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Background: Excessive inflammation poses significant risks to human physical and mental health. Astilbe grandis, a traditional Miao medicine, is renowned for its anti-inflammatory properties. However, the specific anti-inflammatory effects and mechanisms of many compounds within this plant remain unclear. This study aims to investigate the anti-inflammatory effects and mechanisms of two characteristic oleanane triterpenoids, 3α-acetoxyolean-12-en-27-oic acid (1) and 3ß-acetoxyolean-12-en-27-oic acid (2), isolated from Astilbe grandis, using lipopolysaccharide (LPS)-induced Macrophages. Methods: The anti-inflammatory effects and mechanisms of compounds 1 and 2 were investigated by establishing an LPS-induced inflammation model in RAW 264.7 cells and THP-1 cells. Nitric oxide (NO) levels were assessed using the Griess method. The concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1beta (IL-1ß) were measured via enzyme-linked immunosorbent assay (ELISA). The expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) was determined using western blotting and quantitative real-time PCR (qRT-PCR). Additionally, the phosphorylation level of p65 in nuclear factor-kappa B (NF-κB) was assessed through western blotting. The nuclear translocation of NF-κB p65 was assessed through immunofluorescence staining. Finally, the binding affinity of the compounds to NF-κB p65 target was validated through molecular docking. Results: Compounds 1 and 2 significantly inhibited the expression of NO, TNF-α, IL-6, IL-1ß, COX-2, and iNOS in LPS-induced Macrophages. Mechanistically, they attenuated the activation of the NF-κB signaling pathway by downregulating the phosphorylation level and nuclear translocation of p65. Conclusion: This study elucidates the anti-inflammatory activities and potential mechanism of the characteristic oleanane triterpenoids with C-14 carboxyl group, compounds 1 and 2, in LPS-induced Macrophages by inhibiting the NF-κB signaling pathway for the first time. These findings suggest that these two compounds hold promise as potential candidates for anti-inflammatory interventions in the future.
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BACKGROUND: Despite previous studies suggesting that developmental care can provide benign stimulation to promote neural development of newborns, more evidence is needed regarding the other clinical benefits of developmental care. OBJECTIVE: To evaluate the effect of implementing developmental care on the length of hospital stay, the improvement of care practice in neonatal intensive care units, as well as the short-term outcome of very low birth weight infants. DESIGN: Cluster-randomized controlled trial. SETTING(S) AND PARTICIPANTS: From March 1, 2021 to March 1, 2022, 1400 very low birth weight infants were recruited from 14 tertiary neonatal intensive care units in China. METHODS: We assigned 14 neonatal intensive care units to either developmental care or standard care. The length of hospital stay of the infants was the primary outcome analyzed at the individual level. Secondary outcomes were family centered care practice including parental involvement, the skin to skin care, exclusive breast milk, oral immune therapy and breastfeeding. The environmental management (noise and light) and the short-term outcomes were also evaluated. RESULTS: The length of hospital stay for the developmental care group was 65â¯% as long as that for the control group (HR: 0.65, 95â¯% CI, 0.451-0936, pâ¯=â¯0.021). After controlling the covariables, the adjusted HRâ¯=â¯0.755 (95â¯% CI, 0.515 to 1.107, pâ¯=â¯0.150). When compared to the control group, the developmental care group had greater access to SSC, with 22 infants (3.8â¯%) in the developmental care group compared to 13 infants (1.7â¯%) in the standard care group (pâ¯=â¯0.013). A greater proportion of infants in the developmental care group were fed at the breast, than those in the standard care group (136 [23.6â¯%] vs 9 [1.1â¯%]; pâ¯=â¯0.029). Compared to the control group, exclusively breast milk was significantly more favorable in the developmental care group (435 [75.6â¯%] vs 114 [15.0â¯%]; pâ¯=â¯0.001). The difference remained significant even after adjusting for covariates. However, the rate of oral immune therapy and parental involvement was similar in the two groups. The average noise and light levels in the developmental care group were significantly lower than those in the standard care group. After adjusting for confounders, the difference remained significant. There were no significant differences among groups in the mortality and major morbidity. CONCLUSIONS: Developmental care might have developed an accumulated effect over time on the length of hospital stay among very low birth weight infants. The implementation of developmental care can greatly improve family centered care practices and the neonatal intensive care unit environment. REGISTRATION: ClinicalTrials.govNCT05166720. Registration date: 1 March, 2021.
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Recém-Nascido de muito Baixo Peso , Unidades de Terapia Intensiva Neonatal , Tempo de Internação , Humanos , Recém-Nascido , Feminino , Masculino , China , Análise por ConglomeradosRESUMO
Mylnudones A-G (1-7), unprecedented 1,10-seco-aromadendrane-benzoquinone-type heterodimers, and a highly rearranged aromadendrane-type sesquiterpenoid (8), along with four known analogs (9-12), were isolated from the liverwort Mylia nuda. Compounds 1-6 and 7, bearing tricyclo[6.2.1.02,7] undecane and tricyclo[5.3.1.02,6] undecane backbones, likely formed via a Diels-Alder reaction and radical cyclization, respectively. Their structures were determined by spectroscopic analysis, computational calculation, and single-crystal X-ray diffraction analysis. Dimeric compounds displayed cytoprotective effects against glutamic acid-induced neurological deficits.
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Alcanos , Hepatófitas , Sesquiterpenos de Guaiano , Sesquiterpenos , Hepatófitas/química , Estrutura Molecular , Sesquiterpenos/farmacologia , Sesquiterpenos/química , ChinaRESUMO
INTRODUCTION: Dry eye (DE) is a multifactorial ocular surface disease causing considerable medical, social and financial implications. Currently, there is no recognised long-term, effective treatment to alleviate DE. Clinical evidence shows that electroacupuncture (EA) can improve DE symptoms, tear secretion and tear film stability, but it remains controversial whether it is just a placebo effect. We aim to provide solid clinical evidence for the EA treatment of DE. METHODS AND ANALYSIS: This is a multicentre, randomised, sham-controlled trial. A total of 168 patients with DE will be enrolled and randomly assigned to EA or sham EA groups to receive 4-week consecutive treatments and follow-up for 24 weeks. The primary outcome is the change in the non-invasive tear break-up time (NIBUT) from baseline to week 4. The secondary outcomes include tear meniscus height, the Schirmer I test, corneal and conjunctival sensation, the ocular surface disease index, corneal fluorescein staining, the numerical rating scale and the Chinese DE-related quality of life scale. ETHICS AND DISSEMINATION: The trial protocol and informed consent were approved by the Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine (identifier: 2021-119), Shanghai Eye Disease Prevention and Treatment Center (identifier: 2022SQ003) and Eye and ENT Hospital of Fudan University (identifier: 2022014). TRIAL REGISTRATION NUMBER: NCT05552820.
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Síndromes do Olho Seco , Eletroacupuntura , Humanos , Qualidade de Vida , Método Simples-Cego , China , Resultado do Tratamento , Síndromes do Olho Seco/terapia , Síndromes do Olho Seco/diagnóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
The current study aimed to investigate the antitumor effects and potent mechanism of cytokine-induced killer (CIK) cells combined with irreversible electroporation (IRE) via Panc02 cell-bearing mouse model in vivo. CIK cells were isolated from the spleens of Panc02 pancreatic-cancer (PC) subcutaneous-xenograft model and the proportion of different lymphocytes was also determined. The antitumor effect of the combination of IRE and CIK cells in a PC subcutaneous-xenograft model was also investigated. The proportion of cells that were positive for CD3+CD8+ and the proportion of CD3+CD56+ cells were both significantly increased after 21 days of in vitro culture. Combined treatment of IRE and CIK cell significantly inhibited tumor growth and increased the survival rate of Panc02 cell-bearing mice. Furthermore, infiltration of lymphocytes into tumor tissue was significantly increased by this combination therapy compared with the untreated group or monotherapy group. In addition, IRE significantly enhanced the expression of chemokine receptors elicited by CIK cells. In conclusion, IRE combined with CIK cells showed superior antitumor efficacy in a PC xenograft model, which we attributed to the promotion of lymphocytic infiltration, as well as to upregulation of chemokine receptor expression and the regulators of CIK cell proliferation.
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Fructus psoraleae (FP) is a commonly used herb with potential reproductive toxicity. Bavachin (BV), one of essential active ingredients of FP, was found to exhibit estrogenic activity, but its effect on female reproductive system remains unknown. In this study, the impact of BV on the female zebrafish reproductive system and underlying molecular mechanism were determined in vivo and ex vivo. The results showed that BV could accumulate in zebrafish ovary, leading to obvious follicular atresia and increase in gonadal index and vitellogenin content. Endoplasmic reticulum (ER) swelling and hypertrophy were observed in the BV-treated zebrafish ovary, accompanied by an increase in the expressions of ER stress and unfolded protein response (UPR) related genes, namely atf6, ire-1α and xbp1s. In the ex vivo study, BV was found to decrease the survival rate and maturation rate of oocytes, while increasing the expression of Ca2+. Additionally, BV led to an elevation in the level of estrogen receptor ESR1 and the expressions of genes involved in ER stress and UPR, including atf6, ire-1α, xbp1s, chop and perk. Moreover, molecular docking revealed that BV could directly bind to immunoglobulin heavy chain binding protein (BiP) and estrogen receptor 1 (ESR1). Besides, the alterations induced by BV could be partially reversed by fulvestrant (FULV) and 4-phenylbutyric acid (4-PBA), respectively. Thus, long-termed BV-containing medicine treatment could generate reproductive toxicity in female zebrafish by causing follicular atresia through BiP- and ESR-mediated ER stress and UPR, providing a potential target for the prevention of reproductive toxicity caused by BV.
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Ovário , Peixe-Zebra , Feminino , Animais , Atresia Folicular , Simulação de Acoplamento Molecular , Transdução de Sinais , Estresse do Retículo Endoplasmático , Resposta a Proteínas não Dobradas , ApoptoseRESUMO
The roots of Astilbe grandis, known as "Ma sang gou bang", are used as a Miao traditional medicine with anti-inflammatory and analgesic properties. However, the active components and mechanism of action of this plant remain mostly uncharacterized. The aim of this study was to identify its active components and verify their pharmacological activity. The extract of A. grandis root was separated using various chromatographic methods. As a result, we obtained one novel triterpenoid, named astigranlactone (1), which has an unusual lactone moiety formed between C-7 and C-27. Additionally, a known coumarin compound, 11-O-galloyl bergenin (2) was isolated from this plant. The structures of these two compounds were elucidated by extensive NMR experiments in conjunction with HR-ESI-MS data. To the best of our knowledge, both compounds were isolated from this species for the first time. Moreover, we tested the anti-inflammation effect of the two compounds by establishing a cellular inflammation model induced by LPS in RAW264.7 cells. The effect of different concentrations of these compounds on the activity of RAW264.7 cells was assessed using a CCK8 assay. The levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) in the supernatant of each group were evaluated using the Griess method and an enzyme-linked immunosorbent assay (ELISA). Western blot and quantitative real-time PCR (qRT-RCR) were used to measure the levels of cyclooxygenase 2 (COX-2) and nitric oxide synthase (iNOS) gene expression. Our findings revealed that these two compounds inhibited the high levels of NO, TNF-α, IL-6, IL-1ß, COX-2, and iNOS (induced by LPS). Mechanistic studies demonstrated that these two compounds reduced the activation of the nuclear transcription factor-B (NF-κB) signaling pathway by inhibiting the phosphorylation of p65. Therefore, our study indicates that compounds 1 and 2 can exert a definite anti-inflammatory effect by inhibiting the NF-κB signaling pathway.
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Lipopolissacarídeos , NF-kappa B , Animais , Camundongos , NF-kappa B/metabolismo , Lipopolissacarídeos/farmacologia , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Macrófagos , Células RAW 264.7 , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/metabolismo , Cumarínicos/farmacologia , Cumarínicos/metabolismo , Óxido Nítrico/metabolismoRESUMO
At present, many infectious pathogens, especially emerging/re-emerging pathogens, exist in the blood of voluntary blood donors and may be transmitted through blood transfusions. However, most of Chinese blood centers only routinely screen for HBV, HCV, HIV, and syphilis. We employed metagenomic next-generation sequencing (mNGS) to investigate the microbiome in healthy voluntary blood donors to help assess blood safety in China by identifying infectious pathogens presented in donations that could lead to transfusion-acquired infections. We collected 10,720 plasma samples from voluntary blood donors from seven blood centers in different cities during 2012-2018 in China. A total of 562 GB of clean data was obtained. By analyzing the sequencing data, it was found that the most commonly identified bacteria found in the healthy blood were Serratia spp. (5.0176%), Pseudomonas spp. (0.6637%), and Burkholderia spp. (0.5544%). The principal eukaryote were Leishmania spp (1.3723%), Toxoplasma gondii (0.6352%), and Candida dubliniensis (0.1848%). Among viruses, Human Parvovirus B19 (B19V) accounts for the highest proportion (0.1490%), followed by Torque teno midi virus (0.0032%) and Torque teno virus (0.0015%). Since that B19V is a non-negligible threat to blood safety, we evaluated the positive samples for B19V tested by mNGS using quantitative polymerase chain reaction, Sanger sequencing, and phylogenetic analysis to achieve a better understanding of B19V in Chinese blood donors. Subsequently, 9 (0.07%) donations were positive for B19V DNA. The quantitative DNA levels ranged from 5.58 × 102 to 7.24 × 104 IU/ml. The phylogenic analyses showed that prevalent genotypes belonged to the B19-1A subtype, which disclosed previously unknown regional variability in the B19V positivity rate. The investigation revealed that many microbes dwell in the blood of healthy donors, including some pathogens that may be dormant in the blood and only cause disease under specific conditions. Thus, investigating the range and nature of potential pathogens in the qualified donations provided a framework for targeted interventions to help prevent emerging and re-emerging infectious diseases.
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This study aimed to identify the risk factors associated with puncture site bleeding following percutaneous puncture of the common femoral artery during interventional treatment of cerebrovascular disease (CVD). A retrospective analysis was conducted on 710 patients who underwent interventional treatment for CVD via femoral artery puncture. Among them, 26 individuals (3.66%) experienced bleeding at the femoral artery puncture site. Binary logistic regression analysis was performed to identify risk factors for puncture site bleeding. The impact of salt bag compression on postoperative bleeding was evaluated in patients with intermediate to high bleeding risk scores. The bleeding group showed higher blood pressure, lower platelet counts, longer prothrombin time and activated partial thromboplastin time, as well as a higher prevalence of larger vascular sheath sizes and variations in the timing of anti-coagulant and anti-platelet therapy administration. The bleeding risk score was higher in the bleeding group, indicating its predictive value for bleeding risk. Higher bleeding risk score, unstable blood pressure, repeated puncture, and serious vascular conditions were significant risk factors for puncture site bleeding. Application of salt bag compression for a duration of 2 hours reduced postoperative puncture site bleeding in patients with intermediate to high bleeding risk scores. Our study identified several significant risk factors for puncture site bleeding after cerebral vascular intervention via femoral artery puncture, including the bleeding risk score, blood pressure, repeated puncture, and vascular conditions. Implementing salt bag compression as a preventive measure can help mitigate bleeding complications in these high-risk patients.
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Doenças Cardiovasculares , Transtornos Cerebrovasculares , Humanos , Artéria Femoral/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Hemorragia , Punções/efeitos adversos , Fatores de Risco , Transtornos Cerebrovasculares/complicações , Doenças Cardiovasculares/complicaçõesRESUMO
[This corrects the article DOI: 10.3389/fcvm.2022.983532.].
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Objective: To analyze the comfort and influencing factors in patients with enterocutaneous intestinal fistula (ECF) on hospital admission and propose targeted nursing intervention countermeasures. Methods: A total of 193 patients with EDF admitted to Hunan Provincial People's Hospital in China from May 2018 to February 2021 were selected for this study. Basic patient data were collected upon admission and the Kolcaba Comfort Scale was used to score comfort status. Univariate and multivariate analysis methods were used to analyze the influencing factors. Results: Patients with ECF have low comfort scores; the social, psychological, physiological and environmental dimensions were affected by 8, 7, 4 and 2 factors, respectively. The number of fistulas and skin condition in patients with ECF were the main physiological factors affecting patients. Conclusion: Paying attention to the fistula and surrounding skin care and strengthening psychological counseling can improve the comfort of patients with ECF.
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Fístula Intestinal , Humanos , Fístula Intestinal/terapia , ChinaRESUMO
Objective: To explore the influences of Heider balance on knowledge, attitude, practice (KAP), and quality of life in bladder cancer patients after urinary diversion. Methods: A set of bladder cancer patients after urinary diversion in our hospital from January 2016 to December 2020 were included in this study. Patients who received out-hospital intervention based on Heider balance were included in the observation group (85 cases). Meanwhile, patients who received routine out-hospital intervention were included in the control group (85 cases), and these patients matched with the observation group by gender, age, and education level. The scores of KAP, WHO quality of life-100 (WHOQOL-100) before discharge and at 6 months after discharge, and the rate of complications were compared in the two groups. Results: At 6 months after discharge, the score of these items of KAP including basic knowledge of disease, procedure of pouch replacement, dealing with pouch leakage, skin care of stoma, purchase and storage of pouch, dealing with stoma complications, optimistic mentality for disease, optimistic mentality for stoma, trust in medical staff, willingness to correct bad habits, confidence in maintaining health behavior, maintaining in health dietary habit, maintaining in health behavior, learning from relevant books, learning from relevant videos, experienced in pouch replacement, and experienced in care of stoma of the observation group were significantly higher than those of the control group (t = 6.144, 9.366, 3.129, 3.809, 4.173, 5.923, 2.788, 8.871, 3.291, 10.797, 7.067, 7.805, 3.828, 9.454, 2.827, 4.059, and 8.662, respectively, all P < 0.05). The scores of 16 items of WHOQOL-100 such as energy and fatigue, sleep and rest, positive feelings, thinking, learning, memory and concentration, self-esteem, body image and appearance, negative feelings, mobility, activities of daily living, dependence on medical support, personal relationships, social support, health and social care: availability and quality, opportunities to get new information/skills, opportunities for recreation and leisure, and quality of life from viewpoint in the observation group were significantly higher than those in the control group (t = 2.666, 2.571, 2.961, 3.453, 4.279, 2.781, 3.775, 4.807, 5.850, 4.194, 3.324, 3.873, 5.118, 3.244, 2.956, and 4.218, respectively, all P < 0.05). The rate of complications of the observation group was significantly lower than that of the control group (x 2 = 5.829, P < 0.05). Conclusion: The Heider balance can help to reduce the rate of complications, improve knowledge, attitude, practice, and quality of life in urinary diversion patients. These merits make it an attractive approach in guidance of out-hospital intervention.
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Neoplasias da Bexiga Urinária , Derivação Urinária , Humanos , Atividades Cotidianas , Conhecimentos, Atitudes e Prática em Saúde , Qualidade de Vida , Neoplasias da Bexiga Urinária/cirurgia , Derivação Urinária/psicologiaRESUMO
Background and Aims: The Quzhi formula, a Chinese medicine compound prescription, relieves nonalcoholic steatohepatitis (NASH) symptoms. This study aimed to explore the mechanism of the Quzhi formula against NASH. Methods: A choline-deficient, L-amino acid-defined, high-fat diet induced a NASH mouse model and a free fatty acid-induced mouse hepatocyte cell model were used to evaluate the function of Quzhi formula in vivo and in vitro. Network pharmacology and molecular docking technology were performed to uncover the possible protective mechanisms of the Quzhi formula against NASH. Key factors in liver lipid metabolism and endoplasmic reticulum (ER) stress pathway were evaluated to verify the mechanism. Results: The positive contribution of the Quzhi formula on NASH was confirmed in vivo and in vitro. Abnormal accumulation of lipid in the liver and inflammatory responses were significantly decreased by the Quzhi formula. Network pharmacological analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the Quzhi formula protected against NASH by regulating ER stress and inflammatory responses, which was enhanced by further molecular docking analysis. In addition, mechanism exploration showed that Quzhi formula mainly reduced ER stress by downregulating Bip/eIF2α signaling. Conclusions: The Quzhi formula protected against NASH by inhibiting lipid accumulation, ER stress, and inflammatory responses, which supports the potential use of Quzhi formula as an alternative treatment for NASH.
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Background: It is controversial whether the short-axis out-of-plane or long-axis in-plane approach is a better needling technique for ultrasound-guidance radial artery cannulation. We aimed to compare the efficacy and safety of the two approaches for ultrasound-guided radial artery cannulation. Methods: A systematic search of Medline, Embase, the Cochrane Library, and Web of Science for relevant articles published until 1 May 2021 was conducted. Randomised controlled trials comparing the long-axis in-plane with short-axis out-of-plane approaches were included. Review Manager software version 5.4, STATA version 14.2, and trial sequential analysis (TSA) version 0.9.5.10 Beta were used for statistical analysis. Risk of bias and methodological quality of all studies included in this review were assessed according to the Cochrane Collaboration tool for the risk of bias. Subgroup analyses and meta-regression were performed to explore sources of heterogeneity. Results: The rate of cannula insertion success on the first attempt was similar between the short-axis out-of-plane and long-axis in-plane approaches (RR = 1.03; 95% CI: 0.83 to 1.28; P = 0.79; I 2 = 83.0%). No significant differences were observed in total time to successful cannulation between the two approaches (MD = -3.9; 95% CI:-18.30 to 10.49; P = 0.6; I 2 = 97%). However, the required information size for the success rate of the first attempt and total time to successful cannulation was not reached. Conclusion: It remains inconclusive whether short-axis out-of-plane is a better choice for radial arterial cannulation than the long-axis in-plane approach. Inexperienced operators may need more attempts and longer ultrasound location time with the short-axis out-of-plane technique. Systematic review registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021236098].
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Malignant syphilis (MS) is a rare dermatological manifestation of secondary syphilis. This case report describes a young woman that presented with a 15-day history of generalized condyloma lata and seborrheic dermatitis-like lesions at various stages. Laboratory tests showed a toluidine red unheated serum test titre of 1:128 and Treponema pallidum particle agglutination positivity. Serology for HIV antibodies was repeatedly negative. MS was diagnosed according to established MS diagnostic criteria. The lesions regressed after treatment with 2 400 000 units penicillin G benzathine by intramuscular injection weekly for three consecutive weeks. MS is more frequently associated with HIV-infected patients, which makes this current case more interesting because MS in HIV-negative patients has rarely been reported.
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Infecções por HIV , HIV-1 , Sífilis , Feminino , Anticorpos Anti-HIV , Humanos , Penicilina G Benzatina/uso terapêutico , Sífilis/complicações , Sífilis/diagnóstico , Sífilis/tratamento farmacológicoRESUMO
Pinelliae rhizoma (PR), one kind of commonly-used Chinese herbs, is generally prescribed to treat various respiratory diseases, including acute lung injury (ALI). However, the accurate bioactive ingredients of PR and the underlying pharmacological mechanism have both not been fully elucidated. Therefore, this study aimed to identify the bioactive ingredients that could alleviate lipopolysaccharide (LPS)-induced ALI and explore the possible mechanism involved. Our results confirmed that LPS infection indeed caused acute inflammatory damage in mice lung, accompanying with the enhancement of IL-1ß contents and the activation of the NLRP3 inflammasome in lung tissue and macrophagocyte, all of which were remarkably ameliorated by PR treatment. Next, mechanistically, LPS was found to trigger endoplasmic reticulum (ER) stress and downstream cellular calcium ions (Ca2+) release via activating Bip/ATF4/CHOP signaling pathway. Like PR, 4-PBA (a specific inhibitor of ER stress) not only obviously reversed Bip/ATF4/CHOP-mediated ER stress, but also significantly attenuated LPS-induced activation of the NLRP3 inflammasome. Furthermore, the bioactive ingredients of PR, which generated the anti-inflammatory effects, were screened by metabolomics and network pharmacology. In vitro experiments showed that chrysin, dihydrocapsaicin, and 7,8-dihydroxyflavone (7,8-DHF) notably suppressed LPS-induced ER stress and following NLRP3 inflammasome activation. In conclusion, our findings suggested that PR alleviated LPS-induced ALI by inhibiting ER stress-mediated NLRP3 inflammasome activation, which is mainly relevant with these three bioactive ingredients. This study provided a theoretical basis for the clinical application of PR to treat ALI, and these bioactive ingredients of PR would be promising therapeutic drugs for the treatment of ALI.
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BACKGROUND: Postoperative delirium in elderly patients is a common and costly complication after surgery. Propofol and sevoflurane are commonly used anesthetics during general anesthesia, and the sedative and anti-inflammatory mechanisms of the two medications are different. The aim of this trial is to compare the impact of propofol with sevoflurane on the incidence of postoperative delirium in elderly patients after spine surgery. METHODS: A single-center randomized controlled trial will be performed at First Affiliated Hospital of Shandong First Medical University, China. A total of 298 participants will be enrolled in the study and randomized to propofol infusion or sevoflurane inhalation groups. The primary outcome is the incidence of delirium within 7 days after surgery. Secondary outcomes include the day of postoperative delirium onset, duration (time from first to last delirium-positive day), and total delirium-positive days among patients who developed delirium; tracheal intubation time in PACU; the length of stay in PACU; the rate of postoperative shivering; the rate of postoperative nausea and vomiting; the rate of emergence agitation; pain severity; QoR40 at the first day after surgery; the length of stay in hospital after surgery; and the incidence of non-delirium complications within 30 days after surgery. DISCUSSION: The primary objective of this study is to compare the impact of propofol and sevoflurane on the incidence of postoperative delirium for elderly patients undergoing spine surgery. The results may help inform strategies to the optimal selection of maintenance drugs for general anesthesia in elderly patients undergoing spine surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT05158998 . Registered on 14 December 2021.
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Anestésicos Inalatórios , Delírio , Propofol , Idoso , Anestésicos Inalatórios/efeitos adversos , Delírio/diagnóstico , Delírio/epidemiologia , Delírio/etiologia , Humanos , Incidência , Propofol/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sevoflurano/efeitos adversosRESUMO
The nephrotoxicity of Fructus Psoraleae, an effective traditional Chinese medicine for vitiligo treatment, has been reported. As one of the main toxic components in Fructus Psoraleae, bavachin (BV) was considered to be related to Fructus Psoraleae-caused adverse outcomes, but the direct evidence and molecular mechanism underlying BV-induced nephrotoxicity are not well elucidated. Therefore, this study was designed to confirm whether BV would cause toxic effects on the kidney and explore the possible mode of action. Our results demonstrated that days' treatment with 0.5 µM BV indeed caused obvious renal fibrosis in the zebrafish kidney. The obvious E- to N-cadherin switch and the expressions of proteins promoting epithelial-mesenchymal transition (EMT) were observed in BV-treated human renal tubular epithelial and zebrafish kidneys. In addition, elevated reactive oxygen species (ROS) levels and Bip/eIF2α/CHOP-mediated endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) were caused by BV, both of which could be reversed by ROS scavenger N-acetyl-L-cysteine (NAC). Also, blocking ER stress-caused cytoplasmic Ca2+ overload with 4-PBA notably alleviated BV-induced alterations in key molecular events related to EMT and renal fibrosis. Furthermore, of the natural compounds subjected to screening, ginsenoside Rb1 significantly downregulated BV-induced ER stress by inhibiting ROS generation and following the activation of Bip/eIF2α/CHOP signaling in HK2 cells. Subsequently, BV-triggered EMT and renal fibrosis were both ameliorated by ginsenoside Rb1. In summary, our findings suggested that BV-induced ROS promoted the appearance of EMT and renal fibrosis mainly via Bip/eIF2α/CHOP-mediated ER stress. This ER stress-related toxic pathway might be a potential intervention target for BV-caused renal fibrosis, and ginsenoside Rb1 would be a promising drug against BV- or Fructus Psoraleae-induced nephrotoxicity.
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BACKGROUND: Chinese medicine (CM) has become a popular interventional treatment for rheumatoid arthritis (RA). However, limited knowledge about general characteristics and long-term clinical outcomes hampers the development of CM for RA. PURPOSE: The main objectives of the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) were to describe the population of RA patients receiving CM treatment in multiple centers in China using different variables and compare these findings with internationally reported data. STUDY DESIGN: The CERTAIN is a prospective, multicenter, observational disease registry. METHODS: Adult RA patients who fulfilled the 2010 American College of Rheumatology/ European League Against Rheumatism classification criteria for RA and received CM treatment were recruited into the CERTAIN by rheumatologists from 145 hospitals across 30 provinces in China. Data on demographics, disease characteristics, comorbidities, treatments, and adverse events, with a 2-year follow-up, were collected and documented using a predefined protocol. RESULTS: In the 2 years since the study began in September 2019, 11,764 patients have been enrolled (enrolment is ongoing), and 13.10% of participants have completed the 6-month follow-up. We present the baseline characteristics of the first 11,764 enrollees. CONCLUSIONS: The CERTAIN is the first nationwide registry to document comprehensive data on CM treatment in patients with RA. The development of the CERTAIN resource is a significant step forward for Chinese RA patients, herbal medicine users, and research communities and will deepen our understanding of CM for RA. REGISTRATION: The study was registered at ClinicalTrials.gov (NCT05219214).
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Antirreumáticos , Artrite Reumatoide , Adulto , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , China/epidemiologia , Humanos , Medicina Tradicional Chinesa , Estudos Prospectivos , Sistema de RegistrosRESUMO
Modern oncology increasingly relies on pathological, molecular, and genomic assessments of biopsied tumor tissue. However, the concern for bleeding complication and malignant seeding severely hinders the application of the biopsy tumor. Here, we developed a 16 G biopsy needle to contain two electrodes insulated from each other and connect to an radiofrequency generator. For evaluating hemostatic efficacy, 50 rabbits were randomly divided into two groups: warfarinization and non-warfarinization group. Two liver biopsies and two splenic biopsies per animal were performed using a 16 G biopsy needle. Each group was further equally divided into five groups according to different hemostatic measures, including non-intervention, embolization using an absorbable gelatin sponge, and ablation by RF with three different needle temperatures (50°C, 70°C, and 90°C). Than, we used VX2 rabbit models (n = 25) and applied the five analogous biopsies to the tumor. The flush fluid from the biopsy needle underwent cytomorphological analysis. Our results that the groups using ablation by RF showed significantly less blood loss than the control group for liver and spleen in both groups (P < 0.001). After RF ablation, thermal coagulation of the tissue surrounding the needle tract was observed on both the macroscopic and histological level. Cytological smears showed that tumor cells were degenerated after RF at 70°C and 90°C. Our findings showed that bipolar RF biopsy needle is a promising tool for reducing hemorrhage after biopsy and avoiding implanting tumor cells in the tract.