BACKGROUND:Traditional Chinese medicine has been proved to have a significant role in anti-osteoporosis,and the effectiveness and mechanism of Ligustri Lucidi Fructus and its the active ingredients against osteoporosis have gradually gained the attention of scholars.OBJECTIVE:To analyze and summarize the research progress of Ligustri Lucidi Fructus and its active ingredients against osteoporosis in vitro and in vivo.METHODS:We searched the relevant literature included in CNKI and PubMed databases using the search terms of"Osteoporosis,Bone marrow mesenchymal stem cells,Osteoblast,Osteoclast,Ligustri Lucidi Fructus,Signal path"in Chinese and English,respectively.According to the needs of the research,we established the corresponding criteria and screened the literature.A total of 82 papers were included in the final review.RESULTS AND CONCLUSION:(1)The active ingredients of Ligustri Lucidi Fructus that exert anti-osteoporotic effects in vitro and in vivo mainly involve the following:Salidroside activates the Wnt/β-catenin signaling pathway by inhibiting the expression of Sclerostin and Dickkopf-related protein 1.This activation process enhances the expression of phosphorylated low-density lipoprotein receptor-related protein 6 in ovariectomized rats and primary osteoblasts,while decreasing the expression of glycogen synthase kinase 3β.Further,it promotes the expression of β-catenin,runt-related transcription factor 2 and cellular myelocytomatosis oncogene in the nucleus,thereby promoting the bone formation capacity of osteoblasts.The advantage is that it acts directly on osteoblasts to promote bone formation,which provides a new strategy for the treatment of osteoporosis.(2)Olive bittersweet significantly increases bone mineral density and regulates bone metabolism by decreasing terminal interleukin-6 and alkaline phosphatase concentrations in Sprague-Dawley rats.In vitro experiments showed that olive bittersweet promotes the proliferation of osteoblasts and up-regulates the protein and mRNA expression of osteoprotegerin,while inhibiting the protein and mRNA expression of receptor activator of nuclear factor-κB ligand.This mechanism of action is closely related to the regulation of the balance of the osteoprotegerin/receptor activator of nuclear factor-κB ligand system,demonstrating the advantage of increasing bone mineral density and maintaining bone health by regulating factors related to bone metabolism,but there is no significant effect on Ca2+concentration,which may limit its use in some specific types of osteoporosis.(3)By decreasing the expression of phosphatidylinositol 3 kinase,reducing the phosphorylation of protein kinase B and the expression of osteoclast-specific marker protein c-Fos,pineconiferin effectively inhibits the activation of phosphatidylinositol 3 kinase/protein kinase B/c-Fos pathway in osteoclasts.This inhibition reduces the proliferation and maturation of osteoclasts,which can help to reduce bone resorption.The advantage of this inhibition is that it can directly target osteoclasts,which provides a new target for osteoporosis treatment.However,the specific regulatory mechanism of osteoclasts needs to be studied in depth,and its long-term effect and safety need to be further evaluated.(4)The active ingredients of Ligustri Lucidi Fructus have shown good therapeutic effects on osteoporosis,but their mechanism of action is complex,involving the interaction of multiple genes,proteins and signaling pathways.In the future,large-scale clinical trials need to be carried out to verify its effectiveness and safety,and the strategy of combining the active ingredients of Ligustri Lucidi Fructus with other drugs needs to be further explored in order to obtain better therapeutic effects.

Objective To investigate the effect of α/β hydrolase folded protein 5(ABHD5)and cellular immunity markers on the response to tirellizumab targeted therapy in patients with advanced non-small cell lung cancer(NSCLC).Methods A total of 123 patients with advanced NSCLC who received tiralizumab in Kailuan General Hospital from October 2020 to December 2023 were selected.The efficacy of the target lesions was evaluated 4 weeks after treatment,and the patients were divided into response group and non-response group according to the treatment effect.Quantitative real time polymerase chain reaction(RT-qPCR)was used to detect the relative expression of ABHD5 in lesion tissues.The expression level of ABHD5,immune indexes[CD4+T,CD8+T,CD4+T/CD8+T,regulatory T cell(Treg),T helper cell 17(Th17),Treg/Th17]and other clinical indexes were compared between the two groups.Multivariate logistic regression analysis of independent factors influencing response to tirelizumab targeted therapy.The predictive value of ABHD5,CD4+T and CD8+T in non-response to treatment of advanced NSCLC was analyzed by receiver operating characteristic(ROC).ABHD5 expression was correlated with CD4+T and CD8+T cells by Pearson correlation analysis.Results Among the 123 patients enrolled,90 responded to treatment and 33 did not respond.The expression of ABHD5(1.16±0.18)and the levels of CD4+T(31.52%±4.26%)and CD8+T(24.39%±1.87%)cells in the non-response group were lower than those in the response group(1.47±0.21,36.43%±4.08%,29.13%±2.15%),and the levels of Treg(7.24%±0.89%)and Th17(6.23%±1.10%)cells were higher than those in the response group(6.37%±0.91%,5.42%±0.66%),and the differences were statistically significant(t=4.725～11.200,all P<0.05).There were significant differences in tumor size,number of metastases and levels of carcinoembryonic antigen(CEA),albumin(ALB)and total bilirubin(TBIL)between the two groups,and the differences were statistically significant(t=2.969～6.523,all P<0.05).ABHD5 expression and CD4+T,CD8+T cell levels were independent protective factors affecting the response to tirelizumab targeted therapy in advanced NSCLC(Wald χ2=15.803,7.954,8.631,all P<0.05).ABHD5 predicted that the AUC of non-response to treatment of advanced NSCLC was 0.897,which was higher than that of 0.860 and 0.835 predicted by CD4+T and CD8+T cells,and the prediction sensitivity and specificity were 72.73%and 94.45%,respectively.ABHD5 expression was positively correlated with the levels of CD4+T and CD8+T cells(r=0.367,0.355,all P<0.05).Conclusion The response to tirelizumab targeted therapy in advanced NSCLC is significantly correlated with the expression of ABHD5 and the levels of CD4+T and CD8+T cells,and ABHD5 has high predictive value in the treatment of advanced NSCLC.

ObjectiveTo explore the changes in volatile components， total polysaccharides， enzyme activity， and chromaticity value of Myristicae Semen Koji（MSK） during the fermentation process， and conduct correlation analysis. MethodsBased on gas chromatography-mass spectrometry（GC-MS）， the changes of volatile components in MSK at different fermentation times were identified. The phenol sulfuric acid method， dinitrosalicylic acid method（DNS）， and carboxymethyl cellulose sodium salt method（CMC-Na） were used to investigate the total polysaccharide content， amylase activity， and cellulase activity during the fermentation process. Visual analysis technology was used to explore the changes in chromaticity values， revealing the fermentation process of MSK and the dynamic changes of various measurement indicators， partial least squares-discriminant analysis（PLS-DA） was used to explore the differential compounds of MSK at different fermentation degrees， and Pearson correlation analysis was used to explore the correlation between volatile components of MSK and total polysaccharides， enzyme activity， and chromaticity values. ResultsA total of 60 volatile compounds were identified from MSK， the relative contents of components such as （+）-α-pinene， β-phellandrene， β-pinene， （+）-limonene， and p-cymene obviously increased， while the relative contents of components such as safrole， methyl isoeugenol， methyleugenol， myristicin， and elemicin significantly decreased. During the fermentation process， the total polysaccharide content showed an upward trend， while the activities of amylase and cellulase showed an initial increase followed by a decrease， and reached their maximum value at 40 h. the overall brightness（L^*） and total color difference（ΔE^*） gradually increased， while the changes in red-green value（a^*） and yellow-blue value（b^*） were not obvious. PLS-DA results showed that MSK could be clearly distinguished at different fermentation times， and 13 differential biomarkers were screened out. Pearson correlation analysis results showed that the contents of α-terpinene， β-phellandrene， methyleugenol， β-cubebene and myristic acid had an obvious correlation with chromaticity values. ConclusionAfter fermentation， the volatile components， total polysaccharides， amylase activity， and cellulase activity of MSK undergo significant changes， and there is a clear correlation between them and chromaticity values， which reveals the dynamic changes in the fermentation process and related indicators of MSK， laying a foundation for the quality control.

The Healthy China 2030 Plan set the goal of reducing premature deaths from diabetes by 30% by 2030. However, there has been a lack of assessment of premature mortality for diabetes since the action plan was issued. This study used data from the Global Burden of Disease Study 2021, calculated the premature deaths for diabetes by sex, provinces, and subtypes from 1990 to 2021. We explored the temporal trend of premature mortality using the average annual percent change (AAPC) for different sexes, provinces, and subtypes from 1990 to 2021. Furthermore, we predicted premature mortality for diabetes through 2030 for China and its provinces according to the average annual change rate from 2010 to 2021. There was a first slow upward trend in premature mortality for diabetes from 0.5% in 1990 to 0.6% in 2004, and then a decline until 2021 with premature mortality of 0.4%. By 2030, only Fujian (30.3%) will achieve the desired level of reduction, with only seven provinces meeting the target for females and none for males. There is a large range in the degree of decline between inland and coastal regions, showing obvious geographic differences, and there should be a focus on balancing medical resources.
Humans ; China/epidemiology* ; Female ; Male ; Mortality, Premature/trends* ; Diabetes Mellitus/mortality* ; Goals ; Middle Aged ; Adult

Objective To systematically compare the efficacy of different virtual reality(VR)technologies on motor dysfunction in patients with Parkinson's disease(PD)through a network meta-analysis(NMA).Methods Following the PRISMA-NMA guidelines,randomized controlled trials(RCT)that compared the effect of at least two interventions on motor function in patients with PD were searched in PubMed,Embase,Cochrane Li-brary,Web of Science,CNKI,Wanfang data and VIP.The interventions included immersive virtual reality(IVR),non-immersive virtual reality(VRT),augmented reality(AR),treatment as usual(TAU)and active control(AC).The primary outcomes included Unified Parkinson's Disease Rating Scale Part Ⅲ(UPDRS-Ⅲ),Berg Balance Scale(BBS)and Timed Up and Go Test(TUGT).A frequentist-based random-effects model was used to conduct NMA,and the surface under the cumulative ranking curve(SUCRA)was used to rank the interventions.Results A total of 20 RCT involving 890 patients were included.IVR performed best in improving the score of UPDRS-Ⅲ(SUCRA=97.7%)and was significantly superior to TAU(SMD=-0.82,95%CI-1.28 to-0.37).IVR showed the highest probability of being the best option for the score of BBS(SUCRA=85.2%)and was signifi-cantly superior to TAU(SMD=3.94,95%CI 1.08 to 6.80).IVR performed best in the outcome of TUGT(SU-CRA=95.1%)and was significantly superior to VRT(SMD=1.06,95%CI 0.40 to 1.72),AR(SMD=-1.09,95%CI-1.98 to-0.19)and TAU(SMD=-1.38,95%CI-1.95 to-0.82).However,subgroup analysis revealed that the efficacy advantage of IVR was mainly confirmed in short-term(four to six weeks)interventions,while the evidence for long-term efficacy was currently very limited.Conclusion The efficacy of interventions on motor rehabilitation in patients with PD appears to be positively correlated with the technology's level of immersion.As the most immersive technology,IVR is the optimal choice for im-proving overall motor function,balance and mobility in patients with PD.VRT and AR serve as effective adju-vants and are superior to TAU.

Objective To investigate the effect of α/β hydrolase folded protein 5(ABHD5)and cellular immunity markers on the response to tirellizumab targeted therapy in patients with advanced non-small cell lung cancer(NSCLC).Methods A total of 123 patients with advanced NSCLC who received tiralizumab in Kailuan General Hospital from October 2020 to December 2023 were selected.The efficacy of the target lesions was evaluated 4 weeks after treatment,and the patients were divided into response group and non-response group according to the treatment effect.Quantitative real time polymerase chain reaction(RT-qPCR)was used to detect the relative expression of ABHD5 in lesion tissues.The expression level of ABHD5,immune indexes[CD4+T,CD8+T,CD4+T/CD8+T,regulatory T cell(Treg),T helper cell 17(Th17),Treg/Th17]and other clinical indexes were compared between the two groups.Multivariate logistic regression analysis of independent factors influencing response to tirelizumab targeted therapy.The predictive value of ABHD5,CD4+T and CD8+T in non-response to treatment of advanced NSCLC was analyzed by receiver operating characteristic(ROC).ABHD5 expression was correlated with CD4+T and CD8+T cells by Pearson correlation analysis.Results Among the 123 patients enrolled,90 responded to treatment and 33 did not respond.The expression of ABHD5(1.16±0.18)and the levels of CD4+T(31.52%±4.26%)and CD8+T(24.39%±1.87%)cells in the non-response group were lower than those in the response group(1.47±0.21,36.43%±4.08%,29.13%±2.15%),and the levels of Treg(7.24%±0.89%)and Th17(6.23%±1.10%)cells were higher than those in the response group(6.37%±0.91%,5.42%±0.66%),and the differences were statistically significant(t=4.725～11.200,all P<0.05).There were significant differences in tumor size,number of metastases and levels of carcinoembryonic antigen(CEA),albumin(ALB)and total bilirubin(TBIL)between the two groups,and the differences were statistically significant(t=2.969～6.523,all P<0.05).ABHD5 expression and CD4+T,CD8+T cell levels were independent protective factors affecting the response to tirelizumab targeted therapy in advanced NSCLC(Wald χ2=15.803,7.954,8.631,all P<0.05).ABHD5 predicted that the AUC of non-response to treatment of advanced NSCLC was 0.897,which was higher than that of 0.860 and 0.835 predicted by CD4+T and CD8+T cells,and the prediction sensitivity and specificity were 72.73%and 94.45%,respectively.ABHD5 expression was positively correlated with the levels of CD4+T and CD8+T cells(r=0.367,0.355,all P<0.05).Conclusion The response to tirelizumab targeted therapy in advanced NSCLC is significantly correlated with the expression of ABHD5 and the levels of CD4+T and CD8+T cells,and ABHD5 has high predictive value in the treatment of advanced NSCLC.

Objective To systematically compare the efficacy of different virtual reality(VR)technologies on motor dysfunction in patients with Parkinson's disease(PD)through a network meta-analysis(NMA).Methods Following the PRISMA-NMA guidelines,randomized controlled trials(RCT)that compared the effect of at least two interventions on motor function in patients with PD were searched in PubMed,Embase,Cochrane Li-brary,Web of Science,CNKI,Wanfang data and VIP.The interventions included immersive virtual reality(IVR),non-immersive virtual reality(VRT),augmented reality(AR),treatment as usual(TAU)and active control(AC).The primary outcomes included Unified Parkinson's Disease Rating Scale Part Ⅲ(UPDRS-Ⅲ),Berg Balance Scale(BBS)and Timed Up and Go Test(TUGT).A frequentist-based random-effects model was used to conduct NMA,and the surface under the cumulative ranking curve(SUCRA)was used to rank the interventions.Results A total of 20 RCT involving 890 patients were included.IVR performed best in improving the score of UPDRS-Ⅲ(SUCRA=97.7%)and was significantly superior to TAU(SMD=-0.82,95%CI-1.28 to-0.37).IVR showed the highest probability of being the best option for the score of BBS(SUCRA=85.2%)and was signifi-cantly superior to TAU(SMD=3.94,95%CI 1.08 to 6.80).IVR performed best in the outcome of TUGT(SU-CRA=95.1%)and was significantly superior to VRT(SMD=1.06,95%CI 0.40 to 1.72),AR(SMD=-1.09,95%CI-1.98 to-0.19)and TAU(SMD=-1.38,95%CI-1.95 to-0.82).However,subgroup analysis revealed that the efficacy advantage of IVR was mainly confirmed in short-term(four to six weeks)interventions,while the evidence for long-term efficacy was currently very limited.Conclusion The efficacy of interventions on motor rehabilitation in patients with PD appears to be positively correlated with the technology's level of immersion.As the most immersive technology,IVR is the optimal choice for im-proving overall motor function,balance and mobility in patients with PD.VRT and AR serve as effective adju-vants and are superior to TAU.

BACKGROUND:Traditional Chinese medicine has been proved to have a significant role in anti-osteoporosis,and the effectiveness and mechanism of Ligustri Lucidi Fructus and its the active ingredients against osteoporosis have gradually gained the attention of scholars.OBJECTIVE:To analyze and summarize the research progress of Ligustri Lucidi Fructus and its active ingredients against osteoporosis in vitro and in vivo.METHODS:We searched the relevant literature included in CNKI and PubMed databases using the search terms of"Osteoporosis,Bone marrow mesenchymal stem cells,Osteoblast,Osteoclast,Ligustri Lucidi Fructus,Signal path"in Chinese and English,respectively.According to the needs of the research,we established the corresponding criteria and screened the literature.A total of 82 papers were included in the final review.RESULTS AND CONCLUSION:(1)The active ingredients of Ligustri Lucidi Fructus that exert anti-osteoporotic effects in vitro and in vivo mainly involve the following:Salidroside activates the Wnt/β-catenin signaling pathway by inhibiting the expression of Sclerostin and Dickkopf-related protein 1.This activation process enhances the expression of phosphorylated low-density lipoprotein receptor-related protein 6 in ovariectomized rats and primary osteoblasts,while decreasing the expression of glycogen synthase kinase 3β.Further,it promotes the expression of β-catenin,runt-related transcription factor 2 and cellular myelocytomatosis oncogene in the nucleus,thereby promoting the bone formation capacity of osteoblasts.The advantage is that it acts directly on osteoblasts to promote bone formation,which provides a new strategy for the treatment of osteoporosis.(2)Olive bittersweet significantly increases bone mineral density and regulates bone metabolism by decreasing terminal interleukin-6 and alkaline phosphatase concentrations in Sprague-Dawley rats.In vitro experiments showed that olive bittersweet promotes the proliferation of osteoblasts and up-regulates the protein and mRNA expression of osteoprotegerin,while inhibiting the protein and mRNA expression of receptor activator of nuclear factor-κB ligand.This mechanism of action is closely related to the regulation of the balance of the osteoprotegerin/receptor activator of nuclear factor-κB ligand system,demonstrating the advantage of increasing bone mineral density and maintaining bone health by regulating factors related to bone metabolism,but there is no significant effect on Ca2+concentration,which may limit its use in some specific types of osteoporosis.(3)By decreasing the expression of phosphatidylinositol 3 kinase,reducing the phosphorylation of protein kinase B and the expression of osteoclast-specific marker protein c-Fos,pineconiferin effectively inhibits the activation of phosphatidylinositol 3 kinase/protein kinase B/c-Fos pathway in osteoclasts.This inhibition reduces the proliferation and maturation of osteoclasts,which can help to reduce bone resorption.The advantage of this inhibition is that it can directly target osteoclasts,which provides a new target for osteoporosis treatment.However,the specific regulatory mechanism of osteoclasts needs to be studied in depth,and its long-term effect and safety need to be further evaluated.(4)The active ingredients of Ligustri Lucidi Fructus have shown good therapeutic effects on osteoporosis,but their mechanism of action is complex,involving the interaction of multiple genes,proteins and signaling pathways.In the future,large-scale clinical trials need to be carried out to verify its effectiveness and safety,and the strategy of combining the active ingredients of Ligustri Lucidi Fructus with other drugs needs to be further explored in order to obtain better therapeutic effects.

Biomaterials have gained substantial attention in the field of regenerative medicine and shown respectable potential in clinical translation. However, the function of biomaterials is hindered by the fibrotic encapsulation of foreign body response (FBR) under some circumstances. FBR also lowers the expected service life of implanted devices and causes pain, distortion of tissue or even malignant diseases. Therefore, the mechanism of FBR and the modulating factors need to be further investigated to improve the tissue biocompatibility of biomaterials. This article reviewed the process of FBR, summarized the properties and modification of biomaterials related to FBR, and discussed strategies to mitigate this immune reaction.

Objective To observe the value of deep learning(DL)models for automatic classification of echocardiographic views.Methods Totally 100 patients after heart transplantation were retrospectively enrolled and divided into training set,validation set and test set at a ratio of 7∶2∶1.ResNet18,ResNet34,Swin Transformer and Swin Transformer V2 models were established based on 2D apical two chamber view,2D apical three chamber view,2D apical four chamber view,2D subcostal view,parasternal long-axis view of left ventricle,short-axis view of great arteries,short-axis view of apex of left ventricle,short-axis view of papillary muscle of left ventricle,short-axis view of mitral valve of left ventricle,also 3D and CDFI views of echocardiography.The accuracy,precision,recall,F1 score and confusion matrix were used to evaluate the performance of each model for automatically classifying echocardiographic views.The interactive interface was designed based on Qt Designer software and deployed on the desktop.Results The performance of models for automatically classifying echocardiographic views in test set were all good,with relatively poor performance for 2D short-axis view of left ventricle and superior performance for 3D and CDFI views.Swin Transformer V2 was the optimal model for automatically classifying echocardiographic views,with high accuracy,precision,recall and F1 score was 92.56％,89.01％,89.97％and 89.31％,respectively,which also had the highest diagonal value in confusion matrix and showed the best classification effect on various views in t-SNE figure.Conclusion DL model had good performance for automatically classifying echocardiographic views,especially Swin Transformer V2 model had the best performance.Using interactive classification interface could improve the interpretability of prediction results to some extent.