Radical Prostatectomy Without Prior Biopsy in Selected Patients Evaluated by 18F-Labeled Prostate-Specific Membrane Antigen-Ligand Positron Emission Tomography/Computed Tomography and Multiparameter Magnetic Resonance Imaging: A Single-Center, Prospective, Single-Arm Trial.

PURPOSE: This study aimed to verify the feasibility and short-term prognosis of prostatectomy without biopsy. MATERIALS AND METHODS: Patients with a rising PSA level ranging from 4 to 30 ng/mL were scheduled for multiparametric (mp) MRI and 18F-labeled prostate-specific membrane antigen (PSMA) positron emission tomography (PET). Forty-seven patients (cT2N0M0) with Prostate Imaging Reporting and Data System ≥ 4 and molecular imaging PSMA score ≥ 2 were enrolled. All candidates underwent robot-assisted laparoscopic radical prostatectomy without biopsy. Prostate cancer detection rate, index tumors localization correspondence rate, positive surgical margin, complications, postoperative hospital stay, and PSA level in a 6-week postoperative follow-up visit were collected. RESULTS: All the patients with positive mpMRI and PSMA PET were diagnosed with clinically significant prostate cancer. A total of 80 lesions were verified as cancer by pathology, of which 63 cancer lesions were clinically significant prostate cancer. Fifty-one lesions were simultaneously found by mpMRI and PSMA PET. A total of 23 lesions were invisible on either image, and all lesions were ≤ International Society of Urological Pathology 2 or ≤ 15 mm. Forty-five (95.7%) index tumors found by mpMRI combined with PSMA PET were consistent with pathology. Nine patients reported positive surgical margin. CONCLUSIONS: Biopsy-free prostatectomy is safe and feasible for patients with evaluation strictly by mpMRI combined with 18F-PSMA PET/CT.

Diagnostic Value of Clear Cell Likelihood Score v1.0 and v2.0 for Common Subtypes of Small Renal Masses: A Multicenter Comparative Study.

BACKGROUND: Clear cell likelihood score (ccLS) is reliable for diagnosing small renal masses (SRMs). However, the diagnostic value of Clear cell likelihood score version 1.0 (ccLS v1.0) and v2.0 for common subtypes of SRMs might be a potential score extension. PURPOSE: To compare the diagnostic performance and interobserver agreement of ccLS v1.0 and v2.0 for characterizing five common subtypes of SRMs. STUDY TYPE: Retrospective. POPULATION: 797 patients (563 males, 234 females; mean age, 53 ± 12 years) with 867 histologically proven renal masses. FIELD STRENGTH/SEQUENCES: 3.0 and 1.5 T/T2 weighted imaging, T1 weighted imaging, diffusion-weighted imaging, a dual-echo chemical shift (in- and opposed-phase) T1 weighted imaging, multiphase dynamic contrast-enhanced imaging. ASSESSMENT: Six abdominal radiologists were trained in the ccLS algorithm and independently scored each SRM using ccLS v1.0 and v2.0, respectively. All SRMs had definite pathological results. The pooled area under curve (AUC), accuracy, sensitivity, and specificity were calculated to evaluate the diagnostic performance of ccLS v1.0 and v2.0 for characterizing common subtypes of SRMs. The average κ values were calculated to evaluate the interobserver agreement of the two scoring versions. STATISTICAL TESTS: Random-effects logistic regression; Receiver operating characteristic analysis; DeLong test; Weighted Kappa test; Z test. The statistical significance level was P < 0.05. RESULTS: The pooled AUCs of clear cell likelihood score version 2.0 (ccLS v2.0) were statistically superior to those of ccLS v1.0 for diagnosing clear cell renal cell carcinoma (ccRCC) (0.907 vs. 0.851), papillary renal cell carcinoma (pRCC) (0.926 vs. 0.888), renal oncocytoma (RO) (0.745 vs. 0.679), and angiomyolipoma without visible fat (AMLwvf) (0.826 vs. 0.766). Interobserver agreement for SRMs between ccLS v1.0 and v2.0 is comparable and was not statistically significant (P = 0.993). CONCLUSION: The diagnostic performance of ccLS v2.0 surpasses that of ccLS v1.0 for characterizing ccRCC, pRCC, RO, and AMLwvf. Especially, the standardized algorithm has optimal performance for ccRCC and pRCC. ccLS has potential as a supportive clinical tool. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 2.

Differentiation between renal epithelioid angiomyolipoma and clear cell renal cell carcinoma using clear cell likelihood score.

PURPOSE: Clear cell likelihood score (ccLS) may be a reliable diagnostic method for distinguishing renal epithelioid angiomyolipoma (EAML) and clear cell renal cell carcinoma (ccRCC). In this study, we aim to explore the value of ccLS in differentiating EAML from ccRCC. METHODS: We performed a retrospective analysis in which 27 EAML patients and 60 ccRCC patients underwent preoperative magnetic resonance imaging (MRI) at our institution. Two radiologists trained in the ccLS algorithm scored independently and the consistency of their interpretation was evaluated. The difference of the ccLS score was compared between EAML and ccRCC in the whole study cohort and two subgroups [small renal masses (SRM; ≤ 4 cm) and large renal masses (LRM; > 4 cm)]. RESULTS: In total, 87 patients (59 men, 28 women; mean age, 55±11 years) with 90 renal masses (EAML: ccRCC = 1: 2) were identified. The interobserver agreement of two radiologists for the ccLS system to differentiate EAML from ccRCC was good (k = 0.71). The ccLS score in the EAML group and the ccRCC group ranged from 1 to 5 (73.3% in scores 1-2) and 2 to 5 (76.7% in scores 4-5), respectively, with statistically significant differences (P < 0.001). With the threshold value of 2, ccLS can distinguish EAML from ccRCC with the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 87.8%, 95.0%, 73.3%, 87.7%, and 88.0%, respectively. The AUC (area under the curve) was 0.913. And the distribution of the ccLS score between the two diseases was not affected by tumor size (P = 0.780). CONCLUSION: The ccLS can distinguish EAML from ccRCC with high accuracy and efficiency.

Tuning charge density of chimeric antigen receptor optimizes tonic signaling and CAR-T cell fitness.

Tonic signaling of chimeric antigen receptor (CAR), i.e., the spontaneous CAR activation in the absence of tumor antigen stimulation, is considered to be a pivotal event controlling CAR-T efficacy. However, the molecular mechanism underlying the spontaneous CAR signals remains elusive. Here, we unveil that positively charged patches (PCPs) on the surface of the CAR antigen-binding domain mediate CAR clustering and result in CAR tonic signaling. For CARs with high tonic signaling (e.g., GD2.CAR and CSPG4.CAR), reducing PCPs on CARs or boosting ionic strength in the culture medium during ex vivo CAR-T cell expansion minimizes spontaneous CAR activation and alleviates CAR-T cell exhaustion. In contrast, introducing PCPs into the CAR with weak tonic signaling, such as CD19.CAR, results in improved in vivo persistence and superior antitumor function. These results demonstrate that CAR tonic signaling is induced and maintained by PCP-mediated CAR clustering. Notably, the mutations we generated to alter the PCPs maintain the antigen-binding affinity and specificity of the CAR. Therefore, our findings suggest that the rational tuning of PCPs to optimize tonic signaling and in vivo fitness of CAR-T cells is a promising design strategy for the next-generation CAR.

Validation of the Nottingham Hip Fracture Score in Predicting Postoperative Outcomes Following Hip Fracture Surgery.

OBJECTIVE: Although several prognostic models have been developed for patients who underwent hip fracture surgery, their preoperative performance was insufficiently validated. We aimed to verify the effectiveness of the Nottingham Hip Fracture Score (NHFS) for predicting postoperative outcomes following hip fracture surgery. METHODS: This was a single-center and retrospective analysis. A total of 702 elderly patients with hip fractures (age ≥ 65 years old) who received treatment in our hospital from June 2020 to August 2021 were selected as the research participants. They were divided into the survival group and the death group based on their survival 30 days after surgery. The multivariate logistic regression model was used to identify the independent risk factors for the 30-day mortality after surgery. The NHFS and American Society of Anaesthesiologists (ASA) grades were used to construct these models, and a receiver operating characteristic curve was plotted to assess their diagnostic significance. A correlation analysis was performed between NHFS and length of hospitalization and mobility 3 months after surgery. RESULTS: There were significant differences in the age, albumin level, NHFS, and ASA grade between both groups (p < 0.05). The length of hospitalization in the death group was longer than the survival group (p < 0.05). The perioperative blood transfusion and postoperative ICU transfer rates in the death group were higher than in the survival group (p < 0.05). The death group's incidence of pulmonary infections, urinary tract infections, cardiovascular events, pressure ulcers, stress ulcers with bleeding, and intestinal obstruction was higher than the survival group (p < 0.05). The NHFS and ASA III were independent risk factors for the 30-day mortality after surgery, regardless of age and albumin level (p < 0.05). The area under the curve (AUC) of the NHFS and ASA grade for predicting the 30-day mortality after surgery was 0.791 (95% confidence interval [CI] 0.709-0.873, p < 0.05) and 0.621 (95% CI 0.477-0.764, p > 0.05), respectively. The NHFS positively correlated with hospitalization length and mobility grade 3 months after surgery (p < 0.05). CONCLUSION: The NHFS demonstrated a better predictive performance than the ASA score for the 30-day mortality after surgery and positively correlated with the hospitalization length and postoperative activity limitation in elderly patients with hip fractures.

Diversity and distribution variation of urban spontaneous vegetation with distinct frequencies along river corridors in a fast-growing city.

River corridors are vital to urban ecology, regulating climate and providing habitats for animals. Spontaneous plants naturally colonize various spaces therein, where they play important roles. Previous studies have explored many factors driving spontaneous plant diversity at the city scale and in specific habitats. However, we lack a holistic understanding of the diversity and distribution of variation of spontaneous vegetation that directly reflects the effects of urbanization. We conducted a field study of 1250 sample plots along river corridors in Chengdu, a fast-growing city in China, and the spontaneous plants in fifteen microhabitat types were surveyed. Diversity and distribution patterns were examined for species with distinct dispersal abilities. There was a far greater richness of occasional species compared to dominant and common species, but occasional species were markedly less abundant. Vacant lots and natural riverbanks harbored the most species, but revetment walls and lawns also supported a considerable number of species, especially in the city center. Species diversity among different urban areas was strongly related to microhabitat conditions. The proportions of dominant, common, and occasional species varied among communities. In communities on vacant lots of less urbanized areas, the richness of dominant species was greater, whereas in green spaces created by planted vegetation, occasional species were more diverse. Green space microenvironments are hospitable to some rare species. Urbanization and microhabitats have co-effects and thus ultimately determine diversity and distribution patterns. Such patterns, if linked to ecological and ornamental value, can provide a new perspective and nature-based solutions to urban rewilding and landscape design.

Carbon/Basalt Fibers Hybrid Composites: Hybrid Design and the Application in Automobile Engine Hood.

The low-velocity impact properties and the optimal hybrid ratio range for improving the property of hybrid composites are studied, and the application of hybrid composites in automobile engine hoods is discussed in this paper. The low-velocity impact properties of the hybrid composite material are simulated under different stacking sequences and hybrid ratios by finite element simulation, and the accuracy of the finite element model (FEM) is verified through experiments. Increasing the proportion of carbon fiber (CF) in the hybrid layer and placing the basalt fiber (BF) on the compression side can improve the energy absorption capacity under low-velocity impact loads. CF/BF hybrid composite hoods are optimized based on the steel hood and the low-velocity impact performance of the hybrid composite. The BCCC layer absorbs the most energy under low-velocity impact loads. Compared with CFRP, the energy absorbed under 10 J and 20 J impact energy is increased by 26.1% and 14.2%, respectively. Through the low-velocity impact properties of hybrid composites, we found that placing BF on the side of the load and keep the ratio below 50%, while increasing the proportion of CF in the hybrid laminate can significantly improve the property of the hybrid laminate. The results show that the stiffness and modal properties of the hybrid composite can meet the design index requirements, and the pedestrian protection capability of the hood will also increase with the increase in the proportion of BF.

Triblock Copolymer Compatibilizers for Enhancing the Mechanical Properties of a Renewable Bio-Polymer.

Poly(lactic acid) (PLA) is an emerging plastic that has insufficient properties (e.g., it is too brittle) for widespread commercial use. Previous research results have shown that the strength and toughness of basalt fiber reinforced PLA composites (PLA/BF) still need to be improved. To address this limitation, this study aimed to obtain an effective compatibilizer for PLA/BF. Melt-blending of poly(butylene adipate-co-terephthalate) (PBAT) with PLA in the presence of 4,4'-methylene diphenyl diisocyanate (MDI: 0.5 wt% of the total resin) afforded PLA/PBAT-MDI triblock copolymers. The triblock copolymers were melt-blended to improve the interfacial adhesion of PLA/BF and thus obtain excellent performance of the PLA-ternary polymers. This work presents the first investigation on the effects of PLA/PBAT-MDI triblock copolymers as compatibilizers for PLA/BF blends. The resultant mechanics, the morphology, interface, crystallinity, and thermal stability of the PLA-bio polymers were comprehensively examined via standard characterization techniques. The crystallinity of the PLA-ternary polymers was as high as 43.6%, 1.44× that of PLA/BF, and 163.5% higher than that of pure PLA. The stored energy of the PLA-ternary polymers reached 20,306.2 MPa, 5.5× than that of PLA/BF, and 18.6× of pure PLA. Moreover, the fatigue life of the PLA-ternary polymers was substantially improved, 5.85× than that of PLA/PBAT-MDI triblock copolymers. Thus, the PLA/PBAT-MDI triblock copolymers are compatibilizers that improve the mechanical properties of PLA/BF.

Exendin-4 promotes proliferation of adipose-derived stem cells through ERK and JNK signaling pathways.

Adipose-derived stem cell (ADSC) transplantation has emerged as a potential tool for the treatment of cardiovascular disease. However, with a limited renewal capacity and the need for mass cells during the engraftment, strategies are needed to enhance ADSC proliferative capacity. In this study, we explored the effects of exendin-4 (Ex-4), a glucagon-like peptide-1 analog, on the growth of ADSCs, focusing in particular on c-Jun NH2-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) signaling pathways. Firstly, ADSCs were isolated and cultured in vitro. Then, flow cytometry demonstrated that ADSCs were positive for CD90 and CD29 but negative for CD31, CD34, and CD45. Ex-4 (0-50 nM) treatment increased ADSC proliferation in a dose-dependent manner but had no effects on stem cell markers of ADSCs. Moreover, we found that Ex-4 treatment elevated the phosphorylation levels of the JNK and ERK signaling pathways. Furthermore, utilization of Ex-4 also promoted cyclin D1 and cyclin E protein expression, which was accompanied by more Edu(+) cells and a higher percentage of cells in the S-phase of the cell cycle after Ex-4 treatment. In parallel, the application of inhibitors SP600125 and PD98059, inhibitors of the JNK and ERK signaling pathways, respectively, not only reversed such effects of Ex-4 on JNK and ERK but also resulted in lower percentages of S-phase cells and fewer numbers of Edu(+) cells. In summary, Ex-4 has no effects on stem cell markers in ADSCs but promotes ADSC growth via JNK and ERK signaling pathways.

Transurethral front-firing Greenlight bladder autoaugmentation for bladder contracture: technique and clinical outcomes.

OBJECTIVE: To describe a novel transurethral front-firing Greenlight bladder autoaugmentation for the treatment of bladder contracture and report initial clinical outcomes. METHODS: Between April 2014 and August 2015, five patients diagnosed with contracted bladder were all refractory to conservative treatment and received novel transurethral autoaugmentation. CT scan and urodynamics examination were conducted before operation for disease assessment. Mucosal and muscular layers of bladder wall in fundus were incised vertically and horizontally with front-firing Greenlight laser to enlarge bladder capacity in the operation. Imaging examination and periodical urodynamics study were performed to evaluate the clinical outcomes of the procedure in postoperative follow-up. RESULTS: Transurethral front-firing Greenlight bladder autoaugmentation was performed successfully on all the patients. The mean operative time was 59 min (range 52-65 min) with no significant blood loss. Urodynamic parameters of these patients after operation improved significantly compared with those before operation. Average maximum cystometric capacity (Vmax) increased from 91.2 to 333 ml (p < 0.01), average maximum flow rate (Qmax) ascended from 12.6 to 18.62 ml/min (p < 0.01), and average flow rate (Q(ave)) also increased from 5.74 to 13.18 ml/min (p < 0.01). At the last follow-up, all the patients could void spontaneously with good bladder emptying and their symptoms improved significantly. CONCLUSION: Our novel transurethral front-firing Greenlight bladder autoaugmentation is a safe and effective treatment for contracted bladders. Future studies with larger sample size and long-term follow-up are needed to confirm our findings.

Expression of tumor necrosis factor receptor-associated protein 1 and its clinical significance in kidney cancer.

OBJECTIVE: To investigate the expression and clinical significance of TRAP1 (tumor necrosis factor receptor-associated protein 1) in kidney cancer. METHODS: TRAP1 expression was detected in kidney cancer and normal kidney tissues by qRT-PCR and immunohistochemistry (IHC), respectively. Then, the correlation of TRAP1 expression with clinicopathological characters and patients' prognosis was evaluated in kidney cancer. RESULTS: IHC results revealed that the high-expression rates of TRAP1 in kidney cancer tissues and normal kidney tissues were 51.3% (41/80), 23.3% (7/30), and the difference was statistically significant (P=0.01). Also, TRAP1 mRNA level in kidney cancer was found to be significantly greater compared with those in normal kidney by qRT-PCR. In addition, TRAP1 expression in kidney cancer significantly correlated with lymph node metastasis and clinical stage (P<0.05). Kaplan-Meier survival analysis indicated that the mean survival time of patients with TRAP1 low-expression was significantly higher (56 months) than those patients with TRAP1 high-expression (47 months). Meanwhile, Kaplan-Meier and Cox survival analysis indicated that TRAP1, lymph node metastasis and clinical stage were correlated with patients' prognosis. CONCLUSION: TRAP1 is highly expressed in kidney cancer and correlates with patients prognosis, which may be served as a potential marker for the diagnosis and treatment of kidney cancer.

Comparison of graft healing in anterior cruciate ligament reconstruction with and without a preserved remnant in rabbits.

BACKGROUND: The remnant of the native anterior cruciate ligament (ACL) might contribute to the biological integration of the graft in ACL reconstruction. The aim of this study was to explore whether the preserved remnant enhanced graft healing in ACL reconstruction. METHODS: Forty New Zealand rabbits underwent bilateral anterior cruciate ligament reconstructions. One knee was treated with a 2-mm remnant preserved on the tibial side (remnant-preservation, RP group) while the contralateral knee underwent a complete removal of the remnants by cauterization (remnant-resection, RR group) in each animal. Gross observations combined with microangiography, histological evaluation, and uniaxial load testing were performed after 4, 8, and 12weeks. RESULTS: The vascular density on the graft surface was statistically higher in the RP group as compared to that of the RR group at 4 (P=0.002) and 8weeks (P=0.020). Additionally, the accelerated intra-articular and intra-tunnel graft integration were histologically observed in the RP group. Histological scores in the RP group were statistically higher than the RR group at 4weeks (P=0.028 for the intra-articular healing and P=0.046 for the intra-tunnel healing) and 8weeks (P=0.031 for the intra-articular healing and P=0.014 for the intra-tunnel healing). The ultimate failure load (P=0.017), yield load (P=0.025), and stiffness (P=0.004) were statistically higher in the RP group as compared to those of the RR group, with corresponding significant differences in the failure mode (P=0.020) between the two groups at 8weeks. CONCLUSIONS: The preserved remnant enhanced ACL graft healing with improved biomechanical properties in the rabbit model. LEVEL OF EVIDENCE: Level II.

[Paratesticular embryonal rhabdomyosarcoma: report of 5 cases and review of the literature].

OBJECTIVE: To improve the diagnosis and treatment of paratesticular embryonal rhabdomyosarcoma (PER). METHODS: We retrospectively studied the clinical data of 5 cases of PER treated from 1997 to 2009 and reviewed the relevant literature, focusing on its clinical manifestations, diagnosis and treatment. RESULTS: The 5 cases of PER, 2 involving the spermatic cord, 2 the testis and 1 the tunica vaginalis, were all treated by radical orchiectomy. Pathologically, 2 cases were classified as stage I, 1 as stage II and 2 as stage IV. Postoperatively, 2 of the patients received chemotherapy and the other 3 refused adjunctive therapy. The patients were followed up for 6, 12, 18 and 28 months, respectively. Four of them remained free from relapse and metastasis, and 1 stage IV patient died of multiple metastasis at 6 months. CONCLUSION: Early diagnosis, radical orchiectomy and adjunctive chemo- or radio-therapy are effective means to the treatment of PER.