ObjectiveAs a common lifestyle habit, alcohol consumption has a controversial association with the onset of Parkinson’s disease (PD). To demonstrate the correlation between alcohol consumption and PD and to identify associated genes, we integrated findings from clinical surveys, genomics, transcriptomics, and animal experiments. MethodsWe investigated the alcohol consumption rates (including both before and after disease onset) among 244 PD patients in China and 177 PD patients from the U.S. NHANES database. Mendelian randomization (MR) analysis was performed using genome-wide association study (GWAS) data for three alcohol-related traits and seven PD-related datasets from the MRC IEU OpenGWAS database. Transcriptomic data from the substantia nigra of PD patients were obtained from three GEO datasets (GSE7621, GSE20141, and GSE49036) to analyze RIT2 gene transcription. Finally, three groups of animal experiments (water/20% ethanol/20% liquor, with 4 C57BL/6J mice per group) were conducted to examine changes in brain RIT2 gene expression and transcriptomic profiles following alcohol consumption. ResultsThe alcohol consumption rates among PD patients in China and the U.S. (9%-18.87%) were significantly lower than the general population rates of 15%-45% in their respective regions (P<0.001), suggesting a possible negative association between alcohol consumption and PD. Subsequently, in 21 bidirectional MR analyses using 3 alcohol-related GWAS datasets and 7 PD-related GWAS datasets, the forward MR analyses (alcohol intake as exposure, PD as outcome) yielded 12 negative associations (OR_IVW<1) and 9 positive associations (OR_IVW>1). Among these, only two negative associations reached statistical significance: alcohol intake frequency (OR_IVW=0.75, 95% CI: 0.60-0.93, P=0.010) and alcohol consumption (OR_IVW=0.20, 95% CI: 0.05-0.83, P=0.026). The forward MR analysis (alcohol intake→PD) identified 235 SNPs, annotated to 316 genes, while the reverse MR analyses (PD→alcohol intake) identified 37 SNPs, annotated to 53 genes. Notably, only the RIT2 gene appeared in both the forward and reverse MR analyses (alcohol intake→PD: rs28597806, rs8083110; PD→alcohol intake: rs4588066). RIT2 is selectively expressed in the human brain (FPKM: 5.259±2.103), with low or no expression in peripheral tissues (FPKM: <1). Analysis of three human substantia nigra transcriptomic datasets revealed a decreasing trend in RIT2 gene expression in PD patients (GSE20141 array signal: 3.49±1.23 vs. 2.33±0.87, P=0.044). Animal experiments demonstrated that administration of 20% ethanol or 20% liquor (approximately 8% ethanol) stimulated a >2-fold upregulation of RIT2 gene expression in the mouse brain. Furthermore, transcriptomic sequencing revealed that the two alcohol-treated groups exhibited 96 (20% ethanol vs. water control) and 4 (20% liquor vs. water control) differentially expressed genes, respectively, indicating that low-dose alcohol consumption can achieve RIT2 upregulation while minimizing impact on other brain genes. In addition to its anti-infective effects, low-dose alcohol consumption primarily influences signaling pathways related to neurodegenerative diseases such as PD and Prion diseases. ConclusionAlcohol consumption is generally considered as a harmful lifestyle habit. However, some studies have also shown a lower risk of mortality among individuals who consume low doses of alcohol (100 g/week of ethanol) or drink occasionally. Currently, one of the research focuses on alcohol consumption is whether the human body can benefit from low-dose alcohol intake. This study provides new evidence supporting a negative association between alcohol consumption and PD, and for the first time, through MR analysis, identifies the RIT2 gene as a potential mediator of the effect of alcohol consumption on PD. RIT2 is selectively expressed in the human brain. Building upon existing evidence indicating downregulated RIT2 gene expression in PD pathogenesis, our experiments confirm that low-dose alcohol consumption can upregulate RIT2 expression in the brain. In brief, alcohol consumption may suppress the pathogenesis of PD by upregulating RIT2 expression in the substantia nigra. China is facing a serious problem of population aging. This study offers important insights for long-term PD prevention and treatment strategies, with the aim of benefiting more potential PD patients through lifestyle modifications, thereby improving the quality of life of the aging population and reducing the economic burden on healthcare.

Apical microsurgery is accurate and minimally invasive, produces few complications, and has a success rate of more than 90%. However, due to the lack of awareness and understanding of apical microsurgery by dental general practitioners and even endodontists, many clinical problems remain to be overcome. The consensus has gathered well-known domestic experts to hold a series of special discussions and reached the consensus. This document specifies the indications, contraindications, preoperative preparations, operational procedures, complication prevention measures, and efficacy evaluation of apical microsurgery and is applicable to dentists who perform apical microsurgery after systematic training.
Microsurgery/standards* ; Humans ; Apicoectomy ; Contraindications, Procedure ; Tooth Apex/diagnostic imaging* ; Postoperative Complications/prevention & control* ; Consensus ; Treatment Outcome

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Computational approaches for predicting drug-target interactions (DTIs) are pivotal in advancing drug discovery. Current methodologies leveraging heterogeneous networks often fall short in fully integrating both local and global network information. To comprehensively consider network information, we propose DHGT-DTI, a novel deep learning-based approach for DTI prediction. Specifically, we capture the local and global structural information of the network from both neighborhood and meta-path perspectives. In the neighborhood perspective, we employ a heterogeneous graph neural network (HGNN), which extends Graph Sample and Aggregate (GraphSAGE) to handle diverse node and edge types, effectively learning local network structures. In the meta-path perspective, we introduce a Graph Transformer with residual connections to model higher-order relationships defined by meta-paths, such as "drug-disease-drug", and use an attention mechanism to fuse information across multiple meta-paths. The learned features from these dual perspectives are synergistically integrated for DTI prediction via a matrix decomposition method. Furthermore, DHGT-DTI reconstructs not only the DTI network but also auxiliary networks to bolster prediction accuracy. Comprehensive experiments on two benchmark datasets validate the superiority of DHGT-DTI over existing baseline methods. Additionally, case studies on six drugs used to treat Parkinson's disease not only validate the practical utility of DHGT-DTI but also highlight its broader potential in accelerating drug discovery for other diseases.

Intraoperative cell salvage (IOCS) has been widely applied as an important blood conservation measure in surgical operations. However, there is currently a lack of clinical practice guidelines for the implementation of IOCS in patients with malignant tumors. This report aims to provide clinicians with recommendations on the use of IOCS in patients with malignant tumors based on the review and assessment of the existed evidence. Data were derived from databases such as PubMed, Embase, the Cochrane Library and Wanfang. The guideline development team formulated recommendations based on the quality of evidence, balance of benefits and harms, patient preferences, and health economic assessments. This study constructed seven major clinical questions. The main conclusions of this guideline are as follows: 1) Compared with no perioperative allogeneic blood transfusion (NPABT), perioperative allogeneic blood transfusion (PABT) leads to a more unfavorable prognosis in cancer patients (Recommended); 2) Compared with the transfusion of allogeneic blood or no transfusion, IOCS does not lead to a more unfavorable prognosis in cancer patients (Recommended); 3) The implementation of IOCS in cancer patients is economically feasible (Recommended); 4) Leukocyte depletion filters (LDF) should be used when implementing IOCS in cancer patients (Strongly Recommended); 5) Irradiation treatment of autologous blood to be reinfused can be used when implementing IOCS in cancer patients (Recommended); 6) A careful assessment of the condition of cancer patients (meeting indications and excluding contraindications) should be conducted before implementing IOCS (Strongly Recommended); 7) Informed consent from cancer patients should be obtained when implementing IOCS, with a thorough pre-assessment of the patient's condition and the likelihood of blood loss, adherence to standardized internally audited management procedures, meeting corresponding conditions, and obtaining corresponding qualifications (Recommended). In brief, current evidence indicates that IOCS can be implemented for some malignant tumor patients who need allogeneic blood transfusion after physician full evaluation, and LDF or irradiation should be used during the implementation process.

BACKGROUND: Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association. METHODS: This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results. RESULTS: During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1-2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3-5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6-7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week ( Ptrend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD ( Ptrend = 0.011) and MCEs ( Ptrend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD ( Pinteraction = 0.037). CONCLUSIONS Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.
Humans ; Male ; Female ; Prospective Studies ; Middle Aged ; Aged ; Vascular Diseases/etiology* ; Risk Factors ; China/epidemiology* ; Adult ; Proportional Hazards Models ; Cerebrovascular Disorders/epidemiology* ; East Asian People

Occlusal reconstruction is an important method of restoring a normal occlusal relationship to the natural dentition.The cor-rect choice of lateral occlusion scheme is necessary for physiological occlusal reconstruction.The main lateral occlusion schemes for the occlusal reconstruction of the natural dentition are canine protection and group function.This article reviews the effects of lateral occlu-sion schemes on the stomatognathic system and factors affecting the choice of lateral occlusion schemes in the occlusal reconstruction of natural dentition.According to the literature review,the lateral occlusion schemes affect the physiological functions of the stomatognath-ic system.Both lateral occlusion schemes have less impact on the temporomandibular joint.Group function produces greater EMG activi-ty,jaw movement velocity,and jaw lateral freedom than canine protection.The lateral occlusion schemes of the natural dentition should be selected according to the degree of lateral movement,types of static occlusion,and age of patients.For patients with Angle's ClassⅢ malocclusion,skeletal Class Ⅱ,Ⅲ malocclusion,and the elderly,group function is recommended,while canine protection is more recommended for young adults.For patients who eventually need to achieve canine protection,it is recommended to design group func-tion in the early stage of lateral movement,and gradually transition to canine protection with the increase of lateral movement.Thus,clinicians need to fully understand the influencing factors of lateral occlusion selection during occlusal reconstruction in natural denti-tion,providing a basis for the development of personalized diagnostic and treatment plans.

Occlusal reconstruction is an important method of restoring a normal occlusal relationship to the natural dentition.The cor-rect choice of lateral occlusion scheme is necessary for physiological occlusal reconstruction.The main lateral occlusion schemes for the occlusal reconstruction of the natural dentition are canine protection and group function.This article reviews the effects of lateral occlu-sion schemes on the stomatognathic system and factors affecting the choice of lateral occlusion schemes in the occlusal reconstruction of natural dentition.According to the literature review,the lateral occlusion schemes affect the physiological functions of the stomatognath-ic system.Both lateral occlusion schemes have less impact on the temporomandibular joint.Group function produces greater EMG activi-ty,jaw movement velocity,and jaw lateral freedom than canine protection.The lateral occlusion schemes of the natural dentition should be selected according to the degree of lateral movement,types of static occlusion,and age of patients.For patients with Angle's ClassⅢ malocclusion,skeletal Class Ⅱ,Ⅲ malocclusion,and the elderly,group function is recommended,while canine protection is more recommended for young adults.For patients who eventually need to achieve canine protection,it is recommended to design group func-tion in the early stage of lateral movement,and gradually transition to canine protection with the increase of lateral movement.Thus,clinicians need to fully understand the influencing factors of lateral occlusion selection during occlusal reconstruction in natural denti-tion,providing a basis for the development of personalized diagnostic and treatment plans.

OBJECTIVE: Myocardial ischemia/reperfusion injury (MIRI) is an obstacle to the success of cardiac reperfusion therapy. This study explores whether luteolin can mitigate MIRI by regulating the p53 signaling pathway. METHODS: Model mice were subjected to a temporary surgical ligation of the left anterior descending coronary artery, and administered luteolin. The myocardial infarct size, myocardial enzyme levels, and cardiac function were measured. Latent targets and signaling pathways were screened using network pharmacology and molecular docking. Then, proteins related to the p53 signaling pathway, apoptosis and oxidative stress were measured. Hypoxia/reoxygenation (HR)-incubated HL1 cells were used to validate the effects of luteolin in vitro. In addition, a p53 agonist and an inhibitor were used to investigate the mechanism. RESULTS: Luteolin reduced the myocardial infarcted size and myocardial enzymes, and restored cardiac function in MIRI mice. Network pharmacology identified p53 as a hub target. The bioinformatic analyses showed that luteolin had anti-apoptotic and anti-oxidative properties. Additionally, luteolin halted the activation of p53, and prevented both apoptosis and oxidative stress in myocardial tissue in vivo. Furthermore, luteolin inhibited cell apoptosis, JC-1 monomer formation, and reactive oxygen species elevation in HR-incubated HL1 cells in vitro. Finally, the p53 agonist NSC319726 downregulated the protective attributes of luteolin in the MIRI mouse model, and both luteolin and the p53 inhibitor pifithrin-α demonstrated a similar therapeutic effect in the MIRI mice. CONCLUSION Luteolin effectively treats MIRI and may ameliorate myocardial damage by regulating apoptosis and oxidative stress through its targeting of the p53 signaling pathway. Please cite this article as: Zhai P, Ouyang XH, Yang ML, Lin L, Li JY, Li YM, Cheng X, Zhu R, Hu DS. Luteolin protects against myocardial ischemia/reperfusion injury by reducing oxidative stress and apoptosis through the p53 pathway. J Integr Med. 2024; 22(6): 652-664.
Luteolin/pharmacology* ; Animals ; Myocardial Reperfusion Injury/metabolism* ; Oxidative Stress/drug effects* ; Tumor Suppressor Protein p53/genetics* ; Apoptosis/drug effects* ; Mice ; Signal Transduction/drug effects* ; Male ; Disease Models, Animal ; Mice, Inbred C57BL ; Myocardial Infarction/prevention & control* ; Reactive Oxygen Species/metabolism*

OBJECTIVE To establish a rapid nondestructive detection method for the sporoderm-broken rate of Ganoderma lucidum spore powder by hyperspectral technology combined with chemometrics. METHODS Hyperspectral images of Ganoderma lucidum spore powder samples with different sporoderm-broken rates were collected, and spectral data in the visible-shortwave near-infrared band(397−1 004 nm) range of each sample were calculated after selecting the region of interest. Compared 6 spectral preprocessing methods[standard normal variable transformation, multivariate scattering correction, Savitsky-Golay(SG) smoothing, wavelet transform, SG smoothing+standard normal variable transformation, and SG smoothing+multivariate scattering correction], 5 characteristic band extraction methods(competitive adaptive reweighting, successive projections algorithm, uninformative variables elimination, least angle regression, and genetic algorithm), and 5 algorithms(partial least squares regression, support vector regression, extreme learning machine, multilayer perceptron, and LightGBM) for constructing quantitative correction models to predicts performance. RESULTS The optimal combination was SG smoothing+competitive adaptive reweighted feature band selection+partial least squares. The quantitative correction model established based on the algorithm combination achieved a prediction set coefficient of 0.868 2, and a root mean square error of 0.011 7 for Ganoderma lucidum spore powder samples with a sporoderm-broken rate range of 90%−100%. The selected optimal algorithm combination was applied to construct a quantitative correction model with a sporoderm-broken rate range of 0−100%, the coefficient of determination for the test set was 0.973 1 and the root mean square error was 0.049 3, showing good generalization ability. CONCLUSION The established quantitative detection model can realize the rapid and non-destructive detection of the sporoderm-broken rate of Ganoderma lucidum spore powder, which provides technical support for the quality control of Ganoderma lucidum spore powder and its products.