Interplay between microglia and environmental risk factors in Alzheimer's disease

Alzheimer s disease,among the most common neurodegenerative disorders,is chara cterized by progressive cognitive impairment.At present,the Alzheimer’s disease main risk remains genetic ris ks,but major environmental fa ctors are increasingly shown to impact Alzheimer’s disease development and progression.Microglia,the most important brain immune cells,play a central role in Alzheimer’s disease pathogenesis and are considered environmental and lifestyle"sensors."Factors like environmental pollution and modern lifestyles(e.g.,chronic stress,poor dietary habits,sleep,and circadian rhythm disorde rs)can cause neuroinflammato ry responses that lead to cognitive impairment via microglial functioning and phenotypic regulation.However,the specific mechanisms underlying interactions among these facto rs and microglia in Alzheimer’s disease are unclear.Herein,we:discuss the biological effects of air pollution,chronic stress,gut micro biota,sleep patterns,physical exercise,cigarette smoking,and caffeine consumption on microglia;consider how unhealthy lifestyle factors influence individual susceptibility to Alzheimer’s disease;and present the neuroprotective effects of a healthy lifestyle.Toward intervening and controlling these environmental risk fa ctors at an early Alzheimer’s disease stage,understanding the role of microglia in Alzheimer’s disease development,and to rgeting strategies to to rget microglia,co uld be essential to future Alzheimer’s disease treatments.

Prevalence and risk factors of depression among patients with perianal fistulizing Crohn’s disease

BACKGROUND Psychological distress,especially depression,associated with perianal fistulizing Crohn’s disease(PFCD)is widespread and refractory.However,there is a surprising paucity of studies to date that have sought to identify the prevalence and risk factors of depression associated with PFCD.AIM To estimate the prevalence of depressive symptoms and investigate the depression-related risk factors in patients with PFCD.METHODS The study was conducted in the form of survey and clinical data collection via questionnaire and specialized medical staff.Depressive symptoms,life quality,and fatigue severity of patients with PFCD were assessed by Patient Health Questionnaire-9,Inflammatory Bowel Disease Patient Quality of Life Questionnaire(IBDQ),and Inflammatory Bowel Disease(IBD)Fatigue Patient Self-assessment Scale.The basic demographic information,overall disease features,perianal clinical information,and laboratory inflammation indicators were also gathered.Multivariate regression analysis was ultimately used to ascertain the risk factors of depression associated with PFCD.RESULTS A total of 123 patients with PFCD were involved,and 56.91%were suffering from depression.According to multivariate logistic regression analysis,Perianal Disease Activity Index(PDAI)score[odds ratio(OR)=0.69,95%confidence interval(CI):0.50 to 0.95],IBDQ score(OR=0.93,95%CI:0.88 to 0.97),modified Van Assche index(OR=1.24,95%CI:1.01 to 1.53),and IBD Fatigue score(OR=1.72,95%CI:1.23 to 2.42)were independent risk factors of depression-related prevalence among patients with PFCD(P<0.05).Multiple linear regression analysis revealed that the increasing perianal modified Van Assche index(βvalue=0.166,95%CI:0.02 to 0.31)and decreasing IBDQ score(βvalue=-0.116,95%CI:-0.14 to-0.09)were independently associated with the severity of depression(P<0.05).CONCLUSION Depressive symptoms in PFCD patients have significantly high prevalence.PDAI score,modified Van Assche index,quality of life,and fatigue severity were the main independent risk factors.

Epidemiological Aspects of Obesity, Overweight and Cardiovascular Risk Factors at Associes in Semi-Urban Areas (Case of Sébikotane)

Introduction: Obesity and overweight are a public health problem. The general objective was to determine the epidemiological aspects of obesity, overweight and associated risk factors in a semi-urban environment. Patients and Methods: This was a cross-sectional, descriptive study conducted on November 28 and 29, 2023 in Sébikotane. It focused on volunteers for screening for chronic non-communicable diseases. Epidemiological and clinical data were evaluated. Results: One hundred and twenty-nine cases of obesity were recorded (28%). Two hundred and eighty-two cases were overweight or obese (61.3%). The mean age was 49.55 years, with a standard deviation of 12.41 years. The age group [40 - 49 years] was the most representative, with 85 cases (30.1%), and the majority were female, with 264 cases (93.6%). Primary education was the most common, with 75 cases (46.3%). Grade 1 obesity concerned ninety-seven cases (75.2%), and diabetes was present in thirty cases (23%). Hypertension was present in ninety-five cases (33.7%). Obesity was more marked in the age group [40 - 49 years] with 45 cases (36%). Conclusion: Obesity and overweight are a major cause of morbidity and mortality. The development and implementation of a prevention and management program is essential.

Sorl1 knockout inhibits expression of brain-derived neurotrophic factor:involvement in the development of late-onset Alzheimer's disease

Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s disease.SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport and metabolism of intracellularβ-amyloid precursor protein.To better understand the underlying mechanisms of SORL1 in the pathogenesis of late-onset Alzheimer s disease,in this study,we established a mouse model of SorI1 gene knockout using cluste red regularly inters paced short palindro mic repeats-associated protein 9 technology.We found that Sorl1-knocko ut mice displayed deficits in learning and memory.Furthermore,the expression of brain-derived neurotrophic factor was significantly downregulated in the hippocampus and co rtex,and amyloidβ-protein deposits were observed in the brains of 5orl1-knockout mice.In vitro,hippocampal neuronal cell synapses from homozygous Sorl1-knockout mice were impaired.The expression of synaptic proteins,including Drebrin and NR2B,was significantly reduced,and also their colocalization.Additionally,by knocking out the Sorl1 gene in N2a cells,we found that expression of the N-methyl-D-aspartate receptor,NR2B,and cyclic adenosine monophosphate-response element binding protein was also inhibited.These findings suggest that SORL1 participates in the pathogenesis of late-onset Alzheimer s disease by regulating the N-methyl-D-aspartate receptor NR2B/cyclic adenosine monophosphate-response element binding protein signaling axis.

Exercise and exerkine upregulation:Brain-derived neurotrophic factor as a potential non-pharmacological therapeutic strategy for Parkinson’s disease

Physical activity and exercise have several beneficial roles in enhancing both physiological and psychological well-being of an individual.In addition to aiding the regulation of aerobic and anaerobic metabolism,exercise can stimulate the synthesis of exerkine hormones in the circulatory system.Among several exerkines that have been investigated for their therapeutic potential,Brain-derived neurotrophic factor(BDNF)is considered the most promising candidate,especially in the management of neurodegenerative diseases.Owing to the ability of physical activity to enhance BDNF synthesis,several experimental studies conducted so far have validated this hypothesis and produced satisfactory results at the pre-clinical level.This review highlights some of the recent animal model studies that have evaluated the efficiency of exercise in enhancing BDNF synthesis and promoting neuroprotective effects.Further,this review focuses on understanding the therapeutic benefits of exercise-induced exerkine synthesis as a non-pharmacological strategy in Parkinson’s disease(PD).Regarding physical activity and exerkine induction,the neuromuscular electrical stimulation(NMES)strategy could be considered as an alternate treatment modality for patients affected with PD.

Health risk assessment of trace metal(loid)s in agricultural soils based on Monte Carlo simulation coupled with positive matrix factorization model in Chongqing, southwest China

This study aimed to investigate the pollution characteristics, source apportionment, and health risks associated with trace metal(loid)s(TMs) in the major agricultural producing areas in Chongqing, China. We analyzed the source apportionment and assessed the health risk of TMs in agricultural soils by using positive matrix factorization(PMF) model and health risk assessment(HRA) model based on Monte Carlo simulation. Meanwhile, we combined PMF and HRA models to explore the health risks of TMs in agricultural soils by different pollution sources to determine the priority control factors. Results showed that the average contents of cadmium(Cd), arsenic (As), lead(Pb), chromium(Cr), copper(Cu), nickel(Ni), and zinc(Zn) in the soil were found to be 0.26, 5.93, 27.14, 61.32, 23.81, 32.45, and 78.65 mg/kg, respectively. Spatial analysis and source apportionment analysis revealed that urban and industrial sources, agricultural sources, and natural sources accounted for 33.0%, 27.7%, and 39.3% of TM accumulation in the soil, respectively. In the HRA model based on Monte Carlo simulation, noncarcinogenic risks were deemed negligible(hazard index <1), the carcinogenic risks were at acceptable level(10^(-6)<total carcinogenic risk ≤ 10^(-4)), with higher risks observed for children compared to adults. The relationship between TMs, their sources, and health risks indicated that urban and industrial sources were primarily associated with As, contributing to 75.1% of carcinogenic risks and 55.7% of non-carcinogenic risks, making them the primary control factors. Meanwhile, agricultural sources were primarily linked to Cd and Pb, contributing to 13.1% of carcinogenic risks and 21.8% of non-carcinogenic risks, designating them as secondary control factors.

Influence of cultural factors on choice of childbirth place among women in Oyigbo Local Government Area,Rivers State,Nigeria

Objectives:This study aims to ascertain if cultural factors influence the childbirth place choice of women in Oyigbo.Materials and Methods:The study used a cross‑sectional study design using a self‑structured questionnaire as the instrument to collect data from 384 volunteers through simple random sampling,and these data were analyzed using frequency and percentage for descriptive statistics while Chi‑square was used for inferential statistics at 0.05 level of significance.Results:The influence of cultural factors such as family traditions(χ^(2)=12.56,P=0.006),beliefs(χ^(2)=70.66,P=0.000),lack of confidence in health facilities(χ^(2)=367.83,P=0.000),and the presence of male skilled birth attendants(χ^(2)=50.85,P=0.000)were statistically significant to the choice of childbirth place,while patriarchal system(χ^(2)=2.99,P=0.393)was not statistically significant to the choices of childbirth places of women in Oyigbo.Religion had a statistically significant influence on childbirth place(χ^(2)=125.46,P=0.000).Conclusion:This study shows that religious and cultural factors have a significant influence on the childbirth place choices of women in Oyigbo Local Government Area of Rivers State.

Scale and Associated Factors of Using Pyrethroid-Impregnated Mosquito Nets as Fishing Tools on Nokoué Lake within Sô-Ava Municipality in Benin, 2020

Background: In lacustrine communities, whether in Benin or elsewhere, populations use impregnated mosquito nets (IMNs) as fishing nets. This depletes the lake of its fishery resources, which in turn are contaminated by the pyrethroids impregnated in the nets. This study aims to determine the scale and factors associated with the use of pyrethroid-impregnated mosquito nets as fishing tools in the municipality of Sô-Ava in Benin. Methods: This is a cross-sectional and analytical study with two components. First, a quantitative component was made up of 280 volunteers who were interviewed in the seven districts of the city. Data collection was done in two phases: the first from September to October 2020, and the second in August 2022. Data were analyzed with Stata and logistic regression was used. Another qualitative component was made up of forty participants chosen by reasoned choice, of which 32 were split into four focus groups of eight members each, and the rest participated in semi-structured interviews. Triangulation of the different sources was used to analyze the data. Results: Around 67% of the population reported using impregnated mosquito nets as fishing tools and 33% exclusively for malaria. Seasonal fishermen (ORa = 2.03, CI = 1.35 - 4.97, P = 0.004) and years of professional experience (ORa = 1.53, CI = 1.00 - 2.05, P = 0.021) increase the risk of using these nets as fishing tools. The use of insecticide-treated mosquito nets against mosquitoes causes skin scratching and impairs breathing because of the impregnation products, as reported by respondents. Conclusion: A high prevalence of inappropriate use of impregnated mosquito nets in fishing practices is highlighted in this study. Interviews in the field revealed that nets are diverted for fishing purposes to increase the volume of catches. Consequently, it will be appropriate to assess the pyrethroid content in water and fishery products.

Factors influencing quality of life in Chinese patients with dementia: a systematic review

Background:Dementia is a group of nervous system diseases characterized by progressive cognitive decline,leading to a loss of self-care ability and a decline in well-being.This places a significant burden on the global healthcare system,with Chinese patients accounting for approximately one-quarter of the world’s dementia cases.Therefore,it is crucial to identify factors that impact the quality of life(QOL)among elderly Chinese individuals with dementia.Method:To achieve this,we conducted a comprehensive search of several databases,including PubMed,Embase,Web of Science,the Cochrane Library,China National Knowledge Infrastructure,Wanfang Data,China VIP Database and China Biomedical Literature Database.We reviewed cross-sectional studies from the inception of these databases until March 27,2022.QOL outcomes were assessed using standardized scales in the studies included in this review.Results:The search yielded a total of 1,235 relevant articles,from which we finally included 21 cross-sectional studies and one longitudinal study after rigorous quality assessment.Among these,10 studies were classified as high quality,while 12 were classified as fair quality.Through our analysis,we identified 28 patient-rated QOL factors and 14 caregiver-rated QOL factors.These factors were categorized into three groups:patient,disease-related and caregiver.Factors commonly found to influence patient-rated QOL included age,education,marital status,depression,self-care ability,dementia severity,cognitive function,behavioral and psychological symptoms of dementia and caregiver burden.Similarly,factors commonly influencing caregiver-rated QOL included economic status,depression,self-care ability,dementia severity,cognitive function,behavioral and psychological symptoms of dementia and caregiving time.Conclusion:This review clarifies the factors that influence the QOL of Chinese individuals with dementia.When implementing interventions,it is crucial to consider the differences between patient-rated QOL and caregiver-proxy-rated QOL,as well as their respective influencing factors.

Exploring the Impact of Factors Affecting the Lifespan of HIVs/AIDS Patient’s Survival: An Investigation Using Advanced Statistical Techniques

This study investigates the impact of various factors on the lifespan and diagnostic time of HIV/AIDS patients using advanced statistical techniques. The Power Chris-Jerry (PCJ) distribution is applied to model CD4 counts of patients, and the goodness-of-fit test confirms a strong fit with a p-value of 0.6196. The PCJ distribution is found to be the best fit based on information criteria (AIC and BIC) with the smallest negative log-likelihood, AIC, and BIC values. The study uses datasets from St. Luke hospital Uyo, Nigeria, containing HIV/AIDS diagnosis date, age, CD4 count, gender, and opportunistic infection dates. Multiple linear regression is employed to analyze the relationship between these variables and HIV/AIDS diagnostic time. The results indicate that age, CD4 count, and opportunistic infection significantly impact the diagnostic time, while gender shows a nonsignificant relationship. The F-test confirms the model's overall significance, indicating the factors are good predictors of HIV/AIDS diagnostic time. The R-squared value of approximately 72% suggests that administering antiretroviral therapy (ART) can improve diagnostic time by suppressing the virus and protecting the immune system. Cox proportional hazard modeling is used to examine the effects of predictor variables on patient survival time. Age and CD4 count are not significant factors in the hazard of HIV/AIDS diagnostic time, while opportunistic infection is a significant predictor with a decreasing effect on the hazard rate. Gender shows a strong but nonsignificant relationship with decreased risk of death. To address the violation of the assumption of proportional hazard, the study employs an assumption-free alternative, Aalen’s model. In the Aalen model, all predictor variables except age and gender are statistically significant in relation to HIV/AIDS diagnostic time. The findings provide valuable insights into the factors influencing diagnostic time and survival of HIV/AIDS patients, which can inform interventions aimed at reducing transmission and improving early diagnosis and treatment. The Power Chris-Jerry distribution proves to be a suitable fit for modeling CD4 counts, while multiple linear regression and survival analysis techniques provide insights into the relationships between predictor variables and diagnostic time. These results contribute to the understanding of HIV/AIDS patient outcomes and can guide public health interventions to enhance early detection, treatment, and care.

Exploring the Impact of Factors Affecting the Lifespan of HIVs/AIDS Patient’s Survival: An Investigation Using Advanced Statistical Techniques

This study investigates the impact of various factors on the lifespan and diagnostic time of HIV/AIDS patients using advanced statistical techniques. The Power Chris-Jerry (PCJ) distribution is applied to model CD4 counts of patients, and the goodness-of-fit test confirms a strong fit with a p-value of 0.6196. The PCJ distribution is found to be the best fit based on information criteria (AIC and BIC) with the smallest negative log-likelihood, AIC, and BIC values. The study uses datasets from St. Luke hospital Uyo, Nigeria, containing HIV/AIDS diagnosis date, age, CD4 count, gender, and opportunistic infection dates. Multiple linear regression is employed to analyze the relationship between these variables and HIV/AIDS diagnostic time. The results indicate that age, CD4 count, and opportunistic infection significantly impact the diagnostic time, while gender shows a nonsignificant relationship. The F-test confirms the model's overall significance, indicating the factors are good predictors of HIV/AIDS diagnostic time. The R-squared value of approximately 72% suggests that administering antiretroviral therapy (ART) can improve diagnostic time by suppressing the virus and protecting the immune system. Cox proportional hazard modeling is used to examine the effects of predictor variables on patient survival time. Age and CD4 count are not significant factors in the hazard of HIV/AIDS diagnostic time, while opportunistic infection is a significant predictor with a decreasing effect on the hazard rate. Gender shows a strong but nonsignificant relationship with decreased risk of death. To address the violation of the assumption of proportional hazard, the study employs an assumption-free alternative, Aalen’s model. In the Aalen model, all predictor variables except age and gender are statistically significant in relation to HIV/AIDS diagnostic time. The findings provide valuable insights into the factors influencing diagnostic time and survival of HIV/AIDS patients, which can inform interventions aimed at reducing transmission and improving early diagnosis and treatment. The Power Chris-Jerry distribution proves to be a suitable fit for modeling CD4 counts, while multiple linear regression and survival analysis techniques provide insights into the relationships between predictor variables and diagnostic time. These results contribute to the understanding of HIV/AIDS patient outcomes and can guide public health interventions to enhance early detection, treatment, and care.

帕金森病患者免疫球蛋白、Th9亚群水平变化及其与IGF-1、S-100B蛋白的相关性

目的:研究帕金森病(PD)患者免疫球蛋白(IgG、IgA和IgM)、辅助性T细胞亚群Th9水平变化及其与胰岛素生长因子-1(IGF-1)、S-100B蛋白的相关性。方法:选取2020年12月至2022年12月期间在河北省中医院确诊的108例PD患者,将其作为研究组,并根据患者病变程度分为轻度组(35例)、中度组(44例)和重度组(29例);另选108例健康成人作为对照组。对比研究组和对照组免疫球蛋白和Th9亚群水平,以及轻度组、中度组及重度组免疫球蛋白、Th9亚群、IGF-1和S-100B蛋白水平,采用Pearson相关性分析免疫球蛋白、Th9亚群和IGF-1、S-100B蛋白的相关性。采用Spearman相关性分析PD患者疾病程度和所有差异指标间的相关性。结果:研究组IgM水平较对照组低,且重度组低于中度组,中度组低于轻度组(P<0.05);研究组IgG、IgA、IL-9和Th9亚群水平较对照组高,且重度组高于中度组,中度组高于轻度组(P<0.05)。重度组IGF-1水平低于中度组,中度组低于轻度组;重度组S-100B蛋白水平高于中度组,中度组高于轻度组(P<0.05)。Pearson相关性分析结果显示,PD患者IgM水平与IGF-1水平呈正相关,与S-100B蛋白水平呈负相关;IgG、IgA、IL-9和Th9亚群水平均与IGF-1水平呈负相关,与S-100B蛋白水平呈正相关(P<0.05)。Spearman相关性分析结果显示,PD患者疾病程度与IgM、IGF-1水平呈负相关,与S-100B蛋白、IgG、IgA、IL-9和Th9亚群水平呈正相关(P<0.05)。结论:PD患者IgM水平降低,IgG、IgA、Th9亚群水平升高,且其水平变化与IGF-1、S-100B明显相关,可以用于评估病情的严重程度。

S-100β CysC和NF-κB对急性缺血性脑卒中患者静脉溶栓后出血转化的预测价值

目的 探讨急性缺血性脑卒中(AIS)外周血中S-100β、CysC和NF-κB水平对静脉溶栓后出血转化的影响及预测价值。方法 收集2019-03—2022-03接受溶栓治疗的AIS患者140例,根据溶栓后24 h是否发生出血转化(HT)将患者分为非HT组(n=112)和HT组(n=28)。比较2组一般临床资料,采用多因Logistic回归分析影响HT发生的危险因素,受试者工作特征(ROC)曲线评估S-100β、CysC和NF-κB预测HT发生的价值。结果 HT组与非HT组相比,患者年龄、发病至溶栓时间、房颤、TOAST分型、C反应蛋白、凝血酶原时间、S-100β、CysC、NF-κB、白质高信号和脑微出血等均有统计学差异(P<0.05)。Logistic多因素回归分析显示,房颤、S-100β、CysC和NF-κB为影响HT发生的危险因素。S-100β、CysC和NF-κB预测AIS患者静脉溶栓后出血转化的曲线下面积分别为0.915(0.902~0.923)、0.874(0.856~0.882)和0.789(0.771~0.796),均具有一定的预测价值。结论 S-100β、CysC和NF-κB为AIS患者静脉溶栓后HT发生的危险因素,对HT发生具有一定的预测价值。

Neurotrophic factor-based pharmacological approaches in neurological disorders

Aging is a physiological event dependent on multiple pathways that are linked to lifespan and processes leading to cognitive decline.This process represents the major risk factor for aging-related diseases such as Alzheimer’s disease,Parkinson’s disease,and ischemic stroke.The incidence of all these pathologies increases exponentially with age.Research on aging biology has currently focused on elucidating molecular mechanisms leading to the development of those pathologies.Cognitive deficit and neurodegeneration,common features of aging-related pathologies,are related to the alteration of the activity and levels of neurotrophic factors,such as brain-derived neurotrophic factor,nerve growth factor,and glial cell-derived neurotrophic factor.For this reason,treatments that modulate neurotrophin levels have acquired a great deal of interest in preventing neurodegeneration and promoting neural regeneration in several neurological diseases.Those treatments include both the direct administration of neurotrophic factors and the induced expression with viral vectors,neurotrophins’binding with biomaterials or other molecules to increase their bioavailability but also cell-based therapies.Considering neurotrophins’crucial role in aging pathologies,here we discuss the involvement of several neurotrophic factors in the most common brain aging-related diseases and the most recent therapeutic approaches that provide direct and sustained neurotrophic support.

Joint Detection of Serum Vitamin D,Body Mass Index,and Tumor Necrosis Factor Alpha for the Diagnosis of Crohn’s Disease

Objective Vitamin D(VD)deficiency was reported to contribute to the progression of Crohn’s disease(CD)and affect the prognosis of CD patients.This study investigated the role of serum VD,body mass index(BMI),and tumor necrosis factor alpha(TNF-α)in the diagnosis of Crohn’s disease.Methods CD patients(n=76)and healthy subjects(n=76)were enrolled between May 2019 and December 2020.The serum 25-hydroxyvitamin D[25(OH)D]levels,BMI,and TNF-αlevels,together with other biochemical parameters,were assessed before treatment.The diagnostic efficacy of the single and joint detection of serum 25(OH)D,BMI,and TNF-αwas determined using receiver operating characteristic(ROC)curves.Results The levels of 25(OH)D,BMI,and nutritional indicators,including hemoglobin,total protein,albumin,and high-density lipoprotein cholesterol,were much lower,and the TNF-αlevels were much higher in the CD patients than in the healthy subjects(P<0.05 for all).The areas under the ROC curve for the single detection of 25(OH)D,BMI,and TNF-αwere 0.887,0.896,and 0.838,respectively,with the optimal cutoff values being 20.64 ng/mL,19.77 kg/m^(2),and 6.85 fmol/mL,respectively.The diagnostic efficacy of the joint detection of 25(OH)D,BMI,and TNF-αwas the highest,with an area under the ROC curve of 0.988(95%CI:0.968–1.000).Conclusion The joint detection of 25(OH)D,TNF-α,and BMI showed high sensitivity,specificity,and accuracy in CD diagnosis;thus,it would be effective for the diagnosis of CD in clinical practice.

AR、SKP2、SOX10、PD-L1及TIL表达在三阴性乳腺癌中的意义

目的:探索雄激素受体(androgen receptor,AR)、S期激酶相关蛋白2(S-phase kinase-associated protein 2,SKP2)、性别决定区Y相关的HMG盒含因子10(sry-related HMG box-containing factor 10,SOX10)、程序性死亡配体1(programmed death-ligand 1,PD-L1)及肿瘤浸润性淋巴细胞(tumor infiltrating lymphocyte,TIL)在三阴性乳腺癌(triple negative breast cancer,TNBC)表达与临床病理特征和预后的关系。方法:根据苏木精-伊红染色(hematoxylineosin, HE)染色切片评判109例TNBC瘤巢内TIL的比例,采用Leica Bond-Max全自动免疫组化仪检测TNBC组织中AR、SKP2、SOX10、PD-L1的表达。分析以上各生物指标与临床病理特征间的关系,并采用kaplan-Meier、Log-rank进行生存分析。结果:95例患者获得随访,中位随访时间为48个月,中位无病生存时间(disease-free survival, DFS)为42个月,中位总生存时间(overall survival, OS)48个月。在TNBC中,AR阳性表达与淋巴结转移阴性(P=0.009)、肿瘤最大径<2 cm(P=0.008)相关,TIL高表达与低级别TNBC相关(P=0.007),SKP2阳性表达与神经/脉管侵犯阳性(P=0.011)、高级别TNBC相关(P=0.002),SOX10阳性表达与淋巴结转移阳性(P=0.022)、高级别TNBC(P=0.005)相关,PD-L1阳性表达与淋巴结转移阳性(P=0.020)、神经/脉管侵犯阳性(P=0.006)、高级别TNBC(P=0.042)相关。生存分析显示,SKP2、SOX10阳性表达与更差的DFS(P=0.007、P<0.001)和OS(P=0.013、P<0.001)相关,TIL高表达与更好的DFS(P=0.016)及OS(P=0.004)相关。在生物表志物的联合表达中,AR+/SKP2-、AR+/SOX10-与更好的DFS(P=0.004、P<0.001)及OS(P=0.007、P=0.001)相关,SOX10+/低TIL、PD-L1+/低TIL与更差的DFS(P<0.001、P=0.008)及OS(P=0.001、P=0.002)相关,AR-/低TIL者具有更差的OS(P=0.014)。SKP2(HR=4.143,95%CI为1.578~10.875)、SOX10(HR=7.578,95%CI为2.067~27.782)的阳性表达是影响TNBC患者DFS的独立预后因子,SKP2(HR=3.758,95%CI为1.400~10.084)、SOX10(HR=5.131,95%CI为1.316~20.000)及TIL(HR=0.375,95%CI为0.154~0.917)的阳性表达是TNBC患者OS的独立预后因子(P均<0.05)。结论:在TNBC中,AR阳性、TIL高表达与具有更好预后的临床病理特征相关,SKP2、SOX10和PD-L1与具侵袭性的临床病理特征相关。SKP2、SOX10及TIL表达与TNBC预后相关,提示这些生物指标可能成为TNBC新的预后因子,同时它们也有可能成为潜在的治疗靶点。

Inflammatory bowel disease:Epidemiology,pathology and risk factors for hypercoagulability

Hypercoagulability observed in patients with inflammatory bowel diseases(IBD)may lead to thromboembolic events(TE),which affect the venous and arterial systems alike and are an important factor in patients’morbidity and mortality.The risk of TE in IBD patients has been demonstrated to be approximately threefold higher as compared to the general population.The pathogenesis of thrombosis in IBD patients is multifactorial and not fully explained.The most commonly listed factors include genetic and immune abnormalities,disequilibrium between procoagulant and anticoagulant factors,although recently,the role of endothelial damage as an IBD-triggering factor is underlined.Several studies report that the levels of some coagulation enzymes,including fibrinogen,factorsⅤ,Ⅶ,Ⅷ,active factorⅪ,tissue factor,prothrombin fragment 1+2and the thrombin-antithrombin complex,are altered in IBD patients.It has been demonstrated that there is a significant decrease of tissue plasminogen activator level,a marked increase of plasminogen activator inhibitor type 1 and thrombin-activable fibrinolysis inhibitor,a significantly lower level of antithrombinⅢand tissue factor pathway inhibitor.IBD patients have been also observed to produce an increased amount of various anticoagulant antibodies.Hyperhomocysteinemia,which is a potential risk factor for TE was also observed in some IBD patients.Further studies are necessary to assess the role of coagulation abnormalities in IBD etiology and to determine indications for thromboprophylactic treatment in patients at high risk of developing TE.

Bullying among people with visual impairment: Prevalence, associated factors and relationship to self-efficacy and life satisfaction

AIM To examine associated factors of bullying and to determine associations between bullying and psychosocial outcomes among individuals with visual impairments(Ⅵ). METHODS We conducted an age-stratified cross-sectional survey of adults with Ⅵ who were recruited from the Norwegian Association of the Blind and Partially Sighted. Data were collected through structural telephone interviews in the period between February and May, 2017. Linear regression models were used to examine factors related to bullying and associations of bullying with self-efficacy and life satisfaction.RESULTS A total of 736 individuals were interviewed. The lifetime and 6-mo prevalence of bullying was 41.7% and8.2%, respectively. The majority of bullied participants reported Ⅵ-specific bullying(65.1%). Victimization of bullying was associated with young age, early onsetage of Ⅵ, and having other impairments. Participants who reported bullying had lower levels of self-efficacy[Adjusted relative risk(ARR): 0.40, 95% confidence interval(CI): 0.19-0.85] and life satisfaction(ARR: 0.68,95%CI: 0.51-0.91).CONCLUSION Bullying is highly prevalent among individuals withⅥ. Our findings suggest that interventions to reduce bullying may be beneficial for improving the well-being and life quality of people with Ⅵ.

Risk factors and implications of anastomotic complications after surgery for Crohn's disease

Anastomotic complications occur more frequently in patients with Crohn's disease leading to postoperative intra-abdominal septic complications(IASC). Patients with IASC often require re-operation or drainage to controlthe sepsis and have an increased frequency of disease recurrence. The aim of this article was to examine the factors affecting postoperative IASC in Crohn's disease after anastomoses, since some risk factors remain controversial. Studies investigating IASC in Crohn's operations were included, and all risk factors associated with IASC were evaluated: nutritional status, presence of abdominal sepsis, medication use, Crohn's disease type, duration of disease, prior operations for Crohn's, anastomotic technique, extent of resection, operative timing, operative length, and perioperative bleeding. In this review, the factors associated with an increased risk of IASC are preoperative weight loss, abdominal abscess present at time of surgery, prior operation, and steroid use. To prevent IASC in Crohn's patients, preoperative optimization with nutritional supplementation or drainage of abscess should be performed, or a diverting stoma should be considered for patients with multiple risk factors.

Neurotrophic factors: from neurodevelopmental regulators to novel therapies for Parkinson's disease

Neuroprotection and neuroregeneration are two of the most promising disease-modifying ther- apies for the incurable and widespread Parkinson＇s disease. In Parkinson＇s disease, progressive degeneration of nigrostriatal dopaminergic neurons causes debilitating motor symptoms. Neurotrophic factors play important regulatory roles in the development, survival and maintenance of specific neuronal populations. These factors have the potential to slow down, halt or reverse the loss of nigrostriatal dopaminergic neurons in Parkinsoffs disease. Several neurotrophic fac- tors have been investigated in this regard. This review article discusses the neurodevelopmental roles and therapeutic potential of three dopaminergic neurotrophic factors： glial cell line-derived neurotrophic factor, neurturin and growth/differentiation factor 5.