OBJECTIVE To study the efficacy of Tianjiang xueshuantong pills in the treatment of coronary heart disease. METHODS In accordance with the common pathogenesis of coronary heart disease， acute myocardial ischemia model， hyperlipidemia model， blood stasis model， and carotid artery thrombosis model were established using Wistar rats or SD rats as the experimental subjects. The effects of Tianjiang xueshuantong pills administered at high， medium， and low doses （0.6， 1.2 and 2.4 g/kg） on hemodynamic parameters and myocardial enzyme markers [lactate dehydrogenase （LDH）， creatine kinase-MB （CK- MB）]， oxidative stress factors [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione （GSH）]， inflammatory cytokines [tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， IL-1β， monocyte chemotactic protein-1 （MCP-1）， intercellular adhesion molecule-1 （ICAM-1）]， myocardial infarction percentage， serum lipid indexes [total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）]， platelet aggregation function 话：022-84845240。E-mail：jiangx@tjipr.com [maximum aggregation rate （MAR）]， and thrombus formation indexes [thrombosis time， thrombus mass， thrombus protein content， plasminogen activator inhibitor-1 （PAI-1）， and tissue-type plasminogen activator （t-PA）] were evaluated in the rat models. RESULTS In myocardial ischemia tests， Tianjiang xueshuantong pills significantly reduced the percentage of myocardial infarction and the levels of CK-MB， LDH， MDA， GSH， IL-6， TNF-α， IL- 1β， and MCP-1 in serum （P＜0.05 or P＜0.01）. In hyperlipidemia tests， high dose of Tianjiang xueshuantong pills significantly reduced the serum levels of TC， LDL and significantly increased the level of HDL in rats after 2 weeks and 4 weeks of administration. In blood stasis tests， different doses of Tianjiang xueshuantong pills significantly reduced MAR of rats （P＜0.01）. In artery thrombosis tests， high dose of Tianjiang xueshuantong pills significantly prolonged the time of thrombosis formation （P＜ 0.01）， significantly reduced the weight and protein content of thrombus and the level of PAI-1 in serum （P＜0.01）. CONCLUSIONS Tianjiang xueshuantong pills exert therapeutic effects on coronary heart disease through multi-dimensional synergistic actions， including anti-myocardial ischemia， lipid-lowering， and anti-thrombotic effects.

Objective:To evaluate the value of prostate specific membrane antigen (PSMA) PET/CT-based radiomics models in differentiation between prostate cancer and benign prostatic hyperplasia (BPH).Methods:Data from 50 patients with prostate cancer (age: (70.0±8.8) years) and 25 patients with BPH (age: (66.9±9.4) years) who underwent 18F-PSMA-1007 PET/CT imaging and prostate biopsy in the First Affiliated Hospital of Xi′an Jiaotong University from May 2020 to September 2022 were retrospectively collected. Patients were divided into the training set ( n=53) and test set ( n=22) in the ratio of 7∶3 by using random seed number. The ROIs were delineated based on PET and CT images, and radiomics features were extracted respectively. Feature selection was performed using the minimum redundancy and maximum relevance (mRMR) and the least absolute shrinkage and selection operator (LASSO) algorithm. PET and PET/CT radiomics models were generated using logistic regression. ROC curve analysis was employed for model evaluation. In addition, comparisons of the 2 radiomics models with parameters including the ratio of free prostate specific antigen (fPSA)/total prostate specific antigen (tPSA), PET metabolic parameters, as well as prostate cancer molecular imaging standardize evaluation (PROMISE) were conducted (Delong test). Results:A total of 7 features were included in the PET radiomics model, and 3 CT-based features and 4 PET-based features were included in the PET/CT radiomics model. The AUCs of PET and PET/CT radiomics models in the training set and test set were 0.941, 0.914 and 0.965, 0.914, respectively, which were higher than those of fPSA/tPSA (0.719 and 0.710), SUV max(0.748 and 0.800), peak of SUV (SUV peak, 0.722 and 0.771), metabolic tumor volume (MTV, 0.640 and 0.595), total lesion uptake (TLU, 0.525 and 0.476) and PROMISE (0.644 and 0.667)[ z values for the training set: from -6.26 to -3.13, all P<0.01; z values for the test set: from -3.16 to -1.08, P>0.05 (fPSA/tPSA, SUV max, SUV peak) or P<0.05 (MTV, TLU, PROMISE)]. The differential diagnostic accuracy, sensitivity and specificity of PET and PET/CT radiomics models in the test set were 86.36%(19/22), 13/15, 6/7 and 90.91%(20/22), 15/15, 5/7, respectively. Conclusion:Compared with the clinical and PET parameters, PSMA PET/CT-based radiomics model can further improve the efficiency of differential diagnosis between prostate cancer and BPH.

【Objective】 To explore the application value of ¹⁸F-PSMA PET/CT on the detection of metastatic lesions of prostate cancer with serum total prostate specific antigen (tPSA) ≤20 ng/mL and the predictive variables affecting the imaging results, and to establish a predictive nomogram for the metastasis of prostate cancer. 【Methods】 The imaging, pathological, serum and clinical data of 175 pathologically confirmed prostate cancer patients who underwent ¹⁸F-PSMA PET/CT examination during Jan.2020 and Oct.2021 were retrospectively collected.The patients were divided into metastatic group and non-metastatic group according to PET/CT imaging results, and the positive detection rate of metastatic lesions was calculated.The independent influencing factors of ¹⁸F-PSMA PET/CT in the positive detection of metastatic lesions were determined with univariate and multivariate logistic regression analyses.The predictive nomogram was established. 【Results】 Of the 175 patients, metastatic lesions were detected in 78 cases and not detected in 97 cases, with a detection rate of 44.6% (78/175).There were statistically significant differences between the metastatic group and the non-metastatic group in urinary tract symptoms, androgen deprivation treatment (ADT) at the time of PET/CT examination and the risk level of Gleason score (GS) (P<0.05).Univariate logistic regression showed that urinary tract symptoms(OR=3.64, P<0.001), GS risk (OR=3.96, P<0.001) and concurrent ADT treatment (OR=3.71, P<0.001) were associated with the positive detection rate of metastatic lesions.Multivariate Logistic regression showed that urinary tract symptoms (OR=3.19, P=0.002), GS high-risk group (OR=2.95, P=0.005) and concurrent ADT treatment (OR=3.27, P=0.001) were independent predictors of positive detection rate. 【Conclusion】 The probability of metastasis in newly diagnosed prostate cancer patients with tPSA≤20 ng/mL is high.¹⁸F-PSMA PET/CT is of high value for the early detection of metastasis.Urinary tract symptoms, GS high-risk group and concurrent ADT treatment are independent predictors of metastatic lesions.The predictive nomogram can help assist clinical optimization of imaging examination path.

Objective:To evaluate the diagnostic value of the 18F-prostate specific membrane antigen (PSMA)-1007 PET/CT in seminal vesicle invasion (SVI) of prostate cancer. Methods:Clinical and pathological materials of 88 patients (age: 51-84 years) who underwent radical prostatectomy (RP) between May 2019 and December 2021 in the First Affiliated Hospital of Xi′an Jiaotong University were analyzed retrospectively. All patients underwent 18F-PSMA-1007 PET/CT examination for primary staging before surgery. The diagnostic efficiency of 18F-PSMA-1007 PET/CT in SVI was obtained using postoperative pathological results as the " gold standard" and ROC curve was drawn. Furthermore, univariate and multivariate logistic regression analyses were used to screen the influencing factors for 18F-PSMA-1007 PET/CT prediction of SVI. Results:The accuracy, sensitivity, specificity, positive predictive value and negative predictive value of 18F-PSMA-1007 PET/CT in diagnosing SVI were 79.55%(70/88), 72.73%(16/22), 81.82%(54/66), 57.14%(16/28) and 90.00%(54/60), respectively. The ROC AUC was 0.77. Results of univariate logistic regression showed that total prostate specific antigen (tPSA), primary SUV max, Gleason score, International Society of Urological Pathology (ISUP) grade group were associated with 18F-PSMA-1007 PET/CT prediction of SVI. Results of multivariate logistic regression showed that Gleason score (odds ratio ( OR)=2.04, 95% CI: 1.19-3.50, P=0.009) was a predictor of SVI in prostate cancer. Conclusion:18F-PSMA-1007 PET/CT has certain diagnostic value in SVI of prostate cancer, and combining with Gleason score can improve the diagnostic efficiency.

Pulmonary fibrosis (PF) is the pathological structure of incurable fibroproliferative lung diseases that are attributed to the repeated lung injury-caused failure of lung alveolar regeneration (LAR). Here, we report that repetitive lung damage results in a progressive accumulation of the transcriptional repressor SLUG in alveolar epithelial type II cells (AEC2s). The abnormal increased SLUG inhibits AEC2s from self-renewal and differentiation into alveolar epithelial type I cells (AEC1s). We found that the elevated SLUG represses the expression of the phosphate transporter SLC34A2 in AEC2s, which reduces intracellular phosphate and represses the phosphorylation of JNK and P38 MAPK, two critical kinases supporting LAR, leading to LAR failure. TRIB3, a stress sensor, interacts with the E3 ligase MDM2 to suppress SLUG degradation in AEC2s by impeding MDM2-catalyzed SLUG ubiquitination. Targeting SLUG degradation by disturbing the TRIB3/MDM2 interaction using a new synthetic staple peptide restores LAR capacity and exhibits potent therapeutic efficacy against experimental PF. Our study reveals a mechanism of the TRIB3-MDM2-SLUG-SLC34A2 axis causing the LAR failure in PF, which confers a potential strategy for treating patients with fibroproliferative lung diseases.

The cell cycle inhibitor P21 has been implicated in cell senescence and plays an important role in the injury-repair process following lung injury. Pulmonary fibrosis (PF) is a fibrotic lung disorder characterized by cell senescence in lung alveolar epithelial cells. In this study, we report that P21 expression was increased in alveolar epithelial type 2 cells (AEC2s) in a time-dependent manner following multiple bleomycin-induced PF. Repeated injury of AEC2s resulted in telomere shortening and triggered P21-dependent cell senescence. AEC2s with elevated expression of P21 lost their self-renewal and differentiation abilities. In particular, elevated P21 not only induced cell cycle arrest in AEC2s but also bound to P300 and β-catenin and inhibited AEC2 differentiation by disturbing the P300-β-catenin interaction. Meanwhile, senescent AEC2s triggered myofibroblast activation by releasing profibrotic cytokines. Knockdown of P21 restored AEC2-mediated lung alveolar regeneration in mice with chronic PF. The results of our study reveal a mechanism of P21-mediated lung regeneration failure during PF development, which suggests a potential strategy for the treatment of fibrotic lung diseases.

Objective:To investigate the effect of teriparatide on residual back pain (RBP) after percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fracture (OVCF).Methods:A retrospective cohort study was used to analyze the clinical data of 90 OVCF patients sustaining RBP after PKP admitted to Second Affiliated Hospital of Kunming Medical University from September 2015 to March 2019, including 18 males and 72 females, at age of 57-85 years［(68.0±5.9) years］. Teriparatide treatment was applied regularly in 32 patients (teriparatide group) and antiosteoporosis drug was administered routinely in 58 patients (routine treatment group). Visual analogue scale (VAS) and Oswestry disability index (ODI) were compared between the two groups before operation, at 24 hours, 1 month, 3 months, 6 months and 12 months after operation. Anterior vertebral body height (ABH), middle vertebral body height (MBH), kyphosis angle (KA), maintenance rate of anterior vertebral body height (MRABH), maintenance rate of middle vertebral body height (MRMBH) and difference of kyphosis angle (DKA) were measured at 24 hours and 12 months after operation to evaluate the maintenance of vertebral height and incidence of vertebral refracture. Levels of type I collagen carboxy-terminal peptide (β-CTX) and serum N-terminal osteocalcin (N-MID) were measured before operation and at 12 months after operation to evaluate the improvement of bone metabolism. The adverse reactions of teriparatide group were observed.Results:All patients were followed up for 12-36 months［(14.3±0.6)months］. VAS and ODI were decreased gradually with time in both groups (all P<0.01). There were no significant differences in VAS between the two groups before operation and at 24 hours after operation (all P>0.05). Teriparatide group showed VAS of (4.4±0.6)points, (3.2±0.5)points, (2.0±0.5)points, (1.1±0.1)points at 1, 3, 6 and 12 months after operation, significantly lower than those in routine treatment group［(4.9±0.6)points, (4.0±0.6)points, (3.2±0.7)points, (2.7±0.1)points, respectively］(all P<0.01). Teriparatide group showed ODI of 26.5±1.3 and 20.6±1.2 at 6 months and 12 months after operation, significantly lower than those in routine treatment group (28.2±1.6, 23.6±1.6) (all P<0.01). There were no significant differences in ODI between the two groups at other time points (all P>0.05). Both groups presented significantly lowered levels of ABH and MBH at 12 months after operation as compared with those at 24 hours after operation (all P<0.01). There were no significant differences in ABH or MBH between the two groups at 24 hours after operation (all P>0.05). ABH, MBH, MRABH and MRMBH in teriparatide group were (1.9±0.2)cm, (1.7±0.2)cm, 0.91±0.02 and 0.92±0.02 at 12 months after operation, significantly higher than those in routine treatment group［(1.7±0.2)cm, (1.6±0.2)cm, 0.86±0.02 and 0.87±0.02］(all P<0.01). KA in both groups showed significant increase at 12 months after operation as compared with that at 24 hours after operation (all P<0.01). There was no significant difference in KA between the two groups at 24 hours after operation ( P>0.05). KA in teriparatide group was (7.3±0.7)° at 12 months after operation, significantly lower than (9.5±0.5)° in routine treatment group ( P<0.01). DKA in teriparatide group was (5.3±1.3)° at 12 months after operation, significantly lower than (6.6±1.4)° in routine treatment group ( P<0.01). Incidence of vertebral refracture in teriparatide group was 7% (2/32), significantly lower than 35% (15/58) in routine treatment group ( P<0.05). Level of β-CTX was not significantly different between and within the two groups before operation and at 12 months after operation (all P>0.05). There was no significant difference in N-MID between the two groups before operation ( P>0.05). After treatment for 12 months, level of N-MID in teriparatide group was significantly increased［19.5 (17.6, 20.9)pg/ml］as compared with that before operation［18.2 (14.6, 21.0)pg/ml］( P<0.01), and was significantly higher than that in routine treatment group［17.6 (15.3, 19.9)pg/ml］( P<0.01). Routine treatment group showed no significant difference in level of N-MID before operation and at 12 months after operation ( P>0.05). Two patients in teriparatide group had orthostatic hypotension after treatment. Conclusion:For OVCF patients with RBP after PKP, teriparatide can effectively alleviate pain, improve motor dysfunction, maintain the height of bone cement vertebral body, reduce incidence of vertebral refracture and enhance the activity of osteoblasts, with less adverse reactions.

Objective:To investigate the risk factors of cement vascular leakage after vertebral augmentation for osteoporotic vertebral compression fracture (OVCF).Methods:A case-control study was conducted to analyze the clinical data of 217 patients with OVCF undergone vertebral augmentation [percutaneous vertebroplasty (PVP) or percutaneous kyphoplasty (PKP)] in First and Second Affiliated Hospital of Kunming Medical University from October 2019 to October 2020. There were 79 males and 138 females, at the age range of 58-88 years [(73.1±6.9)years]. According to the occurrence of bone cement vascular leakage, the patients were divided into vascular leakage group ( n=39) and vascular leakage free group ( n=178). The gender, age, bone mineral density, time from injury to operation, anatomical position of injured vertebrae, degree of vertebral compression, integrity of posterior wall, intravertebral fissure sign, vertebrobasilar venous foramen, surgical approach, surgical method, cement injection period, cement injection speed, cement injection volume and cement injection area were recorded. Univariate analysis was used to detect the correlation of those indices with cement vascular leakage after vertebral augmentation. Multivariate Logistic regression analysis was used to identify the independent risk factors for cement vascular leakage after vertebral augmentation. Results:Univariate analysis showed that there was a correlation of cement vascular leakage after vertebral augmentation with time from injury to operation, degree of vertebral compression, integrity of posterior wall, intravertebral fissure sign, vertebrobasilar venous foramen, surgical method, cement injection period, cement injection speed, cement injection volume and cement injection area (all P<0.05), apart from gender, age, bone mineral density, anatomical position of injured vertebrae or surgical approach (all P>0.05). Multivariate Logistic regression analysis showed intravertebral fissure sign ( OR=7.00, 95% CI 1.57-31.30, P<0.05), vertebrobasilar venous foramen ( OR=7.52, 95% CI 1.94-29.16, P<0.01), PVP ( OR=10.98, 95% CI 2.51-47.94, P<0.01), injection of cement in thinning period ( OR=5.91, 95% CI 1.45-24.15, P<0.05), injection of large volume of cement ( OR=3.60, 95% CI 1.70-7.65, P<0.01) and marginal injection of cement ( OR=24.80, 95% CI 5.28-116.37, P<0.01) were significantly associated with cement vascular leakage after vertebral augmentation for OVCF. Conclusion:Intravertebral fissure sign, vertebrobasilar venous foramen, PVP, injection of cement in thinning period, injection of large volume of cement and marginal injection of cement are independent risk factors for cement vascular leakage after vertebral augmentation for OVCF.

【Objective】 To analyze the correlation of whole body tumor burden of ¹⁸F-prostate specific membrane antigen positron emission computed tomography （¹⁸F-PSMA PET/CT） with prostate specific antigen （PSA） and Gleason score so as to evaluate the value of ¹⁸F-PSMA PET/CT whole body tumor burden for predicting serum PSA progression in prostate cancer. 【Methods】 We retrospectively recruited 213 patients with prostate cancer who underwent ¹⁸F-PSMA PET/CT scanning from March 2019 to April 2021. The serum PSA and Gleason score were collected. Whole body tumor burden was measured by a semi-automatic method. The correlation of tumor burden with serum PSA and Gleason score was analyzed. After radical prostatectomy， the patients were divided into groups according to negative or positive ¹⁸F-PSMA PET/CT. PSA differences between groups were compared， and the receiver operating characteristic curve （ROC） of the subjects was drawn so as to obtain the threshold value of PSA to predict the positive rate of ¹⁸F-PSMA PET/CT. The patients were followed up for PSA after radical surgery， divided into groups according to the progress of PSA， and the differences in tumor burden between groups were compared. 【Results】 In Gleason score ≤7， =8， and ≥9 groups， whole body tumor burden was correlated with PSA in each group （P=0.001）， and tumor burden significantly differed between the groups （P<0.001）. In initial diagnosis and treatment group， biochemical recurrence group， and medication group， the correlation between tumor burden and PSA was statistically significant （P=0.001）. The Gleason score of primary prostate lesion was significantly correlated with systemic tumor burden （P<0.001）. The area under ROC curve of PSA predicting the positive rate of ¹⁸F-PSMA PET/CT after radical prostatectomy was 0.821； when PSA>0.577 ng/mL， the sensitivity and the specificity were 66.7% and 96.8%， respectively. The mean whole body tumor burden in ¹⁸F-PSMA PET/CT positive patients with PSA progression was higher than that in patients without PSA progression. 【Conclusion】 The whole body tumor burden of ¹⁸F-PSMA PET/CT is significantly correlated with PSA， which is helpful in predicting the serum PSA progression in prostate cancer. PSA can predict the positive rate of ¹⁸F-PSMA PET/CT to a certain extent. At the same time， PSA can also predict positive results of ¹⁸F-PSMA PET/CT to a certain extent， and guide clinical rational selection of this examination.

【Objective】 To explore the value of 18F-PSMA-1007 PET/CT in evaluating the primary tumor and infiltration range of prostate cancer. 【Methods】 We retrospectively collected 18F-PSMA-1007 PET/CT whole body imaging data of the patients who came to the Department of Urology， The First Affiliated Hospital of Xi’an Jiaotong University， from March 2019 to June 2021 due to suspected or diagnosed prostate cancer. No treatment was give before the examination. In addition， 51 patients underwent radical surgery after examination and obtained complete pathological results. We used a semi-automatic method to delineate the region of interest （ROI） of 40% SUVmax of prostate cancer foci， and obtained the metabolic parameters， namely， SUVmax， SUVmean， tumor metabolic volume （MTV） and total lesion metabolic （TLM）. We also observed for infiltration of bilateral seminal vesicle glands and bladder. Correlation analysis was used to analyze the correlation of metabolic parameters with Gleason score and tumor grade grouping； McNemar test was used to analyze the accuracy of PSMA in evaluating the extent of prostate invasion. 【Results】 The PET/CT parameters SUVmax， SUVmean， TLM and Gleason score were not significantly correlated， but SUVmean was positively correlated with tumor grade （r=0.306， P=0.041）. The pathological results showed a moderate correlation between the maximum diameter of the tumor and MTV （r=0.479， P=0.003）. The sensitivity evaluated by PSMA-PET/CT to primary prostate tumor， capsule invasion， seminal vesicle gland invasion， and bladder invasion was 72.00%， 64.71%， 83.33%， and 25.00%， respectively； the specificity was 88.46%， 33.33%， 84.61%， and 95.74%， respectively； the accuracy was 80.39%， 52.94%， 86.27%， and 90.19%， respectively. 【Conclusion】 ¹⁸F-PSMA-1007 PET/CT imaging has high accuracy in assessing primary tumor and the extent of invasion of prostate cancer， which indicates its value in clinical application.