A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial to Assess the Efficacy and Safety of Surlorian (ARM210, S48168) in Adults With Autosomal Dominant RYR1-Related Myopathy

This study is testing a medicine called surlorian in adults who have a genetic muscle condition known as autosomal dominant RYR1-related myopathy (RYR1-RM). The goal is to find out whether surlorian improves muscle weakness, and whether it is safe and well tolerated.

开始日期2026-07-01

申办/合作机构

Rycarma Therapeutics, Inc.

CTIS2023-509086-20-00

/ Not yet recruiting临床1期

A SINGLE-CENTER, RANDOMIZED, PLACEBO-CONTROLLED STUDY TO ASSESS SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF REPEAT DOSES OF ARM210 IN HEALTHY SUBJECTS.

开始日期2024-02-13

申办/合作机构-

NCT05122975

/ Terminated临床2期

Treatment of Catecholaminergic Polymorphic Ventricular Tachycardia Type 1 (CPVT1)

The goal of the proposed project is to determine the safety and tolerability as well as the preliminary efficacy of a novel small molecule drug, S48168 (ARM210), for the treatment of Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT1). This disease is associated with fatal changes in heart rhythms leading to sudden death with exercise or excessive excitement. It is due to mutations in the Ryanodine Receptor calcium release channel, which cause leaky channels leading to the disease. S48168 (ARM210) repairs these leaky channels and can be a disease-modifying therapy restoring normal function to the channels. This result would allow patients with CPVT to live normal, active lives. Funding Source- FDA OOPD.

开始日期2023-08-01

申办/合作机构

Rycarma Therapeutics, Inc.

100 项与 Surlorian 相关的临床结果

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100 项与 Surlorian 相关的转化医学

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100 项与 Surlorian 相关的专利（医药）

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项与 Surlorian 相关的文献（医药）

2026-01-01·ChemPlusChem

Ryanodine‐1‐Calstabin Complex Stabilizers in Antidoping Research: Synthesis, Metabolism, and Characterization

Article

作者: Piper, Thomas ; Möller, Tristan ; Thevis, Mario

Awareness of new potential doping agents and the proactive implementation of detection methods are key aspects of preventive antidoping research. Ryanodine receptor‐1‐calstabin complex stabilizers (RYR‐stabilizers) are a novel class of drug candidates for the treatment of various diseases associated with leaky Ca 2+ channels in the cardiac or skeletal muscle. Also, intense physical activity was shown to transiently cause leakage of skeletal muscle Ca 2+ channels, and RYR‐stabilizers have been shown to restore normal activity and, thus, increase endurance performance. Consequently, such compounds are relevant targets in doping controls, and to date, in particular, compounds S107, JTV‐519, ARM 036, and ARM 210 have been subject of antidoping research. In this study, ARM 036 and ARM 210 as well as the commercially available compounds S107 and JTV‐519 were synthesized using a multistep approach. Subsequently, all compounds were investigated concerning their in vitro metabolic behavior, and various metabolites were identified. Selected metabolites were then chemically synthesized for comprehensive structure confirmation. The findings of this study will contribute to routine doping control analytical programs and allow for improving existing detection methods.

2024-10-01·CURRENT OPINION IN NEUROLOGY

Update on RYR1-related myopathies

Review

作者: Nishino, Ichizo ; Ogasawara, Masashi

Purpose of review:

RYR1-related myopathy (RYR1-RM) is a group of myopathies caused by mutations in the RYR1 gene, which encodes the ryanodine receptor 1 (RYR1). This review discusses recent advances in the clinical features, pathology, pathogenesis, and therapeutics of RYR1-RM.

Recent findings:

Although treatments such as salbutamol, pyridostigmine, and N-acetylcysteine have been explored as potential therapies for RYR1-RM, none have been conclusively proven to be effective. However, recent clinical trials of Rycal ARM210 in patients with RYR1-RM have shown promising results, including reduced fatigue and improved proximal muscle strength.Recent advances in three-dimensional structural analysis of RYR1 channels, facilitated by cryo-electron microscopy (cryo-EM), have elucidated the distinct molecular mechanisms underlying RYR1 functionality. Additionally, high-throughput screening methods, including FRET-based and endoplasmic reticulum Ca2+-based assays, have been successful in identifying potential candidates for the treatment of RYR1-RM.

Summary:

Recent advances in clinical and pathological understanding have provided new insights into RYR1-RM. Novel pathomechanisms elucidated by cryo-EM and rapid screening methods have led to the identification of several promising drug candidates. We are hopeful about the potential of Rycal, other new drugs, and gene therapy, offering a promising outlook for the future.

2024-02-01·EClinicalMedicine

Rycal S48168 (ARM210) for RYR1-related myopathies: a phase one, open-label, dose-escalation trial

Article

作者: Pocock, Shavonne ; Colina-Prisco, Claudia ; Jain, Minal S ; Biancavilla, Victoria ; Webb, Yael ; Marcantonio, Eugene E ; Foley, A Reghan ; Chrismer, Irene C ; Bönnemann, Carsten G ; Meilleur, Katherine G ; Cheung, Ken ; Emile-Backer, Magalie ; Norato, Gina ; Waite, Melissa R ; Lawal, Tokunbor A ; Brooks, Kia ; Varma, Pooja ; Grunseich, Christopher ; Riekhof, Willa ; Todd, Joshua J ; Kokkinis, Angela ; Mohassel, Payam ; Marks, Andrew R ; Mendoza, Christopher J

Background:

RYR1-related myopathies (RYR1-RM) are caused by pathogenic variants in the RYR1 gene which encodes the type 1 ryanodine receptor (RyR1). RyR1 is the sarcoplasmic reticulum (SR) calcium release channel that mediates excitation-contraction coupling in skeletal muscle. RyR1 sub-conductance, SR calcium leak, reduced RyR1 expression, and oxidative stress often contribute to RYR1-RM pathogenesis. Loss of RyR1-calstabin1 association, SR calcium leak, and increased RyR1 open probability were observed in 17 RYR1-RM patient skeletal muscle biopsies and improved following ex vivo treatment with Rycal compounds. Thus, we initiated a first-in-patient trial of Rycal S48168 (ARM210) in ambulatory adults with genetically confirmed RYR1-RM.

Methods:

Participants received 120 mg (n = 3) or 200 mg (n = 4) S48168 (ARM210) daily for 29 days. The primary endpoint was safety and tolerability. Exploratory endpoints included S48168 (ARM210) pharmacokinetics (PK), target engagement, motor function measure (MFM)-32, hand grip and pinch strength, timed functional tests, PROMIS fatigue scale, semi-quantitative physical exam strength measurements, and oxidative stress biomarkers. The trial was registered with clinicaltrials.gov (NCT04141670) and was conducted at the National Institutes of Health Clinical Center between October 28, 2019 and December 12, 2021.

Findings:

S48168 (ARM210) was well-tolerated, did not cause any serious adverse events, and exhibited a dose-dependent PK profile. Three of four participants who received the 200 mg/day dose reported improvements in PROMIS-fatigue at 28 days post-dosing, and also demonstrated improved proximal muscle strength on physical examination.

Interpretation:

S48168 (ARM210) demonstrated favorable safety, tolerability, and PK, in RYR1-RM affected individuals. Most participants who received 200 mg/day S48168 (ARM210) reported decreased fatigue, a key symptom of RYR1-RM. These results set the foundation for a randomized, double-blind, placebo-controlled proof of concept trial to determine efficacy of S48168 (ARM210) in RYR1-RM.

Funding:

NINDS and NINR Intramural Research Programs, NIH Clinical Center Bench to Bedside Award (2017-551673), ARMGO Pharma Inc., and its development partner Les Laboratoires Servier.

项与 Surlorian 相关的新闻（医药）

2025-12-20

·今日头条

他汀致肌肉痛分子机制破解，新型“无痛”药物研发路线图浮现

> 全球超过2亿服用他汀类降脂药的患者中，约10%受到肌肉疼痛或无力等副作用的困扰。这一持续数十年的医学谜题，如今在原子级分辨率下被首次清晰揭示。2025年11月，一项发表于《自然-通讯》的研究，为他汀相关肌肉不良反应提供了确凿的分子机制，并为开发更安全的下一代药物指明了方向。 1. 冷冻电镜下：“他汀三联体”强行撬开钙闸门研究由不列颠哥伦比亚大学与威斯康星大学麦迪逊分校的团队完成。他们利用**冷冻电子显微镜技术**，观察到他汀分子并未如预期般仅作用于肝脏，而是“跑错地方”，与骨骼肌细胞中的**兰尼碱受体1（RyR1）** 结合。RyR1是控制细胞内钙离子释放的关键“闸门”，仅在肌肉需要收缩时短暂开启。 ![](blockview://markdown-image-tos-cn-i-tt/6e7fb3db84ac412f9839541b5593b272) 研究发现，以阿托伐他汀为例，其引发肌肉损伤是一个精密的“团伙作案”过程： - **潜伏**：第一个他汀分子在RyR1通道关闭时悄然结合，使其结构松动，处于“一触即发”的预备状态。 - **强攻**：随后，另外两个他汀分子迅速嵌入，形成一个稳定的 **“他汀三联体”** ，像楔子一样卡在通道的关键位置。 ![](blockview://markdown-image-tos-cn-i-tt/0521bb91106c4430b4730c02c1b6ff76) - **溃堤**：三联体通过物理挤压，强行撑开通道结构，导致其无法关闭，引发钙离子持续泄漏。持续的钙泄漏会激活破坏性酶反应，最终导致肌肉细胞损伤、疼痛，严重时甚至可能引发横纹肌溶解。 2. 风险差异：关键在“氟苯基”结构研究进一步指出，能否形成致病性的“三联体”，与他汀分子的特定化学结构密切相关。关键在于是否含有 **“氟苯基”结构**。 - **易引发肌肉反应的他汀**（含氟苯基结构）： - 阿托伐他汀（常用） - 氟伐他汀 - 瑞舒伐他汀（常用） - 西立伐他汀（已退市） - **理论上不易触发该机制的他汀**（不含氟苯基结构）： - 辛伐他汀 - 普伐他汀值得注意的是，即使像瑞舒伐他汀这类**亲水性他汀**，理论上进入肌肉细胞的能力较弱，但因具备形成三联体的化学潜力，仍存在肌肉不良反应风险。 3. 遗传背景：RyR1突变者风险更高研究还解释了为何部分人群对他汀的肌肉副作用异常敏感。那些本身携带**RyR1基因突变**（如R615C、T4709M）的个体，其钙通道的“关门”功能本就存在缺陷。当他汀三联体进行“撬门”攻击时，钙泄漏风险成倍增加，更易出现严重肌肉反应。这为未来的个体化用药与基因筛查提供了重要线索。 4. 解决路径：两条清晰的研发路线图基于这一突破性发现，科学家们已规划出两条明确的解决方案。 **路径一：改造他汀分子** 研究团队指出，他汀分子像一个“双面人”：其**亲水端**负责结合靶点降低胆固醇，是“功臣”；而**疏水端**（苯环结构）则是粘附RyR1引发肌肉痛的“祸首”。 > “现在的药物设计思路已经非常清晰：只要对药物分子的疏水部分进行化学修饰，让它变个样，变得无法再卡进 RyR1 通道里，但同时保留那个负责降脂的亲水端。” **路径二：直接阻止钙泄漏** 另一种策略是加固钙通道本身。哥伦比亚大学的研究团队开发了一种名为 **Rycal的实验性药物**，可以促使RyR1钙通道保持关闭状态。在小鼠实验中，该药物成功阻止了辛伐他汀诱导的钙泄漏，从而预防了肌无力的发生。 5. 未来展望：从罕见病试验走向广泛应用目前，Rycal类药物正在**罕见肌肉疾病患者**中进行临床试验。如果能在这些患者中显示出疗效，下一步就计划在他汀诱导的肌病患者中进行验证。同时，哥伦比亚大学的团队正与化学家合作，研发不与RyR1结合但保留降胆固醇能力的新型他汀。尽管新机制可能无法解释所有他汀肌肉不良反应的案例，但研究资深作者菲利普·范·佩特海姆博士指出，这一发现为设计不与肌肉组织相互作用的新一代他汀提供了清晰的路线图。对于全球数亿依赖他汀保护心脏却受困于副作用的患者而言，这项研究意味着“无痛治疗”的希望之光已经点亮。

2025-01-10

·医药健闻

美敦力前高管加入血管介入大厂；强生紧急叫停一款心脏消融设备；上海允许设立外商独资医院 | 日报

全球医疗行业每日重点资讯文 | 苏丁企业动态 Endologix宣布，总裁兼首席执行官Matt Thompson博士打算卸任并计划转任执行副总裁兼首席医疗官。公司任命John Liddicoat博士为新任总裁兼首席执行官，任命立即生效。在此之前，Liddicoat博士曾在美敦力担任高管超过16年。2018年，被任命为执行副总裁兼美洲地区总裁，并成为美敦力执行委员会成员。Endologix已在2024年上半年连续聘请了美敦力的两名前领导加入其最高管理层。医疗器械公司Endologix致力于为血管疾病的介入治疗提供创新疗法。强生医疗科技在公司官网宣布暂停一款在美国刚上市不久的PFA产品Varipulse的临床使用。该公司称正在调查外部评估中报告的四起患者治疗后发生中风事件的原因，目前尚不清楚何时恢复产品推广。Varipulse于2024年11月获得FDA批准。强生表示，Varipulse自推向全球市场实现商业化以来，截至2025年1月3日，已经治疗了3000多例患者，此前还在美国完成了130多个外部评估案例。公司表示，希望在未来几天内能够就最新的调查结果传达更多信息，并称Varipulse在美国以外的商业化进程不受影响。总部位于波士顿的生物制药公司Armgo Pharma宣布，将更名为RyCarma Therapeutics。新名称借鉴了该公司在兰尼碱受体(RyR) 生物学方面近二十年的经验，在哥伦比亚大学独家许可的RyR技术的帮助下，它利用该技术开发了一类名为Rycals的新型小分子药物，该技术源于RyCarma创始人Andrew Marks医学博士的研究。除了品牌重塑，RyCarma还公布了一项新的计划，以开发其主要候选药物ARM210，用于治疗射血分数降低的心力衰竭。 Light Horse Therapeutics公司宣布完成6200万美元的A轮融资。该公司开发了一种基于基因编辑的专有平台，可发现疾病关键靶点的全新功能位点，然后针对这些全新功能位点开发潜在“first-in-class”小分子疗法。其技术平台可在蛋白质的自然环境中进行研究，从而加速临床候选药物的发现过程。产业动态《上海市深化外商独资医院领域扩大开放试点工作方案》发布，允许在上海市设立外商独资医院（中医类除外，不含并购公立医院）。鼓励在自贸试验区、临港新片区、虹桥商务区、东方枢纽国际商务区等扩大开放试点区域、生物医药产业集聚区域和外籍人士集中居住的中心城区设立外商独资医院。原则上，单个特殊功能区和外籍人士集聚区内设置不超过2家。青峰医药旗下化药1类创新药玛舒拉沙韦片的Ⅲ期临床研究数据，在全球医学科研顶刊《Nature Medicine》发表。作为中国首个自主研发的PA靶点抗流感药，玛舒拉沙韦片注册临床数据全部来源于中国患者，拥有充分中国人群循证证据，预计今年上半年获批上市。青峰医药透露，对于流感预防和流感高风险人群的应用，已纳入玛舒拉沙韦片临床新适应症研究计划，针对服用片剂不便的低龄儿童，公司正积极推动其新剂型的开发。宜联生物宣布与再鼎医药达成一项新的战略合作和全球许可协议，利用宜联生物医药的TMALIN抗体偶联药物（ADC）平台开发一款针对实体瘤的新型LRRC15抗体偶联药物（ADC）ZL-6201，该产品的抗体由再鼎医药内部发现。通过此次合作，再鼎医药进一步扩展了其全球肿瘤管线，有望开发出另一款针对多种实体瘤的潜在“first-in-class”ADC。康诺亚宣布，就潜在同类最优的靶向CD38人源化单克隆抗体CM313与Timberlyne Therapeutics, Inc.达成独家授权许可协议。基于授权许可协议，康诺亚授予Timberlyne在全球（不包括中国内地、香港、澳门及台湾地区）开发、生产及商业化CM313的独家权益。作为回报，康诺亚将获得3,000万美元首付款和近期付款，并获得Timberlyne股权，成为该公司最大股东。在达成若干销售及开发里程碑后，康诺亚可获得最多3.375亿美元的额外付款，及销售净额的分层特许权使用费。百奥赛图与SOTIO Biotech达成许可协议。根据双方已签订的选择权与许可协议，此次授权将助力一款靶向新型肿瘤抗原的创新抗体药物偶联物（ADC）的开发。百奥赛图的全人抗体将支持SOTIO新型ADC候选药物SOT109的研发，该药物旨在治疗结直肠癌及其他胃肠道癌症。SOTIO将在签署许可协议后向百奥赛图支付选择权行使费用。赛诺菲旗下抗CD38单抗赛可益（艾沙妥昔单抗注射液）获得国家药品监督管理局（NMPA）批准，用于与泊马度胺和地塞米松联合用药，治疗既往接受过至少一线治疗（包括来那度胺和蛋白酶体抑制剂）的多发性骨髓瘤成人患者。三生国健自主研发的抗TL1A单抗临床试验申请获国家药品监督管理局受理，成为首个申报临床试验并获受理的国产抗TL1A单抗。TL1A（TNF配体相关分子1A）是肿瘤坏死因子超家族的成员，主要由内皮细胞表达。SSGJ-627是三生国健创新研发，拥有自主知识产权的重组抗TL1A人源化单克隆抗体。强生宣布，其在研Tau单抗Posdinemab获美国FDA快速通道资格，用于治疗早期阿尔茨海默病（AD）患者。Posdinemab是一款靶向Tau蛋白中间区域特定超磷酸化表位的单抗，可以通过抑制病理性Tau蛋白沉积和扩散，从而延缓或预防AD疾病进展。目前，Posdinemab正在开展IIb期AuTonomy临床研究。 FDA将要求GSK和辉瑞在其呼吸道合胞病毒(RSV)疫苗的标签上包含关于患吉兰-巴雷综合征(GBS)风险的警告，这是一种可导致瘫痪的罕见神经系统疾病。该裁决将影响GSK的Arexvy和辉瑞的Abrysvo，这两者都于2023年5月获得该机构批准用于60岁或以上的成年人。但在七个月前，当疾病控制和预防中心（CDC）建议仅供75岁及以上的成年人和60岁及以上因潜在疾病而患重病高风险的人使用时，这两种疫苗的销售潜力都显着下降。生物技术公司DIOSynVax宣布推出新的疫苗组合，包括大流行前禽流感疫苗、超季节性流感疫苗和通用型流感疫苗。该公司的禽流感疫苗现已在包括雪貂在内的动物模型中展现出疗效和安全性，现已准备好进行人体试验。DIOSynVax还成立了一个新的咨询委员会，该委员会由制药和学术领域的顶尖专家组成，将在公司推进流感疫苗候选产品进入临床试验和商业化阶段的过程中提供重要见解。联系美通社 +86-10-5953 9500 info@prnasia.com

高管变更基因疗法

2025-01-07

·FiercePharma

Letting go of Armgo: Biotech rebrands as RyCarma Therapeutics

Alongside its rebrand, RyCarma Therapeutics unveiled a new pipeline program to develop its lead candidate, ARM210, in heart failure with reduced ejection fraction. Armgo Pharma is making a fresh start this new year, as the Boston-based biotech announced Tuesday that it will henceforth be known as RyCarma Therapeutics.The new name draws from the company’s nearly two decades of work in ryanodine receptor (RyR) biology, which it has used to develop a new class of small-molecule drugs dubbed Rycals, with the help of RyR technology licensed exclusively from Columbia University and stemming from the research of RyCarma founder Andrew Marks, M.D.Alongside the rebrand, RyCarma also unveiled a new pipeline program to develop its lead candidate, ARM210, in heart failure with reduced ejection fraction. If ultimately approved, per the company, it stands to become the first heart failure therapy that not only improves heart function but also addresses the common symptom of skeletal muscle weakness. ARM210 is also being tested in the much rarer setting of ryanodine receptor 1-related myopathies (RYR1-RM), which comprise neuromuscular diseases caused by mutations in the RYR1 gene.In another set of changes for the biotech, RyCarma also named a handful of new executives, including the appointments of CEO Adam Rosenberg and of Jonathan Alspaugh and Sanjay Jalota to serve as chief strategy officer and senior vice president of regulatory, respectively.Marks said in a statement that he was “thrilled” with the new direction of the company he founded in 2004.“The past decade has seen an incredible convergence of structural, genetic and physiological data on RyR biology," he added. "RyCarma is at the forefront of advancing therapeutics that target RyR to treat serious and devastating diseases like RYR1-RM and heart failure." RyCarma has previously dabbled in applying its Rycals to cardiac conditions: In its early days, one candidate reached phase 2 trials in heart failure and arrhythmias before being scrapped in favor of a focus on neuromuscular disorders.In 2021, the company then known as Armgo brought in $35 million from Forbion and other VC backers that it said would be used to test ARM210 in a phase 2 trial of catecholaminergic polymorphic ventricular tachycardia, a rare inherited cardiovascular disease that’s characterized by abnormal heart rhythm. At the time, the biotech pitched ARM210 as a potential “pipeline-in-a-product.”As of this week, however, only the heart failure and RYR1-RM programs are listed as ARM210’s ongoing projects on RyCarma’s site.Editor's note: This story was updated to correct a mention of Armgo's founding year. It was founded in 2004, not 2006.

高管变更临床2期IPO

100 项与 Surlorian 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
室性心律失常	临床2期	美国	Rycarma Therapeutics, Inc.	2023-08-01
室性心律失常	临床2期	荷兰	Rycarma Therapeutics, Inc.	2023-08-01
儿茶酚胺敏感性多形性室性心动过速	临床2期	美国	Rycarma Therapeutics, Inc.	2023-07-19
儿茶酚胺敏感性多形性室性心动过速	临床2期	荷兰	Rycarma Therapeutics, Inc.	2023-07-19
心律失常	临床1期	荷兰	-	2024-02-13
Ryanodine Receptor Type 1 Related Myopathies	临床1期	美国	Rycarma Therapeutics, Inc.	2020-08-25
杜氏肌营养不良症	临床1期	美国	Rycarma Therapeutics, Inc.	2014-12-04
杜氏肌营养不良症	临床1期	法国	Les Laboratoires Servier SAS	2014-12-04
心脏衰竭	临床1期	美国	Rycarma Therapeutics, Inc.	-

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04141670 (CTgov)	临床1期	Ryanodine Receptor Type 1 Related Myopathies	7	S48168 (Low Dose Group)	蓋鑰鬱淵網齋憲膚襯壓 = 願積觸壓鹽窪鬱鑰淵選築襯顧膚醖繭簾遞鹽齋 (膚鹹齋蓋製鏇範製憲構, 構築壓淵簾蓋鬱選鑰蓋 ~ 廠網糧鏇繭鏇觸構憲繭) 更多	-	2024-04-19
NCT04141670 (CTgov)	临床1期	Ryanodine Receptor Type 1 Related Myopathies	7	S48168 (High Dose Group)	蓋鑰鬱淵網齋憲膚襯壓 = 醖製繭淵鑰簾選繭築製築襯顧膚醖繭簾遞鹽齋 (膚鹹齋蓋製鏇範製憲構, 衊構餘糧餘廠夢簾襯憲 ~ 淵範範餘鹽壓齋顧夢網) 更多	-	2024-04-19
NCT04141670 (GlobeNewswire) 人工标引	临床1期	Ryanodine Receptor Type 1 Related Myopathies	7	Rycal	窪鹹網積網選衊鑰衊壓(衊糧膚膚齋膚鑰艱廠壓) = S48168 (ARM210) was well-tolerated, did not cause any serious adverse events, and exhibited a dose-dependent PK profile. 齋範鏇糧選獵範築製製 (襯構醖顧積淵鑰窪鏇積 ) 更多	积极	2024-01-29