Comparison of different prediction tools for the risk of intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinoma: a propensity-matched analysis

Objective To compare the predictive performance of the current clinical prediction models for predicting intravesical recurrence (IVR) after radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC). Methods We retrospectively analysed upper tract urothelial carcinoma patients who underwent radical nephroureterectomy in our centre from January 2009 to December 2019. We used the propensity score matching (PSM) method to adjust the confounders between the IVR and non-IVR groups. Additionally, Xylinas’ reduce model and full model, Zhang’s model, and Ishioka’s risk stratification model were used to retrospectively calculate predictions for each patient. Receiver operating characteristic (ROC) curves were generated, and the areas under the curves (AUCs) were compared to identify the method with the highest predictive value. Zesults We included 217 patients with a median follow-up of 41 months, of which 57 had IVR. After PSM analysis, 52 pairs of well-matched patients were included in the comparative study. No significant difference was found in clinical indicators besides hydronephrosis. The model comparison showed that the AUCs of the reduced Xylinas’ model for 12 months, 24 months, and 36 months were 0.69, 0.73, and 0.74, respectively, and those of the full Xylinas’ model were 0.72, 0.75, and 0.74, respectively. The AUC of Zhang’s model for 12 months, 24 months, and 36 months was 0.63, 0.71, and 0.71, respectively, the performance of Ishioka’s model is that the AUC of 12 months, 24 months and 36 months was 0.66, 0.71, and 0.74, respectively. Conclusion The external verification results of the four models show that more comprehensive data and a larger sample size of patients are needed to strengthen the models’ derivation and updating procedure, to better apply them to different populations (AU)

Comparison of different prediction tools for the risk of intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinoma: a propensity-matched analysis.

OBJECTIVE: To compare the predictive performance of the current clinical prediction models for predicting intravesical recurrence (IVR) after radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC). METHODS: We retrospectively analysed upper tract urothelial carcinoma patients who underwent radical nephroureterectomy in our centre from January 2009 to December 2019. We used the propensity score matching (PSM) method to adjust the confounders between the IVR and non-IVR groups. Additionally, Xylinas' reduce model and full model, Zhang's model, and Ishioka's risk stratification model were used to retrospectively calculate predictions for each patient. Receiver operating characteristic (ROC) curves were generated, and the areas under the curves (AUCs) were compared to identify the method with the highest predictive value. RESULTS: We included 217 patients with a median follow-up of 41 months, of which 57 had IVR. After PSM analysis, 52 pairs of well-matched patients were included in the comparative study. No significant difference was found in clinical indicators besides hydronephrosis. The model comparison showed that the AUCs of the reduced Xylinas' model for 12 months, 24 months, and 36 months were 0.69, 0.73, and 0.74, respectively, and those of the full Xylinas' model were 0.72, 0.75, and 0.74, respectively. The AUC of Zhang's model for 12 months, 24 months, and 36 months was 0.63, 0.71, and 0.71, respectively, the performance of Ishioka's model is that the AUC of 12 months, 24 months and 36 months was 0.66, 0.71, and 0.74, respectively. CONCLUSION: The external verification results of the four models show that more comprehensive data and a larger sample size of patients are needed to strengthen the models' derivation and updating procedure, to better apply them to different populations.

Prognostic value of the systemic immune-inflammation index in patients with upper tract urothelial carcinoma after radical nephroureterectomy.

BACKGROUND: To investigate the prognostic significance of the systemic immune-inflammation index (SII) for patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU) and develop nomogram models for predicting overall survival (OS), intravesical recurrence (IVR), and extra-urothelial recurrence (EUR). METHODS: We retrospectively studied the clinical and pathological features of 195 patients who underwent RNU for UTUC. All patients were randomly divided into a training cohort (99 cases) and a validation cohort (96 cases). The training cohort was used to develop nomogram models, and the models were validated by the validation cohort. The least absolute shrinkage and selection operator (LASSO) regression and Cox regression were performed to identify independent predictors. The concordance index (C-index), receiver operator characteristics (ROC) analysis, and calibration plot were used to evaluate the reliability of the models. The clinical utility compared with the pathological T stage was assessed using the net reclassification index (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA). RESULTS: SII was an independent risk factor in predicting OS and EUR. The C-index values of the nomogram predicting OS, IVR, and EUR were 0.675, 0.702, and 0.756 in the training cohort and 0.715, 0.756, and 0.713 in the validation cohort. A high level of SII was correlated with the invasion of the mucosa, muscle layer of the ureter, nerves, vessels, and fat tissues. CONCLUSION: We developed nomogram models to predict the OS, IVR, and EUR of UTUC patients. The efficacy of these models was substantiated through internal validation, demonstrating favorable discrimination, calibration, and clinical utility. A high level of SII was associated with both worse OS and shorter EUR-free survival.

The function of Foxp1 represses ß-adrenergic receptor transcription in the occurrence and development of bladder cancer through STAT3 activity.

Bladder cancer is a common malignant tumor. FOXP1 has been found to be abnormally expressed in tumors such as renal cell carcinoma and endometrial cancer. Here, this investigated the biological roles of Foxp1 in the occurrence and development of bladder cancer. Patients with bladder cancer were obtained from China-Japan Friendship Hospital. Bladder cancer cell lines (5637, UMUC3, J82, and T24 cell) were used in this experiment. Foxp1 mRNA and protein expression levels in patients with bladder cancer were increased, compared with paracancerous tissue (normal). OS and DFS of Foxp1 low expression in patients with bladder cancer were higher than those of Foxp1 high expression. Foxp1 promoted bladder cancer cell growth in vitro model. Foxp1 increased the Warburg effect of bladder cancer. Foxp1 suppressed ß-adrenoceptor (ß-AR) expression in vitro model. ChIP-seq showed that Foxp1 binding site (E1, TTATTTAT) was detected at -2,251 bp upstream of the ß-AR promoter. ß-AR Reduced the effects of Foxp1 on cell growth in vitro model. ß-AR reduced the effects of Foxp1 on the Warburg effect in vitro model by STAT3 activity. Taken together, our findings reveal that Foxp1 promoted the occurrence and development of bladder cancer through the Warburg effect by the activation of STAT3 activity and repressing ß-AR transcription, and which might serve as an important clue for its targeting and treatment of bladder cancer.

Adherence to the Diabetes Risk Reduction Diet and Bladder Cancer Risk in the Prostate, Lung, Colorectal, Ovarian (PLCO) Cohort.

BACKGROUND: This study aimed to explore the relationship between diabetes risk reduction diet (DRRD) and bladder cancer risk in Prostate, Lung, Colorectal, Ovarian (PLCO) cohort. METHODS: Data from 99,001 participants in the PLCO Cancer Screening Trial were analyzed using Cox proportional hazards regression models to estimate HRs and 95% confidence intervals (CI) for the association between DRRD score and bladder cancer incidence. Subgroup analyses were conducted to assess whether variables such as age, sex, body mass index, cigarette smoking status, and history of diabetes influenced the observed association. The DRRD score was formulated on the basis of nine nutrient intake indicators derived from the Dietary History Questionnaire. RESULTS: During the median follow-up of 11.7 years, 761 new bladder cancer cases were identified. Participants with highest DRRD scores exhibited a reduced risk of bladder cancer compared with those in the lowest quartile (unadjusted analysis, HR, 0.65; 95% CI, 0.53-0.82); multivariable adjusted analysis, HR, 0.79; 95% CI, 0.64-0.98; Ptrend = 0.007). A similar risk reduction was seen solely in transitional cell carcinoma (HR, 0.79; 95% CI, 0.64-0.99; P = 0.007). In addition, the significant negative association between DRRD scores and bladder cancer risk persisted even after excluding participants with unique characteristics. CONCLUSIONS: This large prospective population-based study suggests that adherence to a DRRD may contribute to the prevention of bladder cancer. IMPACT: The DRRD could potentially mitigate bladder cancer risk, which warrants further validation in diverse populations.

A novel nomogram for predicting extraurothelial recurrence in patients with upper urinary tract urothelial carcinoma after radical nephroureterectomy.

PURPOSE: We aimed to establish and validate a nomogram for extraurothelial recurrence (EUR) after radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UTUC). METHODS: The data of 521 patients with UTUC after RNU from 2 medical centers were retrospectively studied and were used as training cohort (n = 301) and external validation cohort (n = 220). We used the least absolute shrinkage and selection operator (LASSO) to select variables for multivariable Cox regression, and included independent risk factors into nomogram models predicting EUR-free survival (EURFS). Multiple parameters were used to validate the nomogram, including the concordance index (C-index), the calibration plots, the time-dependent receiver-operator characteristics curve (ROC), and the decision curve analysis (DCA). Patients were stratified into three risk groups according to total points calculated by nomograms. The differences of EURFS in each group were analyzed by the Kaplan-Meier analysis. RESULTS: Four variables were screened through LASSO regression. Bladder cancer history, Ki-67, lymphovascular invasion (LVI), and pathological T stage were shown to be independent predictive factors for EUR. The C-indexes of the model were 0.793 and 0.793 in training and validation cohorts, respectively. In comparison with prediction based on categorized pathological T stage, the DCA curves for 5-year EUR exhibited better performance. The 5-year EURFS rates were 92.2%, 63.8%, and 36.2% in patients stratified to the low-, medium-, and high-risk group. CONCLUSION: Our study provided a new nomogram to predict the probability of EUR in UTUC patients underwent RNU, with perfect performance in discrimination ability and clinical net benefit. The application of the model may help urologists to choose proper treatment and monitoring.

Specific subsets of urothelial bladder carcinoma infiltrating T cells associated with poor prognosis.

Comprehensive investigation of tumor-infiltrating lymphocytes in cancer is crucial to explore the effective immunotherapies, but the composition of infiltrating T cells in urothelial bladder carcinoma (UBC) remains elusive. Here, single-cell RNA sequencing (scRNA-seq) were performed on total 30,905 T cells derived from peripheral blood, adjacent normal and tumor tissues from two UBC patients. We identified 18 distinct T cell subsets based on molecular profiles and functional properties. Specifically, exhausted T (TEx) cells, exhausted NKT (NKTEx) cells, Ki67+ T cells and B cell-like T (B-T) cells were exclusively enriched in UBC. Additionally, the gene signatures of TEx, NKTEx, Ki67+ T and B-T cells were significantly associated with poor survival in patients with BC and various tumor types. Finally, IKZF3 and TRGC2 are the potential biomarkers of TEx cells. Overall, our study demonstrated an exhausted context of T cells in UBC, which layed a theoretical foundation for the development of effective tumor immunotherapies.

Risk factors for extraurothelial recurrence in upper tract urothelial carcinoma after radical nephroureterectomy: a retrospective study based on a Chinese population.

Objectives: The risk factors for extraurothelial recurrence (EUR) after radical nephroureterectomy (RNU) in patients with upper urinary tract urothelial carcinoma (UTUC) are currently inconsistent and unclear. In this study, we aimed to identify these risk factors and develop a grading system for EUR. Methods: We retrospectively analyzed 220 patients who underwent RNU for UTUC in our center from January 2009 to December 2020. Overall survival (OS) and extraurothelial recurrence-free survival (EURFS) were compared using the Kaplan-Meier curve with a log-rank test. Univariate and multivariate Cox regression models were applied to identify the independent risk factors related to EUR. Results: The median follow-up period was 42 (range: 2-143) months. Of the 220 patients, 61 patients developed EUR in our cohort, which had worse survival outcome. Multivariate Cox regression analysis showed pathologic stage, lymph node (LN) status, lymphovascular invasion (LVI), Ki-67, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were independent risk factors for EUR. The Kaplan-Meier curves revealed a significant difference in EUR among the three risk groups. Conclusion: Our study suggests that pathologic stage, LN status, LVI, Ki-67, NLR, and PLR are independent risk factors for EUR in UTUC patients after RNU. The development of a grading system for EUR risk stratification may assist urologists in making clinical decisions regarding the management of UTUC.

Development and external validation of a novel nomogram to predict intravesical recurrence after radical nephroureterectomy: a multicenter study.

OBJECTIVE: This study aimed to establish and validate nomograms to predict the probability of intravesical recurrence (IVR) after radical nephroureterectomy (RNU) for upper urinary tract epithelial carcinoma (UTUC). METHODS: Clinical data of 528 patients with UTUC after RNU were collected from two medical centers between 2009 and 2020. We used the least absolute shrinkage and selection operator (LASSO) regression to select variables for multivariable Cox regression analysis in the training cohort and included independent risk factors into nomogram models predicting IVR-free survival (IVRFS). Another center was applied as the external cohort to validate the predictive accuracy and discriminative ability of the nomogram by performing area under the receiver operating curve (AUC), consistency index (C-index), and calibration curve. RESULTS: History of bladder cancer, tumor size, preoperative urine cytology, postoperative instillation, Ki-67, and platelet-to-lymphocyte ratio (PLR) were identified as independent risk factors for IVR. The prognosis model including these predictors demonstrated excellent discriminatory performance in both the training cohort (C-index, 0.814) and external validation cohort (C-index, 0.748). The calibration plots of the nomogram revealed good consistency in both cohorts. Finally, patients could be classified into two risk groups based on scores obtained from the nomogram, with significant differences in IVRFS. CONCLUSION: Our study provided a reliable nomogram for predicting the probability of IVR in patients with UTUC after RNU. Risk stratification based on this model may assist urologists make optimal clinical decisions on the management of UTUC.

Do patients with metastatic renal cell carcinoma obtain survival benefits from cytoreductive nephrectomy? A population-based study.

PURPOSE: This study aimed to explore the value of cytoreductive nephrectomy (CN) and develop nomograms to predict the prognosis of metastatic renal cell carcinoma (mRCC) patients with receiving radiology therapy or/and chemotherapy (RT/&CT). METHODS: Clinical data of patients with mRCC between 2010 and 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Prognostic nomograms were constructed to predict the overall survival (OS) and cancer-specific survival (CSS) probability for 1-, 3-, and 5- years in patients with mRCC. A series of validation methods were used to validate the accuracy and reliability of the model, including area under the receiver operating curve (AUC), consistency index (C-index), calibration curve, and decision curve analysis (DCA). RESULTS: 1394 patients were enrolled in this study. All patients were randomly divided into the training cohort (n = 976) and the validation cohort (n = 418). In the training cohort, multivariate Cox regression analysis suggested that pathology grade, histology type, T stage, N stage, surgery, and distant metastasis were independent risk factors for OS and CSS. The AUC and C-index were both over 0.65 in both cohorts, indicating that the nomograms for OS and CSS had satisfactory discriminative power. The calibration curves revealed that the predictive nomograms had a good consistency between the observed and the predicted survival. CONCLUSION: This study provided evidence that mRCC patients underwent RT/&CT could gain survival benefits from CN. The prognostic nomogram constructed in our study is reliable and practical, may help guide clinical strategies in the treatment of mRCC.

Wearable Multi-Channel Pulse Signal Acquisition System Based on Flexible MEMS Sensor Arrays with TSV Structure.

Micro-electro-mechanical system (MEMS) pressure sensors play a significant role in pulse wave acquisition. However, existing MEMS pulse pressure sensors bound with a flexible substrate by gold wire are vulnerable to crush fractures, leading to sensor failure. Additionally, establishing an effective mapping between the array sensor signal and pulse width remains a challenge. To solve the above problems, we propose a 24-channel pulse signal acquisition system based on a novel MEMS pressure sensor with a through-silicon-via (TSV) structure, which connects directly to a flexible substrate without gold wire bonding. Firstly, based on the MEMS sensor, we designed a 24-channel pressure sensor flexible array to collect the pulse waves and static pressure. Secondly, we developed a customized pulse preprocessing chip to process the signals. Finally, we built an algorithm to reconstruct the three-dimensional pulse wave from the array signal and calculate the pulse width. The experiments verify the high sensitivity and effectiveness of the sensor array. In particular, the measurement results of pulse width are highly positively correlated with those obtained via infrared images. The small-size sensor and custom-designed acquisition chip meet the needs of wearability and portability, meaning that it has significant research value and commercial prospects.

Correlation between the timing of diagnostic ureteroscopy for upper tract urothelial cancer and intravesical recurrence after radical nephroureterectomy.

Objective: We aimed to evaluate the effect of the timing of diagnostic ureteroscopy (URS) on intravesical recurrence (IVR) following radical nephroureterectomy (RNU). Patients and methods: The clinical data of 220 patients with upper tract urothelial carcinoma (UTUC) treated with RNU at our center from June 2010 to December 2020 were retrospectively analyzed. According to the timing of the URS, all patients were divided into three groups: the no URS group, the 1-session group (diagnostic URS immediately followed by RNU), and the 2-session group (RNU after diagnostic URS). Additionally, we analyzed IVR-free survival (IVRFS) using the Kaplan-Meier and Cox proportional regression methods. Results: The median follow-up period of these 220 patents was 41 (range: 2-143) months. Among them, 58 patients developed IVR following RNU. Kaplan-Meier curve displayed a significantly higher IVR rate in both treatment groups than in the no-URS group (p=0.025). In the subgroup of patients with renal pelvis cancer, the incidence of IVR was significantly higher in both treatment groups than in the group without URS (p=0.006). In univariate Cox proportional regression analysis, the two treatment groups were risk factors for IVR compared to the no-URS group [p=0.027, hazard ratio (HR): 1.93, 95% confidence interval (CI): 1.08-3.46]. The two-stage group (p=0.032, HR: 1.98, 95% CI: 1.08-3.65), positive urine pathology (p<0.001, HR: 8.12, 95% CI: 3.63-18.15), adjuvant chemotherapy (p<0.001, HR: 0.20, 95% CI: 0.10-0.38), and positive margin (p<0.0001, HR: 7.50, 95% CI: 2.44-23.08) were all identified as independent predictors in the multivariate. Conclusion: This study revealed that delayed RNU following diagnostic URS may increase the risk of postoperative IVR in patients with UTUC, preoperatively positive uropathology, and positive surgical margin were risk factors for IVR after RNU, while early postoperative chemotherapy may effectively prevent IVR. Delay of RUN after URS could increase the risk of IVR.

First Report of Fusarium acuminatum Causing Dianthus chinensis root rot and foliage blight in China.

Dianthus chinensis is a popular ornamental plant that is widely cultivated in China. In May 2020, a disease was found at several landscape sites in Xuanwu District, Nanjing, China, causing symptoms of foliage blight and root discoloration on approximately 52% of one-year old D. chinensis plants. To recover the causal pathogen, samples of infected roots and leaves were cut into 5×5 mm2 pieces, surface-disinfected in 75% ethanol for 30 sec, followed by 1% NaClO for 90 sec, rinsed with sterile water three times and placed on potato dextrose agar (PDA) with 0.1 mg/mL of ampicillin at 25 °C. Hyphae growing on PDA were visible from both root and leaf tissues after three days. Individual hyphal tips were transferred to new PDA plates to obtain pure isolates. Three representative isolates were deposited in the China Forestry Culture Collection Center (CFCC 57545,57546, 57547). The hyphae grew radially, densely, and the aerial hyphae were velvety, white, yellow-white, or pink-white. Representative isolate Facu-DCY5 produced three types of conidia (microconidia, macroconidia, and chlamydospores). Macroconidia were sickle-shaped, measuring 25.7-55.4 µm × 3.2-4.6 µm (n=50). Microconidia were numerous, oval or kidney-shaped, measuring 6.8-11.9 µm × 3.5-4.8 µm (n=50). Conidia produced in the aerial mycelium were 16-34 × 2.2-5.3 µm (n=50). The ITS region, TEF1, calmodulin (CMDA), and RNA polymerase II second largest subunit (RPB2) were amplified with primers ITS1/ITS4, EF1/EF2, CL1/CL2A and 5F2/7CR , respectively and sequenced at Sangon Biotech (Nanjing, China). The ITS sequence of isolate Facu-DCY5 (GenBank No. ON307073.1) was identical to HQ165938.1, ON306850.1, OM964482.1. TEF1 (ON331997.1) was identical to LC546967.1, HQ165866.1, MZ158155.1. CMDA (ON331996.1) was identical to HQ412345.1, MZ921595.1 and MZ921597.1. RPB2 (ON331995.1) was identical to MZ997370.1. Maximum parsimony and maximum likelihood phylogenies of the Facu-DCY5 multilocus sequence data and those of several species within the F. tricinctum species complex identified the isolate from D. chinensis as F. acuminatum . Pathogenicity tests were performed using a conidial suspension (104 conidia/mL). Each plant (approx. 0.3 m in -height) was inoculated with 1 mL of the conidial suspension by mixing it into the potting soil (500 g). Control plants were treated with sterile distilled water. All inoculated plants (n=9) in three repeats of the assay exhibited foliage blight and root rot after 15 days, whereas all control plants (n=9) remained asymptomatic. Fusarium isolates with identical morphological features and molecular marker sequences to those of Facu-DCY5 were recovered from foliage blight and root tissues of all the inoculated plants. In China, F. acuminatum has been reported as a pathogen of Cucurbita maxima, Actinidia arguta, Polygonatum odoratumand Schisandra chinensis. This is the first report of F. acuminatum on D. chinensis in China. Considering the importance of D. chinensis to both ornamental nurseries and landscaping industries, we recommend that diseased plants be removed to prevent the spread of F. acuminatum, and that identification of the infecting isolates from D. chinensis at other sites and landscape locations be performed.

First Report of Crown and Root Rot Caused by Fusarium solani on Photinia × fraseri Dress in China.

Photinia × fraseri Dress was introduced to China at the end of the 20th century. It is a kind of colorful ornamental tree species with great ornamental value. From 2020 to 2021, a disease was found in Railway Gymnasium, Xuanwu district of Nanjing which approximately 40% P. × fraseri showed symptoms of blight with discoloration and dieback of crown and root . Symptomatic root tissues collected from three 2-year-old plants were rinsed with water, cut into 2-mm pieces which were surface-sterilized in 70 % ethanol for 60 s, and plated onto Potato Dextrose Agar (PDA), and incubated in the dark at 26 °C for 3 days. Mycelium emerged from 75 % of the samples. Two representative isolates (SG31, SG32) were obtained and deposited in China's Forestry Culture Collection Center. The colony growed in a circular shape, and the early aerial hyphae were white. Later a floccose, white, colony which was dull yellow on the underside was observed . The two isolates had identical morphological features. The macroconidia were sickle-shaped with two to three septa, 22.8 - 43.7 µm × 4.1 - 5.8 µm in size (n=50). The microconidia were numerous, oval, fusiform, renal, or oblong, with zero or one septum, 10.96 - 14.63 µm × 3.89 - 5.76 µm in size (n=50). The hyphae begin to germinate from one or both ends of the spore . Thus, the two isolates were identified as Fusarium solani. For molecular identification, the DNA of the two isolates was extracted. The internal transcribed spacer (ITS) region, ß-tubulin (TUB2), and actin gene (ACT) region were amplified using the primer pairs ITS5 / ITS4, T1 / T2 , and ACT-512F / ACT-783R), respectively. The sequences were deposited in GenBank under accession numbers ON329814, ON366356, and ON366358 for SG31 and ON329813, ON366357, and ON366359 for SG32. The ITS, TUB2, and ACT sequences of isolate SG31 were 99.83% (574 / 575 nt), 99.81% (517 / 518 nt), and 100% (248 / 248 nt) identical to those of SF_450 (MT529726.1), CH64 (KU938961.1), and Co.Karbala-IQ1 (MW080737.1), respectively (The comparison results of SG32 were shown in Appendix.). Based on morphological and molecular analysis, the two isolates were identified as F. solani. The pathogenicity of SG31 and SG32 were tested on potted 1-yr-old (30-cm tall) P. × fraseri. Nine plants were dug up to expose root balls, which were wounded before inoculations with a sterile needle, and then inoculated with conidial suspension (106 conidia / mL). Controls were treated with ddH2O. Three seedlings/isolate were used for each treatment. All plants were repotted using the original sterilized potting mix and pots. After inoculation, the plants were covered with plastic bags, and sterilized H2O was sprayed into the bags twice per day to maintain humidity and kept in a greenhouse at the day/night temperatures at 25 ± 2 / 16 ± 2 ℃. Within 30 days, all the inoculated plants showed lesions similar to those observed in the field, whereas controls were asymptomatic. The isolates were reisolated from the lesions (whereas not from controls) and sequenced as F. solani. Globally, this is the first report of F. solani causing crown blight and root rot of P. × fraseri. Additional surveys are being conducted for mapping the distribution of F. solani in Jiangsu Province of China.

Intravesical recurrence factors and outcome after radical nephroureterectomy for upper tract urothelial carcinoma: Multivariate analysis with propensity score matching.

Objective: The risk factors for intravesical recurrence (IVR) after radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC) remain inconsistent and unclear. Thus, the risk factors of IVR after RNU and the prognostic significance of the risk indicators were explored herein. Methods: We retrospectively analyzed UTUC patients upon RNU in our center from January 2009 to December 2019. After propensity score matching, 139 patients were included in this study. Univariate and multivariate Cox proportional hazard regressions were used to estimate the hazard ratio and 95% confidence intervals. Overall survival (OS), cancer-specific survival (CSS) and recurrence-free survival (RFS) were measured using the Kaplan-Meier curve with a log-rank test. A P-value < 0.05 was considered statistically significant. Results: We included 139 patients with a median follow-up of 42 months, of which 48 patients had an intravesical recurrence. Multivariate Cox regression analysis showed cytological abnormalities in urine (HR=3.101, P=0.002), hydronephrosis (HR=1.852, P=0.042), adjuvant chemotherapy (HR=0.242, P<0.001), and previous history of bladder cancer (HR=5.51, P<0.001) were independent risk factors for IVR. As for clinical outcomes, OS and CSS suggested disadvantages in patients with IVR compared with patients without recurrence (P=0.042 for OS, P<0.0001 for CSS), OS of patients with abnormal urine cytology and OS and CSS of patients receiving adjuvant chemotherapy did not present clinical significance, and other risk factors all affected the clinical outcome. Conclusion: In this propensity-score matching study, cytological abnormality of urine, hydronephrosis, adjuvant chemotherapy and previous history of bladder cancer were shown to be independent risk factors for IVR. Moreover, risk factors also influence clinical outcomes, thereby rendering it necessary to adopt more active postoperative surveillance and treatment strategies for these patients, which may help improve treatment outcomes.

Rapid detection of Phytophthora cinnamomi based on a new target gene Pcinn13739.

Phytophthora cinnamomi causes crown and root wilting in more than 5,000 plant species and represents a significant threat to the health of natural ecosystems and horticultural crops. The early and accurate detection of P. cinnamomi is a fundamental step in disease prevention and appropriate management. In this study, based on public genomic sequence data and bioinformatic analysis of several Phytophthora, Phytopythium, and Pythium species, we have identified a new target gene, Pcinn13739; this allowed us to establish a recombinase polymerase amplification-lateral flow dipstick (RPA-LFD) assay for the detection of P. cinnamomi. Pcinn13739-RPA-LFD assay was highly specific to P. cinnamomi. Test results for 12 isolates of P. cinnamomi were positive, but negative for 50 isolates of 25 kinds of Phytophthora species, 13 isolates of 10 kinds of Phytopythium and Pythium species, 32 isolates of 26 kinds of fungi species, and 11 isolates of two kinds of Bursaphelenchus species. By detecting as little as 10 pg.µl-1 of genomic DNA from P. cinnamomi in a 50-µl reaction, the RPA-LFD assay was 100 times more sensitive than conventional PCR assays. By using RPA-LFD assay, P. cinnamomi was also detected on artificially inoculated fruit from Malus pumila, the leaves of Rhododendron pulchrum, the roots of sterile Lupinus polyphyllus, and the artificially inoculated soil. Results in this study indicated that this sensitive, specific, and rapid RPA-LFD assay has potentially significant applications to diagnosing P. cinnamomi, especially under time- and resource-limited conditions.

Bladder cancer selective chemotherapy with potent NQO1 substrate co-loaded prodrug nanoparticles.

Currently, clinical intravesical instillation chemotherapy has been greatly compromised by the toxicological and physiological factors. New formulations that can specifically and efficiently kill bladder cancer cells are in urgent need to overcome the low residence efficiency and dose limiting toxicity of current ones. The combination of mucoadhesive nanocarriers and cancer cell selective prodrugs can to great extent address these limitations. However, the insignificant endogenous stimulus difference between cancer cells and normal cells in most cases and the high local drug concentration make it essential to develop new drugs with broader selectivity-window. Herein, based on the statistically different NQO1 expression between cancerous and normal bladder tissues, the reactive oxygen species (ROS) activatable epirubicin prodrug and highly potent NQO1 substrate, KP372-1, was co-delivered using a GSH-responsive mucoadhesive nanocarrier. After endocytosis, epirubicin could be promptly activated by the NQO1-dependent ROS production caused by KP372-1, thus specifically inhibiting the proliferation of bladder cancer cells. Since KP372-1 is much more potent than some commonly used NQO1 substrates, for example, ß-lapachone, the cascade drug activation could occur under much lower drug concentration, thus greatly lowering the toxicity in normal cells and broadening the selectivity-window during intravesical bladder cancer chemotherapy.

First Report of Crown and Root Rot Caused by Fusarium oxysporum on Photinia × fraseri Dress in China.

Photinia × fraseri Dress was introduced to China in 1998 and has been widely used in gardens as an ornamental plant. From April 2021 to 2022, a diseasecausing blight and root discoloration in approximately 80% of P. × fraseri at several landscape sites in Xuanwu Lake Park. Symptomatic root tissues were immersed in 75% ethanol for 30 s followed by 1% NaClO for 90 s, rinsed with sterile water 3 times, and placed on Potato Dextrose Agar (PDA). After 3 days of dark incubation at 25 °C, white Fusarium-like colonies grew out from the symptomatic root tissue pieces. Three representative isolates (SG1, SG6, and SG23) were obtained and deposited in China's Forestry Culture Collection Center. The hyphae grew radially and the aerial hyphae were velvety, white or pinkish-white . After 20 days, macroconidia, microconidia, and chlamydospores were produced in the colonies on PDA. Macroconidia are sickle-shaped, slightly curved, 23-50.6 µm × 4-6 µm in size. Microconidia were numerous, oval or kidney-shaped, 6.7-12.6 µm × 3.5-5.7 µm in size, with germinating from one or both ends (Fig S1E, F). Chlamydospores were spherical, smooth, and round, in chains or solitary in hyphae (Fig S1G). All three isolates had identical morphological features. Phylogenetic analysis of concatenated CAMD, RPB2 and TEF1 sequences showed that the three isolates clustered in the same clade as F. oxysporum. Two-year old P. × fraseri potted seedlings (30-cm tall, n=12) were placed at the greenhouse (temperature; 26°C, daylight; 14 hours) for the pathogenicity tests . Roots of P. × fraseri were dipped in a 10 mL of the conidial suspension (106 conidia/mL) of each isolate for 2 hours, and the control plants were inoculated with sterile water. Results showed that after 21 days post-inoculation, all inoculated seedlings (n=9) showed crown and root rot . In contrast, none of the control seedlings (n=3) were affected. Re-isolation of three fungal isolates (infected root) showed that their morphology and gene markers sequence were identical to the original isolates thus fulfilled Koch's postulates. Globally, this is the first report of F. oxysporum causing crown blight and root rot of P. × fraseri, which is also a potential threat to the two parent hosts (P. serratifolia and P. glabra). Additional surveys are being conducted for mapping the distribution of F. oxysporum in the Nanjing Province of China.

What is the Role of the Preoperative Blood-Based Inflammation Biomarkers in the Prognosis of Upper Tract Urothelial Carcinoma With Radical Nephroureterectomy? A Single-Centre Retrospective Study.

Objective: To assess the prognostic value of preoperative blood-based inflammation biomarkers, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR), on the survival outcomes of patients with upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy (RNU). Methods: We retrospectively studied the data of 172 patients who were diagnosed with UTUC after RNU during 2008 to 2018. We determined the cut-off value by using X-tile software. The area under the curve (AUC) and concordance index (C-index) were utilized to compare the predictive accuracy between subgroups. We also performed decision curve analysis (DCA) to evaluate the clinical net benefit of prognostic models. The Kaplan-Meier method and Cox proportional hazards regression models were performed to evaluate the association between these inflammation biomarkers and survival outcomes. Results: The median follow-up period was 45.5 (range: 1-143; interquartile range, IQR: 27-77) months. Kaplan-Meier analyses showed that a high NLR or PLR significantly reduced overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS) and metastasis-free survival (MFS), and a low LMR markedly decreased RFS and MFS. The multivariate Cox proportional hazards model revealed that the NLR plus PLR was an independent predictor of worse survival (all P < .05). Additionally, the AUC and C-index of the new prognostic models were the largest for the 1- to 5-year OS, CSS, RFS, and MFS were the largest. Conclusion: Our study confirms that the combination of preoperative NLR and PLR could be an independent risk factor for UTUC patients who have undergone RNU. The addition of NLR and PLR may improve the accuracy of current prognostic models and help guide clinical strategies in the treatment of UTUC.