Guangzhou University of Chinese Medicine

Objective: This study developed a novel explainable artificial intelligent model DMGNN (Deep mining graph convolutional neural network model) to identify potential oncogenes. Method: RNA transcriptome data from patients with five types of cancers including Stomach Adenocarcinoma (STAD), Lung Squamous Cell Carcinoma (LUSC), Liver Hepatocellular Carcinoma(LIHC), Esophageal Carcinoma(ESCA), and Bladder Urothelial Carcinoma(BLCA), were collected in the TCGA database. A novel explainable intelligent model named DMGNN was developed to identify potential oncogenes and important gene pairs based on the trained GNN model and its explanation algorithm. Potential oncogenes of universal cancers (POUC) and potential oncogenes of specific cancers (POSC), as well as the important gene pairs were identified based on DMGNN. To evaluate the DMGNN model, the numbers of cancers-related genes found in identified POUC, as well as the numbers of related genes of each cancer in this study found in identified POSC, were compared with RF and XGBOOST algorithms. Result: Numbers of cancers-related genes found in identified POUC of DMGNN was much more than RF and XGBOOST. Numbers of related genes of each cancer in this study found in identified POSC of DMGNN was also much more than RF and XGBOOST. Conclusion: DMGNN model may help us to identify potential oncogenes, and open up potential research directions to explore unknown cancer genes.

Andrographolide is a prominent labdane diterpenoid extracted from Andrographis paniculata, celebrated for its exceptional anti‐inflammatory properties. Commercial production of andrographolide relies exclusively on extraction from plant resources. Although the scaffold of andrographolide referring to ent‐copalol has previously been biosynthesized, further oxidative modifications remain elusive. In this study, by taking an integrated analysis of transcriptomes and metabolomes approach, we were able to identify four cytochrome P450 enzymes constituting the minimal set of andrographolide biosynthetic genes. Specifically, ApCYP71D587 catalyzes the conversion of ent‐copalol to 19‐hydroxy‐ent‐copalol. Subsequently, ApCYP71BE50 mediates the formation of the lactone ring, ultimately yielding andrograpanin. Then ApCYP706U5 accomplishes the third step by mediating the C‐3 hydroxylation reaction, thereby allowing the formation of 14‐deoxyandrographolide. Ultimately, ApCYP72F1 completes the biosynthetic generation of andrographolide with C‐14 hydroxylation of the lactone and rearrangement of the olefin bond. In addition, co‐expression of the minimal gene set in N. benthamiana engineered to produce ent‐copalol feasibly produces andrographolide, thus establishing an innovative metabolic engineering strategy to produce this medicine of historical importance, circumventing the need for plant extraction.

Objective This study assessed the safety and efficacy of rechallenging patients in advanced non-small cell lung cancer (NSCLC) without targetable driver mutations using a combination of immune checkpoint inhibitors (ICIs) and anlotinib following progression after prior immunotherapy. Methods A retrospective analysis was performed on 14 patients who received rechallenge with ICIs combined with anlotinib at the First Affiliated Hospital of Guangzhou University of Chinese Medicine. China, between March 2020 and June 2024. Results The study observed an objective response rate of 28.6% and a disease control rate of 92.9%. The median progression-free survival (PFS) was 11.7 months, with programmed death-ligand 1 (PD-L1)-positive patients demonstrating significantly longer PFS (13.0 months) compared with PD-L1-negative or unknown patients (10.3 months, P = 0.048). Toxicity was manageable, with most adverse events being mild to moderate in severity. Only one case (7.1%) of grade 3 adverse events was reported, and no treatment-related fatalities occurred. Conclusion ICIs combined with anlotinib as a rechallenge therapy exhibited promising efficacy and an acceptable safety profile in patients with advanced NSCLC without targetable driver mutations. These findings suggest a potential treatment option for patients with post-immunotherapy progression.

Purpose This study aimed to assess the impact of warm ischemia time on short-term renal function in individuals undergoing partial nephrectomy. Methods We conducted a comprehensive search for primary research articles from 1990 to October 15, 2024 across several databases, including MEDLINE, Embase and the Cochrane Library. A random effects model was applied to determine multivariable adjusted odds ratios (ORs) and their corresponding 95% confidence intervals (CIs). Country and study design were utilised as outcome indicators in the regression model. Results Ten studies including 4,993 patients who underwent partial nephrectomy met the inclusion criteria. The threshold of potentially harmful ischemia time for renal artery occlusion ranges between 10 and 45 min. Our results revealed that long warm ischemia time was associated with decreased postoperative eGFR and poor short-term renal function (OR = 1.08; 95% CI = 1.02–1.15; P = 0.006) after partial nephrectomy. Sensitivity and meta-regression analyses demonstrated the robustness of the study’s findings. Conclusions Extended periods of warm ischemia, specifically exceeding 25–30 min, can inflict damage on kidneys undergoing surgical treatment. Minimising the duration of warm ischemia while simultaneously prioritising surgical safety and achieving clear margins is imperative. Moreover, ischemia time remains a modifiable risk factor and must be reduced to maintain overall short-term renal function. Relevant prospective and randomised controlled trials must be conducted to validate these findings. PROSPERO Registration number CRD42024560051.

The study aimed to explore perspectives on death among rural older adults in mainland China. A semi-structured interview was conducted with 18 rural older adults from Guangzhou, China. Data were sorted and coded using NVivo 12.0 software, and analyzed through thematic analysis. Three themes were extracted, including attitudes toward death (lack of contemplating death, coexistence of death acceptance and death anxiety, avoidance of discussing death), end-of-life preferences (defining a good death, preference of place of death, not desiring to be over-rescued) and needs of death education (participation attitudes, content and form). Results suggested that rural older adults in mainland China lacked contemplating death, avoided discussing death, and experienced a certain degree of death anxiety. In the future, it's important to provide appropriate death-related interventions for them, guide them in actively contemplating death and expressing their perceptions and preferences, and ultimately improve their death competence and enhance quality of death.

Chloroplasts are key organelles for capturing solar energy and establishing plant immunity. During photosynthesis and pathogen defense, highly redox‐active reactions take place in chloroplasts and generate large amounts of reactive oxygen species (ROS). However, our knowledge of chloroplast‐produced ROS biosynthesis in plant immunity under varying light conditions is limited. Here, we report that the chloroplast‐localized protein HYPERSENSITIVE TO HIGH LIGHT 1 (HHL1) functions as a dual regulator of AvrRpt2‐triggered immunity in Arabidopsis (Arabidopsis thaliana), by modulating levels of chloroplast‐produced ROS to activate appropriate responses to pathogen infection under various light intensities. Under normal light conditions, HHL1 positively regulates AvrRpt2‐triggered immunity by promoting AvrRpt2‐induced chloroplast‐produced ROS accumulation, initiating salicylic acid signaling, and inducing the expression of genes encoding ROS‐scavenging enzymes. By contrast, under high light (HL) conditions, HHL1 has an opposite role, functioning as a repressor of these immune responses while HL stress attenuates AvrRpt2‐triggered immunity. These findings reveal that HHL1 modulates AvrRpt2‐triggered immunity by regulating ROS homeostasis in a light intensity‐dependent manner. Collectively, our results offer insight into the role of chloroplasts in the crosstalk between plant immunity and light intensity.

Automatic radiology report generation can enhance diagnostic efficiency and accuracy. However, clean open-source imaging scan-report pairs are limited in scale and variety. Moreover, the vast amount of radiological texts available online is often too noisy to be directly employed. To address this challenge, we introduce a novel task called Noisy Report Refinement (NRR), which generates radiology reports from noisy free-texts. To achieve this, we propose a report refinement pipeline that leverages large language models (LLMs) enhanced with guided self-critique and report selection strategies. To address the inability of existing radiology report generation metrics in measuring cleanliness, radiological usefulness, and factual correctness across various modalities of reports in NRR task, we introduce a new benchmark, NRRBench, for NRR evaluation. This benchmark includes two online-sourced datasets and four clinically explainable LLM-based metrics: two metrics evaluate the matching rate of radiology entities and modality-specific template attributes respectively, one metric assesses report cleanliness, and a combined metric evaluates overall NRR performance. Experiments demonstrate that guided self-critique and report selection strategies significantly improve the quality of refined reports. Additionally, our proposed metrics show a much higher correlation with noisy rate and error count of reports than radiology report generation metrics in evaluating NRR.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder that poses a significant challenge to the health of the global aging population. Despite extensive research, the complex mechanisms underlying AD pathogenesis remain largely elusive. In recent years, a growing number of clinical studies have demonstrated the preventive and therapeutic potential of Traditional Chinese Medicine (TCM) against AD through multiple pathways, targets, and compounds. In this study, we conducted a review of the literature published over the past 20 years through international and domestic databases, including PubMed, Medline, Cochrane Library, CNKI, SinoMed, Wanfang, and VIP Journal Integration Platform. This review systematically evaluates current research advancements regarding single-herb preparations, bioactive constituents, and compound formulations in Traditional Chinese Medicine (TCM), with focused analysis on three therapeutic categories: tonifying herbs, blood-activating and stasis-eliminating agents, as well as orifice-opening, phlegm-resolving, and mind-stabilizing medicinal substances. Furthermore, this review discusses the potential mechanisms underpinning the anti-AD effects of TCMs. By integrating these insights, this review aims to establish a theoretical foundation for the application of TCMs in AD treatment and provide a reference for future pharmacological studies and the development of health-related products.

Aim: This study is aimed at systematically investigating the potential causal impact of basal metabolic rate (BMR) on the risk of Type 2 diabetes (T2D). Methods: Data pertaining to single-nucleotide polymorphisms (SNPs) associated with BMR and T2D were gathered through a genome-wide association study (GWAS). Employing T2D as the dependent variable and BMR as the independent variable, SNPs displaying significant correlation with BMR were identified as instrumental variables (IVs). We also performed multivariable MR (MVMR) analyses using two different BMR datasets. The connection between BMR and the risk of T2D was scrutinized using the inverse-variance weighted (IVW) method, and a sensitivity analysis was executed to evaluate heterogeneity and pleiotropy. Results: A potential causal relationship between higher BMR and increased T2D risk was observed (odds ratio (OR), 1.49; 95% confidence interval (CI), 1.31–1.7; p<0.001). Significant heterogeneity was identified (Cochran’s Q test, p<0.001). However, sensitivity analyses demonstrated the robustness of the findings, with no evidence of horizontal pleiotropy and consistent results in leave-one-out tests. The MR-PRESSO test identified no outliers, confirming the absence of unknown pleiotropic effects. MVMR analyses, however, showed that the evidence became weaker after conditioning on BMI. Conclusion: Our study provides robust evidence of a causal link between higher BMR and increased T2D risk. Despite heterogeneity, sensitivity analyses support our findings, warranting further research to confirm results and explore underlying mechanisms.

Innate immunity is the first line of host defense and contributes to pain. However, how innate immune system interacts with sensory neurons to govern pain remains poorly understood. Here, we report that interleukin 33(IL-33) initiates pain hypersensitivity that requires chemokine (C-C motif) ligand 2 (CCL2) secretion from infiltrated macrophages and neutrophils and activation of transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential melastatin 8 (TRPM8) channels in sensory neurons. Blocking CCL2 receptor (CCR2) attenuates IL-33- induced and Complete Freund’s adjuvant (CFA)-induced thermal hyperalgesia and blocking TRPV1 and TRPM8 attenuates IL-33-induced mechanical and thermal hypersensitivity and cold allodynia respectively. Furthermore, depletion of macrophages reduces IL-33-induced pain and expression of CCL2 and suppression of tumorigenicity 2 (ST2) in hindpaw skin and inhibition of CCR2 prevents recruitment of macrophages and neutrophils. Our findings reveal an unrecognized neuroimmune crosstalk of IL-33-CCL2 signaling from infiltrated immune cells with TRPV1/TRPM8 in sensory neurons to facilitate pain states.

Background As women age, their ovarian follicle pool naturally declines. However, female germline stem cells (FGSCs) possess a unique ability to differentiate into oocytes and continuously self-renew, providing an effective means of delaying ovarian aging by replenishing the primordial follicle pool. Therefore, activating FGSCs is critical in reshaping and safeguarding ovarian function. Methods In this study, we investigated the biological activity of proanthocyanidins (PACs), natural antioxidants that exhibit anti-aging and anti-inflammatory properties beneficial for both male and female reproduction. Our in vivo and in vitro experiments demonstrate that PACs promote FGSCs proliferation while delaying ovarian aging. Results PACs increase the number of primordial follicles, primary follicles, corpus luteum while reducing cystic follicles, and elevate estradiol (E2) levels along with anti-mullerian hormone (AMH) concentration levels in mice. Additionally, PACs significantly boost FGSCs proliferation time- and dose-dependently by upregulating mRNA & protein expressions for FGSCs-specific markers such as MVH and OCT4 while downregulating p53/p21 via activation of silent information regulator 1(Sirt1) signaling pathway. The effects of PACs on FGCSs were found to be impeded by the Sirt1 inhibitor EX527. Conclusion PACS delay premature ovarian insufficiency (POI) through regulating the Sirt1-p53-p21 signaling pathway involving FGSCs.

Respiratory failure (RF) lead to high mortality rates and extended hospital stays in intensive care unit (ICU). The Triglyceride-Glucose (TyG) index, a reliable surrogate marker for insulin resistance (IR), predicted adverse outcomes in various diseases. Combining weight-related indices like body mass index (BMI) with TyG to form the TyG-BMI enhanced the assessment of IR and its impact on patient outcomes. However, the association between TyG-BMI and outcomes in patients with RF remained underexplored. This study retrospectively analyzed data from the MIMIC-IV database, focusing on critically ill patients with RF. From an initial cohort of 19,429 patients, 2177 met the inclusion criteria and were divided into quartiles based on TyG-BMI values. Key clinical information was collected within the first 24 h of ICU admission, including demographics, lab results, vital signs, and scoring systems such as SAPS II and SOFA. Primary outcome was 28-day, secondary outcomes were 180-day and 1-year mortality. Data were analyzed using multivariable Cox regression models, Kaplan–Meier survival curves, and restricted cubic splines to assess the nonlinear relationship between TyG-BMI and mortality. The study found significant differences in baseline characteristics across TyG-BMI quartiles. Kaplan–Meier survival curves indicated a higher survival probability for patients in the lowest TyG-BMI quartile (Q1) compared to higher quartiles (Q2–Q4). Adjusted hazard ratios demonstrated a nonlinear association between higher TyG-BMI values and increased mortality risk at all three time points. The RCS-derived cut-off value of 269 for TyG-BMI was identified as a significant threshold, with higher TyG-BMI values correlating with lower mortality risks. Subgroup analyses reinforced these findings across different patient demographics and clinical profiles. Higher TyG-BMI was associated to lower short-term and long-term mortality, suggesting a potential protective effect. These findings highlighted the importance of the TyG-BMI as a robust prognostic marker, providing valuable insights for improving treatment strategies for patients with RF.

Background Patients in the Trauma Surgery Intensive Care Unit (TSICU) often experience severe stress responses, which may lead to the occurrence of stress hyperglycemia. The stress hyperglycemia ratio (SHR), a biomarker quantifying the relative severity of stress hyperglycemia, has garnered increasing attention. This study aims to investigate the association between SHR and poor outcomes in TSICU patients. Methods A retrospective cohort study was conducted based on the Medical Information Mart for Intensive Care IV database. Patients in the TSICU were stratified into tertiles based on SHR values. The primary outcomes were 30-day and 365-day all-cause mortality, and the secondary outcome was hospital mortality. Kaplan-Meier survival analysis, logistic regression, Cox proportional hazards models, and restricted cubic spline analysis were employed to examine the relationship between SHR and poor outcomes. The potential incremental value of incorporating SHR into traditional disease severity scoring systems was also explored. Results A total of 569 eligible TSICU patients were included. The 30-day and 365-day all-cause mortality rates were 20.7% (118 patients) and 32.5% (185 patients), respectively. Higher SHR was associated with significantly increased risks of 30-day, 365-day, and hospital mortality (HR/OR > 1, P < 0.05). Restricted cubic spline analysis demonstrated no significant non-linear relationship between SHR and mortality risk (P > 0.05). Furthermore, SHR provided incremental prognostic value when integrated into traditional disease severity scoring systems. Conclusion High SHR is significantly associated with increased all-cause mortality in TSICU patients, particularly among non-diabetic individuals. As a prognostic marker, SHR shows potential clinical utility for early risk stratification and management optimization.

Purpose This study aimed to examine the relationships between illness perception, cognitive emotion regulation strategies (CERS), and psychological distress, and the mediating role of CERS in breast cancer patients and their spouses. Methods A cross-sectional study recruited 305 pairs of breast cancer patients and their spouses to complete the sociodemographic and clinical characteristics questionnaire, the Cognitive Emotion Regulation Questionnaire-short, and the Hospital Anxiety and Depression Scale. Descriptive statistics, difference analysis, Pearson’s correlation coefficient, and the actor–partner interdependence mediation model were conducted. Results There was a significant correlation between illness perception, CERS, and psychological distress in breast cancer patients and their spouses (r = -0.416 ~ 0.522, P < 0.05). Both patients’ and spouses’ illness perception could directly produce significant actor effects on psychological distress, or indirectly through the mediator of maladaptive or adaptive CERS of their own. Only spouses’ illness perception could produce significant partner effect on patients’ psychological distress. Moreover, only spouses’ illness perception could produce significant effects on patients’ psychological distress through patients’ or spouses’ maladaptive CERS. Conclusion Our findings offered a new perspective on how illness perception, CERS, and psychological distress were interconnected at both personal and dyadic levels. The findings underscored the significance of intervening with breast cancer patients and spouses as a closely knit dyad to promote the adoption of adaptive CERS while reduce the use of maladaptive CERS, which may be associated with lower levels of psychological distress.

Methylnissolin (also known as Astrapterocarpan) is an isoflavonoid compound featuring a pterocarpan core structure. To date, leguminous plants of the genus Astragalus remain the exclusive natural source of Methylnissolin and its glycoside derivative, Methylnissolin-3-O-glucoside. Upon oral administration, Methylnissolin and its glycosides enter systemic circulation and modulate signaling pathways such as RIPK2/ASK1, PI3K/AKT, IκB/NF-κB, MAPK, and Nrf2/HO-1. Their pharmacological activities span anti-inflammatory, antioxidant, glucose-lipid metabolism regulation, and antitumor effects, underscoring their broad potential for drug development. This review comprehensively evaluates the physicochemical properties, pharmacological activities, mechanisms of action, pharmacokinetic characteristics, and toxicological profile of Methylnissolin and its glycoside derivatives. Notably, we systematically elucidate the metabolic fate of methylnissolin, identifying hydroxylation, demethylation, dimerization, hydration, and dehydrogenation as predominant biotransformation pathways. Furthermore, the influence of factors such as plant variety, geographical origin, and processing methods on Methylnissolin and its glycoside content in Astragalus membranaceus is analyzed, providing crucial insights for drug development and resource utilization.

The progression and metastasis of breast cancer patients are regulated by genetics and epigenetics. Circular RNA (circRNA) plays a pivotal role in modulating the advancement of tumors. The study aimed to explore the clinical performance and regulatory role of hsa-circVIM in breast cancer and its modulatory effect on tamoxifen resistance in hormone receptor (HR) positive breast cancer cells. RT-qPCR was performed to detect hsa-circVIM expression in breast cancer tissues and cells.CCK-8 assay, Transwell assay, and flow cytometric analyses were performed to evaluate the effects of hsa-circVIM on cellular activities in breast cancer cells and TAM sensitivity in MCF7/TR cells. Bioinformatic analyses were conducted to make function and pathway enrichment analyses. hsa-circVIM expression was raised in breast cancer and predicted unsatisfactory overall survival outcomes. Silencing of hsa-circVIM suppressed cell viability, and migration capacities, while simultaneously enhancing TAM sensitivity and inducing apoptosis of HR-positive breast cancer cells by targeting miR-1294. Elevated hsa-circVIM expression in breast cancer suggested its potential as a prognostic biomarker. hsa-circVIM functions as both a cancer-promoting molecule and a regulator of TAM responsiveness in HR-positive breast cancer cells by regulating miR-1294 expression. Therefore, hsa-circVIM serves as a potent biomarker for prognosis, plays a promoting role in breast cancer progression, and may offer a therapeutic avenue to overcome TAM resistance.

Observational studies have shown the potential for cathepsins (CTS) to have an effect on nasopharyngeal carcinoma (NPC), but their conclusions are susceptible to confounding factors. To investigate the causal relationship between CTS and NPC, Mendelian randomization (MR) was conducted. Genetic data for nine CTS (CTS B, E, F, G, H, L2, O, S and Z) was obtained from a genome-wide association study. As the data on outcome, genetic data of NPC was utilized from a FinnGen study. MR was performed using five analytical methods including Inverse Variance-Weighted (IVW) method, MR-Egger test, Weighted Median test, Simple Mode test and Weighted Mode test, with the IVW as the main analysis method. Cochran’s Q test, MR-PRESSO global test and “leave-one-out” sensitivity test were used in sensitivity analysis. Reverse MR was performed to investigate whether there is reverse causality between NPC and CTS. MR Steiger test was used to determine the direction of the interaction between CTS and NPC. Overall, the authors found favorable evidence to support the association between Cathepsin F (CTSF) and NPC. CTSF was associated to increase the risk of NPC (odds ratio [OR] = 1.845, 95% confidence intervals [CI] = 1.086 ~ 3.136, P = 0.024) according to IVW. The results proved to be stable and robust in the sensitivity analysis. In the Steiger test, the causal effect of CTS on NPC was shown to be unidirectional. These findings suggest that CTSF may plays an important role in NPC thus providing new research ideas for future basic research endeavors and clinical applications.