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Objective: Severe infections can lead to neuromyopathy in critically ill patients, resulting in limb weakness and difficulty in weaning from a ventilator. This study aims to assess the electrophysiological test results in patients with severe infection and their correlation with severity scores (APACHE II and SOFA). Methods: Thirty-one patients with severe infection in the EICU were prospectively studied. Factor analysis and principal component regression were applied to develop linear models of electrophysiological diagnostic outcomes with APACHE II and SOFA scores for the entire patient cohort, the younger group (age<55) cohort, and the older group (age>55) cohort of patients with severe infections, respectively. Results: Among patients with a severe infection in the EICU, the proportion of patients without critical neuromyopathy with more than 50% F-wave presence in the median, ulnar, and tibial nerves (64.9%, 56.8%, 48.6%, respectively) was significantly higher than in the group with critical neuromyopathy (52.1%, 35.4%, 29.2%, respectively.), and the proportion of patients with critical neuromyopathy who did not elicit the three types of F wave was significantly higher in the cohort of patients with critical neuromyopathy (40.5%, 32.4%, 35.1%, respectively.) were significantly higher than in the cohort of patients without critical illness (18.8%, 12.5%, 20.8%, respectively). In addition, on average, patients with critical neuromyopathy had a much lower CMAP for the median nerve (wrist, elbow) (2.4, 1.88, respectively) (4.3, 3.9, respectively in undiagnosed cohort), ulnar nerve (wrist, elbow) (2.4, 1.88, respectively) (5.65, 5.4, respectively in undiagnosed cohort), and tibial nerve(ankle, popliteal fossa) (2.7, 1.57, respectively)(6.55, 5.3, respectively in undiagnosed cohort) nerves than patients without critical neuromyopathy, and showed more non-elicitation, which was not seen in the cohort of patients without critical neuromyopathy. The CMAP returned to normal in the cohort of patients without critical neuromyopathy. Therefore, with respect to our selected electrophysiological parameters, the two patient groups showed significant differences in terms of the specific values and statistical analysis (Table 1). Through factor analysis and principal component regression, we found that CMAP and F-wave were highly correlated with APACHE II and SOFA scores, and the correlation between the electrophysiological wave spectrum and the two scores was further quantified by principal component regression. Conclusion: Electrophysiological spectroscopy can serve as an early warning for the development of neuromuscular disease in EICU patients. Abnormal electrophysiological diagnosis prior to actual neuromuscular abnormalities and its subsequent return to normal can help identify high-risk patients and implement early interventions.
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APACHE , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Estudos Prospectivos , Estado Terminal , Análise de Componente Principal , Infecções/fisiopatologia , Eletromiografia , Índice de Gravidade de DoençaRESUMO
Non-pharmaceutical interventions (NPI) have great potential to improve cognitive function but limited investigation to discover NPI repurposing for Alzheimer's Disease (AD). This is the first study to develop an innovative framework to extract and represent NPI information from biomedical literature in a knowledge graph (KG), and train link prediction models to repurpose novel NPIs for AD prevention. We constructed a comprehensive KG, called ADInt, by extracting NPI information from biomedical literature. We used the previously-created SuppKG and NPI lexicon to identify NPI entities. Four KG embedding models (i.e., TransE, RotatE, DistMult and ComplEX) and two novel graph convolutional network models (i.e., R-GCN and CompGCN) were trained and compared to learn the representation of ADInt. Models were evaluated and compared on two test sets (time slice and clinical trial ground truth) and the best performing model was used to predict novel NPIs for AD. Discovery patterns were applied to generate mechanistic pathways for high scoring candidates. The ADInt has 162,212 nodes and 1,017,284 edges. R-GCN performed best in time slice (MR = 5.2054, Hits@10 = 0.8496) and clinical trial ground truth (MR = 3.4996, Hits@10 = 0.9192) test sets. After evaluation by domain experts, 10 novel dietary supplements and 10 complementary and integrative health were proposed from the score table calculated by R-GCN. Among proposed novel NPIs, we found plausible mechanistic pathways for photodynamic therapy and Choerospondias axillaris to prevent AD, and validated psychotherapy and manual therapy techniques using real-world data analysis. The proposed framework shows potential for discovering new NPIs for AD prevention and understanding their mechanistic pathways.
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Doença de Alzheimer , Humanos , Doença de Alzheimer/tratamento farmacológico , AprendizagemRESUMO
Nine metabolites, including three undescribed alkaloids pyripyropenes VW (1-2), penicioxa A (4), two previously reported pyripyropene A (3), oxaline (5), three grisephenone-type xanthone derivatives (6-8), and a diphenyl ether derivative 4-chloro-7,4'-dihydroxy-5,2'-dimethoxy-2-methylformate-6'-methybenzophone (9), were isolated from cultures of the mangrove-derived fungus Penicillium robsamsonii HNNU0006. Their structures were determined by spectroscopic analysis, ECD calculations, together with DP4+ probability analysis. Furthermore, all the isolated compounds were tested for cytotoxicity and anti-phytopathogenic fungal activities. Compounds 6-8 showed moderate cytotoxicity against tumor cell lines A549, with IC50 values ranging from 5.68 ± 0.21 to 9.71 ± 0.34 µg/mL, respectively.
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Alcaloides , Penicillium , Penicillium/química , Estrutura Molecular , Humanos , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Alcaloides/química , Células A549 , Antineoplásicos/farmacologia , Antineoplásicos/isolamento & purificação , Antineoplásicos/química , China , Rhizophoraceae/microbiologiaRESUMO
BACKGROUND: The objective of this study was to evaluate the comparative efficacy of current interventions for the prevention of retinopathy of prematurity (ROP) in premature infants. METHODS: A network meta-analysis (NMA) was performed. We searched PubMed, Web of Science, Scopus, Embase, and the Cochrane Library for relevant studies from their inception to May 5, 2022. Publications were eligible for our study if they were randomized controlled trials (RCTs) involving preterm infants at <37 weeks of gestational age and reported the incidence of any-stage ROP treated with the interventions of interest. The overall effect was pooled using the random effects model. RESULTS: We identified 106 RCTs (involving 23894 participants). This NMA showed that vitamin A supplementation markedly reduced the incidence of ROP, in comparison with placebo (odds ratio [OR] = 0.59, 95% credible interval [95% CrI] 0.33, 0.85), fish oil-based lipid emulsion (OR = 0.57, 95% CrI 0.24, 0.90), early erythropoietin (OR = 0.51, 95% CrI 0.34, 0.98), probiotics (OR = 0.48, 95% CrI 0.32, 0.97), and human milk (OR = 0.50, 95% CrI 0.21, 0.78). Vitamin A supplementation has the highest probability of being the best option for reducing the ROP risk compared with the other 20 interventions based on its surface under the cumulative ranking curve (SUCRA) value (SUCRA = 92.50%, 95% CrI 0.71, 1.00). CONCLUSIONS: Our findings suggest that among 21 interventions, vitamin A supplementation might be the best method of preventing ROP. This NMA offers an important resource for further efforts to develop preventive strategies for ROP.
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Retinopatia da Prematuridade , Recém-Nascido , Humanos , Metanálise em Rede , Vitamina A , Ensaios Clínicos Controlados Aleatórios como Assunto , Recém-Nascido PrematuroRESUMO
OBJECTIVE: To construct an exhaustive Complementary and Integrative Health (CIH) Lexicon (CIHLex) to help better represent the often underrepresented physical and psychological CIH approaches in standard terminologies, and to also apply state-of-the-art natural language processing (NLP) techniques to help recognize them in the biomedical literature. MATERIALS AND METHODS: We constructed the CIHLex by integrating various resources, compiling and integrating data from biomedical literature and relevant sources of knowledge. The Lexicon encompasses 724 unique concepts with 885 corresponding unique terms. We matched these concepts to the Unified Medical Language System (UMLS), and we developed and utilized BERT models comparing their efficiency in CIH named entity recognition to well-established models including MetaMap and CLAMP, as well as the large language model GPT3.5-turbo. RESULTS: Of the 724 unique concepts in CIHLex, 27.2% could be matched to at least one term in the UMLS. About 74.9% of the mapped UMLS Concept Unique Identifiers were categorized as "Therapeutic or Preventive Procedure." Among the models applied to CIH named entity recognition, BLUEBERT delivered the highest macro-average F1-score of 0.91, surpassing other models. CONCLUSION: Our CIHLex significantly augments representation of CIH approaches in biomedical literature. Demonstrating the utility of advanced NLP models, BERT notably excelled in CIH entity recognition. These results highlight promising strategies for enhancing standardization and recognition of CIH terminology in biomedical contexts.
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Algoritmos , Unified Medical Language System , Processamento de Linguagem Natural , IdiomaRESUMO
The antagonistic coculture with tea phytopathogen Colletotrichum pseudomajus induces antifungal cryptic metabolites from isogenesis endophyte Daldinia eschscholtzii against tea phytopathogens. Sixteen new polyketides with six structural frameworks including ten cryptic ones, named coldaldols A-C (1-3), collediol (5), and daldinrins A-L (10-20 and 23), were found from the coculture of C. pseudomajus and D. eschscholtzii by different culture methods. The unique framework of compounds 11 and 12 featured a benzopyran-C7 polyketone hybrid, and compounds 13-16 were characterized by the novel benzopyran dimer. The structures were determined mainly by spectroscopic methods, including extensive one-dimensional (1D), two-dimensional (2D) NMR, high resolution electrospray ionisation mass spectroscopy (HRESIMS), ECD calculation, and single-crystal X-ray diffraction. The configuration of acyclic compounds 5 and 18 were determined by application of the universal NMR database. Most compounds showed significant antifungal activities against the tea pathogens C. pseudomajus and Alternaria sp. with MICs of 1-8 µg/mL. Compound 12 had stronger antifungal activity than that of positive drug nystatin. The ether bond at C-4 of the benzopyran derivative increased the antifungal activity. Compounds 4-9 and 11-23 showed antifeedant activities against silkworms with feeding deterrence indices of 15-100% at the concentration of 50 µg/cm2.
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Colletotrichum , Policetídeos , Antifúngicos/química , Endófitos/metabolismo , Técnicas de Cocultura , Policetídeos/farmacologia , Policetídeos/química , Colletotrichum/metabolismo , Espectroscopia de Ressonância Magnética , Benzopiranos , CháRESUMO
Cinnabaris is a traditional Chinese medicine(TCM) commonly used for sedation and tranquilization in clinics, and its safety has always been a concern. This study intends to investigate the species and tissue distribution of mercury in rats after continuous administration of Cinnabaris. In the experiment, 30 rats were randomly divided into the control group(equivalent to 0.5% carboxy-methyl cellulose sodium), low-dose Cinnabaris group(0.2 g·kg~(-1)), high-dose Cinnabaris group(2 g·kg~(-1)), pseudogerm-free control group(equivalent to 0.5% sodium carboxymethyl cellulose), and pseudogerm-free Cinnabaris group(2 g·kg~(-1)). They were orally administered for 30 consecutive days. Ultrasound-assisted acid extraction method combined with high performance liquid chromatography and inductively coupled plasma-mass spectrometry(HPLC-ICP-MS) was adopted to determine inorganic mercury [Hg(â ¡)], methylmercury(MeHg), and ethylmercury(EtHg) in different tissue, plasma, urine, and feces of rats. The optimal detection conditions and extraction methods were optimized, and the linearity(R~2>0.999 3), precision(RSD<7.0%), and accuracy(spike recoveries ranged from 73.05% to 109.5%) of all the mercury species were satisfied, meeting the requirements of analysis. The results of mercury species detection showed that Hg(â ¡) was detected in all the tissue of the five experimental groups, and the main accumulating organs were the intestinal tract, stomach, and kidney. MeHg existed at a low concentration in most tissue, and EtHg was not detected in all groups. In addition, pathological examination results showed that hepatocyte vacuolar degeneration, loose cytoplasm, light staining, and mononuclear cell infiltration were observed in the high-dose Cinnabaris group, low-dose Cinnabaris group, and pseudogerm-free Cinnabaris group, with slightly milder lesions in the low-dose Cinnabaris group. Hydrous degeneration of renal tubular epithelium could be seen in the high-dose Cinnabaris group and pseudogerm-free Cinnabaris group, but there was no significant difference between the other groups and the control group. No abnormal changes were found in the brain tissue of rats in each group. This paper studied the different mercury species and tissue distribution in normal and pseudogerm-free rats after continuous administration of Cinnabaris for 30 days and clarified its effects on the tissue structure of the liver, kidney, and brain, which provided supporting evidence for the safety evaluation of Cinnabaris.
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Mercúrio , Compostos de Metilmercúrio , Ratos , Animais , Mercúrio/análise , Distribuição Tecidual , Compostos de Metilmercúrio/toxicidade , Compostos de Metilmercúrio/análise , Cromatografia Líquida de Alta Pressão/métodos , SódioRESUMO
Developing smart hydrogels with excellent physicochemical properties and multi-sensing capabilities for various simulation of human skin's functions still remains a great challenge. Here, based on simple and convenient one-step covalent cross-linking method enhanced by dynamic RS-Ag interactions, a skin-inspired multifunctional conductive hydrogel with desirable physicochemical properties (including high stretchability, self-adhesion, self-healing, decomposition and removability) is developed for highly sensitive dual-sensing of temperature and strain. Benefiting from the synergistic action of multiple hydrogen bonds, RS-Ag bonds and S-S bonds, the gel exhibited a novel thermosensitive mechanism. The prepared hydrogels exhibited extremely high mechanical properties (maximum tensile strength of 0.35 MPa, elongation at break nearly 1800%, compressive stress over 4.43 MPa), excellent self-healing (96.82% (stress), 88.45% (temperature), 73.89% (mechanical property)), decomposition (the molecular weight after decomposition is below 700) and self-adhesion (enhanced contact with the material interface). In addition, this conductive hydrogel could also simultaneously achieve highly sensitive temperature-sensing (TCR: 10.89) and stress-sensing (GF: 1.469). As a proof-to-concept, the hydrogel displayed superior capability for simulation of human skin to perception of touch, pressure and ambient temperature simultaneously, indicating promising applications in the fields of wearable devices, personal health care, and human-machine interfaces.
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Essências Florais , Prunella , Percepção do Tato , Humanos , Hidrogéis , Temperatura , Pele , Tato , FebreRESUMO
BACKGROUND: Transcutaneous electrical acupoint stimulation and dexamethasone can reduce postoperative nausea and/or vomiting. In this noninferiority study, we compared the effects of Neiguan acupoint (PC6) transcutaneous electrical acupoint stimulation with dexamethasone to prevent postoperative nausea and/or vomiting in female patients undergoing breast surgery. METHODS: In total, 280 patients were randomized into the following 2 groups: transcutaneous electrical acupoint stimulation (n = 140) and dexamethasone (n = 140). Transcutaneous electrical acupoint stimulation was performed 0.5 hours before anesthesia induction, immediately after entering the post-anesthesia care unit, and every 3 hours after leaving the post-anesthesia care unit. In the postoperative ward, the anesthetist instructed the patient's family members to assist the patient with PC6 patient-controlled transcutaneous electrical acupoint stimulation. Patients in the dexamethasone group were given 8 mg dexamethasone (intravenously) at 0.5 hours before induction of anesthesia. The incidence of nausea, vomiting, need for rescue antiemetics, patient satisfaction score, and the feasibility results of PC6 patient-controlled transcutaneous electrical acupoint stimulation were recorded 24 hours after surgery. RESULT: Within 0 to 24 hours after surgery, the incidence of postoperative nausea and/or vomiting in the transcutaneous electrical acupoint stimulation group was not inferior to the dexamethasone group (31.1% vs 27.9%, per protocol risk difference 3.2; 95% confidence interval -7.7 to 14.0). The results of the intention-to-treat analysis (30.7% vs 27.1%, risk difference 3.6; 95% confidence interval -7.0 to 14.2) agreed with the per protocol analysis. Patient satisfaction score in the transcutaneous electrical acupoint stimulation group was higher than that in the dexamethasone group (3.9 ± 0.1 vs 3.6 ± 0.1, P = .003). The scheme of preventing postoperative nausea and/or vomiting by PC6 patient-controlled transcutaneous electrical acupoint stimulation was feasible. CONCLUSION: Transcutaneous electrical acupoint stimulation was noninferior to dexamethasone in preventing postoperative nausea and/or vomiting within 24 hours after breast surgery. Neiguan acupoint patient-controlled transcutaneous electrical acupoint stimulation was feasible to prevent postoperative nausea and/or vomiting.
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Neoplasias da Mama , Náusea e Vômito Pós-Operatórios , Humanos , Feminino , Náusea e Vômito Pós-Operatórios/prevenção & controle , Pontos de Acupuntura , Anestesia Geral , Dexametasona/uso terapêutico , Neoplasias da Mama/cirurgiaRESUMO
Cephalotaxus fortunei, a potential underutilized oil resource, contains various active ingredients that exert positive effects on human health. In the present study, characteristics of C. fortunei kernel oil and its digestion properties were systematically investigated. Results indicated that C. fortunei kernels contained high oil content (64.59%), of which over 90% was triacylglycerols (TAGs). The kernel oil was rich in oleic acid (C18:1n-9, 42.88%), linoleic acid (C18:2n-6, 31.05%), and sciadonic acid (C20:3n-6, 10.78%). The kernel oil also contained some beneficial fat-soluble nutrients, such as tocopherols (143 mg/kg) and phytosterols (1474 mg/kg). Thirty-five kinds of TAGs were identified, among which O-O-L (17.96%), O-O-O (12.12%), L-L-O (11.79%), O-L-Et (8.59%), and O-O-Et (8.76%) were the most abundant. In vitro digestion experiments showed that after 120 min of small intestine digestion, the maximum FFAs release level of the kernel oil was 75.02%, which was lower than that of soybean oil (89.63%).
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Cephalotaxus , Humanos , Óleo de Soja , Ácidos Graxos não Esterificados , Triglicerídeos , Digestão , Ácidos Graxos , Óleos de PlantasRESUMO
Recently, computational drug repurposing has emerged as a promising method for identifying new pharmaceutical interventions (PI) for Alzheimer's Disease (AD). Non-pharmaceutical interventions (NPI), such as Vitamin E and Music therapy, have great potential to improve cognitive function and slow the progression of AD, but have largely been unexplored. This study predicts novel NPIs for AD through link prediction on our developed biomedical knowledge graph. We constructed a comprehensive knowledge graph containing AD concepts and various potential interventions, called ADInt, by integrating a dietary supplement domain knowledge graph, SuppKG, with semantic relations from SemMedDB database. Four knowledge graph embedding models (TransE, RotatE, DistMult and ComplEX) and two graph convolutional network models (R-GCN and CompGCN) were compared to learn the representation of ADInt. R-GCN outperformed other models by evaluating on the time slice test set and the clinical trial test set and was used to generate the score tables of the link prediction task. Discovery patterns were applied to generate mechanism pathways for high scoring triples. Our ADInt had 162,213 nodes and 1,017,319 edges. The graph convolutional network model, R-GCN, performed best in both the Time Slicing test set (MR = 7.099, MRR = 0.5007, Hits@1 = 0.4112, Hits@3 = 0.5058, Hits@10 = 0.6804) and the Clinical Trials test set (MR = 1.731, MRR = 0.8582, Hits@1 = 0.7906, Hits@3 = 0.9033, Hits@10 = 0.9848). Among high scoring triples in the link prediction results, we found the plausible mechanism pathways of (Photodynamic therapy, PREVENTS, Alzheimer's Disease) and (Choerospondias axillaris, PREVENTS, Alzheimer's Disease) by discovery patterns and discussed them further. In conclusion, we presented a novel methodology to extend an existing knowledge graph and discover NPIs (dietary supplements (DS) and complementary and integrative health (CIH)) for AD. We used discovery patterns to find mechanisms for predicted triples to solve the poor interpretability of artificial neural networks. Our method can potentially be applied to other clinical problems, such as discovering drug adverse reactions and drug-drug interactions.
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Objective To put forward suggestions for improving the scheme of general practice for functional communities from the perspective of supply and demand,guide the efficient use of the resources of general practice by the communities,and incorporate the general practice of communities into hierarchical diagnosis and treatment management. Methods In July 2021,stratified random sampling was employed to conduct the questionnaire surveys of the young and middle-aged (demand side) and the general practitioners (supply side),respectively.SPSS 20.0 was used for data analysis. Results The two sides had the same cognition about the main reasons for not signing a contract with a family doctor,which were the lack of knowledge about general practitioners and the lack of face-to-face communication opportunities.They had the same response about the form of services,with high acceptance of medical services via WeChat,outpatient consultation,and the internet.There were differences in service content between the two sides.The top three demands of the young and middle-aged were appointment registration and referral in superior hospitals,medication guidance,and massage,acupuncture,and moxibustion.The top service self-rated by general practitioners was personalized guidance and report interpretation of physical examination,and the bottom was massage,acupuncture,and moxibustion. Conclusions The general practice varies between the demand and supply sides.General practitioners should be encouraged to enter and learn functional communities and provide personalized services,thus improving the general medical service in functional communities.
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Medicina Geral , Inquéritos e QuestionáriosRESUMO
As one of the key methods of Traditional Chinese Medicine inspection, tongue diagnosis manifests the advantages of simplicity and directness. Sublingual veins can provide essential information about human health. In order to automate tongue diagnosis, sublingual veins segmentation has become one important issue in the field of Chinese medicine medical image processing. At present, the primary methods for sublingual veins segmentation are traditional feature engineering methods and the feature representation methods represented by deep learning. The former, which mainly based on colour space, belongs to unsupervised classification method. The latter, which includes U-Net and other deep neural network models, belongs to supervised classification method. Current feature engineering methods can only capture low dimensional information, which makes it difficult to extract efficient features for sublingual veins. On the other hand, current deep learning methods use down-sampling structures, which manifest weak robustness and low accuracy. So, it is difficult for current segmentation approaches to recognize tiny branches of sublingual veins. To overcome the above limits, this paper proposes a novel two-stage semantic segmentation method for sublingual veins. In the first stage, a fully convolutional network without down-sampling is used to realize the accurate segmentation of the tongue that includes the sublingual veins to be segmented in the next stage. During the tongue segmentation, the proposed networks can effectively reduce the loss of medical images spatial feature information. At the same time, in order to expand the receptive field, the dilated convolution has been introduced to the proposed networks, which can capture multi-scale information of segmentation images. In the second stage, another fully convolutional network has been used to segment the sublingual veins on the base of the results from the first stage. In this model, proper dilated convolutional rates have been selected to avoid gridding issue. In order to keep the quality of the images to be segmented, several particular data pre-processing and post-processing have been used, which includes specular highlight removal, data augmentation, erosion and dilation. Finally, in order to evaluate the performance of the proposed model, segmentation results have been compared with the state-of-the-art methods on the base of the dataset from Shanghai University of Traditional Chinese Medicine. The effectiveness of sublingual veins segmentation has been proved.
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Many traditional Chinese herbs contain pyrrolizidine alkaloids (PAs), which have been reported to be toxic to livestock and humans. However, the lack of PAs standards makes it difficult to effectively conduct a risk assessment in the varied components of traditional Chinese medicine. It is necessary to propose a suitable strategy to obtain the representative occurrence data of PAs in complex systems. A comprehensive approach for annotating the structures, concentration, and mutagenicity of PAs in three Chinese herbs has been proposed in this article. First, feature-based molecular networking (FBMN) combined with network annotation propagation (NAP) on the Global Natural Products Social Molecular Networking web platform speeds up the process of annotating PAs found in Chinese herbs. Second, a semi-quantitative prediction model based on the quantitative structure and ionization intensity relationship (QSIIR) is used to forecast the amounts of PAs in complex substrates. Finally, the T.E.S.T. was used to provide predictions regarding the mutagenicity of annotated PAs. The goal of this study was to develop a strategy for combining the results of several computer models for PA screening to conduct a comprehensive analysis of PAs, which is a crucial step in risk assessment of unknown PAs in traditional Chinese herbal preparations.
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Medicamentos de Ervas Chinesas , Alcaloides de Pirrolizidina , Humanos , Alcaloides de Pirrolizidina/química , Alimento Funcional/análise , Medicamentos de Ervas Chinesas/análise , Medicina Tradicional Chinesa , Preparações de Plantas , Mutagênicos/toxicidade , Mutagênicos/análiseRESUMO
The paraventricular nucleus of the thalamus (PVT) is involved in drug addiction-related behaviors, and morphine is a widely used opioid for the relief of severe pain. Morphine acts via opioid receptors, but the function of opioid receptors in the PVT has not been fully elucidated. Here, we used in vitro electrophysiology to study neuronal activity and synaptic transmission in the PVT of male and female mice. Activation of opioid receptors suppresses the firing and inhibitory synaptic transmission of PVT neurons in brain slices. On the other hand, the involvement of opioid modulation is reduced after chronic morphine exposure, probably because of desensitization and internalization of opioid receptors in the PVT. Overall, the opioid system is essential for the modulation of PVT activities.SIGNIFICANCE STATEMENT Opioid receptors modulate the activities and synaptic transmission in the PVT by suppressing the firing rate and inhibitory synaptic inputs. These modulations were largely diminished after chronic morphine exposure.
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Analgésicos Opioides , Receptores Opioides , Masculino , Feminino , Camundongos , Animais , Analgésicos Opioides/farmacologia , Núcleo Hipotalâmico Paraventricular/fisiologia , Tálamo , Transmissão Sináptica , Morfina/farmacologiaRESUMO
Background: Infertility is one of the three major public health problems in the world, bringing immense physical and psychological damage to men and affecting the quality of men's fertility life. Thus, the purpose of this study was to analyze the status of social support, fertility stress, mindfulness, and fertility quality of life in infertile men, and to explore the dual mediating effects of social support and fertility stress on mindfulness and fertility quality. Methods: A case-control group study was conducted, with 246 men in the case group and 149 in the control group. The Social Support Scale, Fertility Stress Scale, Mindfulness Scale, and Fertility Quality of Life Scale were used to establish a structural equation model using Mplus 8.3 to explore social support and fertility stress. Pathway relationships were drawn between mindfulness and fertility quality of life in infertile men. Results: There were significant differences between infertile and healthy men in each dimension of the core module of fertility quality of life, in the total score of the treatment module, in the total score of social support, in subjective and objective support, and in the total score of fertility stress, social pressure, sexual pressure, marital relationship, and childless pressure (p < 0.05 in each case). Further, the fertility quality of life in infertile men was positively correlated with mindfulness and social support, and negatively correlated with fertility stress (p < 0.05); mindfulness could directly affect the core and treatment modules of fertility life quality, and indirectly affect the core of fertility life quality through social support (mediation effect accounted for 19.0%), while the treatment module (mediation effect accounted for 13.7%), and the core module indirectly affected fertility life quality through fertility stress (mediation effect accounted for 16.8%). Conclusion: The fertility quality of life of infertile men is not optimistic. Mindfulness-related interventions and programs can improve their fertility quality of life.
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BACKGROUND: The immunosuppressive microenvironment of lung cancer serves as an important endogenous contributor to treatment failure. The present study aimed to demonstrate the promotive effect of DHA on immunogenic cell death (ICD) in lung cancer as well as the mechanism. METHODS: The lewis lung cancer cells (LLC), A549 cells and LLC-bearing mice were applied as the lung cancer model. The apoptosis, ferroptosis assay, western blotting, immunofluorescent staining, qPCR, comet assay, flow cytometry, confocal microscopy, transmission electron microscopy and immunohistochemistry were conducted to analyze the functions and the underlying mechanism. RESULTS: An increased apoptosis rate and immunogenicity were detected in DHA-treated LLC and tumor grafts. Further findings showed DHA caused lipid peroxide (LPO) accumulation, thereby initiating ferroptosis. DHA stimulated cellular endoplasmic reticulum (ER) stress and DNA damage simultaneously. However, the ER stress and DNA damage induced by DHA could be abolished by ferroptosis inhibitors, whose immunogenicity enhancement was synchronously attenuated. In contrast, the addition of exogenous iron ions further improved the immunogenicity induced by DHA accompanied by enhanced ER stress and DNA damage. The enhanced immunogenicity could be abated by ER stress and DNA damage inhibitors as well. Finally, DHA activated immunocytes and exhibited excellent anti-cancer efficacy in LLC-bearing mice. CONCLUSIONS: In summary, the current study demonstrates that DHA triggers ferroptosis, facilitating the ICD of lung cancer thereupon. This work reveals for the first time the effect and underlying mechanism by which DHA induces ICD of cancer cells, providing novel insights into the regulation of the immune microenvironment for cancer immunotherapy by Chinese medicine phytopharmaceuticals.
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Carcinoma Pulmonar de Lewis , Ferroptose , Neoplasias Pulmonares , Animais , Camundongos , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Estresse do Retículo Endoplasmático , Imunoterapia , Dano ao DNA , Microambiente TumoralRESUMO
Objective To put forward suggestions for improving the scheme of general practice for functional communities from the perspective of supply and demand,guide the efficient use of the resources of general practice by the communities,and incorporate the general practice of communities into hierarchical diagnosis and treatment management. Methods In July 2021,stratified random sampling was employed to conduct the questionnaire surveys of the young and middle-aged (demand side) and the general practitioners (supply side),respectively.SPSS 20.0 was used for data analysis. Results The two sides had the same cognition about the main reasons for not signing a contract with a family doctor,which were the lack of knowledge about general practitioners and the lack of face-to-face communication opportunities.They had the same response about the form of services,with high acceptance of medical services via WeChat,outpatient consultation,and the internet.There were differences in service content between the two sides.The top three demands of the young and middle-aged were appointment registration and referral in superior hospitals,medication guidance,and massage,acupuncture,and moxibustion.The top service self-rated by general practitioners was personalized guidance and report interpretation of physical examination,and the bottom was massage,acupuncture,and moxibustion. Conclusions The general practice varies between the demand and supply sides.General practitioners should be encouraged to enter and learn functional communities and provide personalized services,thus improving the general medical service in functional communities.
Assuntos
Medicina Geral , Inquéritos e QuestionáriosRESUMO
Objectives: To describe the epidemiological characteristics and medication overview of HFMD in Guangzhou and analyze the factors of length of stay (LOS) based on TCM usage. Method: From January 1, 2014, to June 30, 2019, clinical data of HFMD (ICD-10 B08.401) as the initial diagnosis, based on HIS of five medical institutions for outpatient and inpatient cases, was collected. The inpatient cases of the five hospitals in Guangzhou were utilized for hospitalization analysis. Information extracted from the warehouse was standardized. Descriptive analysis was used for baseline characteristics, medication usage, and inpatient characteristics. Potential factors were analyzed by bivariate analysis. COX regression analysis and Kaplan-Meier analysis for calculating HRs and 95% CIs were adopted to determine the predictors of LOS. Stratified COX regression was applied to analyze the relationship between predictors and LOS and to calculate interaction. Results: A total of 14172 patients with HFMD were included. It showed that HFMD would occur in males, infants, and summer. Cause and symptoms are the two aspects of conventional Western medicine treatments, while TCM treatment of HFMD took clearing heat and detoxification as the basic principle. Inpatients with HFMD were divided into two groups by the use ratio of TCM. Age, season, and disease severity were possible correlated factors of LOS, extrapolating from their disparity in distribution. By stratified Cox regression, three factors following presented as possible contributions to shortening LOS, including TCM ≥ 0.1 (HR = 1.79, 95% CI (1.67-1.92), P < 0.01), winter (HR = 1.28, 95% CI (1.12-1.47)), P < 0.01), mild HFMD (HR = 1.93, 95% CI (1.69-2.22), P < 0.01). Additive interaction of TCM use and disease severity was significant (RERI = 1.014 (0.493-1.534), P < 0.01). Conclusion: Young children and high temperature were the risk factors of HFMD infection, which suggests that increasing surveillance for susceptible particular-age individuals and season is indispensable. Favorable factors to decrease LOS included a higher proportion of TCM use, mild HFMD, and onset in winter. The proportion of TCM use had additive interaction with disease severity, indicating that TCM may have antiviral and other biological effects on HFMD. Increasing the proportion of TCM use was probably beneficial to shortening LOS.