A novel DDIT3 activator dehydroevodiamine effectively inhibits tumor growth and tumor cell stemness in pancreatic cancer.

BACKGROUND: The existence of pancreatic cancer stem cells (PCSCs) results in limited survival benefits from current treatment options. There is a scarcity of effective agents for treating pancreatic cancer patients. Dehydroevodiamine (DeHE), a quinazoline alkaloid isolated from the traditional Chinese herb Evodiae fructus, exhibited potent inhibition of pancreatic ductal adenocarcinoma (PDAC) cell proliferation and tumor growth both in vitro and in vivo. METHODS: The cytotoxic effect of DeHE on PDAC cells was assessed using CCK-8 and colony formation assays. The antitumor efficacy of DeHE were appraised in human PANC-1 xenograft mouse model. Sphere formation assay and flow cytometry were employed to quantify the tumor stemness. RNA-Seq analysis, drug affinity responsive target stability assay (DARTS), and RNA interference transfection were conducted to elucidate potential signaling pathways. Western blotting and immunohistochemistry were utilized to assess protein expression levels. RESULTS: DeHE effectively inhibited PDAC cell proliferation and tumor growth in vitro and in vivo, and exhibited a better safety profile compared to the clinical drug gemcitabine (GEM). DeHE inhibited PCSCs, as evidenced by its suppression of self-renewal capabilities of PCSCs, reduced the proportion of ALDH+ cells and downregulated stemness-associated proteins (Nanog, Sox-2, and Oct-4) both in vitro and in vivo. Furthermore, there is potential involvement of DDIT3 and its downstream DDIT3/TRIB3/AKT/mTOR pathway in the suppression of stemness characteristics within DeHE-treated PDAC cells. Additionally, results from the DARTS assay indicated that DeHE interacts with DDIT3, safeguarding it against degradation mediated by pronase. Notably, the inhibitory capabilities of DeHE on PDAC cell proliferation and tumor stemness were partially restored by siDDIT3 or the AKT activator SC-79. CONCLUSION: In summary, our study has identified DeHE, a novel antitumor natural product, as an activator of DDIT3 with the ability to suppress the AKT/mTOR pathway. This pathway is intricately linked to tumor cell proliferation and stemness characteristics in PDAC. These findings suggest that DeHE holds potential as a promising candidate for the development of innovative anticancer therapeutics.

Inhibition of pathogenic microbes in oral infectious diseases by natural products: Sources, mechanisms, and challenges.

The maintenance of oral health is of utmost importance for an individual's holistic well-being and standard of living. Within the oral cavity, symbiotic microorganisms actively safeguard themselves against potential foreign diseases by upholding a multifaceted equilibrium. Nevertheless, the occurrence of an imbalance can give rise to a range of oral infectious ailments, such as dental caries, periodontitis, and oral candidiasis. Presently, clinical interventions encompass the physical elimination of pathogens and the administration of antibiotics to regulate bacterial and fungal infections. Given the limitations of various antimicrobial drugs frequently employed in dental practice, the rising incidence of oral inflammation, and the escalating bacterial resistance to antibiotics, it is imperative to explore alternative remedies that are dependable, efficacious, and affordable for the prevention and management of oral infectious ailments. There is an increasing interest in the creation of novel antimicrobial agents derived from natural sources, which possess attributes such as safety, cost-effectiveness, and minimal adverse effects. This review provides a comprehensive overview of the impact of natural products on the development and progression of oral infectious diseases. Specifically, these products exert their influences by mitigating dental biofilm formation, impeding the proliferation of oral pathogens, and hindering bacterial adhesion to tooth surfaces. The review also encompasses an examination of the various classes of natural products, their antimicrobial mechanisms, and their potential therapeutic applications and limitations in the context of oral infections. The insights garnered from this review can support the promising application of natural products as viable therapeutic options for managing oral infectious diseases.

Genetic diversity and genome-wide association study of 13 agronomic traits in 977 Beta vulgaris L. germplasms.

BACKGROUND: Sugar beet (Beta vulgaris L.) is an economically essential sugar crop worldwide. Its agronomic traits are highly diverse and phenotypically plastic, influencing taproot yield and quality. The National Beet Medium-term Gene Bank in China maintains more than 1700 beet germplasms with diverse countries of origin. However, it lacks detailed genetic background associated with morphological variability and diversity. RESULTS: Here, a comprehensive genome-wide association study (GWAS) of 13 agronomic traits was conducted in a panel of 977 sugar beet accessions. Almost all phenotypic traits exhibited wide genetic diversity and high coefficient of variation (CV). A total of 170,750 high-quality single-nucleotide polymorphisms (SNPs) were obtained using the genotyping-by-sequencing (GBS). Neighbour-joining phylogenetic analysis, principal component analysis, population structure and kinship showed no obvious relationships among these genotypes based on subgroups or regional sources. GWAS was carried out using a mixed linear model, and 159 significant associations were detected for these traits. Within the 25 kb linkage disequilibrium decay of the associated markers, NRT1/PTR FAMILY 6.3 (BVRB_5g097760); nudix hydrolase 15 (BVRB_8g182070) and TRANSPORT INHIBITOR RESPONSE 1 (BVRB_8g181550); transcription factor MYB77 (BVRB_2g023500); and ethylene-responsive transcription factor ERF014 (BVRB_1g000090) were predicted to be strongly associated with the taproot traits of root groove depth (RGD); root shape (RS); crown size (CS); and flesh colour (FC), respectively. For the aboveground traits, UDP-glycosyltransferase 79B6 (BVRB_9g223780) and NAC domain-containing protein 7 (BVRB_5g097990); F-box protein At1g10780 (BVRB_6g140760); phosphate transporter PHO1 (BVRB_3g048660); F-box protein CPR1 (BVRB_8g181140); and transcription factor MYB77 (BVRB_2g023500) and alcohol acyltransferase 9 (BVRB_2g023460) might be associated with the hypocotyl colour (HC); plant type (PT); petiole length (PL); cotyledon size (C); and fascicled leaf type (FLT) of sugar beet, respectively. AP-2 complex subunit mu (BVRB_5g106130), trihelix transcription factor ASIL2 (BVRB_2g041790) and late embryogenesis abundant protein 18 (BVRB_5g106150) might be involved in pollen quantity (PQ) variation. The candidate genes extensively participated in hormone response, nitrogen and phosphorus transportation, secondary metabolism, fertilization and embryo maturation. CONCLUSIONS: The genetic basis of agronomical traits is complicated in heterozygous diploid sugar beet. The putative valuable genes found in this study will help further elucidate the molecular mechanism of each phenotypic trait for beet breeding.

Magnolol alleviates pulmonary fibrosis inchronic obstructive pulmonary disease by targeting transient receptor potential vanilloid 4-ankyrin repeat domain.

Transient receptor potential vanilloid 4 (TRPV4) plays a role in regulating pulmonary fibrosis (PF). While several TRPV4 antagonists including magnolol (MAG), have been discovered, the mechanism of action is not fully understood. This study aimed to investigate the effect of MAG on alleviating fibrosis in chronic obstructive pulmonary disease (COPD) based on TRPV4, and to further analyze its mechanism of action on TRPV4. COPD was induced using cigarette smoke and LPS. The therapeutic effect of MAG on COPD-induced fibrosis was evaluated. TRPV4 was identified as the main target protein of MAG using target protein capture with MAG probe and drug affinity response target stability assay. The binding sites of MAG at TRPV4 were analyzed using molecular docking and small molecule interaction with TRPV4-ankyrin repeat domain (ARD). The effects of MAG on TRPV4 membrane distribution and channel activity were analyzed by co-immunoprecipitation, fluorescence co-localization, and living cell assay of calcium levels. By targeting TRPV4-ARD, MAG disrupted the binding between phosphatidylinositol 3 kinase γ and TRPV4, leading to hampered membrane distribution on fibroblasts. Additionally, MAG competitively impaired ATP binding to TRPV4-ARD, inhibiting TRPV4 channel opening activity. MAG effectively blocked the fibrotic process caused by mechanical or inflammatory signals, thus alleviating PF in COPD. Targeting TRPV4-ARD presents a novel treatment strategy for PF in COPD.

Transcriptional and proteomic analysis.

Unintended effects of gene edit crops may pose safety issues. Omics is a useful tool for researchers to evaluate these unexpected effects. Transcriptome and proteomics analyses were performed for two gene editors, CRISPR-Cas9 and adenine base editor (ABE) gene edit rice, as well as corresponding wild-type plants (Nipponbare). Transcriptome revealed 520 and 566 rice differentially expressed genes (DEGs) in the Cas9/Nip and ABE/Nip comparisons, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that most DEGs participated in metabolism of terpenoids and polyketones, plant-pathogen interactions, and plant signal transduction. It mainly belongs to environmental adaptation. Proteomics revealed 298 and 54 rice differentially expressed proteins (DEPs) in the Cas9/Nip and ABE/Nip comparisons, respectively. KEGG pathway enrichment analysis showed that most DEPs participated in the biosynthesis of secondary metabolite and metabolic pathways.According to integrated transcriptomes and proteomics analysis, the results showed that no newly generated genes were identified as new transcripts of these differentially expressed genes, and gene edit tools had little effect on rice transcription levels and no new proteins were generated in the gene-edited rice.

Cercospora leaf spot disease of sugar beet.

Leaf spot disease caused by Cercospora beticola Sacc. is the most damaging foliar disease threatening sugar beet production worldwide. The wide spread of disease incurs a reduction of yield and economic losses. The in-depth knowledge of disease epidemiology and virulence factor of pathogen is crucial and basic for preventing fungal disease. The integrated control strategies are needed for an efficient and sustainable disease management. The rotation of fungicides and crop could reduce the initial inoculum and delay the emergence of resistant pathogens. Spraying fungicides under the guide of forecasting models and molecular detecting techniques may hinder the onset of disease prevalence. The resistant varieties of sugar beet to cercospora leaf spot could be obtained by combining classical and molecular breeding methods. More effective approaches are supposed to develop for prevention and control for fungal disease of sugar beet.

Effectiveness and safety of Suhuang Zhike capsule as adjuvant treatment for acute exacerbation of chronic obstructive pulmonary disease: a systematic review and Meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of Suhuang Zhike capsule in the adjuvant treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: The database including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure Database, China Science and Technology Journal Database, Chinese Biomedical Literature Database and Wanfang Data was searched. The retrieval time was from database establishment to May 2021. Randomized controlled trial (RCT) of Suhuang zhike capsule adjuvant treatment for AECOPD was included. The quality of the studies was independently evaluated and cross-checked by two reviewers, and Meta-analysis was performed by using RevMan5.3 software. RESULTS: Thirteen RCT results were included with a total sample number of 1195 cases, including 597 in the experimental group and 598 in the control group. The results showed that Suhuang zhike capsule adjuvant treatment of AECOPD could improve the total clinical effect rate compared with conventional treatment. Suhuang zhike capsule adjuvant treatment could improve forced vital capacity (FVC), forced expiratory volume in one second (FEV), FEV/FVC, peak expiratory flow (PEF) and other pulmonary function indexes; decrease C-reactive protein (CRP), white blood cells, neutrophils and other infectious indicators; besides, the 1-year recurrence rate of the disease was decreased (all 0.05). CONCLUSIONS: Suhuang Zhike capsule can improve the lung function and clinical efficacy of AECOPD, thus increasing the exercise endurance, and reducing the infection and recurrence rate in AECOPD patients.

Drought resistance evaluation of sugar beet germplasms by response of phenotypic indicators.

Sugar beet is a main sugar crop worldwide that often faces drought stress. The identification of drought tolerance of sugar beet germplasms is beneficial for breeding, but the research about it has been rarely reported. In this study, the drought tolerance of germplasms 92005-1, 94002-2 and 92021-1-1 was tested under simulated conditions. Seven days and 9% PEG treatment were the optimal conditions for evaluation, under which more phenotypic indicators showed significant difference in drought tolerance coefficient. The objective weighting and membership function method were established for evaluating the drought tolerance of different sugar beet germplasms. Drought stress decreased the biomass of leaves and roots of sugar beet germplasms. The drought-sensitive germplasm responded faster for leaf weight, root weight, plant height and root length. These indicators declined more significantly under long-term and severe stress. Increasing the root-shoot ratio and proline content were universal strategies of sugar beet germplasms to overcome drought stress. The drought-tolerant germplasms held higher peroxidase activity and better ability to scavenge reactive oxygen for preventing the damage.

Gancao Nourishing-Yin decoction combined with methotrexate in treatment of aging CIA mice: a study based on DIA proteomic analysis.

BACKGROUND: Elderly rheumatoid arthritis (ERA) population faces multiple treatment dilemma. Here we aim to investigate if Gancao Nourishing-Yin decoction (GCNY) added to methotrexate (MTX) exhibit better effects in an ERA mice model. METHODS: ERA mice model was established by adding D-galactose (Dgal) to collagen-induced arthritis (CIA) mice. The model was then assigned into control group (CIA + Dgal), MTX treatment group (MTX), GCNY treatment group (GCNY), and integrative treatment group (MTX + GCNY). Pathological scoring was performed to evaluate the severity between the groups. Proteomic analysis was applied to investigate the secretory phenotype of the ERA mouse model and the underlying mechanism of GCNY, MTX and their combination. Representative cytokines related to proteomic results were further validated by ELISAs. RESULTS: CIA + Dgal mice showed more aggressive joints damage than the CIA mice. Besides changes in the inflammatory pathway such as Pi3k-Akt signaling pathway in both model, differential expressed proteins (DEPs) indicated metabolism-related pathways were more obvious in CIA + Dgal mice. Low-dose MTX failed to show pathological improvement in CIA + Dgal mice, while GCNY improved joints damage significantly. Besides down-regulated inflammation-related targets, GCNY-regulated DEPs (such as Apoc1 ~ 3, Grk2 and Creb3l3) were broadly enriched in metabolism-related pathways. MTX + GCNY showed the best therapeutic effect, and the DEPs enriched in a variety of inflammatory,metabolism and osteoclast differentiation signaling pathway. Notably, MTX + GCNY treatment up-regulated Dhfr, Cbr1, Shmt1 involved in folic acid biosynthesis and anti-folate resistance pathways indicated a coincidence synergic action. ELISAs confirmed CPR and Akt that elevated in CIA + Dgal mice were significantly ameliorated by treatments, and adding on GCNY elevated folic acid levels and its regulator Dhfr. CONCLUSION: Aging aggravated joints damage in CIA, which probably due to metabolic changes rather than more severe inflammation. GCNY showed significant effects in the ERA mice model especially when integrated with MTX to obtain a synergic action.

Tolerance and adaptation characteristics of sugar beet (Beta vulgaris L.) to low nitrogen supply.

Nitrogen (N) is an essential element required for sugar beet growth. Sugar beets with low N (LN) tolerance and high N use efficiency are excellent materials for breeding. Here, we comprehensively evaluated the morphological and physiological responses of nine sugar beet genotypes to LN supply. It was found that 0.5 mmol·L-1 N (LN) significantly influenced the performance of leaves and the topology of roots by reducing the bioproduction of chlorophyll a (Chl a) and soluble protein (SP) and the accumulation of N in leaves and roots (LNA and RNA), thus differentially restricting the growth (hypocotyl diameter, HD; root length, RL) and biomass (leaf and root fresh weight; LFW and RFW; leaf dry weight, LDW) of these sugar beets. Principal component and cluster analyses showed that 780016B/12 superior (F) exhibited excellent tolerance to LN; it had higher SOD activity (62.70%) and APX activity (188.92%) and a higher proline content (131.82%) than 92011 (G, LN sensitive). These attributes helped 780016B/12 superior (F) to better endure LN stress, and the morphology and N distribution changed to adapt to N deficiency, such that the root length increased by 112.48%, leaf area increased by 101.23%, and leaf nitrogen accumulation reached a peak of 14.13 g/plant. It seems that LN-tolerant genotypes increased their root length and surface area by reducing the difference in biomass, thereby expanding the contact between roots and soil, which was conducive to the absorption of nutrients (N) by sugar beets and helped distribute more assimilation products to the roots.

Effects of cadmium stress on the morphology, physiology, cellular ultrastructure, and BvHIPP24 gene expression of sugar beet (Beta vulgaris L.).

To clarify the mechanism of the response of sugar beet (Beta vulgaris L.) to cadmium (Cd) stress, this study investigated changes in the phenotype, physiological indexes, and subcellular structure of B. vulgaris under Cd treatment and the transcriptional pattern of the BvHIPP24 gene (a heavy metal-associated isoprenylated plant protein involved in heavy metal detoxification). The plant height and shoot and root growth of B. vulgaris seedlings were inhibited to some extent under 0.5 and 1 mM Cd, with gradually wilting and yellowing of leaves and dark brown roots. When the Cd concentration was increased, malondialdehyde content and the activities of peroxidase, superoxide dismutase, and glutathione S-transferase increased differentially. qPCR indicated that the expression of BvHIPP24 was induced by different concentrations of Cd. Although transmission electron microscopy revealed damage to nuclei, mitochondria, and chloroplasts, B. vulgaris exhibited strong adaptability to 0.5 mM Cd according to a comprehensive analysis using the membership function. The results showed that B. vulgaris may reduce cell damage and improve its Cd tolerance by regulating functional gene expression and antioxidant enzymes. This study increases our understanding of the Cd-tolerance mechanism of B. vulgaris and provides insights into the use of B. vulgaris in Cd bioremediation.

Sugar beet is a novel energy crop with superior characteristics for both heavy metal phytoremediation and biomass energy development. This work is the first to investigate both the morphological, physiological, and ultrastructural response of sugar beet to cadmium stress and the induction of a functional metallochaperone gene by cadmium. This study explains the cadmium tolerance mechanism of sugar beet based on a comprehensive evaluation and provides an important theoretical basis for further application of beet in heavy metal bioremediation.

The effect and mechanism of metformin on peripheral neuropathy in type 1 diabetic rats / 药学学报

Diabetic peripheral neuropathy (DPN) is one of the most common microvascular complications occurring in both type 1 and type 2 diabetes mellitus patients, which often results in patients suffering from severe hyperalgesia and allodynia. Up to now, the clinical therapeutic effect of DPN is still unsatisfactory. Metformin is an anti-diabetic drug that has been safely and widely used for the treatment of type 2 diabetes for decades. Studies have shown that metformin can improve pain caused by DPN, but its effects on the nerve conduction velocity and morphology of the sciatic nerve of DPN, and the mechanism for improving DPN are not clear. Therefore, the STZ-induced model of type 1 DPN in SD rats was used to study the effects of metformin on DPN, and to preliminarily explore its mechanism in this study. All animal experiments were carried out with approval of the Experimental Animal Welfare Ethics Committee of the Institute of Materia Medica (Chinese Academy of Medical Sciences and Peking Union Medical College). After the model was established successfully, STZ diabetic rats were randomly divided into a model group and a metformin treatment group, and 10 normal SD rats were selected as the normal control group, and the rats were intragastrically administered for 12 weeks. The results showed that metformin significantly reduced blood glucose, glycosylated hemoglobin, food consumption and water consumption in STZ rats. Metformin markedly increased the motor nerve conduction velocity and mechanical stabbing pain threshold, prolonged the hot plate latency threshold, and improved the pathological morphological abnormalities of the sciatic nerve in STZ rats. In addition, metformin increased the content of glutathione (GSH), enhanced the activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and reduced the content of malondialdehyde (MDA) in serum and sciatic nerve of STZ diabetic rats, as well as regulating the expression of genes related to oxidative stress in the sciatic nerve. Metformin obviously reduced the levels of pro-inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 in the serum in STZ rats, and inhibited the gene expression of these inflammatory factors in the sciatic nerve. In summary, metformin significantly increased nerve conduction velocity, improved sciatic nerve morphological abnormalities and pain in DPN rats, which may be related to its effect in improving oxidative stress and reducing inflammation.

Acclimation of sugar beet in morphological, physiological and BvAMT1.2 expression under low and high nitrogen supply.

Understanding the response and tolerance mechanisms of nitrogen (N) stress is essential for the taproot plant of sugar beet. Hence, in this study, low (0.5 and 3 mmol/L; N0.5 and N3), moderate (5 mmol/L; N5; control) and high (10 and 12 mmol/L; N10 and N12) N were imposed to sugar beet to comparatively investigate the growth and physiological changes, and expression pattern of the gene involving ammonia transporting at different seedling stages. The results showed that, different from N5 which could induce maximum biomass of beet seedlings, low N was more likely to inhibit the growth of beet seedlings than high N treatments. Morphological differences and adverse factors increased significantly with extension of stress time, but sugar beet seedlings displayed a variety of physical responses to different N concentrations to adapt to N abnormal. At 14 d, the chlorophyll content, leaf and root surface area, total dry weight and nitrogen content of seedlings treated with N0.5 decreased 15.83%, 53.65%, 73.94%, 78.08% and 24.88% respectively, compared with N12; however, the root shoot ratio increased significantly as well as superoxide dismutase (SOD), peroxidase (POD), glutamine synthetase (GS) activity and malondialdehyde (MDA) and proline content, especially in root. The expression of BvAMT1.2 was also regulated in an N concentration-dependent manner, and was mainly involved in the tolerance of beet leaves to N stress, which significantly positively correlated to GS activity on the basis of its high affinity to N. It can be deduced that the stored nutrients under low N could only maintain relatively stable root growth, and faced difficulty in being transported to the shoots. Sugar beet was relatively resilient to N0.5 stress according to the mean affiliation function analysis. These results provide a theoretical basis for the extensive cultivation of sugar beet in N-stressed soil.

Functional and binding studies of gallic acid showing platelet aggregation inhibitory effect as a thrombin inhibitor / 中草药·英文版

Objective: This study was devoted to identifying natural thrombin inhibitors from traditional Chinese medicine (TCM) and evaluating its biological activity in vitro and binding characteristics. Methods: A combination strategy containing molecular docking, thrombin inhibition assay, surface plasmon resonance (SPR) and molecular dynamics simulation were applied to verify the study result. Results: Gallic acid was confirmed as a direct thrombin inhibitor with IC

Isolation and Characterization of Antibacterial Carotane Sesquiterpenes from Artemisia argyi Associated Endophytic Trichoderma virens QA-8.

Carotane sesquiterpenes are commonly found in plants but are infrequently reported in the fungal kingdom. Chemical investigation of Trichoderma virens QA-8, an endophytic fungus associated with the inner root tissue of the grown medicinal herb Artemisia argyi H. Lév. and Vaniot, resulted in the isolation and characterization of five new carotane sesquiterpenes trichocarotins I-M (1-5), which have diverse substitution patterns, and seven known related analogues (6-12). The structures of these compounds were established on the basis of a detailed interpretation of their NMR and mass spectroscopic data, and the structures including the relative and absolute configurations of compounds 1-3, 5, 9, and 10 were confirmed by X-ray crystallographic analysis. In the antibacterial assays, all isolates exhibited potent activity against Escherichia coli EMBLC-1, with MIC values ranging from 0.5 to 32 µg/mL, while 7ß-hydroxy CAF-603 (7) strongly inhibited Micrococcus luteus QDIO-3 (MIC = 0.5 µg/mL). Structure-activity relationships of these compounds were discussed. The results from this study demonstrate that the endophytic fungus T. virens QA-8 from the planted medicinal herb A. argyi is a rich source of antibacterial carotane sesquiterpenes, and some of them might be interesting for further study to be developed as novel antibacterial agents.

Role of fecal calprotectin in the diagnosis of neonatal necrotizing enterocolitis: a Meta analysis / 中国当代儿科杂志

OBJECTIVE@#To study the value of fecal calprotectin (FC) in the diagnosis of neonatal necrotizing enterocolitis (NEC) through a Meta analysis.@*METHODS@#Web of Science, Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure, Weipu Periodical Database, Wanfang Data, Chinese Biomedical Literature Database were searched for related studies published up to May 2020, with manual search as supplementation. The QUADAS criteria were used to evaluate the quality of the articles included. Meta-DiSc 1.4 and Stata 15.0 software were used to perform the Meta analysis, including the evaluation of specificity, sensitivity, likelihood ratio, and diagnostic odds ratio. The sensitivity analysis and heterogeneity testing were performed, and the summary receiver operating characteristic (SROC) curve and Fagan diagram were plotted.@*RESULTS@#A total of 15 articles were enrolled, involving 1 719 neonates. Among these articles, 4 had low quality, 2 had high quality, and the rest had medium quality. There was high heterogeneity between studies, and there was no threshold effect or publication bias. The random effects model analysis showed that FC had a pooled specificity of 0.80 (95%@*CONCLUSIONS@#FC has high potential and efficiency in the early diagnosis of NEC. FC measurement can be used for the diagnosis of NEC, but it should be combined with clinical manifestations and other related laboratory examinations.

Study on mechanism of Phytolaccae Radix and its split components based on network pharmacology / 中国中药杂志

This paper aimed to explore the mechanism of the split components of Phytolaccae Radix by means of network pharmaco-logy. Based on the theoretical hypothesis of the nature and taste of traditional Chinese medicine, the chemical components of the separated components of Phytolaccae Radix were selected by using Traditional Chinese Medicine Systems Pharmacology Database(TCMSP) and Traditional Chinese Medicines IntegratedDatabase(TCMID) databases in combination with related literatures. Relevant target analysis was carried out based on PubChem and SwissTargetPrediction databases. Targets corresponding to disease were excavated based on GeneCards for each split component, corresponding potential targets were obtained through mapping the target set of target compounds to disease targets. GO biological process analysis and KEGG pathway enrichment analysis were performed on the mapped targets with the help of DAVID database. Based on Cytoscape software and the corresponding efficacy, the network diagram of "medicinal material-split components-compound-target-pathway" was constructed to explore the mechanism of different efficacy of the separated components of Cytoscape. And the target purgation and diuretic mapping was used as the target of the traditional efficacy of smoothening secretion for the first time. The study explored esculentoside component, fatty oil component and phenolic acid component, a total of 30 target compounds and 301 corresponding targets, involving 44 potential targets for "anti-inflammatory", 50 potential targets for "immunoregulation", 52 potential targets for "smoothening secretion", 28 potential targets for "antibacterial activity", 28 potential targets for "antiviral effect", and 29 potential targets for "antitumor effect". Topological analysis revealed 14 key gene targets such as MAPK8, MAPK14, EGFR and PTGS2. A total of 684 GO entries and 235 KEGG pathways were obtained through bioinformatics enrichment analysis, mainly involving TNF signaling pathway, NF-kappaB signaling pathway and MAPK signaling pathway. This study revealed the multi-component, multi-target, and multi-channel action mechanism of the split components of Phytolaccae Radix, which provided certain basis for the next step to clarify the split components of Phytolaccae Radix through the method of system biology, and injected new content and significance into the study of properties and flavors theory.

Evaluation of the clinical efficacy of muscle regions of meridians needling method for refractory facial paralysis based on infrared thermal imaging technology / 针灸推拿医学（英文版）

Objective: To explore the clinical efficacy of muscle regions of meridians needling method for refractory facial paralysis affecting different locations.Methods: A total of 110 participants were randomized into an observation group and a control group, with 55 cases in each group. The observation group was treated with muscle regions of meridians needling method, and the control group was treated with conventional facial three-line needling method. The clinical efficacy was evaluated four weeks after the treatment. And the infrared imaging spectra of the two groups were examined. Results: The total effective rate of the observation group was higher than that of the control group (P<0.05), and its curative effect for refractory facial paralysis located above the geniculate ganglion was better than that of the control group (P<0.05). The color scale distribution of different disease locations in the two groups varied significantly (P<0.05), the higher the disease location, the higher the occurrence rate of cool zone and low temperature zone. After treatment, the reductions of the facial and periotic temperature difference between the healthy side and the affected side in the observation group were statistically different from those in the control group (P<0.05). Conclusion: Muscle regions of meridians needling method has a better effect than facial three-line needling method for refractory facial paralysis. It can promote the microcirculation of the affected side of the face, improve the blood and oxygen supply to local tissues, and thus promote the repair of the peripheral facial nerve.

[Study on mechanism of Fangji Huangqi Decoction on hypouricemic effect and renal protection in hyperuricemia mice].

The aim of this paper was to study the specific mechanism of Fangji Huangqi Decoction(FHT) in decreasing uric acid and improving renal function in mice with hyperuricemia(HUA) induced by potassium oxonate, so as to provide theoretical basis for the research and development of drugs for clinical prevention and treatment of HUA and the modernization of traditional Chinese medicine. Sixty Kunming male mice were randomly divided into 6 groups, with 10 mice in each group, namely normal group, model group(250 mg·kg~(-1) potassium oxonate), FHT high, medium and low-dose groups(10 920, 5 460, and 2 730 mg·kg~(-1)) and positive drug allopurinol group(5 mg·kg~(-1)). Drug administration was given once a day for 7 days. On the 6 th day, mice of each group were kept in metabolic cages, and their urine was collected for 24 hours for determination of uric acid, creatinine, and ß2-microglobulin(ß2-MG) levels. After 7 days, the animals were sacrificed to determine serum uric acid, creatinine ß2-MG and interleukin-1ß(IL-1ß) levels, and their liver and kidney tissues were collected. The liver tissues were used for subsequent determination of xanthine oxidase(XOD) activity, and the kidney tissues were used for subsequent determination of IL-1ß levels, pathological tests and related Western blot experiments. In the cell transfection experiment, the cells were divided into blank group, model group(4.8 mmol·L~(-1) uric acid treatment), FHT administration group(4.8 mmol·L~(-1) uric acid+200 µg·mL~(-1) FHT), leucine-rich repeat kinase 1(LRRK1)-small interfering RNA(siRNA) group(4.8 mmol·L~(-1) uric acid+LRRK1-siRNA transfection) and LRRK1-siRNA+FHT group(4.8 mmol·L~(-1) uric acid+LRRK1-siRNA transfection+200 µg·mL~(-1) FHT). After 24 h incubation, the level of IL-1ß in the cell supernatant was detected, and the cellular proteins were extracted and used to determine LRRK1, epidermal growth factor receptor(EGFR), PDZ kinase 1(PDZK1) and nuclear factor-kappa B(NF-κB) protein expression levels. The results showed that, FHT could significantly reduce the uric acid, creatinine and ß2-MG levels in serum and ß2-MG levels in urine, increase the uric acid and creatinine levels in urine, and improve the renal pathological results of the HUA mice, but showed no effect on liver XOD activity; at the same time, we found that the expression level of IL-1ß in serum and kidney, NF-κB, LRRK1 and EGFR protein levels in kidney of HUA mice were significantly increased, and the expression level of PDZK1 protein was significantly decreased, while FHT could significantly improve the abnormal expression of these proteins, and FHT increased protein expression of renal organic anion transporter 1(OAT1), OAT3 and ATP bin-ding transporter G2(ABCG2) in HUA mice, but FHT had no effect on the expression of urate transporter 1(URAT1). In the cell transfection experiment, after transfection of LRRK1-siRNA, the levels of IL-1ß, EGFR and NF-κB in supernatant were significantly reduced, and the expression of PDZK1 protein was significantly increased. As compared with the LRRK1-siRNA group, the levels of IL-1ß, EGFR, PDZK1 and NF-κB did not change significantly with the additional FHT. This study showed that FHT may regulate the renal uric acid transport system through LRRK1 gene, improve the capacity of uric acid excretion, so as to reduce the level of serum uric acid. At the same time, FHT can not only protect the kidney directly, but also in an indirect manner by reducing the level of uric acid.

Polyketides and Terpenoids with Potent Antibacterial Activities from the Artemisia argyi-Derived Fungus Trichoderma koningiopsis QA-3.

The AcOEt extract of Artemisia argyi-derived fungus Trichoderma koningiopsis QA-3 showed potent inhibitory activity against pathogenic bacteria. Fractionation of the extract resulted in the isolation of three new polyketides (1-3) and two new terpenoids (4 and 5), together with three known metabolites (6-8). Their chemical structures were analyzed by NMR spectra, ECD, HR-ESI-MS or HR-EI-MS, optical rotation, and X-ray crystallographic data, as well as by comparison with literature reports. In the antibacterial assays, 3-hydroxyharziandione (4) showed potent activity against human pathogen Escherichia coli with an MIC value of 0.5 µg/mL, while 6-(3-hydroxypent-1-en-1-yl)-2H-pyran-2-one exhibited strong activity against marine-derived aquatic pathogen Micrococcus luteus with an MIC value of 1.0 µg/mL.