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BACKGROUND: In recent decades, China has experienced a rapid increase in the number of elderly individuals and life expectancy, as well as industrialization, which is associated with an increased prevalence of Parkinson's disease (PD). However, inconsistent results have recently been reported. Therefore, this study aimed to investigate the prevalence and distribution characteristics of PD among individuals aged 45 years and older. METHODS: Using data from the China Health and Retirement Longitudinal Study (CHARLS), we attempted to estimate the prevalence of PD and its distribution characteristics among 19,034 individuals aged 45 years and older residing in 446 communities/villages within 27 provinces/autonomous regions/municipalities in mainland China. Cases were established based on a doctor's previous diagnosis. Crude and age-adjusted prevalence rates were calculated and stratified by age, sex, area of residence, education level, marital status, and geographic region. Logistic regression models were used to identify risk factors associated with PD. RESULTS: We identified 178 patients with PD among 19,034 residents aged 45 years and older. The crude prevalence was 0.94%, and the age-adjusted prevalence was 0.82% for individuals aged 45 years and older. The prevalence of PD increased with age (P < 0.001). No significant differences were found in terms of sex, area of residence, or education level. Stratified by geographic region, the prevalence of PD was greater in North and Northwest China and lower in southern China (p < 0.001). Multiple regression analyses showed that age was a significant risk factor for PD. CONCLUSION: The prevalence of PD increased with age in the Chinese population.
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Enfermedad de Parkinson , Humanos , China/epidemiología , Masculino , Femenino , Anciano , Persona de Mediana Edad , Estudios Transversales , Estudios Longitudinales , Prevalencia , Enfermedad de Parkinson/epidemiología , Anciano de 80 o más Años , Factores de Riesgo , Jubilación/estadística & datos numéricosRESUMEN
Solid-state electrolytes (SSEs) based on sulfides have become a subject of great interest due to their superior Li-ion conductivity, low grain boundary resistance, and adequate mechanical strength. However, they grapple with chemical instability toward moisture hypersensitivity, which decreases their ionic conductivity, leading to more processing requirements. Herein, a Li9.8GeP1.7Sb0.3S11.8I0.2 (LGPSSI) superionic conductor is designed with a Li+ conductivity of 6.6 mS cm-1 and superior air stability based on hard and soft acids and bases (HSAB) theory. The introduction of optimal antimony (Sb) and iodine (I) into the Li10GeP2S12 (LGPS) structure facilitates fast Li-ion migration with low activation energy (Ea) of 20.33 kJ mol-1. The higher air stability of LGPSSI is credited to the strategic substitution of soft acid Sb into (Ge/P)S4 tetrahedral sites, examined by Raman and X-ray photoelectron spectroscopy techniques. Relatively lower acidity of Sb compared to phosphorus (P) realizes a stronger Sb-S bond, minimizing the evolution of toxic H2S (0.1728 cm3 g-1), which is â¼3 times lower than pristine LGPS when LGPSSI is exposed to moist air for 120 min. The NCA//Li-In full cell with a LGPSSI superionic conductor delivered the first discharge capacity of 209.1 mAh g-1 with 86.94% Coulombic efficiency at 0.1 mA cm-2. Furthermore, operating at a current density of 0.3 mA cm-2, LiNbO3@NCA/LGPSSI/Li-In cell demonstrated an exceptional reversible capacity of 117.70 mAh g-1, retaining 92.64% of its original capacity over 100 cycles.
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Cocrystal engineering, which involves the self-assembly of two or more components into a solid-state supramolecular structure through non-covalent interactions, has emerged as a promising approach to tailor the physicochemical properties of active pharmaceutical ingredient (API). Efficient coformer screening for cocrystal remains a challenge. Herein, a prediction strategy based on machine learning algorithms was employed to predict cocrystal formation and seven reliable models with accuracy over 0.890 were successfully constructed. Imatinib was selected as the model drug and the models established were applied to screen 31 potential coformers. Experimental verification results indicated RF-8 is the optimal model among seven models with an accuracy of 0.839. When the seven models were combined for coformer screening of Imatinib, the combinational model achieved an accuracy of 0.903, and eight new solid forms were observed and characterized. Benefiting from intermolecular interactions, the obtained multicomponent crystals displayed enhanced physicochemical properties. Dissolution and solubility experiments showed the prepared multicomponent crystals had higher cumulative dissolution rate and remarkably improved the solubility of imatinib, and IM-MC exhibited comparable solubility to Imatinib mesylate α form. Stability test and cytotoxicity results showed that multicomponent crystals exhibited excellent stability and the drug-drug cocrystal IM-5F exhibited higher cytotoxicity than pure API.
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Química Farmacéutica , Mesilato de Imatinib , Cristalización , Química Farmacéutica/métodos , SolubilidadRESUMEN
Affected by differences in the pharmacokinetics (PK) of lenalidomide, the toxicity of lenalidomide varies among different patients, with serious toxicity leading to dose reduction or discontinuation. The differences in the PK of lenalidomide may be related to factors such as patients' physiological characteristics, pathological characteristics and gene polymorphisms etc., which may also affect its toxicity. The aim of this study is to establish a population pharmacokinetic (PPK) model of lenalidomide and explore factors associated with the adverse events (AEs) of lenalidomide from a PK perspective. Blood samples were collected by opportunistic blood collection. Drug concentrations were determined by using HPLC/MS and genotype of ABCB1 3435 C > T (rs1045642), ABCB1 1236 A > G (rs1128503) and ABCB1 2677 A > C/T (rs2032582) was tested by the first-generation DNA sequencing technology. NONMEM software and SPSS 26.0 software were used respectively to establish PPK model of lenalidomide and explore the correlation between PK parameters and the incidence of serious AEs of lenalidomide. 51 patients were enrolled in the PPK study, and one-compartment model with first-order absorption and elimination agreed well with the observed data. The significant covariate affecting lenalidomide apparent volume of distribution (V/F) were the gene polymorphism of ABCB1 3435 C > T and diet. Safety studies could be conducted in 39 patients. The V/F value in patients suffering from serious AEs was significantly higher than that in others ( median = 67.04 L vs 37.17 L, P = 0.033). According to the covariates screened, the incidence of serious AEs was higher in patients with genotype CT or TT at ABCB1 3435 C > T locus than that in patients with genotype CC (P = 0.039). Additionally, V/F value was the highest in patients carrying genotype TT with postprandial medication, in whom the incidence of serious AEs was higher than others (P = 0.037). In conclusion, the genotype of ABCB1 3435 C > T locus and diet had pharmacokinetically relevant impact on lenalidomide, which may also be related to the incidence of serious AEs. Patients with gene variants of CT or TT at ABCB1 3435 C > T locus may be more susceptible to serious AEs, and monitoring of adverse reactions should be particularly strengthened in patients who carried genotype TT with postprandial medication.
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Subfamilia B de Transportador de Casetes de Unión a ATP , Pueblos del Este de Asia , Lenalidomida , Humanos , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , China , Genotipo , Lenalidomida/efectos adversos , Lenalidomida/farmacocinética , Polimorfismo de Nucleótido Simple , Pueblos del Este de Asia/genéticaRESUMEN
The leaves of Eucommia ulmoides are rich in bioactive constituents that have potential gastrointestinal benefits for animals. In aged laying hens, intestinal health issues contribute to a significant decline in egg-laying capacity during intermediate and later stages. It remains unclear whether E. ulmoides leaf extract (ELE) can improve intestinal health and enhance egg production in elderly laying hens, and the underlying mechanisms are yet to be elucidated. Therefore, we conducted a study with 480 laying hens (65 weeks old) randomly allocated into four groups: a control group fed with the basal diet, and three treatment groups supplemented with 500, 1,000, and 2,000 mg/kg of ELE, respectively. The primary active constituents of ELE include flavonoids, polysaccharides, terpenoids, and phenolic acids. Dietary supplementation with ELE at 1,000 mg/kg (ELE1000) significantly improved laying performance and egg quality compared to the other groups. ELE1000 stimulated the maturation of intestinal epithelial cells, increased villus height, and reduced crypt depth. It also influenced the levels of proteins associated with tight junctions (claudin-1 and claudin-2) and intestinal inflammatory factors (IL-6, IL-1ß, and IL-2) in different intestinal sections. Integrative analysis of serum metabolomics and gut microbiota revealed that ELE1000 improved nutrient metabolism by modulating amino acid and ubiquinone biosynthesis and influenced the abundance of intestinal microbiota by enriching pivotal genera such as Bacteroides and Rikenellaceae_RC9_gut_group. We identified 15 metabolites significantly correlated with both gut microbiota and laying performance, e.g., DL-methionine sulfoxide, THJ2201 N-valerate metabolite, tetracarbonic acid, etc. In conclusion, ELE1000 improved laying performance in elderly laying hens by affecting intestinal morphology, barrier function, microbiota, and serum metabolite profiles. These findings suggest that ELE can be a beneficial feed additive for extending the peak producing period in aged laying hens.
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Recently, the hybrid Broussonetia papyrifera (BP) has been extensively cultivated and predominantly utilized in ruminants because of its high protein and bioactive compound content. In the present study, the effects of an ethanolic extract of BP leaves (BPE, 200 mg/kg) on mitigating 2% dextran sodium sulfate (DSS)-induced intestinal inflammation in mice were evaluated. BPE is rich in flavonoids, polyphenols, and polysaccharides, and displays potent antioxidant and antibacterial activities against pathogenic strains such as Clostridium perfringens, Salmonella Typhimurium, and Salmonella enterica subsp. enterica in vitro. In a mouse study, oral administration of DSS resulted in weight loss, incidence of diarrhea, enlargement of the liver and spleen, impaired colonic morphology, downregulation of both gene and protein expression related to intestinal antioxidant (Nrf2) and barrier function (ZO-1), decreased diversity of colonic microbiota, and 218 differentially altered colonic metabolites; however, co-treatment with BPE did not restore these modified aspects except for the liver index and colonic bacterial diversity. The singular treatment with BPE did not manifest evident side effects in normal mice but induced a mild occurrence of diarrhea and a notable alteration in the colonic metabolite profile. Moreover, a single BPE administration augmented the abundance of the commensal beneficial bacteria Faecalibaculum and Akkermansia genera. Overall, the extract of BP leaves did not demonstrate the anticipated effectiveness in alleviating DSS-induced intestinal inflammation.
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Broussonetia , Colitis , Animales , Ratones , Antioxidantes/uso terapéutico , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/metabolismo , Colon/patología , Inflamación/patología , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Diarrea/tratamiento farmacológico , Sulfato de Dextran/toxicidad , Ratones Endogámicos C57BL , Modelos Animales de EnfermedadRESUMEN
Ramie (Boehmeria nivea, BN) is used as livestock forage through suitable silage fermentation owing to its nutritional value. To date, relatively few studies have investigated the effects of dietary fermented BN (FBN) on gut health in finishing pigs. The aim of the present study was to investigate the effects of dietary supplementation with 20% FBN on intestinal morphology, gene expression, and the functional response of the gut microbiota in finishing pigs. We found that FBN did not significantly affect serum antioxidant enzyme activities, ileal morphology, or the expression of genes encoding antioxidant enzymes, inflammatory cytokines, or tight junction proteins in the liver of the pigs. However, the gene expression levels of aryl hydrocarbon receptor (AHR) and interleukin 6 (IL6) were significantly downregulated in the ileum. A metagenomic analysis demonstrated that, compared with that seen in the control group, the cecal microbiota of pigs in the FBN treatment group was more closely clustered and contained a greater number of unique microbes. Bacteria were the predominant kingdom in the cecal microbiota, while Firmicutes, Bacteroidetes, and Proteobacteria were the dominant phyla, and Streptococcus, Lactobacillus, and Prevotella were the dominant genera. Dietary FBN significantly increased the abundance of the probiotic bacterium Roseburia inulinivorans (p < 0.05). Functional analysis of the cecal microbiota showed that ABC transporter levels and glycolysis/gluconeogenesis-associated functions were diminished in FBN-fed pigs. Meanwhile, CAZyme analysis revealed that dietary FBN significantly downregulated the contents of carbohydrate-active enzymes, such as GT2, GH1, GH25, and GH13_31. In addition, cytochrome P450 analysis revealed that the abundance of CYP51 and CYP512 decreased with FBN treatment. An assessment of antibiotic resistance based on the Comprehensive Antibiotic Resistance Database (CARD) annotation indicated that the cecal microbes from pigs in the FBN treatment group had increased resistance to lincosamide, streptogramin, and chloramphenicol and reduced resistance to amikacin, isepamicin, neomycin, lividomycin, gentamicin, paromomycin, ribostamycin, and butirosin. Finally, virulence factor-related analysis showed that putative hemolysin-associated functions were decreased, whereas fibronectin-binding protein, flagella, and alginate-associated functions were increased. Taken together, our data showed that FBN supplementation exerted only minor effects on intestinal morphology and microbial community composition, suggesting that it is potentially safe for use as a supplement in the diets of finishing pigs. However, more studies are needed to validate its functionality.
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Background: Resection and reconstruction of malignant bone tumors at the proximal femur in adolescent patients has remained a clinical challenge. Considering the growth and development requirements of adolescents, there is no unified standard for the reconstruction of bone defects at the proximal femur. Here, we report a case of 3D-printed titanium alloy customized prosthesis for the construction of proximal femoral bone defects in an adolescent patient with Ewing's sarcoma of the proximal femur. Case presentation: A 7-year-old female patient presented to a local hospital with left hip pain, and was diagnosed with Ewing's sarcoma on the proximal left femur. The patient received two courses of neoadjuvant chemotherapy before surgery according to the standard protocol. Considering growth and development problems associated with adolescents, we adopted a customized 3D-printed prosthesis of proximal femur for preservation of the femoral head and part of the femoral neck in the affected limb. Clinical outcomes, recorded after 12 months of follow-up, revealed excellent functional recovery and satisfactory functional scores of the affected limb, with no immediate complications. Conclusion: 3D-printed prosthesis is a feasible method for preserving femoral head and reconstruction of bone defects in adolescents' proximal femur.
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BACKGROUND: It is widely known that muscle mass influences the outcomes of many chronic diseases. Erector spine mass is a convenient parameter obtained from routine abdominal computed tomography (CT). The clinical application value of erector spine mass, and whether erector spine mass could predict the outcome of disease has not been studied. AIM: To evaluate the role of the erector spine index (ESI) calculated based on abdominal CT imaging in the progression of acute-on-chronic liver failure related to the hepatitis B virus (HBV-ACLF). METHODS: We performed a retrospective study of 118 HBV-ACLF patients and calculated the ESI (the total erector spine area normalized for height2 in meters) for each patient through abdominal CT. The findings were analyzed regarding the progression of HBV-ACLF and the ESI at baseline, including mortality and the development of complications. RESULTS: The ESI level was associated with mortality and the development of complications. During the 90-day follow-up period, patients with a low ESI (<12.05 cm2/m2) had higher mortality than those with a high ESI (≥ 12.05 cm2/m2) (51.7% vs. 26.7%), and the cumulative survival rates were 71.0%±4.6 and 85.8%±3.9, respectively (log-rank P = 0.003). The hazard ratios (HRs) calculated using univariable and multivariable analyses were 2.23(95% confidence interval (CI): 1.25-4.21, P = 0.005) and 2.52 (95% CI: 1.34-9.24, P = 0.011), respectively. Patients with a low ESI (<12.05 cm2/m2) had higher incidences of kidney dysfunction (43.5% vs. 23.2%, P = 0.029; log-rank P = 0.017) and hepatic encephalopathy (39.6% vs. 14.0%, P = 0.003; log-rank P = 0.010) than those with a high ESI. A low ESI was an independent risk factor for kidney dysfunction (adjusted HR = 1.36, 95% CI: 1.05-2.93, P = 0.043) and the development of hepatic encephalopathy (adjusted HR = 2.26; 95% CI: 2.05-3.13, P = 0.036). In addition, the presence of hepatic encephalopathy (the odds ratio (OR) = 2.26, 95% CI: 2.05-3.18, P = 0.006), spontaneous bacterial peritonitis (OR = 3.95, 95% CI: 1.01-5.46, P = 0.037), and kidney dysfunction (OR = 4.47, 95% CI: 1.02-9.64, P = 0.032) was independently associated with a low ESI in patients. CONCLUSION: A low ESI is an independent risk factor for mortality in patients with HBV-ACLF, as well as the development of kidney dysfunction and hepatic encephalopathy.
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Insuficiencia Hepática Crónica Agudizada , Encefalopatía Hepática , Hepatitis B Crónica , Hepatitis B , Humanos , Virus de la Hepatitis B , Estudios Retrospectivos , Insuficiencia Hepática Crónica Agudizada/diagnóstico por imagen , Insuficiencia Hepática Crónica Agudizada/etiología , Factores de Riesgo , Pronóstico , Hepatitis B Crónica/complicaciones , Hepatitis B/complicacionesRESUMEN
Bile acids, such as taurochenodeoxycholic acid (TCDCA), are considered as functional small molecules involved in nutrition regulation or acting with adjuvant therapeutic effects against metabolic or immune diseases. The homeostasis of the intestinal epithelium depends on the conventional cellular proliferation and apoptosis of cells. Herein, mice and normal intestinal epithelial cells (IPEC-J2, a widely used normal intestinal epithelial cell line derived from porcine) were used as models to explore the regulatory effect of TCDCA on the proliferation of intestinal epithelial cells (IECs). In the mouse study, the oral gavage of TCDCA led to a significant reduction in weight gain, small intestinal weight, and the villus height of the intestinal epithelium while inhibiting the gene expression of Ki-67 in the intestinal epithelial crypts of mice (P < 0.05). TCDCA significantly downregulated the expression of the farnesoid X receptor (FXR) and upregulated the expression of caspase-9 in the jejunum (P < 0.05). The results of real-time quantitative PCR (RT-qPCR) suggested that TCDCA significantly inhibited the expression of tight junction proteins zonula occludens (ZO)-1, occludin, claudin-1, and mucin-2 (P < 0.05). In terms of apoptosis-related genes, TCDCA significantly inhibited the expression of Bcl2 and increased the expression of caspase-9 (P < 0.05). At the protein level, TCDCA decreased the expression of Ki-67 and PCNA, as well as FXR (P < 0.05). Caspase inhibitor Q-VD-OPh and guggulsterone, an FXR antagonist, significantly improved the inhibition of TCDCA-induced cell proliferation. Moreover, guggulsterone enhanced TCDCA-induced cell late apoptosis through flow cytometry and significantly lowered the TCDCA-induced up-regulated gene expression of caspase 9, despite both TCDCA and guggulsterone down-regulating the expression of FXR (P < 0.05). Overall, the effect of TCDCA on the induction of apoptosis is not dependent on FXR, whereas it would function via the activation of the caspase system. This provides a new perspective for the application of TCDCA or bile acid as functional small molecules in food, additives, and medicine.
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Mucosa Intestinal , Ácido Tauroquenodesoxicólico , Ratones , Animales , Porcinos , Ácido Tauroquenodesoxicólico/farmacología , Ácido Tauroquenodesoxicólico/metabolismo , Caspasa 9/metabolismo , Antígeno Ki-67/metabolismo , Proliferación Celular , Mucosa Intestinal/metabolismo , Ácidos y Sales Biliares/metabolismo , ApoptosisRESUMEN
There is a need to identify potentially useful biomarker(s) for the prediction of prognostic outcomes in patients diagnosed with gastric cancer. This meta-analysis provided updated evidence on the association of controlling nutritional status (CONUT) score with survival and other clinicopathological outcomes in patients with gastric cancer. PubMed and Scopus databases were systematically searched. The review included studies, observational in design, that were conducted among patients with gastric cancer and had documented the association of CONUT score with outcomes of interest. The primary outcomes of interest were overall survival (OS), cancer-specific survival (CSS) and recurrence-free survival (RFS) along with tumour size and extent (T status), nodal status (N status) and tumour staging (TNM staging). STATA was used for statistical analysis. The meta-analysis was conducted with 17 studies. The 5-year OS [hazard ratio (HR), 1.75; 95% confidence interval (CI): 1.55, 1.96], RFS (HR, 1.58; 95% CI: 1.30, 1.91) and CSS (HR, 1.89; 95% CI: 1.01, 3.52) were comparatively poorer in the high CONUT group, than in low CONUT group. High CONUT score was associated with increased risk of having T3/T4 tumour [odds ratio (OR), 1.64; 95% CI: 1.16, 2.34], N2/N3 nodal status (OR, 1.44; 95% CI: 1.17, 1.77) and stage III/IV tumour (OR, 1.64; 95% CI: 1.43, 1.88). The risk of microvascular invasion (OR, 1.46; 95% CI: 1.20, 1.77) and post-operative complications (OR, 1.64; 95% CI: 1.31, 2.06) was higher in those with high CONUT. There were no differences in the risk of poorly differentiated tumour and need for adjuvant chemotherapy between the two groups. Findings suggested that preoperative assessment of CONUT score may be included in the routine assessment of patients with gastric cancer due to its association with survival and other clinical as well as pathological outcomes.
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Lithium-ion batteries (LIBs) have become the research focus of energy storage products. Due to the combination of Li+ and the Lewis basic sites of polymer chains, anions move more than five times faster, which do not participate in the electrode reaction during the discharge cycles, leading to concentration polarization, voltage losses, and high internal resistance. To solve this phenomenon, in this work, a polymer network structure of single-ion polymer electrolyte-based polyimide (DPI-SIGPE) with plasticizer ethylene carbonate (EC)/dimethyl carbonate (DMC) is formed by in-situ cross-linking double bond polyimide, 4-styrene sulfonyl (benzenesulfonyl) imide, and cross-linking agent pentaerythritol tetra(2-thiol acetate) under UV irradiation. By incorporating the anion as a part of the polymer chain, DPI-SIGPE exhibits high lithium-ion conductivity of 2.7 × 10-4 S cm-1 at 30 °C and transference number of 0.87. Typical lithium stripping/plating cycling of 900 h demonstrates uniform lithium deposition impacted by DPI-SIGPE. Meanwhile, it has good dimensional thermal stability with no obvious shrinkage at 200 °C for 0.5 h and wide electrochemical window of 4.6 V. Thus, the polyimide-based cross-linked single-ion gel polymer electrolyte has the promising potential for application in LIBs.
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Electrólitos , Litio , Iones , Conductividad Eléctrica , PolímerosRESUMEN
Hybrid Broussonetia papyrifera (BP) has been widely planted and commonly used as ruminant forage source after fermentation in China. Very less information is available to know the impact of fermented BP on laying hens, thus, we have investigated effects of dietary supplementation of Lactobacillus plantarum-fermented B. papyrifera (LfBP) on laying performance, egg quality, serum biochemical parameters, lipid metabolism, and follicular development of laying hens. A total of 288 HY-Line Brown hens (age, 23 wk) were randomly assigned into 3 treatment groups: control group (Con, a basal diet), LfBP1 and LfBP5 group (a basal diet supplemented with 1% or 5% LfBP). Each group has 8 replicates of twelve birds each. The results demonstrated that dietary supplementation of LfBP increased average daily feed intake (linear, P < 0.05), feed conversion ratio (linear, P < 0.05), and average egg weight (linear, P < 0.05) during the entire experimental period. In addition, dietary inclusion of LfBP enhanced the egg yolk color (linear, P < 0.01) but decreased the eggshell weight (quadratic, P < 0.05) and eggshell thickness (linear, P < 0.01). In serum, the LfBP supplementation linearly decreased the content of total triglyceride (linear, P < 0.01) but increased the content of high density lipoprotein-cholesterol (linear, P < 0.05). The gene expression related to hepatic lipid metabolism including acetyl-CoA carboxylase, fatty acid synthase, and peroxisome proliferator-activated receptor (PPARα) was down-regulated whereas liver X receptor was up-regulated in LfBP1 group. Moreover, LfBP1 supplementation remarkably reduced the F1 follicle number and ovarian gene expression of reproductive hormone receptors including estrogen receptor, follicle stimulating hormone receptor, luteinizing hormone receptor, progesterone receptor, prolactin receptor, and B cell lymphoma-2. In conclusion, dietary inclusion of LfBP could improve feed intake, egg yolk color, and lipid metabolism, but may cause a decline in eggshell quality with higher inclusion level, herein, 1% is suggested.
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Broussonetia , Animales , Femenino , Pollos , Metabolismo de los Lípidos , Suplementos Dietéticos , Dieta/veterinaria , Alimentación Animal/análisisRESUMEN
5-methylcytosine (m5C) modification, which is mainly induced by the RNA methyltransferase NSUN2 (NOP2/Sun domain family, member 2), is an important chemical posttranscriptional modification in mRNA and has been proven to play important roles in the progression of many cancers. However, the functions and underlying molecular mechanisms of NSUN2-mediated m5C in osteosarcoma (OS) remain unclear. In this study, we found NSUN2 was highly expressed in OS tissues and cells. We also discovered that higher expression of NSUN2 predicted poorer prognosis of OS patients. Our study showed that NSUN2 could promote the progression of OS cells. Moreover, we employed RNA sequencing, RNA immunoprecipitation (RIP), and methylated RIP to screen and validate the candidate targets of NSUN2 and identified FABP5 as the target. We observed that NSUN2 stabilized FABP5 mRNA by inducing m5C modification and further promoted fatty acid metabolism in OS cells. Moreover, both knocking down the expression of FABP5 and adding fatty acid oxidation inhibitor could counterbalance the promoting effect of NSUN2 on the progression of OS. Our study confirms that NSUN2 can up-regulate the expression of FABP5 by improving the stability of FABP5 mRNA via m5C, so as to promote fatty acid metabolism in OS cells, and finally plays the role in promoting the progression of OS. Our findings suggest that NSUN2 is a promising prognostic marker for OS patients and may serve as a potential therapeutic target for OS treatment. A schematic illustration was proposed to summarize our findings.
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Metiltransferasas , Osteosarcoma , Humanos , Metilación , ARN Mensajero/genética , ARN Mensajero/metabolismo , Metiltransferasas/genética , Metiltransferasas/metabolismo , ARN/metabolismo , Osteosarcoma/genética , Ácidos Grasos , Proteínas de Unión a Ácidos Grasos/genética , Proteínas de Unión a Ácidos Grasos/metabolismoRESUMEN
Objective: This study explores the health-related quality of life (HRQoL) scores of Chinese older adults with Cardiovascular Disease(CVD) using the EQ-5D-3L, the aim of this study is to investigate the association between health and HRQoL in older adults with CVD. Methods: The data for this study were obtained from a cross-sectional study involving older adults residing in Chinese communities The EQ-5D-3L is used to measure the HRQoL scores in the older adults with CVD. One-way analyses were conducted using the Wilcoxon rank sum test and the Kruskal-Wallis H test to assess differences between groups. A binary logistic regression model was employed to analyze the influence each variable has on the presence of "any problem" on each dimension of EQ-5D-3L in older adults with CVD. An ordinal least squares (OLS) model is used to assess the relationship between older adults with CVD and HRQoL. Results: The mean EQ-5D-3L score for older adults with CVD is 0.774. 40.0% of older adults with CVD reported problems with pain/discomfort, followed by Mobility (35.9%), Self-care (31.5%), and Anxiety/depression (17.0%). Binary logistic regression models show that financial resources were the main factor influencing the five dimensions of EQ-5D-3L. The OLS model further indicates that younger age, financial resources, and a lower number of chronic conditions among older adults with CVD are associated with higher HRQoL scores. Conclusion: Chinese older adults with CVD have low HRQoL scores. Variousfactors influence both overall HRQoL scores and scores on each EQ-5D-3L dimension. This study is helpful in enhancing society's attention to the HRQoL of older adults with CVD and taking targeted measures to improve them.
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Enfermedades Cardiovasculares , Calidad de Vida , Humanos , Anciano , Estudios Transversales , Enfermedades Cardiovasculares/epidemiología , Encuestas y Cuestionarios , China/epidemiologíaRESUMEN
Objective: To investigate the clinical application and effectiveness of three-dimensional (3D) printed customized prosthesis with preserved epiphysis and articular surface in the reconstruction of large bone defects in treatment of adolescent femoral malignant tumors. Methods: The clinical data of 10 adolescent patients with femoral primary malignant tumor who met the selection criteria and underwent limb salvage surgery with 3D printed customized prosthesis with preserved epiphysis and articular surface between January 2020 and October 2021 were retrospectively analyzed. There were 6 males and 4 females with an average age of 12.5 years ranging from 7 to 18 years. There were 8 cases of osteosarcoma and 2 cases of Ewing's sarcoma. Enneking stage was â ¡b. The length of the lesions ranged from 76 to 240 mm, with an average of 138.0 mm. The length of osteotomy (i. e. length of customized prosthesis) ranged from 130 to 275 mm, with an average of 198.5 mm; the distance between distal osteotomy end and epiphyseal line ranged from 0 to 15 mm, with an average of 8.8 mm; the bone defect after osteotomy accounted for 37.36% to 79.02% of the total length of the lesion bone, with a mean of 49.43%. The operation time, intraoperative blood loss, complications, tumor outcome (refered to RESIST1.1 solid tumor efficacy evaluation criteria), and limb length discrepancy were recorded. The Musculoskeletal Cancer Society (MSTS) 93 score was used to evaluate the function at 6 months after operation, and visual analogue scale (VAS) score was used to evaluate the pain before and after operation. Results: The operation was successfully performed in all the 10 patients, and the postoperative pathological results were consistent with the preoperative pathological results. The operation time was 165-440 minutes, with an average of 263 minutes; and the intraoperative blood loss was 100-800 mL, with an average of 350 mL. All patients were followed up 7-26 months, with an average of 11.8 months. No tumor was found on the osteotomy surface; the customized prosthesis were firmly installed and closely matched with the retained articular surface. The tumor outcome of neoadjuvant chemotherapy was stable in 4 cases and partial remission in 6 cases. No local recurrence or distant metastasis was found in 9 cases after postoperative adjuvant chemotherapy; pulmonary metastasis was found in 1 case at 12 months after operation. Two patients had local incision fat liquefaction, superficial infection, and delayed healing at 14 days after operation; 1 patient had local bone absorption at the contact surface of the prosthesis, and the screw and prosthesis did not loosen at 7 months after operation; the other patients had good incision healing, with no infection, prosthesis loosening, fracture, or other complications. At 6 months after operation, the MSTS93 score was 19-28, with an average of 24.1; 8 cases were excellent and 2 cases were good. The VAS score was 0.9±1.0, which significantly improved when compared with before operation (5.9±1.0) ( t=23.717, P<0.001). The height of the patients increased by 1-12 cm, with an average of 4.6 cm. At last follow-up, 4 patients had limb length discrepancy, with a length difference of 1 cm in 2 cases and 2 cm in 2 cases. Conclusion: The application of 3D printed customized prosthesis in the resection and reconstruction of adolescents femoral primary malignant tumors can achieve the purpose of preserving epiphysis and articular surface, and obtain good effectiveness.
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Miembros Artificiales , Neoplasias Óseas , Neoplasias Femorales , Masculino , Femenino , Adolescente , Humanos , Niño , Neoplasias Óseas/cirugía , Estudios Retrospectivos , Pérdida de Sangre Quirúrgica , Resultado del Tratamiento , Neoplasias Femorales/cirugía , Epífisis/cirugía , Epífisis/patología , Recuperación del MiembroRESUMEN
Objective: To investigate whether there is a curvilinear relationship between burnout and work engagement among staff in Chinese community services for the elderly. Methods: A stratified whole-group random sampling method was used to survey 244 staff members from eight communities in two cities. Data were collected using the Maslach Burnout Inventory scale (MBI) and the Utrecht Work Engagement Scale- 9 (UWES- 9). The curve estimation method explored the functional model of burnout and work engagement scales. Results: Two hundred forty-four staff members completed the survey. Burnout, depersonalization (DP), and personal accomplishment (PA) were found to be related to work engagement in a cubic function (R2 = 0.166, P < 0.05), (R2 = 0.061, P < 0.05), and (R2 = 0.2230, P < 0.05), respectively. There was no statistically significant relationship between emotional exhaustion (EE) and work engagement (P > 0.05). "Personal Accomplishment" is related to work engagement in a U-shaped curve. Conclusions: There was a cubic function relationship between burnout and work engagement, where "personal accomplishment" was related to work engagement in a U-shaped curve. Therefore, the government and related service organizations should understand the impact of different levels of burnout on work engagement and take targeted measures to alleviate burnout and improve work engagement by targeting emotions and stroke.
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Agotamiento Profesional , Servicios de Salud Comunitaria , Compromiso Laboral , Anciano , Agotamiento Profesional/psicología , Correlación de Datos , Humanos , Bienestar Social , Encuestas y CuestionariosRESUMEN
Background: Exosomes play an important role in cell-cell communication by transferring genetic materials such as long non-coding RNAs (lncRNAs) between cancer cells and tumor-associated macrophages (TAMs) in the tumor microenvironment (TME). Recent studies revealed that lncRNA ELFN1-AS1 could function as an oncogene in many human cancers. However, the role of extracellular lncRNA ELFN1-AS1 in cell-to-cell communication of osteosarcoma (OS) has not been fully investigated. Methods: Functional studies, including CCK-8, EdU staining and transwell assay were performed to investigate the role of ELFN1-AS1 in the progression of OS. 143B via xenograft mouse model was established to assess the role of ELFN1-AS1 in vivo. In addition, transmission electron microscopy (TEM) and real-time quantitative PCR (RT-qPCR) assay were used to verify the existence of exosomal ELFN1-AS1. Results: The level of ELFN1-AS1 was markedly upregulated in patients with advanced OS and in OS cells. In addition, overexpression of ELFN1-AS1 significantly promoted the proliferation, migration and invasion of OS cells, while knockdown of ELFN1-AS1 exhibited the opposite effects. Meanwhile, ELFN1-AS1 could be transferred from OS cells to macrophages via exosomes. Exosomal ELFN1-AS1 from 143B cells was able to promote macrophage M2 polarization, and M2 macrophage in return facilitated OS progression. Mechanistically, overexpression of ELFN1-AS1 upregulated CREB1 level via sponging miR-138-5p and miR-1291 in macrophage via. Conclusion: OS cell-derived exosomal ELFN1-AS1 was able to induce macrophage M2 polarization via sponging miR-138-5p and miR-1291, and M2 macrophage notably facilitated the progression of OS. These data suggested that ELFN1-AS1 might serve as a potential therapeutic target for osteosarcoma.
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Shaziling pig, a Chinese indigenous breed, has been classified as a fatty pig model. However, the gut microbial development and role in lipid metabolism in Shaziling pigs has been rarely reported. Here, we compared the lipid metabolic and microbial profiles at 30, 60, 90, 150, 210, and 300 d of age between Shaziling and Yorkshire pigs. Predictably, there were marked differences in the liver lipids (i.e., cholesterol, glucose, and low-density lipoprotein) and the lipid related expressions (i.e., SREBP1/2, LXRα/ß, DGAT1/2, and FABP1-3) between Shaziling and Yorkshire pigs. Bacteria sequencing in the ileal digesta and mucosa showed that Shaziling pigs had a higher α-diversity and higher abundances of probiotics, such as Lactobacillus johnsonii, Lactobacillus amylovorus, and Clostridium butyricum. Thirty-five differentiated metabolites were further identified in the mucosa between Shaziling and Yorkshire pigs, which were enriched in the carbohydrate, protein, glucose and amino acid metabolism and bile acid biosynthesis. Furthermore, 7 differentiated microbial species were markedly correlated with metabolites, indicating the role of gut microbiota in the host metabolism. Next, the role of differentiated L. johnsonii in lipid metabolism was validated in Duroc × Landrace × Yorkshire (DLY) pigs and the results showed that L. johnsonii mono-colonization promoted lipid deposition and metabolism by altering gut microbiota (i.e., Megasphaera elsdenii and L. johnsonii) and DGAT1/DGAT2/CD 36-PPAR γ gene expressions. In conclusion, Shaziling pigs exhibited different metabolic and microbial profiles compared with Yorkshire pigs, which might have contributed to the diverse metabolic phenotypes, and the significant enrichment of L. johnsonii in Shaziling pigs promoted lipid metabolism and obesity of DLY pigs, which provided a novel idea to improve the fat content of lean pigs.
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Background and Aims: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy that causes a poor survival. We aimed to identify its prognostic factors and to develop a nomogram that will predict survival of ICC patients among all stages. Methods: A total of 442 patients with pathology-proven ICC registered at the Fifth Medical Center of PLA General Hospital between July 2007 and December 2019 were enrolled. Subjects were followed for survival status until June 30, 2020. A prognostic model visualized as a nomogram was constructed in the training cohort using multivariate cox model, and was then validated in the validation cohort. Results: The median age was 55 years. With a median follow-up of 50.4 months, 337 patients died. The median survival was 11.6 months, with 1-, 3- and 5-year survival rates of 48.3%, 22.7% and 16.2%, respectively. Factors associated with overall survival were multiple tumors, lymph node involvement, vascular invasion, distant metastasis, decreased albumin, elevated lactate dehydrogenase (LDH), decreased iron, elevated fibrinogen, elevated CA125 and elevated CA19-9. A nomogram predicting survival of ICC patients at the time of diagnosis achieved a Harrel's c-statistic of 0.758, significantly higher than the 0.582 of the TNM stage alone. Predicted median survivals of those within the low, mid and high-risk subgroups were 35.6, 12.1 and 6.2 months, respectively. Conclusions: A nomogram based on imaging data and serum biomarkers at diagnosis showed good ability to predict survival in patients with all stages of ICC. Further studies are needed to validate the prognostic capability of our new model.