OBJECTIVE: To explore and verify the effect and potential mechanism of Brucea javanica Seed Oil Emulsion Injection (YDZI) and Shengmai Injection (SMI) on peripheral microcirculation dysfunction in treatment of gastric cancer (GC). METHODS: The potential mechanisms of YDZI and SMI were explored through network pharmacology and verified by cellular and clinical experiments. Human microvascular endothelial cells (HMECs) were cultured for quantitative real-time polymerase chain reaction, Western blot analysis, and human umbilical vein endothelial cells (HUVECs) were cultured for tube formation assay. Twenty healthy volunteers and 97 patients with GC were enrolled. Patients were divided into surgical resection, surgical resection with chemotherapy, and surgical resection with chemotherapy combining YDZI and SMI groups. Forearm skin blood perfusion was measured and recorded by laser speckle contrast imaging coupled with post-occlusive reactive hyperemia. Cutaneous vascular conductance and microvascular reactivity parameters were calculated and compared across the groups. RESULTS: After network pharmacology analysis, 4 ingredients, 82 active compounds, and 92 related genes in YDZI and SMI were screened out. β-Sitosterol, an active ingredient and intersection compound of YDZI and SMI, upregulated the expression of vascular endothelial growth factor A (VEGFA) and prostaglandin-endoperoxide synthase 2 (PTGS2, P<0.01), downregulated the expression of caspase 9 (CASP9) and estrogen receptor 1 (ESR1, P<0.01) in HMECs under oxaliplatin stimulation, and promoted tube formation through VEGFA. Chemotherapy significantly impaired the microvascular reactivity in GC patients, whereas YDZI and SMI ameliorated this injury (P<0.05 or P<0.01). CONCLUSIONS YDZI and SMI ameliorated peripheral microvascular reactivity in GC patients. β-Sitosterol may improve peripheral microcirculation by regulating VEGFA, PTGS2, ESR1, and CASP9.
Humans ; Microcirculation/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Stomach Neoplasms/physiopathology* ; Emulsions ; Male ; Plant Oils/administration & dosage* ; Brucea/chemistry* ; Middle Aged ; Female ; Drug Combinations ; Human Umbilical Vein Endothelial Cells/metabolism* ; Seeds/chemistry* ; Injections ; Vascular Endothelial Growth Factor A/metabolism* ; Aged ; Network Pharmacology

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

OBJECTIVES: To investigate the inhibitory effect of multimerin-2 (MMRN2) overexpression on growth and metastasis of cutaneous melanoma cells. METHODS: Clinical data of patients with cutaneous melanoma were obtained from the GEO database to compare MMRN2 expressions between normal and tumor tissues. A protein-protein interaction network was constructed using the STRING database, and the intersecting genes from GEPIA2.0 were subjected to GO and KEGG enrichment analysis. The prognostic relevance of MMRN2 expression level was assessed using Cox regression and "timeROC". The correlations of MMRN2 expression level with immune infiltration and angiogenesis-related genes were analyzed using GSCA database and the ssGSEA algorithm. Colony-forming assay, Transwell assay, and wound healing assay were used to examine the changes in proliferation and migration of cultured cutaneous melanoma cells following MMRN2 knockdown. In a mouse model bearing cutaneous melanoma xenograft, the effect of MMRN2 knockdown on vital organ pathologies, survival of the mice and GM-CSF, CXCL9, and TGF‑β1 protein expressions were analyzed. RESULTS: MMRN2 was significantly upregulated in metastatic cutaneous melanoma (P<0.001). Protein interaction network analysis identified 15 intersecting genes, which were enriched in endothelium development and cell-cell junctions. In patients with cutaneous melanoma, a high MMRN2 expression was correlated with a poor prognosis, an advanced T stage, a greater Breslow depth, and ulceration (P<0.05). MMRN2 expression level was strongly correlated with 24 immune cell types (P<0.001), fibroblasts, endothelial cells, and expressions of the pro-angiogenic genes (KCNJ8, SLCO2A1, NRP1, and COL3A1; P<0.001). In cultured B16F10 cells, MMRN2 knockdown significantly suppressed cell proliferation, migration and invasion and caused remo-deling of the immunosuppressive microenvironment. CONCLUSIONS MMRN2 overexpression drives progression of cutaneous melanoma by enhancing tumor metastasis, angiogenesis and immune evasion, highlighting its potential as a therapeutic target for melanomas.
Humans ; Melanoma/metabolism* ; Animals ; Cell Movement ; Prognosis ; Skin Neoplasms/metabolism* ; Mice ; Cell Proliferation ; Neoplasm Invasiveness ; Cell Line, Tumor ; Protein Interaction Maps

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Objective:To compare the efficacy of laminoplasty via the intermuscular approach or posterior midline approach for treating spinal cord injury without radiographic abnormality (SCIWORA).Methods:A multi-center retrospective cohort study was conducted to analyze the clinical data of 135 patients with SCIWORA admitted to Honghui Hospital Affiliated to Xi'an Jiaotong University School of Medicine, Xi'an No.5 Hospital, Henan Provincial People's Hospital, Zhengzhou Orthopedic Hospital, Xuanwu Hospital of Capital Medical University from February 2021 to June 2023, including 75 males and 60 females, aged 35-78 years [(55.3±8.1)years]. The injury segments involved C 3-C 6. All the patients underwent posterior cervical open-door laminoplasty, among whom 70 patients were treated via the intermuscular approach (intermuscular group) and 65 via the posterior midline approach (posterior midline group). The operation duration, intraoperative blood loss, postoperative drainage volume, and length of hospital stay were recorded. The visual analogue scale (VAS) score, Japanese Orthopedic Association (JOA) score, neck disability index (NDI), Barthel index, cervical Cobb angle, and cervical range of motion (ROM) were measured preoperatively, at 3, 6, 12 months postoperatively and at the final follow-up. The American Spinal Injury Association (ASIA) scale was evaluated preoperatively, at 3, 12 months postoperatively and at the final follow-up. The postoperative complication rate was recorded as well. Results:All the patients were followed up for 15-19 months [(16.3±1.6)months]. The operation duration, intraoperative blood loss, postoperative drainage and length of hospital stay were (125.0±23.0)minutes, (210.4±34.8)ml, and (165.3±23.7)ml, and (5.3±0.1)days in the intermuscular group, which were significantly shorter or less than (168.0±27.6)minutes, (260.2±45.3)ml, (196.4±31.6)ml, and (6.4±0.2)days in the posterior midline group ( P<0.01). The preoperative VAS score, JOA score, NDI and Barthel index showed no significant differences between the two groups ( P>0.05). The VAS score and JOA score also showed no significant differences between the two groups at 3, 6, 12 months postoperatively or at the final follow-up ( P>0.05). The NDI and Barthel index also showed no significant differences between the two groups at 3 months postoperatively ( P>0.05). At 6, 12 months postoperatively and at the final follow-up, the NDI were (15.4±2.5)points, (11.8±2.1)points and (8.6±1.5)points in the intermuscular group, significantly lower than (19.1±3.4)points, (14.3±2.4)points and (11.9±1.4)points in the posterior midline group ( P<0.01). At 6, 12 months postoperatively and at the final follow-up, the Barthel index were (71.4±6.2)points, (83.4±5.8)points and (89.2±7.1)points in the intermuscular group, significantly higher than (59.6±4.7)points, (74.2±3.9)points and (78.8±6.2)points in the posterior midline group ( P<0.01). Both groups showed significant improvements in VAS score, JOA score, NDI and Barthel index at 3, 6, 12 months postoperatively and at the final follow-up when compared to those preoperatively ( P<0.05). Among them, the VAS score, NDI and Barthel index were further improved over time ( P<0.05). Simultaneously, the JOA score was significantly improved at 6, 12 months postoperatively and at the last follow-up when compared to that at 3 months postoperatively ( P<0.05), with no significant difference at later time points between the two groups ( P>0.05). The preoperative cervical Cobb angle and ROM showed no significant differences between the two groups ( P>0.05). There was no significant difference in the Cobb angle between the two groups at 3, 6 or 12 months postoperatively ( P>0.05), while it was (13.6±2.4)° in the intermuscular group at the final follow-up, significantly larger than (10.4±2.8)° in the posterior midline group ( P<0.01). At 3, 6, 12 months postoperatively and at the final follow-up, the cervical ROM were (34.1±6.4)°, (32.6±7.3)°, (31.8±9.1)° and (29.6±8.7)° in the intermuscular group, significantly larger than (23.7±8.3)°, (22.3±7.8)°, (22.5±8.1)° and (20.6±9.3)° in the posterior midline group ( P<0.01). In the intermuscular group, the cervical Cobb angle showed no significant changes at 3, 6, 12 months postoperatively and at the final follow-up when compared to those preoperatively ( P>0.05). In the posterior midline group, the Cobb angles were significantly reduced at 3, 6, 12 months postoperatively and at the final follow-up when compared to those preoperatively ( P<0.05), showing significant decrease at 12 months postoperatively and at the final follow-up from those at 3, 6 months postoperatively ( P<0.05), no significant difference at 6 months postoperatively from that at 3 months postoperatively ( P>0.05), and significant decrease at the final follow-up from that at 12 months postoperatively ( P>0.05). In the intermuscular group, the cervical ROM were significantly improved at 3, 6, 12 months postoperatively and at the final follow-up when compared to those preoperatively and showed further improvement over time ( P<0.05). In the posterior midline group, the cervical ROM were significantly improved at 3, 6, 12 months postoperatively and at the final follow-up when compared to those preoperatively ( P<0.05), showing significant decreases at 6, 12 months postoperatively and at the final follow-up from that at 3 months postoperatively ( P<0.05), significant decreases at the final follow-up from those at 6, 12 months postoperatively ( P<0.05), and no significant difference at 12 months postoperatively from that at 6 months postoperatively ( P>0.05). The ASIA grades showed no significant difference between the two groups preoperatively, at 3, 12 months postoperatively and at the final follow-up ( P>0.05) , but were gradually improved over time in both groups ( P<0.05). The postoperative complication rate was 9%(6/70) in the intermuscular group, significantly lower than 48%(31/65) in the posterior midline group ( P<0.01). Conclusion:Compared to the posterior midline approach, the intermuscular approach for laminoplasty in patients with SCIWORA possesses advantages, including shorter operative time and length of hospital stay, reduced intraoperative blood loss and postoperative drainage, less postoperative neck disability, higher daily life quality, better long-term preservation of cervical lordosis and motion, and a lower complication rate.

Objective To propose a multiple regression-variational auto-encoders(MR-VAE)model to realize precise and non-invasive prediction of intra-abdominal pressure(IAP)in critically ill patients.Methods At first,a dataset was constructed by retrospectively analysing baseline characteristics and clinical indicators of 100 critically ill patients admitted to the Intensive Care Unit of Daping Hospital of Army Medical University between 30 August 2019 and 30 March 2021.Then,a MR-VAE prediction model was developed by integrating a feedforward neural network for supervised regression onto a variational autoencoder(VAE)framework and incorporating multiple regression strategies to mitigate feature interference.Finally,the MR-VAE model had its performance evaluated by its comparison with five classical models including support vector machines(SVM),convolutional neural networks(CNN),Scikit-learn integrated model(SIM),multi-layer perceptron(MLP)and K-nearest neighbors(KNN),and its prediction accuracy verified by testing the data of 10 randomly selected patients.Results The MR-VAE model behaved the best when compared with the five classical models,with a mean squared error(MSE)of 0.207,a root mean square error(RMSE)of 0.454,a mean absolute error(MAE)of 0.361,a median absolute deviation(MAD)of 0.243,an explained variance score(EVS)of 0.814 and a R2of 0.823,which also outperformed the five models in fitting performance,convergence and final loss.In random sample testing,the MR-VAE model exhibited high consistency between predicted and actual values.Conclusion The MR-VAE model proposed can accurately predict IAP,which has great potential in reducing the repeated measurements of IAP in critically ill patients and providing new ideas for the early diagnosis and treatment of IAH.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

Objective To propose a multiple regression-variational auto-encoders(MR-VAE)model to realize precise and non-invasive prediction of intra-abdominal pressure(IAP)in critically ill patients.Methods At first,a dataset was constructed by retrospectively analysing baseline characteristics and clinical indicators of 100 critically ill patients admitted to the Intensive Care Unit of Daping Hospital of Army Medical University between 30 August 2019 and 30 March 2021.Then,a MR-VAE prediction model was developed by integrating a feedforward neural network for supervised regression onto a variational autoencoder(VAE)framework and incorporating multiple regression strategies to mitigate feature interference.Finally,the MR-VAE model had its performance evaluated by its comparison with five classical models including support vector machines(SVM),convolutional neural networks(CNN),Scikit-learn integrated model(SIM),multi-layer perceptron(MLP)and K-nearest neighbors(KNN),and its prediction accuracy verified by testing the data of 10 randomly selected patients.Results The MR-VAE model behaved the best when compared with the five classical models,with a mean squared error(MSE)of 0.207,a root mean square error(RMSE)of 0.454,a mean absolute error(MAE)of 0.361,a median absolute deviation(MAD)of 0.243,an explained variance score(EVS)of 0.814 and a R2of 0.823,which also outperformed the five models in fitting performance,convergence and final loss.In random sample testing,the MR-VAE model exhibited high consistency between predicted and actual values.Conclusion The MR-VAE model proposed can accurately predict IAP,which has great potential in reducing the repeated measurements of IAP in critically ill patients and providing new ideas for the early diagnosis and treatment of IAH.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.