ID2 Promotes Lineage Transition of Prostate Cancer through FGFR and JAK-STAT Signaling.

The use of androgen receptor pathway inhibitors (ARPIs) has led to an increase in the proportion of AR-null prostate cancer, including neuroendocrine prostate cancer (NEPC) and double-negative prostate cancer (DNPC), but the mechanism underlying this lineage transition has not been elucidated. We found that ID2 expression was increased in AR-null prostate cancer. In vitro and in vivo studies confirmed that ID2 promotes PCa malignancy and can confer resistance to enzalutamide in PCa cells. We generated an ID2 UP50 signature, which is capable of determining resistance to enzalutamide and is valuable for predicting patient prognosis. Functional experiments showed that ID2 could activate stemness-associated JAK/STAT and FGFR signaling while inhibiting the AR signaling pathway. Our study indicates a potentially strong association between ID2 and the acquisition of a stem-like phenotype in adenocarcinoma cells, leading to resistance to androgen deprivation therapy (ADT) and next-generation ARPIs in prostate cancer.

Species delimitation in Amana (Liliaceae): transcriptomes battle with evolutionary complexity.

Species delimitation has long been a subject of controversy, and there are many alternative concepts and approaches used to define species in plants. The genus Amana (Liliaceae), known as "East Asian tulips" has a number of cryptic species and a huge genome size (1C = 21.48-57.35 pg). It also is intriguing how such a spring ephemeral genus thrives in subtropical areas. However, phylogenetic relationships and species delimitation within Amana are challenging. Here we included all species and 84 populations of Amana, which are collected throughout its distribution range. A variety of methods were used to clarify its species relationships based on a combination of morphological, ecological, genetic, evolutionary and phylogenetic species concepts. This evidence supports the recognition of at least 12 species in Amana. Moreover, we explored the complex evolutionary history within the genus and detected several historical hybridization and introgression events based on phylogenetic trees (transcriptomic and plastid), phylonetworks, admixture and ABBA-BABA analyses. Morphological traits have undergone parallel evolution in the genus. This spring ephemeral genus might have originated from a temperate region, yet finally thrives in subtropical areas, and three hypotheses about its adaptive evolution are proposed for future testing. In addition, we propose a new species, Amana polymorpha, from eastern Zhejiang Province, China. This research also demonstrates that molecular evidence at the genome level (such as transcriptomes) has greatly improved the accuracy and reasonability of species delimitation and taxon classification.

Two new dalbergiphenols from Zhuang medicine Dalbergia rimosa Roxb / 药学学报

Twelve compounds were isolated from the ethyl acetate fraction of the 80% aqueous ethanol extract of the roots and stems of Dalbergia rimosa Roxb. by silica gel, MCI, Sephadex LH-20 column chromatography, and semi-preparative HPLC. Their structures were identified by spectral analysis such as UV, IR, MS, 1D/2D NMR and by comparison with literature information as dalbergiquinol A (1), dalbergiquinol B (2), R-(-)-3′-hydroxy-2,4,5-trimethoxydalbergiquinol (3), neokhriol A (4), mucronulatol (5), (3R)-7,2′,3′-trihydroxy-4′-methoxy-isoflavane (6), isomucronulatol (7), (3S)-violanone (8), 3′-O-methylviolanone (9), eryvarin M (10), (±)-α,3,4,2′,4′-pentahydroxydihydrochalcone (11) and (-)-butin (12). Compound 1 and 2 are new compounds, and compounds 3-12 were isolated from this plant for the first time. Compounds 1, 2, 4, 6, 8, 11, 12 showed good scavenging effect on DPPH free radical.

A dynamic nomogram integrated with blood inflammation markers for predicting overall survival in patients with upper tract urothelial carcinoma.

Background: Upper tract urothelial carcinoma (UTUC) is a relatively rare disease with a poor prognosis. A growing body of evidence demonstrates that inflammation and the inflammatory microenvironment play a crucial role in tumorigenesis and tumor progression. Our aim was to evaluate the prognostic value of blood inflammation markers and develop a prediction model that incorporates inflammation markers in order to predict overall survival (OS) of UTUC. Methods: We included 304 localized UTUC patients from two medical institutions who had undergone radical nephroureterectomy (RNU) (167 in the training cohort, 137 in the validation cohort). Univariate and multivariate Cox regression analyses were performed to screen the prognostic factors, and a nomogram and a web-based calculator were generated based on these predictors. The Harrell's concordance index (C-index), the area under the receiver operating characteristic (ROC) curve, the calibration curve, and decision curve analysis (DCA) were used to evaluate the performance of the nomogram. Results: Independent predictors incorporated in the nomogram were pathological stage, surgical margin, albumin-to-globulin ratio (AGR), and hemoglobin-to-red cell distribution width ratio (HRR). The c-index value was 0.726 in the training cohort and 0.761 in the validation cohort. The area under the ROC of the nomogram at 1-, 3- and 5-year in the training and validation sets were 0.765, 0.755, 0.763, and 0.791, 0.833, 0.802, respectively. Both the internal and external validation calibration plots showed a subtle distinction between the predicted and the actual probabilities. And it appears to provide incremental benefits for clinical decision-making in comparison to the American Joint Committee of Cancer (AJCC) staging system. Conclusions: In patients with UTUC after RNU, lower preoperative AGR and HRR were independent predictors of inferior survival. In addition, we created a novel blood inflammation marker-based dynamic nomogram that may be useful for surgeons or oncologists in risk stratification and patient selection for more intensive therapy and closer follow-up.

A New Landscape of Human Dental Aging: Causes, Consequences, and Intervention Avenues.

Aging is accompanied by physical dysfunction and physiologic degeneration that occurs over an individual's lifetime. Human teeth, like many other organs, inevitably undergo chronological aging and age-related changes throughout the lifespan, resulting in a substantial need for preventive, restorative as well as periodontal dental care. This is particularly the case for seniors at 65 years of age and those older but economically disadvantaged. Dental aging not only interferes with normal chewing and digestion, but also affects daily appearance and interpersonal communications. Further dental aging can incur the case of multiple disorders such as oral cancer, encephalitis, and other systemic diseases. In the next decades or even hundreds of years, the proportion of the elderly in the global population will continue to rise, a tendency that attracts increasing attention across multiple scientific and medical disciplines. Dental aging will bring a variety of problems to the elderly themselves and poses serious challenges to the medical profession and social system. A reduced, but functional dentition comprising 20 teeth in occlusion has been proposed as a measurement index of successful dental aging. Healthy dental aging is critical to healthy aging, from both medical and social perspectives. To date, biomedical research on the causes, processes and regulatory mechanisms of dental aging is still in its infancy. In this article, updated insights into typical manifestations, associated pathologies, preventive strategies and molecular changes of dental aging are provided, with future research directions largely projected.

RNA demethylase ALKBH5 suppresses tumorigenesis via inhibiting proliferation and invasion and promoting CD8+ T cell infiltration in colorectal cancer.

BACKGROUND: ALKBH5 belongs to the ALKB family consists of a Fe (II) and a-ketoglutarate-dependent dioxygenase. ALKBH5 directly catalyzes the oxidative demethylation of m6A-methylated adenosine. ALKBH5 involves in tumorigenesis and tumor progression, and is often dysregulated in a wide range of cancers, including colorectal cancer. Emerging evidence indicates that the expression of ALKBH5 is associated with the abundance of infiltrating immune cells in the microenvironment. However, how ALKBH5 affects immune cell infiltration in the microenvironment in colorectal cancer (CRC) has not been reported. The aim of this study was to identify how the expression of ALKBH5 affects the biological behaviors of CRC cell lines and regulates the effects on infiltrating CD8+ T cells in CRC microenvironment with its specific mechanism. METHODS: Firstly, the transcriptional expression profiles of CRC were downloaded from TCGA database and integrated via R software (4.1.2). Between CRC and normal colorectal tissues, ALKBH5 mRNA expressions were compared (Wilcoxon rank-sum). We further identified the expression levels of ALKBH5 in CRC tissues and cell lines through quantitative PCR, western blot, and immunohistochemistry. Then, how ALKBH5 affects the biological behaviors of CRC cells were confirmed by gain- and loss-of-function analysis. Furthermore, the relationship between ALKBH5 level and 22 tumor-infiltrating immune cells was examined through CIBERSORT in R software. Furthermore, we explored the correlation between ALKBH5 expression and tumor-infiltrated CD8+, CD4+ and regulatory T cells by utilizing the TIMER database. Finally, the association between chemokines and CD8+ T cells infiltration in CRC was analyzed using GEPIA online database. qRT-PCR, WB and IHC were used to further determine the effect of ALKBH5 on NF-κB-CCL5 signaling axis and CD8+ T cells infiltration. RESULTS: Clinically, ALKBH5 expression was downregulated in CRC and low levels of ALKBH5 expression were correlated with poor overall survival (OS). Functionally, overexpression of ALKBH5 reduced the proliferation, migration and invasion of CRC cells, and vice versa. Overexpression of ALKBH5 suppresses NF-κB pathway, thus reduces CCL5 expression and promotes CD8+ T cells infiltration in CRC microenvironment. CONCLUSIONS: ALKBH5 is poorly expressed in CRC, and overexpression of ALKBH5 attenuates CRC malignant progression by inhibiting CRC cell proliferation, migration, invasion and promoting CD8+ T cells infiltration in the tumor microenvironment through NF-κB-CCL5 axis.

Phylogenomics and integrative taxonomy reveal two new species of Amana (Liliaceae).

Until now the genus Amana (Liliaceae), known as 'East Asian tulips', has contained just seven species. In this study, a phylogenomic and integrative taxonomic approach was used to reveal two new species, Amana nanyueensis from Central China and A. tianmuensis from East China. A. nanyueensis resembles Amana edulis in possessing a densely villous-woolly bulb tunic and two opposite bracts, but differs in its leaves and anthers. Amana tianmuensis resembles Amana erythronioides in possessing three verticillate bracts and yellow anthers, but differs in aspects of its leaves and bulbs. These four species are clearly separated from each other in principal components analysis based on morphology. Phylogenomic analyses based on plastid CDS further support the species delimitation of A. nanyueensis and A. tianmuensis and suggests they are closely related to A. edulis. Cytological analysis shows that A. nanyueensis and A. tianmuensis are both diploid (2n = 2x = 24), different from A. edulis, which is either diploid (northern populations) or tetraploid (southern populations, 2n = 4x = 48). The pollen morphology of A. nanyueensis is similar to other Amana species (single-groove germination aperture), but A. tianmuensis is quite different because of the presence of a sulcus membrane, which creates the illusion of double grooves. Ecological niche modelling also revealed a niche differentiation between A. edulis, A. nanyueensis and A. tianmuensis.

Predictive Value of Flank Pain and Gross Hematuria on Long-Term Survival in Patients With Upper Tract Urothelial Carcinoma Treated by Radical Nephroureterectomy.

Background: Assessing the prognosis preoperatively in patients with upper tract urothelial carcinoma (UTUC) remains a challenge for urologists. Gross hematuria (GH) and flank pain (FP) are the 2 most common and easily perceived symptoms of UTUC. Therefore, we aimed to investigate the prognostic values of GH and FP in patients with UTUC after undergoing radical nephroureterectomy (RNU). Methods: This article retrospectively analyzed 179 patients with UTUC who underwent RNU and examined the associations between the FP, GH, and long-term survival. After dividing patients into 4 subgroups (presenting as GH without FP, FP without GH, no FP and GH, FP with GH), we focused on the prognostic values of the 4 subgroups using univariate and multivariate analyses. We then proposed a risk stratification model for UTUC based on the independent prognostic factors for cancer-specific survival (CSS) with external validation (146 additional UTUC patients formed the validation cohort). Results: Patients with FP had worse oncological outcomes than those without FP (P < .05). After dividing the 179 patients into 4 subgroups, the "FP without GH" subgroup suffered the worst oncological outcomes (P < .001). The Cox multivariate regression analysis showed that "FP without GH" (P < .001), tumor multifocality (P = .005), and pathological stage (P = .004) were independent prognostic factors for CSS. Good performance of the risk stratification model was achieved in both the training and external validation cohorts. Conclusion: The presence of "flank pain without gross hematuria" was one of the independent risk factors of CSS and OS besides the pathological stage and tumor multifocality. To our knowledge, this is the first study that adding complaint to risk stratification model in UTUC.

Endoscopic balloon cryoablation plus transurethral resection for bladder cancer: A phase 2, multicenter, randomized, controlled trial.

BACKGROUND: Cryotherapy is a prevalent percutaneous ablative therapy for solid tumors. Here, we report a novel device using liquid nitrogen for endoscopic cryotherapy of bladder cancer. METHODS: In this multicenter, randomized, parallel controlled, Phase 2 trial, we compared endoscopic balloon cryoablation (EBCA) with a single instillation (SI) of pirarubicin after transurethral resection (TUR). Eligible participants were randomly assigned (1:1) to the TUR-EBCA or TUR-SI group. Repeat TUR or tissue biopsies were performed to evaluate residual tumor at 4 to 6 weeks after primary treatment. The primary end point was the local control rate. The secondary end points included the tumor upgrading/upstaging, catheter indwelling duration, and adverse events. RESULTS: In total, 205 patients received EBCA or SI after TUR between November 2017 and September 2020, of whom 163 completed all the required interventions. In the per-protocol set, the local control rate was 91.5% (75/82) in TUR-EBCA group compared with 76.5% (61/81) in TUR-SI group (risk difference, 15%; 95% CI, 0.03-0.27, p < .001), meeting the criteria for noninferiority. Similar results were found in the modified intention-to-treat analysis. Tumor upgrading/upstaging was found in five patients from the TUR-SI group. There was no significant difference in the catheter indwelling duration (5.1 vs. 5.2 days, p = .76) or serious adverse event rate (3.0% vs. 3.9%, p = .52). The median follow-up time of post hoc analysis was 31 (range, 15-50) months. Patients in the TUR-EBCA group had a better recurrence-free survival and progression-free survival. CONCLUSION: EBCA is a safe and effective adjuvant therapy with TUR for non-muscle-invasive bladder cancer. PLAIN LANGUAGE SUMMARY: This is the first randomized trial that evaluated endoscopic cryotherapy after transurethral resection (TUR) of bladder tumors. The efficacy and safety analysis shows endoscopic balloon cryoablation (EBCA) is a promising alternative. Results report that EBCA is not inferior to a single instillation of intravesical chemotherapy in eliminating residual bladder tumor. Further analysis with ∼3 years' median follow-up suggested a better prognosis in patients who received EBCA after TUR.

Effect of ulinastatin injection on left ventricular diastolic function in patients with sepsis / 中华急诊医学杂志

Objective:To investigate the effect of ulinastatin injection on left ventricular diastolic function and prognosis in patients with sepsis.Methods:A total of 100 patients with sepsis admitted to the Intensive Care Unit from January 2021 to March 2022 were selected. According to the random number table, they were randomly (random number) divided into the control group (conventional treatment) and experimental group (conventional treatment + ulinastatin injection). The baseline data on admission were compared between the two groups. The echocardiographic indexes [mitral peak velocity of early filling/early diastolic mitral annular velocity (E/e'), early diastolic mitral annular velocity (e'), mitral peak velocity of early filling/ mitral peak velocity of late filling (E/A), and tricuspid regurgitation rate (TRV)], myocardial damage-related and cardiac function-related indicators [troponin I (cTnI), N terminal pro B type natriuretic peptide (NTproBNP)] and inflammation-related indicators [C-reaction protein (CRP), procalcitonin (PCT), erythrocyte sedimentation rate (ESR)], length of ICU stay, duration of infection control, duration of vasoactive drug use and 28-day mortality were observed and compared between the two groups on admission and 7 days after treatment.Results:On the 7th day after treatment, the levels of e 'and E/A in the experimental group were significantly higher than those in the control group, and the levels of E/e', TRV, cTnI, NTproBNP, CRP and PCT were significantly decreased ( P<0.05). There were no significant differences in duration of infection control and duration of vasoactive drug use between the experimental group and the control group ( P<0.05), but the length of ICU stay was shorter and 28-day mortality was significantly lower in the experimental group than in the control group ( P<0.05). Conclusions:Ulinastatin can reduce the degree of inflammatory response, relieve myocardial injury, improve left ventricular diastolic function, and reduce the length of ICU stay and 28-day mortality in patients with sepsis.

Mechanism of neuroprotective effect of ginsenoside Rg1 regulating Epac1/Rap1 signaling pathway in rats with ischemic stroke / 中国临床药理学与治疗学

AIM: To investigate the neuroprotective effect of ginsenoside Rg1 on rats with ischemic stroke and to investigate its mechanism of action. METHODS: Eighty-four SPF-grade SD male rats at about 13 weeks of age were randomly divided into 7 groups (n=12): sham-operated group, model group, Rg1 low-dose group, Rg1 medium-dose group, Rg1 high-dose group, Epac1 agonist group, and Epac1 inhibitor group. The model group, Rg1 low, medium and high dose groups, Epac1 agonist group and Epac1 inhibitor group were all used to establish a permanent focal cerebral ischemia rat model. Rats in the Rg1 low, medium and high dose groups were treated with 60, 120 and 240 μmol/L Rg1 administered by gavage at a fixed time every morning. The rats in the Epac1 agonist and Epac1 inhibitor groups were administered intraperitoneally at a fixed time each morning with a concentration of 1.0×10

Advances in Molecular Pathology of Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is a common syndrome that features a complex etiology and set of mechanisms. Here we summarized the molecular pathogenesis of OSA, especially the prospective mechanism of upper? airway dilator fatigue and the current breakthroughs. Additionally, we also introduced the molecular mechanism of OSA in terms of related studies on the main signaling pathways and epigenetics alterations, such as microRNA, long non-coding RNA, and DNA methylation. We also reviewed small molecular compounds, which are potential targets for gene regulations in the future, that are involved in the regulation of OSA. This review will be beneficial to point the way for OSA research within the next decade.

Castleman disease of the pancreas mimicking pancreatic malignancy on 68Ga-DOTATATE and 18F-fluorodeoxyglucose positron emission tomography/computed tomography: A case report.

BACKGROUND: Castleman disease is an uncommon nonclonal lymphoproliferative disorder, which frequently mimics both benign and malignant abnormalities in several regions. Depending on the number of lymph nodes or regions involved, Castleman disease (CD) varies in diagnosis, treatment and prognosis. It rarely occurs in the pancreas alone without any distinct clinical feature and tends to be confused with pancreatic paraganglioma (PGL), neuroendocrine tumors (NETs), and primary tumors, thus impeding proper diagnosis and treatment. CASE SUMMARY: A 28-year-old woman presented with a lesion on the neck of the pancreas, detected by ultrasound during a health examination. Physical examination and laboratory findings were normal. The mass showed hypervascularity on enhanced computed tomography (CT), significantly increased 18F-fluorodeoxyglucose uptake on positron emission tomography (PET)/CT, and slightly increased somatostatin receptor (SSTR) expression on 68Ga-DOTATATE PET/CT, suggesting no distant metastases and subdiagnoses such as pancreatic PGL, NET, or primary tumor. Intraoperative pathology suggested lymphatic hyperplasia, and only simple tumor resection was performed. The patient was diagnosed with the hyaline vascular variant of CD, which was confirmed by postoperative immunohistochemistry. The patient was discharged successfully, and no recurrence was observed on regular review. CONCLUSION: High glucose uptake and slightly elevated SSTR expression are potentially new diagnostic features of CD of the pancreas.

Smilax weniae, a New Species of Smilacaceae from Limestone Areas Bordering Guizhou and Guangxi, China.

A new species, Smilax weniae (Smilacaceae), from Southwest China, is described and illustrated. The new species bears peltate leaves, which was previously a unique feature of S. luei. However, it differs from the latter by having a broad ovate leaf blade, longer peduncle, and sexual dimorphic flowers. Further phylogenetic analyses revealed that the new species were placed in a unique position in a subclade of Old World Smilax based on ptDNA and nrITS sequences. Combining detailed morphological comparisons and molecular evidence, we validated that S. weniae is an undescribed new species. Moreover, the plastome characteristics of S. weniae are reported.

VPU: A Video-Based Point Cloud Upsampling Framework.

In this work, we propose a new patch-based framework called VPU for the video-based point cloud upsampling task by effectively exploiting temporal dependency among multiple consecutive point cloud frames, in which each frame consists of a set of unordered, sparse and irregular 3D points. Rather than adopting the sophisticated motion estimation strategy in video analysis, we propose a new spatio-temporal aggregation (STA) module to effectively extract, align and aggregate rich local geometric clues from consecutive frames at the feature level. By more reliably summarizing spatio-temporally consistent and complementary knowledge from multiple frames in the resultant local structural features, our method better infers the local geometry distributions at the current frame. In addition, our STA module can be readily incorporated with various existing single frame-based point upsampling methods (e.g., PU-Net, MPU, PU-GAN and PU-GCN). Comprehensive experiments on multiple point cloud sequence datasets demonstrate our video-based point cloud upsampling framework achieves substantial performance improvement over its single frame-based counterparts.

Exosome-Mediated miR-4792 Transfer Promotes Bladder Cancer Cell Proliferation via Enhanced FOXC1/c-Myc Signaling and Warburg Effect.

Bladder cancer is the second-most common malignancy in the urogenital system and the most common in men. However, our understanding of the driving mechanisms of bladder cancer remains incomplete. The forkhead box (FOX) family of transcription factors is implicated in urogenital development and bladder malignancies. Many exosomal microRNAs have been identified as regulators and mediators of the expression of FOX, including the expression of FOXC1. miR-4792 has been known as a tumor miRNA suppressor. However, the function of miR-4792/FOXC1 signaling in bladder cancer development remains unknown. Here, we studied the role of miR-4792/FOXC1 signaling in bladder cancer by using multiple bladder cancer cell lines and bladder cancer mouse models through in vitro and in vivo approaches. We showed that FOXC1 is highly expressed in multiple bladder cancer cell lines and bladder tumor tissues. The knockdown of FOXC1 expression in bladder cancer cell lines decreases c-Myc expression levels, retards cell growth, and reduces aerobic glycolysis (also known as the Warburg effect) and lactic acid content. By contrast, the overexpression of FOXC1 elicits the opposite effects. FOXC1-downregulated bladder cancer cells form significantly smaller tumors in vivo. The inhibition of c-Myc reverses the effects of FOXC1 overexpression and leads to reduced cell proliferation, aerobic glycolysis, and lactic acid content. miR-4792 expression is downregulated in bladder tumor tissues. miR-4792 exposure to bladder cancer cells reduces the expression levels of FOXC1 and c-Myc, slows down cell growth, and decreases aerobic glycolysis and lactic acid content. However, the enhanced miR-4792 expression elicits opposite effects. These findings provided the first evidence that the exosome-mediated delivery of miR-4792 could play an important role in bladder cancer development through the downregulation of FOXC1 and c-Myc, which further inhibited aerobic glycolysis and lactic acid content.

Risk model based on MRI fusion biopsy characteristics predicts biochemical recurrence after radical prostatectomy.

BACKGROUND: To determine the prostate cancer biochemical recurrence-related fusion biopsy characteristics before radical surgery and to establish the risk prediction model of biochemical recurrence of prostate cancer. METHODS: Three hundred and four patients undergoing radical surgery for prostate cancer at Huadong Hospital affiliated to Fudan University between 2009 and 2020 for preoperative magnetic resonance imaging (MRI) before biopsy with suspicious prostate cancer lesions. Each case was followed by a 10 + x needle combination of targeted biopsy (intentional or robotic fusion) with systematic biopsy. Prostate-specific antigen levels were measured at 1, 3, and 6 months postoperatively, followed by reexamination every 6 months. Survival analysis was performed by the Kaplan-Meier method, univariate and multivariate analysis by Cox, and Logistic risk regression models. RESULTS: Higher Prostate Imaging Reporting And Data System (PI-RADS) scores (p < 0.001), suspicious extracapsular invasion (p < 0.001), and seminal vesicle invasion (p < 0.001) on MRI, the largest lesion diameter on MRI (p = 0.006), higher biopsy International Society of Urological Pathology (ISUP) grade group (p < 0.001) related to higher biochemical recurrence rates, higher pathological staging (p < 0.001), and a greater probability of local lymph node metastasis (p < 0.001). We accurately predicted the biochemical recurrence of prostate cancer after radical surgery based on preoperative features including the long diameter of the largest MRI lesion more than 23 mm, seminal vesicle invasion on MRI, and targeted fusion biopsy ISUP grade >3 Risk stratified classification (AUC = 0.729, p < 0.001). In our cohort, this risk stratification had a larger area under the curve than predictive models based only on magnetic resonance parameters and traditional risk scores. CONCLUSIONS: In this cohort, seminal vesicle invasion on MRI, the long diameter of the largest MRI lesion, and targeted fusion biopsy ISUP grade grope are significantly predictive of pathologic features and biochemical recurrence after prostate surgery. The risk stratification integrating the three parameters could better predict the biochemical recurrence than the traditional model.

Astragaloside IV improves the pharmacokinetics of febuxostat in rats with hyperuricemic nephropathy by regulating urea metabolism in gut microbiota.

Hyperuricemic nephropathy (HN) is a common clinical complication of hyperuricemia. The pathogenesis of HN is directly related to urea metabolism in the gut microbiota. Febuxostat, a potent xanthine oxidase inhibitor, is the first-line drug used for the treatment of hyperuricemia. However, there have been few studies on the pharmacokinetics of febuxostat in HN animal models or in patients. In this study, a high-purine diet-induced HN rat model was established. The pharmacokinetics of febuxostat in HN rats was evaluated using LC-MS/MS. Astragaloside IV (AST) was used to correct the abnormal pharmacokinetics of febuxostat. Gut microbiota diversity analysis was used to evaluate the effect of AST on gut microbiota. The results showed that the delayed elimination of febuxostat caused drug accumulation after multiple administrations. Oral but not i. p. AST improved the pharmacokinetics of febuxostat in HN rats. The mechanistic study showed that AST could regulate urea metabolism in faeces and attenuate urea-ammonia liver-intestine circulation. Urease-related genera, including Eubacterium, Parabacteroides, Ruminococcus, and Clostridia, decreased after AST prevention. In addition, the decrease in pathogenic genera and increase in short-chain fatty acids (SCFA) producing genera also contribute to renal function recovery. In summary, AST improved the pharmacokinetics of febuxostat in HN rats by comprehensive regulation of the gut microbiota, including urea metabolism, anti-calcification, and short-chain fatty acid generation. These results imply that febuxostat might accumulate in HN patients, and AST could reverse the accumulation through gut microbiota regulation.

Human umbilical cord Wharton's jelly-derived mesenchymal stem cell transplantation could improve diabetic intracavernosal pressure.

Mesenchymal stem cells (MSCs) secrete various cytokines with angiogenic and neuroprotective effects. This study aimed to assess the effects of human umbilical cord Wharton's jelly-derived MSCs (hWJ-MSCs) on diabetes-related intracavernosal pressure (ICP) impairment in rats. hWJ-MSCs were isolated from human umbilical cord Wharton's jelly and transplanted into the corpus cavernosum of streptozotocin (STZ)-induced diabetic rats by unilateral injection. The erectile function was evaluated at 4 weeks, as well as the expression levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), endothelial nitric oxide synthase (eNOS), and insulin-like growth factor 1 (IGF1). STZ-induced diabetic rats showed impaired ICP, which was significantly improved by hWJ-MSC treatment. VEGF, eNOS, IGF1, and bFGF expression levels were higher in hWJ-MSC injection sites than those in control ones in STZ-induced diabetic rats. These results suggest that hWJ-MSC transplantation might improve diabetic erectile dysfunction through increased production of paracrine growth factors, highlighting a novel potential therapeutic option for erectile dysfunction.