更新于：2024-09-19

Macrophagic Myofasciitis

巨噬细胞肌筋膜炎（MMF）

更新于：2024-09-19

基本信息

别名

MMF、MMF - Macrophagic myofasciitis、Macrophagic myofasciitis

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简介

A rare systemic inflammatory disease associated with long-lasting biopersistance of post-vaccinal aluminic granulomas. More than 600 cases have been reported to date, most of them in France. This is probably due to large-scale vaccination with aluminium-containing vaccines in France during the 1990s. The disease generally manifests with myalgias of variable intensity, and is usually associated with weakness and chronic fatigue. Belongs to the group of Autoimmune/inflammatory Syndromes Induced by Adjuvants (ASIA): it is triggered, probably in genetically predisposed patients, by injection of vaccines containing aluminium hydroxide and may occur up to 10 years following vaccination.

关联

项与巨噬细胞肌筋膜炎（MMF）相关的临床试验

ChiCTR2100054756 / Recruiting临床4期

Real-world study of topical analgesics in the treatment of myofascial pain syndrome

开始日期-

申办/合作机构

中南大学湘雅三医院

CTR20233730 / Recruiting临床3期

一项在儿童期发病的特发性肾病综合征患者中评价奥妥珠单抗与MMF相比的有效性和安全性的III期、国际多中心、随机、开放性研究

主要目的评价奥妥珠单抗与MMF相比的有效性次要目的评价奥妥珠单抗与MMF相比的有效性评价奥妥珠单抗治疗组受试者与MMF治疗组受试者中的疲乏变化评价奥妥珠单抗治疗组受试者与MMF治疗组受试者中的生活质量变化评价随时间推移的水肿情况评价奥妥珠单抗与MMF相比的安全性表征奥妥珠单抗PK特征表征奥妥珠单抗诱导的PD变化探索性目的评价奥妥珠单抗与MMF相比的有效性探索暴露量-有效性关系和暴露量-安全性关系评价药物暴露量与B细胞耗竭之间的潜在关系评价机体对奥妥珠单抗产生的免疫应答情况评价ADA的潜在影响识别和/或评价可提供奥妥珠单抗活性证据的生物标志物（即药效学生物标志物），或可增加对疾病生物学和药物安全性认识和了解的生物标志物。

开始日期2024-03-29

申办/合作机构

罗氏（中国）投资有限公司

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TCTR20180703005 / CompletedN/AIIT

Effects of Mechanical Bed Massage on Exercise-Induced Back Muscle Fatigue in Athletes

开始日期2017-11-01

申办/合作机构

Khon Kaen University

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100 项与巨噬细胞肌筋膜炎（MMF）相关的临床结果

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100 项与巨噬细胞肌筋膜炎（MMF）相关的转化医学

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0 项与巨噬细胞肌筋膜炎（MMF）相关的专利（医药）

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194

项与巨噬细胞肌筋膜炎（MMF）相关的文献（医药）

2024-02-19·International journal of biological macromolecules

Targeted inhibition of gut bacterial β-glucuronidases by octyl gallate alleviates mycophenolate mofetil-induced gastrointestinal toxicity.

Article

作者: Li-Juan Xia ; Lei Wan ; Ang Gao ; Yong-Xin Yu ; Shi-Ying Zhou ; Qian He ; Gong Li ; Hao Ren ; Xin-Lei Lian ; Dong-Hao Zhao ; Xiao-Ping Liao ; Ya-Hong Liu ; Wei Qiu ; Jian Sun

Mycophenolate mofetil (MMF) is a viable therapeutic option against various immune disorders as a chemotherapeutic agent. Nevertheless, its application has been undermined by the gastrotoxic metabolites (mycophenolic acid glucuronide, MPAG) produced by microbiome-associated β-glucuronidase (βGUS). Therefore, controlling microbiota-produced βGUS underlines the potential strategy to improve MMF efficacy by overcoming the dosage limitation. In this study, the octyl gallate (OG) was identified with promising inhibitory activity on hydrolysis of PNPG in our high throughput screening based on a chemical collection of approximately 2000 natural products. Furthermore, OG was also found to inhibit a broad spectrum of BGUSs, including mini-Loop1, Loop 2, mini-Loop 2, and mini-Loop1,2. The further in vivo experiments demonstrated that administration of 20 mg/kg OG resulted in predominant reduction in the activity of BGUSs while displayed no impact on the overall fecal microbiome in mice. Furthermore, in the MMF-induced colitis model, the administration of OG at a dosage of 20 mg/kg effectively mitigated the gastrointestinal toxicity, and systematically reverted the colitis phenotypes. These findings indicate that the OG holds promising clinical potential for the prevention of MMF-induced gastrointestinal toxicity by inhibition of BGUSs and could be developed as a combinatorial therapy with MFF for better clinical outcomes.

2023-12-05·Maternal & child nutrition

Deteriorating complementary feeding practices and dietary quality in Jordan: Trends and challenges.

Article

作者: Shibani Ghosh ; Robin Shrestha ; Yanlin Ren ; Karuna Salve ; Patrick Webb

Quality complementary feeding (CF) of infants and young children is key to their growth and development. But in Jordan, providing appropriate CF remains a challenge. This study assesses trends in infant and young child feeding (IYCF) practices, and consumption by infants and young children aged 6-23 months of breast milk substitutes (BMSs), sugar-sweetened beverages (SSBs), and micronutrient-rich foods in Jordan from 1990 to 2017. We combined dietary data on infants and young children from six Demographic and Health Surveys (DHS) (n = 14,880 children) to compute IYCF indicators. The latter included minimum dietary diversity (MDD), minimum meal frequency (MMF), and minimum acceptable diet (MAD), as well as intake of micronutrient-rich foods and food groups, specific SSBs, and infant formula. We conducted trend analyses using logistic regression models adjusted for child's age in month, child age squared, governorates, urban/rural residence, mother's educational attainment, and household wealth quintiles. We found that the proportion of consumption of micronutrient-rich food groups declined significantly between 1990 and 2017, with fewer infants and young children consuming eggs (OR = 0.39, p ≤ 0.001, 2002 reference), meat, poultry, and fish (OR = 0.25, p ≤ 0.001, 2002 reference), dairy (OR = 0.59, p ≤ 0.001, 2002 reference) and Vitamin A-rich fruits and vegetables (OR = 0.66, p ≤ 0.001, 2002 reference). Conversely, there was increased use of BMSs and sugar-sweetened juices that paralleled a decline in the share of infants and young children meeting appropriate CF practices and consuming micronutrient-rich foods and food groups. By 2017, children aged 6-23 months were significantly less likely to meet MDD, MMF, and subsequently MAD; the odds of consuming BMSs were almost three times the reference (OR = 3.8, p ≤ 0.001, 1990 reference), as were the odds of consuming sugar sweetened juices (OR = 3.63, p ≤ 0.001, 1990 reference). Food insecurity and undernutrition are low in Jordan; however, overweight and obesity rates are increasing concurrently as are micronutrient deficiencies. This highlights the need for policymakers to address factors at individual and household levels (behaviours and practices) as well as environmental issues (increasing access to unhealthy and ultraprocessed foods).

2023-09-01·Wei sheng yan jiu = Journal of hygiene research

[Status of infant and young child feeding in China in 2016-2017].

Article

作者: Yuying Wang ; Dongmei Yu ; Yifan Duan ; Qiya Guo ; Xuehong Pang ; Xiaoli Xu ; Jie Wang ; Ye Bi ; Zhenyu Yang ; Liyun Zhao

OBJECTIVE:

To describe the feeding status and related factors of infant and young child aged 6-23 months in China.

METHODS:

Data was from the China Nutrition and Health Surveillance among 0-17 Years Old Children and Lactating Women in 2016-2017, and 20 423 children aged 6-23 months were involved in 275 surveillance sites from 31 provinces(autonomous regions and municipalities). The introduction of solid, semi-solid or soft foods, minimum dietary diversity, minimum meal frequency were analyzed with WHO and UNICEF 2021 updated infant and young child feeding indicators. Data analyses were conducted using the complex weight based on national census from National Bureau of Statistics in 2010. Rao-Scott Chi-square was used test for statistical difference.

RESULTS:

The percentage of infants 6-8 months of age who consumed solid, semi-solid or soft foods was 83.2%(95%CI 80.5%-85.9%) in 2016-2017. No significant difference were observed between boys and girls; there was significant difference in different areas(Rao-Scott χ~2=30.85, P<0.01), it was 90.3% in medium and small cities, and reached 75.0% even in poor rural areas. The proportions of children aged 6-23 months meeting minimum dietary diversity(MDD) was 60.6%(95%CI 58.1%-63.1%). It was 71.1% in medium and small cities, and 50.5% in poor rural areas. Except for breast milk, the percentage of eggs(34.4%) and legumes(19.0%) consumption was low, the percentage of grains, vitamin A-rich fruits or vegetables consumption was 89.7%(95%CI 88.4%-91.1%). The percentage of consuming egg and/or flesh food was 76.4%(95%CI 74.2%-78.7%). The percentage of zero vegetables or fruits consumption was 9.1%(95%CI 7.8%-10.4%). The proportions of children aged 6-23 months meeting minimum meal frequency(MMF) was 72.4%(95%CI 70.1%-74.7%). It was over 70% in large cities, medium and small cities, general rural areas; and 60.2% in poor rural areas. The proportions of children aged 6-23 months meeting minimum acceptable diet was 43.4%(95%CI 40.7%-46.1%), it was over 50% in urban areas, and less than 40% in rural areas, 30.1% in poor rural areas. No consistent differences were observed between boys and girls for all 3 indicators(MDD, MMF and MAD), and there was significant difference in different areas and various months of age(P<0.01).

CONCLUSION:

There was no gender difference in the feeding status of children aged 6-23 months in China, the complementary feeding was relatively timely, and the minimum dietary diversity and meal frequency of children were relatively ideal, but the minimum acceptable diet of children in poor rural areas was poor.

项与巨噬细胞肌筋膜炎（MMF）相关的新闻（医药）

2023-11-20

·CPHI制药在线

系统性红斑狼疮药物治疗研究进展

关注并星标CPHI制药在线系统性红斑狼疮（SLE）是一种以局部或全身炎性反应为特征的自身免疫性疾病，发病隐匿，潜在发病率和病死率高，SLE 患者有不同的症状和体征，临床诊断SLE的重要依据是自身抗体的产生。目前SLE 的临床治疗多以激素和免疫抑制剂为主，由于这些药物特异性差，长期使用会伴随严重甚至危及生命的不良反应。近年来，新型靶向药物的出现为SLE的临床治疗提供了新的选择，这些靶向药物具有服用方便、不良反应小、效果明显、代谢快、特异性高等特点。 SLE的抗炎治疗糖皮质激素（GC）是 SLE 患者的临床治疗一线药物，能够有效抑制结缔组织水平的提升，并且能够调控组胺物质水平，抗炎和抑制毛细血管的扩张，使得患者的病态症状得到有效改善。GC还存在稳定溶酶体膜，改善休克等作用，提升临床治疗效果，但该类药物往往会引起一系列不良反应，如骨质疏松、消化系统并发症、库欣综合征以及高血压等心血管疾病。在SLE的治疗上，通常根据疾病是否初发、病情轻重、是否合并感染、肾脏病理类型以及是否合并肾功能损害或血液系统危象等因素，来调整GC的剂量、种类和使用疗程。激素治疗可分为诱导缓解期、维持期及复发治疗3个阶段。大量的GC联合免疫抑制剂治疗在诱导缓解期使用，维持期则逐渐减量直至最小治疗剂量，一旦病情复发，依患者情况增加到合适剂量，待病情稳定后再缓慢减量。GC的合理使用大大提高了SLE患者的存活率。 SLE 免疫抑制治疗免疫抑制剂是风湿疾病治疗的一类常用药物，其通过抑制机体异常免疫表达来控制体内细胞及体液免疫应答，减轻组织免疫损伤，从而达到降低患者免疫力的作用，常采用联合用药的方式来提高疗效。该类药物治疗机制包括：清除致敏淋巴细胞、清除机体异常免疫反应中的淋巴细胞、清除非特异炎症中的非淋巴样细胞和抑制残存的淋巴样细胞的功能。常用的免疫抑制剂有环磷酰胺（CTX）、硫唑嘌呤（AZA）、霉酸酚酯（MMF）、甲氨蝶呤（MTX）、钙调磷酸酶抑制剂、羟氯喹（HCQ）和中药雷公藤多苷等。 ①环磷酰胺（CTX）。CTX是双功能烷化剂及细胞周期非特异性药物，可影响DNA和RNA的功能，对S期作用显著，从而干扰 DNA 合成而产生细胞毒作用。CTX 通过抑制淋巴细胞增殖，强力作用于B细胞，也对T 细胞有毒性作用，同时有抑制体液免疫与细胞免疫的功能。其对SLE的治疗特别是LN有良好疗效，但烷化剂存在骨髓抑制、感染、性腺抑制或增加肿瘤风险等不良反应。长期大剂量的 CTX 治疗正在逐步被 GC和 CTX 联合使用或序贯使用免疫抑制剂所替代。 ②硫唑嘌呤（AZA）。AZA 是嘌呤类似物，其代谢产物巯嘌呤能干扰嘌呤合成，并有细胞毒作用，可以抑制细胞和抗体介导的免疫应答，通过多种途径抑制核酸的生物合成，从而阻止参与免疫识别和免疫放大的细胞的增生；其次向DNA 链内掺入硫代嘌呤类似物可导致 DNA 破坏。临床上 AZA 大多用于轻中型SLE患者，以减少GC的使用剂量，也用于LN中CTX 的替代治疗。AZA 对 LN 患者在临床缓解，巩固疗效、减少复发的疗效显著。 ③霉酸酚酯（MMF）。MMF可抑制嘌呤从头合成途径，但不影响补救途径的嘌呤合成，从而抑制淋巴细胞活化，抑制生成 T 细胞、B 细胞及抗体，减少血小板破坏，其独特的免疫抑制作用使其不发生骨髓和性腺抑制，有较高安全性。MMF 还针对糖蛋白的转化起到抑制作用，能使 T 细胞与内皮细胞间的黏附力下降，还有减少巨噬细胞的和抑制血管平滑肌增生等作用。研究认为 MMF 可减少沉积于肾脏的免疫复合物，对减轻肾脏损害有一定缓解作用。 ④甲氨蝶呤（MTX）。MTX作为二氢叶酸还原酶抑制剂，可阻碍嘌呤正常合成，从而影响胸腺嘧啶合成，其作用于细胞分裂的 S 期，抑制 DNA 的生物合成，并发挥一定的抗炎作用。但临床研究发现，MTX还有免疫介导的药敏反应及其他不良反应，主要表现为皮肤发红瘙痒、胃肠道反应和肝肾功能损害等，严重者发生骨髓抑制，可并发感染甚至死亡，患者用药安全性较差。 ⑤钙调磷酸酶抑制剂(CNI)。CNI包括环孢素和他克莫司。CNI 主要抑制T淋巴细胞钙调磷酸酶，通过抑制活化T细胞核因子与 DNA 结合从而抑制白细胞介素 IL-2 的表达。IL-2 对 T细胞存活和分化起关键作用，CNI 通过降低 IL-2 表达而抑制 T 细胞功能。因对淋巴细胞的作用具有选择性，故CNI 并无骨髓和性腺抑制作用。他克莫司对LN的疗效不劣于MMF，而联合小剂量激素和MMF 治疗 LN 疗效优于环磷酰胺脉冲方案。欧洲SLE 治疗指南推荐对严重肾病综合征或疗效不佳的LN，可加用小剂量CNI。 ⑥羟氯喹（HCQ）。HCQ是临床治疗常用的抗疟药，常与免疫抑制剂联合用药，它的药理机制包括抗炎和免疫调节。多伦多SLE 研究团队的一项研究表明，在疾病的前5年，超过60%的时间使用抗疟药治疗可减少SLE发病次数，降低损伤累积范围和GC累积用量。HCQ 引起的碱化可导致溶酶体的膨胀和空泡化，进而抑制了溶酶体功能，包括酶的释放、受体再循环、质膜修复、细胞信号传导和能量代谢。这类药物的免疫调节作用是由免疫抑制、抗炎、抗凝、光保护等机制介导的，通过免疫调节有助于维持代谢平衡、保护脏器、改善SLE 活动性及降低病死率和感染等并发症的出现。《2020中国系统性红斑狼疮诊疗指南》建议GC联合 HCQ治疗效果不佳或无法将激素剂量调整至相对安全剂量以下的患者应联合使用免疫抑制剂。 ⑦雷公藤多苷。雷公藤多苷是抗炎免疫调节的中药提取物，可阻断5-羟色胺、组胺、前列腺素 E2产生，从而抑制炎性反应，阻断炎性介质的级联反应，还可抑制 IL-2 产生及其受体效应，诱导已活化淋巴细胞凋亡，对 SLE 炎性反应早期血管通透性增高、渗出水肿有明显抑制作用。在免疫调节方面，雷公藤多苷还能直接抑制亢进的 B 细胞功能，达到辅助治疗 SLE，明显改善患者免疫功能的作用。靶向药物近年来，随着医药研究突飞猛进，各种靶向药物相继出现，主要包含两大类，分别为生物制剂和小分子靶向药物，其主要机制包括抑制B和T淋巴细胞的活化，阻断免疫细胞间的相互作用，以及抑制细胞因子的产生等。靶向药物可以作用于特定的病变部位，通过增加目标局部的药物浓度来减轻药物对正常组织和细胞的毒性作用，也提高了治疗的特异性。 ①靶向B淋巴细胞贝利木单抗已于2011年获得 FDA 和欧洲药品监管局（EMA）正式批准，成为首个获批用于SLE 治疗的靶向药物。B淋巴细胞激活因子（BAFF）是一种肿瘤坏死因子（TNF）样细胞因子，支持 B细胞在不同发育阶段的生存和分化。贝利木单抗的作用靶点是与其有较高亲和力的BAFF，药物的结合将影响BAFF作用于B细胞表面上的受体，抑制B细胞的增殖、分化及血清中自身抗体的生成。研究表明，贝利木单抗可明显减缓 SLE 的疾病活动度，减少泼尼松和GC的用量，但长期服用此药有增加抑郁症的风险。利妥昔单抗（RTX）是一种选择性靶向B细胞特异性表面分子CD20的人鼠嵌合型单克隆抗体，CD20是一种局限于B细胞谱系的细胞表面蛋白，它首先在骨髓中的早期前B细胞阶段表达，并在B细胞发育过程中持续存在，直到最终分化为浆细胞RTX治疗SLE 可以通过抗体依赖细胞介导和补体介导的细胞毒作用来诱导细胞凋亡，B细胞的不断消耗，自身免疫对机体的损伤不断减弱。因CD20不在造血干细胞、正常浆细胞和其他正常的组织中出现，所以RTX可有效避免广泛的免疫抑制，提高了用药的安全性。尽管缺乏试验证据，但许多观察性研究显示了RTX在治疗难治性LN和严重非肾性SLE方面的疗效。 Anifrolumab是一种在研的针对 Ⅰ 型干扰素（IFN）受体亚基1的人单克隆抗体，SLE 患者体内 Ⅰ 型IFN基因标志升高明显，而Ⅰ 型IFN是参与炎性反应的细胞因子。因此，Anifrolumab可通过阻断所有Ⅰ型IFN的活性，用于SLE 的治疗。目前，该单抗药物处于治疗SLE关键Ⅲ期临床试验，结果显示 Anifrolumab组患者的不良事件包括呼吸道感染、鼻咽炎、输液相关反应，不良事件的发病例数低于安慰组，还有GC减量情况和皮肤病的严重程度均优于服用安慰剂。 ②靶向T淋巴细胞阿巴西普是一种用于治疗类风湿性关节炎等自身免疫性疾病的药物，它是由一种白细胞分化抗原CTLA-4和细胞外结构融合的免疫球蛋白IgG1的Fc区组成的融合蛋白，可通过中断 CD80/CD86与CD28的相互作用来调节T细胞共刺激分子。阿巴西普可阻断信号通路，使得T细胞不能被激活。虽然阿巴西普对 SLE 治疗的临床试验并未得到阳性结果，抗 CD40L单克隆抗体在 SLE 的Ⅱ期临床试验中也显示无效，但从阿巴西普治疗SLE患者的安全性来看，在难治性病例中，此药可视为一种备用选择。 ③靶向细胞因子西伐木单抗（Sifalimumab）是一种人源性抗IFN-α抗体，最近一项Ⅱb期临床试验表明，Sifalimumab在中度至重度活动性SLE 患者中具有抑制IFN基因表达的作用，患者的疾病活动度和关节损伤得以缓解。除干扰素α外，其他细胞因子也在SLE 的发病机制中发挥重要作用。近年来，研究发现IL-12可促进T细胞向辅助性T细胞 1 ( helper T cell-1 Th1) 分化，而IL-23 则促进Th17分化，针对IL-12/IL-23的乌司奴单克隆抗体在SLE的Ⅱ期临床研究取得了阳性结果。另有研究发现，不阻断细胞因子而直接给予细胞因子也可用于治疗 SLE，如最近报道小剂量 IL-2 能提高调节性 T 细胞比例而治疗SLE。 ④靶向细胞内信号通路 Ⅰ型干扰素在SLE 发病机制中具有重要作用，而JAK /STAT 信号传导通路是Ⅰ型干扰素的主要信号通路，所以阻断 JAK /STAT 通路即可阻断Ⅰ型干扰素的作用。最近研究发现，JAK /STAT 通路在LN 驻留肾脏 T 细胞的维持中发挥重要作用，JAK抑制剂托法替布能抑制此类 T 细胞功能，减轻蛋白尿和肾损害。目前已有多种JAK 抑制剂在临床上用于治疗类风湿关节炎等自身免疫性疾病，但其能否用于治疗 SLE 的证据尚不足。巴瑞替尼在SLE 的Ⅱ期临床研究中也取得了较好疗效，而Ⅲ期临床试验仍在进行中。小规模观察性研究发现托法替布对SLE 患者的皮疹和关节炎具有一定疗效。脾脏酪氨酸激酶抑制剂等能显著减轻狼疮小鼠皮肤和肾脏病变。参考资料 [1]郭佳,李祥,张理涛.系统性红斑狼疮的用药进展[J].中国中西医结合皮肤性病学杂志,2021,20(05):525-528. [2]柴富,王春芳.系统性红斑狼疮相关药物治疗的研究进展[J].检验医学与临床,2022,19(10):1423-1427. [3]杨念生.系统性红斑狼疮药物治疗发展趋势[J].协和医学杂志,2020,11(03):247-251. 金笔奖征文开启，速来投稿参与！来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~

临床研究免疫疗法