BACKGROUND:With the innovation of examination technique,the number of patients with spinal metastases in different stages is increasing year by year.Percutaneous vertebroplasty is an important treatment for spinal metastases;however,there is no report on the biomechanical effect in different stages and different activities after operation. OBJECTIVE:To simulate thoracic T10 bone stress and displacement of the different locations of the tumor metastasis based on the three-dimensional finite element model. METHODS:According to thoracic three-dimensional CT images of a 30-year-old healthy male,Mimics software was used to construct a three-dimensional geometric model of thoracic vertebrae(T9-T11),including ribs,ligaments and intervertebral discs.Three-dimensional models of T9-T11 vertebral bodies and different parts of the posterior thoracic vertebrae invaded by thoracic metastatic tumors were simulated,including the control group with intact vertebral structure,unilateral metastasis involving the vertebral body area(experimental group 1),unilateral metastasis involving the vertebral body and pedicle area(experimental group 2),unilateral metastasis involving the vertebral body,pedicle and transverse process area(experimental group 3),and bilateral metastasis involving the vertebral body,pedicle and transverse process area(experimental group 4).Abaqus software was used to create a three-dimensional finite element model.The von Mises stress distribution and the displacement of the model were analyzed under the loading condition,buckling condition,extension condition,and rotation condition. RESULTS AND CONCLUSION:(1)In the study of the maximum total displacement of loading points in different experimental groups under loading,flexion,extension,and rotation conditions,with the increase of metastatic tumor invasion site and invasion surface,the total displacement of loading points increased,and the overall stiffness decreased,especially the total displacement of loading points in experimental group 4 was the largest.(2)Under flexion condition,the maximum Von Mises stress value increased significantly after vertebral body and pedicle destruction,while the maximum Von Mises stress value was almost unchanged when the thoracocostal joint destruction was added.(3)On the basis of finite element analysis and simulation of bone tumor model,the elements in the bone cement region were set as a single set,and the bone cement region was set as the corresponding material properties to simulate bone cement filling.The results showed that the maximum total displacement under loading,flexion,extension,and rotation conditions was less than that of each experimental group.(4)The maximum stress values of the simulated percutaneous vertebroplasty patients in the loading,flexion,extension and rotation conditions were significantly lower than those of the femoral model.(5)It is concluded that the three-dimensional finite element model based on thoracic T9-T11 conducive to the biomechanics characteristics of thoracic vertebrae tumor metastasis,and on the basis of the thoracic vertebrae tumor metastasis model can accurately simulate load point after percutaneous vertebral body under different conditions of total displacement and the maximum Von Mises stress situation.

ObjectiveTo study the effect of Tanreqing injection （TRQ） on the pulmonary flora in the rat model of chronic obstructive pulmonary disease （COPD）. MethodWistar rats were randomized into control， model， and TRQ groups. The rats in other groups except the control group were treated by smoking combined with intratracheal instillation of lipopolysaccharide for the modeling of COPD. The TRQ group was intraperitoneally injected with TRQ （2 g·kg^-1）. At the end of the experiment， after blood collection from the abdominal aorta of the rats， the lung tissue was collected for hematoxylin-eosin and picric sirius red staining to reveal the pathological changes. The lung lavage fluid was collected， and the diversity and relative abundance of lung flora in different groups were analyzed by 16S rDNA amplicon sequencing. ResultThe lungs of the control group were normal， and those of the model group showed neutrophil infiltration， telangiectasia， lung hemorrhage and emphysema in individual cases， and thickening of collagen fibers in the trachea. Compared with the model group， the TRQ group showed significantly improved lungs and recovered collagen fibers. The MLI analysis showed that compared with the control group， the model group showcased increased alveolar space （P<0.01）， which was reduced in the TRQ group （P<0.05）. Compared with the control group， the model group showed increased wall thickness （P<0.01）， and the increase was attenuated in the TRQ group （P<0.01）. TRQ increased the Simpson index and altered the α diversity of pulmonary flora. The results of principal co-ordinate analysis showed that TRQ changed the β diversity and reduced the β diversity index of pulmonary flora. At the genus level， the model group showed increased relative abundance of g_Bacillus and g_Brevundimonas and decreased relative abundance of g_Pseudomonas， compared with the control group. After treatment with TRQ， the relative abundance of g_Stenotrophomonas increased， and that of g_Bacillus decreased. The LEfSe of differential taxa between groups showed that the modeling increased the relative abundance of g_Lachnospiraceae_NK4A136_group， and TRQ treatment increased the relative abundance of g_Rhodococcus and g_Stenotrophomonas. ConclusionTRQ can regulate the diversity of pulmonary flora and restore the balance of bacterial genera in the rat model of COPD， which may be one of the mechanisms of the prevention and treatment of COPD with TRQ.

Objective:To explore the effectiveness of 18F-deuterated-Florbetapir (D3FSP) PET/CT imaging in detecting β-amyloid (Aβ) deposition in the brain and its correlation with plasma biomarkers. Methods:A retrospective analysis was conducted on 79 patients (32 males, 47 females; age(66±7)years) who underwent 18F-D3FSP PET/CT imaging from June 2022 to November 2023 at the First Affiliated Hospital, Guangzhou Medical University, as a part of the Greater Bay Area Healthy Aging Brain Longitudinal Cohort Study (GHABS). Based on the Alzheimer′s Disease Neuroimaging Initiative cohort standard protocol, patients were categorized into cognitively unimpaired (CU) group, mild cognitive impairment (MCI) group, and Alzheimer′s disease (AD) group. Brain regions were segmented using the AW workstation and the SUV ratio (SUVR) was calculated with the cerebellum as the reference region. One-way analysis of variance, Bonferroni correction and Pearson correlation analysis were used to analyze data. The ROC curve analysis was used to analyze the cut-off value and the diagnostic efficacy of SUVR. Results:There were 48, 15 and 16 cases in CU, MCI and AD groups respectively. During the transition from CU to MCI and then to AD, there was a rising trend in SUVR ( F values: 11.15-22.38, all P<0.001) across the whole brain and various brain regions (bilateral frontal lobes, bilateral anterior cingulate gyrus, bilateral precuneus, bilateral parietal lobes, bilateral lateral temporal lobes, and bilateral occipital lobes). SUVRs of the right anterior cingulate gyrus and bilateral precuneus were different between the CU and MCI groups (all P<0.017), and those of bilateral frontal lobes, right precuneus, bilateral parietal lobes, bilateral lateral temporal lobes, and bilateral occipital lobes were different between the MCI and AD groups (all P<0.017). SUVRs of brain regions were negatively correlated with cognitive scale scores ( r values: from -0.57 to -0.37, all P<0.001), and were positively correlated with plasma phosphorylated tau181 (p-tau181, r values: 0.50-0.61, all P<0.001). The ROC curve analysis suggested that the cut-off value of SUVR in the precuneus for distinguishing CU from AD was 1.20, with the AUC, sensitivity, specificity and accuracy of 0.85, 12/16, 91.7%(44/48)and 87.5%(56/64), respectively. Conclusion:18F-D3FSP PET/CT imaging has good clinical application value in assessing the deposition sites and the extent of Aβ in the brain, which is related to clinical cognition and plasma p-tau181 level.

Objective:To investigate the effects of Guiling Gao on body temperature, gastrointestinal motility, gastrointestinal hormones, Th1/Th2 cytokines and water metabolism in rats with damp-heat syndrome.Methods:Totally 60 SD rats were randomly divided into control group, model group, mosapride group, Guiling Gao low dose group (3.4 g/kg), medium dose group (6.8 g/kg) and high dose group (13.6 g/kg) according to random number table method, with 10 rats in each group. Except for the blank group, the other groups adopted the method of "environmental factors + fat and sweet diet + biological factors" to prepare the rat model of damp heat syndrome of febrile diseases. After modeling, they were administered by gavage for 7 days. During the experiment, the general state, body weight and body temperature were observed, the gastric residue rate of rats was calculated by weighing method, the intestinal propulsion rate of rats was calculated by charcoal propulsion method, and the levels of serum motilin (MTL), gastrin (GAS), somatostatin (SS), substance P (SP),IL-4 and interferon-γ (IFN-γ) were detected by ELISA, and the changes of aquaporin 3 (AQP3) mRNA transcription level were detected by real-time PCR.Results:Compared with the model group, the weight of rats in Guiling Gao high dose group increased after experiment of 22 days ( P<0.05), and body temperature of rats in Guiling Gao medium and high dose group decreased in 19-20 day ( P<0.01); and the gastric emptying rate and the small intestine propulsion rate of small intestine in Guiling Gao medium and high dose group increased significantly ( P<0.01 or P<0.05); the serum MTL, GAS and SP levels increased ( P<0.01 or P<0.05), and SS decreased ( P<0.01 or P<0.05) in the Guiling Gao medium and high dose groups; The levels of IL-4, IFN-γ and IFN-γ/IL-4 ratio decreased ( P<0.01); The expression of AQP3 mRNA (1.16 ± 0.25 vs. 0.23 ± 0.01) in the Guiling Gao high dose group was up-regulated ( P<0.01). Conclusions:Guiling Gao can effectively improve the activity state of damp-heat syndrome model rats caused by complex factors. This mechanism may be related to enhancing gastrointestinal movement, increasing gastrointestinal hormone secretion, restoring the dynamic balance of immune system Th1/Th2 and promoting the transport of water from intestinal cavity.

ObjectiveTo investigate the detoxification mechanism of Chebulae Fructus， Glycyrrhizae Radix et Rhizoma and Prepared Aconiti Kusnezoffii Radix Cocta， and their effective components ellagic acid， liquiritin and aconitine based on cardiac cytochrome P450 （CYP450） system. MethodIn in vivo experiments， rats were randomly divided into control group， prepared Aconiti Kusnezoffii Radix Cocta group （0.25 g·kg^-1）， Chebulae Fructus group （0.252 g·kg^-1）， Glycyrrhizae Radix et Rhizoma group （0.25 g·kg^-1） and combination group （0.25 g·kg^-1 Chebulae Fructus+0.25 g·kg^-1 Glycyrrhizae Radix et Rhizoma+0.25 g·kg^-1 prepared Aconiti Kusnezoffii Radix Cocta， with prepared Aconiti Kusnezoffii Radix Cocta as standard）. After 8 days of administration， creatine kinase （CK） and lactate dehydrogenase （LDH） in rats were detected to observe the pathological changes of heart tissue. Real-time PCR and Western blot were performed to detect the mRNA and protein expressions of CYP2J3， respectively. In in vitro experiments， control group， aconitine group， ellagic acid group， liquiritin group and combination group （aconitine+ellagic acid+liquiritin） were set， and their effects on cell number， DNA content， reactive oxygen species （ROS） and mitochondrial membrane potential （MMP） were detected by high content analysis. The changes in the mRNA and protein expressions of CYP2J3 were also observed. ResultIn vivo experiments， compared with the control group， the prepared Aconiti Kusnezoffii Radix Cocta group had increased CK and LDH in serum （P<0.05， P<0.01）， while the combination group had decreased activities of CK and LDH. Additionally， pathological staining results showed that Chebulae Fructus and Glycyrrhizae Radix et Rhizoma reduced the cardiac toxicity caused by prepared Aconiti Kusnezoffii Radix Cocta. Real-time PCR found that compared with the control group， prepared Aconiti Kusnezoffii Radix Cocta down-regulated the mRNA level of CYP2J3 （P<0.05）， while up-regulated that expression when used in combination with Chebulae Fructus and Glycyrrhizae Radix et Rhizoma （P<0.01）. The protein and mRNA translation levels were basically consistent. In vitro experiments， high content analysis revealed that there was a decrease in the cell number， DNA content and MMP fluorescence value of the aconitine group （P<0.01） and the combination group （P<0.05， P<0.01）， and the fluorescence value of the combination group was higher than that of the aconitine group. Moreover， aconitine down-regulated the mRNA level of CYP2J3 （P<0.05）， but the down-regulating ability of aconitine was reversed in the combination group （P<0.05）. ConclusionThe detoxification mechanism of combined Chebulae Fructus， Glycyrrhizae Radix et Rhizoma and prepared Aconiti Kusnezoffii Radix Cocta is mainly that the combination of ellagic acid， liquiritin and aconitine can up-regulate the expression of CYP2J3， and promote the metabolism of arachidonic acid （AA） to produce epoxyeicosatrienoic acids （EETs）， thus reducing the cardiac toxicity， and this effect may start from the transcriptional link.

Objective To investigate the repairing effect of ursolic acid extracted from Hippophae rhamnoi-des L.on sciatic nerve injury in rats.Methods After preparing a sciatic nerve damage model,thirty 2-month old Wistar rats were randomly divided into ursolic acid and control groups,with 15 rats in each group.Ursolic acid group was given Ursolic acid 150 mg/(kg·d)by gavage,while the control group was given the same dose of normal saline for 6 weeks.After 6 weeks,H&E staining was used to observe the pathological changes of rat sciatic nerves,and SFI and MNCV were calculated;The expression of NGF in sciatic nerve was detected by immunohistochemistry,and the expression of GAP-43 in L4-L6 spinal cord was detected by Western blotting.Results After 6 weeks,compared to the control group,the number of regenerated nerve fibers in the ursolic acid group increased,the arrangement was slightly regular,the capillary structure was abundant,and the proliferation of fibroblasts decreased;SFI and MNCV%were significantly increased(P<0.05),NGF protein positive expression was significantly increased(P<0.05),and the difference was statistically significant(P<0.05).GAP-43 protein expression in sciatic nerve tissue was significantly increased(P<0.05).Conclusions The intervention of ursolic acid extracted from Hippophae rhamnoides L.can improve the function of rats after sciatic nerve injury,promote the increase of regenerated nerve fibers and the repair of myelin sheath in rats with sciatic nerve injury,which may be related to increased NGF and GAP-43 protein expression in rats.

Objective    To summarize the clinical experience of surgical resection of synchronous multiple ground-glass nodules (SMGN), and explore the individualized diagnosis and treatment strategy of SMGN. Methods    Clinical data of 84 patients with SMGN who underwent thoracic surgery in Anhui Chest Hospital from July 2016 to August 2018 were analyzed retrospectively, including 18 males (21.4%) and 66 females (78.6%), aged 32-80 (55.6±10.3) years. The results of operation and the information of GGNs were analyzed. Results    Except for 1 patient who was converted to thoracotomy due to extensive dense adhesion of thoracic, other patients underwent video-assisted thoracoscopic surgery successfully. All patients recuperated successfully after operation, without severe perioperative complications or death. Finally, 79 patients were diagnosed as malignant tumors (94.0%), and 5 patients of benign lesions (6.0%). A total of 240 GGNs were removed, among which there were 168 pGGNs, including 68 benign lesions (40.5%) and 100 malignant tumors (59.5%), and 72 mGGNs, including 2 benign nodules (2.8%) and 70 malignant tumors (97.2%). Nodules diameter (P<0.001), consolidation/maximum diameter of nodule ratio (P<0.001), vacuole sign (P<0.001), air bronchograms sign (P=0.001), spine-like process (P=0.001), pleural indentation sign (P<0.001), lobulation sign (P<0.001), and vascular convergence (P=0.002) were correlated with malignant tumor. Conclusion    Analysis of the imaging features of GGNs by thin-section CT scan and three-dimensional reconstruction is of great value in predicting the benign and malignant nodules, which can guide the surgical decision-making and preoperative planning. Through reasonable preoperative planning and following certain principles, simultaneous surgical treatment for SMGN is safe and feasible.

Objective: To retrospectively analyze the diagnosis time, pathogen distribution, and drug resistance of fungal bloodstream infection in severe burn patients. Methods: Blood samples were collected from 55 severe burn patients with fungal bloodstream infection (including 46 males and 9 females, aged 42 (1, 78) years) admitted to the intensive care unit of the Institute of Burn Research of the First Affiliated Hospital of Army Medical University (the Third Military Medical University) from July 2011 to May 2019 for retrospective analysis. Microbial monitoring system was used to cultivate pathogens, API yeast identification kit and Candida chromogenic medium were used to identify pathogens, and Kirby-Bauer paper disk diffusion method was used to detect drug resistance of fungi to fluconazole, amphotericin B, itraconazole, ketoconazole, and voriconazole. The positive rate of blood fungal culture, mortality rate, distribution of local fungal proliferation sites, the diagnosis time distribution of fungal bloodstream infection, the distribution of fungal species, resistance to commonly-used antifungal drugs, and the use of antibiotics were assessed. The WHONET 5.6 software was applied to analyze the distribution and drug resistance of fungi. Results: (1) Totally 4 839 blood samples were collected during the 9 years, and 122 strains of fungi were isolated, with positive rate of 2.52%. The mortality rate was 14.55% (8 patients) in 55 patients. Catheter fungal proliferation ranked the first among 30 cases of local fungal proliferation. (2) The diagnosis time of fungal bloodstream infection mainly distributed in ≤1 week of hospitalization [32.73% (18/55)]. (3) Among the 55 strains of fungi detected, the detection rate of Candida parapsilosis ranked the first (21.82%, 12 strains), Candida glabrata was the second (18.18%, 10 strains), and Candida tropicalis was tied with Candida albicans in the third place (14.55%, 8 strains). All the detected fungi were sensitive to amphotericin B, and the resistance rates to voriconazole, fluconazole, itraconazole, and ketoconazole were between 4.5% and 9.1%. (4) Droad-spectrum antibiotics were used in all the 55 patients, ≥3 kinds of antibiotics were used in 44 patients, and 37 patients used antibacterial drugs ≥7 days. Conclusions The diagnosis time of fungal bloodstream infection in the 55 severe burn patients was mainly within 1 week of hospitalization. Candida parapsilosis is the most commonly detected fungal species. Catheter fungal proliferation occurs most commonly among the 30 patients with local fungal proliferation. All the detected fungi were sensitive to amphotericin B, with low drug resistance to voriconazole, fluconazole, itraconazole, and ketoconazole. Broad-spectrum antibiotics were overused in the severe burn patients with fungal bloodstream infection.

Objective:To investigate the value of tumor hemodynamics and morphological features from conventional dynamic contrast-enhanced MRI (DCE-MRI) scan before surgery in predicting postoperative recurrence time in breast cancer patients.Methods:A retrospective analysis of 58 patients with breast cancer who had recurred after operation from November 2012 to December 2014 in Liaoning Cancer Hospital was performed. According to the recurrence time, the patients were divided into early recurrence group (≤2 years after surgery, 33 cases) and late recurrence group (>2 years after surgery, 25 cases). All patients underwent routine DCE-MRI scans before surgery, and hemodynamic features of the three-dimensional volume of the tumor and the morphological and textural features of the tumor in each phase were extracted by computer. The counts and measurement data of patients in early recurrence group and late recurrence group were compared by Fisher′s exact probability method and Mann-Whitney U test, and receiver operating characteristic (ROC) curves were drawn. The multivariate logistic regression was used to calculate the combined efficacy in predicting early recurrence and late recurrence. Kaplan-Meier method was used to analyze the survival prognosis, and Log-Rank test was used to compare the differences in survival curves between groups. Results:There was no significant difference in background parenchymal enhancement, lesion margin, lesion internal enhancement characteristics, lesion morphology, time-signal intensity curve type and the degree of whole-breast vascularity increase between early recurrence and late recurrence groups ( P>0.05).There were significant differences in the maximum concentration of contrast (Max Conc), the area under the time signal curve (AUC) and the maximum slope value of the time signal curve (Max Slope) ( P<0.05). Comparative analysis of the radiomics parameters of 8 phases DCE-MRI found that the sphericity of morphological characteristic parameters in the phase 3 was statistically different between the early recurrence and late recurrence groups ( P=0.03). Area under the ROC curve of AUC, Max Conc, Max Slope and parameter sphericity of phase 3 morphological characteristics for predicting early and late recurrence were 0.664, 0.659, 0.684 and 0.670, respectively. The area under the ROC combined with the above four parameters for prediction was 0.765, with a specificity of 63.6% and a sensitivity of 84.0%; the predictive efficacy was higher than that of univariate. Fifty-eight patients were followed up for 17 to 64 months with a median follow-up of 47 months. The disease-free survival and overall survival in the early recurrence group were significantly lower than those in the late recurrence group, and the difference was statistically significant ( P<0.05). Conclusion:It is of certain value to predict the postoperative recurrence time of breast cancer based on the tumor hemodynamic characteristics combined with morphological characteristics from preoperative non-invasive conventional DCE-MRI.

BRAF is a serine/threonine kinase that harbors activating mutations in ∼7% of human malignancies and ∼60% of melanomas. Despite initial clinical responses to BRAF inhibitors, patients frequently develop drug resistance. To identify candidate therapeutic targets for BRAF inhibitor resistant melanoma, we conduct CRISPR screens in melanoma cells harboring an activating BRAF mutation that had also acquired resistance to BRAF inhibitors. To investigate the mechanisms and pathways enabling resistance to BRAF inhibitors in melanomas, we integrate expression, ATAC-seq, and CRISPR screen data. We identify the JUN family transcription factors and the ETS family transcription factor ETV5 as key regulators of CDK6, which together enable resistance to BRAF inhibitors in melanoma cells. Our findings reveal genes contributing to resistance to a selective BRAF inhibitor PLX4720, providing new insights into gene regulation in BRAF inhibitor resistant melanoma cells.