Assuntos

Mutação , Miopatias Congênitas Estruturais , Humanos , Miopatias Congênitas Estruturais/genética , Miopatias Congênitas Estruturais/patologia , Mutação/genética , Masculino , Feminino , Músculo Esquelético/patologia , Proteínas Musculares/genética , Proteínas Tirosina Fosfatases não Receptoras/genética , Adulto , Proteínas de Homeodomínio/genética

RESUMO

Background and objective: Few studies on endoscopic management of primary obstructive megaureter (POM) in adult patients have been reported. Our objective was to describe our technique and long-term outcomes for endoscopic management of adult POM. Methods: We included 76 adult POM patients undergoing endoscopic management between September 2015 and January 2024. Under endoscopic control, the stricture was dilated to 24-30 Fr while maintaining a balloon pressure of 25-35 atm for 3 min. An additional incision of the stenotic ring using either an electrode or holmium laser was performed in 39 patients. Data for patient characteristics, intraoperative variables, surgical complications, and follow-up results were analyzed. A descriptive statistical analysis was performed. Surgical success was defined as no tubes or stents in the body, stable or improved symptoms and renal function, and the absence of reflux or obstruction during the follow-up period. Key findings and limitations: All procedures were completed without conversion to open or laparoscopic surgery. The median operative time was 45 min (range 16-165) with median estimated blood loss of 2 ml (range 0-150). The median postoperative hospital stay was 3 d (range 1-15). No intraoperative complication occurred. At median postoperative follow-up of 42 mo (range 3-100) the overall success rate was 92.1%. Restenosis of the vesicoureteral junction (Clavien-Dindo grade III) occurred in five patients (6.6%), and high-grade vesicoureteral reflux occurred in one patient (1.3%), all of whom required secondary reconstruction surgery. Conclusions and clinical implications: The results indicate that our endoscopic management for adult POM is safe and effective, with favorable long-term outcomes. This approach could potentially serve as a first-line treatment option for adult POM. Patient summary: Primary obstructive megaureter (POM) occurs when the flow of urine is blocked because of a narrow segment in the tube between the kidney and bladder (ureter), which causes widening of the ureter further up. For our minimally invasive technique, a telescope is inserted through the urethra and bladder to reach the ureter for surgical treatment. Our results show that this is a safe procedure for POM in adults.

RESUMO

PURPOSE: To develop a novel adaptation of the Whitaker test for assessing the surgical effects of ileal ureter replacement (IUR), and to evaluate its feasibility and effect in the postoperative evaluation. PATIENTS AND METHODS: From November 2021 to September 2023, patients undergoing the modified Whitaker test following IUR were prospectively enrolled. The relative pressure was defined as the pelvis pressure minus the bladder pressure. Successful nephrostomy removal was defined as absence of symptoms and improved or stable hydronephrosis. RESULTS: The 51 ureters from 39 patients underwent the modified Whitaker test after IUR. The modified Whitaker test was performed successfully on all patients without any reported discomfort. The relative pressure of 47 ureters kept steady (< 15 cmH2O) throughout the examination with well ileal ureter peristalsis and was classified into type I. The relative pressure of 2 ureters increased with perfusion reaching a range of 15-22 cmH2O, with well ileal ureteral peristalsis observed (type II). The relative pressure of 2 ureters increased along with perfusion, with weakening of ileal ureter peristalsis or a leakage of contrast medium, and the relative pressure surpassed 22 cmH2O (type III). Nephrostomy tubes were promptly removed for type I and type II ureters, while removal for type III ureters occurred after a 2-month period. None of the 39 patients required additional interventions for recurrent obstruction. CONCLUSION: The modified Whitaker test was a safe and effective approach for the evaluation of surgical effects of IUR, offering additional evidence to assess the safety of nephrostomy tube removal.

Assuntos

Íleo , Ureter , Humanos , Ureter/cirurgia , Pessoa de Meia-Idade , Feminino , Íleo/cirurgia , Masculino , Estudos Prospectivos , Idoso , Adulto , Estudos de Viabilidade , Pressão , Técnicas de Diagnóstico Urológico

RESUMO

BACKGROUND AND OBJECTIVE: To explore the association between protein quantitative trait loci (pQTL-SNPs) and the risk of LUAD. METHODS: "Blood +" high depth blood proteomics analysis was performed on plasma from female LUAD patients and female healthy controls, and combined with proteomics data from tumors and adjacent non-tumor tissues of female LUAD patients to screen proteins uniformly expressed in plasma and tissues. pQTL-SNPs were then screened through multiple databases and subjected to multilevel screening. The associations between selected pQTL-SNPs and LUAD risk were evaluated by Female Lung Cancer Consortium in Asia GWAS (FLCCA GWAS). Enzyme linked immunosorbent assay (ELISA) is used to determine the levels of candidate protein. RESULTS: A total of 7 pQTL-SNPs were significantly associated with altered LUAD risk (p < 0.05). Meanwhile, the expression of their corresponding target proteins were all decreased in both plasma and tumor tissues of LUAD cases, which may play a role of tumor suppressor proteins. After mutation of 3 pQTL-SNPs (rs7683000, rs73224660, and rs2776937), the expression of corresponding target proteins BST1 and NRP1 decreased, and as potential tumor suppressor proteins, which may promote tumorigenesis and further increasing the risk of developing LUAD (OR >1, p < 0.05); while after mutation the other pQTL-SNP rs62069916, the corresponding target protein APOH expression was increased, while as a potential tumor suppressor protein, which may inhibit tumorigenesis and further reduced the risk of developing LUAD (OR <1, p < 0.05). In addition, the expression of NRP1 and APOH were significant decreased in LUAD cell lines and validated in plasma of LUAD patients. CONCLUSION: A total of 4 pQTL-SNPs (rs7683000, rs73224660, rs2776937, and rs62069916) may associate with altered LUAD risk by regulating the expression of target proteins (BST1, NRP1, and APOH) after mutation.

Assuntos

Adenocarcinoma de Pulmão , Predisposição Genética para Doença , Neoplasias Pulmonares , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Humanos , Feminino , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/sangue , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/sangue , Estudo de Associação Genômica Ampla , Pessoa de Meia-Idade , Proteômica/métodos , Estudos de Casos e Controles , Biomarcadores Tumorais/genética , Proteínas Ligadas por GPI/genética , Antígenos CD/genética , Antígenos CD/metabolismo , Idoso

RESUMO

Construction of a solid electrolyte interphase (SEI) of zinc (Zn) electrode is an effective strategy to stabilize Zn electrode/electrolyte interface. However, single-layer SEIs of Zn electrodes undergo rupture and consequent failure during repeated Zn plating/stripping. Here, we propose the construction of a robust bilayer SEI that simultaneously achieves homogeneous Zn2+ transport and durable mechanical stability for high Zn utilization rate (ZUR) and Coulombic efficiency (CE) of Zn electrode by adding 1,3-Dimethyl-2-imidazolidinone as a representative electrolyte additive. This bilayer SEI on Zn surface consists of a crystalline ZnCO3-rich outer layer and an amorphous ZnS-rich inner layer. The ordered outer layer improves the mechanical stability during cycling, and the amorphous inner layer homogenizes Zn2+ transport for homogeneous, dense Zn deposition. As a result, the bilayer SEI enables reversible Zn plating/stripping for 4800 cycles with an average CE of 99.95% (± 0.06%). Meanwhile, Zn | |Zn symmetric cells show durable lifetime for over 550 h with a high ZUR of 98% under an areal capacity of 28.4 mAh cm-2. Furthermore, the Zn full cells based on the bilayer SEI functionalized Zn negative electrodes coupled with different positive electrodes all exhibit stable cycling performance under high ZUR.

RESUMO

BACKGROUND: Many studies have demonstrated the effectiveness of chimeric antigen receptor-T (CAR-T) cell therapy for relapsed or refractory multiple myeloma (RRMM), but the hematologic toxicity has not been well characterized. METHODS: A total of 111 adults with RRMM who received BCMA CAR-T cells, BCMA + CD19 CAR-T cells or tandem BCMA/CD19 dual-target (BC19) CAR-T cells infusion were enrolled. We characterized cytopenia and hematologic recovery at different time points after CAR-T-cell therapy, analyzed the effect of cytopenia on prognosis and identified the risk factors. RESULTS: Patients had a high probability of cytopenia, with anemia, neutropenia and thrombocytopenia occurring in 92%, 95% and 73%, respectively. There were 60 (54%) patients had prolonged hematologic toxicity (PHT) after D28. The median hemoglobin and platelet count were significantly lower at D28 post-CAR-T cell therapy than at baseline. Hemoglobin increased to above baseline at D90. The median absolute neutrophil count was lower than baseline at D0 and D28, and it recovered to baseline at D180. The baseline level of lactate dehydrogenase was associated with thrombocytopenia. Extramedullary involvement was associated with hemoglobin recovery, while the baseline level of albumin and types of CAR-T were related to platelet recovery. Patients with anemia at baseline and at D0, D180 and D360 had shorter progression-free survival (PFS), while anemia at D0, D60, D180 and D360 was associated with shorter overall survival (OS). Neutropenia at D0 was associated with shorter PFS and patients with neutropenia at D90 or D180 had shorter OS. Patients with thrombocytopenia at any time had shorter PFS and OS. Compared to patients without PHT, patients with PHT had shorter PFS and OS. CONCLUSIONS: The majority of RRMM patients treated with CAR-T cells experienced cytopenia. Cytopenia occurred at specific time points was associated with a poorer prognosis.

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: According to traditional Chinese medicine, Anxiety-induced cardiac blood insufficiency leads to palpitations and restlessness. Suanzaoren Decoction (SD) is effective in replenishing blood and promoting blood circulation. Clinical practice has shown that it has a better therapeutic effect on cardiac insufficiency. However, its mechanism of action is still unclear. AIM OF THE STUDY: The study aims to determine the mechanism by which SD treats chronic restraint stress (CRS)-induced anxiety-induced cardiac insufficiency (ACI). MATERIALS AND METHODS: SD was orally administered to mice with CRS-induced ACI. Firstly, we constructed an anxiety model in mice by CRS. Subsequently, SD was investigated to assess cardiac function and pathological changes through echocardiography, H&E staining, and Masson staining. Thirdly, the function of sympathetic and parasympathetic nerves was evaluated using enzyme-linked immunosorbent assay (ELISA) and enzyme activity assays. Network pharmacology and molecular docking were employed to predict potential targets for SD treatment of cardiac insufficiency. CaMKII expression was scrutinized utilizing publicly accessible databases. CaMKII was identified as a target through immunohistochemistry and Western Blot analysis in mouse hearts. Finally, the therapeutic mechanism of SD was confirmed in injured cardiomyocytes via Western Blot and quantitative PCR. RESULTS: SD exerted anxiolytic effects by increasing the frequency of entries into and the duration spent in open arms while reducing the time spent in the light chamber and increasing the number of transitions between light and dark chambers. Additionally, it mitigated cardiac insufficiency, as evidenced by the enhancement of left ventricular ejection fraction (LVEF) and attenuation of cardiomyocyte damage and inflammatory infiltration. However, SD did not alleviate the elevated norepinephrine (NE) and decreased Acetylcholine (Ach) in anxiety states. To investigate the mechanism of action of SD, we constructed a Drug-Component-Target-Disease network, identifying 13 potential active compounds. Additionally, leveraging bioinformatics analysis and molecular docking targeting heart diseases characterized by clinical left ventricular ejection fraction (LVEF), we focused on the CaMKII target. The ability of SD to modulate CaMKII expression and phosphorylation in the mouse heart was investigated using immunohistochemistry and Western blotting. SD was found to alleviate NE-injured cardiomyocytes by modulating the Ca2+/CaMKII/MEF2 and GATA4 pathways. CONCLUSION: SD is a potential formula for the treatment of chronic restraint stress (CRS)-induced ACI that ameliorates cardiomyocyte injury and improves cardiac function. Its efficacy is associated with the inhibition of the Ca2+/ CaMKII /MEF2 and GATA4 signaling pathways.

RESUMO

Given its nearly ubiquitous expression on plasma cells and limited expression on essential normal tissue, the G protein-coupled receptor class C group 5 member D (GPRC5D) presents a promising opportunity for utilization as an immunotherapy target in multiple myeloma (MM). The therapeutic strategies targeting GPRC5D, such as bispecific antibodies (BsAbs), chimeric antigen receptor (CAR) T cells, and antibody-drug conjugates (ADCs), have been prominently emphasized in relapsed/refractory MM (R/R MM) in recent years. Further clinical trials are necessary to confirm the long-term efficacy of GPRC5D-targeting immunotherapies alone, explore their potentials co-targeting with other specific antigens, or investigate their combinations with existing treatments to overcome MM resistance. This review provides an overview of current research progress in GPRC5D, encompassing its biological characteristics and translational journey from laboratory to clinical application.

Assuntos

Mieloma Múltiplo , Receptores Acoplados a Proteínas G , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/terapia , Mieloma Múltiplo/imunologia , Humanos , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Imunoconjugados/uso terapêutico , Anticorpos Biespecíficos/uso terapêutico , Animais , Imunoterapia/métodos , Terapia de Alvo Molecular/métodos

RESUMO

There are great challenges in the field of natural product isolation and purification and in the pharmacological study of oligosaccharide monomers. And these isolation and purification processes are still universal problems in the study of natural products (NPs), traditional Chinese medicine (TCM), omics, etc. The same polymer-modified materials designed for the special separation of oligosaccharides, named Sil-epoxy-PEI and Sil-chloropropyl-PEI, were synthesized via two different methods and characterized by scanning electron microscopy combined with energy spectrum analysis, Fourier transform infrared spectroscopy, thermogravimetric analysis, zeta potential as well as surface area analysis, etc. Several nucleotide/nucleoside molecules with different polarities and selectivities were successfully isolated in our laboratory using stainless-steel columns filled with the synthesized material. In addition, the separation of saccharide probes and oligosaccharides mixtures in water extracts of Morinda officinalis were compared in HILIC mode. The results showed that the resolution of separations for the representative analytes of the Sil-epoxy-PEI column was higher than for the Sil-chloropropyl-PEI column, and the developed stationary phase exhibited improved performance compared to hydrothermal carbon, amide columns and other HILIC materials previously reported.

Assuntos

Oligossacarídeos , Polietilenoimina , Dióxido de Silício , Oligossacarídeos/química , Oligossacarídeos/síntese química , Oligossacarídeos/isolamento & purificação , Polietilenoimina/química , Dióxido de Silício/química , Espectroscopia de Infravermelho com Transformada de Fourier

RESUMO

Immunothrombosis has emerged as a potential mechanistic link underlying the development and progression of acute respiratory distress syndrome (ARDS), but understanding its specific profile in patients, both locally and systemically, is limited. The objective of this study was to characterize and compare the immunothrombotic signatures in patients diagnosed with pneumonia-related ARDS (p-ARDS) at both the pulmonary and systemic levels and to evaluate their clinical relevance. The study included 23 consecutive patients diagnosed with p-ARDS admitted to the intensive care unit at a tertiary university hospital from July 2022 to May 2023, alongside 40 concurrently hospitalized patients with common pneumonia as controls. Paired bronchoalveolar lavage fluid (BALF) and serum samples were collected from the participants for the analysis of 15 biomarkers to assess and quantify the pulmonary and systemic immunothrombotic signatures. The study results revealed significant pulmonary inflammation and systemic endothelial injury in p-ARDS patients compared to pneumonia controls. These observations were maintained after adjustment for severity of illness (Acute Physiology and Chronic Health Evaluation [APACHE] II scores). In terms of clinical relevance, inflammatory biomarkers (interleukin [IL]-6, IL-8) in BALF were found to correlate with PaO2/FiO2 ratio, while serum levels of ADAMTS-13 and thrombomodulin (TM) showed associations with Sequential Organ Failure Assessment (SOFA) and Disseminated Intravascular Coagulation (DIC) scores. In conclusion, this preliminary investigation identified compartment-specific variations in the immunothrombotic signature between patients with p-ARDS and those with pneumonia alone, with inflammatory responses predominantly localized in the alveolar compartments and coagulation/endothelial injury biomarkers more pronounced in peripheral blood.

RESUMO

Distal hereditary motor neuropathies (dHMN) are a group of heterogeneous diseases and previous studies have reported that the compound heterozygous recessive MME variants cause dHMN. Our study found a novel homozygous MME variant and a reported compound heterozygous MME variant in two Chinese families, respectively. Next-generation sequencing and nerve conduction studies were performed for two probands. The probands in two families presented with the muscle weakness and wasting of both lower limbs and carried a c.2122 A > T (p.K708*) and c.1342 C > T&c.2071_2072delinsTT (p.R448*&p.A691L) variant, respectively. Prominently axonal impairment of motor nerves and slight involvement of sensory nerves were observed in nerve conduction study. Our study reported a "novel" nonsense mutation and a missense variant of autosomal recessive late-onset dHMN and reviewed reported MME variants associated with dHMN phenotype.

Assuntos

Neuropatia Hereditária Motora e Sensorial , Neprilisina , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Idade de Início , Alelos , China , Códon sem Sentido , População do Leste Asiático/genética , Genes Recessivos , Neuropatia Hereditária Motora e Sensorial/genética , Linhagem , Neprilisina/genética

RESUMO

The influence of chimeric antigen receptor T (CAR-T) cell therapy on platelet function in relapsed/refractory (R/R) multiple myeloma (MM) has not been thoroughly investigated. Our cohort comprised fifty MM patients treated with CAR-T cells. The mean platelet closure time (PCT) induced by collagen/adenosine diphosphate (CADP) in peripheral blood was significantly prolonged before lymphodepletion (195.24 ± 11.740 s) and notably reduced post-CAR-T cell therapy (128.02 ± 5.60 s), with a statistically significant improvement (67.22, 95% CI 46.91-87.53, P < 0.001). This post-treatment PCT was not significantly different from that of healthy controls (10.64, 95% CI 1.11-22.40, P > 0.05). Furthermore, a pronounced enhancement in PCT was observed in patients with a response greater than partial remission (PR) following CAR-T cell infusion compared to pre-treatment values (P < 0.001). An extended PCT was also associated with a less favorable remission status. In patients with cytokine release syndrome (CRS) grades 0-2, those with a PCT over 240.5 s exhibited a shorter progression-free survival (PFS), with median PFS times of 10.2 months for the PCT > 240.5 s group versus 22.0 months for the PCT ≤ 240.5 s group. Multivariate analysis revealed that a PCT value exceeding 240.5 s is an independent prognostic factor for overall survival (OS) in R/R MM patients after CAR-T cell therapy. The study demonstrates that CAR-T cell therapy enhances platelet function in R/R MM patients, and PCT emerges as a potential prognostic biomarker for the efficacy of CAR-T cell therapy.

Assuntos

Plaquetas , Imunoterapia Adotiva , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/terapia , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Resultado do Tratamento , Receptores de Antígenos Quiméricos , Síndrome da Liberação de Citocina/terapia , Testes de Função Plaquetária

RESUMO

The olfactory system of above-ground insects is among the best described perceptual architectures. However, remarkably little is known about how below-ground insects navigate in the dark for foraging. Here, we investigated host plant preferences, olfactory sensilla and characterise olfactory proteins in below-ground larvae of the striped flea beetle (SFB) Phyllotreta striolata Fabricius (Coleoptera: Chrysomelidae). Both the adults and larvae of this coleopteran pest cause serious damage to Brassicaceous crops above and below ground, respectively. To elucidate the role of olfactory system in host location of below-ground larvae, we initially demonstrated that SFB larvae distinctly favoured Brassicaceae over other plant families by two-choice behavioural bioassay. Subsequently, scanning electron microscopy of sensilla in SFB larval head showed a significant reduction in the number of olfactory sensilla in larvae compared with adults. However, essential olfactory sensilla such as sensilla basiconica are underscoring the indispensability of the larval olfactory system. We selected four larval-specific odorant binding proteins for functional validation from our previous transcriptome data. Functional studies revealed that PstrOBP23 exhibits robust binding affinity to 24 volatiles of Brassicaceae plants, including seven isothiocyanate compounds. This suggests a pivotal role of PstrOBP23 in the foraging behaviour of the larvae below the ground. Moreover, two ligands displaying strong binding capacity exhibit apparent attractive or repellent activity towards SFB larvae. Our findings provide a crucial insight into the olfactory system of below-ground larvae in SFB, highlighting the highly selective tuning of larvae specific OBP to host plant volatiles. These results offer potential avenues for developing effective pest control strategies against SFB.

RESUMO

Racial and ethnic disparities persist in cancer survival rates across the United States, despite overall improvements. This comprehensive analysis examines trends in 5-year relative survival rates from 2002-2006 to 2015-2019 for major cancer types, elucidating differences among racial/ethnic groups to guide equitable healthcare strategies. Data from the SEER Program spanning 2000-2020 were analyzed, focusing on breast, colorectal, prostate, lung, pancreatic cancers, non-Hodgkin lymphoma, acute leukemia, and multiple myeloma. Age-standardized relative survival rates were calculated to assess racial (White, Black, American Indian/Alaska Native, Asian/Pacific Islander) and ethnic (Hispanic, Non-Hispanic) disparities, utilizing period analysis for recent estimates and excluding cases identified solely through autopsy or death certificates. While significant survival improvements were observed for most cancers, notable disparities persisted. Non-Hispanic Blacks exhibited the largest gain in breast cancer survival, with an increase of 5.2% points (from 77.6 to 82.8%); however, the survival rate remained lower than that of Non-Hispanic Whites (92.1%). Colorectal cancer survival declined overall (64.7-64.1%), marked by a 6.2% point drop for Non-Hispanic American Indian/Alaska Natives (66.3-60.1%). Prostate cancer survival declined across all races, with Non-Hispanic American Indian/Alaska Natives showing a decrease of 7.7% points (from 96.9 to 89.2%). Lung cancer, acute leukemia, and multiple myeloma showed notable increases across groups. Substantial racial/ethnic disparities in cancer survival underscore the notable need for tailored strategies ensuring equitable access to advanced treatments, particularly addressing significant trends in colorectal and pancreatic cancers among specific minority groups. Careful interpretation of statistical significance is warranted given the large dataset.

Assuntos

Neoplasias , Programa de SEER , Humanos , Neoplasias/mortalidade , Neoplasias/etnologia , Estados Unidos/epidemiologia , Masculino , Feminino , Taxa de Sobrevida , Etnicidade/estatística & dados numéricos , Grupos Raciais/estatística & dados numéricos , Disparidades nos Níveis de Saúde , Pessoa de Meia-Idade , Idoso , Disparidades em Assistência à Saúde/etnologia , Disparidades em Assistência à Saúde/tendências

RESUMO

INTRODUCTION: We aim to compare the safety and effectiveness of the KangDuo (KD)-Surgical Robot-01 (KD-SR-01) system and the da Vinci (DV) system for robot-assisted radical nephroureterectomy (RARNU). MATERIALS AND METHODS: This multicenter prospective randomized controlled trial was conducted between March 2022 and September 2023. Group 1 included 29 patients undergoing KD-RARNU. Group 2 included 29 patients undergoing DV-RARNU. Patient demographic and clinical characteristics, perioperative data, and follow-up outcomes were collected prospectively and compared between the two groups. RESULTS: There were no significant differences in patient baseline demographic and preoperative characteristics between the two groups. The success rates in both groups were 100% without conversion to open or laparoscopic surgery or positive surgical margins. No significant difference was observed in docking time [242 (120-951) s vs 253 (62-498) s, P = 0.780], console time [137 (55-290) min vs 105 (62-220) min, P = 0.114], operative time [207 (121-460) min vs 185 (96-305) min, P = 0.091], EBL [50 (10-600) mL vs 50 (10-700) mL, P = 0.507], National Aeronautics and Space Administration Task Load Index scores, and postoperative serum creatinine levels between the two groups. None of the patients showed evidence of distant metastasis, local recurrence, or equipment-related adverse events during the four-week follow-up. One (3.4%) patient in Group 2 experienced postoperative enterovaginal and enterovesical fistulas (Clavien-Dindo grade III). CONCLUSIONS: The KD-SR-01 system is safe and effective for RARNU compared to the DV Si or Xi system. Further randomized controlled studies with larger sample sizes and longer durations are required.

Assuntos

Nefroureterectomia , Duração da Cirurgia , Procedimentos Cirúrgicos Robóticos , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/instrumentação , Feminino , Masculino , Estudos Prospectivos , Pessoa de Meia-Idade , Nefroureterectomia/métodos , Idoso , Resultado do Tratamento , Neoplasias Renais/cirurgia , Tempo de Internação , Laparoscopia/métodos , Laparoscopia/instrumentação , Reprodutibilidade dos Testes , Complicações Pós-Operatórias

RESUMO

PURPOSE: It has been reported that exhaustive exercise (EE) causes myocyte injury, and eventually damages the function of the myocardia. Albiflorin (AF) has anti-inflammatory, antioxidant, and anti-apoptosis effects. In this study, we determined whether AF could mitigate the EE-induced myocardial injury and research the potential mechanisms. METHODS: The rat model of EE was built by forced treadmill running method. Rats were intraperitoneally injected with AF before EE once daily for one week. The relative factors levels were examined by commercial kits. The apoptosis was appraised using a TdT-mediated dUTP nick end labeling assay kit. The ACSL4, GPX4, Nrf2, pAKT/AKT, and HO-1 contents were assessed by western blot. RESULTS: AF lessened EE-induced cardiac myocytes ischemic/hypoxic injury and reduced the contents of myocardial injury biomarkers in the serum. AF lessened EE-induced cardiac myocyte apoptosis, inflammatory response, oxidative stress, and ferroptosis in myocardial tissues. However, the influences of AF were overturned by the co-treatment of AF and LY294002. AF activated the AKT/Nrf2/HO-1 signaling pathway in myocardial tissues in vivo. CONCLUSIONS: AF could curb cardiac myocytes ferroptosis, thus diminishing the EE-induced myocardial injury through activating the AKT/Nrf2/HO-1 cascade.

Assuntos

Ferroptose , Miócitos Cardíacos , Fator 2 Relacionado a NF-E2 , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Animais , Fator 2 Relacionado a NF-E2/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Masculino , Transdução de Sinais/efeitos dos fármacos , Ferroptose/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Ratos , Estresse Oxidativo/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Ratos Sprague-Dawley , Heme Oxigenase-1/metabolismo , Miocárdio/metabolismo , Miocárdio/patologia , Hidrocarbonetos Aromáticos com Pontes

RESUMO

Glioma, a complex and aggressive brain tumor, is characterized by dysregulated immune responses within the tumor microenvironment (TME). We conducted a comprehensive analysis to elucidate the roles of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) in glioma progression and their impact on the immune landscape. Using transcriptome data, we stratified glioma samples based on MDSC and Treg levels, revealing significant differences in patient survival probabilities. LASSO regression identified a gene panel associated with glioma prognosis, yielding a patient-specific risk score. Multivariate Cox regression confirmed the risk score's correlation with overall survival. An ISS (immune suppressive score) system assessed the immune landscape's impact on glioma progression and therapeutic response. Functional validation showed MDSC and Treg infiltration's relevance in glioma progression and immune modulation. Hub genes in the black module, including CCL2, LINC01503, CXCL8, CLEC2B, TIMP1, and RGS2, were identified through MCODE analysis. RGS2 expression correlated with immune cell populations and varied in glioma cells. This study sheds light on MDSCs' and Tregs' roles in glioma pathogenesis, suggesting their potential as prognostic biomarkers and therapeutic targets for personalized immunotherapeutic strategies in glioma treatment.

Assuntos

Neoplasias Encefálicas , Glioma , Células Supressoras Mieloides , Linfócitos T Reguladores , Microambiente Tumoral , Humanos , Glioma/imunologia , Glioma/genética , Glioma/terapia , Glioma/mortalidade , Células Supressoras Mieloides/imunologia , Linfócitos T Reguladores/imunologia , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Prognóstico , Microambiente Tumoral/imunologia , Regulação Neoplásica da Expressão Gênica , Transcriptoma , Biomarcadores Tumorais/genética

RESUMO

Semiconductive coordination polymers (CPs) have recently garnered a significant amount of attention due to their widespread application in many areas. The "through-space" approach has emerged as the most versatile strategy for constructing semiconductive CPs. However, this approach often leads to the formation of unidirectional charge transport paths, resulting in anisotropic electrically conductive performance and low average conductivities in pressed pellets, thus presenting significant challenges for the practical application of semiconductive CPs. Consequently, there is a strong desire to explore simpler and more versatile strategies for designing semiconductive CPs with dual or multiple charge transport paths. Herein, we report on two semiconductive potassium hydroxamate coordination polymers, denoted as [K(HONDI)(H2O)2]n (1) and [K(HONDI)]n (2). Both compounds theoretically possess dual charge transport paths, occurring internally and externally within the π-π stacking columns of the ligands. Conductivity measurements revealed that compounds 1 and 2 both exhibit semiconductive properties, with their electrical conductivities reaching 2.3 × 10-6 and 1.9 × 10-7 S/cm, respectively, at 30 °C. Their electrically conductive performance could be attributed to theoretically biaxial "band-like" charge transport inside crystals and "hopping" charge transport between grain boundaries.

RESUMO

Hydrogen peroxide (H2O2) production driven by solar energy has received enormous attention due to its high efficiency, low cost, and environmental friendliness characteristics. Searching for new photocatalytic materials for H2O2 production is one of the most important targets. In this work, a new three-dimensional (3D) uranyl-organic framework material was constructed with mixed ligands via a solvothermal reaction and used for photocatalytic H2O2 production. The mixed ligand strategy not only benefits the construction of a 3D uranyl-organic framework but also introduces strong photon absorption groups into the framework. The thiophene and pyridine rings in the framework enhance photon absorption and carrier transfer. In addition, with the assistance of the hydrogen abstraction reaction of uranyl centers, the H2O2 production rate reaches 345 µmol h-1 g-1. This study provides a new blueprint for exploring the artificial photosynthesis of H2O2 through uranium-based metal-organic frameworks.