Genetic diseases are not necessarily inherited: suggestion on its Chinese translation.

From Mendel's discovery of the basic laws of genetics in 1865 to the widespread application of genomics in medicine today, medical genetics has made enormous progress, and the concept of genetic diseases has also been evolved. In 1972, the World Health Organization (WHO) expert group began to use "Genetic Disease" to define hereditary diseases, while early Chinese genetics textbooks used "inferior inheritance", and later introduced terms such as "Genetic Disease" and "Inherited Disease". In the early days, it was generally believed that genetic diseases were inherited from ancestors. However, research in recent years has found that genetic diseases are not necessarily inherited, and some diseases are actually caused by de novo mutations in the offspring. Although the occurrence of this type of genetic disease is related to genetic factors, it is not inherited from ancestors. If we still use "Inherited Disease" or "Hereditary Disease" to describe it, it is not accurate enough. In order to further standardize the translation and use of the concept of "Genetic Disease", this article briefly reviews its development process in both English and Chinese literature, discusses the difference between different Chinese translations, and provides guidance and suggestions for scientifically and accurately describing genetic diseases in Chinese, with a view to promote efficient exchange and cooperation in the field of medical genetics.

Adaptor protein HIP-55 promotes macrophage M1 polarization through promoting AP-1 complex activation.

Overwhelming macrophage M1 polarization induced by malfunction of the renin-angiotensin-aldosterone system (RAAS) initiates inflammatory responses, which play a crucial role in various cardiovascular diseases. However, the underlying regulatory mechanism remains elusive. Here, we identified adaptor protein HIP-55 as a critical regulator of macrophage M1 polarization. The expression of HIP-55 was upregulated in M1 macrophage induced by Ang II. Overexpression of HIP-55 significantly promoted Ang II-induced macrophage M1 polarization, whereas genetic deletion of HIP-55 inhibited the Ang II-induced macrophage M1 polarization. Mechanistically, HIP-55 facilitated activator protein-1 (AP-1) complex activation induced by Ang II via promoting ERK1/2 and JNK phosphorylation. Moreover, blocking AP-1 complex activation can attenuate the function of HIP-55 in macrophage polarization. Collectively, our results reveal the role of HIP-55 in macrophage polarization and provide potential therapeutic insights for cardiovascular diseases associated with RAAS dysfunction.

Effect of sodium-glucose cotransporter-2 inhibitors on myocardial infarction incidence: A systematic review and meta-analysis of randomized controlled trials and cohort studies.

AIM: To assess whether sodium-glucose cotransporter-2 (SGLT2) inhibitors reduce myocardial infarction (MI) incidence in patients with or without type 2 diabetes. METHODS: PubMed, Embase, Web of Science, the Cochrane library, and https://ClinicalTrials.gov were searched up to 7 May 2022. Randomized controlled trials (RCTs) and cohort studies reporting the effects of SGLT2 inhibitor treatment on MI incidence were included. Relative risks (RRs) with a 95% confidence interval (CI) for MI incidence were extracted and pooled. Subgroup analysis and meta-regression were performed to explore the heterogeneity. RESULTS: This meta-analysis included 54 RCTs and 32 cohort studies, with data from six SGLT2 inhibitors and 3 394 423 individuals. In the overall analysis, SGLT2 inhibitors significantly reduced MI incidence in RCTs (RR 0.9, 95% CI 0.84-0.96) and cohort studies (RR 0.89, 95% CI 0.83-0.94). In RCTs, the results of the subgroup analysis revealed no significant alterations in outcomes based on different SGLT2 inhibitor types, control drug types, cardiovascular disease (CVD) status and sources of outcome extraction (p for interaction >0.05). In cohort studies, the presence or absence of CVD led to similar effects of SGLT2 inhibitors on decreasing MI incidence (p for interaction = 0.179). However, variations in results were observed based on the type of control group in cohort studies (p for interaction = 0.036). Meta-regression results did not reveal an association between baseline cardiovascular risk factors, follow-up length, or MI incidence. CONCLUSIONS: In both RCTs and cohort studies, SGLT2 inhibitors reduced MI incidence. The cardioprotective effects of SGLT2 inhibitors were observed in patients with and without a history of CVD.

Status and Quality of Guidelines for Therapeutic Drug Monitoring Based on AGREE II Instrument.

BACKGROUND: With the progress of therapeutic drug monitoring (TDM) technology and the development of evidence-based medicine, many guidelines were developed and implemented in recent decades. OBJECTIVE: The aim was to evaluate the current status of TDM guidelines and provide suggestions for their development and updates based on Appraisal of Guidelines for Research and Evaluation (AGREE) II. METHODS: The TDM guidelines were systematically searched for among databases including PubMed, Embase, China National Knowledge Infrastructure, Wanfang Data, and the Chinese biomedical literature service system and the official websites of TDM-related associations. The search period was from inception to 6 April 2023. Four researchers independently screened the literature and extracted data. Any disagreement was discussed and reconciled by another researcher. The quality of guidelines was assessed using the AGREE II instrument. RESULTS: A total of 92 guidelines were included, including 57 technical guidelines, three management guidelines, and 32 comprehensive guidelines. The number of TDM guidelines has gradually increased since 1979. The United States published the most guidelines (20 guidelines), followed by China (15 guidelines) and the United Kingdom (ten guidelines), and 23 guidelines were developed by international organizations. Most guidelines are aimed at adult patients only, while 28 guidelines include special populations. With respect to formulation methods, there are 23 evidence-based guidelines. As for quality evaluation results based on AGREE II, comprehensive guidelines scored higher (58.16%) than technical guidelines (51.36%) and administrative guidelines (50.00%). CONCLUSION: The number of TDM guidelines, especially technical and comprehensive ones, has significantly increased in recent years. Most guidelines are confronted with the problems of unclear methodology and low quality of evidence according to AGREE II. More evidence-based research on TDM and high-quality guideline development is recommended to promote individualized therapy.

Effects of ß-blockers on all-cause mortality in patients with diabetes and coronary heart disease: A systematic review and meta-analysis.

Beta-blockers have been considered as an effective treatment in secondary prevention of coronary heart disease (CHD). However, there is still disputed whether ß-blockers can increase all-cause mortality in patients with coronary heart disease and diabetes mellitus (DM). Here, our systematic review and meta-analysis is aiming to assess the effects of ß-blockers on all-cause mortality in patients with coronary heart disease and diabetes mellitus. Four databases (PubMed, Embase, Cochrane Library and Web of Science) and other sources were searched to collect randomized controlled trials (RCTs) and cohort studies related to the treatment of ß-blockers for coronary heart disease and diabetes mellitus patients. We further evaluated quality of evidence using the grading of recommendations assessment, development, and evaluation (GRADE) approach. Finally, a total of 16,188 records were identified, and four randomized controlled trials and six cohort studies (206,490 patients) were included. Random effects analysis revealed that ß-blockers combined with routine treatment (RT) significantly decreased all-cause mortality in patients with coronary heart disease and diabetes mellitus compared with RT in control group (RR 0.59, 95% CI 0.47 to 0.75; p < 0.000 01; I2 = 72%). Subgroup analysis of all-cause mortality by the subtype of diabetes mellitus and definite MI patients (RR 0.54, 95% CI 0.45 to 0.65, p < 0.000 01, I2 = 29%) and the subtype of randomized controlled trials (RR 0.49, 95% CI 0.32 to 0.76, p = 0.001, I2 = 0%) indicated a relatively small heterogeneity and stable results. ß-blockers application significantly reduced cardiovascular death as well (RR 0.56, 95% CI 0.42 to 0.74; p < 0.000 1; I2 = 0%). Our meta-analysis provided critical evidence of ß-blockers treatment for patients with coronary heart disease (especially MI type) and diabetes mellitus, and discussed the advantages and potential metabolic risks for the clinical use of ß-blockers. This study suggested that ß-blockers application may improve all-cause mortality and cardiovascular death in coronary heart disease (especially MI type) and diabetes mellitus patients. However, given a small number of included studies, the aforementioned conclusion should be confirmed in a multi-center, large-scale, and strictly designed trial.