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BACKGROUND: Multivisceral en bloc resection with the ipsilateral kidney is commonly performed in patients with retroperitoneal liposarcoma (RLPS). We evaluated the effect of nephrectomy on short- and long-term outcomes in patients with RLPS. METHODS: Data from a prospectively maintained database of the Peking University Cancer Hospital Sarcoma Center between April 2011 and August 2022 were analyzed. We classified the RLPS patients who underwent surgery into nephrectomy group (NP) and non-nephrectomy group (non-NP). Patients were matched using a 1:1 propensity score to eliminate baseline differences between groups. Postoperative renal function outcomes, major morbidity, and mortality were analyzed to compare short-term outcomes after nephrectomy. Differences in local recurrence-free survival (LRFS) and overall survival (OS) were compared by Kaplan-Meier analysis with respect to oncological benefits. RESULTS: In the matched cohort, patients in the NP group had significantly higher postoperative eGFR and CKD stages, but none required dialysis. Patients between NP and non-NP had a comparable major morbidity (p = 0.820) and 60-day mortality (p = 0.475). Patients in the NP group had a higher 5-year LRFS rates than those in the non-NP group (34.5 vs. 17.8%, p = 0.015), and similar 5-year OS rates (52.4 vs. 47.1%, p = 0.401). Nephrectomy was an independent risk factor for LRFS, but not for major morbidity or OS. CONCLUSIONS: RLPS resection with nephrectomy is related to a mild progression of renal impairment; however, dialysis is rare. En bloc nephrectomy for complete resection of RLPS is safe and improves local control.
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Lipossarcoma , Nefrectomia , Pontuação de Propensão , Neoplasias Retroperitoneais , Humanos , Masculino , Feminino , Nefrectomia/métodos , Lipossarcoma/cirurgia , Lipossarcoma/patologia , Lipossarcoma/mortalidade , Pessoa de Meia-Idade , Neoplasias Retroperitoneais/cirurgia , Neoplasias Retroperitoneais/patologia , Neoplasias Retroperitoneais/mortalidade , Idoso , Adulto , Estudos Retrospectivos , Hospitais com Alto Volume de Atendimentos , Estimativa de Kaplan-Meier , Resultado do TratamentoRESUMO
We propose a humidity sensor using an excessively tilted fiber grating (Ex-TFG) coated with agarose fabricated using femtosecond laser processing. The processed grating showcases remarkable differentiation between TE and TM modes, achieving an exceptionally narrow bandwidth of approximately 1.5 nm and an impressive modulation depth of up to 15 dB for both modes. We exposed the agarose-coated TFG sensor to various relative humidity levels and monitored the resonance wavelength to test its humidity sensing capability. Our findings demonstrated that the sensor exhibited a rapid response time (2-4 s) and showed a high response sensitivity (18.5 pm/%RH) between the humidity changes and the resonant wavelength shifts. The high sensitivity, linearity, repeatability, low hysteresis, and excellent long-term stability of the TFG humidity sensor, as demonstrated in our experimental results, make it an attractive option for environmental monitoring or biomedical diagnosis.
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How to mildly structure a high intrinsic activity and stable catalytic electrode to realize long-term catalytic water splitting to produce hydrogen at a wide range of pH values at industrial high current is a challenge. Herein, this work creatively proposes to prepare industrial-grade catalytic electrodes with high efficiency and stability at high current density through carbon quantum dots (CDs) modification nickel sulfide on hydrophilic flexible filter paper via one-step mild chemical plating (denoted as CDs-Ni3 S2 @HFP). The intrinsic activity and surface area, electron transfer ability, and corrosion resistance of Ni3 S2 material are increased due to the regulation, homogenous, and high concentration doping of CDs. The overpotential of the flexible catalytic electrode is only 30, 35, and 87 mV in 1 m KOH, simulated seawater (1 m KOH + 0.5 m NaCl), and neutral electrolyte (0.5 m PBS) at a current density of 10 mA cm-2 . More attractively, the CDs-Ni3 S2 @HFP electrode achieves over 500 h of efficient and stable catalysis at industrial high current density (500 mA cm-2 ). Due to the advantages of mild, universal, and large-area preparation of catalytic materials, this work provides technical support for flexible catalytic electrodes in efficient catalysis toward water splitting, energy storage, and device preparation.
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A microbubble-probe whispering gallery mode resonator with high displacement resolution and spatial resolution for displacement sensing is proposed. The resonator consists of an air bubble and a probe. The probe has a diameter of â¼5â µm that grants micron-level spatial resolution. Fabricated by a CO2 laser machining platform, a universal quality factor of over 106 is achieved. In displacement sensing, the sensor exhibits a displacement resolution of 74.83 pm and an estimated measurement span of 29.44â µm. As the first microbubble probe resonator for displacement measurement, the component shows advantages in performance, and exhibits a potential in sensing with high precision.
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BACKGROUND AND OBJECTIVES: Resection of retroperitoneal sarcoma (RPS) en bloc with pancreas is challenging and controversial. This single-center retrospective study aimed to analyze the impact of pancreatic resection (PR) and its different types on short- and long-term outcomes in patients with RPS. METHODS: Data from 242 consecutive patients with RPS who underwent surgical treatment at the Peking University Cancer Hospital Sarcoma Center between January 2010 and February 2021 were analyzed. Out of these, 90 patients underwent PR, including pancreaticoduodenectomy (PD) in 31 and distal pancreatectomy (DP) in 59. RESULTS: Patients in the PR group had a higher major morbidity (37.8% vs. 14.5%) and mortality (8.9% vs. 1.3%) than those in the non-PR group, with a similar 5-year overall survival (OS) rate (46.9% vs. 53.6%). Patients in the PD and DP groups had a slight difference in major morbidity (48.4% vs. 32.2%), mortality (6.4% vs. 10.2%), and 5-year OS rates (43.3% vs. 49.3%). The PR type was not an independent risk factor for major morbidity or OS. CONCLUSIONS: PR in RPS resection was associated with increased morbidity and mortality with minimal influence on survival. Patients with RPS undergoing PD and DP showed slight differences in terms of safety and OS.
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Neoplasias Pancreáticas , Neoplasias Retroperitoneais , Sarcoma , Humanos , Pancreatectomia , Estudos Retrospectivos , Sarcoma/cirurgia , Neoplasias Retroperitoneais/cirurgia , Resultado do Tratamento , Neoplasias Pancreáticas/cirurgiaRESUMO
Nephrotic syndrome, a common kidney disease syndrome in children, has triggered extensive clinical research to identify safe and effective treatments. Qingxin Lianzi Drink, as a traditional Chinese medicine prescription, has been paid more and more attention in the treatment of nephrotic syndrome in children. Its main ingredients include Shilotus meat, scutellaria skullcap and ground bone skin, etc. These ingredients have the effects of clearing heat and detoxifying, reducing swelling and water, and nourishing liver and kidney. In the treatment of nephrotic syndrome in children, Qingxin Lianzi Drink can play a role in many ways: first, it can inhibit inflammatory response, reduce glomerular inflammatory damage, relieve proteinuria and other symptoms; Secondly, the ingredients such as stone lotus meat can promote the excretion of waste and water in the body, reduce edema and edema and other symptoms; Finally, scutellaria and other ingredients can nourish liver and kidney and promote the recovery of liver and kidney function. At present, a large number of studies have found that Qingxin Lianzi Drink has obvious effect on chronic kidney disease. In addition, Qingxin Lianzi Drink as a natural therapy, compared with traditional western medicine treatment, more safe, natural and effective, has been widely concerned. Therefore, Qingxin Lianzi Drink in the treatment of children with nephrotic syndrome of the mechanism of action and efficacy evaluation of the study is of great significance. In this paper, combining the pathogenesis and treatment status of nephrotic syndrome in children, the mechanism of Qingxin Lianzi Drink in the treatment of nephrotic syndrome is explored, which can better understand its effectiveness in the treatment of nephrotic syndrome in children, and provide scientific basis for its application in clinical practice.
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Síndrome Nefrótica , Criança , Humanos , Síndrome Nefrótica/tratamento farmacológico , Síndrome Nefrótica/diagnóstico , Rim , Medicina Tradicional Chinesa , Edema , ÁguaRESUMO
The beam scanner is a predominant part in the light detection and ranging (LiDAR) system to achieve three-dimensional (3D) imaging. The solid-state beam-steering device has emerged as a promising candidate technology for a beam scanner with the advantages of robustness, stability, and high scanning speed. Here we propose a frequency modulated continuous wave (FMCW) LiDAR system with an in-fiber solid-state beam scanner. A 45° tilted fiber grating (TFG) is first employed to achieve in-fiber solid-state spectral scanning in the LiDAR system. A maximum output efficiency of 93.7% is achieved with proper polarization control. A single-mode fiber is then used to fabricate a 2-cm 45° TFG, which significantly reduces the size and the cost of the beam scanner in the LiDAR system. We experimentally realize 3D imaging of targets placed at a distance of 1.2 m based on our proposed LiDAR system. In addition, the system can achieve a detection distance of 6 m with a ranging precision of 24â mm.
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A wave-band-tunable optical fiber broadband orbital angular momentum (OAM) mode converter based on a helical long-period fiber grating (HLPFG) and dispersion turning point (DTP) tuning technique is demonstrated both theoretically and experimentally. The DTP tuning is achieved by thinning the optical fiber during the HLPFG inscription. As a proof of concept, the DTP wavelength of the LP1,5 mode is successfully tuned from the original â¼2.4 µm to â¼2.0 µm and â¼1.7 µm. With the help of the HLPFG, broadband OAM mode conversion (LP0,1âLP1,5) is demonstrated near the 2.0 µm and 1.7 µm wave bands. This work addresses a longstanding problem that the broadband mode conversion is limited by the intrinsic DTP wavelength of the modes and provides a new, to the best of our knowledge, alternative for broadband OAM mode conversion at the desired wave bands.
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BACKGROUND: Whether coeliac axis resection (CAR) results from tumour topography or a prognostic factor for distal pancreatic ductal adenocarcinoma (PDAC) remains unclear. We aimed to compare the clinicopathological data between distal pancreatectomy with en bloc CAR (DP-CAR) and distal pancreatectomy plus splenectomy (DP-S) and analyse the prognostic factors. METHODS: We retrospectively analysed clinicopathological data from 102 patients who underwent distal pancreatectomy for PDAC and the factors affecting disease-free survival (DFS) and overall survival (OS). Of these patients, 45 and 57 underwent DP-CAR and DP-S, respectively. RESULTS: DP-CAR was associated with more operative challenges than DP-S: more portomesenteric vein resections (48.9% vs. 14.0%), longer operations (320 vs. 242 min), and greater estimated blood loss (EBL) (600 vs. 200 ml). DP-CAR had larger tumours (5 vs. 4 cm), more perineural invasion (91.1% vs. 73.7%), and more microscopically positive surgical margins (20% vs. 3.5%), compared to DP-S. The major complication was clinically relevant postoperative pancreatic fistula (20.6%). The median DFS was 15.8 months and the median OS was 20.1 months. CAR was not associated with DFS or OS. EBL>700 ml, lymphovascular invasion (LVI), and adjuvant chemotherapy independently affected DFS and OS. CONCLUSION: DP-CAR was associated with larger tumours and more surgical challenges but not with poorer DFS and OS than DP-S. CAR was more likely to result from tumour topography rather than from an adverse prognostic factor for resected distal PDAC. EBL>700 ml, LVI, and adjuvant chemotherapy were independent factors affecting the survival of patients with distal PDAC who underwent surgical resection.
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Carcinoma Ductal Pancreático/cirurgia , Artéria Celíaca/cirurgia , Pancreatectomia/métodos , Neoplasias Pancreáticas/cirurgia , Esplenectomia , Idoso , Carcinoma Ductal Pancreático/patologia , Artéria Celíaca/patologia , Quimioterapia Adjuvante , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Complicações Pós-Operatórias , Prognóstico , Estudos Retrospectivos , Neoplasias PancreáticasRESUMO
An all-fiber glucose sensor is proposed and demonstrated based on a helical intermediate-period fiber grating (HIPFG) produced by using a hydrogen/oxygen flame heating method. The HIPFG, with a grating length of 1.7 cm and a period of 35 µm, presents four sets of double dips with low insertion losses and strong coupling strengths in the transmission spectrum. The HIPFG possesses an averaged refractive index (RI) sensitivity of 213.6 nm/RIU nm/RIU in the RI range of 1.33-1.36 and a highest RI sensitivity of 472 nm/RIU at RI of 1.395. In addition, the HIPFG is demonstrated with a low-temperature sensitivity of 3.67 pm/°C, which promises a self-temperature compensation in glucose detection. In the glucose-sensing test, the HIPFG sensor manifests a detection sensitivity of 0.026 nm/(mg/mL) and a limit of detection (LOD) of 1 mg/mL. Moreover, the HIPFG sensor exhibits good stability in 2 h, indicating its capacity for long-time detection. The properties of easy fabrication, high flexibility, insensitivity to temperature, and good stability of the proposed HIPFG endow it with a promising potential for long-term and compact biosensors.
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Fibras Ópticas , Refratometria , Glucose , Hidrogênio , OxigênioRESUMO
Nanomechanical resonators made from suspended graphene combine the properties of ultracompactness and ultrahigh detection sensitivity, making them interesting devices for sensing applications. However, nanomechanical systems can be affected by membrane stress. The present work developed an optomechanical resonator for thermal stress sensing. The proposed resonator consists of a section of hollow core fiber (HCF) and a trampoline graphene-Au membrane. An all-optical system that integrated optical excitation and optical detection was applied. Then, the resonance frequency of the resonator was obtained through this all-optical system. In addition, this system and the resonator were used to detect the membrane's built-in stress, which depended on the ambient temperature, by monitoring the resonance frequency shift. The results verified that the temperature-induced thermal effect had a significant impact on membrane stress. Temperature sensitivities of 2.2646 kHz/°C and 2.3212 kHz/°C were obtained when the temperature rose and fell, respectively. As such, we believe that this device will be beneficial for the quality monitoring of graphene mechanical resonators.
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Localized tilted fiber Bragg gratings (TFBGs) with low insertion loss are reported. A series of second-order TFBGs with tilt angles of 0°, 7°, 14°, and 21° was inscribed line by line directly in a single-mode fiber. For the 7° TFBG, the Bragg resonance was 2.4 dB at 1550 nm, and the maximum cladding-mode resonance reached 24.6 dB with an insertion loss of 0.8 dB, the same level as that for TFBGs fabricated by the phase-mask method. The range in cladding-mode resonance for the TFBGs obtained was wider than 170 nm with an intensity exceeding 20 dB. Combined with microscope images, the formation of these localized TFBGs and their spectral performance are discussed. The effect of an inscription offset along the $y$-axis direction was further investigated. With increasing offset, the intensity of the cladding-mode resonance dropped rapidly. The refractive index response sensitivity of the 7° TFBG was measured at 507.54 nm/RIU.
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Based on the textual research on literature, the key information of Wenjing Decoction were tested and identified, and 15 batches of lyophilized powder samples of Wenjing Decoction were prepared. The specific components, including paeoniflorin, glycyrrhizin, ginsenosides(Rg_1, Re and Rb_1), glycyrrhizic acid, and paeonol, were used as indexes to establish the HPLC method for quantitative evaluation, and the content ranges and transfer rates of these components were determined. The results showed that the contents of paeoniflorin, glycyrrhizin, ginsenosides Rg_1 + Re, ginsenoside Rb_1, glycyrrhizic acid, and paeonol in the 15 batches of samples were 0.62%-0.86%, 0.25%-0.76%, 0.14%-0.30%, 0.07%-0.21%, 0.63%-1.16%, and 0.09%-0.25%, respectively, and their transfer rates from the decoction pieces to the reference materials were 14.99%-19.42%, 28.11%-40.93%, 25.92%-61.88%, 25.03%-64.06%, 23.43%-35.53%, and 5.34%-10.44%, respectively. The consistency of the transfer rates between batches indicated that the preparation process was stable. It is suggested that the contents of paeoniflorin, glycyrrhizin, ginsenosides Rg_1 + Re, ginsenoside Rb_1, glycyrrhizic acid, and paeonol in Wenjing Decoction should not be less than 0.52%, 0.35%, 0.15%, 0.10%, 0.63%, and 0.12%, respectively. In this study, we determined the contents and analyzed the quantity transfer process of the index components in Wenjing Decoction, which can provide a basis for the follow-up development of Wenjing Decoction and the quality control of related preparations.
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Medicamentos de Ervas Chinesas , Cromatografia Líquida de Alta Pressão , Ácido Glicirrízico , Pós , Controle de QualidadeRESUMO
Ligand-dependent differences in the regulation and internalization of the µ-opioid receptor (MOR) have been linked to the severity of adverse effects that limit opiate use in pain management. MOR activation by morphine or [d-Ala2,N-MePhe4, Gly-ol]enkephalin (DAMGO) causes differences in spatiotemporal signaling dependent on MOR distribution at the plasma membrane. Morphine stimulation of MOR activates a Gαi/o-Gßγ-protein kinase C (PKC) α phosphorylation pathway that limits MOR distribution and is associated with a sustained increase in cytosolic extracellular signal-regulated kinase (ERK) activity. In contrast, DAMGO causes a redistribution of the MOR at the plasma membrane (before receptor internalization) that facilitates transient activation of cytosolic and nuclear ERK. Here, we used proximity biotinylation proteomics to dissect the different protein-interaction networks that underlie the spatiotemporal signaling of morphine and DAMGO. We found that DAMGO, but not morphine, activates Ras-related C3 botulinum toxin substrate 1 (Rac1). Both Rac1 and nuclear ERK activity depended on the scaffolding proteins IQ motif-containing GTPase-activating protein-1 (IQGAP1) and Crk-like (CRKL) protein. In contrast, morphine increased the proximity of the MOR to desmosomal proteins, which form specialized and highly-ordered membrane domains. Knockdown of two desmosomal proteins, junction plakoglobin or desmocolin-1, switched the morphine spatiotemporal signaling profile to mimic that of DAMGO, resulting in a transient increase in nuclear ERK activity. The identification of the MOR-interaction networks that control differential spatiotemporal signaling reported here is an important step toward understanding how signal compartmentalization contributes to opioid-induced responses, including anti-nociception and the development of tolerance and dependence.
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Analgésicos Opioides/metabolismo , Receptores Opioides mu/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Analgésicos Opioides/farmacologia , Animais , Membrana Celular/metabolismo , Ala(2)-MePhe(4)-Gly(5)-Encefalina/metabolismo , Ala(2)-MePhe(4)-Gly(5)-Encefalina/farmacologia , Células HEK293 , Humanos , Ligantes , Sistema de Sinalização das MAP Quinases/fisiologia , Morfina/metabolismo , Morfina/farmacologia , Fosforilação , Mapeamento de Interação de Proteínas/métodos , Mapas de Interação de Proteínas , Receptores Opioides mu/genética , Transdução de Sinais/fisiologia , Proteínas rac1 de Ligação ao GTP/fisiologia , Proteínas Ativadoras de ras GTPase/metabolismo , Proteínas Ativadoras de ras GTPase/fisiologiaRESUMO
Peroxisome proliferator-activated receptor α (PPARα) is a transcriptional regulator of lipid metabolism. GW7647 is a potent PPARα agonist that must reach the nucleus to activate this receptor. In cells expressing human fatty acid-binding protein 1 (FABP1), GW7647 treatment increases FABP1's nuclear localization and potentiates GW7647-mediated PPARα activation; GW7647 is less effective in cells that do not express FABP1. To elucidate the underlying mechanism, here we substituted residues in FABP1 known to dictate lipid signaling by other intracellular lipid-binding proteins. Substitutions of Lys-20 and Lys-31 to Ala in the FABP1 helical cap affected neither its nuclear localization nor PPARα activation. In contrast, Ala substitution of Lys-57, Glu-77, and Lys-96, located in the loops adjacent to the ligand-binding portal region, abolished both FABP1 nuclear localization and GW7647-induced PPARα activation but had little effect on GW7647-FABP1 binding affinity. Using solution NMR spectroscopy, we determined the WT FABP1 structure and analyzed the dynamics in the apo and GW7647-bound structures of both the WT and the K57A/E77A/K96A triple mutant. We found that GW7647 binding causes little change in the FABP1 backbone, but solvent exposes several residues in the loops around the portal region, including Lys-57, Glu-77, and Lys-96. These residues also become more solvent-exposed upon binding of FABP1 with the endogenous PPARα agonist oleic acid. Together with previous observations, our findings suggest that GW7647 binding stabilizes a FABP1 conformation that promotes its interaction with PPARα. We conclude that full PPARα agonist activity of GW7647 requires FABP1-dependent transport and nuclear localization processes.
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Butiratos/farmacologia , Proteínas de Ligação a Ácido Graxo/química , Proteínas de Ligação a Ácido Graxo/metabolismo , PPAR alfa/agonistas , Compostos de Fenilureia/farmacologia , Butiratos/metabolismo , Proteínas de Ligação a Ácido Graxo/genética , Humanos , Ligantes , Modelos Moleculares , Mutação , Compostos de Fenilureia/metabolismo , Conformação Proteica/efeitos dos fármacosRESUMO
.To explore the clinicopathological features of solid pseudopapillary neoplasm (SPN) of pancreas and to analyze the related factors of SPNs with aggressive behavior. Clinical data of SPN patients admitted in the Single Center of Peking University Cancer Hospital from January 2007 to September 2017 were retrospectively analyzed. The correlations of clinicopathological features with aggressive SPNs and distant metastasis after curative resection were analyzed using univariate analysis. Twelve of the total 54 SPN patients were diagnosed as aggressive SPNs. Univariate analysis suggested clinical features had no correlations with aggressive SPNs. Patients were followed up for an average of 5.0 years, four of them developed distant metastases. Univariate analysis indicated that distant metastasis of SPNs was correlated with the aggressive behaviors (P=0.031). Moreover, vessels invasion (VI) and Ki-67>4% (P=0.012) were the independent risk factors of distant metastasis of SPNs. The aggressive SPNs, especially VI and Ki-67>4% are the independent factors correlated with distant metastases after SPNs surgery.
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Carcinoma Papilar/patologia , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Adolescente , Adulto , Idoso , Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/epidemiologia , Carcinoma Papilar/cirurgia , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Pâncreas/diagnóstico por imagem , Pâncreas/cirurgia , Pancreatectomia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
BACKGROUND Solid pseudopapillary neoplasms (SPNs) of the pancreas may present widespread peritoneal metastases, but the treatment of this malignancy has not been well described and requires further investigation. MATERIAL AND METHODS Four cases of SPN with significant peritoneal metastases in our department were operated and retrospectively summarized after long-term follow-up. Eight more cases of peritoneal metastatic SPN from the PubMed database were also included in the analysis. RESULTS Peritoneal metastases of SPNs have different gross features. The benign nodules were tenacious and well encapsulated, while the malignant nodules were soft and prone to slow bleeding. However, neither of these nodules invaded the small intestines or mesentery. Of the 12 disseminated cases, 7 had history of primary tumor rupture, whereas the others had tumors malignant in nature. A total of 14 surgical events were documented, including 3 complete cytoreductive surgeries (CCRS), 9 cytoreductive surgeries (CRS), and 2 debulking surgeries. After follow-up ranging from 0.3 to 6.1 years, the results of the Fisher's exact test showed no difference between CCRS and CRS in treating either low-grade or high-grade malignant SPNs (P=0.257 and P=0.203, respectively). For all cases of SPN with peritoneal metastases, the CCRS procedure could significantly improve tumor-free survival (TFS) compared to the CRS procedure (P=0.046). CONCLUSIONS SPN rupture could cause significant peritoneal metastases, and either disruption or biopsy of these lesions should be avoided. Peritoneal metastases from SPNs vary both in gross features and biological mechanisms. CCRS may offer optimal therapeutic outcomes and longer TFS for individuals with significant peritoneal metastases of SPNs.
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Carcinoma Papilar/patologia , Neoplasias Pancreáticas/patologia , Neoplasias Peritoneais/secundário , Adulto , Carcinoma Papilar/cirurgia , Estudos de Coortes , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Neoplasias Pancreáticas/cirurgia , Neoplasias Peritoneais/cirurgiaRESUMO
Nuclear hormone receptors (NHRs) regulate the expression of proteins that control aspects of reproduction, development and metabolism, and are major therapeutic targets. However, NHRs are ubiquitous and participate in multiple physiological processes. Drugs that act at NHRs are therefore commonly restricted by toxicity, often at nontarget organs. For endogenous NHR ligands, intracellular lipid-binding proteins, including the fatty acid-binding proteins (FABPs), can chaperone ligands to the nucleus and promote NHR activation. Drugs also bind FABPs, raising the possibility that FABPs similarly regulate drug activity at the NHRs. Here, we investigate the ability of FABP1 and FABP2 (intracellular lipid-binding proteins that are highly expressed in tissues involved in lipid metabolism, including the liver and intestine) to influence drug-mediated activation of the lipid regulator peroxisome proliferator-activated receptor (PPAR) α. We show by quantitative fluorescence imaging and gene reporter assays that drug binding to FABP1 and FABP2 promotes nuclear localization and PPARα activation in a drug- and FABP-dependent manner. We further show that nuclear accumulation of FABP1 and FABP2 is dependent on the presence of PPARα. Nuclear accumulation of FABP on drug binding is driven largely by reduced nuclear egress rather than an increased rate of nuclear entry. Importin binding assays indicate that nuclear access occurs via an importin-independent mechanism. Together, the data suggest that specific drug-FABP complexes can interact with PPARα to effect nuclear accumulation of FABP and NHR activation. Because FABPs are expressed in a regionally selective manner, this may provide a means to tailor the patterns of NHR drug activation in a tissue-specific manner.
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Proteínas de Ligação a Ácido Graxo/metabolismo , Regulação da Expressão Gênica , PPAR alfa/metabolismo , Animais , Transporte Biológico , Células COS , Calorimetria , Núcleo Celular/metabolismo , Chlorocebus aethiops , Sistemas de Liberação de Medicamentos , Desenho de Fármacos , Transferência Ressonante de Energia de Fluorescência , Humanos , Carioferinas/metabolismo , Ligantes , Lipídeos/química , Plasmídeos/metabolismo , Ligação Proteica , Mapeamento de Interação de ProteínasRESUMO
To analyze the outcome in patients who have undergone multivisceral resection (MVR) for locally advanced gastrointestinal stromal tumors (GISTs), and identify the risk factors for tumor recurrence and postoperative morbidity. Sixty-four patients who operated for locally advanced GISTs with MVR in PPeking University Cancer Hospital Sarcoma Center (PUCHSC) between 2013 and 2021 were identified. Clinicopathologic characteristics, surgical outcomes, recurrence, and 5-year recurrence-free and overall survival were evaluated. The mean age of the patients was 60 years. Mean tumor size was 11.1 cm. Complete resection was achieved in all patients. The estimated 5-year recurrence-free and overall survival were 86.6% and 90.0%, respectively. Independent factor of recurrence following surgery was mitotic count on multivariate analysis. Overall postoperative morbidity was 53.1% (n = 34). Severe morbidity was 21.9% (n = 14). The most common severe complication was clinically relevant pancreatic fistula (n = 12, 18.8%), followed by anastomotic leakage (n = 4, 6.3%) and Intraabdominal abscess (n = 4, 6.3%). Multivariate analysis showed that preoperative imatinib therapy could reduce overall morbidity. Long operation time, combined colectomy and pancreatectomy were independent risk factors for postoperative severe morbidity. Compared to partial pancreatectomy, pancreaticoduodenectomy (PD) was significantly increased the incidence of severe morbidity. In conclusion, compared to systemic therapy alone, the outcome of locally advanced GISTs after MVR was more favorable. Despite the high overall morbidity, the postoperative severe morbidity and mortality of MVR were acceptable. Preoperative imatinib therapy should be recommended whenever possible. Combined pancreatectomy and colectomy are associated with significant postoperative severe morbidities. PD should be thoroughly discussed and be subject to MDT approach before surgery.
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Solid waste management is a critical issue worldwide. Effectively utilizing these solid waste resources presents a viable solution. This study focuses on Iron ore tailings (IOTs), a solid waste generated during iron ore processing, which can be used as supplementary cementitious materials (SCMs) but have low reactivity, hindering their large-scale application in concrete production. To address this, ternary SCMs were prepared using ceramic powder (CP) and steel slag (SS) to enhance the performance of concrete incorporating IOTs. The study found that the synergistic effect of CP and SS significantly improved the compressive strength of concrete, with a notable increase of up to 21% compared to concrete with IOTs alone. Mercury intrusion porosimetry (MIP) and backscattering electron (BSE) analyses revealed that the ternary SCMs significantly optimized the characteristics of the interfacial transition zone (ITZ), which in turn enhanced the compressive properties of the concrete. This contributed to maintaining the structural integrity of the concrete, even amidst variations in the pore structure. Importantly, the incorporation of ternary SCMs led to a 23% reduction in carbon emissions, from 400.01 kg CO2/m3 to 307.48 kg CO2/m3, and elevated eco-strength efficiency from 0.1 to 0.14. The study highlights the role of multi-material synergy in developing composite SCMs systems, fostering the sustainable advancement of green building materials.