Deubiquitination of CDC6 by OTUD6A promotes tumour progression and chemoresistance.

BACKGROUND: CDC6 is an oncogenic protein whose expression level fluctuates during the cell cycle. Although several E3 ubiquitin ligases responsible for the ubiquitin-mediated proteolysis of CDC6 have been identified, the deubiquitination pathway for CDC6 has not been investigated. METHODS: The proteome-wide deubiquitinase (DUB) screening was used to identify the potential regulator of CDC6. Immunofluorescence, protein half-life and deubiquitination assays were performed to determine the protein stability of CDC6. Gain- and loss-of-function experiments were implemented to analyse the impacts of OUTD6A-CDC6 axis on tumour growth and chemosensitivity in vitro. N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced conditional Otud6a knockout (CKO) mouse model and tumour xenograft model were performed to analyse the role of OTUD6A-CDC6 axis in vivo. Tissue specimens were used to determine the association between OTUD6A and CDC6. RESULTS: OTUD6A interacts with, depolyubiquitinates and stabilizes CDC6 by removing K6-, K33-, and K48-linked polyubiquitination. Moreover, OTUD6A promotes cell proliferation and decreases sensitivity to chemotherapy by upregulating CDC6. CKO mice are less prone to BCa tumorigenesis induced by BBN, and knockdown of OTUD6A inhibits tumour progression in vivo. Furthermore, OTUD6A protein level has a positive correlation with CDC6 protein level, and high protein levels of OTUD6A and CDC6 are associated with poor prognosis in patients with bladder cancer. CONCLUSIONS: We reveal an important yet missing piece of novel DUB governing CDC6 stability. In addition, our findings propose a model for the OTUD6A-CDC6 axis that provides novel insights into cell cycle and chemosensitivity regulation, which may become a potential biomarker and promising drug target for cancer treatment.

The ecology of the sewer systems: Microbial composition, function, assembly, and network in different spatial locations.

Microbial induced concrete corrosion (MICC) is the primary deterioration affecting global sewers. Disentangling ecological mechanisms in the sewer system is meaningful for implementing policies to protect sewer pipes using trenchless technology. It is necessary to understand microbial compositions, interaction networks, functions, alongside assembly processes in sewer microbial communities. In this study, sewer wastewater samples and microbial samples from the upper part (UP), middle part (MP) and bottom part (BP) of different pipes were collected for 16S rRNA gene amplicon analysis. It was found that BP harbored distinct microbial communities and the largest proportion of unique species (1141) compared to UP and MP. The community in BP tended to be more clustered. Furthermore, significant differences in microbial functions existed in different spatial locations, including the carbon cycle, nitrogen cycle and sulfur cycle. Active microbial sulfur cycling indicated the corrosion risk of MICC. Among the environmental factors, the oxidation‒reduction potential drove changes in BP, while sulfate managed changes in UP and BP. Stochasticity dominated community assembly in the sewer system. Additionally, the sewer microbial community exhibited numerous positive links. BP possessed a more complex, modular network with higher modularity. These deep insights into microbial ecology in the sewer system may guide engineering safety and disaster prevention in sewer infrastructure.

Knockdown of AK142426 suppresses M2 macrophage polarization and inflammation in peritoneal fibrosis via binding to c-Jun.

BACKGROUND: Peritoneal fibrosis is a common complication of peritoneal dialysis, which may lead to ultrafiltration failure and ultimately treatment discontinuation. LncRNAs participate in many biological processes during tumorigenesis. We investigated the role of AK142426 in peritoneal fibrosis. METHODS: The AK142426 level in peritoneal dialysis (PD) fluid was detected by quantitative real-time-PCR assay. The M2 macrophage distribution was determined by flow cytometry. The inflammatory cytokines of TNF-α and TGF-ß1 were measured by ELISA assay. The direct interaction between AK142426 and c-Jun was evaluated by RNA pull-down assay. In addition, the c-Jun and fibrosis related proteins were assessed by western blot analysis. RESULTS: The PD-induced peritoneal fibrosis mouse model was successfully established. More importantly, PD treatment induced M2 macrophage polarization and the inflammation in PD fluid, which might be associated with exosome transmission. Fortunately, AK142426 was observed to be upregulated in PD fluid. Mechanically, knockdown of AK142426 suppressed M2 macrophage polarization and inflammation. Furthermore, AK142426 could upregulate c-Jun through binding c-Jun protein. In rescue experiments, overexpression of c-Jun could partially abolish the inhibitory effect of sh-AK142426 on the activation of M2 macrophages and inflammation. Consistently, knockdown of AK142426 alleviated peritoneal fibrosis in vivo. CONCLUSIONS: This study demonstrated that knockdown of AK142426 suppressed M2 macrophage polarization and inflammation in peritoneal fibrosis via binding to c-Jun, suggesting that AK142426 might be a promising therapeutic target for patients of peritoneal fibrosis.

Effects of acute normovolemic hemodilution on allogeneic blood transfusion & coagulation in orthognathic surgery: A randomized study.

BACKGROUND: Acute normovolemic hemodilution (ANH) is one of the important techniques predominantly used in cardiac, hepatic, and vascular surgery for decreasing allogeneic blood transfusion. However, the effect of ANH in orthognathic surgery has been rarely studied. Therefore, this study aims to assess the ANH-mediated reduction in the allogeneic red blood cell transfusion for orthognathic surgery patients. STUDY DESIGN AND METHODS: In this single-center study, 18-80 years old patients were recruited. Patients with hemoglobin ≥11 g/dL and normal coagulation function were randomly divided into ANH or standard treatment group. RESULTS: Ninety six patients underwent ANH, and 101 patients received standard treatment. No differences in demographic or major pre-operative characteristics were observed between the two groups. One patient in the ANH and three patients in the standard treatment group received allogeneic blood [3(2.97%) vs. 1(1.16%), control vs. ANH, p = .395]. Multivariate logistic regression analysis revealed that ANH treatment was not associated with transfusion of allogeneic blood (p = .763). After retransfusing autologous blood, PT and APTT in the ANH group significantly increased compared to standard treatment group (PT: -1.73 ± 1.09 vs. -2.15 ± 1.06, p = .035; APTT: -6.39 ± 5.76 vs. -8.16 ± 5.70, p = .031; control vs. ANH). No significant differences between the two groups were observed for changes in coagulation parameters at first postoperative day. However, platelet counts in the ANH group decreased compared to the standard group. No significant difference in major adverse outcomes was observed between the two groups. CONCLUSION: ANH did not reduce the incidence of allogeneic transfusion in patients undergoing orthognathic surgery.

Gut microbiome in men with chronic prostatitis/chronic pelvic pain syndrome: profiling and its predictive significance.

PURPOSE: To investigate the difference in gut microbiome composition between patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and healthy controls, and to assess the potential of gut microbiota as predictive markers for CP/CPPS risk. METHODS: The present study included 41 CP/CPPS patients and 43 healthy controls in China. Fecal specimen data were obtained and analysed using 16S rRNA gene sequencing. Alpha and beta-diversity indices, relative microbiome abundances, cluster analysis, and linear discriminant analysis effect size (LEfSe) were employed. Microbial biomarkers were selected for the development of a diagnostic classification model, and the functional prediction was conducted using PICRUSt2. RESULTS: Alpha-diversity measures revealed no statistically significant difference in bacterial community structure between CP/CPPS patients and controls. However, significant differences were observed in the relative abundances of several bacterial genera. Beta-diversity analysis revealed a distinct separation between the two groups. Significant inter-group differences were noted at various taxonomic levels, with specific bacterial genera being significantly different in abundance. The LEfSe analysis indicated that three bacterial species were highly representative and seven bacterial species were low in CP/CPPS patients as compared to the control group. A diagnostic model for CP/CPPS based on microbial biomarkers exhibited good performance. PICRUSt2 functional profiling indicated significant differences in the development and regeneration pathway. CONCLUSION: Significant differences in the gut microbiome composition were found between groups. The study provided a novel diagnostic model for CP/CPPS based on microbiota, presenting promising potential for future therapeutic targets and non-invasive diagnostic biomarkers for CP/CPPS patients.

Comprehensive analysis of N6-methyladenosine regulators with the tumor immune landscape and correlation between the insulin-like growth factor 2 mRNA-binding protein 3 and programmed death ligand 1 in bladder cancer.

BACKGROUND: N6-methyladenosine (m6A) is one of the most abundant post-transcriptional modifications of RNA. However, there is limited information about the potential roles of m6A regulators in tumor immunity. Therefore, in this study, we aimed to testify the functions of m6A regulators in bladder cancer as well as their association with the tumor immune landscape. METHODS: We reported the variation and expression levels of m6A regulators in the TCGA database and GTEx database of bladder cancer. Clusters, risk score patterns, and nomograms were constructed to evaluate the function and prognostic value of m6A regulators. Furthermore, we constructed nomogram to evaluate the prognosis of the individual patients. The correlation between insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) and programmed cell death ligand 1 (PD-L1) was evaluated both in vitro and in vivo. RESULTS: We found that the tumor grade and DNA damage pathways were strongly correlated with distinct clusters. Furthermore, two risk score groups with six m6A regulators were identified using the least absolute shrinkage and selection operator (LASSO) and multivariable Cox regression analysis, which could be regarded as independent prognostic markers in patients with bladder cancer. The risk score pattern was linked to the tumor immune landscape, indicating a correlation between immune checkpoints and m6A regulators. Moreover, an m6A regulator, IGF2BP3, was found to be highly expressed in the tumor samples, regulating both the total and membrane-bound PD-L1 expression levels. CONCLUSIONS: The results of this study revealed that the m6A clusters and patterns play crucial roles in the regulation of tumor immunity, which may be used to develop comprehensive treatment strategies for the management of bladder cancer.

Role of IGF-1R in epithelial-mesenchymal transdifferentiation of human peritoneal mesothelial cells.

BACKGROUND: Peritoneal fibrosis (PF) is caused by epithelial-mesenchymal transdifferentiation (EMT) in the peritoneum under high glucose (HG) conditions. The study aimed to explored the role of Insulin-like growth factor 1 receptor (IGF-1R) in the regulation of EMT in human peritoneal mesothelial cells (HPMCs). METHODS: We used HG peritoneal dialysis fluid (PDF) to induce in vivo PF in mice, and treated HPMCs with HG in vitro to stimulate EMT. RESULTS: In the mice, the higher the glucose concentration in the dialysate, the more obvious the peritoneal tissue thickening and the more that collagen was deposited. The in vitro study indicated that the expression of IGF-1R, α-SMA, vimentin was upregulated, while the expression of occludin, ZO-1, and E-cadherin was downregulated in HPMCs under HG and IGF-1R overexpression conditions. Conversely, the expression of IGF-1R, α-SMA, and vimentin was downregulated, while the expression of occludin, ZO-1, and E-cadherin was upregulated in IGF-1R-underexpressed HPMCs under HG conditions. The cell migration abilities were increased, while the cell adhesion abilities were reduced in HPMCs under HG and IGF-1R overexpression conditions. In contrast, cell migration abilities were reduced, while cell adhesion abilities were increased in IGF-1Runderexpressed HPMCs under HG conditions. CONCLUSIONS: Targeting at IGF-1R may provide novel insights into the prevention and treatment of PF.

Metformin ameliorates bladder dysfunction in a rat model of partial bladder outlet obstruction.

Alteration of bladder morphology and function was the most important consequence of bladder outlet obstruction (BOO). Using a rat model of partial BOO (pBOO), we found that rats treated with metformin showed lower baseline pressures with a reduced inflammatory reaction in the early phase (2 wk) after pBOO. The NLR family pyrin domain containing 3 inflammasome pathway was inhibited in pBOO rat bladders with treatment of metformin in the early phase. Metformin reduced the activity of NLR family pyrin domain containing 3 in primary urothelial cells. In the chronic phase (9 wk after pBOO), metformin treatment ameliorated bladder fibrosis and improved the reduced compliance. Treatment with metformin suppressed the activation of Smad3 and compensated the diminished autophagy in 9-wk pBOO rat bladders. Autophagy was inhibited with upregulation of profibrotic proteins in primary fibroblasts from chronic pBOO bladders, which could be restored by administration of metformin. The antifibrotic effects of metformin on fibroblasts were diminished after silencing of AMP-activated protein kinase or light chain 3B. In summary, this study elucidates that oral administration of metformin relieves inflammation in the bladder during the early phase of pBOO. Long-term oral administration of metformin can prevent functional and histological changes in the pBOO rat bladder. The current study suggests that metformin might be used to prevent the development of bladder dysfunction secondary to BOO.NEW & NOTEWORTHY The present study in a rat model showed that oral administration of metformin alleviated inflammation following partial bladder outlet obstruction in the early phase and ameliorated bladder fibrosis as well as bladder dysfunction by long-term treatment. Our study indicated that metformin is a potential drug to inhibit bladder remodeling and alleviate bladder dysfunction. Clinical trials are needed to validate the effect of metformin on the bladder dysfunction and bladder fibrosis in the future.

KDM6A-ARHGDIB axis blocks metastasis of bladder cancer by inhibiting Rac1.

BACKGROUND: KDM6A, a histone demethylase, is frequently mutated in bladder cancer (BCa). However, the role and detailed molecular mechanism of KDM6A involved in bladder cancer progression remains unknown. METHODS: Tissue specimens were used to determine the expression levels and prognostic values of KDM6A and ARHGDIB. The MTT, colony formation, wound healing and Transwell migration and invasion assays were employed to detect the BCa cell proliferation, migration and invasion, respectively. Chemotaxis of macrophages was used to evaluate the ability of KDM6A to recruit macrophages. A subcutaneous tumour model and tail vein tumour injection in nude mice were used to assess the role of KDM6A in vivo. RNA sequencing, qPCR, Western blot, ChIP and phalloidin staining assay were performed to investigate the molecular functions of KDM6A. Dual-luciferase reporter assay was used to determine the effects of KDM6A and FOXA1 on the promoters of the ARHGDIB and KDM6A. RESULTS: We showed that the KDM6A inhibited the motility and invasiveness of the BCa cells. Mechanistically, KDM6A promotes the transcription of ARHGDIB by demethylating histone H3 lysine di/trimethylation (H3K27me2/3) and consequently leads to inhibition of Rac1. EZH2, which catalyses the methylation of H3K27, functions to silence ARHGDIB expression, and an EZH2 inhibitor can neutralize the metastatic effect caused by KDM6A deficiency. Furthermore, we demonstrated that FOXA1 directly binds to the KDM6A promoter and thus transactivates KDM6A, leading to diminished metastatic potential. CONCLUSION: Our findings establish the critical role of the FOXA1-KDM6A-ARHGDIB axis in restraining the malignancy of BCa and identify KDM6A and EZH2 as potential therapeutic targets in the management of BCa.

Intestinal fistula accompanied by recurrent peritonitis associated with peritoneal dialysis: a case report.

BACKGROUND: Intestinal perforation from peritoneal dialysis is rare, but the resulting complications are serious. Some patients do not necessarily have symptoms, and it can be difficult to differentiate their condition from PD-related (peritoneal dialysis-related) peritonitis, which may lead to misdiagnosis. Here we report a peritoneal dialysis patient with intestinal fistula associated with recurrent peritonitis. CASE PRESENTATION: A 44-year-old man had been treated for more than 6 years with peritoneal dialysis for chronic kidney disease stage-V. Abdominal computed tomography and electronic colonoscopy revealed an appendiceal fossa with adjacent fistula. The peritoneal dialysis catheter was removed, and the patient recovered with no recurrence of complications. CONCLUSION: We report a case of a rare complication of peritoneal dialysis. The intestinal fistula in this patient was mainly caused by recurrent peritonitis and removal of the catheter could control the peritonitis.

Electroacupuncture Modulates Spinal BDNF/TrκB Signaling Pathway and Ameliorates the Sensitization of Dorsal Horn WDR Neurons in Spared Nerve Injury Rats.

Neuropathic pain is more complex and severely affects the quality of patients' life. However, the therapeutic strategy for neuropathic pain in the clinic is still limited. Previously we have reported that electroacupuncture (EA) has an attenuating effect on neuropathic pain induced by spared nerve injury (SNI), but its potential mechanisms remain to be further elucidated. In this study, we designed to determine whether BDNF/TrκB signaling cascade in the spinal cord is involved in the inhibitory effect of 2 Hz EA on neuropathic pain in SNI rats. The paw withdrawal threshold (PWT) of rats was used to detect SNI-induced mechanical hypersensitivity. The expression of BDNF/TrκB cascade in the spinal cord was evaluated by qRT-PCR and Western blot assay. The C-fiber-evoked discharges of wide dynamic range (WDR) neurons in spinal dorsal horn were applied to indicate the noxious response of WDR neurons. The results showed that 2 Hz EA significantly down-regulated the levels of BDNF and TrκB mRNA and protein expression in the spinal cord of SNI rats, along with ameliorating mechanical hypersensitivity. In addition, intrathecal injection of 100 ng BDNF, not only inhibited the analgesic effect of 2 Hz EA on pain hypersensitivity, but also reversed the decrease of BDNF and TrκB expression induced by 2 Hz EA. Moreover, 2 Hz EA obviously reduced the increase of C-fiber-evoked discharges of dorsal horn WDR neurons by SNI, but exogenous BDNF (100 ng) effectively reversed the inhibitory effect of 2 Hz EA on SNI rats, resulting in a remarkable improvement of excitability of dorsal horn WDR neurons in SNI rats. Taken together, these data suggested that 2 Hz EA alleviates mechanical hypersensitivity by blocking the spinal BDNF/TrκB signaling pathway-mediated central sensitization in SNI rats. Therefore, targeting BDNF/TrκB cascade in the spinal cord may be a potential mechanism of EA against neuropathic pain.

CCL17-CCR4 axis promotes metastasis via ERK/MMP13 pathway in bladder cancer.

As an important chemokine receptor, the role of CCR4 in the progression of bladder cancer (BC) remains unknown. In this study, we have shown that CCR4 expression was upregulated in bladder carcinoma tissues compared with adjacent nontumor tissues. Kaplan-Meier survival analysis revealed that CCR4 expression was an independent prognostic risk factor in BC patients, and the addition of CCL17 induced CCR4 production and promoted migration and invasion of BC cells. In addition, CCR4 knockdown significantly attenuated the migratory and invasive capabilities of BC cells. Mechanistically, CCL17-CCR4 axis is involved in ERK1/2 signaling and could mediate the migration and invasion of BC cells by regulating MMP13 activation. This study suggests that CCR4 might represent a promising prognostic biomarker and a potential therapeutic option for BC.

Vanadium-based nanowires for sodium-ion batteries.

Sodium-ion batteries (SIBs) have received great attention because of the abundance source and low cost. To date, some Na+ storage materials have achieved great performance, but the larger Na+ radius and more complex Na+ storage mechanism compared with Li+ still limit the energy density and power density. This review systematically summarizes emerging synthetic technologies of vanadium-based materials from simple nanowires to complicated modified/optimized structures. In addition, vanadium-based nanowire materials are reviewed at both the cathode and anode side, and advantages and drawbacks are proposed to explain the challenges facing application of novel materials. Furthermore, a vanadium-based single-nanowire device is reported to reveal the Na+ storage mechanism, which contributes to the understanding of the reaction in SIBs. Finally, this review summarizes the current development challenges of SIBs and looks forward to the future development prospects of vanadium-based nanowires, providing a new direction for further applications of SIBs.

A modified relief of unilateral ureteral obstruction model.

Objectives: To improve the mouse model of relief for unilateral ureteral obstruction (RUUO) and explore the pathological process of renal fibrosis after the obstruction was relieved. Methods: C57BL/6 mice in model group were randomly divided into RUUO group, improved RUUO group, and UUO group. After leaving Unilateral Ureteral Obstruction (UUO) for 3 days, the obstruction was released by reimplantation way in RUUO group and in reimplantation + catheter way in improved RUUO group. C57BL/6 mice in observation group were randomly divided into 1d RUUO group, 3d RUUO group, 7d RUUO group, and 14d RUUO group. Three days after UUO, the obstruction was released by reimplantation + catheter in four groups. We detected the renal volume, H&E, Masson staining, and immunohistochemistry of kidney pathology on the seventh day after RUUO in model group and on the 1st, 3rd, 7th, and 14th day after RUUO in observation group. Results: Comparing with mice in RUUO group, mice in improved RUUO group had lower renal volume, tubular damage score, and collagen area percentage. After the obstruction was relieved, the renal volume decreased gradually within 2 weeks. The tubular damage score in 7d RUUO group was lower than that in 1d RUUO and 3d RUUO group. However, the tubular damage score in 14d RUUO group was higher than that in 7d RUUO group. The tendency of collagen area percentage and α-SMA IOD value were consistent with the tubular damage score. Conclusions: Using the method of reimplantation + catheter, a reliable mice model of RUUO can be got. After RUUO, the de-obstructed kidneys are still in damage and fibrosis state.

Mammalian Target of Rapamycin Complex 1 Activation Disrupts the Low-Density Lipoprotein Receptor Pathway: A Novel Mechanism for Extracellular Matrix Accumulation in Human Peritoneal Mesothelial Cells.

Peritoneal fibrosis (PF) is characterized by progressive extracellular matrix (ECM) accumulation. Increasing evidence has suggested that ECM synthesis was increased in human peritoneal mesothelial cells (HPMCs) under high-glucose conditions, but the effects of high-glucose peritoneal dialysis solution (PDS) on ECM synthesis have not been fully elucidated. The aim of this study was to explore the potential mechanisms of high-glucose PDS-induced production of ECM in HPMCs. HPMCs were stimulated by high-glucose PDS. The activity of mammalian target of rapamycin complex 1 (mTORC1) was inhibited by rapamycin or regulatory-associated protein of mTOR (raptor) siRNA. Morphological changes in the cells were observed under an inverted microscope. Oil red O, filipin staining and high-performance liquid chromatography were used to examine lipid accumulation. The expression of low-density lipoprotein receptor (LDLr) regulation, the mTORC1 pathway and ECM-associated markers were assessed by real-time polymerase chain reaction and western blot analysis. The results showed that after treatment with PDS, HPMCs showed notable elongation consistent with the morphology of myofibroblasts, and the expression of ECM proteins such as α-smooth muscle actin, fibroblast specific protein-1 and collagen I was increased. In addition, there was a parallel increase in the ECM and lipid accumulation. Moreover, the effect of intracellular lipid deposition was closely correlated with the dysregulation of LDLr, which was mediated through the upregulation of LDLr, sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP), and SREBP-2 and through the enhanced coexpression of the SCAP with the Golgin. Further analysis showed that PDS enhanced the protein phosphorylation of mTOR, eukaryotic initiation factor 4E-binding protein 1, and p70 S6 kinase. Interestingly, blocking mTORC1 activity reversed the dysregulation of LDLr, even in the presence of PDS. These effects were also accompanied by a decrease in the expression of ECM components. Our findings demonstrated that increased mTORC1 activity exacerbated ECM formation in HPMCs by disrupting LDLr regulation, which contributed to lipid disorder-mediated PF.

Peritoneal catheter fixation combined with straight upward tunnel and low implant position to prevent catheter malfunction.

AIM: Catheter malfunction is the main reason for early peritoneal dialysis (PD) technique failure. This study aimed to evaluate the effect of a new surgery technique with catheter fixation to the lower abdominal wall combined with straight upward tunnel and low implant position in reducing catheter malfunction. METHODS: Patients with end stage renal disease who received PD in our centre from January 2013 to December 2015 were involved in this study. They were randomly divided into three groups according to surgical technique: traditional open surgery group, modified open surgery group and modified open surgery with catheter fixation group. All patients were followed up for six months after surgery. Catheter- related complications were analyzed. RESULTS: A total of 152 patients were involved. Among them, 49 received traditional open surgery (TOS group), 49 received modified open surgery (MOS group), and 54 received modified open surgery with catheter fixation (MOS-F group). During follow-up, no patients (0%) in MOS-F group developed catheter malfunction which was significantly lower than that of the TOS group (0 vs 16.33%, P = 0.002). Although not statistically significant, the incidence of catheter malfunction was lower in MOS-F group than that in MOS group (0 vs 4.08%, P = 0.134). No significant difference was observed in the episodes of infection, bleeding, leakage, inflow or outflow pain, hernia and delayed wound healing among the three groups (all P > 0.05). CONCLUSIONS: Catheter fixation combined with straight upward tunnel and low implant position can effectively prevent catheter malfunction in PD catheter placement.

Prognosis of Peritoneal Dialysis Patients with Different Peritoneal Transport Characteristics: A Retrospective Cohort Study.

INTRODUCTION: We aimed to examine the clinical characteristics of peritoneal dialysis (PD) patients with different baseline peritoneal transport characteristics and the effect of peritoneal transport characteristics on the prognosis of PD patients. METHODS: Patients who received PD for more than 3 months were included. Clinical characteristics, risk factors for high peritoneal transport, and risk factors for death and technique failure were examined. All patients were treated with glucose-containing peritoneal dialysis solution, and the peritoneal dialysis protocol was either day ambulatory peritoneal dialysis (DAPD) or continuous ambulatory peritoneal dialysis (CAPD). RESULTS: A total of 351 patients were enrolled, comprising 70 in the low transport group, 149 in the low average transport group, 88 in the high average transport group, and 44 in the high transport group. Multivariate logistic regression analysis showed that a high Charlson's comorbidity index (CCI) and low albumin were risk factors for a high baseline transport status. In the nonhigh transport group, the proportion of patients with albumin less than 30 g/L, who developed high transport status, was higher than those with albumin more than 30 g/L (P = .029). The survival rate in the high transport group was significantly lower than that in the other three groups (P < .001). Multivariate Cox regression analysis showed that age, systolic blood pressure, CCI, C-reactive protein (CRP) and high transport were independent risk factors for all-cause mortality. Male sex, triglycerides and CRP were independent risk factors for technique failure. CONCLUSION: High peritoneal transport status is an independent risk factor for death. High CCI and low albumin are determinants of baseline high peritoneal transport. To avoid development of a high transport state, serum albumin should be increased to more than 30 g/L.  DOI: 10.52547/ijkd.7617.

Study on Vertical Bearing Capacity of Pile Foundation with Distributed Geopolymer Post-Grouting on Pile Side.

To study the applicability of the new geopolymer grouting material for super-long and large-diameter post-grouting bored piles in silty fine sand geology, this paper compares the bearing capacity of two grouting materials, geopolymer and normal Portland cement, and different grouting volume pile side-distributed grouting piles in silty fine sand based on field model tests are analyzed through the diffusion forms of the two materials in silty fine sand through the morphology of the grouted body after excavation. The results show that the ultimate bearing capacities of P0 (ungrouted pile), P1 (8 kg cement grouted pile), P2 (6 kg geopolymer-grouted pile), P3 (8 kg geopolymer-grouted pile) and P4 (10 kg geopolymer-grouted pile) are 5400 N, 8820 N, 9450 N, 11,700 N and 12,600 N, respectively, and that the ultimate bearing capacity of the grouted pile is improved compared with that of the ungrouted pile since, under the same grouting amount, the maximum bearing capacity of the pile using geopolymer grouting is increased by 133% compared with that of the pile with cement grouting. This further verifies the applicability of the geopolymer grouting material for the post-grouting of the pile foundation in silty fine sand. Under the action of the ultimate load, the pile side friction resistance of P1, P2, P3 and P4 is increased by 200%, 218%, 284% and 319% compared with that of P0. In addition, the excavation results show that the geopolymer post-grouting pile forms the ellipsoidal consolidation body at the pile side grouting location, which mainly comprises extrusion diffusion with a small amount of infiltration diffusion, and the cement grouting pile forms a sheet-like consolidation body at the lower grouting location, which primarily comprises split diffusion. This study can provide a reference basis for the theoretical and engineering application of post-grouting piles using geopolymers.

Multiphase comparative study for WHO/ISUP nuclear grading diagnostic model based on enhanced CT images of clear cell renal cell carcinoma.

To compare and analyze the diagnostic value of different enhancement stages in distinguishing low and high nuclear grade clear cell renal cell carcinoma (ccRCC) based on enhanced computed tomography (CT) images by building machine learning classifiers. A total of 51 patients (Dateset1, including 41 low-grade and 10 high-grade) and 27 patients (Independent Dateset2, including 16 low-grade and 11 high-grade) with pathologically proven ccRCC were enrolled in this retrospective study. Radiomic features were extracted from the corticomedullary phase (CMP), nephrographic phase (NP), and excretory phase (EP) CT images, and selected using the recursive feature elimination cross-validation (RFECV) algorithm, the group differences were assessed using T-test and Mann-Whitney U test for continuous variables. The support vector machine (SVM), random forest (RF), XGBoost (XGB), VGG11, ResNet18, and GoogLeNet classifiers are established to distinguish low-grade and high-grade ccRCC. The classifiers based on CT images of NP (Dateset1, RF: AUC = 0.82 ± 0.05, ResNet18: AUC = 0.81 ± 0.02; Dateset2, XGB: AUC = 0.95 ± 0.02, ResNet18: AUC = 0.87 ± 0.07) obtained the best performance and robustness in distinguishing low-grade and high-grade ccRCC, while the EP-based classifier performance in poorer results. The CT images of enhanced phase NP had the best performance in diagnosing low and high nuclear grade ccRCC. Firstorder_Kurtosis and firstorder_90Percentile feature play a vital role in the classification task.

Pain Trajectory after Short-Stay Anorectal Surgery: A Prospective Observational Study.

The evolution of pain after anorectal surgery has not been well characterized. The main objective of this study is to evaluate patterns in acute postoperative pain in patients undergoing short-stay anorectal surgery. A total of 217 patients were included in the study, which used group-based trajectory modeling to estimate postoperative pain and then examined the relationships between sociodemographic or surgical factors and pain trajectories. Three distinct postoperative pain trajectories were determined: hemorrhoidectomy (OR, 0.15), higher anxiety (OR, 3.26), and a higher preoperative pain behavior score (OR, 3.15). In multivariate analysis, they were associated with an increased likelihood of being on the high pain trajectory. The pain trajectory group was related to postoperative analgesic use (p < 0.001), with the high-low group needing more nonsteroidal analgesics. The study showed that there were three obvious pain trajectories after anorectal surgery, including an unreported low-moderate-low type. More than 60% of patients maintained moderate to severe pain within 7 days after the operation. These postoperative pain trajectories were predominantly defined by surgery factors and patient factors.