The impact of preoperative nutritional status on postoperative outcomes: an insight from Geriatric Nutritional Risk Index in elderly pancreaticoduodenectomy patients.

BACKGROUND: Malnutrition is not uncommon among the elderly undergoing pancreatoduodenectomy (PD) and is related to increased complications. Previous studies have shown that the Geriatric Nutritional Risk Index (GNRI) predicts outcomes in various populations. Nevertheless, the research exploring the correlation between GNRI and postoperative outcomes in PD is scarce. This study aimed to investigate the preoperative malnutrition, as measured by GNRI, on outcomes in elderly patients undergoing PD. MATERIALS AND METHODS: This retrospective analysis enrolled 144 elderly patients underwent PD for periampullary tumors from November 2016 to December 2021. Patients were stratified based on the GNRI value: high/moderate nutrition risk (GNRI ≤ 92, N = 54), low nutrition risk (92 < GNRI ≤ 98, N = 35), and no nutrition risk (GNRI > 98, N = 55). Perioperative outcomes and postoperative surgical complications were compared between these groups. Univariate and multivariate analyses were performed on major postoperative complications and prolonged postoperative length of stay (PLOS). RESULTS: Patients in the high/moderate risk group were significantly older, with lower BMI (P = 0.012), higher mortality rate (11.1%, P = 0.024), longer PLOS (P < 0.001), and higher incidence of over grade IIIB complications (37.0%, P = 0.001), Univariate and multivariate analyses showed the high/moderate risk GNRI group (OR 3.61, P = 0.032), increased age (OR 1.11, P = 0.014) and operative time over 8 h (OR 3.04, P = 0.027) were significantly associated with increased major postoperative complications. The high/moderate risk GNRI group was also a significant predictor for prolonged PLOS (OR 3.91, P = 0.002). CONCLUSIONS: Preoperative GNRI has the potential to be a predictive tool for identifying high-risk elderly patients and monitoring nutritional status preoperatively to improve postoperative surgical outcomes following PD.

Small intestine angioleiomyoma as a rare cause of perforation: A case report.

BACKGROUND: Angioleiomyoma is a rare and benign stromal tumor typically found in subcutaneous tissue. It rarely occurs in the gastrointestinal tract. Among the reported cases, the most common complication was gastrointestinal bleeding. Perforation has only been reported as a complication in the last few decades. CASE SUMMARY: This case report detailed the discovery of intestinal angioleiomyoma in a 47-year-old male presenting with abdominal pain that had persisted for 3 d. After suspecting hollow organ perforation, surgical intervention involving intestinal resection and anastomosis was performed. CONCLUSION: The report underscores the significance of early surgical intervention in effectively treating angioleiomyoma while emphasizing the pivotal role of timely and appropriate measures for favorable outcomes.

The outcomes and biliary complications of a staged biliary reconstruction in living donor liver transplantation: a propensity score matched analysis.

BACKGROUND: Uncontrolled massive bleeding and bowel edema are critical issues during liver transplantation. Temporal intra-abdominal packing with staged biliary reconstruction (SBR) yields acceptable outcomes in deceased donor liver transplantation; however, data on living donor liver transplantation (LDLT) are scarce. METHODS: A retrospective analysis of 1269 patients who underwent LDLT was performed. After one-to-two propensity score matching, patients who underwent LDLT with SBR were compared with those who underwent LDLT with one-stage biliary reconstruction (OSBR). The primary outcomes were graft survival (GS) and overall survival (OS), and the secondary outcomes were postoperative biliary complications. RESULTS: There were 55 and 110 patients in the SBR and OSBR groups, respectively. The median blood loss was 6500 mL in the SBR and 4875 mL in the OSBR group. Patients receiving SBR-LDLT had higher incidence of sepsis (69.0% vs. 43.6%; P < 0.01) and intra-abdominal infections (60.0% vs. 30.9%; P < 0.01). Biliary complication rates (14.5% vs. 19.1%; P = 0.47) and 1-and 5-year GS (87.27%, 74.60% vs. 83.64%, 72.71%; P = 0.98) and OS (89.09%, 78.44% vs. 84.55%, 73.70%; P = 0.752) rates were comparable between the two groups. CONCLUSIONS: SBR could serve as a life-saving procedure for patients undergoing complex critical LDLT, with GS, OS, and biliary outcomes comparable to those of OSBR.

Multi-omics analysis reveals critical metabolic regulators in bladder cancer.

BACKGROUND: The crosstalk between genomic alterations and metabolic dysregulation in bladder cancer is largely unknown. A deep understanding of the interactions between cancer drivers and cancer metabolic changes will provide novel opportunities for targeted therapeutic strategies. METHODS: Three primary bladder cancer specimens with paired normal tissues or blood samples were subjected to whole-exome sequencing, DNA methylation array and whole-transcriptome sequencing by next-generation sequencing technology. We applied the methods to multi-omics data combining the Cancer Genome Atlas (TCGA) bladder cancer samples, including somatic mutation, DNA copy number, DNA methylation and gene expression profile for validation. RESULTS: We identified 34 mutated cancer driver genes in bladder cancer. KDM6A was the most significantly mutated cancer driver gene. Metabolic pathways were enriched in both differentially methylated regions (DMRs) and differentially expressed genes. Twenty-nine DMRs in the TSS200 region were highly correlated with the upregulation of gene expression, and 24 DMRs in the genome were highly correlated with the downregulation of gene expression. A total of 201 genes had highly correlated DNA methylation and expression. Thirty-four genes, including the known metabolic genes CXXC5, PRR5, ABCB8 and BAHD1, were further validated in the TCGA cohort. Multi-omics alterations identified two new candidate driver genes, WIPI2 and GFM2, that warrant future studies. CONCLUSIONS: This study provides a comprehensive and systematic analysis, focusing on identifying key regulatory factors that may lead to cancer metabolic heterogeneity. Further understanding and verification of the cancer genes driving metabolic reprogramming and their role in the progression of bladder cancer will help to identify new therapeutic targets.

Inflow control can be safely used in laparoscopic subsegmentectomy of the liver: a single-center 10-year experience.

BACKGROUND: Several techniques have been developed to reduce blood loss in liver resection. The half-Pringle and Pringle maneuvers are commonly used for inflow control. This study compared the outcomes of different inflow control techniques in laparoscopic subsegmentectomy. METHODS: From October 2010 to December 2020, a total of 362 laparoscopic liver resections were performed by a single surgeon (C.C. Yong) in our institute. We retrospectively enrolled 133 patients who underwent laparoscopic subsegmentectomy during the same period. Perioperative and long-term outcomes were analyzed. RESULTS: The 133 patients were divided into 3 groups: no inflow control (n = 49), half-Pringle maneuver (n = 46), and Pringle maneuver (n = 38). A lower proportion of patients with cirrhosis were included in the half-Pringle maneuver group (P = .02). Fewer patients in the half-Pringle maneuver group had undergone previous abdominal (P = .01) or liver (P = .02) surgery. The no inflow control group had more patients with tumors located in the anterolateral segments (P = .001). The no inflow control group had a shorter operation time (P < .001) and less blood loss (P = .03). The need for blood transfusion, morbidity, and hospital days did not differ among the 3 groups. The overall survival did not significantly differ among the 3 groups (P = .89). CONCLUSIONS: The half-Pringle and Pringle maneuvers did not affect perioperative or long-term outcomes during laparoscopic subsegmentectomy. The inflow control maneuvers could be safely performed in laparoscopic subsegmentectomy.

PABPN1 promotes clear cell renal cell carcinoma progression by suppressing the alternative polyadenylation of SGPL1 and CREG1.

Alternative polyadenylation (APA) is an important post-transcriptional regulatory mechanism in cancer development and progression. Poly(A) binding protein nuclear 1 (PABPN1) is a gene that encodes abundant nuclear protein, binds with high affinity to nascent poly(A) tails, and is crucial for 3'-UTR (3'-untranslated region) APA. Although PABPN1 has been recently reported as a dominant master APA regulator in clear cell renal cell carcinoma (ccRCC), the underlying functional mechanism remain unclear and the genes subject to PABPN1 regulation that contribute to ccRCC progression have not been identified. Here, we found that PABPN1 is upregulated in ccRCC, and its expression is highly associated with the clinical prognosis of ccRCC patients. PABPN1 promotes ccRCC cell proliferation, migration, invasion, and exerts an influence on sphingolipid metabolism and cell cycle. Moreover, PABPN1 depletion significantly suppressed cancer cell growth via induction of cell cycle arrest and apoptosis. In particular, we characterized PABPN1-regulated 3'-UTR APA of sphingosine-1-phosphate lyase 1 (SGPL1) and cellular repressor of E1A stimulated genes 1 (CREG1), which contribute to ccRCC progression. Collectively, our data revealed that PABPN1 promotes ccRCC progression at least in part, by suppressing SGPL1 and CREG1. Thus, PABPN1 may be a potential therapeutic target in ccRCC.

Near-infrared cholangiography can increase the chance of success in laparoscopic approaches to common bile duct stones, even with previous abdominal surgery.

BACKGROUND: The treatment of common bile duct (CBD) stones with minimally invasive surgery (MIS) is more technical demanding than laparoscopic cholecystectomy (LC), especially in patients with history of previous abdominal surgery, cholangitis or cholecystitis. Near-infrared (NIR) cholangiography via systemic or biliary tree administration of indocyanine green (ICG), which enhances the visualization of the biliary tree anatomy, may increase the reassurance of CBD localization. The aim of this study was to identify the benefit of near-infrared cholangiography for laparoscopic common bile duct exploration (LCBDE). METHODS: Three groups of CBD stone patients were included in this retrospective study depending on the surgical methods: 1) open choledocholithotomy (OCC), 2) laparoscopic choledocholithotomy (LCC), and 3) near-infrared cholangiography-assisted laparoscopic choledocholithotomy (NIR-CC). For the NIR-CC group, either 3 ml (concentration: 2.5 mg/mL) of ICG were intravenously administered or 10 ml (concentration: 0.125 mg/mL) of ICG were injected directly into the biliary tree. The enhancement rate of the cystic duct (CD), CBD, the upper and lower margin of the CBD were compared using white light image. RESULTS: A total of 187 patients with a mean age of 68.3 years were included (OCC, n = 56; LCC, n = 110; NIR-CC, n = 21). The rate of previous abdominal surgery was significantly lower in the LCC group. The conversion rate was similar between the LCC and the NIR CC groups (p = 0.746). The postoperative hospital stay was significantly longer in the OCC group. No differences in morbidity and mortality were found between the three groups. In the NIR-CC group, the localization of CBD was as high as 85% compared to 24% with white light imaging. CONCLUSIONS: Near-infrared cholangiography helps increase the chance of success in minimally invasive approaches to CBD stones even in patients with previous abdominal surgeries, without increasing the rate of conversion.

High-performance artificially reeled silkworm silk via a multi-task and high-efficiency centrifugal reeling technique and its application in soft actuators.

Silkworm silks show increasing potential in applications of bioengineering, sensors, optics, electronics, and actuators. However, their inherent irregular morphologies, structures, and properties greatly hinder the translation of these technologies to commercial applications. Herein, we report a facile and comprehensive strategy to fabricate high-performance silk materials by spinning silkworms artificially via a multi-task and high-efficiency centrifugal reeling technique. With this strategy, centrifugally reeled silks (CRSs) with long-uniform morphologies, excellent strength (844.83 ± 319.48 MPa), high toughness (121.07 ± 35.31 MJ m-3), and outstanding Young's modulus (27.72 ± 12.61 GPa) are developed. Remarkably, the maximum strength (1.45 GPa) of CRS is 3 times that of cocoon silk and even comparable to spider silk. Moreover, the centrifugal reeling technique realizes the one-step preparation of centrifugally reeled silk yarn (CRSY) from spinning silkworm, and the CRSYs show higher strength (877.38 ± 377.23 MPa) and superior torsional recovery performances. Furthermore, these CRSY-based soft pneumatic actuators (SPAs) exhibit light weight, high-loading capability, easy programmability in strength and motions, and fast responses, and therefore outperform currently reported elastomer-based SPAs, showing promising applications in flexible sensors, artificial muscles, and soft robotics. This work also provides a new guide for producing high-performance silks from silk-secreting insects and arthropods.

Inhibition of Histone H3K18 Acetylation-Dependent Antioxidant Pathways Involved in Arsenic-Induced Liver Injury in Rats and the Protective Effect of Rosa roxburghii Tratt Juice.

Arsenic is a common environmental toxicant. Long-term arsenic exposure can induce various types of liver injury, but the underlying mechanism remains unclear, so effective prevention and treatment measures are unknown. This study aims to explore the mechanism of arsenic-induced rat liver injury based on the histone H3K18 acetylation-dependent antioxidant pathway and to identify the role of a medicinal and edible resource, Rosa roxburghii Tratt juice, in combating it. Hepatic steatosis and inflammatory cell infiltration were observed in rats exposed to different doses of NaAsO2 using histopathological measurement. Increased 8-OHdG and MDA in liver tissue corroborated hepatic oxidative damage. We further found that a reduction in H3K18ac in the liver showed a dose-response relationship, with an increase in the NaAsO2 treatment dose, and it was remarkably associated with increased 8-OHdG and MDA. The results of ChIP-qPCR identified that the decreased enrichment of H3K18ac in promoters of the Hspa1a and Hspb8 genes culminated in the inhibition of the genes' expression, which was found to be involved in the aggravation of hepatic oxidative damage induced by arsenic. Notably, Rosa roxburghii Tratt juice was found to reduce 8-OHdG and MDA in the liver, thereby alleviating the histopathological lesions induced by arsenic, which was modulated by recovering the H3K18ac-dependent transcriptional activation of the Hspa1a and Hspb8 genes. Taken together, we provide a novel epigenetics insight into clarifying the mechanism of arsenic-induced liver injury and its rescue by Rosa roxburghii Tratt juice.

Fabrication of hierarchical porous ethyl cellulose fibrous membrane by electro-centrifugal spinning for drug delivery systems with excellent integrated properties.

Drug delivery systems (DDSs) based on micro-and nano- fibrous membrane have been developed for decades, in which great attention has been focused on achieving controlled drug release. However, the study on the integrated performance of these drug-loaded membranes in the use of in-vitro drug delivery dressing is lacking, as clinical medication also needs consideration from the perspectives of wound safety and patient convenience. Herein, a trilayered hierarchical porous ethyl cellulose (EC) fibrous membrane based DDS (EC-DDS) was developed by electro-centrifugal spinning. Significantly, the hierarchical porous structure of the EC-DDSs with high specific surface area (34.3 m2g-1) and abundant long-regulative micro-and nano- channels demonstrated its merits in improving the hydrophobicity (long-term splash resistance (CA > 130°) and prolonging the drug release (the release time of ~80 % tetracycline hydrochloride (TCH) prolonged from 10 min to 24 h). Meanwhile, the trilayered EC-DDS also revealed excellent biocompatibility, antibacterial activity, air permeability, moisture permeability, water absorption capacity, mechanical strength, and flexibility. With these excellent integrated features, the EC-DDS could prevent external fluids, avoid infection, and provide comfort. Furthermore, this work also provides a new guide for the high-efficiency fabrication of porous fibrous membranes.

Comprehensive analysis of alternative polyadenylation regulators of CTLA4 and immune infiltration in clear cell renal cell carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC) is the most common renal cancer. Alternative polyadenylation (APA) plays an important role in the progression and immunity of multiple tumors. Although immunotherapy has emerged as an important treatment option for metastatic renal cell carcinoma, whether APA affects the tumor immune microenvironment (TIME) in ccRCC remains unclear. Methods: Patients with ccRCC were classified into two groups by performing a consensus clustering analysis of APA factor expression profiles. The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases were used to assess the association between APA regulators and ccRCC prognosis. Through the use of the R package, GSVA, the correlation between SNRNP70 expression and tumor immune features were analyzed. Results: The TCGA data revealed that APA regulators were associated with Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA4) expression. Cluster 1 exhibited a higher grade and histological tumor stage, as well as a worse prognosis compared to Cluster 2. A ssGSEA analysis demonstrated that Cluster 2 possessed an extensively higher level of immune infiltration. Moreover, high SNRNP70 expression was found to be positively correlated with CTLA4 expression and a poor prognosis in ccRCC. Thus, SNRNP70 might represent a novel immune-related prognostic biomarker in ccRCC. A pan-cancer analysis suggested that SNRNP70 may also play a role in other types of cancer by affecting the TIME. Conclusions: The data from this study indicate that APA regulators play a key role in immune infiltration in ccRCC. SNRNP70 is a promising prognostic biomarker and a potential target for ccRCC's immunotherapy.

Lengthening of 3' Untranslated Regions of mRNAs by Alternative Polyadenylation Is Associated With Tumor Progression and Poor Prognosis of Clear Cell Renal Cell Carcinoma.

Alternative polyadenylation (APA) is emerging as a major posttranscriptional mechanism for gene regulation in cancer. A prevailing hypothesis is that shortening of the 3' untranslated region (3'UTR) increases oncoprotein expression because of the loss of miRNA-binding sites (MBSs). We showed that the longer 3'UTR is associated with a more advanced tumor stage in patients with clear cell renal cell carcinoma (ccRCC). More surprisingly, 3'UTR shortening is correlated with better overall survival in patients with ccRCC. Furthermore, we identified a mechanism by which longer transcripts lead to increased oncogenic protein and decreased tumor-suppressive protein expression compared to the shorter transcripts. In our model, shortening of 3'UTRs by APA may increase the mRNA stability of the majority of the potential tumor-suppressor genes due to the loss of MBSs and AU-rich elements (AREs). Unlike potential tumor-suppressor genes, the potential oncogenes display much lower MBS and ARE density and globally much higher m6A density in distal 3'UTRs. As a result, 3'UTRs shortening decreases the mRNA stability of potential oncogenes and enhances the mRNA stability of potential tumor-suppressor genes. Our findings highlight the cancer-specific pattern of APA regulation and extend our understanding of the mechanism of APA-mediated 3'UTR length changes in cancer biology.

PABPN1 regulates mRNA alternative polyadenylation to inhibit bladder cancer progression.

BACKGROUND: About 10-20% of patients with bladder cancer (BC) progress to muscle-invasive diseases, of which the underlying key molecular events have yet to be addressed. RESULTS: Here, we identified poly(A) binding protein nuclear 1 (PABPN1), a general factor of alternative polyadenylation (APA), was downregulated in BC. Overexpression and knockdown of PABPN1 significantly decreased and increased BC aggressiveness, respectively. Mechanistically, we provide evidence that the preference of PABPN1-bound polyadenylation signals (PASs) depends on the relative location between canonical and non-canonical PASs. PABPN1 shapes inputs converging on Wnt signaling, cell cycle, and lipid biosynthesis. CONCLUSIONS: Together, these findings provide insights into how PABPN1-mediated APA regulation contributes to BC progression, and suggest that pharmacological targeting PABPN1 might have therapeutic potential in patients with BC.

From Death Triad to Death Tetrad-The Addition of a Hypotension Component to the Death Triad Improves Mortality Risk Stratification in Trauma Patients: A Retrospective Cohort Study.

The death triad, including coagulopathy, hypothermia, and acidosis, is shown to be a strong predictor of mortality in trauma patients. We aimed to investigate whether the inclusion of hypotension, defined as systolic blood pressure (SBP) < 60 mmHg, as a fourth factor in the death triad would comprise a death tetrad to help stratify mortality risk in trauma patients. A total of 3361 adult trauma patients between 1 January 2009 and 31 December 2019 were allocated into groups to investigate whether hypotension matters in determining the mortality outcome of trauma patients who possess 1−3 death triad components compared to those without any component. Hypotension was added to the death tetrad, and the adjusted mortality outcome was compared among groups with 0−4 death tetrad components. Herein, we showed that SBP < 60 mmHg could be used to identify patients at risk of mortality among patients with one or two death triad components. Patients with one, two, and three death tetrad components had respective adjusted mortality rates of 3.69-, 10.10-, and 40.18-fold, determined by sex, age, and comorbidities. The mortality rate of trauma patients with all the four death tetrad components was 100%. The study suggested that hypotension, defined as an SBP < 60 mmHg, may act as a proper death tetrad component to stratify the mortality risk of trauma patients.

Comprehensive analysis of alternative polyadenylation regulators concerning CD276 and immune infiltration in bladder cancer.

Alternative polyadenylation (APA) is emerging as a crucial regulatory mechanism in bladder cancer (BC), while it remains elusive whether APA influences the tumor immune microenvironment (TIME) in BC. We identified two distinct subtypes of BC by APA-related regulatory genes expression profiles. The two subtypes have different pathological grades, prognostic outcomes, tumor immune infiltration characteristics, and pathway enrichment. Subsequently, CPSF3 was identified as a potential immune infiltration-related gene in BC. Highly expressed CPSF3 was positively correlated with unfavorable prognosis and high CD276 expression in BC. Moreover, we verified the expression of CPSF3 in BC tissues and cell lines by qRT-PCR. In conclusion, the study indicates that APA regulatory factors play an important role in immune infiltration of BC, and that CPSF3 was a potentially prognostic marker and immunotherapy target for BC.

Electroacupuncture Reduces Anxiety Associated With Inflammatory Bowel Disease By Acting on Cannabinoid CB1 Receptors in the Ventral Hippocampus in Mice.

The therapeutic effects of electroacupuncture (EA) on the comorbidity of visceral pain and anxiety in patients with inflammatory bowel disease (IBD) is well known. It has been known that the ventral hippocampus (vHPC) and the cannabinoid type 1 receptors (CB1R) are involved in regulating anxiety and pain. Therefore, in this study, we determined whether EA reduces visceral pain and IBD-induced anxiety via CB1R in the vHPC. We found that EA alleviated visceral hyperalgesia and anxiety in TNBS-treated IBD mice. EA reversed over-expression of CB1R in IBD mice and decreased the percentage of CB1R-expressed GABAergic neurons in the vHPC. Ablating CB1R of GABAergic neurons in the vHPC alleviated anxiety in TNBS-treated mice and mimicked the anxiolytic effect of EA. While ablating CB1R in glutamatergic neurons in the vHPC induced severe anxiety in wild type mice and inhibited the anxiolytic effect of EA. However, ablating CB1R in either GABAergic or glutamatergic neurons in the vHPC did not alter visceral pain. In conclusion, we found CB1R in both GABAergic neurons and glutamatergic neurons are involved in the inhibitory effect of EA on anxiety but not visceral pain in IBD mice. EA may exert anxiolytic effect via downregulating CB1R in GABAergic neurons and activating CB1R in glutamatergic neurons in the vHPC, thus reducing the release of glutamate and inhibiting the anxiety circuit related to vHPC. Thus, our study provides new information about the cellular and molecular mechanisms of the therapeutic effect of EA on anxiety induced by IBD.

Comprehensive analysis of lower mitochondrial complex I expression is associated with cell metastasis of clear cell renal cell carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC) is characterized by high metastasis potential. It is of great importance to explore the mechanisms underlying ccRCC metastasis and to enable development of potent therapeutics. The mitochondrial complex I (CI) had been considered to play an important role in the development of cancers, but less known in ccRCC. Methods: We utilized available public databases of ccRCC, including single-cell RNA sequencing (scRNA-seq) data GSE73121 and The Cancer Genome Atlas-kidney renal clear cell carcinoma (TCGA-KIRC). Principal component analysis (PCA) and t-Distributed Stochastic Neighbor Embedding (tSNE) analysis were evaluated the heterogeneity of metastatic renal cell carcinoma (mRCC) and primary renal cell carcinoma (pRCC). Protein-protein interaction (PPI) network identified critical gene. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) performed to explore the potential biologic pathways. Results: Our study revealed a significant gene expression heterogeneity between pRCC and mRCC. A PPI network based on differentially expressed genes (DEGs) identified electron transport chain (ETC), especially mitochondrial CI, as the key network hub. Further analysis revealed that the role of mitochondrial CI is associated with tumor metastasis and immune responds of ccRCC. Although CI had low frequency mutations in ccRCC, CI expression is associated with the high frequency mutated genes. A prognosis model included 7 CI genes, and these had a significant effect on overall survival (OS). The area under the curve at 1, 3, and 5 years was 0.717, 0.685, and 0.728, respectively. Transcription factor analysis predicted that PPARG possibly is a potential transcription activator of CI genes in ccRCC. Conclusions: Overall, we found that CI expression is associated with ccRCC progress. CI and PPARG may be potential biomarkers for metastatic ccRCC.

Circ_0004087 interaction with SND1 promotes docetaxel resistance in prostate cancer by boosting the mitosis error correction mechanism.

BACKGROUND: Acquisition of the chemoresistance to docetaxel (DTX), a microtubule-targeting agent, has been a huge obstacle in treatment for metastatic castration-resistant prostate cancer (mCRPC). Recently, strategies targeting the mitosis error correction mechanism including chromosomal passenger complex (CPC) were reported to reverse the resistance to microtubule-targeting anticancer agents. Meanwhile, accumulating evidence indicated the important roles of circRNAs in DTX resistance of prostate cancer (PCa). However, whether circRNAs could regulate DTX chemosensitivity by affecting the mitosis error correction mechanism remains unclear. METHODS: Expression patterns of circ_0004087 and BUB1 were determined through mining the public circRNA datasets and performing western blot and qRT-PCR assays. Agarose gel electrophoresis, Sanger sequencing, and RNase R treatment were conducted to examine the circular characteristics of circ_0004087. CircRNA pull-down, mass spectrometry analysis, Co-IP, and dual-luciferase reporter assays were performed to uncover the interaction among circ_0004087, SND1, and MYB. The effects of circ_0004087 and BUB1 on docetaxel-based chemotherapy were explored by flow cytometry and in vivo drug studies upon xenografted tumor model. RESULTS: In the present study, we revealed the profound interaction between a novel circRNA, circ_0004087, and the mitosis error correction mechanism. Mechanistically, circ_0004087 binding with transcriptional coactivator SND1 could stimulate the transactivation of MYB and enhance the expression of downstream target BUB1. In turn, elevated BUB1 expression further recruited CPC to centromeres and guaranteed the error-free mitosis of PCa cells. Biologically, the overexpression of circ_0004087 conferred while the knockdown impaired DTX resistance in PCa cells. CONCLUSIONS: Our study uncovered the crucial role of circ_0004087/SND1/MYB/BUB1 axis in modulating the error mitosis correction mechanism and DTX chemoresistance, suggesting that circ_0004087 may serve as a valuable prognostic biomarker and a potential therapeutic target in DTX-resistant PCa patients.

Lingual Mucosal Graft Ureteroplasty for Long Proximal Ureteral Stricture: 6 Years of Experience with 41 Cases.

BACKGROUND: Management of a long proximal ureteral stricture is challenging. Lingual mucosal graft ureteroplasty (LMGU) is a novel minimally invasive technique for ureteral reconstruction that avoids the morbidity of bowel interposition or autotransplantation. OBJECTIVE: To evaluate the long-term effectiveness of LMGU for managing long, complex proximal ureteral strictures in a multi-institutional cohort of patients. DESIGN, SETTING, AND PARTICIPANTS: This retrospective study involved data for 41 patients treated with LMGU at three centers between June 2015 and January 2021. SURGICAL PROCEDURE: LMGU was performed using either an onlay ureteroplasty in which the diseased ureter was incised ventrally and repaired with a lingual mucosal graft (LMG) to widen the ureteral lumen, or an augmented anastomotic technique in which the obliterated segment of the ureter was excised and reanastomosed primarily on dorsal side, and an LMG was placed on the ventral side. MEASUREMENTS: Pre-, intra-, and postoperative variables and outcomes were assessed. A descriptive statistical analysis was performed. RESULTS AND LIMITATIONS: Of 41patients, 40 were operated with laparoscopic procedures and one with a robot. Twenty-four (59%) patients underwent an onlay ureteroplasty, and 17 (41%) underwent an augmented anastomotic ureteroplasty. The reconstructed ureter was wrapped with omentum in 90% of cases. The median (range) stricture length was 4.8 cm (2.0-8.0), operative time was 166 min (98-306), and estimated blood loss was 65 ml (15-220). No open conversions and intraoperative complications occurred. At a median follow-up of 35 mo (range 13-80), the overall success rate was 97.6% (40/41). CONCLUSIONS: LMGU is a safe, feasible, and effective long-term technique for managing long, complex proximal ureteral strictures. PATIENT SUMMARY: We reported a novel technique for long proximal complex ureteral strictures using an onlay lingual mucosal graft (LMG). Our 6-yr outcomes demonstrate that onlay LMG ureteroplasty is a safe, feasible, and effective long-term procedure for ureteral reconstruction.

Biodegradable, biomimetic, and nanonet-engineered membranes enable high-flux and highly-efficient oil/water separation.

Porous membranes with fascinating super-wettable surface and tunable porous architecture for oil-water separation have been developed rapidly, however, the serious secondary marine pollution caused by the non-degradable defectiveness of membranes themselves is still a thorny problem. Herein, we create an eco-friendly membrane with biomimetic cobweb-like nanostructure via assembling two-dimensional bacterial cellulose nanonets on the starch nanofibrous membrane on a large scale. The obtained novel composite membranes exhibit integrated properties of sub-micron pore size, ultrahigh porosity, superhydrophilicity, and underwater superoleophobicity, stemming from the synergistic effect of the hydrated nanonet-skin-layer and porous starch matrix. By virtue of the narrow-distributed sub-micron pores, ultrahigh porosity, and ultrathin thickness, the resulting membrane shows outstanding performance of excellent separation efficiency (up to 99.996%), high percolation flux (maximum of 15968 L m-2 h-1), well surpassing the conventional microfiltration membranes. More significantly, with the advantage of biodegradability and anti-oil-fouling property, the membrane could serve as the robust platform for long-term wastewater remediation.