Background Mufangji decoction(MFJD), a classical traditional Chinese medicine formula, has demonstrated significant clinical effects in the treatment of cardiovascular diseases. This study aims to investigate the therapeutic effect of Mufangji decoction (MFJD) on chronic heart failure (CHF) and elucidate its potential mechanisms, with a focus on the PI3K-AKT signaling cascade. Methods A rat model of CHF was induced by transverse aortic constriction. Animals were randomly divided into control, CHF model, and MFJD-treated groups. Cardiac function was assessed using echocardiography, and myocardial fibrosis was evaluated by hematoxylin-eosin and Masson staining. The expression levels of PI3K and AKT were measured by real-time quantitative polymerase chain reaction and Western blotting. Results Compared with the model group, MFJD treatment significantly improved left ventricular systolic function, reduced myocardial fibrosis, and restored cardiac morphology. Moreover, MFJD markedly increased the mRNA and protein levels of PI3K and AKT, suggesting activation of the PI3K-AKT pathway. Conclusion MFJD exerts cardioprotective effects against CHF by improving cardiac function and remodeling, possibly through activation of the PI3K-AKT signaling pathway.
Piezo1 is a mechanically-gated calcium channel. Recent studies have shown that Piezo1, a mechanically-gated calcium channel, can attenuate both psychosine- and lipopolysaccharide-induced demyelination. Because oligodendrocyte damage and demyelination occur in intracerebral hemorrhage, in this study, weinvestigated the role of Piezo1 in intracerebral hemorrhage. We established a mouse model of cerebral hemorrhage by injecting autologous blood into the right basal ganglia and found that Piezo1 was largely expressed soon (within 48 hours) after intracerebral hemorrhage, primarily in oligodendrocytes. Intraperitoneal injection of Dooku1 to inhibit Piezo1 resulted in marked alleviation of brain edema, myelin sheath loss, and degeneration in injured tissue, a substantial reduction in oligodendrocyte apoptosis, and a significant improvement in neurological function. In addition, we found that Dooku1-mediated Piezo1 suppression reduced intracellular endoplasmic reticulum stress and cell apoptosis through the PERK-ATF4-CHOP and inositol-requiring enzyme 1 signaling pathway. These findings suggest that Piezo1 is a potential therapeutic target for intracerebral hemorrhage, as its suppression reduces intracellular endoplasmic reticulum stress and cell apoptosis and protects the myelin sheath, thereby improving neuronal function after intracerebral hemorrhage.
副肿瘤综合征(PNS)是一类少见的免疫介导的肿瘤和神经系统间免疫反应所致临床综合征,特定的副肿瘤自身抗体可以辅助诊断.虽然只有不到1%的肿瘤患者会表现出PNS,但是正确识别PNS有助于早期诊断潜在肿瘤.抗Y染色体性别决定区相关高迁移率组盒蛋白1(SOX1)抗体由于其常与小细胞肺癌(SCLC)并存,近年被认为是PNS部分特征性抗细胞核抗体[1].肿瘤转移多发生于恶性肿瘤进展的晚期,然而临床中有时会首先发现侵袭性肿瘤的转移病灶,但原发病灶位置不明.原发灶不明肿瘤是一类转移性肿瘤的统称,该类肿瘤无法通过各项检查方法确定原发性肿瘤的位置,占所有恶性肿瘤的1%~3%[2].本例患者位于纵隔的肿瘤原发病灶不明,既往鲜见抗SOX1抗体合并纵隔肿瘤的报道[1].我们报道了一例罕见的继发于纵隔肿瘤的表现为慢性副肿瘤性小脑变性伴抗SOX1抗体阳性的患者.
目的 评价肥胖的4种指标与缺血性心脑血管病(ICCVD)风险关系.方法 从国家卒中防治工程委员会2014年度对我国31省整群抽样建立的“脑卒中筛查和干预项目”数据库中,筛选年龄≥60岁的老年人111472例,以是否发生ICCVD分为病例组17420例和对照组94052例,记录入选者体质量指数(BMI),腰围(WC),腰臀比(WHR),腰围身高比(WHtR)等,用BMI、WC、WHR、WHtR的现有标准评价肥胖,并比较4种指标评价肥胖与ICCVD风险关系,用非条件logistic回归模型和ROC曲线评价4种指标对中、高危ICCVD的风险效果.结果 病例组BMI、WC、WHR、WHtR高于对照组(P<0.05).在全因素校正logistic模型中,男女性超出正常体质量(18.50kg/m2≤BMI<24.00 kg/m2)时,ICCVD风险增加,但仅女性相关显著(P趋势<0.01);男性肥胖(WC≥85.00cm、WHR≥0.90、WHtR≥0.50),女性肥胖(WC≥80.00 cm、WHR≥0.85、WHtR≥0.50)时,ICCVD风险增高(P<0.01).男性WC≥89.00 cm、WHtR≥0.515,女性WC≥84.00 cm、WHtR≥0.535时,与ICCVD风险呈正相关(OR>1.0,P<0.05),趋势效应优于BMI、WHR.ROC曲线分析显示,WHtR预测中、高ICCVD风险时,男性和女性ROC曲线下面积分别为[0.629(95%CI:0.623~0.634)、0.637(95%CI:0.632~0.640)],且均优于另外3种指标.结论 WC和WHtR对老年人群中、高危ICCVD风险均具有较好的预测效果,其中WHtR更具优越性.
目的 探讨巴曲酶注射液联合依达拉奉对老年脑梗死患者神经功能缺损评分及血清同型半胱氨酸(Hcy)、血管内皮细胞生长因子(VEGF)、神经生长因子(NGF)、脑源性神经生长因子(BDNF)水平变化的影响.方法 选择2015年10月~2017年10月解放军171医院神经内科住院的初发老年脑梗死患者84例,根据随机数字表法分为对照组42例,依达拉奉组42例.常规治疗基础上对照组给予巴曲酶注射液,依达拉奉组在对照组基础上加用依达拉奉,均治疗14d.比较2组治疗前及疗程结束后日常生活活动能力(ADL)及美国国立卫生研究院卒中量表(NIHSS)评分、临床疗效、血清VEGF、Hcy、BDNF及NGF水平、不良反应.结果 依达拉奉组治疗后ADL评分较治疗前明显升高,NIHSS评分较治疗前明显降低(P<0.01).依达拉奉组治疗后ADL评分明显高于对照组,NIHSS评分明显低于对照组(P<0.01).依达拉奉组总有效率明显高于对照组(90.5% vs 71.4%,P<0.05).2组治疗后VEGF、BDNF及NGF水平明显高于治疗前,Hcy水平明显低于治疗前(P<0.01).依达拉奉组治疗后VEGF、BDNF及NGF水平明显高于对照组,Hcy水平明显低于对照组(P<0.01).结论 巴曲酶注射液联合依达拉奉治疗老年脑梗死,可促使患者神经功能及日常生活能力恢复,提高治疗效果.
Objective To study the relationship between white matter ischemic lesion (WMIL) severity and serum cystatin C (Cys-C) level in >85 years old patients.Methods One hundred and fifteen WMIL patients were divided into mild WMIL group (n=42),moderate WMIL group (n=42) and severe WMIL group (n =31).Their age,history of hypertension,DM,nephrosis,CHD,cronic bronchitis,hyperlipidaemia,lacuna stroke and serum levels of SCr,BUN,Cys-C,creatinine and urea were recorded.Relationship between WMIL severity and serum Cys-C level was analyzed by multivariate logistic regression analysis.Results The incidence of DM was significantly higher in moderate WMIL group and severe WMIL group than in mild WMIL group (P<0.05,P<0.01).The serum Cys-C level was significantly higher in severe WMIL group than in mild WMIL group and moderate WMIL group (1.7±1.8 mg/L vs 0.7±0.6 mg/L,1.7±1.8 mg/L vs 0.9±0.6 mg/L,P<0.05).Multivariate logistic regression analysis showed that serum Cys-C level was an independent risk factor for the WMIL severity after adjustment for age,history of hypertension and DM (OR =2.743,95 %CI:0.497-1.527,P =0.000).Spearman correlation analysis revealed that elevated serum Cys-C level was positively related with the WMIL severity (r=0.344,P=0.000).Conclusion Elevated serum Cys-C level is related with the WMIL severity in very old patients.
目的 探讨中国老老年原发性高血压患者24 h动态血压与脑小血管疾病(SVD)的关系.方法 选择原发性高血压患者106例,进行24 h动态血压监测.SVD包括腔隙性脑梗死(LI)和脑白质病变(WML).根据WML级别分为低级别WML组52例和高级别WML组54例.根据LI数目分为非LI组22例,单发LI组22例,多发LI组62例.根据血压类型分为杓型血压组10例,非杓型血压组96例.结果 与低级别WML组比较,高级别WML组夜间收缩压、昼间舒张压、夜间舒张压、24 h舒张压明显升高(P<0.05,P<0.01).多发LI组夜间收缩压、夜间舒张压较非LI组和单发LI组明显升高[(135.5±13.5)mm Hg vs (125.6±9.0)mm Hg,(129.1±19.6)mm Hg,(67.0±8.7)mm Hg vs (61.8±5.8)mm Hg,(59.9±7.9)mm Hg,1 mm Hg=0.133 kPa,P<0.05],夜间血压下降幅度较非LI组和单发LI组明显减小[(-3.8±6.9)%vs (3.1±6.5)%,(1.7±8.2)%,P<0.01].非杓型血压组多发LI发生率显著高于杓型血压组(62.5% vs 20.0%,P=0.024).结论 中国男性老老年原发性高血压患者异常的血压昼夜节律可能是SVD的一种危险因素.
目的 探讨老年(≥80岁)男性脑白质损伤(white matter lesins,WML)与血清胆红素水平的相关性.方法 严格按入组及排除标准,选择经头颅MRI证实的老年男性WML患者92例,依据年龄相关的脑白质视觉评定法(0~30分)对WML严重程度进行评估后,将患者分为WML轻度(1~4分)组和WMH中~重度(5~ 30分)组两组.着重分析血清总胆红素(TBIL)、直接胆红素(DBIL)、间接胆红素(IBIL)等临床资料,再根据总胆红素水平将患者分为高水平组(10.6 ~ 21.0 μmol/L)和低水平组(0~ 10.5 μmol/L),以评价两组WML的严重程度.结果 WML轻度组和WMH中~重度组患者的TBIL、DBIL、IBIL比较,差异均无统计学意义(P>0.05),胆红素高水平组和低水平组的WML评分差异也无统计学意义(P>0.05).结论 老年男性腔隙性脑梗死患者血清胆红素水平与WML不相关.
Dementia with Lewy bodies (DLB), also known as Lewy body dementia, is the second most commonly degenerative cause of dementia in the elderly. At present, there are few reports about DLB confirmed by autopsy in our country. The main clinical manifestations of the patient were progressive cognitive decline, intermittent mental and behavior disorder, visual hallucination, sensitive to antipsychotic drugs, and parkinsonism and/or autonomic nervous system dysfunctions along with the progress. Here we reported such 1 case. The results of autopsy pathology showed thatα-synuclein positive Lewy bodies existed extensively in the cytoplasm of cortical and subcortical neurons, which verified the clinical diagnosis before the patient’s death. We hope to enhance the recognition of the disease and facilitate its early diagnosis through studying this case.
目的 探讨高龄(≥80岁)男性患者腔隙性脑梗死(lacunar infarction,LI)与血清胆红素水平的相关性.方法 选择经头颅MRI证实的老年男性LI患者98例,根据病灶数目分为LI单发组36例和LI多发组62例.分析血清总胆红素、直接胆红素和间接胆红素等临床资料.再根据总胆红素水平分为高水平患者35例(10.6~21.0μmol/L)和低水平患者63例(0~10.5 pmol/L),评价LI的严重程度.结果 LI单发组与LI多发组总胆红素、直接胆红素和间接胆红素比较,差异无统计学意义(P>0.05),多因素logistic回归分析显示,危险因素与LI的发生无相关性(P>0.05).胆红素低水平患者与高水平患者的LI个数比较,差异无统计学意义[(5.3 vs 4.7)个,P>0.05],校正其他危险因素后,胆红素低水平与高水平LI个数比较,差异无统计学意义(OR=0.97,95%CI:0.90~1.06,P=0.50).结论 高龄男性胆红素水平与LI的严重程度无相关性.
Objective To observe the effects of duloxetine for treatment of pain in very old patients with Parkinson’s disease (PD). Methods Twenty very old patients with PD were treated with duloxetine 60 mg once daily for 12 weeks.The efficacy,tolerability and safety were evaluated.Results The pain and quality of life in patients with PD were improved.No worsening of movement function was observed.Conclusion Duloxetine is effective in the treatment of pain in patients with PD,and has good toleration.
Ionizing radiation (IR) is known to be a cause of telomere dysfunction in tumor cells; however, very few studies have investigated X-ray-related changes in telomere length and the telomerase activity in normal human cells, such as umbilical vein endothelial cells (HUVECs). The loss of a few hundred base pairs from a shortened telomere has been shown to be important with respect to cellular senescence, although it may not be detected according to traditional mean telomere length [assessed as the terminal restriction fragment (TRF)] analyses. In the present study, a continuous time window from irradiation was selected to examine changes in the telomere length, including the mean TRF length, percentage of the telomere length, telomerase activity, apoptotic rate, and survival rate in HUVECs from the first day to the fourth day after the administration of a 0.5-Gy dose of irradiation. The mean TRF length in the irradiated HUVECs showed shorter telomere length in first 3 days, but they were not statistically significant. On the other hand, according to the percentage analysis of the telomere length, a decreasing tendency was noted in the longer telomere lengths (9.4-4.4 kb), with a significant increase in the shortest telomeres (4.4-2.3 kb) among the irradiated cells versus the controls from the first day to the third after irradiation; no significant differences were noted on the fourth day. These results suggest that the shortest telomeres are sensitive to the late stage of radiation damage. The proliferation of irradiated cells was suppressed after IR in contrast to the non-irradiated cells. The apoptotic rate was elevated initially both in IR- and non-IR-cells, but that of IR-cells was maintained at an elevated level thereafter in contrast to that of non-IR-cells decreasing promptly. Therefore, a 0.5-Gy dose of IR induces persistent apoptosis leading to an apparent growth arrest of the normal HUVECs.
OBJECTIVE To study the correlation between lacunar cerebral infarction and level of serum uric acid in elderly male hypertension patients. METHODS Ninety-eight elderly male hypertension patients were enrolled in this study. They all underwent cerebral magnetic resonance imaging (MRI) scan, and their clinical and laboratory data were collected. The patients were divided into the 1st group (n = 32), the 2nd group (n = 32) and the 3rd group (n = 34) according to the level of serum uric acid. RESULTS The numbers of lacuner infarction, serum creatinine, urea and high density lipoprotein(HDL) were significantly diferrent from the other groups. The numbers of lacuner infarction were positively related with serum uric acid and urea. Multiple variant analysis showed that serum uric acid was the independent factor of the numbers of lacuner infarction. CONCLUSION The elevated level of serum uric acid may contribute to the risk factors of lacuner infarction.
BACKGROUNDS AND AIMS:Telomere attrition proceeds with the aging process, and is also associated with aging disease conditions, such as Alzheimer's disease (AD). The aging process also affects subtelomeric methylation status. In the present study, the telomere length and the subtelomeric methylation status in female AD patients were analyzed to see how AD affects telomere structure.METHODS:Terminal restriction fragment length of 23 AD patients' peripheral leukocytes was analyzed with methylation sensitive- and insensitive-isoschizomer by Southern blot.RESULTS:AD patients were found to have normal mean telomere lengths (controls; 6.4 ± 0.9 kb, AD; 6.1 ± 0.8 kb, p = 0.131), a proportionally decreased number of the longest telomeres (>9.4 kb) (controls; 30.3 ± 7.9%, AD; 24.4 ± 8.3%, p = 0.013), increased medium-sized telomeres (controls; 51.7 ± 3.3%, AD 55.5 ± 6.4%, p = 0.015) and unchanged numbers of the shortest telomeres (<4.4 kb) (controls; 18.0 ± 7.8, AD; 20.2 ± 8.9%, p = 0.371) in their peripheral leukocytes. The subtelomeres of telomeres in the shortest range (<4.4 kb) were more methylated in AD subjects than in controls (controls; 0.21 ± 0.23, AD; 0.41 ± 0.26, p = 0.016).CONCLUSIONS:These results may indicate that AD contributes to the loss of cells bearing the shortest telomeres, with hypomethylation of subtelomeres occurring in addition to telomere attrition, resulting in an apparent normal mean telomere length in AD patients. The relatively high subtelomeric methylation status of the shortest telomeres in peripheral blood leukocytes may be a characteristic of AD. This report demonstrates that the epigenetic status of the telomeric region is affected by disease conditions.
Although myasthenia gravis (MG) may begin at any age, it can be overlooked in elderly adults, and the diagnosis is often delayed in elderly adults. One reason is the tendency to attribute the symptoms to more common diagnoses such as cerebrovascular disease. This letter discusses an individual with recurrent dysarthria, dysphagia, and a choking cough after drinking in whom the diagnosis of MG was overlooked. An 84-year-old man presented to the local hospital with dysarthria, dysphagia, and a choking cough after drinking. Magnetic resonance imaging of the brain showed multiple infarctions but no acute ischemic change. He was diagnosed with a cerebral infarction, and therapy was administered. His symptoms were relieved but became worse 1 month later, at which point he was sent to the local hospital again; homologue therapy was applied but did not work, and he was sent to Chinese PLA General Hospital for further therapy. His medical history was relevant for hypertension, chronic hepatitis C, villiform tubular adenoma of the colon, mushroom type tubular adenocarcinoma of the colon, and epidermal cancer of the bladder and urinary tract. On physical examination, he had mild dysarthria and left ptosis (said to be due to surgery to remove a cataract) with mild abnormal up-and-down extraocular movements of the left eye but no apparent diplopia. There was slight facial weakness on the left side but normal jaw strength. Motor testing of the four limbs and trunk revealed normal strength for an elderly man who can walk independently with the help of a cane. Sensation to pin prick was normal. The deep tendon reflexes were normal (++) and symmetric. Babinski sign was positive bilaterally. Findings from the rest of the neurological examination were unremarkable. Standard biological data were unremarkable. Hypertension was well controlled, and thyroid levels were normal. Brain magnetic resonance imaging showed multiple infarctions. During his hospitalization, swallowing function rehabilitation exercise was performed, and the choking cough after drinking improved, but he developed fatigue of the masseter muscle. His son revealed the undulatory property of his dysarthria and that his left ptosis had existed before the surgery on his eye. His ptosis and dysarthria were generally better in the morning and worse in the afternoon. He was admitted to the hospital because of dysarthria and dysphagia, but magnetic resonance imaging of the brain showed no acute ischemic change, and the brain lesions could not explain his left ptosis (Figure 1). Thus, MG was suspected, and the diagnosis was eventually confirmed by decrement on 3-Hz bilateral facial repetitive nerve stimulation and no increment on 20-Hz bilateral facial repetitive nerve stimulation. A chest scan showed no evidence of a thymoma. He was started on oral pyridostigmine bromide therapy. Intravenous immunoglobulin therapy was refused because of economic burden. Prednisone was not given in consideration of his age and cancer history. Within 3 days of therapy, he reported improvement in the fatigue of the masseter muscle, but his ptosis had not resolved. He could chew peanuts, which had been too difficult for him before therapy. Myasthenia gravis in elderly adults has been increasing over the past few decades,1-7 but whether it is similar in China is not known, because no epidemiology data were available. This individual had only partial improvement with therapy, possibly because intravenous immunoglobulin or prednisone and other immunosuppressants were not used. It is not difficult to confirm the diagnosis, because there are many readily available diagnostic tests with high sensitivities and specificities (e.g., repetitive nerve stimulation, single-fiber electromyography, and antiacetylcholine receptor antibodies). However, it is easy to overlook the diagnosis of MG in elderly adults because the symptoms can be easily attributed to stroke, so a high index of suspicion for MG in elderly adults should be maintained. Moreover, once the diagnosis is made, a wide variety of effective therapeutic options is available, but because of complex comorbidities in elderly adults such as cancer and tuberculosis, prednisone and other immune suppressants should be used selectively. Conflict of Interest: The authors have no relevant financial interest in this letter. Author Contributions: Lei Jiang: planning, data collection, preparation of manuscript. Weiping Wu, Weiping Guan, Zhiping Wu, and Yonghui Nie: design, critical revisions. All authors read and approved the final manuscript. Sponsor's Role: There was no sponsor for this letter.
<正>颈动脉粥样硬化性狭窄的临床表现多种多样,可以表现为眼和脑的短暂性缺血发作,也可以表现为相应脑供血区的缺血性脑卒中。如果无脑卒中或短暂性脑缺血发作症状,则被称为无症状性颈动脉狭窄。近年来越来越多的资料表明,无症状性颈动
Objective To study the correlation of 24 h ambulatory blood pressure and nocturnal blood pressure drop magnitude with lacunar cerebral infarction in elderly male hypertensive patients.Methods Ninety-six elderly male hypertensive patients were enrolled in this study.They underwent cerebral MRI and 24 h ambulatory blood pressure monitoring,during which their clinical and laboratory data were collected.The patients were divided into non-single lacunar cerebral infarction group(n=25) and multiple lacunar cerebral infarction group(n=71)according to the number of lacunar cerebral infarctions.Results The nocturnal systolic pressure,nocturnal pressure drop magnitude,and incidence of non-dipping blood pressure were significantly higher in multiple lacunar infarction group than in non-single lacunar cerebral infarction group(P=0.01).Conclusion Nocturnal blood pressure and abnormal circadian rhythms may play an important role in the development of lacunar cerebral infarction in elderly hypertensive patients.
目的 探讨在老老年(≥80岁)原发性高血压患者中,动态血压状况与脑白质病变(WML)的相关性.方法 我们回顾性地选取了高血压患者共130例,均行头颅磁共振检查和动态血压监测,并同时收集患者的临床和实验室数据,并应用年龄相关的脑白质视觉评定法评分将患者分为三组:轻度WML,中度WML,重度WML.结果 在三组患者之间,夜间平均收缩压、夜间平均舒张压及夜间血压下降率的差异有统计学意义;并且与轻度WML组相比,中度WML和重度WML组患者非杓型血压的发生率显著升高.进一步的多因素logistic回归分析示,夜间舒张压升高和夜间血压下降率减小是WML的独立的危险因素.结论 在老老年原发性高血压患者中,夜间血压异常升高以及昼夜节律的异常在WML的进展中起重要作用.
<正>在老年人群中,糖尿病所致的中枢神经系统病变越来越引起人们关注。其中,糖尿病与认知功能障碍的关系,尚不十分明确。本文讨论了糖尿病性认知功能障碍的相关进展。1糖尿病性认知功能障碍的认识过程有关糖尿病和认知功能障碍相关性的研究,早在20世纪60年代就有学者进行了动物实验及人群临床观察的研究,提出并形成了"糖尿病脑病"的概念。糖尿病脑病是指糖尿病所致的慢性进展性认知功能障碍,其神经病理学本身并无特征性的改变。尸体解剖材料显示,仍以阿尔茨海默病为主,血管性痴呆为辅。糖尿病脑病患者的神经生理学和神经放射影像学特点与大脑老化十分相似,特别是海马神经元存在退行性变和代谢紊乱,提示糖尿病脑病是一个加速的脑老