ObjectiveTo investigate the mechanism by which Notoginsenoside R1 （NGR1） ameliorates hypoxia/reoxygenation （H/R）-induced injury in AC16 human cardiomyocyte cell lines through the regulation of mitophagy. MethodsCommon genes linked to hypoxia/reoxygenation injury and mitophagy were identified by intersecting data from GeneCards and MitoCarta databases. AC16 cell viability was assessed via CCK-8 assay under varying NGR1 concentrations （0， 6.25， 12.5， 25， 50， 100， 200， 300， 400， 500 μmol/L）. AC16 cells were divided into the following groups： control group （Control）， model group （H/R）， and treatment groups （H/R + NGR1 at 100， 200 and 300 μmol/L）. Mitochondrial membrane potential （ΔΨm） was measured using 5，5'，6，6'-tetrachloro-1，1'，3，3'-tetraethylbenzimidazolylcarbocyanine iodide （JC-1） staining. Transcriptional levels of mitophagy-related genes （Parkin， Pink1， P62） were quantified by reverse transcription-quantitative PCR （RT-qPCR）. Protein expression of mitophagy-related markers （Parkin， Pink1， P62， and LC3BⅡ） was evaluated via Western blot analysis. Mitochondrial ultrastructure was visualized by transmission electron microscopy （TEM）. ResultsCompared to the control group， cell viability in the H/R group significantly decreased （P<0.01）. Treatment with NGR1 at concentrations above 100 μmol/L significantly enhanced the cell viability of AC16 cells compared to the H/R group （P<0.01）. H/R induced a significant decrease in mitochondrial membrane potential （P<0.01）， which was restored by NGR1 treatment （P<0.01）. The mRNA levels of Parkin， Pink1， and P62 in the H/R group were upregulated compared to the control group （P<0.05）， while NGR1 intervention downregulated their expression （P<0.05）. Protein expression levels of Parkin， Pink1， and LC3BⅡ in the H/R group significantly increased， while P62 expression decreased compared to the control group （P<0.01）. In contrast， different doses of NGR1 treatment significantly reduced the expression of Parkin， Pink1， and LC3BⅡ while increasing P62 expression （P<0.05）. TEM revealed that the mitochondrial structure in the H/R group was severely disrupted， with fragmented and disorganized cristae， which was alleviated by NGR1. ConclusionNGR1 ameliorates H/R-induced AC16 cell injury， and its mechanism may be associated with modulating the Pink1/Parkin pathway to suppress excessive mitophagy.

BACKGROUND:Autologous bone,allogeneic bone or artificial bone has been used to promote bone defect repair in the clinic,but the rate of non-healing is still high.The key is to ignore the importance of periosteum in the bone healing process.In the early stage of the project,the project team constructed an electrospinning membrane loaded with vascular endothelial growth factor to highly simulate the intramembranous osteogenesis of natural periosteum at the bone defect site,which promoted bone regeneration to a certain extent.However,the injured area often faces the dilemma of severe inflammatory response mediated by macrophages and lack of seed cells,resulting in the risk of inactivation or diffusion of delivered biological factors.Therefore,it is necessary to further optimize and coordinate the immune regulation and angiogenesis functions of biomimetic periosteum to promote bone repair.OBJECTIVE:To investigate the physicochemical properties of stem cell-engineered bionic periosteum and its role in regulating the inflammatory microenvironment to promote bone repair.METHODS:By combining L-polylactic acid-based microsol electrospinning,type Ⅰ collagen self-assembly and gel stem cell transplantation technology,a bionic periosteum(M@C-B)was constructed,in which the core layer loaded with vascular endothelial growth factor and the shell layer delivered bone marrow mesenchymal stem cells to regulate the immune microenvironment of bone defects.The physicochemical properties of the periosteum were characterized by scanning electron microscopy,transmission electron microscopy,and Fourier transform infrared spectroscopy.A co-culture system was established between the bionic periosteum and macrophages,bone marrow mesenchymal stem cells and human umbilical vein endothelial cells to explore immune regulation and in vitro osteogenic and angiogenic abilities.Finally,the osteogenic properties of the stem cell engineered bionic periosteum were further verified in a rat femoral condyle defect model.RESULTS AND CONCLUSION:(1)Transmission electron microscopy results showed that the micro-sol electrospinning(MS)formed a distinct core-shell structure.Scanning electron microscopy indicated that after the assembly of the collagen-l artificial periosteum(M@C)on the surface of the vascular endothelial growth factor-loaded micro-sol,a distinct"spider web-like"fibrous structure was deposited.Infrared spectroscopy further confirmed the successful self-assembly of collagen-l.Release experiments demonstrated that the M@C group mitigated the burst release phenomenon compared to the MS group,maintaining internal vascular endothelial growth factor activity and sustained release.(2)Live/dead cell staining and CCK-8 assay showed that bone marrow mesenchymal stem cells proliferated well and survived on three types of artificial periosteum:MS,purely aligned poly(L-lactic acid)(PLLA)surface self-assembled collagen-l artificial periosteum(PLLA@C),and vascular endothelial growth factor-loaded micro-sol fiber surface self-assembled collagen-l-bone marrow mesenchymal stem cells artificial periosteum(M@C-B).Among them,the M@C-B group had the highest number of live cells and the fastest proliferation rate.(3)Alkaline phosphatase staining,alizarin red staining,and osteopontin immunofluorescence staining showed that the PLLA@C and M@C-B groups significantly promoted osteogenic differentiation of bone marrow mesenchymal stem cells.Angiogenesis experiments demonstrated that the vascular endothelial growth factor-loaded groups(MS and M@C-B)had longer blood vessel lengths and more reticular vascular-like structures with more cross-linked nodes,with the M@C-B group being the most prominent.(4)Immunofluorescence and flow cytometry showed that artificial periosteum in the M@C-B group significantly inhibited the pro-inflammatory macrophage phenotype and promoted the polarization of macrophages towards the anti-inflammatory M2 phenotype.(5)In vivo studies further confirmed that the M@C-B group showed superior bone mineral density,trabecular thickness,relative bone volume,and trabecular spacing compared to other groups.(6)These results indicate that bone marrow mesenchymal stem cell-engineered artificial periosteum,through the rapid regulation of the bone defect immune microenvironment by the collagen-l-bone marrow mesenchymal stem cells outer phase and the sustained release of vascular endothelial growth factor by the micro-sol electrospinning core-shell structure of the inner phase,synergistically promotes bone healing.

BACKGROUND:Autologous bone,allogeneic bone or artificial bone has been used to promote bone defect repair in the clinic,but the rate of non-healing is still high.The key is to ignore the importance of periosteum in the bone healing process.In the early stage of the project,the project team constructed an electrospinning membrane loaded with vascular endothelial growth factor to highly simulate the intramembranous osteogenesis of natural periosteum at the bone defect site,which promoted bone regeneration to a certain extent.However,the injured area often faces the dilemma of severe inflammatory response mediated by macrophages and lack of seed cells,resulting in the risk of inactivation or diffusion of delivered biological factors.Therefore,it is necessary to further optimize and coordinate the immune regulation and angiogenesis functions of biomimetic periosteum to promote bone repair.OBJECTIVE:To investigate the physicochemical properties of stem cell-engineered bionic periosteum and its role in regulating the inflammatory microenvironment to promote bone repair.METHODS:By combining L-polylactic acid-based microsol electrospinning,type Ⅰ collagen self-assembly and gel stem cell transplantation technology,a bionic periosteum(M@C-B)was constructed,in which the core layer loaded with vascular endothelial growth factor and the shell layer delivered bone marrow mesenchymal stem cells to regulate the immune microenvironment of bone defects.The physicochemical properties of the periosteum were characterized by scanning electron microscopy,transmission electron microscopy,and Fourier transform infrared spectroscopy.A co-culture system was established between the bionic periosteum and macrophages,bone marrow mesenchymal stem cells and human umbilical vein endothelial cells to explore immune regulation and in vitro osteogenic and angiogenic abilities.Finally,the osteogenic properties of the stem cell engineered bionic periosteum were further verified in a rat femoral condyle defect model.RESULTS AND CONCLUSION:(1)Transmission electron microscopy results showed that the micro-sol electrospinning(MS)formed a distinct core-shell structure.Scanning electron microscopy indicated that after the assembly of the collagen-l artificial periosteum(M@C)on the surface of the vascular endothelial growth factor-loaded micro-sol,a distinct"spider web-like"fibrous structure was deposited.Infrared spectroscopy further confirmed the successful self-assembly of collagen-l.Release experiments demonstrated that the M@C group mitigated the burst release phenomenon compared to the MS group,maintaining internal vascular endothelial growth factor activity and sustained release.(2)Live/dead cell staining and CCK-8 assay showed that bone marrow mesenchymal stem cells proliferated well and survived on three types of artificial periosteum:MS,purely aligned poly(L-lactic acid)(PLLA)surface self-assembled collagen-l artificial periosteum(PLLA@C),and vascular endothelial growth factor-loaded micro-sol fiber surface self-assembled collagen-l-bone marrow mesenchymal stem cells artificial periosteum(M@C-B).Among them,the M@C-B group had the highest number of live cells and the fastest proliferation rate.(3)Alkaline phosphatase staining,alizarin red staining,and osteopontin immunofluorescence staining showed that the PLLA@C and M@C-B groups significantly promoted osteogenic differentiation of bone marrow mesenchymal stem cells.Angiogenesis experiments demonstrated that the vascular endothelial growth factor-loaded groups(MS and M@C-B)had longer blood vessel lengths and more reticular vascular-like structures with more cross-linked nodes,with the M@C-B group being the most prominent.(4)Immunofluorescence and flow cytometry showed that artificial periosteum in the M@C-B group significantly inhibited the pro-inflammatory macrophage phenotype and promoted the polarization of macrophages towards the anti-inflammatory M2 phenotype.(5)In vivo studies further confirmed that the M@C-B group showed superior bone mineral density,trabecular thickness,relative bone volume,and trabecular spacing compared to other groups.(6)These results indicate that bone marrow mesenchymal stem cell-engineered artificial periosteum,through the rapid regulation of the bone defect immune microenvironment by the collagen-l-bone marrow mesenchymal stem cells outer phase and the sustained release of vascular endothelial growth factor by the micro-sol electrospinning core-shell structure of the inner phase,synergistically promotes bone healing.

Triatoma rubrofasciata is currently the most widely distributed species of Triatoma worldwide, and it is also widespread in southern China. T. rubrofasciata has been proven to transmit Trypanosoma cruzi, and is one of vectors transmitting Chagas disease, which poses a potential risk for transmission of imported Chagas disease in China. Findings from latest studies have shown that T. rubrofasciata naturally infects T. lewisi, T. conorhini, and T. rangeli, which undoubtedly increases significant risks of and challenges to trypanosomiasis control in China. This article briefly describes the species of T. rubrofasciata-transmitted trypanosomes, and summarizes the epidemiological characteristics of trypanosomiasis, so as to provide insights into T. rubrofasciata-transmitted trypanosomiasis surveillance and control, and prevention of trypanosomiasis development and transmission in China.

This study explored the active ingredients for anti-angiogenesis in Wenyujin Rhizoma Concisum. Ten sesquiterpenoids were isolated from Wenyujin Rhizoma Concisum by silica gel column chromatography, thin layer chromatography, and high performance liquid chromatography. According to the results of multiple spectroscopic methods and circular dichroism, they were identified as wenyujinlactam A(1),(4S,7S)11-hydroxycurdione(2), 8,9-seco-4β-hydroxy-1α,5βH-7(11)-guaen-8,10-olide(3), curcumadione(4), phaeocaulisin E(5), procurcumadiol(6), zedouronediol(7), epiprocurcumenol(8), gajutsulactone A(9), and(7Z)-1β,4α-dihydroxy-5α,8β(H)-eudesm-7(11)-en-8,12-olide(10). Compounds 1 and 2 were new sesquiterpenoids. Compounds 1, 6, 8, and 10 can inhibit human umbilical vein endothelial cells(HUVEC) proliferation with IC_(50) values of 38.83, 45.19, 32.12, and 37.80 μmol·L~(-1), respectively. Compounds 1 and 10 can inhibit HUVEC migration with IC_(50) values of 29.70 and 36.48 μmol·L~(-1), respectively.
Sesquiterpenes/isolation & purification* ; Humans ; Drugs, Chinese Herbal/isolation & purification* ; Rhizome/chemistry* ; Human Umbilical Vein Endothelial Cells/drug effects* ; Molecular Structure ; Cell Proliferation/drug effects*

As a new type of production factor that can empower the development of new quality productivity, the data element is an important engine to promote the high quality development of the industry. Traditional Chinese medicine(TCM) dispensing is the most basic work of TCM clinical pharmacy, and its quality directly affects the clinical efficacy of TCM. The integration of data elements and TCM dispensing can stimulate the innovation and vitality of the TCM dispensing industry and promote the high-quality and sustainable development of the industry. A large-scale, detailed, and systematic study on TCM dispensing was conducted. The innovative practice path of data fusion construction in the whole process of TCM dispensing was investigated by integrating the digital resources "nine full activities" of TCM dispensing, creating the digital dictionary of "TCM clinical information data elements", and exploring innovative applications of TCM dispensing driven by data and technology, so as to promote the standardized, digital, and intelligent development of TCM dispensing in medical health services. The research content of this project was successfully selected as the second batch of "Data element×" typical cases of National Data Administration in 2024, which is the only selected case in the field of TCM.
Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal ; Humans

This study aims to investigate the therapeutic effects of the Coptidis Rhizoma-Scutellariae Radix on cytokine storm secondary lung injury(CSSLI) induced by CpG1826 in mice, and to elucidate the potential molecular mechanisms by which its major active components, i.e., coptisine and wogonin, alleviate CSSLI by inhibiting the mitochondrial permeability transition pore(mPTP)/nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3) inflammasome pyroptosis pathway. In vivo, a mouse model of CSSLI was established by CpG1826 induction. Pulmonary edema was assessed by lung wet-to-dry weight ratio(W/D), lung injury was evaluated by hematoxylin-eosin(HE) staining, and ultrastructural changes in lung tissue were observed by transmission electron microscopy(TEM). The levels of interleukin(IL)-1β, high mobility group box 1 protein(HMGB1), IL-18, and IL-1α in bronchoalveolar lavage fluid were measured by enzyme-linked immunosorbent assay(ELISA). The results showed that the decoction of the Coptidis Rhizoma-Scutellariae Radix significantly reduced pulmonary edema, alleviated lung injury, and decreased the concentrations of related cytokines in BALF more effectively than either single herb alone, thereby improving CSSLI. In vitro, a CpG1826-induced CSSLI model was established in mouse alveolar macrophage MH-S cells. Calcein-AM quenching was used to screen for the most effective monomer components from the herb pair in inhibiting mPTP opening. Coptisine(5, 10, 20 μmol·L~(-1)) and wogonin(10, 20, 40 μmol·L~(-1)) markedly inhibited mPTP opening, with optimal effects and a clear dose-dependent pattern. These components suppressed mPTP opening, thereby reducing the release of mitochondrial DNA(mtDNA) and the accumulation of reactive oxygen species(ROS), effectively reversing the CpG1826-induced decrease in mitochondrial membrane potential(MMP). Further studies revealed that both coptisine and wogonin inhibited pyroptosis and downregulated the expression of key proteins in the NLRP3/Caspase-1/gasdermin D(GSDMD) pathway. In conclusion, the Coptidis Rhizoma-Scutellariae Radix improves CpG1826-induced CSSLI in mice, and this effect is associated with the inhibition of the mPTP/NLRP3 pyroptosis pathway, providing scientific evidence for its clinical application and further development.
Animals ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Pyroptosis/drug effects* ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology* ; Male ; Lung Injury/immunology* ; Cytokines/immunology* ; Scutellaria baicalensis/chemistry* ; Oligodeoxyribonucleotides/adverse effects* ; Mice, Inbred C57BL ; Coptis chinensis

Osteoporotic fractures(OPF) refer to the fractures caused by minor violence in the state of osteoporosis, seriously threatening the life and health of elderly patients. Drug and surgical therapies have limitations such as single targets, diverse adverse reactions, and poor prognosis. Kidney-tonifying traditional Chinese medicine(TCM) has good potential in the treatment of OPF. TCM can promote the healing of OPF by promoting angiogenesis in the early stage of bone healing, promoting osteogenic differentiation of bone marrow mesenchymal stem cells in the stage of bone repair, maintaining the balance of osteogenic and osteoclastic system in the stage of bone remodeling, and regulating the oxidative stress responses throughout the process of OPF healing. TCM can alleviate the pathological state of osteoporosis and promote fracture healing in OPF patients via multiple pathways and targets, demonstrating the advantages and potential of biphasic regulation.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Osteoporotic Fractures/metabolism* ; Animals ; Fracture Healing/drug effects* ; Medicine, Chinese Traditional ; Kidney/metabolism* ; Osteogenesis/drug effects*

OBJECTIVE: To summarize the research and clinical application progress of foot lengthening surgery. METHODS: Relevant research literature on foot lengthening surgery in recent years at home and abroad was reviewed, and a summary was made from aspects such as the types of lengthening surgery, the types of foot diseases treated by clinical application, effectiveness, and complications. RESULTS: Bone defects and shortening deformities of the foot are relatively common clinically. As an innovative treatment method, foot lengthening surgery has gradually attracted attention, mainly including the Ilizarov technique and one-stage bone grafting lengthening surgery. The former promotes bone regeneration based on the tension-stress principle and is widely used in the treatment of calcaneal defects and congenital metatarsal brachymetatarsia, achieving good curative effects. However, there are also complications such as pin-tract infection, joint stiffness and contracture, non-union and delayed union of bone, re-fracture, and alignment deviation. The latter has a short treatment cycle, but the lengthening length is limited. Bone graft resorption and soft tissue complications are its main complications. CONCLUSION Foot lengthening surgery will develop towards the direction of personalization, intelligence, and precision. With the help of multi-center research, biological materials, and intelligent technologies, the effectiveness and safety will be further improved to better restore the function and appearance of the foot.
Humans ; Bone Transplantation/methods* ; Bone Lengthening/methods* ; Ilizarov Technique ; Osteogenesis, Distraction/methods* ; Foot Deformities/surgery* ; Postoperative Complications ; Treatment Outcome ; Foot/surgery*

OBJECTIVE: To explore, identify, and develop novel blood-based indicators using machine learning algorithms for accurate preoperative assessment and effective prediction of postoperative complication risks in patients with rheumatoid arthritis (RA) undergoing total knee arthroplasty (TKA). METHODS: A retrospective cohort study was conducted including RA patients who underwent unilateral TKA between January 2019 and December 2024. Inpatient and 30-day postoperative outpatient follow-up data were collected. Six machine learning algorithms, including decision tree, random forest, logistic regression, support vector machine, extreme gradient boosting, and light gradient boosting machine, were used to construct predictive models. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), F1-score, accuracy, precision, and recall. SHapley Additive exPlanations (SHAP) values were employed to interpret and rank the importance of individual variables. RESULTS: According to the inclusion criteria, a total of 1 548 patients were enrolled. Ultimately, 18 preoperative indicators were identified as effective predictive features, and 8 postoperative complications were defined as prediction labels for inclusion in the study. Within 30 days after surgery, 453 patients (29.2%) developed one or more complications. Considering overall accuracy, precision, recall, and F1-score, the random forest model [AUC=0.930, 95% CI (0.910, 0.950)] and the extreme gradient boosting model [AUC=0.909, 95% CI (0.880, 0.938)] demonstrated the best predictive performance. SHAP analysis revealed that anti-cyclic citrullinated peptide antibody, C-reactive protein, rheumatoid factor, interleukin-6, body mass index, age, and smoking status made significant contributions to the overall prediction of postoperative complications. CONCLUSION Machine learning-based models enable accurate prediction of postoperative complication risks among RA patients undergoing TKA. Inflammatory and immune-related blood biomarkers, such as anti-cyclic citrullinated peptide antibody, C-reactive protein, and rheumatoid factor, interleukin-6, play key predictive roles, highlighting their potential value in perioperative risk stratification and individualized management.
Humans ; Arthroplasty, Replacement, Knee/adverse effects* ; Arthritis, Rheumatoid/blood* ; Machine Learning ; Postoperative Complications/blood* ; Female ; Male ; Retrospective Studies ; Middle Aged ; Aged ; Risk Factors ; Preoperative Period ; C-Reactive Protein/analysis* ; Risk Assessment