Identification and Nursing Care of a Stroke Patient with Internal Iliac Artery Branch Rupture and Bleeding.

To summarize the experience of identifying and caring for a stroke patient with ruptured internal iliac artery branch bleeding. The experience was summarized in 3 aspects, including how to recognize the presence of active bleeding in the patient, confirmation of the diagnosis and treatment of the bleeding point, prevention of postoperative complications, and rehabilitation care. After aggressive treatment and care, the patient was discharged after 30 days of hospitalization and improved.

The long noncoding RNAs lnc10 and lnc11 regulating flavonoid biosynthesis in Ginkgo biloba.

Although long non-coding RNAs have been recognized to play important roles in plant, their possible functions and potential mechanism in Ginkgo biloba flavonoid biosynthesis are poorly understood. Flavonoids are important secondary metabolites and healthy components of Ginkgo biloba. They have been widely used in food, medicine, and natural health products. Most previous studies have focused on the molecular mechanisms of structural genes and transcription factors that regulate flavonoid biosynthesis. Few reports have examined the biological functions of flavonoid biosynthesis by long non-coding RNAs in G. biloba. Long noncoding RNAs associated with flavonoid biosynthesis in G. biloba have been identified through RNA sequencing, but the function of lncRNAs has not been reported. In this study, the expression levels of lnc10 and lnc11 were identified. Quantitative real-time polymerase chain reaction analysis revealed that lnc10 and lnc11 were expressed in all detected organs, and they showed significantly higher levels in immature and mature leaves than in other organs. In addition, to fully identify the function of lnc10 and lnc11 in flavonoid biosynthesis in G. biloba, lnc10 and lnc11 were cloned from G. biloba, and were transformed into Arabidopsis and overexpressed. Compared with the wild type, the flavonoid content was increased in transgenic plants. Moreover, the RNA-sequencing analysis of wild-type, lnc10-overexpression, and lnc11-overexpression plants screened out 2019 and 2552 differentially expressed genes, and the transcript levels of structural genes and transcription factors associated with flavonoid biosynthesis were higher in transgenic Arabidopsis than in the wild type, indicating that lnc10 and lnc11 activated flavonoid biosynthesis in the transgenic lines. Overall, these results suggest that lnc10 and lnc11 positively regulate flavonoid biosynthesis in G. biloba.

Electrical stimulation therapy for pain and related symptoms in multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: The effectiveness of electrical stimulation therapy (EST) for pain, depression, fatigue, disability, and quality of life in multiple sclerosis (MS) remains uncertain. This study aims to analyze and discuss the efficacy of various EST treatments in alleviating pain among MS patients. METHODS: The primary search was conducted using PubMed, Web of Science, Cochrane Library, Embase, and the Cumulative Index of Nursing and Allied Health Literature databases until September 25, 2023. Randomized controlled trials (RCTs) including patients with MS pain receiving EST compared with other therapies were included. Pain intensity, quality of life, and neuropsychiatric symptoms were reported. The mean difference (MD) with 95 % confidence intervals (CIs) was estimated separately for outcomes to understand the mean effect size. RESULTS: Ten RCTs containing 315 participants were included. The pooled data from 8 trials including 267 participants showed that the EST was superior in alleviating pain (MD = -1.75, 95 % CI -2.85--0.64, P = 0.002, I2=73 %) evaluated by the visual analog scale. In subgroup analysis, medium-term EST treatment showed the highest effect size compared to short-term and long-term treatment (MDmedium-term = -2.17, 95 % CI -3.51--0.84, P = 0.001, I2 = 0 %). However, no significant differences were found in terms of pain-related quality of life, depression, fatigue, and pain-related disability. No adverse events related to EST were reported. A high risk of bias was identified in three of the ten included studies. CONCLUSIONS: EST is effective and safe for alleviating pain in MS, but it should be noted that limited sample sizes and methodological issues were present in the included studies. More robust assessment criteria and high-quality RCTs are required for patients with MS. TRIAL REGISTRATION: CRD42023406787. (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=406787).

Research trends in complementary and alternative treatments for insomnia over the past decade: A bibliometrics analysis.

Insomnia is the most common sleep disorder, with persistent insomnia being associated with greater risk and leading to a range of functional consequences that place a heavy burden on patients and healthcare systems. A weight of evidence has shown that complementary and alternative medicine (CAM) seems to have a positive effect on improving sleep. However, the research trends of CAM intervention for insomnia have not been studied systematically through bibliometrics. We searched the relevant literature over the past decade in the Web of Science Core Collection database on September 20, 2022 and used CiteSpace and gCLUTO to visually analyze and cluster countries, institutions, authors, journals and keywords. Through screening, 1655 papers were included. In the past decade, the number of articles published in this field shown an annual trend of growth, with explosive growth in 2020. The USA has the largest number of publications, the University of Hong Kong is the leading institution in this field, and the most cited journal is Sleep. Mental condition and quality of life in patients with insomnia, insomnia related to cancer, effect of mindfulness meditation, yoga and aromatherapy on insomnia and the psychiatric symptoms resulting from the COVID-19 pandemic are at the forefront of this field. In this study, bibliometrics and visualization analysis were performed on related studies on CAM intervention for insomnia. This will be the focus and development direction of insomnia treatment in the future to formulate structured treatment plans for traditional Chinese medicine-related CAM, validate large-scale clinical trials, solve cancer comorbidity insomnia and related psychiatric symptoms and deal with mental health-related insomnia after public health outbreaks.

Role of bZIP transcription factors in the regulation of plant secondary metabolism.

MAIN CONCLUSION: This study provides an overview of the structure, classification, regulatory mechanisms, and biological functions of the basic (region) leucine zipper transcription factors and their molecular mechanisms in flavonoid, terpenoid, alkaloid, phenolic acid, and lignin biosynthesis. Basic (region) leucine zippers (bZIPs) are evolutionarily conserved transcription factors (TFs) in eukaryotic organisms. The bZIP TFs are widely distributed in plants and play important roles in plant growth and development, photomorphogenesis, signal transduction, resistance to pathogenic microbes, biotic and abiotic stress, and secondary metabolism. Moreover, the expression of bZIP TFs not only promotes or inhibits the accumulation of secondary metabolites in medicinal plants, but also affects the stress response of plants to the external adverse environment. This paper describes the structure, classification, biological function, and regulatory mechanisms of bZIP TFs. In addition, the molecular mechanism of bZIP TFs regulating the biosynthesis of flavonoids, terpenoids, alkaloids, phenolic acids, and lignin are also elaborated. This review provides a summary for in-depth study of the molecular mechanism of bZIP TFs regulating the synthesis pathway of secondary metabolites and plant molecular breeding, which is of significance for the generation of beneficial secondary metabolites and the improvement of plant varieties.

SMRGAT: A traditional Chinese herb recommendation model based on a multi-graph residual attention network and semantic knowledge fusion.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese Medicine (TCM) prescriptions are a product of the Chinese medical theory's distinct thinking and clinical experience. TCM practitioners treat diseases by enhancing the efficacy of TCM prescriptions and reducing their poisonous effects. Some TCM herb recommendation methods have been provided for curing the given symptoms to generate a group of herbs according to the TCM principles. However, they ignored the symptoms' semantic characteristics and herbs' different effects on symptoms. AIM OF THE STUDY: We aim to recommend TCM herbs by considering symptoms' semantic information and the strength of different herbs in curing symptoms. MATERIALS AND METHODS: We propose a herb recommendation model named Multi-Graph Residual Attention Network and Semantic Knowledge Fusion (SMRGAT) to address these problems. Concretely, it uses a multi-head attention mechanism to focus on herbs' different effects on symptoms. Meanwhile, it augments entities' features with a residual network structure while incorporating symptoms' semantic information and external knowledge of herbs. We will verify the effect of SMRGAT on the existing public datasets and the datasets that we have collected and cleaned. RESULTS: Compared with the current best TCM herb recommendation model, on the public dataset, SMRGAT were increased by 15.11%, 20.60%, and 18.25% in Precision@5, Recall@5, and F1 - score@5, respectively; on ours, respectively increased by 9.72%, 9.03%, 9.24%. CONCLUSIONS: Our experimental results on two datasets indicate that SMRGAT is capable of recommending herbs with greater precision and outperforms several comparison methods. It can provide a basis for assisting TCM clinical prescriptions.

Microanalysis Characterization and Immunomodulatory Effect for Selenium-Enriched Polysaccharide from Morchella esculenta (L.) Pers.

Morchella esculenta (L.) Pers., referred to as Morel, is a medicinal and edible homologous fungus, which contains many bioactive substances. In Morel, polysaccharides are the most abundant and have various bioactivities. In the present work, two novel polysaccharides, Se-MPS and MPS, were prepared and purified from selenium-enriched (Se-enriched) and common Morel mycelia, respectively, and their structural and immunomodulatory properties were evaluated. The results show that Se-enriched treatment significantly changed the polysaccharides' chemical composition, molecular weight, and sugar chain configuration. In addition, the Se-enriched treatment also improved the polysaccharides' fragmentation and thermal stability. Importantly, Se-enriched Morel polysaccharide (Se-MPS) could significantly enhance phagocytosis of RAW 264.7 macrophage cells and, remarkably, activate their immune response via activating the TLR4-TRAF6-MAPKs-NF-κB cascade signaling pathway, finally exerting an immunomodulatory function. Based on these findings, selenium-enriched Morel polysaccharide appears to have more potential for development and utilization in functional foods or medicines than ordinary Morel polysaccharide.

Effect of different cooking methods on saponin content and hematopoietic effects of Panax notoginseng-steamed chicken on mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax notoginseng-steamed chicken (PNSC) is a medicinal food with ethnic characteristics developed by the Miao ethnic group in the southeast of Yunnan Province, China. PNSC has been eaten for hundreds of years, and its tonic effect has been widely recognized by the people. However, its cooking conditions and scientific connotation of its effect of toning blood and supplementing deficiency are also lack of in-depth analysis. AIM OF THE STUDY: To optimize the cooking conditions of Panax notoginseng-steamed chicken (PNSC) and to explore its anemia-improving effects. MATERIALS AND METHODS: The ratio of P. notoginseng (PN) to chicken and the steaming time were systematically altered, and the PNSC cooking conditions was optimized with the response surface method. By establishing animal models of postpartum blood-deficiency anemia, acute hemorrhagic anemia and myelosuppressive anemia, the blood replenishing effect of PNSC was explored, and the blood replenishing mechanism of PNSC on myelosuppressive anemia was revealed by immunoblotting analyses and histopathological sectioning. RESULTS: The optimal processing conditions included a ratio of chicken to P. notoginseng of 100:5 and a steaming time of 5.5 h. The amounts of P. notoginseng polysaccharides (PNPS), total protein and blood-enriching P. notoginseng saponins were 44.3 mg/g, 2.48% and 2.04%, respectively. Freeze-dried powder of P. notoginseng steamed chicken soup (FPSC) was found to promote the recovery of routine blood factors and organ indexes in the three models of anemia and to activate the JAK2-STAT5 signaling pathway, induce phosphorylation of JAK2 and STAT5 and normalize the secretion of hematopoietic regulators EPO, IL-3, and TNF-α. CONCLUSION: FPSC improves the symptoms of anemia in mice, and it plays a role in tonifying blood by activating the JAK2-STAT5 signaling pathway and altering the expression of hematopoiesis-related factors.

Effect of weight-bearing Liuzijue Qigong on cardiopulmonary function.

BACKGROUND: Since the outbreak of coronavirus disease 2019, many people have had to reduce their outdoor activities. Therefore, a convenient, simple, at-home training method to improve or maintain cardiopulmonary function is required. This study aimed to explore the therapeutic effect of weight-bearing Liuzijue Qigong on cardiopulmonary function in healthy volunteers. METHODS: This study was a longitudinal trial. The health participants completed a 4-week Liuzijue Qigong exercise with 0.25 kg sandbag wore on each wrist. Each training session took 30 minutes to complete 2 consecutive cycles, and 5 times a week. The cardiopulmonary function of participants was evaluated at baseline (T0) and the end of the intervention (T4). Outcomes measures were pulmonary function, diaphragm movement, and cardiac hemodynamic parameters. Paired t test was used to analyze differences within the group. RESULTS: After 4 weeks of weight-bearing Liuzijue Qigong exercise intervention, the differences in the forced expiratory volume in the 1st second (P = .006), forced vital capacity rate of 1 second (P = .003), maximal mid-expiratory flow curve (P = .002), forced expiratory flow at 50% of forced vital capacity (P = .003), and maximum ventilatory volume (P < .001) of the participants were statistically significant. The diaphragmatic excursion (P = .009) under the calm breathing mode and the diaphragmatic contraction speed (P = .003) under the deep breathing mode improved significantly. The cardiac output (P = .04), cardiac index (P = .035), contractility index (P = .018), early diastolic filling ratio (P = .042), systemic vascular resistance index (P = .019), systemic vascular resistance (P = .017), and estimated ejection fraction (P = .016) of participants improved significantly in the resting stage. At the end stage of fast walking, that is, the sixth minute of six-minute walk test, the stroke volume index (P = .048), heart rate (P = .019), cardiac output (P = .008), cardiac index (P = .003), and left cardiac work index (P = .028) of participants were significantly increased compared with those before training, and the systemic vascular resistance index (P = .003) and systemic vascular resistance (P = .005) were decreased. CONCLUSION: Weight-bearing Liuzijue Qigong training significantly improved cardiopulmonary function in healthy volunteers, thus representing home-based cardiopulmonary rehabilitation training.

Microrna-96 In Human Cancers.

MicroRNAs (miRNAs) are small non-coding RNAs 19-25 nucleotides in size involved in gene regulation and diverse processes in tumor cells. Abnormal expression of miRNAs is closely related to carcinogenesis. MiR-96 is a salient cancer-related miRNA in a variety of tumors. Recent evidence indicates that miR-96 has been observed to be wrapped in exosome and associated with drug resistance or radio-chemosensitivity in cancers. miR-96 is also inextricably linked with the competing endogenous RNAs (ceRNAs) in cancers. Notably, miR-96 plays both a tumor suppressor role and plays a carcinogenic role in the same cancers. This review summarizes the critical role of cancer-related miR-96 in drug resistance or radio-chemosensitivity and ceRNA mechanisms of miR-96 in cancer. And we innovatively propose that miR-96 has a yin-yang effect in cancers. Based on these several major roles of miR-96 in cancer as described above, we speculate that the abnormal expression of miR-96 is likely to be novel potential therapeutic targets in cancers. It is expected to solve the treatment problems such as low chemoradiotherapy sensitivity, poor prognosis quality of life and easy recurrence in cancer patients.

Extracellular matrix modulating enzyme functionalized biomimetic Au nanoplatform-mediated enhanced tumor penetration and synergistic antitumor therapy for pancreatic cancer.

BACKGROUND: Excessive extracellular matrix (ECM) deposition in pancreatic ductal adenocarcinoma (PDAC) severely limits therapeutic drug penetration into tumors and is associated with poor prognosis. Collagen is the most abundant matrix protein in the tumor ECM, which is the main obstacle that severely hinders the diffusion of chemotherapeutic drugs or nanomedicines. METHODS: We designed a collagenase-functionalized biomimetic drug-loaded Au nanoplatform that combined ECM degradation, active targeting, immune evasion, near-infrared (NIR) light-triggered drug release, and synergistic antitumor therapy and diagnosis into one nanoplatform. PDAC tumor cell membranes were extracted and coated onto doxorubicin (Dox)-loaded Au nanocages, and then collagenase was added to functionalize the cell membrane through lipid insertion. We evaluated the physicochemical properties, in vitro and in vivo targeting, penetration and therapeutic efficacy of the nanoplatform. RESULTS: Upon intravenous injection, this nanoplatform efficiently targeted the tumor through the homologous targeting properties of the coated cell membrane. During penetration into the tumor tissue, the dense ECM in the PDAC tissues was gradually degraded by collagenase, leading to a looser ECM structure and deep penetration within the tumor parenchyma. Under NIR irradiation, both photothermal and photodynamic effects were produced and the encapsulated chemotherapeutic drugs were released effectively, exerting a strong synergistic antitumor effect. Moreover, this nanoplatform has X-ray attenuation properties that could serve to guide and monitor treatment by CT imaging. CONCLUSION: This work presented a unique and facile yet effective strategy to modulate ECM components in PDAC, enhance tumor penetration and tumor-killing effects and provide therapeutic guidance and monitoring.

Advances in Research on the Involvement of Selenium in Regulating Plant Ecosystems.

Selenium is an essential trace element which plays an important role in human immune regulation and disease prevention. Plants absorb inorganic selenium (selenite or selenate) from the soil and convert it into various organic selenides (such as seleno amino acids, selenoproteins, and volatile selenides) via the sulfur metabolic pathway. These organic selenides are important sources of dietary selenium supplementation for humans. Organoselenides can promote plant growth, improve nutritional quality, and play an important regulatory function in plant ecosystems. The release of selenium-containing compounds into the soil by Se hyperaccumulators can promote the growth of Se accumulators but inhibit the growth and distribution of non-Se accumulators. Volatile selenides with specific odors have a deterrent effect on herbivores, reducing their feeding on plants. Soil microorganisms can effectively promote the uptake and transformation of selenium in plants, and organic selenides in plants can improve the tolerance of plants to pathogenic bacteria. Although selenium is not an essential trace element for plants, the right amount of selenium has important physiological and ecological benefits for them. This review summarizes recent research related to the functions of selenium in plant ecosystems to provide a deeper understanding of the significance of this element in plant physiology and ecosystems and to serve as a theoretical basis and technical support for the full exploitation and rational application of the ecological functions of selenium-accumulating plants.

Grandiflolines A-F, new anti-inflammatory diterpenoid alkaloids isolated from Delphinium grandiflorum.

Delphinium grandiflorum L. (family Ranunculaceae), one of the most important and widely distributed Delphinium species, has received considerable interest due to its extremely high medicinal value. The discovery of novel metabolites from D. grandiflorum supported and broadened its application as an herbal medicine. In this study, the whole herb of D. grandiflorum was phytochemically investigated to obtain fourteen C19-lycaconitine-type diterpenoid alkaloids (1-14), including six undescribed alkaloids, grandiflolines A-F (1-6). The structural elucidation of them was accomplished by detailed spectroscopic analyses, mainly including HR-MS, 1D and 2D NMR (1H-1H COSY, NOESY, HMBC and HSQC), and IR spectra. New alkaloids 1-3 and 5 possess a characteristic △2,3 functional group in the A ring, while compounds 5 and 6 feature a rare OH-16 substituent. In addition, known compounds 7-12 were isolated from D. grandiflorum for the first time. Moreover, according to its medicinal use, new alkaloids 1-6 were estimated for their potential in vitro anti-inflammatory effects, and some of them exhibited inhibitory effects on NO production in LPS-activated RAW 264.7 macrophages. Our work enriched the chemical diversity of D. grandiflorum and the genus Delphinium and presented beneficial information for further investigations.

Production of Minor Ginsenosides from Panax notoginseng Flowers by Cladosporium xylophilum.

Panax notoginseng flowers have the highest content of saponins compared to the other parts of Panax notoginseng, but minor ginsenosides have higher pharmacological activity than the main natural ginsenosides. Therefore, this study focused on the transformation of the main ginsenosides in Panax notoginseng flowers to minor ginsenosides using the fungus of Cladosporium xylophilum isolated from soil. The main ginsenosides Rb1, Rb2, Rb3, and Rc and the notoginsenoside Fa in Panax notoginseng flowers were transformed into the ginsenosides F2 and Rd2, the notoginsenosides Fd and Fe, and the ginsenoside R7; the conversion rates were 100, 100, 100, 88.5, and 100%, respectively. The transformation products were studied by TLC, HPLC, and MS analyses, and the biotransformation pathways of the major ginsenosides were proposed. In addition, the purified enzyme of the fungus was prepared with the molecular weight of 66.4 kDa. The transformation of the monomer ginsenosides by the crude enzyme is consistent with that by the fungus. Additionally, three saponins were isolated from the transformation products and identified as the ginsenoside Rd2 and the notoginsenosides Fe and Fd by NMR and MS analyses. This study provided a unique and powerful microbial strain for efficiently transformating major ginsenosides in P. notoginseng flowers to minor ginsenosides, which will help raise the functional and economic value of the P. notoginseng flower.

Comparative physiological and transcriptome analysis reveals the potential mechanism of selenium accumulation and tolerance to selenate toxicity of Broussonetia papyrifera.

Broussonetia papyrifera is an important fodder tree that is widely distributed in China. Enhancing the selenium (Se) content in B. papyrifera may help to improve the nutritional value of the feed. In this study, sodium selenite and selenate were foliar applied to investigate the mechanisms of Se tolerance and accumulation in B. papyrifera. The results showed that both Se forms significantly increased the total Se content, and the proportion of organic Se was significantly higher in the sodium selenite treatment than in the control. In addition, the soluble sugar, phenolic acid and flavonoid contents and antioxidant enzyme activities were increased by exogenous Se. The de novo RNA sequencing results showed that 644 and 1804 differentially expressed genes were identified in the selenite and selenate comparison groups, respectively. Pathway enrichment analysis demonstrated that 24 of the 108 pathways were significantly enriched, of which sulfur assimilation genes in the sodium selenite-treated groups were upregulated, whereas Se conjugation and transporter genes, such as SBP1, PCS, GSTs, ABCs and GPX, were significantly induced under selenate treatment. The hub genes identified by weighted-gene co-expression network analysis further confirmed that sulfur assimilation, conjugation and transporter genes might play a vital role in Se assimilation and tolerance. From this, a model of Se metabolism in B. papyrifera was proposed based on the above physiological and RNA sequencing data. This study is the first study to report that B. papyrifera has a strong ability to accumulate and tolerate exogenous Se, thereby providing a foundation for further characterization of the accumulation and tolerance mechanism of B. papyrifera. Our findings can provide technical support for producing Se-enriched fodder.

Electroacupuncture Promotes Autophagy by Regulating the AKT/mTOR Signaling Pathway in Temporal Lobe Epilepsy.

Temporal lobe epilepsy (TLE) is a complex neurological disease, and its occurrence and development are closely related to the autophagy signaling pathway. However, the mechanism by which electroacupuncture (EA) affects the regulation of autophagy has not been fully elucidated. TLE gene chip dataset GSE27166 and data from rats without epilepsy (n = 6) and rats with epilepsy (n = 6) were downloaded from Gene Expression Omnibus. The differentially expressed genes (DEGs) in the TLE and control groups were identified with the online tool GEO2R. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to analyse the functional and pathway enrichment of genes in the most important modules. A rat model of TLE induced by lithium-pilocarpine treatment was established. EA treatment at DU20 and DU14 in TLE rats was performed for 2 weeks. Neuronal regeneration was determined using immunofluorescence staining. The protein levels of AKT/mTOR signaling pathway and autophagy markers were detected through western blotting and immunohistochemistry. This study identified 1837 DEGs, including 798 upregulated genes and 1039 downregulated genes. GO enrichment and KEGG analyses were performed on DEGs and revealed functional enrichment mainly in the mTOR signaling pathway and autophagy-animal. Furthermore, the number of mature neurons was significantly increased upon coexpressing BrdU/NeuN in TLE rats treated with EA. Western blotting and immunohistochemistry results showed significantly decreased levels of the phosphorylated-AKT and p-mTOR in the hippocampal CA3 and DG regions of TLE rats with EA treatment. And increased p-ULK1/ULK1, LC3-II/LC3-I and p62 levels in TLE rats with EA stimulation. Therefore, this study suggested that EA promoted autophagy in hippocampal neurons during the onset of epilepsy by regulating the AKT/mTOR signaling pathway to treat epilepsy.

HPE-GCN: Predicting efficacy of tonic formulae via graph convolutional networks integrating traditionally defined herbal properties.

Chinese herbal formulae are the heritage of traditional Chinese medicine (TCM) in treating diseases through thousands of years. The formula function is not just a simple herbal efficacy addition, but produces complex and nonlinear relationships between different herbs and their overall efficacy, which brings challenges to the formula efficacy analysis. In our study, we proposed a model called HPE-GCN that combines graph convolutional networks (GCN) with TCM-defined herbal properties (TCM-HPs) to predict formulae efficacy. In addition, to process the unstructured natural language in the formula text, we proposed a weighting calculation method related to herb frequency and the number of herbs in a formula called Formula-Herb dependence degree (FHDD), to assess the dependency degree of a formula with its herbs. In our research, 214 classic tonic formulae from ancient TCM books such as Synopsis of the Golden Chamber, Jingyue's Complete Works and the Golden Mirror of Medicin were collected as datasets. The performance of HPE-GCN on multi-classification of tonic formulae reached the best result compared with classic machine learning models, such as support vector machine, naive Bayes, logistic regression, gradient boosting decision tree, and K-nearest neighbors. The evaluated index Macro-Precision, Macro-Recall, Macro-F1 of HPE-GCN on the test set were 87.70%, 84.08% and 83.51% respectively, increased by 7.27%, 7.41% and 7.30% respectively from second best compared models. GCN has the advantage of low-dimensional feature expression for herbs and formulae, and is an effective analysis tool for TCM research. HPE-GCN integrates TCM-HPs and fits the complex nonlinear mapping relationship between TCM-HPs and formulae efficacy, which provides new ideas for related research.

Early Vitamin A Supplementation for Prevention of Short-Term Morbidity and Mortality in Very-Low-Birth-Weight Infants: A Systematic Review and Meta-Analysis.

Background: Vitamin A plays an important role in the development and maintenance of the normal function of organs and systems. Premature infants have low levels of vitamin A, which may be associated with an increased risk of developing disease. This study aimed to evaluate the effects of vitamin A supplementation on short-term morbidity and mortality in very-low-birth-weight (VLBW) infants. Methods: We used PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and Web of Science to conduct a literature search of studies published before January 1, 2022, to be included in our meta-analysis. The analysis included randomized controlled trials that compared the effects of vitamin A supplementation on VLBW infants (birth weight <1,500 g) and controls given a placebo or no treatment. The certainty of evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluation (GRADE) guidelines. Results: Twelve randomized controlled trials were included in the meta-analysis, and 2,111 infants were pooled and analyzed. The overall risk of bias was not serious in the included studies. Vitamin A supplementation for reducing the incidence of bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age seems to be limited [risk ratio (RR):0.85; 95% confidence intervals (CI): 0.70-1.04; 8 studies, 1,595 infants, very-low-certainty evidence], which is different from the previous systematic review. Length of hospital stay (mean difference: -12.67, 95% CI: -23.55 to -1.79; 6 studies, 739 infants, low-certainty evidence), and the incidence of vitamin A deficiency at 28 days postnatal age (RR: 0.08; 95% CI: 0.02-0.38; 3 studies, 358 infants, low-certainty evidence) were reduced in the vitamin A group. Besides, vitamin A supplementation seems to reduce the incidence of periventricular leukomalacia (RR: 0.68; 95% CI: 0.47-0.97; 4 studies, 1,224 infants, low-certainty evidence) and retinopathy of prematurity of any grade (RR: 0.61; 95% CI: 0.48-0.76; 4 studies, 463 infants, moderate-certainty evidence). Conclusions: There is no sufficient evidence regarding vitamin A supplementation preventing BPD in VLBW infants. Vitamin A supplementation can reduce the incidence of vitamin A deficiency and retinopathy of prematurity of any grade, and may exert an effect of preventing periventricular leukomalacia. Systematic Review Registration: http://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42020211070.

Identification and Tetramer Structure of Hemin-Binding Protein SPD_0310 Linked to Iron Homeostasis and Virulence of Streptococcus pneumoniae.

Iron and iron-containing compounds are essential for bacterial virulence and host infection. Hemin is an important supplement compound for bacterial survival in an iron-deficient environment. Despite strong interest in hemin metabolism, the detailed mechanism of hemin transportation in Gram-positive bacteria is yet to be reported. The results of our study revealed that the homologous proteins of SPD_0310 were significantly conservative in Gram-positive bacteria (P < 0.001), and these proteins were identified as belonging to an uncharacterized protein family (UPF0371). The results of thermodynamic and kinetic studies have shown that SPD_0310 has a high hemin-binding affinity. Interestingly, we found that the crystal structure of SPD_0310 presented a homotetramer conformation, which is required for hemin binding. SPD_0310 can interact with many hemin-binding proteins (SPD_0090, SPD_1609, and GAPDH) located on the cell surface, which contributes to hemin transfer to the cytoplasm. It also has a high affinity with other iron transporters in the cytoplasm (SPD_0226 and SPD_0227), which facilitates iron redistribution in cells. More importantly, the knockout of the spd_0310 gene (Δspd_0310) resulted in a decrease in the iron content and protein expression levels of many bacterial adhesion factors. Moreover, the animal model showed that the Δspd_0310 strain has a lower virulence than the wild type. Based on the crystallographic and biochemical studies, we inferred that SPD_0310 is a hemin intermediate transporter which contributes to iron homeostasis and further affects the virulence of Streptococcus pneumoniae in the host. Our study provides not only an important theoretical basis for the in-depth elucidation of the hemin transport mechanism in bacteria but also an important candidate target for the development of novel antimicrobial agents based on metal transport systems. IMPORTANCE Iron is an essential element for bacterial virulence and infection of the host. The detailed hemin metabolism in Gram-positive bacteria has rarely been studied. SPD_0310 belongs to the UPF0371 family of proteins, and results of homology analysis and evolutionary tree analysis suggested that it was widely distributed and highly conserved in Gram-positive bacteria. However, the function of the UPF0371 family remains unknown. We successfully determined the crystal structure of apo-SPD_0310, which is a homotetramer. We found that cytoplasmic protein SPD_0310 with a special tetramer structure has a strong hemin-binding ability and interacts with many iron transporters, which facilitates hemin transfer from the extracellular space to the cytoplasm. The results of detailed functional analyses indicated that SPD_0310 may function as a hemin transporter similar to hemoglobin in animals and contributes to bacterial iron homeostasis and virulence. This study provides a novel target for the development of antimicrobial drugs against pathogenic Gram-positive bacteria.

The prospective multiple-centre randomized controlled clinical study of high-dose amoxicillin-proton pump inhibitor dual therapy for H. pylori infection in Sichuan areas.

OBJECTIVES: To evaluate the safety and efficacy of high-dose amoxicillin-proton pump inhibitor dual therapy, and to provide a new eradication regimen as a first-line option for patients with H. pylori infection. METHODS: A total of 971 H. pylori positive patients who received initial treatment were recruited from March to August 2020, and randomly divided into treatment group and control group. The treatment group received of 20 mg esomeprazole four times daily and 750 mg amoxicillin four times daily for 14 days. Control group received of 220 mg bismuth potassium citrate twice daily, 20 mg esomeprazole twice daily, 1000 mg amoxicillin twice daily and 250 mg clarithromycin capsule twice daily for 14 days. Four weeks after the end of treatment, the urea breath test was reviewed to detect whether H. pylori was eradicated. RESULTS: There were no statistical differences in age, gender, the total clinical symptom scores before and after initial treatment, the compliance, and the degree of remission of symptoms before and after initial treatment between the two groups. The eradication rates of H. pylori between dual therapy and quadruple therapy were 88.31% and 85.26% (p=.158) by intention-to-treat (ITT) analysis, 88.66% and 85.44% (p=.186) by modified intention-to-treat (mITT) analysis, and 91.63% and 90.60% (p=.116) by PP analysis, respectively. Adverse events in dual therapy group were significantly lower than quadruple therapy group (13.3% vs. 28.2% (p<.01)). CONCLUSIONS: For the initial treatment of H. pylori infection, the high-dose dual therapy regimen has the same efficacy as the bismuth-containing quadruple therapy regimen, good compliance, less adverse reactions and high safety, so it can be recommended as the empirical first-line treatment regimen for the eradication of H. pylori (KY2019173).