Evidence-based expert consensus on clinical management of safety of Bruton’s tyrosine kinase inhibitors(2024)

Bruton’s tyrosine kinase inhibitors(BTKis)have revolutionized the treatment of B-cell lymphomas.However,safety issues related to the use of BTKis may hinder treatment continuity and further affect clinical efficacy.A comprehensive and systematic expert consensus from a pharmacological perspective is lacking for safety issues associated with BTKi treatment.A multidisciplinary consensus working group was established,comprising 35 members from the fields of hematology,cardiovascular disease,cardio-oncology,clinical pharmacy,and evidencebased medicine.This evidence-based expert consensus was formulated using an evidence-based approach and the Delphi method.The Joanna Briggs Institute Critical Appraisal(JBI)tool and Grading of Recommendations Assessment,Development,and Evaluation(GRADE)approach were used to rate the quality of evidence and grade the strength of recommendations,respectively.This consensus provides practical recommendations for BTKis medication based on nine aspects within three domains,including the management of common adverse drug events such as bleeding,cardiovascular events,and hematological toxicity,as well as the management of drug-drug interactions and guidance for special populations.This multidisciplinary expert consensus could contribute to promoting a multi-dimensional,comprehensive and standardized management of BTKis.

Electroacupuncture targeting the immune system to alleviate sepsis

Sepsis is a life-threatening inflammatory syndrome with high morbidity and mortality rates.However,options for sepsis are still limited to general treatment in intensive care units(ICUs),and effective therapies that improve sepsis survival are required.Immune disturbances play a vital role in the pathology of sepsis and are associated with protracted inflammation,susceptibility to infections,and death.Therefore,many investigators have focused on the potential benefits of immunomodulation therapy for sepsis.Electroacupuncture(EA)has been practiced in clinics for many years and has shown advantages in treating infectious diseases.Over the last few decades,our understanding of the efficacy and mechanisms of EA in sepsis has undergone considerable developments.We searched the literature regarding“CNKI,Wan Fang Data,VIP Database,PubMed,and Ingenta Connect”from 2010 to 2023,using the keywords“sepsis”“septic”and“electroacupuncture”and 336 sources were searched.Finally,we included 82 studies that targeted the immune system to determine EA’s anti-inflammatory and immunomodulatory effects on sepsis.In this review,we found that EA has clinical benefits in relieving septic inflammation,improving immune function,and attenuating related multi-organ injury through several mechanisms,such as activation of the cholinergic anti-inflammatory pathway(CAP),vagaladrenal axis,inhibition of the nuclear factor Kappa-B(NF-κB)signaling pathway,signal transducers and activators of transcription(STAT)signaling pathway,and improvement of immune cell function.Therefore,EA may be a promising complementary therapy for sepsis treatment.We also expect these data will contribute to further studies on EA in sepsis.

Auricular vagus nerve acupressure for patients with emotional distress under the COVID-19 pandemic:A smartphone-based,randomized controlled trial

Objective: To confirm whether self-administered AVNA treatment is effective in improving emotional distressunder the COVID-19 pandemic.Methods: A smartphone-based online, randomized, controlled trial was designed from 26 February 2020 to 28April 2020 in four study sites, including Wuhan, Beijing, Shenyang, and Guangzhou of China. Local residentswho had considerable emotional distress with a score of the Hospital Anxiety and Depression Scale (HADS) ≥9 were recruited. Participants were randomly assigned to three times of AVNA (n = 191) per day, in morning,around noon, and in evening or usual care (UC, n = 215) once daily for 14 days. The primary outcome was theresponse rate, which was the proportion of participants whose Hospital Anxiety and Depression Scale (HADS)score reduced from baseline by ≥ 50%. The assessment was conducted at baseline, 3 days, and 14 days.Results: The AVNA group had a markedly higher response rate than the UC group at 3 days (35.6% vs. 24.9%,P = 0.02) and at 14 days (70.7% vs. 60.6%, P = 0.02). The AVNA group showed significantly greater reductionin scores of HADS at the two measurement points and BAI at 3 days (P ≤ 0.03), with average respective effectsize of 0.217 and 0.195. Participants with AVNA spent less time falling asleep and rated their sleep qualitybeing remarkably higher than those with UC at endpoint.Conclusion: During COVID-19 pandemic period, treatment with self-administrated AVNA was more effectivethan UC in reducing emotional distress of isolated populations. These findings support self-administered AVNAas a treatment option for patients with emotional distress under the COVID-19 pandemic or other emergentevents.

Mechanism of acupuncture regulating visceral sensation and mobility

Chinese ancient medical scientists have long focused on the internal and external contacts between acupoints on the surface of the body and the viscera.The Miraculous Pivot(it is one of the earliest medical classics in China)stated,“Twelve regular channels belong to the zang-fu organs internally,and connect to the extremities and joints externally.”Traditional Chinese medicine considers acupoints as defined areas where the Qi of viscera and meridians are transfused.These include the reaction points of visceral diseases on the body surface as well as the acupuncture trigger points that promote the flow of Qi and blood,and regulate visceral function.Chinese ancient medical scientists classified the specificity of the main acupoints in the body based on the meridian doctrine,which has been instructing clinical application for about 2000 years.Laws on the domino effect of acupoints have mainly focused on conclusions to clinical experiences.Indications of some acupoints exceed the practical paradigm since the excessive extension occurred during theory derivation.The current research direction on acupuncture focuses on three aspects:the effectiveness of acupuncture and moxibustion;the relevances and associations between meridians and viscera;and the physical and chemical properties and relevant physical basis of acupoints.The relevance between meridians and viscera is the central theory in the meridian doctrine,and acupoints are regarded as an important link in the relationship between meridians and viscera.Specific relationships between acupoints and target organs exist.Stimulating different acupoints on the body surface can help deal with different diseases,especially visceral diseases.In addition,acupoints have a dual function of reflecting and treating visceral diseases.There is no systemic research available on acupoint specificity,despite current knowledge and clinical experiences,which results in a weak foundation for acupuncture theory.This study focuses on the relevance and associations between meridians and viscera.A summary of the mechanisms of acupuncture regulating visceral sensation and mobility and the specific relationships between acupoints and their target organs are presented in this review.

KaiA调控蓝藻生物钟的分子机制研究进展

蓝藻生物钟系统主要包括输入途径、核心振荡器和输出途径3部分,核心振荡器主要由时钟蛋白KaiA、KaiB、KaiC构成。3种蛋白之间的相互作用产生节律信号及调控输入、输出信号进而维持生物振荡的精确与稳定。文中围绕蓝藻生物钟核心振荡器及核心振荡器组成蛋白的结构、功能与相互作用特点,结合本实验室近期取得的研究成果,针对时钟蛋白KaiA调节KaiC的酶活性、介导核心振荡器的时相重置、与CikA竞争KaiB的结合位点等方面近年来的研究进展进行了综述。

蟛蜞菊内酯上调miR-190表达抑制高糖诱导的人视网膜血管内皮细胞凋亡

目的探讨蟛蜞菊内酯(WEL)对高糖(HG)诱导的人视网膜血管内皮细胞(HRECs)损伤的影响和分子机制。方法采用低(10μmol/L)、中(20μmol/L)、高(40μmol/L)剂量WEL(WEL-L、WEL-M、WEL-H)处理或miR-190模拟物/抑制剂转染HRECs后,用30mmol/L葡萄糖孵育HRECs24h建立细胞损伤模型。试剂盒检测细胞中活性氧(ROS)水平、超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量:流式细胞测量术分析细胞凋亡;RT-qPCR检测miR-190表达。采用独立样本t检验和单因素方差分析进行统计学差异比较。结果WEL-L、WEL-M、WEL-H处理可降低HG诱导的HRECs调亡率[(24.22±2.16)%、(17.17±1.19)%、(9.89±0.86)%比(31.67±3.02)%]、MDA含量、ROS水平,升高miR-190表达(0.42±0.04、0.59±0.04、0.72±0.06比0.28±0.03)和SOD活性(P<0.01)。过表达miR-190降低HG诱导的HRECs调亡率[(12.98±1.06)%比(32.28±3.03)%]、MDA含量、ROS水平,增高SOD活性(P<0.01)。下调miR-190逆转了WEL对HG诱导的HRECs调亡率[(25.57±2.49)%比(9.79±0.87)%]、MDA含量、ROS水平及SOD活性的影响(P<0.01)。结论蟛蜞菊内酯减轻HG诱导的HRECs氧化应激损伤和凋亡,其机制与上调miR-190有关。