Objective:To investigate the value of biparametric-MRI (bpMRI) based peritumoral radiomics for preoperative prediction of extraprostatic extension (EPE) in prostate cancer (PCa).Methods:In this cross-sectional study, consecutive bpMRI of patients undergoing prostatectomy for PCa were retrospectively collected from the First Medical Center (center 1) and the Third Medical Center (center 2) of Chinese PLA General Hospital. A total of 274 patients were finally enrolled. Patients at center 1 from January 2020 to December 2022 were randomly divided into a training set (149 cases) and an internal validation set (63 cases) by stratified random sampling. Patients at center 2 from January 2023 to March 2024 were assigned to the external test set (62 cases). Patients were categorized into EPE-positive group and EPE-negative group according to pathological assessment postoperatively. In the training set, there were 49 cases in EPE-positive group and 100 cases in EPE-negative group. In the internal validation set, there were 26 cases in EPE-positive group and 37 cases in EPE-negative group. In the external test set, there were 22 cases in EPE-positive group and 40 cases in EPE-negative group. Axial T 2WI and apparent diffusion coefficient (ADC) images were manually annotated to obtain index lesion regions of interest (ROIs), with the peritumoral ROIs subsequently delineated by semi-automatic segmentation technique. Radiomics features were extracted from intra-tumoral, peri-tumoral, and intra-tumoral plus peri-tumoral ROIs. The training set data was employed to select and optimize features to build the radiomics models. The logistic regression analysis was used to develop radiomics, clinical, and integrated models. The predictive performance was assessed by the area under the receiver operating characteristic curve (AUC) in the external test set, and compared by the DeLong test. The sensitivity and specificity were compared by the exact McNemar test. Results:In the external test set, the peri-tumoral radiomics model based on bpMRI showed the highest performance in evaluating EPE, with an AUC of 0.739 (95% CI 0.611-0.842), which was identified as the optimal radiomics model. EPE grade ( OR=6.151, 95% CI 3.371-11.226, P<0.001) was incorporated into the clinical model, with an AUC of 0.780 (95% CI 0.657-0.875) in the external test set. The integrated model had an AUC of 0.817 (95% CI 0.698-0.904) in the external test set. There was no statistically significant difference in comparisons of AUCs among the three models (all P>0.05). The sensitivity of the integrated model (68.2%) showed no significant difference from those of the clinical model and the optimal radiomics model (77.3% and 86.4%, respectively; P=0.500 and P=0.289). However, the specificity of the integrated model (85.0%) was significantly higher than those of the clinical model (67.5%, P=0.016) and the optimal radiomics model (50.0%, P<0.001). Conclusion:A bpMRI-based peritumoral radiomics integrating clinical model demonstrates high performance for preoperative prediction of EPE in PCa.

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

Objective:To investigate the value of biparametric-MRI (bpMRI) based peritumoral radiomics for preoperative prediction of extraprostatic extension (EPE) in prostate cancer (PCa).Methods:In this cross-sectional study, consecutive bpMRI of patients undergoing prostatectomy for PCa were retrospectively collected from the First Medical Center (center 1) and the Third Medical Center (center 2) of Chinese PLA General Hospital. A total of 274 patients were finally enrolled. Patients at center 1 from January 2020 to December 2022 were randomly divided into a training set (149 cases) and an internal validation set (63 cases) by stratified random sampling. Patients at center 2 from January 2023 to March 2024 were assigned to the external test set (62 cases). Patients were categorized into EPE-positive group and EPE-negative group according to pathological assessment postoperatively. In the training set, there were 49 cases in EPE-positive group and 100 cases in EPE-negative group. In the internal validation set, there were 26 cases in EPE-positive group and 37 cases in EPE-negative group. In the external test set, there were 22 cases in EPE-positive group and 40 cases in EPE-negative group. Axial T 2WI and apparent diffusion coefficient (ADC) images were manually annotated to obtain index lesion regions of interest (ROIs), with the peritumoral ROIs subsequently delineated by semi-automatic segmentation technique. Radiomics features were extracted from intra-tumoral, peri-tumoral, and intra-tumoral plus peri-tumoral ROIs. The training set data was employed to select and optimize features to build the radiomics models. The logistic regression analysis was used to develop radiomics, clinical, and integrated models. The predictive performance was assessed by the area under the receiver operating characteristic curve (AUC) in the external test set, and compared by the DeLong test. The sensitivity and specificity were compared by the exact McNemar test. Results:In the external test set, the peri-tumoral radiomics model based on bpMRI showed the highest performance in evaluating EPE, with an AUC of 0.739 (95% CI 0.611-0.842), which was identified as the optimal radiomics model. EPE grade ( OR=6.151, 95% CI 3.371-11.226, P<0.001) was incorporated into the clinical model, with an AUC of 0.780 (95% CI 0.657-0.875) in the external test set. The integrated model had an AUC of 0.817 (95% CI 0.698-0.904) in the external test set. There was no statistically significant difference in comparisons of AUCs among the three models (all P>0.05). The sensitivity of the integrated model (68.2%) showed no significant difference from those of the clinical model and the optimal radiomics model (77.3% and 86.4%, respectively; P=0.500 and P=0.289). However, the specificity of the integrated model (85.0%) was significantly higher than those of the clinical model (67.5%, P=0.016) and the optimal radiomics model (50.0%, P<0.001). Conclusion:A bpMRI-based peritumoral radiomics integrating clinical model demonstrates high performance for preoperative prediction of EPE in PCa.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

To explore the effect of tanshinone IIA (TanIIA) on the occurrence and development of breast cancer, we employed the mouse mammary tumor virus-polyomavirus middle T antigen (MMTV-PyMT) transgenic mice as a spontaneous breast cancer mouse model. Animal welfare and experimental procedures were in accordance with the regulations of the Animal Ethics Committee of Nanjing University of Chinese Medicine. The animals were divided into control group, low-dose TanIIA treatment group (30 mg·kg^-1·day^-1), and high-dose TanIIA treatment group (60 mg·kg^-1·day^-1). The treatment was administered orally and daily for 5 weeks. The mice were sacrificed after final treatment. Mammary gland and lung were collected for histopathology studies. We evaluated the chemoprophylaxis effect of TanIIA on breast cancer in mice according to the pathological characteristics of breast cancer at different stages of development. Immunofluorescence staining were employed for blood vessel analysis. The expression levels of E-cadherin, proliferating nuclear antigen (PCNA), and oncogene c-Myc were detected by immunohistochemistry. Flow cytometry was used to analyze cell cycle and Cytoscape was used to construct drug-disease protein-protein interaction (PPI) network. Our results showed that TanIIA inhibits breast tumor progression by delaying malignancy from adenoma to early carcinoma, and inhibits blood vessel formation during tumor development. TanIIA (60 mg·kg^-1·day^-1) inhibits the expression levels of PCNA and c-Myc, upregulates the expression of E-cadherin. In addition, cell cycle experiments showed that the cell cycle of PyMT primary mammary cells in the high-dose TanIIA group was arrested in the G0/G1 phase. Our study demonstrated that TanIIA can significantly inhibit breast tumor progression in MMTV-PyMT mouse model, which may be related to the inhibition of angiogenic switch and cell cycle arrest.

Betacoronavirus ; China ; epidemiology ; Coronavirus Infections ; prevention & control ; Disease Outbreaks ; Emergencies ; Hospitals, General ; Humans ; Internet ; Pandemics ; prevention & control ; Pneumonia, Viral ; prevention & control

Objective: To evaluate the characteristics of left ventricular structure, function, myocardial mechanics, hemodynamics and synchrony in different phenotypes of hypertrophic cardiomyopathy (HCM) using state-of-the-art echocardiography. Methods: A consecutive series of 85 adult HCM patients who were admitted to the Xi Jing HCM center from January 2016 to November 2017 were collected. According to the peak left ventricular outflow tract pressure gradient in exercise stress echocardiography, the patients were divided into three groups: patients with non-obstructive HCM (n=28), those with labile-obstructive HCM (n=27), and those with obstructive HCM (n=30). In addition, 16 normal family members of HCM patients were included as control group. Two-dimensional speckle tracking imaging, tissue Doppler imaging and exercise stress echocardiography were used to evaluate the left ventricular function in resting and exercise states. Results: ①As compared with the control group, left ventricular end-diastolic diameter decreased and left ventricular ejection fraction increased in all three HCM groups(all P<0.05). Left ventricular maximum wall thickness and left ventricular mass index were the highest in obstructive HCM, followed by labile-obstructive and non-obstructive HCM, and the lowest in the control group (all P<0.05). ②At rest, the left ventricular global longitudinal, circumferential and radial strain (GLS, GCS and GRS), as well as the twist of obstructive HCM were significantly lower than the other three groups (all P<0.05). As compared with the control group, the GLS and twist decreased in the labile-obstructive and non-obstructive HCM(all P<0.05), but there were no significant changes of GCS and GRS (all P>0.05). The obstructive HCM had the lowest mitral annular plane systolic excursion (MAPSE) and s′, and the longest systolic peaking time standard deviation(Ts-SD) and early diastolic peaking time standard deviation(Te-SD) (all P<0.05). The left ventricular diastolic function of obstructive HCM (e′, the E/e′ ratio and the left atrial volume index) was the worst, labile-obstruction and non-obstructive HCM were better, and the control group was the best (all P<0.001). ③During exercise, the GLS, GCS, GRS, twist of the left ventricle and the MAPSE were the lowest in the obstructive HCM, which increased in the labile-obstructive and non-obstructive HCM, and were best in the control group. The Ts-SD and Te-SD were the shortest in the control group, were prolonged in non-obstructive and labile-obstruction HCM, and were longest in obstructive HCM (all P<0.05). Additionally, the exercise time of the control group was the longest, followed by non-obstructive and labile-obstruction HCM, and the shortest in the obstructive HCM (all P<0.05). The METs of obstructive HCM were significantly lower than the other three groups (all P<0.05). Conclusions In obstructive HCM, the left ventricular systolic strain and synchronization, as well as the MAPSE, are significantly impaired in patients both at rest and during exercise. The patients with labile-obstructive and non-obstructive HCM have reduced left ventricular GLS, twist, and e′, but normal left ventricular GCS, GRS, synchrony, and MAPSE at rest, which are all impaired during exercise.

Objective To evaluate the characteristics of left ventricular structure ,function ,myocardial mechanics ,hemodynamics and synchrony in different phenotypes of hypertrophic cardiomyopathy ( HCM ) using state‐of‐the‐art echocardiography . Methods A consecutive series of 85 adult HCM patients w ho were admitted to the Xi Jing HCM center from January 2016 to November 2017 were collected . According to the peak left ventricular outflow tract pressure gradient in exercise stress echocardiography ,the patients were divided into three groups :patients with non‐obstructive HCM ( n ＝28) ,those with labile‐obstructive HCM ( n ＝27) ,and those with obstructive HCM ( n ＝ 30 ) . In addition ,16 normal family members of HCM patients were included as control group . T wo‐dimensional speckle tracking imaging ,tissue Doppler imaging and exercise stress echocardiography were used to evaluate the left ventricular function in resting and exercise states . Results ① As compared with the control group ,left ventricular end‐diastolic diameter decreased and left ventricular ejection fraction increased in all three HCM groups ( all P ＜ 0 .05 ) . Left ventricular maximum wall thickness and left ventricular mass index were the highest in obstructive HCM , followed by labile‐obstructive and non‐obstructive HCM ,and the lowest in the control group ( all P ＜0 .05) . ②A t rest ,the left ventricular global longitudinal ,circumferential and radial strain ( GLS ,GCS and GRS) ,as well as the twist of obstructive HCM were significantly lower than the other three groups ( all P ＜0 .05) . As compared with the control group ,the GLS and twist decreased in the labile‐obstructive and non‐obstructive HCM ( all P ＜0 .05 ) ,but there were no significant changes of GCS and GRS ( all P ＞ 0 .05 ) . T he obstructive HCM had the lowest mitral annular plane systolic excursion ( M APSE ) and s′,and the longest systolic peaking time standard deviation( T s‐SD) and early diastolic peaking time standard deviation ( Te‐SD) ( all P ＜0 .05) . T he left ventricular diastolic function of obstructive HCM ( e′,the E/e′ratio and the left atrial volume index ) was the worst ,labile‐obstruction and non‐obstructive HCM were better ,and the control group was the best ( all P ＜ 0 .001 ) . ③ During exercise ,the GLS ,GCS ,GRS ,twist of the left ventricle and the M APSE were the lowest in the obstructive HCM ,which increased in the labile‐obstructive and non‐obstructive HCM ,and were best in the control group . T he T s‐SD and Te‐SD were the shortest in the control group ,were prolonged in non‐obstructive and labile‐obstruction HCM ,and were longest in obstructive HCM ( all P ＜ 0 .05 ) . Additionally ,the exercise time of the control group was the longest , followed by non‐obstructive and labile‐obstruction HCM ,and the shortest in the obstructive HCM ( all P ＜0 .05) . T he M ET s of obstructive HCM were significantly lower than the other three groups ( all P ＜0 .05) . Conclusions In obstructive HCM ,the left ventricular systolic strain and synchronization ,as well as the M APSE ,are significantly impaired in patients both at rest and during exercise . T he patients with labile‐obstructive and non‐obstructive HCM have reduced left ventricular GLS , twist ,and e′,but normal left ventricular GCS ,GRS ,synchrony ,and M APSE at rest ,which are all impaired during exercise .