BACKGROUND:One-hole split endoscope as a new type of endoscopic technique is suitable for the treatment of far lateral lumbar disc disease.However,there are few research data on L5/S1,which has a very low incidence of far lateral lumbar disc herniation at home and abroad,and there is no detailed image anatomical data describing the one-hole split endoscope treatment of L5/S1 far lateral lumbar disc herniation. OBJECTIVE:Through the three-dimensional image reconstruction,the bony landmarks were determined to accurately locate the positional relationship between the L5 outlet nerve root,the L5/S1 intervertebral space and other structures.One-hole split endoscope via posterolateral approach was used to accurately,safely and effectively decompress the L5 outlet nerve root and treat the L5/S1 far lateral lumbar disc herniation. METHODS:Twenty-nine patients with L5/S1 unilateral far lateral lumbar disc herniation who met the inclusion and exclusion criteria were selected,including 12 males and 17 females at the age of 48-74 years.The lumbar CT data of the patients were imported into Mimics 21.0 software to reconstruct the three-dimensional lumbar model.Measurement of L5/S1 related parameters:(1)Measurement on the sagittal plane at the intersection(H)of the lower edge of the transverse process and the lateral edge of the isthmus:The vertical distance between H and the upper and lower edges of L5 outlet nerve root(a1,a2);the vertical distance between H and the lower endplate of L5 and the upper endplate of S1(b1,b2);vertical distance from the lower edge of the pedicle from H to L5(c).(2)Horizontal distance between the left and right sides of the sagittal surface where the medial wall of the pedicle was located from H to L5(d).(3)The horizontal distance from H to the left and right side of the sagittal plane where the lateral margin of the dura was located(e).(4)Horizontal distance(f)between the left and right sides of the sagittal plane at the outermost edge of the lower endplate from H to L5.(5)Measurements were made on the sagittal plane where the outermost edge of the lower endplate of L5:The vertical distance between the cross section of H and the upper and lower edges of L5 outlet nerve root(g1,g2);vertical distance(h1,h2)between the transverse section of H and the lower endplate of L5 and the upper endplate of S1,respectively;(6)anteroposterior horizontal distance from H to L5 in the coronal plane where the last edge of the nerve root exits(i);(7)anteroposterior horizontal distance from the highest point of the posterior margin of the sacral wing to the last margin of the inferior endplate of L5 in the coronal plane(j). RESULTS AND CONCLUSION:(1)There was no significant difference in the relevant measurement parameters between men and women(P>0.05).(2)a1,a2,b1,b2,c,d,e,f,h1,h2,g1,g2,i,and j on the affected side were not significantly different from the healthy side(P>0.05).(3)There was no significant difference between a1 and c(P>0.05),indicating that the lower edge of the pedicle was the upper edge of the L5 outlet nerve root;the L5 outlet nerve root was close to the lower edge of the pedicle and ran anterolateral behind the L5 vertebral body,and H was located above the L5 outlet nerve root.(4)With H as the bony marker point,it was not necessary to probe upward or to remove the isthmus,but only to grind part of the bone downward and laterally to reveal the L5 outlet nerve root and vertebral space,and to have enough safe distance to avoid damage to the dural membrane to complete exploration and decompression of the lateral recess and foraminal region.(5)The surgeon could operate in the sagittal plane where the most lateral edge of the L5 inferior endplate was located,and in the"rectangular area"formed by the L5 transverse process and the sacral wing.The closer to the medial and inferior area(Kambin triangle),the safer the operation was.(6)It is suggested that using H as the bony landmark point to locate the L5 outlet nerve root and intervertebral space through one-hole split endoscope via posterolateral approach can achieve accurate,safe and effective decompression of L5/S1 far lateral lumbar disc herniation.

Drug repurposing offers a promising alternative to traditional drug development and significantly reduces costs and timelines by identifying new therapeutic uses for existing drugs. However, the current approaches often rely on limited data sources and simplistic hypotheses, which restrict their ability to capture the multi-faceted nature of biological systems. This study introduces adaptive multi-view learning (AMVL), a novel methodology that integrates chemical-induced transcriptional profiles (CTPs), knowledge graph (KG) embeddings, and large language model (LLM) representations, to enhance drug repurposing predictions. AMVL incorporates an innovative similarity matrix expansion strategy and leverages multi-view learning (MVL), matrix factorization, and ensemble optimization techniques to integrate heterogeneous multi-source data. Comprehensive evaluations on benchmark datasets (Fdataset, Cdataset, and Ydataset) and the large-scale iDrug dataset demonstrate that AMVL outperforms state-of-the-art (SOTA) methods, achieving superior accuracy in predicting drug-disease associations across multiple metrics. Literature-based validation further confirmed the model's predictive capabilities, with seven out of the top ten predictions corroborated by post-2011 evidence. To promote transparency and reproducibility, all data and codes used in this study were open-sourced, providing resources for processing CTPs, KG, and LLM-based similarity calculations, along with the complete AMVL algorithm and benchmarking procedures. By unifying diverse data modalities, AMVL offers a robust and scalable solution for accelerating drug discovery, fostering advancements in translational medicine and integrating multi-omics data. We aim to inspire further innovations in multi-source data integration and support the development of more precise and efficient strategies for advancing drug discovery and translational medicine.

Objective:To propose a model that could improve image quality of cone-beam computed tomography(CBCT),which based on region-discriminative generative adversarial networks(GAN),in radiotherapy for cervical cancer,so as to meet the requirements of self-adaptive radiotherapy for image quality.Methods:We employed a region-discriminative strategy and a generative adversarial networks idea to construct a model of improving CBCT image quality that could focus on local details of the images of radiotherapy for cervical cancer,which discriminator could improve the quality of generating local details of images.This model of image quality was applied to CBCT images of radiotherapy for cervical cancer.And then,the effects of processing image were evaluated through quantitative indicators and visualization.Results:Both texture clarity and contrast were significantly enhanced after CBCT image quality was improved.The signal to noise ratio of peak value of images was increased by 47.2%,and the indicator of similarity of structure was enhanced to>0.838.Compared with other model,both visualization and indicators can appear better efficiency of model.Compared with Unet network and CycleGAN network,the similarities of structure were respectively increased by 11.88% and 19.54%,and the signal to noise ratios were respectively increased by 19.75% and 25.99%.Conclusion:The GAN bases on region-discrimination can significantly improve the quality of generating integral and detailed CBCT image of radiotherapy for cervical cancer,which can provide new technical pathway for image quality of CBCT with low dose,and can play an important role for improving safety and effectiveness of radiotherapy.It has importantly clinical value for formulating and executing radiotherapy plan.

Objective:To develop a machine learning algorithm based on habitat imaging(HI),which can be used in the grading of gliomas by using multimodal magnetic resonance imaging(MRI),so as to construct the model of support vector machine(SVM)and the visualized heterogeneous regions of gliomas.Methods:A total of 335 glioma patients were collected from the 2019 brain tumor segmentation(BraTS)challenge competition of World Health Organization(WHO),which included 259 cases with high-grade gliomas(HGG)and 76 cases with low-grade gliomas(LGG).Subregions were divided based on HI technology.The PyRadiomics open-source package was used to extract the image features of region of interest(ROI),and to screen the features that stronger correlated with the high and low-grade gliomas.An SVM model was used to classify and predict the screened feature data.The heterogeneity of gliomas in images was analyzed through visualized characterization.The efficacy of glioma grading was assessed by using the area under curve(AUC)of the receiver operating characteristic(ROC)curve.Results:The AUC of test set exceeded 90%.The average accuracy of the performance indicators of test set was(92.74±2.88)%,and the average sensitivity was(93.90±2.10)%,and the average specificity was(90.36±4.59)%,and the average F1 score was(95.24±0.66)%when the tumors were divided into six habitat regions.The SVM model could showed important sub-regions in glioma grading in three-dimensional space.Conclusion:The study method based on HI has significant advantages in glioma grading,which can effectively realize visualized heterogeneity of tumor and construct model of the heterogeneity of tumor.

BACKGROUND:One-hole split endoscope technique has been widely used in the treatment of lumbar degenerative diseases,but there is no relevant literature on the safety analysis of this technique in the treatment of upper lumbar disc herniation. OBJECTIVE:To observe the position relationship of nerve roots,intervertebral space and bone landmarks in the upper lumbar spine by three-dimensional lumbar CT reconstruction technology,and to provide a basis for the clinical operation of one-hole split endoscope surgery. METHODS:Twenty-six patients with upper lumbar disc herniation underwent a lumbar CT scan.Mimics 17.0 software was imported to measure the related imaging parameters of L1/2 to L3/4 segments:(1)Measurement of vertical distance:In coronal view,the distance(a)from the intersection point of the medial facet of the superior articular process and the superior endplate(N)to the apex of the articular process(S);in the coronal view,the distance(b)from the sagittal intersection(M)of N and the inferior endplate to the apex of the inferior articular process(X).(2)Measured horizontal distance:the distance(c)between the cross-section of N and the lower edge of the outlet nerve root(N2);distance(d)between the cross-section of N and the intersection point of neural tissue(N1);N1 to N2 distance(e);distance(f)between the cross-section of M and the lateral edge of the nerve tissue(M1);M to M cross-section and exit nerve root intersection(M2)distance(g);distance(h)from M1 to M2;distance(i)from M2 to N1;distance(j)from the posterior edge of the articular surface(R)to M2 in sagittal view of the superior articular process. RESULTS AND CONCLUSION:(1)With the decrease of the segment,the distances a and b gradually increased,and the distance j gradually decreased.There was no significant difference between L1/2 and L2/3 segments(P>0.05).(2)With the decrease of the segment,distance d first decreased and then increased;distance f gradually decreased;distances c,e,g,h and i gradually increased;and there was no significant difference between L2/3 and L3/4 segments(P>0.05).(3)Distance i was the shortest distance without pulling nerve roots in the natural state,and the area of the safety zone was between four points M1,M2,N1,and N2.The bone was removed to the upper and lower endplates by biting the bone downward and upward through S and X,respectively,to expose the intervertebral space,and the window of distance g to M2 could be opened outward to avoid injury of the outlet nerve roots.(4)In conclusion,the upper lumbar vertebrae have unique anatomical characteristics.Based on the relevant measurements of nerve roots,spinal dura and intervertebral space,the parameters of the one-hole split endoscope technique are more accurate and safe during operation.

Objective To investigate the surgical method and clinical outcome using the free anterolateral thigh flap with the medial gastrocnemius artery as the recipient artery for the repair of complex wounds in the lower leg. Methods A retrospective analysis was conducted on the clinical data of 11 patients with complex wounds in the lower leg admitted to Suzhou Ruihua Orthopedic Hospital from October 2020 to September 2022. All patients had extensive skin and subcutaneous soft tissue defects in the lower leg and received free anterolateral thigh flap repair with the medial gastrocnemius artery as the recipient artery. The skin of donor site was directly sutured. Results All 11 free skin flap survived in 11 patients, and both the donor and recipient sites healed in stage I. All patients were followed up after discharge, with a follow-up time of 12 to 35 months. The follow-up results at 12 months postoperatively showed good wound healing, good flap appearance and elasticity, restoration of normal knee and ankle joint function, and independent living ability. The donor site wounds healed well without significant scar hyperplasia. At the last follow-up, the flap sensory function was graded as S₃ in 2 patients and S₂ in 9 patients. The functional score of the affected limb was excellent in 5 patients and good in 6 patients, with an excellent and good rate of 100%. Conclusion The medial gastrocnemius artery has a suitable vessel caliber for anastomosis and a constant location. The use of the free anterolateral thigh flap with this artery as the recipient artery for the repair of severe wounds in the lower leg can effectively cover soft tissue defects and avoid injuring the residual main vessels in the lower leg, resulting in satisfactory outcomes.

OBJECTIVE: To explore the role of the Notch signaling pathway in regulating neuronal differentiation and sensorimotor ability in a zebrafish model of fetal alcohol spectrum disorder. METHODS: Zebrafish embryos treated with DMSO or 50 μmol/L DAPT (a Notch signaling pathway inhibitor) were examined for mortality rate, hatching rate, malformation rate, and body length at 15 days post fertilization (dpf). The mRNA expression levels of sox2, neurogenin1 and huc in the treated zebrafish embryos were detected using in situ hybridization and qRT-PCR, and their behavioral responses to strong light and vibration stimulation were observed. The zebrafish embryos were then exposed to DMSO, 1.5% ethanol, DAPT, or both ethanol and DAPT, and the changes in mRNA expression levels of sox2, neurogenin1, huc, and the Notch signaling pathway genes as well as behavioral responses were evaluated. RESULTS: Exposure to 50 μmol/L DAPT significantly increased the mortality rate of 1 dpf zebrafish embryos (P < 0.01), decreased the hatching rate of 2 dpf embryos (P < 0.01), increased the malformation rate of 3 dpf embryos (P < 0.001), and reduced the body length of 15 dpf embryos (P < 0.05). DAPT treatment significantly downregulated sox2 mRNA expression (P < 0.01) and increased neurogenin1 (P < 0.05) and huc (P < 0.01) mRNA expressions in zebrafish embryos. The zebrafish with DAPT treatment exhibited significantly shortened movement distance (P < 0.001) and lowered movement speed (P < 0.05) in response to all the stimulation conditions. Compared with treatment with 1.5% ethanol alone, which obviously upregulated notch1a, her8a and NICD mRNA expressions in zebrafish embryos (P < 0.05), the combined treatment with ethanol and DAPT significantly increased neurogenin1 and huc mRNA expression, decreased sox2 mRNA expression (P < 0.01), and increased the moving distance and moving speed of zebrafish embryos in response to strong light stimulation (P < 0.05). CONCLUSION Ethanol exposure causes upregulation of the Notch signaling pathway and impairs neuronal differentiation and sensorimotor ability of zebrafish embryos, and these detrimental effects can be lessened by inhibiting the Notch signaling pathway.
Animals ; Zebrafish ; Amyloid Precursor Protein Secretases ; Dimethyl Sulfoxide ; Platelet Aggregation Inhibitors ; Antineoplastic Agents ; Ethanol/adverse effects* ; Signal Transduction

Objective:To investigate the predictive value of neutrophil/lymphocyte ratio (NLR) at admission for stroke associated pneumonia (SAP) in patients with acute ischemic stroke (AIS).Methods:Patients with AIS admitted to the First Affiliated Hospital of Kunming Medical University from January 2019 to June 2020 were retrospectively included. The demographic information, vascular risk factors, severity of stroke at admission, and NLR data of the patients were collected. Multivariate logistic regression was used to analyze the independent correlation between NLR and SAP. The NLR was divided into quartile groups to further analyze the trend relationship between NLR and SAP. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of NLR for SAP. Results:A total of 316 patients with AIS were enrolled, including 200 males (63.29%) with an age of 63.86±13.78 years. The median baseline Nationanl Institutes of Health Stroke Scale score was 4 (interquartile range, 2-9), and the median NLR was 4.42 (interquartile range, 3.17-6.70). Ninety-three patients (29.43%) experienced SAP. Multivariate logistic regression analysis showed that NLR was an independent risk factor for SAP in patients with AIS (odds ratio 1.189, 95% confidence interval 1.077-1.313; P<0.001). Moreover, SAP risk increases with the increase of NLR ( Ptrend<0.001). Compared to the first quartile, the risk of SAP increased 9.991 times in the fourth quartile (95% confidence interval 2.912-34.279; P<0.001). ROC curve analysis showed that the area under the curve of NLR for SAP prediction was 0.793 (95% confidence interval 0.737-0.850), with an optimal cutoff value of 5.475. The sensitivity and specificity for predicting SAP were 66.67% and 79.82%, respectively. Conclusion:NLR at admission is an independent risk factor for SAP in patients with AIS and has certain predictive value for SAP.

Objective: Due to the complicated compounds and the synergistic effect of multi-compounds, the quality control and assessment of Chinese materia medica (CMM) encounters a great challenge about how to identify the key compounds, which are directly correlated with its efficacy and safety. On the guidance of study on quality marker (Q-Marker), identification of Q-Markers was performed from Hedan Tablet (HDT) by the aid of the “spider-web” mode and hepatotoxicity evaluation derived from our previous researches and literatures. Methods: By the established ultra performance liquid chromatography with photodiode array detector (UPLC-PDA) method, online UPLC-DPPH· and offline antioxidant assay, 21 candidate compounds of HDT were systematically investigated and comprehensively evaluated by the “spider-web” mode for them properties of Q-Marker based on “content-stability-activity”. In addition, the Q-Markers related with hepatotoxicity based on our previous researches and literatures were identified. Results: Salvianolic acid B (SaB), quercetin-3-O-glucuronide (Qug), isoquercitrin (IQ) and hyperoside (Hyp) were adopted as the preferable Q-Markers of HDT according to the shaded area (A) of tested compounds in “spider-web” mode. Psoralen (Ps), isopsoralen (IP), psoralenoside (PO) and isopsoralenoside (IPO) were also strongly recommended as Q-Markers closely related with safety by considering hepatotoxicity of the accumulated Ps and IP and conversion between glycoside (PO and IPO) and aglycone (Ps and IP). Conclusion: This study provided scientific evidence for quality control and assessment of HDT, and also provided a meaningful reference for application of Q-Markers in CMM.

Anti-virulence strategy has been considered as one of the most promising approaches to combat drug-resistant bacterial infections. Pore-forming toxins (PFTs) are the largest class of bacterial toxins, inflicting their virulence effect through creating pores on the cell membrane. However, current solutions for eliminating PFTs are mostly designed based on their molecular structure, requiring customized design for different interactions. In the present study, we employed erythroliposome (denoted as RM-PL), a biomimetic platform constructed by artificial lipid membranes and natural erythrocyte membranes, to neutralize different hemolytic PFTs regardless of their molecular structure. When tested with model PFTs, including α-hemolysin, listeriolysin O, and streptolysin O, RM-PL could completely inhibit toxin-induced hemolysis in a concentration-dependent manner. In vivo studies further confirmed that RM-PL could efficiently neutralize various toxins and save animals' lives without causing damage to organs or tissues. In addition, we explored the underlying mechanisms of this efficient detoxification ability and found that it was mainly macrophages in the spleen and the liver that took up RM-PL-absorbed toxins through a variety of endocytosis pathways and digested them in lysosomes. In summary, the biomimetic RM-PL presented a promising system for broad-spectrum and powerful toxin neutralization with a mechanism of lysosome-mediated toxin degradation.