Serological response and immune-related adverse events following COVID-19 vaccination in cancer patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis.

With the popularity of Coronavirus disease 2019 (COVID-19) vaccine and the development of vaccination strategies, the impact of COVID-19 vaccine on cancer patients receiving immune checkpoint inhibitors (ICIs) is still unclear. In the systematic review and meta-analysis of patients with ICIs, we assessed the serological response of cancer patients receiving COVID-19 vaccine, and explored the risk of immune related adverse events (irAEs). We searched PubMed, EMBASE and Cochrane Library as of 10 June 2023, and included cancer patients who received ICIs and COVID-19 vaccine. The systematic review and meta-analysis include cohort study, cross-sectional study and case report. The outcome included the serological response, Spike-specific T-cell response, irAEs and rare adverse events. When possible, the data were analysed by random effect analysis, and the statistical heterogeneity was assessed by Q-test and I2 statistics. We explored the sources of heterogeneity through L'Abbe plots, Galbraith radial plots, and sensitivity analysis. The publication bias was evaluated by Egger's, Begg's linear regression test and funnel plot, and the impact of publication bias was further analysed by trim and fill method. 27 studies were eligible (19 cohort studies, 1 cross-sectional study and 7 case reports), involving 8331 patients (with 4724 receiving ICIs). Most studies used mRNA vaccine (BNT162b2 or mRNA-1273). Compared with cancer patients receiving chemotherapy, cancer patients receiving ICIs were significantly more likely to have seroconversion (RR = 1.05, 95%CI 1.01-1.10, P = 0.02). There were no statistically significant differences in seroconversion rates when comparing cancer patients receiving ICIs with controls without cancer (RR = 0.95, 95% CI 0.89-1.01, P = 0.09) or with cancer patients receiving targeted therapy (RR = 1.05, 95% CI 0.79-1.39, P = 0.75). The incidence of irAEs in patients receiving ICIs before and after COVID-19 vaccination was (21.96%, 95%CI 16.66%-28.94%) and (14.88%, 95%CI 8.65%-25.57%), respectively. The most common irAEs were endocrine abnormalities, skin disorders, etc. The certainty of evidence was low in cancer patients with ICIs, compared with those receiving chemotherapy, and very low versus controls without cancer. Cancer patients treated with ICIs seem to be able to receive COVID-19 vaccine safely without increasing the incidence of irAEs.

Targeting mitochondrial quality control for diabetic cardiomyopathy: Therapeutic potential of hypoglycemic drugs.

Diabetic cardiomyopathy is a chronic cardiovascular complication caused by diabetes that is characterized by changes in myocardial structure and function, ultimately leading to heart failure and even death. Mitochondria serve as the provider of energy to cardiomyocytes, and mitochondrial dysfunction plays a central role in the development of diabetic cardiomyopathy. In response to a series of pathological changes caused by mitochondrial dysfunction, the mitochondrial quality control system is activated. The mitochondrial quality control system (including mitochondrial biogenesis, fusion and fission, and mitophagy) is core to maintaining the normal structure of mitochondria and performing their normal physiological functions. However, mitochondrial quality control is abnormal in diabetic cardiomyopathy, resulting in insufficient mitochondrial fusion and excessive fission within the cardiomyocyte, and fragmented mitochondria are not phagocytosed in a timely manner, accumulating within the cardiomyocyte resulting in cardiomyocyte injury. Currently, there is no specific therapy or prevention for diabetic cardiomyopathy, and glycemic control remains the mainstay. In this review, we first elucidate the pathogenesis of diabetic cardiomyopathy and explore the link between pathological mitochondrial quality control and the development of diabetic cardiomyopathy. Then, we summarize how clinically used hypoglycemic agents (including sodium-glucose cotransport protein 2 inhibitions, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, thiazolidinediones, metformin, and α-glucosidase inhibitors) exert cardioprotective effects to treat and prevent diabetic cardiomyopathy by targeting the mitochondrial quality control system. In addition, the mechanisms of complementary alternative therapies, such as active ingredients of traditional Chinese medicine, exercise, and lifestyle, targeting mitochondrial quality control for the treatment of diabetic cardiomyopathy are also added, which lays the foundation for the excavation of new diabetic cardioprotective drugs.

Efficacy and safety of non-pharmacological therapy under the guidance of TCM theory in the treatment of anxiety in patients with myocardial infarction: A protocol for systematic review and meta-analysis.

BACKGROUND: With the increasing pressures of modern life and work, combined with a growing older population, the incidence of comorbid anxiety and myocardial infarction (MI) is increasing. Anxiety increases the risk of adverse cardiovascular events in patients with MI and significantly affects their quality of life. However, there is an ongoing controversy regarding the pharmacological treatment of anxiety in patients with MI. The concomitant use of commonly prescribed selective serotonin reuptake inhibitors (SSRIs) and antiplatelet medications such as aspirin and clopidogrel may increase the risk of bleeding. Conventional exercise-based rehabilitation therapies have shown limited success in alleviating anxiety symptoms. Fortunately, non-pharmacological therapies based on traditional Chinese medicine (TCM) theory, such as acupuncture, massage, and qigong, have demonstrated promising efficacy in treating MI and comorbid anxiety. These therapies have been widely used in community and tertiary hospital settings in China to provide new treatment options for patients with anxiety and MI. However, current studies on non-pharmacological TCM-based therapies have predominantly featured small sample sizes. This study aims to comprehensively analyze and explore the effectiveness and safety of these therapies in treating anxiety in patients with MI. METHOD: We will systematically search six English and four Chinese databases by employing a pre-defined search strategy and adhering to the unique rules and regulations of each database to identify studies that fulfilled our inclusion criteria, to qualify for inclusion, patients must be diagnosed with both MI and anxiety, and they must have undergone non-pharmacological TCM therapies, such as acupuncture, massage, or qigong, whereas the control group received standard treatments. The primary outcome measure will be alterations in anxiety scores, as assessed using anxiety scales, with secondary outcomes encompassing the evaluations of cardiopulmonary function and quality of life. We will utilize RevMan 5.3 to conduct a meta-analysis of the collected data, and subgroup analyses will be executed based on distinct types of non-pharmacological TCM therapies and outcome measures. RESULTS: A narrative summary and quantitative analysis of the existing evidence on the treatment of anxiety patients with MI using non-pharmacological therapies guided by Traditional Chinese Medicine theory. CONCLUSION: This systematic review will investigate whether non-pharmacological interventions guided by TCM theory are effective and safe for anxiety in patients with MI, and provide evidence-based support for their clinical application. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022378391.

Syn-Selective Chlorosulfonylation of Alkynes via a Copper-Powder-Initiated Atom Transfer Radical Addition Reaction and Mechanistic Studies.

Copper-powder-catalyzed syn-selective chlorosulfonylation of readily available alkynes by an atom transfer radical addition (ATAR) process has been developed, providing straightforward access to a broad range of (Z)-ß-chlorovinylsulfones in good yields under mild conditions. In addition, this method is ligand-free and features excellent stereoselectivity and high atom economy. Moreover, the product was obtained without an apparent loss of yield when the reaction was performed on the gram scale at a low catalyst loading. In this reaction, the copper powder not only acts as a sulfone radical initiator but also produces the catalytically active CuCl species. Mechanistic investigations and DFT calculation studies revealed that the stereoselectivity is controlled by the thermodynamic stabilities of the in situ-generated cyclic alkenyl CuII complex intermediate, which can serve as a chlorine atom transfer agent.

Targeting epigenetics in diabetic cardiomyopathy: Therapeutic potential of flavonoids.

The pathophysiological mechanisms of diabetic cardiomyopathy have been extensively studied, but there is still a lack of effective prevention and treatment methods. The ability of flavonoids to protect the heart from diabetic cardiomyopathy has been extensively described. In recent years, epigenetics has received increasing attention from scholars in exploring the etiology and treatment of diabetes and its complications. DNA methylation, histone modifications and non-coding RNAs play key functions in the development, maintenance and progression of diabetic cardiomyopathy. Hence, prevention or reversal of the epigenetic alterations that have occurred during the development of diabetic cardiomyopathy may alleviate the personal and social burden of the disease. Flavonoids can be used as natural epigenetic modulators in alternative therapies for diabetic cardiomyopathy. In this review, we discuss the epigenetic effects of different flavonoid subtypes in diabetic cardiomyopathy and summarize the evidence from preclinical and clinical studies that already exist. However, limited research is available on the potential beneficial effects of flavonoids on the epigenetics of diabetic cardiomyopathy. In the future, clinical trials in which different flavonoids exert their antidiabetic and cardioprotective effects through various epigenetic mechanisms should be further explored.

Oxidative dehydrogenation of hydrazines and diarylamines using a polyoxomolybdate-based iron catalyst.

We report an efficient method for the oxidative dehydrogenation of hydrazines and diarylamines in aqueous ethanol using Anderson-type polyoxomolybdate-based iron(iii) as a catalyst and hydrogen peroxide as an oxidant. A series of azo compounds and tetraarylhydrazines were obtained in moderate to excellent yields. The reaction conditions and substrate scopes are complementary or superior to those of more established protocols. In addition, the catalyst shows good stability and reusability in water. The preliminary mechanistic studies suggest that a radical process is involved in the reaction.