Review of the pharmacological effects of astragalosideⅣand its autophagic mechanism in association with inflammation

Astragalus membranaceus Bunge,known as Huangqi,has been used to treat various diseases for a long time.AstragalosideⅣ(AS-Ⅳ)is one of the primary active ingredients of the aqueous Huangqi extract.Many experimental models have shown that AS-Ⅳexerts broad beneficial effects on cardiovascular disease,nervous system diseases,lung disease,diabetes,organ injury,kidney disease,and gynaecological diseases.This review demonstrates and summarizes the structure,solubility,pharmacokinetics,toxicity,pharmacological effects,and autophagic mechanism of AS-Ⅳ.The autophagic effects are associated with multiple signalling pathways in experimental models,including the PI3KI/Akt/m TOR,PI3KⅢ/Beclin-1/Bcl-2,PI3K/Akt,AMPK/m TOR,PI3K/Akt/m TOR,SIRT1–NF-κB,PI3K/AKT/AS160,and TGF-β/Smad signalling pathways.Based on this evidence,AS-Ⅳcould be used as a replacement therapy for treating the multiple diseases referenced above.

AstragalosideⅣameliorates insulin induced insulin resistance in HepG2 cells through reactive oxygen species mediated c-Jun N-terminal kinase pathway

OBJECTIVE:To investigate the effects and elucidate the mechanism of Astragaloside IV(AS-IV)for insulin resistance(IR)and type 2 diabet es mellitus(T2DM).METHODS:CCK8 kit was used to detect cell viability,glucose detection kit was used to detect the concentration of glucose in cell supernatant,reactive oxygen species(ROS)detection kit and Western blot were used to explore the mechanism of Astragaloside IV(AS-IV)in improving IR.A diabetic rat model was also established by feeding high sugar and fat diet and streptozotocin(STZ)injection.After treatment with AS-IV,rosiglitazone(ROZ),or normal saline,the fasting blood glucose(FBG),C peptide(C-P),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and the glucose tolerance were assessed.RESULTS:AS-IV could effectively reduce the content of ROS and increase the glucose uptake in high insulintreated IR-type HepG 2 cells.The results of molecular mechanisms indicated that AS-IV could improve insulin resistance by reducing JNK phosphorylation and regulating c-Jun N-terminal kinase(JNK)downstream protein expression.Additionally,AS-IV could significantly reduce the levels of FBG,TNF-α,IL-6 and the glucose tolerance in diabetic rats(P<0.05 or<0.01).The high and medium dose groups of AS-IV could significantly increase the C-P levels in diabetic rats(P<0.05 or<0.01).CONCLUSIONS:Our results indicated that AS-IV improve liver IR through the JNK pathway and ROS,which meant a new molecular target for the treatment of diabetes.The AS-IV also helped to prevent and improved the insulin resistance of rats.

AstragalosideⅣplays a role in reducing radiation-induced liver inflammation in mice by inhibiting thioredoxin-interacting protein/nod-like receptor protein 3 signaling pathway

OBJECTIVE:To investigate the efficacy of Astragaloside IV(AS-IV)on radiation-induced liver inflammation in mice.METHODS:The mice were divided into normal group,dimethyl sulfoxide solvent group,irradiation group(IR),irradiation+AS-IV(20 mg/kg)group(IR+AS-20)and irradiation+AS-IV(40 mg/kg)group(IR+AS-40).One month after intraperitoneal injection of AS-IV,the mice were irradiated with 8Gry Co60γ,the blood was collected for biochemical analysis,and the liver was collected for hematoxylin-eosin staining,immunofluorescence and electron microscopic observation,oxidative stress,and Western blot analysis.RESULTS:The AS-IV treatment significantly ameliorated the pathological morphology of liver and reduced the alanine aminotransferase and aspertate aminotransferase levels in serum induced by radiation;AS-IV treatment also significantly reduced the expression of inflammatory factors tumor necrosis factor alpha and interleukin 6 and antagonized malonaldehyde content and superoxide dismutase activity in liver caused by radiation;in addition,AS-IV treatment can significantly inhibited the positive expression of thioredoxin-interacting protein(TXNIP)and nod-like receptor protein 3(NLRP3)inflammasome in liver tissue after radiation;The expression of TXNIP,NLRP3 inflammasome,apoptosisassociated speck-like protein containing a CARD,cysteinyl aspartate-specific proteinase 1 and interleukin 1beta in the AS-IV prevention group decreased significantly compared to the radiation group.CONCLUSIONS:These findings suggested that Co60γradiation can cause structural and functional damage to the liver,which may be related to the NLRP3 mediated inflammatory pathway;AS-IV may play a protective role by inhibiting the TXNIP/NLRP3 inflammasome signaling pathway in the radiation-induced liver injury model.

Anti-inflammatory and DNA Repair Effects of Astragaloside IV on PC12 Cells Damaged by Lipopolysaccharide

Objective This study aimed to establish a neural cell injury model in vitro by stimulating PC12 cells with lipopolysaccharide(LPS)and to examine the effects of astragaloside IV on key targets using high-throughput sequence technology and bioinformatics analyses.Methods PC12 cells in the logarithmic growth phase were treated with LPS at final concentrations of 0.25,0.5,0.75,1,and 1.25 mg/mL for 24 h.Cell morphology was evaluated,and cell survival rates were calculated.A neurocyte inflammatory model was established with LPS treatment,which reached a 50%cell survival rate.PC12 cells were treated with 0.01,0.1,1,10,or 100µmol/L astragaloside IV for 24 h.The concentration of astragaloside IV that did not affect the cell survival rate was selected as the treatment group for subsequent experiments.NOS activity was detected by colorimetry;the expression levels of ERCC2,XRCC4,XRCC2,TNF-α,IL-1β,TLR4,NOS and COX-2 mRNA and protein were detected by RT-qPCR and Western blotting.The differentially expressed genes(DEGs)between the groups were screened using a second-generation sequence(fold change>2,P<0.05)with the following KEGG enrichment analysis,RT-qPCR and Western blotting were used to detect the mRNA and protein expression of DEGs related to the IL-17 pathway in different groups of PC12 cells.Results The viability of PC12 cells was not altered by treatment with 0.01,0.1,or 1µmol/L astragaloside IV for 24 h(P>0.05).However,after treatment with 0.5,0.75,1,or 1.25 mg/mL LPS for 24 h,the viability steadily decreased(P<0.01).The mRNA and protein expression levels of ERCC2,XRCC4,XRCC2,TNF-α,IL-1β,TLR4,NOS,and COX-2 were significantly increased after PC12 cells were treated with 1 mg/mL LPS for 24 h(P<0.01);however,these changes were reversed when PC12 cells were pretreated with 0.01,0.1,or 1µmol/L astragaloside IV in PC12 cells and then treated with 1 mg/mL LPS for 24 h(P<0.05).Second-generation sequencing revealed that 1026 genes were upregulated,while 1287 genes were downregulated.The DEGs were associated with autophagy,TNF-α,interleukin-17,MAPK,P53,Toll-like receptor,and NOD-like receptor signaling pathways.Furthermore,PC12 cells treated with a 1 mg/mL LPS for 24 h exhibited increased mRNA and protein expression of CCL2,CCL11,CCL7,MMP3,and MMP10,which are associated with the IL-17 pathway.RT-qPCR and Western blotting analyses confirmed that the DEGs listed above corresponded to the sequence assay results.Conclusion LPS can damage PC12 cells and cause inflammatory reactions in nerve cells and DNA damage.astragaloside IV plays an anti-inflammatory and DNA damage protective role and inhibits the IL-17 signaling pathway to exert a neuroprotective effect in vitro.

Astragaloside Ⅳ Protects Against Aβ1-42-induced Oxidative Stress, Neuroinflammation and Cognitive Impairment in Rats

Objective To investigate the neuroprotective action of astragaloside Ⅳ(AS-Ⅳ) on spatial learning and memory impairment induced by amyloid-beta 1-42(Aβ1-42) in rats and elucidate its underlying molecular mechanisms.Methods Adult-male Sprague-Dawley rats(230-250 g) were divided into six groups randomly: control, Aβ1-42, AS-Ⅳ, Aβ1-42 plus 5 mg/kg·d AS-Ⅳ, Aβ1-42 plus 25 mg/kg·d AS-Ⅳ, and Aβ1-42 plus 50 mg/kg·d AS-Ⅳ groups. Aβ1-42 were delivered by intracerebroventricular injection under the guidance of a brain stereotaxic apparatus. The Morris water maze test(hidden platform test, probe trials, visible platform test) was performed one week after Aβ1-42 injection to obtain the ability of rat spatial learning and memory. AS-Ⅳ(5, 25 and 50 mg/kg·d) was administrated intraperitoneally once per day from the 8 th day after Aβ1-42 injection for 5 consecutive days. Average escape latencies, distances for searching for the platform under water and the percentage of total time elapsed and distance swam in the right quadrant after removing platform were determined by behavior softwaresystem. The vision and swim speeds of rats were also determined to exclude the effect of these factors on the parameters of learning and memory. After behavioral tests, the rats were sacrificed immediately by decapitation. Hippocampus were collected. The enzyme activities of superoxide dismutase(SOD), glutathione peroxidase(GSH-px) and catalase(CAT) in the hippocampus obtained from different-treated rat brain were measured by following the manufacturer’s instructions. The levels of interleukin-1 beta(IL-1β) and tumor necrosis factor-alpha(TNF-α) in tissue lysates were assayed with ELISA.Results The water maze test results indicated that chronic treatments with AS-Ⅳ effectively protected the rats from Aβ1-42-induced spatial learning and memory impairment. Furthermore, the activities of SOD, GSH-px and CAT decreased by Aβ1-42 were also restored by AS-Ⅳ treatment in the hippocampus of rats. In addition, AS-Ⅳ significantly decreased the levels of IL-1β and TNF-α in the hippocampus of Aβ1-42-induced amnesia’s rats. Conclusion Our findings suggest that AS-Ⅳ might be a useful chemical in improving the spatial memory and relieving the oxidative stress and neuroinflammation in Alzheimer patients.

Effect of astragaloside Ⅳ on lipid and glucose metabolism in acute myocardial infarction through PPARγ pathway

OBJECTIVE To investigate the effects of astragaloside IV(which can be extracted from the traditional Chinese medicine Astragalus membranaceus)on lipid and glucose metabolism in acute myocardial infarction(AMI).METHODS Model of heart failure(HF)after AMI was established with ligation of left anterior descending artery on Sprague-Dawley(SD)rats.The rats were divided into three groups:sham,model and astragaloside IV treatment group.Twenty-eight days after treatment(astragaloside IV,20 mg·kg-1 daily),hematoxylin-eosin(HE)staining was applied to visualize cardiomyocyte morphological changes.High performance liquid chromatography(HPLC)was performed to assess the contents of adenosine phosphates in heart.Positron emission tomography and computed tomography(PET-CT)was conducted to evaluate the cardiac glucose metabolism.Expressions of key molecules such as peroxisome proliferatoractivated receptor γ(PPARγ),sterol carrier protein 2(SCP2)and long chain acyl CoA dehydrogenase(ACADL)were measured by Western blotting and immunohistochemistry.Oxygen-glucose deprivation-reperfusion(OGD/R)-induced H9C2 injury cardiomyocyte model was adopted for potential mechanism research in vitro.RESULTS Treatment with astragaloside Ⅳ rescued hearts from structural and functional damages as well as inflammatory infiltration.Levels of adenosine triphosphate(ATP)and energy charge(EC)in astragaloside IV group were also up-regulated compared to model group.Further results demonstrated that critical enzymes both in lipid metabolism and glucose metabolism compro mised in model group compared to sham group.Intriguingly,astragalosideⅣcould up-regulate critical enzymes including ACADL and SCP2 in lipid metabolism accompanying with promoting effect on molecules in glycolysis simultaneously.Results on upstreaming signaling pathway demonstrated that astragaloside Ⅳ could dramatically increase the expres sions of PPARγ.In vitro study suggested the efficacy of astragalosideⅣcould be blocked by T0070907,a selective PPARγ inhibitor.CONCLUSION Astragaloside IV has cardioprotective effect in improving cardiac function and energy metabolism through regulating lipid and glucose metabolism.The effects may be mediated by PPARγ pathway.

CroweⅢ-Ⅳ型DDH患者全髋关节置换术后不满意及相关因素分析

目的:探讨全髋关节置换术的CroweⅢ-Ⅳ型发育性髋关节发育不良(developmental dysplasia of the hip,DDH)患者的满意度及造成不满意的相关因素。方法:回顾性分析2013年3月至2018年3月行全髋关节置换术的169例CroweⅢ-Ⅳ型DDH患者,通过微信进行调查问卷,调查患者对手术总体满意度、10项日常功能满意度和患者认为对自己日常生活影响比较大的前5个问题。手术前后采用髋关节Harris评分进行功能评价。结果:收到完整调查问卷145份,所有患者获随访,时间1~5(3.23±1.22)年。145例患者分成两组,其中对手术疗效满意的118例,不满意的27例,手术总体满意率81.38%(118/145)。患者认为对生活影响比较大的前5个问题分别是术后髋部疼痛,肢体明显不等长、行走、上下楼梯、蹲起。两组术前Harris评分比较,差异无统计学意义(P>0.05),不满意组术后Harris评分较低。术后髋关节疼痛、肢体不等长是影响手术不满意的直接因素。结论:采用全髋关节置换术治疗CroweⅢ-Ⅳ型DDH患者手术难度大;术后髋关节疼痛(轻度以上),肢体不等长(>2 cm)是术后不满意的独立危险因素。

辽宁第Ⅳ金刚石成矿带东部潘家沟辉绿岩中铬铁矿的矿物化学特征及其意义

辽宁省永宁地区因发现原生金刚石而被划分为辽宁第Ⅳ金刚石成矿带,但尚未厘定出金刚石的来源,有必要加强对与金刚石伴生的指示矿物的研究。对该成矿带东部潘家沟地区辉绿岩中选获的铬铁矿开展电子探针成分分析,并与辽宁典型金伯利岩管中的铬铁矿成分进行对比,以探讨该地区铬铁矿的成因及其与金刚石的关系。根据铬铁矿样品电子探针背散射图像显示的粒径、形态及熔蚀特征,以及铬铁矿电子探针成分测试显示的高Cr、富Mg、低Al及贫Ti的特征,推测该地区的铬铁矿来自地幔捕掳晶,属于镁铬铁矿亚类,主要为镁铁-铬铝铁亚种和镁铁-铬铝亚种。计算得到铬铁矿的形成温度为1 252~1 307℃,与前人报道的瓦房店典型金伯利岩中铬铁矿的形成温度基本一致,也接近金刚石的形成温度,表明潘家沟地区辉绿岩中铬铁矿的成因与金刚石关系密切,该地区具有良好的金刚石成矿潜力和找矿前景。研究成果对潘家沟地区金刚石原生矿的勘查及探明该地区金刚石的来源具有指导意义。

腹腔镜下侧腹壁悬吊术与阴道后壁修补术联合治疗POP-QⅢ或Ⅳ期盆腔器官脱垂的效果分析

目的:探究腹腔镜下侧腹壁悬吊术联合阴道后壁修补术在盆腔器官脱垂定量分期法(POP-Q)Ⅲ或Ⅳ期盆腔器官脱垂患者中的应用效果。方法:选择2021年2月—2023年6月厦门市第三医院收治的90例POP-QⅢ或Ⅳ期盆腔器官脱垂患者,根据随机数字表法分为对照组和观察组,各45例。对照组进行阴式子宫切除术联合阴道前后壁修补术治疗,观察组则进行腹腔镜下侧腹壁悬吊术联合阴道后壁修补术治疗。比较两组的治疗总有效率、手术指标(手术时间、术中出血量、排气时间、住院时间)、并发症发生率、手术前后的盆底相关参数[阴道总长度(TVL)、阴道前壁中线离处女膜缘3 cm处(Aa)、前穹隆或阴道顶端到Aa点之间阴道前壁上段中距离处女膜的最远点(Ba)及宫颈或子宫切除后阴道顶端所处的最远端(C)]及盆底功能障碍问卷(PFDI-20)评分。结果:观察组治疗总有效率高于对照组,手术指标均优于对照组,并发症发生率显著低于对照组,差异均有统计学意义(P<0.05)。术后6个月,观察组盆底相关参数及PFDI-20各项评分均显著低于对照组,差异均有统计学意义(P<0.05)。结论:腹腔镜下侧腹壁悬吊术联合阴道后壁修补术在POP-QⅢ或Ⅳ期盆腔器官脱垂患者中的应用效果更好,可显著改善患者的盆底相关参数及盆底功能,且安全性较高。

二肽基肽酶-Ⅳ有机小分子荧光探针的研究进展

二肽基肽酶-IV(DPP-IV)是一种重要的跨膜糖蛋白水解酶,与各种生理过程和疾病密切相关,检测DPP-IV的有机小分子荧光探针被相继报道,是当前研究生物酶检测的热点。首次综述了用于DPP-IV体外和体内检测及成像的3类有机小分子荧光探针,分别是非近红外荧光探针(λ_(em)<650nm)、近红外荧光探针(λ_(em)>650nm)和双光子荧光探针,对比并总结了三种探针的设计原理、结构特点、生物应用情况及其在DPP-IV相关疾病诊断中的应用,并探讨了DPP-IV活性检测在未来发展方向上所面临的挑战。

热淋清颗粒治疗尿路感染的多中心、开放性、Ⅳ期临床研究

目的评价热淋清颗粒在临床使用中的安全性与有效性,以指导优化临床给药方案和提高合理用药水平。方法在51家医院进行开放性、Ⅳ期临床试验,受试者为下焦湿热型单纯性或复杂性尿路感染,单纯性尿路感染患者给予热淋清颗粒每次8 g、每天3次,疗程5 d。复杂性尿路感染患者给予热淋清颗粒每次8 g、每天3次,同时联合喹诺酮类抗生素,疗程7~14 d。结局指标为临床疗效、中医证候疗效、细菌清除率以及安全性。结果共纳入2009例受试者,其中11患者失访脱落。全分析集纳入1998例,其中单纯性尿路感染患者1532例,复杂性尿路感染患者466例。临床治愈率为68.57%,单纯性和复杂性尿路感染患者分别为74.41%和49.36%。中医证候痊显率为72.22%,单纯性和复杂性尿路感染患者分别为75.13%和62.66%。单纯性尿路感染中细菌培养阳性者的细菌转阴率为57.75%,细菌清除率为58.02%;复杂性尿路感染中细菌培养阳性者的细菌转阴率为45.59%,细菌清除率为43.92%。药物相关的不良反应发生24例次,其中单纯性尿路感染17例次,复杂性尿路感染7例次。结论热淋清颗粒治疗单纯性尿路感染的有效性和安全性较好,也可改善下焦湿热证中医证候。

经食管超声心动图在肾切除术联合MayoⅢ~Ⅳ级静脉瘤栓取栓术不同手术方式中的临床作用

目的:比较经食管超声心动图(transesophageal echocardiography,TEE)在肾切除术联合下腔静脉MayoⅢ~Ⅳ级瘤栓取栓术不同手术方式中的临床作用。方法:纳入2022年1月至2024年2月在北京大学第三医院行根治性肾切除联合MayoⅢ~Ⅳ级瘤栓取栓手术的患者28例,其中,机器人手术16例,腹腔镜手术2例,开腹手术10例,收集患者的各项临床资料进行分析比较。结果:机器人手术的患者中有9例采用TEE,其中7例术中TEE影像结果较术前发生变化,包括2例术中TEE提示瘤栓进入右心房,2例显示下腔静脉瘤栓由MayoⅢ级升至Ⅳ级,3例提示瘤栓与下腔静脉粘连,及时调整了手术方案;开腹手术的患者中有6例采用TEE,其中4例术中TEE提示Mayo分级较术前发生变化,包括3例提示瘤栓与下腔静脉粘连,1例提示瘤栓伴血栓形成,调整了手术方案,旷置或节段性切除瘤栓;腹腔镜手术的2例患者未采用术中TEE。术中采用TEE的作用包括开腹手术术中探查结合TEE监测瘤栓切除过程,机器人手术完全通过TEE监测瘤栓脱出,术中TEE还实时监测患者循环状态和心脏功能变化。结论:肾切除术联合MayoⅢ~Ⅳ级瘤栓取栓术的不同术式中,术中TEE均可再次确定瘤栓分级、粘连程度,并实时动态跟踪取栓过程,监测患者循环状态和心脏功能变化,具有重要的辅助作用,但其临床应用仍不足,建议这类手术均采用术中TEE。

张守琳运用“温阳解毒通络”法治疗糖尿病肾脏病(Ⅳ-Ⅴ期)经验探析

糖尿病肾脏病属中医学的“肾消(消肾)”“下消”“水肿”等范畴,目前已成为终末期肾病的主要原因。张守琳教授认为“阳虚毒瘀肾络”是糖尿病肾脏病(Ⅳ-Ⅴ期)的基本病机,阳气受损为发病之本,毒瘀肾络是发病的关键环节,并确立了“温阳解毒通络”的治疗原则,有效延缓了肾功能损伤的进展和进入透析的进程。

纳武利尤单抗联合安罗替尼对Ⅲb~Ⅳ期NSCLC的疗效观察及对miR-1269、miR-204-5p表达的影响

目的探究纳武利尤单抗联合安罗替尼治疗Ⅲb~Ⅳ期非小细胞肺癌(NSCLC)患者的效果及对微小RNA-1269(miR-1269)、miR-204-5p表达的影响。方法选取Ⅲb~Ⅳ期NSCLC患者82例,患者分配为对照组、观察组,各41例,使用随机数字表法,对照组采用安罗替尼治疗,观察组在对照组的基础上采用纳武利尤单抗治疗;比较两组患者的疗效、治疗前后肿瘤标志物癌胚抗原(CEA)、细胞角蛋白19片段抗原21-1(CYFRA21-1)、miR-1269、miR-204-5p表达水平和不良反应的发生率。结果观察组患者治疗后疾病控制率(87.80%,36/41)显著高于对照组(68.29%,28/41)(χ^(2)=4.556,P=0.033);与治疗前相比,治疗后观察组和对照组的CEA、CYFRA21-1、miR-1269水平显著降低,miR-204-5p水平显著升高(P<0.05);治疗后与对照组相比,观察组的CEA、CYFRA21-1、miR-1269水平显著降低,miR-204-5p水平显著升高(P<0.05);不良反应两组间比较,差异无统计学意义(P>0.05)。结论纳武利尤单抗联合安罗替尼治疗Ⅲb~Ⅳ期NSCLC患者可降低患者肿瘤标志物的水平,调节miR-1269、miR-204-5p的表达,效果更好。

P92钢接头Ⅳ型开裂蠕变孔洞临界值的分析及应用

【目的】分析P92管道接头热影响区发生Ⅳ型开裂的蠕变孔洞临界值的影响因素,得到蠕变孔洞临界值计算方法,为评估接头开裂风险提供依据。【方法】收集服役后发生Ⅳ型开裂的P92接头,在未开裂处取样进行610℃下不同应力条件的高温持久蠕变试验,然后使用光学显微镜、电子显微镜观察服役开裂接头和持久断裂接头热影响区的蠕变孔洞分布形貌,并借助图像分析软件测量蠕变孔洞的面积分数,同时使用硬度仪测试热影响区软化情况,最后综合测试结果分析细晶区软化程度和接头应力水平对蠕变孔洞临界值的影响,并拟合应力、显微硬度、孔洞临界值三者之间的函数关系。【结果】研究发现,P92钢接头细晶区相比于接头其它区域软化速度更快,但软化作用并非其发生Ⅳ型开裂的必要条件,当应力水平较高时,细晶区没有发生明显软化时就可以触发蠕变开裂;得到接头轴向应力水平、蠕变孔洞面积分数临界值和显微硬度的函数关系式。【结论】引起Ⅳ型开裂的蠕变孔洞面积分数临界值与相对应力水平(轴向应力与硬度的比值)有关,相对应力水平越高,蠕变孔洞临界值越小,接头安全性就越低;通过测量接头细晶热影响区的蠕变孔洞面积分数和显微硬度,可以估算开裂接头的轴向应力水平,也可以评估在役未开裂接头的Ⅳ型开裂风险。

基于MIMIC-Ⅳ数据库的脓毒性心肌病风险预测模型构建与评价

目的分析脓毒性心肌病(SC)的危险因素,构建与评价SC风险预测模型。方法从MIMIC-Ⅳ数据库中提取脓毒症患者的临床数据,按7∶3比例随机分为训练集和验证集。根据是否患有SC,分为SC组和非SC组。通过单因素和多因素Logistic回归分析筛选SC的独立危险因素,构建风险预测模型,并绘制列线图。采用受试者工作特征曲线下面积(AUC)评估模型的区分度,校正曲线评估模型的校准度,决策曲线分析(DCA)评估模型的临床适用度。结果共纳入2628例脓毒症患者,其中训练集1865例,验证集763例。训练集和验证集SC发病率差异无统计学意义(58.98%比62.25%,P=0.120)。除慢性阻塞性肺疾病(P=0.015)和重症监护室住院时长(P=0.016),其余临床指标两组间差异均无统计学意义(P均>0.05)。Logistic回归分析结果显示,既往患有冠心病(P=0.028)、心力衰竭(P<0.001)、中性粒细胞计数升高(P=0.001)、淋巴细胞计数降低(P=0.036)、肌酸激酶同工酶升高(P<0.001)、尿素氮升高(P=0.042)是SC的独立危险因素。训练集列线图预测模型的AUC为0.759(95%CI=0.732~0.785),验证集列线图预测模型的AUC为0.765(95%CI=0.723~0.807);两个数据集拟合度较好(训练集P=0.075,验证集P=0.067);DCA结果显示列线图预测模型具有良好的临床适用度。结论基于基础疾病及临床生化指标构建的列线图预测模型能够较好地预测SC的发生风险。

1例糖原累积病Ⅳ型合并急性肝衰竭患儿急性期的护理

总结2022年7月我科收治的1例糖原累积病Ⅳ型(glycogen storage disease typeⅣ,GSDⅣ)合并急性肝衰竭患儿急性期的护理经验。护理要点:监测血流动力学,积极抗休克;监测消化道出血量,实施止血治疗;开展人工肝治疗及预防相关并发症;连续监测血糖,根据病情与血糖动态调整营养治疗方案;开展远程探视和音乐治疗。经过6 d的救治和护理,患儿病情好转,顺利进行肝移植。术后18 d好转出院;随访1年,恢复良好。

瞬时感受器电位离子通道香草素受体亚家族Ⅳ在帕金森病细胞模型中介导PC12细胞炎症反应的机制

目的探讨瞬时感受器电位离子通道香草素受体亚家族Ⅳ(TRPV4)在帕金森病(PD)细胞模型中介导PC12细胞炎症反应的机制。方法2023年6―8月,用1-甲基-4-苯基吡啶离子(MPP^(+))建立PD细胞模型,用TRPV4特异性抑制剂HC067047抑制TRPV4。将培养的PC12细胞采用随机数字表法分为四组:对照组、HC067047组、MPP^(+)组、HC067047+MPP^(+)组。细胞毒性检测试剂盒(CCK-8)检测各组细胞的增殖活力。蛋白印迹法和酶联免疫吸附测定(ELISA)检测各组细胞TRPV4和炎症因子白细胞介素-18(IL-18)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)的水平变化。结果与对照组1.00±0.08相比,MPP^(+)组TRPV4的表达量2.14±0.20明显升高(P<0.001)。与对照组1.00±0.01相比,MPP^(+)组的PC12细胞活力0.65±0.08明显降低(P<0.01),而HC067047能明显回复MPP^(+)引起的细胞活力0.83±0.07降低(P<0.01)。与对照组相比,MPP^(+)组的IL-181.96±0.27和IL-61.92±0.18、IL-1β(874.61±108.09)ng/L和TNF-α(791.28±106.88)ng/L明显升高(P<0.001),HC067047能明显抑制MPP^(+)引起的IL-181.45±0.11和IL-61.58±0.22、IL-1β(626.28±84.53)ng/L和TNF-α(592.94±86.9)4 ng/L明显升高(P<0.01或P<0.05)。结论TRPV4参与了MPP^(+)诱导的PD细胞模型的炎症反应,抑制TRPV4有抗炎作用。

水平半规管良性阵发性位置性眩晕的临床特征及SRM-Ⅳ诊疗疗效观察

目的探讨水平半规管良性阵发性位置性眩晕(horizontal canal benign paroxysmal positional vertigo,HC-BPPV)的临床特征及SRM-Ⅳ诊疗疗效。方法选取2022年9月至2023年6月温州医科大学附属第一医院耳鼻咽喉科经SRM-Ⅳ系统确诊为HC-BPPV的患者182例。根据水平半规管BPPV发生机制分为管结石症组(144例)和嵴帽结石症组(38例),比较两组的性别、年龄、累及侧别、眼震特征及SRM-Ⅳ系统辅助下不同亚HC-BPPV的复位次数和复位疗效。结果182例患者中,男79例,女103例,年龄23~85岁,平均(52.8±13.1)岁;左侧总受累57例(31.3%),右侧总受累125例(68.7%);管结石症组首次复位治疗次数低于嵴帽结石症组[(1.3±0.5)次比(2.0±0.7)次],差异有统计学意义(t=-6.976,P<0.001);复位治疗1周后,管结石症组有效率为93.1%(134/144),嵴帽结石症组为86.8%(33/38),差异无统计学意义(χ^(2)=1.820,P=0.403)。结论HC-BPPV患者女性多于男性,右侧更易受累。SRM-Ⅳ系统辅助诊疗下,嵴帽结石症患者复位难度更大。SRM-Ⅳ辅助诊疗系统在诊断和复位治疗HC-BPPV患者中能达到预期治疗效果。

皮肤石蜡组织Ⅳ型胶原免疫荧光抗原修复方法的评估

目的 寻找皮肤石蜡包埋组织Ⅳ型胶原免疫荧光(IF-PE)最佳抗原修复方法。方法以2021年1月至2022年12月在上海交通大学医学院附属儿童医院确诊的X-连锁Alport综合征患儿和父(母)亲共14例皮肤组织,冰冻组织免疫荧光(IF-FT)为自身对照,比较不同抗原修复法IF-PE染色部位和强度。结果 与Ⅳ型胶原IF-FT自身对照比较,采用蛋白酶K修复,仅部分患儿基膜正常分布(6/14),而角质层均异常表达;微波、高温水浴和高压蒸汽3种修复方法,基膜均无正常分布,角质层异常分布(分别为2/14,11/14,12/14);微波联合酶修复法仅2例基膜正常分布,未见角质层异常表达;高压蒸汽联合酶和高温水浴联合酶2种修复法基膜全部正常分布,角质层异常表达(分别为14/14和2/14),表达强度两者接近。结论高温水浴联合蛋白酶K可作为皮肤石蜡包埋组织Ⅳ型胶原免疫荧光理想的抗原修复法。