Machine learning model based on RCA-PDCA nursing methods and differentiating factors to predict hypotension during cesarean section surgery.

BACKGROUND: Intraoperative hypotension during cesarean section has become a serious complication for maternal and fetal healthy. It is commonly encountered by subarachnoid anesthesia. However, currently used control methods have varying degrees of side effects, such as drugs. The Root Cause Analysis (RCA) - Plan, Do, Check, Act (PDCA) is a new model of care that identifies the root causes of problems. The study aimed to demonstrate the usefulness of RCA-PDCA nursing methods in preventing intraoperative hypotension during cesarean section and to predict the occurrence of intraoperative hypotension through a machine learning model. METHODS: Patients who underwent cesarean section at Traditional Chinese Medicine of Southwest Medical University from January 2023 to December 2023 were retrospectively screened, and the data of their gestational times, age, height, weight, history of allergies, intraoperative vital signs, fetal condition, operative time, fluid out and in, adverse effects, use of vasopressor drugs, anxiety-depression-pain scores, and satisfaction were collected and analyzed. The statistically different features were screened and five machine learning models were used as predictive models to assess the usefulness of the RCA-PDCA model of care. RESULTS: (1) Compared with the general nursing model, the RCA-PDCA nursing model significantly reduces the incidence of intraoperative hypotension and postoperative complications in cesarean delivery, and the patient experience is comfortable and satisfactory. (2) Among the five machine learning models, the RF model has the best predictive performance, and the accuracy of the random forest model in preventing intraoperative hypotension is as high as 90%. CONCLUSION: Through computer machine learning model analysis, we prove the importance of the RCA-PDCA nursing method in the prevention of intraoperative hypotension during cesarean section, especially the Random Forest model which performed well and promoted the application of artificial intelligence computer learning methods in the field of medical analysis.

The key role of unsaturated olefin content on polysulfides prepared via inverse vulcanization of waste plant oils for mercury removal from wastewater.

Three waste plant oils (olive oil, coconut oil, and soybean oil) were utilized as monomer crosslinking agents to synthesize polysulfides by inverse vulcanization with elemental sulfur, for mercury removal from wastewater. NMR analysis showed that 92.1% of the olefins participated in the inverse vulcanization reaction, indicating that the quantity of unsaturated olefins in plant oil mainly affects the ring-opening ratio of sulfur for the formation of sulfur-based polymers. The experimental results showed that olive oil polysulfide (S-r-olive) achieved 100% Hg2+ removal within 2 h at a pH of 6. The S-r-olive, S-r-soybean, and S-r-coconut exhibited adsorption capacities of 130.23, 42.72, and 28.08 mg/g, respectively. The kinetic and adsorption isotherm illustrated that the Hg2+ adsorption by polysulfides conformed to the pseudo-second-order and Freundlich models, showing that the reaction rate constant of S-r-olive is approximately 14 times and 4.6 times greater than that of S-r-soybean and S-r-coconut, respectively. The adsorption mechanism is concluded that Hg2+ first enters the suspended S-r-olive by physical adsorption, then combined with sulfur to form HgS by chemical action and fixed in the S-r-olive adsorbent. This study demonstrates that utilizing waste plant oils as monomer crosslinking agents to synthesize adsorbents for Hg2+ removal is feasible and effective.

Dendrobium nobile Lindl ameliorates learning and memory deficits in scopolamine-treated mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Dendrobium nobile Lindl (DNL), a valued time-honored herb, possesses immune-boosting and age-delaying properties, has been widely used to treat hyperglycemia and neurological diseases, and is probably a potential drug for improving learning and memory. Scopolamine (Scop), an antagonist for muscarinic receptors, potentially impairing intelligence and memory. AIM OF THE STUDY: This investigation aimed to assess the efficacy of DNL in alleviating scopolamine-induced cognitive deficits in mice and its mechanisms. MATERIALS AND METHODS: We utilized the open-field test, novel object recognition test (NOR), and Morris water maze test (MWM) to assess the potential of DNL in ameliorating learning and memory dysfunction caused by scopolamine in mice. Enzyme-linked immunosorbent assay (ELISA) was employed to measure Choline acetyltransferase (ChAT) content and Acetylcholinesterase (AChE) activities in the brain, and oxidative stress-related factors in the serum, including Malondialdehyde (MDA), Superoxide dismutase (SOD), and glutathione (GSH) content. RESULTS: Scopolamine injection significantly reduced the discrimination index of mice in the NOR test and impaired their performance in the MWM test, as demonstrated by longer escape latency, fewer target crossings, and less time spent in the target quadrant in the MWM. After 25 days of administration, DNL increased the discrimination index of the scopolamine-treated mice in the NOR test. DNL reduced the escape latency in the MWM test in the model mice. DNL increased the target crossing number and the percentage of time spent in the target quadrant in the MWM test. ELISA experiments indicated that DNL decreased the AChE activities, increased the ChAT activities, and modulated oxidative stress makers (GSH, SOD, and MDA) in scopolamine-induced mice. CONCLUSIONS: DNL may improve the learning and memory in mice treated with scopolamine, possibly by modulating oxidative stress and impaired cholinergic function.

Efficacy and safety of Tripterygium wilfordii multiglucoside for idiopathic membranous nephropathy: a systematic review with bayesian meta-analysis.

Background: Currently, the optimal therapy plan for idiopathic membranous nephropathy (IMN) remains controversial as there has been no comprehensive and systematic comparison of therapy plans for IMN. Therefore, in this study, a Bayesian meta-analysis was used to systematically evaluate the clinical efficacy and safety of various intervention plans involving traditional Chinese medicine TWM in the treatment of IMN. Methods: An electronic search in 7 databases was conducted from their inception to August 2022 for all published randomized controlled trials (RCTs) of various intervention plans for IMN. Network meta-analysis (NMA) was performed by using software R, and the surface under the cumulative ranking area (SUCRA) probability curve was plotted for each outcome indicator to rank the efficacy and safety of different intervention plans. Results: A total of 30 RCTs were included, involving 13 interventions. The results showed that (1) in terms of total remission (TR), ① GC + CNI + TWM was the best effective among all plans, and the addition and subtraction plan of CNI + TWM was the best effective for IMN; ② All plans involving TWM were more effective than GG; ③ Among monotherapy plans for IMN, TWM was more effective distinctly than GC, while TWM and CNI were similarly effective; ④ Among multidrug therapy plans for IMN, the addition of TWM to previously established therapy plans made the original plans more effective; ⑤The efficacy of combining TWM with other plans was superior to that of TWM alone. (2) In terms of lowering 24 h-UTP, GC + TWM was the best effective and more effective than TWM. (3) In terms of safety, there was no statistically significant difference between all groups. However, CNI + TWM was the safest. No serious adverse events (AEs) occurred in all the included studies. Conclusion: The addition of TWM may be beneficial to patients with IMN. It may enhance the efficacy of previously established treatment protocols without leading to additional safety risks. In particular, GC + CNI + TWM, GC + TWM, and CNI + TWM with better efficacy and higher safety can be preferred in clinical decision-making as the therapy plans for IMN.

Combination of Shengmai San and Radix puerariae ameliorates depression-like symptoms in diabetic rats at the nexus of PI3K/BDNF/SYN protein expression.

BACKGROUND: Hyperglycemia is a characteristic feature of diabetes that often results in neuropsychological complications such as depression. Diabetic individuals are more vulnerable to experience depression compared to the normal population. Thus, novel treatment approaches are required to reduce depressive symptoms among diabetic individuals. Traditional Chinese medicines (TCMs) such as Shengmai San (SMS) and Radix puerariae (R) are usually widely used to treat ailments such as neurological complications since ancient time. METHODS: In this study, SMS was combined with R to prepare an R-SMS formulation and screened for their antidepressant activity in diabetic rats. The antidepressant potential of the prepared combination was evaluated behaviorally using open field test, novelty-induced hypophagia, and forced swim test in diabetic rats with biochemical and protein expression (PI3K, BDNF [brain-derived neurotrophic factor], and SYN [presynaptic vesicle protein]) analysis. RESULTS: Diabetic rats (streptozotocin, 45 mg/kg) showed elevated fasting blood glucose (FBG) >12 mM with depressive symptoms throughout the study. Treatment with R-SMS (0.5, 1.5, and 4.5 g/kg) significantly reverted depressive symptoms in diabetic rats as evinced by significantly (p < 0.05) reduced immobility time with an increased tendency to eat food in a novel environment. Treatment with R-SMS also significantly increased the protein expression of PI3K, BDNF, and SYN protein, which play a crucial role in depression. CONCLUSION: This study showed that R-SMS formulation antagonized depressive symptoms in diabetic rats; thus, this formulation might be studied further to develop as an antidepressant.

Transcriptomics and metabolomics revealed the pulmonary protective mechanism of Xixin-Ganjiang Herb Pair for warming the lungs to dissolve phlegm in COPD rats.

Xixin-Ganjiang Herb Pair (XGHP), a classic combination treatment to warm the lungs and dissolve phlegm, is widely used in the treatment of various pulmonary diseases. Chronic obstructive pulmonary disease (COPD) refers to a group of chronic obstructive airway diseases that can seriously harm human health. However, the effective components, targets, and pathways that underlie XGHP in the treatment of COPD remain unclear. Therefore, this study initially identified the effective components of XGHP through the use of UPLC-MS/MS and pharmacologic methods of traditional Chinese medicine. Secondly, transcriptomic analysis of the lung tissues of rats revealed the pharmacodynamic transcripts of each group, and metabolomics analysis revealed the differential metabolites associated with XGHP treatment. Finally, molecular docking of effective components with transcriptome genes was performed and western blotting was performed in order to determine the expression of related proteins in rat lung tissue. Overall, 30 effective components of XGHP were identified, including L-asarinin, 6-gingerol, sesamin, kaempferol, and quercetin. Transcriptomic studies demonstrated that expression of 386 genes recovered after XGHP treatment, and that they were mainly enriched in the oxidative phosphorylation and AMPK signaling pathways. According to the metabolomics studies, expression of eight metabolites differed between the COPD and the XGHP groups. These metabolites were mainly involved the biosynthesis of unsaturated fatty acids. Finally, the transcriptomic and metabolomics data were integrated. FASN and SCD in AMPK signaling pathway were directly linked to certain metabolites, including linoleic acid, palmitic acid, and oleic acid. These results indicate that XGHP can inhibit pAMPK expression and negatively regulate FASN and SCD expression during treatment of COPD in order to enhance the biosynthesis of unsaturated fatty acids and maintain energy homeostasis.

Integration of LC-LTQ-Orbitrap-MS and Network Pharmacology to Analyze the Active Components of Sijunzi Decoction and their Mechanism of Action Against Cytotoxicity-associated Premature Ovarian Insufficiency.

INTRODUCTION: Sijunzi Decoction (SJZD) is a classical prescription in traditional Chinese medicine that enhances neuroimmune endocrine function to alleviate inflammatory aging, a key pathogenic mechanism underlying premature ovarian insufficiency (POI). However, the mechanism through which SJZD alleviates POI remains unknown. Hence, we aimed to identify the active components of SJZD and its mechanism of therapeutic action against POI. METHODS: We identified compounds in SJZD using liquid chromatography-linear trap quadrupole- Orbitrap-mass spectrometry (LC-LTQ-Orbitrap-MS). Traditional Chinese Medicine Systems (TCMSP) and HERB databases were used to identify the ingredients and potential targets of SJZD. We analyzed Gene Ontology (GO) terms and enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways using RStudio and constructed a visual network using Cytoscape3.9.1. RESULTS: We identified 98 compounds using LC-LTQ-Orbitrap-MS, among which 29 were bioactive. The screen outputted yielded 151 predicted targets of these compounds that were associated with POI. The results of the GO and KEGG analyses showed that these compounds play key roles in cell growth, division, migration, and survival signaling pathways. Therefore, phosphatidylinositol 3-kinase (PI3K)/AKT, mitogen-activated protein kinase (MAPK), and epidermal growth factor receptor (EGFR) pathways might be closely associated with the pharmacological effects of SJZD on the pathological processes of POI. CONCLUSION: Our findings provide a scientific basis for rapidly analyzing bioactive compounds in SJZD and their pharmacological mechanisms.

Mechanisms by which kidney-tonifying Chinese herbs inhibit osteoclastogenesis: Emphasis on immune cells.

The immune system plays a crucial role in regulating osteoclast formation and function and has significance for the occurrence and development of immune-mediated bone diseases. Kidney-tonifying Chinese herbs, based on the theory of traditional Chinese medicine (TCM) to unify the kidney and strengthen the bone, have been widely used in the prevention and treatment of bone diseases. The common botanical drugs are tonifying kidney-yang and nourishing kidney-yin herbs, which are divided into two parts: one is the compound prescription of TCM, and the other is the single preparation of TCM and its active ingredients. These botanical drugs regulate osteoclastogenesis directly and indirectly by immune cells, however, we have limited information on the differences between the two botanical drugs in osteoimmunology. In this review, the mechanism by which kidney-tonifying Chinese herbs inhibiting osteoclastogenesis was investigated, emphasizing the immune response. The differences in the mechanism of action between tonifying kidney-yang herbs and nourishing kidney-yin herbs were analysed, and the therapeutic value for immune-mediated bone diseases was evaluated.

Wumei Wan attenuates angiogenesis and inflammation by modulating RAGE signaling pathway in IBD: Network pharmacology analysis and experimental evidence.

BACKGROUND: Wumei Wan (WMW) has been used to address digestive disorder for centuries in traditional Chinese medicine. Previous studies have demonstrated its anti-colitis efficacy, but the underlying mechanism of its action remains to be further clarified. PURPOSE: To investigate the underlying mechanisms of WMW in the treatment of chronic ulcerative colitis (UC) through network pharmacology and experimental validation. METHODS: Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform were used to identify the ingredients and potential targets of WMW. The microarray gene data GSE75214 datasets from GEO database was used to define UC-associated targets. Cytoscape3.7.2 was employed to construct the protein-protein interaction (PPI) network and compounds-disease targets network. GO enrichment analysis and KEGG pathway analysis were performed by R software for functional annotation. UPLC-TOF-MS/MS method was used to quantitatively analyze the active ingredients of WMW. For experimental validation, three cycles of 2% dextran sulfate sodium salt (DSS) were used to construct chronic colitis model. The hub targets and signal pathway were detected by qPCR, ELISA, western blotting , immunohistochemical and immunofluorescence. RESULTS: Through network analysis, 104 active ingredients were obtained from WMW, and 47 of these ingredients had potential targets for UC. A total of 41 potential targets of WMW and 13 hub targets were identified. KEGG analysis showed that WMW involved in advanced glycation end products-receptor of advanced glycation end products (AGE-RAGE) signaling pathway. Taxifolin, rutaecarpine, kaempferol, quercetin, and luteolin of WMW were the more highly predictive components related to the AGE-RAGE signaling pathway. In vivo validation, WMW improved DSS-induced colitis, reduced the expression of inflammatory cytokines and chemokines. Notably, it significantly decreased the mRNA expression of Spp1, Serpine1, Mmp2, Mmp9, Ptgs2, Nos2, Kdr and Icam1, which were associated with angiogenesis. In addition, we confirmed WMW inhibited RAGE expression and diminished DSS-induced epithelial barrier alterations CONCLUSION: Our results initially demonstrated the effective components and the strong anti-angiogenic activity of WMW in experimental chronic colitis. Sufficient evidence of the satisfactory anti-colitis action of WMW was verified in this study, suggesting its potential as a quite prospective agent for the therapy of UC.

Qihuang Zhuyu Formula Attenuates Atherosclerosis via Targeting PPARγ to Regulate Cholesterol Efflux and Endothelial Cell Inflammation.

At present, due to the limitations of drug therapy targets for atherosclerosis, some patients fail to achieve satisfactory efficacy. Cholesterol efflux dysfunction and endothelial cell inflammation are considered to be important factors in the development of atherosclerosis. Peroxisome proliferator-activated receptor gamma (PPARγ), a promising therapeutic target for atherosclerosis, plays a dual role in regulating cholesterol efflux and endothelial cell inflammation. However, the use of PPARγ agonist in clinical practice is greatly limited as it could lead to water and sodium retention and hence result in congestive heart failure. Qihuang Zhuyu Formula (QHZYF) is a hospital preparation of Jiangsu Province Hospital of Chinese Medicine which has definite effect in the treatment of atherosclerosis, but its pharmacological mechanism has not been clear. In this study, we successfully predicted that QHZYF might regulate cholesterol efflux and endothelial inflammation via targeting PPARγ-mediated PPARγ/LXRα/ABCA1-ABCG1 and PPARγ/NF-κB p65 pathways by using UPLC-Q-TOF/MS, network pharmacology, bioinformatics analysis, and molecular docking technology. Subsequently, we confirmed in vivo that QHZYF could attenuate atherosclerosis in ApoE-/- mice and regulate the expression levels of related molecules in PPARγ/LXRα/ABCA1-ABCG1 and PPARγ/NF-κB p65 pathways of ApoE-/- mice and C57BL/6 wild-type mice. Finally, in in vitro experiments, we found that QHZYF could reduce lipid content and increase cholesterol efflux rate of RAW 264.7 cells, inhibit the inflammatory response of HUVECs, and regulate the expression levels of related molecules in the two pathways. In addition, the above effects of QHZYF were significantly weakened after PPARγ knockdown in the two kinds of cells. In conclusion, our study revealed that QHZYF attenuates atherosclerosis via targeting PPARγ-mediated PPARγ/LXRα/ABCA1-ABCG1 and PPARγ/NF-κB p65 pathways to regulate cholesterol efflux and endothelial cell inflammation. More importantly, our study offers a promising complementary and alternative therapy which is expected to make up for the limitation of current drug treatment methods and provide a valuable reference for new drugs development in the future.

Effects of PD-1 inhibitor combined with anti-angiogenic drugs on efficacy and immune function of non-small cell lung cancer.

OBJECTIVE: To investigate the effect of PD-1 inhibitor combined with anti-angiogenic drugs on the therapeutic efficacy and immune function of patients with non-small cell lung cancer (NSCLC). METHODS: Clinical data of 60 NSCLC patients who admitted to a regional Hospital of Traditional Chinese Medicine from May 2020 to August 2021 were analyzed retrospectively. Among them, 23 patients who received sintilimab and anlotinib were in group A, 20 patients treated with sintilimab were in group B, and 17 patients intervened by anlotinib alone were in group C. The changes of clinical efficacy, objective remission rate (ORR) and disease control rate (DCR) among the three groups were compared. The levels of cluster of differentiation 4 (CD4)+, cluster of differentiation 8 (CD8)+ and CD4+/CD8+ were assessed before and 6 weeks after treatment. The progression-free survival (PFS) was calculated and the prognostic factors were analyzed by Cox regression. The adverse reactions of immunotherapy in three groups were evaluated. RESULTS: There was no obvious difference in ORR among the three groups (P>0.05). The proportion of DCR in group A was dramatically higher than that in group B and C (P<0.05). After treatment, the CD4+ and CD4+/CD8+ levels were markedly higher, while the CD8+ level in group A was lower in group A than those in the other two groups (P<0.05). There was no obvious difference in the incidence of immune-related adverse reactions among the three groups (P>0.05). The median PFS of patients was 6.03 months. Cox regression analysis revealed that Eastern Cooperative Oncology Group score, tumor metastasis and treatment regimen were independent prognostic factors affecting PFS. CONCLUSION: Sintilimab combined with anlotinib can effectively improve DCR and prolong PFS in NSCLC patients, and this regimen does not increase immune-related adverse reactions during treatment.

Acupuncture for gastrointestinal urticaria: A protocol for systematic review and network meta-analysis.

Introduction: The purpose of this review is to evaluate the effectiveness and safety of acupuncture in the treatment of patients with gastrointestinal urticaria (GU) and to provide a clinician's guide to GU treatment options. Methods and analysis: We plan to search multiple databases (i.e., PubMed, EMBASE, Springer, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Literature Database and Wanfang Database) for studies published before September 1, 2022. We will electronically search for all relevant studies concerning clinical acupuncture treatments of GU, including unpublished conference articles and other gray literature. The language limit of this systematic review is Chinese and English. Any reports of clinical randomized controlled trials of acupuncture for the treatment of GU will be included in the study. Two researchers will perform independent data extraction to increase the quality of the data extraction. The primary outcome was the Urticaria Activity Score 7 (UAS7). Abdominal visual analog scale (VAS) for abdominal pain, dermatological life quality index (DLQI), the total effective rate, recurrence rate, and occurrence of adverse events were secondary outcomes. We will use RevMan V.5.3 statistical software for pairwise meta-analysis and ADDIS V.1.16.8 software for Bayesian network meta-analysis. If feasible, meta-regression and subgroup analyses will also be performed to address the potential causes of inconsistency and heterogeneity. We will conduct a GRADE assessment of the quality of evidence for the interventions included in this review. Discussion: This study may validate acupuncture as an alternative therapy for the effective treatment of GU. Trial registration number: PROSPERO CRD42022333977.

Integrated Metabolomics and Network Pharmacology to Reveal the Mechanisms of Guizhi-Fuling Treatment for Myocardial Ischemia.

Myocardial ischemia is a cardio-physiological condition due to a decrease in blood perfusion to the heart, leading to reduced oxygen supply and abnormal myocardial energy metabolism. Guizhi-Fuling (GZFL) is effective in treating Myocardial ischemia. However, its mechanism of action is unclear and requires further exploration. We attempt to decipher the mechanisms behind GZFL treating Myocardial ischemia by integrating metabolomics and network pharmacology. In this study, myocardial metabolomic analysis was performed using GC/MS to identify the potential mechanism of action of GZFL during myocardial ischemia. Then, network pharmacology was utilized to analyze key pathways and construct a pathway-core target network. Molecular docking was incorporated to validate core targets within network pharmacological signaling pathways. Finally, western blots were utilized to verify core targets of metabolomics, network pharmacology integrated pathways, and key signaling targets. Thus, 22 critical biomarkers of GZFL for treating myocardial ischemia were identified. Most of these metabolites were restored using modulation after GZFL treatment. Based on the network pharmacology, 297 targets of GZFL in treating myocardial ischemia were identified. The further comprehensive analysis focused on three key targets, such as Tyrosine hydroxylase (TH), myeloperoxidase (MPO), and phosphatidylinositol 3-kinases (PIK3CA), and their related metabolites and pathways. Compared with the model group, the protein expression levels of TH, MPO and PIK3CA were reduced in GZFL. Therefore, the mechanism of GZFL for treating myocardial ischemia could inhibit myocardial inflammatory factors, reduce myocardial inflammation, and restore endothelial function while controlling norepinephrine release and uric acid concentration.

Effect of Qingfei Huaxian Decoction combined with prednisone acetate on serum inflammatory factors and pulmonary function of patients with idiopathic pulmonary fibrosis.

OBJECTIVE: To determine the effect of Qingfei Huaxian Decoction combined with prednisone acetate on serum inflammatory factors and pulmonary function in patients with idiopathic pulmonary fibrosis (IPF). METHODS: The clinical data of 118 patients with IPF treated in Wuhan Hospital of Traditional Chinese Medicine from June 2019 to August 2021 were retrospectively analyzed. Among the patients, 56 patients treated with prednisone acetate were assigned to the control group, and the remaining 62 patients treated with Qingfei Huaxian Decoction combined with prednisone acetate were assigned to the observation group. The efficacy and incidence of adverse reactions were compared between the two groups, and forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, interleukin-6 (IL-6), interleukin-12 (IL-12), interleukin-18 (IL-18), hyaluronic acid (HA) and laminin (LN) in the two groups were evaluated before and after therapy. Logistic regression was conducted to analyze the risk factors impacting the treatment efficacy in patients. RESULTS: After therapy, the observation group showed significantly higher efficacy than the control group. Compared with the control group, the observation group showed significantly higher levels of FEV1, FVC and FEV1/FVC, significantly lower levels of HA and LN, and a significantly higher IL-12 level (all P < 0.05). Therapeutic regimen, IL-6, IL-12, IL-18 and HA were independent risk factors impacting the efficacy of treatment in patients (P < 0.05). CONCLUSION: Qingfei Huaxian Decoction combined with prednisone acetate has greater treatmetn efficacy in patients with IPF by improving the serum inflammatory factors and pulmonary function.

Identification of candidate genes in cotton associated with specific seed traits and their initial functional characterization in Arabidopsis.

Oilseed crops are used to produce vegetable oil to satisfy the requirements of humans and livestock. Cotton (Gossypium spp.) is of great economic value because it is used as both an important textile commodity and a nutrient-rich resource. Cottonseed oil is rich in polyunsaturated fatty acids and does not contain trans fatty acids; hence, it is considered a healthy vegetable oil. However, research on the genetic basis for cottonseed protein content, oil production, and fatty acid composition is lacking. Here, we investigated the protein content, oil content, and fatty acid composition in terms of oleic acid (C18:1) and linoleic acid (C18:2) in mature cottonseeds from 318 Gossypium hirsutum accessions. Moreover, we examined the dynamic change of protein content and lipid composition including palmitic acid (C16:0), stearic acid (C18:0), oleic acid (C18:1), linoleic acid (C18:2), and linolenic acid (C18:3) in developing seeds from 258 accessions at 10 and 20 days post-anthesis. Then, we conducted a genome-wide association study and identified 152 trait-associated loci and 64 candidate genes responsible for protein and oil-related contents in mature cottonseeds and ovules. Finally, six candidate genes were experimentally validated to be involved in the regulation of fatty acid biosynthesis through heterologous expression in Arabidopsis. These results comprise a solid foundation for expanding our understanding of lipid biosynthesis in cotton, which will help breeders manipulate protein and oil contents to make it a fully developed 'fiber, food, and oil crop'.

Integration of metabolomics and transcriptomics to reveal anti-chronic myocardial ischemia mechanism of Gualou Xiebai decoction.

ETHNOPHARMACOLOGICAL RELEVANCE: Gualou Xiebai decoction (GLXB), a well-known classic traditional Chinese medicine formula, is a recorded and proven therapy for the management of cardiac diseases. However, its pharmacological characteristics and mechanism of action are unclear. MATERIALS AND METHODS: The effects of GLXB and its mechanism of action in an isoprenaline-induced rat model of chronic myocardial ischemia (CMI) were investigated by incorporating metabonomics and transcriptomics. Meanwhile, the echocardiographic evaluation, histopathological analysis, serum biochemistry assay, TUNEL assay and western blot analysis were detected to revealed the protective effects of GLXB on CMI. RESULTS: The results of echocardiographic evaluation, histopathological analysis and serum biochemistry assay revealed that GLXB had a significantly cardioprotective performance by reversing echocardiographic abnormalities, restoring pathological disorders and converting the serum biochemistry perturbations. Further, the omics analysis indicated that many genes and metabolites were regulated after modeling and GLXB administration, and maintained the marked "high-low" or "low-high" trends. Meanwhile, the results from integrated bioinformatics analysis suggested that the interaction network mainly consisted of amino acid and organic acid metabolism. The results of TUNEL assay and western blot analysis complemented the findings of integrated analysis of metabolomics and transcriptomics. CONCLUSION: These findings suggested that GLXB has a curative effect in isoproterenol-induced CMI in rats. Integrated analysis based on transcriptomics and metabolomics studies revealed that the mechanism of GLXB in alleviating CMI was principally by the regulation of energy homeostasis and apoptosis, which was through a multi-component and multi-target treatment modality.

Synergistic Effect of Polydatin and Polygonatum sibiricum Polysaccharides in Combating Atherosclerosis via Suppressing TLR4-Mediated NF-κB Activation in ApoE-Deficient Mice.

Objective: Atherosclerosis is a chronic inflammatory disease, which is closely related to hyperlipidemia, inflammatory responses, and oxidative stress. As natural products, polydatin (PD) and Polygonatum sibiricum polysaccharides (PSP) have remarkable pharmacological effects in anti-inflammatory, antioxidant stress, and lipid regulation. In this study, we sought to investigate whether the combination of polydatin and P. sibiricum polysaccharides play an anti-atherosclerotic role in alleviating inflammatory responses by inhibiting the toll-like receptor4 (TLR4)/myeloid differentiation factor88(MyD88)/nuclear factor-kappa B(NF-κB) signaling pathway. Methods: Thirty-two ApoE-/- mice were fed with a high-fat diet (HFD) starting at the age of 8 weeks. Mice were randomly divided into four groups; (1) model group, (2) PD (100 mg/kg) + PSP (50 mg/kg) group, (3) TAK-242 (3 mg/kg) (TLR4 inhibitor) group, (4) PD (100 mg/kg) + PSP (50 mg/kg) + TAK-242 (3 mg/kg) group. Eight age-matched wild-type C57BL/6J mice fed an ordinary diet were used as a control group. Blood lipid levels were measured with an automatic biochemical analyzer. The lipid accumulation and histopathological changes in the aorta and liver were observed by Oil Red O and hematoxylin and eosin (H&E) staining, respectively. ELISA was performed to measure the serum levels of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). Western blot analysis was performed to analyze the expression of key proteins in the TLR4/MyD88/NF-κB signaling pathway. Results: Compared with the model group, the combination of PD and PSP significantly inhibit serum lipids (low-density lipoprotein cholesterol, total cholesterol, and triglyceride) and cell adhesion molecules (VCAM-1, ICAM-1). Oil Red O staining indicated that the combination of PD and PSP decrease lipid accumulation in the aorta and liver. Moreover, H&E staining suggested that the combination of PD and PSP alleviate aortic intimal hyperplasia, inflammatory cell infiltration, and hepatic steatosis. Finally, the combination of PD and PSP inhibit the expression of TLR4, MyD88, and the phosphorylation level of NF-κB p65 protein in the aorta. Conclusions: Polydatin synergizes with P. sibiricum polysaccharides in preventing the development of atherosclerosis in ApoE-/- mice by inhibiting the TLR4/MyD88/NF-κB signaling pathway.

Traditional use and safety evaluation of combination Traditional Chinese Medicine in European registration: with XiaoYao Tablets as an example.

Mental health disorders such as stress, anxiety, depression and insomnia caused by COVID-19 have attracted worldwide attention. Traditional Chinese medicines (TCMs) have been proven to be a safe and effective option for treating mental health disorders. Recently, after assessing its efficacy and safety fully, the Netherlands Medicines Evaluation Board approved XiaoYao Tablets as a traditional herbal medicinal product (THMP), indicated for an alternative self-care for patients in Europe to relieve the symptoms of mental stress and exhaustion. Despite the fact that TCMs have gradually become one of the therapeutic choices worldwide, to-date, only a few TCMs have been successfully registered in the European Union (EU) as THMPs, and XiaoYao Tablets is the first successfully registered combination TCM from China. In this article, traditional use efficacy and clinical safety of XiaoYao Tablets in the treatment of mental health disorders were summarized and analyzed from the perspective of traditional use registration (TUR). Additionally a safety evolution pathway of combination TCMs was established. This article will not only seek to enhance our understanding about traditional use efficacy and clinical safety of XiaoYao Tablets, but also summarize the experience of XiaoYao Tablets as the first successfully registered combination TCM from China, which could serve as role model for the others to overcome registration difficulties in the EU.

Soy isoflavones protects against cognitive deficits induced by chronic sleep deprivation via alleviating oxidative stress and suppressing neuroinflammation.

Mounting evidence suggests that there is a close association between chronic sleep deprivation (CSD) and cognitive deficits. The animal model of CSD-induced cognitive deficits is commonly used to seek potential treatments. Soy isoflavones (SI) have been reported to possess antioxidant, anti-inflammation, and neuroprotective effects. In the present study, the effects of SI on CSD-induced memory impairment were investigated. The mice were subjected to the sleep interruption apparatus and continuously sleep deprived for 2 weeks, while orally administrated with SI (10, 20, and 40 mg/kg) or Modafinil (MOD,100 mg/kg) during the CSD process. Immediately after the SD protocol, cognitive performance of mice was evaluated by the object location recognition (OLR) test, the novel object recognition (NOR) test, and the Morris water maze (MWM) task, as well as the hippocampus, was extracted for evaluation of oxidative stress parameters and inflammation levels through biochemical parameter assay and western blotting analysis. The results showed that SI administration remarkably improved the cognitive performance of CSD-treated mice in OLR, NOR, and MWM tests. In addition, SI significantly elevated total antioxidant capacity and superoxide dismutase enzyme activities, decreased malondialdehyde level, promoting antioxidant element nuclear erythroid-2-related factor 2, and its downstream targets, including heme oxygenase 1, and quinone oxidoreductase 1 protein expressions. Moreover, SI treatment significantly suppressed nuclear factor kappa B p65, nitric oxide synthase, and cyclooxygenase 2 activation, as well as the pro-inflammatory cytokines (Tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6], and interleukin-1ß [IL-1ß]) release in the hippocampus of CSD-treated mice. In summary, the current study provides an insight into the potential of SI in treatment of cognitive deficits by CSD.

An automated quantification method for the Agatston coronary artery calcium score on coronary computed tomography angiography.

Background: A coronary artery calcium (CAC) score can provide supplementary information for predicting the risk of cardiovascular disease (CVD). Although CAC is clinically measured with non-contrast cardiac computed tomography (CT), coronary CT angiography (CCTA) may also be used, allowing for the simultaneous evaluation of coronary artery vessels and calcified plaques. This study proposes a method for the automated quantification of the Agatston CAC score from CCTA and compares our method's performance with that of non-contrast cardiac CT. Methods: Sixty-two patients were selected from a clinical registry and divided into four CAC categories. They underwent both non-contrast cardiac CT and CCTA. The Agatston CAC score derived from non-contrast cardiac CT (standard Agatston CAC score) was used as the reference standard. Calcifications were automatically identified and quantified using different thresholds after a deep learning-based coronary artery segmentation model pretrained on CCTA images. Comparisons were made between the standard Agatston CAC score and the CCTA-based Agatston CAC score (CCTA-CAC score) on a per-patient and per-vessel basis. Spearman's rank-order correlation coefficient (R) and intra-class correlation (ICC) values were used to calculate the correlation between the two methods. Results: After comparison, the optimal lower threshold in CCTA-CAC score calculations was found to be 650 Hounsfield units (HU). Using this threshold on a per-patient basis, the automatically computed CCTA-CAC score showed a high correlation (R =0.959; P<0.01) and ICC (R =0.8219; P<0.01) with the standard Agatston CAC score. On a per-vessel basis, the standard Agatston CAC score was also highly correlated with the CCTA-CAC score (R =0.889; P<0.01 and ICC =0.717; P<0.01). Of the 62 patients enrolled, 47 (76%) were classified into the same cardiovascular risk category using the CCTA-CAC score quantification method as when the standard Agatston CAC score was used. Agreement within the CAC categories was also good (kappa =0.7560). Conclusions: Fully automated quantification of the Agatston CAC score on CCTA images is feasible and shows a high correlation with the reference standard. This method could simplify the quantification procedure and has the potential to reduce the radiation dose and save time by eliminating the non-contrast cardiac CT stage.