The impact of COVID-19 infections on pregnancy outcomes in women.

BACKGROUND: Given that viral infections can increase the risk of adverse pregnancy outcomes, such as spontaneous miscarriage, preterm premature rupture of membranes, and preterm birth, the effects of COVID-19, a novel emerging coronavirus disease rapidly spreading globally, on pregnancy outcomes have garnered significant attention. METHODS: We conducted a review of studies related to pregnant women infected with SARS-CoV-2 over the past five years (December 2019 to April 2023), utilizing search engines such as PubMed, Web of Science, and the China National Knowledge Infrastructure (CNKI). This study was registered with PROSPERO with ID: CRD42024540849. RESULTS: A total of 218 articles were screened, with 15 studies meeting the inclusion criteria for this research, including 12 cohort studies, one cross-sectional study, one case-control study, and one case series. Six studies found that the preterm birth rate was higher in the infected group compared to the control group; five studies showed that the cesarean section rate was higher in the infected group; three studies found that the APGAR scores of newborns were higher in the control group than in the infected group; three studies indicated that the mortality rate of newborns in the infected group was higher than that in the control group. CONCLUSIONS: Our retrospective review suggests that compared to pregnant women not infected with SARS-CoV-2, those diagnosed with COVID-19 are more likely to experience adverse outcomes such as preterm birth, cesarean delivery, and low birth weight in newborns.

A Novel Estrone Degradation Gene Cluster and Catabolic Mechanism in Microbacterium oxydans ML-6.

Global-scale estrone (E1) contamination of soil and aquatic environments results from the widespread use of animal manure as fertilizer, threatening both human health and environmental security. A detailed understanding of the degradation of E1 by microorganisms and the associated catabolic mechanism remains a key challenge for the bioremediation of E1-contaminated soil. Here, Microbacterium oxydans ML-6, isolated from estrogen-contaminated soil, was shown to efficiently degrade E1. A complete catabolic pathway for E1 was proposed via liquid chromatography-tandem mass spectrometry (LC-MS/MS), genome sequencing, transcriptomic analysis, and quantitative reverse transcription-PCR (qRT-PCR). In particular, a novel gene cluster (moc) associated with E1 catabolism was predicted. The combination of heterologous expression, gene knockout, and complementation experiments demonstrated that the 3-hydroxybenzoate 4-monooxygenase (MocA; a single-component flavoprotein monooxygenase) encoded by the mocA gene was responsible for the initial hydroxylation of E1. Furthermore, to demonstrate the detoxification of E1 by strain ML-6, phytotoxicity tests were performed. Overall, our findings provide new insight into the molecular mechanism underlying the diversity of E1 catabolism in microorganisms and suggest that M. oxydans ML-6 and its enzymes have potential applications in E1 bioremediation to reduce or eliminate E1-related environmental pollution. IMPORTANCE Steroidal estrogens (SEs) are mainly produced by animals, while bacteria are major consumers of SEs in the biosphere. However, the understanding of the gene clusters that participate in E1 degradation is still limited, and the enzymes involved in the biodegradation of E1 have not been well characterized. The present study reports that M. oxydans ML-6 has effective SE degradation capacity, which facilitates the development of strain ML-6 as a broad-spectrum biocatalyst for the production of certain desired compounds. A novel gene cluster (moc) associated with E1 catabolism was predicted. The 3-hydroxybenzoate 4-monooxygenase (MocA; a single-component flavoprotein monooxygenase) identified in the moc cluster was found to be necessary and specific for the initial hydroxylation of E1 to generate 4-OHE1, providing new insight into the biological role of flavoprotein monooxygenase.

PRMT5 Prevents Dilated Cardiomyopathy via Suppression of Protein O-GlcNAcylation.

[Figure: see text].

Insight into the soil aggregate-mediated restoration mechanism of degraded black soil via biochar addition: Emphasizing the driving role of core microbial communities and nutrient cycling.

Soil microbial communities are responsive to biochar application. However, few studies have investigated the synergistic effects of biochar application in the restoration of degraded black soil, especially soil aggregate-mediated microbial community changes that improve soil quality. From the perspective of soil aggregates, this study explored the potential microbial driving mechanism of biochar (derived from soybean straw) addition in black soil restoration in Northeast China. The results showed that biochar significantly improved the soil organic carbon, cation exchange capacity and water content, which play crucial roles in aggregate stability. The addition of biochar also significantly increased the concentration of the bacterial community in mega-aggregates (ME; 0.25-2 mm) compared with micro-aggregates (MI; <0.25 mm). Microbial co-occurrence networks analysis showed that biochar enhanced microbial interactions in terms of the number of links and modularity, particularly in ME. 16 S rRNA sequencing predicted that the expression of genes related to carbon (rbcL, acsA, gltS, aclB, and mcrA) and nitrogen (nifH and amoA) transformation increased after the addition of biochar. Furthermore, the functional microbes involved in carbon fixation (Firmicutes and Bacteroidetes) and nitrification (Proteobacteria) were significantly enriched and are the key regulators of carbon and nitrogen kinetics. Structural equation model (SEM) analysis further showed that the application of biochar promoted soil aggregates to positively regulate the abundance of soil nutrient conversion-related microorganisms, thereby increasing soil nutrient content and enzyme activities. These results provide new insights into the mechanisms of soil restoration through biochar addition.

Surface integrity of laser-assisted turning of the GH4169 alloy.

The unique properties of GH4169, such as low thermal conductivity, high strength at high temperatures, and work hardening characteristics, make it difficult to machine. As an effective way to improve the machinability of materials, laser-assisted machining (LAM) has the advantages of reducing the cutting force, restraining chatter, improving productivity, and prolonging tool life. This study investigates the surface integrity of GH4169 in LAM, including the surface roughness, surface defects, microhardness, residual stress, and white-layer formation. First, the depth of the heat-affected layer from 380 to 760 r/min was determined to ascertain the depth of cutting. Secondly, at different cutting parameters, the surface roughness was found to be significantly reduced. LAM leads to a more severe plastic deformation, producing a thicker hardened layer and higher surface hardness on the fabricated substrate, but its internal hardness is less than that of samples made by conventional machining (CM), owing to thermal softening. Both machining methods produce residual tensile stresses, which are larger in LAM. Thirdly, the results of a surface integrity experiment show that white-layer generation is a consequence of the combination of phase change, heat, and plastic deformation. Finally, a comprehensive fuzzy evaluation considering the surface roughness, surface defects, microhardness, residual stress, and thickness of the white layer is established, which verifies that LAM significantly improves the surface integrity of GH4169, setting up a theoretical foundation and technical reference for the laser-assisted turning of nickel-based superalloys.

Structure-based screening and biological validation of the anti-thrombotic drug-dicoumarol as a novel and potent PPARγ-modulating ligand.

PPARγ full agonists, thiazolidinediones (TZDs), have been known as a class of most effective drugs for the treatment of type 2 diabetes mellitus (T2DM). However, recently their therapeutic benefits have been compromised by several undesirable side effects. In this study, a host-based repurposing strategy and in combination with comprehensive biological evaluations were synergistically employed to seek for potent PPARγ ligands, which led to the identification of an anti-thrombotic drug, dicoumarol (Dic), as the novel and safer selectively PPARγ modulator (SPPARγM) with advantages over current TZD drugs. The results in vitro showed that Dic had a potent binding affinity and weakly agonistic activity for PPARγ and its downstream key genes. Moreover, in diabetic model, it significantly reduced blood glucose without leading to the weight gain of both body and main organ tissues. Further mechanistic investigations revealed that Dic possessed such desired pharmacological properties mainly through effectively inhibiting the phosphorylation of PPARγ-Ser273 and selectively regulating the expressions of insulin-sensitive and resistance genes. Finally, the docking studies on the analysis of the potent binding mode of Dic with PPARγ revealed a remarkable difference on interaction region compared with other developed PPARγ agonists, which not only gave a proof of concept for the abovementioned mechanism but also provided the molecular basis for the discrimination of Dic from other PPARγ ligands, especially TZD drugs. Taken together, our findings suggested that Dic could serve as a new and promising candidate with good therapeutic index for treating T2DM, especially for those T2DM patients with thrombosis.

A Deep-Learning-Based Collaborative Edge-Cloud Telemedicine System for Retinopathy of Prematurity.

Retinopathy of prematurity is an ophthalmic disease with a very high blindness rate. With its increasing incidence year by year, its timely diagnosis and treatment are of great significance. Due to the lack of timely and effective fundus screening for premature infants in remote areas, leading to an aggravation of the disease and even blindness, in this paper, a deep learning-based collaborative edge-cloud telemedicine system is proposed to mitigate this issue. In the proposed system, deep learning algorithms are mainly used for classification of processed images. Our algorithm is based on ResNet101 and uses undersampling and resampling to improve the data imbalance problem in the field of medical image processing. Artificial intelligence algorithms are combined with a collaborative edge-cloud architecture to implement a comprehensive telemedicine system to realize timely screening and diagnosis of retinopathy of prematurity in remote areas with shortages or a complete lack of expert medical staff. Finally, the algorithm is successfully embedded in a mobile terminal device and deployed through the support of a core hospital of Guangdong Province. The results show that we achieved 75% ACC and 60% AUC. This research is of great significance for the development of telemedicine systems and aims to mitigate the lack of medical resources and their uneven distribution in rural areas.

TCM-Blast for traditional Chinese medicine genome alignment with integrated resources.

The traditional Chinese medicine (TCM) genome project aims to reveal the genetic information and regulatory network of herbal medicines, and to clarify their molecular mechanisms in the prevention and treatment of human diseases. Moreover, the TCM genome could provide the basis for the discovery of the functional genes of active ingredients in TCM, and for the breeding and improvement of TCM. The traditional Chinese Medicine Basic Local Alignment Search Tool (TCM-Blast) is a web interface for TCM protein and DNA sequence similarity searches. It contains approximately 40G of genome data on TCMs, including protein and DNA sequence for 36 TCMs with high medical value.The development of a publicly accessible TCM genome alignment database hosted on the TCM-Blast website ( http://viroblast.pungentdb.org.cn/TCM-Blast/viroblast.php ) has expanded to query multiple sequence databases to obtain TCM genome data, and provide user-friendly output for easy analysis and browsing of BLAST results. The genome sequencing of TCMs helps to elucidate the biosynthetic pathways of important secondary metabolites and provides an essential resource for gene discovery studies and molecular breeding. The TCMs genome provides a valuable resource for the investigation of novel bioactive compounds and drugs from these TCMs under the guidance of TCM clinical practice. Our database could be expanded to other TCMs after the determination of their genome data.

Identification of the anti-fungal drug fenticonazole nitrate as a novel PPARγ-modulating ligand with good therapeutic index: Structure-based screening and biological validation.

In this study, SB-VHTS of the old drug library was conducted to seek for novel PPARγ ligand. In the end, an antifungal drug, FN, was identified in vitro and in vivo as a new and potent PPARγ-modulating ligand to demonstrate significantly anti-diabetic and anti-NAFLD efficacies with minimized side effects induced by PPARγ full agonists TZDs drugs. Further mechanistic investigations revealed that FN showed such desired pharmacological properties mainly through selectively activating the expressions of Adiponectin and GLUT4, effectively promoting the Akt Ser473 phosphorylation, inhibiting the expressions of proinflammatory genes including TNF-α, IL-1ß and IL-6 and blocking the PPARγ Ser273 phosphorylation mediated by CDK5 without leading to adipogenesis and increasing the expressions of key adipogenic genes CD36, AP2, LPL, C/EBPα, FASN and PPARγ. Subsequently, a molecular docking study revealed an interesting binding mode between FN and PPARγ LBD including the hydrogen-bonding network among oxygen atom, sulfur atom and nitrogen atom in FN respectively with the PPARγ residues Cys285, Tyr327 and Ser342, which gave proof of concept for the above anti-diabetic action mechanism. Taken together, our findings not only suggest that FN can serve as the new, safe and highly efficacious anti-diabetic and anti-NAFLD agents for clinical use, they can also provide a molecular basis for the future development of PPARγ modulators with a high therapeutic index and the possibility to explore new uses of old drugs for immediate drug discovery.

Puerarin ameliorated pressure overload-induced cardiac hypertrophy in ovariectomized rats through activation of the PPARα/PGC-1 pathway.

Estrogen deficiency induces cardiac dysfunction and increases the risk of cardiovascular disease in postmenopausal women and in those who underwent bilateral oophorectomy. Previous evidence suggests that puerarin, a phytoestrogen, exerts beneficial effects on cardiac function in patients with cardiac hypertrophy. In this study, we investigated whether puerarin could prevent cardiac hypertrophy and remodeling in ovariectomized, aortic-banded rats. Female SD rats subjected to bilateral ovariectomy (OVX) plus abdominal aortic constriction (AAC). The rats were treated with puerarin (50 mg·kg-1 ·d-1, ip) for 8 weeks. Then echocardiography was assessed, and the rats were sacrificed, their heart tissues were extracted and allocated for further experiments. We showed that puerarin administration significantly attenuated cardiac hypertrophy and remodeling in AAC-treated OVX rats, which could be attributed to activation of PPARα/PPARγ coactivator-1 (PGC-1) pathway. Puerarin administration significantly increased the expression of estrogen-related receptor α, nuclear respiratory factor 1, and mitochondrial transcription factor A in hearts. Moreover, puerarin administration regulated the expression of metabolic genes in AAC-treated OVX rats. Hypertrophic changes could be induced in neonatal rat cardiomyocytes (NRCM) in vitro by treatment with angiotensin II (Ang II, 1 µM), which was attenuated by co-treatemnt with puerarin (100 µM). We further showed that puerarin decreased Ang II-induced accumulation of non-esterified fatty acids (NEFAs) and deletion of ATP, attenuated the Ang II-induced dissipation of the mitochondrial membrane potential, and improved the mitochondrial dysfunction in NRCM. Furthermore, addition of PPARα antagonist GW6471 (10 µM) partially abolished the anti-hypertrophic effects and metabolic effects of puerarin in NRCM. In conclusion, puerarin prevents cardiac hypertrophy in AAC-treated OVX rats through activation of PPARα/PGC-1 pathway and regulation of energy metabolism remodeling. This may provide a new approach to prevent the development of heart failure in postmenopausal women.

Urolithin B, a gut microbiota metabolite, protects against myocardial ischemia/reperfusion injury via p62/Keap1/Nrf2 signaling pathway.

Ischemia/reperfusion (IR) induces additional damage during the restoration of blood flow to ischemic myocardium. Urolithin B (UB) is one of the gut metabolites of ellagitannins, a class of antioxidant polyphenols, which was found to be protective against oxidative stress in multiple organs. However, the role of UB in cardiovascular disease remains elusive. Adult Sprague Dawley rats were subjected to left anterior descending artery ligation for 30 min followed by 120 min of reperfusion, with or without UB treatment. In vitro, the H9c2 cardiomyocytes were subjected to hypoxia (94 %N2/5 %CO2/1 %O2) for 3 h, followed by reoxygenation (74 %N2/5 %CO2/21 %O2) for 3 h (HR). UB was found to decrease myocardial infarct size and attenuate the cardiac dysfunction in the rats after IR, and protect against HR injury in H9c2 cardiomyocytes. Mechanistically, UB inhibited autophagy by activating Akt/mTOR/ULK1 pathway and protected against oxidative stress and caspase 3-dependent cell apoptosis. In particular, UB induced accumulation of p62 and its interaction with Keap1, which promoted Nrf2 nuclear translocation during HR insult. Of note, the protection of UB against superoxide production and apoptotic cell death was compromised with Nrf2 gene silencing. Taken together, our findings suggested that UB protected against myocardial IR injury at least partially via the p62/Keap1/Nrf2 signaling pathway, which highlights the potential of UB as a novel therapy for ischemic heart disease.

Vancomycin-induced reversible pancytopenia and rash in a 16-month-old boy with osteomyelitis: A case report
.

OBJECTIVE: Vancomycin is a commonly used glycopeptide antibiotic due to its effectiveness in treating serious Gram-positive bacterial infections, especially methicillin-resistant Staphylococcus aureus (MRSA) infection. Pancytopenia is a rare, yet serious, complication of vancomycin. Previous isolated cases have been reported in adults but none in children. CASE REPORT: A 16-month-old boy received vancomycin for treatment of osteomyelitis caused by MRSA. During his administration of vancomycin, reversible pancytopenia, pulmonary infection, and skin rash developed, which resolved after withdrawal. CONCLUSION: This is the first known case of vancomycin causing reversible pancytopenia and skin rash in a child, suggesting that pancytopenia caused by vancomycin could complicate treatment of children, and the hypothesis that pancytopenia is an immune-mediated reaction seems to be preferable. According to drug hypersensitivity syndrome (DHS) risk assessment in 10-D assessment system, this case was at grade of no risk.

A New Long-Term Downward Surface Solar Radiation Dataset over China from 1958 to 2015.

Downward surface solar radiation (Rs) plays a dominant role in determining the climate and environment on the Earth. However, the densely distributed ground observations of Rs are usually insufficient to meet the increasing demand of the climate diagnosis and analysis well, so it is essential to build a long-term accurate Rs dataset. The extremely randomized trees (ERT) algorithm was used to generate Rs using routine meteorological observations (2000-2015) from the Climate Data Center of the Chinese Meteorological Administration (CDC/CMA). The estimated Rs values were validated against ground measurements at the national scale with an overall correlation coefficient value of 0.97, a mean bias of 0.04 Wm-2, a root-mean-square-error value of 23.12 Wm-2, and a mean relative error of 9.81%. It indicates that the estimated Rs from the ERT-based model is reasonably accurate. Moreover, the ERT-based model was used to generate a new daily Rs dataset at 756 CDC/CMA stations from 1958 to 2015. The long-term variation trends of Rs at 454 stations covering 46 consecutive years (1970-2015) were also analyzed. The Rs in China showed a significant decline trend (-1.1 Wm-2 per decade) during 1970-2015. A decreasing trend (-2.8 Wm-2 per decade) in Rs during 1970-1992 was observed, followed by a recovery trend (0.23 Wm-2 per decade) during 1992-2015. The recovery trends at individual stations were found at 233 out of 454 stations during 1970-2015, which were mainly located in southern and northern China. The new Rs dataset would substantially provide basic data for the related studies in agriculture, ecology, and meteorology.

Epigenetic regulation of miR396 expression by SWR1-C and the effect of miR396 on leaf growth and developmental phase transition in Arabidopsis.

In this study, we investigated the regulatory function of miR396 in the phase transition in Arabidopsis thaliana. Using AtMIR396a/b knockout mutants generated through clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9)-directed genome editing, we showed that miR396 negatively regulates the leaf size and vegetative phase transition, and the first leaf with abaxial trichomes appeared earlier in the mir396ab double mutant than in the wild type (WT) and was significantly delayed in miR396 overexpression lines. Moreover, mir396ab exhibited early flowering, whereas 35S:MIR396a/b and cib4-1 delayed flowering, and the flowering time was negatively correlated with FT gene expression. Furthermore, in arp6 and pie1 mutants, which are deficient in the ATP-dependent chromatin remodeling complex (SWR1-C), miR396 expression was significantly repressed. Compared with the WT, reduced H2A.Z deposit and stronger relative nucleosome occupancy in the promoter region of MIR396a was found in the arp6 mutant, indicating that SWR1-C contributes to the transcriptional activation of MIR396a via nucleosome dynamics. In addition, miR396 displayed specific spatio-temporal expression patterns in the leaf, which was altered in arp6 and pie1, and therefore affected the transcript levels of CIB4 and FT in these mutants. We propose that miR396 is not only a marker of cell differentiation, but also an age signal for leaf development and phase change. Meanwhile, SWR1-C-mediated epigenetic regulation contributes to the age-dependent enhancement of miR396 expression and differential miR396 accumulation among leaves.

Dynamic changes in insulin and glucagon during disease progression in rhesus monkeys with obesity-related type 2 diabetes mellitus.

AIMS: To investigate the progression of obesity-related type 2 diabetes mellitus (T2DM) in rhesus monkeys, especially dynamic changes in insulin and glucagon. MATERIALS AND METHODS: We followed a cohort of 52 rhesus monkeys for 7 years throughout the progression of obesity-related T2DM. Intravenous glucose tolerance tests were performed every 6 months to evaluate dynamic changes in glucose, insulin and glucagon levels. RESULTS: Obesity in rhesus monkeys increased the overall mortality and T2DM morbidity. During the progression of T2DM, glucagon remained consistently elevated, while insulin initially increased in compensation but then dropped to below normal levels when the monkeys developed overt T2DM. After a glucose challenge, both the first and second phases of insulin secretion increased during the early stage of T2DM; in later stages the first phase was delayed and the second phase was diminished. CONCLUSION: Our findings showed that, beside the decreased insulin level, hyperglucagonaemia also plays an important role in the development of T2DM.

Carnosol as a Nrf2 Activator Improves Endothelial Barrier Function Through Antioxidative Mechanisms.

Oxidative stress is the main pathogenesis of diabetic microangiopathy, which can cause microvascular endothelial cell damage and destroy vascular barrier. In this study, it is found that carnosol protects human microvascular endothelial cells (HMVEC) through antioxidative mechanisms. First, we measured the antioxidant activity of carnosol. We showed that carnosol pretreatment suppressed tert-butyl hydroperoxide (t-BHP)-induced cell viability, affected the production of lactate dehydrogenase (LDH) as well as reactive oxygen species (ROS), and increased the produce of nitric oxide (NO). Additionally, carnosol promotes the protein expression of vascular endothelial cadherin (VE-cadherin) to keep the integrity of intercellular junctions, which indicated that it protected microvascular barrier in oxidative stress. Meanwhile, we investigated that carnosol can interrupt Nrf2-Keap1 protein-protein interaction and stimulated antioxidant-responsive element (ARE)-driven luciferase activity in vitro. Mechanistically, we showed that carnosol promotes the expression of heme oxygenase 1(HO-1) and nuclear factor-erythroid 2 related factor 2(Nrf2). It can also promote the expression of endothelial nitric oxide synthase (eNOS). Collectively, our data support the notion that carnosol is a protective agent in HMVECs and has the potential for therapeutic use in the treatments of microvascular endothelial cell injury.

[Nature-effect relationship research of cold and warm medicinal properties of traditional Chinese medicine for promoting blood circulation and removing blood stasis based on nature combination].

Traditional Chinese medicine for promoting blood circulation and removing blood stasis is a kind of drug with cold or warm medicinal properties which is commonly used in clinical practice. It is an excellent carrier for studying the nature-effect relationship of traditional Chinese medicine. Therefore,this study will acquire the main active components and targets based on the drug-based research method. The Cytoscape 3. 5. 1 platform was used to construct the protein interaction network,and the Bin GO plug-in was used to perform functional annotation and statistical analysis on the identified functional modules. The results showed that the bitter-liver protein interaction network mainly participates in cell cycle process,lipid catabolic process,blood circulation to exert the effect of promoting blood circulation and removing blood stasis; the cold protein interaction network mainly participates in vasoconstriction through targets such as EDNRA,regulates blood coagulation through targets such as PLAU,and thus exerts the effect of cooling blood and eliminating phlegm; warm protein interaction network mainly participates in the regulation of platelet activation through targets such as P2 RY12,thereby exerting the effect of promoting blood circulation,relieving pain and relieving pain. This study explains the common characteristics of the bitter-liver combination and the specific characteristics of cold or warm medicinal properties from the molecular network level,which provides a new idea for the intrinsic relationship between the medicinal properties and efficacy of traditional Chinese medicine.

[Nature-effect relationship research of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos based on nature combination].

Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos are commonly traditional Chinese medicines with invigorating blood circulation and eliminating blood stasis,but they are different in effects due to differences in five tastes and four properties. In this study,Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos are selected as research vectors to obtain the active ingredients and targets through TCMD,TCMSP database and Ch EMBL database. The protein interaction information of the target is used to obtain from STRING online database,then imported into Cytoscape software to plot the protein interaction network and perform GO enrichment analysis.The results show that the heart-liver protein interaction network,involving blood circulation and hepatic lipid metabolism,thereby exerting the effect of activating blood circulation. The cold-bitter protein interaction network involves the biological process of vasoconstriction,thereby exerting cooling blood and the efficacy of eliminating phlegm. The warm-pungent protein interaction network involves blood coagulation,lipid metabolism and other biological processes to play the role of phlegm pain. Through analysis,it is found that the relationship between pharmacological efficacy and medicinal properties has a certain degree of specificity,which facilitates the subsequent scientific and systematic study of medicinal properties on the basis of this study.

[Nature-effect relationship research between pungent and bitter taste of traditional Chinese medicine for promoting blood circulation and removing blood stasis based on nature combination].

The herbs for promoting blood circulation and removing blood stasis were used commonly in clinical,and most of them are pungent and bitter. In order to study the nature-effect interrelationship of the herbs for promoting blood circulation and removing blood stasis,the TCMSP platform and Cytoscape 3. 5. 1 platform were used to construct warm-pungent-liver and warm-bitter-liver of the complement and intersection protein interaction network and the target-disease network and the network module was analyzed. As a result,warm-liver target-disease network is associated with diseases such as cancer,hypertension,and depression,which exerts the efficacy of warming Yang and transforming Qi,promoting Qi and activating blood,removing blood stasis and dispersing phlegm. The bitter taste target-disease network is associated with diseases such as myocardial infarction,cancer,inflammation and other diseases,which exerts the efficacy of dissipating the stasis. The pungent taste target-disease network is associated with diseases such as cancer,cardiovascular disease,osteoporosis and other diseases,which exerts the efficacy of invigorating the circulation of blood and eliminating stagnation. The research shows that the medicinal combination of warm-pungent-liver and warm-bitter-liver has the efficacy of promoting blood circulation and removing blood stasis by regulating different targets in different disease processes.

[Nature-effect relationship research of Curcumae Longae Rhizoma,Curcumae Radix,and Curcumae Rhizoma based on nature combination].

Curcumae Longae Rhizoma,Curcumae Radix and Curcumae Rhizoma are different medicinal parts of the same plant.Nevertheless,they are different in medicinal effects due to the different Chinese herbal nature. In this study,traditional Chinese medicines database( TCMD2009),traditional Chinese medicine system( TCMSP),and Ch EMBL database were retrieved to screen the active components and targets,and construct the target PPI network. By a graph theoretic clustering algorithm identifying protein complex algorithm( IPCA),the protein modules were identified and analyzed by gene ontology( GO) enrichment. A comparative study of Curcumae Longae Rhizoma and Curcumae Radix illustrate that Curcumae Longae Rhizoma regulates blood coagulation through P2 RY12,GNG2 and other genes to exert the analgesic effect. Curcumae Radix regulates lipid metabolism,plasma lipoprotein particle levels,platelet activation,response to oxidative stress,apoptotic process through LDLR,APOB,PRKCA,SOD1,TP53 and other genes to perform a function in clearing the heart and cooling the blood. A comparative study of Curcumae Radix and Curcumae Rhizoma demonstrate that Curcumae Rhizoma on regulates the nervous system by GRIA2,GRIA4 and other genes to exert blood-breaking effect; Curcumae Radix regulates lipid metabolism,plasma lipoprotein particle levels,platelet activation,response to oxidative stress,apoptotic process by genes such as CALM1,LPL,APOB,SOD1 and TP53 to play the role of clearing heart and cooling blood. Cluster analysis of the protein interaction network of the nature combination is helpful to explain the intrinsic link between the nature combination and efficacy.