Co Complexes as a Corrosion Inhibitor for 316 L Stainless Steel in H2SO4 Solution

The effect of Co complexes with a Schiff base ligand on the electrochemical corrosion behavior of 316 L SS in 0.1 M H2SO4 at 25℃ has been investigated at various inhibitor concentration using electrochemical techniques (impedance spectroscopy (EIS), polarization curves). Corrosion measurements indicate that Co complex act as moderately inhibitors. Results revealed that increasing the concentration of Co complex increases the corresponding IE% values till 100 ppm. Co complex acts as mixed type inhibitors with predominant effect on the anodic dissolution of iron. Adsorption studies showed that the process follows Langmuir adsorption isotherm.

CRYSTAL STRUCTURE OF THE COMPLEX OF MUNG BEAN TRYPSIN INHIBITOR LYSINE ACTIVE FRAGMENT WITH BOVINE TRYPSIN AT 1.8 A RESOLUTION

The structure of the complex of mung bean trypsin inhibitor lysine active fragment with bovine trypsin has been determined at a resolution of 1.8 A by A-ray crystallographic analysis and the complex model refined by restrained least-squares minimization with the data between 10 and 1.8 resolution.The current conventional R factor is 17.3%,and the model con- tains 1648 protein atoms,219 inhibitor atoms and 126 water molecules.The most prominent feature of the inhibitor fragment is that it does not contain any alpha-helices.Most of the chain fold in an irregular fashion.The seven residues of the binding segment of the inhibitor lysine active frag- ment are in specific contact with bovine trypsin.The binding interaction and geometry around the reactive site are similar to that observed in other studies of trypsin-inhibitor complexes.

Crystal Structures of Human 17<i>β</i>-Hydroxysteroid Dehydrogenase Type 1 Complexed with the Dual-Site Inhibitor EM-139

Human 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) catalyzes the biosynthesis of the most potent natural estrogen 17β-estradiol (E2) from estrone (E1) in the ovary and peripheral tissues, playing a pivotal role in the progression of estrogen-dependent diseases. N-n-Butyl-N-methyl-ll-(16'α-chloro-3',17'β-dihydroxyestra-1',3',5'(10')-trien-7'α-yl)undecanamide (EM-139) was previously described as a dual-site inhibitor that can inhibit 17β-HSD1 transforming E1 into E2 and also inhibit estrogen receptor. In the present report, we describe the co-crystallization of EM-139 with 17β-HSD1 as well as the analysis of the three-dimensional structure of the enzyme/inhibitor complex. The crystal is grown under similar condition as native crystals, whereas the space group is changed to I121 never observed in other 17β-HSD1 crystals before. The steroidal moiety of the bound EM-139 molecule has shown a binding pattern similar to E2 in the E2 binary complex. The O-3 of the inhibitor develops hydrogen bonds with residues His221 and Glu282, whereas the O-17 makes hydrogen bonds with Ser142 and Tyr155. The bulky 7α-alkyl moiety of the inhibitor, which is essential for its anti-estrogenic activity but cannot be defined in the electron density, may compromise the inhibitory effect of EM-139 to 17β-HSD1. Moreover, the 16α-Cl atom shows no obvious interaction with surrounding residues. The atomic level understanding of the inhibitory mechanism of EM-139 provides important information for the inhibitor design of 17β-HSD1, which will facilitate future development of more potent and selective inhibitors of the enzyme for therapeutic purposes.

A Copper(Ⅱ)Complex Based on N-(4-hydroxybenzyl)-L-serine:Synthesis,Crystal Structure and Inhibitory Activity on PTP1B and TCPTP

A novel copper（II） complex with the reduced Schiff base, [Cu（L）2]·H2O （I, HL = N-（4-hydroxybenzyl）-L-serine）, was prepared in aqueous solution and characterized by elemental analysis, FT-IR, electrospray ionization mass spectrometry and single-crystal X-ray diffraction. Complex I crystallizes in the orthorhombic system, space group P212121, with a = 8.9040（18）, b = 9.1530（18）, c = 24.891（5）A^°, V = 2028.6（7） A^°3, Z = 4, C20H26CuN2O9, Mr = 501.97, Dc = 1.644g·cm^3, μ = 1.135 mm^-1, F（000） = 1044, GOOF = 1.194, the final R = 0.0484 and wR = 0.1420 for 6186 observed reflections （I 〉 2σ（I））. In I, two L^- anions are coordinated to the copper ion in tridentate and bidentate chelating modes, respectively, resulting in the coordinated geometry of copper ion to be a distorted square pyramid. The intermolecular hydrogen bonds between the complexes, complexes and lattice water molecules lead to a 2D supramolecular network. The bioactivity of the complex as a potential PTPs inhibitory agent in vitro was investigated, displaying potent inhibition against PTP1B （IC50, 0.27 μM） and TCPTP （IC50, 0.57 μM） with a moderate selectivity.

Thrombin Activatable Fibrinolysis Inhibitor in Preeclmapsia and Gestational Hypertension throughout the Gestation

To clarify the role of TAFI in hypertensive disorders in pregnancy, 22 subjects, including 10 with pre-eclampsia （PE） and 12 with gestational hypertension were examined for the levels of TAFI and thrombin-antithrombin （TAT） complex. Thirty normal pregnant women served as controls. ELISA was employed for the detection. The results showed that the TAFI antigen levels in normal pregnancy group, gestational hypertension group and PE group were （85.35±24.69）%, （99.65±18.27）%, （110.12±23.36）%; （97.06±21.40）%, （114.08±27.76）%, （125.49±24.70）%; （106.6±19.21）%, （129.2±25.07）%, （139.1±30.12）%, in the 1st, 2nd and 3rd trimester respectively. No significant differences were found between the normal pregnancy group and gestational hypertension group but significant difference existed between normal pregnancy group and PE group in each trimester （P〈0.05）. TAT complexes were significantly higher in patients with PE than that in controls （P〈0.05）, but no correlation was found between TAT and TAFI. It is concluded that TAFI may contributed to the impairment of fibrinolysis in the patients with PE and may serves as a sensitive indicator for PE, but it may not help in the diagnosis of the gestational hypertension.

Efficacy of EGFR Tyrosine Kinase Inhibitors in Non-small Cell Lung Cancer Patients Harboring Different Types of EGFR Mutations:A Retrospective Analysis

With the development of molecular pathology, many types of epidermal growth factor receptor（EGFR） mutations have been identified. The efficacy of EGFR tyrosine kinase inhibitors（EGFR-TKIs） in non-small cell lung cancer（NSCLC） patients with different types of EGFR mutations, especially in patients with single rare mutations or complex mutations（co-occurrence of two or more different mutations）, has not been fully understood. This study aimed to examine the efficacy of EGFR-TKIs in NSCLC patients with different types of EGFR mutations. Clinical data of 809 NSCLC patients who harbored different types of EGFR mutations and treated from January 2012 to October 2016 at Renmin Hospital and Zhongnan Hospital, Wuhan, were retrospectively reviewed. The clinical characteristics of these patients and the efficacy of EGFR-TKIs were analyzed. Among these patients, 377 patients had only the EGFR del-19 mutation, 362 patients the EGFR L858R mutation in exon 21, 33 patients single rare mutations and 37 patients complex mutations. Among these 809 patients, 239 patients were treated with EGFR-TKIs. In all the 239 patients, the disease control rate（DCR） was 93.7% with two patients（0.2%） achieving complete response（CR）, the median progression free survival（PFS） was 13.0 months（95% confidence interval [CI], 11.6–14.4 months）, and the median overall survival（OS） was 55.0 months（95% CI, 26.3–83.7 months）. Subgroup analysis revealed that the DCR in patients harboring single rare or complex mutations of EGFR was significantly lower than in those with del-19 or L858 R mutation（P〈0.001）. Patients with classic mutations（del-19 and/or L858 R mutations） demonstrated longer PFS（P〈0.001） and OS（P=0.017） than those with uncommon mutations（single rare and/or complex mutations）. Furthermore, the patients with single rare mutations had shorter median OS than in those with other mutations. Multivariate Cox regression analysis identified that the type of EGFR mutations was an independent risk factor for PFS（hazard ratio [HR]=0.308, 95% CI, 0.191–0.494, P〈0.001） and OS（HR=0.221, 95% CI, 0.101–0.480, P〈0.001）. The results suggest that the single rare or complex EGFR mutations confer inferior efficacy of EGFR-TKIs treatment to the classic mutations. The prognosis of the single rare EGFR mutations is depressing. EGFR-TKIs may be not a good choice for NSCLC patients with single rare mutations of EGFR. Further studies in these patients with uncommon mutations（especially for the patients with single rare mutations） are needed to determine a better precision treatment.

Synthesis,biochemical evaluation and computational simulations of new cytochrome bc1 complex inhibitors based on N-(4-aryloxyphenyl)phthalimides

The cytochrome bc1complex(the bc1complex or complex Ⅲ) is an attractive target for the discovery of numerous pharmaceuticals and pesticides. In order to identify new lead structures for this target, a new series of molecules, N-(4-aryloxyphenyl)phthalimides, were designed and synthesized in a straightforward manner. Our design strategy was to introduce a 4-aryloxyphenyl group, a fragment which exhibited promising bc1complex-inhibiting properties, into the aryl group of the valuable N-arylphthalimide backbone. Afterward, the biochemical evaluation of the newly synthesized compounds was carried out,and the results implied that several compounds demonstrated good activities against succinatecytochrome reductase(SCR, a mixture of mitochondrial complex Ⅱ and the bc1complex). Further studies confirmed that 3e’, a representative compound in this paper, was identified as an inhibitor of the bc1complex. Furthermore, computational simulations were also performed to better understand binding of 3e’ to the enzyme complex, which indicated that 3e’ should bind to the Qosite of the bc1complex.Consequently, we harbor the idea that this paper can provide a solid platform for synthesis and discovery of other bc1complex inhibitors.

Metal complexes of anthranilic acid derivatives: A new class of noncompetitive α-glucosidase inhibitors

Metal complexes of anthranilic acid derivatives that constitute a novel class of non-sugar-type α- glucosidase inhibitors were synthesized and assessed in vitro for inhibitory activity. All of the AgO） complexes （9-16） inhibited α-glucosidase at the nanomolar scale, while 3,5-dichloroanthranilic acid silver（1） （9） was the most potent （ICso = 3.21 nmol/L）. Analysis of the kinetics of enzyme inhibition indicated that the mechanism of the newly prepared silver complexes was noncompetitive. The structure-activity relationships were also analyzed, and thev are discussed in this report.

Lipoprotein(a)and Benefit of PCSK9 Inhibition in Emergency Complex Higher-risk and Indicated Patients

Objective There is a large population of patients classified as complex higher-risk and indicated patients(CHIPs)in China with a poor prognosis.The treatment of these patients is complex and challenging,especially when acute cardiac events occur,such as acute coronary syndrome(ACS)or heart failure.Pharmacotherapy and some mechanical circulatory support(MCS)therapeutic devices can provide stable hemodynamic support for CHIPs-percutaneous coronary intervention(PCI).LDL-C is an important pathogenic factor in atherosclerosis,and the target of blood lipid control.Recent studies have revealed that lipoprotein(a)[Lp(a)],which is formed when a covalent bond between apolipoprotein(a)and apolipoprotein B-100 is made,produces an LDL-like particle.This particle is an independent risk factor for the development of atherosclerosis,and is closely correlated to stent thrombosis and restenosis.Furthermore,this requires active intervention.PCSK9 inhibitors have been used in lipid-lowering treatment,and preventing atherosclerosis.The present study explores the efficacy of PCSK9 inhibitors in CHIPs-ACS,and the association between the change in Lp(a)and survival after 2 years of follow-up.Methods The present real-world,prospective control study enrolled 321 CHIPs-ACS who underwent emergency PCI from August 2019 to November 2020,and these patients were followed up for 2 years.These patients were divided into two groups:PCSK9 group(n=161)given the combined PCSK9 inhibitor(140 mg of evolocumab every 2 weeks)and statins-based therapy,and SOC group(n=160)treated with statin-based lipid-lowering therapy alone.Then,the change in lipid index was measured,and the cardiovascular(CV)event recurrence rate was evaluated after one month and 2 years.Afterwards,the contribution of serum lipid parameters,especially the Lp(a)alteration,in patients with earlier initiation of the PCSK9 inhibitor to the CV outcome was analyzed.Results The LDL-C level was significantly reduced in both groups:52.3%in the PCSK9 group and 32.3%(P<0.001)in the SOC group.It is noteworthy that the Lp(a)level decreased by 13.2%in the PCSK9 group,but increased by 30.3%in the SOC group(P<0.001).Furthermore,the number of CV events was not significantly different between the PCSK9 and SOC groups after the 2-year follow-up period.In the PCSK9 group,the Lp(a)reduction was associated with the baseline Lp(a)levels of the patients(r2=−0.315,P<0.001).Moreover,the decrease in Lp(a)contributed to the decline in CV events in patients who received ACS CHIPs-PCI,and the decrease in Lp(a)level was independent of the LDL-C level reduction.Conclusion The early initiation of PCSK9 inhibitors can significantly reduce the LDL-C and Lp(a)levels in ACS CHIPs-PCI.However,further studies are needed to confirm whether PCSK9 inhibitors can reduce the incidence of CV disease in CHIPs.

Discovery of a novel small inhibitor R J19 targeting to human Hsp90

Heat shock protein 90(Hsp90) can promote growth and proliferation of cancer cells by helping in folding, conformational maturation, and activation of various client proteins. Therefore, Hsp90 has been paid more attention to as an anticancer drug target. Reported Hsp90 inhibitors have several limitations such as poor solubility, limited bioavailability, and hepatotoxicity. Here, a novel small inhibitor RJ19 has been designed using fragment-based drug discovery and synthesized. Additionally, a crystal structure of Hsp90 N-RJ19 was determined by X-ray diffraction(resolution limit, 2.0 A, PDB code 4 L90). The crystal structure of Hsp90 N-RJ19 was analyzed in detail and compared with that of native Hsp90 N, Hsp90 N-ATP, and Hsp90 N-GDM,respectively. It was indicated that RJ19 interacted with Hsp90~N at the ATP-binding pocket, which suggests that RJ19 may replace nucleotides to bind with Hsp90~N to result in chaperone function failure of Hsp90. RJ19, therefore, has emerged as a promising anticancer lead compound. Rearrangement and displacement of L2 Loop in Hsp90~N-RJ 19 play a key role in the function failure, which also makes the pocket wider and longer facilitating structure modification of RJ19 later. The complex crystal structure and interaction between RJ19 and Hsp90~N provide a rational basis for the design and optimization of novel anticancer drugs.

Exploration of Zinc(II)Complexes as Potent Inhibitors Against Protein Tyrosine Phosphatase IB

Although protein tyrosine phosphatases(PTPs)do not contain any metals,their activities can be inhibited by some metal complexes.Here we investigated the inhibition of two zinc complexes with Schiff base ligands against PTPs activity to explore their effect on the cellular metabolism.It has been found that they are potent inhibitors against four recombinant PIPs5 including protein tyrosine phosphatase 1B(PTP1B),T cell protein tyrosine phosphatase(TCPTP),megakaryocyte protein tyrosine phosphatase 2(PTP-MEG2)S and Src-homology phosphatase 1(SHP-1),with exception of Src-homology phosphatase 2(SHP-2).Moreover,tlaey showed moderate selective inhibition against PTP1B with the IG50 values of 0.15 and 0.36μmol/L.Meanwhile,the complexes also inhibited cellular phosphatase activities efficiently.Comparing the inhibitory potency over PTPs mediated by the zinc ion,we found that zinc complexes might be easily developed into potent and selective inhibitors against certain PTP by rationally modifying the organic ligands moieties.

Chemical and structural biology of nucleic acids and protein-nucleic acid complexes for novel drug discovery

Since nucleic acids(DNA and RNA) play very important roles in cells,they are molecular targets of many clinically used drugs,such as anticancer drugs and antibiotics.Because of clinical demands for treating various deadly cancers and drug-resistant strains of pathogens,there are urgent needs to develop novel therapeutic agents.Targeting nucleic acids hasn’t been the mainstream of drug discovery in the past,and the lack of 3D structural information for designing and developing drug specificity is one of the main reasons.Fortunately,many important structures of nucleic acids and their protein complexes have been determined over the past decade,which provide novel platforms for future drug design and discovery.In this review,we describe some useful nucleic acid structures,particularly their interactions with the ligands and therapeutic candidates or even drugs.We summarize important information for designing novel potent drugs and for targeting nucleic acids and protein-nucleic acid complexes to treat cancers and overcome the drug-resistant problems.

Targeting metabolic vulnerability in mitochondria conquers MEK inhibitor resistance in KRAS-mutant lung cancer

MEK is a canonical effector of mutant KRAS;however,MEK inhibitors fail to yield satisfactory clinical outcomes in KRAS-mutant cancers.Here,we identified mitochondrial oxidative phosphorylation(OXPHOS)induction as a profound metabolic alteration to confer KRAS-mutant non-small cell lung cancer(NSCLC)resistance to the clinical MEK inhibitor trametinib.Metabolic flux analysis demonstrated that pyruvate metabolism and fatty acid oxidation were markedly enhanced and coordinately powered the OXPHOS system in resistant cells after trametinib treatment,satisfying their energy demand and protecting them from apoptosis.As molecular events in this process,the pyruvate dehydrogenase complex(PDHc)and carnitine palmitoyl transferase IA(CPTIA),two rate-limiting enzymes that control the metabolic flux of pyruvate and palmitic acid to mitochondrial respiration were activated through phosphorylation and transcriptional regulation.Importantly,the co-administration of trametinib and IACS-010759,a clinical mitochondrial complex I inhibitor that blocks OXPHOS,significantly impeded tumor growth and prolonged mouse survival.Overall,our findings reveal that MEK inhibitor therapy creates a metabolic vulnerability in the mitochondria and further develop an effective combinatorial strategy to circumvent MEK inhibitors resistance in KRAS-driven NSCLC.

Beclin 1-Vps34 complex architecture： Understanding the nuts and bolts of therapeutic targets

Autophagy is an important lysosomal degradation pathway that aids in the maintenance of cellular homeostasis by breaking down and recycling intracellular contents. Dysregulation of autophagy is linked to a growing number of human diseases. The Beclin 1-Vps34 protein-protein interaction network is critical for autophagy regulation and is therefore essential to cellular integrity. Manipulation of autophagy, in particular via modulation of the action of the Beclin I-Vps34 complexes, is considered a promising route to combat autophagy-related diseases. Here we summarize recent findings on the core components and structural architecture of the Beclin 1-Vps34 complexes, and how these findings provide valuable insights into the molecular mechanisms that underlie the multiple functions of these complexes and for devising therapeutic strategies.

Mitochondrial complex Ⅰ as a therapeutic target for Alzheimer’s disease

Alzheimer’s disease(AD),the most prominent form of dementia in the elderly,has no cure.Strategies focused on the reduction of amyloid beta or hyperphosphorylated Tau protein have largely failed in clinical trials.Novel therapeutic targets and strategies are urgently needed.Emerging data suggest that in response to environmental stress,mitochondria initiate an integrated stress response(ISR)shown to be beneficial for healthy aging and neuroprotection.Here,we review data that implicate mitochondrial electron transport complexes involved in oxidative phosphorylation as a hub for small molecule-targeted therapeutics that could induce beneficial mitochondrial ISR.Specifically,partial inhibition of mitochondrial complex I has been exploited as a novel strategy for multiple human conditions,including AD,with several small molecules being tested in clinical trials.We discuss current understanding of the molecular mechanisms involved in this counterintuitive approach.Since this strategy has also been shown to enhance health and life span,the development of safe and efficacious complex Ⅰ inhibitors could promote healthy aging,delaying the onset of age-related neurodegenerative diseases.

Role of renin-angiotensin system/angiotensin converting enzyme-2 mechanism and enhanced COVID-19 susceptibility in type 2 diabetes mellitus

Coronavirus disease 2019(COVID-19)is a disease that caused a global pandemic and is caused by infection of severe acute respiratory syndrome coronavirus 2 virus.It has affected over 768 million people worldwide,resulting in approx-imately 6900000 deaths.High-risk groups,identified by the Centers for Disease Control and Prevention,include individuals with conditions like type 2 diabetes mellitus(T2DM),obesity,chronic lung disease,serious heart conditions,and chronic kidney disease.Research indicates that those with T2DM face a hei-ghtened susceptibility to COVID-19 and increased mortality compared to non-diabetic individuals.Examining the renin-angiotensin system(RAS),a vital regulator of blood pressure and pulmonary stability,reveals the significance of the angiotensin-converting enzyme(ACE)and ACE2 enzymes.ACE converts angiotensin-I to the vasoconstrictor angiotensin-II,while ACE2 counters this by converting angiotensin-II to angiotensin 1-7,a vasodilator.Reduced ACE2 exp-ression,common in diabetes,intensifies RAS activity,contributing to conditions like inflammation and fibrosis.Although ACE inhibitors and angiotensin receptor blockers can be therapeutically beneficial by increasing ACE2 levels,concerns arise regarding the potential elevation of ACE2 receptors on cell membranes,potentially facilitating COVID-19 entry.This review explored the role of the RAS/ACE2 mechanism in amplifying severe acute respiratory syndrome cor-onavirus 2 infection and associated complications in T2DM.Potential treatment strategies,including recombinant human ACE2 therapy,broad-spectrum antiviral drugs,and epigenetic signature detection,are discussed as promising avenues in the battle against this pandemic.

新凝血标志物在新生儿弥漫性血管内凝血诊断及预后评估中的价值

目的探讨新凝血标志物血栓调节蛋白(TM)、凝血酶-抗凝血酶复合物(TAT)、纤溶酶-α2抗纤溶酶复合物(PIC)和组织型纤溶酶原激活剂-纤溶酶原激活剂抑制剂-1复合物(t-PAIC)在新生儿弥漫性血管内凝血(DIC)诊断及预后评估中的价值。方法纳入87例DIC患儿(观察组),根据其出院时的转归情况分为存活组(66例)和死亡组(21例),另外以同期出生的50例健康新生儿作为对照组。收集新生儿的临床资料,采用Logistic回归分析新生儿发生DIC的危险因素。分析不同组别TM、TAT、PIC和t-PAIC水平差异。采用受试者工作特征(ROC)曲线分析TM、TAT、PIC和t-PAIC在新生儿DIC诊断和预后评估中的价值。结果观察组低Apgar评分、出生窒息、IVH、脓毒症和PIH的发生率高于对照组(P<0.05)。多因素Logistic回归分析显示,低Apgar评分、出生窒息、脓毒症和PIH是新生儿发生DIC的独立危险因素。观察组TM、TAT、PIC和t-PAIC水平均高于对照组(P<0.05)。ROC曲线显示,TM、TAT、PIC和t-PAIC联合诊断新生儿DIC的价值优于单独诊断。死亡组TM、TAT水平高于存活组(P<0.05),2组PIC、t-PAIC差异无统计学意义;多因素Logistic回归分析显示,TAT水平升高是影响新生儿DIC预后的独立危险因素。ROC曲线显示,当TAT为21.72μg/L时,其预测新生儿DIC预后的曲线下面积为0.772(95%CI:0.666~0.878),敏感度和特异度分别为76.2%和71.2%。结论TM、TAT、PIC和t-PAIC联合应用对新生儿DIC诊断和预后评估具有重要的临床价值。

TAT、TM、PIC、t-PAIC与重型血液毒毒蛇咬伤中毒患者DIC的相关性及预测价值

目的评估凝血酶抗凝酶复合物(TAT)、血栓调节蛋白(TM)、纤溶酶-抗纤溶酶复合物(PIC)和组织型纤溶酶原激活抑制复合物(t-PAIC)与重型血液毒毒蛇咬伤中毒后弥散性血管内凝血(DIC)的临床相关性及预测价值。方法连续纳入2019年4月至2023年4月收治的重型血液毒毒蛇咬伤中毒患者作为研究对象,共132例。依据住院期间是否出现DIC分为观察组(发生DIC,n=37)及对照组(未发生DIC,n=95)。检测2组血浆TAT、TM、PIC、t-PAIC浓度。应用二元、无分类协变量的非条件Logistic回归分析TAT、TM、PIC、t-PAIC浓度与重型血液毒毒蛇咬伤中毒后DIC的临床相关性,建立受试者工作特征(ROC)曲线分析TAT、TM、PIC、t-PAIC对重型血液毒毒蛇咬伤中毒后DIC的预测能力。结果观察组TAT、TM、PIC、t-PAIC显著高于对照组(P<0.05)。二元、无分类协变量的非条件Logistic回归分析显示,TAT[OR=1.517(95%CI:1.155,1.879)]、TM[OR=1.647(95%CI:1.108,2.186)]、PIC[OR=3.989(95%CI:2.986,4.992)]、t-PAIC[OR=1.111(95%CI:0.854,1.368)]是重型血液毒毒蛇咬伤中毒患者发生DIC的危险因素(P<0.05)。ROC曲线分析显示,TAT、TM、PIC、t-PAIC是预测重型血液毒毒蛇咬伤中毒患者DIC的有效指标(P<0.05),其曲线下面积(AUC)分别为0.865(95%CI:0.790,0.939)、0.771(95%CI:0.673,0.870)、0.847(95%CI:0.804,0.889)、0.680(95%CI:0.573,0.787),联合预测效能更优异(P<0.001),AUC为0.904(95%CI:0.875,0.933)。结论TAT、TM、PIC和t-PAIC检测对判断重型血液毒毒蛇咬伤中毒患者是否发生DIC有重要参考价值,可以较好地评估患者凝血功能状态,4个指标联合预测DIC的效能更优。

技术复杂性与信息技术知识普及对任务绩效的影响机制:一个有调节的中介模型

数字化技术的发展改变了员工的办公环境,在提高办公效率的同时也可能产生技术压力等负面影响。本研究以多个中小高科技企业的443名中基层员工为研究对象,基于工作要求—资源理论,构建了一个有调节的中介模型,针对性地探讨了技术压力来源因素中的技术复杂性和技术压力抑制因素中的信息技术知识普及如何对任务绩效产生影响,并探索了多个边界条件。实证研究结果表明,一方面,工作倦怠在技术复杂性和任务绩效之间起到中介作用,且技术自我效能感和信息技术知识普及分别负向调节该中介效应;另一方面,工作投入在信息技术知识普及和任务绩效之间也起到中介作用,且技术自我效能感和技术复杂性分别正向调节该中介效应。本研究从组织和员工的双重角度探索了技术复杂性及其针对性缓解策略对任务绩效的抑制与强化机制,揭示了数字化办公情境下员工所面临技术复杂性的影响机制和应对办法,为技术压力挑战下的员工绩效改善提供有益启示。

mTOR抑制剂治疗结节性硬化症相关癫痫发作的研究进展

结节性硬化症相关癫痫发作因其特定的基因机制,通常对一般抗癫痫发作药物的反应不佳。结节性硬化症的主要致病通路为TSC1或TSC2基因异常逐步导致mTOR通路的过度激活。鉴于mTOR是一个较好的抗癫痫靶点,近十余年来,有关mTOR抑制剂的有效性和安全性的临床前研究和临床研究陆续进行,为现有mTOR抑制剂的使用提供了较为充分的证据。目前第一代mTOR抑制剂中的雷帕霉素及其衍生物依维莫司已进入临床应用。本文通过综述总结证据表明,虽然没有充分证据证实雷帕霉素和依维莫司对于结节性硬化症中的皮质结节具有明显逆转作用,但是有充分证据证实雷帕霉素和依维莫司能够减少结节性硬化症相关癫痫发作的频率,且多见轻中度不良事件。此外,雷帕霉素和依维莫司仍存在局限性,即少见的严重不良事件,以及停药后癫痫发作易复发等问题。目前研究中的一些新型mTOR抑制剂可能具有不劣于雷帕霉素和依维莫司的有效性和安全性。