ObjectiveBased on the clinical characteristics of chronic gouty arthritis （CGA） in both traditional Chinese and western medicine， this study aims to systematically evaluate the clinical concordance of existing CGA animal models， providing recommendations for establishing animal models that align with the pathological characteristics of CGA and the manifestations of traditional Chinese medicine syndromes. MethodsBy comprehensively retrieving Chinese and international databases such as China National Knowledge Infrastructure， Wanfang， VIP Chinese Science and Technology Periodical Database （VIP）， and PubMed， all relevant literature on CGA animal models was collected. Based on the guidelines， the diagnostic criteria of both traditional Chinese and western medicine were summarized and organized. The evaluation indicators for the CGA model were constructed with reference to existing evaluation modes， and the CGA animal models were analyzed to systematically evaluate the clinical concordance of existing models. ResultsThe current methods used to construct CGA animal models mainly include monosodium urate crystal induction， high-protein diet induction （poultry lack urate oxidase）， and high-fat diet combined with urate oxidase inhibitors and joint injection. Based on 11 pieces of included literature， the traditional Chinese and western medicine scoring data of each model were extracted， and the average scoring values of all models were ultimately calculated. The results show that the average clinical concordances of existing CGA animal models in both traditional Chinese and western medicine are 43.33% and 64.44%， respectively. Among them， the model with the highest clinical concordance rate is the one with a high-fat diet combined with potassium oxonate to induce hyperuricemia plus joint injection， achieving 83.33% clinical concordance in western medicine and 60% in traditional Chinese medicine. This model aligns well with the pathogenic characteristics and pathological changes of clinical CGA. ConclusionAlthough current CGA animal models can simulate some pathological characteristics of CGA， they struggle to comprehensively reflect the complex pathological processes of CGA and the characteristics of traditional Chinese medicine syndromes. Therefore， in the future， it is necessary to establish the CGA animal models that incorporate the clinical disease and syndrome characteristics of traditional Chinese and western medicine and formulate the uniform model evaluation criteria， providing more precise tools for CGA mechanism research and the development of traditional Chinese medicine.

Objective To explore the factors affecting the quality of psychological assistance hotline connections in Shaanxi Province, and to provide a basis for optimizing services. Methods A total of 149 calls with suicidal tendencies were included from January to March 2022, and data were collected by 31 trained assessors through standardized questionnaires (general information, suicide risk, emotional intensity, and wiring characteristics). Results The results showed that 56.38% of the callers were female, with age groups concentrated between ≤ 18 years old (29.53%) and 19-34 years old (43.62%). The call duration was mainly between 31 and 45 minutes (50.34%). Operators conducted a suicide risk assessment on the callers, with 38.9% having a comprehensive assessment, 38.9% having an incomplete assessment, and 22.1% having no assessment. The main mental disorders of the callers were depression (48.32%), anxiety (15.44%), and bipolar disorder (14.77%), with 25.50% having comorbidities of ≥ 2 disorders. Emotional scores were as follows: depression (4.11 ± 0.76), sadness (3.97 ± 1.03), and despair (3.78 ± 1.05). There were significant differences in depression, anger, despair, and sadness among the callers with different levels of danger (t=4.79, 3.35, 15.79, 4.24, all P<0.05). Women had higher levels of fear than men (t=3.10, P<0.01). The longer the call duration, the higher the level of despair (t=5.66, P<0.01). Multiple regression analysis showed that incomplete suicide risk assessment by operators (B=-2.36), general procedures for operators' connections (B=5.44), and technical factors (B=2.01) significantly affected the quality of psychological assistance hotlines (all P<0.05). Conclusion Callers with suicidal tendencies generally have serious mental and psychological problems and prominent negative emotions. Strengthening the suicide risk assessment ability of operators and standardizing processes and service attitudes are key to improving the quality of psychological assistance hotlines.

BACKGROUND:Total knee arthroplasty serves as an effective intervention for the treatment of late-stage knee joint disorders.However,prosthetic liners are prone to wear and failure due to internal stress variations,resulting in limited lifespan and decreased postoperative patient activity.Addressing how to enhance prosthetic design to meet a broader range of patient needs constitutes a significant focus in prosthesis research. OBJECTIVE:Based on the morphological design of the meniscus,we propose an asymmetric design prosthesis and compare it with a symmetric posterior stabilized prosthesis.The stress distribution patterns and variations in the contact area of the liners for both prostheses were analyzed to explore whether the asymmetric prosthesis design offers advantages over the symmetric design. METHODS:Using the finite element method,we simulated the osteotomy and prosthesis assembly in a knee osteoarthritis patient.Two different prostheses(asymmetric design and posterior stabilized)were employed to establish post-total knee arthroplasty knee joint models.Under flexion conditions at 0°,10°,20°,and 30°,we investigated the Mises stress on the femoral and tibial components as well as the liner.Additionally,by comparing the contact area on the inner and outer sides of the liner,we aimed to explore the changes in biomechanics and alterations in motion behavior in the post-total knee arthroplasty knee joint. RESULTS AND CONCLUSION:(1)Throughout the flexion range from 0 to 30 degrees,the Mises stress peak on the liner exhibited a trend of initial decrease followed by an increase,with the stress on the medial side consistently surpassing that on the lateral side.(2)In comparison to the posterior stabilized prosthesis,the asymmetrically designed prosthesis demonstrated smaller stress peaks.At a flexion angle of 30 degrees,the Mises stress peak values of the medial and lateral parts of the asymmetric prosthesis were 15.81 MPa and 11.95 MPa,and those of the posterior stabilization prosthesis were 16.70 MPa and 13.76 MPa.The difference of Mises stress on the medial part was 5.33%,and the difference of Mises stress on the lateral part was 13.15%.Comparing the peak Mises stress on the femoral and tibial components,the asymmetric component was always lower than the posterior stable component during knee flexion.(3)In the upright position at 0 degrees,the medial contact area of the posterior stabilization prosthesis was 17.96 mm2,and the lateral contact area was 34.10 mm2.The contact area on the inner and outer sides of the asymmetric design prosthesis liner was 105.47 mm2 and 107.80 mm2,respectively,indicating a larger contact area with a smaller difference between the inner and outer sides.(4)These results suggest that the biomechanical performance of the asymmetric prosthesis is superior,contributing to the maintenance of knee joint stability and improved joint mobility.This design,to a certain extent,mimics the rotational motion mechanism of the knee joint about the medial condyle as an axis,making it a more effective choice for knee joint prosthesis selection.

The zebrafish has emerged as a powerful model organism in life science owing to its remarkable biological characteristics and wide-ranging applications. This review provides a comprehensive overview of the recent advancements in research on zebrafish within the field of environmental toxicology, highlighting specific studies where this species was used to investigate various pollutants to elucidate their impacts and underlying mechanisms. The findings of these studies underscore the significant potential of zebrafish as a model to gain crucial insights into the ecological consequences of environmental contamination and toxicity pathways. By incorporating cutting-edge technologies such as artificial intelligence (AI), high-throughput screening, and omics approaches, the use of zebrafish as a model organism is poised to significantly accelerate toxicological investigations, promote environmental conservation efforts, contribute to safeguarding human health, and advance sustainable development objectives.
Animals ; Zebrafish ; Ecotoxicology/methods* ; Artificial Intelligence ; Humans ; Models, Animal ; Environmental Pollutants/toxicity*

Recently, photodynamic therapy (PDT) has gained considerable attention as a promising therapeutic approach for the treatment of psoriasis. Unfortunately, the activation of high mobility group box 1 protein (HMGB1) by PDT triggers innate and adaptive immune responses, which exacerbate skin inflammation. Herein, we combined glycyrrhizic acid (GA), a natural anti-inflammatory compound and immunomodulator derived from the herb Glycyrrhiza uralensis Fisch., with PDT actuated by the photosensitizer chlorin e6 (Ce6) by co-loading them in GA-based lipid nanoparticles coated with a catechol-modified quaternary chitosan salt (GC NPs/QCS-C). GC NPs/QCS-C exhibited high drug loading efficacy, uniform size distribution, an ideal topical adhesive property, enhanced skin retention and penetration in psoriasis-like lesions, and high intracellular uptake in epidermal cells compared with the counterparts. Subsequently, the transdermal administration of GC NPs/QCS-C followed by near-infrared laser radiation in an imiquimod-induced psoriasis-like mouse model significantly ameliorated psoriasis symptoms, promoted the apoptosis of hyperproliferative epidermal cells, and alleviated the inflammatory cascade. The significant therapeutic outcomes of GC NPs/QCS-C were attributed to the synergistic effects of GA and PDT on modulating immune cell recruitment and inhibiting dendritic cell maturation. Our results demonstrated that the topical bio-adhesive nanosystem that combines GA and Ce6 offers a synergistic chemo-phototherapeutic strategy for psoriasis treatment.

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

OBJECTIVE: Observational studies have shown inconsistent associations of loneliness or social isolation (SI) with ischemic heart disease (IHD), with unknown mediators. METHODS: Using data from genome-wide association studies of predominantly European ancestry, we performed a bidirectional two-sample Mendelian Randomization (MR) study to estimate causal effects of loneliness ( N = 487,647) and SI traits on IHD ( N = 184,305). SI traits included whether individuals lived alone, participated in various types of social activities, and how often they had contact with friends or family ( N = 459,830 to 461,369). A network MR study was conducted to evaluate the mediating roles of 20 candidate mediators, including metabolic, behavioral and psychological factors. RESULTS: Loneliness increased IHD risk ( OR= 2.129; 95% confidence interval [ CI]: 1.380 to 3.285), mediated by body fat percentage, waist-hip ratio, total cholesterol, and low-density lipoprotein cholesterol. For SI traits, only fewer social activities increased IHD risk ( OR= 1.815; 95% CI: 1.189 to 2.772), mediated by hypertension, high-density lipoprotein cholesterol, triglycerides, fasting insulin, and smoking cessation. No reverse causality of IHD with loneliness and SI was found. CONCLUSION These findings suggested more attention should be paid to individuals who feel lonely and have fewer social activities to prevent IHD, with several mediators as prioritized targets for intervention.
Loneliness/psychology* ; Humans ; Mendelian Randomization Analysis ; Social Isolation ; Myocardial Ischemia/etiology* ; Male ; Female ; Middle Aged ; Genome-Wide Association Study ; Risk Factors ; Aged

Objective To construct a conditional knockout mice model of cysteine-rich angiogenesis inducer 61(Cyr61,also known as Ccn1)gene in myocardium and skeletal muscle regulated by CRE recombinant enzyme.Methods C57BL/6 mice were used to create CKmm-Cre+/-Cyr61flox/flox mice by using CRISPR/Cas9 technology.The successful construction of conditional knockout mice was confirmed by identifying the Cyr61flox/flox,3'LoxP and Cre enzyme sequences in mice.The knockout efficiency of Cyr61 was confirmed by Western blot.The skeletal mus-cle function of Cyr61 knockout mice was evaluated and following related indicators in the myocardium and skeletal muscle were detected by Western blot:Aging(p53,p21),inflammatory response(TNF-α,IL-18,IL-1β),fibrosis(vimentin,TGF-β,α-SMA,COL1).Results The mice were successfully bred and identified.In comparison with the control group,Cyr61 protein level showed a significant decrease in both myocardium and skeletal muscle in the experimental group(P＜0.01).Compared with the control group,the experimental group mice showed increased skeletal muscle grip strength(P＜0.05),enhanced maximum single contraction force(P＜0.01),and increased average cross-sectional area of the anterior tibialis muscle(P＜0.05).The expression level of p21,TNF-α,IL-18,IL-1β,TGF-β,and COL1 proteins in the myocardium and skeletal muscle of the experimental group was all lower than those of the control group(P＜0.05).Conclusions Myocardial and skeletal muscle-specific Cyr61 gene condi-tional knockout mice were successfully constructed based on Cre-LoxP technology and heritable trait could be passed stably.

Lung cancer has the highest incidence and mortality among malignant tumors in China.Persistent subsolid nodules(SSNs)are closely associated with early-stage lung adenocarcinoma.Artificial intelligence(AI),as an emerging technology,is capable of performing in-depth analysis of large-scale imaging data through autonomous learning and possesses the ability to predict outcomes from new data,demonstrating great potential and application prospects in the assessment of SSNs.AI can not only effectively assist radiologists in diagnosis and treatment,but also improve work efficiency while reducing misdiagnosis and missed diagnosis rates.This review summarizes the recent applications and research progress of AI in the assessment of SSNs,to provide new insights for the diagnosis and treatment of SSNs.

Objective To investigate the evaluation value of serum 25-hydroxyvitamin D[25-(OH)D],heart-type fatty acid-binding protein(H-FABP),and N-terminal pro-brain natriuret-ic peptide(NT-ProBNP)in early myocardial injury in patients with acute exacerbation of chronic ob-structive pulmonary disease(AECOPD).Methods A total of 120 patients with AECOPD(AECOPD group)were enrolled in this study.Based on the presence of early myocardial injury,they were divided into injury group(n=68)and non-injury group(n=52).Additionally,40 healthy individuals undergoing physical examinations during the same period were included as control group.The differences in serum 25-(OH)D,H-FABP,and NT-ProBNP levels were compared,and the correlations between these markers and clinical data were analyzed.Binary logistic regression analysis was used to explore the relationships between these markers and the occurrence of early myocardial injury.Receiver op-erating characteristic(ROC)curve analysis was employed to assess the diagnostic value of these markers for early myocardial injury in AECOPD patients.Results The forced expiratory volume in the first second(FEV1),forced vital capacity(FVC),the ratio of FEV1 to FVC(FEV1/FVC),and arterial partial pressure of oxygen[pa(O2)]levels in the AECOPD group were lower than those in the control group,while the arterial partial pressure of carbon dioxide[p a(CO2)]level was high-er,with statistically significant differences(P＜0.05).The serum 25-(OH)D levels in the AECOPD group and the injury group were lower than those in the control group and the non-injury group,re-spectively,while the H-FABP and NT-ProBNP levels were higher,with statistically significant differences(P＜0.05).In AECOPD patients,serum 25-(OH)D was positively correlated with FEV1,FVC,FEV1/FVC,and pa(O2),and negatively correlated with pa(CO2)(P＜0.05).In contrast,H-FABP and NT-ProBNP were negatively correlated with FEV1,FVC,FEV1/FVC,and pa(O2),and positively correlated with pa(CO2)(P＜0.05).Binary Logistic regression analysis revealed that 25-(OH)D,H-FABP,and NT-ProBNP were related influencing factors for early myo-cardial injury in AECOPD patients(P＜0.05).ROC curve analysis showed that the areas under the curve(AUCs)for evaluating myocardial injury status based on 25-(OH)D,H-FABP,and NT-ProBNP values were 0.814,0.959,and 0.837,respectively.The AUC of their combination was 0.983,with a sensitivity of 97.06％and a specificity of 80.77％.Conclusion During early myocardial injury in AECOPD patients,there is low expression of serum 25-(OH)D and high ex-pression of H-FABP and NT-ProBNP.These three markers are correlated with early myocardial inju-ry and can serve as reference indicators for clinical diagnosis.