Feasibility and safety of dual-console telesurgery with the KangDuo Surgical Robot-1500 System using fifth-generation and wired networks: an animal experiment and sea-spanning clinical study.

BACKGROUND: To evaluate the feasibility and safety of dual-console telesurgery with the new KangDuo system in an animal experiment and clinical study. METHODS: Six canine models were performed radical prostatectomy with dual-console KanDuo surgical robot-1500 (KD-SR-1500-RARP). The perioperative outcomes, physical and mental workload of the surgeon were collected. Physical workload was evaluated with surface electromyography. Mental workload was evaluated with NASA-TLX. After conducting animal experiments to verify safety of dual-console KD-SR-1500-RARP, we conducted the clinical trial using 5G and wired networks. RESULTS: In the animal experiment, all surgeries were performed successfully. The operative time was 80.2±32.1 min. The docking time was 2.4±0.5 min. The console time was 49.7±25.3 min. There were no perioperative complications or equipment related adverse events. All dogs can micturate after catheter removal at one week postoperatively. The mental workload was at a low level (a scale ranging from 0 to 60), which scored 15.7±6.9. Among the eight recorded muscles, the fatigue degree of the right radial flexor and left biceps was the highest two (iEMG, resection, 299.8±344 uV, 109.9±16.9 uV; suture, 849.4±1252.5 uV, 423.1±621.3 uV, respectively). In the clinical study, the console time was 136 min. The mean latency time was ≤200 ms. The data pocket loss was <1%. The operation was successfully completed without malfunctions occurring throughout the entire process. CONCLUSIONS: Dual-console telesurgery with the KD-SR-1500 system was shown to be feasible and safe in radical prostatectomy using 5G and wired networks.

Trogocytosis of CAR molecule regulates CAR-T cell dysfunction and tumor antigen escape.

Chimeric antigen receptor (CAR) T-cell therapy has demonstrated clinical response in treating both hematologic malignancies and solid tumors. Although instances of rapid tumor remissions have been observed in animal models and clinical trials, tumor relapses occur with multiple therapeutic resistance mechanisms. Furthermore, while the mechanisms underlying the long-term therapeutic resistance are well-known, short-term adaptation remains less understood. However, more views shed light on short-term adaptation and hold that it provides an opportunity window for long-term resistance. In this study, we explore a previously unreported mechanism in which tumor cells employ trogocytosis to acquire CAR molecules from CAR-T cells, a reversal of previously documented processes. This mechanism results in the depletion of CAR molecules and subsequent CAR-T cell dysfunction, also leading to short-term antigen loss and antigen masking. Such type of intercellular communication is independent of CAR downstream signaling, CAR-T cell condition, target antigen, and tumor cell type. However, it is mainly dependent on antigen density and CAR sensitivity, and is associated with tumor cell cholesterol metabolism. Partial mitigation of this trogocytosis-induced CAR molecule transfer can be achieved by adaptively administering CAR-T cells with antigen density-individualized CAR sensitivities. Together, our study reveals a dynamic process of CAR molecule transfer and refining the framework of clinical CAR-T therapy for solid tumors.

Surgical techniques and oncological outcomes of pure transperitoneal laparoscopic radical nephroureterectomy for upper urinary tract urothelial carcinoma.

Background: Open radical nephroureterectomy (RNU) with bladder cuff excision is the standard treatment for upper urinary tract urothelial carcinoma (UTUC). Traditional laparoscopic radical nephroureterectomy (LSRNU) is not minimally invasive enough due to the complex surgical procedure. This study aims to discuss the clinical feasibility and oncological outcomes of pure transperitoneal LSRNU for UTUC. Methods: Between July 2010 and December 2020, 115 patients were admitted to the hospital with the diagnosis of UTUC treated with pure LSRNU by one surgeon. A special laparoscopic bulldog clamp was placed at the bladder cuff before cutting and suturing. The clinical and follow-up data were preoperatively collected and analyzed. Overall survival (OS) and cancer-specific survival (CSS) were estimated by the Kaplan-Meier method. Results: All surgeries were completed uneventfully in this cohort. The mean operative time was 145.69 minutes. The mean estimated blood loss was 56.61 mL. The mean removal time of the drain was 3.46 days. The mean time of having liquid diet was 1.32 days, and the ambulation time was 1.50 days. All surgeries were effectively completed, and no case required open conversion. According to the Clavien-Dindo classification system, postoperative complications occurred in two patients (II, III). The mean length of postoperative hospital stay was 5.78 days. The mean follow-up duration was 54.50 months. Recurrence in the bladder was 16.0% (15/94), compared with 4.6% (4/87) in the contralateral upper tract. The 5-year OS and CSS rates were 78.9% and 81.4%, respectively. Conclusions: Pure transperitoneal LSRNU is a safe and effective minimally invasive technology for the treatment of UTUC.

Early Drought-Responsive Genes Are Variable and Relevant to Drought Tolerance.

Drought stress is an important crop yield limiting factor worldwide. Plant physiological responses to drought stress are driven by changes in gene expression. While drought-responsive genes (DRGs) have been identified in maize, regulation patterns of gene expression during progressive water deficits remain to be elucidated. In this study, we generated time-series transcriptomic data from the maize inbred line B73 under well-watered and drought conditions. Comparisons between the two conditions identified 8,626 DRGs and the stages (early, middle, and late drought) at which DRGs occurred. Different functional groups of genes were regulated at the three stages. Specifically, early and middle DRGs display higher copy number variation among diverse Zea mays lines, and they exhibited stronger associations with drought tolerance as compared to late DRGs. In addition, correlation of expression between small RNAs (sRNAs) and DRGs from the same samples identified 201 negatively sRNA/DRG correlated pairs, including genes showing high levels of association with drought tolerance, such as two glutamine synthetase genes, gln2 and gln6 The characterization of dynamic gene responses to progressive drought stresses indicates important adaptive roles of early and middle DRGs, as well as roles played by sRNAs in gene expression regulation upon drought stress.

Preoperative PI-RADS Version 2 scores helps improve accuracy of clinical nomograms for predicting pelvic lymph node metastasis at radical prostatectomy.

BACKGROUND: Lymph node invasion (LNI) is a strong adverse prognostic factor in prostate cancer (PCa). The purpose of this study was to evaluate the role of Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) scores for estimating the risk of LN metastasis. The study also aimed to investigate the additional value of PI-RADSv2 scores when used in combination with clinical nomograms for the prediction of LNI in patients with PCa. METHODS: We retrospectively identified 308 patients who underwent multiparametric magnetic resonance imaging (mpMRI) and RP with pelvic lymph node dissection (PLND). Clinicopathological parameters and PI-RADSv2 scores were assessed. Univariate and multivariate logistic analyses were performed. The area under the receiver operating characteristic curves (AUCs) and decision curve analysis (DCA) were generated for assessing the incremental value of PI-RADSv2 scores combined with the Briganti and Memorial Sloan Kettering Cancer Center (MSKCC) nomograms. RESULTS: Overall, 20 (6.5%) patients had LNI. At univariate analysis, all clinicopathological characteristics and PI-RADSv2 scores were significantly associated to LNI (p < 0.04). However, multivariate analysis revealed that only PI-RADSv2 scores and percentage of positive cores were independently significant (p ≤ 0.006). The PI-RADSv2 score was the most accurate predictor (AUC, 80.2%). The threshold of PI-RADSv2 score was 5, which provided high sensitivity (18/20, 90.0%) and negative predictive value (203/205, 99.0%). When PI-RADSv2 scores were combined with Briganti and MSKCC nomograms, the AUC value increased from 75.1 to 86.3% and from 79.2 to 87.9%, respectively (p ≤ 0.001). The DCA also demonstrated that the two nomograms plus PI-RADSv2 scores improved clinical risk prediction of LNI. CONCLUSIONS: The patients with a PI-RADSv2 score <5 were associated with a very low risk of LNI in PCa. Preoperative PI-RADSv2 scores could help improve the accuracy of clinical nomograms for predicting pelvic LN metastasis at radical prostatectomy.

Temporal Small RNA Expression Profiling under Drought Reveals a Potential Regulatory Role of Small Nucleolar RNAs in the Drought Responses of Maize.

Small RNAs (sRNAs) are short noncoding RNAs that play roles in many biological processes, including drought responses in plants. However, how the expression of sRNAs dynamically changes with the gradual imposition of drought stress in plants is largely unknown. We generated time-series sRNA sequence data from maize ( L.) seedlings under drought stress (DS) and under well-watered (WW) conditions at the same time points. Analyses of length, functional annotation, and abundance of 736,372 nonredundant sRNAs from both DS and WW data, as well as genome copy numbers at the corresponding genomic regions, revealed distinct patterns of abundance and genome organization for different sRNA classes. The analysis identified 6646 sRNAs whose regulation was altered in response to drought stress. Among drought-responsive sRNAs, 1325 showed transient downregulation by the seventh day, coinciding with visible symptoms of drought stress. The profiles revealed drought-responsive microRNAs, as well as other sRNAs that originated from ribosomal RNAs (rRNAs), splicing small nuclear RNAs, and small nucleolar RNAs (snoRNA). Expression profiles of their sRNA derivers indicated that snoRNAs might play a regulatory role through regulating the stability of rRNAs and splicing small nuclear RNAs under drought condition.

Maize glossy6 is involved in cuticular wax deposition and drought tolerance.

Cuticular waxes, long-chain hydrocarbon compounds, form the outermost layer of plant surfaces in most terrestrial plants. The presence of cuticular waxes protects plants from water loss and other environmental stresses. Cloning and characterization of genes involved in the regulation, biosynthesis, and extracellular transport of cuticular waxes onto the surface of epidermal cells have revealed the molecular basis of cuticular wax accumulation. However, intracellular trafficking of synthesized waxes to the plasma membrane for cellular secretion is poorly understood. Here, we characterized a maize glossy (gl6) mutant that exhibited decreased epicuticular wax load, increased cuticle permeability, and reduced seedling drought tolerance relative to wild-type. We combined an RNA-sequencing-based mapping approach (BSR-Seq) and chromosome walking to identify the gl6 candidate gene, which was confirmed via the analysis of multiple independent mutant alleles. The gl6 gene represents a novel maize glossy gene containing a conserved, but uncharacterized, DUF538 domain. This study suggests that the GL6 protein may be involved in the intracellular trafficking of cuticular waxes, opening the door to elucidating the poorly understood process by which cuticular wax is transported from its site of biosynthesis to the plasma membrane.

Prevalence, clinicopathological features, and prognosis in upper tract urinary carcinoma patients with severe preoperative chronic kidney disease.

BACKGROUND: Studies regarding the prevalence and factors associated with severe pre-operative chronic kidney disease (CKD) in upper tract urinary carcinoma (UTUC) patients were rare due to the low prevalence of UTUC. We conducted the present study to investigate the prevalence, clinicopathological features, and prognosis in UTUC patients with severe preoperative CKD. METHODS: The study included 731 patients with UTUC treated with radical nephroureterectomy (RNU) in a large Chinese center. Estimated glomerular filtration rate (eGFR) was calculated by re-expressed Modification of Diet in Renal Disease (MDRD) formulas for the Chinese population. Severe preoperative CKD was defined as CKD stage 4-5 (eGFR <30 mL/min). Relationships of CKD stage 4-5 with clinicopathological characteristics, overall survival (OS), cancer-specific survival (CSS), contralateral recurrence-free survival and intravesical recurrence (IVR)-free survival were analyzed. RESULTS: A total of 73 (10.0%) patients presented severe preoperative CKD in this cohort. Multivariate logistic analysis indicated that female gender (OR =1.791; 95% CI: 1.018-3.150; P=0.043), lower BMI (OR =0.452; 95% CI: 0.262-0.778; P=0.004), concomitant bladder tumor (OR =2.944; 95% CI: 1.360-6.373; P=0.006), lower pathological T stage (OR =0.578; 95% CI: 0.339-0.984; P=0.043), tumor necrosis (OR =2.764; 95% CI: 1.411-5.416; P=0.003), and exposure of aristolochic acid (AA) (OR =3.115; 95% CI: 1.536-6.316; P=0.002) were significantly related to severe CKD. Multivariate Cox's regression analysis showed that severe preoperative CKD was significantly associated with worse OS (HR =1.840; 95% CI: 1.150-2.944; P=0.011) and worse contralateral recurrence-free survival (HR =3.269; 95% CI: 1.607-6.650; P=0.001), while no statistical difference in terms of CSS or IVR-free survival were noticed. CONCLUSIONS: Female gender, lower BMI, concomitant bladder tumor, lower pathological T stage, exposure of AA, and tumor necrosis were independently associated with severe preoperative CKD in UTUC patients. UTUC patients with severe preoperative CKD possess worse OS and higher possibility of contralateral upper urinary tract recurrence.

Positive urinary fluorescence in situ hybridization indicates poor prognosis in patients with upper tract urothelial carcinoma.

Here, we evaluated the potential contribution of fluorescent in situ hybridization (FISH) as a prognostic risk factor of bladder recurrence and survival in patients with upper tract urothelial carcinoma (UTUC). A total of 159 UTUC patients were enrolled in this study from January 2012 to May 2016. The 159 voided urine samples before surgery were analyzed using the UroVysion® kit to detect the copy numbers of chromosomes 3, 7, 17 and 9p21 (p16). Patients were classified using an optimal cutoff value of chromosomes 3, 7, 17, and 9p21. Cox's proportional hazards regression model was used to assess the prognostic value of FISH for bladder recurrence and survival. We found that 27 (17.6%) patients experienced bladder recurrence and 26 (16.4%) patients died from cancer, with a median follow-up of 27 months. The patients with positive FISH result were more likely to present bladder recurrence (p = 0.077). However, positive FISH was not associated with cancer specific-free survival (CSS) (p = 0.944). Tumor multifocality, the percentage of abnormal chromosome 3 > 5%, chromosome 7 > 6%, chromosome 17 > 11% and deletion of p16 > 4% were significant prognostic risk factors for BRFS in univariate analysis. In multivariate analysis, only tumor multifocality (hazard ratio [HR] = 3.487, 95%CI: 1.605-7.576, p = 0.002) and the percentage of p16 loss > 4% were both prognostic risk factors for bladder recurrence (HR = 3.487, 95%CI: 1.605-7.576, p = 0.002). These data consider that the urinary FISH test could be a powerful tool in predicting the risk of bladder recurrence in patients with UTUC.

Ileal Ureter Replacement Combined With Boari Flap-Psoas Hitch to Treat Full-Length Ureteral Defects: Technique and Initial Experience.

OBJECTIVE: To evaluate the feasibility of ileal ureter replacement combined with Boari flap-psoas hitch procedure for the management of full-length ureteral defects (>20 cm). METHODS: Three patients diagnosed with full-length ureteral defect were treated with our technique performed by a single surgeon between January 2015 to January 2016. All the patients had borderline renal function preoperatively. In each case, the ureteral reconstruction was performed by combining ileal ureter replacement with Boari flap-psoas hitch. Data on indications for surgery, intraoperative and postoperative outcomes, and changes in renal function were collected. RESULTS: Surgery was performed successfully with an operation duration between 210 and 250 minutes. The mean estimated blood loss was 230 mL. The mean length of hospital stay was 11 days, and no major complications (grade ≥3) occurred. Postoperative follow-up showed radiological resolution of hydronephrosis and improved renal function in all 3 patients. CONCLUSION: Ileal ureter replacement combined with Boari flap-psoas hitch is a feasible option for bridging full-length ureteral defects. This technique minimizes the length of ileal graft required as well as limitations concerning patient selection. Larger series with longer follow-up to confirm the value of the technique are warranted.

The Application of Internal Suspension Technique in Retroperitoneal Laparoscopic Partial Nephrectomy for Renal Ventral Tumors.

OBJECTIVE: To evaluate the feasibility of an internal suspension technique in retroperitoneal laparoscopic partial nephrectomy for the management of renal ventral tumors. METHODS: Between January 2013 and July 2016, a total of 145 patients underwent retroperitoneal laparoscopic partial nephrectomy with or without internal suspension technique. For patients who underwent internal suspension technique, the surgeons preserved the external fat of the renal tumor as a suspension traction measure when separating the kidney. Propensity score matching (PSM) was performed according to age, gender, body mass index, tumor size, tumor location, and RENAL nephrometry score. Patient characteristics and intraoperative and postoperative outcomes were compared between the groups. RESULTS: After PSM, 32 patients treated with the internal suspension technique were compared with 32 cases treated without such technique. Baseline characteristics were statistically similar for the cohorts. The use of our new technique resulted in shorter warm ischemia time (WIT: 15.0 versus 19.0 minutes, P = .002) and tumor resection time (4.0 versus 7.5 minutes, P < 0.001). The rate of WIT >25 minutes decreased (6.3% versus 25%, P = .04) and the trifecta outcomes were significantly improved (87.5% versus 62.5%, P = .02). CONCLUSION: Internal suspension technique is a feasible and safe procedure in retroperitoneal laparoscopic partial nephrectomy for renal ventral tumors.

Mutations in the maize zeta-carotene desaturase gene lead to viviparous kernel.

Preharvest sprouting reduces the maize quality and causes a significant yield loss in maize production. vp-wl2 is a Mutator (Mu)-induced viviparous mutant in maize, causing white or pale yellow kernels, dramatically reduced carotenoid and ABA content, and a high level of zeta-carotene accumulation. Here, we reported the cloning of the vp-wl2 gene using a modified digestion-ligation-amplification method (DLA). The results showed that an insertion of Mu9 in the first intron of the zeta-carotene desaturase (ZDS) gene results in the vp-wl2 mutation. Previous studies have suggested that ZDS is likely the structural gene of the viviparous9 (vp9) locus. Therefore, we performed an allelic test using vp-wl2 and three vp9 mutants. The results showed that vp-wl2 is a novel allele of the vp9 locus. In addition, the sequences of ZDS gene were identified in these three vp9 alleles. The vp-wl2 mutant gene was subsequently introgressed into four maize inbred lines, and a viviparous phenotype was observed with yield losses from 7.69% to 13.33%.

Key Technology of Real-Time Road Navigation Method Based on Intelligent Data Research.

The effect of traffic flow prediction plays an important role in routing selection. Traditional traffic flow forecasting methods mainly include linear, nonlinear, neural network, and Time Series Analysis method. However, all of them have some shortcomings. This paper analyzes the existing algorithms on traffic flow prediction and characteristics of city traffic flow and proposes a road traffic flow prediction method based on transfer probability. This method first analyzes the transfer probability of upstream of the target road and then makes the prediction of the traffic flow at the next time by using the traffic flow equation. Newton Interior-Point Method is used to obtain the optimal value of parameters. Finally, it uses the proposed model to predict the traffic flow at the next time. By comparing the existing prediction methods, the proposed model has proven to have good performance. It can fast get the optimal value of parameters faster and has higher prediction accuracy, which can be used to make real-time traffic flow prediction.