Background The association between occupational physical activity (OPA) and cardiometabolic risk factors remains controversial, potentially due to differences in the associations between OPA and various cardiometabolic indicators, as well as the lack of a clearly defined optimal OPA range for multiple-indicator synergistic benefits. Objective To investigate the relationship between OPA and cardiometabolic risk factors in individuals at high risk of cardiovascular disease (CVD) in Hubei Province, and to explore an optimal OPA range for multi-indicator improvements. Methods Data were derived from the Hubei Province dataset of the China Health Evaluation And Risk Reduction Through Nationwide Teamwork from 2015 to 2023, including 19028 high-risk CVD individuals. OPA (metabolic equivalent·h·d⁻¹, MET·h·d⁻¹) was assessed using the China Kadoorie Biobank physical activity questionnaire, anthropometric measurements (height, weight, waist circumference) and cardiometabolic indicators (blood pressure, fasting blood glucose, lipid profiles) were measured. Multivariate logistic regression was used to analyze the association between logOPA quartiles (Q1-Q4) and abnormal cardiometabolic indicators, while restricted cubic spline (RCS) models were employed to explore their dose-response relationships. Subgroup and interaction analyses were also conducted by gender. Results The median OPA of all participants was 12.86 MET·h·d⁻¹ (male: 14.40 MET·h·d⁻¹, female: 11.14 MET·h·d⁻¹). After adjusting for confounders, compared with the Q1 group, logOPA in the Q4 group was associated with 20% (OR=0.80, 95%CI: 0.72, 0.89), 14% (OR=0.86, 95%CI: 0.78, 0.96), and 13% (OR=0.87, 95%CI: 0.79, 0.95) reduction in the risk of abdominal obesity, low high-density lipoprotein cholesterol (HDL-C), and metabolic syndrome (MS), respectively, and 33% (OR=1.33, 95%CI: 1.18, 1.49), 33% (OR=1.33, 95%CI: 1.18, 1.50), and 38% (OR=1.38, 95%CI: 1.21, 1.57) increase in the risk of high total cholesterol (TC), high low-density lipoprotein cholesterol (LDL-C), and high non-HDL-C, respectively. Similar trends were observed in males and females, with significant positive associations of logOPA with high TC and high non-HDL-C in males (P_interaction<0.05). The risk of low HDL-C decreased rapidly when logOPA was more than 2.213 (OPA>9.14 MET·h·d⁻¹), showing an inverted L-shaped trend. The risk of high TC, high LDL-C, and high non-HDL-C increased beyond logOPA thresholds of 3.244, 2.476, and 3.377 (OPA >25.64, 11.89, and 29.28 MET·h·d⁻¹), respectively, showing a J-shaped trend. However, logOPA exhibited a U-shaped nonlinear dose-response relationship with blood pressure and fasting blood glucose abnormalities (P_non-linear<0.05) , with minimal risks at logOPA 2.969 and 2.372 (OPA of 19.47 and 10.72 MET·h·d⁻¹). Conclusion OPA exhibits heterogeneous dose-response patterns across cardiometabolic indicators. Integrating the inverted L-, J-, and U-shaped association patterns, we suggest an optimal OPA range of 9.14−25.64 MET·h·d⁻¹ for multiple cardiometabolic indicators in total individuals at high-risk of CVD, with ranges of 9.61−31.34 MET·h·d⁻¹ for males and 8.97−22.87 MET·h·d⁻¹ for females. These findings provide critical evidence for developing OPA interventions strategies targeting high-risk population for CVD.

BACKGROUND: Approximately 40% of individuals with diabetes worldwide are at risk of developing diabetic kidney disease (DKD), which is not only the leading cause of kidney failure, but also significantly increases the risk of cardiovascular disease, causing significant societal health and financial burdens. This study aimed to describe the burden of DKD and explore its cross-country epidemiological status, predict development trends, and assess its risk factors and sociodemographic transitions. METHODS: Based on the Global Burden of Diseases (GBD) Study 2021, data on DKD due to type 1 diabetes (DKD-T1DM) and type 2 diabetes (DKD-T2DM) were analyzed by sex, age, year, and location. Numbers and age-standardized rates were used to compare the disease burden between DKD-T1DM and DKD-T2DM among locations. Decomposition analysis was used to assess the potential drivers. Locally weighted scatter plot smoothing and Frontier analysis were used to estimate sociodemographic transitions of DKD disability-adjusted life years (DALYs). RESULTS: The DALYs due to DKD increased markedly from 1990 to 2021, with a 74.0% (from 2,227,518 to 3,875,628) and 173.6% (from 4,122,919 to 11,278,935) increase for DKD-T1DM and DKD-T2DM, respectively. In 2030, the estimated DALYs for DKD-T1DM surpassed 4.4 million, with that of DKD-T2DM exceeding 14.6 million. Notably, middle-sociodemographic index (SDI) quintile was responsible for the most significant DALYs. Decomposition analysis revealed that population growth and aging were major drivers for the increased DKD DALYs in most regions. Interestingly, the most pronounced effect of positive DALYs change from 1990 to 2021 was presented in high-SDI quintile, while in low-SDI quintile, DALYs for DKD-T1DM and DKD-T2DM presented a decreasing trend over the past years. Frontiers analysis revealed that there was a negative association between SDI quintiles and age-standardized DALY rates (ASDRs) in DKD-T1DM and DKD-T2DM. Countries with middle-SDI shouldered disproportionately high DKD burden. Kidney dysfunction (nearly 100.0% for DKD-T1DM and DKD-T2DM), high fasting plasma glucose (70.8% for DKD-T1DM and 87.4% for DKD-T2DM), and non-optimal temperatures (low and high, 5.0% for DKD-T1DM and 5.1% for DKD-T2DM) were common risk factors for age-standardized DALYs in T1DM-DKD and T2DM-DKD. There were other specific risk factors for DKD-T2DM such as high body mass index (38.2%), high systolic blood pressure (10.2%), dietary risks (17.8%), low physical activity (6.2%), lead exposure (1.2%), and other environmental risks. CONCLUSIONS DKD markedly increased and varied significantly across regions, contributing to a substantial disease burden, especially in middle-SDI countries. The rise in DKD is primarily driven by population growth, aging, and key risk factors such as high fasting plasma glucose and kidney dysfunction, with projections suggesting continued escalation of the burden by 2030.
Humans ; Global Burden of Disease ; Risk Factors ; Male ; Female ; Disability-Adjusted Life Years ; Diabetic Nephropathies/epidemiology* ; Middle Aged ; Diabetes Mellitus, Type 2/epidemiology* ; Adult ; Diabetes Mellitus, Type 1/complications* ; Aged ; Adolescent ; Young Adult ; Quality-Adjusted Life Years

BACKGROUND: Lung adenocarcinoma is an important pathohistologic subtype of non-small cell lung cancer (NSCLC). Invasive non-mucinous pulmonary adenocarcinomas (INMA) tend to have a poor prognosis due to their significant heterogeneity and diverse histologic components. Establishing a histologic grading system for INMA is crucial for evaluating its malignancy. In 2021, the International Association for the Study of Lung Cancer (IASLC) proposed that a new histological grading system could better stratify the prognosis of INMA patients. The aim of this study was to establish a visualized nomogram model to predict INMA IASLC grading preoperatively by means of dual-energy computed tomography (DECT), fractal dimension (FD), clinical features and conventional CT parameters. METHODS: A total of 112 patients with INMA who underwent preoperative DECT were retrospectively enrolled from March 2021 to January 2025. Patients were categorized into low-intermediate grade and high grade groups based on IASLC grading. The clinical characteristics and conventional CT parameters, including baseline features, biochemical markers, and serum tumor markers, were collected. DECT-derived parameters, including iodine concentration (IC), effective atomic number (eff-Z), and normalized IC (NIC), were collected and determined as NIC ratio (NICr) and fractal dimension (FD). Univariate analysis was employed to compare differences in conventional characteristics and DECT parameters between the two groups. Variables demonstrating statistical significance were subsequently incorporated into a multivariate Logistic regression analysis. A nomogram model integrating clinical data, conventional CT parameters, and DECT parameters was developed to identify independent predictors for IASLC grading of INMA. The discriminatory performance of the model was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: Multivariate analysis identified smoking history [odds ratio (OR)=2.848, P=0.041], lobulation sign (OR=2.163, P=0.004), air bronchogram (OR=7.833, P=0.005), eff-Z in arterial phase (OR=4.266, P<0.001), and IC in arterial phase (OR=1.290, P=0.012) as independent and significant predictors for IASLC grading of INMA. The nomogram model constructed based on these indicators demonstrated optimal predictive performance, achieving an area under the curve (AUC) of 0.804 (95%CI: 0.725-0.883), with specificity and sensitivity of 85.3% and 65.7%, respectively. CONCLUSIONS The nomogram model based on clinical features, imaging features and spectral CT parameters have a large potential for application in the preoperative noninvasive assessment of INMA IASLC grading.
Humans ; Nomograms ; Female ; Male ; Middle Aged ; Tomography, X-Ray Computed/methods* ; Lung Neoplasms/pathology* ; Aged ; Retrospective Studies ; Adenocarcinoma of Lung/pathology* ; Neoplasm Grading ; Adult

Metastasis serves as an indicator of malignancy and is a biological characteristic of carcinomas. Epithelial-mesenchymal transition (EMT) plays a key role in the promotion of tumor invasion and metastasis and in the enhancement of tumor cell aggressiveness. Prostaglandin E synthase 3 (p23) is a cochaperone for heat shock protein 90 (HSP90). Our previous study showed that p23 is an HSP90-independent transcription factor in cancer-associated inflammation. The effect and mechanism of action of p23 on lung cancer metastasis are tested in this study. By utilizing cell models in vitro and mouse tail vein metastasis models in vivo, the results provide solid evidence that p23 is critical for promoting lung cancer metastases by regulating downstream CXCL1 expression. Rather than acting independently, p23 forms a complex with RNA-binding motif protein 14 (RBM14) to facilitate EMT progression in lung cancer. Therefore, our study provides evidence for the potential role of the RBM14-p23-CXCL1-EMT axis in the metastasis of lung cancer.

Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors, including non-small cell lung cancer (NSCLC). However, its detailed molecular mechanism has not been adequately demonstrated. In this research, it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft (PDX) model. Mechanistically, employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis (MST), microRNA-145-5p (miR-145-5p) was pinpointed as a critical target through which elemene exerts its anti-tumor effects. Interestingly, elemene serves as a binding stabilizer for miR-145-5p, demonstrating a strong binding affinity (dissociation constant (K _D) = 0.39 ± 0.17 μg/mL) and preventing its degradation both in vitro and in vivo, while not interfering with the synthesis of the primary microRNA transcripts (pri-miRNAs) and precursor miRNAs (pre-miRNAs). The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA, subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated protein kinase kinase kinase 3 (MAP3K3)/nuclear factor kappaB (NF-κB) pathway. Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.

Objective:To investigate the relationship between the inflammatory cytokines level in the plasma of nasopharyngeal carcinoma patients before radiotherapy and acute radiotherapy adverse reactions, and to establish a preliminary model for predicting the risk of severe acute adverse reactions during radiotherapy.Methods:A cross-sectional study was conducted. A total of 85 nasopharyngeal carcinoma patients who received radical radiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from May 2016 to March 2019 were retrospectively collected. The highest grade adverse reactions of radiation oral mucositis, radiation dermatitis and xerostomia during radiotherapy were evaluated according to the American Cancer Radiotherapy Collaboration (RTOG) acute radiation injury evaluation criteria, and the above adverse reactions ≥ grade 3 were treated as the severity. Olink proteomics technology was used to detect the level of 92 inflammatory cytokines (the standardized protein expression values) in the plasma of patients before radiotherapy for the first time. Single factor analysis of variance and independent sample t-test were used to analyze the relationship between inflammatory cytokines and clinical factors, as well as acute adverse reactions during radiotherapy. Based on inflammatory cytokines and/or the clinical factors, binary logistic regression was used to construct a predictive model for the risk of severe acute radiotherapy adverse reactions. Whether the most severe adverse reactions assessed by the American RTOG acute radiation injury evaluation criteria during radiotherapy were severe or not were taken as the gold standard. Receiver operating characteristic (ROC) curve was used to analyze the effectiveness of the established models for judging the severe acute adverse reactions. Results:Among the 85 patients, 68 were males and 17 were females, with the median age [ M ( Q1, Q3)] of 49 years (43 years, 60 years). All patients received radical radiotherapy, of which 64 cases were treated with combination chemotherapy or targeted therapy. A total of 19 cases (22.1%) experienced severe acute radiotherapy adverse reactions. There were statistically significant differences in the levels of interleukin (IL)-22 receptor A1 (IL-22RA1), IL-18 receptor 1(IL-18R1), eotaxin-1 (CCL11), tumor necrosis factor ligand superfamily member 14 (TNFSF14), FMS-like tyrosine kinase 3 ligand (Flt3L), and monocyte chemotactic protein 2 (MCP-2) in the plasma of patients with grade 1, 2, 3 acute radiation oral mucositis before radiotherapy; there were statistically significant differences in the levels of CD244 (all P < 0.05); there were statistically significant differences in the levels of CD244, CC chemokines ligand 20 (CCL20), leukemia inhibitory factor ligand (LIF-R) and IL-4 in the plasma of patients with grade 1, 2, 3 acute radiation dermatitis before radiotherapy (all P < 0.05); there were statistically significant differences in the levels of IL-12B, CXC chemokines ligand 11 (CCL11), LIF-R and IL-33 in the plasma between patients with grade 1 and grade 2 xerostomia before radiotherapy (all P<0.05). The result of single factor analysis of variance showed that the clinical factors were not associated with severe acute radiation adverse reactions (all P > 0.05). Binary logistic regression model M1 was established by selecting 6 clinical factors including age, T staging, N staging, clinical staging, whether to receive chemotherapy or not and whether to suffer from diabetes or not in the literatures. Based on cytokine function and previous literatures, the binary logistic regression model M2 was established by selecting IL-22RA1, IL-18R1, MCP-2, CCL11, CD244, CCL20 and IL-33 from the differential cytokines. A binary logistic regression model M3 was established by combining the above clinical factors with cytokines. The ROC curve analysis showed that the area under the curve of the M1, M2, M3 predictive models for judging the severe acute radiation adverse reactions was 0.781, 0.841, 0.868, respectively. Conclusions:There were differences in the expression levels of various inflammatory cytokines in plasma before radiotherapy among patients with different grades of acute radiotherapy adverse reactions. Building the models based on plasma inflammatory cytokine levels combined with clinical factors before the first radiotherapy could effectively predict the risk of severe acute radiotherapy adverse reactions in patients with nasopharyngeal carcinoma.

Objective To observe the value of grey-level histogram analysis based on T2WI for differentiating consistency of meningioma.Methods Data of 109 patients with meningioma were retrospectively analyzed.The patients were divided into hard group(n=71)and soft group(n=38)according to the consistency of tumors.Tumor ROI was outlined on axial T2WI showing the largest tumor section,gray levels were extracted and histogram analysis was performed.The value of each histogram parameter were compared between groups.Then receiver operating characteristic curve was drawn,and the area under the curve(AUC)was calculated to evaluate the efficiency for differentiating soft and hard meningioma.Results P1,P10,P50,P90,P99 and the mean grey levels on T2WI in soft group were all higher than those in hard group(all P＜0.05),while the variance,the kurtosis and the skewness were not significantly different between groups(all P＞0.05).The differentiating efficiency of P1,P10,P50,P90,P99 and the mean grey levels on T2WI were all fine,with AUC of 0.774 to 0.833,and no significant difference was found(all P＞0.05).Conclusion Parameters of grey-level histogram analysis such as P1,P10,Ps0,P90,P99 and the mean values based on T2WI were all valuable for differentiating soft and hard meningioma.

Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal tract,and they are also genetically heterogeneous tumors.c-KIT gene or PDGFRA gene mutation is the main driving factor leading to its occurrence,and it is also one of the key factors affecting the treatment and prognosis of patients with GISTs.Imaging examination is non-invasive and can display tumors from multiple angles and directions,making it the main method for preoperative evaluation of GISTs.With the continuous development of imaging technology,non-invasive and definite genotyping of GISTs by imaging methods before surgery plays a positive role in the selection of targeted drugs and doses for patients and the evaluation of targeted treatment efficacy.This article reviews the imaging progress on the genotype of GISTs and the efficacy of targeted therapy.

Intensity-modulated radiotherapy (IMRT) is a radical treatment for oropharyngeal carcinoma. The 5-year overall survival (OS) is approximately 60%, and 80% for human papillomavirus (HPV)-related oropharyngeal carcinoma patients. Late toxicities after IMRT, including xerostomia, dysphagia, hypothyroidism, trismus, osteoradionecrosis and caries, and lower cranial neuropathy, seriously affect the quality of life of long-term survivors. The research on treatment de-intensification for HPV-related oropharyngeal cancer has been widely carried out at home and abroad, but there is little research focusing on late toxicity. In this article, related research progress in the incidence, treatment, prediction of late toxicity after IMRT was reviewed, aiming to provide reference for research on radiation-induced injury in de-intensification therapy research, thereby further optimizing comprehensive treatment strategies.

Objective:To compare the efficacy and safety of internal fixation using the olecranon osteotomy approach versus the bilateral triceps approach for the treatment of AO type C distal humeral fractures.Methods:We conducted a systematic search of China National Knowledge Infrastructure (CNKI), Wanfang, VIP, Chinese Medical Journal Full-Text Database, PubMed, Embase, Web of Science, and Cochrane Library for clinical studies comparing the olecranon osteotomy approach with the bilateral triceps approach for the treatment of AO type C distal humeral fractures. The search period was from January 2017 to March 2023. A meta-analysis was performed on the included studies. Random-effects models were used for analyses with high inter-group heterogeneity, while fixed-effects models were applied for those with low inter-group heterogeneity.Results:A total of 15 studies were included in the meta-analysis, comprising 480 cases treated via the olecranon osteotomy approach and 443 cases via the bilateral triceps approach. Meta-analysis results showed that the olecranon osteotomy approach was associated with longer operative time [ SMD=0.96, 95% CI(0.23, 1.70), P=0.010] and more intraoperative blood loss [ SMD=1.00, 95% CI(0.22, 1.78), P=0.012]compared to the bilateral triceps approach. There were no statistically significant differences between the two groups in postoperative Mayo Elbow Performance Score [ SMD=0.55, 95% CI(-0.23, 1.32), P=0.167], excellent and good reduction rate [ OR=0.98, 95% CI(0.75, 1.27), P=0.856], postoperative complication rate [ OR=1.27, 95% CI(0.77, 2.09), P=0.344], healing time [ SMD= -0.13, 95% CI(-0.37, 0.11), P=0.280], and range of motion of the elbow joint [ SMD=-0.02, 95% CI(-0.29, 0.26), P=0.891]. Conclusion:The bilateral triceps approach for internal fixation of AO type C distal humeral fractures is associated with shorter operative time and lower intraoperative blood loss compared to the olecranon osteotomy approach. The bilateral triceps approach for internal fixation of AO type C distal humeral fractures is associated with shorter operative time and lower intraoperative blood loss compared to the olecranon osteotomy approach.