Resistant hypertension(RH) has a prevalence of around 12% and is associated with an increased risk of cardiovascular disease, progression to end-stage renal disease, and even mortality. In 2017, the American College o...Resistant hypertension(RH) has a prevalence of around 12% and is associated with an increased risk of cardiovascular disease, progression to end-stage renal disease, and even mortality. In 2017, the American College of Cardiology and American Heart Association released updated guidelines that detail steps to ensure proper diagnosis of RH, including the exclusion of pseudoresistance.Lifestyle modifications, such as low salt diet and physical exercise, remain at the forefront of optimizing blood pressure control. Secondary causes of RH also need to be investigated, including screening for obstructive sleep apnea. Notably, the guidelines demonstrate a major change in medication management recommendations to include mineralocorticoid receptor antagonists. In addition to advances in medication optimization, there are several device-based therapies that have been showing efficacy in the treatment of RH. Renal denervation therapy has struggled to show efficacy for blood pressure control, but with a redesigned catheter device, it is once again being tested in clinical trials. Carotid baroreceptor activation therapy(BAT) via an implantable pulse generator has been shown to be effective in lowering blood pressure both acutely and in longterm follow up data, but there is some concern about the safety profile. Both a second-generation pulse generator and an endovascular implant are being tested in new clinical trials with hopes for improved safety profiles while maintaining therapeutic efficacy. Both renal denervation and carotid BAT need continued study before widespread clinical implementation. Central arteriovenous anastomosis has emerged as another possible therapy and is being actively explored. The ongoing pursuit of blood pressure control is a vital part of minimizing adverse patient outcomes. The future landscape appears hopeful for helping patients achieve blood pressure goals not only through the optimization of antihypertensive medications but also through device-based therapies in select individuals.展开更多
Hepatocellular carcinoma(HCC)remains the third leading cause of cancer-related deaths worldwide;however,its therapeutic options are limited.Understanding the molecular mechanisms of HCC could provide insight into new ...Hepatocellular carcinoma(HCC)remains the third leading cause of cancer-related deaths worldwide;however,its therapeutic options are limited.Understanding the molecular mechanisms of HCC could provide insight into new therapies.Emerging studies indicate the important role of long-noncoding RNAs(lncRNAs)in the pathogenesis of HCC.The expression of the well-studied lncRNA taurine upregulated gene 1(TUG1)is upregulated in HCC tissues,but its transcriptomic effects in HCC cells remain unexplored.We established TUG1-knockdown and control HCC cells for RNA-seq experiments.KEGG analysis revealed glycolysis as the top enriched pathway upon TUG1 silencing.Accordingly,TUG1-depleted HCC cells showed impairments in glucose uptake,ATP synthesis,and lactate production.Clinical HCC tissue data revealed positive gene expression correlations between TUG1 and several glycolysis-related genes.To identify a molecular function of TUG1 in glycolysis,we explored the competing endogenous model and used bioinformatic tools to find the five microRNAs(miRNAs)that had the most binding sites for TUG1.Among these miRNAs,miR-122-5p exhibited an inverse correlation in gene expression with most TUG1-regulated glycolysis genes,including PKM,ALDOA,ENO2,and PFKM.Dual-luciferase assays demonstrated the direct interaction between TUG1 and miR-122-5p and between miR-122-5p and the 3ʹuntranslated regions of both PKM and ALDOA.We further showed that inhibition of miR-122-5p alleviated the suppression of glycolysis induced by TUG1 depletion.Together,our RNA-seq analysis of TUG1-depleted HCC cells,combined with clinical data,reveals a critical role of TUG1 in regulating glycolysis and provides new insight into its oncogenic function in HCC.展开更多
With advancements in systemic therapy,the incidence of brain metastases(BMs)continues to rise,leading to severe neurological complications.Effective and precise treatment modalities are,therefore,critically important ...With advancements in systemic therapy,the incidence of brain metastases(BMs)continues to rise,leading to severe neurological complications.Effective and precise treatment modalities are,therefore,critically important for managing BMs.Radiation therapy(RT),including photon therapy,has been essential in managing BMs.Recent technological advances have significantly enhanced the precision,efficacy,and safety of these treatments.This comprehensive review provides an in-depth examination of the latest advancements in radiation and photon therapy technologies for treating BMs,focusing on innovations such as stereotactic radiosurgery(SRS),whole-brain radiation therapy(WBRT),laser interstitial thermal therapy(LITT),and other radiation-related treatment modalities.Additionally,we discuss clinical outcomes,challenges,and future directions in this rapidly evolving field.While a detailed comparison of techniques is beyond the scope of this paper,this paper provides up-to-date technical information for physicians,medical physicists,patients,and researchers in related fields,potentially enhancing clinical outcomes.Among the treatment modalities,SRS has become a cornerstone of RT for BMs,with its implementation spanning multiple modalities over the past few decades.Given its inherent minimally invasive nature and growing clinical acceptance,SRS is positioned to further evolve as a key therapeutic tool in both neurosurgery and radiotherapy.展开更多
Background and Objective Patients with glioma experience a high symptom burden and have diverse palliative care needs.However,the assessment scales used in palliative care remain non-standardized and highly heterogene...Background and Objective Patients with glioma experience a high symptom burden and have diverse palliative care needs.However,the assessment scales used in palliative care remain non-standardized and highly heterogeneous.To evaluate the application patterns of the current scales used in palliative care for glioma,we aim to identify gaps and assess the need for disease-specific scales in glioma palliative care.Methods We conducted a systematic search of five databases including PubMed,Web of Science,Medline,EMBASE,and CINAHL for quantitative studies that reported scale-based assessments in glioma palliative care.We extracted data on scale characteristics,domains,frequency,and psychometric properties.Quality assessments were performed using the Cochrane ROB 2.0 and ROBINS-I tools.Results Of the 3,405 records initially identified,72 studies were included.These studies contained 75 distinct scales that were used 193 times.Mood(21.7%),quality of life(24.4%),and supportive care needs(5.2%)assessments were the most frequently assessed items,exceeding half of all scale applications.Among the various assessment dimensions,the Distress Thermometer(DT)was the most frequently used tool for assessing mood,while the Short Form-36 Health Survey Questionnaire(SF-36)was the most frequently used tool for assessing quality of life.The Mini Mental Status Examination(MMSE)was the most common tool for cognitive assessment.Performance status(5.2%)and social support(6.8%)were underrepresented.Only three brain tumor-specific scales were identified.Caregiver-focused scales were limited and predominantly burden-oriented.Conclusions There are significant heterogeneity,domain imbalances,and validation gaps in the current use of assessment scales for patients with glioma receiving palliative care.The scale selected for use should be comprehensive and user-friendly.展开更多
AIM:To comprehensively investigate the current state of research on the application of neurotrophic factors in glaucoma therapy and identify potential research hotspots.METHODS:On September 30,2023,a literature search...AIM:To comprehensively investigate the current state of research on the application of neurotrophic factors in glaucoma therapy and identify potential research hotspots.METHODS:On September 30,2023,a literature search was conducted on Scopus using specific keywords related to neurotrophic factors and glaucoma.Of the 918 articles retrieved,780 met the inclusion criteria.These articles were subsequently analyzed and visualized using Google Sheets,Biblioshiny 3.1,and VosViewer 1.6.18.RESULTS:A total of 780 studies published between 1989 and 2023 were included,and the global publication count showed an upward trend through 2023(projected to continue rising by 2030).The United States,China,Japan,Italy,and Australia were the most significant contributors to the publication output.Research in this field had been published in 313 journals,spanning categories such as pharmacology and drug development,ophthalmology,genetics and gene therapy,and neuroscience.A total of 2622 authors had contributed to these studies,with the most prolific author publishing 14 articles.The focus of research in this field had evolved sequentially from“glutamate”to“CNTF”and“GDNF”,and finally to“optic nerve injury”.Co-occurrence analysis identified five clusters:glaucoma and ocular health,neuroinflammation in ophthalmology,neuroprotection in ophthalmology,ocular drug delivery,and stem cell therapy.Several areas in this field require further exploration,including the neurophysiological mechanisms underlying glaucoma,ocular drug delivery systems,and the clinical value of specific neurotrophic factors.CONCLUSION:This study systematically reviews global research trends on neurotrophic factors in glaucoma therapy,clarifying the current research status and future directions.展开更多
BACKGROUND Giant cell tumor of bone(GCTB)is a rare,locally aggressive neoplasm that should be treated surgically,whenever possible.This treatment approach may be linked with greater morbidity besides functional impair...BACKGROUND Giant cell tumor of bone(GCTB)is a rare,locally aggressive neoplasm that should be treated surgically,whenever possible.This treatment approach may be linked with greater morbidity besides functional impairment.Denosumab is a human monoclonal antibody.Its administration inhibits bone resorption and has become part of the therapeutic armamentarium against GCTB,as it allows local control with a view to downstaging for a more conservative surgical procedure.However,there is no consensus in the literature regarding the optimal denosumab regimen for GCTB.Therefore,a wide discussion of denosumab regimen is necessary.AIM To assess the effectiveness of various therapy protocols employing denosumab in individuals with GCTB.METHODS A broad and systematic literature search was carried out using the PRISMA guidelines.We analyzed studies that reported skeletally mature patients with GCTB regardless of sex or ethnicity treated with denosumab.Articles with fewer than five patients and in languages except Spanish,Portuguese and English were excluded.Statistical analysis with proportion meta-analysis was performed due to the dichotomous nature of the data.RESULTS 1005 articles were screened,of which 26 articles met the inclusion criteria and were selected,totaling 1742 patients,51.8%women and 48.2%men,with an average of 35 years of age.Treatment with denosumab was associated with high rates of clinical benefit(CB)and imaging response(IR),without changing local recurrence rates when compared to patients treated without denosumab,regardless of the therapeutic regimen adopted and the number of doses applied.The adverse events(AE)presented were mostly mild,with the exception of a malignant transformation to osteosarcoma.CONCLUSION Treatment of GCTB with denosumab is effective,showing high rates of CB and IR.The AE that occurred were mostly mild.We found no differences between the articles considering the researched outcomes regardless of the therapeutic regimen adopted.展开更多
Vitiligo is an acquired disease characterized principally by patchy depigmentation of skin and overlying hair. Generalized vitiligo （GV）, the predominant form of the disorder, results from autoimmune loss of melanoc...Vitiligo is an acquired disease characterized principally by patchy depigmentation of skin and overlying hair. Generalized vitiligo （GV）, the predominant form of the disorder, results from autoimmune loss of melanocytes from affected regions. GV is a ＂complex trait＂, inherited in a non-Mendelian polygenic, multifactorial manner. GV is epidemiologically associated with other autoimmune diseases, both in GV patients and in their close relatives, suggesting that shared genes underlie susceptibility to this group of diseases. Early candidate gene association studies yielded a few successes, such as PTPN22, but most such reports now appear to be false-positives. Subsequent genomewide linkage studies identified NLRP1 and XBP1, apparent true GV susceptibility genes involved in immune regulation, and recent genome-wide association studies （GWAS） of GV in Caucasian and Chinese populations have yielded a large number of additional validated GV susceptibility genes. Together, these genes highlight biological systems and pathways that reach from the immune cells to the melanocyte, and provide insights into both disease pathogenesis and potential new targets for both treatment and even prevention of GV and other autoimmune diseases in genetically susceptible individuals.展开更多
Hepatocellular carcinoma(HCC) is one of the most commonly diagnosed and deadly cancers worldwide; its incidence has been rising in the United States due to the increase in hepatitis C associated cirrhosis and the grow...Hepatocellular carcinoma(HCC) is one of the most commonly diagnosed and deadly cancers worldwide; its incidence has been rising in the United States due to the increase in hepatitis C associated cirrhosis and the growing epidemic of obesity. There have been no effective therapeutic options in the advanced disease setting beyond sorafenib, a multi-targeted tyrosine kinase inhibitor that showed significant survival benefit. Because of this, there is an urgent need to search for novel pathways in sorafenib experienced patients. This review will focus on the role of hypoxia and hypoxiainducible factor alpha(HIF-1α) in cancer development, specifically in HCC. We will discuss the biology of HIF-1α, the pathways with which it interacts, and the function of HIF-1α in HCC. Furthermore, we will review studies highlighting the relevance of HIF-1α in the clinical setting, as well as the pre-clinical data supporting its further investigation. Finally, we will conclude with a discussion of the potential role of a HIF-1α m RNA antagonist for the treatment of HCC, and hypothesize the ways in which such an inhibitor may be best utilized in the management of advanced HCC. Hypoxia plays a significant role in the development of HCC. HIF-1α is a key transcription factor involved in the hypoxic response of cancer cells. It activates transcription of genes responsible for angiogenesis, glucose metabolism, proliferation, invasion and metastasis in HCC. Its involvement in multiple, essential tumor pathways makes it an attractive potential therapeutic target in HCC.展开更多
AIM: To evaluate the effect of age and acoustic stress on gastric myoelectrical activity (GMA) and autonomic nervous system function. METHODS: Twenty-one male subjects (age range 22-71 years, mean 44 years) were recru...AIM: To evaluate the effect of age and acoustic stress on gastric myoelectrical activity (GMA) and autonomic nervous system function. METHODS: Twenty-one male subjects (age range 22-71 years, mean 44 years) were recruited and exposed, in random order, to three auditory stimuli (Hospital noise, conversation babble and traffic noise) after a 20-min baseline. All periods lasted 20 min and were interspersed with a 10 min of recovery. GMA was obtained using a Synectics Microdigitrapper. Autonomic nerve function was assessed by monitoring blood pressure and heart rate using an automatic recording device. RESULTS: Dominant power tended to decrease with increase of age (P < 0.05). The overall percentage of three cycle per minute (CPM) activity decreased during exposure to hospital noise (12.0%, P < 0.05), traffic noise (13.9%, P < 0.05), and conversation babble (7.1%). The subjects in the younger group (< 50 years) showed a consistent reduction in the percentage of 3 CPM activity during hospital noise (22.9%, P < 0.05), traffic noise (19.0%, P < 0.05), and conversation babble (15.5%). These observations were accompanied by a significant increase in bradygastria: hospital noise (P < 0.05) and traffic noise (P < 0.05). In contrast, the subjects over 50 years of age did not exhibit a significant decrease in 3 CPM activity. Regardless of age, noise did not alter blood pressure or heart rate. CONCLUSION: GMA changes with age. Loud noise can alter GMA, especially in younger individuals. Our data indicate that even short-term exposure to noise may alter the contractility of the stomach.展开更多
目的比较启动降尿酸治疗初期不采用预防措施及采用不同药物预防痛风发作的成本效果。方法本研究采用决策树模型,基于日本FORTUNE-1临床试验和美国IQVIA~(TM)健康计划索赔数据库开展回顾性研究,以3个月为研究时长,选取卫生体系视角,评估...目的比较启动降尿酸治疗初期不采用预防措施及采用不同药物预防痛风发作的成本效果。方法本研究采用决策树模型,基于日本FORTUNE-1临床试验和美国IQVIA~(TM)健康计划索赔数据库开展回顾性研究,以3个月为研究时长,选取卫生体系视角,评估在降尿酸治疗初期不采用预防措施,以及采用小剂量秋水仙碱、小剂量非甾体抗炎药(nonsteroidal antiinflammatory drug,NSAID,以萘普生为例)预防痛风发作的成本效果,以增量成本效果比(incremental cost-effectiveness ratio,ICER)和增量净货币效益(incremental net monetary benefit,INMB)为结果指标。结果基础分析显示,秋水仙碱以55.29元获得0.2480质量调整生命年(quality adjustment of life year,QALY),NSAID以196.96元获得0.2482 QALY,无预防措施以82.41元获得0.2451 QALY。与无预防措施相比,秋水仙碱、NSAID的ICER分别为-9197.73元/QALY(绝对优势)、36514.08元/QALY;秋水仙碱、NSAID的INMB分别为785.35元、691.97元。情境分析结果证实了模型的稳健性。单因素敏感性分析表明,秋水仙碱/NSAID较无预防措施在各参数变化范围内始终具有成本效果优势;在两种预防措施的比较中,NSAID的价格、秋水仙碱引起腹泻的概率对结果影响较大;概率敏感性分析则表明,在当前支付意愿阈值(257094元/QALY),秋水仙碱预防、NSAID、无预防措施可被接受的概率分别为67.6%、3.1%、29.3%。结论在当前经济水平下,降尿酸药物治疗初期,同时使用小剂量秋水仙碱预防痛风急性发作最具经济学效益。展开更多
文摘Resistant hypertension(RH) has a prevalence of around 12% and is associated with an increased risk of cardiovascular disease, progression to end-stage renal disease, and even mortality. In 2017, the American College of Cardiology and American Heart Association released updated guidelines that detail steps to ensure proper diagnosis of RH, including the exclusion of pseudoresistance.Lifestyle modifications, such as low salt diet and physical exercise, remain at the forefront of optimizing blood pressure control. Secondary causes of RH also need to be investigated, including screening for obstructive sleep apnea. Notably, the guidelines demonstrate a major change in medication management recommendations to include mineralocorticoid receptor antagonists. In addition to advances in medication optimization, there are several device-based therapies that have been showing efficacy in the treatment of RH. Renal denervation therapy has struggled to show efficacy for blood pressure control, but with a redesigned catheter device, it is once again being tested in clinical trials. Carotid baroreceptor activation therapy(BAT) via an implantable pulse generator has been shown to be effective in lowering blood pressure both acutely and in longterm follow up data, but there is some concern about the safety profile. Both a second-generation pulse generator and an endovascular implant are being tested in new clinical trials with hopes for improved safety profiles while maintaining therapeutic efficacy. Both renal denervation and carotid BAT need continued study before widespread clinical implementation. Central arteriovenous anastomosis has emerged as another possible therapy and is being actively explored. The ongoing pursuit of blood pressure control is a vital part of minimizing adverse patient outcomes. The future landscape appears hopeful for helping patients achieve blood pressure goals not only through the optimization of antihypertensive medications but also through device-based therapies in select individuals.
基金supported by the Thailand Science Research and Innovation Fund Chulalongkorn University(Grant No.HEAF67300078)the 90th Anniversary Scholarship,Chulalongkorn University Ratchadapisek Sompoch Fund(Grant No.Batch#55,T.Boonto)the Center of Excellence in Hepatitis and Liver Cancer,Faculty of Medicine,Chulalongkorn University.T.Boonto was supported by the scholarship from the Graduate School,Chulalongkorn University,to commemorate the 72^(nd) anniversary of His Majesty King Bhumibol Adulyadej(Grant No.Batch#22).
文摘Hepatocellular carcinoma(HCC)remains the third leading cause of cancer-related deaths worldwide;however,its therapeutic options are limited.Understanding the molecular mechanisms of HCC could provide insight into new therapies.Emerging studies indicate the important role of long-noncoding RNAs(lncRNAs)in the pathogenesis of HCC.The expression of the well-studied lncRNA taurine upregulated gene 1(TUG1)is upregulated in HCC tissues,but its transcriptomic effects in HCC cells remain unexplored.We established TUG1-knockdown and control HCC cells for RNA-seq experiments.KEGG analysis revealed glycolysis as the top enriched pathway upon TUG1 silencing.Accordingly,TUG1-depleted HCC cells showed impairments in glucose uptake,ATP synthesis,and lactate production.Clinical HCC tissue data revealed positive gene expression correlations between TUG1 and several glycolysis-related genes.To identify a molecular function of TUG1 in glycolysis,we explored the competing endogenous model and used bioinformatic tools to find the five microRNAs(miRNAs)that had the most binding sites for TUG1.Among these miRNAs,miR-122-5p exhibited an inverse correlation in gene expression with most TUG1-regulated glycolysis genes,including PKM,ALDOA,ENO2,and PFKM.Dual-luciferase assays demonstrated the direct interaction between TUG1 and miR-122-5p and between miR-122-5p and the 3ʹuntranslated regions of both PKM and ALDOA.We further showed that inhibition of miR-122-5p alleviated the suppression of glycolysis induced by TUG1 depletion.Together,our RNA-seq analysis of TUG1-depleted HCC cells,combined with clinical data,reveals a critical role of TUG1 in regulating glycolysis and provides new insight into its oncogenic function in HCC.
基金supported by the Natural Science Foundation of Zhejiang Province,China(Grant No.LTGY23H220001).
文摘With advancements in systemic therapy,the incidence of brain metastases(BMs)continues to rise,leading to severe neurological complications.Effective and precise treatment modalities are,therefore,critically important for managing BMs.Radiation therapy(RT),including photon therapy,has been essential in managing BMs.Recent technological advances have significantly enhanced the precision,efficacy,and safety of these treatments.This comprehensive review provides an in-depth examination of the latest advancements in radiation and photon therapy technologies for treating BMs,focusing on innovations such as stereotactic radiosurgery(SRS),whole-brain radiation therapy(WBRT),laser interstitial thermal therapy(LITT),and other radiation-related treatment modalities.Additionally,we discuss clinical outcomes,challenges,and future directions in this rapidly evolving field.While a detailed comparison of techniques is beyond the scope of this paper,this paper provides up-to-date technical information for physicians,medical physicists,patients,and researchers in related fields,potentially enhancing clinical outcomes.Among the treatment modalities,SRS has become a cornerstone of RT for BMs,with its implementation spanning multiple modalities over the past few decades.Given its inherent minimally invasive nature and growing clinical acceptance,SRS is positioned to further evolve as a key therapeutic tool in both neurosurgery and radiotherapy.
文摘Background and Objective Patients with glioma experience a high symptom burden and have diverse palliative care needs.However,the assessment scales used in palliative care remain non-standardized and highly heterogeneous.To evaluate the application patterns of the current scales used in palliative care for glioma,we aim to identify gaps and assess the need for disease-specific scales in glioma palliative care.Methods We conducted a systematic search of five databases including PubMed,Web of Science,Medline,EMBASE,and CINAHL for quantitative studies that reported scale-based assessments in glioma palliative care.We extracted data on scale characteristics,domains,frequency,and psychometric properties.Quality assessments were performed using the Cochrane ROB 2.0 and ROBINS-I tools.Results Of the 3,405 records initially identified,72 studies were included.These studies contained 75 distinct scales that were used 193 times.Mood(21.7%),quality of life(24.4%),and supportive care needs(5.2%)assessments were the most frequently assessed items,exceeding half of all scale applications.Among the various assessment dimensions,the Distress Thermometer(DT)was the most frequently used tool for assessing mood,while the Short Form-36 Health Survey Questionnaire(SF-36)was the most frequently used tool for assessing quality of life.The Mini Mental Status Examination(MMSE)was the most common tool for cognitive assessment.Performance status(5.2%)and social support(6.8%)were underrepresented.Only three brain tumor-specific scales were identified.Caregiver-focused scales were limited and predominantly burden-oriented.Conclusions There are significant heterogeneity,domain imbalances,and validation gaps in the current use of assessment scales for patients with glioma receiving palliative care.The scale selected for use should be comprehensive and user-friendly.
文摘AIM:To comprehensively investigate the current state of research on the application of neurotrophic factors in glaucoma therapy and identify potential research hotspots.METHODS:On September 30,2023,a literature search was conducted on Scopus using specific keywords related to neurotrophic factors and glaucoma.Of the 918 articles retrieved,780 met the inclusion criteria.These articles were subsequently analyzed and visualized using Google Sheets,Biblioshiny 3.1,and VosViewer 1.6.18.RESULTS:A total of 780 studies published between 1989 and 2023 were included,and the global publication count showed an upward trend through 2023(projected to continue rising by 2030).The United States,China,Japan,Italy,and Australia were the most significant contributors to the publication output.Research in this field had been published in 313 journals,spanning categories such as pharmacology and drug development,ophthalmology,genetics and gene therapy,and neuroscience.A total of 2622 authors had contributed to these studies,with the most prolific author publishing 14 articles.The focus of research in this field had evolved sequentially from“glutamate”to“CNTF”and“GDNF”,and finally to“optic nerve injury”.Co-occurrence analysis identified five clusters:glaucoma and ocular health,neuroinflammation in ophthalmology,neuroprotection in ophthalmology,ocular drug delivery,and stem cell therapy.Several areas in this field require further exploration,including the neurophysiological mechanisms underlying glaucoma,ocular drug delivery systems,and the clinical value of specific neurotrophic factors.CONCLUSION:This study systematically reviews global research trends on neurotrophic factors in glaucoma therapy,clarifying the current research status and future directions.
文摘BACKGROUND Giant cell tumor of bone(GCTB)is a rare,locally aggressive neoplasm that should be treated surgically,whenever possible.This treatment approach may be linked with greater morbidity besides functional impairment.Denosumab is a human monoclonal antibody.Its administration inhibits bone resorption and has become part of the therapeutic armamentarium against GCTB,as it allows local control with a view to downstaging for a more conservative surgical procedure.However,there is no consensus in the literature regarding the optimal denosumab regimen for GCTB.Therefore,a wide discussion of denosumab regimen is necessary.AIM To assess the effectiveness of various therapy protocols employing denosumab in individuals with GCTB.METHODS A broad and systematic literature search was carried out using the PRISMA guidelines.We analyzed studies that reported skeletally mature patients with GCTB regardless of sex or ethnicity treated with denosumab.Articles with fewer than five patients and in languages except Spanish,Portuguese and English were excluded.Statistical analysis with proportion meta-analysis was performed due to the dichotomous nature of the data.RESULTS 1005 articles were screened,of which 26 articles met the inclusion criteria and were selected,totaling 1742 patients,51.8%women and 48.2%men,with an average of 35 years of age.Treatment with denosumab was associated with high rates of clinical benefit(CB)and imaging response(IR),without changing local recurrence rates when compared to patients treated without denosumab,regardless of the therapeutic regimen adopted and the number of doses applied.The adverse events(AE)presented were mostly mild,with the exception of a malignant transformation to osteosarcoma.CONCLUSION Treatment of GCTB with denosumab is effective,showing high rates of CB and IR.The AE that occurred were mostly mild.We found no differences between the articles considering the researched outcomes regardless of the therapeutic regimen adopted.
基金supported in part by the grants R01 AR45585 and R01 AR056292 from the National Institutes of Health,USA
文摘Vitiligo is an acquired disease characterized principally by patchy depigmentation of skin and overlying hair. Generalized vitiligo （GV）, the predominant form of the disorder, results from autoimmune loss of melanocytes from affected regions. GV is a ＂complex trait＂, inherited in a non-Mendelian polygenic, multifactorial manner. GV is epidemiologically associated with other autoimmune diseases, both in GV patients and in their close relatives, suggesting that shared genes underlie susceptibility to this group of diseases. Early candidate gene association studies yielded a few successes, such as PTPN22, but most such reports now appear to be false-positives. Subsequent genomewide linkage studies identified NLRP1 and XBP1, apparent true GV susceptibility genes involved in immune regulation, and recent genome-wide association studies （GWAS） of GV in Caucasian and Chinese populations have yielded a large number of additional validated GV susceptibility genes. Together, these genes highlight biological systems and pathways that reach from the immune cells to the melanocyte, and provide insights into both disease pathogenesis and potential new targets for both treatment and even prevention of GV and other autoimmune diseases in genetically susceptible individuals.
文摘Hepatocellular carcinoma(HCC) is one of the most commonly diagnosed and deadly cancers worldwide; its incidence has been rising in the United States due to the increase in hepatitis C associated cirrhosis and the growing epidemic of obesity. There have been no effective therapeutic options in the advanced disease setting beyond sorafenib, a multi-targeted tyrosine kinase inhibitor that showed significant survival benefit. Because of this, there is an urgent need to search for novel pathways in sorafenib experienced patients. This review will focus on the role of hypoxia and hypoxiainducible factor alpha(HIF-1α) in cancer development, specifically in HCC. We will discuss the biology of HIF-1α, the pathways with which it interacts, and the function of HIF-1α in HCC. Furthermore, we will review studies highlighting the relevance of HIF-1α in the clinical setting, as well as the pre-clinical data supporting its further investigation. Finally, we will conclude with a discussion of the potential role of a HIF-1α m RNA antagonist for the treatment of HCC, and hypothesize the ways in which such an inhibitor may be best utilized in the management of advanced HCC. Hypoxia plays a significant role in the development of HCC. HIF-1α is a key transcription factor involved in the hypoxic response of cancer cells. It activates transcription of genes responsible for angiogenesis, glucose metabolism, proliferation, invasion and metastasis in HCC. Its involvement in multiple, essential tumor pathways makes it an attractive potential therapeutic target in HCC.
文摘AIM: To evaluate the effect of age and acoustic stress on gastric myoelectrical activity (GMA) and autonomic nervous system function. METHODS: Twenty-one male subjects (age range 22-71 years, mean 44 years) were recruited and exposed, in random order, to three auditory stimuli (Hospital noise, conversation babble and traffic noise) after a 20-min baseline. All periods lasted 20 min and were interspersed with a 10 min of recovery. GMA was obtained using a Synectics Microdigitrapper. Autonomic nerve function was assessed by monitoring blood pressure and heart rate using an automatic recording device. RESULTS: Dominant power tended to decrease with increase of age (P < 0.05). The overall percentage of three cycle per minute (CPM) activity decreased during exposure to hospital noise (12.0%, P < 0.05), traffic noise (13.9%, P < 0.05), and conversation babble (7.1%). The subjects in the younger group (< 50 years) showed a consistent reduction in the percentage of 3 CPM activity during hospital noise (22.9%, P < 0.05), traffic noise (19.0%, P < 0.05), and conversation babble (15.5%). These observations were accompanied by a significant increase in bradygastria: hospital noise (P < 0.05) and traffic noise (P < 0.05). In contrast, the subjects over 50 years of age did not exhibit a significant decrease in 3 CPM activity. Regardless of age, noise did not alter blood pressure or heart rate. CONCLUSION: GMA changes with age. Loud noise can alter GMA, especially in younger individuals. Our data indicate that even short-term exposure to noise may alter the contractility of the stomach.
文摘目的比较启动降尿酸治疗初期不采用预防措施及采用不同药物预防痛风发作的成本效果。方法本研究采用决策树模型,基于日本FORTUNE-1临床试验和美国IQVIA~(TM)健康计划索赔数据库开展回顾性研究,以3个月为研究时长,选取卫生体系视角,评估在降尿酸治疗初期不采用预防措施,以及采用小剂量秋水仙碱、小剂量非甾体抗炎药(nonsteroidal antiinflammatory drug,NSAID,以萘普生为例)预防痛风发作的成本效果,以增量成本效果比(incremental cost-effectiveness ratio,ICER)和增量净货币效益(incremental net monetary benefit,INMB)为结果指标。结果基础分析显示,秋水仙碱以55.29元获得0.2480质量调整生命年(quality adjustment of life year,QALY),NSAID以196.96元获得0.2482 QALY,无预防措施以82.41元获得0.2451 QALY。与无预防措施相比,秋水仙碱、NSAID的ICER分别为-9197.73元/QALY(绝对优势)、36514.08元/QALY;秋水仙碱、NSAID的INMB分别为785.35元、691.97元。情境分析结果证实了模型的稳健性。单因素敏感性分析表明,秋水仙碱/NSAID较无预防措施在各参数变化范围内始终具有成本效果优势;在两种预防措施的比较中,NSAID的价格、秋水仙碱引起腹泻的概率对结果影响较大;概率敏感性分析则表明,在当前支付意愿阈值(257094元/QALY),秋水仙碱预防、NSAID、无预防措施可被接受的概率分别为67.6%、3.1%、29.3%。结论在当前经济水平下,降尿酸药物治疗初期,同时使用小剂量秋水仙碱预防痛风急性发作最具经济学效益。
