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Precautions in the management of opioid agonist therapy: from target population characteristics to new formulations and post-marketing monitoring - a focus on the Italian system. 阿片类受体激动剂治疗管理中的注意事项:从目标人群特征到新配方和上市后监测--聚焦意大利系统。
Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-08-24 eCollection Date: 2023-01-01 DOI: 10.7573/dic.2023-2-6
Guido Mannaioni, Fabio Lugoboni

Opioid use disorder (OUD) is a serious medical condition with vast social, health and economic impact. Individuals with OUD are prescribed opioid agonist therapies, such as methadone, levomethadone, buprenorphine or naloxone/buprenorphine, to reduce the risks associated with illegal substance abuse, eventually leading to opioid use abstinence. The OUD population has peculiar frailties, mainly related to the psychiatric sphere, which may jeopardize their therapeutic course. Amongst the possible phenomena that may contribute to treatment failure, opioid agonist therapy misuse and diversion are of utmost importance, leading to serious repercussions for patients as well as for national health systems. To minimize the consequences related to these practices, it is necessary to implement cross-cutting precautions, from the formulation of abuse-deterrent drugs to the implementation of a national monitoring system that oversees the health situation and signals when action is needed. Based on these premises, this article focuses on data and insights concerning the Italian territory.

阿片类药物使用失调症(OUD)是一种严重的疾病,对社会、健康和经济造成巨大影响。阿片类药物滥用失调症患者接受美沙酮、左美沙酮、丁丙诺啡或纳洛酮/丁丙诺啡等阿片类药物激动剂治疗,以减少非法药物滥用带来的风险,最终达到戒断阿片类药物滥用的目的。OUD 患者有一些特殊的弱点,主要与精神疾病有关,这可能会危及他们的治疗过程。在可能导致治疗失败的各种现象中,阿片类激动剂疗法的滥用和转用最为重要,会对患者和国家卫生系统造成严重影响。为了最大限度地减少与这些做法有关的后果,有必要采取贯穿各领域的预防措施,包括配制抑制滥用的药物,以及实施国家监测系统,以监督健康状况并在需要采取行动时发出信号。基于上述前提,本文重点介绍意大利境内的数据和见解。
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引用次数: 1
Corrigendum: Precautions in the management of opioid agonist therapy: from target population characteristics to new formulations and post-marketing monitoring - a focus on the Italian system. 更正:阿片类受体激动剂治疗管理中的注意事项:从目标人群特征到新配方和上市后监测--聚焦意大利系统。
Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-08-24 eCollection Date: 2023-01-01 DOI: 10.7573/dic.2023-11-7

[This corrects the article DOI: 10.7573/dic.2023-2-6.].

[此处更正了文章 DOI:10.7573/dic.2023-2-6]。
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引用次数: 0
Clinical experience with pemigatinib for previously treated metastatic cholangiocarcinoma: practical considerations from clinical cases. 使用培美加替尼治疗既往接受过治疗的转移性胆管癌的临床经验:临床病例中的实际考虑因素。
Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-08-14 eCollection Date: 2023-01-01 DOI: 10.7573/dic.2023-5-5
Jonathan Wadsley, Alan Christie, Roopinder Gillmore, Amy Trinh, Rachel Greig

The management of advanced cholangiocarcinoma (CCA) is challenging. In patients with advanced CCA, gemcitabine/cisplatin combination is the standard frontline chemotherapy, with 5-fluorouracil-based regimens preserved for subsequent lines; however, the expected survival is poor. Pemigatinib was approved for locally advanced or metastatic CCA with FGFR2 fusions or rearrangement. Pemigatinib has a manageable safety profile and achieves a durable response. Nearly 50 patients with CCA have been treated with pemigatinib in the United Kingdom. However, clinical experience with pemigatinib is lacking. We present our experience with three clinical cases to illustrate the position of pemigatinib in the management of CCA and related toxicities.

晚期胆管癌(CCA)的治疗具有挑战性。对于晚期CCA患者,吉西他滨/顺铂联合化疗是标准的一线化疗方案,随后保留以5-氟尿嘧啶为基础的方案;然而,预期生存率较低。佩吉加替尼被批准用于治疗 FGFR2 融合或重排的局部晚期或转移性 CCA。佩吉加替尼具有可控的安全性,并可获得持久的应答。在英国,已有近 50 名 CCA 患者接受了培美加替尼的治疗。然而,目前尚缺乏使用培美加替尼的临床经验。我们介绍了三个临床病例的经验,以说明培美加替尼在治疗CCA及相关毒性反应中的地位。
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引用次数: 0
Real-world management of abnormal scarring using topical silicone gel: expert consensus and case series from the Asian SCARS Expert Group. 使用局部硅胶治疗异常疤痕的现实世界管理:专家共识和来自亚洲疤痕专家组的病例系列。
Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-07-03 eCollection Date: 2023-01-01 DOI: 10.7573/dic.2023-4-3
Xiaonan Yang, Visnu Lohsiriwat, Frank Chun Shin Chang, Tan Thiam Chye, Catherine J Howard, Liang Qiao, Steven W Shaw, Tu Nguyen Anh Tran, Chan Yung, Daniel Dellosa, Dinesh Nagrale

Preventing abnormal scar formation and correcting non-aesthetic mature scars are important to prevent physical and psychosocial consequences of abnormal scarring. Evidence-based guidelines for scar management in Asian patients recommend first-line silicone-based products. Dermatix®* Ultra and Dermatix Ultra Kids are topical silicone gels containing a vitamin C ester that helps lighten scar tissue. Herein, we report a case series including patients with hypertrophic and keloid scars treated with Dermatix, showing that Dermatix is effective for scar treatment and prevention, as well as expert consensus supporting the safe and effective use of Dermatix.

预防异常疤痕形成和纠正非美学成熟疤痕对于防止异常疤痕的生理和心理后果是重要的。亚洲患者疤痕管理循证指南推荐一线硅基产品。Dermatix®* Ultra和Dermatix Ultra Kids是含有维生素C酯的局部硅胶凝胶,有助于减轻疤痕组织。在此,我们报告了一个病例系列,包括使用Dermatix治疗增生性和瘢痕疙瘩疤痕的患者,表明Dermatix对疤痕治疗和预防有效,以及专家共识支持安全有效地使用Dermatix。
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引用次数: 0
Changes in nasal, pharyngeal and salivary secretory IgA levels in patients with COVID-19 and the possibility of correction of their secretion using combined intranasal and oral administration of a pharmaceutical containing antigens of opportunistic microorganisms. COVID-19 患者鼻腔、咽部和唾液分泌型 IgA 水平的变化,以及使用含有机会性微生物抗原的药物联合鼻腔和口腔给药纠正其分泌的可能性。
Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-06-12 eCollection Date: 2023-01-01 DOI: 10.7573/dic.2022-10-4
Mikhail Kostinov, Oksana Svitich, Alexander Chuchalin, Natalya Abramova, Valery Osiptsov, Ekaterina Khromova, Dmitry Pakhomov, Vitaly Tatevosov, Anna Vlasenko, Vilia Gainitdinova, Kirill Mashilov, Nadezhda Kryukova, Irina Baranova, Anton Kostinov
<p><strong>Background: </strong>Although extensive research has been conducted on the role of local immunity in patients with SARS-CoV-2, little is known about the production and concentrations of secretory IgA (SIgA) in different mucosal compartments. This article aims to assess the secretion of SIgA in the nasal and pharyngeal compartments and saliva of patients with COVID-19 and to investigate the possibility and efficiency of correction of their secretion using combined intranasal and oral administration of a pharmaceutical containing antigens of opportunistic microorganisms.</p><p><strong>Methods: </strong>This study included 78 inpatients, aged between 18 and 60 years, who had confirmed COVID-19 with moderate lung involvement. The control group (<i>n</i>=45) received basic therapy, and the treatment group (<i>n</i>=33) was additionally administered the bacteria-based pharmaceutical Immunovac VP4 from day 1 to day 10 of hospitalization. SIgA levels were measured by ELISA at baseline and on days 14 and 30.</p><p><strong>Results: </strong>No systemic or local reactions associated with Immunovac VP4 were reported. We observed a statistically significant reduction in the duration of fever and hospitalization in patients who received Immunovac VP4 compared with those from the control group (<i>p</i>=0.03 and <i>p</i>=0.05, respectively). Changes over time in SIgA levels in nasal swabs were found to be significantly different in the two treatment groups (F=7.9, <i>p</i>[78.0]<0.001). On day 14 of observation, patients in the control group showed a statistically significant reduction in SIgA levels from baseline (<i>p</i>=0.02), whereas patients in the Immunovac VP4 group had stable SIgA levels (<i>p</i>=0.07). On day 30 after the start of treatment, there was a statistically significant increase in SIgA levels in the Immunovac VP4 group compared with baseline (from 77.7 (40.5-98.7) μg/L to 113.4 (39.8-156.7) μg/L; <i>p</i>=0.05) and the levels measured on day 14 (from 60.2 (23.3-102.9) μg/L to 113.4 (39.8-156.7) μg/L; <i>p</i>=0.03). The control group showed a statistically significant decrease in levels of nasal SIgA (to 37.3) on day 30 (<i>p</i>=0.007 for comparison with baseline values and <i>p</i>=0.04 for comparison with levels measured on day 14). Changes over time in SIgA levels measured in pharyngeal swabs were also different between the two treatment groups, and this difference reached statistical significance (F=6.5, <i>p</i>[73.0]=0.003). In the control group, this parameter did not change throughout the study (<i>p</i>=0.17 for a comparison between the levels measured on day 14 and the baseline values, and <i>p</i>=0.12 for a comparison between the levels measured on day 30 and the baseline values). In the Immunovac VP4 group, there was a statistically significant increase from baseline in SIgA levels on study day 30: from 1.5 (0.2-16.5) μg/L to 29.8 (3.6-106.8) μg/L (<i>p</i>=0.02). Changes over time in salivary SIgA did not show a si
背景:尽管对 SARS-CoV-2 患者局部免疫的作用进行了广泛的研究,但对不同粘膜区分泌型 IgA(SIgA)的产生和浓度却知之甚少。本文旨在评估 COVID-19 患者鼻腔、咽部和唾液中分泌的 SIgA,并研究使用含有机会性微生物抗原的药物联合鼻腔和口腔给药纠正其分泌的可能性和效率:这项研究包括78名确诊为COVID-19并中度肺部受累的住院病人,年龄在18至60岁之间。对照组(45 人)接受基本治疗,治疗组(33 人)在住院第 1 天至第 10 天期间额外服用细菌药物 Immunovac VP4。在基线、第14天和第30天,用酶联免疫吸附法测定SIgA水平:结果:未发现与 Immunovac VP4 相关的全身或局部反应。我们观察到,与对照组相比,接受Immunovac VP4治疗的患者发烧和住院时间明显缩短(分别为p=0.03和p=0.05)。鼻拭子中的SIgA水平随时间的变化在两个治疗组中有显著差异(F=7.9,p[78.0]p=0.02),而Immunovac VP4组患者的SIgA水平稳定(p=0.07)。在治疗开始后的第 30 天,Immunovac VP4 组的 SIgA 水平与基线(从 77.7 (40.5-98.7) μg/L 升至 113.4 (39.8-156.7) μg/L;p=0.05)和第 14 天测量的水平(从 60.2 (23.3-102.9) μg/L 升至 113.4 (39.8-156.7) μg/L;p=0.03)相比有显著的统计学增长。对照组的鼻腔 SIgA 水平在第 30 天出现了统计学意义上的显著下降(降至 37.3)(与基线值相比,p=0.007;与第 14 天测量的水平相比,p=0.04)。咽拭子中测得的 SIgA 水平随时间的变化在两个治疗组之间也存在差异,而且这种差异具有统计学意义(F=6.5,p[73.0]=0.003)。在对照组中,这一参数在整个研究期间没有变化(第 14 天测量的水平与基线值比较,p=0.17;第 30 天测量的水平与基线值比较,p=0.12)。在 Immunovac VP4 组,研究第 30 天的 SIgA 水平与基线值相比有显著的统计学增长:从 1.5(0.2-16.5)微克/升增至 29.8(3.6-106.8)微克/升(p=0.02)。研究组之间唾液 SIgA 随时间的变化没有显著差异(F=0.3,p[66.3]=0.75):结论:作为联合疗法的一部分,基于细菌的免疫刺激剂 Immunovac VP4 可提高鼻腔和咽部的 SIgA 水平,并诱导临床症状改善。诱导粘膜免疫是预防呼吸道感染的核心,尤其是对 COVID-19 后综合征患者而言。
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引用次数: 0
Management of non-alcoholic fatty liver disease incidentally detected during other medical assessments. 管理在其他医疗评估中偶然发现的非酒精性脂肪肝。
Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-05-11 eCollection Date: 2023-01-01 DOI: 10.7573/dic.2023-1-3
Yeong Yeh Lee, Vincent Tee

Elevated liver enzyme levels are a frequent incidental finding in primary care, and non-alcoholic fatty liver disease is the main cause of incidental elevation of liver enzymes worldwide. The features of the disease vary from simple steatosis, characterized by a benign prognosis, to non-alcoholic steatohepatitis and cirrhosis, increasing morbidity and mortality. In this case report, abnormal liver activity was incidentally detected during other medical assessments. The patient was treated with silymarin 140 mg three times daily, resulting in decreased serum liver enzyme levels over treatment with a good safety profile. This article is part of the Current clinical use of silymarin in the treatment of toxic liver diseases: a case series Special Issue: https://www.drugsincontext.com/special_issues/current-clinical-use-of-silymarin-in-the-treatment-of-toxic-liver-diseases-a-case-series.

肝酶水平升高是初级保健中经常出现的偶然发现,而非酒精性脂肪肝是全球肝酶偶然升高的主要原因。该病的特征各不相同,从以良性预后为特征的单纯脂肪变性,到增加发病率和死亡率的非酒精性脂肪性肝炎和肝硬化。在本病例报告中,肝脏活动异常是在其他医疗评估中偶然发现的。患者接受了水飞蓟素 140 毫克、每日三次的治疗,结果治疗期间血清肝酶水平下降,安全性良好。本文是《水飞蓟素在治疗中毒性肝病中的临床应用:病例系列》特刊的一部分:https://www.drugsincontext.com/special_issues/current-clinical-use-of-silymarin-in-the-treatment-of-toxic-liver-diseases-a-case-series。
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引用次数: 0
The expanding scenario of advanced non-small-cell lung cancer between emerging evidence and clinical tasks. 晚期非小细胞肺癌在新证据和临床任务之间不断扩展。
Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-05-02 eCollection Date: 2023-01-01 DOI: 10.7573/dic.2022-11-4
Andrea De Giglio, Biagio Ricciuti, Giulio Metro

This Editorial by De Giglio, Ricciuti and Metro introduces the series Treatment of advanced non-small-cell lung cancer: one size does not fit all: https://www.drugsincontext.com/special_issues/treatment-of-advanced-non-small-cell-lung-cancer-one-size-does-not-fit-all/.

这篇由 De Giglio、Ricciuti 和 Metro 撰写的社论介绍了晚期非小细胞肺癌的治疗系列:不能一刀切:https://www.drugsincontext.com/special_issues/treatment-of-advanced-non-small-cell-lung-cancer-one-size-does-not-fit-all/。
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引用次数: 0
COVID-19 therapy and vaccination: a clinical narrative review. COVID-19 治疗和疫苗接种:临床叙述性综述。
Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-02-07 eCollection Date: 2023-01-01 DOI: 10.7573/dic.2022-7-2
Siddharth Chinta, Miguel Rodriguez-Guerra, Mohammed Shaban, Neelanjana Pandey, Maria Jaquez-Duran, Timothy J Vittorio

The SARS-CoV-2 pandemic is the most globally impacting health issue our world has faced over the last century. As of January 7, 2022, around 300 million cases have been reported worldwide, with over 5 million deaths. The SARS-CoV-2 infection causes a hyperactive host immune response leading to an excessive inflammatory reaction with the release of many cytokines - cytokine storm - commonly noticed in acute respiratory distress syndrome, sepsis and fulminant multiorgan failure. Since the beginning of the pandemic, the scientific medical community has worked on therapeutic procedures that interfere with the exaggerated immune response. Thromboembolic complications are widespread in patients who are critically ill with COVID-19. Anticoagulant therapy was initially considered a cornerstone in hospitalized patients and even in the early post-discharge period; however, later trials have aborted the clinical benefits except for suspicion of or confirmed thrombosis. Immunomodulatory therapies are still crucial in moderate to severe COVID-19. Immunomodulator therapies include various medications from steroids to hydroxychloroquine, tocilizumab and Anakinra. Anti-inflammatory agents, vitamin supplements and antimicrobial therapy had initial encouraging evidence, but there are limited data to review. Convalescent plasma, immunoglobulins, eculizumab, neutralizing IgG1 monoclonal antibodies and remdesivir have positively impacted inpatient mortality and hospital length of stay. Eventually, wide population vaccination was proven to be the best tool to overcome the SARS-CoV-2 pandemic and help humanity return to regular life. Many vaccines and various strategies have been used since December 2020. This review discusses how the SARS-CoV-2 pandemic has progressed and surged, and summarizes the safety and efficacy of the most used therapies and vaccines in the light of recent evidence.

SARS-CoV-2 大流行是我们这个世界在上个世纪面临的最具全球性影响的健康问题。截至 2022 年 1 月 7 日,全球已报告约 3 亿病例,死亡人数超过 500 万。SARS-CoV-2 感染会引起宿主免疫反应亢进,导致过度炎症反应,释放多种细胞因子--细胞因子风暴--常见于急性呼吸窘迫综合征、败血症和暴发性多器官功能衰竭。自大流行病开始以来,医学科学界一直在研究干扰过度免疫反应的治疗程序。在 COVID-19 重症患者中,血栓栓塞并发症非常普遍。抗凝疗法最初被认为是住院病人甚至出院后早期治疗的基石;然而,除了怀疑或确诊血栓形成的情况外,后来的试验都放弃了抗凝疗法的临床益处。免疫调节疗法对于中度至重度 COVID-19 仍至关重要。免疫调节疗法包括从类固醇到羟氯喹、妥西珠单抗和 Anakinra 等各种药物。抗炎药物、维生素补充剂和抗菌疗法的初步证据令人鼓舞,但可供回顾的数据有限。康复血浆、免疫球蛋白、依库珠单抗、中和 IgG1 单克隆抗体和雷米替韦对住院病人死亡率和住院时间产生了积极影响。最终,广泛接种疫苗被证明是战胜 SARS-CoV-2 大流行并帮助人类恢复正常生活的最佳工具。自 2020 年 12 月以来,已经使用了许多疫苗和各种策略。本综述讨论了 SARS-CoV-2 大流行是如何发展和蔓延的,并根据最新证据总结了最常用疗法和疫苗的安全性和有效性。
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引用次数: 0
The multimodal management of patients with tendinopathy: percutaneous electrolysis, nutraceuticals and lifestyle – report from the 2022 I.S.Mu.L.T. Congress 肌腱病变患者的多模式管理:经皮电解、营养药品和生活方式——来自2022年i.s.m.u.l.t的报告。国会
Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-01-09 DOI: 10.7573/dic.2022-9-1
M. Di Gesù, D. Tiso
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引用次数: 0
Emerging concepts in heart failure management and treatment: focus on SGLT2 inhibitors in heart failure with preserved ejection fraction. 心力衰竭管理和治疗的新概念:聚焦射血分数保留型心力衰竭中的 SGLT2 抑制剂。
Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-01-04 eCollection Date: 2023-01-01 DOI: 10.7573/dic.2022-7-1
Andrea Beatriz De Lorenzi, Edgardo Kaplinsky, Marx Rivera Zambrano, Laia Tomás Chaume, Joan Monell Rosas

The role of sodium-glucose cotransporter 2 inhibitors (SLTG2i), developed initially as glucose-lowering agents, has represented a novelty in patients with heart failure (HF) and reduced ejection fraction (HFrEF) since dapagliflozin (DAPA-HF study) and empagliflozin (EMPEROR-Reduced study) were able to reduce morbidity and mortality in this setting regardless of the presence or absence of diabetes. In previous large clinical trials (EMPA-REG OUTCOME study, CANVAS, DECLARE-TIMI 58), SGLT2i have been shown to attenuate HF progression expressed by reducing the risk of HF hospitalizations in patients with type 2 diabetes mellitus mostly without HF at baseline. This benefit was then corroborated with positive results in HF outcomes (cardiovascular mortality and HF hospitalizations) in patients with HF with preserved ejection fraction (HFpEF) in the EMPEROR-Preserved (empagliflozin) and DELIVER (dapagliflozin) trials. Several biological mechanisms apart from the glycosuria are attributed to these agents in this last context, including anti-inflammatory effects, reduction of fibrosis and apoptosis, improvement of myocardial metabolism, mitochondrial function optimization, and oxidative stress protection. Moreover, SGLT2i can also improve ventricular loading conditions by forcing diuresis and natriuresis, and by enhancing vascular and renal function. In addition, SGLT2i can reduce myocardial passive stiffness (diastolic function) by enforcing the phosphorylation of myofilament modulatory proteins. This article provided an overview of the main pathophysiological characteristics of HFpEF and of the diverse mechanisms of action of SGLT2i in this setting. The supporting clinical evidence of SGLT2i in HFpEF (EMPEROR-Preserved and DELIVER trials) is also reviewed. This article is part of the Emerging concepts in heart failure management and treatment Special Issue: https://www.drugsincontext.com/special_issues/emerging-concepts-in-heart-failure-management-and-treatment.

钠-葡萄糖共转运体 2 抑制剂(SLTG2i)最初是作为降糖药物开发的,在心力衰竭(HF)和射血分数降低(HFrEF)患者中发挥了新的作用,因为无论患者是否患有糖尿病,达帕格列净(DAPA-HF 研究)和恩帕格列净(EMPEROR-Reduced 研究)都能在这种情况下降低发病率和死亡率。在之前的大型临床试验(EMPA-REG OUTCOME 研究、CANVAS、DECLARE-TIMI 58)中,SGLT2i 已被证明可以通过降低 2 型糖尿病患者(大多基线时无 HF)的 HF 住院风险来减轻 HF 进展。EMPEROR-Preserved(empagliflozin)和DELIVER(dapagliflozin)试验中,射血分数保留型心房颤动(HFpEF)患者的心房颤动结果(心血管死亡率和心房颤动住院率)也证实了这一益处。在这种情况下,除了糖尿之外,这些药物还具有多种生物机制,包括抗炎作用、减少纤维化和细胞凋亡、改善心肌代谢、优化线粒体功能和保护氧化应激。此外,SGLT2i 还能通过强制利尿和利钠以及增强血管和肾功能来改善心室负荷状况。此外,SGLT2i 还能通过加强肌丝调节蛋白的磷酸化,降低心肌被动僵硬度(舒张功能)。本文概述了高频心衰的主要病理生理学特征以及 SGLT2i 在这种情况下的不同作用机制。文章还回顾了 SGLT2i 在高频心衰中的辅助临床证据(EMPEROR-Preserved 和 DELIVER 试验)。本文是心力衰竭管理和治疗新概念特刊:https://www.drugsincontext.com/special_issues/emerging-concepts-in-heart-failure-management-and-treatment 的一部分。
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引用次数: 0
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