Factors associated with pregnant women's willingness to receive maternal pertussis vaccination in Guizhou Province, China: An exploratory cross-sectional study.

The rise in pertussis incidence among infants in Guizhou, China underscores the need for maternal acellular pertussis vaccine (aP) immunization, a key strategy in protecting infants from severe health consequences. However, the willingness of pregnant women in Guizhou to receive this vaccine is not well-understood. This study aimed to explore pregnant women's intentions toward maternal pertussis vaccination in Guizhou and identify the associated factors. A questionnaire based on the health belief model, was administered in an exploratory cross-sectional study from January to February 2022. Data from 564 participants were collected and analyzed. The chi-square test, Mann-Whitney U test, and Poisson regression were used to identify potential factors associated with vaccination intentions. Participants' median age was 27 y (interquartile range (IQR): 24-31), and the median number of children per participant was one. The study found that only 36.0% of the participants intended to receive the aP vaccine while 64.0% were uncertain or negative in this regard. Significant factors associated with intentions to vaccinate included perceived barriers and cues for action and perceived benefits. The major barriers for low vaccination intentions were safety concerns for both the fetus and the mother, and family members' negative attitudes. Free vaccines, perceiving preventive benefits, observing other pregnant women getting vaccinated, and healthcare provider recommendations may facilitate vaccination intentions. Multiple immune strategies should be developed or optimized to cope with the resurgence of pertussis.

Role of Additional MRI-Based Morphologic Measurements on the Performance of VI-RADS for Muscle-Invasive Bladder Cancer.

BACKGROUND: Vesical Imaging-Reporting and Data System (VI-RADS) is a pathway for the standardized imaging and reporting of bladder cancer staging using multiparametric (mp) MRI. PURPOSE: To investigate additional role of morphological (MOR) measurements to VI-RADS for the detection of muscle-invasive bladder cancer (MIBC) with mpMRI. STUDY TYPE: Retrospective. POPULATION: A total of 198 patients (72 MIBC and 126 NMIBC) underwent bladder mpMRI was included. FIELD STRENGTH/SEQUENCE: 3.0 T/T2-weighted imaging with fast-spin-echo sequence, spin-echo-planar diffusion-weighted imaging and dynamic contrast-enhanced imaging with fast 3D gradient-echo sequence. ASSESSMENT: VI-RADS score and MOR measurement including tumor location, number, stalk, cauliflower-like surface, type of tumor growth, tumor-muscle contact margin (TCM), tumor-longitudinal length (TLL), and tumor cellularity index (TCI) were analyzed by three uroradiologists (3-year, 8-year, and 15-year experience of bladder MRI, respectively) who were blinded to histopathology. STATISTICAL TESTS: Significant MOR measurements associated with MIBC were tested by univariable and multivariable logistic regression (LR) analysis with odds ratio (OR). Area under receiver operating characteristic curve (AUC) with DeLong's test and decision curve analysis (DCA) were used to compared the performance of unadjusted vs. adjusted VI-RADS. A P-value <0.05 was considered statistically significant. RESULTS: TCM (OR 9.98; 95% confidence interval [CI] 4.77-20.8), TCI (OR 5.72; 95% CI 2.37-13.8), and TLL (OR 3.35; 95% CI 1.40-8.03) were independently associated with MIBC at multivariable LR analysis. VI-RADS adjusted by three MORs achieved significantly higher AUC (reader 1 0.908 vs. 0.798; reader 2 0.906 vs. 0.855; reader 3 0.907 vs. 0.831) and better clinical benefits than unadjusted VI-RADS at DCA. Specially in VI-RADS-defined equivocal lesions, MOR-based adjustment resulted in 55.5% (25/45), 70.4% (38/54), and 46.4% (26/56) improvement in accuracy for discriminating MIBC in three readers, respectively. DATA CONCLUSION: MOR measurements improved the performance of VI-RADS in detecting MIBC with mpMRI, especially for equivocal lesions. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Biopsy-free AI-aided precision MRI assessment in prediction of prostate cancer biochemical recurrence.

BACKGROUND: To investigate the predictive ability of high-throughput MRI with deep survival networks for biochemical recurrence (BCR) of prostate cancer (PCa) after prostatectomy. METHODS: Clinical-MRI and histopathologic data of 579 (train/test, 463/116) PCa patients were retrospectively collected. The deep survival network (iBCR-Net) is based on stepwise processing operations, which first built an MRI radiomics signature (RadS) for BCR, and predicted the T3 stage and lymph node metastasis (LN+) of tumour using two predefined AI models. Subsequently, clinical, imaging and histopathological variables were integrated into iBCR-Net for BCR prediction. RESULTS: RadS, derived from 2554 MRI features, was identified as an independent predictor of BCR. Two predefined AI models achieved an accuracy of 82.6% and 78.4% in staging T3 and LN+. The iBCR-Net, when expressed as a presurgical model by integrating RadS, AI-diagnosed T3 stage and PSA, can match a state-of-the-art histopathological model (C-index, 0.81 to 0.83 vs 0.79 to 0.81, p > 0.05); and has maximally 5.16-fold, 12.8-fold, and 2.09-fold (p < 0.05) benefit to conventional D'Amico score, the Cancer of the Prostate Risk Assessment (CAPRA) score and the CAPRA Postsurgical score. CONCLUSIONS: AI-aided iBCR-Net using high-throughput MRI can predict PCa BCR accurately and thus may provide an alternative to the conventional method for PCa risk stratification.

Enzalutamide and olaparib synergistically suppress castration-resistant prostate cancer progression by promoting apoptosis through inhibiting nonhomologous end joining pathway.

Recent studies revealed the relationship among homologous recombination repair (HRR), androgen receptor (AR), and poly(adenosine diphosphate-ribose) polymerase (PARP); however, the synergy between anti-androgen enzalutamide (ENZ) and PARP inhibitor olaparib (OLA) remains unclear. Here, we showed that the synergistic effect of ENZ and OLA significantly reduced proliferation and induced apoptosis in AR-positive prostate cancer cell lines. Next-generation sequencing followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed the significant effects of ENZ plus OLA on nonhomologous end joining (NHEJ) and apoptosis pathways. ENZ combined with OLA synergistically inhibited the NHEJ pathway by repressing DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and X-ray repair cross complementing 4 (XRCC4). Moreover, our data showed that ENZ could enhance the response of prostate cancer cells to the combination therapy by reversing the anti-apoptotic effect of OLA through the downregulation of anti-apoptotic gene insulin-like growth factor 1 receptor ( IGF1R ) and the upregulation of pro-apoptotic gene death-associated protein kinase 1 ( DAPK1 ). Collectively, our results suggested that ENZ combined with OLA can promote prostate cancer cell apoptosis by multiple pathways other than inducing HRR defects, providing evidence for the combined use of ENZ and OLA in prostate cancer regardless of HRR gene mutation status.

Renal Lipoma-Like Angiomyolipoma of Tumour Thrombus Extending to the Confluence of Inferior Vena Cava with Right Atrium: A Rare Case Report and Literature Review.

Angiomyolipoma (AML) complicated with tumour thrombus extending to the confluence of inferior vena cava (IVC) with right atrium is rarely observed. We report a female AML patient admitted to our centre on January 21, 2020, with complication of tumour thrombus extending to the confluence of IVC with right atrium and had no sign of difficult breathing. She underwent whole-abdominal enhanced CT for abdominal pain and was diagnosed with a possible renal AML with tumour thrombus. Open radical nephrectomy and thrombectomy of vena cava were performed. Intraoperative transoesophageal echocardiography indicated that the tumour thrombus has reached the confluence of IVC with right atrium. The operation took 255 min with an intraoperative haemorrhage of 800mL. The patient was discharged 7 days after surgery. Pathology revealed lipoma-like AML. Immunohistochemistry showed vimentin (+), EMA (-), HMB45 (+), S-100 (-), SMA (+), TFE-3 (-), melan A (+). After 2 years of follow-up, we found that the patient showed full recovery and had no recurrence. Therefore, lipoma-like AML should also be followed closely for recurrence and metastasis. When AML involves IVC tumour thrombus, open thrombectomy and radical nephrectomy are safe and effective methods.

Exploring employment preferences of nurses to improve retention in rural China.

BACKGROUND: The scarcity of nurses in rural China deserves serious consideration in light of the widening gap in health outcomes between rural and urban populations. The outflow of primary care nurses suggests the value of examining their employment preferences to identify possible effective incentives for their retention. METHODS: Our research used discrete choice experiment methodology designed to quantitatively measure the relative importance of various job attributes valued by primary care nurses using conditional logit and mixed logit models. Willingness to pay and uptake rates were also calculated. RESULTS: A total of 1744 registered nurses in township health centres were surveyed. Participants considered all the job attributes included in the study to be significant, with pay increases demonstrating the greatest potential to improve the retention of nurses. Among the non-monetary aspects of work, nurse-patient relationships, bianzhi (positions allocated to each unit by the Chinese government with special benefits) and educational opportunities ranked highest in importance for respondents. Responses to hypothetical policy proposals suggest that incentive packages are also likely to be effective. CONCLUSIONS: Policy making regarding rural nurses' retention is an important undertaking that requires an evidence-based approach. Our findings provide a range of policy options that shed light on effective retention strategies. Tailoring policy incentives to primary care nurses is also necessary.

Eliciting primary healthcare physicians' preferences for job characteristics in rural China: a discrete choice experiment.

INTRODUCTION: The outflow and scarcity of physicians in rural areas can adversely affect universal health coverage and population health outcomes, which are critical concerns in China. This study explored primary healthcare physicians' job preferences using a discrete choice experiment to identify appropriate incentives for retention. METHODS: Eight job characteristics were identified through a literature review and qualitative studies as the attributes relevant to designing the discrete choice experiment, with levels varying between two hypothetical jobs. The data were analysed using conditional logit model, mixed logit model and latent class model. RESULTS: A total of 1781 licensed physicians (including licensed assistant physicians) from township health centres in rural areas were surveyed. Policy simulation suggested that they were sensitive to both monetary and non-monetary policy incentives. As for non-monetary job characteristics, a highly intense doctor-patient relationship, bianzhi (the number of personnel allocated to each employer by the government) and educational opportunities were highly valued by the respondents. The latent class model could identify distinct groups with different job preferences according to their memberships. CONCLUSION: Urban jobs were much preferred to rural ones. However, policy incentives can lend themselves to effective retention strategies. It is also important to tailor policy incentives to different subgroups.

Trigred motif 36 regulates neuroendocrine differentiation of prostate cancer via HK2 ubiquitination and GPx4 deficiency.

Neuroendocrine prostate cancer (NEPC), the most lethal subtype of castration-resistant prostate cancer (PCa), may evolve from the neuroendocrine differentiation (NED) of PCa cells. However, the molecular mechanism that triggers NED is unknown. Trigred motif 36 (TRIM36), a member of the TRIM protein family, exhibits oncogenic or anti-oncogenic roles in various cancers. We have previously reported that TRIM36 is highly expressed to inhibit the invasion and proliferation of PCa. In the present study, we first found that TRIM36 was lowly expressed in NEPC and its overexpression suppressed the NED of PCa. Next, based on proteomic analysis, we found that TRIM36 inhibited the glycolysis pathway through suppressing hexokinase 2 (HK2), a crucial glycolytic enzyme catalyzing the conversion of glucose to glucose-6-phosphate. TRIM36 specifically bound to HK2 through lysine 48 (lys48)-mediated ubiquitination of HK2. Moreover, TRIM36-mediated ubiquitination degradation of HK2 downregulated the level of glutathione peroxidase 4 (GPx4), a process that contributed to ferroptosis. In conclusion, TRIM36 can inhibit glycolysis via lys48-mediated HK2 ubiquitination to reduce GPX4 expression and activate ferroptosis, thereby inhibiting the NED in PCa. Targeting TRIM36 might be a promising approach to retard NED and treat NEPC.

Performance of Artificial Intelligence-Aided Diagnosis System for Clinically Significant Prostate Cancer with MRI: A Diagnostic Comparison Study.

BACKGROUND: The high level of expertise required for accurate interpretation of prostate MRI. PURPOSE: To develop and test an artificial intelligence (AI) system for diagnosis of clinically significant prostate cancer (CsPC) with MRI. STUDY TYPE: Retrospective. SUBJECTS: One thousand two hundred thirty patients from derivation cohort between Jan 2012 and Oct 2019, and 169 patients from a publicly available data (U-Net: 423 for training/validation and 49 for test and TrumpeNet: 820 for training/validation and 579 for test). FIELD STRENGTH/SEQUENCE: 3.0T/scanners, T2 -weighted imaging (T2 WI), diffusion-weighted imaging, and apparent diffusion coefficient map. ASSESSMENT: Close-loop AI system was trained with an Unet for prostate segmentation and a TrumpetNet for CsPC detection. Performance of AI was tested in 410 internal and 169 external sets against 24 radiologists categorizing into junior, general and subspecialist group. Gleason score >6 was identified as CsPC at pathology. STATISTICAL TESTS: Area under the receiver operating characteristic curve (AUC-ROC); Delong test; Meta-regression I2 analysis. RESULTS: In average, for internal test, AI had lower AUC-ROC than subspecialists (0.85 vs. 0.92, P < 0.05), and was comparable to junior (0.84, P = 0.76) and general group (0.86, P = 0.35). For external test, both AI (0.86) and subspecialist (0.86) had higher AUC than junior (0.80, P < 0.05) and general reader (0.83, P < 0.05). In individual, it revealed moderate diagnostic heterogeneity in 24 readers (Mantel-Haenszel I2  = 56.8%, P < 0.01), and AI outperformed 54.2% (13/24) of readers in summary ROC analysis. In multivariate test, Gleason score, zonal location, PI-RADS score and lesion size significantly impacted the accuracy of AI; while effect of data source, MR device and parameter settings on AI performance is insignificant (P > 0.05). DATA CONCLUSION: Our AI system can match and to some case exceed clinicians for the diagnosis of CsPC with prostate MRI. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

[Gonadoblastoma: Clinicopathological study and literature review of 3 cases].

OBJECTIVE: To investigate the clinical feature, pathological morphology, special histopathological subtype and immunohistochemical characteristic of gonadoblastoma. METHODS: Three patients of gonadoblastoma treated from 2014 to 2020 were enrolled, and the clinical characteristics, histological morphology and immunophenotype were analyzed, and the literatures were also reviewed. RESULT: Three phenotypical females were 14,17 and 27 years old. Case 1 was 46,XX with normal gonadal development. Case 2 was 46,XY and case 3 was chromosomal chimeric type (46, XY 90%/45,X 10%), both with dysgenetic gonads. Microscopically, the morphology of classic type was observed in all cases more or less, manifesting small nests of primitive germ cells and surrounding clustered sex cord-like cells, usually with Call-Exner like bodies and calcification. In additon, the morphology of special subtype can be seen in case 1,exhibiting cord-like tumor cells, which was segmentated by cellular fibrous stroma. Cases 2 and 3 were accompanied by dysgerminoma components. Immunohistochemically,all the primal germ cells were positive for OCT3/4, PLAP and CDll7 , and sexcord-like cells were positive for inhibin, SF-1, SOX9 and FOXL2 . Patients were followed up for 10 years, 6 years and 4 years respectively without recurrence. CONCLUSION: Gonadoblastoma is a rare germ cell-sex cord stromal tumor, which is usually accompanied by gonadal hypoplasia. As a special subtype, dissecting gonadoblastoma will be easily confused with dysgerminoma/seminoma, but the prognosis is better. So we should improve the understanding of this subtype and avoid overdiagnosis.

The application value of multi-parameter cystoscope in improving the accuracy of preoperative bladder cancer grading.

PURPOSE: To develop and validate a preoperative cystoscopic-based predictive model for predicting postoperative high-grade bladder cancer (BCa), which could be used to guide the surgical selection and postoperative treatment strategies. MATERIALS AND METHODS: We retrospectively recruited 366 patients with cystoscopy biopsy for pathology and morphology evaluation between October 2010 and January 2021. A binary logistic regression model was used to assess the risk factors for postoperative high-grade BCa. Diagnostic performance was analyzed by plotting receiver operating characteristic curve and calculating area under the curve (AUC), sensitivity, specificity. From January 2021 to July 2021, we collected 105 BCa prospectively to validate the model's accuracy. RESULTS: A total of 366 individuals who underwent transurethral resection of bladder tumor (TURBT) or radical cystectomy following cystoscopy biopsy were included for analysis. 261 (71.3%) had a biopsy pathology grade that was consistent with postoperative pathology grade. We discovered five cystoscopic parameters, including tumor diameter, site, non-pedicled, high-grade biopsy pathology, morphology, were associated with high-grade BCa. The established multi-parameter logistic regression model ("JSPH" model) revealed AUC was 0.917 (P < 0.001). Sensitivity and specificity were 86.2% and 84.0%, respectively. And the consistency of pre- and post-operative high-grade pathology was improved from biopsy-based 70.5% to JSPH model-based 85.2%. In a 105-patients prospective validation cohort, the consistency of pre- and post-operative high-grade pathology was increased from 63.1 to 84.2% after incorporation into JSPH model for prediction. CONCLUSION: The cystoscopic parameters based "JSPH model" is accurate at predicting postoperative pathological high-grade tumors prior to operations.

A comprehensive prostate biopsy standardization system according to quantitative multiparametric MRI and PSA value: P.R.O.S.T score.

BACKGROUND: Although most studies believe that systematic biopsy (SB) and targeted biopsy (TB) should be performed simultaneously in patients with suspected prostate cancer, we believe that patients with the Prostate Imaging-Reporting and Data System (PI-RADS) score of 4/5 may be able to perform TB only. METHODS: We retrospectively analyzed the pathological results of patients undergoing transperineal prostate biopsy with PI-RADS 4 and 5 in our center. We use the data from 2019 to 2020 as the training set to establish the prediction model and the data from 2021 as the verification set to test the effectiveness. Through stepwise logistics regression analysis, we integrate statistically significant clinical factors and establish a model to further predict whether the target area is tumor. RESULTS: The results showed that age (O), total number of lesions (T), histological region (R), PI-RADS score (S), and PSA density (P) were significantly correlated with the results of TB, and the formula was: p = 1/[1 + e^(- 11.387 + 0.058 × O + (- 0.736 × T) + 0.587 × R + 1.574 × S + 7.338 × P)]. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve of the prediction model was 0.840 (95% CI 0.802-0.877), with the optimal threshold of 0.762. And the corresponding specificity and sensitivity were 0.765 and 0.752. In the validation set, the AUC of the prediction model was 0.816 (95% CI 0.759-0.874), which means that it has good prediction efficiency. CONCLUSION: The P.R.O.S.T score can effectively screen PI-RADS 4/5 lesions, which may help physicians shunt patients who need prostate biopsy to reduce unnecessary systematic biopsies.

Diagnosis and Management of Primary Prostatic Signet Ring Cell Carcinoma: Single-Center Experience.

The purpose of the study was to retrospectively summarize the diagnosis and management of 10 primary prostatic signet ring cell carcinoma (PPSRCC) cases in our center. Ten PPSRCC patients diagnosed at the First Affiliated Hospital of Nanjing Medical University from November 2014 to December 2020 were included. Clinical characteristics, image features, therapeutic procedures, histological diagnosis, and outcomes were retrospectively analyzed. All patients received prostate-specific antigen (PSA) examination preoperatively. Nine of them accepted multiparametric magnetic resonance imaging (mpMRI) due to elevated PSA value, and further biopsied. Among them, five patients were diagnosed as prostatic adenocarcinoma and the other four cases were found a mixture of signet ring cell carcinoma (SRCC) and adenocarcinoma. Furthermore, gastrointestinal endoscope and abdominal computed tomography (CT) did not find SRCC originating in gastrointestinal tract. Therefore, these cases were considered to be PPSRCC. Nine patients accepted laparoscopic or robot-assisted RP. Only one patient with normal PSA adopted transurethral resection of the prostate. Postoperative pathological results confirmed SRCC mixed with prostatic adenocarcinoma in nine cases, and only one patient with pure SRCC. After surgery, nine patients received adjuvant hormone therapy, one of which accepted radiotherapy simultaneously. The patient with pure SRCC did not accept any adjuvant therapy postoperatively. During a mean follow-up of 31.9 months, only four patients were alive without disease progression. In summary, PPSRCC is a rare malignant tumor with few specific symptoms, rapid disease progression, and poor prognosis and is frequently accompanied by high-grade prostate adenocarcinoma patterns. There is still no clear and effective strategy to improve the prognosis.

A clinical available decision support scheme for optimizing prostate biopsy based on mpMRI.

BACKGROUND: Combined MRI/Ultrasound fusion targeted biopsy (TBx) and systematic biopsy (SBx) results in better prostate cancer (PCa) detection relative to either TBx or SBx alone, while at the cost of higher number of biopsy cores and greater detection of clinically insignificant PCa. We therefore developed and evaluated a simple decision support scheme for optimizing prostate biopsy based on multiparametric (mp) MRI assessment. METHODS: Total 229 patients with suspicion of PCa underwent mpMRI before combined TBx/SBx were retrospectively included. Impacts of MRI characteristics such as Prostate Imaging-Reporting and Data System (PI-RADS) score, lesion size, zonal origination, and location on biopsy performance were evaluated. A clinically available decision support scheme relying on mpMRI assessment was subsequently developed as a triage test to optimize prostate biopsy process. Cost (downgrade, upgrade, and biopsy core)-to-Effectiveness (detection rate) was systemically compared. RESULTS: TBx achieved comparable detection rate to combined TBx/SBx in diagnosis of PCa and clinically significant PCa (csPCa) (PCa, 59% [135/229] vs 60.7% [139/229]; csPCa, 45.9% [105/229] vs 47.2% [108/229]; p-values > 0.05) and outperformed SBx (PCa, 42.4% [97/229]; csPCa, 28.4% [65/229]; p-values < 0.001). Specially, in personalized decision support scheme, TBx accurately detected all PCa (72.5% [74/102]) in PI-RADS 5 and larger (≥1 cm) PI-RADS 3-4 observations, adding SBx to TBx only resulted in 1.4% (1/74) upgrading csPCa. For smaller (<1 cm) PI-RADS 3-4 lesions, combined TBx/SBx resulted in relatively higher detection rate (51.2% [65/127] vs 48.0% [61/127]) and lower upgrading rate (30.6% [15/49] vs 36.7% [18/49]) than TBx. CONCLUSIONS: The benefit of SBx added to TBx was largely restricted to smaller PI-RADS score 3-4 lesions. Using our personalized strategy of solo TBx for PI-RADS 5 and larger (≥1 cm) PI-RADS score 3-4 lesions would avoid excess SBx in 44.5% (102/229) of all biopsy-naïve patients without compromising detection rate.

Protective effect of rosuvastatin against the formation of benign esophageal stricture.

BACKGROUND: Benign esophageal strictures result from caustic or radiation injury or surgical procedures. Statins have anti-inflammatory and anti-fibrotic activities. We examined the role of rosuvastatin in preventing benign esophageal fibrosis and stricture formation in a rabbit model. METHODS: Twenty-six rabbits were assigned to control and rosuvastatin groups. The rabbits in the rosuvastatin group were administered rosuvastatin 5 mg/day, 2 weeks prior to the esophageal stricture phase. Esophageal strictures were established by applying 4% sodium hydroxide solution to the middle esophagus. Esophagography was performed to evaluate the degree of esophageal stenosis, and histopathologic assessment of esophageal tissue damage was performed with hematoxylin-eosin and Masson staining. The expressions of transforming growth factor-ß1 (TGF-ß1), connective tissue growth factor (CTGF), and α-smooth muscle actin (α-SMA) were examined by immunohistochemistry. RESULTS: The incidence of strictures was significantly lower in the rosuvastatin group. Esophagography demonstrated mild stenosis in the narrowest inner esophageal diameter in the rosuvastatin group than in the control group, and Masson staining demonstrated significantly less collagen deposition in the rosuvastatin group. In addition, immunohistochemistry results showed that the expressions of TGF-ß1, CTGF, and α-SMA significantly reduced in the rosuvastatin group. CONCLUSIONS: The present study demonstrated that rosuvastatin prevents benign esophageal stricture formation. This effect may be exerted through the anti-fibrotic activity of rosuvastatin, which may be exerted by the inhibition of CTGF and α-SMA production induced by TGF-ß1.

Clusterin suppresses invasion and metastasis of testicular seminoma by upregulating COL15a1.

Seminoma is the most common subtype of testicular germ cell tumor, with an increasing incidence worldwide. Clusterin (CLU) expression was found to be downregulated in testicular seminoma in our previous study. We now expanded the sample size, and further indicated that CLU expression correlates with tumor stage. Tcam-2 cell line was used to investigate the CLU function in testicular seminoma, and CLU was found to inhibit the proliferation and metastasis abilities. Besides, extracellular matrix protein COL15a1 was demonstrated as the downstream of CLU to affect the epithelial-mesenchymal transition (EMT) process via competitively binding to DDR1 with COL1A1 and inhibiting the phosphorylation of PYK2. MEF2A was found to interact with CLU and bind to the promoter of COL15a1 and so upregulate its expression. This is the first study using testicular xenografts in situ to simulate testicular seminoma metastatic and proliferative capacities. In conclusion, CLU acts as a tumor suppressor to inhibit the metastasis of testicular seminoma by interacting with MEF2A to upregulate COL15a1 and blocking the EMT process.

Longitudinal Multiparametric MRI Assessment of Irradiated Salivary Gland in a Rat Model: Correlated With Histological Findings.

BACKGROUND: Several magnetic resonance imaging (MRI) sequences have been applied to assess injured glands but without histological validation. PURPOSE: To evaluate longitudinal changes in multiparametric MRI (mp-MRI) of irradiated salivary glands in a rat model and investigate correlations between mp-MRI and histological findings. STUDY TYPE: Prospective. ANIMAL MODEL: Submandibular glands of 36 rats were radiated using a single dose of 15 Gy X-ray (irradiation [IR] group), and 6 other rats were enrolled into sham-IR group. mp-MRI were scanned 1 day after sham-IR (n = 6), or 1, 2, 4, 8, 12, 24 weeks after IR (n = 36, 6 per subgroup). FIELD STRENGTH/SEQUENCE: A 3.0-T/Diffusion-weighted imaging (DWI), readout-segmented echo-planar imaging (EPI) sequence; intravoxel incoherent motion DWI, single-shot EPI sequence; T1 mapping, dual-flip-angle gradient-echo sequence with volumetric interpolated breath-hold examination; T2 mapping, turbo spin-echo sequence. ASSESSMENT: Parameters including apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudo-diffusion coefficient (D* ), perfusion fraction (f), T1 and T2 value were obtained. Histological examinations, including hematoxylin and eosin staining (for acinar cell fraction [AC%] detection), Masson's trichrome staining (for degree of fibrosis [F%] determination) and CD34-immunohistochemical staining (for microvessel density [MVD] calculation), were performed at corresponding time points. STATISTICAL TESTS: One-way analysis of variance was used to compare the mp-MRI and histological parameters among different groups. Spearman correlation analysis was applied to determine the correlation between mp-MRI and histological parameters. Two-sided P ≤ 0.05 was considered statistically significant. RESULTS: Changes of mp-MRI parameters (ADC, D, D* , f, T1, T2) and histological results (AC%, F%, MVD) among the seven groups were all significant. ADC, D, and T2 values negatively correlated with AC% (ADC, r = -0.728; D, r = -0.773; T2, r = -0.600), f positively correlated with MVD (r = 0.496), and T1 values positively correlated with F% (r = 0.714). DATA CONCLUSION: mp-MRI might be able to noninvasively and quantitatively evaluate the dynamic pathological changes within the irradiated salivary glands. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Integration of clinicopathologic identification and deep transferrable image feature representation improves predictions of lymph node metastasis in prostate cancer.

BACKGROUND: Accurate identification of pelvic lymph node metastasis (PLNM) in patients with prostate cancer (PCa) is crucial for determining appropriate treatment options. Here, we built a PLNM-Risk calculator to obtain a precisely informed decision about whether to perform extended pelvic lymph node dissection (ePLND). METHODS: The PLNM-Risk calculator was developed in 280 patients and verified internally in 71 patients and externally in 50 patients by integrating a set of radiologists' interpretations, clinicopathological factors and newly refined imaging indicators from MR images with radiomics machine learning and deep transfer learning algorithms. Its clinical applicability was compared with Briganti and Memorial Sloan Kettering Cancer Center (MSKCC) nomograms. FINDINGS: The PLNM-Risk achieved good diagnostic discrimination with areas under the receiver operating characteristic curve (AUCs) of 0.93 (95% CI, 0.90-0.96), 0.92 (95% CI, 0.84-0.97) and 0.76 (95% CI, 0.62-0.87) in the training/validation, internal test and external test cohorts, respectively. If the number of ePLNDs missed was controlled at < 2%, PLNM-Risk provided both a higher number of ePLNDs spared (PLNM-Risk 59.6% vs MSKCC 44.9% vs Briganti 38.9%) and a lower number of false positives (PLNM-Risk 59.3% vs MSKCC 70.1% and Briganti 72.7%). In follow-up, patients stratified by the PLNM-Risk calculator showed significantly different biochemical recurrence rates after surgery. INTERPRETATION: The PLNM-Risk calculator offers a noninvasive clinical biomarker to predict PLNM for patients with PCa. It shows improved accuracy of diagnosis support and reduced overtreatment burdens for patients with findings suggestive of PCa. FUNDING: This work was supported by the Key Research and Development Program of Jiangsu Province (BE2017756) and the Suzhou Science and Technology Bureau-Science and Technology Demonstration Project (SS201808).

Artificial intelligence is a promising prospect for the detection of prostate cancer extracapsular extension with mpMRI: a two-center comparative study.

PURPOSE: A balance between preserving urinary continence as well as sexual potency and achieving negative surgical margins is of clinical relevance while implementary difficulty. Accurate detection of extracapsular extension (ECE) of prostate cancer (PCa) is thus crucial for determining appropriate treatment options. We aimed to develop and validate an artificial intelligence (AI)-based tool for detecting ECE of PCa using multiparametric magnetic resonance imaging (mpMRI). METHODS: Eight hundred and forty nine consecutive PCa patients who underwent mpMRI and prostatectomy without previous radio- or hormonal therapy from two medical centers were retrospectively included. The AI tool was built on a ResNeXt network embedded with a spatial attention map of experts' prior knowledge (PAGNet) from 596 training patients. Model validation was performed in 150 internal and 103 external patients. Performance comparison was made between AI, two experts using a criteria-based ECE grading system, and expert-AI interaction. RESULTS: An index PAGNet model using a single-slice image yielded the highest areas under the receiver operating characteristic curve (AUC) of 0.857 (95% confidence interval [CI], 0.827-0.884), 0.807 (95% CI, 0.735-0.867), and 0.728 (95% CI, 0.631-0.811) in training, internal, and external validation data, respectively. The performance of two experts (AUC, 0.632 to 0.741 vs 0.715 to 0.857) was lower (paired comparison, all p values < 0.05) than that of AI assessment. When experts' interpretations were adjusted by AI assessments, the performance of two experts was improved. CONCLUSION: Our AI tool, showing improved accuracy, offers a promising alternative to human experts for ECE staging using mpMRI.

Comfortable suture angle with optimized trocar position aids renorrhaphy during retroperitoneal laparoscopic partial nephrectomy.

BACKGROUND: This study investigated a comfortable suture angle (CSA) with optimized trocar position for closing the defect during renorrhaphy in retroperitoneal laparoscopic partial nephrectomy (LPN). The feasibility, usefulness, and safety of achieving the CSA with modified trocar position were determined for different tumor types. METHODS: Two optimized trocar positions were introduced for different tumor types. A suture angle was based on the tumor plane of the superficial parenchyma defect and the line formed by the needle holder. Preliminary surgical simulations determined a CSA that combined the least suture time with the greatest ease of performance. Achieving the CSA was attempted during renorrhaphy of 106 enrolled patients undergoing retroperitoneal LPN. Patients' characteristics, operative features, and follow-up information were collected and analyzed. RESULTS: For 89 (83.96%) patients, a CSA was successfully reached and parenchyma recovered. The remaining 17 patients were successfully sutured, but the attempt to achieve a CSA failed. For the CSA group, the suture, clamping, and overall operative times were significantly less than that of the non-CSA patients. The groups were similar regarding estimated blood loss, positive surgical margin, and rates of glomerular filtration reduction and complications. Univariable analyses determined that tumor location, growth pattern, and R.E.N.A.L. nephrometry score (RNS) may influence the success of this approach. Multivariable analyses indicated that only tumor location and RNS were independent factors affecting successful achievement of the CSA. CONCLUSIONS: Through different kidney position changes, the CSA could be used to ease the suture process. It is feasible and safe to perform a CSA with optimized trocar position during LPN. Tumor location and RNS may influence the approach to get a CSA.