目的:分析孔源性视网膜脱离玻璃体切除硅油填充术后不明原因视力下降(SORVL)的临床特征,探讨其发生机制。方法:回顾性分析在2019年1月~2023年6月在青岛大学附属医院眼科首诊为孔源性视网膜脱离(RRD)并且行玻璃体切除联合硅油填充术患眼...目的:分析孔源性视网膜脱离玻璃体切除硅油填充术后不明原因视力下降(SORVL)的临床特征,探讨其发生机制。方法:回顾性分析在2019年1月~2023年6月在青岛大学附属医院眼科首诊为孔源性视网膜脱离(RRD)并且行玻璃体切除联合硅油填充术患眼293例,进行最佳矫正视力(BCVA)、OCT、静态视野、VEP、ERG等检查,并分析相关数据。结果:孔源性视网膜脱离玻璃体切除硅油填充293眼,发生视力下降(SORVL) 20眼(6.83%)。术前黄斑附着眼的SORVL发生率约为13.33%,黄斑脱离眼的SORVL发生率约为4.59%;发现SORVL患者术后黄斑区神经节细胞层(GCL)平均厚度较术前明显变薄(P Objective: To analyze the clinical features of unexplained vision loss following vitrectomy with silicone oil tamponade for rhegmatogenous retinal detachment and explore the underlying mechanisms. Methods: A retrospective analysis was conducted on 293 patients initially diagnosed at the Department of Ophthalmology of the Affiliated Hospital of Qingdao University from January 2019 to September 2023, who suffered from rhegmatogenous retinal detachment (RRD) and underwent vitrectomy combined with silicone oil tamponade. A comprehensive range of ophthalmic examinations was conducted, encompassing best-corrected visual acuity (BCVA), optical coherence tomography (OCT), static visual field, visual evoked potential (VEP), and electroretinography (ERG). Results: In 293 eyes that underwent vitrectomy with silicone oil tamponade for RRD, 20 eyes (6.83%) demonstrated a decline in vision (SORVL). The incidence of silicone oil-related vision loss (SORVL) was approximately 13.33% in eyes with macular attachment before surgery and 4.59% in eyes with macular detachment. The mean thickness of the ganglion cell layer (GCL) in the macular region of patients who developed SORVL was significantly thinner after surgery than before surgery (P < 0.001), and P-VEP 15 min showed a significant delay in the peak of the P100 wave and a significant decrease in its amplitude;FVEP showed a significant decrease in the amplitude of the P2 wave. Conclusion: Eyes with macular attachment are at a higher risk of experiencing silicone oil-related vision loss than those with macular detachment, and patients with SORVL may have damage to the ganglion cells of the macular central sulcus. In the event of SORVL, silicone oil should be removed as soon as the retina is well restored.展开更多
目的探究脂肪含量和肥胖相关蛋白(fat mass and obesity-associated protein,FTO)和丝氨酸-苏氨酸激酶蛋白激酶D2(serine-threonine kinase protein kinase D2,PRKD2)在糖尿病肾病(diabetic kidney disease,DKD)进展中的调控作用和调节...目的探究脂肪含量和肥胖相关蛋白(fat mass and obesity-associated protein,FTO)和丝氨酸-苏氨酸激酶蛋白激酶D2(serine-threonine kinase protein kinase D2,PRKD2)在糖尿病肾病(diabetic kidney disease,DKD)进展中的调控作用和调节机制。方法采用35 mmol/L葡萄糖对足细胞(MPC5细胞)进行高糖刺激24h构建DKD体外模型。采用FTO过表达载体(pcDNA-FTO)和PRKD2过表达载体(pcDNA-PRKD2),或空载体(vector)转染高糖诱导的MPC5细胞。通过RT-qPCR检测FTO和PRKD2过表达效率;MeRIP检测PRKD2 mRNA的N6-甲基腺苷(N6-methyladenosine,m6A)修饰水平;ELISA检测Caspase-3活性、IL-6,TNF-α和单核细胞趋化蛋白-1(monocyte chemotactic protein-1,MCP-1)分泌量;流式细胞术分析细胞凋亡率;Western blot评估FTO和PRKD2蛋白水平,以及SIRT1/HIF-1α通路关键蛋白表达水平;Pearson分析FTO和PRKD2水平的相关性。结果与无高糖诱导对照组比较,高糖诱导的足细胞中FTO蛋白(0.51±0.04 vs 1.00±0.03)和PRKD2蛋白(0.45±0.03 vs 1.01±0.04)水平显著下调,差异具有统计学意义(t=13.17,16.76,均P<0.001)。高糖诱导的足细胞中FTO蛋白水平和PRKD2蛋白水平呈正相关(r2=0.7051,P<0.001)。与vector组相比,pcDNA-FTO组PRKD2 mRNA的m6A水平(0.56±0.09 vs1.01±0.13)降低,PRKD2 mRNA水平(3.16±0.14 vs 1.03±0.02)显著升高,差异具有统计学意义(t=51.37,11.82,均P<0.001)。与control组(IL-6:512.76±61.85 pg/ml,TNF-α:28.17±2.83 pg/ml,MCP-1:157.31±17.69 pg/ml)和vector组(IL-6:498.41±87.51 pg/ml,TNF-α:26.35±5.47 pg/ml,MCP-1:165.52±16.87 pg/ml)比较,pcDNA-PRKD2组IL-6(301.86±21.85 pg/ml),TNF-α(11.06±4.12 pg/ml),MCP-1分泌量(81.45±9.03pg/ml)显著减少,差异具有统计学意义(F=7.51,10.47,61.97,均P<0.01)。与control组(Caspase-3:689.65±79.5U/L,细胞凋亡率:22.31%±2.69%)和vector组(Caspase-3:715.91±113.58 U/L,细胞凋亡率:21.07%±3.28%)比较,pcDNA-PRKD2组Caspase-3活性(437.64±104.76 U/L)和细胞凋亡率(8.41%±3.15%)下降,差异具有统计学意义(F=2.35,79.13,均P<0.01)。与control组(SIRT1:1.01±0.05,HIF-1α:1.03±0.07)和vector组(SIRT1:0.97±0.05,HIF-1α:1.02±0.03)相比,pcDNA-PRKD2组SIRT1蛋白(3.51±0.15)水平升高,HIF-1α蛋白(0.37±0.07)水平降低,差异具有统计学意义(F=31.54,8.31,均P<0.01)。结论FTO介导m6A修饰的PRKD2通过SIRT1/HIF-1α通路抑制高糖诱导的足细胞炎症反应和细胞凋亡。展开更多
目的:克罗恩病和痛风发病率逐年增高,但其关联性尚未明确。本研究利用孟德尔随机化方法,探讨克罗恩病与痛风之间的潜在因果关系。方法:我们选取与克罗恩病和痛风显著关联的单核苷酸多态性作为工具变量,利用公开的全基因组关联研究的汇...目的:克罗恩病和痛风发病率逐年增高,但其关联性尚未明确。本研究利用孟德尔随机化方法,探讨克罗恩病与痛风之间的潜在因果关系。方法:我们选取与克罗恩病和痛风显著关联的单核苷酸多态性作为工具变量,利用公开的全基因组关联研究的汇总统计数据进行分析。我们采用多种MR方法并进行了敏感性分析。结果:克罗恩病与痛风的发病风险正相关(OR = 1.00060493,95%置信区间1.00013013~1.00107996,P值 = 0.01251316)。敏感性分析进一步印证了该发现,未见明显的异质性和水平多效性。结论:我们的研究结果表明克罗恩病与痛风之间存在正相关关系。这一发现为克罗恩病与痛风之间的关系及其病理生理机制提供了新的见解,并为痛风的预防和治疗提出了新策略。Objective: The incidence of Crohn’s disease and gout is increasing year by year, but the correlation is not clear, so we conducted a two-sample bidirectional mendelian randomization study to examine the association between them. Method: We selected single nucleotide polymorphisms significantly associated with Crohn’s disease and gout as instrumental variables and analyzed them using summary statistics from publicly available genome-wide association studies. We used multiple MR methods and performed sensitivity analyses. Results: The results revealed that Crohn’s disease was positively associated with the risk of developing gout (Odds Ratio, OR = 1.00060493, 95% Confidence Interval, CI, 1.00013013~1.00107996, P value = 0.01251316). Sensitivity analyses further corroborated the finding, with no significant heterogeneity or horizontal pleiotropy seen. Conclusions: Our findings suggest a positive association between Crohn’s disease and gout. This finding provides new insights into the relationship between Crohn’s disease and gout and its pathophysiologic mechanisms, and new strategies for the prevention and treatment of gout.展开更多
目的探讨新型过氧化物酶体增殖物激活受体(PPARs)泛激动剂西格列他钠治疗2型糖尿病的临床效果与安全性。方法选取2022年1月至6月联勤保障部队第九七〇医院威海医疗区收治的68例2型糖尿病患者作为研究对象,按照随机数字表法分为观察组(n=...目的探讨新型过氧化物酶体增殖物激活受体(PPARs)泛激动剂西格列他钠治疗2型糖尿病的临床效果与安全性。方法选取2022年1月至6月联勤保障部队第九七〇医院威海医疗区收治的68例2型糖尿病患者作为研究对象,按照随机数字表法分为观察组(n=34)和对照组(n=34)。对照组采用门冬胰岛素30注射液治疗,观察组在对照组的基础上联合西格列他钠治疗。比较两组患者治疗前后的胰岛素抵抗指数(HOMA-IR)、胰岛β细胞功能指数(HOMA-β)、体重指数(BMI)、血糖情况[糖化血红蛋白(HbA1c)、空腹血糖(FPG)、餐后2 h血糖(2 h PG)]、PPARs水平及不良反应的差别。结果观察组治疗总有效率高于对照组,差异有统计学意义(P<0.05);观察组的HOMA-IR、HbA1c、FPG、2hPG均低于对照组,差异有统计学意义(P<0.05);观察组的HOMA-β、PPARα、PPARβ、PPARγ水平均高于对照组,差异有统计学意义(P<0.05);两组患者BMI和不良反应比较,差异无统计学意义(P>0.05)。结论西格列他钠可有效改善2型糖尿病患者胰岛功能及胰岛素抵抗,提升PPARs水平,改善血糖控制,提高治疗效果,减少不良反应。展开更多
背景:尿酸作为一种内源性的抗氧化剂,其抗氧化、抗DNA损害作用及发挥促成骨作用近年受到关注。目的:探讨不同浓度尿酸对人骨髓间充质干细胞向成骨细胞分化过程中Wnt/β-catenin信号通路相关基因表达的影响。方法:采用全骨髓贴壁法体外...背景:尿酸作为一种内源性的抗氧化剂,其抗氧化、抗DNA损害作用及发挥促成骨作用近年受到关注。目的:探讨不同浓度尿酸对人骨髓间充质干细胞向成骨细胞分化过程中Wnt/β-catenin信号通路相关基因表达的影响。方法:采用全骨髓贴壁法体外分离培养健康成年人骨髓间充质干细胞,培养至第3代时,用含不同浓度尿酸(0,140,280,560μmol/L)的成骨诱导液进行成骨向诱导分化培养,检测细胞成骨分化过程中碱性磷酸酶活性、增殖能力以及Wnt信号通路中Wnt-3α,β-catenin m RNA的表达。结果与结论:各组细胞碱性磷酸酶染色为阳性,尿酸干预后各组细胞碱性磷酸酶活性和增殖能力增高,Wnt信号通路相关基因Wnt-3a、β-catenin的表达上调,且呈现浓度依赖性,各指标在实验组与对照组间比较以及实验组组间比较,差异均有显著性意义(P<0.05)。结果显示尿酸可通过促进Wnt-3a/β-catenin信号通路进而促进骨髓间充质干细胞向成骨细胞增殖和分化,具有浓度依赖性。展开更多
文摘目的:分析孔源性视网膜脱离玻璃体切除硅油填充术后不明原因视力下降(SORVL)的临床特征,探讨其发生机制。方法:回顾性分析在2019年1月~2023年6月在青岛大学附属医院眼科首诊为孔源性视网膜脱离(RRD)并且行玻璃体切除联合硅油填充术患眼293例,进行最佳矫正视力(BCVA)、OCT、静态视野、VEP、ERG等检查,并分析相关数据。结果:孔源性视网膜脱离玻璃体切除硅油填充293眼,发生视力下降(SORVL) 20眼(6.83%)。术前黄斑附着眼的SORVL发生率约为13.33%,黄斑脱离眼的SORVL发生率约为4.59%;发现SORVL患者术后黄斑区神经节细胞层(GCL)平均厚度较术前明显变薄(P Objective: To analyze the clinical features of unexplained vision loss following vitrectomy with silicone oil tamponade for rhegmatogenous retinal detachment and explore the underlying mechanisms. Methods: A retrospective analysis was conducted on 293 patients initially diagnosed at the Department of Ophthalmology of the Affiliated Hospital of Qingdao University from January 2019 to September 2023, who suffered from rhegmatogenous retinal detachment (RRD) and underwent vitrectomy combined with silicone oil tamponade. A comprehensive range of ophthalmic examinations was conducted, encompassing best-corrected visual acuity (BCVA), optical coherence tomography (OCT), static visual field, visual evoked potential (VEP), and electroretinography (ERG). Results: In 293 eyes that underwent vitrectomy with silicone oil tamponade for RRD, 20 eyes (6.83%) demonstrated a decline in vision (SORVL). The incidence of silicone oil-related vision loss (SORVL) was approximately 13.33% in eyes with macular attachment before surgery and 4.59% in eyes with macular detachment. The mean thickness of the ganglion cell layer (GCL) in the macular region of patients who developed SORVL was significantly thinner after surgery than before surgery (P < 0.001), and P-VEP 15 min showed a significant delay in the peak of the P100 wave and a significant decrease in its amplitude;FVEP showed a significant decrease in the amplitude of the P2 wave. Conclusion: Eyes with macular attachment are at a higher risk of experiencing silicone oil-related vision loss than those with macular detachment, and patients with SORVL may have damage to the ganglion cells of the macular central sulcus. In the event of SORVL, silicone oil should be removed as soon as the retina is well restored.
文摘目的:克罗恩病和痛风发病率逐年增高,但其关联性尚未明确。本研究利用孟德尔随机化方法,探讨克罗恩病与痛风之间的潜在因果关系。方法:我们选取与克罗恩病和痛风显著关联的单核苷酸多态性作为工具变量,利用公开的全基因组关联研究的汇总统计数据进行分析。我们采用多种MR方法并进行了敏感性分析。结果:克罗恩病与痛风的发病风险正相关(OR = 1.00060493,95%置信区间1.00013013~1.00107996,P值 = 0.01251316)。敏感性分析进一步印证了该发现,未见明显的异质性和水平多效性。结论:我们的研究结果表明克罗恩病与痛风之间存在正相关关系。这一发现为克罗恩病与痛风之间的关系及其病理生理机制提供了新的见解,并为痛风的预防和治疗提出了新策略。Objective: The incidence of Crohn’s disease and gout is increasing year by year, but the correlation is not clear, so we conducted a two-sample bidirectional mendelian randomization study to examine the association between them. Method: We selected single nucleotide polymorphisms significantly associated with Crohn’s disease and gout as instrumental variables and analyzed them using summary statistics from publicly available genome-wide association studies. We used multiple MR methods and performed sensitivity analyses. Results: The results revealed that Crohn’s disease was positively associated with the risk of developing gout (Odds Ratio, OR = 1.00060493, 95% Confidence Interval, CI, 1.00013013~1.00107996, P value = 0.01251316). Sensitivity analyses further corroborated the finding, with no significant heterogeneity or horizontal pleiotropy seen. Conclusions: Our findings suggest a positive association between Crohn’s disease and gout. This finding provides new insights into the relationship between Crohn’s disease and gout and its pathophysiologic mechanisms, and new strategies for the prevention and treatment of gout.
文摘目的探讨新型过氧化物酶体增殖物激活受体(PPARs)泛激动剂西格列他钠治疗2型糖尿病的临床效果与安全性。方法选取2022年1月至6月联勤保障部队第九七〇医院威海医疗区收治的68例2型糖尿病患者作为研究对象,按照随机数字表法分为观察组(n=34)和对照组(n=34)。对照组采用门冬胰岛素30注射液治疗,观察组在对照组的基础上联合西格列他钠治疗。比较两组患者治疗前后的胰岛素抵抗指数(HOMA-IR)、胰岛β细胞功能指数(HOMA-β)、体重指数(BMI)、血糖情况[糖化血红蛋白(HbA1c)、空腹血糖(FPG)、餐后2 h血糖(2 h PG)]、PPARs水平及不良反应的差别。结果观察组治疗总有效率高于对照组,差异有统计学意义(P<0.05);观察组的HOMA-IR、HbA1c、FPG、2hPG均低于对照组,差异有统计学意义(P<0.05);观察组的HOMA-β、PPARα、PPARβ、PPARγ水平均高于对照组,差异有统计学意义(P<0.05);两组患者BMI和不良反应比较,差异无统计学意义(P>0.05)。结论西格列他钠可有效改善2型糖尿病患者胰岛功能及胰岛素抵抗,提升PPARs水平,改善血糖控制,提高治疗效果,减少不良反应。
文摘背景:尿酸作为一种内源性的抗氧化剂,其抗氧化、抗DNA损害作用及发挥促成骨作用近年受到关注。目的:探讨不同浓度尿酸对人骨髓间充质干细胞向成骨细胞分化过程中Wnt/β-catenin信号通路相关基因表达的影响。方法:采用全骨髓贴壁法体外分离培养健康成年人骨髓间充质干细胞,培养至第3代时,用含不同浓度尿酸(0,140,280,560μmol/L)的成骨诱导液进行成骨向诱导分化培养,检测细胞成骨分化过程中碱性磷酸酶活性、增殖能力以及Wnt信号通路中Wnt-3α,β-catenin m RNA的表达。结果与结论:各组细胞碱性磷酸酶染色为阳性,尿酸干预后各组细胞碱性磷酸酶活性和增殖能力增高,Wnt信号通路相关基因Wnt-3a、β-catenin的表达上调,且呈现浓度依赖性,各指标在实验组与对照组间比较以及实验组组间比较,差异均有显著性意义(P<0.05)。结果显示尿酸可通过促进Wnt-3a/β-catenin信号通路进而促进骨髓间充质干细胞向成骨细胞增殖和分化,具有浓度依赖性。