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.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

ObjectiveTo investigate the effect of Huangqi jiuni decoction （HQJND） on acute liver injury in severely scalded rats and its possible molecular mechanism by animal experiments and modern pharmacological tools. MethodsFirstly， the rat model of sepsis was established and randomly divided into 4 groups. The normal saline group was given 1 mL of normal saline twice a day， and the traditional Chinese medicine group was given 1 mL of concentrated huangqi jiuni decoction twice a day. After 72 hours of shock， the samples were sacrificed， and then the serum liver function and （+）-haematoxylin eosin staining were performed to verify the efficacy of the drug. Sham Operation Group and sepsis group were fed normally without any special treatment. Then， network pharmacology was used to screen the targets of drugs and drug responses and predict the signaling pathways that might play a role in the treatment of diseases. Finally， fluorescence quantitative PCR （RT-qPCR） was performed to detect gene expression， Western blot （WB） was performed to detect tumor necrosis factor （TNF-α）， P65， phosphorylated P65 （P-P65）， and immunohistochemical （IHC） were performed assays to verify drug efficacy and explore the mechanism of drug treatment. ResultsSerum liver function and histopathology in rats showed that HQJND significantly improved liver function in severely burned rats. Network pharmacology screening was used to identify 353 disease-related marker genes and 286 drug targets. It was predicted that tumor necrosis/NF-NF-κB pathway （TNF/NF-NF-κB pathway） might be a key pathway for HQJND to treat acute liver injury after severe burns. The results of immunohistochemistry （IHC） showed that the staining of TNF-α in the liver of the sepsis group was more than that of the sham operation group and the traditional Chinese medicine group. The results of RT-qPCR and WB showed that the expression of TNF-α， TNFR1 and P65 proteins in the liver of rats in the sepsis group was significantly higher than that in the sham operation group and the traditional Chinese medicine group； on the contrary， the expression of TNF-α， TNFR1 and P65 proteins in the liver of rats in the sepsis group was significantly higher than that in the sham operation group and the traditional Chinese medicine group. The expression level of nuclear factor-kappa B（IκBα） was higher in the sham operation group and the traditional Chinese medicine group， indicating that drug treatment effectively inhibited the activation of the TNF/NF-κb signaling pathway. ConclusionAnimal experiments and network pharmacology results confirm that HQJND has a protective effect on acute liver injury in severely burned rats， which may be related to the inhibition of TNF/NF-κB signaling pathway.

Pan vascular disease （PVD） is a systemic vascular disorder that has become the leading cause of death among the Chinese residents， and there is currently a lack of effective systemic treatment options. Clinical practice has found that the traditional Chinese medicine （TCM） method of kidney tonification can effectively intervene in PVD and target key pathological mechanisms of PVD recognized in Western medicine. Accordingly， this paper conducts research from the following three aspects： First， it clarifies that immune dysregulation， metabolic disorders， and genetic susceptibility constitute the core pathological mechanisms of PVD in Western medicine. Typical pathological manifestations include progressive vascular endothelial injury， lipid deposition， and plaque formation， ultimately leading to multi-organ damage and dysfunction. PVD activates pathways such as the NOD-like receptor thermal protein domain-associated protein 3 （NLRP3） inflammasome， triggering immune dysregulation； it also induces disorders of mitochondrial energy metabolism， water-salt metabolism， and hormonal metabolism， synergizing with genetic susceptibility factors （e.g.， apolipoprotein E gene） to accelerate vascular homeostasis imbalance. Second， this study analyzes the intrinsic relationship between the TCM theory of "kidney deficiency" and the "immune-metabolic-genetic" axis， revealing the theoretical basis for kidney tonification in intervening PVD. The kidney stores essence， governs bones， and produces marrow， which is related to the generation and differentiation of immune cells. It regulates Qi transformation and governs water， overseeing material and energy metabolism. The kidney is the root of congenital essence and governs reproduction， closely related to genetic mechanisms. Third， by integrating modern clinical research， this study elaborates on the unique advantages and clinical value of kidney tonification in targeting the "immune-metabolic-genetic" axis of heart， brain， and kidney organs. Traditional kidney-tonifying formulas and their active ingredients improve immune-inflammatory responses， enhance material and energy metabolism homeostasis， and modulate epigenetic pathways through multiple pathways， targeting various pathways to intervene in PVD. This study systematically elucidates the scientific connotation of kidney tonification in treating PVD， providing theoretical support and practical guidance for integrated TCM-Western medicine approaches and contributing to innovation and improvement in diagnostic and treatment strategies for PVD.

Objective To summarize the clinical efficacy of modified Morrow surgery in the treatment of hypertrophic obstructive cardiomyopathy. Methods A retrospective analysis was conducted on the clinical data of patients with hypertrophic obstructive cardiomyopathy treated with modified Morrow surgery at Zhongshan Hospital Affiliated to Fudan University from 2020 to 2023. Results A total of 318 patients were enrolled, including 156 males and 162 females, with an average age of (55.6±13.1) years. Preoperative echocardiography showed a mean interventricular septal thickness of (18.1±3.8) mm, peak left ventricular outflow tract pressure difference of (86.4±24.9) mm Hg. The surgery time was (162.3±51.0) min, extracorporeal circulation time was (80.9±31.0) min, and aortic occlusion time was (44.8±20.8) min. After the surgery, transesophageal echocardiography showed that the interventricular septal thickness was (11.0±1.8) mm and left ventricular outflow tract peak pressure difference was (9.4±5.1) mm Hg. The incidence rate of postoperative complete left bundle branch block was 45.3%, Ⅲ° atrioventricular block was 3.8%, and postoperative newly developed atrial fibrillation was 3.1%. The postoperative hospital stay was (6.6±4.9) days, and one perioperative death occurred, with a mortality rate of 0.3%. The follow-up time was (10.3±9.4) months, during which the transthoracic echocardiography revealed a ventricular septal thickness of (12.9±2.9) mm and a peak left ventricular outflow tract pressure difference of (13.9±10.0) mm Hg. Conclusion The modified Morrow procedure for the treatment of hypertrophic obstructive cardiomyopathy is safe and effective, with good results in the short and medium term.

Angiogenesis， as a core mechanism for maintaining tissue perfusion and repairing ischemic injury， plays a crucial role in ischemic diseases such as coronary heart disease and peripheral arterial disease. Traditional Chinese medicine（TCM）， with its advantages of multi-target and synergistic regulation， provides a unique perspective for therapeutic angiogenesis. Based on this， this article intends to delve into the synergistic effects of key signaling pathways， including vascular endothelial growth factor（VEGF）/VEGF receptor（VEGFR）， Notch， phosphoinositide 3-kinase/ protein kinase B/mammalian target of rapamycin（PI3K/Akt/mTOR）， and angiopoietin/endothelial TEK tyrosine kinase（Ang/Tie2）， and elucidate the driving mechanisms of endothelial cell metabolic reprogramming and exosome-mediated intercellular communication within this process. Based on existing literature， it summarizes the microenvironment-dependent and bidirectional regulatory characteristics of natural active components of TCM（such as terpenes， tanshinones， and flavonoids） on angiogenesis. Furthermore， it systematically discusses how classical TCM formulas achieve blood vessel formation and functional maturation by protecting the neurovascular units， recruiting pericytes， and remodeling the microenvironment. Current evidence highlights the advantages of multi-target synergy and temporal regulation in TCM， but also reveals challenges such as high heterogeneity and a lack of functional evaluations and high-quality clinical trials. Future efforts should integrate multi-omics to decipher network mechanisms， optimize formula compatibility， and conduct multicenter studies to promote the development of innovative preparations. This review highlights the academic value of TCM in angiogenesis， provides an evidence base for treating ischemic diseases， and supports multidisciplinary integration and innovation.

ObjectiveTo investigate the relationship between solute carrier family 7 member 11 （SLC7A11） expression in esophageal squamous cell carcinoma （ESCC） and clinical prognosis， and to determine its effects on ESCC cell growth， migration， and other biological activities. MethodsSLC7A11 protein expression was measured in 310 ESCC tissues and 259 adjacent normal tissues using immunohistochemistry to statistically assess the association of SLC7A11 with clinicopathologic characteristics and prognosis in ESCC patients. The expression of SLC7A11 in ESCC cell lines was suppressed through siRNA-mediated knockdown. The specific effects of SLC7A11 knockdown on proliferation and migration were evaluated using CCK-8， clonogenic assay， and Transwell assays. Adenosine triphosphate （ATP）， lactic acid and pyruvate assays were used to measure ESCC metabolism. ResultsSLC7A11 protein expression was localized predominantly in the cytoplasm of ESCC tissues. Significantly higher SLC7A11 expression levels were observed in ESCC tissues compared to adjacent normal tissues （P<0.001）. High SLC7A11 expression was associated with poorer differentiation in patients （P<0.01）. Kaplan-Meier survival analysis demonstrated significantly shorter overall survival in patients with high SLC7A11 expression compared to those with low expression （P<0.05）. CCK-8 and colony formation assays demonstrated that the knockdown of SLC7A11 expression significantly suppressed the proliferative capacity of tumor cells （P<0.001）. Furthermore， Transwell assays revealed a marked decline in tumor cell migration capacity following SLC7A11 suppression （P<0.001）. Critically， SLC7A11 knockdown also reduced intracellular levels of ATP， lactate， and pyruvate， demonstrating that SLC7A11 modulated metabolic activity in ESCC cells（P<0.001）. ConclusionThe expression level of SLC7A11 is relatively high in ESCC and is strongly associated with poor prognosis. Silencing SLC7A11 significantly inhibits esophageal cancer cell growth and migration. SLC7A11 has the ability to regulate glucose， lactic acid and ATP metabolism levels in ESCC， thereby affecting the metabolic microenvironment of ESCC.

ObjectiveTo explore the application of virtual reality biofeedback training combined with oral localization therapy in dysphagia after oral cancer surgery. MethodsFrom May, 2023 to July, 2024, 86 patients with dysphagia after oral cancer surgery in Zhejiang Provincial People's Hospital were randomly divided into control group (n = 43) and experimental group (n = 43). The control group received conventional swallowing function training, while the experimental group added virtual reality biofeedback training combined with oral positioning therapy, for four weeks. The Standardized Swallowing Function Assessment Scale (SSA), Functional Oral Intake Scale (FOIS) and M.D.Anderson Dysphagia Inventory (MDADI) were used for evaluation before intervention, and two weeks, four weeks and eight weeks after intervention. ResultsFor scores of SSA , the main effects of group (F = 150.190, P < 0.001, η²_p = 0.641) and time (F = 230.870, P < 0.001, η²_p = 0.733), as well as the interaction effect (F = 16.910, P < 0.001, η²_p = 0.168) were all significant. For scores of FOIS, the main effects of group (F = 59.601, P < 0.001, η²_p = 0.415) and time (F = 89.464, P < 0.001, η²_p = 0.516), as well as the interaction effect (F = 7.990, P < 0.001, η²_p = 0.087) were all significant. For scores of MDADI, the main effects of group (F = 33.133, P < 0.001, η²_p = 0.283) and time (F = 49.650, P < 0.001, η²_p = 0.371), as well as the interaction effect (F = 3.224, P = 0.023, η²_p = 0.037) were all significant. ConclusionVirtual reality biofeedback training combined with oral localization therapy could improve the swallowing function, oral feeding ability and overall quality of life of patients with dysphagia after oral cancer surgery.

ObjectiveThis study aims to explore the potential of different orders of magnitude single-nucleotide polymorphism (SNP) locus combinations for predicting distant kinship relationships. A high-density SNP locus set was constructed, and a comprehensive assessment of its inference capability was conducted. MethodsFirstly, we selected three commercial chip panels, CGA (Chinese genotyping array, Illumina), GSA (Global screening array, Illumina), Affy (23MF_V2 high-density SNP array, Affymetrix) and merged them after quality control, forming a high-density SNP locus panel(1 180 k). Secondly, we selected 161 samples and collected their peripheral blood samples by using whole-genome sequencing technology. Within this sample population, the levels of kinship relationships fully covered the range from level 1 to level 9, and the number of kinship pairs at each level was consistently maintained at over 50 pairs. From 161 samples data of whole-genome sequencing, the 1 180 k locus set was extracted, which is referred to as the high-density SNP locus set in the following text. The kinship inference was conducted using the identity-by-descent (IBD) algorithm with the selected optimal parameters. To comprehensively evaluate the performance of the high-density SNP locus set in kinship inference, we compared it with the three commercial chip panels, the intersection of these three chip loci, and the control sets constructed by randomly reducing the number of the high-density SNP locus set. Based on the changes in the IBD lengths, as well as the dynamic trends in prediction accuracy, we conducted a scientific assessment of the kinship inference capability of the high-density SNP locus set. ResultsAfter screening, a set of 1 184 334 autosomal SNPs was obtained. During the process of screening the optimal IBD length threshold, the result revealed that 0 cM, 1 cM, and 2 cM all demonstrated good applicability. However, to avoid the issue of a large amount of redundant information caused by setting a too low IBD length threshold, this study ultimately selected 2 cM as the optimal threshold. Compared with the average results of three chip panels, the high-density SNP locus set increased the total IBD length and the average IBD length across levels 1-9; the accuracy of the confidence interval for level 8 was 70.97%, which represented a 3.50% improvement; the average confidence interval accuracy for levels 1-8 was 91.39%, representing a 1.00% increase; and the false negative rates at levels 8 and 9 were reduced by 2.42% and 6.76%, respectively. The system efficacy of the high-density SNP locus set for kinship inference of first to eighth degree relationships reached 98.91%. Through random reduction of the high-density SNP locus set results, it is found that increasing the number of SNPs with the panel, the detection efficiency of IBD length showed a significant upward trend. At the same time, the overall trend in the accuracy of kinship relationship prediction as well as the confidence interval accuracy also indicated that both metrics steadily increased with the addition of more loci. ConclusionThe results show that the high-density SNPs panel significantly enhances the efficacy of distant kinship inference, accurately covering kinship degrees, with the average confidence interval accuracy for first to eighth degree relationships stably above 90%. The study finds that increasing the number of SNPs panel can improve the ability to predict distant kinship.