Nomogram to predict the risk of adverse outcomes in patients with residual stones following percutaneous nephrolithotomy.

PURPOSE: To investigate the risk factors associated with adverse outcomes in patients with residual stones after percutaneous nephrolithotomy (PCNL) and to establish a nomogram to predict the probability of adverse outcomes based on these risk factors. METHODS: We conducted a retrospective review of 233 patients who underwent PCNL for upper urinary tract calculi and had postoperative residual stones. The patients were divided into two groups according to whether adverse outcomes occurred, and the risk factors for adverse outcomes were explored by univariate and multivariate analyses. Finally, we created a nomogram for predicting the risk of adverse outcomes in patients with residual stones after PCNL. RESULTS: In this study, adverse outcomes occurred in 125 (53.6%) patients. Multivariate logistic regression analysis indicated that the independent risk factors for adverse outcomes were the diameter of the postoperative residual stones (P < 0.001), a positive urine culture (P = 0.022), and previous stone surgery (P = 0.004). The above independent risk factors were used as variables to construct the nomogram. The nomogram model was internally validated. The calculated concordance index was 0.772. The Hosmer-Lemeshow goodness-of-fit test was performed (P > 0.05). The area under the ROC curve of this model was 0.772. CONCLUSIONS: Larger diameter of residual stones, positive urine culture, and previous stone surgery were significant predictors associated with adverse outcomes in patients with residual stones after PCNL. Our nomogram could help to assess the risk of adverse outcomes quickly and effectively in patients with residual stones after PCNL.

NEAT1 promotes the malignant development of bladder cancer by regulating the miR-101/VEGF-C pathway in vitro and in vivo.

BACKGROUND: NEAT1 has been shown to play an oncogenic role in many kinds of cancers. However, detailed roles of NEAT1 in bladder cancer are largely unknown. METHODS: In the present study, the expression of NEAT1, miR-101 and VEGF-C was detected in human bladder cancer samples. The relationship between NEAT1 and the prognosis of patients with bladder cancer was analysed. In vitro experiments explored the effects of NEAT1 on biological behaviours of bladder cancer T24 and 5637 cells. Bioinformatics prediction and luciferase assays were used to assay the regulatory mechanism of action of NEAT1 and miR-101. Loss and gain of the expression of miR-101 and VEGF-C were used to explore the effects of the NEAT1/miR-101/VEGF-C pathway on T24 and 5637 cells. The effect of NEAT1 on the growth of bladder cancer in vivo was explored using an orthotopic tumourigenesis model. RESULTS: NEAT1 and VEGF-C were significantly upregulated in bladder cancer samples, and miR-101 was significantly downregulated. NEAT1 upregulation was associated with poorer recurrence-free survival of patients with bladder cancer. Overexpression of NEAT1 promoted the proliferation, migration and invasion of bladder cancer cells. The results of the luciferase assay indicated that miR-101 was a target of NEAT1. The promoting effects of NEAT1 on bladder cancer cells were reversed by miR-101 upregulation, and inhibition of miR-101 enhanced the effects of NEAT1. Overexpression of VEGF-C had a clear synergistic effect with the action of NEAT1. Overexpression of NEAT1 increased tumour growth and induced the development of liver metastasis. CONCLUSIONS: In conclusion, our data indicated that NEAT1 was expressed at high levels in bladder cancer patients and correlated with unfavourable prognosis. NEAT1 promoted malignant development of bladder cancer in vitro and in vivo by regulating the miR-101/VEGF-C pathway.

[A new dimeric xanthanolide from fruits of Xanthium chinense].

Through the methods of polyamide resin， Sephadex LH-20， ODS column chromatography and preparative HPLC etc.， 7 compounds were isolated from the 70% ethanol extract of the fruits of Xanthium chinense. Based on ESI-MS and NMR data， the structures of these compounds were identified as pungiolide O(1)， grasshopper ketone(2)， icariside F2(3)， 7-[(ß-D-apiofuranosyl-(1→6)-ß-D-glucopyranosyl)oxymethy]-8，8-dimethyl-4，8-dihydrobenzo[1，4]thiazine-3，5-dione(4)，(6R，9S)-3-oxo-α-ionol ß-D-glucopyranoside(5)， cryptochlorogenic acid methyl ester(6)， and chlorogenic acid methyl ester(7). Among them， compound 1 is a new compound.

Preference for diagnosing and treating renal colic during pregnancy: a survey among Chinese urologists.

To explore the preference for diagnosing and treating renal colic during pregnancy among Chinese urologists. A questionnaire was designed using the Sojump® platform. WeChat, the largest social networking platform in China, was used to distribute the questionnaire to urologists at hospitals of all levels in China. In total, 110 responses were included. Of the respondents, 100.0% used ultrasound to diagnose renal colic during pregnancy, followed by magnetic resonance imaging (17.3%) and low-dose CT (3.6%). Phloroglucinol (80.9%) and progesterone (72.7%) were the most commonly used antispasmodics and analgesics. Opioid analgesics were not commonly used (12.7%). Most of the respondents (63.6%) indicated that no more than 20% of the patients needed surgical intervention. If surgery was unavoidable, 95.5% preferred temporary renal drainage, including ureteral stenting (92.7%) and percutaneous nephrostomy (2.7%). However, some respondents still preferred definitive stone treatment, such as ureteroscopy lithotripsy (3.6%) and percutaneous nephrolithotomy (0.9%). Moreover, there were no differences in the choices of urologists with different professional titles regarding diagnostic tools, most therapeutic medications, or surgical methods (p > 0.05). Ultrasound is the preferred tool for diagnosing renal colic during pregnancy. Low-dose CT is still not widely accepted. Pregnant patients with renal colic are initially treated conservatively. Urologists prefer ureteral stenting when there are clinical indications for intervention.

Comparison of safety and efficacy of tubeless vs. conventional mini percutaneous nephrolithotomy in patients with Escherichia coli bacteriuria.

To evaluate the safety and efficacy of tubeless percutaneous nephrolithotomy (PCNL) in patients with Escherichia coli (E. coli) bacteriuria. We conducted a retrospective review of 84 patients with E. coli bacteriuria who underwent PCNL. Patients were divided into two groups according to whether a nephrostomy tube is placed at the end of the procedure. Preoperative clinical data, surgical outcomes, and postoperative complications were compared. Then, regression analysis of factors predicting success rate of PCNL in patients with E. coli bacteriuria was performed. After PCNL, residual fragments ≤ 4 mm were considered as success. At baseline, the two groups were similar with regard to age, gender, BMI, underlying disease, hydronephrosis, stone characteristics, and urinalysis. Postoperative fever occurred in 1 patient (3.8%) in the tubeless PCNL group, and in 5 patients (8.6%) in the conventional PCNL group (p > 0.05). There were no significant differences in terms of successful rate, decrease in hemoglobin, pain scores, blood transfusion, and hospitalization expenses. However, the tubeless PCNL group had significantly shorter operative time (60 vs. 70 min, p = 0.033), indwelling time of catheter (2 vs. 4 days, p < 0.001), and hospital stays (3 vs. 5 days, p < 0.001) than the conventional PCNL group. In the analysis of factors predicting success, the stone diameter, stone burden, and operative time were associated with success rate of PCNL. It is safe and effective to perform tubeless PCNL in patients with E. coli bacteriuria. Compared to conventional PCNL, tubeless PCNL accelerates patient recovery and shortens hospital stays.

Dynamic immune landscape in vaccinated-BA.5-XBB.1.9.1 reinfections revealed a 5-month protection-duration against XBB infection and a shift in immune imprinting.

BACKGROUND: The impact of previous vaccination on protective immunity, duration, and immune imprinting in the context of BA.5-XBB.1.9.1 reinfection remains unknown. METHODS: Based on a 2-year longitudinal cohort from vaccination, BA.5 infection and XBB reinfection, several immune effectors, including neutralizing antibodies (Nabs), antibody-dependent cellular cytotoxicity (ADCC), virus-specific T cell immunity were measured to investigate the impact of previous vaccination on host immunity induced by BA.5 breakthrough infection and BA.5-XBB.1.9.1 reinfection. FINDINGS: In absence of BA.5 Nabs, plasma collected 3 months after receiving three doses of inactivated vaccine (I-I-I) showed high ADCC that protected hACE2-K18 mice from fatality and significantly reduced viral load in the lungs and brain upon BA.5 challenge, compared to plasma collected 12 months after I-I-I. Nabs against XBB.1.9.1 induced by BA.5 breakthrough infection were low at day 14 and decreased to a GMT of 10 at 4 months and 28% (9/32) had GMT ≤4, among whom 67% (6/9) were reinfected with XBB.1.9.1 within 1 month. However, 63% (20/32) were not reinfected with XBB.1.9.1 at 5 months post BA.5 infection. Interestingly, XBB.1.9.1 reinfection increased Nabs against XBB.1.9.1 by 24.5-fold at 14 days post-reinfection, which was much higher than that against BA.5 (7.3-fold) and WT (4.5-fold), indicating an immune imprinting shifting from WT to XBB antigenic side. INTERPRETATION: Overall, I-I-I can provide protection against BA.5 infection and elicit rapid immune response upon BA.5 infection. Furthermore, BA.5 breakthrough infection effectively protects against XBB.1.9.1 lasting more than 5 months, and XBB.1.9.1 reinfection results in immune imprinting shifting from WT antigen induced by previous vaccination to the new XBB.1.9.1 antigen. These findings strongly suggest that future vaccines should target variant strain antigens, replacing prototype strain antigens. FUNDING: This study was supported by R&D Program of Guangzhou National Laboratory (SRPG23-005), National Key Research and Development Program of China (2022YFC2604104, 2019YFC0810900), S&T Program of Guangzhou Laboratory (SRPG22-006), and National Natural Science Foundation of China (81971485, 82271801, 81970038), Emergency Key Program of Guangzhou Laboratory (EKPG21-30-3), Zhongnanshan Medical Foundation of Guangdong Province (ZNSA-2020013), and State Key Laboratory of Respiratory Disease (J19112006202304).

Initial COVID-19 severity influenced by SARS-CoV-2-specific T cells imprints T-cell memory and inversely affects reinfection.

The immunoprotective components control COVID-19 disease severity, as well as long-term adaptive immunity maintenance and subsequent reinfection risk discrepancies across initial COVID-19 severity, remain unclarified. Here, we longitudinally analyzed SARS-CoV-2-specific immune effectors during the acute infection and convalescent phases of 165 patients with COVID-19 categorized by severity. We found that early and robust SARS-CoV-2-specific CD4+ and CD8+ T cell responses ameliorate disease progression and shortened hospital stay, while delayed and attenuated virus-specific CD8+ T cell responses are prominent severe COVID-19 features. Delayed antiviral antibody generation rather than titer level associates with severe outcomes. Conversely, initial COVID-19 severity imprints the long-term maintenance of SARS-CoV-2-specific adaptive immunity, demonstrating that severe convalescents exhibited more sustained virus-specific antibodies and memory T cell responses compared to mild/moderate counterparts. Moreover, initial COVID-19 severity inversely correlates with SARS-CoV-2 reinfection risk. Overall, our study unravels the complicated interaction between temporal characteristics of virus-specific T cell responses and COVID-19 severity to guide future SARS-CoV-2 wave management.

Nomogram to predict the risk of adverse outcomes in patients with residual stones following percutaneous nephrolithotomy

ABSTRACT Purpose: To investigate the risk factors associated with adverse outcomes in patients with residual stones after percutaneous nephrolithotomy (PCNL) and to establish a nomogram to predict the probability of adverse outcomes based on these risk factors. Methods: We conducted a retrospective review of 233 patients who underwent PCNL for upper urinary tract calculi and had postoperative residual stones. The patients were divided into two groups according to whether adverse outcomes occurred, and the risk factors for adverse outcomes were explored by univariate and multivariate analyses. Finally, we created a nomogram for predicting the risk of adverse outcomes in patients with residual stones after PCNL. Results: In this study, adverse outcomes occurred in 125 (53.6%) patients. Multivariate logistic regression analysis indicated that the independent risk factors for adverse outcomes were the diameter of the postoperative residual stones (P < 0.001), a positive urine culture (P = 0.022), and previous stone surgery (P = 0.004). The above independent risk factors were used as variables to construct the nomogram. The nomogram model was internally validated. The calculated concordance index was 0.772. The Hosmer- Lemeshow goodness-of-fit test was performed (P > 0.05). The area under the ROC curve of this model was 0.772. Conclusions: Larger diameter of residual stones, positive urine culture, and previous stone surgery were significant predictors associated with adverse outcomes in patients with residual stones after PCNL. Our nomogram could help to assess the risk of adverse outcomes quickly and effectively in patients with residual stones after PCNL

Cytotoxic dimeric xanthanolides from fruits of Xanthium chinense.

Nine dimeric xanthanolides, pungiolides F-N, and five known analogues, pungiolides A-E, were isolated from fruits of Xanthium chinense. Their structures were elucidated through spectroscopic and electronic circular dichroism (ECD) analyses. Pungiolide F is a xanthanolide dimer with an acyclic linkage. Five of the dimers, pungiolides H, L, A, C and E, exhibited moderate cytotoxicities with IC50 values in the range of 0.90-6.84 µM using taxol as the positive control, which had, by comparison, IC50 values in the range of 0.00118-0.0675 µM. These findings enrich the structural diversity of dimeric sesquiterpene lactones.