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A highly efficient, atom-economical α-allylation reaction of NH2-unprotected amino acid esters and alkynes is achieved by chiral aldehyde/palladium combined catalysis. A diverse range of α,α-disubstituted nonproteinogenic α-amino acid esters are produced in 31-92% yields and 84-97% ee values. The allylation products are utilized for the synthesis of drug molecule BMS561392 and other chiral molecules possessing complex structures. Mechanistic investigations reveal that this reaction proceeds via a chiral aldehyde-/palladium-mediated triple cascade catalytic cycle.
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BACKGROUND: Inhibitors of programmed cell death ligand 1 (PD-L1) and vascular endothelial growth factor receptor 2 (VEGFR2) are commonly used in the clinic, but they are beneficial for only a minority of glioblastoma multiforme (GBM) patients. GBM has significant immunosuppressive properties, and there are many immunosuppressive cells and dysfunctional effector T-cell in the tumor microenvironment (TME), which is one of the important reasons for the failure of clinical treatment of GBM. P21-activated kinase 4 (PAK4) is a threonine protein kinase, and as a pivotal immune suppressor in the TME. PAK4 knockdown attenuates vascular abnormalities and promotes T-cell infiltration. METHODS: Using RNA sequencing (RNA-seq) technology, western blotting, and immunofluorescence, we identified changes in genes expression following VEGFR2 knockdown. The impact of anti-PD-L1 and anti-VEGFR2 on GBM cells apoptosis was assessed using coculture assays, western blotting, and flow cytometry. Additionally, the therapeutic efficacy of anti-PD-L1 and anti-VEGFR2 therapy was evaluated through in vivo experiments, immunohistochemistry, and immunofluorescence. RESULTS: Our studies revealed that VEGFR2 binds and phosphorylates signal transducer and activator of transcription 3 (p-STAT3), thereby regulating the expression of PAK4. Anti-PD-L1 and anti-VEGFR2 therapy can increase the secretion of interferon-gamma (IFN-γ), granzyme B, and perforin by immune cells and promoting the cytotoxic effects of cytotoxic cluster of differentiation 8 (CD8)+ T cells, and overexpression of PAK4 could reverse this effect. We also demonstrated that combination therapy with anti-PD-L1 and anti-VEGFR2 agents prevents tumor growth in an intracranial tumor model. CONCLUSIONS: Our results support that anti-VEGFR2 therapy can downregulate PAK4, reprogram the TME by increasing CD8+ T cells infiltration and activation, and enhance the therapeutic effect of anti-PD-L1 therapy on GBM cells.
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Antígeno B7-H1 , Glioblastoma , Microambiente Tumoral , Receptor 2 de Factores de Crecimiento Endotelial Vascular , Glioblastoma/tratamiento farmacológico , Glioblastoma/patología , Humanos , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Antígeno B7-H1/metabolismo , Ratones , Animales , Línea Celular TumoralRESUMEN
BACKGROUND: This study reports the 2-year outcomes and biomarker analysis results of patients with locally advanced gastric and gastroesophageal junction (G/GEJ) adenocarcinoma who received neoadjuvant chemotherapy and immunotherapy in a phase II WuhanUHGI001 trial. METHODS: Eligible patients with cT3/4aN+M0 locally advanced G/GEJ adenocarcinoma were screened, enrolled, and treated with 3 cycles of neoadjuvant tislelizumab and SOX followed by D2 gastrectomy and another 5 cycles of postoperative adjuvant SOX. The primary endpoint was major pathological response. RESULTS: Of the 49 included patients, 24 (49.0%) achieved major pathological response and 13 (26.5%) achieved pathological complete response. During a median follow-up of 26.8 months, the 2-year progression-free survival (PFS) and overall survival (OS) rates were 69.4% and 81.2%, respectively. Grade 3-4 adverse events occurred in six patients (12.2%) during the neoadjuvant period, eight patients (17.0%) during the postoperative period, and seven patients (15.2%) during the adjuvant period. Biomarker analysis revealed that the pathological complete response showed no association with 2-year PFS and OS. Major pathological response showed a potentially strong association with improved 2-year PFS and OS rates. In addition, preoperative circulating tumor cells combined with pathological responses are helpful in prognosis assessment. In addition, our results showed that T downstaging, lymphocyte-to-monocyte ratio, and CD3+ T cells were independent factors that affect PFS. The signet ring cell component (SRCC), T downstaging, and neutrophil-to-lymphocyte ratio were independent factors affecting OS. Prognostic nomograms of PFS and OS constructed based on the multivariate Cox regression results demonstrated suitable calibration and discrimination ability. CONCLUSIONS: Neoadjuvant tislelizumab plus SOX exhibits promising efficacy and acceptable toxicity in patients with locally advanced G/GEJ adenocarcinoma. In addition, our study established a prognostic risk signature and nomograms based on clinicopathological characteristics, which can accurately predict patient outcomes and aid in personalized treatment planning.
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OBJECTIVE: This study aimed to investigate the safety and efficacy of a new Chinese device using microwave ablation for treating symptomatic great saphenous vein (GSV) varicose veins (VVs). METHODS: This prospective, single-arm, single-center, cohort study investigated the safety and efficacy of endovenous microwave ablation for the treatment of symptomatic VVs. A total of 50 patients with lower limb varicose veins were enrolled from the Hospital of Chengdu University of Traditional Chinese Medicine. The clinical outcomes and complications were assessed at 1, 6, and 12 months after the procedure. The primary outcome was the occlusion rate of GSV immediately and at 1, 6, and 12 months after the treatment. The secondary outcomes included the venous clinical severity score (VCSS), the chronic venous insufficiency questionnaire 14 items (CIVIQ-14) score, the Aberdeen varicose vein questionnaire (AVVQ) score, and the pain visual analog scale (VAS) score. This study protocol was registered at ClinicalTrials.gov (ID: NCT04645771). RESULTS: In total, 50 limbs from 50 patients (26 female; mean age: 53.45 ± 9.78 years) were treated. A technical success rate of 100% was achieved and no serious adverse events were recorded. During the follow-up period, the occlusion rate of the major/minor saphenous vein trunk remained 100% at 1, 6, and 12 months after surgery except one patient fell off. The median 24-h VAS value was 2 (2,3). The VCSS score, CIVIQ-14 score, and AVVQ score (p < .05) at 1, 6, and 12 months improved significantly compared with the value preoperative (p < .05). CONCLUSION: EMA was safe and effective for treating varicose veins in the lower limbs, with a high rate of venous trunk occlusion and few complications, thus improving patients' postoperative quality of life.
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OBJECTIVE: This study compared the outcomes of radiofrequency ablation (RFA) and microwave ablation (EMA) for treating lower limb varicose veins. METHODS: Patients who underwent RFA (n = 240) or EMA (n = 209) at our institute from December 2020 to August 2022 were included in this retrospective investigation. Follow-up outcomes included active vein occlusion rate, Venous Clinical Severity Score (VCSS), the Aberdeen Varicose Vein Questionnaire (AVVQ), and Chronic Insufficiency Venous Quality of Life questionnaire-14 (CIVIQ-14)score. RESULTS: There was no significant difference in the active vein occlusion rate between the two groups after the operation (p > .05). Compared to pre-surgery scores, both groups showed substantial improvement in VCSS, AVVQ, and CIVIQ-14 scores(p < .05), there was no significant difference in these scores in either group (p > .05). CONCLUSION: Intravenous radiofrequency and microwave ablation effectively improve the quality of life for patients with lower limb varicose veins, with low post-operative complication and recurrence rates.
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BACKGROUND: Older chronic kidney disease (CKD) patients frequently face unrecognized cognitive impairment and excess mortality. Physical activity (PA) reduces cognitive decline but whether PA modifies cognitive impairment-associated mortality remains unknown. METHODS: From 2005 to 2011, 30,561 older Taiwanese CKD patients were enrolled. Patients were divided into intact cognition (≥8 scores), mild (6-7 scores), and severe (≤5 scores) cognitive impairment groups by the Short Portable Mental Status Questionnaire (SPMSQ), and were also categorized into high-PA (≥60 min/week of moderate-intensity PA), low-PA (20-60 min/week) or inactive (<20 min/week) groups. Cox regression was conducted to evaluate the individual and joint associations of cognitive impairment and PA on all-cause and cardiovascular mortality. RESULTS: After a median follow-up of 4.52 years, the all-cause mortality were higher in CKD patients with severe (multivariable-adjusted hazard ratio [aHR] 2.31; 95% confidence interval [CI] 2.05-2.60) and mild (aHR 1.74; CI 1.51-1.99) cognitive impairment than cognitively intact ones. Remarkably, decreased PA amount interacted and amplified the cognitive impairment-associated mortality risks. Notably, the high-PA status linked to lower overall mortality risks both in mild (aHR 0.65; CI 0.45-0.93) and severe (aHR 0.73; CI 0.54-0.99) cognitively-impaired patients as compared to inactivity. Survival tree analysis indicated the least mortality in those with high PA and >8 SPMSQ scores. Similar associations were found in the cardiovascular mortality. LIMITATIONS: Residual confounding and single ethnicity. CONCLUSIONS: Cognitive impairment defined by SPMSQ was progressively associated with higher mortality among elderly CKD. Higher PA linked to lower cognitive impairment-associated death risks, and could be promoted for longevity benefits.
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Disfunción Cognitiva , Ejercicio Físico , Insuficiencia Renal Crónica , Humanos , Masculino , Femenino , Insuficiencia Renal Crónica/mortalidad , Disfunción Cognitiva/mortalidad , Anciano , Taiwán/epidemiología , Modelos de Riesgos Proporcionales , Enfermedades Cardiovasculares/mortalidad , Anciano de 80 o más Años , Persona de Mediana Edad , Factores de RiesgoRESUMEN
Post-induction hypotension (PIH) is a common and potentially serious complication of general anesthesia. This meta-analysis (Prospero registration number: CRD42024566321) aimed to evaluate the predictive efficacy of the perfusion index (PI) for PIH in patients undergoing general anesthesia. A comprehensive literature search was performed using multiple electronic databases (Google Scholar, EMBASE, Cochrane Library, and MEDLINE). Studies involving adult patients undergoing general anesthesia, with the PI measured before anesthesia induction and reporting PIH incidence, were included. The primary outcome was the diagnostic accuracy of the PI in predicting the probability of PIH. The secondary outcome was the pooled PIH incidence. Eight studies with 678 patients were included. The pooled incidence of PIH was 44.8% (95% confidence interval [CI]: 29.9%-60.8%). The combined sensitivity and specificity of the PI for predicting PIH were 0.84 (95% CI: 0.65-0.94) and 0.82 (95% CI: 0.70-0.90), respectively. The summary receiver operating characteristic (sROC) analysis revealed an area under curve of 0.89 (95% CI: 0.86-0.92). The Deek's funnel plot asymmetry test indicated no significant publication bias. The PI demonstrates high predictive efficacy for PIH in patients undergoing general anesthesia, indicating that it can be a valuable tool for identifying those at risk of PIH.
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This meta-analysis investigated the effects of intravenous magnesium sulfate on the postoperative recovery quality, as assessed using the Quality of Recovery (QoR) questionnaire, in adult surgical patients. Seven randomized controlled trials involving 622 patients were included. Compared with the placebo, magnesium sulfate significantly improved the global QoR score on postoperative day 1 (standardized mean difference [SMD]: 1.24; 95% confidence interval: 0.70-1.78; p < 0.00001). It also enhanced specific QoR dimensions, with substantial effects on pain (SMD: 1, p < 0.00001) and physical comfort (SMD: 0.85, p < 0.0001), a moderate effect on emotional state (SMD: 0.65, p = 0.002), and small improvements in physical independence (SMD: 0.43, p < 0.00001) and psychological support (SMD: 0.37, p < 0.0001). In addition, magnesium sulfate reduced the intraoperative opioid consumption (SMD: -0.66, p < 0.0001), postoperative pain severity, and the incidence of postoperative nausea and vomiting (risk ratio: 0.48, p = 0.008). The extubation times were unaffected, whereas the post-anesthesia care unit stay was slightly prolonged. These findings highlight the potential of magnesium sulfate as a valuable adjunct for multimodal analgesia and enhanced recovery. Future studies should aim to elucidate the optimal dosing strategies, timing of administration, and specific surgical populations that may derive maximum benefits.
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Sulfato de Magnesio , Dolor Postoperatorio , Ensayos Clínicos Controlados Aleatorios como Asunto , Sulfato de Magnesio/administración & dosificación , Humanos , Dolor Postoperatorio/tratamiento farmacológico , Infusiones Intravenosas , Periodo Posoperatorio , Náusea y Vómito Posoperatorios , Adulto , Femenino , Encuestas y CuestionariosRESUMEN
Diabetic kidney disease (DKD) is often featured with redox dyshomeostatis. Pyruvate dehydrogenase kinase 4 (PDK4) is the hub for DKD development. However, the mechanism by which PDK4 mediates DKD is poorly understood. The current work aimed to elucidate the relationship between PDK4 and DKD from the perspective of redox manipulation. Oxidative stress was observed in the human proximal tubular cell line (HK-2 cells) treated with a high concentration of glucose and palmitic acid (HGL). The mechanistic study showed that PDK4 could upregulate Kelch-like ECH-associated protein 1 (Keap1) in HGL-treated HK-2 cells through the suppression of autophagy, resulting in the depletion of nuclear factor erythroid 2-related factor 2 (Nrf2), the master regulator of redox homeostasis. At the cellular level, pharmacological inhibition or genetic knockdown of PDK4 could boost Nrf2, followed by the increase of a plethora of antioxidant enzymes and ferroptosis-suppression enzymes. Meanwhile, the inhibition or knockdown of PDK4 remodeled iron metabolism, further mitigating oxidative stress and lipid peroxidation. The same trend was observed in the DKD mice model. The current work highlighted the role of PDK4 in the development of DKD and suggested that PDK4 might be a promising target for the management of DKD.
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Nefropatías Diabéticas , Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo/efectos de los fármacos , Humanos , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Animales , Ratones , Ratones Endogámicos C57BL , Masculino , Piruvato Deshidrogenasa Quinasa Acetil-Transferidora/metabolismo , Línea Celular , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/patologíaRESUMEN
The current research focuses on the effects of nutritional supplementation and exercise on dialysis patients, but whether physical activity (PA) can reduce the risk of adverse outcomes for patients with different nutritional status is not clear. The maintenance hemodialysis (MHD) patients were recruited from April 2021 to April 2022. The information of PA was obtained from the international physical activity questionnaire (IPAQ). The outcomes were cardiovascular death, myocardial infarction, stroke, heart failure, atrial fibrillation, tumor and all-cause death. We used COX proportional risk model to estimate the association between PA and the outcomes of MHD patients. Patients are classified into two groups based on geriatric nutritional risk index (GNRI) and classified by age, and we used COX proportional risk model to estimate the association of PA and outcomes in subgroups. The isotemporal substitution model (ISM) was used to estimate the effects of replacing light physical activity (LPA) with moderate physical activity (MPA) or vigorous physical activity (VPA) on risk of cardiovascular events, tumors, and all-cause death in different subgroups. The effects of PA on ankle-brachial index (ABI) and body fat content were analyzed in different IPAQ groups. A total of 241 maintenance hemodialysis patients were included, 105 peoples developed cardiovascular death, myocardial infarction, stroke, heart failure, atrial fibrillation, tumor and all-cause death (43.6%). The median follow-up time was 12 months. MPA reduced the risk of outcome in MHD patients or high GNRI patients (40% vs 39%).In MHD patients who was under 65 years with high GNRI, MPA reduced cardiovascular death, myocardial infarction, stroke, heart failure, atrial fibrillation, tumor and all-cause death by 55%.PA reduced the risk of cardiovascular event by 65%, but did not reduce the risk of tumor or all-cause death. Replacing LPA with VPA did not improve clinical outcomes. It actually increases the risk of heart failure 0.4%. MPA reduced the risk of cardiovascular death, myocardial infarction, stroke, heart failure, atrial fibrillation, tumor, all-cause death in MHD patients under 65 years, while VPA had no health benefit.Trial registration: ChiCTR210050998.
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Enfermedades Cardiovasculares , Ejercicio Físico , Neoplasias , Estado Nutricional , Diálisis Renal , Humanos , Masculino , Diálisis Renal/efectos adversos , Femenino , Persona de Mediana Edad , Anciano , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/etiología , Neoplasias/mortalidad , Causas de Muerte , Factores de Riesgo , Modelos de Riesgos ProporcionalesRESUMEN
BACKGROUND: The adverse effects of sepsis-associated acute kidney injury (SA-AKI) highlight the need for new biomarkers. Signal Peptide-Complement C1r/C1s, Uegf, Bmp1-Epidermal Growth Factor-like Domain-Containing Protein 2 (SCUBE2), important for angiogenesis and endothelial integrity, has been linked to increased mortality in models of lipopolysaccharide-induced lung injury. This research aimed to assess the utility of plasma SCUBE2 levels as a prognostic indicator for SA-AKI in intensive care unit (ICU) patients. METHODS: Between September 2020 and December 2022, our study enrolled ICU patients diagnosed with stage 3 SA-AKI. We collected demographic information, illness severity indices, and laboratory data, including plasma SCUBE2 and sepsis-triggered cytokine levels. We employed receiver operating characteristic curves and DeLong tests to assess the predictive accuracy for survival, Kaplan-Meier curves to evaluate the relative risk of death, and multivariate logistic regression to identify independent mortality predictors. RESULTS: Among the total of 200 participants, the survivors had significantly higher plasma SCUBE2 levels (115.9 ng/mL) compared to those who died (35.6 ng/mL). SCUBE2 levels showed a positive correlation with the anti-inflammatory cytokine IL-10 and a negative correlation with the APACHE II score, SOFA score, C-reactive protein, and monocyte chemoattractant protein-1. Multivariate analysis revealed that elevated SCUBE2 and IL-10 levels were independently protective against mortality, and associated with the most favorable 30-day survival outcomes. CONCLUSIONS: In ICU patients with stage 3 SA-AKI, lower plasma levels of SCUBE2 were correlated with elevated pro-inflammatory factors, which impacted survival outcomes. This suggests that SCUBE2 could be a potential biomarker for predicting prognosis in patients with SA-AKI.
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Background and Objective: A significant number of individuals diagnosed with non-small cell lung cancer (NSCLC) have distant metastases, and the concept of oligometastatic NSCLC has shown promise in achieving a cure. Stereotactic body radiation therapy (SBRT) is currently considered a viable treatment option for a limited number of tumor metastases. It has also been demonstrated that third-generation tyrosine kinase inhibitors (TKIs) are effective in extending the survival of patients with epidermal growth factor receptor (EGFR)-mutated NSCLC. Hence, the combination of SBRT with third-generation TKIs holds the potential to enhance treatment efficacy in patients with oligometastatic EGFR-mutated NSCLC. This review aimed to assess the possibility of combining SBRT with TKIs as an optimum treatment option for patients with oligometastatic EGFR-mutated NSCLC. Methods: We performed a narrative review by searching the PubMed, Web of Science, Elsevier and ClinicalTrials.gov databases for articles published in the English language from January 2009 to February 2024 and by reviewing the bibliographies of key references to identify important literature related to combining SBRT with third-generation TKIs in oligometastatic EGFR-mutated NSCLC. Key Content and Findings: This review aimed to assess the viability of combining SBRT and EGFR-TKIs in oligometastatic EGFR-mutated NSCLC. Current clinical trials suggest that the combined therapies have better progression free survival (PFS) when using SBRT as either concurrent with EGFR-TKIs or consolidated with EGFR-TKIs. Furthermore, research with third-generation EGFR-TKIs and SBRT combinations has demonstrated tolerable toxicity levels without significant additional adverse effects as compared to prior therapies. However, further clinical trials are required to establish its effectiveness. Conclusions: The combined approach of SBRT and TKIs can effectively impede the progression of oligometastatic NSCLC in patients harboring EGFR mutations and, most notably, can prolong progression-free survival rates. However, the feasibility of combining SBRT with third-generation TKIs in clinical trials remains unclear.
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While Kawasaki disease (KD) induced coronary artery aneurysms (KD CAAs) in children are well studied, the features and prognosis of non-KD induced CAAs (non-KD CAAs) in the pediatric population are poorly documented. This case series study is to analyze the etiology and prognosis of non-KD CAAs in children and compare the characteristics of non-KD CAAs and KD CAAs. Non-KD CAA and KD CAA cases at our department from January 2022 to December 2023 were retrospectively collected. Etiologies and prognosis of non-KD CAAs were analyzed. Furthermore, demographic data, biochemical parameters and outcomes between children with Non-KD CAAs and children with KD CAAs were comparatively studied. Fifteen children with non-KD CAAs with a median age of 6 years and 117 children with KD CAAs with a median age of 2.0 years (p = 0.022) were included in this study. The causes of non-KD CAAs include: unknown etiologies (2 cases), coronary artery structural abnormalities (4), Takayasu arteritis (2), virus infection (2), cardiomyopathy (2), aplastic anemia with agranulocytosis (1), ANCA-associated vasculitis (1), and mucopolysaccharidosis (1). In the non-KD CAA group, there were a total of 19 CAAs with 3 being giant, 5 medium, and 11 small; 4 patients had complete CAA regression; an infant with a fistula between the right coronary artery and the coronary sinus complicated with cardiac enlargement died of heart failure. The KD group had significantly higher levels of CRP, white cells counts and ESR with zero mortality. Non-KD CAA cases had a significantly lower regression rate than KD-CAA cases (26.7% vs 66.7%, p = 0.004), and the probability of CAA regression in non-KD patients was 0.341 of that in KD patients (p = 0.006, OR = 0.341, 95% CI: 0.179-0.647). CONCLUSIONS: Various etiologies for Non-KD CAAs are identified. Patients with Non-KD CAAs were observed to have lower inflammatory indexes but poorer recovery than patients with KD CAAs. Therapeutic strategies different than those for KD may be needed for non-KD CAAs. WHAT IS KNOWN: ⢠Coronary artery aneurysm (CAA) in children is most commonly induced by Kawasaki disease (KD CAA), with a 50 ~ 70% regression rate in 1 to 2 years. ⢠CAA induced by diseases other than KD (non-KD CAA) in children is rare and its prognosis remains largely unknown. WHAT IS NEW: ⢠Most non-KD CAA cases are caused by coronary artery structural malformations. ⢠Non-KD CAA in children has poorer prognosis and lower regression rate compared with KD CAA. ⢠In addition to guideline directed anti-platelet and anti-coagulant therapies, treatments targeting the causal factor are necessary for non-KD CAA.
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Aneurisma Coronario , Síndrome Mucocutáneo Linfonodular , Humanos , Aneurisma Coronario/etiología , Aneurisma Coronario/diagnóstico , Estudios Retrospectivos , Masculino , Femenino , Síndrome Mucocutáneo Linfonodular/complicaciones , Preescolar , Pronóstico , Niño , LactanteRESUMEN
As the most abundant messenger RNA (mRNA) modification in mRNA, N 6-methyladenosine (m6A) plays a crucial role in RNA fate, impacting cellular and physiological processes in various tumor types. However, our understanding of the function and role of the m6A methylome in tumor heterogeneity remains limited. Herein, we collected and analyzed m6A methylomes across nine human tissues from 97 m6A sequencing (m6A-seq) and RNA sequencing samples. Our findings demonstrate that m6A exhibits different heterogeneity in most tumor tissues compared to normal tissues, which contributes to the diverse clinical outcomes in different cancer types. We also found that the cancer type-specific m6A level regulated the expression of different cancer-related genes in distinct cancer types. Utilizing a novel and reliable method called "m6A-express", we predicted m6A-regulated genes and revealed that cancer type-specific m6A-regulated genes contributed to the prognosis, tumor origin, and infiltration level of immune cells in diverse patient populations. Furthermore, we identified cell-specific m6A regulators that regulate cancer-specific m6A and constructed a regulatory network. Experimental validation was performed, confirming that the cell-specific m6A regulator CAPRIN1 controls the m6A level of TP53. Overall, our work reveals the clinical relevance of m6A in various tumor tissues and explains how such heterogeneity is established. These results further suggest the potential of m6A for cancer precision medicine for patients with different cancer types.
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Background: The association of Remnant cholesterol (RC) with renal function and its progression in patients with Type 2 diabetes (T2DM) related chronic kidney disease (CKD) remains unclear. Methods: 8,678 patients with T2DM-related CKD were included in cross-sectional analysis, and 6,165 patients were enrolled in longitudinal analysis and followed up for a median of 36.0 months. The outcomes were renal composite endpoint event and rapid progression of renal function. Results: 24.54% developed a renal composite endpoint event, and 27.64% rapid progression of renal function. RC levels above 0.56 mmol/L independently increased the risk of both renal composite endpoint (HR, 1.17; 95% CIs, 1.03-1.33) and rapid progression of renal function (OR, 1.17; 95% CIs, 1.01- 1.37). TG levels above 1.65 mmol/L only increased the risk of renal composite endpoint (HR, 1.16; 95% CIs, 1.02 -1.32). TC levels above 5.21 mmol/L increased the risk of renal composite endpoint (HR, 1.14; 95% CIs, 1.01-1.29) only in patients with proteinuria≥0.5g/d. Conversely, HDL-C levels below 1.20 mmol/L or above 1.84 mmol/L increased the risk of rapid progression of renal function (OR, 0.88; 95% CIs, 0.70 -0.99) in patients with proteinuria<0.5g/d (all P<0.05). Conclusion: In patients with T2DM-related CKD, RC was an independent risk factor for progression of renal function, and maintaining it below 0.56 mmol/L could reduce the risk of renal function progression.
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Colesterol , Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Progresión de la Enfermedad , Insuficiencia Renal Crónica , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/sangre , Masculino , Femenino , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/metabolismo , Persona de Mediana Edad , Colesterol/sangre , Estudios Transversales , Anciano , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/fisiopatología , Tasa de Filtración Glomerular , Estudios Longitudinales , Estudios de Seguimiento , Riñón/fisiopatología , Riñón/metabolismo , Factores de RiesgoRESUMEN
OBJECTIVE: We conducted this study to determine the impact of serum glycosaminoglycan hyaluronan (HA) on the prognosis of coronavirus disease 2019 (COVID-19). METHODS: A total of 497 hospitalized patients with COVID-19 were included. Patients were divided into two subgroups based on the severity of infection: mild (n=344) and severe (n=153). The levels of HA, lymphocyte count, C-reactive protein (CRP), ferritin, interleukin 6 (IL-6), and D-dimer were measured and the correlation of these parameters with the prognosis of COVID-19 was assessed. RESULTS: The mean HA level of the severe group was significantly higher than that of the mild group (204.4 ng/mL versus 850.6 ng/mL, P<0.01). In receiver operating characteristic curve analysis, an HA level ≥607.8 ng/mL predicted severe COVID-19 with a sensitivity of 62.3% and specificity of 88.6%. Multivariate regression analysis demonstrated that serum HA level was a significant predictor of disease severity (odds ratio=60.56, P<0.01). CONCLUSION: Our findings show that higher serum HA concentrations are associated with severe COVID-19 disease. Early analysis of HA level in patients with COVID-19 might effectively predict disease severity.
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COVID-19 , Ácido Hialurónico , Índice de Severidad de la Enfermedad , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Proteína C-Reactiva/análisis , COVID-19/sangre , COVID-19/diagnóstico , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Ácido Hialurónico/sangre , Interleucina-6/sangre , Recuento de Linfocitos , Pronóstico , Estudios Retrospectivos , Curva ROCRESUMEN
OBJECTIVE: The specific anatomic characteristics of the right internal spermatic vein (ISV) are pivotal factors in embolism failure. However, the inherent angles and configurations of the right ISV remain incompletely explored. This study aimed to address this gap by conducting a thorough investigation into the specific anatomic characteristics of the right ISV using imaging analysis in southwest China. METHODS: This retrospective study analyzed the imaging data of 1000 male patients who underwent multidetector spiral computed tomography (MCT). Anatomic characteristics of the right ISV, including position, type, distance, and angle, were also evaluated. RESULTS: The most common anatomic type (87.8%) of the right ISV was direct drainage into the inferior vena cava, with 90% of the angles below 25.7°. There were 22 cases (2.2%) with parallel right spermatic veins. In the axial plane, the right ISV (86.4%) was located in the third and fourth quadrants. The diameter at the entrance of the right ISV ranged from 2.7-3.8 mm. When the right ISV drained into the inferior vena cava, 83% of cases were located within 40 mm distance below the ostium of the right renal vein, while during draining into the right renal vein, the average distance from the main vein was 6.3 mm. CONCLUSION: This study concluded that MCT can be used to evaluate the anatomical characteristics of the right ISV. The optimal interventional approach was through the jugular vein route to locate the ISV opening and improve the success rate of the embolization.
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The progress of proton exchange membrane fuel cells (PEMFCs) in the clean energy sector is notable for its efficiency and eco-friendliness, although challenges remain in terms of durability, cost and power density. The oxygen reduction reaction (ORR) is a key sluggish process and although current platinum-based catalysts are effective, their high cost and instability is a significant barrier. Single-atom catalysts (SACs) offer an economically viable alternative with comparable catalytic activity for ORR. The primary concern regarding SACs is their operational stability under PEMFCs conditions. In this article, we review current strategies for increasing the catalytic activity of SACs, including increasing active site density, optimizing metal center coordination through heteroatom doping, and engineering porous substrates. To enhance durability, we discuss methods to stabilize metal centers, mitigate the effects of the Fenton reaction, and improve graphitization of the carbon matrix. Future research should apply computational chemistry to predict catalyst properties, develop in situ characterization for real-time active site analysis, explore novel catalysts without the use of platinum-based catalysts to reduce dependence on rare and noble metal, and investigate the long-term stability of catalyst under operating conditions. The aim is to engineer SACs that meet and surpass the performance benchmarks of PEMFCs, contributing to a sustainable energy future.
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The degree of the carbohydrate antigen 125 (CA-125) level in serum is positively correlated with the severity of ovarian cancer. In this study, a facile photoelectrochemical (PEC) immunoassay was devised for sensitive detection of CA-125 employing enzyme-catalyzed precipitation to weaken the photocurrent of hollow porous In2O3 nanotubes incorporating CdS nanoparticles. Upon the addition of the target analyte, horseradish peroxidase (HRP) enriches as a result of the formation of the sandwich immunocomplex, which can catalyze the conversion of 4-chloro1-naphthol (4-CN) to benzo-4-chlorohexadienone (4-CD) employing H2O2 as a cofactor. The as-produced insoluble precipitate acts as an obstacle to hinder the absorption of visible light by photoactive materials, thereby resulting in a decrease in photocurrent. Moreover, the weakened signal can be easily read out by a digital multimeter (DMM), advancing the convenience of the detection system. The preliminary analysis data indicate that the PEC immunoassay shows an efficient response to CA-125 levels ranging from 0.1 to 100 U mL-1 with a limit of detection (LOD) as low as 0.046 U mL-1 (S/N = 3). Most importantly, the proposed portable method has shown satisfactory performance in terms of selectivity, reproducibility, stability, and analysis in complex biological matrices.
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Antígeno Ca-125 , Técnicas Electroquímicas , Antígeno Ca-125/sangre , Humanos , Inmunoensayo/métodos , Técnicas Electroquímicas/métodos , Límite de Detección , Peroxidasa de Rábano Silvestre/química , Compuestos de Cadmio/química , Femenino , Sulfuros/química , Nanotubos/química , Peróxido de Hidrógeno/química , Naftoles/química , Neoplasias Ováricas/sangre , Procesos FotoquímicosRESUMEN
BACKGROUND: Inflammatory bowel disease (IBD) represents a significant global health challenge, and there is an urgent need to explore novel therapeutic interventions. Natural products have demonstrated highly promising effectiveness in the treatment of IBD. PURPOSE: This study systematically reviews the latest research advancements in leveraging natural products for IBD treatment. METHODS: This manuscript strictly adheres to the PRISMA guidelines. Relevant literature on the effects of natural products on IBD was retrieved from the PubMed, Web of Science and Cochrane Library databases using the search terms "natural product," "inflammatory bowel disease," "colitis," "metagenomics", "target identification", "drug delivery systems", "polyphenols," "alkaloids," "terpenoids," and so on. The retrieved data were then systematically summarized and reviewed. RESULTS: This review assessed the different effects of various natural products, such as polyphenols, alkaloids, terpenoids, quinones, and others, in the treatment of IBD. While these natural products offer promising avenues for IBD management, they also face challenges in terms of clinical translation and drug discovery. The advent of metagenomics, single-cell sequencing, target identification techniques, drug delivery systems, and other cutting-edge technologies heralds a new era in overcoming these challenges. CONCLUSION: This paper provides an overview of current research progress in utilizing natural products for the treatment of IBD, exploring how contemporary technological innovations can aid in discovering and harnessing bioactive natural products for the treatment of IBD.