基于Hippo信号通路的野黄芩苷抗结直肠癌HCT116细胞的研究

本文旨在探究野黄芩苷(scutellarin,SCU)对人结直肠癌HCT116细胞的作用及机制。不同浓度SCU处理人结直肠癌HCT116细胞,采用显微镜观察法、MTT法、平板克隆形成试验、细胞划痕试验、Hoechst 33342/PI双染法、流式细胞术、qRT-PCR以及Western blot等多种手段进行检测。结果显示,SCU能明显改变HCT116细胞形态,降低细胞活力;抑制HCT116细胞克隆和迁移(P<0.01);诱导细胞核致密浓染,促进细胞凋亡,使细胞凋亡率显著增加(P<0.05或P<0.01)。机制研究结果表明,SCU能显著上调caspase-9、caspase-3的mRNA表达水平(P<0.01),下调Bcl-2的mRNA和蛋白表达水平(P<0.01),上调Bax的mRNA和蛋白表达水平(P<0.01)。此外,SCU能明显升高MST1、LATS1的mRNA和蛋白表达量(P<0.05或P<0.01),升高p-YAP(Ser127)的蛋白表达量(P<0.05或P<0.01),降低YAP1、TAZ和下游靶点c-Myc的mRNA和蛋白表达量(P<0.05或P<0.01)。综上所述,SCU能通过调节Hippo信号通路的活性,抑制HCT116细胞的增殖和迁移,并诱导细胞凋亡,从而发挥抗结直肠癌的作用。

A 4H-SiC trench IGBT with controllable hole-extracting path for low loss

A novel 4H-Si C trench insulated gate bipolar transistor(IGBT)with a controllable hole-extracting(CHE)path is proposed and investigated in this paper.The CHE path is controlled by metal semiconductor gate(MES gate)and metal oxide semiconductor gate(MOS gate)in the p-shield region.The grounded p-shield region can significantly suppress the high electric field around gate oxide in Si C devices,but it weakens the conductivity modulation in the Si C trench IGBT by rapidly sweeping out holes.This effect can be eliminated by introducing the CHE path.The CHE path is pinched off by the high gate bias voltage at on-state to maintain high conductivity modulation and obtain a comparatively low on-state voltage(VON).During the turn-off transient,the CHE path is formed,which contributes to a decreased turn-off loss(EOFF).Based on numerical simulation,the EOFFof the proposed IGBT is reduced by 89%compared with the conventional IGBT at the same VONand the VONof the proposed IGBT is reduced by 50%compared to the grounded p-shield IGBT at the same EOFF.In addition,the average power reduction for the proposed device can be 51.0%to 81.7%and 58.2%to 72.1%with its counterparts at a wide frequency range of 500 Hz to 10 k Hz,revealing a great improvement of frequency characteristics.

IGF-I induced phosphorylation of PTH receptor enhances osteoblast to osteocyte transition

Parathyroid hormone(PTH) regulates bone remodeling by activating PTH type 1 receptor(PTH1R) in osteoblasts/osteocytes. Insulinlike growth factor type 1(IGF-1) stimulates mesenchymal stem cell differentiation to osteoblasts. However, little is known about the signaling mechanisms that regulates the osteoblast-to-osteocyte transition. Here we report that PTH and IGF-I synergistically enhance osteoblast-to-osteocyte differentiation. We identified that a specific tyrosine residue, Y494, on the cytoplasmic domain of PTH1R can be phosphorylated by insulin-like growth factor type I receptor(IGF1R) in vitro. Phosphorylated PTH1R localized to the barbed ends of actin filaments and increased actin polymerization during morphological change of osteoblasts into osteocytes.Disruption of the phosphorylation site reduced actin polymerization and dendrite length. Mouse models with conditional ablation of PTH1R in osteoblasts demonstrated a reduction in the number of osteoctyes and dendrites per osteocyte, with complete overlap of PTH1R with phosphorylated-PTH1R positioning in osteocyte dendrites in wild-type mice. Thus, our findings reveal a novel signaling mechanism that enhances osteoblast-to-osteocyte transition by direct phosphorylation of PTH1R by IGF1R.

IGF-1 Signaling is Essential for Differentiation of Mesenchymal Stem Cells for Peak Bone Mass

Survival of children with chronic medical illnesses is leading to an increase in secondary osteoporosis due to impaired peak bone mass （PBM）. Insulin-like growth factor type Ⅰ （IGF-1） levels correlate with the pattern of bone mass accrual and many chronic illnesses are associated with low IGF-1 levels. Reduced serum levels of IGF-1 minimally affect the integrity of the skeleton, whereas recent studies suggest that skeletal IGF-I regulates PBM. To determine the role of IGF-1 in postnatal bone mass accrual regardless of source, we established an inducible type 1 Igf receptor Cre/lox knockout mouse model, in which the type 1 Igf receptor was deleted inducibely in the mesenchymal stem cells （MSCs） from 3-7 weeks of age. The size of the mouse was not affected as knockout and wild type mice had similar body weights and nasoanal and femoral lengths. However, bone volume and trabecular bone thickness were decreased in the secondary spongiosa of female knockout mice relative to wild type controls, indicating that IGF-1 is critical for bone mass. IGF-1 signaling in MSCs in vitro has been implicated to be involved in both migration to the bone surface and differentiation into bone forming osteoblasts. To clarify the exact role of IGF-1 in bone, we found by immunohistochemical analysis that a similar number of Osterix-positive osteoprogenitors were on the bone perimeter, indicating migration of MSCs was not affected. Most importantly, 56% fewer osteocalcin-positive mature osteoblasts were present on the bone perimeter in the secondary spongiosa in knockout mice versus wild type littermates. These in vivo data demonstrate that the primary role of skeletal IGF-1 is for the terminal differentiation of osteoprogenitors, but refute the role of IGF-1 in MSC migration in vivo. Additionally, these findings confirm that impaired IGF-1 signaling in bone MSCs is sufficient to impair bone mass acquisition.

Growth kinetics and mechanism of microarc oxidation coating on Ti-6Al-4V alloy in phosphate/silicate electrolyte

Microarc oxidation(MAO)is an effective surface treatment method for Ti alloys to allow their application in extreme environments.Here,binary electrolytes consisting of different amounts of sodium phosphate and sodium silicate were designed for MAO.The surface morphology,composition,and properties of MAO coatings on Ti-6Al-4V alloy treated in 0.10 mol/L electrolyte were investigated to reveal the effect of PO_(4)^(3-)and SiO_(3)^(2-)ray diffraction,and potentiodynamic polarization.The results showed that PO_(4)^(3-)is beneficial for generating microarcs and forming pores within the coating,resulting in a thick but porous coating.SiO_(3)^(2-)eration of microarcs,resulting in a thin dense coating.The thickness,density,phases content,and polarization resistance of the MAO coatings are primarily affected by the intensity of microarcs for low SiO_(3)^(2-)ciently high.The thickness of MAO coatings obtained in P/Si electrolytes shows a piecewise linear increase with increasing process time during the three stages of microarc discharge.SiO_(3)^(2-)discharge,but slows down the growth of the coating formed in the next stage.

Ursolic acid ameliorates azoxymethane/dextran sulfate sodium-caused colorectal cancer by inhibition of Wnt signaling cascade

OBJECTIVE To investigate the pharmacological effect of ursolic acid(UA)on colitis-associated colorectal cancer(CAC)and its underlying mechanism based on the Wnt signaling pathway.METHODS The CAC model in mice was established by azoxymethane(AOM)combined and dextran sulfate sodium salt(DSS),accompanied by treatment with various dosages of UA and concomitant appraisal of body weight,stool and physical state of the mice.After the sacrifice of the mice,the tumor and length of the colorectum were measured,followed by retrieval of the liver,spleen,thymus and tumor tissue for downstream assays.The levels of inflammatory factors interleukin-6(IL-6),IL^(-1)βand C-reactive protein(CRP)in the tumor and serum were examined by enzyme-linked immunosorbent assay(ELISA).The pathological changes of colorectal tissues were observed by HE staining.The levels in tumors of Wnt/β-catenin signaling pathway-related proteins Wnt4,GSK-3β,β-catenin,TCF4,LEF1,c-Myc,cyclin D1 and apoptosis-related protein Bcl-2 were assayed by immunohistochemistry(IHC).The mRNA expressions of Wnt4,GSK-3β,β-catenin,TCF4,LEF1,c-Myc,cyclin D1,Bcl-2,Bax,caspase-9 and caspase-3 in tumors were detected by real-time quantitative RT-PCR(RT-qPCR).The protein levels of Wnt4,GSK-3β,β-catenin,TCF4,LEF1,c-Myc,cyclin D1,phospho-β-catenin,phospho-GSK-3β,Bcl-2 and Bax in tumors were probed by analyzed by Western blotting(WB).Also,RNA-seq was employed to assess the gut microbiota in the mice.RESULTS UA significantly ameliorated the symptoms of AOM/DSS-induced mouse CAC,evidenced by improved physical state,body weight,survival rate,colorectal length,the mass of liver,thymus,spleen,and decreased CAC load and colorectal mass.UA attenuated the levels of IL-6,IL^(-1)βand CRP in the mouse serum and colorectal tumor in a dose-dependent manner.HE staining showed that UA lessened carcinogenesis in the colorectum,with lower infiltration of lymphocytes,versus the control.IHC indicated that UA mitigated the expression of Wnt4,β-catenin,TCF4,LEF1,c-Myc,cyclin D1,Bcl-2,and promoted the GSK-3βexpression,compared with the control.Furthermore,UA diminished the mRNA expressions of Wnt4,β-catenin,TCF4,LEF1,c-Myc,cyclin D1,Bcl-2,and heightened the mRNA levels of GSK-3β,caspase-3,capase-9 and Bax in CAC.The results of mRNA expressions were verified by WB analysis,which revealed that UA impeded the protein expression of Wnt4,β-catenin,c-Myc,cyclin D1,Bcl-2,TCF4,LEF1,and elevated the protein levels of GSK-3βand Bax,phospho-β-catenin in mouse CAC.In addition,UA substantially ameliorated the gut microbiota to store the metabolic function in the mice with CAC.CONCLUSION Ursolic acid may protect against CAC,potentially by downregulation of Wnt/β-catenin signaling pathway activity and restoration of gut microbiota.

Modeling and Control of Welding Flexible Manufacturing Cell Using Petri Net

A new welding flexible manufacturing cell (WFMC) with intelligent welding sensors was investigated. Based on the analysis of information flow in WFMC, automation Petri net control model has been studied, Which can be extended to complex welding flexible manufacturing system in the future.

Subclavian artery stenting via bilateral radial artery access:Four case reports

BACKGROUND Subclavian artery stenosis refers to the stenosis in the lumen caused by the presence of plaque or thrombus in the subclavian artery.It is a common problem in endovascular interventions.In fact,conventional subclavian artery stenting via the femoral artery approach is effective and safe.Nevertheless,because femoral artery puncture is not easy to stop bleeding,it requires longer femoral artery compression or more expensive hemostatic materials,such as staplers.Patients need to be catheterized and bedridden for a longer time,which may lead to many complications,such as pseudoaneurysm.CASE SUMMARY Herein,we reported a new interventional therapy of subclavian artery.From March 1,2020 to August 31,2021,we operated on four patients with subclavian artery stenting via bilateral radial artery access.CONCLUSION After reviewing four cases of successful placement of clavicular artery stents via bilateral radial arteries,we concluded that bilateral radial artery approach is feasible.Clavicular artery stenting is safe,effective,and timesaving.It is an excellent alternative to the traditional femoral artery procedure,with few complications and high comfort degree.

Hydrogel-Assisted Electrokinetics for High-Resolution and Non-invasive Flow Monitoring in Microfluidic Chips

Convenient non-invasive flow monitoring would facilitate the operation and control in microfluidic chips,but is challenging due to the small space of microchannels and complex operation required in traditional optical methods.In this work,we propose a novel non-invasive strategy to probe microfluidic flows via streaming potential phenomenon.By sealing one side of the microchannel with a piece of hydrogel film,streaming potential inside the channel can be clearly detected by electrodes at outer surface of the hydrogel due to ion diffusion in the hydrogel.Flow is detected without sensors contacting with the internal liquid.Moreover,the electrodes shape like a tiny probe,which can move around mapping the flow distribution in a chip with the spatial resolution of 1 mm and flow rate detection limit of 3μL·min–1.Bubbles inside the channels can also be detected,due to the fluctuation of streaming voltage when gas-liquid interface flows through the electrode,showing an easy and potential way for multi-functional flow monitoring in microfluidic chips.

基于SLC7A11/GSH/GPX4信号轴的姜黄素诱导结直肠癌SW620细胞铁死亡的研究

目的:基于溶负荷转运体家族7成员11(SLC7A11)/谷胱甘肽(GSH)/谷胱甘肽过氧化物酶4(GPX4)信号轴研究姜黄素抑制人结直肠癌SW620细胞增殖和诱导铁死亡的作用机制。方法:MTT法检测姜黄素对SW620细胞增殖的影响;克隆形成试验研究姜黄素对SW620细胞克隆形成能力的影响;透射电子显微镜观察姜黄素对SW620细胞铁死亡形态的影响;荧光探针法检测姜黄素对SW620细胞内Fe^(2+)和脂质过氧化物水平的影响;试剂盒检测姜黄素对SW620细胞内MDA含量和GSH/GSSG比值的影响;qRT-PCR法检测姜黄素对SW620细胞铁死亡相关mRNA表达的影响;Western blot法检测姜黄素对SW620细胞铁死亡相关蛋白表达的影响。结果:与模型对照组比较,姜黄素能有效地抑制人结直肠癌SW620细胞的增殖。姜黄素20μmol/L处理后,SW620细胞线粒体呈现铁死亡典型形态,并且姜黄素能够升高SW620细胞内MDA、Fe^(2+)和脂质过氧化物的含量,降低GSH/GSSG比值(P<0.01),提示姜黄素能够诱导SW620细胞铁死亡;与模型对照组比较,姜黄素20、40μmol/L组均能够明显上调SW620细胞P53 mRNA和蛋白表达(P<0.05或P<0.01),同时显著下调Slc7a11、Gpx4 mRNA和蛋白表达(P<0.05或P<0.01),从而诱导结直肠癌细胞铁死亡。结论:姜黄素具有抗结直肠癌的作用,并通过抑制SLC7A11/GSH/GPX4信号轴,诱导结直肠癌细胞铁死亡。

白藜芦醇通过调控Notch信号通路诱导结直肠癌HCT116细胞凋亡的研究

目的:基于Notch信号通路探究白藜芦醇抑制人结直肠癌HCT116细胞增殖和诱导凋亡的作用和机制。方法:MTT法检测白藜芦醇对HCT116细胞增殖的影响;显微镜观察白藜芦醇对HCT116细胞形态的影响;细胞划痕实验检测白藜芦醇对HCT116细胞迁移能力的影响;Hoechst 33342/PI染色法和流式细胞术检测白藜芦醇对HCT116细胞凋亡的影响;Real-time PCR法检测白藜芦醇对细胞凋亡相关因子B淋巴细胞瘤-2(Bcl2)、Bcl2关联X蛋白(Bax)以及Notch信号通路相关因子缺口蛋白1(Notch1)、齿状蛋白1(Jagged1)、多毛增强子1(Hes1)、原癌基因蛋白(Cmyc)mRNA表达的影响;Western blot法检测白藜芦醇对细胞凋亡相关蛋白BCL-2、BAX以及Notch信号通路相关蛋白Notch1、Jagged1、缺口胞内域1(NICD1)、HES1、CMYC表达的影响。结果:与模型对照组相比,白藜芦醇80μg/mL~160μg/mL时间剂量依赖性地抑制HCT116细胞增殖(P<0.01),7.5、15、30μg/mL白藜芦醇干预改变HCT116细胞形态,明显降低其迁移能力(P<0.05或P<0.01),细胞Hoechst荧光强度从51.45±6.20增加到79.54±6.60(P<0.05),细胞总体凋亡率从(9.14±0.80)%增加到(64.74±3.36)%(P<0.01),此外促凋亡因子Bax mRNA和蛋白表达显著上调(P<0.01),抑凋亡因子Bcl2 mRNA和蛋白表达明显下调(P<0.05或P<0.01),Notch信号通路中Notch1、Jagged1、NICD1、Hes1、Cmyc mRNA和蛋白表达显著下调,NICD1蛋白表达下调(P<0.05或P<0.01)。结论:白藜芦醇能够抑制HCT116细胞增殖、迁移,并诱导细胞发生凋亡,其机制可能与抑制Notch信号通路激活相关。

基于Hedgehog信号通路探析白头翁汤抗结直肠癌HCT116细胞机制

目的:探讨白头翁汤水煎液通过调控经典Hedgehog(Hh)信号通路诱导人结直肠癌细胞HCT116凋亡的作用及其机制。方法:用白头翁汤(25、50、100、200、500、750、1000 mg·L^(-1))处理HCT116细胞24 h,然后用噻唑蓝(MTT)比色法检测白头翁汤对细胞增殖的影响;分别设置空白组、白头翁汤组(125、250、500 mg·L^(-1))和五氟尿嘧啶(5-FU)组(40 mmol·L^(-1)),显微镜观察细胞给药前后形态变化;划痕实验检测白头翁汤对细胞迁移的影响;Hoechest 33324/碘化丙锭(PI)染色法评价白头翁汤对细胞凋亡的影响;流式细胞术检测白头翁汤对HCT116细胞凋亡的影响;蛋白免疫印迹法(Western blot)检测细胞凋亡相关B细胞淋巴瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)的表达水平及Hh信号通路关键因子音猬因子(SHh)、GLI家族锌指蛋白1(Gli1)、G蛋白偶联受体蛋白Smoothened(Smo)、苏氨酸蛋白激酶Fused抑制因子(SuFu)、c-核蛋白类基因(c-Myc)蛋白表达水平;实时荧光定量聚合酶链式反应(Real-time PCR)检测凋亡相关基因Bax、Bcl-2和Hh通路相关基因SHh、Gli1、Smo、SuFu、c-Myc mRNA表达水平。结果:与空白组比较,白头翁汤组(125、250、500 mg·L^(-1))HCT116细胞形态发生明显改变,细胞变圆,其增殖被抑制,且呈浓度依赖性,迁移能力下降(P<0.05,P<0.01),细胞核出现致密浓染,凋亡数量增加。与空白组比较,白头翁汤(500 mg·L^(-1))处理HCT116细胞24 h,Bax蛋白和mRNA表达水平升高(P<0.05,P<0.01),Bcl-2蛋白和mRNA表达水平降低(P<0.05,P<0.01)。与空白组比较,白头翁汤组(500 mg·L^(-1))处理24 h后,Hh信号通路关键因子SHh、Gli1、Smo、c-Myc的mRNA和蛋白水平表达降低(P<0.05,P<0.01),Hh信号通路负调控因子SuFu表达水平升高(P<0.05,P<0.01)。结论:白头翁汤通过降低Hh信号通路活性来抑制结直肠癌细胞HCT116增殖和迁移,诱导癌细胞凋亡。

头帽式肌激动器矫治儿童骨性Ⅱ类错[牙合]畸形1例

骨性Ⅱ类错[牙合]畸形是一种常见的青少年儿童错[牙合]畸形类型,若得不到及时的矫正,可能引起口腔肌肉功能异常、口腔颌面发育畸形,影响患者身心健康。本文报道1例生长发育高峰期混合牙列期的9岁男性患儿,患骨性Ⅱ类错[牙合]畸形伴开唇露齿和下颌后缩,通过13个月的头帽式肌激动器治疗,成功纠正了骨性Ⅱ类错[牙合]畸形,随访1年,疗效稳定,面部生长型良好。

Epigenetic regulation of mesenchymal stem cell aging through histone modifications

Stem cell senescence and exhaustion,a hallmark of aging,lead to declines in tissue repair and regeneration in aged individuals.Emerging evidence has revealed that epigenetic regulation plays critical roles in the self-renew,lineage-commitment,survival,and function of stem cells.Moreover,epigenetic alterations are considered important drivers of stem cell dysfunction during aging.In this review,we focused on current knowledge of the histone modifications in the aging of mesenchymal stem cells(MSCs).The aberrant epigenetic modifications on histones,including methylation and acetylation,have been found in aging MSCs.By disturbing the expression of specific genes,these epigenetic modifications affect the self-renew,survival,and differentiation of MSCs.A set of epigenetic enzymes that write or erase these modifications are critical in regulating the aging of MSCs.Furthermore,we discussed the rejuvenation strategies based on epigenetics to prevent stem cell aging and/or rejuvenate senescent MSCs.

Hepatocellular SETDB1 Regulates Hepatic Ischemia-Reperfusion Injury through Targeting Lysine Methylation of ASK1 Signal

Background: Hepatic ischemia-reperfusion injury (HIRI) stands as an unavoidable complication arising from liver surgery, profoundly intertwined with its prognosis. The role of lysine methyltransferase SET domain bifurcated 1 (SETDB1) in HIRI remains elusive, despite its confirmation as a potential therapeutic target for diverse diseases. Here, we investigated the mechanism by which SETDB1 regulated HIRI. Methods: RNA sequencing data were used to identify the expression and potential targets of SETDB1 through bioinformatics analysis. To elucidate the impact of SETDB1 on HIRI, both an in vivo model of HIRI in mice and an in vitro model of hepatocyte hypoxia/reoxygenation were established. Biochemical and histological analyses were used to investigate the influence of SETDB1 on liver damage mediated by HIRI. Chromatin immunoprecipitation and coimmunoprecipitation were implemented to explore the in-depth mechanism of SETDB1 regulating HIRI. Results: We confirmed that hepatocellular SETDB1 was up-regulated during HIRI and had a close correlation with HIRI-related inflammation and apoptosis. Moreover, inhibition of SETDB1 could mitigate HIRI-induced liver damage, inflammation, and apoptosis. Through our comprehensive mechanistic investigation, we revealed that SETDB1 interacts with apoptosis-signal-regulating kinase 1 (ASK1) and facilitates the methylation of its lysine residues. Inhibition of SETDB1 resulted in reduced phosphorylation of ASK1, leading to a marked suppression of downstream c-Jun N-terminal kinase (JNK)/p38 signaling pathway activation. The therapeutic effect on inflammation and apoptosis achieved through SETDB1 inhibition was nullified by the restoration of JNK/p38 signaling activation through ASK1 overexpression. Conclusions: The findings from our study indicate that SETDB1 mediates lysine methylation of ASK1 and modulates the activation of the ASK1–JNK/p38 pathway, thus involved in HIRI-induced inflammation and apoptosis. These results suggest that SETDB1 holds promise as a potential therapeutic target for mitigating HIRI.

吴茱萸碱通过调控Hedgehog信号通路诱导结直肠癌HCT-116细胞凋亡的研究

目的:基于Hedgehog信号通路研究吴茱萸碱抑制人结直肠癌HCT-116细胞增殖和诱导凋亡的作用及机制。方法:采用MTT法检测吴茱萸碱对HCT-116细胞和人正常结肠上皮NCM-460细胞增殖的影响;显微镜观察吴茱萸碱对HCT-116细胞形态的影响;结晶紫染色考察吴茱萸碱对HCT-116细胞克隆形成能力的影响;细胞划痕试验检测吴茱萸碱对细胞水平迁移的影响;Hoechest33324/PI染色观察吴茱萸碱对HCT-116细胞凋亡的影响;试剂盒检测吴茱萸碱对HCT-116细胞凋亡相关因子Caspase-9和Caspase-3活性的影响;蛋白免疫印迹试验(Western blotting)检测吴茱萸碱对细胞凋亡相关蛋白BAX、BCL-2、细胞周期相关蛋白Cyclin D1以及Hedgehog信号通路相关蛋白SHH、Gli1、SMO、c-Myc表达的影响;实时荧光定量PCR(qRT-PCR)检测吴茱萸碱对细胞凋亡相关因子Bax、Bcl-2、Cyclin D1以及Hedgehog信号通路相关因子Shh、Gli1、Smo、c-Myc mRNA表达的影响。结果:吴茱萸碱抑制HCT-116细胞的增殖且在高剂量和长时间给药情况下对人正常结肠上皮NCM-460细胞产生一定的抑制效应。此外,HCT-116细胞经吴茱萸碱5、10、20μmol/L干预后形态发生改变,细胞水平迁移能力和克隆形成能力显著下降,染色质固缩,细胞核呈致密浓染,Caspase-9和Caspase-3活性升高(P<0.01);吴茱萸碱10、20μmol/L作用HCT-116细胞48 h后,Bax mRNA和蛋白表达随吴茱萸碱浓度增高而上调,Bcl-2 mRNA和蛋白表达明显下调(P<0.05或P<0.01);吴茱萸10、20μmol/L碱诱导了周期调节因子Cyclin D1 mRNA和蛋白的下调(P<0.01);Hedgehog信号通路中的关键因子Shh、Gli1、Smo、c-Myc mRNA和蛋白表达也在吴茱萸碱干预后显著下降(P<0.05或P<0.01)。结论:吴茱萸碱抑制HCT-116细胞的生长、增殖,诱导细胞凋亡,其机制可能涉及抑制Hedgehog信号通路的激活。

致敏受者肾移植四例并文献复习

肾移植作为终末期肾病的有效治疗手段,已在世界范围内得到广泛开展。然而,部分患者自身因素可导致移植物功能恢复不佳,甚至导致移植物早期失功。供者特异性抗体(donor specific antibody,DSA)所致抗体介导的排斥反应(antibody-mediated rejection,AMR)是移植肾失功的重要原因。DSA主要包括预存DSA和移植后新生DSA,均会影响移植物功能恢复,其中预存DSA是术后超急性排斥反应发生的重要原因,曾被认为是肾移植禁忌证之一,部分尿毒症患者因此失去了肾移植机会。近年来,随着研究的深入和临床经验的积累,很多移植中心对术前DSA阳性受者进行预处理后(如利妥昔单抗清除B细胞、血浆置换清除预存DSA和丙种球蛋白封闭抗体等)再行移植,取得了良好的临床效果[1,2]。本文回顾性分析武汉大学人民医院开展的4例预存DSA阳性肾移植受者资料,并结合相关文献探讨DSA阳性肾移植可行性及处理策略。

供肾Remuzzi评分对肾移植受者预后的指导作用

目的分析不同Remuzzi评分供肾移植后受者/移植肾预后情况。方法回顾性分析武汉大学人民医院2018年11月至2020年8月接受单肾移植的81例受者临床资料。根据供肾Remuzzi评分将81例受者分为低分组(Remuzzi评分0~3分,n=38)及高分组(43例)(Remuzzi评分4~6分,n=43)。正态分布计量资料采用两独立样本t检验比较;非正态分布计量资料采用Mann-Whitney U检验比较。计数资料采用χ^(2)检验或Fisher确切概率法比较。采用Graphpad 8.0.2绘制受者/移植肾生存曲线,并采用log-rank检验比较。P<0.05为差异有统计学意义。结果低分组38例受者供肾Remuzzi评分为(2.23±0.87)分,高分组43例受者供肾Remuzzi评分为(4.56±0.66)分,差异有统计学意义(t=-13.449,P<0.05)。低分组术后1、3个月血清肌酐分别为(143±92)和(136±75)μmol/L,高分组分别为(138±80)和(123±39)μmol/L,差异均无统计学意义(t=0.237和1.031,P均>0.05)。低分组术后6个月血清肌酐[107.5(60,821)μmol/L]低于高分组[113.0(67,224)μmol/L],差异有统计学意义(U=-0.371,P<0.05)。低分组术后1、3和6个月估算肾小球滤过率分别为(60±24)、(59±26)和(61±27)mL/min,高分组分别为(64±25)、(64±21)和(66±20)mL/min,差异均无统计学意义(t=-0.823、-0.903和-0.756,P均>0.05)。截至2022年2月14日,受者随访时间(29±6)个月(1~36个月)。低分组16例受者(42.1%)移植术后发生移植肾功能延迟恢复(DGF),高分组12例受者(27.9%)移植术后发生DGF,差异无统计学意义(χ^(2)=0.180,P>0.05)。两组受者术后生存率差异无统计学意义(χ^(2)=0.668,P>0.05)。两组受者移植肾存活率差异有统计学意义(χ^(2)=4.078,P<0.05)。低分组发生DGF、低分组未发生DGF、高分组发生DGF和高分组未发生DGF受者术后生存率及移植肾存活率差异均无统计学意义(P均>0.05)。结论Remuzzi评分作为供肾病理学评估的重要部分,为肾移植受者术后治疗提供一定指导,评分较高供肾移植后受者也能获得良好预后。

COVID-19 in the immunocompromised population:data from renal allograft recipients throughout full cycle of the outbreak in Hubei province,China

Coronavirus disease 2019(COVID-19)is an infectious disease caused by a newly discovered coronavirus and has rapidly spread to most of the world and resulted in a global pandemic.However,there is a paucity of information available to characterize the immunodeficient population in the COVID-19 pandemic,especially information that focuses on patients after renal transplantation as the typical representative of this population.

Empirical Likelihood for Response Differences in Two Linear Regression Models with Missing Data

Oonsider two linear models Xi = U＇β ＋ ei, Yj = V1/2y ＋ ηj with response variables missing at random. In this paper, we assume that X, Y are missing at random （MAR） and use the inverse probability weighted imputation to produce ＇complete＇ data sets for X and Y. Based on these data sets, we construct an empirical likelihood （EL） statistic for the difference of X and Y （denoted as A）, and show that the EL statistic has the limiting distribution of X~, which is used to construct a confidence interval for A. Results of a simulation study on the finite sample performance of EL-based confidence intervals on A are reported.