Chinese Medical Journal最新文献

Abstract: Breast cancer (BC) is the most prevalent malignancy among women and presents significant challenges, such as drug resistance and relapse, particularly triple-negative breast cancer (TNBC). Mitophagy is the primary process by which damaged mitochondria are degraded via the autophagy-lysosomal pathway to maintain mitochondrial homeostasis. The regulatory mechanisms of mitophagy and its role in BC progression are crucial for the discovery of new biomarkers and therapeutic targets. This review provides a comprehensive summary of the current understanding of mitophagy in BC, highlighting the gaps in knowledge related to reliable biomarkers and personalized treatment strategies. The pathways and mechanisms of mitophagy and their importance in BC are also summarized. Key findings include the dual role of mitophagy in BC development, the association of mitophagy-related genes/proteins with BC pathogenesis, and the potential of mitophagy modulators in enhancing treatment outcomes. This review further discusses the design of biosensors for detecting mitophagy in BC metastasis and explores the potential of mitophagy-related genes as biomarkers and prognostic factors. The unique value of this manuscript lies in its in-depth exploration of the regulatory mechanisms of mitophagy in BC, providing a scientific basis for clinical management and treatment while offering guidance for future research directions.

Background: Clonal hematopoiesis is a proposed marker of aging. Clonal hematopoiesis of indeterminate potential (CHIP) is a candidate risk factor for atherosclerotic cardiovascular diseases, hematological malignancies, and all-cause mortality, while its associations with the diseases of other systems and cause-specific mortality remain inconclusive.

Methods: We estimated the longitudinal risk for CHIP with 70 common diseases, all-cause, and cause-specific mortality among 431,546 participants in the UK Biobank. Two-sample MR analyses were performed to test the causal associations of CHIP with incident diseases. Cox proportional hazard regression model was used to generate the hazard ratio [HR] and 95% confidence interval [CI] for each CHIP phenotype with the common health-related outcomes. Also evaluated the joint associations between CHIP and TL for diseases and mortalities.

Results: This study included 431,546 participants (mean age, 56.49 years; 45.7% male), of whom 20,274 had CHIP. CHIP at baseline was associated with increased risk of cancers (HR = 1.14, 95% CI 1.10-1.17), infections (HR = 1.12, 95% CI 1.07-1.16), ischemic heart diseases (HR = 1.07, 95% CI 1.02-1.12), diseases of the blood (HR = 1.31, 95% CI 1.26-1.37), nervous (HR = 1.05, 95% CI 1.01-1.10), respiratory (HR = 1.10, 95% CI 1.06-1.13), and genitourinary systems (HR = 1.10, 95% CI 1.07-1.14), and related mortality (false discovery rate <0.05). CHIP carriers were also at elevated risk of incident mental (HR = 1.07, 95% CI 1.03-1.12) and dermatological (HR = 1.07 95% CI 1.03-1.11) disorders and mortality due to circulatory system (HR = 1.19, 95% CI 1.11-1.28). Most of the associations between CHIP and diseases or mortalities were robust after adjustment for inflammatory parameters. Large clone size CHIP had higher longitudinal risks compared with small clone size or overall CHIP. CHIP due to TET2 mutation was associated with more outcomes than other common CHIP driver genes. Significant interactions were observed between CHIP and short telomere length, the additive and multiplicative effects on the risk of diseases and mortalities were more obvious among large clone size CHIP.

Conclusion: This study showed that CHIP was associated with diseases and mortalities of multiple systems, suggesting CHIP was a candidate risk factor for human health.

Background: Psoriasis is a systemic disease that brings enormous mental pressure and economic burden to patients and has a significant impact on patients' quality of life (QoL). This study aimed to explore factors affecting the dermatology life quality index (DLQI) in patients with psoriasis.

Methods: This retrospective cross-sectional study used data sourced from the Psoriasis Diagnosis and Treatment Real-world Database, and 8839 patients with psoriasis (recruited between June 24, 2020 and September 2, 2021) were included. Demographic and clinical characteristics and DLQI scores were retrospectively analyzed, and correlations between DLQI score and age, disease course, psoriasis area and severity index (PASI) score were calculated. Regression analysis was conducted to explore the factors affecting the DLQI scores of patients with psoriasis.

Results: The average DLQI scores were significantly higher in young (8.58 ± 7.22) and middle-aged individuals (8.09 ± 6.61) than those in juveniles (6.00 ± 5.79) and older individuals (7.39 ± 6.29) (P = 1.70E-15). The average DLQI scores gradually decreased among individuals whose work status were unemployment (10.4 ± 7.83), part-time (9.02 ± 6.83), full-time (8.43 ± 6.90), retired (7.93 ± 6.07), and students (7.10 ± 6.31) (P = 9.82E-23). Except for those with disease course ≥20 years, DLQI scores increased gradually with prolongation of the disease course (P = 4.72E-22). The higher the severity of psoriasis, the higher the average DLQI score (P = 3.79E-113). The presence of psoriatic lesions at the exposed sites significantly affected DLQI scores (P <0.001). The average DLQI scores were significantly higher among individuals with nail holes, joint pain, and comorbidities than among those without these conditions (P <0.05). Correlation analysis indicated that the PASI scores were positively correlated with the DLQI scores (r = 0.26, P = 4.19E-134). Multinomial logistic regression analysis showed significant influencing factors (excluding comorbidity) with different degrees of impact based on the DLQI score (P <0.05).

Conclusion: Physicians should focus on significant factors, such as sex, age, marital status, education, work status, sub-types, disease course, PASI score, without joint pain, and without nail holes, to improve the QoL of patients with psoriasis.

Background: Current clinical assessment of atopic dermatitis (AD) severity and systemic treatment initiation remains problematic due to complex, time-consuming evaluation protocols. This complexity often leads to over-reliance on subjective clinical judgment, particularly in primary care settings, frequently resulting in delayed therapeutic intervention and suboptimal disease management. The project was designed to overcome these limitations by developing simplified, standardized tools for AD severity assessment and systemic treatment decision-making, with the ultimate goals of enhancing clinical efficiency and improving patient outcomes.

Methods: An initial pool of indicators for the Simplified AD Assessment Scale was created through a comprehensive literature review and expert consultations. A two-round electronic Delphi survey was subsequently conducted with 16 senior dermatologists from China to evaluate and refine these indicators and to establish consensus criteria for initiating systemic treatment. The study was conducted from November 2023 to June 2024.

Results: Through a two-round Delphi consensus process, we developed: First, a Simplified AD Assessment Scale comprising three primary indicators (pruritus, skin lesions, and quality of life) and five secondary indicators (intensity of itch, impact of itching on sleep, skin lesion involvement of body surface area (BSA), comprehensive evaluation of the intensity of skin lesion signs, and comprehensive evaluation of the impact on daily activities). Second, a Simplified Criteria for Initiating Systemic Treatment, including (A) skin lesion involvement >10% of BSA, or <10% BSA involving sensitive or highly visible areas, or inadequate response to prior topical therapies; (B) severe sleep disruption due to itching, necessitating sleep aids or causing awakening; and (C) significant impairment of daily activities, including work, study, or social activities. Systemic therapy was recommended when it co-occurs with either B or C. The Simplified AD Assessment Scale and systemic therapy initiation criteria offer three distinct clinical advantages for Chinese practice settings: (1) superior practicality through qualitative descriptors replacing cumbersome quantitative measures; (2) comprehensive evaluation via integrated patient-reported and physician-assessed parameters; and (3) regionally adapted decision-making as the first Chinese consensus-derived assessment tool. While demonstrating immediate clinical utility, further validation studies are necessary to establish the reliability, validity, and clinical applicability of these newly proposed tools.

Conclusion: The Simplified AD Assessment Scale and the associated criteria for initiating systemic therapy could enhance clinical efficiency and streamline decision-making processes for Chinese dermatologists in AD management.