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.

ObjectiveTo construct a multifunctional liposomal delivery system by replacing cholesterol（Chol） in conventional liposomes with saikosaponin D（SSD） and modifying with poloxamer 407（P407） for co-delivery of curcumin（Cur）. The system was evaluated for in vivo tumor targeting and inhibitory effects on mouse subcutaneous solid tumors. MethodsSingle-factor and orthogonal tests combined with information entropy weighting were used to optimize the formulation process of the liposome with encapsulation efficiency and absolute Zeta potential as indexes， and validation studies and liposomal characterization were performed. A subcutaneous solid tumor model was established by injecting H22 hepatocellular carcinoma cells subcutaneously into the dorsal surface of the right forelimb of mice. DiR-loaded traditional Chol liposomes（P407-DiR-Chol-LPs， PDCL） and novel SSD-based liposomes（P407-DiR-SSD-LPs， PDSL） were prepared by the optimized formulation process， and tail vein injection was performed to investigate the impact of SSD on liposome tumor targeting with small animal in vivo imaging. Mice were randomly divided into eight groups， including blank group， model group， free doxorubicin（DOX） group（2 mg·kg^-1）， free Cur group（8 mg·kg^-1）， free SSD group（10 mg·kg^-1）， P407-Cur-Chol-LPs（PCCL） group， P407-SSD-LPs（PSL） group， and P407-Cur-SSD-Lps（PCSL） group. Treatments were administered intraperitoneally every other day for seven doses. Antitumor efficacy and biocompatibility were evaluated by monitoring body weight change， organ indices， tumor volume and mass， relative tumor proliferation rate（T/C）， and tumor growth inhibition rate（TGI）. Histopathological analysis of liver， kidney， and tumor tissues was performed using hematoxylin-eosin（HE） staining. Serum levels of aspartate aminotransferase（AST）， alanine aminotransferase （ALT）， blood urea nitrogen（BUN）， and creatinine（Crea）in mice were quantified by fully automated biochemical analyzer. ResultsOrthogonal test yielded optimal ratios of Cur， SSD， and P407 to soybean phosphatidylcholine（SPC） as 1∶25， 1∶20， and 1∶4. The optimized PCSL exhibited spherical morphology with a particle size of 179.15 nm， a Zeta potential of -47.25 mV， and an encapsulation efficiency of 96.40%. Its in vitro release profile conformed to first-order kinetics， demonstrating excellent storage stability and hemocompatibility. In vivo imaging revealed that the fluorescence signal in tumor tissues and the fluorescence intensity ratio between tumors and organs were significantly higher in the PDSL group than in the PDCL group（P<0.05， P<0.01）. Among the treatment groups， PCSL group showed superior efficacy over free Cur group， free SSD group， PCCL group， and PSL group， with TGI>40% and T/C<60%， indicating pronounced anti-hepatocellular carcinoma effects（P<0.05， P<0.01）. Histopathology and serum biochemistry indicated minimal hepatorenal toxicity and improved hepatic and renal function in PCSL-treated mice. ConclusionReplacing Chol with SSD in preparing multifunctional drug delivery systems not only stabilizes liposomes but also yields superior anti-hepatocellular carcinoma efficacy， achieving the effect of drug-excipient integration. Co-delivery of Cur via this system can be used for treating subcutaneous solid tumors in hepatocellular carcinoma， providing new insights and technical approaches for anti-hepatocellular carcinoma research and the meridian-guiding and messenger-directing theory in traditional Chinese medicine.

OBJECTIVE To study the improvement effect and mechanism of Dendrobium officinale on skin damage in mice with xeroderma. METHODS The mice were randomly divided into control group， model group， and D. officinale group， with 5 mice in each group. Except for the control group （which only underwent shaving treatment）， the mice in all other groups were induced to develop a xeroderma model using an acetone-ether mixture for five consecutive days. The mice in D. officinale group were treated with 200 μL of D. officinale suspension （0.2 mg/mL） two hours after the first modeling each day. Mice in the control group and the model group were applied with an equal volume of pure water； once a day， until the end of the modeling process. After last medication， skin lesions and pathological morphology of the mice were observed. Immunofluorescence was used to detect the expressions of Filaggrin， Loricrin and Ki67 proteins in skin tissue of the mice. The core pathways through which D. officinale improves skin damage in xeroderma were screened using 16S rRNA sequencing combined with gene ontology and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses， and subsequent validation was conducted. RESULTS Compared with the control group， the mice in the model group exhibited obvious scratching behavior， with a large amount of scale on the skin， excessive epidermal keratinization， and thickened stratum spinosum. The skin scale score， epidermal thickness， and the expression levels of Ki67， Filaggrin， and Loricrin proteins in the skin tissue were significantly increased/elevated （ P ＜0.05）. Compared with model group， the mice in the D. officinale group exhibited reduced scratching behavior and scaling， along with a mitigated degree of skin keratinization. The aforementioned quantitative indicators were significantly decreased/reduced （ P ＜0.05）. The results of core pathway screening revealed that the KEGG pathways involving differentially expressed genes included signaling pathways such as interleukin-17 （IL-17） and tumor necrosis factor （TNF）. Further validation experim ents found that after intervention with D. officinale ， mRNA expression of downstream effector molecules CCN1， Hbegf， Tnfrsf12a， and Thbs1 genes in skin tissues were all significantly reduced （ P ＜0.05）. CONCLUSIONS D. officinale can repair skin damage in mice with xeroderma， and its mechanism of action is related to restoring the balance of proliferation and differentiation in keratinocytes and down-regulating the mRNA expressions of CCN1， Hbegf， Tnfrsf12a， and Thbs1.

This article further reveals the significance of "tiangui （天癸）" in female reproductive genetic diseases by analyzing the core influence of the "kidney-tiangui-chong and ren mai （冲任）-uterus" reproductive axis on the processes of birth， growth， robustness， and aging in females. Approaching tiangui through its heredity， material basis， temporality， rhythmicity， functional diversity and genetic polymorphism， and integrating reproductive genetics with epigenetics， it explores the potential associations between the characteristics of tiangui and the pathogenesis， clinical features， and therapeutic targets of female reproductive genetic diseases. This study furnishes a novel genetic interpretation of the physiological and pathological features of tiangui， offering scientific basis for the integrated prevention and treatment of female reproductive genetic diseases with traditional Chinese and western medicine.

This article further reveals the significance of "tiangui （天癸）" in female reproductive genetic diseases by analyzing the core influence of the "kidney-tiangui-chong and ren mai （冲任）-uterus" reproductive axis on the processes of birth， growth， robustness， and aging in females. Approaching tiangui through its heredity， material basis， temporality， rhythmicity， functional diversity and genetic polymorphism， and integrating reproductive genetics with epigenetics， it explores the potential associations between the characteristics of tiangui and the pathogenesis， clinical features， and therapeutic targets of female reproductive genetic diseases. This study furnishes a novel genetic interpretation of the physiological and pathological features of tiangui， offering scientific basis for the integrated prevention and treatment of female reproductive genetic diseases with traditional Chinese and western medicine.

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.

Objective To compare the performance of seasonal difference autoregressive moving average exogenous variable model (SARIMAX), backpropagation neural network (BPNN), long short-term memory network (LSTM), and various combination models in fitting and predicting the incidence of hand, foot, and mouth disease (HFMD), and to provide a reference for optimizing HFMD prediction and prevention and control decisions. Methods Taking the monthly HFMD incidence data in Changsha from 2010 to 2024 as the training set, and the monthly HFMD incidence data from January to August 2025 as the validation set, the single models, SARIMAX-BPNN, SARIMAX-LSTM and weight combination models were constructed respectively. The R², mean absolute percentage error (MAPE), mean absolute error (MAE), and root mean square error (RMSE) were used to evaluate the model fitting and prediction performance. Results Based solely on MAPE, the LSTM model showed the best fitting and prediction performance. A comprehensive analysis of multiple indicators including R², MAPE, MAE, and RMSE indicated that the combination models had superior prediction performance. Compared with the LSTM, RMSE predicted by equal weight combination, different weight combination and SARIMAX-BPNN decreased by 40.97%, 37.50%, and 25.00%, respectively, while MAPE increased by 124.84%, 96.90%, and 89.69%, respectively. The fitting effect was as follows: LSTM > unequal weight combination > equal weight combination > SARIMAX-LSTM > SARIMAX-BPNN > BPNN > SARIMAX. The prediction performance was as follows: SARIMAX-BPNN > unequal weight combination > equal weight combination > LSTM > SARIMAX-LSTM > BPNN > SARIMAX. Conclusion SARIMAX-BPNN combination or weighted combination of multiple different models are two more robust combination strategies for predicting the incidence trend of hand, foot and mouth disease in Changsha.

Total-body PET/CT, with its long axial field of view and high sensitivity detector, has shown potential for reducing the dose of radiopharmaceuticals. However, pediatric patients are significantly more sensitive to radiation and have a higher long-term cancer risk than adults, posing fundamental challenges for dose management in PET/CT examinations for these patients. In this article, the technical characteristics of total-body PET/CT and its radiation exposure status in children were systematically analyzed. The radiation exposure could be controlled by the following optimization strategies: adjusting the CT exposure parameters, optimizing the scanning mode, adding reconstruction algorithm, and reducing the injected dose of radioactive tracer. By addressing both external and internal radiation during the PET/CT scanning process, the overall radiation dose received by pediatric patients can be reduced within a certain range. In addition, this article also discusses the technical differences between “total-body” and “whole-body” concepts, and emphasizes that the future optimization of radiation dose in pediatric PET/CT should be realized by integration of personalized scanning protocols. Through reasonable management of scanning protocols and processes, low-dose and high-quality PET/CT imaging can be achieved in clinical environments, thus maximizing protection of pediatric patient health while minimizing the risks associated with ionizing radiation exposure.

Objective　To investigate the expression of neutrophil elastase (ELANE) mRNA in peripheral blood mononuclear cells (PBMCs) under different infection states of Mycobacterium tuberculosis (MTB), and analyze the feasibility of ELANE as a diagnostic marker for MTB infection. Methods　PBMCs were isolated from peripheral blood of active tuberculosis patients (ATB), latent infection of Mycobacterium tuberculosis (LTBI) and healthy control (HC) Luanzhou People's Hospital, Hebei Province, February-November 2023 and cell RNA was extracted. After reversing into cDNA, the difference of ELANE mRNA level in PBMCs in each group was detected by fluorescence quantitative PCR. The whole cell lysate of Mycobacterium tuberculosis H37Rv was used to stimulate PBMCs in each group, and total RNA was extracted. Fluorescence quantitative PCR was also used to detect the expression differences of ELANE gene before and after cell stimulation in each group; these expression differences were analyzed for identifying the feasibility of ATB. Results　The expression of ELANE gene in peripheral blood mononuclear cells of ATB patients was significantly higher than that of LTBI and healthy individuals (t=4.550, P<0.001; t=4.540, P<0.001). ROC analysis showed that the area under the curve for ELANE differential diagnosis of ATB and LTBI, ATB and HC were 0.802 and 0.805, respectively. H37Rv whole cell lysate can upregulate the expression of ELANE gene in PBMCs of ATB patients, with a significant difference before and after stimulation (t=4.717, P<0.001). However, there was no significant difference in ELANE gene expression in PBMCs of LTBI and HC populations before and after H37Rv bacterial lysate stimulation. Conclusion 　Compared with LTBI and healthy individuals, the expression level of ELANE mRNA in peripheral blood mononuclear cells of ATB was significantly upregulated; After stimulation with MTB whole cell lysate antigen, the expression level of ELANE in PBMCs of ATB population significantly increased. ELANE can serve as a diagnostic biomarker for active pulmonary tuberculosis to differentiate ATB from LTBI and healthy individuals.

OBJECTIVE: To observe the clinical efficacy of acupuncture based on the "head qijie" theory combined with endovascular intervention in the treatment of ischemic stroke (IS). METHODS: Sixty-six IS patients were randomly divided into an experimental group (33 cases, 3 cases dropped out) and a control group (33 cases, 3 cases dropped out). The control group received endovascular intervention. On the basis of the treatment in the control group, the experimental group received acupuncture based on the "head qijie" theory starting from the second day after surgery, Baihui (GV20) and bilateral Fengchi (GB20), Tianzhu (BL10), etc. were selected, once a day, 6 times a week for 2 weeks. Before and after treatment, the scores of National Institutes of Health stroke scale (NIHSS), modified Barthel index (MBI) and modified Rankin scale (mRS) were observed in the two groups, the clinical efficacy and safety were evaluated. RESULTS: After treatment, the NIHSS and mRS scores were decreased compared with those before treatment in both groups (P<0.01), the NIHSS and mRS scores in the experimental group were lower than those in the control group (P<0.05). After treatment, the MBI scores were increased compared with those before treatment in both groups (P<0.01), the MBI score in the experimental group was higher than that in the control group (P<0.05). The total effective rate in the experimental group was 86.7% (26/30), which was higher than 66.7% (20/30) in the control group (P<0.05). The incidence of adverse events in the experimental group was 6.7% (2/30), which was lower than 13.3% (4/30) in the control group (P<0.05). CONCLUSION Acupuncture based on the "head qijie" theory combined with endovascular intervention in treating IS has good efficacy, improves neurological function, and enhances daily living ability.
Humans ; Male ; Female ; Acupuncture Therapy ; Middle Aged ; Aged ; Ischemic Stroke/therapy* ; Acupuncture Points ; Endovascular Procedures ; Treatment Outcome ; Adult ; Combined Modality Therapy