Preparation and brain targeting effects study of recombinant human ferritin nanoparticles.

Human heavy-chain ferritin is a naturally occurring protein with high stability and multifunctionality in biological systems. This study aims to utilize a prokaryotic expression system to produce recombinant human heavy-chain ferritin nanoparticles and investigate their targeting ability in brain tissue. The human heavy-chain ferritin gene was cloned into the prokaryotic expression vector pET28a and transformed into Escherichia coli BL21 (DE3) competent cells to explore optimal expression conditions. The recombinant protein was then purified to evaluate its immunoreactivity and characteristics. Additionally, the distribution of the administered protein in normal mice and its permeability in an in vitro blood-brain barrier (BBB) model were measured. The results demonstrate that the purified protein can self-assemble extracellularly into nano-cage structures of approximately 10 nm and is recognized by corresponding antibodies. The protein effectively penetrates the blood-brain barrier and exhibits slow clearance in mouse brain tissue, showing excellent permeability in the in vitro BBB model. This study highlights the stable expression of recombinant human heavy-chain ferritin using the Escherichia coli prokaryotic expression system, characterized by favorable nano-cage structures and biological activity. Its exceptional brain tissue targeting and slow metabolism lay an experimental foundation for its application in neuropharmaceutical delivery and vaccine development fields.

Impaired TFEB-mediated autophagy-lysosome fusion promotes tubular cell cycle G2/M arrest and renal fibrosis by suppressing ATP6V0C expression and interacting with SNAREs.

Increasing evidence suggests that autophagy plays a major role during renal fibrosis. Transcription factor EB (TFEB) is a critical regulator of autophagy- and lysosome-related gene transcription. However, the pathophysiological roles of TFEB in renal fibrosis and fine-tuned mechanisms by which TFEB regulates fibrosis remain largely unknown. Here, we found that TFEB was downregulated in unilateral ureteral obstruction (UUO)-induced human and mouse fibrotic kidneys, and kidney-specific TFEB overexpression using recombinant AAV serotype 9 (rAAV9)-TFEB in UUO mice alleviated renal fibrosis pathogenesis. Mechanically, we found that TFEB's prevention of extracellular matrix (ECM) deposition depended on autophagic flux integrity and its subsequent blockade of G2/M arrest in tubular cells, rather than the autophagosome synthesis. In addition, we together RNA-seq with CUT&Tag analysis to determine the TFEB targeted gene ATP6V0C, and revealed that TFEB was directly bound to the ATP6V0C promoter only at specific site to promote its expression through CUT&Run-qPCR and luciferase reporter assay. Interestingly, TFEB induced autophagic flux integrity, mainly dependent on scaffold protein ATP6V0C-mediated autophagosome-lysosome fusion by bridging with STX17 and VAMP8 (major SNARE complex) by co-immunoprecipitation analysis, rather than its mediated lysosomal acidification and degradation function. Moreover, we further investigated the underlying mechanism behind the low expression of TEFB in UUO-induced renal fibrosis, and clearly revealed that TFEB suppression in fibrotic kidney was due to DNMT3a-associated TFEB promoter hypermethylation by utilizing methylation specific PCR (MSP) and bisulfite-sequencing PCR (BSP), which could be effectively recovered by 5-Aza-2'-deoxycytidine (5A-za) to alleviate renal fibrosis pathogenesis. These findings reveal for the first time that impaired TFEB-mediated autophagosome-lysosome fusion disorder, tubular cell G2/M arrest and renal fibrosis appear to be sequentially linked in UUO-induced renal fibrosis and suggest that DNMT3a/TFEB/ATP6V0C may serve as potential therapeutic targets to prevent renal fibrosis.

Lipid concomitant γ-oryzanol decreased oil absorbency of French fries by changing the microstructure of French fries and physical properties of frying oil.

BACKGROUND: The aim of this research was to evaluate the possibility of lipid concomitant γ-oryzanol reducing oil absorbency of fried foods and the underlying mechanism. Therefore, the influence of γ-oryzanol on moisture and oil content, and distribution and micromorphology of French fries and the viscosity, fatty acid composition and total polar compounds content of rice bran oil (RBO) after frying were studied. RESULTS: Our results showed that the incorporation of low concentration of γ-oryzanol [low addition group (LAG)] (5.754 g/kg) decreased the oil absorbency and porous structure of French fries during frying. Additionally, LAG incorporation inhibited the degradation of linoleic acid, decreased the growth rate of saturated fatty acids, total polar compounds and viscosity of frying oil. CONCLUSIONS: Consequently, it was recommended to incorporate a small amount of γ-oryzanol in frying oil because it could inhibit oil absorption behavior of French fries. © 2023 Society of Chemical Industry.

Detection of the CD8+ T cell immune response in mice infected with OVA-Listeriamonocytogenes.

T cells are able to recognize and kill pathogens that infect host cells, including bacteria, viruses, and tumor cells. Here, we present a protocol to detect T cell function and bacterial load in OVA-Listeria monocytogenes-infected mice. We provide a detailed description of the steps for detecting OVA-specific CD8+ T cells and their cytokine expression levels in splenocytes using flow cytometry on day 7 after infecting mice with OVA-Listeriamonocytogenes. Additionally, we describe the steps for detecting the OVA-Listeriamonocytogenes load in the mouse liver. For complete details on the use and execution of this protocol, please refer to Chen et al.1.

Improved spatial-temporal graph convolutional networks for upper limb rehabilitation assessment based on precise posture measurement.

After regular rehabilitation training, paralysis sequelae can be significantly reduced in patients with limb movement disorders caused by stroke. Rehabilitation assessment is the basis for the formulation of rehabilitation training programs and the objective standard for evaluating the effectiveness of training. However, the quantitative rehabilitation assessment is still in the experimental stage and has not been put into clinical practice. In this work, we propose improved spatial-temporal graph convolutional networks based on precise posture measurement for upper limb rehabilitation assessment. Two Azure Kinect are used to enlarge the angle range of the visual field. The rigid body model of the upper limb with multiple degrees of freedom is established. And the inverse kinematics is optimized based on the hybrid particle swarm optimization algorithm. The self-attention mechanism map is calculated to analyze the role of each upper limb joint in rehabilitation assessment, to improve the spatial-temporal graph convolution neural network model. Long short-term memory is built to explore the sequence dependence in spatial-temporal feature vectors. An exercise protocol for detecting the distal reachable workspace and proximal self-care ability of the upper limb is designed, and a virtual environment is built. The experimental results indicate that the proposed posture measurement method can reduce position jumps caused by occlusion, improve measurement accuracy and stability, and increase Signal Noise Ratio. By comparing with other models, our rehabilitation assessment model achieved the lowest mean absolute deviation, root mean square error, and mean absolute percentage error. The proposed method can effectively quantitatively evaluate the upper limb motor function of stroke patients.

Frailty as a risk marker of adverse lower urinary symptom outcomes in patients with benign prostatic hyperplasia undergoing transurethral resection of prostate.

Purpose: Lower urinary symptoms (LUTS) may persist in a proportion of patients with benign prostatic hyperplasia (BPH) following transurethral resection of prostate (TURP), which is a major cause of reduced quality-of-life. We aimed to investigate the effect of frailty on LUTS in patients with BPH treated with TURP. Methods: We longitudinally evaluated LUTS and health-related quality-of-life (HRQOL) in patients with BPH treated with TURP from February 2019 and January 2022 using International Prostate Symptom Score (IPSS) and Short Form-8 (SF-8), respectively. Patients were divided into frail and non-frail groups according to the Fried phenotype (FP). The primary purpose was comparing the outcomes of LUTS and HRQOL between two groups. Secondary purposes were investigating the frailty as a preoperative predictor of postoperative adverse LUTS outcomes following TURP using logistic regression analysis. A 1:2 propensity score matching (PSM) was performed to reduce the effects of selection bias and potential confounders. Results: Of the 567 patients enrolled, 495 (87.3%) patients were non-frail (FP = 0-2), and the remaining 72 (12.7%) patients were classified into the frail group. There were no significant differences in body mass index (BMI), urine white blood cell (UWBC), creatinine, prostate-specific antigen (PSA) and prostate volume in both groups at baseline (all p > 0.05). However, patients with frailty were older, higher comorbidity rates, lower peak flow rates and lower HRQOL. In the frail group, although LUTS and HRQOL at 6 months following TURP improved significantly compared to those at baseline, it did not show a significant improvement compared with the non-frail group (both p < 0.001). Moreover, multivariable logistic regression analysis demonstrated that preoperative frailty was significantly associated with poor LUTS improvement in both the entire cohort and PSM subset (both p < 0.05), whereas age and comorbidities were not after PSM analysis. Conclusion: In patients with frail or non-frail, TURP for BPH provides overall good results. However, frail individuals are at higher risk of postoperative adverse LUTS outcomes. Frailty has the potential to be a strong objective tool for risk stratification and should be considered during the perioperative evaluation.

Recent Advances in Imaging Agents Anchored with pH (Low) Insertion Peptides for Cancer Theranostics.

The acidic extracellular microenvironment has become an effective target for diagnosing and treating tumors. A pH (low) insertion peptide (pHLIP) is a kind of peptide that can spontaneously fold into a transmembrane helix in an acidic microenvironment, and then insert into and cross the cell membrane for material transfer. The characteristics of the acidic tumor microenvironment provide a new method for pH-targeted molecular imaging and tumor-targeted therapy. As research has increased, the role of pHLIP as an imaging agent carrier in the field of tumor theranostics has become increasingly prominent. In this paper, we describe the current applications of pHLIP-anchored imaging agents for tumor diagnosis and treatment in terms of different molecular imaging methods, including magnetic resonance T1 imaging, magnetic resonance T2 imaging, SPECT/PET, fluorescence imaging, and photoacoustic imaging. Additionally, we discuss relevant challenges and future development prospects.

Hypertension Resolution after Laparoscopic Adrenal Tumor Resection in Patients of Adrenal Incidentaloma with Normal Hormone Levels.

INTRODUCTION: Postoperative hypertension resolution among patients with adrenal incidentalomas and normal hormone levels was unknown. Identifying the predictive factors was beneficial to the management of adrenal incidentalomas. METHODS: We conducted a retrospective cohort study, recruiting patients undergoing laparoscopic adrenal tumor resection for adrenal incidentaloma with hypertension and normal hormone levels. Demographic, clinical, treatment, and laboratory data were collected and compared. We used univariable and multivariable logistic regression methods to identify the predictive factors of postoperative hypertension resolution. RESULTS: Of the 171 patients in our study, 130 (76.0%) patients performed a resolution of hypertension, and 57 (33.3%) patients had a significant reduction. Multivariate logistic regression analysis showed that the male sex (odds ratio (OR) 0.305, 95% confidence interval (CI): 0.098-0.948, p = 0.040), body mass index (BMI) (OR 0.973, 95% CI: 0.670-0.938, p = 0.007), aldosterone and plasma renin activity ratio (APR) in erect position (OR 1.206, 95% CI: 1.042-1.397, p = 0.012), and preoperative systolic pressure (OR 1.044, 95% CI: 1.009-1.080, p = 0.014), were significantly associated with the outcomes of hypertension resolution. DISCUSSION/CONCLUSION: Adrenal incidentalomas patients with hypertension and normal hormone levels would perform hypertension resolution after laparoscopic adrenal tumor resection, especially for females with low BMI, high preoperative systolic blood pressure, and high APR (erect position).

Evaluation of a questionnaire as a screening tool for benign paroxysmal position vertigo.

OBJECTIVE: To determine the value of a questionnaire as a screening tool for benign paroxysmal position vertigo (BPPV). STUDY DESIGN: Retrospective chart review. SETTING: Tertiary care centers. METHODS: A total of 520 vertigo adults completed the questionnaire before the diagnosis was confirmed. After vestibular function examination and other diagnostic examination, the diagnosis of all participants was confirmed by experts. By validating valuable items from the questionnaire with 47 items, a new questionnaire of 5 items was formed to quickly diagnose BPPV. The internal consistency of the new questionnaire and validity were evaluated. The correlation between the score obtained from the new questionnaire and diagnosis was investigated. The mean score was also compared between groups with and without BPPV and diagnostic precision measures were calculated. RESULTS: 520 vertigo participants answered all the question completely and BPPV was identified in 138 participants (26.5%). The responses to questionnaire revealed preferable reproducibility (r = 0.898, P < 0.05) and internal consistency (Cronbach's α = 0.702) as well as the validity (Kaiser-Meyer-Olkin, KMO = 0.731). The higher the individual score, the more likely to be BPPV (B = 2.082; P < 0.05). The mean score of answers was greater in the group with a clinical diagnosis of BPPV compared to those without BPPV (F = 58.459, P < 0.05). The sensitivity of the screening tool was 92.8% and specificity was 88.5%, with an area under the ROC curve of 0.946 (95% confidence interval 0.926-0.965; P < 0.05). CONCLUSION: The questionnaire proved to be of great value to screen for individuals with possible BPPV.

Development of Hydroxamate Derivatives Containing a Pyrazoline Moiety as APN Inhibitors to Overcome Angiogenesis.

Aminopeptidase N (APN) was closely associated with cancer invasion, metastasis, and angiogenesis. Therefore, APN inhibitors have attracted more and more attention of scientists as antitumor agents. In the current study, we designed, synthesized, and evaluated one new series of pyrazoline-based hydroxamate derivatives as APN inhibitors. Moreover, the structure-activity relationships of those were discussed in detail. 2,6-Dichloro substituted compound 14o with R1 = CH3, showed the best capacity for inhibiting APN with an IC50 value of 0.0062 ± 0.0004 µM, which was three orders of magnitude better than that of the positive control bestatin. Compound 14o possessed both potent anti-proliferative activities against tumor cells and potent anti-angiogenic activity. At the same concentration of 50 µM, compound 14o exhibited much better capacity for inhibiting the micro-vessel growth relative to bestatin in the rat thoracic aorta ring model. Additionally, the putative interactions of 14o with the active site of APN are also discussed. The hydroxamate moiety chelated the zinc ion and formed four hydrogen bonds with His297, Glu298 and His301. Meanwhile, the terminal phenyl group and another phenyl group of 14o interacted with S2' and S1 pockets via hydrophobic effects, respectively.

Vulnerable frequency as an independent prognostic factor for sudden sensorineural hearing loss.

Objectives: Sudden sensorineural hearing loss (SSNHL) is a common otology emergency in the practice. Its severe hearing impairment and prognosis impair the quality of life. Given that cochlear hair cell vulnerability is not consistent across frequencies, this study aims to investigate the impact of frequency-specific hearing loss on prognosis in SSNHL. Methods: The study included 255 patients with full-frequency SSNHL. The baseline, clinical, and hearing characteristics, as well as possible cardiovascular predictors in blood, were collected for analysis. Results: The 4,000 and 8,000 Hz hearing levels in the responder group were significantly lower than those in the non-responder group (p = 0.008, p < 0.001), while the average hearing was not (p = 0.081). Logistic regression showed that only vertigo (OR, 95% CI, 0.265, 0.102-0.684, p = 0.006) and 8,000 Hz hearing level (OR, 95% CI, 0.943, 0.916-0.971, p < 0.001) were strongly associated with treatment outcome. Conclusions: Compared with other frequencies, 8,000 Hz hearing level was closely related to prognosis in SSNHL. In an adjusted model, our study did not find an effect of mean hearing on prognosis in SSNHL. However, further multicenter prospective studies are needed for validation.

Comparison of Different Therapeutic Effects of T-MIST for Chronic Idiopathic Tinnitus.

Objective: Tinnitus, as a common clinical symptom, has the characteristics of high incidence and great heterogeneity among different patients. As one of the common treatment strategies for tinnitus, this study is aimed at exploring the factors influencing tinnitus sound therapy and the correlation between different tinnitus acoustic characteristics. Methods: 315 patients with chronic tinnitus were enrolled and divided into three groups according to the tinnitus multielement integration sound therapy (T-MIST): (1) vanishing, (2) remission, and (3) unchanged. The general characteristics, psychoacoustic scores (tinnitus handicap inventory (THI) and visual analog scale (VAS)), residual inhibition (RI), degree of hearing loss, and tinnitus characteristics of each group were compared. Finally, we analyze the predictive significance of different features for acoustic effects. Results: The frequency of tinnitus in the vanishing group was higher than that in the remission and unchanged groups (P < 0.05). There were no differences in age, initial onset time, course of the disease, and VSAD between the vanishing group and the unchanged group (P > 0.05). High-frequency tinnitus may predict the vanishing of tinnitus after treatment (P < 0.05), but the degree of hearing loss, tinnitus characteristics (loudness and frequency), and psychoacoustic score (THI and VAS) were only weakly correlated (P < 0.05). Residual inhibition test (RI) was an independent risk factor for the efficacy of acoustic therapy (P < 0.001). Conclusion: The patients were divided into three groups by T-MIST treatment effect; Kruskal-Wallis test and chi-square test were used to compare the baseline information of each group. Then, we analyzed the correlation between patient characteristics and psychoacoustic scores. Finally, logistic regression was performed to explore predictors that might influence the treatment effect. High-frequency tinnitus may have a better therapeutic effect; age, disease course, and other factors can not be stable explanation factors for a poor therapeutic effect of tinnitus. The residual inhibition (RI) test was an independent factor in predicting the efficacy of T-MIST.

A Multilayer Nanofibrous Mat for the Topical Chemotherapy of the Positive Margin in Bladder Cancer.

Treatment of positive margins after solid tumor resection remains a significant challenge for clinicians. Owing to unique structural features, electrospun nanofibrous mats are promised to be an implantable antitumor system through the delivery of active agents in a controlled manner. In this study, we utilized sequential electrospinning to fabricate a multilayer mat in which gemcitabine (GEM) and cisplatin (CDDP) were electrospun individually in distinct layers. By designing the structure, the multilayer mat could deliver antitumor agents sustainedly and prolong the release of GEM, which is loaded in the inner layer. In vitro assays show that the multilayer mats effectively inhibit bladder cancer (BC) cells and elevate apoptosis. In animal models of BC, the implantable drug-loaded fibrous mat can effectively treat positive margins and prevent local recurrence. Moreover, the local delivery of GEM and CDDP significantly lowers liver toxicity compared with systemic chemotherapy. In summary, a multilayer nanofibrous mat is developed for the localized and controlled delivery of GEM, dramatically improving the treatment of residual tumors and preventing BC recurrence. Impact statement The designed multilayer nanofibrous mats can achieve two chemotherapeutic drugs (gemcitabine and cisplatin) co-loading and time-programmed sustained release, significantly improving our previous study. The antitumor effect of the drug-loaded mat in vivo and in vitro was sufficiently demonstrated. We expect to bring a new strategy of topical chemotherapy for treating positive surgical margins in bladder cancer.

Integrated bioinformatical analysis, machine learning and in vitro experiment-identified m6A subtype, and predictive drug target signatures for diagnosing renal fibrosis.

Renal biopsy is the gold standard for defining renal fibrosis which causes calcium deposits in the kidneys. Persistent calcium deposition leads to kidney inflammation, cell necrosis, and is related to serious kidney diseases. However, it is invasive and involves the risk of complications such as bleeding, especially in patients with end-stage renal diseases. Therefore, it is necessary to identify specific diagnostic biomarkers for renal fibrosis. This study aimed to develop a predictive drug target signature to diagnose renal fibrosis based on m6A subtypes. We then performed an unsupervised consensus clustering analysis to identify three different m6A subtypes of renal fibrosis based on the expressions of 21 m6A regulators. We evaluated the immune infiltration characteristics and expression of canonical immune checkpoints and immune-related genes with distinct m6A modification patterns. Subsequently, we performed the WGCNA analysis using the expression data of 1,611 drug targets to identify 474 genes associated with the m6A modification. 92 overlapping drug targets between WGCNA and DEGs (renal fibrosis vs. normal samples) were defined as key drug targets. A five target gene predictive model was developed through the combination of LASSO regression and stepwise logistic regression (LASSO-SLR) to diagnose renal fibrosis. We further performed drug sensitivity analysis and extracellular matrix analysis on model genes. The ROC curve showed that the risk score (AUC = 0.863) performed well in diagnosing renal fibrosis in the training dataset. In addition, the external validation dataset further confirmed the outstanding predictive performance of the risk score (AUC = 0.755). These results indicate that the risk model has an excellent predictive performance for diagnosing the disease. Furthermore, our results show that this 5-target gene model is significantly associated with many drugs and extracellular matrix activities. Finally, the expression levels of both predictive signature genes EGR1 and PLA2G4A were validated in renal fibrosis and adjacent normal tissues by using qRT-PCR and Western blot method.

Tislelizumab in combination with gemcitabine plus cisplatin chemotherapy as first-line adjuvant treatment for locally advanced or metastatic bladder cancer: a retrospective study.

BACKGROUND: Combining immune checkpoint inhibitors with chemotherapy can synergistically improve antitumor activity and are generally well tolerated. Recently, the efficacy and safety of combination therapy has been demonstrated for many cancers, including urothelial carcinomas. The aim of this retrospective pilot study was to evaluate the efficacy and safety of tislelizumab plus chemotherapy as first-line adjuvant treatment for locally advanced or metastatic bladder cancer. METHODS: We conducted a retrospective analysis of 31 patients with locally advanced or metastatic bladder cancer from December 2020 to January 2022 with an Eastern Cooperative Oncology Group performance status of 0/1. Of the 31 patients, 14 patients received tislelizumab (200 mg i.v. every 3 weeks, Q3W) plus 21 days cycles of chemotherapy (gemcitabine, 1000 mg/m2 i.v. on days 1 and 8 of each cycle + cisplatin, 70 mg/m2 i.v. on day 2 of each cycle) (TGC) treatment and 17 patients received gemcitabine plus cisplatin chemotherapy (GC) treatment. All patients treated with bladder cytoreductive surgery and were treated for four 21 days cycles until disease progression or intolerable treatment-related adverse events (TRAEs). The objective progression-free survival (PFS), overall survival (OS), overall response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR) and TRAEs were recorded and reviewed. RESULTS: As of the cut-off date (March 25, 2022), PFS, OS, ORR, DCR, CBR and TRAEs were evaluated in 14 patients receiving combination therapy and 17 patients in the chemotherapy alone group. The median PFS was 36.0 [95% confidence interval (CI) 33.1-38.9] weeks in the TGC group and 29.0 (95% CI 25.4-32.6) weeks in the GC group [hazard ratio (HR) 0.15 (95% CI 0.04-0.55)]. In the GC group, the median OS was 48.0 (95% CI 39.7-56.3) weeks; the median OS was not yet mature for the TGC group [HR 0.26 (95% CI 0.07-0.94)]. Treatment with TGC resulted in improved DCR (TGC 71.4%; GC 65.0%) and CBR (TGC 64.3%; GC 52.9%) compared with GC. However, although higher incidences of grade ≥ 3 TRAEs were observed with TGC compared with GC (35.7% vs 23.5%), the difference was not statistically significant (p = 0.47). CONCLUSION: This study suggested that TGC provided survivors of locally advanced or metastatic bladder cancer with encouraging antitumor activity and was generally well tolerated.

An Efficient YOLO Algorithm with an Attention Mechanism for Vision-Based Defect Inspection Deployed on FPGA.

Industry 4.0 features intelligent manufacturing. Among them, the vision-based defect inspection algorithm is remarkable for quality control in parts manufacturing. With the help of AI and machine learning, auto-adaptive instead of manual operation is achievable in this field, and much progress has been made in recent years. In this study, considering the demand of inspection features in industrialization, we made further improvement in smart defect inspection. An efficient algorithm using Field Programmable Gate Array (FPGA)-accelerated You Only Look Once (YOLO) v3 based on an attention mechanism is proposed. First, because of the relatively fixed camera angle and defect features, an attention mechanism based on the concept of directing the focus of defect inspection is proposed. The attention mechanism consists of three improvements: (a) image preprocessing, which is to tailor images for selectively concentrating on the defect relevant things. Image preprocessing mainly includes cutting, zooming and splicing, named CZS operations. (b) Tailoring the YOLOv3 backbone network, which is to ignore invalid inspection regions in deep neural networks and optimize the network structure. (c) Data augmentation. First, two improvements can be made to efficiently reduce deep learning operations and accelerate the inspection speed, but the preprocessed images are similar and the lack of diversity will reduce network accuracy. So, (c) is added to mitigate the lack of considerable amounts of training data. Second, the algorithm is deployed on a PYNQ-Z2 FPGA board to meet the industrialization production requirements for accuracy, efficiency and extensibility. FPGA can provide a low-latency, low-cost, high-power-efficiency and flexible architecture that enables deep learning acceleration for industrial scenarios. A Xilinx Deep Neural Network Development Kit (DNNDK) converted the improved YOLOv3 to Programmable Logic (PL), which can be deployed on FPGA. The conversion process mainly consists of pruning, quantization and compilation. Experimental results showed that the algorithm had high efficiency, inspection accuracy reached 99.2%, processing speed reached 1.54 Frames per Second (FPS), and power consumption was only 10 W.

Clinicopathological factors associated with pathological upgrading from biopsy to prostatectomy in patients with ISUP grade group ≤2 prostate cancer.

We performed this study to investigate pathological upgrading from biopsy to prostatectomy and clinicopathological factors associated with grade group (GG) upgrading in patients with International Society of Urological Pathology (ISUP) GG 1 and 2 prostate cancer (PCa) in a Chinese cohort. We included patients diagnosed with PCa with ISUP GG 1 and 2 at biopsy, who underwent RP at our institution. Pre- and postoperative clinical variables were examined. Univariate and multivariate logistic regression analyses were conducted to identify independent factors associated with GG upgrading. Patients in GG upgraded group had higher total prostate-specific antigen (tPSA; median: 14.43 ng ml-1 vs 10.52 ng ml-1, P = 0.001) and PSA density (PSAD; median: 0.45 ng ml-2 vs 0.27 ng ml-2, P < 0.001) than those in GG nonupgraded group. Patients in upgraded group had a higher ratio for Prostate Imaging-Reporting and Data System (PI-RADS) score >3 (86.4% vs 67.9%, P < 0.001). Those with GG 1 in biopsy were more likely to experience GG upgrading after RP than those with GG 2 (71 vs 54, P = 0.016). Independent preoperative factors predicting GG upgrading were PI-RADS score >3 (odds ratio [OR]: 2.471, 95% confidence interval [CI]: 1.132-5.393; P = 0.023), higher PSAD (P = 0.001), and GG in biopsy (OR: 0.241, 95% CI: 0.123-0.471; P < 0.001). The histopathological analyses of RP specimens revealed that perineural invasion (PNI; OR: 1.839, 95% CI: 1.027-3.490; P = 0.041) was identified as an independent factor associated with GG upgrading. Our results revealed that GG in the biopsy, PSAD, PI-RADS score >3, and PNI were independent factors of GG upgrading. These factors should be considered for patients with ISUP grade ≤2 PCa.

IL-17 is a Potential Therapeutic Target in a Rodent Model of Otitis Media with Effusion.

BACKGROUND: Otitis media with effusion (OME) is a non-suppurative inflammation of the middle ear that is characterized by middle ear effusion and hearing loss. However, the mechanisms of OME are not fully understood. The aim of this study was to determine the function and the mechanism of the IL-17 cytokine in the pathogenesis of OME and to investigate IL-17 as a potential strategy for the treatment of OME. METHODS: In this study, the OME rat model was induced by ovalbumin (OVA) as previously described. The severity of OME was determined with an oto-endoscope, by histochemical analysis, and by acoustic immittance. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of RNA-sequencing (RNA-seq) data was carried out to analyze the signaling pathways related to the pathogenesis of OME, which indicated that IL-17 is involved in OME. The anti-IL-17A monoclonal antibody was administrated by nasal drip to block IL-17 to treat OME in the rat model. The rats were finally injected intraperitoneally with the inhibitor of Notch signaling pathway to study the mechanisms of IL-17-induced inflammation. Serum and lavage fluid were collected for the detection of related cytokines, and middle ear tissue was collected for Western blot, quantitative real-time PCR (qRT-PCR), and immunohistochemical and immunofluorescence analysis. RESULTS: KEGG analysis of RNA-seq data suggested that the IL-17 signaling pathway might be involved in the onset of OME. IL-17 expression was confirmed to be increased in both the serum and the middle ear of the rat model. The monoclonal antibody against IL-17 neutralized IL-17, inhibited the inflammation in the middle ear, and reduced the overall severity of OME in vivo. Furthermore, the Notch signaling pathway was activated upon IL-17 upregulation in OME and was suppressed by IL-17 blockage. However, there was no change in IL-17 expression after Notch inhibitor treatment, which reduced the severity of OME in the rat middle ear. CONCLUSION: IL-17 plays a key role in the pathogenesis of the OVA-induced OME rat model. IL-17 induced inflammatory responses via the Notch signaling pathway and targeting IL-17 might be an effective approach for OME therapy.

Association of Extrarenal Invasion Patterns and Tumor Size with the Differences in Survival Outcomes of T3a Renal Cell Carcinoma: A Proposal Modified T3a Stage System is Needed.

OBJECTIVE: T3a renal cell carcinoma (RCC) did not consider tumor size and different extrarenal invasion patterns in the current TNM staging system. Here, we want to investigate the association of survival outcomes with different extrarenal invasion patterns and tumor size of T3a RCC. METHODS: We identified T3a RCC patients from the Surveillance, Epidemiology, and End Results database in 2004-2015. The extrarenal invasion patterns included renal vein invasion, renal sinus/peri-sinus fat invasion, or perinephric fat invasion. Cox proportional hazards models and Fine and Gray models were used to estimate overall survival (OS) and cancer-specific survival (CSS), and the hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. C-index is used to evaluate the predictive ability of the model. Restricted cubic splines were used to estimate the HRs of tumor size on the risk of OS and CSS. RESULTS: In total, 4834 T3a RCC patients were included in the analysis. Of them, 1403 (29%) present isolated extrarenal invasion pattern, while 1403 (71%) were any combined invasion pattern, which was associated with a higher risk of lymph-node/distant metastasis and a worse OS and CSS compared with isolated extrarenal invasion pattern, but a comparable CSS and OS were observed between each isolated invasion pattern. In restricted cubic splines, a non-linear shape was observed for the association between the tumor size and OS and CSS, compared with the smallest tumor size group (≤4cm), the adjusted HR of the largest tumor size group (≥10cm) was 1.59 for all-cause mortality, and 2.27 for tumor-specific mortality, respectively. However, in a cohort of T3a RCC with a combined invasion pattern, tumor size is not an independent risk factor for prognosis. Finally, the model added two covariates of tumor size and invasion patterns that could improve the predictive ability of OS and CSS for T3a patients (c-index: +1.2%, +1.3%, respectively). CONCLUSION: Tumor size and extrarenal invasion type are valid parameters of the OS and CSS for T3a RCC patients and need to be considered for the next generation of the T-stage system.

Comparison of prognosis between patients undergoing radical nephrectomy versus partial nephrectomy for renal cell carcinoma ≤7 cm T3aN0/xM0: Survival benefit is biased toward partial nephrectomy.

BACKGROUND: There is limited and controversial evidence on the prognosis of partial nephrectomy (PN) versus radical nephrectomy (RN) in patients with T3aN0/xM0 renal cell carcinoma (RCC) upstaged from clinical T1 RCC. In this study, we aimed to assess the prognosis difference following PN versus RN in patients with ≤7 cm T3aN0/xM0 RCC. METHODS: From the Surveillance, Epidemiology, and End Results database, a total of 3196 patients receiving treatment of PN/RN for ≤7 cm T3aN0/xM0 RCC with only extrarenal fat extension in 2010-2017 were identified. An inverse probability of treatment weighting (IPTW)-adjusted cause-specific Cox model with hazard ratio (HR) and 95% confidence interval (CI) was used for overall survival (OS) and cancer-specific survival (CSS) analyses. Sensitivity analysis was based on the propensity score matching of PN and RN groups and from the dataset of 2010-2013. RESULTS: A total of 872 patients underwent PN, compared with 2324 undergoing RN. After IPTW adjustment, there was no significant difference in preoperative baseline characteristics between the PN and RN cohorts. Patients who underwent RN had worse OS (HRIPTW-adjusted , 1.46; 95% CI, 1.16-1.84; p = 0.001) and comparable CSS (HRIPTW-adjusted , 1.03; 95% CI, 0.64-1.66; p = 0.890) than those receiving PN in all cohorts and subgroups with T3a RCC of ≤4 cm and perinephric fat extension. Further, in patients with 4-7 cm T3a RCC with perinephric-fat invasion and all sizes of T3a RCC with sinus/perisinus fat extension, PN led to comparable OS and CSS. Sensitivity analyses validated these results. CONCLUSION: PN provides comparable CSS and OS or even better OS than RN for patients with RCC ≤7 cm T3aN0/xM0. Although our study has some limitations, our results indicated that PN might oncologically safe for clinical T1 RCC, even confirmed a pathologically T3a upstaging post-PN.