BACKGROUND:A large number of studies have demonstrated that stem cell exosomes play an important role in the repair of bone defects,either directly as carriers for loading other small molecules or surface modifications,or by binding to biomaterials to promote the repair and regeneration of bone tissue.OBJECTIVE:To summarize the osteogenic mechanisms of stem cell exosomes from different sources and their research progress in bone defect repair.METHODS:Chinese search terms"stem cell,exosome,bone,biomaterial,carrier,bioceramic,polymer,metal,hydrogel,engineered exosome"were used to search CNKI.English search terms"stem cell,exosome,bone defect,biomaterial,carrier,bioceramic,ploymer,metal material,hydrogel,engineering exosome"were used to search PubMed database.According to the inclusion and exclusion criteria,77 relevant articles were finally included for summary.RESULTS AND CONCLUSION:Exosomes from stem cells of different origins can promote osteoblast proliferation and differentiation,promote angiogenesis,and regulate osteoclast activity and macrophage phenotype to promote bone formation and bone mineralization.In addition,many achievements of exosomes in the field of bone defect repair were described from two aspects:biomaterial-assisted exosomes and engineered exosomes.However,the current research on stem cell exosomes in bone tissue engineering is still insufficient,and most of these studies are limited to small animal models,while the treatment of bone defects in large animals,including humans,will be more complex,which will also become a major challenge for the treatment of bone defects.This will also be a great challenge in the dissemination of exosome therapy.

BACKGROUND:A large number of studies have demonstrated that stem cell exosomes play an important role in the repair of bone defects,either directly as carriers for loading other small molecules or surface modifications,or by binding to biomaterials to promote the repair and regeneration of bone tissue.OBJECTIVE:To summarize the osteogenic mechanisms of stem cell exosomes from different sources and their research progress in bone defect repair.METHODS:Chinese search terms"stem cell,exosome,bone,biomaterial,carrier,bioceramic,polymer,metal,hydrogel,engineered exosome"were used to search CNKI.English search terms"stem cell,exosome,bone defect,biomaterial,carrier,bioceramic,ploymer,metal material,hydrogel,engineering exosome"were used to search PubMed database.According to the inclusion and exclusion criteria,77 relevant articles were finally included for summary.RESULTS AND CONCLUSION:Exosomes from stem cells of different origins can promote osteoblast proliferation and differentiation,promote angiogenesis,and regulate osteoclast activity and macrophage phenotype to promote bone formation and bone mineralization.In addition,many achievements of exosomes in the field of bone defect repair were described from two aspects:biomaterial-assisted exosomes and engineered exosomes.However,the current research on stem cell exosomes in bone tissue engineering is still insufficient,and most of these studies are limited to small animal models,while the treatment of bone defects in large animals,including humans,will be more complex,which will also become a major challenge for the treatment of bone defects.This will also be a great challenge in the dissemination of exosome therapy.

Objective To explore the effects of indole-3-acetic acid (IAA) on metabolic dysfunction associated steatohepatitis (MASH) related liver fibrosis and its molecular mechanism. Methods A human-derived 3D liver spheroid was established and free fatty acid (FFA) was added to induce the MASH model. The spheroids were divided into five groups: control group, MASH group, low dose IAA group (FFA＋4 μmol/L IAA), medium dose IAA group (FFA＋20 μmol/L IAA) and high dose IAA group (FFA＋100 μmol/L IAA). Transforming growth factor-β1 (TGF-β1) was administrated to hepatic stellate cell lines LX-2. LX-2 cells were divided into four groups: control group, TGF-β1 group, medium dose IAA group (TGF-β1＋20 μmol/L IAA) and high dose IAA group (TGF-β1＋100 μmol/L IAA). Hematoxylin and eosin staining and Sirius red staining were performed to estimate pathological change. Immunofluorescence was performed to evaluate smooth muscle actin α (α-SMA), COL1A1, β-catenin level. Real-time quantitative reverse transcription polymerase chain reaction was performed to evaluate COL1A1, TGFB, CTNNB1, CCND1, MMP7, ACTA2 levels. Western blotting was performed to evaluate α-SMA and β-catenin level. CCK-8 was performed to evaluate cell proliferation. Wnt pathway agonist CHIR99021 was administrated in rescue experiments. Results FFA treatment successfully induced the MASH phenotype in 3D liver spheroids. Compared with the MASH group, the percentage of collagen area was reduced in all IAA dose groups (P＜0.05), and the expression levels of hepatic stellate cell activation markers α-SMA and COL1A1 were decreased (P＜0.05). In cell experiments, the expression of hepatic stellate cell activation-related genes (TGFB1, ACTA2, COL1A1) in medium dose and high dose IAA groups was lower than that in the TGF-β1 group (P＜0.05), and the cell proliferation level in the high dose IAA group was lower than that in the TGF-β1 group (P＜0.05). Compared with the TGF-β1 group, IAA downregulated β-catenin levels and inhibited the expression of downstream genes in the Wnt pathway (P＜0.05); activation of the Wnt pathway could partially reverse the effects of IAA. Conclusions IAA may inhibit the proliferation and activation of hepatic stellate cells by suppressing the Wnt/β-catenin signaling pathway and alleviate MASH-related liver fibrosis.

ObjectiveTo explore the establishment of performance assessment indicators for the classification and grading of public health staff in district-level Centers for Disease Control and Prevention (CDCs), and to provide a basis for such evaluations. MethodsThrough literature review and group interviews, performance evaluation indicators were developed based on competency evaluation. Experts were invited to evaluate the weight of performance evaluation indicators for public health staff from different categories, with the average value used to represent the weight of each indicator. ResultsTwenty-nine experts from universities in Shanghai, municipal CDCs, and district CDCs participated, yielding an expert authority coefficient of 0.86. The performance evaluation indicators for department managers were categorized into three levels, with 4 indicators at the primary level, 16 indicators at the secondary level, and 42 indicators at the tertiary level, while those for general staff included 4 primary indicators, 15 secondary indicators, and 36 tertiary indicators. Significant differences were observed in the weight coefficients of the primary indicators (internal operations, professional work, and learning and growth) between department managers and general staff. The top three secondary indicators for department managers were department management, monitoring and prevention, and level of expertise. For mid-level and senior staff, the top three secondary indicators were monitoring and prevention, level of expertise, and research work. The top three secondary indicators for junior staff were monitoring and prevention, professional expertise, and professional attitude. No significant statistical differences were found among tertiary indicators. ConclusionThe developed performance evaluation indicators are reliable. Staff at different levels and classifications should be evaluated using different performance evaluation standards to accurately reflect individual performance and contributions.

OBJECTIVE: To observe the clinical efficacy of 3D printing spinal external fixator combined with McKenzie therapy for patients with lumbar dics herniation (LDH). METHODS: Sixty patients with LDH between January 2022 and January 2023 were enrolled. Among them, 30 patients were given McKinsey training. According to different treatment methods, all patients were divided into McKenzie group and McKenzie + 3D printing group, 30 patients in each group. The McKenzie group provided McKenzie therapy. The McKenzie + 3D printing group were treated with 3D printing spinal external fixation brace on the basis of McKenzie therapy. Patients in both groups were between 25 and 60 years of age and had their first illness. In the McKenzie group, there were 19 males and 11 females, with an average age of (48.57±5.86) years old, and the disease duration was (7.03 ±2.39) months. The McKenzie + 3D printing group, there were 21 males and 9 females, with an average age of (48.80±5.92) years old, and the disease duration was(7.30±2.56) months. Pain was evaluated using the visual analogue scale (VAS), and lumbar spine function was assessed using the Oswestry disability index (ODI) and the Japanese Orthopaedic Association (JOA) score. VAS, ODI and JOA scores were compared between two groups before treatment and at 1, 3, 6, 9 and 12 months after treatment. RESULTS: All patients were followed up for 12 months. The VAS for the McKenzie combined with 3D printing group before treatment and at 1, 3, 6, 9, and 12 months post-treatment were(6.533±0.860), (5.133±1.008), (3.933±0.868), (2.900±0.759), (2.067±0.640), (1.433±0.504), respectively. In the McKenzie group, the corresponding scores were (6.467±0.860), (5.067±1.048), (4.600±0.968), (3.533±1.008), (2.567±0.728), (1.967±0.809), respectively. The ODI of the McKenzie group before treatment and at 1, 3, 6, 9, and 12 months post-treatment were (41.033±6.810)%, (37.933±6.209)%, (35.467±6.962)%, (27.567±10.081)%, (20.800±7.531)%, (13.533±5.158)%, respectively. For the McKenzie combined with 3D printing group, the corresponding ODI were(38.033±5.605)%, (33.000±6.192)%, (28.767±7.045)%, (22.200±5.517)%, (17.700±4.836)%, (11.900±2.771)%, respectively. The JOA scores of the McKenzie combined with 3D printing group before treatment and at 1, 3, 6, 9, and 12 months post-treatment were(8.900±2.074), (13.133±2.330), (15.700±3.583), (20.400±3.480), (22.267±3.084), (24.833±2.640), respectively. In the McKenzie group, the corresponding scores were(9.200±2.091), (12.267±2.406), (15.333±3.198), (18.467±2.240), (20.133±2.751), (22.467±2.849), respectively. Before the initiation of treatment, no statistically significant differences were observed in the VAS, ODI, and JOA scores between two groups (P>0.05). At 3, 6, 9, and 12 months post-treatment, the VAS in the McKenzie combined with 3D printing group was significantly lower than that in the McKenzie group, and the difference was statistically significant (P<0.05). The comparison of ODI between two groups at 1, 3, 6, 9, and 12 months post-treatment revealed statistically significant differences (P<0.05). At 6, 9, and 12 months post-treatment, the JOA score in the McKenzie combined with 3D printing group was significantly higher than that in the McKenzie-only group, and the difference was statistically significant (P<0.05). CONCLUSION The combination of 3D printed functional spinal external fixation brace with McKenzie therapy can significantly improve and maintain lumbar function in patients with LDH.
Humans ; Male ; Female ; Middle Aged ; Printing, Three-Dimensional ; Intervertebral Disc Displacement/surgery* ; External Fixators ; Lumbar Vertebrae/surgery* ; Adult ; Braces ; Treatment Outcome

Objective:To investigate the correlation between non-Hodgkin lymphoma (NHL) and chronic hepatitis B virus (HBV) infection by using the method of two-sample bidirectional Mendelian randomization (MR) analysis.Methods:Genetic variation data for NHL came from the Finnish database (FinnGen) Consortium 2021 public genome-wide association study (GWAS) dataset including 1 088 patients with NHL and 299 952 control subjects. The GWAS dataset for chronic HBV infection was derived from GWAS analysis published in 2021, including 145 NHL patients and 351 740 control subjects. NHL was used as an exposure factor, single nucleotide polymorphism (SNP) significantly associated with NHL was used as an instrumental variable (IV), chronic HBV infection was used as an outcome variable. The two-sample MR analysis was performed by using inverse-variance weighted (IVW) method. Chronic HBV infection was taken as an exposure factor, SNP significantly associated with chronic HBV infection was taken as IV, and NHL was taken as outcome variable, and then reverse two-sample MR analysis was performed. The IVW method used the inverse variance of each IV as the weight to fit, and the ratio method was used to measure SNP one by one and make weighted regression analysis, so as to obtain the overall estimate. MR-Egger regression and the weighted median (WME) method were also used to supplement the IVW method. In sensitivity analysis, leave-one-out sensitivity analysis was used to evaluate the impact of a single SNP. Cochran Q test was used to analyze the heterogeneity of the selected IV. MR-Egger regression was used to measure the average horizontal pleiotropy of IV, and the P-value of directivity was calculated. The MR-pleiotropy residual sum and outlier (MR-PRESSO) Global Test was used to exclude possible horizontal pleiotropic outliers and reduce bias. Results:In the leave-one-out sensitivity analysis, SNP with significant effects on causal associations was excluded. In forward MR analysis, IVs were 10 SNPs associated with NHL; the IVW method indicated that there was no causal association between NHL and chronic HBV infection ( OR = 0.979, 95% CI: 0.925-1.036, P = 0.465). MR-Egger regression ( OR = 0.992, 95% CI: 0.926-1.062, P = 0.825) and WME method ( OR = 0.992, 95% CI: 0.934-1.055, P = 0.805) were used as supplementary methods to obtain the consistent results. In sensitivity analysis, Cochran Q test showed no heterogeneity among IVs (IVW method: P = 0.271, MR-Egger regression: P = 0.239). Horizontal pleiotropy was not found in the MR-Egger regression (intercept was -0.01, P = 0.778) and the MR-PRESSO Global Test ( P > 0.05), suggesting robust results. In the reverse MR analysis, IVs were 8 SNPs associated with NHL; the IVW method ( OR = 1.117, 95% CI: 0.942-1.324, P = 0.202) also found no significant causal relationship between chronic HBV infection and NHL; MR-Egger regression ( OR = 0.777, 95% CI: 0.450-1.343, P = 0.401) and WME method ( OR = 1.120, 95% CI: 0.887-1.415, P = 0.351) also showed similar risk estimates. Sensitivity analysis also suggested the consistency and reliability of the results. Cochran Q test showed no heterogeneity among IVs (IVW method: P = 0.775, MR-Egger regression: P = 0.903). Horizontal pleiotropy was not found by MR-Egger regression (intercept was 0.102, P = 0.548) and MR-PRESSO Global Test ( P > 0.05). Conclusions:MR analysis suggests no causal relationship between NHL and chronic HBV infection.

To address the economic challenge associated with acquiring labeled sample data for white paeony,a semi-supervised learning model based on metric learning and consistency constraints was proposed to predict the content of trace heavy metal pollutants Pb and Cd in white paeony.The model was comprised of two multi-task deep learning networks with the same structure but different parameters,namely the teacher model and the student model.The multi-task deep learning network utilized metric learning within the classification branch to ensure the clustering of different samples,thereby enhancing the predictive performance of the regression branch for heavy metal content in white peony samples.The student model effectively utilized unlabeled data by constraining the consistency of outputs between the teacher and student models.Experimental results showed that the proposed multi-task deep learning network combined with the regression subnetwork model significantly reduced the average relative errors of Pb and Cd in the test set to 7.01%and 8.16%when predicting trace heavy metal pollutants in paeony.Furthermore,after integrating the metric learning loss function-constrained and the consistency-constrained teacher-student semi-supervised learning model,the same samples exhibited clustering phenomena,with faster convergence speed and convergence values closer to 0 in the loss function,reducing the average relative errors of Pb and Cd in the test set to 3.32%and 4.77%.The above results indicated that the model proposed in this work could effectively enhance the accuracy and reliability of LIBS in quantitative analysis of trace heavy metal elements in paeony,strengthening the advantages of LIBS in practical applications for quality supervision in the traditional Chinese medicine market.

China has become the country with the highest global burden of heart failure(HF).Despite the widespread use of prognostic-improving medications today,the mortality rate of HF remains high,reaching 13.7％at one year-particularly among patients with heart failure with reduced ejection fraction(HFrEF).HF interventional device therapy(structural intervention)targets the structural factors underlying HF,including atrial pressure,ventricular remodeling,and valvular intervention.It leverages the heart's intrinsic physiological properties and pathological progression mechanisms to deliver treatments through interventions without external active forces,achieving anatomical or functional repair.This field has emerged as a rapidly growing area and plays an increasingly critical role in HF management.This article provides a comprehensive review and summary of the latest advancements in HF and cardiomyopathy interventional therapy over the past year.It covers various novel technologies and products currently in the research phase,aiming to provide an in-depth analysis of the current status and future directions of HF interventional therapy,and further advance the development of this discipline.

China has become the country with the highest global burden of heart failure(HF).Despite the widespread use of prognostic-improving medications today,the mortality rate of HF remains high,reaching 13.7％at one year-particularly among patients with heart failure with reduced ejection fraction(HFrEF).HF interventional device therapy(structural intervention)targets the structural factors underlying HF,including atrial pressure,ventricular remodeling,and valvular intervention.It leverages the heart's intrinsic physiological properties and pathological progression mechanisms to deliver treatments through interventions without external active forces,achieving anatomical or functional repair.This field has emerged as a rapidly growing area and plays an increasingly critical role in HF management.This article provides a comprehensive review and summary of the latest advancements in HF and cardiomyopathy interventional therapy over the past year.It covers various novel technologies and products currently in the research phase,aiming to provide an in-depth analysis of the current status and future directions of HF interventional therapy,and further advance the development of this discipline.

Objective To analyze the literature on artificial intelligence in forensic research from 2012 to 2022 in the Web of Science Core Collection Database,to explore research hotspots and developmen-tal trends.Methods A total of 736 articles on artificial intelligence in forensic medicine in the Web of Science Core Collection Database from 2012 to 2022 were visualized and analyzed through the litera-ture measuring tool CiteSpace.The authors,institution,country(region),title,journal,keywords,cited references and other information of relevant literatures were analyzed.Results A total of 736 articles published in 220 journals by 355 authors from 289 institutions in 69 countries(regions)were identi-fied,with the number of articles published showing an increasing trend year by year.Among them,the United States had the highest number of publications and China ranked the second.Academy of Forensic Science had the highest number of publications among the institutions.Forensic Science Inter-national,Journal of Forensic Sciences,International Journal of Legal Medicine ranked high in publica-tion and citation frequency.Through the analysis of keywords,it was found that the research hotspots of artificial intelligence in the forensic field mainly focused on the use of artificial intelligence technol-ogy for sex and age estimation,cause of death analysis,postmortem interval estimation,individual identification and so on.Conclusion It is necessary to pay attention to international and institutional cooperation and to strengthen the cross-disciplinary research.Exploring the combination of advanced ar-tificial intelligence technologies with forensic research will be a hotspot and direction for future re-search.