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Background Although favorable outcomes have been reported with radiofrequency ablation (RFA) for secondary hyperparathyroidism (SHPT), the long-term efficacy remains insufficiently investigated. Purpose To evaluate the long-term efficacy and safety of US-guided percutaneous RFA in patients with SHPT undergoing dialysis and to identify possible predictors associated with treatment failure. Materials and Methods This retrospective study included consecutive patients with SHPT with at least one enlarged parathyroid gland accessible for RFA who were undergoing dialysis at seven tertiary centers from May 2013 to July 2022. The primary end point was the proportion of patients with parathyroid hormone (PTH) levels less than or equal to 585 pg/mL at the end of follow-up. Secondary end points were the proportion of patients with normal calcium and phosphorus levels, the technical success rate, procedure-related complications, and improvement in self-rated hyperparathyroidism-related symptoms (0-3 ranking scale). The Wilcoxon signed rank test and generalized estimating equation model were used to evaluate treatment outcomes. Univariable and multivariable regression analyses identified variables associated with treatment failure (recurrent or persistent hyperparathyroidism). Results This study included 165 patients (median age, 51 years [IQR, 44-60 years]; 92 female) and 582 glands. RFA effectively reduced PTH, calcium, and phosphorus levels, with targeted ranges achieved in 78.2% (129 of 165), 72.7% (120 of 165), and 60.0% (99 of 165) of patients, respectively, at the end of follow-up (mean, 51 months). For the RFA sessions, the technical success rate was 100% (214 of 214). Median symptom scores (ostealgia, arthralgia, pruritus) decreased (all P < .001). Regarding complications, only hypocalcemia (45.8%, 98 of 214) was common. Treatment failure occurred in 36 patients (recurrent [n = 5] or persistent [n = 31] hyperparathyroidism). The only potential independent predictor of treatment failure was having less than four treated glands (odds ratio, 17.18; 95% CI: 4.34, 67.95; P < .001). Conclusion US-guided percutaneous RFA was effective and safe in the long term as a nonsurgical alternative for patients with SHPT undergoing dialysis; the only potential independent predictor of treatment failure was a lower number (<4) of treated glands. © RSNA, 2024 Supplemental material is available for this article.
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Cálcio , Hiperparatireoidismo Secundário , Humanos , Feminino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Hiperparatireoidismo Secundário/diagnóstico por imagem , Hiperparatireoidismo Secundário/cirurgia , FósforoRESUMO
Coenzyme Q10 (CoQ10) is an important cofactor and antioxidant for numerous cellular processes, and its deficiency has been linked to human disorders including mitochondrial disease, heart failure, Parkinson's disease, and hypertension. Unfortunately, treatment with exogenous CoQ10 is often ineffective, likely due to its extreme hydrophobicity and high molecular weight. Here, we show that less hydrophobic CoQ species with shorter isoprenoid tails can serve as viable substitutes for CoQ10 in human cells. We demonstrate that CoQ4 can perform multiple functions of CoQ10 in CoQ-deficient cells at markedly lower treatment concentrations, motivating further investigation of CoQ4 as a supplement for CoQ10 deficiencies. In addition, we describe the synthesis and evaluation of an initial set of compounds designed to target CoQ4 selectively to mitochondria using triphenylphosphonium. Our results indicate that select versions of these compounds can successfully be delivered to mitochondria in a cell model and be cleaved to produce CoQ4, laying the groundwork for further development.
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Ataxia , Mitocôndrias , Doenças Mitocondriais , Debilidade Muscular , Ubiquinona , Humanos , Mitocôndrias/enzimologia , Doenças Mitocondriais/enzimologia , Doenças Mitocondriais/genética , Debilidade Muscular/enzimologia , Debilidade Muscular/genética , Ubiquinona/análogos & derivados , Ubiquinona/deficiência , Células Hep G2RESUMO
Polygonum multiflorum Thunb. (PM) and derived products are broadly utilized in Chinese traditional medicine. According to our previous research, PM mostly contains polysaccharides, which display a wide range of biological activities. Two water-soluble polysaccharides (PMPs-1 and PMPs-2) were obtained from PM by DEAE-Cellulose and Sephadex G-100 column chromatography. Colorimetry, HPGPC-MALLS-RID, HPLC-PDA, methylation, FT-IR, NMR, and SEM were used to characterize these polysaccharides. PMPs-1 and PMPs-2 had average molecular weights of 255.5 and 55.7 kDa, respectively. PMPs-1 consisted of Man, Glc, Gal, and Ara at 0.9:78.6:1.0:1.6 and was a glucan with â 4)-Glcp-(1 â as a backbone. Meanwhile, PMPs-2, an acidic polysaccharide, comprised Rha, GalA, Glc, Gal, and Ara at 3.2:20.3:2.7:1.0:8.3. PMPs-1 and PMPs-2 significantly improved the proliferation of RAW 264.7 cells and induced NO, TNF-α, and IL-6 release. This study reveals that these two polysaccharides can be explored as novel immunomodulators and provide a basis for further development of PM in food and pharmaceutical industries.
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Polygonum multiflorum Thunb (PM) is used to slow the aging process. Although polysaccharides are a major constituent of PM, their anti-aging properties have not been thoroughly investigated. Therefore, this study aimed to examine the anti-aging effects of polysaccharides extracted from PM using the Caenorhabditis elegans (C. elegans) model. Two types of water-soluble heteropolysaccharides, namely a neutral polysaccharide (RPMP-N) and an acidic polysaccharide (RPMP-A), were obtained from PM. Their structures were elucidated by various methods. The effects of these polysaccharides on the lifespan, levels of antioxidants, and activities of antioxidant-related enzymes in C. elegans were also evaluated. The results showed that RPMP-A had higher GalA content compared with RPMP-N. The average molecular weights of RPMP-N and RPMP-A were 245.30 and 28.45 kDa, respectively. RPMP-N is a α-1,4-linked dextran as the main chain, and contains a small amount of branched dextran with O-6 as the branched linkage siteï¼RPMP-A may be a complex of α-1,4-linked dextran, HG and RG-I. Treatment with RPMP-N and RPMP-A increased the mean lifespan of C. elegans, and significantly regulated oxidative stress. RPMP-A exhibited stronger anti-aging effects compared with RPMP-N. These findings suggest that RPMP-A may be a potent antioxidant and anti-aging component that can be used for developing functional food products and effective dietary supplements.
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Caenorhabditis elegans , Fallopia multiflora , Animais , Antioxidantes/farmacologia , Dextranos/farmacologia , Envelhecimento , Estresse Oxidativo , Polissacarídeos/farmacologia , Polissacarídeos/químicaRESUMO
BACKGROUND: The purpose of this study was to investigate the mechanism of sanguinarine (SAN) against nasopharyngeal carcinoma (NPC) by means of network pharmacology, molecular docking technique, and experimental verification. METHODS: The SAN action targets were predicted using the Swiss Target Prediction database, the related NPC targets were determined using the GEO database, and the intersection of drug and disease pathway targets were considered to be the potential targets of SAN against NPC. The target-protein interaction network map was constructed using the STRING database, and the core target genes of SAN against NPC were obtained via topological network analysis. "R" language gene ontology (GO) function and Kyoto encyclopedia of genes and genome (KEGG) pathway enrichment analyses were used to dock the core target genes with SAN with the help of AutodockVina. Cell proliferation was detected using MTT and xCELLigence real-time cell analysis. Apoptosis was identified via Hoechst 33342 staining, JC-1 mitochondrial membrane staining, and annexin V-FITC/PI double fluorescence staining, while protein expression was quantified using western blotting. RESULTS: A total of 95 SAN against NPC targets were obtained using target intersection, and 8 core targets were obtained by topological analysis and included EGFR, TP53, F2, FN1, PLAU, MMP9, SERPINE1, and CDK1. Gene ontology enrichment analysis identified 530 items, and 42 items were obtained by Kyoto encyclopedia of genes and genome pathway enrichment analysis and were mainly related to the PI3K/AKT, MAPK, and p53 signaling pathways. Molecular docking results showed that SAN had good binding activity to the core target. SAN inhibited the proliferation of NPC cells, induced apoptosis, reduced the expression levels of survivin and Bcl2, and increased the expression levels of Bax and cleaved caspase-8. It also decreased the expression levels of the key proteins p-c-Raf, p-MEK, and p-ERK1/2 in the MAPK/ERK signaling pathway in NPC cells. CONCLUSION: SAN inhibits the proliferation and induces the apoptosis of NPC cells through the MAPK/ERK signaling pathway.
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Medicamentos de Ervas Chinesas , Neoplasias Nasofaríngeas , Humanos , Simulação de Acoplamento Molecular , Farmacologia em Rede , Carcinoma Nasofaríngeo/tratamento farmacológico , Fosfatidilinositol 3-QuinasesRESUMO
PURPOSE: There has been a persistent claim that dairy products contain calcium-leaching proteins, although the soundness of such a claim has been challenged. A meta-analysis of randomized controlled trials (RCTs) on the effects of milk-derived protein supplementation on bone health indices in adults was performed to reconcile the controversy surrounding the potential skeletal safety concerns of proteins of dairy origin. METHODS: The PubMed and Web of Science databases were searched for relevant RCTs. A random-effects model was used to generate pooled effect sizes and 95% confidence intervals. RESULTS: Milk-derived protein supplementation did not significantly affect whole-body BMD (n = 7 RCTs) and BMD at the lumbar spine (n = 10), hip (n = 8), femoral neck (n = 9), trochanter (n = 5), intertrochanter (n = 2), and ultradistal radius (n = 2). The concentrations of bone formation markers (bone-specific alkaline phosphatase [n = 11], osteocalcin [n = 6], procollagen type 1 amino-terminal propeptide [n = 5]), bone resorption markers (N-terminal telopeptide of type 1 collagen [n = 7], C-terminal telopeptide of type 1 collagen [n = 7], deoxypyridinoline [n = 4]), and parathyroid hormone (n = 7) were not significantly affected. However, increased insulin-like growth factor-1 (IGF-1) concentrations (n = 13) were observed. Reduced IGF-1 concentrations were observed when soy protein was used as a comparator, and increased IGF-1 concentrations were observed when carbohydrate was used. CONCLUSION: Our findings do not support the claim that proteins of dairy origin are detrimental to bone health.
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Epidemiological data show people with diabetes mellitus (DM) have three-fold increase in risk of periodontitis. A vitamin D insufficiency can affect the progression of DM and periodontitis. This study evaluated the effects of different-dose vitamin D supplementation to nonsurgical periodontal therapy for vitamin-D-insufficient diabetic patients coexisting with periodontitis and changes of gingival bone morphogenetic protein-2 (BMP-2) levels. The study included 30 vitamin-D-insufficient patients receiving nonsurgical treatment followed by administration of 25,000 international units (IU) vitamin D3 per week (the low-VD group) and 30 patients receiving 50,000 UI vitamin D per week (the high-VD group). The decreases of probing pocket depth, clinical attachment loss, bleeding index, and periodontal plaque index values of patients after the six-month supplementation of 50,000 UI vitamin D3 per week to nonsurgical treatment were more significant than those after the six-month supplementation of 25,000 UI vitamin D3 per week to nonsurgical treatment. It was found that 50,000 IU per week vitamin D supplementation for 6 months could lead to a better glycemic control for vitamin-D-insufficient diabetic patients coexisting with periodontitis after nonsurgical periodontal therapy. Increased levels of serum 25(OH) vitamin D3 and gingival BMP-2 were found in both low- and high-dose VD groups, and the high-dose VD group exhibited higher levels than the low-dose VD group. Vitamin D supplementation in large doses for 6 months tended to improve the treatment of periodontitis and increase gingival BMP-2 levels in diabetic patients coexisting with periodontitis who were vitamin D deficient.
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Danggui Buxue Decoction is a classic formula for replenishing qi and nourishing blood. Despite its widespread use, its dynamic metabolism involved remains unclear. Based on the sequential metabolism strategy, blood samples from different metabolic sites were obtained via in situ closed intestine ring integrated with a jugular venous continuous blood supply technique. An ultra-high-performance liquid chromatography-linear triple quadruple-Orbitrap-tandem mass spectrometry method was developed for the identification of prototypes and metabolites in rat plasma. The dynamic absorption and metabolic landscape of flavonoids, saponins, and phthalides were characterized. Flavonoids could be deglycosylated, deacetylated, demethylated, dehydroxylated, and glucuronicated in the gut and then absorbed for further metabolism. Jejunum is an important metabolic site for saponins biotransformation. Saponins that are substituted by Acetyl groups tend to lose their acetyl groups and convert to Astragaloside IV in the jejunum. Phthalides could be hydroxylated and glucuronidated in the gut and then absorbed for further metabolism. Seven components serve as crucial joints in the metabolic network and are potential candidates for the quality control of Danggui Buxue Decoction. The sequential metabolism strategy described in this study could be useful for characterizing the metabolic pathways of Chinese medicine and natural products in the digestive system.
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Medicamentos de Ervas Chinesas , Saponinas , Ratos , Animais , Espectrometria de Massas em Tandem , Medicamentos de Ervas Chinesas/análise , Cromatografia Líquida de Alta Pressão/métodos , Flavonoides/análise , Saponinas/análiseRESUMO
Objective: This pilot study explored interactions of domains of physical, psychologic, and social factors in the Patient-Reported Outcomes Measurement Information System® (PROMIS®)-29 system and their dynamic changes during acupuncture treatment of chronic musculoskeletal pain. Materials and Methods: PROMIS-29 profile, version 2.1 was applied among participants with chronic musculoskeletal pain, who received acupuncture treatment for 5 weeks. Data from function-oriented and symptom-oriented domains as well as changes in pain intensity were evaluated at weeks 0, 3, and 5, in 9 patients who completed full sessions. Scores of the domains were analyzed by hierarchical cluster analysis at each timepoint to identify the patterns of interactions of PROMIS domains. Results: Hierarchical cluster analysis revealed the existence of 2 main clusters: one consisting of pain, fatigue, and emotional domains; the other comprising physical function and social domains. The general pattern was stable but interactions were found throughout the treatment. The score for sleep disturbance did not improve but was correlated with different domains at varying stages of treatment. Conclusions: Interaction between 2 clusters of pain with fatigue and emotional domains; and physical function with social domains showed that acupuncture produces holistic reductions in chronic musculoskeletal pain. However, the limitation of sample size and bias in this pilot study requires future research on the need to adopt an interdisciplinary and holistic approach to the recovery of patients with chronic musculoskeletal pain, who have dynamic needs.
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OBJECTIVE: To observe the effect of electroacupuncture(EA) on pain-ralated behaviors, morphology of hippocampus, concentrations of inflammatory cytokines and expression of ionized calcium binding adapter molecule 1(Iba-1) in dorsal horn of the spinal cord and the hippocampus, and brain-derived neurotrophic factor (BDNF) in hippocampus of rats with knee osteoarthritis (KOA), so as to explore the mechanism of EA in improving chronic pain of KOA. METHODS: Forty SD rats were randomly divided into blank group, saline group, model group and EA group, with 10 rats in each group. Monosodium iodoacetate(MIA, 80 mg/mL, 50 µL) was injected into the left knee joint cavity of rats in the model group and EA group to establish the chronic pain model of KOA, while the same volume of normal saline was injected into the left knee joint cavity of rats in the saline group. Rats in the EA group received EA stimulation(2 Hz/100 Hz, 1-2 mA) at left "Yanglingquan"(GB34) and "Neixiyan"(EX-LE4) for 15 min, 14 d after MIA injection. The treatment was given once daily, 5 d as 1 session and 2 sessions of treatment were required. Methanical withdrawl threshold(MWT) and weight-bearing capacity tests on left hind limbs were carried out 1 d before, 7 dï¼14 d, 20 d and 26 d after MIA injection. At the 27th day, rats were sacrificed and HE staining was used to observe the morphology of hippocampal CA1 area. Concentrations of interleukin(IL)-1ß and tumor necrosis factor(TNF)-α in the left L3-L5 spinal dorsal horn and hippocampal CA1 area were detected by ELISA, the expressions of Iba-1 in the spinal dorsal horn and hippo-campal CA1 area were detected by immunofluorescence, and the expression of BDNF in left hippocampal CA1 area was detected by Western blot. RESULTS: The HE staining results of the hippocampal CA1 area showed reduced number of neurons, unclear cell contour and boundary between nucleus and cytoplasm, and nuclear pyknosis in the model group, which was relatively milder in the EA group. Compared with the blank group, MWT and weight-bearing capacity of rats' left hind limbs, and expression of BDNF protein in hippocampal CA1 area were significantly decreased (P<0.01), while the contents of IL-1ß and TNF-α, the expression of Iba-1 in spinal dorsal horn and hippocampal CA1 area were significantly increased (P<0.01) in the model group. In comparison with the model group, MWT and weight-bearing capacity of rats' left hind limbs, and protein expression of BDNF in hippocampal CA1 area were significantly increased (P<0.01), while the contents of IL-1ß and TNF-α, and the expression of Iba-1 protein in spinal dorsal horn and hippocampal CA1 area were significantly decreased after EA intervention(P<0.01). CONCLUSION: EA at GB34 and EX-LE4 can alleviate the pain-related behaviors of KOA rats. The mechanism might be related to the inhibition of inflammatory reaction mediated by microglia in spinal dorsal horn and hippocampus, and the up-regulation of BDNF expression in hippocampus.
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Dor Crônica , Eletroacupuntura , Osteoartrite do Joelho , Ratos , Animais , Ratos Sprague-Dawley , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Osteoartrite do Joelho/genética , Osteoartrite do Joelho/terapia , Eletroacupuntura/métodos , Fator de Necrose Tumoral alfa/metabolismo , Hipocampo/metabolismo , Corno Dorsal da Medula Espinal/metabolismoRESUMO
Intracellular α-ketoglutarate is an indispensable substrate for the Jumonji family of histone demethylases (JHDMs) mediating most of the histone demethylation reactions. Since α-ketoglutarate is an intermediate of the tricarboxylic acid cycle and a product of transamination, its availability is governed by the metabolism of several amino acids. Here, we show that asparagine starvation suppresses global histone demethylation. This process is neither due to the change of expression of histone-modifying enzymes nor due to the change of intracellular levels of α-ketoglutarate. Rather, asparagine starvation reduces the intracellular pool of labile iron, a key co-factor for the JHDMs to function. Mechanistically, asparagine starvation suppresses the expression of the transferrin receptor to limit iron uptake. Furthermore, iron supplementation to the culture medium restores histone demethylation and alters gene expression to accelerate cell death upon asparagine depletion. These results suggest that suppressing iron-dependent histone demethylation is part of the cellular adaptive response to asparagine starvation.
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Objective: To evaluate the efficacy of acupuncture in treating Parkinson's disease-related constipation (PDC). Materials and methods: This was a randomized, controlled trial in which patients, outcome assessors, and statisticians were all blinded. Seventy-eight eligible patients were randomly assigned to either the manual acupuncture (MA) or sham acupuncture (SA) groups and received 12 sessions of treatment over a 4-week period. Following treatment, patients were monitored until the eighth week. The primary outcome was the change in weekly complete spontaneous bowel movements (CSBMs) from baseline after treatment and follow-up. The Constipation Symptom and Efficacy Assessment Scale (CSEAS), the Patient-Assessment of Constipation Quality of Life questionnaire (PAC-QOL), and the Unified Parkinson's Disease Rating Scale (UPDRS) were used as secondary outcomes. Results: In the intention-to-treat analysis, 78 patients with PDC were included, with 71 completing the 4-week intervention and 4-week follow-up. When compared to the SA group, weekly CSBMs were significantly increased after treatment with the MA group (P < 0.001). Weekly CSBMs in the MA group were 3.36 [standard deviation (SD) 1.44] at baseline and increased to 4.62 (SD, 1.84) after treatment (week 4). The SA group's weekly CSBMs were 3.10 (SD, 1.45) at baseline and 3.03 (SD, 1.25) after treatment, with no significant change from baseline. The effect on weekly CSBMs improvement in the MA group lasted through the follow-up period (P < 0.001). Conclusion: Acupuncture was found to be effective and safe in treating PDC in this study, and the treatment effect lasted up to 4 weeks. Clinical trial registration: http://www.chictr.org.cn/index.aspx, identifier ChiCTR2200059979.
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The raw and processed Polygonum multiflorum Thunb (PM) are used to treat different diseases, and PM has also been reported to have hepatotoxic effects. Moreover, mounting evidence indicates that processed PM is less toxic than raw PM. The changes in efficacy and toxicity of PM during the processing are closely related to the changes in chemical composition. Previous studies have mainly focused on the changes of anthraquinone and stilbene glycosides during process. Polysaccharides, as main components of PM, showed many pharmacological effects, but its changes in the processing has been neglected for a long time. In this study, the polysaccharides of PM in the raw (RPMPs) and processed products (PPMPs) were determined and the liver injury model induced by acetaminophen was utilized to evaluate the impact of polysaccharides on the liver. Results showed that the heteropolysaccharides RPMPs and PPMPs both comprised Man, Rha, GlcA, GalA, Glc, Ara and Xyl, but markedly differed in polysaccharide yield, molar ratio of monosaccharide composition and Mw. In vivo analysis, results showed that demonstrated that RPMPs and PPMPs both exerted hepatoprotective effects by upregulating antioxidant enzymes and repressing lipid peroxidation. It is noteworthy that the polysaccharide yield of processed PM was seven-fold higher than that of raw PM, so it is speculated that processed PM has better hepatoprotective effects at the same dose of decoction. The present work provides an important foundation for studying the polysaccharide activity of PM and further revealing the processing mechanism of PM. This study also proposed a new hypothesis that the significant increase of polysaccharide content in processed PM may be another reason that the product PM causes less liver injury.
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Medicamentos de Ervas Chinesas , Fallopia multiflora , Humanos , Masculino , Fallopia multiflora/química , Polissacarídeos/farmacologia , Medicamentos de Ervas Chinesas/química , Fígado , Antioxidantes/farmacologiaRESUMO
Erhuangquzhi granules (EQG) have been clinically proven to be effective in nonalcoholic steatohepatitis (NASH) treatment. However, the active components and molecular mechanisms remain unknown. This study aimed to screen active components targeting tumor necrosis factor α (TNF-α) in EQG for the treatment of NASH by a surface plasmon resonance (SPR) biosensor-based active ingredient recognition system (SPR-AIRS). The amine-coupling method was used to immobilize recombinant TNF-α protein on an SPR chip, the specificity of the TNF-α-immobilized chip was validated, and nine medicinal herbs in EQG were prescreened. Nuciferine (NF), lirinidine (ID), and O-nornuciferine (NNF) from lotus leaves were found and identified as TNF-α ligands by UPLCâMS/MS, and the affinity constants of NF, ID, and NNF to TNF-α were determined by SPR experiments (Kd = 61.19, 31.02, and 20.71 µM, respectively). NF, ID, and NNF inhibited TNF-α-induced apoptosis in L929 cells, the levels of secreted IL-6 and IL-1ß were reduced, and the phosphorylation of IKKß and IκB was inhibited in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. In conclusion, a class of new active small-molecule TNF-α inhibitors was discovered, which also provides a valuable reference for the material basis and mechanism of EQG action in NASH treatment.
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Técnicas Biossensoriais , Hepatopatia Gordurosa não Alcoólica , Humanos , Cromatografia Líquida , Fatores Imunológicos , Espectrometria de Massas em Tandem , Fator de Necrose Tumoral alfa/metabolismo , Lotus/química , Folhas de Planta/químicaRESUMO
Danggui Buxue Decoction is a classic formula containing Astragali Radix and Angelicae Sinensis Radix in a 5:1 ratio and has been extensively used to treat blood deficiency for thousands of years. The aim of the study was to investigate the differences in plasma protein binding, pharmacokinetics, and tissue distribution of Danggui Buxue Decoction in normal and blood-deficient rats by ultra-performance liquid chromatography-tandem mass spectrometry. The effects on peripheral blood routine were verified. The compounds exhibited higher plasma protein binding and absorption in the model group compared to the control group, except formononetin. The six ingredients were distributed widely, and the highest concentrations were detected in the heart and uterus. As has been demonstrated in the previous study of the effect of Danggui Buxue Decoction, its potential is to serve as an effective traditional Chinese medicine formula for treating cardiovascular diseases and impacting estrogenic properties, which reveals the potential target organs of Danggui Buxue Decoction the heart and uterus. Our findings suggested that the absorption and distribution of different components in Danggui Buxue Decoction varies depending on the pathological state, molecular weight, lipid solubility, transporter-mediated efflux, and other factors.
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Medicamentos de Ervas Chinesas , Espectrometria de Massas em Tandem , Feminino , Ratos , Animais , Medicamentos de Ervas Chinesas/química , Cromatografia Líquida , Administração OralRESUMO
OBJECTIVE: The purpose of our study was to compare the quality of life (QOL) of patients with hematopoietic stem cell transplantation (HSCT) for more than 2 years for ß -thalassemia major (ß-TM) with that of ß-TM patients with conventional therapy (blood infusion and iron chelation) and that of the general population. METHODS: This was a cross-sectional comparative study on the QOL of 225 ß-TM patients treated with blood transfusion and iron chelation therapy, 133 ß-TM patients who had undergone HSCT or 270 ageand sex-matched healthy individuals from Guangxi, China. Child-self and parent-proxy reports of the PedsQL 4.0 Generic Core Scales were used to prospectively evaluate QOL. RESULTS: The incidence of acute GVHD was 14.3% (grade III-IV in 4.5% of patients), and that of chronic GVHD was 3.8%. This was lower than that of previous studies since the inclusion of anti-thymocyte globulin (ATG). Patients who underwent transplantation from a voluntary donor had higher QOL scores and lower rates of acute GVHD, chronic GVHD and comorbidities than those receiving stem cell sources from an HLA mismatched related donor (haploidentical donor). Transplants with PBSCs or UCBT, PBSCT+BMT, BMT, or BMT+UCBT as stem cell sources did not have any impact on QOL. The QOL of ß-TM patients was very similar to that of the general population. More complications (P<0.001), shorter post-transplantation time (P<0.001), and older age at HSCT (P=0.01) were associated with poorer child QOL (P=0.020). Additional analyses investigating QOL of ß-TM patients receiving conventional treatment with ß-TM revealed poorer outcomes than the cohort of transplanted patients. CONCLUSION: ß-TM patients can be cured by HSCT and regain QOL as good as that of the general population. ß-TM patients are suggested to undergo HSCT as soon as possible to avoid complications related to iron overload and blood infusion.
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Síndrome de Bronquiolite Obliterante , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Talassemia beta , Humanos , Estudos Transversais , Qualidade de Vida , Talassemia beta/terapia , ChinaRESUMO
BACKGROUND: Pisa syndrome (PS) refers to marked lateral flexion of the trunk with a Cobb angle greater than 10°, which is typically mobile and can be resolved by lying down. PS is one of the most common postural deformities secondary to Parkinson's disease (PD) and can aggravate scoliosis in the advanced stages of PD. CASE SUMMARY: Here, we present the case of a 53-year-old woman who presented with lateral curvature for 6 mo. Full spine X-ray films in the correct position showed that the thoracolumbar spine was bent to the right without any rotation of the vertebrae. The patient was diagnosed with Pisa syndrome. After receiving a month's treatment with electroacupuncture, the Cobb angle decreased from 18.14° to 13.41°. CONCLUSION: This case demonstrates that electroacupuncture can effectively improve Pisa syndrome secondary to PD with few side effects and a low risk of recurrence. Additionally, early accurate diagnosis and timely intervention are meaningful for the prognosis of PS.
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Background: Obese type 2 diabetes mellitus (obese T2DM) is one of the prime diseases that endangers human health. Clinical studies have confirmed the ability of the Huanglian Huazhuo capsule to treat obese T2DM; however, its mechanism of action is still unclear. In this study, effects and mechanisms of the Huanglian Huazhuo capsule in obese T2DM were systematically investigated using network pharmacology and molecular docking techniques. Methods: The active ingredients and targets of the Huanglian Huazhuo capsule were extracted from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Obese T2DM diabetes-related targets were retrieved from a geographic dataset combined with a gene card database. A protein-protein interaction (PPI) network was constructed to screen core targets. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using Database for Annotation Visualization and Integrated Discovery (DAVID). Interactions between potential targets and active compounds were assessed using molecular docking. Molecular docking was performed on the best core protein complexes obtained using molecular docking. Results: A total of 89 and 108 active ingredients and targets, respectively, were identified. Seven core targets were obtained using a topological analysis of the PPI network. The GO and KEGG pathway enrichment analyses showed that the effects of the Huanglian Huazhuo capsules were mediated by inflammation, lipid response, oxidative stress-related genes, and HIF-1 and IL-17 signaling pathways. Good binding ability was observed between the active compounds and screened targets using molecular docking. Conclusions: The active ingredients, potential targets, and pathways of the Huanglian Huazhuo capsule for the treatment of obese T2DM were successfully predicted, providing a new strategy for further investigation of its molecular mechanisms. In addition, the potential active ingredients provide a reliable source for drug screening in obese T2DM.
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Importance: One of the ordinary manifestations of Parkinson disease (PD) is anxiety, which remains untreated. Anxiety is closely associated with the accelerated progression of PD. Efficacy of acupuncture for anxiety has been reported. However, to date, there are no data on acupuncture's effectiveness on anxiety for patients with PD. Objective: To investigate the effect of acupuncture vs sham acupuncture for treating anxiety in patients with PD. Design, Setting, and Participants: This is randomized, double-blinded, clinical trial enrolled patients between June 20, 2021, and February 26, 2022. Final follow-up was April 15, 2022. Patients with Parkinson disease and anxiety were allocated randomly (1:1) to receive acupuncture or sham acupuncture for 8 weeks. Acupuncture operators, outcome measures evaluators, and statistical analysts were blinded to the grouping of patients. Patients were blinded to their own grouping during the study. This study took place in the Parkinson clinic of a hospital in China. Interventions: Real acupuncture or sham acupuncture for 8 weeks. Main Outcomes and Measures: Primary outcome was Hamilton Anxiety Scale (HAM-A) score. Secondary outcomes were scores on the Unified Parkinson Disease Rating Scale (UPDRS), 39-item Parkinson Disease Questionnaire (PDQ-39), and serum levels of the adrenocorticotropic hormone (ACTH) and cortisol (CORT). Results: Seventy eligible patients were enrolled, including 34 women (48.5%) and 36 men (51.4%). Sixty-four patients (91%) completed the intervention and the 8-week follow-up, including 30 women (46.9%) and 34 men (53.1%) with a mean (SD) age of 61.84 (8.47) years. At the end of treatment, the variation of HAM-A score was 0.22 (95% CI, -0.63 to 1.07; P = .62) between the real acupuncture and sham acupuncture groups. At the end of follow-up, the real acupuncture group had a significant 7.03-point greater (95% CI, 6.18 to 7.88; P < .001) reduction in HAM-A score compared with the sham acupuncture group. Four mild adverse reactions occurred during the study. Conclusions and Relevance: This study found acupuncture to be an effective treatment for anxiety in patients with PD. These findings suggest that acupuncture may enhance the wellbeing of patients who have Parkinson disease and anxiety. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2100047253.
Assuntos
Terapia por Acupuntura , Doença de Parkinson , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hormônio Adrenocorticotrópico , Ansiedade/terapia , Hidrocortisona , Doença de Parkinson/complicações , Doença de Parkinson/terapiaRESUMO
BACKGROUND: Stent implantation has been increasingly applied for the treatment of obstructive coronary artery disease, which, albeit effective, often harasses patients by in-stent restenosis (ISR). PURPOSE: The present study was to explore the role of compound Chinese medicine Cardiotonic Pills® (CP) in attenuating ISR-evoked myocardial injury and fibrosis. STUDY DESIGN: Chinese miniature pigs were used to establish ISR model by implanting obsolete degradable stents into coronary arteries. Quantitative coronary angiography (QCA) was performed to confirm the success of the model. METHODS: CP was given at 0.2 g/kg daily for 30 days after ISR. On day 30 and 60 after stent implantation, the myocardial infarct and myocardial blood flow (MBF) were assessed. Myocardial histology was evaluated by hematoxylin-eosin and Masson's trichrome staining. The content of ATP, MPO, and the activity of mitochondrial respiratory chain complex â £ were determined by ELISA. Western blot was performed to assess the expression of ATP5D and related signaling proteins, and the mediators of myocardial fibrosis. RESULTS: Treatment with CP diminished myocardial infarct size, retained myocardium structure, attenuated myocardial fibrosis, and restored MBF. CP ameliorated energy metabolism disorder, attenuated TGFß1 up-regulation and reversed its downstream gene expression, such as Smad6 and Smad7, and inhibited the increased expression of MCP-1, PR S19, MMP-2 and MMP-9. CONCLUSION: CP effectively protects myocardial structure and function from ISR challenge, possibly by regulating energy metabolism via inactivation of RhoA/ROCK signaling pathway and inhibition of monocyte chemotaxis and TGF ß1/Smads signaling pathway.