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Purpose. To analyse the efficacy of high-dose methotrexate + adriamycin + cisplatin (HD-MTX + ADR + PDD, MAP) regimens applied to osteosarcoma and the pretreatment and resolution of chemotherapeutic reactions. Methods. The clinical data of 21 patients with osteosarcoma in our hospital from January 2015 to January 2018 were retrospectively analysed. All patients were treated with the MAP protocol, 21 days for 1 cycle, and treated with artificial joint replacement or amputation after 3∼4 cycles of treatment. The tumour tissue necrosis rate, limb preservation success rate after treatment, and chemotherapy response during chemotherapy were counted and analysed for all patients. A local recurrence rate, a distant metastasis rate, and an overall survival rate were recorded during the 3-year follow-up period. Results. After treatment, the percentage of tumour tissue necrosis ≥90% was 85.71% (18/21) and the percentage of successful limb preservation was 57.14% (12/21) in 21 patients with osteosarcoma. During chemotherapy, all 21 patients with osteosarcoma experienced various degrees of chemotherapy reactions, mainly bone marrow suppression of 100% (21/21), gastrointestinal reactions of 100% (21/21), liver function impairment of 66.67% (14/21), and cardiotoxicity of 52.38% (11/21), all of which improved and completed treatment after treatment. During the 3-year follow-up period, the 21 patients with osteosarcoma had a local recurrence rate of 9.52% (2/21), a distant metastasis rate of 28.57% (6/21), and an overall survival rate of 80.95% (17/21). Conclusion. With stringent protection and relief measures, patients with osteosarcoma treated with the MAP regimen have promising near-term outcomes, with high survival rates over 3 years and tolerable chemotherapy responses. The clinical trial is registered under L2015093.

Synthetic signalling receptors enable programmable cellular responses coupling with a customized input. However, engineering a designer force-sensing receptor to rewire mechanotransduction remains largely unexplored. Herein, we introduce nongenetically engineered artificial mechanoreceptors (AMRs) capable of reprogramming non-mechanoresponsive receptor tyrosine kinases (RTKs) to sense user-defined force cues, enabling a de novo designed mechanotransduction. AMR is a modular DNA-protein chimera comprising a mechanosensing-and-transmitting DNA nanodevice grafted on natural RTKs via aptameric anchors. AMR senses intercellular tensile force via an allosteric DNA mechano-switch with tuneable piconewton-sensitive force tolerance, actuating a force-triggered dynamic DNA assembly to manipulate RTK dimerization and activate intracellular signalling. By swapping the force-reception ligands, we demonstrate the AMR-mediated activation of c-Met, a representative RTK, in response to the cellular tensile forces mediated by cell-adhesion proteins (integrin, E-cadherin) or membrane protein endocytosis (CI-M6PR). Moreover, the versatility of AMR allows the reprogramming of FGFR1, another RTK, to customize mechanobiological function, e.g., adhesion-mediated neural stem cell maintenance.

A novel 9,9a-BN anthracene 5 has been synthesized by the Ru-catalyzed electrocyclization of BN-aromatic enynes. The photophysical properties of 5 are different from those of all-carbon anthracene and other reported BN-anthracenes. The reactivity of 5 has been investigated by treating 5 with organolithium compounds, Br2, or N-iodosuccinimide. The resulting halogenated compounds can be easily functionalized via cross-coupling reactions. UV-vis and fluorescence spectroscopy of 5 have been investigated to explore the photophysical properties of these BN-anthracenes.

Sarcopenia has been proved to be related to the prognosis of patients with bladder cancer (BC) after radical cystectomy (RC). The relationship between sarcopenia and the occurrence of venous thromboembolism (VTE) after RC is unclear. We collected data of 252 BC patients treated with RC at our institution. Data was obtained from the electronic medical record database. Sarcopenia was defined by the third lumbar vertebra skeletal muscle index (SMI) which was measured using preoperative computed tomography. The primary outcome was the incidence of VTE within 30 days after the surgery in sarcopenia and non-sarcopenia groups. Outcomes between the two cohorts were compared using univariate analysis. Multivariate logistic regression was used to control for differences between cohorts. Two hundred fifty-two patients were enrolled, of which 85 (33.7%) patients were in sarcopenia group, while 167 (66.3%) patients were not in sarcopenia group. The incidence of total VTE in sarcopenia group was higher than that in the extended group (10.6% vs. 1.8%, p = 0.005). Sarcopenia did not cause an increase in other postoperation 30 days complications (all p > 0.05). Multivariate analysis confirmed sarcopenia was independently associated with increased odds of VTE (OR = 4.18, 95% CI [1.01–17.27]; p = 0.048). Subgroup analysis showed that patients with VTE tended to be older (76.5 vs 66.0, p = 0.025) and have higher proportion of diabetes (58.3% vs 14.2%, p

This article mainly focuses on the attack location and defense of cyber-physical power systems under dynamic load altering attacks. Taking the smart grid as an example, first, the cyber-physical power system model under attack is established to provide conditions for attack detection. On this basis, an adaptive observer with [Formula: see text] performance is designed to realize detection and location through residual signal and attack estimation, respectively. Furthermore, a power redistribution strategy based on optimal economic scheduling is presented to realize attack defense by means of the observer data. Finally, theoretical analysis proves the feasibility of the algorithm, and simulation cases prove the effectiveness of attack location and defense strategies.

Chitosan/organic rectorite (CTS/OREC) composites were prepared and characterized by Fourier transform infrared spectrometry and X-ray diffraction. Polyphenol oxidase (PPO) was immobilized on CTS/OREC by physical adsorption (APPO) and covalent binding (CPPO). Taguchi method was applied in the optimization of immobilization conditions resulting in the highest enzyme activity of 16.37 × 103 and 8.92 × 103U/g for APPO and CPPO, respectively. APPO enzyme activity was higher than that of CPPO, while CPPO showed the higher enzyme loading capacity than that of APPO. The removal percentage of phenolic compound, including phenol (PH), 4-chlorophenol (4-CP) and 2,4-dichlorophenol (2,4-DCP), by immobilized PPO was also explored. The results indicated that APPO was more efficient in phenolic compounds removal than CPPO. APPO contributed to a quick removal in the first hour, and the removal percentage of PH, 4-CP and 2,4-DCP could reach 69.3 ± 4.2%, 89.8 ± 2.5% and 93.8 ± 1.7% within 2 h, respectively. The order of removal percentage of phenolic compounds for both immobilized PPO was 2,4-DCP > 4-CP > PH. After 10 consecutive operations, the removal percentage of 2,4-DCP reached 73.2 ± 2.6% and 60.3 ± 1.5% for APPO and CPPO, respectively. The results introduced a novel support for PPO immobilization, and the immobilized PPO had great potential in wastewater treatment.

A series of semi-internally BN-substituted annulated thiophenes were synthesized from easily accessible 2,1-borazaronaphthalenes. Crystal structure studies and DFT calculations on the semi-internally BN-substituted annulated thiophene 3a revealed that the six-membered BN-embedded ring and five-membered BS-embedded ring in 3a had lower aromaticity than the corresponding all-carbon rings in 3a′. 3a possesses quite similar frontier molecular orbital energies and absorption and emission maxima compared to the carbonaceous analogue 3a′. The reactivity of these previously unknown BN-aromatic compounds toward organolithium compounds and Br2 has been studied. The afforded bromo-substituted compounds could be further functionalized via Suzuki couplings. The photophysical properties of these BN-substituted annulated thiophenes were investigated by UV–vis and fluorescence spectroscopy.

To evaluate the comprehensive complication index(CCI) and Clavien-Dindo classification(CDC) for short-term postoperative complications in radical cystectomy and assess cumulative surgical morbidity to compare sufficient surgical skill.From September 30, 2010, to October 1, 2020, clinical data of patients with urothelial carcinoma who underwent radical cystectomy with urinary diversion were gathered, patients who had only a urinary diversion, bladder sparing surgery, additional abdominal surgeries at the same time were all excluded. The CDC and CCI were utilized to evaluate 30-d complications after radical cystectomy and the relevance of hospital stay was compared between CCI and CDC. The cumulative sum control models (CUSUM) were used to evaluate the overall surgical morbidity of radical cystectomy in our facility and for comparisons between surgeons.This study enrolled a total of 635 individuals, 548 (86.3%) of whom had 1124 problems. The incidence of severe complications (CDC≥ Grade III) was 10.2%. The average CCI was 20.2 ± 14.7. Gender, urinary diversion subtype, procedure method, and surgeon were significantly correlated with the increase of CCI (p 0.05). The CCI demonstrated a better relationship with hospital stay (RCCI can better reflect the incidence of complications for radical cystectomy than CDC, and CCI is more strongly correlated with postoperative hospital stay. The CUSUM-CCI model can reflect the quality of surgical skill for each surgeon instantaneously.

Introduction The effect of repeated cystoscopy on bladder cancer (BC) patient anxiety and feelings is rarely evaluated. Aim To compare the difference of patients’ anxiety and subjective feelings caused by different cystoscopes. Material and methods We prospectively included 192 BC patients who accepted regular cystoscopy follow-up after transurethral resection of bladder tumor (TURBT): 93 in the flexible group and 99 in the rigid group. The method of anesthesia and the order of examinations were consistent between different groups. We analyzed the anxiety level before cystoscopy, the maximum pain during the examination and the change of lower urinary tract symptoms (LUTS) before and after cystoscopy. Meanwhile, we analyzed the rate of gross hematuria and pyuria after cystoscopy. The anxiety and pain levels were evaluated by the Amsterdam Preoperative Anxiety and Information Scale (APAIS) and visual analogue scale (VAS). LUTS was reflected by the Core Lower Urinary Tract Symptom Score (CLSS). We distinguished gender during analysis. Results The median APAIS score of male patients undergoing flexible or rigid cystoscopy was 8 vs. 12 (p < 0.01), and this result for females was 8 vs. 9 (p = 0.048). The median pain scores for men in the two groups was 1 vs. 2 (p < 0.01), respectively, and this outcome in female patients was 0 vs. 1 (p < 0.01). Patients in the rigid group had more CLSS change (0 vs. 1, p < 0.01). There was no difference in pyuria or gross hematuria rate after examination. Analysis in respective groups showed that men have more severe pain than women, 1 vs. 0 (p = 0.001) in the flexible group and 2 vs. 1 (p = 0.009) in the rigid group. Conclusions A flexible cystoscope can improve anxiety and subjective feelings of BC patients during cystoscopy follow-up.

Bladder cancer (BC) is a serious malignancy worldwide due to its distant metastasis and high recurrence rates. Increasing evidence has indicated that dysregulated long non‑coding RNAs (lncRNAs) are involved in tumorigenesis and progression in multiple malignancies. However, their clinical significances, biological functions and molecular mechanisms in BC remain poorly understood. Hence, the present study investigated the expression profile of lncRNAs and mRNAs in five BC tissues and the corresponding adjacent normal specimens using high‑throughput RNA sequencing (RNA‑seq). A total of 103 differentially expressed (DE) lncRNAs were identified, including 35 upregulated and 68 downregulated ones in BC tissues. Similarly, a total of 2,756 DE‑mRNAs were detected, including 1,467 upregulated and 1,289 downregulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses, and lncRNA‑miRNA‑mRNA network analyses suggested that these dysregulated lncRNAs are potentially implicated in the onset and progression of BC. Subsequently, four lncRNAs (upregulated ENST00000433108; downregulated ENST00000598996, ENST00000524265 and ENST00000398461) and two mRNAs (upregulated CCNB1 and CDK1) in 64 pairs of BC and adjacent normal tissues and four BC cell lines were detected using reverse transcription‑quantitative PCR and these results were consistent with the sequencing data. Additionally, Fisher's exact test, Kaplan‑Meier plots, and Cox regression analyses were used for elucidating the clinical values of ENST00000598996 and ENST00000524265. Furthermore, a receiver operating characteristic curve was constructed to assess their diagnostic values. The low expression level of ENST00000598996 and ENST00000524265 was correlated with unfavorable clinicopathological parameters, and shorter progression‑free and overall survival time, whereas, ENST00000433108 was not associated with either. The in vitro functional experiments also revealed that the overexpression of ENST00000598996 and ENST00000524265 decreased the proliferation, migration, and invasion abilities of BC cells. Collectively, the results of the present study provide a novel landscape of lncRNA and mRNA expression profiles in BC. In addition, the results also indicated that ENST00000598996 and ENST00000524265 may serve as tumor suppressors, potential diagnostic biomarkers and prognostic predictors for patients with BC.

Growing evidence has indicated that circular RNAs (circRNAs) play crucial roles in multiple biological processes. However, alterations in circRNA profiles during bladder cancer progression and the clinical significance thereof remain unclear. Therefore, high‐throughput RNA sequencing was conducted to identify circRNA and mRNA profiles in five pairs of bladder cancer tissues and adjacent noncancerous tissues. A total of 87 differentially expressed circRNAs and 2756 mRNAs were detected in above bladder cancer samples compared with paired noncancerous samples. Functional enrichment analyses, circRNA‐microRNA‐mRNA, and protein‐protein interaction networks revealed that these dysregulated circRNAs were potentially involved in carcinogenesis and evolution of bladder cancer. Subsequently, the differential expression of eight circRNAs was detected by real‐time qPCR. Hsa_circ_0003141 and hsa_circ_0008039 were significantly upregulated as well as hsa_circ_0026782, hsa_circ_0077837, hsa_circ_0004826, and hsa_circ_0001946 were significantly downregulated among validation of 70 matched bladder cancer tissues (≥75%). Moreover, hsa_circ_0077837 and hsa_circ_0004826 were also verified as markedly downregulated in four bladder cancer cells (100%). Naturally, hsa_circ_0077837 and hsa_circ_0004826 were also demonstrated using RNase‐R+ resistance experiments. In addition, Fisherʹs exact test, Kaplan‐Meier plots, Cox regression analyses, and receiver operating characteristic curve was performed to assess their clinical value. Downregulation of hsa_circ_0077837 and hsa_circ_0004826 all was significantly correlated with worse clinicopathological features and poor prognosis of bladder cancer patients. The area under the receiver operating characteristic curve of them was 0.775 (P, The transcriptional data of circRNAs and mRNAs were deeply detected by high‐throughput RNA sequencing and systematically analyzed using bioinformatics in patients with BC; and these eight dysregulated circRNAs were also verified by real‐time qRT‐PCR. Correlation analysis of clinicopathological features and survival analyses of circRNAs in BC were conducted. Functional experiments with circ_0077837 and circ_0004826 overexpression significantly weakened the progression of BC cells.

Objective: To study the psychological tension in electroencephalogram (EEG) of pilots selection in order to provide the evidence for obtaining accurate and reliable results. Methods: A total of 250 senior high school students, aged 17–21 years old, were randomly selected to take part in the physical examination of pilot selection from 2019 to 2020, and were divided into the non-teaching group and the education group (self control), respectively. In the process of EEG examination, the students’ comprehension, cooperation and physiological indicators were evaluated through video demonstration and teaching before examination and heart rate monitoring during examination. Results: Compared with the non-teaching group, the video demonstration helps the participating students to understand the inspection items, get familiar with the inspection process, and get good cooperation. After the beginning of the examination, the heart rate of the education group did not change significantly, and remained at the same level until the end of the examination. There was no significant difference between the heart rate after the examination and the heart rate during the examination (P > 0.05). The heart rate of the uneducated group increased and remained at the same level until the end of the examination, which was significantly different from that of the basal heart rate (P < 0.05). Conclusion: Video education and heart rate detection can effectively improve the students’ understanding and cooperation on the examination items, reduce psychological tension and fear, and enhance the reliability and effectiveness of the selection results.

Objective. To study the effects of 8-h simulated flight task on cognitive function and performance of volunteers, and to evaluate the workload of simulated flight. Methods. The subjects started the simulated flight at 9 am and continued to operate for 8 h to complete the simulated flight task. The flight control ability, reaction time, motion time, critical flicker fusion frequency (CFF) and subjective scale were measured. Workload evaluation indicators were detected before, half and after the simulated flight. Results. There were no significant differences in reaction time, motion time, critical flicker fusion frequency and Stanford Sleepiness Scale (SSS) between before, half and after the simulated flight. Compared with preflight, the rating of perceived exertion scale (RPE) scores was significantly increased after 8-h simulated flight. There was no significant difference in the ability of simulated flight control between preflight and postflight. Conclusions. There was no significant effect on the cognitive function and performance of volunteers during the 8-h simulated flight task in the daytime.

To observe the effect of modafinil on the visual function of 16-h flight. Methods 5 male healthy subjects were double-blind: placebo group (n = 5) and modafinil group (n = 5), Autologous control. Carry out 16 h (h) continuous simulated long flight test across day and night. First, the visual function is detected before flight, In pairs, at the same time, First phase 8 h at 15:30, After 200 mg, of modafenib or placebo 00:00 Completion of phase 2 h 8 flights, After the flight, the visual function was detected again and the state changes of far and near vision were compared before and after the flight. Results Compared with placebo, the use of modafinil had no significant effect on far and near vision, but increased the long vision of both eyes during flight. Conclusion Routine single dose of modafinil has no significant adverse effect on visual function and can reduce human fatigue perception.

Objective: This study intends to select a simple and easy method for screening people who are prone to seasickness and seasickness by observing the physiological parameters, seasickness, and navigation fatigue of the crew after a long voyage. Method: Data (including data, weight, Body Mass Index (BMI), their susceptibility to motion sickness, motion sickness symptoms, fatigue degree, etc.,) of 49 subjects who participated in the 200-day long voyage were collected data and the relevance between the above factors and motion sickness symptoms and fatigue symptoms was analyzed. Results: After the voyage, a total of 16 subjects had symptoms of motion sickness, and 41 subjects had symptoms of fatigue. 16 subjects had both seasickness and fatigue symptoms. BMI was positively correlated with motion sickness and fatigue scores. Conclusion: People with a higher BMI index may be more susceptible to motion sickness and fatigue during a long voyage.

A series of novel bis-BN-naphthalene-fused oxepin derivatives were synthesized via a Pd-catalyzed tandem reaction from brominated 2,1-borazaronaphthalenes and cis-bis(boryl)alkenes. X-ray crystallographic analysis revealed that bis-BN-naphthalene-fused oxepins feature a planar framework. The electronic and photophysical properties of the novel BN-naphthalene-fused oxepins were investigated by UV–vis and fluorescence spectroscopies and density functional theory (DFT) calculations, which disclosed the distinct electronic and photophysical properties of the analogous hydrocarbon system. Interestingly, dual-fluorescent emissions were observed upon dissolving N-substituted derivatives 10–14 in dimethyl sulfoxide. Tunable emission colors especially for white-light emissions can be achieved by controlling the ratio of solvents, concentration, or temperature using only a single-molecule compound.

Background: The stabilization of vertical unstable sacral fractures has been a complex problem that is a challenge to current standard approaches. Here, we attempted to evaluate a modified technique for sacral fractures. Methods: In the modified triangular osteosynthesis technique, we adopted a vertical and transverse fixation with a rod and pedicle screw system to reduce and fix sacral fractures in 28 subjects. The postsurgery effect of this technique was evaluated by physical examination and radiography. Results: In the postoperative day 1, the patients were able to move body position passively from the lateral side to supine and exercise their legs by themselves. After a follow up of 20 months, radiological evaluation showed that fracture fragment reduction was excellent in 18 (64%), good (displacement 5–10 mm) in 8 (29%), and fair (displacement 10–15 mm) in 2 (7%) patients. Three patients with a preoperative perineal neurological impairment had a complete recovery after surgical decompression. All patients had achieved bone union of fractures, and no loss of fracture reduction was detected. Conclusions: The modified procedures offered an easier approach to fix vertical unstable sacral fractures, thereby achieving quicker and stable functionality. This suggests an alternative approach to manage unstable sacral fractures. Level of Evidence: 4. Clinical Relevance: The stabilization of vertical unstable sacral fractures has been a complex problem that is a challenge to current standard approaches. We attempted to introduce a modified technique for sacral fractures.

Long non-coding RNAs (lncRNAs) govern fundamental biochemical and cellular processes. Bladder cancer is one of the most common genitourinary malignancies, and its proliferation, migration and invasion also regulated by many functional lncRNAs. In our study, we found that lncRNA MNX1-AS1 was highly-expressed in bladder cancer tissues and cell lines. Moreover, higher MNX1-AS1 expression was correlated with poor survival of MNX1-AS1 patients. Mechanistically, we showed that MNX1-AS1 could interact with YBX1 and promotes its location at the promoter region of β-catenin, then to promote transcriptional activation of β-catenin. In addition, MNX1-AS1/YBX1 could promote bladder cancer cells proliferation, migration and invasion through active Wnt/β-catenin signaling by induce β-catenin transcriptional activation. Consistently, we find a new functional lncRNA MNX1-AS1 can regulate bladder cancer cells proliferation, migration and invasion by target β-catenin transcriptional activation together with YBX1.

Discourse topic structure is the key to the cohesion of the discourse and reflects the essence of the text. Current Chinese discourse corpus are constructed mainly based on rhetoric and semantic relations, which ignore the functional information in discourse. To alleviate this problem, we introduce a new Chinese discourse analysis dataset called CTRD, which stands for Chinese Theme-Rheme Discourse dataset. Different from previous discourse banks, CTRD was annotated according to a novel discourse annotation scheme based on the Chinese theme-rheme theory and thematic progression patterns from Halliday’s systemic functional grammar. As a result, we manually annotated 525 news documents from OntoNotes 4.0 with a Kappa value greater than 0.6. And preliminary experiments on this corpus verify the computability of CTRD. Finally, we make CTRD available at https://github.com/ydc/ctrd.

In the past several decades, despite the continuous improvement of mobile devices, mobile applications requiring resources are still beyond its capacity to be completed on a single device. Due to high fairness and distribution efficiency, cloud auctions of mobile device allocation has recently attracted a lot of attention. However, most of them focus on efficiency but ignore the privacy-preserving issues in cloud auction process, which will have a significant impact on the authenticity of auctions. In this paper, we propose PAHTA, a privacy-preserving auction for heterogeneous task assignment in mobile device clouds by using Yao’s garbled circuits and homomorphic encryption. Meanwhile, we design a set of sub-protocols to support secure arithmetic operations, including secure division protocol and secure selection protocol. We further analyze the security and effectiveness of the system theoretically and prove that it can ensure sufficient and strong privacy protection under the semi-honest adversary model. Based on a large number of experiments, these results are consistent with the theoretical analysis.

4589 Background: The current strategy for bladder preservation is focused on trimodality treatment, including complete transurethral resection of bladder tumor (cTURBT), with concurrent chemotherapy and radiotherapy. Chemotherapy is usually a cisplatin-based regimen. However, many pts cannot tolerate cisplatin-based chemotherapy and radiation therapy. It fails to meet clinical needs. Meanwhile, the efficacy and safety of checkpoint inhibitors (ICIs) have now been demonstrated. We conduct a study to evaluate ICIs in combination with second-line chemotherapy agents for patients with MIBC. Methods: TRUCE-01 is a phase II trial (NCT04730219) of tislelizumab combined with nab-paclitaxel before cTURBT or radical cystectomy. Pts with pure or mixed urothelial bladder cancer (T2-4a Nx M0) received tislelizumab 200mg on days 1 plus paclitaxel 200mg on days 2 every 3 weeks (Q3W) x 3 cycles followed by cTURBT or radical cystectomy. Imaging evaluation is usually done before and after the drug administration using the same tests to assess the efficacy. Pts who choose to preserve bladder usually continue their medication after cTURBT. This abstract focuses on patients with bladder preservation. Results: Between July 2020 and November 2021, 47 pts completed at least 2 cycles of treatment, 22 (47%) pts received cTURBT, 16 (34%) pts received radical cystectomy and 9 (19%) pts refuse surgery. As for radiological response, 22 achieved complete response (CR), 16 achieved partial response (PR). In the bladder-preserving subgroup, 13 CR pts and 9 PR pts selected cTURBT, pathology showed 17 pT0, 1 pTa, 3 pT1 and 1 pTis. The median medication cycle is 9 (6-11). There were 3 pts experienced grade 3-4 adverse events (CTCAE), a grade 3 rash, a grade 3 gastric perforation and a grade 4 acute renal failure. In addition, The most common grade 1-2 adverse events include alopecia (86%), fatigue (77%), rash (41%), appetite decreases (41%), hyperglycemia (36%), fever (18%), and creatinine increased (14%). Median follow-up 357 (438-291) days with 3 recurrences and 1 death. The 1-year recurrence-free survival rate was 82%. Conclusions: The early efficacy data further support the role of tislelizumab combined with paclitaxel in bladder preservation setting with an acceptable adverse events. Patients with imaging CR or PR after neoadjuvant therapy are preferred for bladder preservation. Enrollment is ongoing. Clinical trial information: NCT04730219.

4507 Background: Pts with multiple or tumors with large invasion areas which are un-completely-resectable through TURBT would be recommended radical cystectomy in the clinical treatment. The KEYNOTE-057 study has illuminated the efficiency of immune checkpoint inhibitors monotherapy in HR-NMIBC pts, with acceptable adverse events (AEs). However, the role of PD-1/PD-L1 inhibitor in combination with chemotherapy in NMIBC pts remains unclear. We report preliminary treatment efficiency, safety data, and exploratory work of TRUCE-02 trial. Methods: TRUCE-02 is a phase II study for NMIBC pts with uncompletely resectable tumour by TURBT. The primary endpoint was complete response(absence of non-muscle-invasive bladder cancer or progressive disease). Pts that meet the criteria would receive tislelizumab 200mg on days 1 plus paclitaxel 200mg on days 2 every 3 weeks (Q3W) x 3 or 4 cycles followed by a comprehensive assessment including pathology, urine cytology, and imageology. Meanwhile, biomarker analyses included programmed death-ligand 1 (PD-L1) expression using the combined positive score (CPS; Dako 22C3 pharmDx assay) and whole transcriptome RNA sequencing of the tumor. Results: Between July 2020 and January 2022, 54 pts were enrolled. 42 pts have completed whole 3 or 4 treatment cycles and reached the primary endpoint. 23 pts achieved CR condition (56%, 95%CI, 43.6% and 74.4%). ORR of 60% (N=25/42, 95%CI, 45.2% and 74.8%). As a secondary endpoint, 33 pts remain cystectomy-free condition (78.6%, 95%CI, 66.2% and 91%). Grade 3-4 AEs were lower than 2%. Urine cytology showed its diagnostic efficiency of 68.42% (95%CI, 61.3% and 75.6%), urine FISH showed a diagnostic efficiency of 45.71% (95%CI, 37.7% and 53.4%) before pathological assessment. As for PD-L1 expression, 47.3% (N = 9/19) of response pts (CR+PR) showed positive, 50% (N = 5/10) of un-response pts (PD+SD) showed positive. We also found out through sequencing results that AR, TCF7L2 might be underlying markers that predict adverse outcomes for pts in this crew. HRR mutation may predict a positive prognosis and mutations in NMIBC which might predict the prognosis of this treatment plan. Conclusions: Tislelizumab with nab-paclitaxel represents a novel treatment option with a satisfactory benefit in treating NMIBC. PD-L1 expression has no obvious correlation with the efficiency of this treatment plan. WGS result also showed that there are mutation markers that may predict whether pts would benefit from this treatment plan. Clinical trial information: NCT04730232. [Table: see text]

4590 Background: Urine cytology is a noninvasive and relatively inexpensive approach that plays an important role in both screening/initial diagnosis of urothelial carcinoma, and surveillance of tumor recurrence; However, interpretation of urine cytology is labor-intensive and time-consuming. Artificial intelligence (AI) has been widely used in the field of medically assisted diagnosis, but it is almost blank in the field of urothelial carcinoma diagnosis based on urine cytology. In this study, artificial intelligence (AI) algorithms have been developed to efficiently and automatically analyze urinary cytological specimens stained with Acridine orange fluorescence for screening and diagnosis of urothelial carcinoma with a good clinical application prospect. Methods: To develop the algorithms, images of urinary cytological specimens with Acridine orange Fluorescence staining were collected from patients who underwent examination, surgery, or both at the Second Hospital of Tianjin Medical University from August 2015 to August 2021. To standardize the urine cytological determination, the images were determined by 3 certified and experienced cytopathologists in this hospital. Images were collected to establish a dataset containing two major categories: Malignant (Defined as images containing malignant cells) and Benign (Defined as images containing malignant cells). From the acquired database, 2794 malignant and 2787 benign eligible images were selected for AI training/validation/testing. Inception V3, a specific type of neural network optimized for image classification called a deep convolutional neural network was trained based on the database. To prevent the model from over-fitting during training, data augmentation methods, such as rotation and flipping were adopted. The diagnosing performance of the binary classification model was analyzed using accuracy, F1 score, operating characteristic (ROC), and the area under the curve (AUC) generated from the sensitivity and specificity to evaluate. Results: A total of 21022 slides of urine cytological specimens with Acridine orange Fluorescence staining were collected. The AI algorithms achieved excellent performance, which showed the best prediction with an accuracy of 92.25%, a sensitivity of 98.50% along with a specificity of 86.00%, the F1score was 0.9271, and the area under the ROC curve was 0.96. Conclusions: Our novel artificial intelligence algorithms could accurately classify urine specimens as malignant or benign efficiently and automatically. The use of AI during cytopathology screening provides a new strategy and technical support for the diagnosis and screen of urothelial carcinoma. [Table: see text]

Tasks based on deep learning have make great progress in accuracy with the development of deep learning in recent years. However, algorithms base on deep learning are both computationally intensive and memory intensive, makes it difficult to deploy on resource-constrained devices. Therefore, it is worth studying how to compress the architecture of existing network while achieving a comparable performance, so that the model can be deployed on devices with limited resources. This paper performs model compression and acceleration in multi-person pose estimation by replacing the feature extraction network, parameter pruning and knowledge distillation, achieve a $2.6\times$ MACs reduction and $2\times$ acceleration but only 25% drop in accuracy compared with a lightweight model. The compressed model can be deployed on the embedded device Jetson Nano with a 12 FPS inference speed.

Background: Bladder cancer (BC) is the 10th most common cancer worldwide with significantly varied prognosis in different pathological subtypes. MMPs, a group of enzymes, could involve in the invasion and metastasis of numerous malignancies. The function of MMPs in BC is partly reported in several studies but with a great conflicts; hence, a systematic analysis of expression levels and prognostic values of these MMP genes are still to be determined. Methods: Firstly, differentially expressed genes (DEGs) of MMPs were identified in ONCOMINE, GEPIA and UALCAN databases; and these DEGs were also detected by real-time RT-qPCR. More importantly, we investigated the clinical significance of these DEGs in BC patients via Kaplan-Meier (KM) Plotter, UALCAN and cBioPortal databases. Results: The study found that mRNA expression of MMP1/11 in BC samples was significantly higher than that in normal bladder tissues, and MMP2/3 were lower in the former than in the latter. The expression level of MMP1/2/7/9/11/13/23B were significantly related to the tumour stages. Furthermore, the prognostic analysis suggested that the high transcription levels of MMP7 and low transcription levels of MMP23A were correlated with favorable relapse-free survival and overall survival in the patients with BC, respectively. Notably, high MMP11/13 expression levels indicated poor overall survival (OS) and relapse-free survival (RFS) in patients with BC. Conclusion: This study revealed that MMP1/2/3/7/9/11/13/23A/23B are possible prognostic biomarkers and clinical therapeutic targets for patients with BC.

Introduction Little is known about small cell carcinoma of the upper urinary tract (UUT-SCC), the aim of this study is to identify the risk factors in relation to survival of patients with UUT-SCC. Evidence acquisition Literature search on UUT-SCC was performed in databases including MEDLINE, EMBASE, Wangfang, and CNKI. Studies were eligible for inclusion if outcomes of patients with histopathologically confirmed UUT-SCC were reported. The relevant data on clinic, pathology, and therapy were collected. Progress survival was evaluated using the Cox regression model with the robust sandwich estimates of the covariance matrix. Evidence synthesis There were 55 eligible publications identified, contributing 76 patients in total. The median of overall survival (OS) was 14 months. In univariable analyses, pathological stage and platinum-based chemotherapy regimen were associated with OS (pT3-pT4 versus pT1-pT2, HR=3.228, P=0.005; other chemotherapies versus platinum-based, HR=6.249, P=0.035). The median of cancer-specific survival (CSS) was 15 months. In univariable analyses, pathological stage and platinum-based chemotherapy regimen were associated with CCS (pT3-pT4 versus pT1-pT2, HR=3.332, P=0.004; non-platinum based versus platinum-based, HR=7.784, P=0.025). Conclusions In multivariable analyses, no variables were associated with OS and CSS. UUT-SCC is a rare tumor characterized by an aggressive clinical course. Pathological stage and platinum-based chemotherapy regimen are the most important factors related to OS and CSS.

Objective: To investigate the workload of 12 h simulated long-haul flight continuously across day and night. Methods: Six healthy male young volunteers, aged from 19 to 21 years, were trained in simulated flight and skilled in operating flight simulation software before the experiment. Subjects began the simulated flight every day at 20:00 and lasted for 12 h that ended at 8:00. Subjects flew for three consecutive days and slept at least 6 h during the day. Workload evaluation indicators were tested before and after simulated flights on the first, second, and third days, respectively. Reaction time (RT), motion time (MT), critical flicker fusion frequency (CFF), Stanford Sleepiness Scale (SSS), and rating of perceived exertion scale (RPE) were measured. Results: RT increased after simulated flights on the second and third days, but there was no significant difference between before and after flights. MT increased after the first and second days of simulated flight, but the difference was statistically significant only after the first day of flight. There was no significant difference in CFF between before and after three consecutive days of simulated flight. SSS and RPE scores were significantly increased after 12 h simulated flight for three consecutive days. Conclusions: 12 h simulated long-haul flight continuously across day and night could aggravate the flight workload and heavy fatigue.

We report on the first observation of mesospheric cloud (MC) at the altitude range of 50-65 km with lidars at Yanqing (40.5°N, 116°E) and Pingquan (41°N, 118.7°E) on 30 October 2018. The MC occurred at the 51-56 km altitude range during the hours of dawn. It had an obvious double-layer structure, but the cloud layer was sparse. The MC was re-observed at the 56-62 km altitude range in the twilight, and the double-layer structure was still obvious. However, the cloud layer became thicker with a maximum volume backscatter coefficient (BSC) 3.1×10−10m−1sr−1. Atmospheric temperature structure was derived according to the lidar observations, and it was found that, several hours before the MC occurrence, a temperature anomaly with coldest temperature ~185 K was propagating downward at the altitudes of 50-65 km. This MC layer was simultaneously observed with lidar at Pingquan in the twilight. It could be a regional MC event and possibly formed locally by a transient cooling due to small-scale disturbances in the mesosphere.

Neddylation has been researched in many different human carcinomas. However, the roles of neural precursor cell expressed, developmentally downregulated 8 (NEDD8) in bladder cancer are still unknown. Our study was the first study which systematically investigated the possible functions of NEDD8 in bladder cancer (BC) progression. We carried out immunohistochemistry to explore associations between the expression of NEDD8 in tumor tissues and clinical outcomes of patients. RT-qPCR and western blot were used to detect the expressional levels of genes. The biological abilities of cell proliferation, migration and invasion were researched by in vitro and in vivo experiments. Results were as follows: Data from The Cancer Genome Atlas (TCGA) database showed that NEDD8 was overexpressed in BC tissues and was associated with poor patient survival. Results of immunohistochemistry found that NEDD8 was significantly associated with poor clinical outcomes of BC patients. Suppression of NEDD8 could inhibit the proliferation, migration and invasion of tumor cells. Knocking down NEDD8 could induce apoptosis and G2 phase arrest of cell cycle progression. In vivo, suppression of NEDD8 restricted growth and metastasis of tumors in mice. In conclusion, NEDD8 has important roles in regulating the progression of BC cells and was associated with poor prognosis of patients; hence, it may become a potential therapeutic target of BC.