Mid-to-late stage ankle arthritis is a chronic degenerative disease that is extremely common in clinical practice.It is characterized by significant cartilage degeneration and subchondral bone sclerosis,accompanied by the formation of osteophytes around the joint,often leading to joint deformity.This condition causes severe pain in the patients during walking,severely restricts their activities,and affects their qualities of life.In recent years,with the continuous improvement of medical standards,the treatment methods for mid-to-late stage ankle arthritis have shown a diversified development trend.Non-surgical treatments primarily include activity restriction,orthotic devices,oral non-steroidal anti-inflammatory drugs(NSAIDs),and intra-articular injections of the talocrural joint.The surgical treatments primarily include joint distraction arthroplasty,periacetabular osteotomy,total ankle arthroplasty,and ankle arthrodesis.Tissue engineering therapy,as an emerging method,has also received considerable attention.This article systematically reviewed the selection principles and research progress of various treatment options for mid-to-late stage ankle arthritis,including traditional treatments,non-surgical treatments,surgical treatments,and tissue engineering treatments.By deeply analyzing the basic principles and advantages and disadvantages of each treatment method,and combining the latest research findings on clinical outcomes,a scientific and comprehensive clinical decision-making reference system was constructed to provide clearer and more comprehensive treatment choices for both doctors and patients,thereby effectively improving treatment outcomes and enhancing the quality of life for the patients.

Chiropractic therapy is a therapeutic approach for regulating the spine and is widely employed in clinical practice for multiple disorders, including constipation. The theory of "bone strengthening and tendon softening" originated from Huang Di Nei Jing, holding that bones maintain normal anatomical forms and relative positional relationships, and tendons are supple and free from damage. Only when the structures and functions of both are normal can the human body sustain normal physiological activities. In accordance with this theory, clinical treatment mainly aims at adjusting the relationship between tendons and bones and restoring the balance between them to address diseases. Based on the theory of "bone strengthening and tendon softening" and taking the essence of "tendons" as the starting point, this article explored the pathogenic mechanism of outlet obstructive constipation and the clinical application of chiropractic therapy in the treatment of outlet obstructive constipation. Pathological changes of the musculotendinous meridians and abnormal spinal structures are significant pathogenic factors for outlet obstructive constipation. Therefore, in clinical practice, spinal techniques such as guided manipulation, massage, and reconstructive techniques can be used to soften muscles, correct bones, and regulate intestinal stagnation.

BACKGROUND: Recent studies have provided compelling evidence that exposure to brominated flame retardants (BFRs) can adversely affect human health. We aim to explore the potential impact of BFRs on adiposity and central obesity. METHODS: Data from the National Health and Nutrition Examination Surveys (NHANES) cycles conducted between 2009 and 2014 was used to study the connections between variables. After filtering, we analyzed a sample of 4,110 adults aged 20 years and above. Our goal was to examine the potential association between BFRs and consequences and investigate the part played by oxidative stress and inflammatory markers as intermediaries. To achieve this, we used advanced statistical methods such as weighted quantile sum (WQS) regression, quantile-based g-computation (QGC), and the Bayesian kernel machine regression (BKMR). RESULTS: The findings showed that among the examined chemicals, exposure to PBDE85 (weight: 41%), PBDE100 (24%), and PBB153 (23%) may be the dominant contributors to general obesity risk. Upon controlling for all variables that could impact the results, it was found that the QGC outcomes indicated a positive correlation between exposure to mixtures of brominated flame retardants and the occurrence of abdominal obesity (OR = 1.187, 95% CI: 1.056-1.334, p = 0.004). Significant contributions were made by PBDE85 (52%), PBB153 (27%), and PBDE100 (21%). Mediation analysis shows that lymphatic cells (LC) and albumin (ALB) partially mediate the link between brominated flame retardants and obesity. The results of BKMR are generally consistent with those of WQS and QGC. CONCLUSION At a population level, our research has revealed a noteworthy correlation between BFRs and obesity. However, further investigation is required through prospective cohort studies and in-depth mechanistic exploratory studies.
Humans ; Flame Retardants/adverse effects* ; Oxidative Stress/drug effects* ; Adult ; Male ; Female ; Middle Aged ; Inflammation/epidemiology* ; Obesity/chemically induced* ; Biomarkers/blood* ; Nutrition Surveys ; Mediation Analysis ; Young Adult ; United States/epidemiology* ; Environmental Exposure/adverse effects* ; Aged ; Environmental Pollutants/adverse effects* ; Halogenated Diphenyl Ethers/adverse effects*

This study aimed to explore the effects and mechanisms of total extracts from Anthriscus sylvestris on pulmonary hypertension in rats. Sixty male SD rats were divided into normal(NC) group, model(M) group, positive drug sildenafil(Y) group, low-dose A. sylvestris(ES-L) group, medium-dose A. sylvestris(ES-M) group, and high-dose A. sylvestris(ES-H) group. On day 1, rats were intraperitoneally injected with monocrotaline(60 mg·kg~(-1)) to induce pulmonary hypertension, and the rat model was established on day 28. From days 15 to 28, intragastric administration of the respective treatments was performed. After modeling and treatment, small animal echocardiography was used to detect the right heart function of the rats. Arterial blood gas was measured using a blood gas analyzer. Hematoxylin and eosin(HE) staining and Masson staining were performed to observe cardiopulmonary pathological damage. Flow cytometry was used to detect apoptosis in the lung and myocardial tissues and reactive oxygen species(ROS) levels. Western blot was applied to detect the expression levels of transforming growth factor-β1(TGF-β1), phosphorylated mothers against decapentaplegic homolog 3(p-Smad3), Smad3, tissue plasminogen activator(t-PA), and plasminogen activator inhibitor-1(PAI-1) in lung tissue. A blood routine analyzer was used to measure inflammatory immune cell levels in the blood. Enzyme-linked immunosorbent assay(ELISA) was used to detect the expression levels of P-selectin and thromboxane A2(TXA2) in plasma. The results showed that, compared with the NC group, right heart hypertrophy index, right ventricular free wall thickness, right heart internal diameter, partial carbon dioxide pressure(PaCO_2), apoptosis in cardiopulmonary tissue, and ROS levels were significantly increased in the M group. In contrast, the ratio of pulmonary blood flow acceleration time(PAT)/ejection time(PET), right cardiac output, change rate of right ventricular systolic area, systolic displacement of the tricuspid ring, oxygen partial pressure(PaO_2), and blood oxygen saturation(SaO_2) were significantly decreased in the M group. After administration of the total extract of A. sylvestris, right heart function and blood gas levels were significantly improved, while apoptosis in cardiopulmonary tissue and ROS levels significantly decreased. Further testing revealed that the total extract of A. sylvestris significantly decreased the levels of interleukin-1β(IL-1β), interleukin-6(IL-6), and PAI-1 proteins in lung tissue, while increasing the expression of t-PA. Additionally, the extract reduced the levels of inflammatory cells such as leukocytes, lymphocytes, granulocytes, and monocytes in the blood, as well as the levels of P-selectin and TXA2 in plasma. Metabolomics results showed that the total extract of A. sylvestris significantly affected metabolic pathways, including arginine biosynthesis, tyrosine metabolism, and taurine and hypotaurine metabolism. In conclusion, the total extract of A. sylvestris may exert an anti-pulmonary hypertension effect by inhibiting the TGF-β1/Smad3 signaling pathway, thereby alleviating immune-inflammatory responses and thrombosis.
Animals ; Male ; Smad3 Protein/metabolism* ; Transforming Growth Factor beta1/metabolism* ; Rats, Sprague-Dawley ; Rats ; Signal Transduction/drug effects* ; Hypertension, Pulmonary/genetics* ; Thrombosis/immunology* ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Apoptosis/drug effects*

Diabetic foot (DF) is one of the most serious chronic complications of diabetes. The incidence rate among global diabetes patients is as high as 15% to 25%, and about 50% of patients will develop contralateral foot ulcers within 5 years after the first unilateral ulcer. As a non-invasive prevention and control solution, the application progress of functional insoles is mainly reflected in the following aspects:(1) Material innovation. The application of new composite materials and smart materials has significantly enhanced the pressure reduction effect and comfort. (2) Structural optimization. The development of multi-layer design and local pressure reduction structure has achieved more precise pressure distribution regulation. (3) Manufacturing process. 3D printing and parametric design have enabled the personalized customization of functional insoles. (4) Intelligent monitoring. It integrates functions such as pressure sensing and temperature monitoring, achieving real-time monitoring and early warning of foot conditions. Clinical research has confirmed that personalized functional insoles could reduce the incidence of foot ulcers and shorten the healing time of ulcers. At present, the research hotspots mainly focus on the development of smart materials, the construction of multi-functional integration and remote monitoring systems. However, in-depth research is still needed in the aspects of biomechanical mechanisms, standardized evaluation systems and long-term efficacy assessment. The development of future functional insoles should focus on the coordinated advancement of "personalization-intelligence-standardization", with the aim of providing more effective solutions for the prevention and treatment of DF.
Humans ; Diabetic Foot/therapy* ; Foot Orthoses

Objective:To establish a flow cytometric bead assay (FCBA) for detecting von Willebrand factor (vWF) activity based on mutant GPⅠbα and to perform its clinical validation.Methods:Recombinant GPⅠbα protein with M239V, D235Y, and C65A point mutations was constructed and bound to flow cytometric beads. vWF in samples bound to the recombinant protein, and FITC-labeled rabbit anti-human vWF polyclonal antibody was added for detection and analysis using flow cytometry. A total of 32 patients with von Willebrand disease (10 males and 22 females, aged 26.81±6.96 years) admitted to the Department of Hematology at the First Affiliated Hospital of Soochow University from January 1, 2022, to November 30, 2023, were enrolled. Additionally, 51 healthy controls (17 males and 34 females, aged 31.56±8.98 years) were included. Plasma from 20 healthy controls was pooled in equal proportions to create standard plasma. Fourteen dilutions were prepared, ranging from the original plasma to a 1∶8, 192 dilution, and a curve was plotted according to the FCBA protocol to determine the optimal dilution. Plasma from one healthy control was aliquoted and frozen, and FCBA was performed on days 1, 5, 15, 30, 45, and 60 after bead coating to evaluate stability. The same healthy control plasma sample was tested 20 times using both FCBA and vWF enzyme-linked immunesorbent assay (ELISA) to calculate within-batch precision. The same sample was tested daily for 10 consecutive days using both FCBA and vWF-ELISA to calculate between-batch precision. All samples were tested using FCBA, and the same samples were also tested using vWF-ELISA. The χ2 test was used to compare the positive rates, negative rates, and accuracy of the two methods. One sample was used as the base sample, and another sample with a known activity of 100% was diluted to high, medium, and low activities and added to the base sample. Recovery rates were calculated using both FCBA and vWF-ELISA. Re-collected 11 cases of vWD patient samples and 10 cases of healthy subjects, and detected vWF activity using the FCBA method to validate the concordance of FCBA in clinical applications. Results:The optimal dilution for standard plasma was determined to be 1∶64. The coated beads remained stable for detection up to 60 days, with correlation coefficients of the standard curve on days 1, 5, 15, 30, 45, and 60 being 0.98, 0.98, 0.97, 0.95, 0.95, and 0.95, respectively. The within-batch coefficients of variation for FCBA and vWF-ELISA were 5.35% and 6.08%, respectively, while the between-batch coefficients of variation were 7.02% and 7.98%, respectively. The correlation coefficient between FCBA and vWF-ELISA was R2=0.798 ( P0.01). The positive rates were 90.63% and 84.38% ( χ2=0.571, P0.05), the negative rates were 92.16% and 94.12% ( χ2=0.153, P0.05), and the accuracy rates were 91.57% and 90.36% ( χ2=0.073, P0.05) for FCBA and vWF-ELISA, respectively. In the recovery experiment, the high-value recovery rates for FCBA and ELISA were 102.11% and 99.32%, respectively, the medium-value recovery rates were 98.50% and 95.66%, and the low-value recovery rates were 95.34% and 88.51%. The FCBA method achieved a 100% concordance rate in detecting type 1, type 2, and type 3 vWD, as well as healthy subjects. Conclusion:A ristocetin-independent FCBA method for detecting vWF activity based on mutant GPⅠbα is successfully established.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

Objective:To establish a flow cytometric bead assay (FCBA) for detecting von Willebrand factor (vWF) activity based on mutant GPⅠbα and to perform its clinical validation.Methods:Recombinant GPⅠbα protein with M239V, D235Y, and C65A point mutations was constructed and bound to flow cytometric beads. vWF in samples bound to the recombinant protein, and FITC-labeled rabbit anti-human vWF polyclonal antibody was added for detection and analysis using flow cytometry. A total of 32 patients with von Willebrand disease (10 males and 22 females, aged 26.81±6.96 years) admitted to the Department of Hematology at the First Affiliated Hospital of Soochow University from January 1, 2022, to November 30, 2023, were enrolled. Additionally, 51 healthy controls (17 males and 34 females, aged 31.56±8.98 years) were included. Plasma from 20 healthy controls was pooled in equal proportions to create standard plasma. Fourteen dilutions were prepared, ranging from the original plasma to a 1∶8, 192 dilution, and a curve was plotted according to the FCBA protocol to determine the optimal dilution. Plasma from one healthy control was aliquoted and frozen, and FCBA was performed on days 1, 5, 15, 30, 45, and 60 after bead coating to evaluate stability. The same healthy control plasma sample was tested 20 times using both FCBA and vWF enzyme-linked immunesorbent assay (ELISA) to calculate within-batch precision. The same sample was tested daily for 10 consecutive days using both FCBA and vWF-ELISA to calculate between-batch precision. All samples were tested using FCBA, and the same samples were also tested using vWF-ELISA. The χ2 test was used to compare the positive rates, negative rates, and accuracy of the two methods. One sample was used as the base sample, and another sample with a known activity of 100% was diluted to high, medium, and low activities and added to the base sample. Recovery rates were calculated using both FCBA and vWF-ELISA. Re-collected 11 cases of vWD patient samples and 10 cases of healthy subjects, and detected vWF activity using the FCBA method to validate the concordance of FCBA in clinical applications. Results:The optimal dilution for standard plasma was determined to be 1∶64. The coated beads remained stable for detection up to 60 days, with correlation coefficients of the standard curve on days 1, 5, 15, 30, 45, and 60 being 0.98, 0.98, 0.97, 0.95, 0.95, and 0.95, respectively. The within-batch coefficients of variation for FCBA and vWF-ELISA were 5.35% and 6.08%, respectively, while the between-batch coefficients of variation were 7.02% and 7.98%, respectively. The correlation coefficient between FCBA and vWF-ELISA was R2=0.798 ( P0.01). The positive rates were 90.63% and 84.38% ( χ2=0.571, P0.05), the negative rates were 92.16% and 94.12% ( χ2=0.153, P0.05), and the accuracy rates were 91.57% and 90.36% ( χ2=0.073, P0.05) for FCBA and vWF-ELISA, respectively. In the recovery experiment, the high-value recovery rates for FCBA and ELISA were 102.11% and 99.32%, respectively, the medium-value recovery rates were 98.50% and 95.66%, and the low-value recovery rates were 95.34% and 88.51%. The FCBA method achieved a 100% concordance rate in detecting type 1, type 2, and type 3 vWD, as well as healthy subjects. Conclusion:A ristocetin-independent FCBA method for detecting vWF activity based on mutant GPⅠbα is successfully established.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.