Influence of duration of preoperative treatment with phenoxybenzamine and secretory phenotypes on perioperative hemodynamics and postoperative outcomes in pheochromocytoma and paraganglioma

ObjectivesResection of pheochromocytoma and paraganglioma (PPGL) carries risks with perioperative hemodynamic instability. Phenoxybenzamine (PXB) is a commonly used α-blockade to prevent it. It is unclear whether lengthening the preoperative duration of PXB is better for hemodynamic stability and postoperative outcomes. Furthermore, different types of catecholamines have varying effects on perioperative hemodynamics. Thus, our study aimed to investigate the impact of the duration of preoperative preparation with PXB and secretory phenotypes of the patients on intraoperative hemodynamic stability and postoperative complications in PPGL.MethodsBetween Dec 2014 and Jan 2022, 166 patients with PPGL were operated on by the same team at Sun Yat-sen Memorial Hospital. They were divided into group A(1-14d), Group B(15-21d), and Group C(>21d) based on the duration of management with PXB and into the adrenergic and the noradrenergic phenotype group based on secretory profiles. Data on intraoperative hemodynamics and postoperative outcomes were collected and compared among groups.ResultsA total of 96 patients occurred intraoperative hemodynamic instability, and 24 patients had 29 postoperative complications related to the surgery. Among the 145 patients treated with PXB, no significant differences were found in the cumulative time outside the target blood pressure(6.67%[0-17.16%] vs. 5.97%[0-23.08%] vs. 1.22%[0-17.27%], p=0.736) or in the median total HI-score(42.00[30.00-91.00] vs. 89.00[30.00-113.00] vs. 49.00[30.00-93.00], p=0.150) among group A(n=45), B(n=51) and C(n=49). Multivariate analysis demonstrated that the level of plasma-free metanephrine(MN) was an independent risk factor for intraoperative hemodynamic instability. And the median cumulative time outside of the target blood pressure in the adrenergic phenotype group was significantly greater than that in the noradrenergic phenotype group(8.17%[0-26.22%] vs. 1.86%[0-11.74%], p=0.029). However, the median total HI-score(99.50[85.00-113.25] vs. 90.00[78.00-105.00], p=0.570) and postoperative outcomes showed no differences between the two groups.ConclusionsA preoperative duration of nearly 14 days with PXB is sufficient for ensuring intraoperative hemodynamic stability in PPGL. And lengthening the preparation duration may not provide additional benefits in the era of widespread application and advanced techniques of laparoscopic surgery. Additionally, patients with the adrenergic phenotype are more prone to intraoperative hemodynamic instability than the noradrenergic phenotype. Thus, more attention should be given to the adrenergic phenotype during surgery

Knockdown of a novel lincRNA AATBC suppresses proliferation and induces apoptosis in bladder cancer

Long intergenic noncoding RNAs (lincRNAs) play important roles in regulating various biological processes in cancer, including proliferation and apoptosis. However, the roles of lincRNAs in bladder cancer remain elusive. In this study, we identified a novel lincRNA, which we termed AATBC. We found that AATBC was overexpressed in bladder cancer patient tissues and positively correlated with tumor grade and pT stage. We also found that inhibition of AATBC resulted in cell proliferation arrest through G1 cell cycle mediated by cyclin D1, CDK4, p18 and phosphorylated Rb. In addition, inhibition of AATBC induced cell apoptosis through the intrinsic apoptosis signaling pathway, as evidenced by the activation of caspase-9 and caspase-3. The investigation for the signaling pathway revealed that the apoptosis following AATBC knockdown was mediated by activation of phosphorylated JNK and suppression of NRF2. Furthermore, JNK inhibitor SP600125 could attenuate the apoptotic effect achieved by AATBC knockdown, confirming the involvement of JNK signaling in the induced apoptosis. Moreover, mouse xenograft model revealed that knockdown of AATBC led to suppress tumorigenesis in vivo. Taken together, our study indicated that AATBC might play a critical role in pro-proliferation and anti-apoptosis in bladder cancer by regulating cell cycle, intrinsic apoptosis signaling, JNK signaling and NRF2. AATBC could be a potential therapeutic target and molecular biomarker for bladder cancer

KLF4 Deletion Alters Gastric Cell Lineage and Induces MUC2 Expression

Gastric cancer is one of the most common types of cancer in the world, particularly in underdeveloped countries. The mechanism of gastric cancer is less understood compared with other types of gastrointestinal (GI) cancers. Krüppel-like factor 4 (KLF4) is a zinc-finger transcription factor and is a potential tumor suppressor in GI cancers. In this study, we have generated two mouse models, Rosa-Cre;Klf4fl/fl and Lgr5-Cre;Klf4fl/fl. KLF4 was deleted by Rosa-Cre in the gastric epithelia cells or by Lgr5-Cre in the antral stem cells in the adult mice. KLF4 deletion resulted in increased proliferating cells and decreased pit mucous cells. Surprisingly, the intestinal goblet cell marker, MUC2, which is not expressed in normal gastric tissues, was strongly induced at the base of the KLF4-deleted antral glands. To understand the clinical relevance of these findings, we analyzed the expression of KLF4 and MUC2 in human gastric cancer. In a subset of human gastric cancer, the expression of KLF4 is negatively associated with MUC2 expression. In conclusion, KLF4 is essential for normal homeostasis of antral stem cells; loss of KLF4 and expression of MUC2 could be important markers for gastric cancer diagnosis

Effect of the application of peanut shell, bamboo, and maize straw biochars on the bioavailability of Cd and growth of maize in Cd-contaminated soil

Biochar is a versatile, carbon-rich, organic material that can effectively immobilize Cd in the soil. In this study, peanut shell biochar (SP), maize straw biochar (MS), and bamboo straw biochar (BS) were applied in different proportions to evaluate their effects on the remediation of Cd-contaminated farmland soil and plant growth. The results revealed that both single and mixed applications of biochar substantially increased corn biomass and chlorophyll content compared to the unamended control treatment, while the malondialdehyde (MDA) and proline contents were largely unaffected. The bamboo straw block biochar with maize straw biochar at a mass ratio of 2:1 (DBM) significantly increased the dry total biomass of maize (+107.24% compared to the unamended soil). SP application has highly increased the SPAD value. PB with BS application at a mass ratio of 1:1 (MSB) significantly decreased the soluble sugar content (+21.81% compared to the unamended control soil). Soil pH was increased by the application of biochar alone and in combination with feedstocks. The soil content of Fe/Mn oxide-bound (OX) and exchangeable-bound Cd (EX) was decreased, whereas that of carbonate-bound Cd (CA), residue-bound Cd (RE), and organic-bound Cd (OM) contents increased. The Cd content in corn grains under MSB and SP application was markedly reduced by 42.62% and 31.48%, respectively, compared to the unamended control soil. Overall, MSB and SP applications were effective in improving soil quality and crop growth

A MicroRNA-7 Binding Site Polymorphism in HOXB5 Leads to Differential Gene Expression in Bladder Cancer

PURPOSE: To investigate the biological function of HOXB5 in human bladder cancer and explore whether the HOXB5 3'-UTR SNP (1010A/G), which is located within the microRNA-7 binding site, was correlated with clinical features of bladder cancer. METHODS: Expression of HOXB5 in 35 human bladder cancer tissues and 8 cell lines were examined using real-time PCR and immunohistochemistry. Next, we explored the biological function of HOXB5 in vitro using cell proliferation, migration and colony formation assays. Using bioinformatics, a SNP (1010A/G) was found located within the microRNA-7 binding site in the 3'-UTR of HOXB5. Real-time PCR was used to test HOXB5 expression affected by different alleles. Finally, multivariate logistic regression analysis was used to determine the relationship between SNP (1010A/G) frequency and clinical features in 391 cases. RESULTS: HOXB5 was frequently over-expressed both in bladder cancer tissues and cell lines. Inhibition of HOXB5 suppressed the oncogenic function of cancer cells. Next, we demonstrated that a SNP (1010A/G), located within the microRNA-7 binding site in the 3'-UTR of HOXB5, could affect HOXB5 expression in bladder cancer mainly by differential binding activity of microRNA-7 and SNP-related mRNA stability. Finally, we also showed the frequency of 1010G genotype was higher in cancer group compared to normal controls and correlated with the risk of high grade and high stage. CONCLUSION: HOXB5 is overexpressed in bladder cancer. A miRNA-binding SNP (1010A/G) located within 3'-UTR of HOXB5 is associated with gene expression and may be a promising prognostic factor for bladder cancer

Acute kidney injury in adult idiopathic nephrotic syndrome. Ren Fail

Abstract Objective: This study aims to investigate the epidemiology, clinical and histological features, and prognosis of acute kidney injury (AKI) according to RIFLE classification in adult patients with idiopathic nephrotic syndrome. Methods: In this retrospective study, 277 patients with idiopathic nephrotic syndrome were reviewed from June 2005 to June 2009. Results: Fifty-one (18%) patients entered RIFLE class Risk (AKI-R); 24 (9%) patients entered RIFLE class Injury (AKI-I); and 20 (7%) patients entered RIFLE class Failure (AKI-F). Logistic regression analysis showed that severe hypoalbuminemia, increase in age, and being male were risk factors of AKI. Cumulative recovery rates in 3 months for groups AKI-R, AKI-I, and AKI-F were 95%, 100%, and 94%, respectively (p = 0.21). The mean time to recovery for groups AKI-R, AKI-I, and AKI-F was 20 ± 3, 25 ± 4, and 30 ± 5 days, respectively. Cumulative complete remission rates in 3 months for groups AKI-R, AKI-I, and AKI-F were 92%, 86%, and 65%, respectively (p = 0.002). The mean time to remission for groups AKI-R, AKI-I, and AKI-F was 28 ± 3, 39 ± 6, and 62 ± 8 days, respectively. Conclusion: AKI is not uncommon in adult idiopathic nephrotic syndrome. More severe AKI was associated with longer time of nephrotic syndrome complete remission. Renal function can recover completely in most of the patients

Experimental Study on the Road Performance of Phosphogypsum-Modified Lime-Fly Ash Stabilized Red Clay

To assess the impact of solid waste phosphogypsum on the road performance of lime-fly ash-stabilized red clay, we conducted comprehensive tests on the road performance, swelling and shrinkage characteristics, and mechanical properties of lime-fly ash soil with varying phosphogypsum content and curing age. Additionally, we analyzed the microstructure and composition changes using scanning electron microscopy and X-ray diffraction tests. The results revealed that phosphogypsum significantly enhances the early strength and moisture stability of lime-fly ash soil. The mechanical properties of lime-fly ash soil continue to improve with increased curing age, with performance improvements tapering off after 60 days and eventually stabilizing. Moreover, as the phosphogypsum content increases, the unconfined compressive strength (UCS), splitting strength, and CBR value of the lime-fly ash soil initially increase and then decrease. The optimal mixing ratio was determined to be 4% phosphogypsum, resulting in a 7-day UCS increase of 67.2%, a 28-day UCS increase of 3 times, and a 28-day splitting strength increase of 4.3 times. The moisture stability coefficient also exhibited a 43% increase after 7 days, and its anti-disintegration ability was enhanced, reaching 0.91 after 28 days, which meets the specified standards. Microscopic analysis revealed that the addition of phosphogypsum improved the overall integrity of the lime-fly ash soil, and the formation of ettringite effectively filled the soil’s pores. However, excessive ettringite caused increased expansion and deformation. To optimize the use of phosphogypsum-modified lime-fly ash-stabilized red clay as subgrade filler, it is advisable to incorporate additives to further reduce swelling deformation

Up-regulated microRNA-143 in cancer stem cells differentiation promotes prostate cancer cells metastasis by modulating FNDC3B expression

Abstract Background Metastatic prostate cancer is a leading cause of cancer-related death in men. Cancer stem cells (CSCs) are involved in tumor progression and metastasis, including in prostate cancer. There is an obvious and urgent need for effective cancer stem cells specific therapies in metastatic prostate cancer. MicroRNAs (miRNAs) are an important class of pervasive genes that are involved in a variety of biological functions, especially in cancer. The goal of this study was to identify miRNAs involved in prostate cancer metastasis and cancer stem cells. Methods A microarray and qRT-PCR were performed to investigate the miRNA expression profiles in PC-3 sphere cells and adherent cells. A transwell assay was used to evaluate the migration of PC-3 sphere cells and adherent cells. MiR-143 was silenced with antisense oligonucleotides in PC-3, PC-3-M and LNCaP cells. The role of miR-143 in prostate cancer metastasis was measured by wound-healing and transwell assays in vitro and bioluminescence imaging in vivo. Bioinformatics and luciferase report assays were used to identify the target of miR-143. Results The expression of miR-143 and the migration capability were reduced in PC-3 sphere cells and progressively increased during sphere re-adherent culture. Moreover, the down-regulation of miR-143 suppressed prostate cancer cells migration and invasion in vitro and systemically inhibited metastasis in vivo. Fibronectin type III domain containing 3B (FNDC3B), which regulates cell motility, was identified as a target of miR-143. The inhibition of miR-143 increased the expression of FNDC3B protein but not FNDC3B mRNA in vitro and vivo. Conclusions These data demonstrate for the first time that miR-143 was up-regulated during the differentiation of prostate cancer stem cells and promoted prostate cancer metastasis by repressing FNDC3B expression. This sheds a new insight into the post-transcriptional regulation of cancer stem cells differentiation by miRNAs, a potential approach for the treatment of prostate cancer.</p

Understanding the Role of a Cr Transition Layer in the Hot-Salt Corrosion Behavior of an AlSi Alloy Coating

The effect of a chromium (Cr) transition layer on the hot-salt corrosion behavior of an AlSi alloy coating was studied. Hot-salt corrosion experiments were performed at 650 &deg;C and corrosion kinetic curves were plotted. The weight gain of the AlSi-coated samples increased to 0.89 mg/cm2 at 100 h and then decreased steadily to 0.77 mg/cm2 at 200 h. The weight of the AlSi-coated samples with the addition of a Cr transition layer increased immediately to 0.79 mg/cm2 at 20 h and then gradually increased to 0.85 mg/cm2 at 200 h. This Cr diffusion promoted the preferential creation of an Al2O3 layer, which effectively hindered the upward diffusion of Fe and also resulted in the production of a Cr2O3-SiO2 layer, which impeded the multi-scale salt mixture&rsquo;s penetration. The Cr diffusion also caused a notable seal-healing effect, which healed the micro-pores. These oxidation and degradation reactions were considerably repressed by the high barrier properties of these oxide layers and the dense surface, resulting in the increased hot-salt corrosion resistance of the AlSi alloy coating. The current findings provide a feasible strategy for the design of a diffusion barrier layer of a thermal protective coating on martensitic stainless steel