Defects in phospholipase C zeta cause polyspermy and low fertilization after conventional IVF: not just ICSI failure.

ABSTRACT: Phospholipase C zeta (PLCζ) is a key sperm-borne oocyte-activating factor that triggers Ca2+ oscillations and the subsequent block to polyspermy following gamete fusion. Mutations in PLCZ1, the gene encoding PLCζ, cause male infertility and intracytoplasmic sperm injection (ICSI) fertilization failure; and PLCζ expression and localization patterns are significantly correlated with ICSI fertilization rate (FR). However, in conventional in vitro fertilization (cIVF), whether and how sperm PLCζ affects fertilization remain unclear. Herein, we identified one previously reported and two novel PLCZ1 mutations associated with polyspermy in vitro that are characterized by excessive sperm-zona binding and a delay in pronuclei (PN) formation. Immunofluorescence staining and oocyte activation testing revealed that virtually all spermatozoa from patients lacked functional PLCζ and were thus unable to evoke Ca2+ oscillations. ICSI with an artificial oocyte activation treatment successfully rescued the polyspermic phenotype and resulted in a live birth. Furthermore, we analyzed PLCζ in an additional 58 males after cIVF treatment in the Reproductive and Genetic Hospital of CITIC-Xiangya (Changsha, China) between February 2019 and January 2022. We found that the proportion of spermatozoa that expressed PLCζ was positively correlated with both 2PN rate and total FR. The optimal cutoff value below which males were likely to experience low FR (total FR ≤30%) after cIVF was 56.7% for the proportion of spermatozoa expressing PLCζ. Our study expands the mutation and the phenotypic spectrum of PLCZ1 and further suggests that PLCζ constitutes a promising biomarker for identifying low FRs cases in cIVF due to sperm-related oocyte activation deficiency and that sperm PLCζ analysis may benefit the wider male population and not only men with ICSI failure.

Emerging role of autophagy in colorectal cancer: Progress and prospects for clinical intervention.

Autophagy is a physiological mechanism in which cells degrade themselves and quickly recover the degraded cell components. Recent studies have shown that autophagy plays an important role in the occurrence, development, treatment, and prognosis of colorectal cancer. In the early stages of colorectal cancer, autophagy can inhibit the production and development of tumors through multiple mechanisms such as maintaining DNA stability, inducing tumor death, and enhancing immune surveillance. However, as colorectal cancer progresses, autophagy may mediate tumor resistance, enhance tumor metabolism, and other pathways to promote tumor development. Therefore, intervening in autophagy at the appropriate time has broad clinical application prospects. This article summarizes the recent research progress of autophagy and colorectal cancer and is expected to provide new theoretical basis and reference for clinical treatment of colorectal cancer.

Identity-Aware and Shape-Aware Propagation of Face Editing in Videos.

The development of deep generative models has inspired various facial image editing methods, but many of them are difficult to be directly applied to video editing due to various challenges ranging from imposing 3D constraints, preserving identity consistency, ensuring temporal coherence, etc. To address these challenges, we propose a new framework operating on the StyleGAN2 latent space for identity-aware and shape-aware edit propagation on face videos. In order to reduce the difficulties of maintaining the identity, keeping the original 3D motion, and avoiding shape distortions, we disentangle the StyleGAN2 latent vectors of human face video frames to decouple the appearance, shape, expression, and motion from identity. An edit encoding module is used to map a sequence of image frames to continuous latent codes with 3D parametric control and is trained in a self-supervised manner with identity loss and triple shape losses. Our model supports propagation of edits in various forms: I. direct appearance editing on a specific keyframe, II. implicit editing of face shape via a given reference image, and III. existing latent-based semantic edits. Experiments show that our method works well for various forms of videos in the wild and outperforms an animation-based approach and the recent deep generative techniques.

[Role of NLRP3 inflammasome in diabetic neuropathy and prevention and treatment with traditional Chinese medicine].

As one of the most frequent complications of diabetes, diabetic neuropathy often involves peripheral and central nervous systems. Neuroinflammation is the key pathogenic factor of secondary nerve injury in diabetes. NOD-like receptor pyrin domain-containing 3(NLRP3) inflammasome is a group of subcellular multiprotein complexes, including NLRP3, apoptosis associated speck-like protein(ASC), and pro-cysteinyl aspartate specific proteinase 1(pro-caspase-1). NLRP3 inflammasome is an inducer of innate immune responses. Its activation stimulates the inflammatory cascade reaction, promotes the release of inflammatory mediators, triggers cell death and uncontrolled autophagy, activates glial cells, facilitates peripheral immune cell infiltration, and initiates amyoid ß(Aß)-tau cascade reactions. As a result, it contributes to the central nerve, somatic nerve, autonomic nerve, and retinal nerve cell damage secondary to diabetes. Therefore, due to its key role in the neuroinflammation responses of the body, NLRP3 inflammasome may provide new targets for the treatment of diabetic neuropathy. With multi-target and low-toxicity advantages, traditional Chinese medicine plays a vital role in the treatment of diabetic neuropathy. Accumulating evidence has shown that traditional Chinese medicine exerts curative effects on diabetic neuropathy possibly through regulating NLRP3 inflammasome. Although the role of NLRP3 inflammasome in diabetes and related complications has been investigated in the literature, systematical studies on drugs and mechanism analysis for secondary neuropathy are still lacking. In this article, the role of NLRP3 inflammasome in diabetic neuropathy was explored, and the research progress on traditional Chinese medicine in the treatment of diabetic neuropathy through NLRP3 inflammasome was reviewed.

Apigenin ameliorates non-eosinophilic inflammation, dysregulated immune homeostasis and mitochondria-mediated airway epithelial cell apoptosis in chronic obese asthma via the ROS-ASK1-MAPK pathway.

BACKGROUND: Obese asthma is one of the important asthma phenotypes that have received wide attention in recent years. Excessive oxidative stress and different inflammatory endotypes may be important reasons for the complex symptoms, frequent aggravation, and resistance to traditional treatments of obese asthma. Apigenin (API), is a flavonoid natural small molecule compound with good anti-inflammatory and antioxidant activity in various diseases and proved to have the potential efficacy to combat obese asthma. METHODS: In vivo, this study fed C57BL/6 J mice with high-fat diets(HFD)for 12 weeks and then stimulated them with OVA for 6 weeks to establish a model of chronic obese asthma, while different doses of oral API or dexamethasone were used for therapeutic interventions. In vitro, this study used HDM to stimulate human bronchial cells (HBEs) to establish the model and intervened with API or Selonsertib (SEL). RESULTS: This study clarified that OVAinduced a type of mixed granulocytic asthma with elevated neutrophils and eosinophils in obese male mice fed with long-term HFD, which also exhibited mixed TH17/TH1/TH2 inflammation. Apigenin effectively suppressed this complex inflammation and acted as a regulator of immune homeostasis. Meanwhile, apigenin reduced AHR, inflammatory cell infiltration, airway epithelial cell apoptosis, airway collagen deposition, and lung oxidative stress via the ROS-ASK1-MAPK pathway in an obese asthma mouse model. In vitro, this study found that apigenin altered the binding status of TRAF6 to ASK1, inhibited ASK1 phosphorylation, and protected against ubiquitin-dependent degradation of ASK1, suggesting that ROS-activated ASK1 may be an important target for apigenin to exert anti-inflammatory and anti-apoptotic effects. To further verify the intervention mechanism, this study clarified that apigenin improved cell viability and mitochondrial function and inhibited apoptosis by interfering with the ROS-ASK1-MAPK pathway. CONCLUSIONS: This study demonstrates for the first time the therapeutic effect of apigenin in chronic obese asthma and further clarifies its potential therapeutic targets. In addition, this study clarifies the specificity of chronic obese asthma and provides new options for its treatment.

The gut microbiota-astrocyte axis: Implications for type 2 diabetic cognitive dysfunction.

BACKGROUND: Diabetic cognitive dysfunction (DCD) is one of the most insidious complications of type 2 diabetes mellitus, which can seriously affect the ability to self-monitoring of blood glucose and the quality of life in the elderly. Previous pathological studies of cognitive dysfunction have focused on neuronal dysfunction, characterized by extracellular beta-amyloid deposition and intracellular tau hyperphosphorylation. In recent years, astrocytes have been recognized as a potential therapeutic target for cognitive dysfunction and important participants in the central control of metabolism. The disorder of gut microbiota and their metabolites have been linked to a series of metabolic diseases such as diabetes mellitus. The imbalance of intestinal flora has the effect of promoting the occurrence and deterioration of several diabetes-related complications. Gut microbes and their metabolites can drive astrocyte activation. AIMS: We reviewed the pathological progress of DCD related to the "gut microbiota-astrocyte" axis in terms of peripheral and central inflammation, intestinal and blood-brain barrier (BBB) dysfunction, systemic and brain energy metabolism disorders to deepen the pathological research progress of DCD and explore the potential therapeutic targets. CONCLUSION: "Gut microbiota-astrocyte" axis, unique bidirectional crosstalk in the brain-gut axis, mediates the intermediate pathological process of neurocognitive dysfunction secondary to metabolic disorders in diabetes mellitus.

Human Motion Transfer With 3D Constraints and Detail Enhancement.

We propose a new method for realistic human motion transfer using a generative adversarial network (GAN), which generates a motion video of a target character imitating actions of a source character, while maintaining high authenticity of the generated results. We tackle the problem by decoupling and recombining the posture information and appearance information of both the source and target characters. The innovation of our approach lies in the use of the projection of a reconstructed 3D human model as the condition of GAN to better maintain the structural integrity of transfer results in different poses. We further introduce a detail enhancement net to enhance the details of transfer results by exploiting the details in real source frames. Extensive experiments show that our approach yields better results both qualitatively and quantitatively than the state-of-the-art methods.

Evaluation of the radiation shielding effect of the novel self-shielding radiotherapy system Zap-X / 中国辐射卫生

Objective Based on the measurement of the ambient dose equivalent rate of points around the novel self-shielding Zap-X radiotherapy system, its self-shielding effect was evaluated and analyzed, and suggestions were proposed for the revision and improvement of related standards in China. Methods The ambient dose equivalent rates were measured at 15 points around the Zap-X system under 6 system operating conditions. The radiation shielding effect of the Zap-X system was evaluated according to the domestic and international radiation protection standards of radiotherapy equipment. Results Measurement of ambient dose equivalent rate and dose evaluation showed that the shielding effect of the Zap-X system met the requirements of international standards, but the dose rates at some points failed to satisfy the reference control levels in the domestic standards. Conclusion Without the shielded treatment room, the self-shielding effect of the Zap-X radiotherapy system is insufficient to meet the requirements of domestic standards for radiation safety and protection. The system should be operated in the treatment room to meet domestic standards.

The effect of CT detector width and signal acquisition positions on image quality / 中华放射学杂志

Objective:To evaluate the influence of different detector widths and signal acquisition positions of wide-detector CT in different scanning modes on CT number and noise, and to provide a basis for reasonable selection of scanning modes and related parameters in clinical practice.Methods:The body dose phantom was scanned by GE Revolution CT. The scan was performed with detector widths of 40, 80 and 160 mm in sequential scanning mode and with detector width/pitch combinations of 40 mm/0.516, 40 mm/0.984, 80 mm/0.508 and 80 mm/0.992 in spiral scanning mode. The phantom was placed at the central and peripheral of the selected detector widths, and the adjacent positions between two axial scans. The images of the phantom were evaluated subjectively and the CT numbers and SDs were measured. The differences between the measured values at different imaging parameters were compared. The multi-group Friedman test was used to compare CT numbers and SD under different scanning parameters in sequential scanning mode, and the Wilcoxon test was used to compare CT numbers and SD in spiral scanning mode.Results:There was no statistically significant difference in the geometric shapes of the phantom images obtained at any combination of parameters. In sequential scanning mode, the differences at different detector widths were statistically significant (χ 2=14.00, P=0.001) with CT numbers at 40 mm and 160 mm greater than CT numbers at 80 mm ( P<0.05). The differences at different signal acquisition positions were statistically significant (χ 2=12.04, P=0.002) with CT numbers at peripheral and adjacent greater than CT numbers at central ( P<0.05). In spiral scanning mode CT numbers at detector width at 80 mm were greater than CT numbers at 40 mm ( Z=-2.10, P=0.036). For SD, the differences at different detector widths were statistically significant in sequential scanning modes (χ 2=8.17, P=0.017) with SD at 160 mm greater than SD at 80 mm ( P<0.05). The differences at different signal acquisition positions were statistically significant (χ 2=13.50, P=0.001) with SD at peripheral greater than SD at central ( P<0.05). In spiral scanning mode SDs at pitches 0.984 and 0.992 were greater than SDs at 0.516 and 0.508 ( Z=-2.66, P=0.008). There were no significant differences among other groups. Conclusion:The selection of scanning mode, detector width and signal acquisition position of wide-detector CT will affect the image CT numbers and SDs.

Unusual Rapid Growth of Primary Splenic Diffuse Large B-Cell Lymphoma with Extensive Necrosis.

The primary splenic lymphoma is extremely uncommon with an incidence rate of <1% of all the lymphomas under the strict criteria for diagnosis expounded by Das Gupta et al. Clinical presentations of nonspecific symptoms are weight loss, weakness, fever, and left upper quadrant pain or discomfort due to enlarged spleen. Abdominal ultrasound and CT are the most widely used imaging modality for the assessment of lymphoma. The imaged features of splenic lymphoma are nonspecific; typical lymphoma presents as a diffusely enlarged spleen. The abdominal CT scan in our case showed a large cystic splenic mass measuring 14 cm without enhancement after contrast medium. Lymphoma is often described as an aggressive tumor because its rapid doubling time can quickly increase the size of a tumor. In our case, the tumor grew to more than 100 times its original size in 4 months. So, we present this unusual rapid growth of primary splenic lymphoma.

The experimental study of the effect of detector combination on image resolution in wide-detector CT / 中华放射医学与防护杂志

Objective:To investigate the effect of different scanning modes, detector width and location in detector on high and low contrast resolution of wide-detector CT image.Methods:The Catphan600 phantom with high and low contrast resolution modules was scanned with GE Revolution CT at the same CTDI vol. The scans were performed with the detector widths of 40, 80 and 160 mm for sequential scanning mode and with the detector width/pitch combinations of 40 mm/0.516, 40 mm/0.984, 80 mm/0.508 and 80 mm/0.992 for spiral scanning mode. The resolution modules were placed at the adjacent region between two sequential scans, central and foot side edge in the longitudinal scanning range seperately. The subjective evaluation of the high and low contrast resolution was performed by two radiologists. Results:The high contrast resolution was 8 LP/cm at adjacent region between two sequential scans with the detector width of 80 mm or 160 mm in sequential scanning mode, and at the pitch of 0.5 in spiral scanning mode, while it was 7 LP/cm for the rest of detector combinations. The distinguishable diameter was 3 mm at 1% low contrast resolution at foot side edge with the detector widths of 80 mm or 160 mm in the sequential scanning mode, and it was 2 mm for all the other conditions. The distinguishable diameter was 2 mm at 1% low contrast resolution with the detector width of 40 mm and pitch 0.516 in the spiral scanning mode and it was worse with the wider detector and larger pitch.Conclusions:For the wide-detector CT, scanning mode, detector width, location in detector and pitches will affect the high and low contrast resolution to some degree. Appropriate selection should be done according to actual needs in clinical practice.

Study on discovery of efficacy markers for Dachaihu Decoction and its action mechanism / 中国中药杂志

Dachaihu Decoction is a classical Chinese herbal prescription that is effective in harmonizing lesser yang and purging internal accumulated heat. At present, it has been widely used in clinical practice, and the resulting outcomes are satisfactory. However, its quality indicators and action mechanism are still not clear. Therefore, this paper explored the efficacy markers of Dachaihu Decoction and its action mechanism based on literature mining, molecular biology, and network pharmacology, so as to better control its quality and ensure its clinical efficacy. The efficacy markers of Dachaihu Decoction were predicted and analyzed according to the "five principles" for Q-markers of Chinese herbs. Then the anti-inflammatory activity of the efficacy markers of Dachaihu Decoction was evaluated with Griess reagent after the establishment of RAW264.7 cell inflammation model in vitro with lipopolysaccharide(LPS). The potential targets of efficacy markers were predicted by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), ChEMBL, and SwissTargetPrediction, followed by the construction of the protein-protein interaction(PPI) network of the efficacy markers of Dachaihu Decoction. Topological, GO, and KEGG enrichment analysis was carried out to construct the "key target-signaling pathway-biological process" network, thus elucidating the action mechanism of the efficacy markers of Dachaihu Decoction. Saikosaponin B_2, baicalin, baicalein, wogonoside, neohesperidin, naringin, hesperidin, and paeoniflorin were considered as the potential efficacy markers of Dachaihu Decoction. The anti-inflammatory activity evaluation showed that the potential efficacy markers effectively inhibited the release of NO, exhibiting good anti-inflammatory activities. As demonstrated by network pharmacology, the efficacy markers of Dachaihu Decoction regulated the inflammatory response by acting on MAPK and NF-κB signaling pathways, the carbohydrate metabolism by HIF-1 and PI3 K-AKT signaling pathways, and the lipid metabolism by AMPK and PI3 K-AKT signaling pathways. This study discovered the efficacy markers of Dachaihu Decoction based on literature mining combined with molecular biological experiments and explored its action mechanism at the molecular level based on network pharmacology, which would provide reference for the quality control of Dachaihu Decoction and scientific basis for its clinical application.

Study on Q-markers of Da Chaihu decoction based on specific chromatogram and network pharmacology / 药学学报

Da Chaihu decoction is a classic prescription for the treatment of cholecystitis that is widely used in clinical practice, and has a definite curative effect. However, due to its diverse components and complex functions, the traditional indexes fail to capture its overall efficacy. Therefore, this study analyzed and predicted the quality markers (Q-markers) of Da Chaihu decoction based on specific chromatogram and network pharmacology to provide a reference for the comprehensive control of the quality. The study obtained 35 potential practical components of Da Chaihu decoction through virtual screening. The specific chromatogram of 15 batches of Da Chaihu decoction was established by HPLC-DAD with neohesperidin as a reference. Compared with the chromatographic peaks and the reference substance, the chemical components were assigned to predict the nine components of albiflorin, paeoniflorin, naringin, hesperidin, neohesperidin, baicalin, wogonoside, saikosaponin b2, saikosaponin b1 as Q-markers of Da Chaihu decoction. Finally, the network of the "components-key targets-signal pathways-biological processes" was constructed by network pharmacology to explore the mechanism of Da Chaihu decoction in treating cholecystitis to clarify the accuracy of Q-markers. The results indicated that potential Q-markers could act on multiple targets to regulate inflammatory and metabolism, and then combine to treat cholecystitis. Q-markers could combine with the pharmacologic action of Da Chaihu decoction, which could elucidate the overall efficacy of Da Chaihu decoction. This study explored the Q-markers of Da Chaihu decoction combined with the specific chromatogram and network pharmacology, which provided a basis for the quality control and evaluation of Da Chaihu decoction.

Mechanism of Didangtang Against Inflammatory Cascade Triggered by Foam Cell Pyroptosis in High-glucose Environment / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Didangtang （DDT） against the inflammatory cascade triggered by foam cell pyroptosis in high-glucose environment. MethodOxidized low density lipoprotein （ox-LDL， 100 mg·L-1） was used to induce pyroptosis of foam cells. The control group （5.5 mmol·L-1 glucose）， foam cell group （100 mg·L-1 ox-LDL）， high-glucose group （33.3 mmol·L-1 glucose）， DDT group （10% DDT-containing serum）， and NOD-like receptor family pyrin domain-containing 3 （NLRP3） inhibitor group （MCC950， 10 nmmol·L-1） were designed. The cell membrane damage was observed by lactate dehydrogenase （LDH） release assay. The expression of cysteinyl aspartate-specific proteinase-1 （Caspase-1） was detected by immunofluorescence method， and expression of key proteins NLRP3， Caspase-1， gastermin D （GSDMD）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18） in the pyroptosis pathway was determined by Western blot. The release of IL-18 and IL-1β， monocyte chemoattractant protein-1 （MCP-1）， and tumor necrosis factor α （TNF-α） in cell supernatant was measured by enzyme-linked immunosorbent assay （ELISA）. ResultThe expression of NLRP3， Caspase-1， and GSDMD was up-regulated （P<0.01） and the release of IL-1β， IL-18， MCP-1， IL-1α， and TNF-α was increased （P<0.01） in foam cell group compared with those in the control group. The expression of NLRP3， Caspase-1， and GSDMD was higher （P<0.01） and the release of inflammatory factors was more （P<0.01） in the high-glucose group than in the foam cell group. DDT and MCC950 can inhibit expression of NLRP3， Caspase-1， GSDMD and reduce the release of IL-1β， IL-18， MCP-1， IL-1α， and TNF-α. ConclusionDDT can suppress the pyroptosis of foam cells induced by NLRP3/Caspase-1 pathway in high-glucose environment and thereby alleviate the inflammatory cascade.

Identification of active components in Xuefu Zhuyu Decoction based on targets of blood-activating function / 中国中药杂志

As a classic prescription for promoting blood circulation to remove blood stasis, Xuefu Zhuyu Decoction(XFZYD) is widely used in clinical practice and has notable curative effect. Based on the key targets of activating blood circulation, this study identified the active components of XFZYD to reveal the material basis. The components of XFZYD were collected from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The molecular docking models were built for the blood-activating targets obtained from the previous study with the components of XFZYD. The top five active components with measurability for each target were selected as the potential blood-activating components in the prescription. The efficacy of the prescription can embody key pharmacological and high-content components. In this study, anti-platelet aggregation activity was used to characterize the effect of activating blood, and the in vivo experiments were conducted to verify the accuracy of the active components. A total of 210 chemical components of XFZYD were screened out from TCMSP and docked with the key targets with the function of activating blood. Ligustrazine, acteoside, naringin, etc. were selected as the potential active components for activating blood in XFZYD. The anti-platelet aggregation activity of the combination of Chuanxiong Rhizoma, Rehmanniae Radix, Aurantii Fructus, Glycyrrhizae Radix et Rhizoma, and Carthami Flos was 9.82%±5.11%. Compared with that in the control group, the platelet aggregation induced by adenosine diphosphate(ADP) was significantly inhibited in the test group(P<0.01), which verified the accuracy of the active components. This study can guide the research on the material basis of XFZYD and provide insights into the development and utilization of the classical prescription.

Potential therapeutic effect of Saussureae Involucratae Herba on breast cancer and its mechanism based on network pharmacology / 中国中药杂志

As one of the most commonly diagnosed cancers in the world, female breast cancer is induced by the high level of estrogen. Saussureae Involucratae Herba(SIH), a gynecological medicinal, regulates estrogen-induced diseases. However, the therapeutic effect of SIH on breast cancer has not been reported. Therefore, this study aims to explore the potential efficacy of SIH on breast cancer based on in vitro experiment and network pharmacology. The inhibitory effect of SIH water extract on proliferation and migration of breast cancer MDA-MB-231 cells was examined. The result demonstrated SIH water extract significantly suppressed the proliferation of breast cancer cells(IC_(50)=6.47 mg·mL~(-1)) and also restricted the migration. A total of 39 components of SIH were retrieved from traditional Chinese medicine database(TCMD) and 160 targets of SIH were screened by target fishing with the PharmaDB database. The Online Mendelian Inheritance in Man(OMIM) was used to establish a 1 001-targets data set of breast cancer. Based on the overlaps(45) of targets between SIH and breast cancer, a protein-protein interaction(PPI) network was built to analyze the interactions among these targets with STRING platform and Cytoscape. Finally, through topology and GO and KEGG analysis, 8 targets, 101 pathways and 85 biological processes were found to involve the treatment of breast cancer by SIH. SIH may exert the anti-breast cancer effect by regulating cell cycle, inhibiting proliferation, migration and adhesion of cancer cells, and modulating estrogen receptor. This study clarified the mechanism of SIH in treating breast cancer, which lays a foundation for the further development of SIH.

Analysis on targets of regulating Qi and activating blood based on activity spectrum of targets / 中国中药杂志

The traditional Chinese medicines(TCM) for activating blood circulation and the TCM for regulating Qi are often used in combination in clinical practice. However, their mechanisms are still unclear. The activity spectrum of targets can fuse the active components, targets and intensity of action, which provides support for the discussion of efficacy targets. The chemical components of common TCM sets for activating blood circulation and regulating Qi, as well as the negative sets not for activating blood circulation and re-gulating Qi were obtained from the database of TCM. By the similarity analysis of chemical components in TCM for activating blood circulation and DrugBank database, the predicted targets of chemical components in TCM for activating blood circulation were obtained, and the similarity value of the two was taken as the activity value of the active components and predicted targets. Then, the component-target activity value was weighted. The activity values of herb acting on the same target were fused to construct activity spectra of targets of the herbs for activating blood circulation, herbs for regulating Qi and negative herbs. The targets whose activity values of activating blood circulation and regulating Qi were higher than those of negative herbs were selected as potential targets of efficacy. Protein-protein interaction networks were constructed for topological, GO and KEGG enrichment analysis to determine the key targets of efficacy of activating blood circulation and regulating Qi. The component-target activity information collected from DrugBank database contained 4 499 compounds, 627 targets and 11 295 action relationships. The activating blood function protein-protein interaction network contained 206 nodes and 1 728 edges, while the regulating Qi function protein-protein interaction network contained 230 nodes and 986 edges. The enrichment analysis of topology, GO and KEGG showed that TCM for activating blood circulation mainly exerted its anti-inflammatory, neuroprotective and angiogenic effects on signaling cascade pathway mediated by VEGF/VEGFR2, ERK signaling pathway, calcium signaling pathway and PI3 K-AKT signaling pathway, and the key targets included mitogen activated protein kinases 3(MAPK3), proto-oncogene tyrosine-protein kinase Src(SRC), mitogen activated protein kinases 1(MAPK1), epidermal growth factor receptor(EGFR), phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform(PIK3 CA), peroxisome proliferators-activated receptor gamma(PPARG), nitric oxide synthase 3(NOS3), prostaglandin G/H synthetase 2(PTGS2), matrix metalloproteinase-9(MMP9), and vascular endothelial growth factor A(VEGFA). TCM for regulating Qi mainly exerted anti-inflammatory and neuroprotective effects by acting on MAPK signaling pathway and PI3 K-AKT signaling pathway, and the key targets included mitogen activated protein kinases 8(MAPK8), SRC, mitogen activated protein kinases 14(MAPK14), and RAC-alpha serine/threonine-protein kinase(AKT1), mitogen activated protein kinases 3(MAPK3). Based on the activity spectrum of targets, the targets of the TCM for activating blood and the targets of the TCM for regulating Qi were analyzed to provide reference for the study of efficacy targets of TCM, and also provide some scientific basis for clinical application.

Mechanism of Wuwei Ganlu in treatment of knee osteoarthritis:a study based on network pharmacology and molecular docking / 中国中药杂志

Wuwei Ganlu, a formula for medicated bath, consists of medicinal materials of Ephedra sinica, Platycladus orientalis, Myricaria squamosa, Artemisia carvifolia, and Rhododendron anthopogonoides, which is effective in inducing perspiration, resisting inflammation, relieving pain, regulating yellow water disease, and activating blood circulation. On this basis, a variety of formulas for Tibetan medicated bath have been derived for the treatment of diseases in internal organs, joints, nerves, etc. Modern studies have confirmed that Wuwei Ganlu has a good therapeutic efficacy on knee osteoarthritis(KOA). The present study explored the mechanism of Wuwei Ganlu in treating KOA based on network pharmacology and molecular docking. Firstly, the chemical components of Wuwei Ganlu were obtained through literature mining and database retrieval, and corresponding potential targets were predicted according to the BATMAN-TCM database. The protein-protein interaction(PPI) network was obtained after the potential targets were input into the STRING database. The network function modules were analyzed by the Molecular Complex Detection(MCODE) algorithm, and the functions of the modules were annotated to analyze the action mode of Wuwei Ganlu. Secondly, the related targets of KOA were collected through the DisGeNET database, and the overlapping targets were confirmed to analyze the mechanism of Wuwei Ganlu in treating KOA. Finally, the key targets were selected for molecular docking with the main components of Wuwei Ganlu to verify the component-target interaction. A total of 550 chemical components and 1 365 potential targets of Wuwei Ganlu were obtained. PPI analysis indicated that this formula could exert the effects of oxidation-reduction, inflammation resistance, bone absorption, bone mineralization, etc. Nineteen common targets were obtained from the intersection of potential targets of Wuwei Ganlu and KOA disease targets. It was found that the Wuwei Ganlu mainly acts on nuclear factor-κB(NF-κB), interleukin-1 beta(IL1β), tumor necrosis factor(TNF), IL6, IL1 receptor antagonist(IL1 RN), and prostaglandin-endoperoxide synthase-2(PTGS2) to treat KOA. Among the 550 chemical components of Wuwei Ganlu, 252 potential active components were docked with TNF and 163 with PTGS2, indicating good binding of the components with potential key targets. The study preliminarily explored the mechanism of Wuwei Ganlu in treating KOA to provide a reference for the further development and utilization of Tibetan medicated bath that has been included in the UN Intangible Cultural Heritage.

Mechanism of Didangtang in Inhibiting Aortic NLRP3 Inflammasome Cascade of Mice with Diabetic Macrovascular Disease / 中国实验方剂学杂志

Objective:To explore the progression of diabetic macrovascular disease and the effects of Didangtang at different doses on it. Method:Four-week-old male apolipoprotein-E knockout （ApoE^-/-） mice with diabetic macrovascular disease induced by exposure to high-fat diet combined with streptozotocin （STZ） were randomly divided into the model， simvastatin， as well as high-， medium-， and low-dose Didangtang groups. The age-matched ApoE^-/- mice of the same batch only fed with a high-fat diet were classified into the ApoE^-/- （model control） group， and C57BL/6 mice with the same genetic background receiving a regular diet into the normal group. The sampling was conducted at the 8th and 20th weeks of the experiment for observing the pathological characteristics of the aorta and the proportion of plaque area in mice of each group at different time points， followed by the comparison of blood glucose， blood lipid， and oxidized low-density lipoprotein （ox-LDL） levels. The aortic NOD-like receptor protein 3 （NLRP3） and cysteinyl aspartate-specific proteinase-1 （Caspase-1） protein expression was detected by Western blot assay， and the serum interleukin-1<italic>β</italic> （IL-1<italic>β</italic>）， interleukin-18 （IL-18）， interleukin-1<italic>α</italic> （IL-1<italic>α</italic>）， and tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>） levels by enzyme-linked immunosorbent assay （ELISA）. Result:The comparison with the normal group revealed that the proportions of plaque area in the ApoE^-/- group and the model group were increased （<italic>P</italic><0.01）， while the proportion of plaque area in each administration group was significantly reduced in contrast to that of the model group （<italic>P</italic><0.05）. The aortic NLRP3 and Caspase-1 protein expression levels as well as the serum IL-1<italic>β</italic>， IL-18， IL-1<italic>α</italic>， and TNF-<italic>α </italic>levels in the ApoE^-/- group and the model group were significantly higher than those in the normal group （<italic>P</italic><0.01）. Compared with the model group， each administration group exhibited a significant reduction in aortic NLRP3 and Caspase-1 protein expression and serum IL-1<italic>β</italic>， IL-18， IL-1<italic>α</italic>， and TNF-<italic>α</italic> levels （<italic>P</italic><0.05）， with the strongest inhibitory effect detected in the medium-dose Didangtang group （<italic>P</italic><0.05）. Conclusion:Didangtang directly alleviates diabetic macrovascular disease possibly by down-regulating NLRP3 and Caspase-1 protein expression and easing the inflammatory cascade.

The Potential Roles of Artemisinin and Its Derivatives in the Treatment of Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is a chronic disease that has become a global public health problem. Studies on T2DM prevention and treatment mostly focus on discovering therapeutic drugs. Artemisinin and its derivatives were originally used as antimalarial treatments. In recent years, the roles of artemisinins in T2DM have attracted much attention. Artemisinin treatments not only attenuate insulin resistance and restore islet ß-cell function in T2DM but also have potential therapeutic effects on diabetic complications, including diabetic kidney disease, cognitive impairment, diabetic retinopathy, and diabetic cardiovascular disease. Many in vitro and in vivo experiments have confirmed the therapeutic utility of artemisinin and its derivatives on T2DM, but no article has systematically demonstrated the specific role artemisinin plays in the treatment of T2DM. This review summarizes the potential therapeutic effects and mechanism of artemisinin and its derivatives in T2DM and associated complications, providing a reference for subsequent related research.