Novel insights into D-Pinitol based therapies:a link between tau hyperphosphorylation and insulin resistance

Alzheimer’s disease is a neurodegenerative disorder characterized by the amyloid accumulation in the brains of patients with Alzheimer’s disease.The pathogenesis of Alzheimer’s disease is mainly mediated by the phosphorylation and aggregation of tau protein.Among the multiple causes of tau hyperphosphorylation,brain insulin resistance has generated much attention,and inositols as insulin sensitizers,are currently considered candidates for drug development.The present narrative review revises the interactions between these three elements:Alzheimer’s disease-tau-inositols,which can eventually identify targets for new disease modifiers capable of bringing hope to the millions of people affected by this devastating disease.

The Impact and Intervention of Handheld Tai Chi Water-Resistance Fitness Ball on Middle-Aged and Elderly Patients with Parkinson’s Disease

Through the use of a survey and statistical methods, this study explores the effects and interventions of handheld Tai Chi water resistance fitness balls on the elderly with Parkinson’s disease. Firstly, a questionnaire on exercise compliance for patients with Parkinson’s disease was developed, and its reliability and validity were tested. Then, a survey was conducted to investigate the current status of exercise compliance among Parkinson’s disease patients, including general information, scoring status, and single and multiple factor analyses of influencing factors [1]. The results of the study show that through qualitative research, the dimensions and item pools of the questionnaire were initially constructed, and the reliability analysis of the questionnaire was conducted through Delphi expert consultation, with favorable results in terms of its reliability and validity [2]. Regarding the current status of exercise compliance among Parkinson’s disease patients, the study found that the level of exercise compliance needs improvement, and there are significant differences in exercise compliance levels among patients under different circumstances. Finally, the research results were discussed and conclusions were drawn. The innovation of this study lies in the development of a questionnaire on exercise compliance for patients with Parkinson’s disease and the preliminary qualitative research and Delphi expert consultation conducted on it, providing new ideas and methods for the study of exercise compliance. However, the study also has limitations as it did not examine the effects of other interventions on Parkinson’s disease, so further research should be conducted [3].

Type 2 Diabetes Meilitus Easily Develops into Alzheimer’s Disease via Hyperglycemia and Insulin Resistance

With the acceleration of population aging,the incidence of type 2 diabetes mellitus(T2DM)and Alzheimer’s disease(AD)is progressively increasing due to the age-relatedness of these two diseases.The association between T2DM and AD-like dementia is receiving much attention,and T2DM is reported to be a significant risk factor for AD.The aims of this review were to reveal the brain changes caused by T2DM as well as to explore the roles of hyperglycemia and insulin resistance in the development of AD.

Resistance to Anti-Thyroid Drugs in Graves’ Disease: Clinical-Biological Characteristics and Alternative Therapy in Tropical Area

Background: Resistance to anti-thyroid drugs (ATDs) is a rare entity recently described. We report two African observations in the treatment of Graves’ disease. Case 1: A 19-year-old Senegalese woman presented on admission with thyrotoxicosis syndrome associated with diffuse goitre and Grave’s orbitopathy. TSH levels were low (0.005 mIU/ml;N = 0.27 - 4.20) and fT4 elevated (60 pmol/L;N = 12 - 22]. Combination therapy with propranolol (40 mg/day) and carbimazole (starting dose of 45 mg/day and increased to 60 mg/day) was initiated. In view of the persistence of symptoms despite good therapeutic compliance, carbimazole was replaced by methimazole with an initial starting dose of 40 mg/day, followed by 60 mg/day. Despite the change in therapy, clinical symptoms of thyrotoxicosis persisted, and fT4 levels remained elevated. The patient was diagnosed with resistance to ATDs in Graves’ disease. Total thyroidectomy following 10 days of preoperative preparation with 1% Lugol’s solution was performed successfully. Case 2: A 22-year-old woman was referred for continued management of Graves’ disease with elevated thyroid-stimulating hormone receptor antibody (TRAb) levels (34 UI/mL;N < 1.75). Treatment included propranolol (80 mg/day) and carbimazole at an unusual dose of 80 mg/day. Combined therapy was clinically and biologically ineffective, with an fT4 level of 100 pmol/L [N: 12 - 22]. Upon admission, methimazole (40 mg/day) followed by propylthiouracil (800 mg/day) replaced carbimazole. Despite good patient compliance, the patient’s symptoms remained unaltered and fT4 levels elevated. A total robot thyroidectomy using the right axillary approach was performed successfully after 10 days of preoperative preparation, including prednisone (40 mg/day) combined with 1% Lugol’s solution. Conclusion: Resistance to ATDs complicates the management of Graves’ disease. Total thyroidectomy following preoperative preparation with Lugol’s solution and/or corticosteroids was shown to be successful.

Resistance to activated protein C is a risk factor for fibrostenosis in Crohn’s disease

AIM: To evaluate the effect of resistance to activated protein C (aPCR), the most common known inherited thrombophilic disorder, on the risk of intestinal operation of fi brostenosis in patients with Crohn’s disease (CD). METHODS: In a previous study, we assessed the prevalence of aPCR in CD. In a retrospective case- controlled study, 8 of these CD patients with aPCR were now compared with 24 CD patients without aPCR, matched by gender, age at diagnosis and duration of disease in a 1:3 fashion. The primary end point was the occurrence of an intestinal CD-related operation with evidence of fibrostenosis in the bowel resection specimen. RESULTS: The Kaplan-Meier analysis revealed that patients with aPCR had a lower probability of remaining free of operation with f ibrostenosis than patients without aPCR (P = 0.0372; exact log-rank test) resulting in a signifi cantly shorter median time interval from diagnosis of CD to the fi rst operation with fi brostenosis (32 vs 160 mo). At 10 years, the likelihood of remaining free of operation with fi brostenosis was 25% for patients with aPCR and 57.8% for patients without aPCR. CONCLUSION: CD patients with aPCR are at higher risk to undergo intestinal operation of fi brostenosis than those without aPCR. This supports our hypothesis of aPCR being a possible risk factor for fi brostenosis in CD.

Insulin Resistance in Alzheimer＇s Disease and the Role of p53 Protein

Recent evidence reveals significant metabolic changes in AD （Alzheimer＇s disease）, in which brain glucose utilization and energy production are impaired. The complex picture of metabolic disturbances in AD brains could be explained by increase of p53 protein stabilization and activation in neurons exposed to diverse metabolic stress conditions. Activated p53 helps cells to adapt to various types of metabolic stresses. Chronic stress and long lasting p53 increase lead to inhibition of glucose uptake, downregulation of glycolysis, enhancement of lipid catabolism and fatty acid β-oxidation, also promote function of tricarboxylic acid cycle and force an oxidative phosphorylation. These effects are opposite to those of insulin, thus p53 activation leads to insulin resistance of cells. However, prolonged stress conditions unveil deleterious effects of p53-evoked insulin resistance in neurons; enhancement of transcription of pro-oxidant factors, accumulation of toxic rnetabolites （e.g., cerarnide, products of advanced glycation） and ROS （reactive oxygen species）---modified cellular components, together with activation of proapoptotic genes, could finally move a suicide death program of autophagy/apoptosis in neurons. The important role of p53 in driving insulin resistance in AD brains validates attempts to inhibit p53 activity in neurons since it could promise an improvement of the disease therapy.

胰岛素抵抗与阿尔茨海默病的关联性研究进展

随着中国老龄化人口的比例不断增加,阿尔茨海默病的发病率也随之升高。阿尔茨海默病作为最常见的神经退行性疾病,会表现出不可逆转的认知功能障碍。多项研究表明,胰岛素抵抗与阿尔茨海默病的β淀粉样蛋白异常积累、tau蛋白的异常以及神经炎症等发病机制具有关联性。本文系统总结了胰岛素抵抗与阿尔茨海默病的关联性及其可能机制。

Role of metabolic dysfunction and inflammation along the liver-brain axis in animal models with obesity-induced neurodegeneration

The interaction between metabolic dysfunction and inflammation is central to the development of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease.Obesity-related conditions like type 2 diabetes and non-alcoholic fatty liver disease exacerbate this relationship.Peripheral lipid accumulation,particularly in the liver,initiates a cascade of inflammatory processes that extend to the brain,influencing critical metabolic regulatory regions.Ceramide and palmitate,key lipid components,along with lipid transporters lipocalin-2 and apolipoprotein E,contribute to neuroinflammation by disrupting blood–brain barrier integrity and promoting gliosis.Peripheral insulin resistance further exacerbates brain insulin resistance and neuroinflammation.Preclinical interventions targeting peripheral lipid metabolism and insulin signaling pathways have shown promise in reducing neuroinflammation in animal models.However,translating these findings to clinical practice requires further investigation into human subjects.In conclusion,metabolic dysfunction,peripheral inflammation,and insulin resistance are integral to neuroinflammation and neurodegeneration.Understanding these complex mechanisms holds potential for identifying novel therapeutic targets and improving outcomes for neurodegenerative diseases.

rTMS联合抗阻训练对老年帕金森病患者的干预价值及非运动症状观察

目的观察重复经颅磁刺激(rTMS)联合抗阻训练对老年帕金森患者的干预价值及对非运动症状的影响。方法选取106例老年帕金森患者,随机分为2组,所有受试者均给予常规西药治疗,观察组53例另给予rTMS联合抗阻运动,对照组53例给予rTMS治疗。比较2组患者临床疗效、下肢肌群肌力、帕金森病非运动症状评价量表(NMSS)评分、帕金森患者生活质量问卷(PDQ-39)评分。结果观察组疗效优于对照组(P<0.05);治疗后,2组患者小腿踝关节背屈肌群、膝关节伸肌群、髋关节伸肌群肌力均有所提升(P<0.05);治疗后,观察组小腿踝关节背屈肌群、膝关节伸肌群、髋关节伸肌群肌力高于对照组(P<0.05);治疗后,2组患者NMSS评分中非运动症状频率、严重程度的评分均有所降低(P<0.05);治疗后观察组NMSS评分中非运动症状频率、严重程度的评分低于对照组(P<0.05);治疗后4、8、12周,2组患者PDQ-39评分逐渐下降(P<0.05);治疗后4、8、12周,观察组PDQ-39评分均低于对照组(P<0.05)。结论rTMS联合抗阻运动治疗老年帕金森患者在改善下肢肌群肌力、非运动症状及生活质量方面均有良好效果。

山新杨谷胱甘肽S-转移酶编码基因PdbGSTU功能分析

【目的】本研究旨在通过分析山新杨谷胱甘肽S-转移酶编码基因PdbGSTU的抗病功能,为林木抗性育种提供基因资源与抗性种质。【方法】克隆PdbGSTU基因序列并对其进行生物信息学分析,利用荧光定量PCR技术分析该基因的组织特异性表达及植物激素诱导下的表达模式。利用转基因技术获得山新杨的过/抑制表达PdbGSTU基因植株,通过观察比较接种细链格孢菌后各植株叶片的表型和病斑面积,验证该基因的抗病功能;同时测定接种病原菌前后,野生型和转基因山新杨植株内过氧化氢含量和抗氧化相关酶活性。【结果】(1)山新杨PdbGSTU基因开放阅读框全长753 bp,编码氨基酸250个,对应的蛋白质相对分子质量为29.01 kDa,为稳定的酸性亲水蛋白,定位于细胞质中;系统进化分析显示,PdbGSTU蛋白与银中杨的蛋白KAJ6918316亲缘关系最近;启动子序列分析显示,PdbGSTU基因启动子序列含多种响应植物激素和逆境胁迫的顺式作用元件。(2)RT-qPCR结果显示,PdbGSTU基因在山新杨顶芽表达量最高,在其根部表达量最低,且该基因受茉莉酸甲酯、水杨酸和1-氨基环丙基-1-羧酸3种植物激素诱导,均上调表达。(3)接种细链格孢菌后,野生型和抑制表达PdbGSTU基因植株的叶片上,病斑面积分别为6.42和16.46 mm2,而过表达PdbGSTU基因的植株叶片上,少部分接种点出现明显病斑,其余接种部分仅出现褪色。【结论】PdbGSTU正向参与山新杨对细链格孢菌侵染的抵御过程,可通过清除活性氧提高杨树对病原菌的抗性。

Hyperinsulinemia,Insulin Resistance and Cognitive Decline in Older Cohort

Objective decline of resistance whether H Type 2 diabetes has been recently recognized as an important risk factor for cognitive patients with Alzheimer＇s disease （AD）. But the roles of hyperinsulinemia （HI） and insulin （IR） in the development of AD are still controversial. This study was designed to evaluate or IR influenced the cognitive functions of older cohort. Methods The cognitive functions of 328 consecutive elderly patients were evaluated with a battery of cognitive rating scales. Their fasting blood glucose （FBG） and fasting insulin （FINS） were analyzed and IR was calculated with modified-Homa. The cognitive scores in different groups and the correlation of cognitive functions with HI or IR were analyzed. Results In our study, there were 180 participants with HI and 148 without HI, and 192 with iR and 136 without IR. The participants with HI showed worse cognitive functions than those without HI in MMSE, MOCA, CDR, orientation, delayed memory, and attention/calculation domains. Similarly, the elderly with IR had lower cognitive scores than those without IR in MMSE, MOCA, CDR, GDS, orientation, delayed memory, and attention/calculation domains. The insulin levels and Homa IR had negative correlation with the scores of MMSE and delayed memory, not only in the model I adjusted for FBG and diabetes history, but also in the model 2 adjusted for all nine demographic characteristics. Conclusion HI and IR are important risk factors for cognitive decline of the elderly, especially for the dysfunctions in delayed memory domains.

The Use of Anti-Diabetic Drugs in Alzheimer’s Disease, New Therapeutic Options and Future Perspective

Alzheimer’s disease (AD) is a neurodegenerative disorder that is characterized by progressive loss of memory, confusion, inability of speech and decline in the cognitive behavior. It is considered one of the most common forms of dementia. Clinical studies and preclinical data in the last decade proved that AD and Diabetes mellitus share a pathophysiological pathway, indicating that insulin resistance, oxidative stress and inflammatory response would increase the risks of developing AD in diabetic patients. This review presents briefly the etiology of AD and Diabetes, discusses the possible theories about the interplaying risk factors and the mechanism of action of anti-diabetic medications recommended for the treatment of AD. It is concluded that antidiabetics have good potential to improve dementia, especially in earlier AD stages. However, many of the underlying intricate molecular pathways are still unclear and thus thorough future research is required.

油菜BnPMEI1基因的克隆及功能分析

以高抗菌核病的油菜品种湘油15和高感菌核病的油菜品种98C40为材料,采用RT–PCR方法克隆BnPMEI1基因的编码区全长,利用生物信息学软件和实时荧光定量PCR分析BnPMEI1的结构和表达特性,并构建该基因超表达载体,分析该基因的功能。序列分析结果表明,该基因编码区全长615bp,编码204个氨基酸,具有1个信号肽和1个PMEI结构域,属于PMEI家族基因,命名为BnPMEI1(GenBank登录号为ON254917)。表达分析结果表明,BnPMEI1在根、茎、花、叶、角果皮和籽粒中均有表达,在叶中的表达量最高,根中的表达量最低;湘油15的茎、叶、花中的表达量均显著高于98C40的。在核盘菌、茉莉酸甲酯(Me JA)和水杨酸(SA)处理下,BnPMEI1在湘油15中的表达上调,在98C40中的表达则受到抑制;乙烯处理下,BnPMEI1在2个品种中的表达均下调,在湘油15中下调的幅度更大;离体叶片接种结果显示,超表达Bn PMEI1的油菜突变体叶片病斑明显小于野生型叶片的。综合分析,BnPMEI1基因可能介导了SA和茉莉酸途径的调控,诱导油菜菌核病抗性的提高。

拟南芥AtTrx5增强植物菌核病的抗性研究

核盘菌是危害十字花科作物生产的重要病原菌。核盘菌诱导寄主产生过量活性氧(ROS),造成寄主细胞死亡,硫氧还蛋白(Trx)在寄主抗氧化过程中起重要作用。筛选并鉴定硫氧还蛋白(Trx),分析其与核盘菌抗性的关系,将为植物抗菌核病育种提供基因资源。本研究通过生物信息学及转录组数据分析,从拟南芥中筛选到一个关键Trx基因AtTrx5。AtTrx5与甘蓝型油菜BnaA08g04320D的亲缘关系最近,氨基酸相似性为85%。油菜同源基因Trx5表现出上调表达。AtTrx5超表达植株在接种核盘菌24 h后的菌斑面积相比野生型(WT)减小30%~39%,而At-Trx5基因T-DNA突变体的菌斑面积比WT增加39.2%。在侵染过程中超表达转基因拟南芥中AtTrx5的表达量均高于WT,而T-DNA突变体中AtTrx5的表达量则低于WT。DAB染色、H2O2含量、·O2-含量测定结果表明,侵染过程中拟南芥T-DNA突变体中积累的ROS高于WT,超表达转基因拟南芥中积累的ROS少于WT。

Tuberculosis of the spine

Pott’s spine,commonly known as spinal tuberculosis(TB),is an extrapulmonary form of TB caused by Mycobacterium TB.Pott’s paraplegia occurs when the spine is involved.Spinal TB is usually caused by the hematogenous spread of infection from a central focus,which can be in the lungs or another location.Spinal TB is distinguished by intervertebral disc involvement caused by the same segmental arterial supply,which can result in severe morbidity even after years of approved therapy.Neurological impairments and spine deformities are caused by progressive damage to the anterior vertebral body.The clinical,radiographic,microbiological,and histological data are used to make the diagnosis of spinal TB.In Pott’s spine,combination multidrug antitubercular therapy is the basis of treatment.The recent appearance of multidrug-resistant/extremely drug-resistant TB and the growth of human immunodeficiency virus infection have presented significant challenges in the battle against TB infection.Patients who come with significant kyphosis or neurological impairments are the only ones who require surgical care.Debride-ment,fusion stabilization,and correction of spinal deformity are the cornerstones of surgical treatment.Clinical results for the treatment of spinal TB are generally quite good with adequate and prompt care.

油菜菌核病抗性鉴定及抗病资源筛选

油菜菌核病是由核盘菌引起的世界性真菌病害,是油菜的主要病害,主要危害油菜的茎秆部分。目前,选育或筛选适合当地种植的菌核病抗性品种是生产中防治油菜菌核病最为经济安全的方法。研究采用成株期大田接种法,对120个商业油菜品种的菌核病抗性进行了鉴定。结果表明:不同油菜品种对菌核病的抗性有较大差异,在120份材料中筛选出相对抗性最好的品种1个(秦油三号)、相对中抗品种1个(秦优1699)、相对低抗品种19个、相对低感品种70个、相对中感品种26个、相对高感品种3个。该结果为油菜抗菌核病品种的选育提供了参考。

耳穴电刺激配合下颏抗阻力训练在老年帕金森病合并吞咽障碍病人中的应用

目的:观察老年帕金森病合并吞咽障碍病人应用耳穴电刺激联合下颏抗阻力训练的效果及对舌骨表面肌电的影响。方法:选取医院2020年7月—2021年12月收治的86例老年帕金森病合并吞咽障碍病人作为研究对象,采用抽签法分为对照组、观察组,每组43例。两组均给予常规吞咽功能训练,对照组给予下颏抗阻力训练,观察组在此基础上增加耳穴电刺激。比较两组病人吞咽功能[标准吞咽功能评价量表(SSA)、电视透视吞咽功能检查(VFSS)、洼田饮水试验]、吞咽时间参数、舌骨肌群表面肌电图。结果:观察组病人SSA评分、洼田饮水试验评分均低于对照组(P<0.05),VFSS评分高于对照组(P<0.05);观察组病人吞咽反应时间、口腔运送时间、喉关闭时间、咽运送时间均低于对照组(P<0.05);观察组病人舌骨上肌群吞咽时程、舌骨下肌群吞咽时程均短于对照组(P<0.05),舌骨上肌群最大波幅、舌骨下肌群最大波幅均高于对照组(P<0.05)。结论:老年帕金森病合并吞咽障碍病人应用耳穴电刺激配合下颏抗阻力训练效果确切,能有效提高吞咽功能,调节舌骨肌群神经传导,缩短吞咽时间。

双低油菜湘油15(B.napus)对菌核病抗性的研究

经苗期菌丝块接种鉴定和花期带菌牙签鉴定表明 ,双低油菜湘油 15对菌核病有高抗性。当病原危害后 ,湘油15体内酚类物质含量和几丁质酶活性迅速升高 ,且维持时间长 ,湘油 15与感病品种 98C4 0和中抗品种中油 82 1杂交后代抗性表现为双亲平均值 。

芸芥(Eruca sativa Mill.)对菌核病的抗性研究

经对芸芥和甘蓝型油菜进行苗期菌丝块接种鉴定和花期带菌牙签鉴定表明,芸芥品种总体抗性水平高于甘蓝型油菜。所鉴定的32个芸芥品种中,抗病品种22个,占供试品种68.8％,感病品种10个,占供试品种31.2％,没有中感和高感品种。所鉴定的32个甘蓝型油菜品种中,抗病品种10个,占供试品种的31.3％,感病品种22个,占供试品种的68.8％。在芸芥中有毛类型与无毛类型有一定差异,有毛类型抗性较强。当接种菌核菌后,芸芥体内酚类物质含量迅速增加,36h后达较高水平,以后略有升高。

向日葵菌核病接种方法及品种抗病性鉴定

为建立有效的向日葵菌核病田间接种鉴定方法,以核盘菌菌丝体悬浮液和孢子悬浮液作为接种物,分别对抗、感向日葵品种在现蕾期、始花期和盛花期进行人工接种,并对接种后保湿材料和保湿时间进行比较。试验结果表明：两种接种物均可使向日葵抗、感品种产生盘腐症状。用菌丝体悬浮液和孢子悬浮液接种时,浓度分别为10.0-15.0g/L和200-500个/mL,始花期接种,牛皮纸袋保湿2-4d,即可区分出向日葵品种间抗感性差异。用此方法鉴定出13个对盘腐型菌核病表现抗病的向日葵品种。