Objective:To investigate the protective effects and mechanisms of targeted inhibition of type 3 deiodinase (Dio3) on skeletal muscle mitochondria in sepsis.Methods:① In vivo experiments: adeno-associated virus (AAV) was employed to specifically target Dio3 expression in the anterior tibial muscle of rats, and a septic rat model was generated using cecal ligation and puncture (CLP). The male Sprague-Dawley (SD) rats were divided into shNC+Sham group, shD3+Sham group, shNC+CLP group, and shD3+CLP group by random number table method, with 8 rats in each group. After CLP modeling, tibial samples were collected and Western blotting analysis was conducted to assess the protein levels of Dio3, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α), and silence-regulatory protein 1 (SIRT1). Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was utilized to examine mRNA expression of genes including thyroid hormone receptors (THRα, THRβ), monocarboxylate transporter 10 (MCT10), mitochondrial DNA (mtDNA), and PGC1α. Transmission electron microscopy was employed to investigate mitochondrial morphology. ② In vitro experiments: involved culturing C2C12 myoblasts, interfering with Dio3 expression using lentivirus, and constructing an endotoxin cell model by treating cells with lipopolysaccharide (LPS). C2C12 cells were divided into shNC group, shD3 group, shNC+LPS group, and shD3+LPS group. Immunofluorescence colocalization analysis was performed to determine the intracellular distribution of PGC1α. Co-immunoprecipitation assay coupled with Western blotting was carried out to evaluate the acetylation level of PGC1α. Results:① In vivo experiments: compared with the shNC+Sham group, the expression of Dio3 protein in skeletal muscle of the shNC+CLP group was significantly increased (Dio3/β-Tubulin: 3.32±0.70 vs. 1.00±0.49, P < 0.05), however, there was no significant difference in the shD3+Sham group. Dio3 expression in the shD3+CLP group was markedly reduced relative to the shNC+CLP group (Dio3/β-Tubulin: 1.42±0.54 vs. 3.32±0.70, P < 0.05). Compared with the shNC+CLP group, the expression of T3-regulated genes in the shD3+CLP group were restored [THRα mRNA (2 -ΔΔCt): 0.67±0.05 vs. 0.33±0.01, THRβ mRNA (2 -ΔΔCt): 0.94±0.05 vs. 0.67±0.02, MCT10 mRNA (2 -ΔΔCt): 0.65±0.03 vs. 0.57±0.02, all P < 0.05]. Morphology analysis by electron microscopy suggested prominent mitochondrial damage in the skeletal muscle of the shNC+CLP group, while the shD3+CLP group exhibited a marked improvement. Compared with the shNC+Sham group, the shNC+CLP group significantly reduced the number of mitochondria (cells/HP: 10.375±1.375 vs. 13.750±2.063, P < 0.05), while the shD3+CLP group significantly increased the number of mitochondria compared to the shNC+CLP group (cells/HP: 11.250±2.063 vs. 10.375±1.375, P < 0.05). The expression of mtDNA in shNC+CLP group was markedly reduced compared with shNC+Sham group (copies: 0.842±0.035 vs. 1.002±0.064, P < 0.05). Although no difference was detected in the mtDNA expression between shD3+CLP group and shNC+CLP group, but significant increase was found when compared with the shD3+Sham group (copies: 0.758±0.035 vs. 0.474±0.050, P < 0.05). In the shD3+CLP group, PGC1α expression was significantly improved at both transcriptional and protein levels relative to the shNC+CLP group [PGC1α mRNA (2 -ΔΔCt): 1.49±0.13 vs. 0.68±0.06, PGC1α/β-Tubulin: 0.76±0.02 vs. 0.62±0.04, both P < 0.05]. ② In vitro experiments: post-24-hour LPS treatment of C2C12 cells, the cellular localization of PGC1α became diffuse; interference with Dio3 expression promoted PGC1α translocation to the perinuclear region and nucleus. Moreover, the acetylated PGC1α level in the shD3+LPS group was significantly lower than that in the shNC+LPS group (acetylated PGC1α/β-Tubulin: 0.59±0.01 vs. 1.24±0.01, P < 0.05), while the expression of the deacetylating agent SIRT1 was substantially elevated following Dio3 inhibition (SIRT1/β-Tubulin: 1.04±0.04 vs. 0.58±0.03, P < 0.05). When SIRT1 activity was inhibited by using EX527, PGC1α protein expression was notably decreased compared to the shD3+LPS group (PGC1α/β-Tubulin: 0.92±0.03 vs. 1.58±0.03, P < 0.05). Conclusion:Inhibition of Dio3 in skeletal muscle reduced the acetylation of PGC1α through activating SIRT1, facilitating nuclear translocation of PGC1α, thereby offering protection against sepsis-induced skeletal muscle mitochondrial damage.

【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.

Objectives:To investigate the prevalence,clinical characteristics and risk factors of coronavirus disease-2019(COVID-19)in patients with pulmonary hypertension(PH). Methods:A questionnaire survey was conducted from December 30,2022 to January 6,2023 through the WeChat official account of the PH Patients Mutual Aid Organization.PH patients aged≥18 years from 26 province(municipality/autonomous region)were recruited to fill in the electronic survey questionnaire. Results:A total of 293 valid questionnaires were collected from PH patients.The mean age of patients was(40.6±12.7)years,and 226 patients(77.1%)of them were female.The vaccination rate was 59.7%(175/293),117 patients(39.9%)received three or more doses of vaccine,145 patients(49.5%)received inactivated vaccine.242 patients(82.6%)had COVID-19.The most common symptoms during infection were fever(85.5%),cough(77.7%),and fatigue(66.5%).10.7%of the patients had severe or critical COVID-19.Age(OR =1.057,95%CI:1.027-1.087,P<0.001)and comorbid pulmonary disease(OR=3.341,95%CI:1.215-9.184,P=0.019)were associated with severe or critical COVID-19.After adjusting for confounding factors,age was an independent risk factor for severe or critical COVID-19(OR=1.049,95%CI:1.019-1.080,P=0.001).Severe or critical COVID-19 was an independent risk factor for worsening heart failure in PH patients during COVID-19 pandemic(OR=10.522,95%CI:4.311-25.682,P<0.001). Conclusions:The immunization coverage of PH patients is insufficient.PH patients have a higher risk of developing severe or critical COVID-19 than general population.Ageing is an independent risk factor for severe or critical COVID-19,and the risk of worsening heart failure in PH patients with severe or critical COVID-19 is significantly increased during COVID-19 pandemic.

【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.

【Objective】 To investigate the value of prostate-specific antigen （PSA） level， Gleason score， and PSMA PET/CT maximum standardized uptake value （SUVmax） in predicting prostate cancer （PCa） metastasis and the treatment option of oligometastatic PCa. 【Methods】 We retrospectively recruited 170 patients with PCa confirmed by pathology， 97 of whom were untreated， and divided them into nonmetastatic group， oligometastatic group （metastasis≤5）， and polymetastatic group. In addition， 28 patients with oligometastatic PCa underwent radical prostatectomy and 45 patients underwent androgen-deprivation therapy. We compared the differences in SUVmax， PSA， and Gleason scores between the three sub-groups of untreated patients， and also analyzed the correlation between SUVmax of local cancer lesions， Gleason score and PSA level. We further compared the differences in SUVmax and PSA levels between radical prostatectomy and androgen-deprivation therapy of oligometastatic PCa patients. According to Gleason score， patients with oligometastatic PCa were divided into two groups （low-intermediate risk group with Gleason score ≤7 and high-risk group with Gleason score ≥8）， and the levels of SUVmax and PSA between the groups were compared. 【Results】 With the increasing number of metastases， SUVmax， PSA levels and Gleason scores all showed an upward trend， and there were significant differences among the three groups （P=0.029， P=0.001， P=0.046）. The post-hoc test found significant difference in Gleason score between the oligometastatic group and the other two groups （P=0.043， P=0.002） as well as correlation of SUVmax level of the primary tumor with Gleason score and PSA （P=0.002， r=0.315； P<0.001， r=0.430）. There was significant difference in PSA level between the two groups after radical prostatectomy and androgen-deprivation therapy （P=0.017）. The difference in PSA between the two treatments persisted in the low-intermediate risk groups （P=0.021）. 【Conclusion】 PSA level， Gleason score and SUVmax have some value in predicting PCa metastasis. Radical prostatectomy is an effective treatment strategy for patients with oligometastatic PCa， especially those with low-intermediate Gleason score.

【Objective】 To investigate the diagnostic efficiency of ¹⁸F-PSMA-1007 PET/CT in assessing the metastasis of newly diagnosed prostate cancer （PC）， and evaluate its relationship with clinical risk classification. 【Methods】 The clinical data of 257 newly diagnosed PC patients who underwent ¹⁸F-PSMA-1007 PET/CT between March 2019 and April 2021 were retrospectively reviewed in this study. All images were interpreted by two senior PET/CT diagnostic specialists. According to the D’Amico risk classification， the patients were divided into low-， intermediate- and high-risk groups. According to Gleason score （GS）， the patients were divided into GS≤6， GS=7， and GS≥8 groups. According to the level of serum total prostate-specific antigen （tPSA）， the patients were divided into <10 ng/mL， 10-20 ng/mL， and >20 ng/mL groups. Finally， in the groups with D’Amico risk classification， the subgroups were divided according to tPSA level and GS， and the differences of ¹⁸F-PSMA-1007 PET/CT in the detection of metastasis were compared among the subgroups. 【Results】 A total of 257 patients were enrolled with a median tPSA 16.34 （3.38-783.12） ng/mL and median Gleason score （GS） 8 （range： 6-10）. There were 10 （3.89%）， 36 （15.01%）， and 211（80.10%） PC patients in the low-， intermediate-， and high-risk groups， respectively. The rate of metastasis in high-risk group， GS ≥ 8 group， and tPSA >20 ng/mL group was 45.02%， 46.50%， and 47.02%， respectively. The rate of metastasis in low-risk group， GS ≤6 group and tPSA <10 ng/mL group was 0， 8.82%， and 15.63%， respectively. When tPSA <10 ng/mL， the rate of metastasis in low-risk group （0） was lower than that in high-risk group （33.33%）. When tPSA was 10-20 ng/mL， the rate of metastasis in intermediate-risk group （7.69%） was lower than that in high-risk group （38.71%）. When GS ≤6， the rate of metastasis in low-risk group （0） was lower than that in high-risk group （38.71%）. 【Conclusion】 The detection rate of metastasis in patients with newly diagnosed prostate cancer by ¹⁸F-PSMA-1007 PET/CT is positively correlated with GS， preoperative tPSA level， and D’Amico risk grade.

【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.

Objective:To establish and verify the prediction model of benign or malignant of solitary pulmonary nodules (SPNs≤20 mm) based on artificial intelligence.Methods:Totally 338 SPNs (≤20 mm) from 279 patients, confirmed by operation and pathology, were selected in Zhongshan Hospital Xiamen University from November 2018 to May 2020. Clinical data (age, gender, smoking history, individual and family history of malignancy), image features (maximum diameter, minimum diameter, solid proportion, volume, lobulation sign, burr sign, vacuole sign, cavity sign, pleural indentation sign, and radiomic features (maximum CT value, minimum CT value, average CT value, median CT value, CT value standard deviation, skewness, peak, energy, entropy) were analyzed retrospectively. All the data of patients were randomly divided into training set (271 SPNs) and test set (67 SPNs). In the training set, the clinical, image features and radiomic features were first selected by the least absolute shrinkage and selection operator (LASSO) regression, then the independent risk factors of SPN (≤20 mm) were screened out by multi-variate logistic regression analysis, and the nomogram prediction models were constructed. Finally, the data of test set were used to verify the prediction model by the ROC curve and calibration curve (CC).Results:In the training set of 271 SPNs, 81 SPNs were benign and 190 malignant. After analysis of LASSO regression and multi-factor logistics regression, the independent predictors of benign or malignant SPN were age, gender, largest diameter, vacuole sign and solid proportion. The prediction model was P=e x/(1+e x), x=-2.583+0.027×age+1.519×gender+0.127×maximum diameter-2.132×solid proportion+1.720×vacuole sign. The results of the model showed that the area under curve (AUC) of ROC was 0.850, and the sensitivity was 73.7%, specificity was 82.7% and accuracy was 82.3%. In the test set of 67 SPNs, 22 SPNs were benign and 45 malignant. The results showed that the AUC of ROC was 0.882, and the sensitivity was 82.2%, specificity was 81.8% and accuracy was 85.1%. The calibration nomogram of prediction model showed that CC from training set or test set well coincided with its individual ideal curve ( Ptraining=0.688, Ptest=0.618). Conclusion:Prediction model of benign or malignant SPN ≤20 mm is established based on AI; it can obtain the prediction probability and has good diagnostic efficiency.