Objective:Obesity-induced kidney injury contributes to the development of diabetic nephropathy(DN).Here,we identified the functions of ubiquitin-specific peptidase 19(USP19)in HK-2 cells exposed to a combination of high glucose(HG)and free fatty acid(FFA)and determined its association with TGF-beta-activated kinase 1(TAK1).Methods:HK-2 cells were exposed to a combination of HG and FFA.USP19 mRNA expression was detected by quantitative RT-PCR(qRT-PCR),and protein analysis was performed by immunoblotting(IB).Cell growth was assessed by Cell Counting Kit-8(CCK-8)viability and 5-ethynyl-2'-deoxyuridine(EdU)proliferation assays.Cell cycle distribution and apoptosis were detected by flow cytometry.The USP19/TAK1 interaction and ubiquitinated TAK1 levels were assayed by coimmunoprecipitation(Co-IP)assays and IB.Results:In HG+FFA-challenged HK-2 cells,USP19 was highly expressed.USP19 knockdown attenuated HG+FFA-triggered growth inhibition and apoptosis promotion in HK-2 cells.Moreover,USP19 knockdown alleviated HG+FFA-mediated PTEN-induced putative kinase 1(PINK1)/Parkin pathway inactivation and increased mitochondrial reactive oxygen species(ROS)generation in HK-2 cells.Mechanistically,USP19 stabilized the TAK1 protein through deubiquitination.Importantly,increased TAK1 expression reversed the USP19 knockdown-mediated phenotypic changes and PINKl/Parkin pathway activation in HG+FFA-challenged HK-2 cells.Conclusion:The findings revealed that USP19 plays a crucial role in promoting HK-2 cell dysfunction induced by combined stimulation with HG and FFAs by stabilizing TAK1,providing a potential therapeutic strategy for combating DN.

Objective:Icariin(ICA)has a good neuroprotective effect and can upregulate neuronal basal autophagy in naturally aging rats.Mitochondrial dysfunction is associated with brain aging-related neurodegenerative diseases.Abnormal opening of the mitochondrial permeability transition pore(mPTP)is a crucial factor in mitochondrial dysfunction and is associated with excessive autophagy.This study aimed to explore that ICA protects against neuronal injury by blocking the mPTP opening and down-regulating autophagy levels in a D-galactose(D-gal)-induced cell injury model.Methods:A cell model of neuronal injury was established in rat pheochromocytoma cells(PC 12 cells)treated with 200 mmol/L D-gal for 48 h.In this cell model,PC12 cells were pre-treated with different concentrations of ICA for 24 h.MTT was used to detect cell viability.Senescence associated β-galactosidase(SA-β-Gal)staining was used to observe cell senescence.Western blot analysis was performed to detect the expression levels of a senescence-related protein(p21),autophagy markers(LC3B,p62,Atg7,Atg5 and Beclin 1),mitochondrial fission and fusion-related proteins(Drp1,Mfn2 and Opa1),and mitophagy markers(Pink1 and Parkin).The changes of autophagic flow were detected by using mRFP-GFP-LC3 adenovirus.The intracellular ultrastructure was observed by transmission electron microscopy.Immunofluorescence was used to detect mPTP,mitochondrial membrane potential(MMP),mitochondrial reactive oxygen species(mtROS)and ROS levels.ROS and apoptosis levels were detected by flow cytometry.Results:D-gal treatment significantly decreased the viability of PC12 cells,and markedly increased the SA-β-Gal positive cells as compared to the control group.With the D-gal stimulation,the expression of p21 was significantly up-regulated.Furthermore,D-gal stimulation resulted in an elevated LC3B Ⅱ/Ⅰ ratio and decreased p62 expression.Meanwhile,autophagosomes and autolysosomes were significantly increased,indicating abnormal activation of autophagy levels.In addition,in this D-gal-induced model of cell injury,the mPTP was abnormally open,the ROS generation was continuously increased,the MMP was gradually decreased,and the apoptosis was increased.ICA effectively improved mitochondrial dysfunction to protect against D-gal-induced cell injury and apoptosis.It strongly inhibited excessive autophagy by blocking the opening of the mPTP.Cotreatment with ICA and an mPTP inhibitor(cyclosporin A)did not ameliorate mitochondrial dysfunction.However,the protective effects were attenuated by cotreatment with ICA and an mPTP activator(lonidamine).Conclusion:ICA inhibits the activation of excessive autophagy and thus improves mitochondrial dysfunction by blocking the mPTP opening.

Intestinal ischemia/reperfusion (II/R) is a severe clinical circumstance which is frequently apparent in situations including midgut volvulus,superior mesenteric vessels closure and hemorrhagic shock. II/R not only brings about severe intestinal local damage but also leads to remote organs injury including lung,liver etc[1]. Lung injury is the most common and severe complications which manifested as pulmonary susceptibility,respiratory dysfunction,and even acute respiratory distress syndrome (ARDS)[2].

背景 重复经颅磁刺激(rTMS)+抗抑郁药物已成为治疗儿童和青少年抑郁症的新兴疗法,但如何早期预测疗效仍是一大挑战.目的 探讨rTMS+抗抑郁药物治疗过程中预测远期疗效的潜在因子.设计 回顾性队列研究.方法 首次诊断中重度单相或双相抑郁症的年龄＜18 岁、始于住院时连续≥20 次的rTMS治疗且有每日症状指数(DI-5)的评分记录、有rTMS治疗前和第 20 次时的汉密尔顿抑郁量表(HAMD)评分记录的儿童青少年为队列人群,以rTMS治疗最后 1次较基线HAMD评分减少≥50%分为应答组和未应答组,对20 次DI-5评估结果与HAMD评估行相关性分析,当存在较好的相关结果时,考察rTMS+抗抑郁药物治疗中的DI-5评估是否能更早预测应答结果.主要结局指标 DI-5与HAMD评分相关性.结果 符合本文纳入排除标准的中重度单相或双相抑郁症的儿童青少年 228 例,平均年龄(14.0±3.0)岁,男 111例(48.6%),rTMS治疗前和后DI-5分数与HAMD分数Pearson相关系数分别为 0.70 和 0.72,差异均有统计学意义(P均＜0.001).rTMS治疗 20 次后应答组 101 例,未应答组 127 例,两组在性别分布、年龄、单亲家庭比例、留守儿童比例、家族精神病史、症状始发年龄、症状持续时间、学习障碍、语言障碍、运动发育障碍、体重、身高、服药时长、心理咨询次数、甲状腺功能异常、入睡时长、经常做梦比例和饮食习惯-挑食差异均无统计学意义(P＞0.05);DI-5 和HAMD基线分数应答组较未应答组差异均无统计学意义(P＞0.05);第 20 次rTMS治疗后DI-5 分数应答组较未应答组差异有统计学意义(P＜0.001);HAMD最后 1 次评分应答组较未应答组差异有统计学意义(P＜0.001).第11 次rTMS治疗时DI-5分数应答组较未应答组DI-5分数差异有统计学意义(P＜0.001),应答组较未应答组DI-5中位数分数减少2 分并以此作为分层依据,DI-5量表减少分数＜2 分组 107 例(46.9%)在第 20 次rTMS治疗时有 98.1%的概率为未应答,DI-5 量表减少分数≥2 分组 64 例(87.4%)在第 20 次TMS治疗时有 89.2%的概率为应答.结论 第 11 次rTMS较治疗前DI-5减分≥2 分可能是预测儿童青少年抑郁症rTMS+抗抑郁药物疗效的早期预测因子.

目的:在甲状腺术中,评估近红外自体荧光成像技术(NIRAF)联合示踪用盐酸米托蒽醌注射液(MHI)能否提高甲状旁腺的识别率,从而降低甲状腺术后低钙血症及甲状旁腺功能减退的发生率.方法:前瞻性连续选取2022年10月-2023年3月在潍坊市益都中心医院行甲状腺手术治疗的患者80例,根据入院时间随机将患者分为联合组和对照组,每组40例.联合组术中于甲状腺内注射MHI 0.6 mL并联合NIRAF识别甲状旁腺,对照组仅于术中使用NIRAF.比较两组术前血钙、甲状旁腺激素(PTH)水平,术中甲状旁腺识别准确率、自体移植率,术后甲状旁腺激素(PTH)、血钙水平、甲状旁腺误切率及低钙症状发生率.结果:联合组行甲状旁腺移植术4例(10.0％),对照组12例(30.0％),两组之间差异有统计学意义(x2=3.828,P=0.049).联合组甲状旁腺识别准确率高于对照组(98.11％比85.96％,x2=3.899,P=0.048),且联合组存在误切甲状旁腺2例(5.0％),对照组10例(25.0％),两组对比差异有统计学意义(x2=4.804,P=0.028).术后1 d,联合组及对照组血钙水平分别为(2.24±0.11)mmol/L及(2.16±0.17)mmol/L,PTH 水平分别为(27.18±11.77)ng/L 及(18.57±9.55)ng/L,差异均有统计学意义(P＜0.05).术后3d,联合组血钙水平为(2.32±0.17)mmol/L,对照组为(2.23±0.12)mmol/L;联合组PTH水平为(33.03±7.88)ng/L,对照组为(24.89±9.29)ng/L;两组差异均有统计学意义(P＜0.05).联合组术后出现手足或口周麻木症状3例(7.5％),对照组10例(25.0％),差异有统计学意义(P=0.034).结论:自体荧光联合示踪用盐酸米托蒽醌注射液可以有效提高甲状腺术中甲状旁腺识别的准确率,从而避免误切,减少术后低钙血症及甲状旁腺功能减退发生率,降低患者术后手足、口周麻木感的发生,提高患者就医体验.

原发性骨质疏松症(primary osteoporosis,POP)作为一种全身代谢性疾病,易引发骨折,近年来发病率逐年递增,已经成为亟待研究并解决的一个健康问题.本文通过阐释对POP的中医认识,提出POP与中医理论中的骨痿最为相似,并引出其发病机制与脾虚相关,进而提出"脾为之卫"理论.文章梳理了"脾为之卫"理论源流及理论内涵,脾为之卫,即脾作为后天之本,通过运化水谷精微之悍气,生成卫气来行使维护机体的功能,即人体之免疫力.脾为气血生化之源,化生血液以充养肾精,精生髓,髓居骨中,影响POP的发生、发展与防治;另外治痿者独取"阳明",从"阳明"之意的三方面分别加以论述脾为之卫对POP防治的理论依据;最后通过探讨脾为之卫在POP的发病机制中的重要意义,以期对临床治疗POP带来帮助.

目的 探讨血清miR-125b对依普利酮抗纤维化治疗反应评估的价值.方法 前瞻性纳入 2020 年 8 月 9日—2021 年 4月 1日在太原市急救中心心内科接受依普利酮治疗的 89例急性心肌梗死(AMI)伴或不伴ST段抬高且伴有左心室收缩功能障碍患者.采集受试者依普利酮治疗前和治疗 6 个月后的外周血浆样本.二维超声心动和多普勒超声心动图评估心脏收缩功能.采用实时荧光定量PCR法检测血浆中循环miR-125b表达水平;采用放射免疫测定法和酶联免疫吸附法分别检测血清Ⅲ型胶原氨基末端前肽(PⅢNP)和Ⅰ型胶原羧基末端前肽(PⅠCP)水平,计算基线至第 6 个月血清PⅢNP(?PⅢNP)和PⅠCP(?PⅠCP)水平变化.并记录依普利酮治疗 6 个月期间患者的主要不良心血管事件(MACEs).结果 依普利酮治疗 6 个月后,AMI患者收缩压与超声心动图参数较基线值显著改善(P＜0.05),收缩压、血清PⅢNP和PⅠCP水平降低(P＜0.05),但同时血钾和血钠浓度有所升高(P＜0.05).其中50例患者第6个月时血清PⅢNP水平值较基线值绝对减少,纳入PⅢNP降低亚组,其他 39例患者?PⅢNP≤0,被纳入PⅢNP稳定/增加亚组.Logistic回归分析显示,女性、经皮冠状动脉介入治疗、血清miR-125b是PⅢNP降低的独立预测因子(P＜0.05).Spearman等级相关系数分析显示,PⅢNP降低的患者基线血清miR-125b与?PⅢNP(rs=-0.566,P＜0.001)和?PⅠCP(rs=-0.524,P＜0.001)存在负相关关系.进一步校正危险因素后,基线血清miR-125b仍是影响血清PⅢNP和PⅠCP降低程度的独立负相关因素(P＜0.05).此外,在AMI患者中,PⅢNP降低的患者累积MACEs发生率更低(调整后HR=0.431,95%CI:0.129～1.440,P=0.171),同样血清miR-125b水平＞2.23 患者无MACEs事件累积生存率更低(Log rank=32.568,P＜0.001).结论 血清miR-125b高表达水平有助于识别依普利酮抗纤维化作用更显著的AMI患者.

内皮素(endothelin, ET)是由内皮细胞产生的一种强效血管收缩肽，与血管内皮功能障碍和心脑血管病密切相关。近年来的研究显示，ET-1基因Lys198Asn多态性可作为脑血管病的一种新型生物标志物。文章综述了该基因多态性与缺血性卒中易感性之间关系的研究进展并探讨其临床意义。

目的:探究代谢相关脂肪性肝病（MAFLD）合并慢性乙型肝炎（CHB）患者肝脏病理特点，以及与进展期纤维化之间的关系。方法:病例对照研究。收集2016年6月至2019年9月在天津市第二人民医院进行肝组织活检的CHB患者数据。根据是否合并MAFLD将患者分为MAFLD-CHB组和CHB组，采用 t检验和卡方检验比较两组间病理特点及一般基本特征，采用logistic回归分析进展期纤维化相关因素。 结果:本研究共纳入272例MAFLD-CHB患者和110例单独CHB 患者，两组在吸烟、饮酒、高血压发生率、身体代谢指标（BMI）、丙氨酸转氨酶（ALT）、γ-谷氨酰转肽酶（GGT）、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）、空腹血糖水平（FPG）、血小板计数（PLT）方面差异均有统计学意义（均 P<0.05）。MAFLD-CHB组进展期纤维化发生率高于CHB组（ P<0.05）。logistic回归分析显示，合并MAFLD（ OR=2.204，95 %CI 1.018~4.774， P=0.045）、GGT（ OR=1.008，95 %CI 1.002~1.013， P=0.005）、PLT（ OR=0.995，95 %CI 0.991~0.999， P=0.019）与进展期纤维化发生相关。在MAFLD-CHB组中，合并2型糖尿病（ OR=3.281，95 %CI 1.375~7.832， P=0.007）、GGT（ OR=1.011，95 %CI 1.003~1.018， P=0.005）、PLT（ OR=0.993，95 %CI 0.988~0.998， P=0.004）与进展期纤维化发生相关。 结论:MAFLD-CHB患者进展期纤维化发生率高于单独CHB患者。在MAFLD-CHB组中，合并2型糖尿病与进展期肝纤维化发生相关。对于MAFLD-CHB患者，应更加严格控制相关危险因素，尤其对于合并2型糖尿病的患者。

目的:观察腔隙性脑梗死轻度认知障碍患者伴抑郁的相关因素。方法:收集2016-2019年开滦总医院收治的114例腔隙性脑梗死轻度认知功能障碍患者为研究对象，于入院后72 h之内完成核磁共振颅脑扫描，并于1周内应用Zung氏抑郁自评量表(self-rating depression scale，SDS)对情绪测评。根据SDS评定结果，选择腔隙性脑梗死轻度认知功能障碍无抑郁患者69例为对照组；选择腔隙性脑梗死轻度认知功能障碍伴轻度抑郁患者45例为病例组。观察两组患者一般临床资料、不同脑区腔隙性脑梗死患者比例特点及认知功能，运用Logistic回归法分析腔隙性脑梗死轻度认知功能障碍发生抑郁的危险因素，并观察临床躯体化症状表现特点。结果:(1)对照组患者男53例(76.81%，53/69)，女16例(23.19%，16/69)；病例组男29例(64.44%，29/45)，女16例(35.55%，16/45)，两组性别比较差异有统计学意义( P＝0.049)；对照组和病例组高同型半胱氨酸血症发生率分别为31.88%(22/69)、53.33%(24/45)，两组比较差异有统计学意义( P＝0.003)。(2)病例组患者基底节区和半卵圆中心腔隙性脑梗死灶发病率分别为80.00%(36/45)、71.11%(32/45)，对照组分别为59.42%(41/69)、18.84%(13/69)，两组比较差异均有统计学意义( P值分别为0.001、<0.001)；其余脑区梗死灶比例比较差异均无统计学意义( P均>0.05)。(3)病例组注意力和计算力受损比例为88.89%(40/45)，高于对照组的78.26%(54/69)，两组比较差异有统计学意义( P＝0.036)。(4)多因素Logistic回归分析结果显示，高同型半胱氨酸血症( OR＝2.659，95% CI 1.041~6.793， P<0.05)、半卵圆中心梗死灶( OR＝10.332，95% CI 4.069~26.235， P<0.01)是腔隙性脑梗死轻度认知功能障碍伴抑郁的独立危险因素。(5)躯体化症状失眠和流泪的比例病例组分别为35.56%(16/45)、37.77%(17/45)，均高于对照组8.70%(6/69)、2.90%(2/69)，两组比较差异均有计学意义( P值均为0.000)。 结论:高同型半胱氨酸血症和半卵圆中心脑梗死病灶是腔隙性脑梗死轻度认知功能障碍患者发生抑郁的独立危险因素，且患者可伴有失眠和流泪的躯体化症状。