Functional aspects of the brain lymphatic drainage system in aging and neurodegenerative diseases

The phenomenon of an aging population is advancing at a precipitous rate.Alzheimer's disease(AD)and Parkinson's disease(PD)are two of the most common age-associated neurodegenerative diseases,both of which are primarily characterized by the accumulation of toxic proteins and the progressive demise of neuronal structures.Recent discoveries about the brain lymphatic drainage system have precipitated a growing body of investigations substantiating its novel roles,including the clearance of macromolecular waste and the trafficking of immune cells.Notably,aquaporin 4-mediated glymphatic transport,crucial for maintaining neural homeostasis,becomes disrupted during the aging process and is further compromised in the pathogenesis of AD and PD.Functional meningeal lymphatic vessels,which facilitate the drainage of cerebrospinal fluid into the deep cervical lymph nodes,are integral in bridging the central nervous system with peripheral immune responses.Dysfunction in these meningeal lymphatic vessels exacerbates pathological trajectory of the age-related neurodegenerative disease.This review explores modulatory influence of the glymphatic system and meningeal lymphatic vessels on the aging brain and its associated neurodegenerative disorders.It also encapsulates the insights of potential mechanisms and prospects of the targeted non-pharmacological interventions.

Genetic Cell Therapy in Anti-Aging Regenerative Cosmetology

As post-WWII baby boomer approaching age 80, Anti-Aging Regenerative Cosmetology (AARC) has been developed and patented for beautifying and strengthening the human body using live cells;to enhance the appearance and function of various bodily parts to provide health and aestheticism of human being throughout life. It is a combined cosmetic and preventive medicine to intervene with and to correct the undesirable phenotypic expression of aging. The intrinsic properties of myoblasts and foreskin fibroblasts in development and regeneration are harnessed to formulate a genetic cell therapy program which is safe and efficacious as previously been tested in FDA Phase III clinical trials. Myoblasts are selected for strength development and foreskin fibroblasts for tenacity and smooth-to-the-touch. Both cell types are highly mitotic and non-carcinogenic. In additional to providing large quantities of nuclei as regenerative gene medicine, and of mitochondria as energy generators, myoblasts secret tumor necrosis factor alpha (TNF-α) for skin whitening and melanoma prevention. Myoblasts, because of their small size, spindle shape, and resilience, grow readily on collagen and laminin within wrinkles of skin surfaces, thus enhancing the color, luster, and texture of the skin “plated” with them. Alternatively, they can be injected subcutaneously as cell filler to reduce wrinkles. Intramuscular injection of myoblasts can augment the size, shape, consistency, tone, and strength of muscle groups, improving the lines, contours, and vitality to sculpt a youthful appearance. By improving cell genetics and organ functions, the program holds promise to sustain the human subject in good health and appearance, with a good quality of life and life prolongation.

Non-pharmacological cognitive intervention for aging and dementia:Current perspectives

In recent years, cognitive difficulties associated with normal aging and dementia have been receiving increased attention from both public and scientific communities. With an increase in overall lifespan, promoting healthy cognition has become a priority and a necessity for minimizing and preventing individual and societal burdens associated with cognitive dysfunctions in the elderly. The general awareness concerning the efficacy of preventive(e.g., lifestyles) and palliative treatment strategies of cognitive impairments, related to either healthy or unhealthy trajectories in cognitive aging, is continuously rising. There are several therapeutic strategies which can be broadly classified as either pharmacological or non-pharmacological/psychosocial. In face of the modest evidence for success of pharmacological treatments, especially for dementia related impairments, psychosocial interventions are progressively considered as a complementary treatment. Despite the relative spread of psychosocial interventions in clinical settings, research in this area is rather scarce with evidence for success of these therapies remaining controversial. In this work we provide an evidence based perspective on cognitive intervention(s) for healthy aging, pre-dementia(mild cognitive impairment), and dementia populations. Current evidence and future directions for improving cognitive functions in the elderly are discussed as well.

Aging men-Challenges ahead

The prolongation of life expectancy and the drastic reduction of fertility rate are the primary cause of an agingworld. It is projected that the elderly (above 65) will increase within the next 25 years by 82% , whereas the new bornonly by 3% . Despite the enormous medical progress during the past few decades, the last years of life are still accom-panied by increasing ill health and disability. The ability to maintain active and independent living for as long as possi-ble is a crucial factor for aging in health and dignity. Therefore, the promotion of healthy aging and the prevention ofdisability in men, must assume a central role in medical research and medical practice as well as in the formulation ofnational health and social policies. Effective programs promoting health and aging will ensure a more efficient use ofhealth and social services and improve the quality of life in older persons by enabling them to remain independent andproductive. The most important and drastic gender differences in aging are related to organs and or systems dependantor influenced by reproductive hormones. In distinction to the course of reproductive aging in women, with the rapid de-cline in sex hormones and expressed by the cessation of menses, aging men experience a slow and continuous decline ofhormones. This decline in endocrine function involves; A decrease of testosterone, dehydroepiandrosterone (DHEA),oestrogens, thyroid stimulating hormone (TSH), growth hormone (GH), insulin-like growth factor-1 (IGF-1), andmelatonin. This decrease is concomitant with an increase of LH and FSH. In addition sex hormone binding globulin's(SHBG) increase with age resulting in further lowering the concentrations of free biologically active androgens. Inter-ventions such as hormone replacement therapy may prevent, delay or alleviate the debilitating conditions which may re-sult from secondary partial endocrine deficiency. Primary and secondary preventive strategies such as the promotion of asafe environment, healthy lifestyle including proper nutrition, appropriate exercise, avoidance of smoking, avoidanceof drug and alcohol abuses, if done effectively, should result in a significant reduction of the health and social costs,reduce pain and suffering, increase the quality of life of the elderly and enable them to remain productive and contributeto the well-being of society. In light of this, public awareness of medical knowledge needs to be increased and basic,clinical, socio-economic and epidemiological research intensified. (Asian J Androl 2001 Sep; 3; 161 - 168)

Aging: A cell source limiting factor in tissue engineering

Tissue engineering has yet to reach its ideal goal,i.e.creating profitable off-theshelf tissues and organs,designing scaffolds and three-dimensional tissue architectures that can maintain the blood supply,proper biomaterial selection,and identifying the most efficient cell source for use in cell therapy and tissue engineering.These are still the major challenges in this field.Regarding the identification of the most appropriate cell source,aging as a factor that affects both somatic and stem cells and limits their function and applications is a preventable and,at least to some extents,a reversible phenomenon.Here,we reviewed different stem cell types,namely embryonic stem cells,adult stem cells,induced pluripotent stem cells,and genetically modified stem cells,as well as their sources,i.e.autologous,allogeneic,and xenogeneic sources.Afterward,we approached aging by discussing the functional decline of aged stem cells and different intrinsic and extrinsic factors that are involved in stem cell aging including replicative senescence and Hayflick limit,autophagy,epigenetic changes,miRNAs,mTOR and AMPK pathways,and the role of mitochondria in stem cell senescence.Finally,various interventions for rejuvenation and geroprotection of stem cells are discussed.These interventions can be applied in cell therapy and tissue engineering methods to conquer aging as a limiting factor,both in original cell source and in the in vitro proliferated cells.

Combination of ranibizumab with photodynamic therapy vs ranibizumab monotherapy in the treatment of age-related macular degeneration: a systematic review and meta-analysis of randomized controlled trials

AIM:To compare the efficacy and safety of combination of ranibizumab with photodynamic therapy(PDT)vs ranibizumab monotherapy in the treatment of age-related macular degeneration(AMD).METHODS:The Cochrane Central Register of Controlled Trials(CENTRAL)in the Cochrane Library,Pubmed,and Embase were searched.There were no language or data restrictions in the search for trials.Only randomized controlled trials(RCTs)were included.Methodological quality of the literatures was evaluated according to the Jadad Score.RevMan 5.2.6 software was used to do the meta-analysis.RESULTS:Seven studies were included in our systematic review,among which four of them were included in quantitative analysis.The result shows that the ranibizumab monotherapy group had a better mean best corrected visual acuity(BCVA)change vs baseline at month 12 compared with that of the combination treatment group,and the statistical difference was significant(WMD,-2.61;95%CI,-5.08 to-0.13;P=0.04).However,after the removal of one study,the difference between the two groups showed no significant difference(WMD,-2.29;95%CI,-4.81 to 0.23;P=0.07).Meanwhile,no significant central retinal thickness(CRT)reduction was found in the combination treatment group and the ranibizumab monotherapy group at 12 months follow-up.Nevertheless,the combination group tended to have a greater reduction in CRT(WMD,-4.13μm;95%CI,-25.88to 17.63,P=0.71).The proportion of patients gaining more than 3 lines at month 12 in the ranibizumab group was higher than in the combination group and there was a significant difference(RR,0.72;95%CI,0.54 to 0.95;P=0.02).Whereas there was no significant difference for the proportion of patients gaining more than 0 line at month12 between the two groups(RR,0.93;95%CI,0.76 to1.15;P=0.52).The general tendency shows a reduction in ranibizumab retreatment number in the combination treatment group compared with the ranibizumab monotherapy group.As major adverse events,the differences in the number of eye pain,endophthalmitis,hypertension and arterial thromboembolic events were not significant between the two groups,and the incidence of serious adverse events in the two groups was very low.CONCLUSION:For the maintenance of vision,the comparison of the combination of ranibizumab with PDT vs ranibizumab monotherapy shows no apparent difference.Compared with the combination of ranibizumab and PDT,patients treated with ranibizumab monothearpy may gain more visual acuity(VA)improvement.The combination treatment group had a tendency to reduce the number of ranibizumab retreatment.Both the two treatment strategies were well tolerated.

Temporal pattern of resolution/recurrence of choroidal neovascularization during bevacizumab therapy for wet age-related macular degeneration

AIMTo characterize temporal pattern of resolution and recurrence of naive choroidal neovascularization (CNV) secondary to wet age-related macular degeneration (AMD) treated with intravitreal bevacizumab on as needed regimen, and to analyze baseline risk factors for CNV resolution or recurrence.

Photodynamic Therapy for Age-related Macular Degeneration

Purpose: To evaluate short-term effects of single photodynamic therapy (PDT) for age-related macular degeneration (AMD) accompanied with choroidal neovascularization (CNV).Methods: We analyzed retrospectively the effects of single PDT for 20 patients (20 eyes) with CNV caused by AMD. Corrected visual acuity, fluorescein angiography (FA) and optic coherence tomography (OCT) were examined before and after PDT. All patients were followed up at least 3 months. Results: At the end of 3-month follow-up, 5 eyes had vision progress, 15 eyes had vision stable and no eye had vision deterioration. Fluorescein angiography one week post PDT showed cessation of fluorescein leakage in 8 eyes with predominant classic CNV, and reduction of fluorescein leakage in 12 eyes with minimal classic CNV or occult CNV without classic component. At the 3-month following PDT fluorescein angiography showed fluorescein leakage reappeared in 4 of 8 eyes with predominant classic CNV. Among 12 eyes with minimal classic CNV or occult CNV without classic component, 9 eyes showed decreased or unchanged fluorescein leakage, 3 eyes had a progression of fluorescein leakage. Optic coherence tomography showed obvious recovery of serous sensory retinal detachment after PDT. Conclusion: PDT may occlude or inhibit CNV caused by AMD in short term. No obvious side effects were noticed.

CLINICAL OBSERVATION OF THE EFFECT OF HEALTH-PRESERVING MOXIBUSTION ON DELAYING AGING

The present paper reports a clinical observation of the effect of health-preservingmoxibustion in the aged people without apparent organic diseases. Results show that the health-preserving moxibustion has an evident action in lessening aging symptoms and improving physio-logic functions of the senile body. It is held in traditional Chinese medicine that from the middle-aged period on, the decline of kidney Qi is an important cause of senility and deficiency of thespleen and blood stasis also play a role in some degree. Health-preserving moxibustion ofShenque and Zusanli has actions in warming Yang, reinforcing Qi and promoting blood circulationto remove obstruction in meridians. It is thus a method for self health protection.

Magnetic nanoparticles conjugated with “RPE cell-MCP-1 antibody-VEGF antibody” compounds for the targeted therapy of age-related macular degeneration: a hypothesis

Age-related macular degeneration（AMD） is the leading cause of vision loss in the elderly throughout the world. Treatment of AMD utilizing retinal pigment epithelium（RPE） transplantation represents a promising therapy. However, simplex RPE transplantation can only replace the diseased RPE cells, but has no abilities to stop the development of AMD. It has been indicated that oxidization triggers the development of AMD by inducing the dysfunction and degeneration of RPE cells, which results in the upregulation of local monocyte chemotactic protein-1（MCP-1） expression. MCP-1 induces macrophage recruiment which triggers local inflammation. As a result, the expression of vascular endothelial growth factor（VEGF） is upregulated by MCP-1mediated inflammation and results in the formation of choroidal neovascularization（CNV）. We accordingly propose a targeted therapy of AMD by subretinal transplanting the compound of RPE cell, MCP-1 antibody, and VEGF antibody and using a magnetic system to guide RPE cell compounds conjugated with superparamagnetic iron oxide nanoparticles（SPIONs）. Furthermore, SPION-labelled RPE cells can be tracked and detected in vivo by non-invasive magnetic resonance imaging（MRI）. This novel RPE cell transplantation methodology seems very promising to provide a new therapeutic approach for the treatment of AMD.

Low-fluence photodynamic therapy combinations in the treatment of exudative age-related macular degeneration

AIM:To compare the efficacy of low-fluence photodynamic therapy(PDT) combinations in the treatment of age-related macular degeneration(AMD).· METHODS:Forty-five previously untreated eyes of 45 patients with exudative AMD whose best-corrected visual acuity(BCVA) was ≥0.3(Snellen) were enrolled.15 patients in Group I underwent low-fluence PDT(25J/cm2-300mW/cm2-83sec) and intravitreal pegaptanib combination,15 patients in Group II underwent PDT(50J/cm2-600mW/cm2-83sec) and intravitreal pegaptanib combination while,15 patients in Group III underwent intravitreal pegaptanib monotherapy.Complete ophthalmologic examinations were performed in pre and post treatment visits,and the results were statistically analised.A clinical activity score(CAS) was calculated by using changes in lesion size,amount of hemorrhage,staining pattern in FA and OCT measurement of intra/subretinal fluid.≤3 logMAR lines of decrease in BCVA and decrease in CAS were considered as successful treatment.· RESULTS:The mean age of 19 female(42.2%) and 26 male(57.8%) patients was(72.82±8.02) years.Mean follow-up was(13.93±5.87) months.Lesion type was occult in 28 eyes(62.2%).Treatment success rates according to BCVA assessments were 86.7%,80%,60% and mean BCVA decrease were 0.3,1.0,2.2 logMAR lines in Group I,II and III,respectively(P >0.05).According to the changes in central macular thickness and CAS,no difference was found among the study groups(P =0.850 and P =0.811,respectively).Patients treated with combination regimens had lower intravitreal injection frequencies(P =0.015).· CONCLUSION:Combination regimen with intravitreal pegaptanib and low-fluence PDT seems to be safe and effective in stabilizing the clinical activity and BCVA in exudative AMD.·

Surgical salvage therapy of anal cancer

AIM:To evaluate the results of salvage resection in the management of persistent or locally recurrent anal canal cancer.METHODS: Details of all patients with anal canal cancer treated from 1978 to 1994 at Cancer Hospital of Chinese Academy of Medical Sciences (CAMS) were reviewed retrospectively.Sixteen patients who presented with persistent or locally recurrent anal canal cancer received salvage surgery. Before surgery all of the patients had received radiotherapy alone as their primary treatments.RESULTS:Of the 16 patients, 14 received salvage abdominoperineal resection (APR) and two had transanal local excision. There were no deaths attributable to operation.Delayed healing of the perineal wound occurred in eight patients. Complications unrelated to the perineal wound were found in five patients. The median follow-up time was 120 (range 5-245) months after salvage surgery. Nine patients died of disease progression, with a median survival time of 16 (range 5-27) months. Six patients had a long-term survival.CONCLUSION:Salvage resection after radiotherapy can yield a long-time survival in selected patients with anal canal cancer. However it offers little hope to patients with T4 and/or N2-3 tumors.

接纳承诺疗法对中青年肝癌介入治疗病人复发恐惧及自我感受负担的影响

目的:分析接纳承诺疗法对中青年肝癌介入治疗病人复发恐惧及自我感受负担的影响。方法:采用方便抽样法,选取2019年7月—2023年6月在郑州大学第一附属医院行肝癌介入治疗的124例中青年肝癌病人,随机分为对照组和观察组各62例。对照组给予常规护理,观察组给予接纳承诺疗法干预。采用癌症复发恐惧量表(FCRI)及自我感受负担量表(SPBS)比较两组病人复发恐惧及自我感受负担水平,并对比两组病人护理满意度。结果:干预6周后观察组FCRI、SPBS评分均低于对照组(P<0.05),观察组护理满意度高于对照组(P<0.05)。结论:接纳承诺疗法可以有效降低中青年肝癌介入治疗病人复发恐惧感,减轻病人自我感受负担,并提高病人护理满意度。

The Therapeutic Effects of the Radiotherapy Plus TCM Treatment Observed in Senile Non-Parvicellular Lung Cancer Patients at the Late Stage

47 senile non-parvicellular lung cancer patients at stage Ⅲ or Ⅳ were randomly divided into a treatment group (26 cases) treated by radiotherapy plus traditional Chinese medicine (TCM) and a control group (21 cases) treated only by radiotherapy for observation of the therapeutic effects.

Effects of Physical Exercise and Music Therapy on Cognitive Aspects in Tunisian Patients with Mild Alzheimer’s Type Dementia

Aim: The objective of this research is to highlight the effectiveness of physical exercise and music therapy in older patients with Alzheimer’s disease (AD). Methods: Patients with a mild level of AD were included in this study, divided into the therapy group (TG;N = 30, aged 68 ± 3.2 years) and the control group (CG;N=30, aged 65 ± 2.6 years). The therapy group was enrolled in an exercise-training program (walking, resistance and balance exercises) combined with musical therapy for 10 weeks (three sessions of 60 minutes per week). The Control group was instructed to follow their daily rhythm of life (e.g., rest, reading) under the same conditions. The intervention program was enrolled under the supervision of;one psychologist;a neurologist;two music therapists, and two physiotherapists, all belonging to the same hospital unit. After 10 weeks of participation in the combined program, cognitive parameters were improved in the therapy group measured with the Behavior Pathology in Alzheimer Disease (BEHAVE-AD), (p < 0.05) for activity disturbance, diurnal rhythm disturbances, anxieties and phobias, affective disturbance. The percentage range of improvements is 1.07% to 2.96%. Results: Our results demonstrate that physical exercise combined with music therapy improves cognitive function in patients with Alzheimer’s disease. Conclusions: Physical exercise and music therapy are beneficial combined treatments for improving life quality in older patients. This approach may be useful to help patients with a mild level of Alzheimer’s disease improve their behavioral and psychological parameters.

临床医生应重视老年人心脏淀粉样变的诊断与处理

心脏淀粉样变(CA)是淀粉样蛋白错误折叠沉积于心肌细胞外基质所致的心脏疾病。CA好发于老年人,由于症状缺乏特异性且既往被认为是一种罕见病,老年CA患者极易被误诊和漏诊。近年来随着对该病诊断意识的提高及无创性影像学诊断方法的进步,诊断为CA的患者有所增加;治疗CA的药物研究也有重大突破,研发了多种特异性治疗药物。早期治疗可以防止淀粉样蛋白进一步沉积导致的器官损伤,从而改善老年CA患者预后。因此,临床医生应该充分了解老年CA患者的临床特征,重视老年CA的诊断及治疗。

《中国老年代谢综合征药物治疗专家共识(2022)》解读

老年代谢综合征是一组复杂的代谢紊乱症候群,其作为一种共病发病率高,临床表现多样,机制复杂且涉及联合用药,发生药物不良反应的风险高。老年代谢综合征严重损害老年人的生活质量和健康,给我国医疗系统及社会造成沉重的负担。《中国老年代谢综合征药物治疗专家共识(2022)》全面梳理和总结了老年代谢综合征的诊断标准和治疗目标、最新治疗药物及其相互作用,并做出10条推荐意见。该文就共识要点特别是药物治疗方面进行解读,以期为老年代谢综合征药物治疗决策与健康管理提供相关参考。

血清Cx43、Gal-9水平对老年急性脑梗死患者超早期静脉溶栓治疗预后的评估价值

目的探讨血清间隙连接蛋白43(Cx43)、半乳糖凝集素-9(Gal-9)水平对老年急性脑梗死(ACI)患者超早期静脉溶栓治疗预后的评估价值。方法选取2020年9月至2022年9月在该院行超早期静脉溶栓治疗的106例老年ACI患者作为研究组,另外选取同期来该院体检的100例体检健康者作为健康组。采用酶联免疫吸附试验(ELISA)检测所有研究对象的血清Cx43、Gal-9水平。治疗2周后参考美国国立卫生院卒中量表(NIHSS)评分将106例老年ACI患者分为预后良好组(81例)与预后不良组(25例)。采用受试者工作特征(ROC)曲线分析血清Cx43、Gal-9水平对老年ACI患者超早期静脉溶栓治疗预后的评估价值,采用多因素Logistic回归分析探讨老年ACI患者超早期静脉溶栓治疗预后不良的影响因素。结果研究组血清Cx43、Gal-9水平高于健康组(P<0.05);预后不良组血清Cx43、Gal-9水平高于预后良好组(P<0.05);血清Cx43、Gal-9预测老年ACI患者预后不良的曲线下面积(AUC)分别为0.721(95%CI:0.673~0.758)、0.837(95%CI:0.787~0.886),二者联合预测的AUC为0.901(95%CI:0.857~0.946)。预后不良组高血压占比高于预后良好组(P<0.05);多因素Logistic回归分析显示,高血压(OR=3.487,95%CI:1.564~7.773),血清Cx43≥106.53 pg/mL(OR=4.586,95%CI:1.982~10.611),血清Gal-9≥11.84 ng/mL(OR=4.345,95%CI:1.957~9.648)是老年ACI患者超早期静脉溶栓治疗预后不良的危险因素(P<0.05)。结论血清Cx43、Gal-9在老年ACI患者中均呈高表达,可用于评估老年ACI患者超早期静脉溶栓治疗的预后,二者联合检测的评估价值更高。

非剥脱点阵激光联合透明质酸钠复合溶液注射治疗颈部老化疗效观察

目的:观察非剥脱点阵激光联合透明质酸钠复合溶液注射治疗颈部老化的临床疗效。方法:选取2020年7月-2022年7月于笔者医院就诊的30例颈部老化女性就医者,按随机数字表法分为对照组和联合组各15例。对照组给予1 565 nm M22-ResurFx非剥脱点阵激光治疗;联合组给予1 565 nm M22-ResurFx非剥脱点阵激光联合透明质酸钠复合溶液注射治疗。对照组激光治疗3次;联合组激光及透明质酸钠复合溶液联合治疗3次,收集每次治疗前、后照片,评估治疗前、后就医者颈部老化的改善程度和治疗后不良反应。结果:联合组改善率为66.67%,明显高于对照组的20.00%(P<0.05);联合组就医者满意率为80.00%,高于对照组的53.33%;联合组颈部老化分级明显优于对照组(P<0.05)。激光治疗后治疗区域均即刻出现红斑及风团,3~5 d消退,无结痂及出血发生。两组均未有其他严重不良反应发生。结论:非剥脱点阵激光联合透明质酸钠复合溶液注射治疗颈部老化疗效好,患者满意度高,值得临床推广应用。

沙盘游戏联合药物干预对学龄期ADHD患儿负性情绪及行为管理能力的影响

目的研究沙盘游戏疗法联合药物干预对学龄期注意缺陷多动障碍(ADHD)患儿负性情绪及行为管理能力的影响。方法选取2019年6月至2022年1月于本院治疗的120例ADHD患儿为研究对象,将其随机分为观察组和对照组,每组60例。对照组给予药物治疗,观察组在对照组的基础上进行沙盘游戏干预。分别于干预前后比较2组患儿症状积分[中文版注意缺陷多动障碍筛查量表(SNAP-IV)父母版]、情绪状态[儿童焦虑性情绪障碍筛查表(SCARED)和儿童抑郁障碍自评量表(DSRSC)]和行为管理能力。结果干预后,观察组对抗性行为、多动-冲动、注意力不集中症状积分和SCARED得分、DSRSC得分均明显低于对照组(P<0.05),注意力商数、控制力商数、综合控制力商数和综合注意力商数明显高于对照组(P<0.05)。结论沙盘游戏疗法联合药物干预可有效改善学龄期ADHD患儿各项临床症状,缓解患儿焦虑、抑郁等不良情绪,提高患儿行为管理能力。