intolerance in the MMF group.These findings may influence future guidelines,potentially leading to a significant modification in the first-line treatment of autoimmune hepatitis.Until recently,the only alternative to corticosteroids was lifelong maintenance treatment with AZA,which comes with notable risks,such as skin cancer and lymphoma.Prospective trials are essential for a more comprehensive assessment of treatment suspension strategies,whether relying on histological criteria,strict biochemical criteria,or a combination of both.Single-center studies using chloroquine diphosphate have shown promising results in significantly reducing relapse rates compared to placebo.However,these interesting findings have yet to be replicated by other research groups.Additionally,second-line drugs,such as tacrolimus,rituximab,and infliximab,should be subjected to controlled trials for further evaluation.
文摘Alcohol consumption accounts for 3.8% of annual global mortality worldwide, and the majority of these deaths are due to alcoholic liver disease(ALD), mainly alcoholic cirrhosis. ALD is one of the most common indications for liver transplantation(LT). However, it remains a complicated topic on both medical and ethical grounds, as it is seen by many as a "self-inflicted disease". One of the strongest ethical arguments against LT for ALD is the probability of relapse. However, ALD remains a common indication for LT worldwide. For a patient to be placed on an LT waiting list, 6 mo of abstinence must have been achieved for most LT centers. However, this "6-mo rule" is an arbitrary threshold and has never been shown to affect survival, sobriety, or other outcomes. Recent studies have shown similar survival rates among individuals who undergo LT for ALD and those who undergo LT for other chronic causes of end-stage liver disease. There are specific factors that should be addressed when evaluating LT patients with ALD because these patients commonly have a high prevalence of multisystem alcohol-related changes. Risk factors for relapse include the presence of anxiety or depressive disorders, short pre-LT duration of sobriety, and lack of social support. Identification of risk factors and strengthening of the social support system may decrease relapse among these patients. Family counseling for LT candidates is highly encouraged to prevent alcohol consumption relapse. Relapse has been associated with unique histopathological changes, graft damage, graft loss, and even decreased survival in some studies. Research has demonstrated the importance of a multidisciplinary evaluation of LT candidates. Complete abstinence should be attempted to overcome addiction issues and to allow spontaneous liver recovery. Abstinence is the cornerstone of ALD therapy. Psychotherapies, including 12-step facilitation therapy, cognitive-behavioral therapy, and motivational enhancement therapy, help support abstinence. Nutritional therapy helps to reverse muscle wasting, weight loss, vitamin deficiencies, and trace element deficiencies associated with ALD. For muscular recovery, supervised physical activity has been shown to lead to a gain in muscle mass and improvement of functional activity. Early LT for acute alcoholic hepatitis has been the subject of recent clinical studies, with encouraging results in highly selected patients. The survival rates after LT for ALD are comparable to those of patients who underwent LT for other indications. Patients that undergo LT for ALD and survive over 5 years have a higher risk of cardiorespiratory disease, cerebrovascular events, and de novo malignancy.
文摘Inflammatory bowel diseases(IBD)are chronic inflammatory disorders of the gastrointestinal tract associated with multifactorial conditions such as ulcerative colitis and Crohn’s disease.Although the underlying mechanisms of IBD remain unclear,growing evidence has shown that dysregulated immune system reactions in genetically susceptible individuals contribute to mucosal inflammation.However,conventional treatments have been effective in inducing remission of IBD but not in preventing the relapse of them.In this way,mesenchymal stromal cells(MSC)therapy has been recognized as a promising treatment for IBD due to their immunomodulatory properties,ability to differentiate into several tissues,and homing to inflammatory sites.Even so,literature is conflicted regarding the location and persistence of MSC in the body after transplantation.For this reason,recent studies have focused on the paracrine effect of the biofactors secreted by MSC,especially in relation to the immunomodulatory potential of soluble factors(cytokines,chemokines,and growth factors)and extracellular vehicles that are involved in cell communication and in the transfer of cellular material,such as proteins,lipids,and nucleic acids.Moreover,treatment with interferon-γ,tumor necrosis factor-α,and interleukin-1βcauses MSC to express immunomodulatory molecules that mediate the suppression via cell-contact dependent mechanisms.Taken together,we present an overview of the role of bioactive factors and cell membrane proteins derived from MSC as a cell-free therapy that can improve IBD treatment.
文摘BACKGROUND Gastroenteropancreatic neuroendocrine tumours(GEP-NETs)are slow-growing cancers that arise from diffuse endocrine cells in the gastrointestinal tract(GINETs)or the pancreas(P-NETs).They are relatively uncommon,accounting for 2%of all gastrointestinal malignancies.The usual treatment options in advanced GEP-NET patients with metastatic disease include chemotherapy,biological therapies,and peptide receptor radionuclide therapy.Understanding the impact of treatment on GEP-NET patients is paramount given the nature of the disease.Health-related quality of life(HRQoL)is increasingly important as a concept reflecting the patients’perspective in conjunction with the disease presentation,severity and treatment.AIM To conduct a systematic literature review to identify literature reporting HRQoL data in patients with GEP-NETs between January 1985 and November 2019.METHODS The PRISMA guiding principles were applied.MEDLINE,Embase and the Cochrane library were searched.Data extracted from the publications included type of study,patient population data(mid-gut/hind-gut/GI-NET/P-NET),sample size,intervention/comparators,HRQoL instruments,average and data spread of overall and sub-scores,and follow-up time for data collection.RESULTS Forty-three publications met the inclusion criteria.The heterogeneous nature of the different study populations was evident;the percentage of female participants ranged between 30%-60%,whilst average age ranged from 53.8 to 67.0 years.Eight studies investigated GI-NET patients only,six studies focused exclusively on P-NET patients and the remaining studies involved both patient populations or did not report the location of the primary tumour.The most commonly used instrument was the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30(n=28)with consistent results across studies;the GI-NET-specific module Quality of Life Questionnaire-GINET21 was used in six of these studies.A number of randomised trials demonstrated no HRQoL changes between active treatment and placebo arms.The Phase III NETTER-1 study provides the best data available for advanced GEP-NET patients;it shows that peptide receptor radionuclide therapy can significantly improve GEP-NET patients’HRQoL.CONCLUSION HRQoL instruments offer a means to monitor patients’general disease condition,disease progression and their physical and mental well-being.Instruments including the commonly used European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 and GINET21 lack,however,validation and a defined minimal clinical important difference specifically for GINET and P-NET patients.
文摘Orthobiologics are biological materials that are intended for the regeneration or healing of bone,cartilage and soft tissues.In this review we discuss the use of orthobiologics for hip disorders providing an update.The orthobiologics included in this article are hyaluronic acid,platelet rich plasma,bone marrow,adipose tissue and expanded mesenchymal stem cells.We explain the concepts and definitions of each orthobiological product,and the literature regarding its use in the hip joint.The paucity of guidelines for the production and characterization of the biological products leads to uneven results across the literature.Each biologic therapy has indications and benefits;however,noteworthy are the characterization of the orthobiologics,the application method and outcome analysis for further improvement of each technique.
