Objective To develop a predictive model for postoperative pulmonary complications (PPC) following video-assisted thoracic surgery (VATS) in lung cancer patients by integrating cardiopulmonary exercise testing (CPET) parameters and machine learning techniques. Methods A retrospective analysis was conducted on patients with early-stage non-small cell lung cancer who underwent CPET and VATS at Guangdong Provincial People’s Hospital between October 2021 and July 2023. Patients were divided into a PPC group and a non-PPC group. The least absolute shrinkage and selection operator (LASSO) regression was used to select important features associated with PPC. Six machine learning algorithms were utilized to construct prediction models, including logistic regression, support vector machine, k-nearest neighbors, random forest, gradient boosting machine, and extreme gradient boosting. The optimal model was interpreted using SHapley Additive exPlanations (SHAP). Results A total of 325 patients were included, with an average age of 60.36 years, and 55.1% were male. Significant differences were observed between the PPC and non-PPC groups in age, diabetes, coronary heart disease, surgical approach, forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FVC% predicted, peak oxygen uptake (peak VO2), anaerobic threshold (AT), and ventilatory equivalent for carbon dioxide slope (VE/VCO2 slope) (P<0.05). In the predictive model constructed by selecting 7 key features using LASSO regression, the random forest model demonstrated the best overall performance across various metrics, with an area under the receiver operating curve of 0.930, an F1 score of 0.836, and a Brier score of 0.133 in the training set. It also exhibited good predictive ability and calibration in the test set. SHAP analysis ranked feature importance as follows: peak VO2, VE/VCO2 slope, age, FEV1, smoking history, diabetes, and surgical approach. Conclusion Integrating CPET parameters, the random forest model can effectively identify high-risk patients for PPC and has the potential for clinical application.

Metabolic associated fatty liver disease （MAFLD） is a chronic liver disease closely associated with metabolic syndrome， characterized by a complex pathogenesis involving genetic， environmental， and lifestyle factors. Recent studies have shown significant disparities in the prevalence rate and clinical features of MAFLD across different racial and ethnic groups， and such disparities might be associated with various factors such as genetic background， environmental factors， socioeconomic disparities， and metabolic profiles. This article reviews the latest research advances in racial and ethnic differences in MAFLD in China and globally， discusses its potential pathogenic mechanisms and clinical significance， proposes future research directions and interventional measures， and emphasizes the critical need to enhance MAFLD screening and preventive health education in multiethnic populations.

Traditional Chinese medicine formula (TCMF) represents a fundamental component of Chinese medical practice, incorporating medical knowledge and practices from both Han Chinese and various ethnic minorities, while providing comprehensive insights into health and disease. The foundation of TCMF lies in its holistic approach, manifested through herbal compatibility theory, which has emerged from extensive clinical experience and evolved into a highly refined knowledge system. Within this framework, Chinese herbal medicines exhibit intricated characteristics, including multi-component interactions, diverse target sites, and varied biological pathways. These complexities pose significant challenges for understanding their molecular mechanisms. Contemporary advances in artificial intelligence (AI) are reshaping research in traditional Chinese medicine (TCM), offering immense potential to transform our understanding of the molecular mechanisms underlying TCMFs. This review explores the application of AI in uncovering these mechanisms, highlighting its role in compound absorption, distribution, metabolism, and excretion (ADME) prediction, molecular target identification, compound and target synergy recognition, pharmacological mechanisms exploration, and herbal formula optimization. Furthermore, the review discusses the challenges and opportunities in AI-assisted research on TCMF molecular mechanisms, promoting the modernization and globalization of TCM.
Artificial Intelligence ; Drugs, Chinese Herbal/pharmacokinetics* ; Humans ; Medicine, Chinese Traditional ; Animals

Human carboxylesterase 2A (hCES2A) plays pivotal roles in prodrug activation and hydrolytic metabolism of ester-bearing chemicals. Targeted inhibition of intestinal hCES2A represents a feasible strategy to mitigate irinotecan-triggered gut toxicity (ITGT), but the orally active, selective, and efficacious hCES2A inhibitors are rarely reported. Here, a novel drug-like hCES2A inhibitor was developed via three rounds of structure-based drug design (SBDD) and structural optimization. Initially, donepezil was identified as a moderate hCES2A inhibitor from 2000 US Food and Drug Administration (FDA)-approved drugs. Following two rounds of SBDD and structural optimization, a donepezil derivative (B7) was identified as a strong reversible hCES2A inhibitor. Subsequently, nine B7 carbamates were rationally designed, synthesized and biologically assayed. Among all synthesized carbamates, C3 showed the most potent time-dependent inhibition on hCES2A (IC₅₀ = 0.56 nmol/L), excellent specificity and favorable drug-like properties. C3 could covalently modify the catalytic serine of hCES2A with high selectivity, while this agent also showed favorable safety profiles, high intestinal exposure, and impressive effects for ameliorating ITGT in both human intestinal organoids and tumor-bearing mice. Collectively, this study showcases a rational strategy for developing drug-like and serine-targeting covalent inhibitors against target serine hydrolase(s), while C3 emerges as a promising orally active drug candidate for ameliorating ITGT.

OBJECTIVES: To explore the value of serum cystatin C (CysC) levels in evaluating renal prognosis in IgA nephropathy (IgAN) patients. METHODS: We retrospectively collected the clinical data of IgAN patients diagnosed by renal biopsy at Guangdong Provincial People's Hospital from January, 2014 to December, 2018. Based on baseline serum CysC levels, the patients were divided into high serum CysC (>1.03 mg/L) group and normal serum CysC (≤1.03 mg/L) group. The composite endpoint for poor renal prognosis was defined as ≥50% decline in estimated glomerular filtration rate (eGFR) and/or progression to end-stage renal disease (ESRD). Lasso regression, multivariate Cox regression and Kaplan-Meier survival analysis were used to identify the risk factors and compare renal survival rates between the two groups. Smooth curves fitting and threshold effect analysis were used to explore the relationship between serum CysC levels and the outcomes. A nomogram model was constructed and its predictive performance was evaluated using concordance index, calibration curve, receiver operating characteristic (ROC) curve and the area under curve (AUC). RESULTS: A total of 356 IgAN patients were enrolled, who were followed up for 4.65±0.93 years. The composite endpoint occurred in 74 patients. High serum CysC was identified as an independent risk factor for poor renal prognosis in IgAN (HR=2.142, 95% CI 1.222 to 3.755), and the patients with high serum CysC levels had a lower renal survival rate (Log-rank χ²=47.970, P<0.001). In patients with serum CysC below 2.12 mg/L, a higher CysC level was associated with an increased risk of poor renal prognosis (β=3.487, 95% CI: 2.561-4.413, P<0.001), while above this level, the increase of the risk was not significant (β=0.676, 95% CI: -0.642-1.995, P=0.315). The nomogram model based on serum CysC and 3 other independent risk factors demonstrated good internal validity with a concordance index of 0.873 (95% CI: 0.839-0.907) and an AUC of 0.909 (95% CI: 0.873-0.945). CONCLUSIONS Serum CysC levels are associated with renal prognosis in IgAN patients, and high serum CysC an independent risk factor for poor renal prognosis.
Humans ; Glomerulonephritis, IGA/diagnosis* ; Cystatin C/blood* ; Prognosis ; Risk Factors ; Retrospective Studies ; Glomerular Filtration Rate ; Kidney Failure, Chronic ; Male ; Female ; Adult ; Nomograms ; Middle Aged

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*

RNA methylation is a key process in the epigenetic regulation of post-transcriptional gene expression.5-Methylcytosine(m⁵C)is a type of RNA methylation,commonly existing in eukaryotic mRNA and non-coding RNAs.It mainly regulates transfer RNA stability,ribosomal RNA assembly,and mRNA translation,stability,and translation.RNA methylation is dynamically reversible and regulated by methyltransferase,demethylase,and methylation recognition protein.It has been confirmed that aberrant m⁵C RNA methylation is involved in the pathogenesis of non-neoplastic kidney diseases.This article summarizes the current progress of m⁵C RNA methylation associated with non-neoplastic acute and chronic kidney diseases,aiming to provide potential targets for the diagnosis and treatment of such diseases.
Humans ; Methylation ; 5-Methylcytosine/metabolism* ; Kidney Diseases/metabolism* ; Epigenesis, Genetic ; RNA Methylation

Objective To explore the clinical efficacy of wrist arthroscopy assisted closed reduction with external fixation in the treatment of intra-articular comminuted fractures of the distal radius(type C3).Methods A retrospective analysis was conducted on 98 patients with type C3 intra-articular comminuted fractures of the distal radius admitted to our hospital from March 2022 to February 2023.Among them,48 patients underwent wrist arthroscopy assisted closed reduction with external fixation with a bracket(arthroscopy group),and another 50 patients underwent open reduction with steel plate internal fixation surgery(control group).The two groups were compared in terms of operation time,intraoperative bleeding volume,incision length,fracture union time,range of motion(ROM)of joint,Visual Analogue Scale(VAS),and Gartland-Werley wrist scores,as well as radiographic parameters(palmar tilt,ulnar inclination,and radial height)evaluated at various follow-up intervals.Results The arthroscopy group had an operation time of(55.3±10.5)min,which was significantly shorter than that in the control group[(83.4±14.6)min;t=-10.979,P=0.000].The intraoperative bleeding volume in the arthroscopy group was(42.3±8.6)ml,which was less than that in the control group[(71.4±10.5)ml;t=-14.953,P=0.000].The incision length of the arthroscopy group was(1.3±0.3)cm,which was shorter than that of the control group[(5.1±1.5)cm;t=-18.550,P=0.000].The arthroscopy group had a fracture healing time of(10.7±1.4)weeks,which was shorter than that in the control group[(12.2±1.6)weeks;t=-4.855,P=0.000].The palmar flexion ROM in the arthroscopy group was 68.8°±8.3°,which was significantly higher than that in the control group(61.5°±9.4°;t=4.002,P=0.000).The dorsiflexion ROM in the arthroscopy group was 63.9°±7.5°,which was significantly higher than that in the comtrol group(59.2°±8.3°;t=2.931,P=0.004).The pronation ROM in the arthroscopy group was 67.4°±10.3°,which was significantly higher than that in the control group(62.1°±9.9°;t=2.604,P=0.011).The supination ROM in the arthroscopy group was 70.5°±7.4°,which was significantly higher than that in the control group(64.4°±8.6°;t=3.777,P=0.000).The VAS score of the arthroscopy group was(1.3±0.6)points,which was significantly lower than that in the control group[(1.7±0.5)points;t=-3.941,P=0.000].After 6 months,the Gartland-Werley wrist scores of the arthroscopy group was significantly higher than that of the control group(Z=-2.614,P=0.009).The wrist joint imaging showed significantly higher radial height,palmar inclination angle,and ulnar deviation angle in the arthroscopy group than the control group(all P=0.000),while there were no significant differences in palmar inclination angle and ulnar deviation angle at different time points within each group(P＞0.05).Except for significant differences in radial height at 3 d,1 month,and 6 months after surgery(P=0.015,P=0.035),there were no significant differences between any other time points(P＞0.05).The interaction between time and group was not significant for palm inclination angle,ulnar deviation angle,and radial height(P＞0.05).Conclusion Wrist arthroscopy assisted closed reduction with external fixation for intra-articular comminuted fractures of distal radius has advantages of short operation time,less intraoperative blood loss,and good recovery of wrist joint functions.

Objective:To investigate the clinical, phenotypic and genotypic features of hereditary hyperhomocysteinemia mainly involving the nervous system.Methods:The clinical data, physical examination, imaging results, blood-urine tandem mass spectrometry analysis and genetic results of 8 patients with hyperhomocysteinemia from the Department of Neurology of the Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from September 2020 to December 2023 were collected, and the clinical, genetic features and pathogenic mechanisms of these patients were summarized and analyzed.Results:Among all the 8 patients (male∶female=5∶3), the age of onset was 7 to 74 (40.4±7.4) years. Seven had adult-onset and 1 had juvenile-onset, with various types of onset symptoms, including progressive stiffness in lower limbs and walking difficulty, limb numbness, tremor, mental and behavioral abnormalities, cerebrovascular events, etc. Moderate to severe hyperhomocysteine (38.4-190.6 μmol/L) was present in all patients at first diagnosis. Among the 5 patients with cranial imaging examinations, all had white matter lesions. The genetic testing showed 7 patients with MTHFR gene pathogenic mutations (1 case with c.416C>T, and 6 cases with c.665C>T), and 1 patient with MMACHC gene pathogenic mutation (c.482G>A). Conclusions:Hereditary hyperhomocysteinemia is a metabolic disease, with complicated manifestations, varying degrees of severity, and diverse pathogenic genes. The cases with neurological involvement are not rare, such as spastic paraplegia-like manifestations, tremor, peripheral neuropathy, mental and behavioral abnormalities, cerebrovascular events.

Objective To explore the risk factors of hemodynamic abnormalities in patients with coronary heart disease(CHD)after percutaneous coronary intervention(PCI)and to determine the contribution of these factors.Methods A total of 150 CHD patients undergoing PCI in our de-partment from January 2021 to December 2023 were prospectively recruited in the study.Accord-ing to the hemodynamic conditions,they were divided into a normal group(104 cases)and an abnor-mal group(46 cases).The causes of hemodynamic abnormalities were analyzed,and attributable risk percentage and population attributable risk percentage of these factors were estimated with logistic regression analysis.Results The hemodynamic abnormalities incidence was 30.7％.The abnormal group had significantly larger proportions of diabetes,smoking,and failures to take medication on time and in the prescribed dosage after surgery,longer stent length,and more stents,but lower level of high density lipoprotein cholesterol(HDLC)when compared with the normal group(P＜0.05,P＜0.01).Multivariate logistic regression analysis identified the following risk factors,estimated attributable risk percentage and population attributable risk percentage,diabetes,HDL-C,stent length,smoking,number of stents,and postoperative medication use in turn accord-ing to their contribution levels.Conclusion Rather complex causes lead to hemodynamic abnor-malities in CHD patients after PCI.In order of the contribution levels from high to low,they are diabetes,HDL-C,stent length,smoking,number of stents,and postoperative medication use.