A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigati...A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.展开更多
An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease prog...An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control.展开更多
Background: Studies have shown a strong correlation between the growth of E2 in serum and estrone-3-glucuronide (E1-3G) in urine during ovarian stimulation. Thus, we developed theoretical models for using urinary E1-3...Background: Studies have shown a strong correlation between the growth of E2 in serum and estrone-3-glucuronide (E1-3G) in urine during ovarian stimulation. Thus, we developed theoretical models for using urinary E1-3G in ovarian stimulation and focused on their experimental verification and analysis. Methods: A prospective, observational pilot study was conducted involving 54 patients who underwent 54 cycles of ovarian stimulation. The goal was to establish the growth rate of urinary E1-3G during the course of stimulation and to determine the daily upper and lower limits of growth rates at which stimulation is appropriate and safe. Controlled ovarian stimulation was performed using two different stimulation protocols—an antagonist protocol in 25 cases and a progestin-primed ovarian stimulation protocol (PPOS) in 29 cases, with fixed doses of gonadotropins. From the second day of stimulation, patients self-measured their daily urine E1-3G levels at home using a portable analyzer. In parallel, a standard ultrasound follow-up protocol accompanied by a determination of E2, LH, and P levels was applied to optimally control stimulation. Results: The average daily growth rates in both groups were about 50%. The daily increase in E1-3G for the antagonist protocol ranged from 14% to 79%, while they were 28% to 79% for the PPOS protocol. Conclusion: This is the first study to analyze the dynamics of E1-3G in two different protocols and to estimate the limits of its increase during the entire course of the stimulation. The results confirm our theoretical model for the viability of using urinary E1-3G for monitoring ovarian stimulation.展开更多
目的分析糖尿病肾病患者单独使用胰高血糖素样肽-1(GLP-1)受体激动剂利拉鲁肽以及联合钠-葡萄糖协同转运蛋白2抑制剂恩格列净治疗的效果,以及对心肾功能,血管内皮生长因子(VEGF)、VEGF-A水平的影响。方法选择该院2022年4月至2023年5月...目的分析糖尿病肾病患者单独使用胰高血糖素样肽-1(GLP-1)受体激动剂利拉鲁肽以及联合钠-葡萄糖协同转运蛋白2抑制剂恩格列净治疗的效果,以及对心肾功能,血管内皮生长因子(VEGF)、VEGF-A水平的影响。方法选择该院2022年4月至2023年5月收治的84例糖尿病肾病患者纳入研究对象,分为对照组和试验组,各42例。对照组患者单独使用GLP-1受体激动剂利拉鲁肽治疗,试验组使用GLP-1受体激动剂利拉鲁肽与恩格列净治疗,分析、比较两种不同方案对患者疗效的影响。结果治疗前,两组糖化血红蛋白(HbA1c)、餐后2 h血糖(2 h PG)、空腹血糖(FBG)、左室射血分数(LVEF)、左室后壁厚度(LVPWT)、左室舒张末期内径(LVEDD)、左室舒张早期充盈峰/舒张末期充盈峰(E/A)、尿微量清蛋白/尿肌酐(ACR)、血肌酐(Scr)、尿肌酐(Ucr)、胰岛素用量比较,差异均无统计学意义(P>0.05),治疗后,与对照组比较,试验组HbA1c、2 h PG、FBG、LVPWT、LVEDD、ACR、Scr、Ucr水平更低,胰岛素用量更少,E/A、LVEF更高,差异均有统计学意义(P<0.05)。治疗前,两组患者VEGF、VEGF-A比较,差异均无统计学意义(P>0.05),治疗后,试验组VEGF、VEGF-A水平低于对照组(P<0.05)。试验组与对照组患者的低血糖、腹泻、低血压等不良反应总发生率比较,差异无统计学意义(P>0.05)。结论糖尿病肾病患者使用GLP-1受体激动剂利拉鲁肽联合恩格列净治疗的降糖效果较好且安全,还可以改善心肾功能,抑制VEGF、VEGF-A的过度表达,并减少胰岛素用量。展开更多
GLP-1RA及SGLT-2i是ADA和中华医学会糖尿病学分会推荐的新型降糖药物,具有低血糖风险小、兼具心血管保护及降低体重等代谢获益的特点。高尿酸血症是2型糖尿病的独立危险因素,在临床实践中,人们一直在关注预防SUA的升高。据估计,患者SUA...GLP-1RA及SGLT-2i是ADA和中华医学会糖尿病学分会推荐的新型降糖药物,具有低血糖风险小、兼具心血管保护及降低体重等代谢获益的特点。高尿酸血症是2型糖尿病的独立危险因素,在临床实践中,人们一直在关注预防SUA的升高。据估计,患者SUA每升高1 mg/dl,发生T2DM的风险就会增加17%。国内外学者研究结果提示SGLT-2i能兼顾降糖的同时降低SUA水平;最近国外研究显示GLP-1RA还可以降低SUA水平,但仍存在矛盾。国内学者对此研究报告甚少。还需要更多的研究填补此领域的空白,为更好地预防2型糖尿的发生及发展作出贡献。GLP-1RA and SGLT-2i are new hypoglycemic drugs recommended by ADA and Diabetes Branch of Chinese Medical Association, which have the characteristics of low risk of hypoglycemia, metabolic benefits such as cardiovascular protection and weight reduction. Hyperuricemia is an independent risk factor for type 2 diabetes, and much attention has been paid to the prevention of elevated SUA in clinical practice. It is estimated that every 1 mg/dl elevation of patient SUA causes a 17% increase in the risk of developing T2DM. The results of domestic and foreign scholars suggest that SGLT-2i can reduce SUA level while lowering glucose;recent foreign studies show that GLP-1RA can also reduce SUA level, but there are still contradictions. Domestic scholars have few reports on this. More studies are needed to fill the gap in this field to contribute to better prevention of the occurrence and development of type 2 diabetes mellitus.展开更多
Spinal cord injury often leads to severe motor and sensory deficits,and prognosis using the currently available therapies remains poor.Therefore,we aimed to explore a novel therapeutic approach for improving the progn...Spinal cord injury often leads to severe motor and sensory deficits,and prognosis using the currently available therapies remains poor.Therefore,we aimed to explore a novel therapeutic approach for improving the prognosis of spinal cord injury.In this study,we implanted oscillating field stimulation devices and transplanted neural stem cells into the thoracic region(T9–T10)of rats with a spinal cord contusion.Basso-Beattie-Bresnahan scoring revealed that oscillating field stimulation combined with neural stem cells transplantation promoted motor function recovery following spinal cord injury.In addition,we investigated the regulation of oscillating field stimulation on the miR-124/Tal1 axis in neural stem cells.Transfection of lentivirus was performed to investigate the role of Tal1 in neurogenesis of neural stem cells induced by oscillating field stimulation.Quantitative reverse transcription-polymerase chain reaction,immunofluorescence and western blotting showed that oscillating field stimulation promoted neurogenesis of neural stem cells in vitro and in vivo.Hematoxylin and eosin staining showed that oscillating field stimulation combined with neural stem cells transplantation alleviated cavities formation after spinal cord injury.Taking the results together,we concluded that oscillating field stimulation decreased miR-124 expression and increased Tal1 content,thereby promoting the neurogenesis of neural stem cells.The combination of oscillating field stimulation and neural stem cells transplantation improved neurogenesis,and thereby promoted structural and functional recovery after spinal cord injury.展开更多
目的对比胰高血糖素样肽-1(GLP-1)受体激动剂和二肽基肽酶-4(DPP-4)抑制剂分别联合二甲双胍治疗2型糖尿病(T2DM)的疗效及对其血清抗氧因子、炎症因子的影响。方法将2020年5月至2022年5月中国中医科学院广安门医院南区收治的120例T2DM患...目的对比胰高血糖素样肽-1(GLP-1)受体激动剂和二肽基肽酶-4(DPP-4)抑制剂分别联合二甲双胍治疗2型糖尿病(T2DM)的疗效及对其血清抗氧因子、炎症因子的影响。方法将2020年5月至2022年5月中国中医科学院广安门医院南区收治的120例T2DM患者纳入本次前瞻性研究,采用随机数字表法分成GLP-1联合组(n=40)、DPP-4联合组(n=40)和对照组(n=40)。GLP-1联合组患者治疗方案为二甲双胍治疗+利拉鲁肽,DPP-4联合组患者治疗方案为二甲双胍+沙格列汀,对照组患者仅口服二甲双胍治疗。治疗为期6个月。比较3组患者治疗前后的血糖相关指标[空腹血糖、餐后2 h血糖(2 h PPG)、糖化血红蛋白(HbA1c)]及胰岛素抵抗指数(HOMA-IR)、氧化应激指标[超氧化物歧化酶(SOD)和6-酮-前列环素F1α(6-Keto-PGF1α)]和炎症因子[肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和超敏C反应蛋白(hs-CRP)]表达情况。结果GLP-1联合组治疗后的空腹血糖、2 hPPG、HbA1c和HOMA-IR分别为(5.05±0.69)mmol/L、(7.42±0.98)mmol/L、(6.11±0.70)%和(3.20±0.45),DPP-4联合组分别为(5.58±0.61)mmol/L、(8.09±1.04)mmol/L、(6.65±0.76)%和(3.78±0.50),对照组分别为(6.50±0.75)mmol/L、(10.14±1.22)mmol/L、(7.80±0.81)%和(4.61±0.59),GLP-1联合组与DPP-4联合组治疗后的上述血糖相关指标及HOMA-IR均较对照组显著下降,且GLP-1联合组显著低于DPP-4联合组,差异均有统计学意义(P<0.05)。GLP-1联合组治疗后的SOD和6-Keto-PGF1α分别为(95.09±9.97)U/mL、(76.19±6.80)ng/L,DPP-4联合组分别为(85.17±10.18)U/mL、(67.32±6.39)ng/L,对照组分别为(76.89±9.06)U/mL、(60.46±6.02)ng/L,GLP-1联合组与DPP-4联合组治疗后的血清SOD、6-Keto-PGF1α均较对照组显著上升,且GLP-1联合组血清SOD、6-Keto-PGF1α均较DPP-4联合组显著上升,差异均有统计学意义(P<0.05)。GLP-1联合组TNF-α、IL-6和hs-CRP分别为(7.05±1.16)ng/L、(5.01±1.35)pg/mL、(4.04±0.51)mg/L,DPP-4联合组为(7.93±1.29)ng/L、(5.97±1.40)pg/mL、(4.99±0.59)mg/L,对照组为(10.34±1.58)ng/L、(7.58±1.49)pg/mL、(5.94±0.64)mg/L,GLP-1联合组与DPP-4联合组治疗后的上述血清炎症因子均较对照组显著下降,且GLP-1联合组显著低于DPP-4联合组,差异均有统计学意义(P<0.05)。结论GLP-1受体激动剂联合二甲双胍治疗T2DM的降糖效果优于DPP-4受体抑制剂联合二甲双胍,在改善胰岛素抵抗和氧化应激,降低炎症反应方面同样优于DPP-4受体抑制剂联合二甲双胍治疗。展开更多
基金supported by the National Natural Science Foundation of China,No.82001155(to LL)the Natural Science Foundation of Zhejiang Province,No.LY23H090004(to LL)+5 种基金the Natural Science Foundation of Ningbo,No.2023J068(to LL)the Fundamental Research Funds for the Provincial Universities of Zhejiang Province,No.SJLY2023008(to LL)the College Students'Scientific and Technological Innovation Project(Xin Miao Talent Plan)of Zhejiang Province,No.2022R405A045(to CC)the Student ResearchInnovation Program(SRIP)of Ningbo University,Nos.20235RIP1919(to CZ),2023SRIP1938(to YZ)the K.C.Wong Magna Fund in Ningbo University。
文摘A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.
基金supported by a grant from Ministry of Science,Technological Development and Innovation,Serbia,No.451-03-68/2022-14/200178(to NN)University of Defence,No.MFVMA/02/22-24(to MN)。
文摘An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control.
文摘Background: Studies have shown a strong correlation between the growth of E2 in serum and estrone-3-glucuronide (E1-3G) in urine during ovarian stimulation. Thus, we developed theoretical models for using urinary E1-3G in ovarian stimulation and focused on their experimental verification and analysis. Methods: A prospective, observational pilot study was conducted involving 54 patients who underwent 54 cycles of ovarian stimulation. The goal was to establish the growth rate of urinary E1-3G during the course of stimulation and to determine the daily upper and lower limits of growth rates at which stimulation is appropriate and safe. Controlled ovarian stimulation was performed using two different stimulation protocols—an antagonist protocol in 25 cases and a progestin-primed ovarian stimulation protocol (PPOS) in 29 cases, with fixed doses of gonadotropins. From the second day of stimulation, patients self-measured their daily urine E1-3G levels at home using a portable analyzer. In parallel, a standard ultrasound follow-up protocol accompanied by a determination of E2, LH, and P levels was applied to optimally control stimulation. Results: The average daily growth rates in both groups were about 50%. The daily increase in E1-3G for the antagonist protocol ranged from 14% to 79%, while they were 28% to 79% for the PPOS protocol. Conclusion: This is the first study to analyze the dynamics of E1-3G in two different protocols and to estimate the limits of its increase during the entire course of the stimulation. The results confirm our theoretical model for the viability of using urinary E1-3G for monitoring ovarian stimulation.
文摘目的分析糖尿病肾病患者单独使用胰高血糖素样肽-1(GLP-1)受体激动剂利拉鲁肽以及联合钠-葡萄糖协同转运蛋白2抑制剂恩格列净治疗的效果,以及对心肾功能,血管内皮生长因子(VEGF)、VEGF-A水平的影响。方法选择该院2022年4月至2023年5月收治的84例糖尿病肾病患者纳入研究对象,分为对照组和试验组,各42例。对照组患者单独使用GLP-1受体激动剂利拉鲁肽治疗,试验组使用GLP-1受体激动剂利拉鲁肽与恩格列净治疗,分析、比较两种不同方案对患者疗效的影响。结果治疗前,两组糖化血红蛋白(HbA1c)、餐后2 h血糖(2 h PG)、空腹血糖(FBG)、左室射血分数(LVEF)、左室后壁厚度(LVPWT)、左室舒张末期内径(LVEDD)、左室舒张早期充盈峰/舒张末期充盈峰(E/A)、尿微量清蛋白/尿肌酐(ACR)、血肌酐(Scr)、尿肌酐(Ucr)、胰岛素用量比较,差异均无统计学意义(P>0.05),治疗后,与对照组比较,试验组HbA1c、2 h PG、FBG、LVPWT、LVEDD、ACR、Scr、Ucr水平更低,胰岛素用量更少,E/A、LVEF更高,差异均有统计学意义(P<0.05)。治疗前,两组患者VEGF、VEGF-A比较,差异均无统计学意义(P>0.05),治疗后,试验组VEGF、VEGF-A水平低于对照组(P<0.05)。试验组与对照组患者的低血糖、腹泻、低血压等不良反应总发生率比较,差异无统计学意义(P>0.05)。结论糖尿病肾病患者使用GLP-1受体激动剂利拉鲁肽联合恩格列净治疗的降糖效果较好且安全,还可以改善心肾功能,抑制VEGF、VEGF-A的过度表达,并减少胰岛素用量。
文摘GLP-1RA及SGLT-2i是ADA和中华医学会糖尿病学分会推荐的新型降糖药物,具有低血糖风险小、兼具心血管保护及降低体重等代谢获益的特点。高尿酸血症是2型糖尿病的独立危险因素,在临床实践中,人们一直在关注预防SUA的升高。据估计,患者SUA每升高1 mg/dl,发生T2DM的风险就会增加17%。国内外学者研究结果提示SGLT-2i能兼顾降糖的同时降低SUA水平;最近国外研究显示GLP-1RA还可以降低SUA水平,但仍存在矛盾。国内学者对此研究报告甚少。还需要更多的研究填补此领域的空白,为更好地预防2型糖尿的发生及发展作出贡献。GLP-1RA and SGLT-2i are new hypoglycemic drugs recommended by ADA and Diabetes Branch of Chinese Medical Association, which have the characteristics of low risk of hypoglycemia, metabolic benefits such as cardiovascular protection and weight reduction. Hyperuricemia is an independent risk factor for type 2 diabetes, and much attention has been paid to the prevention of elevated SUA in clinical practice. It is estimated that every 1 mg/dl elevation of patient SUA causes a 17% increase in the risk of developing T2DM. The results of domestic and foreign scholars suggest that SGLT-2i can reduce SUA level while lowering glucose;recent foreign studies show that GLP-1RA can also reduce SUA level, but there are still contradictions. Domestic scholars have few reports on this. More studies are needed to fill the gap in this field to contribute to better prevention of the occurrence and development of type 2 diabetes mellitus.
基金supported by the National Natural Science Foundation of China,Nos.81471273(to JQ),and 81472088(to CLS)the Natural Science Research Projects in Colleges and Universities of Anhui Province,No.KJ2020ZD23(to JQ)the Natural Science Foundation of Anhui Province,No.2208085MH210(to JQ)。
文摘Spinal cord injury often leads to severe motor and sensory deficits,and prognosis using the currently available therapies remains poor.Therefore,we aimed to explore a novel therapeutic approach for improving the prognosis of spinal cord injury.In this study,we implanted oscillating field stimulation devices and transplanted neural stem cells into the thoracic region(T9–T10)of rats with a spinal cord contusion.Basso-Beattie-Bresnahan scoring revealed that oscillating field stimulation combined with neural stem cells transplantation promoted motor function recovery following spinal cord injury.In addition,we investigated the regulation of oscillating field stimulation on the miR-124/Tal1 axis in neural stem cells.Transfection of lentivirus was performed to investigate the role of Tal1 in neurogenesis of neural stem cells induced by oscillating field stimulation.Quantitative reverse transcription-polymerase chain reaction,immunofluorescence and western blotting showed that oscillating field stimulation promoted neurogenesis of neural stem cells in vitro and in vivo.Hematoxylin and eosin staining showed that oscillating field stimulation combined with neural stem cells transplantation alleviated cavities formation after spinal cord injury.Taking the results together,we concluded that oscillating field stimulation decreased miR-124 expression and increased Tal1 content,thereby promoting the neurogenesis of neural stem cells.The combination of oscillating field stimulation and neural stem cells transplantation improved neurogenesis,and thereby promoted structural and functional recovery after spinal cord injury.
文摘目的对比胰高血糖素样肽-1(GLP-1)受体激动剂和二肽基肽酶-4(DPP-4)抑制剂分别联合二甲双胍治疗2型糖尿病(T2DM)的疗效及对其血清抗氧因子、炎症因子的影响。方法将2020年5月至2022年5月中国中医科学院广安门医院南区收治的120例T2DM患者纳入本次前瞻性研究,采用随机数字表法分成GLP-1联合组(n=40)、DPP-4联合组(n=40)和对照组(n=40)。GLP-1联合组患者治疗方案为二甲双胍治疗+利拉鲁肽,DPP-4联合组患者治疗方案为二甲双胍+沙格列汀,对照组患者仅口服二甲双胍治疗。治疗为期6个月。比较3组患者治疗前后的血糖相关指标[空腹血糖、餐后2 h血糖(2 h PPG)、糖化血红蛋白(HbA1c)]及胰岛素抵抗指数(HOMA-IR)、氧化应激指标[超氧化物歧化酶(SOD)和6-酮-前列环素F1α(6-Keto-PGF1α)]和炎症因子[肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和超敏C反应蛋白(hs-CRP)]表达情况。结果GLP-1联合组治疗后的空腹血糖、2 hPPG、HbA1c和HOMA-IR分别为(5.05±0.69)mmol/L、(7.42±0.98)mmol/L、(6.11±0.70)%和(3.20±0.45),DPP-4联合组分别为(5.58±0.61)mmol/L、(8.09±1.04)mmol/L、(6.65±0.76)%和(3.78±0.50),对照组分别为(6.50±0.75)mmol/L、(10.14±1.22)mmol/L、(7.80±0.81)%和(4.61±0.59),GLP-1联合组与DPP-4联合组治疗后的上述血糖相关指标及HOMA-IR均较对照组显著下降,且GLP-1联合组显著低于DPP-4联合组,差异均有统计学意义(P<0.05)。GLP-1联合组治疗后的SOD和6-Keto-PGF1α分别为(95.09±9.97)U/mL、(76.19±6.80)ng/L,DPP-4联合组分别为(85.17±10.18)U/mL、(67.32±6.39)ng/L,对照组分别为(76.89±9.06)U/mL、(60.46±6.02)ng/L,GLP-1联合组与DPP-4联合组治疗后的血清SOD、6-Keto-PGF1α均较对照组显著上升,且GLP-1联合组血清SOD、6-Keto-PGF1α均较DPP-4联合组显著上升,差异均有统计学意义(P<0.05)。GLP-1联合组TNF-α、IL-6和hs-CRP分别为(7.05±1.16)ng/L、(5.01±1.35)pg/mL、(4.04±0.51)mg/L,DPP-4联合组为(7.93±1.29)ng/L、(5.97±1.40)pg/mL、(4.99±0.59)mg/L,对照组为(10.34±1.58)ng/L、(7.58±1.49)pg/mL、(5.94±0.64)mg/L,GLP-1联合组与DPP-4联合组治疗后的上述血清炎症因子均较对照组显著下降,且GLP-1联合组显著低于DPP-4联合组,差异均有统计学意义(P<0.05)。结论GLP-1受体激动剂联合二甲双胍治疗T2DM的降糖效果优于DPP-4受体抑制剂联合二甲双胍,在改善胰岛素抵抗和氧化应激,降低炎症反应方面同样优于DPP-4受体抑制剂联合二甲双胍治疗。
