Novel treatments and genetics of age-related macular degeneration-a narrative review

Age-related macular degeneration(AMD)remains a leading cause of severe visual impairment in developing countries.Although dry-type AMD and geographic atrophy(GA)are progressive conditions with the associated decrease of visual functions,no well-established treatment regimen was proposed for the disease.Wet-type AMD is effectively treated with intravitreal anti-angiogenic agents,but frequent injections are a major issue for the affected patients.Recent advances in AMD genetics have provided new insights into the pathogenesis and novel therapeutic targets of AMD,but the benefits of using genetic testing and genotype-based risk models for AMD development and progression still lacks evidence.Novel AMD treatments aim to increase the interval among intravitreal injections through new therapeutic agents and modern delivery devices.Simultaneously,gene therapy for dry and wet AMD is widely studied.Although gene therapy possesses a major superiority over other novel treatments regarding a persistent cure of disease,many challenges exist in the way of its broad impact on the ocular health of AMD patients.

Local immunotherapy with interleukin - 2 delivered from biodegradable polymer microspheres combined with interstitial chemotherapy: a novel treatment for experimental malignant glioma.

OBJECTIVE:Local delivery of carmustine(BCNU)from biodegradablepolymers prolongs survival against experi-mental brain tumors.Moreover,paracrine administration of interleukin-2(IL-2)has been shown to elicit apotent antitumor immune response and to improve survival in animal brain tumor models.We report the use of anovel polymeric microsphere delivery vehicle to release IL-2.We demonstrate both in vitro release of cytokinefrom the microspheres and histological evidence of the inflammatory response elicited by IL-2 released from themicrospheres in the rat brain.Thees microspheres are used to deliver IL-2,and biodegradable polymer wafers

The Influence of Integrated Chinese and Western Medicine Treatment on the Quality of Life and Laboratory Indicators of Patients with Novel Coronavirus Pneumonia

Objective: To investigate the influence of integrated Chinese and Western medicine treatment on the quality of life and laboratory indicators of patients with novel coronavirus pneumonia (COVID-19). Methods: A prospective, self-controlled study was conducted to analyze the changes in corresponding laboratory indicators and quality of life in 75 confirmed COVID-19 patients treated with integrated Chinese and Western medicine in our hospital during the early stage, middle stage, recovery period, and two weeks after discharge. The effectiveness and safety of the treatment regimen were evaluated in conjunction with the time for 2019-nCoV nucleic acid conversion, disease progression, and adverse reactions. Results: The PLT levels in the initial stage were significantly lower than those in the recovery period in 75 patients. The CRP levels in the initial stage were significantly lower than those after discharge for 2 weeks. The TBIL, IBTL, and DHIL levels in the initial stage were significantly lower than those in the middle stage. The K+ levels in the initial stage were significantly lower than those in the recovery period and after discharge for 2 weeks. The LYMGH levels in the initial stage were significantly lower than those in the recovery period and after discharge for 2 weeks. The TP and ALB levels in the initial stage were higher than those in the middle stage and the recovery period. The LDH levels, scores of daily activity limitation, scores of respiratory distress symptoms, scores of psychological emotions, CT imaging scores, and positive rate of nucleic acid were significantly lower than those in the recovery period and after discharge for 2 weeks. The AG, CK, CK-MB, and α-HBDH levels in the initial stage were significantly higher than those in the recovery period. However, the AMY level in the initial stage was significantly lower than that in the recovery period and after discharge for 2 weeks (p Conclusion: Integrated Chinese and Western medicine treatment has a significant impact on laboratory indicators such as PLT, LYMGH, CRP, TBIL, IBTL, DHIL, TP, ALB, K+, AG, LDH, CK, CK-MB, α-HBDH, AMY, CT imaging, and 2019-nCoV nucleic acid in COVID-19 patients. It has good clinical efficacy and safety, and can improve the quality of life of patients.

Glyco-sphingo biology: a novel perspective for potential new treatments in Huntington's disease

Huntington＇s disease （HD） is the most common dominantly inherited neurodegenerative disorder, mainly characterized by the progressive striatal and cortical neurodegeneration and as- sociated motor, cognitive and behavioural disturbances （Zuccato et al., 2010）. The disease-causing mutation is an expansion of a GAG trinucleotide repeat （〉 36 repeats） encoding a polygluta- mine stretch in the N-terminal region ofhuntingtin （Htt） （Zuc- cato et al., 2010）, a ubiquitous protein whose function is still unclear （Zuccato et al., 2010）. Expansion of the polyQ stretch endows mutant Htt （mHtt） with toxic properties, and results in the development of a broad array of undesirable effects in both neuronal and non-neuronal cells （Zuccato et al., 2010）. Among all cellular dysfunctions and biochemical imbalances classically associated with HD, perturbed metabolism of （glyco） sphingolipids appears to play a crucial role in the pathogenesis of the disease. Over the last years, we and other have extensively contributed to these findings （Desplats et al., 2007;

Interferon beta(IFN-β) treatment exerts potential neuroprotective effects through neurotrophic factors and novel neurotensin/neurotensin high affinity receptor 1 pathway

Multiple sclerosis（MS）is a chronic autoimmune disease of the central nervous system（CNS）characterized by coexisting processes of inflammation,demyelination,axonal neurodegeneration,and gliosis.It is the most common disabling neurological disease in young adulthood.

精神分裂症的药物治疗进展

精神分裂症是导致严重精神残疾的重性疾病之一,给社会、患者及其家属带来了重大负担。随着科技进步,不仅传统药物有了新的用法,而且新型药物的涌现也提供了更个体化和有效的治疗选择,如占诺美林-曲司氯铵(xanomeline-trospium,KarXT)、Emraclidine和微量胺相关受体1(trace-amine-associated receptor 1,TAAR1)调节剂等。本文将深入研究这些药物的临床应用疗效及治疗机制,以及新药物引入也带来治疗领域的挑战,如药物的停药时间、不良反应和药物预测动物模型的建立等,并在最后提出这些挑战并展望未来研究方向。本文旨在探讨精神分裂症药物治疗方面的最新进展,为研究者和临床医生提供最新的参考。

Treatment repurposing for inflammatory bowel disease using literature-related discovery and innovation

Inflammatory bowel disease(IBD)incidence has been increasing steadily,most dramatically in the Western developed countries.Treatment often includes lifelong immunosuppressive therapy and surgery.There is a critical need to reduce the burden of IBD and to discover medical therapies with better efficacy and fewer potential side-effects.Repurposing of treatments originally studied in other diseases with similar pathogenesis is less costly and time intensive than de novo drug discovery.This study used a treatment repurposing methodology,the literature-related discovery and innovation(LRDI)text mining system,to identify potential treatments(developed for non-IBD diseases)with sufficient promise for extrapolation to treatment of IBD.By searching for desirable patterns of twenty key biomarkers relevant to IBD(e.g.,inflammation,reactive oxygen species,autophagy,barrier function),the LRDI-based query retrieved approximately 9500 records from Medline.The most recent 350 records were further analyzed for proof-of-concept.Approximately 18%(64/350)met the criteria for discovery(not previously studied in IBD human or animal models)and relevance for application to IBD treatment.Many of the treatments were compounds derived from herbal remedies,and the majority of treatments were being studied in cancer,diabetes,and central nervous system disease,such as depression and dementia.As further validation of the search strategy,the query identified ten treatments that have just recently begun testing in IBD models in the last three years.Literature-related discovery and innovation text mining contains a unique search strategy with tremendous potential to identify treatments for repurposing.A more comprehensive query with additional key biomarkers would have retrieved many thousands more records,further increasing the yield of IBD treatment repurposing discovery.

Cronkhite-Canada综合征合并无症状新型冠状病毒感染一例

本文报道Cronkhite⁃Canada综合征合并无症状新型冠状病毒感染1例。该患者临床表现为食欲减退,毛发及指甲脱落,皮肤色素沉着。内镜检查见胃、十二指肠及结肠黏膜呈弥漫性、大小不一、密集分布的息肉样改变。病程中检出新型冠状病毒核酸阳性。经中等剂量泼尼松治疗后,患者毛发恢复生长,皮肤色素沉着减退。本文总结该患者的诊疗经过并结合文献复习,以期提升临床医生对该病的认知。

Biotoxicity dynamic change and key toxic organics identification of coal chemical wastewater along a novel full-scale treatment process

It is particularly important to comprehensively assess the biotoxicity variation of industrial wastewater along the treatment process for ensuring the water environment security.However,intensive studies on the biotoxicity reduction of industrial wastewater are still limited.In this study,the toxic organics removal and biotoxicity reduction of coal chemical wastewater(CCW)along a novel full-scale treatment process based on the pretreatment process-anaerobic process-biological enhanced(BE)process-anoxic/oxic(A/O)process-advanced treatment process was evaluated.This process performed great removal efficiency of COD,total phenol,NH_(4)^(+)-N and total nitrogen.And the biotoxicity variation along the treatment units was analyzed from the perspective of acute biotoxicity,genotixicity and oxidative damage.The results indicated that the effluent of pretreatment process presented relatively high acute biotoxicity to Tetrahymena thermophila.But the acute biotoxicity was significantly reduced in BE-A/O process.And the genotoxicity and oxidative damage to Tetrahymena thermophila were significantly decreased after advanced treatment.The polar organics in CCW were identified as the main biotoxicity contributors.Phenols were positively correlated with acute biotoxicity,while the nitrogenous heterocyclic compounds and polycyclic aromatic hydrocarbons were positively correlated with genotoxicity.Although the biotoxicity was effectively reduced in the novel full-scale treatment process,the effluent still performed potential biotoxicity,which need to be further explored in order to reduce environmental risk.

咖啡渣在纺织领域的研究现状

生物质能是环境友好型能源,具有低成本、易获得、无污染等优点。咖啡渣作为生物质能中的食品废弃物类,因其含有咖啡因、油脂、蛋白质等有效成分以及单宁酸、咖啡酸等多酚类物质,可广泛应用于农业、食品、环境、医药、纺织等领域,制得的产品具有成本低廉、绿色环保等优点并展现出优良特性。概述近年来咖啡渣用于纺织领域中染色、印染废水处理以及新型纤维开发3个方面的研究情况。从基本应用性能(染色、吸附性能等)、附加性能(抗氧化、抗紫外线、抗菌性能等)以及处理中能源耗用情况、处理后二次废弃物处理情况等方面,分析当前咖啡渣材料用于纺织领域的发展现状及存在的问题,并对其发展前景进行展望。

科马克·麦卡锡小说的暴力审美与治疗

科马克·麦卡锡的小说浓墨重彩地书写暴力,但麦卡锡并非暴力展示狂。麦卡锡的小说不仅书写自然暴力、动物暴力,还书写人类对自然的暴力与人类世界中的暴力。麦卡锡以极具美学张力的手法书写自然暴力,展现自然之美与崇高,书写人类暴力,揭示人类暴力对自然崇高与美的侵蚀,以及人类暴力带来的灾难与死亡的悲剧性后果。麦卡锡在小说中通过书写自然暴力展现自然之美与崇高,唤起人类对自然与生命的敬畏之情,消解人类中心主义的自大与傲慢;通过呈现人类暴力给自然和人类带来的灾难与死亡,警示人类暴力产生的悲剧性后果,以此净化人、教化人,起到文学艺术的治疗作用,从而更好地防范暴力、减少暴力,甚至放弃暴力。

新型气管导管固定方法在全麻下侧卧位消化内镜治疗中的应用

目的探讨在消化内镜治疗手术中,新型气管导管固定方法在侧卧位气管插管中的可靠性及安全性。方法选取2022年3~8月在南京大学医学院附属鼓楼医院消化内镜中心实施全麻下内镜治疗的患者80例,其中男44例,女36例,年龄20~45岁,体质量50~76 kg,ASA分级Ⅰ或Ⅱ级,采用随机数字表法将患者分为对照组(n=40)和观察组(n=40)。对照组采用传统医用胶布固定气管导管,将胶布固定上侧面颊,呈“>”型,并在胶布上贴上3M透明贴膜;观察组采用新型气管导管固定方法固定导管,观察和比较两种固定方法的临床效果。结果观察组患者气管导管位移发生率5.0%,口腔、嘴角及面部皮肤损伤发生率6.7%,均低于对照组,差异具有统计学意义(P<0.05)。观察组患者在舒适度评分<3分占比72.5%,<6分占比97.5%,均低于对照组,差异具有统计学意义(P<0.05)。结论在侧卧位状态下经口内镜治疗的患者,使用新型气管导管固定方法可以明显降低气管导管位移度和脱管率,并可降低相关不良反应的发生率。操作简单快捷、取材方便、安全可靠,可以在临床上常规使用。

新型混凝剂应用于水处理的研究进展

在污废水治理过程中,混凝技术因其操作简便、处理经济、效果显著等特点应用广泛。随着整个社会和环境的发展,传统混凝剂逐渐满足不了标准和实际治理的要求,因此,新型混凝剂的研究成为发展趋势。文章综述了新型混凝剂的种类,阐述了混凝由传统混凝剂到新型混凝剂的发展历程,并总结了新型混凝剂在水体富营养化及其它水处理领域的应用,以及对未来混凝剂的研发方向进行展望。

肿瘤可塑性与药物治疗抵抗

药物治疗抵抗在临床实践中成为肿瘤治疗失败的主因。最近的研究指出,肿瘤细胞的耐药性可能源于其内部高度的细胞异质性,而这种异质性的基础则是肿瘤可塑性。肿瘤细胞可塑性可能引发一系列反应,包括对治疗的耐药性发展、免疫系统逃逸以及对周围组织和血管系统的侵袭和转移等。本文简要介绍肿瘤细胞可塑性的表现形式以及其在药物治疗抵抗的非遗传适应性机制与靶向治疗新策略。

《美国荒野医学会关于急性高原病预防、诊断和治疗的临床实践指南:2024年更新》解读

2023年12月27日,美国荒野医学会(the wilderness medical society,WMS)在《荒野与环境医学杂志(Wilderness&Environmental Medicine)》发布了《美国荒野医学会关于急性高原病预防、诊断和治疗的临床实践指南:2024年更新》(以下简称2024版指南)。该指南详细介绍了急性高原病的主要预防、诊断和治疗方法,并就这些方法在疾病管理中的作用提出了建议。与2019版指南相比,2024版指南增加了“诊断”的内容,阐述了急性高原病的诊断方法。2024版指南还针对2019年新型冠状病毒感染(C0VID-19)患者进行高海拔旅行提出了额外的推荐意见。本文对2024版指南进行解读,以期给临床医生提供最佳实践指导。

国医大师张学文从毒论治新型冠状病毒感染咳嗽经验介绍

张学文教授认为新型冠状病毒感染咳嗽的病机为毒邪与湿交结,痰邪内生,肺失宣降及肺之经气郁滞或肺经血行瘀滞。治疗时总体应从毒论治,立足于解毒和理肺止咳,采用清热解毒、宣透解毒、化浊解毒、扶正解毒之法及宣降肺气止咳、理气解郁、活血解郁之法进行治疗,疗效显著。

中医辨证论治新型冠状病毒肺炎心得体会

新型冠状病毒肺炎(新冠肺炎)属于中医学疫病范畴,中医在新冠肺炎的防治中发挥了重要作用。笔者认为新冠肺炎属于外感疾病,正确使用发汗法非常重要,同时要配合通利二便法,以期驱邪务尽。早期新冠肺炎患者可以按照三阳合病思路来辨治;治疗全程需要重视祛湿法的使用;感染新冠肺炎后要警惕逆传心包;根据中医治未病的理念,时常顾护人体正气,以期五脏元气通畅,人即安和。

卡铂+依托泊苷联合阿比特龙+强的松治疗转移性去势抵抗性前列腺患者的疗效和安全性

目的:评价转移性去势抵抗性前列腺癌(metastatic castration-resistant prostate cancer,mCRPC)患者多西他赛+强的松(docetaxel+prednisone,DP)方案化疗和(或)新型内分泌治疗(novel hormone therapy,NHT)进展后应用卡铂+依托泊苷(carboplatin+etoposide,CE)方案联合阿比特龙+强的松(abiraterone+prednisone,AAP)治疗的疗效和安全性。方法:回顾性分析mCRPC患者接受DP方案化疗和(或)NHT治疗后进展,进行CE方案+AAP治疗,每3周为1周期×6周期。观察指标包括前列腺特异性抗原(prostate specific antigen,PSA)缓解率、PSA进展时间(time to PSA progression,TTPP)、影像学无进展生存期(radiographic progression-free survival,rPFS)、PSA下降30%、PSA下降90%、客观缓解率和总生存期(overall survival,OS)。结果:2019年3月至2024年2月,在北京市朝阳区桓兴肿瘤医院和中国医学科学院肿瘤医院收治的符合条件的37例mCRPC患者,进展后应用CE方案联合AAP方案治疗,中位年龄66.0岁,中位随访12.0(3.0~57.0)个月,中位治疗4个周期。PSA缓解率42.1%,中位TTPP 4.0个月,中位rPFS 8.9个月,中位OS 15.0个月。客观缓解率24.3%,PSA下降30%者占59.5%,PSA下降90%者占16.2%;安全性方面,3级及以上不良反应10例。结论:联合应用CE方案和AAP对初始DP方案化疗和(或)NHT治疗失败的去势抵抗性前列腺癌(castration-resistant prostate cancer,CRPC)患者显示出良好的临床疗效和耐受性,但需要更多的样本量和随访时间进一步验证其疗效。

Atopic eczema treatment now and in the future:Targeting the skin barrier and key immune mechanisms in human skin

The skin facilitates a number of key roles but its functioning can be impaired by disease. Atopic eczema is a chronic inflammatory disease where the skin barrier has become leaky, and inflammation occurs. It affects up to 20% of children and 3% of adults worldwide, manifesting as red itchy patches of skin with varying severity. This review aims to investigate the leaky skin barrier and immune mechanisms from the perspective of potential novel treatments. The complexity of atopic eczema as a disease is what makes it difficult to treat. Genome-wide association studies have highlighted possible genetic variations associated with atopic eczema, however in some cases, individuals develop the disease without these genetic risk factors. Loss of function mutations in the filaggrin gene are one of these associations and this is plausible due to its key role in barrier function. The Th2 immune response is the link with regards to the immune mechanisms as atopic inflammation often occurs through increased levels of interleukin(IL)-4 and IL-13. Eczematous inflammation also creates susceptibility to colonisation and damage by bacteria such as Staphylococcus aureus. Potential novel treatments are becoming ever more specific, offering the hope of fewer side effects and better disease control. The best new treatments highlighted in this review target the immune response with human beta defensin 2, phosphodiesterase-4 inhibitors and monoclonal antibodies all showing promise.

The pathophysiology of AHF<br>—New insights from recent studies of novel diuretics and vascular modulating therapies</br>

Treatment of chronic congestive heart failure (HF) has improved substantially during the past decades, with the introduction of modulators of the renin angiotensin aldosterone system (RAAS) such as angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs) and aldosterone antagonists and the introduction of the lifesaving beta-blockers as well as device therapy. Despite the dramatic improvement in the treatment of chronic HF, no such progress was achieved in the treatment of acute heart failure (AHF). Diuretics that were never rigorously examined in well controlled large prospective randomized studies remain the cornerstone and almost exclusively the only intravenous therapeutic option for AHF and no further effective therapy as introduced in more than 30 years. As a result, the short term morbidity and most importantly mortality of AHF remains extremely high with up to 20% of patients dying in the first months after admission for AHF and an additional 20% being readmitted to the hospital. In the current manuscript we will address the practical concerns regarding established and novel diuretic and vascular modulating therapies in patients with AHF, examine their recommended use and seek to determine a path to developing better and more effective therapies for AHF.