辛伐他汀和替米沙坦对大鼠视网膜衰老的延缓作用及其机制

背景他汀类药物具有显著的降脂、抗氧化、抗炎及调节血管内皮细胞功能等作用，而沙坦类药物能促进细胞因子的表达和调控细胞的生长。鉴于他汀类和沙坦类作用机制和药效的多效性，推测其对预防视网膜衰老具有一定的作用。目的研究辛伐他汀和替米沙坦对大鼠视网膜自然衰老的预防作用。方法选择3月龄健康无眼疾sD大鼠66只，其中6只为青年组，其他大鼠常规饲养至9月龄后按随机数字表法将大鼠随机分为辛伐他汀组、替米沙坦组和对照组，每组各20只。辛伐他汀组和替米沙坦组大鼠分别用5mg／（kg·d）辛伐他汀和8mg／（kg·d）替米沙坦灌胃，对照组大鼠用等容量生理盐水灌胃，3个组大鼠均饲养至17月龄，将存活的辛伐他汀组12只、替米沙坦组10只和对照组8只大鼠经心脏灌注质量分数4％多聚甲醛溶液后摘取右侧眼球制备眼组织切片；青年组大鼠于5月龄时以同样方法获取眼组织切片。采用苏木精-伊红染色法检查各组大鼠视网膜厚度；采用免疫荧光染色技术检测视网膜神经节细胞（RGCs）标志物Thy-1、双极细胞标志物蛋白激酶C-“（PKC—a）、视锥细胞标志物opsin和视杆细胞标志物rhodopsin的表达，分别评估视网膜各级神经元的形态和视网膜各层的厚度。结果视网膜病理组织学检查显示，青年组大鼠视网膜结构清晰，细胞排列整齐；辛伐他汀组和替米沙坦组大鼠RGCs排列紊乱，细胞形态不规则；对照组大鼠视网膜感光细胞层内节（Is）、外节（0s）结构及RGCs排列紊乱。与青年组相比，辛伐他汀组、替米沙坦组和对照组大鼠视网膜总厚度及外核层（ONL）、外丛状层（OPL）、内核层（INL）、内丛状层（IPL）厚度均不同程度变薄，而感光细胞层厚度增加，差异均有统计学意义（均P〈0．01）。Thy-1免疫荧光染色显示，与青年组相比，辛伐他汀组、替米沙坦组和对照组大鼠RGCs数量均减少，但辛伐他汀组大鼠RGCs数量较对照组增多，差异均有统计学意义（均P〈0．01）。PKC-a荧光染色显示，辛伐他汀组、替米沙坦组和对照组轴突终扣密度均较青年组减少，辛伐他汀组大鼠双极细胞密度高于青年组和对照组，轴突终扣密度较对照组减少，差异均有统计学意义（均P=0．000）。Opsin和rhodopsin荧光染色显示，辛伐他汀组、替米沙坦组和对照组大鼠视网膜0s厚度较青年组增加，替米沙坦组大鼠0s厚度较对照组下降，差异均有统计学意义（均P〈0．01）。结论随年龄增加，sD大鼠视网膜各层结构变薄，RGCs数量减少，双极细胞密度虽无明显变化，但突触联系减少，且视细胞0s层增厚。辛伐他汀可使RGCs数量和双极细胞密度增加，而替米沙坦可使增厚的视细胞OS层变薄，从而延缓视网膜的衰老。

年龄相关性白内障患者睑板腺与眼表状况分析

背景睑板腺是位于上下睑板内一种特殊分化的皮脂腺，其形态学和功能学的严重改变与多种眼表疾病有关，研究睑板腺形态学和功能变化与干眼的关系具有重要的临床意义。目的观察年龄相关性白内障患者的睑板腺形态、结构及功能变化，探讨衰老与睑板腺功能障碍（MGD）及眼表健康状态的关系。方法采用系列病例观察研究方法，选取2016年3—9月在山西省眼科医院就诊的45岁以上年龄相关性白内障患者93例93眼作为研究对象，按照年龄将患者分为45—59岁组和≥60岁组；按照睑板腺缺失范围将受检眼分为睑板腺缺失范围≥1／3组和睑板腺缺失范围〈1／3组。采用裂隙灯显微镜检查眼表组织、睑缘形态、睑板腺开口形态和睑脂性状；采用眼表疾病指数（OSDI）量表问卷对眼表症状进行调查和评分；采用眼表综合分析仪测定受检眼泪膜破裂时间（BUT）、泪河高度、睑板腺缺失、结膜充血及角膜荧光素染色情况。结果93例受检者均无干眼主观症状，OSDI问卷评分均〈12分。裂隙灯显微镜检查受检眼均未发现睑缘及皮肤黏膜交界线的形态学变化，无睑板腺开口、睑脂排出及睑脂性状的异常。眼表综合分析仪检查发现，42眼BUT缩短，占45．16％；52眼泪河高度下降，占55．91％；58眼睑板腺缺失范围≥1／3，占62．27％。45-59岁组受检眼睑板腺缺失评分为1．65±0．79，≥60岁组为1．86±0．72，差异无统计学意义（t=1．301，P=0．197）。但相关分析示年龄与睑板腺缺失评分呈弱正相关（rs=0．323，P=0．002），与BUT及泪河高度均无明显相关性（0=0．154，P=0．141；rs=-0．024，P=0．821）；睑板腺缺失评分与BUT呈负相关（rs=-0．251，P=0．015），睑板腺缺失范围≥1／3组BUT异常的发生眼数明显多于缺失范围〈1／3组，差异有统计学意义（P=0．018）。结论中老年人随着年龄的增长，睑板腺缺失逐渐加重；睑板腺缺失范围较大者发生泪膜不稳定的风险增加；早期MGD患者体征先于症状出现，临床工作中应重视无症状的MGD患者。

Effects of Water Deficit and Increased Nitrogen Application in the Late Growth Stage on Physiological Characters of Anti-aging of Leaves in Different Hybrid Rice Varieties

[Objective] This study aimed to explore the effects of water and fertilizer regulation on the function of leaves in the filling stage. [Method] Six hybrid rice vari- eties including prematurely aged types and non-prematurely aged ones were selected as experimental materials. Limiting water treatment （with soil water potential of about -25 kpa） and increasing nitrogen treatment （additional 10% of granular nitrogen fertiliz- er in addition to limiting water treatment） were applied after heading to analyse the rates of aging and physiological responses of anti-aging in different hybrid rice vari- eties under water deficit and increased nitrogen conditions taking regular water and fertilizer as control. [Result] The results showed that water deficit accelerated the leaf senescence, and prematurely aged types-＇Zhongyou838＇, ＇Tianyou998＇ and ＇Long- ping601 ＇-were more markedly affected by water deficit, of which the rates of chloro- phyll degradation were 6%-8% higher compared to that in another three hybrids. In- creasing nitrogen treatment raised chlorophyll content and slowed down its degrada- tion. Water deficit caused the increase of abscisic acid （ABA） content to obviously varying degrees in leaves of six hybried rice varieties. Responses of ABA content in six hybried rice varieties to increased nitrogen fertilizer were not consistent. Except in ＇Zhongyou838＇, ABA content in the other five hybrids had varying degrees of in- crease. The responses of the activity of antioxidant enzymes in different hybried rice varieties were inconsistent. In response to increased nitrogen fertilizer in combination with water deficit, the activity of each antioxidant enzyme changed differently. Water deficit enhanced the accumulation of malondialdehyde （MDA） in leaves of each hybrid rice. The correlation analysis showed that chlorophyll content was extremely signifi- cantly positively correlated to the resistance of each antioxidant enzyme; SOD activity in leaves also positively related to ABA content. [Conclusion] The rate of leaf aging, physiological activity of anti-aging, and response to water deficit varied in different hy- bried rice varieties. The activity of antioxidant enzymes were not all induced to improve by ABA. SOD activity can be an indicator of resistance to stress. Increasing nitrogen ap- plication significantly postponed leave senescence in the late growth stage of rice.

Isolation and physiological characteristics of a premature senescence mutant in rice(Oryza sativa L.)

A rice pse（t） （premature senescence, tentatively） mutant line, was isolated from 4500 independent T-DNA inserted transgenic lines. The symptoms of premature senescence appeared more severely than those of the control plants （Zhonghua 11, japonica） at the last development stage. To characterize the mutant and provide basic information on the candidate genes by mapping to a physical region of 220-kb, experiments were carried out in two phytotrons under controlled temperature of 24 ℃ and 28 ℃, respectively. The content of chlorophyll, soluble protein and MDA （malondialdehyde）, net photosynthesis, the antioxidant enzyme activities of SOD （superoxide dismuase） （EC 1.15.1.1 ） and POD （peroxidase） （EC 1.11.1.7） and the peptidase activities of leaves were measured from top to bottom according to the leaf positions at the flowering stage. Compared with the control plant, the mutant showed the following characteristics： （1） Higher net photosynthesis rate （Pn） appeared in the 1st and 2nd leaves, contents of chlorophyll and soluble protein were also higher in the 1st leaf; （2） The activities of SOD, POD and peptidase were higher according to the leaf position from top to bottom; （3） The symptom of premature senescence was accelerated in the mutant at 28 ℃ treatment. The MDA content and the SOD and POD activities between the 24 ℃ and 28 ℃ treatment mutants were not significantly different. Content of chlorophyll and soluble protein of leaves mutant decreased rapidly at 28 ℃ treatment. The results show thatpse（t） is sensitive to high temperature. The probable function of PSE（T） is discussed.

Geriatric assessment for oncologists

The world is experiencing aging of its population. Age-specific incidence rates of cancer are higher and cancer is now recognized as a part of aging. Treating older patients can be challenging. The clinical behavior of some tumors changes with age and the aging process itself brings physiological changes leading to decline in the function of organs. It is essential to identify those patients with longer life expectancy, potentially more likely to benefit from aggressive treatment vs. those that are more vulnerable to adverse outcomes. A primary determination when considering therapy for an older cancer patient is a patient's physiologic, rather than chronologic age. In order to differentiate amongst patients of the same age, it is useful to determine if a patient is fit or frail. Frail older adults have multiple chronic conditions and difficulties maintaining independence. They may be more vulnerable to therapy toxicities, and may not have substantial lasting benefits from therapy. Geriatric assessment(GA) may be used as a tool to determine reversible deficits and devise treatment strategies to mitigate such deficits. GA is also used in treatment decision making by clinicians, helping to risk stratify patients prior to potentially high-risk therapy. An important practical aspect of GA is the feasibility of incorporating it into a busy oncology practice. Key considerations in performing the GA include: available resources, patient population, GA tools to use, and who will be responsible for using the GA results and develop care plans. Challenges in implementing GA in clinical practice will be discussed.

Determinants of uterine aging:lessons from rodent models

The uterus is an indispensable organ for the development of a new life in eutherian mammals.The female mammalian reproductive capacity diminishes with age.In this respect,the senescence of uterine endometrium is convinced to contribute to this failure.This review focuses on the physiological function of the uterus and the related influence of aging mainly in rodent models.A better understanding of the underlying mechanisms governing the process of uterine aging is hoped to generate new strategies to prolong the reproductive lifespan in humans.