The dual role of cellular senescence in human tumor progression and therapy.

Cellular senescence, one of the hallmarks of cancer, is characterized by cell cycle arrest and the loss of most normal cellular functions while acquiring a hypersecretory, proinflammatory phenotype. The function of senescent cells in cancer cells varies depending on the cellular conditions. Before the occurrence of cancer, senescent cells act as a barrier to prevent its development. But once cancer has occurred, senescent cells play a procancer role. However, few of the current studies have adequately explained the diversity of cellular senescence across cancers. Herein, we concluded the latest intrinsic mechanisms of cellular senescence in detail and emphasized the senescence-associated secretory phenotype as a key contributor to heterogeneity of senescent cells in tumor. We also discussed five kinds of inducers of cellular senescence and the advancement of senolytics in cancer, which are drugs that tend to clear senescent cells. Finally, we summarized the various effects of senescent cells in different cancers and manifested that their functions may be diametrically opposed under different circumstances. In short, this paper contributes to the understanding of the diversity of cellular senescence in cancers and provides novel insight for tumor therapy.

Prognostic factors for lacrimal gland adenoid cystic carcinoma: a retrospective study in Chinese patients.

AIM: To explore the prognostic factors for lacrimal gland adenoid cystic carcinoma (LGACC) in Chinese patients. METHODS: Clinical and histopathological data were reviewed in patients with pathologically confirmed LGACC. Local recurrence, metastasis, and disease-specific death were the main outcome measures. Univariate and multivariate analyses were performed by the Kaplan-Meier method and a Cox proportional hazard model. RESULTS: This retrospective cohort study included 45 patients with pathologically confirmed LGACC between January 2008 and June 2022. Tumor (T) classification (P=0.005), nodal metastasis (N) classification (P=0.018) and positive margin (P=0.008) were independent risk factors of recurrence; T (P=0.013) and N (P=0.003) classification and the basaloid tumor type (P=0.032) were independent risk factors for metastasis; T classification (P<0.001) was an independent factor of death of disease. In the further analysis, the durations from first surgery to radiotherapy is correlated with metastatic risk in LGACC patients with basaloid component (P=0.022). CONCLUSION: Histological subtype should be emphasized when evaluating prognosis and guiding treatment. Timely radiotherapy may reduce the risk of metastasis in patients with basaloid component.

Prediction models of intravenous glucocorticoids therapy response in thyroid eye disease.

Background: Thyroid eye disease (TED) is an autoimmune orbital disease, with intravenous glucocorticoid (IVGC) therapy as the first-line treatment. Due to uncertain response rates and possible side effects, various prediction models have been developed to predict IVGC therapy outcomes. Methods: A thorough search was conducted in PubMed, Embase, and Web of Science databases. Data extraction included publication details, prediction model content, and performance. Statistical analysis was performed using R software, including heterogeneity evaluation, publication bias, subgroup analysis, and sensitivity analysis. Forest plots were utilized for result visualization. Results: Of the 12 eligible studies, 47 prediction models were extracted. All included studies exhibited a low-to-moderate risk of bias. The pooled area under the receiver operating characteristic curve (AUC) and the combined sensitivity and specificity for the models were 0.81, 0.75, and 0.79, respectively. In view of heterogeneity, multiple meta-regression and subgroup analysis were conducted, which showed that marker and modeling types may be the possible causes of heterogeneity (P < 0.001). Notably, imaging metrics alone (AUC = 0.81) or clinical characteristics combined with other markers (AUC = 0.87), incorporating with multivariate regression (AUC = 0.84) or radiomics analysis (AUC = 0.91), yielded robust and reliable prediction outcomes. Conclusion: This meta-analysis comprehensively reviews the predictive models for IVGC therapy response in TED. It underscores that integrating clinical characteristics with laboratory or imaging indicators and employing advanced techniques like multivariate regression or radiomics analysis significantly enhance the efficacy of prediction. Our research findings offer valuable insights that can guide future studies on prediction models for IVGC therapy in TED.

Advances in Extracellular-Vesicles-Based Diagnostic and Therapeutic Approaches for Ocular Diseases.

Extracellular vesicles (EVs) are nanoscale membrane vesicles of various sizes that can be secreted by most cells. EVs contain a diverse array of cargo, including RNAs, lipids, proteins, and other molecules with functions of intercellular communication, immune modulation, and regulation of physiological and pathological processes. The biofluids in the eye, including tears, aqueous humor, and vitreous humor, are important sources for EV-based diagnosis of ocular disease. Because the molecular cargos may reflect the biology of their parental cells, EVs in these biofluids, as well as in the blood, have been recognized as promising candidates as biomarkers for early diagnosis of ocular disease. Moreover, EVs have also been used as therapeutics and targeted drug delivery nanocarriers in many ocular disorders because of their low immunogenicity and superior biocompatibility in nature. In this review, we provide an overview of the recent advances in the field of EV-based studies on the diagnosis and therapeutics of ocular disease. We summarized the origins of EVs applied in ocular disease, assessed different methods for EV isolation from ocular biofluid samples, highlighted bioengineering strategies of EVs as drug delivery systems, introduced the latest applications in the diagnosis and treatment of ocular disease, and presented their potential in the current clinical trials. Finally, we briefly discussed the challenges of EV-based studies in ocular disease and some issues of concern for better focusing on clinical translational studies of EVs in the future.

Optic nerve compression associated with visual cortex functional alteration in dysthyroid optic neuropathy: A combined orbital and brain imaging study.

AIMS: To investigate the alterations of the optic nerve and visual cortex in dysthyroid optic neuropathy (DON), a subgroup of thyroid eye disease (TED). METHODS: Multiple orbital imaging biomarkers related to optic nerve compression and the amplitude of low-frequency fluctuations (ALFF) of the brain were obtained from 47 patients with DON, 56 TED patients without DON (nDON), and 37 healthy controls (HC). Correlation analyses and diagnostic tests were implemented. RESULTS: Compared with HC, the nDON group showed alterations in orbital imaging biomarkers related to optic nerve compression in posterior segments, as well as ALFF of the right inferior temporal gyrus and left fusiform gyrus. DON differed from nDON group mainly in the modified muscle index of the posterior segment of optic nerve, and ALFF of orbital part of right superior frontal gyrus, right hippocampus, and right superior temporal gyrus. Orbital and brain imaging biomarkers were significantly correlated with each other. Diagnostic models attained an area under a curve of 0.80 for the detection of DON. CONCLUSION: The combined orbital and brain imaging study revealed alterations of the visual pathway in patients with TED and DON as well as provided diagnostic value. The initiation of alterations in the visual cortex in TED may precede the onset of DON.

Radiomics in ophthalmology: a systematic review.

BACKGROUND: Radiomics holds great potential in medical image analysis for various ophthalmic diseases. In recent times, there have been numerous endeavors in this area of research. This systematic review aims to provide a comprehensive assessment of the strengths and limitations of radiomics in ophthalmology. METHOD: Conforming to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, we conducted a systematic review with a pre-registered protocol (PROSPERO: CRD42023446317). We explored the PubMed, Embase, and Cochrane databases for original studies on this topic and made a comprehensive descriptive integration. Furthermore, the included studies underwent quality assessment by the radiomics quality score (RQS). RESULTS: A total of 41 articles from an initial search of 227 studies were finally selected for further analysis. These articles included research across five disease categories and covered seven imaging modalities. The radiomics models demonstrated robust performance, with area under the curve (AUC) values mostly falling within 0.7-1.0. The moderate RQS (mean score: 11.17/36) indicated that most studies were retrospectively, single-center analyses without external validation. CONCLUSIONS: Radiomics holds promising utility in the field of ophthalmology, assisting diagnosis, early-stage screening, and prognostication of treatment response. Artificial intelligence algorithms significantly contribute to the construction of radiomics models in ophthalmology. This study highlights the strengths and challenges of radiomics in ophthalmology and suggests potential avenues for future improvement. CLINICAL RELEVANCE STATEMENT: Radiomics represents a valuable approach for generating innovative imaging markers, enhancing efficiency in clinical diagnosis and treatment, and aiding decision-making in clinical contexts of many ophthalmic diseases, thereby improving overall patient prognosis. KEY POINTS: Radiomics has attracted extensive attention in the field of ophthalmology. Articles included five disease categories over seven imaging modalities, consistently yielding AUCs mostly above 0.7. Current research has few prospective and multi-center studies, underlining the necessity for future high-quality studies.

Lactate/lactylation in ocular development and diseases.

Lactylation, a post-translational modification (PTM) induced by lactate, has crucial roles in the regulation of transcription, DNA repair, and mitochondrial metabolism. Here, we discuss the role of lactate/lactylation signaling in regulating eye morphogenesis and retinal homeostasis, as well as various ophthalmic disorders, such as myopia, intraocular malignancies, and retinal angiogenesis.

Single-cell sequencing depicts tumor architecture and empowers clinical decision in metastatic conjunctival melanoma.

Conjunctival melanoma (CoM) is a potentially devastating tumor that can lead to distant metastasis. Despite various therapeutic strategies for distant metastatic CoM, the clinical outcomes remain unfavorable. Herein, we performed single-cell RNA sequencing (scRNA-seq) of 47,017 cells obtained from normal conjunctival samples (n = 3) and conjunctival melanomas (n = 7). Notably, we noticed a higher abundance of cancer-associated fibroblasts (CAFs) in tumor microenvironment (TME), correlated with enhanced angiogenic capacity and increased VEGFR expression in distal metastatic CoM. Additionally, we observed a significant decrease in the proportion of total CD8+ T cells and an increase in the proportion of naive CD8+ T cells, contributing to a relatively quiescent immunological environment in distal metastatic CoM. These findings were confirmed through the analyses of 70,303 single-cell transcriptomes of 7 individual CoM samples, as well as spatially resolved proteomes of an additional 10 samples of CoMs. Due to the increase of VEGFR-mediated angiogenesis and a less active T cell environment in distal metastatic CoMs, a clinical trial (ChiCTR2100045061) has been initiated to evaluate the efficacy of VEGFR blockade in combination with anti-PD1 therapy for patients with distant metastatic CoM, showing promising tumor-inhibitory effects. In conclusion, our study uncovered the landscape and heterogeneity of the TME during CoM tumorigenesis and progression, empowering clinical decisions in the management of distal metastatic CoM. To our knowledge, this is the initial exploration to translate scRNA-seq analysis to a clinical trial dealing with cancer, providing a novel concept by accommodating scRNA-seq data in cancer therapy.

Mg-Cross-Linked Alginate Hydrogel Induces BMSC/Macrophage Crosstalk to Enhance Bone Tissue Regeneration via Dual Promotion of the Ligand-Receptor Pairing of the OSM/miR-370-3p-gp130 Signaling Pathway.

Macrophages play a pivotal role in the crosstalk between the immune and skeletal systems, while Mg-based biomaterials demonstrate immunomodulatory capabilities in this procedure. However, the mechanism of how Mg2+ promotes osteogenesis through the interplay of bone marrow-derived mesenchymal stem cells (BMSCs) and macrophages remains undescribed. Here, we demonstrated that a Mg-cross-linked alginate hydrogel exerted a dual enhancement of BMSCs osteogenic differentiation through the ligand-receptor pairing of the OSM/miR-370-3p-gp130 axis. On the one hand, Mg2+, released from the Mg-cross-linked hydrogel, stimulates bone marrow-derived macrophages to produce and secrete more OSM. On the other hand, Mg2+ lowers the miR-370-3p level in BMSCs and in turn, reverses its suppression on gp130. Then, the OSM binds to the gp130 heterodimer receptor and activates intracellular osteogenic programs in BMSCs. Taken together, this study reveals a novel cross-talk pattern between the skeletal and immune systems under Mg2+ stimulation. This study not only brings new insights into the immunomodulatory properties of Mg-based biomaterials for orthopedic applications but also enriches the miRNA regulatory network and provides a promising target to facilitate bone regeneration in large bone defects.

An Overview of Optic Pathway Glioma With Neurofibromatosis Type 1: Pathogenesis, Risk Factors, and Therapeutic Strategies.

Optic pathway gliomas (OPGs) are most predominant pilocytic astrocytomas, which are typically diagnosed within the first decade of life. The majority of affected children with OPGs also present with neurofibromatosis type 1 (NF1), the most common tumor predisposition syndrome. OPGs in individuals with NF1 primarily affect the optic pathway and lead to visual disturbance. However, it is challenging to assess risk in asymptomatic patients without valid biomarkers. On the other hand, for symptomatic patients, there is still no effective treatment to prevent or recover vision loss. Therefore, this review summarizes current knowledge regarding the pathogenesis of NF1-associated OPGs (NF1-OPGs) from preclinical studies to seek potential prognostic markers and therapeutic targets. First, the loss of the NF1 gene activates 3 distinct Ras effector pathways, including the PI3K/AKT/mTOR pathway, the MEK/ERK pathway, and the cAMP pathway, which mediate glioma tumorigenesis. Meanwhile, non-neoplastic cells from the tumor microenvironment (microglia, T cells, neurons, etc.) also contribute to gliomagenesis via various soluble factors. Subsequently, we investigated potential genetic risk factors, molecularly targeted therapies, and neuroprotective strategies for tumor prevention and vision recovery. Last, potential directions and promising preclinical models of NF1-OPGs are presented for further research. On the whole, NF1-OPGs develop as a result of the interaction between glioma cells and the tumor microenvironment. Developing effective treatments require a better understanding of tumor molecular characteristics, as well as multistage interventions targeting both neoplastic cells and non-neoplastic cells.

Advanced intraocular retinoblastoma: evolving criteria for group E disease.

With evolving criteria for classifying intraocular retinoblastoma (RB) from International Intraocular Retinoblastoma Classification (IIRC, 2005) to International Classification of Retinoblastoma (ICRB, 2006), there have been changes in the inclusion criteria for groups E eyes that have not been widely recognized. This brief review highlights issues with the current classification systems (ICRB and IIRC) and layouts a theoretical framework arguing for merging of 2 existing classifications into 1 and subdividing the expanded group E RB, thereby preserving the possibility to reanalyze existing published data.

Recent progress in retinoblastoma: Pathogenesis, presentation, diagnosis and management.

Retinoblastoma, the primary ocular malignancy in pediatric patients, poses a substantial threat to mortality without prompt and effective management. The prognosis for survival and preservation of visual acuity hinges upon the disease severity at the time of initial diagnosis. Notably, retinoblastoma has played a crucial role in unraveling the genetic foundations of oncogenesis. The process of tumorigenesis commonly begins with the occurrence of biallelic mutation in the RB1 tumor suppressor gene, which is then followed by a cascade of genetic and epigenetic alterations that correspond to the clinical stage and pathological features of the tumor. The RB1 gene, recognized as a tumor suppressor, encodes the retinoblastoma protein, which plays a vital role in governing cellular replication through interactions with E2F transcription factors and chromatin remodeling proteins. The diagnosis and treatment of retinoblastoma necessitate consideration of numerous factors, including disease staging, germline mutation status, family psychosocial factors, and the resources available within the institution. This review has systematically compiled and categorized the latest developments in the diagnosis and treatment of retinoblastoma which enhanced the quality of care for this pediatric malignancy.

EHMT2 promotes tumorigenesis in GNAQ/11-mutant uveal melanoma via ARHGAP29-mediated RhoA pathway.

Constitutive activation of GNAQ/11 is the initiative oncogenic event in uveal melanoma (UM). Direct targeting GNAQ/11 has yet to be proven feasible as they are vital for a plethora of cellular functions. In search of genetic vulnerability for UM, we found that inhibition of euchromatic histone lysine methyltransferase 2 (EHMT2) expression or activity significantly reduced the proliferation and migration capacity of cancer cells. Notably, elevated expression of EHMT2 had been validated in UM samples. Furthermore, Kaplan-Meier survival analysis indicated high EHMT2 protein level was related to poor recurrence-free survival and a more advanced T stage. Chromatin immunoprecipitation sequencing analysis and the following mechanistic investigation showed that ARHGAP29 was a downstream target of EHMT2. Its transcription was suppressed by EHMT2 in a methyltransferase-dependent pattern in GNAQ/11-mutant UM cells, leading to elevated RhoA activity. Rescuing constitutively active RhoA in UM cells lacking EHMT2 restored oncogenic phenotypes. Simultaneously blocking EHMT2 and GNAQ/11 signaling in vitro and in vivo showed a synergistic effect on UM growth, suggesting the driver role of these two key molecules. In summary, our study shows evidence for an epigenetic program of EHMT2 regulation that influences UM progression and indicates inhibiting EHMT2 and MEK/ERK simultaneously as a therapeutic strategy in GNAQ/11-mutant UM.

Genetic landscape and prognosis of conjunctival melanoma in Chinese patients.

AIMS: Conjunctival melanoma (CoM) is a rare but highly lethal ocular melanoma and there is limited understanding of its genetic background. To update the genetic landscape of CoM, whole-exome sequencing (WES) and targeted next-generation sequencing (NGS) were performed. METHODS: Among 30 patients who were diagnosed and treated at Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, from January 2018 to January 2023, WES was performed on 16 patients, while targeted NGS was conducted on 14 patients. Samples were analysed to identify the mutated genes, and the potential predictive factors for progression-free survival were evaluated. Furthermore, the expression of the mutated gene was detected and validated in a 30-patient cohort by immunofluorescence. RESULTS: Mutations were verified in classic genes, such as BRAF (n=9), NRAS (n=5) and NF1 (n=6). Mutated FAT4 and BRAF were associated with an increased risk for the progression of CoM. Moreover, decreased expression of FAT4 was detected in CoM patients with a worse prognosis. CONCLUSIONS: The molecular landscape of CoM in Chinese patients was updated with new findings. A relatively high frequency of mutated FAT4 was determined in Chinese CoM patients, and decreased expression of FAT4 was found in patients with worse prognoses. In addition, both BRAF mutations and FAT4 mutations could serve as predictive factors for CoM patients.

High-risk histopathologic features in local advanced conjunctival melanoma.

PURPOSE: To identify high-risk histopathologic and molecular features of local recurrence, nodal metastasis, distant metastasis (DM) and disease-specific death (DSD) in conjunctival melanoma (CoM). METHODS: Ninety patients with pathologically diagnosed CoM between 2008 and 2023 were enrolled. Immunohistochemistry staining of BRAFV600E, NRASQ61R, CD117, PD-1 and PD-L1 was performed in 65 and 45 patients, respectively. Cox regression and Kaplan-Meier survival analysis were conducted to identify risk factors for local recurrence, nodal metastasis, DM and DSD. RESULTS: Pathologically, ulceration (hazard ratio [HR]: 3.170; 95% CI: 1.312-7.659; p = 0.01) and regression (HR: 3.196; 95% CI: 1.094-9.335; p = 0.034) were risk factors for DM. Tumour thickness ≥ 4 mm (HR: 4.889; 95% CI: 1.846-12.946; p = 0.001) and regression (HR: 4.011; 95% CI: 1.464-10.991; p = 0.007) were risk factors for DSD. For patients with tumour thickness < 4 mm, the presence of ulceration indicated a higher risk of nodal metastasis (log-rank p = 0.0011), DM (log-rank p = 0.00051) and DSD (log-rank p = 0.02). Patients with regression (+)/tumour-infiltrating lymphocytes (TILs) (+) had a higher risk for DM (log-rank p = 0.011) and DSD (log-rank p = 0.0032). Molecularly, the positive rate of BRAFV600E, NRASQ61R, CD117, PD-1 and PD-L1 was 40.00% (26/65), 43.08% (28/65), 70.77% (46/65), 46.67% (21/45) and 28.89% (13/45), respectively. Positive BRAFV600E was identified as an independent risk factor for DM (HR: 2.533; 95% CI: 1.046-6.136, p = 0.039). The expression level of BRAFV600E was positively correlated with vascular invasion (p = 0.01), as well as the expression levels of PD-1 (p = 0.038) and PD-L1 (p = 0.049). CONCLUSIONS: Tumour thickness ≥ 4 mm, ulceration, the coexistence of regression and TILs, and positive BRAFV600E were risk factors for poor prognosis of CoM patients. Besides, expression level of BRAFV600E was positively correlated with the expression levels of PD-1 and PD-L1.

The insular cortex is not insular in thyroid eye disease: neuroimaging revelations of central-peripheral system interaction.

BACKGROUND: Thyroid eye disease (TED) is highly correlated with dysregulated immunoendocrine status. The insular cortex was found to regulate peripheral inflammation and immunomodulation in mice. This study aimed to explore whether the insular cortex in patients with TED played a modulatory role including the aberrant brain functional alteration and its association with immunoendocrine status. METHODS: This study included 34 active patients (AP), 30 inactive patients (IP) with TED, and 45 healthy controls (HC) matched for age, sex, and educational level. Comprehensive clinical details (especially immunoendocrine markers) and resting-state functional magnetic resonance imaging data were collected from each participant. The amplitude of low-frequency fluctuation (ALFF) was used to probe the aberrant alterations of local neural activity. The seed-based functional connectivity (FC) analysis was used to explore the relationship between the insular cortex and each voxel throughout the whole brain. The correlation analysis was conducted to assess the association between insular neurobiomarkers and immunoendocrine parameters. RESULTS: When compared with the IP and HC groups, the AP group displayed significantly higher ALFF values in the right insular cortex (INS.R) and lower FC values between the INS.R and the bilateral cerebellum. None of the neurobiomarkers differed between the IP and HC groups. Besides, correlations between insular neurobiomarkers and immunoendocrine markers (free thyroxine, the proportion of T cells, and natural killer cells) were identified in both AP and IP groups. CONCLUSIONS: This study was novel in reporting that the dysregulation of the insular cortex activity in TED was associated with abnormal peripheral immunoendocrine status. The insular cortex might play a key role in central-peripheral system interaction in TED. Further research is crucial to enhance our understanding of the central-peripheral system interaction mechanisms involved in autoimmune diseases.

Whole-orbit radiomics: machine learning-based multi- and fused- region radiomics signatures for intravenous glucocorticoid response prediction in thyroid eye disease.

BACKGROUND: Radiomics analysis of orbital magnetic resonance imaging (MRI) shows preliminary potential for intravenous glucocorticoid (IVGC) response prediction of thyroid eye disease (TED). The current region of interest segmentation contains only a single organ as extraocular muscles (EOMs). It would be of great value to consider all orbital soft tissues and construct a better prediction model. METHODS: In this retrospective study, we enrolled 127 patients with TED that received 4·5 g IVGC therapy and had complete follow-up examinations. Pre-treatment orbital T2-weighted imaging (T2WI) was acquired for all subjects. Using multi-organ segmentation (MOS) strategy, we contoured the EOMs, lacrimal gland (LG), orbital fat (OF), and optic nerve (ON), respectively. By fused-organ segmentation (FOS), we contoured the aforementioned structures as a cohesive unit. Whole-orbit radiomics (WOR) models consisting of a multi-regional radiomics (MRR) model and a fused-regional radiomics (FRR) model were further constructed using six machine learning (ML) algorithms. RESULTS: The support vector machine (SVM) classifier had the best performance on the MRR model (AUC = 0·961). The MRR model outperformed the single-regional radiomics (SRR) models (highest AUC = 0·766, XGBoost on EOMs, or LR on OF) and conventional semiquantitative imaging model (highest AUC = 0·760, NaiveBayes). The application of different ML algorithms for the comparison between the MRR model and the FRR model (highest AUC = 0·916, LR) led to different conclusions. CONCLUSIONS: The WOR models achieved a satisfactory result in IVGC response prediction of TED. It would be beneficial to include more orbital structures and implement ML algorithms while constructing radiomics models. The selection of separate or overall segmentation of orbital soft tissues has not yet attained its final optimal result.

FBXO38 deficiency promotes lysosome-dependent STING degradation and inhibits cGAS-STING pathway activation.

F-box only protein 38 (FBXO38) is a member of the F-box family that mediates the ubiquitination and proteasome degradation of programmed death 1 (PD-1), and thus has important effects on T cell-related immunity. While its powerful role in adaptive immunity has attracted much attention, its regulatory roles in innate immune pathways remain unknown. The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is an important innate immune pathway that regulates type I interferons. STING protein is the core component of this pathway. In this study, we identified that FBXO38 deficiency enhanced tumor proliferation and reduced tumor CD8+ T cells infiltration. Loss of FBXO38 resulted in reduced STING protein levels in vitro and in vivo, further leading to preventing cGAS-STING pathway activation, and decreased downstream product IFNA1 and CCL5. The mechanism of reduced STING protein was associated with lysosome-mediated degradation rather than proteasomal function. Our results demonstrate a critical role for FBXO38 in the cGAS-STING pathway.

Mental health disparities between physicians and nurses: Analyzing the impact of occupational stress and work environment fitness using random forest algorithm.

BACKGROUND: The impact of occupational stress and work environment fitness on mental health disparities between physicians and nurses are not well understood. This study aims to identify and rank key determinants of mental health in physicians and nurses in China and compare the differences in their impact on mental health between physicians and nurses. METHODS: A large cross-sectional survey with multistage cluster sampling was conducted. The survey included the Self-Rating Anxiety Scale (SAS Scale), the Center for Epidemiologic Studies Depression Scale (CES-D Scale), the Maslach Burnout Inventory-General Survey (MBI-GS) and the Person-Environment (PE) Fit. We applied a principled, machine learning-based variable selection algorithm, using random forests, to identify and rank the determinants of the mental health in physicians and nurses. RESULTS: In our study, we analyzed a sample of 9964 healthcare workers, and 2729 (27 %) were physicians. The prevalence of anxiety and depressive disorders among physicians and nurses was 31.0 % and 53.3 %, 30.8 % and 47.9 %, respectively. Among physicians with anxiety disorder, we observed a higher likelihood of cynicism, emotional exhaustion, reduced personal accomplishment, and poor organization fitness, job fitness, group fitness, and supervisor fitness, in order of importance. When comparing the effects on depressive disorder in physicians, group fitness and supervisor fitness did not have significant impacts. For nurses, emotional exhaustion had a more significant effect on depressive disorder compared to cynicism. Supervisor fitness did not have a significant impact on anxiety disorder in nurses. LIMITATIONS: Cross-sectional design, self-reporting screening scales. CONCLUSIONS: Compared to individual and hospital characteristics, the primary factors influencing mental health disorders are occupational burnout and the compatibility of the work environment. Additionally, the key determinants of depressive and anxiety disorders among doctors and nurses exhibit slight variations. Employing machine learning methods proves beneficial for identifying determinants of mental health disorders among physicians and nurses in China. These findings could help improve policymaking aimed at addressing the mental well-being of healthcare professionals.