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BACKGROUND: This study delves into the intricate landscape of atherosclerosis (AS), a chronic inflammatory disorder with significant implications for cardiovascular health. AS poses a considerable burden on global healthcare systems, elevating both mortality and morbidity rates. The pathological underpinnings of AS involve a marked metabolic disequilibrium, particularly within pyrimidine metabolism (PyM), a crucial enzymatic network central to nucleotide synthesis and degradation. While the therapeutic relevance of pyrimidine metabolism in diverse diseases is acknowledged, the explicit role of pyrimidine metabolism genes (PyMGs) in the context of AS remains elusive. Utilizing bioinformatics methodologies, this investigation aims to reveal and substantiate PyMGs intricately linked with AS. METHODS: A set of 41 candidate PyMGs was scrutinized through differential expression analysis. GSEA and GSVA were employed to illuminate potential biological pathways and functions associated with the identified PyMGs. Simultaneously, Lasso regression and SVM-RFE were utilized to distill core genes and assess the diagnostic potential of four quintessential PyMGs (CMPK1, CMPK2, NT5C2, RRM1) in discriminating AS. The relationship between key PyMGs and clinical presentations was also explored. Validation of the expression levels of the four PyMGs was performed using the GSE43292 and GSE9820 datasets. RESULTS: This investigation identified four PyMGs, with NT5C2 and RRM1 emerging as key players, intricately linked to AS pathogenesis. Functional analysis underscored their critical involvement in metabolic processes, including pyrimidine-containing compound metabolism and nucleotide biosynthesis. Diagnostic evaluation of these PyMGs in distinguishing AS showcased promising results. CONCLUSION: In conclusion, this exploration has illuminated a constellation of four PyMGs with a potential nexus to AS pathogenesis. These findings unveil emerging biomarkers, paving the way for novel approaches to disease monitoring and progression, and providing new avenues for therapeutic intervention in the realm of atherosclerosis.
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Aterosclerose , Doença da Artéria Coronariana , Humanos , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/genética , Aterosclerose/diagnóstico , Aterosclerose/genética , Biomarcadores , Biologia Computacional , Aprendizado de Máquina , NucleotídeosRESUMO
Puerarin (Pue) has significant antioxidant and anti-inflammatory properties. This work was designed to clarify and investigate the potential mechanisms of Pue in atherosclerosis (AS) progression. In vivo, acrolein (Acr) was inhaled through drinking water to construct AS model. In vitro, CCK-8 assay and lactate dehydrogenase (LDH) assay kit were used to detect cell viability. Apoptosis was detected by flow cytometry. The content of malondialdehyde (MDA) was determined by commercial kit, the level of inflammatory factors was detected by ELISA, and proteins were determined by western blot. Pue administration could effectively reduce blood lipid level in Acr-fed mice. Pue suppressed oxidative stress, the formation of atherosclerotic plaques, and the process of aortic histological changes. Pue pretreatment decreased MDA in HUVECs and maintained the activity of antioxidant enzymes. Pue upregulated SIRT1/Nrf2 cascade in HUVECs. Pue increased MYH9 and inhibited NLRP3 inflammasome-related proteins, and the inhibition of MYH9 significantly impaired Pue-induced Nrf2 activation. Moreover, HUVEC cytotoxicity and apoptosis are alleviated by Pue, in addition to NLRP3-mediated pyroptosis in HUVECs induced by Acr. MYH9 inhibitors effectively suppressed the pyroptosis induced by Acr and prevented injury to HUVECs. In addition, Pue promoted SIRT1/Nrf2 cascade activation in HUVECs. Pue may alleviate Acr-induced AS by activating the MYH9-mediated SIRT1/Nrf2 cascade to inhibit inflammasome activation.
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A novel nitrogen-doped ordered mesoporous carbon (OMC) pore-embedded growth Pt-Ru-Fe nanoparticles (Pt1-Ru7.5-Fex@N-OMCs) composite was designed and synthesized for the first time. SBA-15 was used as a template, and dopamine was used as a carbon and nitrogen source and metal linking reagent. The oxidative self-polymerization reaction of dopamine was utilized to polymerize dopamine into two-dimensional ordered SBA-15 template pores. Iron porphyrin was introduced as an iron source at the same time as polymerization of dopamine, which was introduced inside and outside the pores using dopamine-metal linkage. Carbonization of polydopamine, nitrogen doping and iron nanoparticle formation were achieved by one-step calcination. Then the templates were etched to form Fex@N-OMCs, and finally the Pt1-Ru7.5-Fex@N-OMCs composites were stabilized by the successful introduction of platinum-ruthenium nanoparticles through the substitution reaction. The composite uniformly embeds the transition metal nanoparticles inside the OMC pores with high specific surface area, which limits the size of the metal nanoparticles inside the pores. At the same time, the metal nanoparticles are also loaded onto the surface of the OMCs, realizing the uniform loading of metal nanoparticles both inside and outside the pores. This enhances the active sites of the composite, promotes the mass transfer process inside and outside the pores, and greatly enhances the electrocatalytic performance of the catalyst. The material shows high electrocatalytic performance for adrenaline, which is characterized by a wide linear range, high sensitivity and low detection limit, and can realize the detection of actual samples.
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BACKGROUND: Effective interprofessional teamwork is essential for the efficiency, safety and quality of healthcare system services and requires interprofessional education for medical students. Physical education is a simple and easy way to teach teamwork, which translates into team performance in the work environment. This study was conducted to examine the effectiveness of the physical education competition model, instead of the exams model, for improving teamwork skills among medical students. METHODS: A quasiexperimental intervention design was used to measure the effect of a 16-week cheerleading programme on subjects' teamwork skills by completing a teamwork scale comprising four subdimensions, namely, personal characteristics, teamwork, leadership, and conflict management, before the start and at the end of the programme, and by comparing nonwinning to winning students to measure the effect of teamwork skills on team performance. RESULTS: A total of 179 students completed the valid baseline and posttest (effective rate = 95.21%). The teamwork scale scores (B M = 4.81, R M = 5.05, p < 0.001) and 4 subdimension scores (personal characteristics p = 0.002, teamwork p = 0.028, leadership p < 0.001, conflict management p < 0.001) were statistically significant. Twenty-two of the 44 items in the scale improved significantly. The differences between students who won the competition and those who did not (N M=4.86, W M=5.14, p<0.01) were statistically significant, with no significant differences in personal characteristics p = 0.183; significant differences in the 3 subdimensions of teamwork p < 0.01, leadership p = 0.024, and conflict management p = 0.037; and a significant increase in 13 out of 44 self-efficacy items on the scale. CONCLUSIONS: The "race for exams" physical education programme improved teamwork among medical students, and increased teamwork improved team performance. The "competition instead of examination" physical education programme provides a quantifiable method for improving interprofessional teamwork among medical students.
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Currículo , Relações Interprofissionais , Estudantes de Medicina , Humanos , Masculino , Feminino , Esportes , Adulto Jovem , Liderança , Comportamento Cooperativo , Comportamento Competitivo , Educação de Graduação em Medicina , Equipe de Assistência ao PacienteRESUMO
RATIONALE: Diterpene lactones (DL) in Andrographis paniculata (AP) are known as "natural antibiotics" for their excellent antibacterial activity. During mass spectrometry (MS) analysis, the hydroxyl groups in the AP DL skeleton are prone to neutral loss of H2 O, producing high in-source fragment peaks and affecting the characterization of these components. METHODS: Mass tags were applied during the MS data acquisition step, and special adduct ion form was used to guide the data processing and characterization steps. Besides, the total number of characterized AP DLs significantly increased when combining the number of neutrally lost H2 O from AP DLs, incorporating information on the diagnostic ions, and adopting molecular networks generated with the Global Natural Products Social Molecular Networking database. RESULTS: Ninety-nine DLs, comprising 6 monohydroxyl groups, 20 dihydroxyl groups, 27 trihydroxy groups, and 46 DLs with more than 3 hydroxyl groups, were characterized from AP. In addition, based on the characteristic fragments in the product ions (C3 H4 , Δm/z = 40.03 Da), it could be assumed that 90 DLs had the C19-OH structure among the identified DLs. The current study provides a new approach for collecting, processing, and characterizing MS analysis of natural DLs prone to in-source fragmentation. CONCLUSIONS: MS characterization of AP DLs was significantly improved, and many potential new compounds were identified in AP. This characterization provides new methods for the purification and identification of AP DLs.
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Andrographis , Diterpenos , Andrographis paniculata , Lactonas/química , Andrographis/química , Espectrometria de Massas , Extratos Vegetais/química , Diterpenos/químicaRESUMO
INTRODUCTION: Cognitive function is considered to be correlated with the older adults' mobility. Flanker task, reflecting the conflict resolution, is barely explored as a simple approach to train the older adults' cognitive function. Hence, the first aim of this study was to explore the effect of cognitive intervention adopting flanker task on mobility. The second aim of this study was to assess the effect of cognitive training by comparing it with physical training to disclose how much dosage of cognitive training can have the equal improvement of mobility with physical training. METHODS: 232 older adults (age, mean ± SD: 66.16 ± 7.08, female: 74.3%) were retrained and assigned into three groups (cognitive intervention group, physical exercise intervention group, and control group). The intervention lasted for 22 weeks (cognitive intervention: flanker task, 30 min per session, 3 sessions a week; physical exercise intervention: 30 min muscle and balance training session, twice a week, and 30 min daily walking and housework, 2-4 times a week). Grip strength, 30-s chair-stand test, single leg balance with eyes closed, and the timed "Up & Go" (TUG) were used as indicators of mobility. A mixed model analysis of variance (ANOVA), interaction effect, and simple effect were performed in statistical analysis. RESULTS: Both intervention groups improved mobility, and the results were similar behaviorally. However, the exercise intervention group performed better in 30-s chair-stand test (25.14 ± 0.67 vs. 23.71 ± 0.76 with p = 0.01) and single leg balance with eyes closed (8.15 ± 0.69 vs. 6.14 ± 0.43 with p < 0.001). CONCLUSION: 22-week cognitive intervention (for total 1,980 min) could improve the older adults' mobility to the similar extent of mild-to-moderate physical exercises (1,320 min of functional muscle and balance training and 1,980 daily physical activities), which ascertained the far transfer effects from cognition to untrained mobility domain and found a comparable dosage of cognitive and physical exercise training.
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Treino Cognitivo , Equilíbrio Postural , Idoso , Feminino , Humanos , Exercício Físico/fisiologia , Terapia por Exercício/métodos , Força da Mão , Equilíbrio Postural/fisiologia , Caminhada/fisiologiaRESUMO
Recently, the supra-normal left ventricular ejection fraction (snLVEF) has been proposed, based on extensive datasets indicating increased all-cause mortality in individuals with an LVEF exceeding 65%. However, the implications of an LVEF > 65% in the context of acute coronary syndrome (ACS) remain underexplored.The aim of the present study was to investigate the correlation between supra-normal left ventricular ejection fraction (snLVEF) and major adverse cardiovascular events (MACE) in patients with ACS.Methods: A total of 874 ACS patients (560 men, mean age 59.5 ± 10.0; 314 women, mean age 61.5 ± 8.9) who underwent their first coronary angiography during the period from March 2013 to October 2015 were divided into 2 groups: normal LVEF (nLVEF) (55% ≤ EF ≤ 65%) and snLVEF (EF > 65%), according to their echocardiography results. The patients were evaluated for MACE after surgery by collecting clinical data and long-term follow-up data. This correlation was further analyzed by Kaplan-Meier analysis and Cox regression analysis.The follow-up data revealed a significantly higher incidence of MACE among snLVEF patients compared to the nLVEF group (15.6% versus 7.4%; P = 0.020). This heightened risk persisted even after adjustment for multiple variables, indicating a strong association between snLVEF and increased MACE risk (HR: 2.346; 95% CI: 1.196-4.602; P = 0.013).SnLVEF was independently associated with poor prognosis after ACS. Enhanced management strategies for snLVEF patients could potentially reduce the incidence of MACE in ACS patients.
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Síndrome Coronariana Aguda , Função Ventricular Esquerda , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Volume Sistólico , Prognóstico , Análise de RegressãoRESUMO
OBJECTIVES: To explore the etiology composition and outcomes of pediatric chronic critical illness (PCCI) in the pediatric intensive care unit (PICU). METHODS: The children who were hospitalized in the PICU of Dongguan Children's Hospital Affiliated to Guangdong Medical University and met the diagnostic criteria for PCCI from January 2017 to December 2022 were included in the study. The etiology of the children was classified based on their medical records and discharge diagnoses. Relevant clinical data during hospitalization were collected and analyzed. RESULTS: Among the 3 955 hospitalized children in the PICU from January 2017 to December 2022, 321 cases (8.12%) met the diagnostic criteria for PCCI. Among the 321 cases, the most common etiology was infection (71.3%, 229 cases), followed by unintentional injury (12.8%, 41 cases), postoperation (5.9%, 19 cases), tumors/immune system diseases (5.0%, 16 cases), and genetic and chromosomal diseases (5.0%, 16 cases). Among the 321 cases, 249 cases (77.6%) were discharged after improvement, 37 cases (11.5%) were discharged at the request of the family, and 35 cases (10.9%) died in the hospital. Among the deaths, infection accounted for 74% (26/35), unintentional injury accounted for 17% (6/35), tumors/immune system diseases accounted for 6% (2/35), and genetic and chromosomal diseases accounted for 3% (1/35). From 2017 to 2022, the proportion of PCCI in PICU diseases showed an increasing trend year by year (P<0.05). Among the 321 children with PCCI, there were 148 infants and young children (46.1%), 57 preschool children (17.8%), 54 school-aged children (16.8%), and 62 adolescents (19.3%), with the highest proportion in the infant and young children group (P<0.05). The in-hospital mortality rates of the four age groups were 14.9% (22/148), 8.8% (5/57), 5.6% (3/54), and 8.1% (5/62), respectively. The infant and young children group had the highest mortality rate, but there was no statistically significant difference among the four groups (P>0.05). CONCLUSIONS: The proportion of PCCI in PICU diseases is increasing, and the main causes are infection and unintentional injury. The most common cause of death in children with PCCI is infection. The PCCI patient population is mainly infants and young children, and the in-hospital mortality rate of infant and young children with PCCI is relatively high.
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Criança Hospitalizada , Estado Terminal , Adolescente , Lactente , Pré-Escolar , Humanos , Criança , Prognóstico , Doença Crônica , Unidades de Terapia Intensiva PediátricaRESUMO
Four novel Gelsemium elegans cyclic peptides (GEPs) were isolated in an antihuman cervical carcinoma activity tracking method, and their amino acid sequences were identified. The GEP-1 cyclic-(Trp-Leu-His-Val)-peptide inhibited HeLa cell proliferation in a dose- and time-dependent manner. GEP-1 induced intracellular reactive oxygen species (ROS) overproduction and induced HeLa cells apoptosis in a caspase-dependent manner. GEP-1 also induced collapse of the mitochondrial membrane potential and promoted the mitochondrial release of cytochrome c (cyt c), apoptosis-inducing factor (AIF), and endonuclease G (Endo G) in HeLa cells. Furthermore, GEP-1 triggered the extrinsic death receptor-dependent pathway, which was characterized by activating Fas and FADD. Notably, GEP-1 is a potential antihuman cervical carcinoma peptide.
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Carcinoma , Gelsemium , Apoptose , Linhagem Celular Tumoral , Gelsemium/metabolismo , Células HeLa , Humanos , Potencial da Membrana Mitocondrial , Peptídeos Cíclicos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de SinaisRESUMO
The human immunodeficiency virus type 1 (HIV-1) is the major etiological agent responsible for the acquired immunodeficiency syndrome (AIDS), which is a serious infectious disease and remains one of the most prevalent problems at present. Currently, combined antiretroviral therapy is the primary modality for the treatment and management of HIV/AIDS, but the long-term use can result in major drawbacks such as the development of multidrug-resistant viruses and multiple side effects. 1,2,3-Triazole is the common framework in the development of new drugs, and its derivatives have the potential to inhibit various HIV-1 enzymes such as reverse transcriptase, integrase, and protease, consequently possessing a potential anti-HIV-1 activity. This review covers the recent advances regarding the 1,2,3-triazole hybrids with potential anti-HIV-1 activity; it focuses on the chemical structures, structure-activity relationship, and mechanisms of action, covering articles published from 2010 to 2020.
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Fármacos Anti-HIV/farmacologia , Infecções por HIV/tratamento farmacológico , Triazóis/farmacologia , Fármacos Anti-HIV/química , Humanos , Relação Estrutura-Atividade , Triazóis/químicaRESUMO
OBJECTIVE: The purpose of this study was to review the literature on the effect of scraping therapy on chronic low back pain (LBP) from randomized controlled trials (RCTs). METHODS: Three English medical electronic databases (PubMed, Embase, and the Cochrane Library) and 2 Chinese databases (China National Knowledge Infrastructure and Wanfang) were searched. Only randomized controlled trials related to the effects of scraping therapy on chronic LBP were included in this systematic review. Study selection, data extraction, and validation were conducted independently by 2 reviewers. The methodological quality of the studies was evaluated by the Cochrane risk-of-bias tool. RevMan 5.3 software was applied to perform meta-analysis of the data. RESULTS: Ten studies comprising 627 participants were included. Overall, the quality of evidence was moderate owing to a lack of blinding and allocation concealment in some studies and unclear risk of selective reporting. Meta-analysis of 9 RCTs indicated that scraping therapy had a statistically significant effect on pain reduction (standard mean differenceâ¯=â¯-0.66, 95% confidence interval [CI], -0.83 to -0.49, P < .001). However, if only a single scrape treatment was carried out, the results did not show that scraping was superior to the control group regarding pain relief (mean differenceâ¯=â¯-0.35, 95% CI, -1.23 to 0.53, Pâ¯=â¯.44). Moreover, the results of 6 RCTs involving 468 participants showed significantly greater improvement in lumbar dysfunction (mean differenceâ¯=â¯-10.05, 95% CI, -13.52 to -2.32, P < .001). In addition, the results of 5 RCTs involving 393 participants showed a favorably significant effect on the overall efficacy (odds ratioâ¯=â¯4.74, 95% CI, 2.34-9.62, P < .001). As for follow-up effects, meta-analysis of 3 RCTs involving 241 participants showed a promising effect on pain reduction and lumbar function improvement at 1 month and 3 months after the end of treatment, respectively. Only 1 study reported adverse effects, and none were serious. CONCLUSION: Scraping therapy may have a therapeutic effect for some individuals with chronic LBP. However, due to the limited amount of research and the low methodological quality of the included studies, additional large-scale, multicenter, high-quality RCTs on relieving pain intensity and improving lumbar dysfunction are still necessary.
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Dor Crônica/terapia , Dor Lombar/terapia , Medicina Tradicional Chinesa/métodos , Qi , China , Humanos , Medição da Dor , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
BACKGROUND The aim of this study was to study the feasibility and acceptability of electroacupuncture (EA) for preventing postoperative gastrointestinal complications in patients undergoing thoracoscopic segmentectomy/lobectomy. MATERIAL AND METHODS Sixty patients who underwent video-assisted thoracoscopic (VATS) segmentectomy/lobectomy received either EA treatments plus usual care (EA group) or usual care alone (UC group). Patients in the EA group were given 30 minutes of bilateral electroacupuncture on 3 acupoints [Neiguan (PC6), Zusanli (ST36), and Shangjuxu (ST37)] at 3 time points (24 hours before surgery, and 4 hours and 24 hours after surgery). The primary outcomes were recruitment, retention, acceptability of the EA intervention, incidence and severity of abdominal distension (AD), and time to first flatus and defecation. Secondary outcomes included postoperative nausea and vomiting (PONV), pain intensity, and duration of hospital stay. RESULTS We recruited 60 participants and 59 were randomized into 2 groups for this study: 30 in the EA group and 29 in the UC group. In total, 57 participants completed the study. With the exception of one participant in the EA group, all participants completed all three sessions of EA. The one exclusion was a case where a paravertebral block was not used during the surgery. Qualitative findings from the acceptability questionnaire indicated that participants viewed the EA treatment as acceptable. After EA treatment, there was a small but statistically significant improvement in participants' acceptance of EA for alleviating postoperative gastrointestinal discomfort (P=0.001). The EA group showed improved outcomes compared to the UC group in terms of time to first flatus (20.8±4.6 versus 24.1±6.2 hours, P=0.026) and defecation (53.9±6.0 versus 57.5±7.2 hours, P=0.046). No significant differences appeared regarding AD, rescue medication, or duration of hospitalization. PONV and pain intensity were similar in both groups at the recorded time periods. CONCLUSIONS EA is feasible and acceptable to patients undergoing VATS surgery. Our preliminary findings of EA promoting postoperative recovery of gastrointestinal function warrants large randomized controlled trials.
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Eletroacupuntura/métodos , Náusea e Vômito Pós-Operatórios/terapia , Toracoscopia/métodos , Pontos de Acupuntura , Adulto , Idoso , Anestesia Geral , Estudos de Viabilidade , Feminino , Trato Gastrointestinal/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Náusea e Vômito Pós-Operatórios/prevenção & controle , Período Pós-Operatório , Recuperação de Função Fisiológica/fisiologiaRESUMO
Background The aim of this study was to assess the normal values of the Smith-Madigan inotropy index (SMII) and oxygen delivery index (DO2I) in low-birth-weight (LBW) and very-low-birth-weight (VLBW) newborns on the first 3 days of life, and to identify how different degrees of maturity influence cardiovascular alterations during the transitional period compared with term neonates. Methods Twenty-eight VLBW newborns, 46 LBW newborns and 50 normal full-term newborns admitted to our department were studied. Hemodynamics of the left heart were measured in all neonates over the first 3 days using the Ultrasonic Cardiac Output Monitor (USCOM). This was combined with hemoglobin concentration and pulse oximetry to calculate DO2I. Blood pressure was combined with the hemodynamic measures and hemoglobin concentration to calculate SMII. Results SMII showed statistically significant differences among the three groups (VLBW 0.48 ± 0.11; LBW 0.54 ± 0.13; term 0.69 ± 0.17 W/m2 P < 0.001), which was in line with the following myocardial parameters: stroke volume index (SVI) and cardiac index (CI) (P < 0.001 and <0.001). For systemic oxygen delivery (DO2) parameters, significant differences were found for DO2I (P < 0.001) while hemoglobin concentration and pulse oximetry demonstrated no significant differences. In the VLBW group, SMII and DO2I showed no significant change over the 3 days. Conclusion Normal inotropy and systemic DO2I values in VLBW neonates over the first 3 days of life were assessed. SMII and DO2I were significantly lower in VLBW neonates during the first 72 h of life. With increasing birth weight, higher myocardial inotropy and DO2 were found. The addition of USCOM examination to standard neonatal echocardiography may provide further important information regarding cardiac function.
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Débito Cardíaco , Recém-Nascido de Baixo Peso/fisiologia , Feminino , Humanos , Recém-Nascido , Masculino , Estudos Prospectivos , Ultrassonografia DopplerRESUMO
BACKGROUND: Acute postoperative pain remains a major clinical problem that affects patient recovery. Distal acupoint and peri-incisional stimulation are both used for relieving acute postoperative pain in hospital. Our objective was to assess and compare the effects of distal and peri-incisional stimulation on postoperative pain in open abdominal surgery. METHODS: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Chinese databases CNKI and Wanfangdata were searched to identify eligible randomized controlled trials. Intensity of postoperative pain, opioid consumption and related data were extracted and analyzed using a random effects model. Risk of bias was assessed. Subgroup analyses were conducted when data were enough. RESULTS: Thirty-five trials were included, in which 17 trials studied distal stimulation, another 17 trials studied peri-incisional stimulation and one studied the combination of the two approaches. No studies that directly compared the two approaches were identified. Subgroup analysis showed that both distal and peri-incisional stimulation significantly alleviated postoperative resting and movement pain from 4 h to 48 h after surgery by 6 to 25 mm on a 100 mm visual analogue scale. Peri-incisional stimulation showed a better reduction in postoperative opioid consumption. No studies compared the effects of the combined peri-incisional and distal stimulation with either mode alone. Overall the quality of evidence was moderate due to a lack of blinding in some studies, and unclear risk of allocation concealment. CONCLUSION: Both distal and peri-incisional modes of stimulation were effective in reducing postoperative pain. Whether a combined peri-incisional stimulation and distal acupuncture has superior results requires further studies.
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Abdome/cirurgia , Pontos de Acupuntura , Terapia por Acupuntura , Dor Pós-Operatória/terapia , Feminino , Humanos , Masculino , Medição da Dor , Resultado do TratamentoRESUMO
The use of arctigenin (ARG), a traditional medicine with many pharmacological activities, has been restricted due to its poor solubility in water. Five amino acid derivatives of ARG have been synthesized using glycine, o-alanine, valine, leucine, and isoleucine, which have t-butyloxy carbonyl (BOC) as a protective group. In this study, we examined the effects of removing these protective groups. The results showed that the amino acid derivatives have better solubility and nitrite-clearing ability than ARG. Among the compounds tested, the amino acid derivatives without protective group were the best. Based on these results, ARG and its two amino acid derivatives without protective group (ARG8, ARG10) were selected to evaluate their anti-tumor activity in vivo at a dosage of 40 mg/kg. The results indicated that ARG8 and ARG10 both exhibit more anti-tumor activity than ARG in H22 tumor-bearing mice. The tumor inhibition rates of ARG8 and ARG10 were 69.27 and 43.58%, which was much higher than ARG. Furthermore, the mice treated with these compounds exhibited less damage to the liver, kidney and immune organs compared with the positive group. Furthermore, ARG8 and ARG10 improved the serum cytokine levels significantly compared to ARG. In brief, this study provides a method to improve the water solubility of drugs, and we also provide a reference basis for new drug development.
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Aminoácidos/farmacologia , Antineoplásicos/farmacologia , Ésteres/farmacologia , Furanos/farmacologia , Lignanas/farmacologia , Neoplasias Experimentais/tratamento farmacológico , Aminoácidos/síntese química , Aminoácidos/química , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Ésteres/síntese química , Ésteres/química , Furanos/síntese química , Furanos/química , Lignanas/síntese química , Lignanas/química , Camundongos , Estrutura Molecular , Neoplasias Experimentais/patologia , Relação Estrutura-AtividadeRESUMO
OBJECTIVE: Atherosclerosis (AS) is a common pathogenesis of cardiovascular diseases. Puerarin (Pue) is a Chinese herbal remedy used to prevent and treat AS. Here, this research investigated the effect of Pue on AS progression. METHODS: ApoE-/- mice were induced with acrolein. Body weight, blood lipid index, inflammatory factors, mitochondrial oxidative stress, and lipid deposition were detected. IL-6 and TNF-α were detected by ELISA. Oil red staining and H&E staining were used to observe the aortic sinus plaque lesions. Serum expressions of inflammatory factors IL-6, TNF-a, SOD, GSH and MDA were detected by ELISA, the mRNA expression levels of HDAC1 in the aorta were detected by RT-qPCR, and IL-6 and TNF-α in the aorta were detected by immunohistochemistry. JNK, p-JNK, OPA-1, and HDAC1 were detected by Western blotting. RESULTS: Pue administration can effectively reduce lipid accumulation in AS mice induced by acrolein. Pue promoted the activity of SOD, GSH and MDA, and inhibited the formation of atherosclerotic plaques and the process of aortic histological changes. Pue reduced IL-6 and TNF-α. HDAC1 expression was down-regulated and p-JNK-1 and JNK protein expression was up-regulated. CONCLUSION: Pue reduces inflammation and alleviates AS induced by acrolein by mediating the JNK pathway to inhibit HDAC1-mediated oxidative stress disorder.
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Acroleína , Aterosclerose , Histona Desacetilase 1 , Isoflavonas , Estresse Oxidativo , Animais , Aterosclerose/induzido quimicamente , Aterosclerose/metabolismo , Aterosclerose/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Histona Desacetilase 1/metabolismo , Isoflavonas/farmacologia , Isoflavonas/uso terapêutico , Acroleína/farmacologia , Masculino , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Western Blotting , Aorta/efeitos dos fármacos , Aorta/patologiaRESUMO
Twelve polyphenol derivatives were obtained in a protective activity-guided isolation from the Portulaca oleracea L. extract on a cell model of human umbilical vein endothelial cells (HUVECs) under diethylhexyl phthalate (DEHP) exposure. Among them, methyl (3,4,5-trimethoxybenzoyl) valylprolinate (PP-10) performed the most protective activity and inhibited DEHP exposure-induced HUVECs' apoptosis. PP-10 also inhibited the DEHP-induced inflammatory cytokines (TNF-α, IL-6, IL-1ß, and IL-8) and adhesion molecule (ICAM-1 andVCAM-1) overexpression. Furthermore, DEHP-induced NLRP3 inflammasomes' and NF-κB signaling pathway activation was significantly inhibited after the PP-10 treatments. Of note, the current results suggest the potential application of Portulaca oleracea L. and PP-10 in the prevention of DEHP-induced inflammatory damages in HUVECs.
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Background: Studies of chylothorax after congenital heart disease in infants are rare. Chylothorax has a higher incidence in infancy, but its risk factors are not well understood. Objective: The purpose of this study is to investigate the risk factors of chylothorax after congenital heart surgery in infants. Methods: This retrospective study included 176 infants who underwent congenital heart disease surgery at the Guangdong Cardiovascular Institute, China, between 2016 and 2020. According to the occurrence of chylothorax, the patients were divided into a control group (n = 88) and a case group (n = 88). Univariate and multivariate logistic regression were performed to analyse the incidence and influencing factors of chylothorax after congenital heart surgery in infants. Results: Between 2016 and 2020, the annual incidence rate fluctuated between 1.55% and 3.17%, and the total incidence of chylothorax was 2.02%. Multivariate logistic regression analysis showed that postoperative albumin (p = 0.041; odds ratio [OR] = 0.095), preoperative mechanical ventilation (p = 0.001; OR = 1.053) and preterm birth (p = 0.002; OR = 5.783) were risk factors for postoperative chylothorax in infants with congenital heart disease. Conclusion: The total incidence of chylothorax was 2.02% and the annual incidence rate fluctuated between 1.55% and 3.17% between 2016 and 2020. Premature infants, longer preoperative mechanical ventilation and lower albumin after congenital heart surgery may be risk factors for chylothorax. In addition, infants with chylothorax are inclined to be infected, need more respiratory support, use a chest drainage tube for longer and remain longer in hospital.
RESUMO
OBJECTIVE: To clone and express Der f7 gene of Dermatophagoides farinae, and identify its immunogenicity. METHODS: Total RNA was extracted from D. farinae mites. A reference sequence (Accession No. AY283292) was used to design specific primers. The Der f7 gene fragment was amplified by RT-PCR, and cloned into pET-32a vector. The recombinant plasmid was transformed into E. coli BL21 (DE3) and induced with IPTG for protein expression. The recombinant protein was purified by Ni2+ chelating affinity chromatography and analyzed by SDS-PAGE and Western blotting. RESULTS: The Der f7 gene fragment was about 650 bp, and shared 99% homology with the published one (Accession No. FJ436108). SDS-PAGE result showed its relative molecular weight (M(r)) of 23 000. The recombinant protein showed appropriate combination ability with IgE in sera of mite allergic patients. CONCLUSION: Der f 7 gene has been expressed in prokaryotic expression system and shows allergenicity.
Assuntos
Antígenos de Dermatophagoides/genética , Antígenos de Dermatophagoides/imunologia , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Dermatophagoides farinae/genética , Alérgenos/genética , Alérgenos/imunologia , Animais , Antígenos de Dermatophagoides/isolamento & purificação , Proteínas de Artrópodes/isolamento & purificação , Clonagem Molecular , Dermatophagoides farinae/imunologia , Expressão Gênica , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologiaRESUMO
Inflammation and oxidative stress play pivotal role in the process of atherosclerosis. Scorpion venom is widely used as anti-cancer agent, however, the anti-inflammatory and antioxidant activities of scorpion venom peptides (SVPs) are rarely explored. In the current study, seven novel SVPs were isolated in a protective activity tracking isolation method in a cell model of benzo(α)pyrene (BaP)-induced human umbilical vein endothelial cells (HUVECs). The current study showed that SVP-1 [Tyr-Thr-Trp-Glu-Ala] significantly attenuated BaP-induced reactive oxygen species (ROS) over-production and inflammatory cytokines (IL-6, IL-1ß, TNF-α, NO and PGE2) over-expression. Furthermore, SVP-1 attenuated BaP-induced adhesion molecules over-expression and inhibited the NF-κB and AhR signalling pathways activation. Collectively, the present study, for the first time, shows that SVPs inhibit the NF-κB and AhR signalling pathways in HUVECs under BaP-exposure, which strongly suggests the therapeutic potential of SVPs against atherosclerosis.