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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.
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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.
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Objective:To explore the risk factors of adjacent segment diseases (ASDis) after lumbar fusion, summarize the prevention strategies and provide reference for clinical treatment.Methods:All of 258 patients who underwent lumbar interbody fusion from March 2014 to March 2019 were retrospectively analyzed, including 95 males and 163 females, the age of whom was 61.8±8.4 years (range, 39-77 years). The patients were divided into ASDis group and non-ASDis group according to whether ASDis occurred at the follow-up of 24 months after operation. The patient's individual factors [gender, age, body mass index (BMI), main diagnosis, preoperative paraspinal muscle fatty degree, etc.] and surgical factors (operation type, fixed segment, fusion segment, etc.), sagittal parameters [lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), PI-LL] were recorded. After univariate analysis of potential risk factors, the factors with P<0.05 were substituted into logistic regression model for multivariate analysis to determine the risk factors of ASDis after lumbar fusion. Results:ASDis occurred in 24 patients after lumbar fusion, with an incidence of 9.3% (24/258); univariate analysis showed that age ≥ 60 years old, complicated with osteoporosis, preoperative fatty degree of paraspinal muscle (GCS grade≥3), PLIF operation, suspension fixation, total laminectomy and multi-segment fusion (≥ 3 segments) were the potential risk factors for ASDis after operation (P<0.05); Gender, education level, partner status, type of work, BMI, obesity (BMI≥24 kg/m 2) , smoking, use of bisphosphonates, concomitant lumbar spinal stenosis, lumbar lordosis angle, pelvic incidence angle, pelvic tilt angle, sacral slope angle, and PI-LL had no significant correlation with ASDis. Logistic regression analysis showed that age ≥ 60 years ( OR=5.63, 95% CI: 1.56, 20.29, P=0.008), preoperative paravertebral muscle fatty GCS ≥ 3 ( OR=4.82, 95% CI: 1.36, 17.13, P=0.015), combined with osteoporosis ( OR=14.04, 95% CI: 2.53, 77.79, P=0.002), PLIF ( OR=9.69, 95% CI: 1.91, 49.03, P=0.001), and multi-segment fixation ( OR=9.36, 95% CI: 1.77, 49.41, P=0.008) were the risk factors for ASDis after lumbar fusion; Incomplete laminectomy ( OR=0.09, 95% CI: 0.02, 0.37, P=0.001) and suspension fixation ( OR=0.16, 95% CI: 0.02, 0.94, P=0.042) were the protective factors of ASDis after lumbar fusion. Conclusion:The patients with age ≥ 60 years old, osteoporosis and preoperative paraspinal muscle fatty degree ≥ 3 grade GCS should be more careful in choosing the surgical methods, and try to choose transforaminal interbody fusion, posterolateral fusion, short segment fusion, decompression with preservation of vertebral lamina, suspension fixation and other surgical methods to reduce the incidence of postoperative ASDis.
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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.
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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.
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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.
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【Objective】 To investigate the value of prostate cancer prevention trial risk calculator （PCPT-RC） combined with biopsy Gleason score for predicting the risk of metastasis in newly diagnosed prostate cancer patients. 【Methods】 We retrospectively collected the data of 74 patients with newly diagnosed prostate cancer confirmed by biopsy from April 2019 to August 2021， concurrent with 18F-PSMA-1007 PET/CT whole body imaging in the same period. Based on this， a binary logistic regression model was established to obtain the high risk probability of PCPT. We calculated the receiver operating characteristic curve （ROC） was drawn and the area under the curve， Yuden index， sensitivity， specificity， positive predictive value and negative predictive value. We compared the predictive value of the prostate cancer prevention trial risk calculator and Gleason score alone or in combination in predicting the risk of prostate cancer metastasis. 【Results】 Based on the PSMA PET/CT results， 74 patients were divided into non-metastatic group （46/74） and metastatic group （28/74）. PCPT high risk probability ［41.14% （16%-67%）］ vs. ［30.89% （5%-65%）］， Gleason score ［8.5（6-10） score］ vs. ［7.7（6-9） score］， tPSA ［26.24（5.70-42.32） ng/mL］ vs. ［19.58（2.47-49.35） ng/mL］， and fPSA ［3.94（0.82-12.00） ng/mL］ vs. ［2.33（0.35-10.20） ng/mL］ were significantly higher in metastatic group than in non-metastatic group. Binary Logistic regression analysis showed that Gleason score and PCPT low risk probability may be independent predictors of prostate cancer metastasis. PCPT low risk probability alone did not predict the risk of prostate cancer metastasis （P=0.172）. The predictive accuracy of Gleason score and high probability of PCPT in predicting prostate cancer metastasis were 0.715 and 0.679， respectively， and the accuracy of the combined prediction was 0.809. 【Conclusion】 PCPT-RC combined with Gleason score is valuable for predicting the metastasis risk of newly diagnosed prostate cancer patients， which has certain guiding significance for clinical individualized treatment.
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【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.
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【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.
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【Objective】 To analyze the correlation between metabolic parameters of 18F-deoxyglucose-labeledpositron emission tomography/computed tomography（18F-FDG PET/CT） scan and the immunohistochemistry （IHC） expression in patients with primary breast cancer so as to explore the predictive value of the metabolic parameters for molecular subtypes. 【Methods】 We retrospectively recruited 97 patients who underwent 18F-FDG PET/CT scan from November 2016 to June 2020 with breast cancer. The clinical stages （Ⅰ,Ⅱ,Ⅲ and Ⅳ） and menstrual status （pre-menopause or menopause） were collected. Metabolic parameters， including the maximum standardized uptake value （SUVmax）， mean standardized uptake value （SUVmean）， metabolic tumor volume （MTV） and total lesion glycolysis （TLG） of the primary tumor， were calculated by physician according to the 40% SUVmax principle. The IHC expressions （positive or negative） of the estrogen receptor （ER）， progesterone receptor （PR）， human epidermal growth factor receptor 2 （HER2）， proliferating cell nuclear antigen （Ki-67） and p53； the ipsilateral axillary lymph node metastasis （with or without）， and the molecular subtypes （Luminal A， Luminal B， HER2 overexpression， and triple negative） were determined by an experienced pathologist. The correlations between the metabolic parameters and IHC expression were analyzed by Pearson test or Spearman test， and were further stratified by different menstrual status and ipsilateral axillary lymph node metastasis. Finally， we analyzed metabolic parameters among different molecular subtypes. 【Results】 For all the patients， SUVmax and SUVmean had significantly negative correlation with ER and PR expressions （P<0.05）； SUVmax， SUVmean， and TLG were significantly positively correlated with Ki-67 expression （P<0.05）. SUVmax， SUVmean， and TLG of premenopausal patients （n=57） were negatively correlated with ER and PR expressions （P<0.05）， but positively correlated with Ki-67 expression （P<0.05）. MTV， TLG and PR expressions in postmenopausal patients （n=40） were positively correlated （P<0.05）. In patients with （n=27） or without （n=57） ipsilateral axillary lymph node metastasis， Ki-67 was negatively correlated with SUVmax and SUVmean （P<0.05）； in patients without ipsilateral axillary lymph node metastasis， SUVmax， SUVmean， and TLG were negatively correlated with PR （P<0.05）. Among different molecular types， SUVmax of HER2 overexpression was significantly higher than that of Luminal A （P<0.05）. 【Conclusion】 The 18F-FDG PET/CT metabolic parameters of breast cancer patients have a good correlation with the expression of immunohistochemistry， and SUVmax has predictive value for the expression of hetergeneous molecular types.