Flap transplantation is a critical surgical strategy for the reconstruction of tissue defects caused by trauma, tumor resection, and congenital malformations, and its survival rate directly determines surgical efficacy and patient prognosis. Following transplantation, flaps inevitably undergo ischemia-reperfusion (I/R) injury, during which oxidative stress, inflammatory responses, and metabolic disturbances are intricately intertwined, ultimately leading to cellular injury and tissue necrosis. Recent studies have demonstrated that multiple forms of programmed cell death—including apoptosis, pyroptosis, ferroptosis, necroptosis, and PANoptosis—play central roles in flap I/R injury. The extensive crosstalk and molecular interactions among these pathways form a highly complex cell death network. Specifically, apoptosis is mediated by the imbalance of Bcl-2 family proteins and the activation of cysteine-dependent aspartate-specific protease (caspase) cascades; pyroptosis is driven by the NLRP3-caspase-1-GSDMD axis, resulting in membrane pore formation and the release of pro-inflammatory cytokines; ferroptosis is characterized by iron-dependent lipid peroxidation and dysfunction of glutathione peroxidase 4 (GPX4); necroptosis is triggered by the receptor-interacting serine/threonine-protein kinase 1 (RIPK1)-RIPK3-MLKL signaling complex, leading to membrane rupture; and PANoptosis represents an integrated form of inflammatory cell death that coordinates multiple death pathways. Importantly, these forms of programmed cell death are not independent but are interconnected through extensive signaling crosstalk. Key regulatory molecules, including caspase-8, reactive oxygen species (ROS), nuclear factor-κB (NF-κB), and nuclear factor erythroid 2-related factor 2 (Nrf2), collectively modulate the dynamic balance among these pathways. Therefore, the multidimensional interplay and spatiotemporal dynamics of programmed cell death constitute a fundamental pathological basis of flap I/R injury. This review systematically summarizes the latest advances in the mechanisms and interactions of various programmed cell death pathways in flap I/R injury, aiming to elucidate the underlying regulatory network. These insights may provide novel theoretical foundations for optimizing flap protection strategies, improving flap survival, and promoting tissue repair.

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

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 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 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.

To clarify the genetic diversity and structure of the nucleus population of F1-generation Litopenaeus vannamei, this study utilized 15 pairs of highly polymorphic microsatellite primers to analyze the simple sequence repeat (SSR) markers and genetic diversity in 15 full-sib families of L. vannamei. A total of 112 alleles (N_a) and 60.453 effective alleles (N_e) were identified among the selected 15 SSR loci, with the average polymorphic information content (PIC) of 0.648. The average N_e, observed heterozygosity (H_o), and expected heterozygosity (H_e) in the 15 F1 families varied from 1.925 to 2.626, 0.425 to 0.783, and 0.403 to 0.572, respectively. The 15 full-sib families were primarily clustered into three categories in the phylogenetic analysis, with the genetic distance between families ranging from 0.252 to 0.574. Additionally, the genetic differentiation coefficient (F_st) among the families varied from 0.112 to 0.278, indicating substantial genetic differentiation. Overall, this study suggested that the genetic diversity of the 15 full-sib families was moderate, providing valuable genetic insights for the subsequent breeding initiatives aimed at enhancing the tolerance of L. vannamei to high levels of soybean meal.
Penaeidae/classification* ; Microsatellite Repeats/genetics* ; Animals ; Genetic Variation ; Polymorphism, Genetic ; Phylogeny ; Alleles ; Genetic Markers