HDAC3抑制剂RGFP966通过下调TGF-β1/SMAD3/STAT-1信号通路抑制AIM2炎症小体活化和EMT缓解子宫内膜纤维化

目的探讨HDAC3抑制剂RGFP966缓解子宫内膜纤维化的分子机制。方法将18只6~8周雌性SD大鼠随机分为3组,Control组、IUA模型组(即宫内粘连大鼠模型组)、RGFP966治疗组(IUA模型组给予HDAC3抑制剂RGFP966治疗),每组6只。建立IUA大鼠模型。ELISA测定大鼠血清炎症因子TNF-α、IL-1β和IL-6水平。qPCR法测定大鼠子宫内膜组织上皮间质转化标志物E-cadherin、N-cadherin、α-SMA、Vimentin mRNA相对表达水平。蛋白质印迹法测定大鼠子宫内膜组织TGF-β1、SMAD3、p-STAT-1、STAT-1、AIM2、IL-18、cleaved-IL-1β、IL-1β的表达水平。结果与Control组相比,IUA模型组大鼠子宫角壁变薄,血清炎症因子TNF-α、IL-1β、IL-6水平升高(P<0.05);E-cadherin mRNA相对表达水平降低,N-cadherin、α-SMA、Vimentin mRNA相对表达水平升高(P<0.05);TGF-β1、SMAD3、p-STAT-1蛋白质表达水平增强(P<0.05);AIM2、IL-18、cleaved-IL-1β的表达水平增强(P<0.05)。与IUA模型组相比,RGFP966治疗组部分逆转(P<0.05)了上述指标。STAT-1和IL-1β的表达水平在上述3个分组中无明显差异(P>0.05)。结论HDAC3的抑制剂RGFP966可通过下调TGF-β1/SMAD3/STAT-1信号通路抑制AIM2炎症小体和EMT,缓解子宫内膜纤维化。

Kaempferol ameliorated levodopa-induced dyskinesia in experimental rats: A role of brain monoamines, cFOS, FosB, Parkin, Pdyn, TH, and p-JNK

Background:L-dopa(Levodopa)is well known for managing PD(Parkinson’s disease);however,its prolonged use caused dyskinesia(LID).Due to the varied presentation of LID,effective treatment options are scarce.Flavonoids reported their neuroprotective activity by ameliorating acetylcholinesterase,monoamine oxidase,and neuroinflammation.Kaempferol is anotherflavonoid bearing these potentials.Aim:To evaluate neuroprotective activity of kaempferol in dyskinetic rats.Methods:PD was developed in Sprague-Dawley rats by injecting combination of L-ascorbic acid(10µL)+6-OHDA(12µg)in medial forebrain bundle to induce neuronal damage in substantial nigra(SNr).LID was induced by administrating combination of L-dopa(20 mg/kg)+benserazide HCl(5 mg/kg)for 42 days.Rats were concomitantly treated with amantadine(40 mg/kg)or kaempferol(25,50,and 100 mg/kg,p.o.).Results:Kaempferol(50 and 100 mg/kg)markedly(p<0.05)inhibited LID-induced abnormal involuntary movements(AIMs)and alternation in motor function.Kaempferol administration considerably(p<0.05)inhibited reduced mitochondrial complex activities,serotonin and dopamine levels,Bcl-2,and Tyrosine hydroxylase protein expressions in SNr.Additionally,kaempferol considerably(p<0.05)attenuated increased cFOS,FosB,Parkin,and Pdyn mRNAs expressions,Bax,cleaved caspase-3,caspase-3,and pJNK proteins levels;DOPAC and 5-HIAA levels in SNr.A positive correlation was reported between cFOS,FosB,Parkin,Pdyn,apoptosis,and TH with AIMs.Conclusion:Kaempferol effectively attenuated L-dopa-induced AIMs and dyskinesia via amelioration of alterations in cFOS,FosB,Parkin,Pdyn,Tyrosine hydroxylase,and apoptosis in the brain SNr.

醋酸靛胭脂混合三明治染色法联合智能分光比色技术结肠镜下Pit pattern分型对结直肠病变的诊断价值

目的探讨醋酸靛胭脂混合(AIM)三明治染色法联合智能分光比色技术(FICE)结肠镜下Pit pattern分型对结直肠病变的诊断价值。方法选择2022年6月-2023年10月该院收治的100例结直肠病变患者作为研究对象,共222处病灶;分别采用普通内镜、FICE和AIM三明治染色+FICE进行检查,并记录Pit pattern分型的检出情况、病理学类型;计算不同模式下Pit pattern分型诊断的敏感度、特异度、阳性预测值(PPV)、阴性预测值(NPV)和准确度,采用Kappa检验评估不同模式下Pit pattern分型诊断与病理学检查的一致性,采用受试者操作特征曲线(ROC curve)评估诊断效能。结果与普通内镜(74.32%)相比,FICE(92.34%)和AIM三明治染色+FICE(97.30%)Pit pattern分型检出与病理结果符合率更高,且AIM三明治染色+FICE高于FICE,差异均有统计学意义(P<0.05);与普通内镜相比,FICE和AIM三明治染色+FICE诊断结直肠肿瘤性病变的准确度更高,且AIM三明治染色+FICE高于FICE,差异均有统计学意义(P<0.05);与普通内镜相比,FICE和AIM三明治染色+FICE诊断早期结直肠癌的准确度更高,差异均有统计学意义(P<0.05);普通内镜、FICE和AIM三明治染色+FICE预测结直肠肿瘤性病变的曲线下面积(AUC)分别为0.815(95%CI:0.711~0.859)、0.881(95%CI:0.752~0.904)和0.933(95%CI:0.793~0.961);普通内镜、FICE和AIM三明治染色+FICE预测早期结直肠癌的AUC分别为0.850(95%CI:0.720~0.866)、0.938(95%CI:0.764~0.951)和0.947(95%CI:0.803~0.972);AIM三明治染色+FICE预测结直肠肿瘤性病变和早期结直肠癌的Youden指数最大,分别为0.955和0.968。结论AIM三明治染色+FICE下Pit pattern分型诊断结直肠肿瘤性病变和早期结直肠癌的准确度较高,可有效提高内镜的诊治质量。

Institute of Policy and Management: Aiming at the Ranks of World-class Think Tanks

Established on June 26, 1986 by the consolidation of four former CAS subordinates (namely,the Office of Policy Research, Division of Management Science, Editorial Department of the Journal of Dialectics of Nature, and Section of Optimization and Overall Planning under the CAS Institute of Applied Mathematics), the Institute of Policy and Management (IPM), CAS, is characterized by interdisciplinary studies of social and natural sciences. It applies itself to theoretical, methodological and applied research into national strategies, policies and management for S&T development. It also provides consultancy services for government departments, local authorities and CAS on issues concerning S&T development, social and economic growth, S&T management and administration of enterprises.……

AIMS65: A promising upper gastrointestinal bleeding risk score but further validation required

A novel upper gastrointestinal bleeding risk stratification score(AIMS65) has recently been developed and validated. It has advantages over existing risk scores including being easy to remember and lack of subjectivity in calculation. We comment on a recent study that has cast doubt on the applicability of AIMS65 in the peptic ulcer disease population. Although promising, further studies are required to evaluate the validity of AIMS65 in various populations.

Streptococcus mutans activates the AIM2, NLRP3 and NLRC4 inflammasomes in human THP-1 macrophages

Streptococcus mutans(S. mutans), a major aetiologic agent of dental caries, is involved in systemic diseases, such as bacterial endocarditis, if it enters the bloodstream through temporary bacteraemia. Interleukin(IL)-1β, a proinflammatory cytokine, is related to the host defences against pathogens, and its synthesis, maturation, and secretion are tightly regulated by the activation of the inflammasome, an inflammatory signalling complex. This study examined the signalling mechanism of IL-1β secretion and the inflammasome pathway induced by S. mutans to explain the molecular mechanism through which systemic infection by oral streptococci can occur. After infection of THP-1 cells with S. mutans, the expression of inflammasome components was detected using various methods. S. mutans induced IL-1β secretion via caspase-1 activation, and S. mutans-induced IL-1β secretion required absent in melanoma(AIM2), NLR family pyrin domain-containing 3(NLRP3) and NLR family CARD domain-containing 4(NLRC4)inflammasome activation. In particular, the S. mutans-induced NLRP3 inflammasome was mediated by adenosine triphosphate(ATP) release, potassium depletion and lysosomal damage. Our study provides novel insight into the innate immune response against S. mutans infection.

Herpesvirus gene vectors and applications to human gene therapy

Herpes simplex virus type 1 (HSV-1) naturallyestablishes latency in neurons of the nervous systemwith the concommitant expression of the latencyassociated transcripts (LATS) and the loss in

Effect of the firing position on aiming error and probability of hit

Sources of dispersions that contribute to delivery error and reduce the soldier performance in terms of hit probability are numerous.In order to improve the warfighter performance,the source of the errors contributing to the inaccuracy and dispersion of the weapon systems must be understood.They include ammunition dispersion error,gun dispersion,aerodynamic jump and the aiming error.The aiming error or gun pointing error is defined as the angle between the gun muzzle at the instant the trigger is pulled and the line of fire that corresponds to the intendent aim point.This is a round-to-round error.In weapons systems that include the rifle,the ammunition,a sight and a gunner,the aiming error was shown to be the single most important source of dispersion for the regular infantryman.In other words,for the general purpose rifle weapon system,the weak link is often the human.In order to verify and quantify this assertion,an experimental investigation was carried out to determine the aiming error associated with general purpose rifle fired by infantryman.The aiming error was evaluated for various firing positions and scenarios using infantryman for ranges varying between 100 m and 500 m.The results show that the aiming error is the main contributor to dispersion for the general purpose rifle fired by a non-specialized infantryman.The aiming error induced dispersion for unstressed and rested gunners is shown to be at best equivalent to that of the weapon fired from a bench rest by a marksman.Crown Copyright(?) 2019 Production and hosting by Elsevier B.V.on behalf of China Ordnance Society.

Advanced glycation end products inhibit production and activity of matrix metalloproteinase-2 in human umbilical vein endothelial cells

Objective It has been reported that advanced glycation end products (AGEs) participate in pathogenesis of accelerated atherosclerosis in diabetes through damaging endothelial function. Matrix metalloproteinases (MMPs) can be synthesized by endothelial cell and contribute to maintain endothelial homeostasis. The present work are aimed

Addressing Human Factors in Burnout and the Delivery of Healthcare: Quality & Safety Imperative of the Quadruple Aim

Human factors in the delivery of service are considered in many occupations of high impact on others such as airline industry and nuclear power industry, but not sufficiently in healthcare delivery. A common administrative framework of healthcare involves focus upon costs, quality and patient satisfaction (The Triple Aim). Many industries which support healthcare and healthcare administrators do not have firsthand knowledge of the complexities in delivering care. As a result, the experience and human factors of providing care are often overlooked at high level decision-making unless incorporated into the healthcare delivery framework, proposed as the fourth aim of The Quadruple Aim framework. Research is pointing to consequent negative effects on quality, safety, joy, meaning and sustainability of healthcare practice. High acute occupational stress and chronic occupational stress can cause direct and indirect effects on safety and quality of care. The biological, psychological and social consequences of burnout from excessive acute and chronic occupational stress are more of a threat to healthcare than commonly acknowledged. Patient safety, quality of care and clinician well-being are inextricably linked. This report will describe the process of transition from The Triple Aim to The Quadruple Aim administrative framework of healthcare delivery at the University of Rochester Medical Center. Developing the fourth aim of improving the experience of providing care, had high acceptability and aligned with other health system goals of optimization of safety, quality, and performance by applying a human factors/ergonomic (HFE) framework that considers human capabilities and human limitations. The goal of HFE is to fit the healthcare system to the human instead of the human to the healthcare system. Concepts include removal of extraneous cognitive load, using clinician neural resource (brain power) optimally for highest order decision making in patient care. An integrative model of patient safety and clinician wellbeing is a product of this effort.

Efficacy of Telbivudine in the Treatment of Chronic Hepatitis B and Liver Cirrhosis and Its Effect on Immunological Responses

This study was aimed to evaluate the long-term effects of telbivudine（Ld T） in the treatment of chronic hepatitis B（CHB） and HBV-related liver cirrhosis（LC） and to observe the changes of immunological responses during Ld T treatment. Clinical data of 80 CHB and 28 HBV-related LC patients who were administered with Ld T for 108 weeks and followed up were retrospectively analyzed. The liver function indicators including ALT, AST and γ-GT, HBV DNA copy number in serum and the rates of hepatitis B e antigen（HBe Ag） seroconversion were analyzed before and 12, 24, 36, 48, 60, 72, 84, 96 and 108 weeks after Ld T treatment in CHB and LC groups. Four serum fibrosis-related markers, including hyaluronic acid（HA）, human laminin（LN）, human type Ⅳ collagen（Ⅳ-C） and human N-terminal procollagen Ⅲ peptide（PC-Ⅲ）, were detected before and after Ld T treatment in LC group. The results showed favorable viral suppression and biochemical responses after treatment with Ld T for 12 weeks, and a high rate of virological and biochemical control was maintained during the course of 108-week treatment in both CHB and LC groups. The four fibrosis-related markers, especially HA and LN, were down-regulated to some degrees in LC group. Moreover, Ld T treatment led to the fluctuation of the circulating interferon-γ（IFN-γ） and interleukin-10（IL-10） levels at different time points in CHB group. It was concluded that Ld T could favorably lead to the virological suppression and biochemical remission. Besides, IFN-γ and IL-10 may represent a suitable and effective predictor of responsiveness during Ld T therapy.

A STATISTICAL STUDY ON RELATIONSHIP OF EL NINO EVENTS TO THE HYDROGRAPHY ALONG 137°E IN WINTER

Principal component analysis (PCA) as used by meteorologists and oceanographers is a powerful tool for analysis of the spatial and temporal variability of physical fields.This study was aimed at applying "quasi-local PCA for singular factor" to make the cumulative percentage for the first principal component as great as possible, so that a multi-dimensional problem can be reduced to a single-dimensional one, and then stepwise regression analysis can be used to parameterize the relationship between El Nino events and the hydrographic factor anomalies along 137 癊 in winter.The results show that the salinity anomalies on 30 m level, the sigmat on 250 m level, and the temperature on 300 m level at 8 癗 are most closely related with El Nino events because of thermocline movement caused by enhanced upwelling in this area during El Nino years.

Thermodynamic Analysis of Ag_3Ge Phase Formation

In the present work a thermodynamic model is presented for the nucleation of metastable Ag3Ge phase from the undercooled melt in Ag-Ge alloy system. It is shown that under kinetically induced favourable condition, nucleation of a single phase compound with an approximate stoichiometry Ag3Ge has greater affinity for nucleation over Ag and Ge based phases requiring diffusion in the liquid.

Comparison of Prognostic Scores for Upper Gastrointestinal Bleeding in the Hepato-Gastro-Enterology Department of Campus Teaching Hospital of Lome

Objective: To evaluate and compare the prognostic contribution of different UGIB prognostic scores. Patients and Method: Descriptive cross-sectional study with retrospective collection conducted from January 2014 to December 2019. Patients hospitalized in the Gastroenterology Department of Campus Teaching Hospital of Lome for upper gastrointestinal hemorrhage were included. The analytical component of this study had consisted of an evaluation of the sensitivity and specificity of different prognostic scores (GBS, mGBS, FRS, CRS, AIMS65) in predicting the occurrence of death and/or re-bleeding within 42 days. These different scores were compared using ROC (Receiver Operating Characteristic) curves. Results: We included 314 patients in our study. The male to female sex ratio was 2.48. Fibroscopy found non-related portal hypertension UGIB in 70.94% of the cases. The “FRS” was the most accurate score in predicting death or re-bleeding in all patients. The “FRS” was the most precise score in predicting the occurrence of spotting in all patients. The “FRS” was the most accurate score in predicting death among all patients. The mortality of patients at low risk of death (below the threshold value) was 2.2% for the “FRS”, 9.3% for the “CRS”, 0% for the “GBS” (p = 0.565), 50% for the “mGBS” and 11.4% for the “AIMS65”. Scores were more accurate for non-related portal hypertension UGIB. Conclusion: The “FRS” and the “CRS” are two precise scores in predicting the occurrence of an incident in the event of upper gastrointestinal hemorrhage. However, these scores were less effective in related portal hypertension UGIB.

China Aiming at Capacity Cooperation Worldwide

At present,global industrial structure adjustment accelerates,infrastructure construction is still booming,and developing countries are vigorously promoting the industrialization and urbanization,all providing great opportunities for international cooperation on capacity and equipment manufacturing.In May 2015,the'Guiding Opinions of the State Council of the Peoples Republic of China on Promoting

Persistence of Uropathogenic Escherichia Coli in the Bladders of Female Patients with Sterile Urine after Antibiotic Therapies

This study aimed to provide evidence of persistent uropathogenic Escherichia coli（UPEC） in female patients with recurrent urinary tract infection（UTI） after antibiotic therapy. We collected biopsies of the bladder, and clean-catch urine samples from 32 women who had episodes of recurrent UTI and were given antibiotic therapy. Urine samples and biopsies were analyzed by conventional bacteriological techniques. Phylogenetic group and 16 virulence factors（VFs） of UPEC were determined using polymerase chain reaction（PCR）. The infection capability of UPEC was confirmed in a mouse model. Immunofluorescence and electron microscopy were used to detect intracellular bacterial communities（IBCs） in the mouse model. The results showed that all urine specimens were detected sterile. E. coli was found in 6 of 32 biopsies（18.75%）, and was identified to be UPEC by PCR. Different VFs associated with the formation of IBCs were identified in all six UPEC isolates. Each UPEC isolate was capable of forming IBCs within the bladder epithelial cells of mice. In conclusion, UPEC with distinctive pathological traits and the capability of IBC formation was first found in the bladders of women after antibiotic therapy, suggesting that the IBC pathogenic pathway may occur in humans and it plays an important role in UTI recurrence.

The Tendency of Current College English Education for Non-majors

The reform of college English education has been a heated discussion in recent years.The traditional means of teach ing paid too much attention to the examination and the teaching materials are out of date when facing the rapid increasing of Chi nese economy,while the new vision emphasizes the learner-centredness,communicating,learning of culture,and it will take the background of International Understanding into consideration.In addition,New "Profession + English" Learning Pattern has al so been highlighted The paper is going to analyze and summarize the current situation of college English education briefly,and predict its development in the future.

Investigation of the Substituent Effects on π-Type Pnicogen Bond Interaction

Intermolecular interactions between PH2Cl and Ar–R（R = H,OH,NH2,CH3,Br,Cl,F,CN,NO2） were calculated by using MP2/aug-cc-p VDZ quantum chemical method.It has been shown from our calculations that the aromatic rings with electron-withdrawing groups represent much weaker binding affinities than those with electron-donating groups.The charge-transfer interaction between PH2Cl and Ar–R plays an important role in the formation of pnicogen bond complexes,as revealed by NBO analysis.Nevertheless,AIM analysis shows that the nature of the interactions between PH2Cl and Ar–R is electrostatic,and the interaction energies of the complexes are correlated positively with the electron densities in the bond critical points（BCPs）.RDG/ELF graphical analyses were performed to visualize the positions and strengths of the pnicogen bonding,as well as the spatial change of the electron localization upon the formation of complexes.The π-type halogen bond was also calculated,and it has been revealed that the π-type pnicogen bond systems are more stable than the halogen bond ones.

OBSERVATION ON THE CURATIVE EFFECT OF 120 CASES OF AUDITORY HALLUCINATION TREATED WITH AURICULAR ACUPUNCTURE

Auditory hallucination is one of commonsymptoms of psychosis.From 1979-1985,wehad treated 120 cases of auditory hallucinationdue to various kinds of psychosis with auricularacupuncture at our out-patient department.

STATISTICAL STUDY ON RELATIONSHIP OF EL NIO EVENTS AND THE HYDROGRAPHY ALONG 137 °E IN SUMMER

Principal component analysis (PCA) used by meteorologists and oceanographers is a powerful tool for the analysis of the spatial and temporal variability of physical fields .This study is aimed at applying " quasi-local PCA for singular factor " to make the cumulative percentage for the first principal component as great as possible , so that the many-dimension problem can be reduced to a single-dimension one , and at combining PCA with stepwise regression analysis to parameterize the relationship between El Nino events and the anomalies in hydrographic factors along 137°E in summer.The results show that the hydrography on 30-50 m levels at 7-9° N along 137° E in summer is very closely correlated with El Nino events because of the thermocline movement caused by enhanced upwelling in this area during El Nino years .