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BACKGROUND: The progression of atherosclerosis in small and medium-sized vessels has been associated with Type 2 diabetes (T2D). However, the influence of T2D on postoperative vascular remodeling and arteriovenous fistula (AVF) maturation is inconclusive. Besides, hemodynamic changes of postoperative vessel are also associated with AVF maturation. This study is intended to investigate the link between T2D and the occurrence of AVF non-maturation, as well as to delve into the impact of postoperative vascular hemodynamic parameters in this process. METHODS: A total of 477 hemodialysis patients, with or without type 2 diabetes, underwent AVF creation at Beijing Haidian Hospital (Haidian Section of Pecking University Third Hospital) from August 2018 to March 2022 were collected, and were followed for 1-5 years. Logistic regression was applied to analyze the association of T2D, postoperative vascular hemodynamic parameters with the risk of AVF non-maturation. To verify the stability of the results, the sensitivity analyses were performed using propensity scores to match patients. We further investigated the regulatory role of the postoperative vascular hemodynamics. RESULTS: There were 173 patients with T2D and 304 patients without T2D in this study. The maturation rate in T2D and non-T2D group was 47.977% and 63.816%, respectively. The findings of logistic regression analysis suggested that T2D significantly increased the risk of AVF immaturity [OR 1.716 (1.019-2.890), P = 0.042]. Besides, T2D was associated with the restriction of postoperative vascular hemodynamic parameters changes, including with decreased diameter of forearm cephalic radial artery and dilation rate of radial artery. The result of logistic regression analysis indicated that cephalic vein diameter at 1-month [0.402 (0.237-0.681), P = 0.001] and cephalic vein diameter at 2-month [0.501 (0.355-0.708), P < 0.001] were independently correlated with AVF maturation. Besides, the results of sensitivity analysis were consistent with that of logistic regression analysis. Moreover, the mediating effects of cephalic vein diameter were significant. CONCLUSION: Our findings discovered that T2D significantly increased the risk of arteriovenous fistula non-maturation, which was mainly mediated by the changes of cephalic vein diameter.
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BACKGROUND: The complex etiology of Ischemia-Reperfusion Injury (IRI) induced by liver transplantation (LT) and the "one-target-focused" method limit the development of effective therapeutic interventions. We aimed to reveal the specific active ingredients and mechanisms involved in the Chinese herb Scutellaria baicalensis Georgi (SBG) in alleviating IRI in LT. METHODS: The active ingredients and potential macromolecular targets of SBG were screened through related databases. The differentially expressed genes of LT were obtained from GSE151648. The protein-protein interaction network was constructed by the STRING database, and Cytoscape 3.7.1 was used to construct a compound-target-disease network. GO and KEGG enrichment analyses were performed on the DAVID database. Finally, the main active components of SBG and the corresponding mechanisms were verified in a donation after circulatory death (DCD) rat LT model. RESULTS: Thirty-two active ingredients of SBG and their targets were identified, and a total of 38 intersection targets were obtained. GO function and KEGG pathway enrichment analyses demonstrated that the plasma membrane and its components play an important role. Molecular docking showed baicalein, the core component of SBG, had a strong binding ability to all hub targets. Next, in DCD rats, baicalein was proven to improve liver function, alleviate pathological injury and apoptosis, and increase the survival rate. Baicalein also significantly affected the expression of 7 hub genes. Furthermore, baicalein could inhibit ferroptosis by inhibiting phospholipid peroxidation. CONCLUSION: Baicalein, the main component of SBG, could alleviate IRI, affect the expression of hub genes, and inhibit ferroptosis in LT.
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OBJECTIVES: This study aimed to evaluate the efficacy of adjuvant chemotherapy (AC) in patients with different midpoint-radiotherapy (mid-RT) Epstein-Barr virus (EBV) DNA plasma loads for locoregionally advanced nasopharyngeal carcinoma (NPC), and to provide decision-making regarding the use of AC. MATERIALS AND METHODS: A total of 675 consecutive patients diagnosed with stage III-IVa NPC were enrolled in this study. All patients underwent concurrent chemoradiotherapy (CCRT), either with or without induction chemotherapy or AC, or a combination of both. The primary endpoint of this study was progression-free survival (PFS). RESULTS: Among the 675 enrolled patients, 248 (36.7 %) received AC and 427 (63.3 %) were only observed after CCRT. In total, 149 (22.1 %) patients had detectable mid-RT EBV DNA levels, whereas 526 (77.9 %) had undetectable mid-RT EBV DNA levels. Patients with detectable mid-RT EBV DNA had worse 5-year PFS than those with undetectable mid-RT EBV DNA (74.8 % vs. 81.9 %, P = 0.045). AC group showed significantly better 5-year PFS than observation in patients with detectable mid-RT EBV DNA (82.8 % vs. 66.8 %; HR, 0.480; 95 % CI 0.250-0.919, P = 0.027). Multivariate analyses demonstrated that the treatment methods (AC vs. observation) were independent prognostic factors for PFS (HR, 0.37; 95 % CI 0.19-0.74, P = 0.005). However, in patients with undetectable mid-RT EBV DNA (5-year PFS: HR 0.873, 95 % CI 0.565-1.349, P = 0.52), AC group showed no survival benefit for observation. CONCLUSION: AC could reduce the risk of disease progression compared to observation in patients with detectable mid-RT EBV DNA. Our findings suggest that AC is effective in patients at a high risk of treatment failure.
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ADN Viral , Herpesvirus Humano 4 , Humanos , Masculino , Femenino , Persona de Mediana Edad , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , ADN Viral/sangre , Quimioterapia Adyuvante/métodos , Adulto , Anciano , Carga Viral , Neoplasias Nasofaríngeas/virología , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/tratamiento farmacológico , Quimioradioterapia/métodos , Infecciones por Virus de Epstein-Barr , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/virología , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/tratamiento farmacológico , Adulto Joven , AdolescenteRESUMEN
Ischemia-reperfusion injury (IRI) can seriously affect graft survival and prognosis and is an unavoidable event during liver transplantation. Ferroptosis is a novel iron-dependent form of cell death characterized by iron accumulation and overwhelming lipid peroxidation; it differs morphologically, genetically, and biochemically from other well-known cell death types (autophagy, necrosis, and apoptosis). Accumulating evidence has shown that ferroptosis is involved in the pathogenesis of hepatic IRI, and targeting ferroptosis may be a promising therapeutic approach. Here, we review the pathways and phenomena involved in ferroptosis, explore the associations and implications of ferroptosis and hepatic IRI, and discuss possible strategies for modulating ferroptosis to alleviate the hepatic IRI.
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ETHNOPHARMACOLOGICAL RELEVANCE: Huangqin Tang (HQT), a traditional Chinese medicine formula, is commonly used in clinical practice for the treatment of inflammatory bowel diseases. It has been reported that HQT exerts antitumor effects on colitis-associated colorectal cancer (CAC). However, the mechanism by which HQT interferes with the inflammation-to-cancer transformation remains unclear. AIMS OF THE STUDY: The purpose of this study was to dynamically evaluate the efficacy of HQT in alleviating or delaying CAC and to reveal the underlying mechanism. METHODS: We established a mouse model of CAC using azoxymethane combined with 1.5% dextran sodium sulphate. The efficacy of HQT was evaluated based on pathological sections and serum biochemical indices. Subsequently, amino acids (AAs) metabolism analyses were performed using ultra-performance liquid chromatography-tandem mass spectrometry, and the phosphatidylinositol 3 kinase/protein kinase B/mechanistic target of rapamycin (PI3K/AKT/mTOR) pathway was detected by western blotting. RESULTS: The data demonstrated that HQT could alleviate the development of CAC in the animal model. HQT effectively reduced the inflammatory response, particularly interleukin-6 (IL-6), in the inflammation induction stage, as well as in the stages of proliferation initiation and tumorigenesis. During the proliferation initiation and tumorigenesis stages, immunohistochemistry staining showed that the expression of the proliferation marker Ki67 was reduced, while apoptosis was increased in the HQT group. Accordingly, HQT substantially decreased the levels of specific AAs in the colon with CAC, including glutamic acid, glutamine, arginine, and isoleucine. Furthermore, HQT significantly inhibited the activated PI3K/AKT/mTOR pathway, which may contribute to suppression of cell proliferation and enhancement of apoptosis. CONCLUSION: HQT is effective in alleviating and delaying the colon "inflammation-to-cancer". The mechanism of action may involve HQT maintained AAs metabolism homeostasis and regulated PI3K/AKT/mTOR pathway, so as to maintain the balance between proliferation and apoptosis, and then interfere in the occurrence and development of CAC.
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Aminoácidos , Neoplasias Asociadas a Colitis , Sulfato de Dextran , Medicamentos Herbarios Chinos , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Serina-Treonina Quinasas TOR , Animales , Serina-Treonina Quinasas TOR/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Transducción de Señal/efectos de los fármacos , Masculino , Neoplasias Asociadas a Colitis/tratamiento farmacológico , Fosfatidilinositol 3-Quinasas/metabolismo , Ratones , Azoximetano/toxicidad , Modelos Animales de Enfermedad , Homeostasis/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Ratones Endogámicos C57BL , Colitis/tratamiento farmacológico , Colitis/inducido químicamente , Colitis/complicaciones , Colitis/metabolismo , Apoptosis/efectos de los fármacos , Fosfatidilinositol 3-Quinasa/metabolismo , Proliferación Celular/efectos de los fármacosRESUMEN
Diabetes, particularly Type 2 Diabetes Mellitus (T2DM), is a chronic metabolic disorder with high and increasing global prevalence, characterized by insulin resistance and inadequate insulin secretion. Despite advancements in novel drug delivery systems, widespread and systematic treatment of advanced glycation end products (AGEs) remains challenging due to issues like drug toxicity, low water solubility, and uncontrolled release. Thus, developing nanoplatforms with controlled release capabilities has become a major research focus. Due to its excellent biocompatibility and drug delivery properties, chitosan has attracted considerable attention as a typical biopolymer. In this study, we designed and synthesized an intelligent fluorescence-pH sensitive nanopolymer material using chitosan. We loaded drug 1 and chromium phthalocyanine (CrPc) into folic acid-conjugated carboxymethyl chitosan (FA-CMCS) nanocarriers, forming FA-CMCS@1-CrPc. Comprehensive characterization of FA-CMCS@1-CrPc was conducted using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), thermal gravimetric analysis (TGA), and gas adsorption analysis (BET). The results indicate that the nanomaterial was successfully synthesized and exhibits excellent specific surface area, biocompatibility, and fluorescence response. Further research revealed that FA-CMCS@1-CrPc not only achieved controlled drug release but also could regulate drug release by adjusting pH. Additionally, due to its strong fluorescence performance, the nanomaterial demonstrated higher detection sensitivity, especially for monitoring the release of 5% trace drugs. An in vitro model of insulin-resistant cells was established to evaluate the effects of the drug delivery system on glucose degradation and AGE-RAGE regulation, providing a foundation for the development of new T2DM drugs.
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Myostatin (MSTN) has long been recognized as a critical regulator of muscle mass. Recently, there has been an increasing interest in its role in metabolism. In our study, we specifically knocked out MSTN in brown adipose tissue (BAT) from mice (MSTNΔUCP1) and found that the mice gained more weight than controls when fed a high-fat diet, with progressive hepatosteatosis and impaired skeletal muscle activity. RNA-seq analysis indicated signatures of mitochondrial dysfunction and inflammation in the MSTN-ablation BAT. Further studies demonstrated that the the Kruppel-like factor 4 (KLF4) was responsible for the metabolic phenotypes observed, while FGF21 contributed to the microenvironment communication between adipocytes and macrophages induced by the loss of MSTN. Moreover, the MSTN-SMAD2/3-p38 signaling pathway mediated the expression of KLF4 and FGF21 in adipocytes. In summary, our findings suggest that brown adipocytes-derived MSTN regulates BAT thermogenesis via autocrine and paracrine effects on adipocytes or macrophages, ultimately regulating systemic energy homeostasis.
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Objective: The aim of this study was to observe the remission of primary membranous nephropathy (PMN) and evaluate the efficacy of tacrolimus (TAC) monotherapy for PMN in comparison with TAC combined with a low-dose glucocorticoid (GC) protocol (TAC + GC). Methods: This was tested in a prospective monocentric observational trial of 70 patients with PMN, of whom 34 received TAC (0.05-0.075 mg/kg/day) or 36 received TAC (0.05-0.075 mg/kg/day) and GC (0.3-0.5 mg/kg/day of prednisone). Results: At 3, 6, 9, and 12 months of treatment, the effective rates in the TAC group and the TAC + GC group were similar (P > 0.05). The urinary protein quantification was reduced in patients under both therapeutic protocols, and the differences in the proteinuria quantification at 3, 6, 9, and 12 months of treatment were not statistically significant between the two groups (P > 0.05). The overall incidence of adverse reactions in the TAC group was lower than that in the TAC + GC group (23.5% < 36.1%), and the difference was statistically significant (P < 0.05). Conclusion: TAC monotherapy for PMN could effectively reduce urinary protein quantification and increase serum albumin levels. Compared with TAC + GC, TAC monotherapy for PMN had no difference in efficacy and fewer incidences of adverse reactions.
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Demand for the exploration of botanical pesticides continues to increase due to the detrimental effects of synthetic chemicals on human health and the environment and the development of resistance by pests. Under the guidance of a bioactivity-guided approach and HSQC-based DeepSAT, 16 coumarin derivatives were discovered from the leaves of Ailanthus altissima (Mill.) Swingle, including seven undescribed monoterpenoid coumarins, three undescribed monoterpenoid phenylpropanoids, and two new coumarin derivatives. The structure and configurations of these compounds were established and validated via extensive spectroscopic analysis, acetonide analysis, and quantum chemical calculations. Biologically, 5 exhibited significant antifeedant activity toward the Plutella xylostella. Moreover, tyrosinase being closely related to the growth and development of larva, the inhibitory potentials of 5 against tyrosinase was evaluated in vitro and in silico. The bioactivity evaluation results highlight the prospect of 5 as a novel category of botanical insecticide.
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Ailanthus , Cumarinas , Insecticidas , Extractos Vegetales , Hojas de la Planta , Hojas de la Planta/química , Animales , Cumarinas/farmacología , Cumarinas/química , Ailanthus/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Insecticidas/química , Insecticidas/farmacología , Estructura Molecular , Larva/efectos de los fármacos , Larva/crecimiento & desarrollo , Mariposas Nocturnas/efectos de los fármacos , Mariposas Nocturnas/crecimiento & desarrollo , Monofenol Monooxigenasa/antagonistas & inhibidores , Monofenol Monooxigenasa/metabolismo , Bioensayo , Monoterpenos/farmacología , Monoterpenos/química , Conducta Alimentaria/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/químicaRESUMEN
Hepatocellular carcinoma (HCC) ranks as the second leading cause of cancer-related deaths globally. Disulfidptosis is a newly identified form of regulated cell death that is induced by glucose starvation. However, the clinical prognostic characteristics of disulfidptosis-associated genes in HCC remain poorly understood. We conducted an analysis of the single-cell datasets GSE149614 and performed weighted co-expression network analysis (WGCNA) on the Cancer Genome Atlas (TCGA) datasets to identify the genes related to disulfidptosis. A prognostic model was constructed using univariate COX and Lasso regression. Survival analysis, immune microenvironment analysis, and mutation analysis were performed. Additionally, a nomogram associated with disulfidptosis-related signature was constructed to identify the prognosis of HCC patients. Patients with HCC in the TCGA and GSE14520 datasets were categorized using a disulfidptosis-related model, revealing significant differences in survival times between the high- and low-disulfidptosis groups. High-disulfidptosis patients exhibited increased expression of immune checkpoint-related genes, implying that immunotherapy and certain chemotherapies may be beneficial for them. Meanwhile, the ROC and decision curves analysis (DCA) indicated that the nomogram has satisfying prognostic efficacy. Moreover, the experimental results of GATM in this prognostic model indicated that GATM is low expressed in HCC tissues, and GATM knockdown promotes the proliferation and migration of HCC cells. By analyzing single-cell and bulk multi-omics sequencing data, we developed a prognostic signature related to disulfidptosis and explored the relationship between high- and low-disulfidptosis groups in HCC. This study offers a novel reference for gaining a deeper understanding of the role of disulfidptosis in HCC.
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BACKGROUND: In acute kidney injury (AKI), ferroptosis is the main mechanism of cell death in the renal tubular epithelium. Baicalein, a traditional Chinese medicine monomer, plays a protective role in various kidney diseases; however, the effect of baicalein on ferroptosis in AKI still needs further exploration. PURPOSE: In this study, we explored the role of baicalein and its specific mechanism in mediating ferroptosis in cisplatin-induced AKI. METHODS: We used a cisplatin-induced AKI model to study the effects of baicalein on renal tissue and tubular epithelial cell injury. The effects of baicalein on tubular epithelial cell ferroptosis were detected in cisplatin-induced AKI and further verified by folic acid-induced AKI. The Swiss Target Prediction online database was used to predict the possible mechanism by which baicalein regulates ferroptosis, and the specific target proteins were further verified. Molecular docking and SPR were used to further determine the binding potential of baicalein to the target protein. Finally, RNA interference (RNAi) technology and enzymatic inhibition were used to determine whether baicalein regulates ferroptosis through target proteins. RESULTS: Baicalein alleviated cisplatin- and folic acid-induced renal dysfunction and pathological damage and improved cisplatin-induced HK2 cell injury. Mechanistically, baicalein reduced the expression of 12-lipoxygenase (ALOX12), which inhibits phospholipid peroxidation and ferroptosis in AKI. Molecular docking and SPR demonstrated direct binding between baicalein and ALOX12. Finally, we found that silencing ALOX12 had a regulatory effect similar to that of baicalein. Comparable results were also obtained with the ALOX12 inhibitor ML355. CONCLUSION: This was the first study to confirm that baicalein regulates ferroptosis both in vitro and in vivo in cisplatin-induced AKI and to verify the regulatory effect of baicalein in folic acid-induced AKI. Our results reveal the critical role of ALOX12 in kidney damage and ferroptosis caused by cisplatin and emphasize the regulatory effect of baicalein on renal tubular epithelial cell ferroptosis mediated by ALOX12. Baicalein is an effective drug for treating AKI, and ALOX12 is a potential drug target.
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Lesión Renal Aguda , Araquidonato 12-Lipooxigenasa , Cisplatino , Ferroptosis , Flavanonas , Animales , Humanos , Masculino , Ratones , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/metabolismo , Araquidonato 12-Lipooxigenasa/metabolismo , Línea Celular , Cisplatino/efectos adversos , Células Epiteliales/efectos de los fármacos , Ferroptosis/efectos de los fármacos , Flavanonas/farmacología , Ácido Fólico/farmacología , Túbulos Renales/efectos de los fármacos , Ratones Endogámicos C57BL , Simulación del Acoplamiento MolecularRESUMEN
Context: Shenyu Ningshen (SYNS) tablet is the first pure Chinese medicinal small compound preparation approved for clinical trials for the treatment of depression in China. Clinical experiments confirmed that the formulation had a significant Improvement effect against depression due to the deficiency of both qi and yin. It has been shown to exhibit noticeable anti-inflammatory effect in an animal model of depression. Our previous study showed that SYNS could effectively inhibit the inflammatory response in a depression model. Aim of the study: The purpose of this study was to investigate the protective effects of SYNS on neurons and explore whether the underlying mechanism was associated with A1s. Materials and methods: The depression model of solitary raising-chronic restraint stress (CRS) rats was established; body weight examination, sugar water preference test, open field test, and histological analysis were performed to preliminarily verify the efficacy of the formulation. Subsequently, neuronal nucleus (NeuN) and synaptic-associated proteins (MAP2 and PSD95) were labeled, and the protective effect of SYNS on hippocampal neurons was observed based on the fluorescence intensity of the above indicators. Western blotting, histological examination, and immunofluorescence were used to evaluate the inhibitory effects of SYNS on neuroinflammation and activation of A1s in CRS depression model. Results: SYNS improved behavioral indicators such as weight loss, pleasure loss, and reduced exercise volume in CRS rat model. SYNS restored the CRS-induced histopathological changes in the hippocampus. SYNS showed a certain degree of protective effect on synapses. Further, SYNS inhibited the activation of A1s by inhibiting neuroinflammatory factors in the hippocampus. Conclusion: Our results showed that SYNS had a certain degree of neuroprotective effect, which might be related to its inhibition of the inflammatory response and A1s.
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Pathogens detected by metagenomic next-generation sequencing (mNGS) and the laboratory blood culture flask method were compared to understand the advantages and clinical significance of mNGS assays in the etiological diagnosis of peritoneal dialysis-associated peritonitis (PDAP). The study involved a total of 37 patients from the hospital's peritoneal dialysis centre, six of whom were patients with non-peritoneal dialysis-associated peritonitis. Peritoneal dialysis samples were collected from the 37 patients, who were divided into two groups. One group's samples were cultured using conventional blood culture flasks, and the other samples underwent pathogen testing using mNGS. The results showed that the positive rate of mNGS was 96.77%, while that of the blood culture flask method was 70.97% (p < 0.05). A total of 29 pathogens were detected by mNGS, namely 24 bacteria, one fungus, and four viruses. A total of 10 pathogens were detected using the bacterial blood culture method, namely nine bacteria and one fungus. The final judgment of the PDAP's causative pathogenic microorganism was made by combining the clinical condition, response to therapy, and the whole-genome sequencing findings. For mNGS, the sensitivity was 96.77%, the specificity was 83.33%, the positive predictive value was 96.77%, and the negative predictive value was 83.33%. For the blood culture flask method, the sensitivity was 70.97%, the specificity was 100%, the positive predictive value was 100%, and the negative predictive value was 0%. In conclusion, mNGS had a shorter detection time for diagnosing peritoneal dialysis-related peritonitis pathogens, with a higher positive rate than traditional bacterial cultures, providing significant advantages in diagnosing rare pathogens.
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Objective: Obesity, hypertension and diabetes are high prevalent that are often associated with poor outcomes. They have become major global health concern. Little research has been done on the impact of lymphocyte-to-monocyte ratio (LMR) on outcomes in these patients. Thus, we aimed to explore the association between LMR and all-cause mortality in obese hypertensive patients with diabetes and without diabetes. Methods: The researchers analyzed data from the National Health and Nutrition Examination Survey (2001-2018), which included 4,706 participants. Kaplan-Meier analysis was employed to compare survival rate between different groups. Multivariate Cox proportional hazards regression models with trend tests and restricted cubic splines (RCS) analysis and were used to investigate the relationship between the LMR and all-cause mortality. Subgroup analysis was performed to assess whether there was an interaction between the variables. Results: The study included a total of 4706 participants with obese hypertension (48.78% male), of whom 960 cases (20.40%) died during follow-up (median follow-up of 90 months). Kaplan-Meier curves suggested a remarkable decrease in all-cause mortality with increasing LMR value in patients with diabetes and non-diabetes (P for log-rank test < 0.001). Moreover, multivariable Cox models demonstrated that the risk of mortality was considerably higher in the lowest quartile of the LMR and no linear trend was observed (P > 0.05). Furthermore, the RCS analysis indicated a non-linear decline in the risk of death as LMR values increased (P for nonlinearity < 0.001). Conclusions: Increased LMR is independently related with reduced all-cause mortality in patients with obese hypertension, regardless of whether they have combined diabetes.
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Diabetes Mellitus , Hipertensión , Linfocitos , Monocitos , Encuestas Nutricionales , Obesidad , Humanos , Masculino , Femenino , Hipertensión/complicaciones , Hipertensión/mortalidad , Hipertensión/epidemiología , Obesidad/complicaciones , Obesidad/mortalidad , Obesidad/sangre , Persona de Mediana Edad , Diabetes Mellitus/mortalidad , Diabetes Mellitus/epidemiología , Adulto , Estudios de Cohortes , Anciano , Estudios de SeguimientoRESUMEN
ABSTRACT: Chimeric antigen receptor (CAR) natural killer (NK) cells can eliminate tumors not only through the ability of the CAR molecule to recognize antigen-expressed cancer cells but also through NK-cell receptors themselves. This overcomes some of the limitations of CAR T cells, paving the way for CAR NK cells for safer and more effective off-the-shelf cellular therapy. In this study, CD70-specific (a pan-target of lymphoma) fourth-generation CAR with 4-1BB costimulatory domain and interleukin-15 (IL-15) was constructed and transduced into cord blood-derived NK cells by Baboon envelope pseudotyped lentiviral vector. CD70-CAR NK cells displayed superior cytotoxic activity in vitro and in vivo against CD19-negative B-cell lymphoma when compared with nontransduced NK cells and CD19-specific CAR NK cells. Importantly, mice that received 2 doses of CD70-CAR NK cells showed effective eradication of tumors, accompanied by increased concentration of plasma IL-15 and enhanced CAR NK cell proliferation and persistence. Our study suggests that repetitive administration-based CAR NK-cell therapy has clinical advantage compared with a single dose of CAR NK cells for the treatment of B-cell lymphoma.
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Antígenos CD19 , Ligando CD27 , Inmunoterapia Adoptiva , Interleucina-15 , Células Asesinas Naturales , Linfoma de Células B , Receptores Quiméricos de Antígenos , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Animales , Humanos , Ratones , Linfoma de Células B/terapia , Linfoma de Células B/inmunología , Receptores Quiméricos de Antígenos/inmunología , Receptores Quiméricos de Antígenos/metabolismo , Receptores Quiméricos de Antígenos/genética , Inmunoterapia Adoptiva/métodos , Antígenos CD19/inmunología , Ensayos Antitumor por Modelo de Xenoinjerto , Línea Celular Tumoral , Citotoxicidad InmunológicaRESUMEN
PURPOSE: To evaluate the influence of anisodamine injection at the Zusanli (ST36) on early postoperative recovery quality in patients who have undergone laparoscopic sleeve gastrectomy. MATERIALS AND METHODS: 141 patients undergoing laparoscopic sleeve gastrectomy were randomly divided into the control group (group C), the normal saline group (group S) and the anisodamine group (group A). Acupuncture point injections were administered after induction of general anesthesia. The quality of recovery-40 questionnaire (QoR-40) scores were documented preoperatively (D0) and on the 1st (D1), 3rd (D3) and 7th (D7) days postoperatively. Additional metrics included: the numerical rating scale (NRS) for pain, postoperative nausea and vomiting (PONV), assessment and analgesic consumption 24-h post-extubation and the initial postoperative times for ambulation and anal exhaust. Substance P (SP), ß-endorphin (ß-EP), motilin (MTL) and gastrin (GAS) were quantified at 24-h post-surgery. RESULTS: Compared with group C, group A demonstrated an elevation in QoR-40 scores and physical comfort dimensions during D1-3, and an increased pain scores during D1-7; group S exhibited an augmentation in QoR-40 scores and pain scores on D1 (p < 0.05). Compared with group S, group A improved QoR-40 scores on D1 and pain scores during D1-3 (p < 0.05). SP, ß-EP, MTL and GAS presented significant variances among the groups 24-h post-surgery (p < 0.05). There were significant differences between the groups in NRS pain scores and PONV scores at 24-h postoperatively, dosage of dizocin on the first postoperative day, and time to first anal defecation (p < 0.05). CONCLUSION: The administration of anisodamine via ST36 acupoint injections has been demonstrated to facilitate the recuperation of gastrointestinal functionality, to alleviate postoperative pain and nausea, and substantially to enhance the quality of early postoperative recovery.
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Cirugía Bariátrica , Laparoscopía , Obesidad Mórbida , Alcaloides Solanáceos , Humanos , Náusea y Vómito Posoperatorios , Puntos de Acupuntura , Obesidad Mórbida/cirugía , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & controlRESUMEN
OBJECTIVE: Benign prostatic hyperplasia (BPH) is common in elder men. The current study aims to identify differentially expressed genes (DEGs) in hyperplastic prostate and to explore the role of Nik related kinase (NRK) in BPH. METHODS: Four datasets including three bulk and one single cell RNA-seq (scRNA-seq) were obtained to perform integrated bioinformatics. Cell clusters and specific metabolism pathways were analyzed. The localization, expression and functional activity of NRK was investigated via RT-PCR, western-blot, immunohistochemical staining, flow cytometry, wound healing assay, transwell assay and CCK-8 assay. RESULTS: A total of 17 DEGs were identified by merging three bulk RNA-seq datasets. The findings of integrated single-cell analysis showed that NRK remarkably upregulated in fibroblasts and SM cells of hyperplasia prostate. Meanwhile, NRK was upregulated in BPH samples and localized almost in stroma. The expression level of NRK was significantly correlated with IPSS and Qmax of BPH patients. Silencing of NRK inhibited stromal cell proliferation, migration, fibrosis and EMT process, promoted apoptosis and induced cell cycle arrest, while overexpression of NRK in prostate epithelial cells showed opposite results. Meanwhile, induced fibrosis and EMT process were rescued by knockdown of NRK. Furthermore, expression level of NRK was positively correlated with that of α-SMA, collagen-I and N-cadherin, negatively correlated with that of E-cadherin. CONCLUSION: Our novel data identified NRK was upregulated in hyperplastic prostate and associated with prostatic stromal cell proliferation, apoptosis, cell cycle, migration, fibrosis and EMT process. NRK may play important roles in the development of BPH and may be a promising therapeutic target for BPH/LUTS.
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Péptidos y Proteínas de Señalización Intracelular , Próstata , Hiperplasia Prostática , Proteínas Serina-Treonina Quinasas , Masculino , Humanos , Anciano , Próstata/metabolismo , Hiperplasia/metabolismo , Hiperplasia/patología , Hiperplasia Prostática/genética , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patología , FibrosisRESUMEN
BACKGROUND: Recent years have seen increasing attention to improving depressive symptoms through dietary intakes, yet the association between thiamine intake and depression remains unclear. The present study aimed to explore this association using data from an American cross-sectional study. METHODS: We explored the association of covariates, exposure, and outcome with logistic regression equations. Multivariable regression models were performed to further exclude confounding factors. To investigate nonlinear relationships, we employed restricted cubic splines. Recursive algorithms were utilized to identify inflection points. Additionally, we conducted stratified analyses by age and sex to uncover differences among subgroups. RESULTS: When all covariates were adjusted, the association between thiamine intake and depression was not statistically significant [0.93 (0.82, 1.07)]. In the linear trend test using Q1 as the reference, the ORs (95%CI) for Q2, Q3, and Q4 were 0.87 (0.73, 1.04), 0.83 (0.68, 1.00), and 0.92 (0.73, 1.16), which suggested that the association might be nonlinear. We then confirmed this nonlinear relationship with a restricted cubic spline, and the inflection point of 1.35 mg/day was calculated. Before the inflection point, the effect value of the relationship was 0.68 (0.53, 0.89). After the inflection point, no significant association was found [1.10 (0.92, 1.31)]. Stratified analyses revealed that this nonlinear relationship was consistent among women and individuals aged <60 years. DISCUSSION: In this cross-sectional study among American general adults, we found a nonlinear association between thiamine intake and depression and further observed differences by age and sex.
Asunto(s)
Depresión , Estado Nutricional , Adulto , Humanos , Femenino , Estudios Transversales , Depresión/epidemiología , Algoritmos , Tiamina , Encuestas NutricionalesRESUMEN
PURPOSE: The present research seeks to clarify the consequences of two specific preoperative oral carbohydrate (POC) amounts on insulin resistance (IR) and stomach evacuation in laparoscopic cholecystectomy (LC) patients. METHODS: A total of 129 patients set for elective LC procedures were randomly assigned to a control group (C, n = 45), a 200 mL POC group (P1, n = 42), and a 400 mL POC group (P2, n = 42). The C group was fasted from midnight until surgery, whereas the P1 and P2 groups received their respective carbohydrate volumes 2-4 h before anesthesia. Fasting blood glucose, insulin, and glucagon concentrations were measured at three junctures. IR metrics were derived by employing the homeostasis model assessment. Gastric volume was measured before anesthesia using gastric ultrasound. Inter-group comparisons included IR indicators, subjective comfort scores, and hemodynamic data. RESULTS: At T2, the C group exhibited reduced glucose concentrations compared to the P2 group (4.73 ± 0.64 vs. 5.26 ± 1.02 mmol/L, p < 0.05). The Perlas grading indicated that grade 1 was more prevalent in the P2 group than in the P1 and C groups (18 [42.9%] vs. 6 [14.3%] and 1 [2.2%], p < 0.05). Additionally, thirst and hunger metrics for the P2 group were notably reduced compared to the C group at both T2 and T3. CONCLUSION: Administering either 200 mL or 400 mL of carbohydrates 2-4 h pre-surgery had no detectable impact on IR or gastric volume in LC patients. TRIAL REGISTRATION: ChiCTR, ChiCTR2200065648. Registered January 13, 2023, http://www.chictr.org.cn .
Asunto(s)
Colecistectomía Laparoscópica , Resistencia a la Insulina , Humanos , Insulina , Estómago , CarbohidratosRESUMEN
Two surgically treated haematomyelia cases were documented. One dog and one cat were presented for acute progressive paraplegia following a fall from height incident. Neurological examinations suggested a L4-S3 myelopathy in both cases. Radiography and magnetic resonance imaging in both cases revealed no fracture or subluxation of the spine, but well-defined intramedullary mass lesions in lower lumbar regions compatible with haemorrhage and haematoma formation. Exploratory surgeries were performed over the lesions. Dark-red friable masses were removed via myelotomy. Histopathological examinations revealed organizing haematomas at the acute to subacute stage. Postoperatively, both cases improved and regained ambulation. The dog walked normally but remained urinary and faecal incontinent 9 months after the surgery. The cat was continent and ambulatory with a paraparetic gait 5 months after the surgery. In both cases, the outcomes and the patients' quality of life were considered satisfactory by the owners.