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BACKGROUND: The mechanism of improvement of type 2 diabetes after duodenal-jejunal bypass (DJB) surgery is not clear. AIM: To study the morphological and functional changes in adipose tissue after DJB and explore the potential mechanisms contributing to postoperative insulin sensitivity improvement of adipose tissue in a diabetic male rat model. METHODS: DJB and sham surgery was performed in a-high-fat-diet/streptozotocin-induced diabetic rat model. All adipose tissue was weighed and observed under microscope. Use inguinal fat to represent subcutaneous adipose tissue (SAT) and mesangial fat to represent visceral adipose tissue. RNA-sequencing was utilized to evaluate gene expression alterations adipocytes. The hematoxylin and eosin staining, reverse transcription-quantitative polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay were used to study the changes. Insulin resistance was evaluated by immunofluorescence. RESULTS: After DJB, whole body blood glucose metabolism and insulin sensitivity in adipose tissue improved. Fat cell volume in both visceral adipose tissue (VAT) and SAT increased. Compared to SAT, VAT showed more significantly functional alterations after DJB and KEGG analysis indicated growth hormone (GH) pathway and downstream adiponectin secretion were involved in metabolic regulation. The circulating GH and adiponectin levels and GH receptor and adiponectin levels in VAT increased. Cytological experiment showed that GH stimulated adiponectin secretion and improve insulin sensitivity. CONCLUSION: GH improves insulin resistance in VAT in male diabetic rats after receiving DJB, possibly by increasing adiponectin secretion.
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[This corrects the article DOI: 10.1371/journal.pone.0125429.].
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Despite recent progress in multiple myeloma (MM) treatments, most patients will relapse and require additional treatment. Intravenous daratumumab, a human IgGκ monoclonal antibody targeting CD38, has shown good efficacy in the treatment of MM. A subcutaneous version of daratumumab was formulated to reduce the burden of intravenous infusions. We aimed to investigate the efficacy and safety of subcutaneous daratumumab in Chinese patients with relapsed/refractory MM based on the demonstrated noninferiority of subcutaneous daratumumab to intravenous daratumumab, with a shorter administration time and reduced infusion-related reaction rate in global studies. This phase 1, multicenter study (MMY1010; ClinicalTrials.gov Identifier: NCT04121260) evaluated subcutaneous daratumumab in Chinese patients with relapsed/refractory MM after 1 prior line (n = 1) or ≥2 prior lines (n = 20) of therapy, including a proteasome inhibitor and an immunomodulatory drug. Primary endpoints were pharmacokinetics and safety. Mean (standard deviation) maximum trough concentration of daratumumab was 826 (335) µg/mL, which was consistent with prior studies of subcutaneous daratumumab and intravenous daratumumab. Safety was consistent with safety profiles observed in other daratumumab studies, with no new safety concerns identified. Incidences of infusion-related reactions and injection-site reactions were low and consistent with other subcutaneous daratumumab studies. At a median follow-up of 7.5 months, the overall response rate was 57.1%, with a very good partial response or better rate of 38.1% and complete response or better rate of 19.0%. Our results demonstrate a favorable benefit/risk profile of subcutaneous daratumumab in Chinese patients with relapsed/refractory MM, potentially impacting clinical administration of daratumumab in this population.
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Dissolved organic matter (DOM) plays an important role in regulating the fate of mercury (Hg), e.g., mobility, bioavailability, and toxicity. Clarifying the role of DOM in binding Hg in the treatment processes of sewage sludge is important for relieving Hg contamination risks in land applications. However, the impacts of DOM on Hg binding in sewage sludge are still unclear. In this study, we investigated the evolution of Hg and its speciation in full-scale sludge anaerobic digestion (AD) with thermal hydrolysis. The role of DOM in binding Hg(II) was further analyzed. The results showed that AD with thermal hydrolysis led to an increase in the Hg content in the sludge (from 3.72 ± 0.47 mg/kg to 10.75 ± 0.16 mg/kg) but a decrease in Hg mobility (the mercury sulfide fraction increased from 60.56 % to 79.78 %). Further adsorption experiments revealed that at equivalent DOM concentrations, DOM with a low molecular weight (MW<1 kDa) in activated sludge, DOM with a medium molecular weight (1 kDa
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Mercurio , Aguas del Alcantarillado , Mercurio/química , Aguas del Alcantarillado/química , Anaerobiosis , Hidrólisis , Adsorción , Contaminantes Químicos del Agua/química , Compuestos Orgánicos/química , Eliminación de Residuos Líquidos/métodosRESUMEN
OBJECTIVES: GL-V9 exhibited anti-tumour effects on various types of tumours. This study aimed to verify if GL-V9 synergized with oxaliplatin in suppressing colorectal cancer (CRC) and to explore the synergistic mechanism. METHODS: The synergy effect was tested by MTT assays and the mechanism was examined by comet assay, western blotting and immunohistochemistry (IHC). Xenograft model was constructed to substantiated the synergy effect and its mechanism in vivo. RESULTS: GL-V9 was verified to enhance the DNA damage effect of oxaliplatin, so as to synergistically suppress colon cancer cells in vitro and in vivo. In HCT-116 cells, GL-V9 accelerated the degradation of Wee1 and induced the abrogation of cell cycle arrest and mis-entry into mitosis, bypassing the DNA damage response caused by oxaliplatin. Our findings suggested that GL-V9 binding to HSP90 was responsible for the degradation of Wee1 and the vulnerability of colon cancer cells to oxaliplatin. Functionally, overexpression of either HSP90 or WEE1 annulled the synergistic effect of GL-V9 and oxaliplatin. CONCLUSIONS: Collectively, our findings revealed that GL-V9 synergized with oxaliplatin to suppress CRC and displayed a promising strategy to improve the efficacy of oxaliplatin.
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Proteínas de Ciclo Celular , Neoplasias Colorrectales , Sinergismo Farmacológico , Proteínas HSP90 de Choque Térmico , Ratones Desnudos , Oxaliplatino , Proteínas Tirosina Quinasas , Oxaliplatino/farmacología , Humanos , Proteínas de Ciclo Celular/metabolismo , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Proteínas Tirosina Quinasas/metabolismo , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Animales , Proteínas HSP90 de Choque Térmico/metabolismo , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Células HCT116 , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones , Ratones Endogámicos BALB C , Línea Celular Tumoral , Daño del ADN/efectos de los fármacos , Antineoplásicos/farmacología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Pirimidinonas/farmacología , Pirimidinas/farmacología , Pirazoles/farmacologíaRESUMEN
Given the important advantages of the mid-infrared optical range (2.5 to 25 µm) for biomedical sensing, optical communications, and molecular spectroscopy, extending quantum information technology to this region is highly attractive. However, the development of mid-infrared quantum information technology is still in its infancy. Here, we report on the generation of a time-energy entangled photon pair in the mid-infrared wavelength band. By using frequency upconversion detection technology, we observe the two-photon Hong-Ou-Mandel interference and demonstrate the time-energy entanglement between twin photons at 3082 nm via the Franson-type interferometer, verifying the indistinguishability and nonlocality of the photons. This work is very promising for future applications of optical quantum technology in the mid-infrared band, which will bring more opportunities in the fields of quantum communication, precision sensing, and imaging.
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INTRODUCTION: Mortality from acute myocardial infarction (AMI) remains substantial. The current study is aimed at developing a novel simple risk score for AMI. METHODS: The Coronary Artery Tree description and Lesion EvaluaTion (CatLet) extended validation trial (ChiCTR2000033730) and the CatLet validation trial (ChiCTR-POC-17013536), both being registered with
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Infarto del Miocardio , Intervención Coronaria Percutánea , Humanos , Intervención Coronaria Percutánea/efectos adversos , Infarto del Miocardio/etiología , Factores de Riesgo , Creatinina , Medición de Riesgo/métodosRESUMEN
Objective To evaluate the effects of transcutaneous electrical acupoint stimulation(TEAS)combined with Chinese medicine emotional intervention on immune function and psychological stress in patients undergoing laparoscopic radical rectal cancer surgery.Methods A total of 100 patients hospitalized for laparoscopic radical surgery for rectal cancer were randomly divided into 4 groups of Group A,B,C,and D,25 patients in each group.Group A was given TEAS for 30 minutes before anesthesia,Group B was given TEAS continuously until the end of the surgery,Group C was given TEAS for 30 minutes and Chinese medicine emotional intervention before anesthesia,Group D was given TEAS continuously until the end of the surgery together with Chinese medicine emotional intervention.TEAS was performed at bilateral Zusanli(ST36)points,bilateral Sanyinjiao(SP6)points,Baihui(GV20)points,bilateral Neiguan(PC6)points.The changes of perioperative outcomes and the changes of parameters associated with the immune function,molecular mechanism of Th1/Th2 cells,and psychological stress response before the surgery and 3 days after the surgery in each group were observed.Moreover,the occurrence of adverse reactions in each group was compared.Results(1)The differences of perioperative outcomes operation time,bleeding volume and infusion amount were not statistically significant among the 4 groups(P>0.05).The Sufentanil dosage,Remifentanil dosage,postoperative awakening time,and 24-hour postoperative pain Visual Analogue Scale(VAS)scores of group D were lower than those of Groups A,B,and C(P<0.05),and the above indexes of group B and group C were all lower than those of Group A(P<0.05).(2)Three days after the surgery,the levels of immune function indicators of T lymphocyte subsets CD3+,CD4+ and natural killer(NK)cells in Group D were higher than those in Groups A,B,and C(P<0.05),while the above indexes in Groups B and C were higher than those in Group A(P<0.05).(3)Three days after the surgery,the levels of parameters associated with the molecular mechanism of Th1/Th2 cells such as interleukin 2(IL-2)and interferon gamma(IFN-γ)in Group D were higher(P<0.05),and the serum interleukin 10(IL-10)level was lower than those in Groups A,B,and C(P<0.05);the serum IL-2 and IFN-γ levels in Group B and C were higher(P<0.05)and serum IL-10 level was lower than those in Group A(P<0.05).(4)Three days after the surgery,the scores of the psychological stress response indicators of self-rating anxiety scale(SAS)and self-rating depression scale(SDS)in Group D were lower than those in Groups A,B,and C(P<0.05),while the above scores in Groups B and C were lower than those in Group A(P<0.05).(5)In Group A,there was one case of nausea and vomiting;in Group B,there were two cases of nausea and vomiting and one case of dizziness;no adverse reaction occurred in Group C,and there was one case of nausea and vomiting in Group D.The incidences of adverse reactions in Groups A,B,C and D were 4.0%(1/25),12.0%(3/25),0.0%(0/25),and 4.0%(1/25),respectively.The intergroup comparison showed no statistically significant difference among the 4 groups(χ2 = 0.400,P = 0.527).Conclusion In treating patients undergoing laparoscopic radical surgery for rectal cancer,TEAS combined with Chinese medicine emotional intervention can effectively regulate the perioperative immune function,reduce the stress response,and alleviate the anxiety of the patients.Moreover,the therapy exerts certain analgesic effect,which leads to the reduction of the dosage of opioids and the increase of perioperative comfort and surgical tolerance of the patients.
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BACKGROUND: Diabetic cardiomyopathy is a serious complication of obesity with type 2 diabetes and is a major cause of mortality. Metabolic surgery, such as duodenal-jejunal bypass (DJB), can effectively improve diabetic cardiomyopathy; however, the underlying mechanisms remain elusive. Oxidative stress is one of the pivotal mechanisms of diabetic cardiomyopathy. Our objective was to investigate the effect and potential mechanisms of DJB on oxidative stress in the heart of diabetic cardiomyopathy rats. METHODS: High-fat diet combined with intraperitoneal injection of streptozotocin was used to establish diabetic cardiomyopathy rats. DJB was performed on diabetic cardiomyopathy rats, and high glucose and palmitate were used to simulate diabetic cardiomyopathy in H9C2 cells in vitro. Sera from different groups of rats were used for experiments in vivo and in vitro. RESULTS: DJB effectively improved oxidative stress and activated the adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway to increase endothelial nitric oxide synthase (eNOS) phosphorylation level and the expression of antioxidative system-related proteins and genes in the heart of diabetic cardiomyopathy rats. AMPK agonists and serum from DJB rats activated the AMPK pathway to increase eNOS phosphorylation level and the expression of antioxidative system-related proteins and genes and decreased the content of reactive oxygen species in H9C2 cells, but this improvement was almost eliminated by the addition of AMPK inhibitors. CONCLUSIONS: DJB activates eNOS and enhances the antioxidant system by activating the AMPK pathway-and not solely by improving blood glucose-to improve oxidative stress in the heart of diabetic cardiomyopathy rats.
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Objective: QL0911, a recombinant human thrombopoietin mimetic peptide-Fc fusion protein, is a romiplostim (Nplate®) biosimilar used to treat primary immune thrombocytopenia (ITP). This phase III study aimed to assess the efficacy and safety of QL0911 in adult patients with chronic primary ITP over a 24-week treatment period. Methods: We conducted a double-blind, placebo-controlled, phase III study in patients diagnosed with primary ITP for at least 12 months who had received at least one first-line ITP treatment with no response or recurrence after treatment, or who relapsed after splenectomy at 44 sites in China. Patients were randomly allocated (2:1 ratio) to QL0911 or placebo injection subcutaneously once weekly at an initial dose of 1 µg/kg for 24 weeks. The doses were adjusted to maintain the target platelet counts from 50 × 109/L to 200 × 109/L. Patients and investigators were blinded to the assignment. The primary endpoints were the proportion of patients who achieved a durable platelet response at week 24 (platelet count, ≥ 50 × 109/L during 6 of the last 8 weeks of treatment) and safety. The study was registered at ClinicalTrials.gov (NCT05621330). Results: Between October 2019 and December 2021, 216 patients were randomly assigned (QL0911,144; placebo,72). A durable platelet response was achieved by significantly more patients in the QL0911 group (61.8%, 95% CI: 53.3-69.8; P < 0.0001) than in the placebo group (0%). The mean duration of platelet responses was 15.9 (SE: 0.43) weeks with QL0911, and 1.9 (SE:0.26) week with placebo. Consistent results were achieved in subgroup analyses categorized by baseline splenectomy status (yes/no), concomitant ITP treatment (yes/no), and baseline platelet count (≤ 10 × 109/L, > 10 × 109/L, ≤ 20 × 109/L, > 20 × 109/L, and < 30 × 109/L). The incidence of TEAEs was comparable between the QL0911 and the placebo groups (91.7% and 88.9%, respectively). The most common adverse events overall were ecchymosis (28.5% for QL0911 vs. 37.5% for placebo), upper respiratory tract infections respiratory tract infections (31.9% for QL0911 vs. 27.8% for placebo), and gingival bleeding (17.4% for QL0911 vs. 26.4% for placebo). Conclusion: QL0911 was well-tolerated and increased and maintained platelet counts in adults with ITP. QL0911, a biosimilar to romiplostim (Nplate®), may be a novel treatment option for patients with ITP who have failed or relapsed from first-line treatment in China. Ongoing studies will provide further data on long-term efficacy and safety in such patient populations.
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OBJECTIVE: This study aimed to investigate the safety and efficacy of endovascular aortic repair (EVAR) for the treatment of an abdominal aortic aneurysm (AAA) with a hostile neck anatomy (HNA). METHODS: From January 1, 2015 to December 31, 2019, a total of 259 patients diagnosed with an AAA who underwent EVAR were recruited into this study. Based on the morphological characteristics of the proximal neck anatomy, the patients were divided into the HNA group and the friendly neck anatomy (FNA) group. The patients were followed up for up to 4 years. RESULTS: The average follow-up time was 1056.1±535.5 days. Type I endoleak occurred in 4 patients in the HNA group, and 2 patients in the FNA group. Neither death nor intraoperative switch to open repair occurred in either group. The time of the operation was significantly longer in the HNA group (FNA vs. HNA, 99.2±51.1 min vs. 117.5±63.8 min, P=0.011). There were no significant differences in short-term clinical success rate (P=0.228) or midterm clinical success rate (P=0.889) between the two groups. The overall mortality rate was 10.4%, and Kaplan-Meier survival analysis indicated that the two groups had similar cumulative survival rates at the end of the follow-up period (P=0.889). CONCLUSION: EVAR was feasible and safe in patients with an AAA with a proximal HNA. The early and midterm results were promising; however, further studies are needed to verify the long-term effectiveness of EVAR.
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Aneurisma de la Aorta Abdominal , Reparación Endovascular de Aneurismas , Humanos , Aneurisma de la Aorta Abdominal/cirugía , Estimación de Kaplan-MeierRESUMEN
Skeleton builders are essential for achieving deep sludge dewatering. In this study, a novel spent coffee ground (SCG)-based skeleton builder was developed to attain deep sludge dewatering by combined conditioning with FeCl3, and possible mechanisms were examined. Through different surface analysis techniques, it was demonstrated that at a pyrolysis temperature of 300 °C, the spent coffee ground biochar (SCGB-300) has an intact pore structure, a rigid carbon skeleton, and large oxygen-containing functional groups, making it the best skeleton builder for sludge dewatering. When combined with FeCl3 for conditioning, the structure of SCGB-300 remained intact under high pressure and played important role. The rich porous structure facilitated water drainage. During the sludge conditioning, small amount of positive charge on the surface of SCGB-300 further increased the zeta potential of sludge through charge neutralization. At the same time, the adsorption of SCGB-300 removed viscous hydrophilic substances and further improved the dewatering performance. At an optimum dosage of 6% (dry solid, DS) FeCl3 and 30% SCGB-300 (DS), the moisture content of sludge was reduced from 85.47% to 63.35%, and the dewatering rate was increased from 46.08% to 70.03%. Therefore, SCGB is a promising skeleton builder for sludge conditioning and deep dewatering.
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BACKGROUND: Preventive colostomy is required for colorectal surgery, and the incidence of complications associated with ileostomy and colostomy remains controversial. This study aimed to compare the incidence of postoperative complications between ileostomy and colostomy procedures. METHODS: Data analysis was conducted on 30 studies, and meta-analysis and trial sequential analysis (TSA) were performed on five studies. The basic indicators, such as stoma prolapse, leak, wound infection, ileus, and a series of other indicators, were compared. RESULTS: No statistically significant differences were observed with complications other than stoma prolapse. Meta-analysis and TSA showed that the incidence of ileostomy prolapse was lower than that of colostomy prolapse, and the difference was statistically significant. Apart from the four complications listed above, the general data analysis showed differences in incidence between the two groups. The incidence of skin irritation, parastomal hernia, dehydration, pneumonia, and urinary tract infections was higher with ileostomy than with colostomy. In contrast, the incidence of parastomal fistula, stenosis, hemorrhage, and enterocutaneous fistula was higher with colostomy than with ileostomy. CONCLUSIONS: There were differences in the incidence of ileostomy and colostomy complications in the selected studies, with a low incidence of ileostomy prolapse. PROSPERO REGISTRATION NUMBER: CRD42022303133.
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Colostomía , Ileostomía , Humanos , Colostomía/efectos adversos , Colostomía/métodos , Ileostomía/efectos adversos , Ileostomía/métodos , Anastomosis Quirúrgica/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , ProlapsoRESUMEN
A risk-adapted treatment strategy is of crucial importance in patients with myelodysplastic syndromes (MDS). Previous risk prognostic scoring systems did not integrate molecular abnormalities. The new IPSS-Molecular (IPSS-M) model, combing genomic profiling with hematologic and cytogenetic parameters, was recently developed to evaluate the associations with leukemia-free survival (LFS), leukemic transformation, and overall survival (OS). However, it has not yet been widely validated in clinics. This study aims to further validate the prognostic power of IPSS-M based on real-world data and to compare the prognostic value of different scoring systems in patients with MDS. IPSS-M Web calculator was used to calculate a tailored IPSS-M score of the enrolled patient (N = 255), and the risk category was defined correspondingly. We next compared the IPSS-M prognostic power to that of IPSS, IPSS-R, and WPSS. We found that IPSS-M risk classification was statistically significant for 3-year OS and LFS. Compared with other tools, IPSS-M was superior in sensitivity and accuracy for 3-year OS and LFS. The mapping C-index between IPSS-R and IPSS-M categories resulted in improved discrimination across the OS, but not LFS and leukemic transformation. The result of different treatment options indicated that allogeneic hematopoietic stem cell transplantation (allo-HSCT) can result in a better OS than those without allo-HSCT. In conclusion, IPSS-M was a valuable tool for risk stratification compared with other risk prognostic scoring systems. However, more studies should be conducted to explore the appropriate treatment options for different groups stratified by IPSS-M.
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OBJECTIVE: This study explored the relationship between the activation of the jak/stat3 signaling pathway and the CSN5 gene transcript and protein expression levels in the hematopoietic stem cells of patients with myelodysplastic syndromes (MDSs). This study also aimed to investigate the correlation between the expression level of CSN5 and the deubiquitination of HSF1, as well as the transcript level of the spi1/pu.1 genes to explore the pathogenesis of MDS. MATERIALS AND METHODS: We isolated cells from normal individuals and MDS patients, and the mRNA and protein expression levels of spi1/pu.1 in cd34+ cells (hematopoietic stem cells) were measured by PCR and western blotting, respectively. A ChIP assay was used to detect the binding of HSF1 to the spi1/pu.1 promoter in cd34+ cells. The ubiquitination of HSF1 in cd34+ cells was detected by CO-IP. The binding of HSF1 and Fbxw7α was detected in in cd34+ cells by CO-IP. The binding of HSF1 and CSN5 was evaluated. A luciferase reporter assay was used to detect the effect of STAT3 on CSN5 promoter activation in cd34+ cells. Western blotting was used to detect the phosphorylation of STAT3 in cd34+ cells of MDS patients. The binding of STAT3 and C/EBP beta in cd34+ cells was detected by CO-IP. RESULTS: Inhibition of SPI1/PU.1 expression was observed in MDS samples with low proliferation ability. Further experiments proved that phosphorylation of STAT3 affected CSN5 function and mediated the ubiquitination of HSF, the upstream regulator of SPI1/PU.1 transcription, which led to the inhibition of SPI1/PU.1 expression. Restoration of CSN5 rescued the inhibition of HSF1 ubiquitination, causing SPI1/PU.1 transcription to resume and increasing SPI1/PU.1 expression, promoting the recovery of cell proliferation in hypocellular MDS. CONCLUSIONS: Our research revealed the regulatory role of the CSN5/HSF/SPI1/PU.1 axis in hypocellular MDS, providing a probable target for clinical intervention.
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A nonlinear process based on backward quasi-phase matching (BQPM) can be used to realize mirrorless optical parametric oscillation, the generation of paired photons with a separable joint spectral amplitude and narrow wavelength bandwidth, and the preparation of counterpropagating polarization-entangled photons, which shows distinct advantages over some applications based on forward quasi-phase matching. In this work, three types of BQPM in a bulk periodically poled potassium titanyl phosphate crystal with a single period are theoretically analyzed. Experimentally, the harmonic wave generated by second-harmonic generation in type 0 and type I exhibits a narrow bandwidth of 15.5â GHz. Furthermore, photon pairs generated by spontaneous parametric downconversion in all types of BQPM (type 0, type I, and type II) at 7th order are observed and characterized. Their coincidence-to-accidental ratios are all greater than 5 × 103 in the pump power range from 10â mW to 500â mW. This research lays the foundation for further applications of BQPM in nonlinear optics, quantum optics, and quantum information processing.
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[This corrects the article DOI: 10.7150/jca.52648.].
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Acute myeloid leukemia (AML) is a high-mortality malignancy with poor outcomes. Azacitidine induces cell death and demonstrates treatment effectiveness against AML. Selinexor (KPT-330) exhibited significant benefits in combination with typical induction treatment for AML patients. Here, we explore the antitumor effect of KPT-330 combined with AZA in AML through CCK-8, flow cytometry, RT-qPCR, western blot, and RNA-seq. Our results showed that KPT-330 combined with AZA synergistically reduced cell proliferation and induced apoptosis in AML primary cells and cell lines. Compared to the control, the KPT-330 plus AZA down-regulates the expression of XPO1, eIF4E, and c-MYC in AML. Moreover, the knockdown of c-MYC could sensitize the synergy of the combination on suppression of cell proliferation and promotion of apoptosis in AML. Moreover, the expression of XPO1 and eIF4E was elevated in AML patient cohorts, respectively. XPO1 and elF4E overexpression was associated with poor prognosis. In summary, KPT-330 with AZA exerted synergistic effects by suppressing XPO1/eIF4E/c-MYC signaling, which provided preclinical evidence for further clinical application of the novel combination in AML.
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Antineoplásicos , Leucemia Mieloide Aguda , Humanos , Azacitidina/farmacología , Antineoplásicos/farmacología , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , Carioferinas/metabolismo , Factor 4E Eucariótico de Iniciación/genética , Factor 4E Eucariótico de Iniciación/metabolismo , Línea Celular Tumoral , Transducción de Señal , Leucemia Mieloide Aguda/metabolismo , ApoptosisRESUMEN
This study aimed to assess the outcomes of modified onlay island flap (MOIF) urethroplasty for hypospadias reoperation. A retrospective analysis was conducted using clinical data on children reoperated with MOIF or tubularized incised plate (TIP) urethroplasty for hypospadias in the Children's Hospital of Nanjing Medical University (Nanjing, China) from December 2016 to September 2020. A total of 90 children with hypospadias who failed primary repair and were reoperated on with MOIF (MOIF group, n = 46) or TIP urethroplasty (TIP group, n = 44) were recruited. All children were postoperatively followed up for at least 6 months. Six patients with postoperative urinary fistula, 2 patients with glans dehiscence, and 1 patient with urethral diverticulum were reported in the MOIF group, while 7 patients with postoperative urinary fistula, 2 patients with urethral stricture, and 1 patient with glans dehiscence were reported in the TIP group. Postoperative infection, flap necrosis and other complications were not recorded. A total of 37 (80.4%) patients in the MOIF group and 34 (77.3%) patients in the TIP group were successfully reoperated. Although the success rates of MOIF and TIP urethroplasty are comparable, pediatricians should master different types of repair techniques for individualized hypospadias reoperation. MOIF urethroplasty can be recommended after failure of the primary repair.