Differentiation of true progression from treatment response in high-grade glioma treated with chemoradiation: a comparison study of 3D-APTW and 3D-PcASL imaging and DWI.

PURPOSE: To assess and compare the diagnostic performance of 3D amide proton-transfer-weighted (3D-APTW) imaging, 3D pseudocontinuous arterial spin-labeling (3D-PcASL) imaging, and diffusion-weighted imaging in distinguishing true progression (TP) from treatment response (TR) in posttreatment malignant glioma patients. MATERIALS AND METHODS: Forty-eight patients with suspected tumor recurrence were prospectively enrolled. Histological or longitudinal routine MRI follow-up over six months was assessed to confirm lesion type. The apparent diffusion coefficient (ADC), relative APTWmax (rAPTW), and relative CBFmax values (rCBF) were measured in lesions with enhancing regions on post-gadolinium T1 -weighted MRI. MRI parameters between the TP and TR groups were compared using Student's t tests. In addition, a receiver operating characteristic (ROC) curve was constructed, and the area under the ROC curve (AUC) was calculated to assess the differentiation diagnostic performance of each parameter. RESULTS: The TP group showed a significantly higher rAPTW and rCBF than the TR group; the AUCs of rAPTW and rCBF to distinguish between TP and TR were 0.911 (with sensitivity of 90.3% and specificity of 82.4%) and 0.852 (with sensitivity of 80.6% and specificity of 82.4%), respectively. By adding the rAPTW values to rCBF values, the diagnostic ability was improved from 0.852 to 0.951. ADC showed no significant differences between the TP and TR groups, with an AUC lower than 0.70. CONCLUSION: Both 3D-PcASL and 3D-APTW imaging could distinguish TP from TR, and 3D-APTW had a better diagnostic performance. Combining the rAPTW values and rCBF values achieved a better diagnostic performance.

Prognostic models for upper urinary tract urothelial carcinoma patients after radical nephroureterectomy based on a novel systemic immune-inflammation score with machine learning.

PURPOSE: This study aimed to evaluate the clinical significance of a novel systemic immune-inflammation score (SIIS) to predict oncological outcomes in upper urinary tract urothelial carcinoma(UTUC) after radical nephroureterectomy(RNU). METHOD: The clinical data of 483 patients with nonmetastatic UTUC underwent surgery in our center were analyzed. Five inflammation-related biomarkers were screened in the Lasso-Cox model and then aggregated to generate the SIIS based on the regression coefficients. Overall survival (OS) was assessed using Kaplan-Meier analyses. The Cox proportional hazards regression and random survival forest model were adopted to build the prognostic model. Then we established an effective nomogram for UTUC after RNU based on SIIS. The discrimination and calibration of the nomogram were evaluated using the concordance index (C-index), area under the time-dependent receiver operating characteristic curve (time-dependent AUC), and calibration curves. Decision curve analysis (DCA) was used to assess the net benefits of the nomogram at different threshold probabilities. RESULT: According to the median value SIIS computed by the lasso Cox model, the high-risk group had worse OS (p<0.0001) than low risk-group. Variables with a minimum depth greater than the depth threshold or negative variable importance were excluded, and the remaining six variables were included in the model. The area under the ROC curve (AUROC) of the Cox and random survival forest models were 0.801 and 0.872 for OS at five years, respectively. Multivariate Cox analysis showed that elevated SIIS was significantly associated with poorer OS (p<0.001). In terms of predicting overall survival, a nomogram that considered the SIIS and clinical prognostic factors performed better than the AJCC staging. CONCLUSION: The pretreatment levels of SIIS were an independent predictor of prognosis in upper urinary tract urothelial carcinoma after RNU. Therefore, incorporating SIIS into currently available clinical parameters helps predict the long-term survival of UTUC.

Coalescence-Induced Droplet Jumping on Superhydrophobic Surfaces with Annular Wedge-Shaped Micropillar Arrays.

The coalescence-induced droplet jumping on superhydrophobic surfaces has extensive application potential in water harvesting, thermal management of electronic devices, and microfluidics. The rational design of the surface structure can influence the interaction between the droplet and the surface, thereby controlling the velocity and direction of the droplet's jumping. In this study, we fabricate the superhydrophobic surface with annular wedge-shaped micropillar arrays, examine the dynamic behavior of condensate droplets on the surface, and measure the temporal and spatial variations of droplet density, average radius, and surface coverage with wedge-shaped micropillars of varying sizes. In addition, the energy analysis of the coalescence-induced droplet jumping reveals that the two primary factors influencing the jumping are the relative size and position of the droplets and micropillars. Further numerical simulations find that the wedge-shaped micropillars cause an asymmetric distribution of pressure within the droplet and at the solid-liquid contact surface, which generates an unbalanced force driving the droplet in the gradient direction of the wedge-shaped micropillar, causing the droplet to jump off the surface with both vertical and gradient-direction velocities. The capacity of the wedge-shaped micropillar surface to transport droplets in the gradient direction increases and then decreases as the relative size of the droplets and micropillars increases. The relative position of the droplet center-of-mass line perpendicular to the bottom edge of the wedge micropillars' trapezoidal shape is more favorable for droplet transport. This work reveals the influence mechanism of surface structure on the velocity and direction of droplet jumping, and the results can guide the microstructure design of superhydrophobic surfaces, which has significant implications for the application of droplet jumping.

An Oscillation System Based on a Liquid Metal Droplet and Pillars under a Direct Current Electric Field.

Gallium-based liquid metal is a new class of material that has attracted extensive attention due to its excellent deformation characteristics and great potential in applications. Based on the deformation characteristics of liquid metal droplets, researchers have developed many oscillation systems composed of gallium indium tin alloy (GaInSn) droplet and graphite, or aluminum-doped gallium indium alloy (Al-GaIn24.5) droplet and iron, and so on. Rather than the oxidation and deoxidation mechanisms used in previous systems, an oscillation system that can achieve gallium indium alloy (EGaIn) droplet oscillation with the frequency of 0-29 Hz is designed depending on the interactions between the electric field, pillars, sodium hydroxide, and the droplet. The forces on the droplet are analyzed specifically, which have a great influence on droplet deformation. Additionally, the effects of factors such as voltage, the concentration of sodium hydroxide (NaOH) solution, and droplet size on the droplet oscillation are elucidated based on the force analysis, enabling the flexible control of the oscillation frequency and amplitude of the droplet. This work provides a new perspective on the design of oscillation systems and further enhances our understanding of the deformation of gallium-based liquid metal droplets.

Dendrocandin U from Dendrobium officinale Kimura et Migo Inhibits M1 Polarization in Alveolar Macrophage by Suppressing NF-κB Signaling Pathway.

Dendrobium officinale Kimura et Migo is a valuable and homologous medicine and food traditional Chinese medicine. Currently there are few studies on the anti-inflammatory activity of lipophilic components. The aim of this study was to explore the anti-inflammatory effect and mechanism of the lipophilic compounds in Dendrobium officinale. Six compounds were isolated and identified, including three bibenzyl compounds, dendrocandin U, dendronbibisline B, erianin, and three lignans, (-)-syringaresinol, (+)-syringaresinol-O-ß-D-glucopyranoside, 5-methoxy-(+)-isolariciresinol. Among them, dendronbibisline B and 5-methoxy-(+)-isolariciresinol were isolated from Dendrobium officinale for the first time. Besides, we found dendrocandin U, dendronbibisline B and (-)-syringaresinol exhibited the anti-inflammation to inhibit nitric oxide secretion induced by lipopolysaccharide (LPS)/interferon (IFN-γ) in MH-S cells. Furthermore, dendrocandin U could inhibit the expression of tumor necrosis factor-α (TNF-α), Cluster of Differentiation 86 (CD86), and reduce inflammatory morphological changes of macrophages. Meanwhile, we confirmed that the anti-inflammation mechanism of dendrocandin U was to inhibit M1 polarization by suppressing toll-like receptor 4 (TLR4)/recombinant myeloid differentiation factor 88 (MyD88)/nuclear factor kappa B (NF-κB) signaling pathway. In this paper, dendrocandin U with significant anti-inflammatory activity was found from Dendrobium officinale, which could provide a basis for the study of its anti-inflammatory drugs.

Is it necessary for all patients with suspicious lesions undergo systematic biopsy in the era of MRI-TRUS fusion targeted biopsy?

PURPOSE: Targeted biopsy (TB) combined with systematic biopsy (SB) is an optimized mode of prostate biopsy but can often lead to oversampling and overdiagnosis accompanied by potential biopsy-related complications and patient discomfort. Here, we attempted to reasonably stratify the patient population based on multi-parameter indicators with the aim of avoiding unnecessary SB. METHODS: In total, 340 biopsy-naïve men with suspected lesions, prostate-specific antigen (PSA) < 20 ng/mL and prostate imaging-reporting and data system (PI-RADS) ≥ 3 enrolled for study underwent both TB and SB. The primary outcome was to determine independent predictors for a valid diagnosis, assuming that only TB was performed and SB omitted (defined as mono-TB), taking TB + SB as the reference standard. The secondary outcomes were exploration of the predictive factors of mono-TB and TB + SB in detection of prostate cancer (PCa) and clinically significant PCa (csPCa). RESULTS: The mean PSA density (PSAD) of patient group was 0.27 ng/mL/mL. Multiparametric MRI PI-RADS scores were 3-5 in 146 (42.94%), 105 (30.88%), and 89 (26.18%) cases, respectively. PCa and csPCa were detected in 178/340 (52.35%) and 162/340 (47.65%) patients, respectively. Overall, 116/178 (65.17%) patients diagnosed with PCa displayed pathological consistencies between mono-TB and TB + SB modes. PSAD and PI-RADS were independent predictors of valid diagnosis using mono-TB. CONCLUSIONS: PSAD combined with PI-RADS showed utility in guiding optimization of the prostate biopsy mode. Higher PSAD and PI-RADS values were associated with greater confidence in implementing mono-TB and safely omitting SB, thus effectively balancing the benefits and risks.

Clinicopathological and Prognostic Significance of Preoperative Prognostic Nutritional Index in Patients with Upper Urinary Tract Urothelial Carcinoma.

To investigate the prognostic value of preoperative prognostic nutritional index (PNI) to predict oncological outcome and intravesical recurrence (IVR) in upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU).This study involved the clinical data of 255 patients with UTUC who had undergone RNU from 2004 to 2019 at our institution. Patients were grouped according to an optimal value of preoperative PNI. Kaplan-Meier analyses and Cox proportional hazards models were used to analyze the associations of preoperative PNI with progression-free survival (PFS), cancer-specific survival (CSS), overall survival (OS), and IVR.Patients with low PNI were more likely to be older, have higher tumor stage, higher eGFR, and multifocal lesions. No significant association was found between PNI and CSS, IVR. In subgroup analysis according to the risk stratification, low PNI was associated with worse PFS, CSS, and OS for patients with higher risk. Multivariate analyses showed that elevated PNI was an independent prognostic indicator for PFS (P = 0.014) and OS (P = 0.048).A low PNI is an independent predictor of PFS and OS in patients with UTUC after RNU. By subgroup analysis, the prognostic value of PNI was limited to patients with higher risk. PNI may become a useful biomarker to predict oncological outcomes in patients with UTUC after RNU.

The impact of atrial fibrillation on outcomes in patients undergoing radical prostatectomy.

PURPOSE: To assess the role of atrial fibrillation (AF) on complicating inpatient outcomes of radical prostatectomy (RP). MATERIALS AND METHODS: We identified patients treated with RP during 2012-2014 within National Inpatient Sample (NIS) database. Length of stay, cost of hospitalization, and in-hospital complications were compared between patients with or without diagnosis of AF. Propensity score matching methods and multivariable regression analysis were used to adjust for potential confounders and a trend analysis was conducted. RESULTS: Patients with AF had a significantly longer hospital stay (coefficient 0.19, 95% CI 0.09-0.29, P < 0.001) and higher cost (coefficient 0.10, 95% CI 0.06-0.15, P < 0.001). Post-operative cardiac complications were significantly higher for patients with AF (OR 16.38, 95% CI 7.72-34.74, P < 0.001), while no differences were found in other complications between the two groups. Similar results were shown in propensity score matching methods. The cardiac complications after laparoscopic RP (OR: 37.71, 95% CI 1.85-768.73, P = 0.018) and open RP (OR: 16.78, 95% CI 1.41-199.51, P = 0.026) were significantly higher than robot-assisted RP (RARP) in patients with AF. The results of trend study indicated that postoperative cardiac complication rates showed a trend of decreasing year by year while the prevalence of AF was rising. CONCLUSIONS: Perioperative AF is associated with increased cardiac complications, longer hospital stay and higher cost in PCa patients undergoing RP. RARP may be a preferred choice for patients with AF. Attention should be paid to this special patient population. Reasonable pre-operative risk stratification and standardized management should be done to decrease perioperative complications.

Does Xylinas' nomogram accurately predict intravesical recurrence risk after radical nephroureterectomy for primary upper urinary tract urothelial carcinoma when applied to Asian populations?

OBJECTIVE: To validate a prognostic nomogram (Xylinas' nomogram) for intravesical recurrence after radical nephroureterectomy for primary upper urinary tract urothelial carcinoma patients of Asian descent. METHODS: Clinicopathological and survival data from 243 primary urinary tract urothelial carcinoma patients who underwent radical nephroureterectomy with bladder cuff excision between January 2004 and May 2017 were collated. Univariate and multivariable Cox regression analyses were performed to identify independent risk factors associated with intravesical recurrence-free survival. External validation was determined using regression coefficients abstracted from previously published data. Performance was then quantified through calibration and discrimination, according to concordance indexes (c-index) in receiver operating characteristic curves. RESULTS: 163 patients met our eligibility criteria and were finally included in this study. At a median follow-up of 60 months, intravesical recurrence occurred in 29.4% (n = 48). Multivariable analysis revealed that being male, ureteral tumor location, tumor multifocality and previous bladder cancer were independent prognostic factors of intravesical recurrence-free survival. When Xylinas' nomogram was applied to our cohort, the discriminatory power was found to be roughly equivalent with a c-index of 68.3% for the reduced model and 68.4% for the full model. Calibration plots also revealed intravesical recurrence predictions at 3, 6, 12, 18, 24 and 36 months had relative concordance. Contrasting the respective performances of the reduced and full model suggests there is no significant difference between the two (all P > 0.05). CONCLUSIONS: This nomogram appears accurate at predicting intravesical recurrence after radical nephroureterectomy for primary urinary tract urothelial carcinoma in Asian populations. However, it remains necessary to data mine for unknown prognostic factors for optimization. Further external validation is required across larger, ethically diverse populations before applying this nomogram in clinical practice.

Developing a nomogram for predicting intravesical recurrence after radical nephroureterectomy: a retrospective cohort study of mainland Chinese patients.

OBJECTIVE: To evaluate the role of Ki-67 in predicting subsequent intravesical recurrence following radical nephroureterectomy and to develop a predictive nomogram for upper tract urothelial carcinoma patients. METHODS: This retrospective analysis involved 489 upper tract urothelial carcinoma patients who underwent radical nephroureterectomy with bladder cuff excision. The data set was randomly split into a training cohort of 293 patients and a validation cohort of 196 patients. Immunohistochemical analysis was used to assess the immunoreactivity of the biomarker Ki-67 in the tumor tissues. A multivariable Cox regression model was utilized to identify independent intravesical recurrence predictors after radical nephroureterectomy before constructing a nomographic model. Predictive accuracy was quantified using time-dependent receiver operating characteristic curve. Decision curve analysis was performed to evaluate the clinical benefit of models. RESULTS: With a median follow-up of 54 months, intravesical recurrence developed in 28.2% of this sample (n = 137). Tumor location, multifocality, pathological T stage, surgical approach, bladder cancer history and Ki-67 expression levels were independently associated with intravesical recurrence (all P < 0.05). The full model, which intercalated Ki-67 with traditional clinicopathological parameters, outperformed both the basic model and Xylinas' model in terms of discriminative capacity (all P < 0.05). Decision-making analysis suggests that the more comprehensive model can also improve patients' net benefit. CONCLUSIONS: This new model, which intercalates the Ki-67 biomarker with traditional clinicopathological factors, appears to be more sensitive than nomograms previously tested across mainland Chinese populations. The findings suggest that Ki-67 could be useful for determining risk-stratified surveillance protocols following radical nephroureterectomy and in generating an individualized strategy based around intravesical recurrence predictions.

Demographic history and genetic differentiation of an endemic and endangered Ulmus lamellosa (Ulmus).

BACKGROUND: Ulmus lamellosa (one of the ancient species of Ulmus) is an endemic and endangered plant that has undergone climatic oscillations and geographical changes. The elucidation of its demographic history and genetic differentiation is critical for understanding the evolutionary process and ecological adaption to forests in Northern China. RESULTS: Polymorphic haplotypes were detected in most populations of U. lamellosa via DNA sequencing. All haplotypes were divided into three phylogeographic clades fundamentally corresponding to their geographical distribution, namely THM (Taihang Mountains), YM (Yinshan Mountains), and YSM (Yanshan Mountains) groups. The YSM group, which is regarded as ancestral, possessed higher genetic diversity and significant genetic variability in contrast to the YSM and YM groups. Meanwhile, the divergence time of intraspecies haplotypes occurred during the Miocene-Pliocene, which was associated with major Tertiary geological and/or climatic events. Different degrees of gene exchanges were identified between the three groups. During glaciation, the YSM and THM regions might have served as refugia for U. lamellosa. Based on ITS data, range expansion was not expected through evolutionary processes, except for the THM group. A series of mountain uplifts (e.g., Yanshan Mountains and Taihang Mountains) following the Miocene-Pliocene, and subsequently quaternary climatic oscillations in Northern China, further promoted divergence between U. lamellosa populations. CONCLUSIONS: Geographical topology and climate change in Northern China played a critical role in establishing the current phylogeographic structural patterns of U. lamellosa. These results provide important data and clues that facilitate the demographic study of tree species in Northern China.

Comparative Effectiveness of Tadalafil versus Tamsulosin in Treating Lower Urinary Tract Symptoms Suggestive of Benign Prostate Hyperplasia: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND Evidence directly evaluating the efficacy of tadalafil vs. tamsulosin for lower urinary tract symptoms (LUTS) secondary to benign prostate hyperplasia (BPH) is limited. We performed a meta-analysis of published studies to assess the comparative effectiveness of tadalafil vs. tamsulosin in treating LUTS suggestive of BPH. MATERIAL AND METHODS After performing a comprehensive publication search with PubMed, EMBASE, and Cochrane Controlled Trials Register using the search terms "tadalafil", "tamsulosin", "lower urinary tract symptoms", and "controlled", 335 articles were screened, out of which 7 randomized controlled trials published up to July 2019 were identified and included in this meta-analysis review. RESULTS From 335 screened articles, 7 studies (totalling 1601 patients) were finally included in our analysis. There was no statistically significant difference between tadalafil and tamsulosin in improving the clinical outcomes of total International Prostate Symptom Score (IPSS),voiding subscores, storage subscores, quality of life (QoL) scores, maximum flow rate (Qmax), and postvoid residual urine (PVR), but a statistically significant difference was observed in the International Index of Erectile Function scores (IIEF scores). CONCLUSIONS Tadalafil and tamsulosin have similar effects in managing LUTS secondary to BPH. Tadalafil is superior to tamsulosin in treating LUTS suggestive of BPH when associated with erectile dysfunction (ED).

Positive node burden rather than the number of removed nodes impacts survival in patients with node-positive prostate cancer.

BACKGROUND: The value of pelvic lymphadenectomy during radical prostatectomy (RP) remains controversial. This study aims to test the effects of the number of removed lymph nodes (RLN), positive nodes (pLN), and pLN ratio (pLNR) on cancer-specific survival (CSS) in patients with node-positive prostate cancer (PCa). METHODS: A total of 2458 patients with a greater than 5% probability of lymph node invasion according to the updated Briganti nomogram who harboured pathologically confirmed positive nodes in the Surveillance, Epidemiology, and End Results database between 2004 and 2015 were identified. Multivariable Cox regression with forward stepwise selection was performed to identify independent risk factors for CSS. Maximally selected rank statistics were used to determine the most informative cut-off value for pLN and pLNR. RESULTS: The median pLN counts and RLN in the study were two (interquartile range [IQR] 1- 3) and 18 (IQR 15-23), respectively. The RLN counts could not predict CSS, while the higher pLN and pLNR were associated with worse CSS (hazard ratio [HR], 1.11; p < 0.001 and HR, 1.01; p < 0.001, respectively). Patients with ≤ 2 pLN or pLNR ≤ 20% had significantly better CSS than those with pLN > 2 or pLNR > 20% (HR, 1.38 (1.08-1.77); p = 0.009; HR, 1.77 (1.41-2.22); p < 0.001, respectively). CONCLUSIONS: In patients with node-positive PCa, pelvic lymphadenectomy provides important information for staging, prognosis, and guiding after RP therapy; however, it does not play a therapeutic role. The pLN counts and pLNR were independent predictors of CSS.

Impact of prostate cancer radiotherapy on the biological behavior and specific mortality of subsequent bladder cancer.

BACKGROUND: The impact of different radiotherapy modalities on the development and characteristics of second primary bladder cancers (BCa) and BCa-specific mortality (BCa-SM) remains unclear. Thus, we evaluated the incidence and biological behavior of subsequent BCa and related survival in patients who underwent radiation therapy for prostate cancer (PCa). METHODS: A total of 530,581 patients in the surveillance, epidemiology, and end results database with localized PCa between 1988 and 2013 were identified. PCa treatments included radical prostatectomy (RP), external beam radiotherapy (EBRT), radioactive implants (RI), and combined EBRT and RI (EBRI). A multivariable competing risk analysis based on a proportional sub distribution hazards model was used to determine the impact of different radiotherapy modalities on BCa incidence and specific mortality. RESULTS: Incidence of BCa was significantly high in patients treated with EBRT, RI, and EBRI vs. RP [sub distribution hazard ratio (SHR) 1.41, P < 0.001; SHR 1.58, P < 0.001; SHR 1.56, P < 0.001, respectively]. BCa following EBRT, RI, and EBRI were more commonly non-urothelial (3.3%, 2.9%, 3.3%, respectively, versus 1.2%) and T4 (3.5%, 6.1%, 5.0%, respectively, versus 1.6%) compared with RP. RI associated with a higher rate of BCa metastasis than RP (2.6% vs. 1.1%). Prior EBRT, RI, and EBRI increased BCa-SM (SHR 1.44, P = 0.001; SHR 1.21, P = 0.047; and SHR 1.42, P = 0.032, respectively). CONCLUSIONS: Patients receiving radiotherapy for PCa have a higher risk of BCa. BCa after EBRT, RI, and EBRI is more likely to be non-urothelial, stage T4, and with increased BCa-SM. Prior RI associated with a higher rate of BCa metastasis.

Impact of different color fiber sleeves on beam hazards of 532-nm laser and vaporization efficiency.

The 532-nm laser has become increasingly popular for the treatment of urologic diseases. However, laser beam will pose significant hazards for the health of surgeons. In order to reduce beam hazards during surgery, we compared the beam hazards of laser fiber with black sleeves to the traditional fiber with transparent sleeves, and the vaporization efficiency. A total of 18 porcine kidney specimens were vaporized in normal saline at a room temperature under 532-nm laser delivered through a 760-µm core diameter side firing fiber. Two groups were divided according to the color of fiber sleeves: the transparent and the black. Each group was then divided into another three subgroups by laser power: the 80 W group, the 120 W group, and the 160 W group. The beam hazard was evaluated by light intensity measured in a sector area at a distance of 0 m, 0.5 m, and 1 m from the irradiation center. The vaporization efficiency was measured by the vaporization groove depth under the working power of 80 W, 120 W, and 160 W with a working distance of 5 mm and irradiation time of 10 s. The light intensity measured in the black fiber sleeve group is significantly lower than that in the transparent one (P < 0.01), regardless of the measuring distance (0 m, 0.5 m, and 1.0 m) and laser power (80 W, 120 W, and 160 W). No statistical difference was found on the vaporization efficiency between the groups protected by fiber sleeves of different colors (transparent/black, p > 0.05). Compared to the traditional transparent fiber sleeves, more beam hazards will be reduced in the operative region with the protection of black fiber sleeves, especially those from the irradiation center. The vaporization efficiency is not affected by the color of fiber sleeves. Such findings may offer a completely new idea for the protection of surgeons in surgeries with 532-nm lasers.

A system for fluid pumping by liquid metal multi-droplets.

The transportation and control of microfluidics have an important influence on the fields of biology, chemistry, and medicine. Pump systems based on the electrocapillary effect and room-temperature liquid metal droplets have attracted extensive attention. Flow rate is an important parameter that reflects the delivery performance of the pump systems. In the systems of previous studies, cylindrical structures are mostly used to constrain the droplet. The analysis and quantitative description of the influence of voltage frequency, alternating voltage, direct current voltage bias, and solution concentration on the flow rate are not yet comprehensive. Furthermore, the systems are driven by only one droplet, which limits the increase in flow rate. Therefore, a pump with a cuboid structure is designed and the droplet is bound by pillars, and the flow rate of the pump is increased by more than 200% compared with the cylindrical pump. For this structure, the mechanism of various factors on the flow rate is analyzed. To further enhance the flow rate, a pump system with multi-droplets is proposed. Moreover, the expression of flow velocity of the solution on the surface of each droplet and the relationship between the flow rate, alternating voltage, and the number of droplets are deduced. Finally, the potential of applying the multi-droplet cuboid pump system in drug delivery and analytical chemistry is demonstrated. Additionally, the core of the pump, the droplet area, is modularized, which breaks the overall structural limitations of the liquid metal pump and provides ideas for pump design.

Oxidative Stress Factors Mediate the Association Between Life's Essential 8 and Accelerated Phenotypic Aging: NHANES 2005-2018.

Cardiovascular health (CVH) is a well-known predictor of morbidity and mortality, while phenotypic age (PhenoAge) is a promising biomarker of aging. This study aimed to explore the association between Life's Essential 8 (LE8), a novel CVH measure, and PhenoAge acceleration (PhenoAgeAccel), as well as the potential mediating role of oxidative stress biomarkers in this relationship. A total of 23 896 individuals were included in the National Health and Nutrition Examination Survey database (2005-2018). Life's Essential 8 scores were categorized into low, moderate, and high groups. PhenoAge, measured through clinical laboratory blood chemistries, served as a marker of biological aging. Weighted linear regression analyses were performed to assess the association between LE8 scores and PhenoAgeAceel. In the multivariable linear regression, LE8 scores were significantly and inversely associated with PhenoAgeAccel, showing a decreased risk in the moderate CVH group (ß -2.98; 95% CI -3.29, -2.66) and high CVH group (ß -4.72; 95% CI -5.08, -4.35) compared to the low CVH group. When treated as a continuous variable, each 10-point increase in LE8 scores corresponded to a 1.14-year decrease in PhenoAge (ß -1.14; 95% CI -1.21, -1.06). Among the 8 individual components in LE8, 7 exhibited a significant negative correlation with PhenoAgeAccel, except for blood lipids. Additionally, mediation analysis revealed that oxidative stress biomarkers, including γ-glutamyltransferase, bilirubin, and uric acid, collectively mediated 17.1% of the associations between LE8 scores and PhenoAgeAccel (p < .001). Higher LE8 scores, representing ideal CVH, are significantly related to a deceleration in PhenoAge, and oxidative stress biomarkers may play a mediating role in this relationship.

Deciphering the significance of anoikis in bladder cancer and systematic analysis of S100A7 as a potential therapeutic target.

BACKGROUND: Bladder cancer is an epidemic and life-threating urologic carcinoma. Anoikis is a unusual type of programmed cell death which plays a vital role in tumor survival, invasion and metastasis. Nevertheless, the relationship between anoikis and bladder cancer has not been understood thoroughly. METHODS: We downloaded the transcriptome and clinical information of BLCA patients from TCGA and GEO databases. Then, we analyzed different expression of anoikis-related genes and established a prognostic model based on TCGA database by univariate Cox regression, lasso regression, and multivariate Cox regression. Then the Kaplan-Meier survival analysis and receiver operating characteristic (ROC) curves were performed. GEO database was used for external validation. BLCA patients in TCGA database were divided into two subgroups by non-negative matrix factorization (NMF) classification. Survival analysis, different gene expression, immune cell infiltration and drug sensitivity were calculated. Finally, we verified the function of S100A7 in two BLCA cell lines. RESULTS: We developed a prognostic risk model based on three anoikis-related genes including TPM1, RAC3 and S100A7. The overall survival of BLCA patients in low-risk groups was significantly better than high-risk groups in training sets, test sets and external validation sets. Subsequently, the checkpoint and immune cell infiltration had significant difference between two groups. Then we identified two subtypes (CA and CB) through NMF analysis and found CA had better OS and PFS than CB. Besides, the accuracy of risk model was verified by ROC analysis. Finally, we identified that knocking down S100A7 gene expression restrained the proliferation and invasion of bladder cancer cells. CONCLUSION: We established and validated a bladder cancer prognostic model consisting of three genes, which can effectively evaluate the prognosis of bladder cancer patients. Additionally, through cellular experiments, we demonstrated the significant role of S100A7 in the metastasis and invasion of bladder cancer, suggesting its potential as a novel target for future treatments.

TFRC, associated with hypoxia and immune, is a prognostic factor and potential therapeutic target for bladder cancer.

BACKGROUND: Bladder cancer is a common malignancy of the urinary system, and the survival rate and recurrence rate of patients with muscular aggressive (MIBC) bladder cancer are not ideal. Hypoxia is a pathological process in which cells acquire special characteristics to adapt to anoxic environment, which can directly affect the proliferation, invasion and immune response of bladder cancer cells. Understanding the exact effects of hypoxia and immune-related genes in BLCA is helpful for early assessment of the prognosis of BLCA. However, the prognostic model of BLCA based on hypoxia and immune-related genes has not been reported. PURPOSE: Hypoxia and immune cell have important role in the prognosis of bladder cancer (BLCA). The aim of this study was to investigate whether hypoxia and immune related genes could be a novel tools to predict the overall survival and immunotherapy of BLCA patients. METHODS: First, we downloaded transcriptomic data and clinical information of BLCA patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A combined hypoxia and immune signature was then constructed on the basis of the training cohort via least absolute shrinkage and selection operator (LASSO) analysis and validated in test cohort. Afterwards, Kaplan-Meier curves, univariate and multivariate Cox and subgroup analysis were employed to assess the accuracy of our signature. Immune cell infiltration, checkpoint and the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm were used to investigate the immune environment and immunotherapy of BLCA patients. Furthermore, we confirmed the role of TFRC in bladder cancer cell lines T24 and UMUC-3 through cell experiments. RESULTS: A combined hypoxia and immune signature containing 8 genes were successfully established. High-risk group in both training and test cohorts had significantly poorer OS than low-risk group. Univariate and multivariate Cox analysis indicated our signature could be regarded as an independent prognostic factor. Different checkpoint was differently expressed between two groups, including CTLA4, HAVCR2, LAG3, PD-L1 and PDCD1. TIDE analysis indicated high-risk patients had poor response to immunotherapy and easier to have immune escape. The drug sensitivity analysis showed that high-risk group patients were more potentially sensitive to many drugs. Meanwhile, TFRC could inhibit the proliferation and invasion ability of T24 and UMUC-3 cells. CONCLUSION: A combined hypoxia and immune-related gene could be a novel predictive model for OS and immunotherapy estimation of BLCA patients and TFRC could be used as a potential therapeutic target in the future.