A primary hallmark of pathological cardiac hypertrophy is excess protein synthesis due to enhanced translational activity. However, regulatory mechanisms at the translational level under cardiac stress remain poorly understood. Here we examined the translational regulations in a mouse cardiac hypertrophy model induced by transaortic constriction (TAC) and explored the conservative networks versus the translatome pattern in human dilated cardiomyopathy (DCM). The results showed that the heart weight to body weight ratio was significantly elevated, and the ejection fraction and fractional shortening significantly decreased 8 weeks after TAC. Puromycin incorporation assay showed that TAC significantly increased protein synthesis rate in the left ventricle. RNA-seq revealed 1,632 differentially expressed genes showing functional enrichment in pathways including extracellular matrix remodeling, metabolic processes, and signaling cascades associated with pathological cardiomyocyte growth. When combined with ribosome profiling analysis, we revealed that translation efficiency (TE) of 1,495 genes was enhanced, while the TE of 933 genes was inhibited following TAC. In DCM patients, 1,354 genes were upregulated versus 1,213 genes were downregulated at the translation level. Although the majority of the genes were not shared between mouse and human, we identified 93 genes, including Nos3, Kcnj8, Adcy4, Itpr1, Fasn, Scd1, etc., with highly conserved translational regulations. These genes were remarkably associated with myocardial function, signal transduction, and energy metabolism, particularly related to cGMP-PKG signaling and fatty acid metabolism. Motif analysis revealed enriched regulatory elements in the 5' untranslated regions (5'UTRs) of transcripts with differential TE, which exhibited strong cross-species sequence conservation. Our study revealed novel regulatory mechanisms at the translational level in cardiac hypertrophy and identified conserved translation-sensitive targets with potential applications to treat cardiac hypertrophy and heart failure in the clinic.
Animals ; Humans ; Cardiomegaly/physiopathology* ; Ribosomes/physiology* ; Protein Biosynthesis/physiology* ; Mice ; Cardiomyopathy, Dilated/genetics* ; Ribosome Profiling

The tumor microenvironment is a crucial factor in tumor occurrence and progression. The hypoxic microenvironment is widely present in tumor tissue and is a key endogenous factor accelerating tumor deterioration. The "blood stasis toxin" theory, as an emerging perspective in tumor research, is regarded as the unique "soil" in tumor progression from the perspective of traditional Chinese medicine(TCM) due to its dynamic evolution mechanism, which closely resembles the formation of the hypoxic microenvironment. Scientifically integrating TCM theories with the biological characteristics of tumors and exploring precise syndrome differentiation and treatment strategies are key to achieving comprehensive tumor prevention and control. This article focused on the hypoxic microenvironment of the tumor, elucidating its formation mechanisms and evolutionary processes and carefully analyzing the internal relationship between the "blood stasis toxin" theory and the hypoxic microenvironment. Additionally, it explored the interaction among blood stasis, toxic pathogens, and hypoxic environment and proposed micro-level prevention and treatment strategies targeting the hypoxic microenvironment based on the "blood stasis toxin" theory, aiming to provide TCM-based theoretical support and therapeutic approaches for precise regulation of the hypoxic microenvironment.
Humans ; Tumor Microenvironment/drug effects* ; Neoplasms/therapy* ; Animals ; Medicine, Chinese Traditional ; Disease Progression ; Drugs, Chinese Herbal

OBJECTIVE: To investigate the expression levels of EZH2 and KMT2D in patients with diffuse large B-cell lymphoma (DLBCL) and their relationship with pathological features. METHODS: 84 patients with DLBCL treated in our hospital from January 2021 to June 2022 were selected as the study subjects, and clinical characteristics such as sex, age and pathological classification of the patients were collected. Immunohistochemistry was used to detecet the expression of KMT2D and EZH2 proteins in tumor tissue cells of the DLBCL patients. The differential expression of KMT2D and EZH2 in subgroups of different sexes, ages, primary sites, clinical stages, Hans subtypes, etc. were compared. The correlation between the expression of KMT2D and EZH2 protein and BCL-6, CD79A was analyzed and validated through the interaction of protein molecular structures. We followed up and recorded the survival status of the patients for 12 months, and analyzed the factors that affect the mortality of DLBCL patients. RESULTS: The positive rate of KMT2D and EZH2 was high (over 95%) in DLBCL patients. There was no significant difference in the expression of EZH2 and KMT2D among subgroups of different sexes, ages and stages (P >0.05). However, patients with different levels of BCL-6 and CD79A expression showed differences in EZH2 and KMT2D expression (P < 0.05). EZH2 and KMT2D were positively correlated with BCL-6 (r =0.391, r =0.332) and CD79A (r =0.309, r =0.258), respectively, and there were interactions in the protein molecular structures. The risk factors for mortality in DLBCL patients include male sex (OR =1.106, 95%CI : 1.082-1.130, P < 0.001), stage II (OR =1.778, 95%CI : 1.567-2.016, P < 0.001), stage IV (OR =2.233, 95%CI : 2.021-2.467, P < 0.001), EZH2 positive (OR =2.762, 95%CI : 1.304-5.850, P =0.008), BCL-6 positive (OR =7.309, 95%CI : 1.340-39.859, P =0.022), age≥74 years (OR =3.080, 95%CI : 1.658-5.723, P < 0.001), and 63-73 years old (OR =2.400, 95%CI : 1.564-3.682, P < 0.001), while KMT2D positive (OR =0.180, 95%CI : 0.054-0.608, P =0.006) and 41-51 years old (OR =0.406, 95%CI : 0.274-0.603, P < 0.001) were factors which could reduce the risk of mortality. CONCLUSION EZH2 and KMT2D are highly expressed in patients with DLBCL, and they are positively correlated with BCL-6 and CD79A, and affect the prognosis of DLBCL patients.
Humans ; Enhancer of Zeste Homolog 2 Protein/metabolism* ; Lymphoma, Large B-Cell, Diffuse/metabolism* ; DNA-Binding Proteins/metabolism* ; Female ; Male ; Middle Aged ; Adult ; Neoplasm Proteins/metabolism* ; Aged ; Immunohistochemistry ; Proto-Oncogene Proteins c-bcl-6/metabolism* ; Prognosis

BACKGROUND: Modern acupuncture anesthesia is a combination of Chinese and Western medicine that integrates the theories of acupuncture with anesthesia. However, some clinical studies of acupuncture anesthesia lack specific descriptions of randomization, allocation concealment, and blinding processes, with subsequent systematic reviews indicating a risk of bias. OBJECTIVE: Clinical trial registration is essential for the enhancement of the quality of clinical trials. This study aims to summarize the status of clinical trial registrations for acupuncture anesthesia listed on the World Health Organization International Clinical Trials Registry Platform (ICTRP). SEARCH STRATEGY: We searched the ICTRP for clinical trials related to acupuncture anesthesia registered between January 1, 2001 and May 31, 2023. Additionally, related publications were retrieved from PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Data. Registrations and publications were analyzed for consistency in trial design characteristics. INCLUSION CRITERIA: Clinical trials that utilized one of several acupuncture-related therapies in combination with pharmacological anesthesia during the perioperative period were eligible for this review. DATA EXTRACTION AND ANALYSIS: Data extracted from articles included type of surgical procedure, perioperative symptoms, study methodology, type of intervention, trial recruitment information, and publication information related to clinical enrollment. RESULTS: A total of 166 trials related to acupuncture anesthesia from 21 countries were included in the analysis. The commonly reported symptoms in the included studies were postoperative nausea and vomiting (19.9%) and postoperative pain (13.3%). The concordance between the publications and the trial protocols in the clinical registry records was poor, with only 31.7% of the studies being fully compatible. Inconsistency rates were high for sample size (39.0%, 16/41), blinding (36.6%, 15/41), and secondary outcome indicators (24.4%, 10/41). CONCLUSION The volume of acupuncture anesthesia clinical trials registered in international trial registries over the last 20 years is low, with insufficient disclosure of results. Postoperative nausea and vomiting as well as postoperative pain, are the most investigated for acupuncture intervention. Please cite this article as: Li Y, Liu YN, Guo Z, Gu ME, Wang WJ, Zhu Y, Zhuang XJ, Chen LM, Zhou J, Li J. Current situation of clinical trial registration in acupuncture anesthesia: A scoping review. J Integr Med. 2025; 23(3): 256-263.
Humans ; Acupuncture Analgesia ; Acupuncture Therapy ; Anesthesia ; Clinical Trials as Topic ; Registries

Objective:To investigate the value of biparametric-MRI (bpMRI) based peritumoral radiomics for preoperative prediction of extraprostatic extension (EPE) in prostate cancer (PCa).Methods:In this cross-sectional study, consecutive bpMRI of patients undergoing prostatectomy for PCa were retrospectively collected from the First Medical Center (center 1) and the Third Medical Center (center 2) of Chinese PLA General Hospital. A total of 274 patients were finally enrolled. Patients at center 1 from January 2020 to December 2022 were randomly divided into a training set (149 cases) and an internal validation set (63 cases) by stratified random sampling. Patients at center 2 from January 2023 to March 2024 were assigned to the external test set (62 cases). Patients were categorized into EPE-positive group and EPE-negative group according to pathological assessment postoperatively. In the training set, there were 49 cases in EPE-positive group and 100 cases in EPE-negative group. In the internal validation set, there were 26 cases in EPE-positive group and 37 cases in EPE-negative group. In the external test set, there were 22 cases in EPE-positive group and 40 cases in EPE-negative group. Axial T 2WI and apparent diffusion coefficient (ADC) images were manually annotated to obtain index lesion regions of interest (ROIs), with the peritumoral ROIs subsequently delineated by semi-automatic segmentation technique. Radiomics features were extracted from intra-tumoral, peri-tumoral, and intra-tumoral plus peri-tumoral ROIs. The training set data was employed to select and optimize features to build the radiomics models. The logistic regression analysis was used to develop radiomics, clinical, and integrated models. The predictive performance was assessed by the area under the receiver operating characteristic curve (AUC) in the external test set, and compared by the DeLong test. The sensitivity and specificity were compared by the exact McNemar test. Results:In the external test set, the peri-tumoral radiomics model based on bpMRI showed the highest performance in evaluating EPE, with an AUC of 0.739 (95% CI 0.611-0.842), which was identified as the optimal radiomics model. EPE grade ( OR=6.151, 95% CI 3.371-11.226, P<0.001) was incorporated into the clinical model, with an AUC of 0.780 (95% CI 0.657-0.875) in the external test set. The integrated model had an AUC of 0.817 (95% CI 0.698-0.904) in the external test set. There was no statistically significant difference in comparisons of AUCs among the three models (all P>0.05). The sensitivity of the integrated model (68.2%) showed no significant difference from those of the clinical model and the optimal radiomics model (77.3% and 86.4%, respectively; P=0.500 and P=0.289). However, the specificity of the integrated model (85.0%) was significantly higher than those of the clinical model (67.5%, P=0.016) and the optimal radiomics model (50.0%, P<0.001). Conclusion:A bpMRI-based peritumoral radiomics integrating clinical model demonstrates high performance for preoperative prediction of EPE in PCa.

Objective:To explore the clinical characteristics and prognosis of primary renal dedifferentiated liposarcoma.Methods:A retrospective analysis was conducted on the clinical data of 10 patients diagnosed with renal dedifferentiated liposarcoma in the First Affiliated Hospital of Zhengzhou University from January 2017 to December 2023. The cohort consisted of 8 males and 2 females, with a mean age of (59.0±6.8) years. Tumors were located in the left kidney in 8 cases and in the right kidney in 2 cases. Presentations included flank or abdominal masses in 4 patients, back pain in 3 patients, and asymptomatic in 3 patients. Imaging studies revealed solitary lesions in 9 cases and multiple lesions in 1 case. The maximum tumor diameter ranged from 95 to 178 mm, with a median of 119.5 mm. CT showed tumors within the renal parenchyma with unclear boundaries and displayed a "slow in, slow out" pattern of gradual enhancement. Clinical staging revealed T 2N 0M 0 in 3 cases, T 3N 0M 0 in 4 cases, T 4N 0M 0 in 3 cases, and T 2N 1M 0 in 1 case. Nine patients underwent radical nephrectomy, including 4 laparoscopic surgeries, 4 open surgeries, and 1 robotic-assisted with thrombectomy. One patient, presenting with multiple lymph node metastases confirmed by PET-CT, underwent a diagnostic biopsy. Postoperative pathological features, follow-up and prognosis were analyzed. Results:Pathological specimens appeared grayish-red, grayish-yellow or grayish-white cut surfaces with soft to moderate texture. Microscopically, tumor cells were ovoid or short spindle-shaped with significant atypia and cytoplasmic vacuoles, with visible pathological mitoses. Six cases showed only dedifferentiated components with tumor giant cells and multinucleated giant cells resembling pleomorphic undifferentiated sarcoma, with focal tumor necrosis. Fluorescence in situ hybridization showed MDM2 gene amplification in all cases. All cases were diagnosed as primary renal dedifferentiated liposarcoma. Pathological staging showed 4 cases as pT 2N 0M 0, 3 cases as pT 3N 0M 0, 2 cases as pT 4N 0M 0, and 1 case lacked pathological staging due to biopsy only. Five patients received postoperative adjuvant therapy, including two pT 2N 0M 0 cases who received immunotherapy and apatinib treatment respectively, with no recurrence. One pT 3N 0M 0 case received anlotinib treatment, with local recurrence after 12 months, followed by radiofrequency ablation combined with chemotherapy. Two pT 4N 0M 0 cases received ifosfamide combined with epirubicin and pirarubicin combined with lobaplatin respectively, with one case showing no progression at 11 months follow-up, and another case developing splenic metastasis 3 months post-surgery, followed by chemotherapy combined with targeted therapy, surviving for 20 months. Among the 4 cases without adjuvant therapy, two pT 2N 0M 0 cases developed multiple metastases within 1 month post-surgery and received immunotherapy combined with targeted therapy and/or chemotherapy, surviving 4-5 months.One of the two pT 3N 0M 0 cases developed local recurrence 2 months post-surgery and received chemotherapy, surviving 6 months, and another pT 3N 0M 0 case developed gluteal subcutaneous metastasis 1 month post-surgery and received immunotherapy combined with targeted therapy, surviving 8 months.One non-surgical pT 2N 1M 0 patient received chemotherapy and survived for 15 months. All patients were followed up for 4-52 months, with a median follow-up time of 11 months. At the last follow-up, 6 patients died and 4 survived. Conclusions:Primary renal dedifferentiated liposarcoma is clinically rare, with atypical symptoms and difficult preoperative diagnosis, relying on pathology for confirmation. Radical nephrectomy is the main treatment method, but surgery alone has poor prognosis with high recurrence and metastasis rates. Adjuvant therapy based on surgery may improve patient prognosis.Larger sample studies are needed for confirmation.

OBJECTIVE: The study aim was to investigate the effects of exposure to multiple environmental organic pollutants on cardiopulmonary health with a focus on the potential mediating role of oxidative stress. METHODS: A repeated-measures randomized crossover study involving healthy college students in Beijing was conducted. Biological samples, including morning urine and venous blood, were collected to measure concentrations of 29 typical organic pollutants, including hydroxy polycyclic aromatic hydrocarbons (OH-PAHs), bisphenol A and its substitutes, phthalates and their metabolites, parabens, and five biomarkers of oxidative stress. Health assessments included blood pressure measurements and lung function indicators. RESULTS: Urinary concentrations of 2-hydroxyphenanthrene (2-OH-PHE) ( β = 4.35% [95% confidence interval ( CI): 0.85%, 7.97%]), 3-hydroxyphenanthrene ( β = 3.44% [95% CI: 0.19%, 6.79%]), and 4-hydroxyphenanthrene (4-OH-PHE) ( β = 5.78% [95% CI: 1.27%, 10.5%]) were significantly and positively associated with systolic blood pressure. Exposures to 1-hydroxypyrene (1-OH-PYR) ( β = 3.05% [95% CI: -4.66%, -1.41%]), 2-OH-PHE ( β = 2.68% [95% CI: -4%, -1.34%]), and 4-OH-PHE ( β = 3% [95% CI: -4.68%, -1.29%]) were negatively associated with the ratio of forced expiratory volume in the first second to forced vital capacity. These findings highlight the adverse effects of exposure to multiple pollutants on cardiopulmonary health. Biomarkers of oxidative stress, including 8-hydroxy-2'-deoxyguanosine and extracellular superoxide dismutase, mediated the effects of multiple OH-PAHs on blood pressure and lung function. CONCLUSION Exposure to multiple organic pollutants can adversely affect cardiopulmonary health. Oxidative stress is a key mediator of the effects of OH-PAHs on blood pressure and lung function.
Humans ; Oxidative Stress/drug effects* ; Male ; Cross-Over Studies ; Female ; Young Adult ; Environmental Pollutants/toxicity* ; Environmental Exposure/adverse effects* ; Biomarkers/blood* ; Adult ; Blood Pressure/drug effects* ; Polycyclic Aromatic Hydrocarbons/urine* ; Beijing

Insulin is an important protein hormone that participates in multiple metabolic pathways.Biosynthetic insulin has been widely used in the treatment of type 1 and type 2 diabetes.Currently,the number of reported cases of insulin overdose both at home and abroad is gradually increasing,and insulin homicide is no longer a means of"committing murder without leaving a trace".At present,there are no systematic protocols for the identification of insulin overdose in the field of forensic medi-cine in China.This article introduces the causes,toxicological characteristics,forensic examination,labo-ratory testing methods and indicator reference of insulin overdose.Based on the identification practice and research results and referring to relevant studies on insulin overdose at home and abroad,this pa-per aims to provide recommendations and references for the formulation of forensic identification guide-lines for insulin overdose cases.

Objective To investigate the prevalence and risk factors of work-related musculoskeletal disorders (WMSDs) among construction workers. Methods A total of 5 783 workers were selected as participants from 12 construction companies in Guangdong Province, Guangxi Zhuang Autonomous Region and Zhejiang Province using a convenient sampling method. The revised Musculoskeletal Disorders Questionnaire was used to investigate the prevalence and influencing factors of WMSDs. Results The prevalence of WMSDs was 27.4% among the construction workers. The prevalence of WMSDs in shoulder, neck, waist/lower back and hand/wrist was 10.6%, 9.5%, 9.5% and 9.4% respectively, which was higher than that in other body parts. Bianry logistic regression analysis showed that the risk of WMSDs in construction workers with junior high school education and below was higher than that of high school/ college and above (P<0.05). The risk of WMSDs was higher in drinkers than that in non-drinkers (P<0.01). The worse the health status of construction workers, the higher the risk of WMSDs (P<0.01). The risk of WMSDs in those who exercised once or twice a month was lower than that in those who did not exercise (P<0.05). The risk of WMSDs was higher in construction workers with longer working hours in uncomfortable postures and greater back bending amplitude at work (all P<0.01). The risk of WMSDs in construction workers with hands holding above the shoulder was higher than that with hands below the shoulder (P<0.05). Construction workers who repeated the same work daily, involved in high-temperature work, often worked overtime, had insufficient rest time, and had a shortage of department personnel had a relatively high risk of WMSDs (all P<0.01). Conclusion The prevalence of WMSDs among the construction workers was relatively high, and the most common WMSDs occurred in shoulder, neck, waist/lower back and hand/wrist. Individual characteristic, work type, work posture and work organization are the influencing factors of WMSDs. Comprehensive measures, especially ergonomic measures based on personal and occupational characteristics should be taken to reduce the risk of WMSDs among construction workers.

Diabetes is a very complex endocrine disease whose common feature is the increase in blood glucose concentration. Persistent hyperglycemia can lead to blindness, kidney and heart disease, neurodegeneration, and many other serious complications that have a significant impact on human health and quality of life. The number of people with diabetes is increasing yearly. The global diabetes prevalence in 20-79 year olds in 2021 was estimated to be 10.5% (536.6 million), and it will rise to 12.2% (783.2 million) in 2045. The main modes of intervention for diabetes include medication, dietary management, and exercise conditioning. Medication is the mainstay of treatment. Marketed diabetes drugs such as metformin and insulin, as well as GLP-1 receptor agonists, are effective in controlling blood sugar levels to some extent, but the preventive and therapeutic effects are still unsatisfactory. Peptide drugs have many advantages such as low toxicity, high target specificity, and good biocompatibility, which opens up new avenues for the treatment of diabetes and other diseases. Currently, insulin and its analogs are by far the main life-saving drugs in clinical diabetes treatment, enabling effective control of blood glucose levels, but the risk of hypoglycemia is relatively high and treatment is limited by the route of delivery. New and oral anti-diabetic drugs have always been a market demand and research hotspot. Inhibitor cystine knot (ICK) peptides are a class of multifunctional cyclic peptides. In structure, they contain three conserved disulfide bonds (C3-C20, C7-C22, and C15-C32) form a compact “knot” structure, which can resist degradation of digestive protease. Recent studies have shown that ICK peptides derived from legume, such as PA1b, Aglycin, Vglycin, Iglycin, Dglycin, and aM₁, exhibit excellent regulatory activities on glucose and lipid metabolism at the cellular and animal levels. Mechanistically, ICK peptides promote glucose utilization by muscle and liver through activation of IR/AKT signaling pathway, which also improves insulin resistance. They can repair the damaged pancrease through activation of PI3K/AKT/Erk signaling pathway, thus lowering blood glucose. The biostability and hypoglycemic efficacy of the ICK peptides meet the requirements for commercialization of oral drugs, and in theory, they can be developed into natural oral anti-diabetes peptide drugs. In this review, the structural properties, activity and mechanism of ICK pattern peptides in regulating glucose and lipid metabolism were summaried, which provided a reference for the development of new oral peptides for diabetes.