MedNexus
2025年 · 第11卷第02期
MedNexus
Substantial research has been conducted to identify an efficient treatment for Alzheimer's disease (AD). Existing treatments, including cholinesterase inhibitors and N-methyl D-aspartate (NMDA) receptor antagonists, do not reverse or slow the disease course but only treat its manifestations. This limitation has brought attention to the need for treatments that modify the amyloid-beta (Aβ) and tau pathology of the disease. One recent advancement in AD treatment is donanemab, a monoclonal antibody intended to clear Aβ plaques in the brain. It targets pyroglutamyl(3)-Aβ protein (3–42) to remove Aβ deposits and alter the disease course. This review explores the timeline of donanemab use from discovery to clinical use. The pharmacodynamics and pharmacokinetics of the drug are discussed along with typical and suboptimal preclinical and clinical trial results in terms of efficacy, safety, and tolerability. Thus, donanemab is more effective than donepezil and rivastigmine in removing plaques and improving cognition. At the same time, it is not devoid of safety concerns that are typical of the majority of amyloid-targeted medicines. The control to end the treatment after plaque cleaning is a unique selling point for some patients, making it more attractive. The innovation and development of donanemab from research to clinical practice are a clear representation of the role of the field of translational medicine in the practical application of new knowledge in the treatment of AD.
The prevalence of renal diseases and its associated burden on healthcare have tremendously risen in the past few years. From simple markers assessing kidney function, current renal research delves into understanding the diseases at the cellular and molecular levels and not just at treating, but at improving quality of life, arresting progression and providing personalized diagnostics and therapy. This narrative review highlights the improvements in diagnostic applications of kidney disease and briefly discusses a few notable biomarkers emphasizing the high throughput omics technologies, as well as contemporary perspectives on renal research. A thorough literature search was performed on PubMed, Scopus, Web of Science, and Medline. Suitable Mesh terms were included for the search strategy, and relevant evidence was documented. Language models and pharmacognosy, along with other omics strategies, impose a better understanding of the renal disease, and the remarkable discoveries of noninvasive biomarkers, urine 273-peptide classifier, and urine peptides-based fibrosis classifier have unraveled the associations between mechanistic studies and novel therapeutic drugs. Strides in biomarker research have been able to delineate stages and types with superior specificity and sensitivity, thereby providing a better diagnosis. Renal research reflects a powerful, dynamic, and multifaceted field that drives better advancements and discoveries in personalized medicine, drug interventions, and patient-centered outcomes. Understanding the tangled relationship of the etiology of kidney disease, these developments and future research hold promise for individuals affected by kidney diseases
Wearable technology in the management of chronic diseases has emerged as a significant and growing concern in healthcare. These technologies, including smartwatches, fitness trackers, and other sensor-based devices, offer continuous monitoring and real-time data collection for individuals with chronic conditions. The data collected can include vital signs, activity levels, sleep patterns, and more, providing valuable insights into a patient's health. This trend is particularly relevant in the context of chronic diseases, such as diabetes, cardiovascular conditions, and respiratory disorders, where continuous monitoring is crucial for effective management. Wearable devices empower patients to actively participate in their healthcare by facilitating self-monitoring and promoting healthy behaviors. Healthcare providers can also leverage the data generated by these devices to make informed decisions, personalize treatment plans, and intervene proactively. However, challenges exist, such as data security and privacy concerns, the accuracy of the collected information, and the need for effective integration into existing healthcare systems. Despite these challenges, the increasing adoption of wearable technology in chronic disease management reflects a promising avenue for improving patient outcomes and reducing healthcare costs through preventive and personalized care.
Statins are the first line of treatment for dyslipidemia, but their side effects often reduce medication compliance. Natto and red yeast rice are natural ingredients with lipid-lowering effects. However, the efficacy of Natto Red Yeast Rice (NRYR) supplement in combination with statins in regulating blood lipid levels has not been fully evaluated.
A multicenter, double-blinded, randomized-controlled trial was conducted among individuals with low-density lipoprotein cholesterol (LDL-C) of 3.4 to 5.0 mmol/L at six sites in China, of those at moderate risk of cardiovascular disease (CVD) are prioritized. Participants are enrolled and randomly assigned into four groups by a combination of NRYR (or its placebo) and Simvastatin (or its placebo) in a ratio of 1:1:1:1. After examination at baseline, all participants underwent intervention for 3 months and two follow-up visits at 1 month and 3 months after the intervention. The primary outcome is the change in LDL-C level at 3 months, and secondary outcomes include changes in levels of other lipid profiles and biomarkers, as well as calculated 10-year CVD risk. A total of 1136 participants were randomly assigned, of whom 1110 received the intervention.
This study may provide new evidence for the efficacy of NRYR supplement in combination with statins to regulate lipid levels and optimize lipid management.
Chinese Clinical Trial Registry database: registration nos. ChiCTR2200064214, ChiCTR2200064215.
The increasing incidence of inflammatory bowel disease (IBD) presents significant medical and societal challenges. A well-designed IBD database is crucial for both epidemiological studies and clinical management. However, inconsistencies between regional databases hinder cross-institutional and international research, especially between Eastern and Western societies.
We developed a new IBD database, the 301 IBD database, integrating the IBD clinical characteristics from the Penn IBD database (USA) and the latest IBD guidelines and consensus and clinical practices of the Chinese PLA General Hospital (PLAGH). We applied this database to analyze clinical data of IBD inpatients at PLAGH from 2008 to 2023.
The 301 IBD database contains 490 items in 6 sections including demographic characteristics, personal history, clinical phenotype, disease activity, laboratory tests and examinations, and treatment. Features of the 301 IBD database include inpatient focus, biochemical indicators and opportunistic infection focus, and more about ulcerative colitis (UC)-associated complications. Single-center analysis revealed an increasing hospitalization trend, from 2.35% in 2008 to 3.94% in 2023. We found that the clinical characteristics of our UC inpatients are predominantly male (62.5%), extensive lesions (55.1%), low usage of biologics (4.1%), and a high incidence of UC-CRC (3.0%). The clinical characteristics of CD inpatients included male predominance (68.39%), early onset age (35.43 ± 14.75-year-old), and high rate of surgery (25.81%).
The 301 IBD database, integrating Eastern and Western clinical data, provides a valuable tool for IBD clinical research. Future international, multicenter collaborations are expected to further enhance its utility.
Computer-aided detection (CAD) software has been introduced to automatically interpret digital chest X-rays. This study aimed to evaluate the performance of CAD software (JF CXR-1 v3.0, which was developed by a domestic Hi-tech enterprise) in tuberculosis (TB) case finding in China.
In 2019, we conducted an internal evaluation of the performance of JF CXR-1 v3.0 by reading standard images annotated by a panel of experts. In 2020, using the reading results of chest X-rays by a panel of experts as the reference standard, we conducted an on-site prospective study to evaluate the performance of JF CXR-1 v3.0 and local radiologists in TB case finding in 13 township health centers in Zhongmu County, Henan Province.
Internal assessment results based on 277 standard images showed that JF CXR-1 v3.0 had a sensitivity of 85.94% (95% confidence interval [CI]: 77.42%, 94.45%) and a specificity of 74.65% (95% CI: 68.81%, 80.49%) to distinguish active TB from other imaging conditions. In the on-site evaluation phase, images from 3705 outpatients who underwent chest X-ray detection were read by JF CXR-1 v3.0 and local radiologists in parallel. The imaging diagnosis of local radiologists for active TB had a sensitivity of 32.89% (95% CI: 22.33%, 43.46%) and a specificity of 99.28% (95% CI: 99.01%, 99.56%), while JF CXR-1 v3.0 showed a significantly higher sensitivity of 92.11% (95% CI: 86.04%, 98.17%) (p < 0.05) and maintained high specificity at 94.54% (95% CI: 93.81%, 95.28%).
CAD software could play a positive role in improving the TB case finding capability of township health centers.
Type 2 diabetes (T2D), but not type 1, protected against amyotrophic lateral sclerosis (ALS). In T2D serum insulin is normal or elevated in the early stages. Type 1 diabetes, characterized by a total lack of insulin, is associated with an increased risk of ALS. The antidiabetic metformin also protects against ALS. Connexin 43 (Cx43), an astrocyte protein, operates as an open channel via which toxic substances from astrocytes reach motor neurons to cause ALS.
In the current study we analyzed FDA MedWatch data to determine whether insulin or metformin could reduce the risk of ALS. We performed in silico molecular docking studies and molecular dynamics simulation with Cx43 to determine if insulin or metformin dock within the Cx43 channel and can block it effectively, again reducing risk of ALS.
In MedWatch, Insulin use is associated with a significantly reduced risk of ALS (Proportional Reporting Ratio 0.401). Metformin use is associated with a significantly reduced risk of ALS (PRR 0.567). The Human insulin heterodimer docked within center of the Cx43 channel, effectively blocking it. Molecular dynamics simulation showed that the block is highly stable and may be responsible for the protective effect of T2D on ALS. Metformin docks within the Cx43 channel, but the relatively small size of the metformin molecule may not allow it to obstruct the passage of toxic substances from astrocytes to motor neurons.
MedWatch data indicate that both insulin and metformin reduce risk of ALS. The results of our in silico docking study and molecular dynamics simulation corroborate our previous findings with Cx31. Insulin docks within the open hemichannel of hexameric Cx43, potentially blocking it. Molecular dynamics simulation showed that the block is stable and may be responsible for the protective effect of T2D and insulin on ALS.
大动脉炎（TA）是一种慢性炎性血管炎，优先累及主动脉及其近端分支，可累及肺动脉和冠状动脉。TA最早见于日本，在亚洲发病率最高。虽然最常见于年轻女性，但也可能影响儿童[
S.Lehrer和P.H.Rheinstein，“人KAT2A(GCN5)组蛋白乙酰转移酶和新型冠状病毒Orf8病毒蛋白的比对”慢性病与转化医学9(2023):263–265.https://doi.org/10.1002/cdt3.56.
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