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Colorectal cancer (CRC) is often diagnosed at later stages after it has metastasized to other organs. The development of chemoresistance also contributes to a poor prognosis. Therefore, an increased understanding of the metastatic properties of CRC and chemoresistance could improve patient survival. CUGBP elav-like family member 1 (CELF1) is an RNA-binding protein, which is overexpressed in many human malignant tumors. However, the influence of CELF1 in CRC is unclear. V-ets erythroblastosis virus E26 oncogene homologue 2 (ETS2) is an evolutionarily conserved proto-oncogene known to be overexpressed in a variety of human cancers including CRC. In thespresent tudy, we investigated the association between CELF1 and ETS2 in CRC tumorigenesis and oxaliplatin (L-OHP) resistance. We found a positive correlation between the elevated expression of CELF1 and ETS2 in human CRC tissues. Overexpression of CELF1 increased CRC cell proliferation, migration, and invasion in vitro and in a xenograft tumor growth model in vivo, and induced resistance to L-OHP. In contrast, CELF1 knockdown improved the response of CRC cells to L-OHP. Overexpression of ETS2 increased the malignant behavior of CRC cells (growth, migration, and invasion) and L-OHP resistance in vitro. Moreover, L-OHP resistance induced by CELF1 overexpression was reversed by ETS2 knockdown. The results of luciferase reporter and ribonucleoprotein immunoprecipitation assays indicated that CELF1 up-regulates ETS2 by binding to its 3'-UTR. Taken together, our findings have identified that CELF1 regulates ETS2 in a mechanism that results in CRC tumorigenesis and L-OHP resistance, and CELF1 may be a promising target for overcoming chemoresistance in CRC.
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Proteínas CELF1/metabolismo , Carcinogênese , Neoplasias Colorretais/metabolismo , Resistencia a Medicamentos Antineoplásicos , Proteína Proto-Oncogênica c-ets-2/metabolismo , Animais , Antineoplásicos , Movimento Celular , Transição Epitelial-Mesenquimal , Feminino , Células HCT116 , Células HT29 , Humanos , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Oxaliplatina , Proto-Oncogene Mas , Proteína Proto-Oncogênica c-ets-2/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Porous carbon nanosheets have the advantages of longitudinal continuity, transverse ultrathin, high specific surface area, and surface atomic activity, as well as the synergistic effect of micro and nanoproperties, so the research on their preparation, structure, and properties has attracted wide attention. A series of ultrathin hierarchical porous carbon nanosheets (HPCNs) is fabricated through carbonization of precursors obtained through the Friedel-Crafts reaction-assisted loading of polystyrene on graphene oxide. Hierarchical pore structures consist of three parts: (1) the micropores (1.3 nm), which were provided by porous polystyrene through the Friedel-Crafts reaction; (2) the mesopores (3.8 nm), which were provided by slab pores from the stack of carbon nanosheets; and (3) the pores (>5 nm) formed from the random stack of carbon nanosheets. Controlling the carbonization time and temperature adds to a prominent increase in specific surface area from 405.8 to 1420 m2 g-1. It was found that excessive carbonization would destroy the hierarchical pore structure. These porous carbon materials were used as cathode materials for lithium-sulfur battery and showed good performance. HPCN/sulfur cathode has good rate performance and cycle performance, and the capacity retention rate is 87% after the current density rises from 1 to 3 C and 91% after 200 cycles.
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Wet-adhesive hydrogels have been developed as an attractive strategy for tissue repair. However, achieving simultaneously low swelling and high burst pressure tolerance of wet-adhesive hydrogels is crucial for in vivo application which remains challenges. Herein, a novel super-structured porous hydrogel (denoted as PVA/PAAc-N+ ) is designed via facile moisture-induced phase separation-solvent exchange process for obtaining porous polyvinyl alcohol (PVA) hydrogel as dissipative layer and in situ photocuring technology for entangling quaternary ammonium-functionalized poly(acrylic acid)-based wet-adhesive layer (PAAc-N+ ) with the porous surface of PVA layer. Benefitting from the ionic crosslinking between quaternary ammonium ions and carboxylate ions in PAAc-N+ wet-adhesive layer as well as the high crystallinity induced by abundant hydrogen bonds of PVA layer, the hydrogel has unique ultralow swelling property (0.29) without sacrificing adhesion strength (63.1 kPa). The porous structure of PVA facilitates the mechanical interlock at the interface between PAAc-N+ wet-adhesive layer and tough PVA dissipative layer, leading to the ultrahigh burst pressure tolerance up to 493 mm Hg and effective repair for porcine heart rupture; the PVA layer surface of PVA/PAAc-N+ hydrogel can prevent postoperative adhesion. By integrating ultralow swelling, ultrahigh burst pressure tolerance, and anti-postoperative adhesion properties, PVA/PAAc-N+ hydrogel shows an appealing application prospect for tissue repair.
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Compostos de Amônio , Hidrogéis , Animais , Suínos , Hidrogéis/química , Aderências Teciduais/prevenção & controle , Materiais Biocompatíveis/química , Íons , Álcool de Polivinil/químicaRESUMO
The integration of hydrogels with bio-friendly functional components through simple and efficient strategies to construct wound dressings with broad-spectrum antibacterial and immunomodulatory properties to promote the healing of infected diabetic wounds is highly desirable but remains a major challenge. Here, wormwood essential oil (WEO) is effectively encapsulated in the hydrogel via an O/W-Pickering emulsion during the polymerization of methacrylic anhydride gelatin (GelMA), acrylamide (AM), and acrylic acid N-hydroxysuccinimide ester (AAc-NHS) to form a multifunctional hydrogel dressing (HD-WEO). Compared with conventional emulsions, Pickering emulsions not only improve the encapsulation stability of the WEO, but also enhance the tensile and swelling properties of hydrogel. The synergistic interaction of WEO's diverse bioactive components provides a broad-spectrum antibacterial activity against S. aureus, E. coli, and MRSA. In addition, the HD-WEO can induce the polarization of macrophages from M1 to M2 phenotype. With these advantages, the broad-spectrum antibacterial and immunomodulatory HD-WEO effectively promotes the collagen deposition and neovascularization, thereby accelerating the healing of MRSA-infected diabetic wounds.
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Acrilatos , Artemisia , Diabetes Mellitus , Óleos Voláteis , Hidrogéis , Escherichia coli , Staphylococcus aureus , Cicatrização , Antibacterianos/farmacologia , ÉsteresRESUMO
Contamination tolerance and long-term mechanical support are the two critical properties of meshes for contaminated abdominal wall defect repair. However, biological meshes with excellent pollution tolerance fail to provide bio-adaptive long-term mechanical support due to their rapid degradation. Here, a novel double-layer asymmetric porous mesh (SIS/PVA-EXO) is designed by simple and efficient in situ freeze-thaw of sticky polyvinyl alcohol (PVA) solution on the loosely porous surface of small intestinal submucosal decellularized matrix (SIS), which can successfully repair the contaminated abdominal wall defect with bio-adaptive dynamic mechanical support through only single-stage surgery. The exosome-loaded degradable loosely porous SIS layer accelerates the tissue healing; meanwhile, the exosome-loaded densely porous PVA layer can maintain long-term mechanical support without any abdominal adhesion. In addition, the tensile strength and strain at break of SIS/PVA-EXO mesh change gradually from 0.37 MPa and 210% to 0.10 MPa and 385% with the degradation of SIS layer. This unique performance can dynamically adapt to the variable mechanical demands during different periods of contaminated abdominal wall reconstruction. As a result, this SIS/PVA-EXO mesh shows an attractive prospect in the treatment of contaminated abdominal wall defect without recurrence by integrating local immune regulation, tissue remodeling, and dynamic mechanical supporting.
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Parede Abdominal , Álcool de Polivinil , Telas Cirúrgicas , Porosidade , Parede Abdominal/cirurgia , Animais , Álcool de Polivinil/química , Resistência à Tração , Cicatrização , Materiais Biocompatíveis/químicaRESUMO
Many hydrogel patches are developed to solve the pervasive and severe challenge of complex wound healing, while most of them still lack satisfactory controllability and comprehensive functionality. Herein, inspired by multiple creatures, including octopuses and snails, a novel muti-functional hydrogel patch is presented with controlled adhesion, antibacterial, drug release features, and multiple monitoring functions for intelligent wound healing management. The patch with micro suction-cup actuator array and a tensile backing layer is composed of tannin grafted gelatin, Ag-tannin nanoparticles, polyacrylamide (PAAm) and poly(N-isopropylacrylamide) (PNIPAm). In virtue of the photothermal gel-sol transition of tannin grafted gelatin and Ag-tannin nanoparticles, the patches exert a dual anti-microbial effect and temperature-sensitive snail mucus-like features. In addition, as the "suction-cups" consisting of thermal responsive PNIPAm can undergo a contract-relax transformation, the medical patches can adhere to the objects reversibly and responsively, and release their loaded vascular endothelial growth factor (VEGF) controllably for wound healing. More attractively, benefiting from their fatigue resistance, self-healing ability of the tensile double network hydrogel, and electrical conductivity of Ag-tannin nanoparticles, the proposed patches can report multiple wound physiology parameters sensitively and continuously. Thus, it is believed that this multi-bioinspired patch has immense potential for future wound healing management.
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Gelatina , Hidrogéis , Fator A de Crescimento do Endotélio Vascular , Cicatrização , Condutividade ElétricaRESUMO
To deal with intra-abdominal sepsis, one of the major global causes of death in hospitalized patients, efficient abscess drainage is crucial. Despite decades of advances, traditional catheters have demonstrated poor drainage and absorption properties due to their simple tubular structures and their dense nonporous surface. Herein, inspired by porous sponges and fractal roots, a multifaceted hydrogel catheter with effective drainage, absorptive, and robust properties, is presented. Its unique fractal structures provide extensive internal branching and a high specific surface area for effective drainage, while the hierarchical porous structures provide a wide range of absorption capabilities. Additionally, its distinctive multi-interpenetration network maintains robust and appropriate mechanical properties, even after absorption multiple times of liquid and mechanical disturbance, allowing for intact removal from the abdominal cavity without harm to the animal in vivo. Besides, the loaded antimicrobial peptides are capable of being released in situ to inhibit the potential for infections. In vivo experiments have demonstrated that this hydrogel catheter efficiently removes lethal abscesses and improves survival. It is believed that this innovative and practical catheter will create a future precedent for hydrogel drainage devices for more effective management of intra-abdominal sepsis.
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Doenças Transmissíveis , Sepse , Humanos , Hidrogéis , Fractais , Abscesso , Catéteres , Sepse/terapiaRESUMO
Due to the complex microenvironment and healing process of diabetic wounds, developing wound dressing with good biocompatibility, mechanical stability, breathability, exudate management, antibacterial ability, and immunomodulatory property is highly desired but remains a huge challenge. Herein, a multifunctional cryogel is designed and prepared with bio-friendly bacterial cellulose, gelatin, and dopamine under the condition of sodium periodate oxidation. Bacterial cellulose can enhance the mechanical stability of the cryogel by improving the skeleton supporting effect and crosslinking degree. The cryogel shows outstanding breathability and exudate management capability thanks to the interpenetrated porous structures. I2 and sodium iodides produced in situ by reduction of sodium periodate provide efficient antibacterial properties for the cryogel. The cryogel facilitates macrophage polarization from M1 to M2, thus regulating the immune microenvironment of infected diabetic wounds. With these advantages, the multifunctional cryogel effectively promotes collagen deposition and neovascularization, thus accelerating the healing of infected diabetic wounds.
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Criogéis , Diabetes Mellitus , Humanos , Cicatrização , Bactérias , Celulose , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antibacterianos/químicaRESUMO
Submucosal injection material has shown protective effect against gastrointestinal injury during endoscopic surgery in clinic. However, the protective ability of existing submucosal injection material is strictly limited by their difficult injectability and short barrier time. Herein, we report a shear-thinning gellan gum hydrogel that simultaneously has easy injectability and long-lasting barrier function, together with good hemostatic property and biocompatibility. Shear-thinning property endows our gellan gum hydrogel with excellent endoscopic injection performance, and the injection pressure of our gellan gum hydrogel is much lower than that of the small molecule solution (50 wt% dextrose) when injected through the endoscopic needle. More importantly, our gellan gum hydrogel shows much stronger barrier retention ability than normal saline and sodium hyaluronate solution in the ex vivo and in vivo models. Furthermore, our epinephrine-containing gellan gum hydrogel has a satisfactory hemostatic effect in the mucosal lesion resection model of pig. These results indicate an appealing application prospect for gellan gum hydrogel utilizing as a submucosal injection material in endoscopic surgery.
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Manipulation of gut microbiota by bacterial metabolites has shown protective effects against colitis; while the efficacy is strictly limited by the poor oral delivery efficiency and single drug usage. Here, a novel prebiotics and postbiotics synergistic delivery microcapsule composed of indole-3-propionic acid (IPA) postbiotic and three prebiotics including alginate sodium, resistant starch (RS), and chitosan via microfluidic electrospray for preventing and treating colitis are proposed. It is found that oral administration of IPA microcapsules (IPA@MC) to mice can exert significant protective effects to colitis, suggesting the therapeutic synergy between prebiotics and postbiotics. Furthermore, the mechanism of the IPA@MC is revealed in modulating the gut microbiota, that is by significantly increasing the overall richness and abundance of short-chain fatty acids (SCFA) producing bacteria such as Faecalibacterium and Roseburia. These results indicate that the prebiotics and postbiotics synergistic delivery microcapsules are ideal candidates for treating colitis.
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Colite , Microbioma Gastrointestinal , Animais , Bactérias , Cápsulas/metabolismo , Cápsulas/farmacologia , Cápsulas/uso terapêutico , Colite/tratamento farmacológico , Camundongos , Microfluídica , PrebióticosRESUMO
Implantable meshes used in tension-free repair operations facilitate treatment of internal soft-tissue defects. However, clinical meshes fail to achieve anti-deformation, anti-adhesion, and pro-healing properties simultaneously, leading to undesirable surgery outcomes. Herein, inspired by the peritoneum, a novel biocompatible Janus porous poly(vinyl alcohol) hydrogel (JPVA hydrogel) is developed to achieve efficient repair of internal soft-tissue defects by a facile yet efficient strategy based on top-down solvent exchange. The densely porous and smooth bottom-surface of JPVA hydrogel minimizes adhesion of fibroblasts and does not trigger any visceral adhesion, and its loose extracellular-matrix-like porous and rough top-surface can significantly improve fibroblast adhesion and tissue growth, leading to superior abdominal wall defect treatment to commercially available PP and PCO meshes. With unique anti-swelling property (maximum swelling ratio: 6.4%), JPVA hydrogel has long-lasting anti-deformation performance and maintains high mechanical strength after immersion in phosphate-buffered saline (PBS) for 14 days, enabling tolerance to the maximum abdominal pressure in an internal wet environment. By integrating visceral anti-adhesion and defect pro-healing with anti-deformation, the JPVA hydrogel patch shows great prospects for efficient internal soft-tissue defect repair.
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Parede Abdominal , Peritônio , Parede Abdominal/cirurgia , Materiais Biocompatíveis/farmacologia , Humanos , Hidrogéis , Porosidade , Aderências TeciduaisRESUMO
Background: Microsatellite has been proved to be an important prognostic factor and a treatment reference in colon cancer. The transcriptome profile and tumor microenvironment of different microsatellite statuses are different. Metastatic colon cancer patients with microsatellite instability-high (MSI-H) are sensitive to immune checkpoint inhibitors (ICIs), but not fluorouracil. Efforts have been devoted to identify the predictive factors of immunotherapy. Methods: We analyzed the transcriptome profile of different microsatellite statuses in colon cancer by using single-cell and bulk transcriptome data from publicly available databases. The immune cells in the tumor microenvironment were analyzed by the ESTIMATION algorithm. The microsatellite-related gene signature (MSRS) was constructed by the least absolute shrinkage and selection operator (LASSO) Cox regression based on the differentially expressed genes (DEGs) and its prognostic value and predictive value of response to immunotherapy were assessed. The prognostic value of the MSRS was also validated in another cohort. Results: The MSI-H cancers cells were clustered differentially in the dimension reduction plot. Most of the immune cells have a higher proportion in the tumor immune microenvironment, except for CD56 bright natural killer cells. A total of 238 DEGs were identified. Based on the 238 DEGs, a neural network was constructed with a Kappa coefficient of 0.706 in the testing cohort. The MSRS is a favorable prognostic factor of overall survival, which was also validated in another cohort (GSE39582). Besides, MSRS is correlated with tumor mutation burden in MSI-H colon cancer. However, the MSRS is a barely satisfactory factor in predicting immunotherapy with the area under the curve (AUC) of 0.624. Conclusion: We developed the MSRS, which is a robust prognostic factor of overall survival in spite of a barely satisfactory immunotherapy predictor. Further studies may need to improve the predictive ability.
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Medical patches play an important role in wound healing because of their tissue conformality, drug release capacity, and convenient operation. Great efforts have been devoted to developing new-generation patches with distinctive features promoting wound healing. Here, inspired by the structure of octopus suction cups and the component of natural tissue, a biocompatible wound patch with selective adhesiveness and individualized design using a combined strategy of template-replication and mask-guided lithography is presented. Such patches are based on Ecoflex film with suction-cup-mimicking microstructures to adhere to normal skin and with biocompatible gelatin methacryloyl (GelMA) hydrogel to contact wounded areas. An ultraviolet mask with a tailorable pattern is employed to shape the GelMA hydrogel into customized geometry replicating individual wound areas, and thus both adhesion and antiadhesion properties are integrated into the same patch. In addition, vascular endothelial growth factor is loaded to accelerate the healing process. Based on these advantages, the authors demonstrate that the present patches not only adhere to different skin surfaces, but also promote the treatment of a rat cutaneous wound model. Thus, it is believed that this versatile patch can break through the limitation of traditional patches and be ideal candidates for wound healing and related biomedical applications.
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Adesivos , Gelatina , Metacrilatos , Adesivo Transdérmico , Fator A de Crescimento do Endotélio Vascular/administração & dosagem , Cicatrização , Animais , Materiais Biocompatíveis/administração & dosagem , Desenho de Equipamento , Hidrogéis , Modelos Animais , Ratos , Ratos Sprague-Dawley , SucçãoRESUMO
BACKGROUND: Creation of a temporary diverting stoma during rectal cancer surgery is used widely to prevent undesirable outcomes related to anastomotic leakage (AL). The transition from temporary stoma (TS) to permanent stoma (PS) is a frequent outcome. Elderly patients may have a greater probability of PS. We aimed to identify risk factors of PS and developed a nomogram to predict the rate of PS for elderly patients. METHODS: We enrolled elderly patients (≥70 years) who underwent rectal cancer surgery with a TS between January 2014 and December 2017 at our hospital. We divided patients into two groups: a TS group and a PS group. We then identified the risk factors for PS and developed a nomogram to predict the possibility of PS. RESULTS: Of the 278 elderly patients who received a diverting stoma, 220 (79.14%) eventually underwent stoma reversal, and 58 (20.86%) had PS. The proportion of males in the PS group was significantly higher than that of the TS group (P=0.048). Univariate and multivariate analysis showed that American Society of Anesthesiologists (ASA) score (P<0.001), laparotomy (P=0.004), AL (P<0.001), and tumor recurrence (P<0.001) were significantly correlated with PS. These four factors were included to construct the nomogram. The consistency index of the nomogram was 0.833 and the model yielded an area under the curve of 0.833. CONCLUSIONS: ASA score (≥3), laparotomy, AL, and tumor recurrence were independent risk factors for PS in elderly patients. Our nomogram exhibited moderate predictive ability.
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BACKGROUND: Ileostomy was widely used during colorectal cancer (CRC) surgery and peristomal dermatitis was one of the most common stoma-relative complications. Stoma education class may reduce the rate of peristomal dermatitis. METHODS: We enrolled patients who were diagnosed with rectal cancer and underwent surgery with ileostomy between January 2018 to December 2018 at a single tertiary hospital. The general demographic information of patients along with the participation in stoma education class and the occurrence of peristomal dermatitis were analyzed. RESULTS: A total of 491 patients were included in the study, and 162 patients (32.99%) participated in the stoma education class. Eighty-five patients (17.31%) suffered peristomal dermatitis within one month after ileostomy. The rate of peristomal dermatitis in the stoma education group was significantly lower than that in the control group (11.11% vs. 20.36%, P=0.011). Regardless of the education level, the risk of peristomal dermatitis in the education group was reduced (P<0.05). Lower peristomal dermatitis rates were found in patients who were younger than 60 years (P=0.012), whose stoma were taken care of by other people (P=0.014), or without diabetes (P=0.026). Univariate and Multivariate analysis showed that stoma education was the only factor associated with the decrease in rates of peristomal dermatitis (OR =0.458, P=0.008), while diabetes was an independent risk factor (OR =3.732, P<0.001). CONCLUSIONS: Postoperative stoma education class significantly decreased the rate of peristomal dermatitis in the early postoperative period in CRC patients with ileostomy, especially for those who were younger than 60 years, received stoma care from others or without diabetes.
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PURPOSE: The aim of this study was to identify the risk factors associated with delayed recovery of gastrointestinal function after ileostomy reversal for rectal cancer patients. METHODS: In this retrospective study, the data of rectal cancer patients who underwent ileostomy reversal from January 2018 to December 2019 at the Sixth Affiliated Hospital of Sun Yat-sen University were assessed to investigate potential risk factors of delayed flatus after ileostomy reversal. RESULTS: A total of 282 patients were eligible for this study. Postoperative first flatus time ranged from 1 to 9 days, of which 58.8% patients presented with delayed flatus that was longer than 3 days. Univariate analysis showed that delayed postoperative flatus was significantly associated with the length of postoperative hospital stay (P<0.001) and postoperative complications (P=0.037). Multivariate analysis showed that intravenous fluid infusion at postoperative day 1 (POD1) (OR=1.001, 95% CI: 1.001-1.002, P=0.001) and duration of stoma ≥6 months (OR=2.005, 95% CI:1.155-3.657, P=0.014) were independent risk factors for delayed flatus. CONCLUSION: Increased intravenous fluid infusion at POD1 and duration of stoma ≥6 months were related to delayed recovery of gastrointestinal function after ileostomy reversal for rectal cancer patients.
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Treatment of wounds in special areas is challenging due to inevitable movements and difficult fixation. Common cotton gauze suffers from incomplete joint surface coverage, confinement of joint movement, lack of antibacterial function, and frequent replacements. Hydrogels have been considered as good candidates for wound dressing because of their good flexibility and biocompatibility. Nevertheless, the adhesive, mechanical, and antibacterial properties of conventional hydrogels are not satisfactory. Herein, cationic polyelectrolyte brushes grafted from bacterial cellulose (BC) nanofibers are introduced into polydopamine/polyacrylamide hydrogels. The 1D polymer brushes have rigid BC backbones to enhance mechanical property of hydrogels, realizing high tensile strength (21-51 kPa), large tensile strain (899-1047%), and ideal compressive property. Positively charged quaternary ammonium groups of tethered polymer brushes provide long-lasting antibacterial property to hydrogels and promote crawling and proliferation of negatively charged epidermis cells. Moreover, the hydrogels are rich in catechol groups and capable of adhering to various surfaces, meeting adhesive demand of large movement for special areas. With the above merits, the hydrogels demonstrate less inflammatory response and faster healing speed for in vivo wound healing on rats. Therefore, the multifunctional hydrogels show stable covering, little displacement, long-lasting antibacteria, and fast wound healing, demonstrating promise in wound dressing.
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Antibacterianos/farmacologia , Curativos Hidrocoloides , Materiais Biocompatíveis/uso terapêutico , Hidrogéis/uso terapêutico , Adesividade , Animais , Modelos Animais de Doenças , Ratos , Resistência à Tração , CicatrizaçãoRESUMO
BACKGROUND: Fluid and electrolyte disturbance, which impairs renal function, has been reported in patients with temporary ileostomy. However, the dynamic changes in serum electrolytes and renal function in rectal cancer patients with ileostomy have not been well described. In the present study, we aimed to evaluate alterations in serum electrolytes and renal function in rectal cancer patients undergoing ileostomy creation and closure. METHODS: The levels of serum potassium, serum sodium, serum blood urea nitrogen, serum creatinine and estimated glomerular filtration rate (eGFR) were analyzed in 320 patients with rectal cancer including 156 patients with an ileostomy (the ileostomy group) and 164 patients without an ileostomy (the control group). RESULTS: After index surgery, the levels of serum potassium and serum creatinine in the ileostomy group were significantly higher than those in the control group (P<0.05). In contrast, the levels of serum sodium and the eGFR showed decreases in the ileostomy group compared to the control group after index surgery (P<0.05). At 3 months after ileostomy creation, the ileostomy group had a significantly increased rate of eGFR <60 mL/min/1.73 m2 compared to the control group (5.8% vs. 1.2%, P=0.032). In line with the results of univariate analysis, multivariable analysis identified ileostomy and diabetes as independent risk factors for a decreased eGFR (P=0.005 and P=0.022, respectively). Furthermore, a significantly rebound of eGFR was observed in patients after ileostomy closure (P=0.013). CONCLUSIONS: Ileostomy can cause temporary electrolyte disturbance and renal function impairment in patients with rectal cancer. Diabetes is an independent risk factor for renal function damage in patients with rectal cancer who receive a temporary ileostomy.
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PURPOSE: Anastomotic leakage after rectal cancer surgery in elderly patients is a critical challenge. Many risk factors have been found and many interventions tried, but anastomotic leakage in elderly patients remains difficult to deal with. This study aimed to create a nomogram for predicting anastomotic leakage after rectal surgery in elderly rectal cancer patients with dysfunctional stomata. METHODS: We collected data from 326 consecutive elderly patients with dysfunctional stomata after rectal cancer surgery at the Sixth Affiliated Hospital, Sun Yat-Sen University from January 2014 to December 2019. Risk factors of anastomotic leakage were identified with multivariate logistic regression and used to create a nomogram. Predictive performance was evaluated by the area under the receiver-operating characteristic (ROC) curve. RESULTS: American Society of Anesthesiologists score ≥3, male sex, and neoadjuvant radiotherapy were identified as significantly associated factors that could be combined for accurate prediction of anastomotic leakage on multivariate logistic regression and development of a nomogram.The area under the ROC curve for this model was 0.645. The C-index value for this model was 0.645, indicating moderate predictive ability of the risk of anastomotic leakage. CONCLUSION: The nomogram showed good ability to predict anastomotic leakage in elderly patients with rectal cancer after surgery, and might be helpful in providing a reference point for selection of surgical procedures and perioperative treatment.
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The total syntheses of aspidospermidine, N-methylaspidospermidine, N-acetylaspidospermidine, and aspidospermine were achieved from a common pentacyclic indoline intermediate. The common pentacyclic indoline intermediate was synthesized on a gram scale through a Stork-enamine alkylation of 1H-pyrrolo[2,3-d]carbazole derivatives, which were prepared through a Brønsted acid-catalyzed tandem cyclization of tryptamine-ynamide. The scalable synthesis of 1H-pyrrolo[2,3-d]carbazole afforded facile access and a practical approach to the Aspidosperma indole alkaloid family.