ObjectiveTo explore the potential mechanisms of action of the modified Duhuo Jisheng Mixture （JDJM） in treating synovial lesions in knee osteoarthritis （KOA）. MethodsA total of 43 male New Zealand white rabbits were randomly allocated into a blank group （n=8） and a model group （n=35）. The KOA model was induced by immobilizing the right hind limb with a high-molecular resin plaster bandage， with a modeling period of 6 weeks， resulting in successful modeling in 32 rabbits. These rabbits were then randomly allocated to the model group， celecoxib group， JDJM group and JDJM+740Y-P group， each consisting of 8 rabbits. The celecoxib group received celecoxib via gavage at a single dose of 0.009 3 g·kg^-1， while the JDJM was administered a single dose of 6.8 mL·kg^-1 （4.515 2 g·kg^-1） of the herbal preparation via gavage. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） pathway activator + JDJM group received 4.515 2 g·kg^-1 of the herbal preparation via gavage along with an auricular vein injection of 0.15 μmol·kg^-1 740Y-P. For a period of 6 weeks， the remaining groups received an equal volume of physiological saline via gavage daily. After the medication period， the knee joint pain threshold and circumference were measured， and hematoxylin-eosin （HE） staining was performed to assess the pathological changes in the synovial tissues. Enzyme-linked immunosorbent assay （ELISA） measured the levels of interleukin-1β （IL-1β）， interleukin-6 （IL-18） and tumor necrosis factor-α （TNF-α） in the joint fluid. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to assess the mRNA expression of PI3K， Akt， mTOR， NOD-like receptor protein 3 （NLRP3）， cysteine-requiring aspartate protease-1 （Caspase-1） and gasdermin D （GSDMD） in the synovial tissues. Immunohistochemical （IHC） assay was performed to assess the protein expression of NLRP3， Caspase-1 and GSDMD. Western blot was carried out to analyze the protein expression of p-PI3K/PI3K， p-Akt/Akt， p-mTOR/mTOR， NLRP3， Caspase-1 and GSDMD. ResultsCompared to the blank group， the model group showed a significant increase in knee joint circumference and decrease in pain threshold， the synovial tissue pathology score was higher （P<0.05）， and the levels of IL-1β， IL-18， and TNF-α in the joint fluid significantly increased （P<0.01）. PI3K， Akt， mTOR phosphorylation as well as mRNA and protein expression increased （P<0.01）， while the mRNA and protein expression levels of NLRP3， Caspase-1 and GSDMD also significantly increased （P<0.01）. Compared to the model group， the celecoxib and JDJM groups exhibited a significant reduction in knee joint circumference and increase in pain threshold， the synovial tissue pathology score was lower （P<0.05）， and the levels of IL-1β， IL-18， and TNF-α in the joint fluid decreased （P<0.01）. The mRNA and protein expression of p-PI3K， p-Akt， p-mTOR， NLRP3， Caspase-1 and GSDMD were reduced （P<0.01）. Compared to the JDJM group， the JDJM+740Y-P group showed a decrease in the improvement of synovial lesions， an increase in knee joint circumference， and a decrease in pain threshold. The synovial tissue pathology score was lower （P<0.05）， and the levels of IL-1β， IL-18， and TNF-α in the joint fluid were higher （P<0.01）. The mRNA and protein expression of p-PI3K/PI3K， p-Akt/Akt， p-mTOR/mTOR， NLRP3， Caspase-1 and GSDMD increased （P<0.01）. ConclusionJDJM is effective in treating KOA. Its mechanism may involve modulating the PI3K/Akt/mTOR pathway in synovial tissues， inhibiting pyroptosis， reducing inflammatory factor release， and protecting bony structures.

OBJECTIVE To provide references for medical institutions’ outpatient pharmacies to increase the scanning rate， scanning efficiency and scanning accuracy of drug traceability codes.METHODS A total of 4 157 unscanned traceability code records from the first two‑week period of June 2025 were selected from the outpatient pharmacy of our hospital. Pareto chart was adopted to analyze the reasons for unscanned codes， and the Objective-Rules-Training-Check-Culture （ORTCC） model was utilized to carry out fine management. The traceability code scanning rate， pharmacists’ work efficiency （number of prescriptions dispensed per pharmacist per hour， number of drug boxes dispensed per pharmacist per hour）， patients’ medication-waiting time and dispensing errors were compared among four periods： before scanning implementation （June 2024）， before management intervention （June 2025）， the first phase after management （September 2025）， and the second phase after management （December 2025）， so as to evaluate the management effects.RESULTS The traceability code scanning rates in the first phase and second phase after management were remarkably higher than those before management （ P ＜0.05）， and the scanning rate in the second phase after management was obviously higher than that in the first phase after management （ P ＜0.05）. Compared with the period before scanning implementation， the number of prescriptions dispensed per pharmacist per hour， the number of drug boxes dispensed per pharmacist per hour， decreased significantly and patients’ medication-waiting time prolonged markedly before management （ P ＜0.05）. In the second phase after management， both the number of prescriptions dispensed per pharmacist per hour and the number of drug boxes dispensed per pharmacist per hour increased significantly， and patients’ medication-waiting time shortened greatly in contrast with the status before management （ P ＜0.05）. Besides， no statistically significant differences were found in the number of drug boxes dispensed per pharmacist per hour and patients’ medication-waiting time between the second phase after management and the period before scanning implementation （ P ＞0.05）.After the implementation of traceability-code scanning management， dispensing errors presented a gradually declining trend in each stage.CONCLUSIONS The fine management system for outpatient drug traceability codes constructed based on Pareto chart and ORTCC model can improve the traceability code scanning rate and pharmacists’ work efficiency of outpatient pharmacies， and reduce drug dispensing errors.

Objective To analyze the risk factors and clinical outcomes of cognitive impairment in elderly patients with heart disease after surgery.Methods A total of 156 patients with heart valve diseases undergoing coronary artery bypass surgery admitted to the First Affiliated Hospital of H ainan Medical University from October 2021 to December 2023 were prospectively recruited.At 7 d postoperatively,Montreal cognitive assessment(MoCA)scale was used to assess their cogni-tive function,and based on MoCA score＜26 or not,they patients were divided into a cognitive impairment group(n=61)and a control group(n=95).The clinical features were compared be-tween the two groups,and the risk factors for cognitive impairment were analyzed.All patients were followed up for 1 year to compare the outcomes of the two groups.Results The cognitive impairment group had significantly advanced age,larger proportions of concomitant chronic respiratory diseases and sarcopenia,increased ratio of undergoing open heart surgery,and elevated incidence of intraoperative hypotension than the control group(P＜0.05,P＜0.01).Multivariate logistic regression analysis indicated that age,chronic respiratory diseases,sarcopenia,open heart surgery,and intraoperative hypotension were independent risk factors for postoperative cognitive impairment in elderly patients with heart diseases(OR=1.081,95％CI:1.007-1.161,P=0.030;OR=2.538,95％CI:1.062-6.066,P=0.036;OR=2.650,95％CI:1.174-5.985,P=0.019;OR=3.104,95％CI:1.391-6.929,P=0.006;OR=3.478,95％CI:1.298-9.322,P=0.0013).There was no statistical difference in preoperative MoCA scores between the two groups(27.90±1.40 vs 28.20±1.40,P=0.195).The MoCA score at 7 d and 6 and 12 months after surgery were obviously lower in the cognitive impairment group than the control group(22.90±1.27 vs 27.73±1.08,P=0.000;24.72±1.66 vs 27.73±1.23,P=0.000;25.48±1.73 vs 27.62±1.22,P=0.000).Age was identified as an independent factor affecting the outcome of cognitive function in the patients(OR=1.168,95％CI:1.035-1.318).Conclusion The incidence of postoperative cog-nitive impairment is relatively high in elderly patients with heart disease.So,relevant risk factors should be addressed to strengthen the prevention and management.

Objective:To describe epidemiological characteristics and their influencing factors of diabetes and pre-diabetes among adult residents in Hainan Province and provide a theoretical basis to develop epidemic prevention and control strategies for diabetes.Methods:This study used a two-stage unequal proportion cluster sampling method, and 32 857 subjects (≥18 years old) were collected from 24 cities/counties/districts in Hainan Province. All the subjects were investigated with questionnaires, physical examination, and laboratory tests from January to June 2023. The χ2 and Mantel-Haenszel trend χ2 tests were used to analyze the data. Multivariate logistic regression was used to analyze the factors influencing diabetes and pre-diabetes. SPSS 23.0 software was used to analyze the data. Results:The crude prevalence of diabetes and pre-diabetes in adult residents of Hainan Province were 18.1% and 22.8%, while the weighted rates were 13.7% and 20.7%, respectively. The results of multivariate logistic regression analysis showed that: aging (30-39 years old: OR=2.65, 95% CI: 2.06-3.41; 40-49 years old: OR=5.64, 95% CI: 4.40-7.24; 50- 59 years old: OR=9.88, 95% CI: 7.71-12.67; 60-69 years old: OR=18.34, 95% CI: 14.28-23.55; 70-79 years old: OR=21.30, 95% CI: 16.41-27.65; 80 years old and above: OR=24.13, 95% CI: 17.94-32.46), nationality (Li minority group: OR=1.50, 95% CI: 1.38-1.63; other ethnic groups: OR=1.53, 95% CI: 1.20-1.94), urban ( OR=1.12, 95% CI: 1.04-1.21), central obesity ( OR=2.14, 95% CI: 2.01-2.29), higher frequency of alcohol consumption (5-7 day/week: OR=1.24, 95% CI: 1.11-1.38), physical inactivity ( OR=1.09, 95% CI: 1.02-1.17) were risk factors for diabetes, while aging (30-39 years old: OR=1.53, 95% CI: 1.31-1.79; 40-49 years old: OR=2.36, 95% CI: 2.01-2.76; 50-59 years old: OR=3.03, 95% CI: 2.58-3.55; 60-69 years old: OR=4.22, 95% CI: 3.58-4.97; 70-79 years old: OR=5.05, 95% CI: 4.23-6.04; 80 years old and above: OR=6.08, 95% CI: 4.86-7.61), nationality: (Li minority group: OR=1.18, 95% CI: 1.10-1.28; other ethnic groups: OR=1.40, 95% CI: 1.14-1.71), urban ( OR=1.12, 95% CI: 1.04-1.19), central obesity ( OR=1.72, 95% CI: 1.62-1.83), higher frequency of alcohol consumption (1-4 day/week: OR=1.12, 95% CI: 1.01-1.23; 5-7 day/week: OR=1.35, 95% CI: 1.22-1.49) were risk factors for pre-diabetes. Conclusions:The epidemic situation of diabetes and pre-diabetes among adult residents in Hainan Province was not optimistic. In order to control the development of abnormal blood glucose, measures and targeted health education should be carried out to strengthen the screening, treatment, and management of people with abnormal blood glucose among different populations.

Objective:To investigate the laboratory diagnostic value of 5 new blood routine indexes in chronic hepatitis B (CHB), liver cirrhosis and hepatocellular carcinoma (HCC).Methods:The retrospective study included 65 patients with chronic HBV infection, 72 patients with liver cirrhosis and 163 patients with HCC recruited at Liver Disease Center in First Affiliated Hospital of Fujian Medical University, as well as 52 healthy controls recruited from the Physical Examination Center of the First Affiliated Hospital of Fujian Medical University from October 2022 to April 2023. Five new parameters [early granulated cell percent (EGC%), early granulated cell absolute count (EGC#), microcytic anemia factor (MAF), leukocyte estimate(corrected)from the DIFF optical channel (WDOP) and leukocyte estimate(corrected)from the NRBC optical channel (WNOP)] were detected by UniCel DxH 900 blood cell analyzer. Univariate analysis of the expression levels of the 5 new parameterswere compared among CHB, liver cirrhosis and HCC groups. Pearson correlation analysis was used to explore the correlation between the 5 new parameters and HBV-related markers in CHB and Child-Pugh score in liver cirrhosis. Receiver operating characteristic (ROC) curve and AUC were used to estimate the diagnostic capacity of the 5 new blood routine indexes in CHB, liver cirrhosis and HCC.Results:In patients with CHB, the levels of EGC% ( Z=4.613, P<0.001) and EGC# ( Z=4.220, P<0.001) were higher than those of healthy controls; EGC# was positively correlated with HBsAg and HBeAg (both P<0.05). In patients with cirrhosis, the level of MAF ( Z=-4.928, P<0.001) was lower than that of healthy controls, and Child-Pugh score was found to be negatively correlated with MAF ( r=-0.349, P<0.05). In HCC patients, WDOP ( Z=2.45, P=0.017) and WNOP ( Z=2.90, P=0.017) levels were higher in patients with tumor volume>3 cm 3 than those in patients with volume ≤3 cm 3. The AUCs of combination of 5 new parameters to diagnose CHB, liver cirrhosis and HCC were 0.901 (95% CI 0.830-0.973, P<0.001), 0.946 (95% CI 0.909-0.984, P<0.001), and 0.904 (95% CI 0.858-0.950, P<0.001). Conclusions:The 5 new parameters based on peripheral blood cell analysis have good clinical value in the diagnosis of CHB, liver cirrhosis and HCC diseases.

As a new manner of cell death,cuproptosis depends on the accumulation of copper ions in cells.Copper ion is an essential trace element in normal physiological state of organisms.The excess of free copper in cells not only has toxic effect on normal cells,but also plays its specific killing function on tumor cells.Copper transporter 1(CTR1)is a key transporter of transmembrane uptake of copper ions by cells.As a regulator of cuproptosis,its mutation and expression changes in tumors have an impact on the distribution of copper ions inside and outside the cells.It may participate in multiple biological processes such as proliferation,invasion and migration of tumor cells by regulating the pathway of cuproptosis.This article reviews the cuproptosis pathway mediated by CTR1 and the potential value of CTR1 in tumor treatment,elaborates the importance of copper ion homeostasis regulation for normal life activities and the mechanism of CTR1 in regulating cuproptosis,and discusses the potential value of CTR1 as a new target for tumor therapy,so as to provide a theoretical basis for the treatment of tumor patients.

BACKGROUND:Fibromyalgia syndrome,as a common rheumatic disease,is related to central sensitization and immune abnormalities.However,the specific mechanism has not been elucidated,and there is a lack of specific diagnostic markers.Exploring the possible pathogenesis of this disease has important clinical significance. OBJECTIVE:To screen the potential diagnostic marker genes of fibromyalgia syndrome and analyze the possible immune infiltration characteristics based on bioinformatics methods,such as weighted gene co-expression network analysis(WGCNA),and machine learning. METHODS:Gene expression profiles in peripheral serum of fibromyalgia syndrome patients and healthy controls were obtained from the gene expression omnibus(GEO)database.The differentially co-expressed genes were screened in the expression profile by differential analysis and WGCNA analysis.Least absolute shrinkage and selection operator(LASSO)and support vector machine-recursive feature elimination(SVM-RFE)machine learning algorithm were further used to identify hub biomarkers,and draw receiver operating characteristic curve(ROC)to evaluate the accuracy of diagnosing fibromyalgia syndrome.Finally,single sample gene set enrichment analysis(ssGSEA)and gene set enrichment analysis(GSEA)were used to evaluate the immune cell infiltration and pathway enrichment in patients with fibromyalgia syndrome. RESULTS AND CONCLUSION:Eight down-regulated differentially expressed genes(DEGs)were obtained after differential analysis of the GSE67311 dataset according to the conditions of log2|(FC)|>0 and P<0.05.After WGCNA analysis,497 genes were included in the module(MEdarkviolet)with the highest positive correlation(r=0.22,P=0.04),and 19 genes were included in the module(MEsalmon2)with the highest negative correlation(r=-0.41,P=6×10-5).After intersecting DEGs and the module genes of WGCNA,seven genes were obtained.Four genes were screened out by LASSO regression algorithm and five genes were screened out by SVM-RFE machine learning algorithm.After the intersection of the two,three core genes were identified,which were germinal center associated signaling and motility like,integrin beta-8,and carboxypeptidase A3.The areas under the ROC curve of the three core genes were 0.744,0.739,and 0.734,respectively,indicating that they have good diagnostic value and can be used as biomarkers for fibromyalgia syndrome.The results of immune infiltration analysis showed that memory B cells,CD56 bright NK cells,and mast cells were significantly down-regulated in patients with fibromyalgia syndrome compared with the control group(P<0.05),and were significantly positively correlated with the above three biomarkers(P<0.05).The enrichment analysis suggested that there were nine fibromyalgia syndrome enrichment pathways,mainly related to olfactory transduction pathway,neuroactive ligand-receptor interaction,and infection pathway.The above results showed that the occurrence and development of fibromyalgia syndrome are related to the involvement of multiple genes,abnormal immune regulation,and multiple pathways imbalance.However,the interactions between these genes and immune cells,as well as their relationships with various pathways need to be further investigated.

BACKGROUND: The contraction behaviors of cardiomyocytes (CMs), especially contraction synchrony, are crucial factors reflecting their maturity and response to drugs. A wider field of view helps to observe more pronounced synchrony differences, but the accompanied greater computational load, requiring more computing power or longer computational time. METHODS: We proposed a method that directly correlates variations in optical field brightness with cardiac tissue contraction status (CVB method), based on principles from physics and photometry, for rapid video analysis in wide field of view to obtain contraction parameters, such as period and contraction propagation direction and speed. RESULTS: Through video analysis of human induced pluripotent stem cell (hiPSC)-derived CMs labeled with green fluorescent protein (GFP) cultured on aligned and random nanofiber scaffolds, the CVB method was demonstrated to obtain contraction parameters and quantify the direction and speed of contraction within regions of interest (ROIs) in wide field of view. The CVB method required less computation time compared to one of the contour tracking methods, the LucasKanade (LK) optical flow method, and provided better stability and accuracy in the results. CONCLUSION This method has a smaller computational load, is less affected by motion blur and out-of-focus conditions, and provides a potential tool for accurate and rapid analysis of cardiac tissue contraction synchrony in wide field of view without the need for more powerful hardware.

BACKGROUND: The contraction behaviors of cardiomyocytes (CMs), especially contraction synchrony, are crucial factors reflecting their maturity and response to drugs. A wider field of view helps to observe more pronounced synchrony differences, but the accompanied greater computational load, requiring more computing power or longer computational time. METHODS: We proposed a method that directly correlates variations in optical field brightness with cardiac tissue contraction status (CVB method), based on principles from physics and photometry, for rapid video analysis in wide field of view to obtain contraction parameters, such as period and contraction propagation direction and speed. RESULTS: Through video analysis of human induced pluripotent stem cell (hiPSC)-derived CMs labeled with green fluorescent protein (GFP) cultured on aligned and random nanofiber scaffolds, the CVB method was demonstrated to obtain contraction parameters and quantify the direction and speed of contraction within regions of interest (ROIs) in wide field of view. The CVB method required less computation time compared to one of the contour tracking methods, the LucasKanade (LK) optical flow method, and provided better stability and accuracy in the results. CONCLUSION This method has a smaller computational load, is less affected by motion blur and out-of-focus conditions, and provides a potential tool for accurate and rapid analysis of cardiac tissue contraction synchrony in wide field of view without the need for more powerful hardware.

BACKGROUND: The mechanisms distinguishing metabolically healthy from unhealthy phenotypes within the same BMI categories remain unclear. This study aimed to investigate the associations between regional fat distribution and metabolically unhealthy phenotypes in Chinese adults across different BMI categories. METHODS: This cross-sectional study involving 11833 Chinese adults aged 20 years and older. Covariance analysis, adjusted for age, compared the percentage of regional fat (trunk, leg, or arm fat divided by whole-body fat) between metabolically healthy and unhealthy participants. Trends in regional fat percentage with the number of metabolic abnormalities were assessed by the Jonckheere-Terpstra test. Odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated by logistic regression models. All analyses were performed separately by sex. RESULTS: In non-obese individuals, metabolically unhealthy participants exhibited higher percent trunk fat and lower percent leg fat compared to healthy participants. Additionally, percent trunk fat increased and percent leg fat decreased with the number of metabolic abnormalities. After adjustment for demographic and lifestyle factors, as well as BMI, higher percent trunk fat was associated with increased odds of being metabolically unhealthy [highest vs. lowest quartile: ORs (95%CI) of 1.64 (1.35, 2.00) for men and 2.00 (1.63, 2.46) for women]. Conversely, compared with the lowest quartile, the ORs (95%CI) of metabolically unhealthy phenotype in the highest quartile for percent arm and leg fat were 0.64 (0.53, 0.78) and 0.60 (0.49, 0.74) for men, and 0.72 (0.56, 0.93) and 0.46 (0.36, 0.59) for women, respectively. Significant interactions between BMI and percentage of trunk and leg fat were observed in both sexes, with stronger associations found in individuals with normal weight and overweight. CONCLUSIONS Trunk fat is associated with a higher risk of metabolically unhealthy phenotype, while leg and arm fat are protective factors. Regional fat distribution assessments are crucial for identifying metabolically unhealthy phenotypes, particularly in non-obese individuals.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Adipose Tissue ; Body Fat Distribution ; Body Mass Index ; China/epidemiology* ; Cross-Sectional Studies ; Health Surveys ; Phenotype