Acanthopanax senticosus cultures fermented by Lactobacillus rhamnosus enhanced immune response through improvement of antioxidant activity and inflammation in crucian carp (Carassius auratus).

Lactic acid bacteria (LAB) have been recognized as safe microorganism that improve micro-flora disturbances and enhance immune response. A well-know traditional herbal medicine, Acanthopanax senticosus (As) was extensively utilized in aquaculture to improve growth performance and disease resistance. Particularly, the septicemia, skin wound and gastroenteritis caused by Aeromonas hydrophila threaten the health of aquatic animals and human. However, the effects of probiotic fermented with A. senticosus product on the immune regulation and pathogen prevention in fish remain unclear. Here, the aim of the present study was to elucidate whether the A. senticosus fermentation by Lactobacillus rhamnosus improve immune barrier function. The crucian carp were fed with basal diet supplemented with L. rhamnosus fermented A. senticosus cultures at 2 %, 4 %, 6 % and 8 % bacterial inoculum for 8 weeks. After trials, the weight gain rate (WGR), specific growth rate (SGR) were significantly increased, especially in LGG-6 group. The results confirmed that the level of the CAT, GSH-PX, SOD, lysozyme, and MDA was enhanced in fish received with probiotic fermented product. Moreover, the L. rhamnosus fermented A. senticosus cultures could trigger innate and adaptive immunity, including the up-regulation of the C3, C4, and IgM concentration. The results of qRT-PCR revealed that stronger mRNA transcription of IL-1ß, IL-10, IFN-γ, TNF-α, and MyD88 genes in the liver, spleen, kidney, intestine and gills tissues of fish treated with probiotic fermented with A. senticosus product. After infected with A. hydrophila, the survival rate of the LGG-2 (40 %), LGG-4 (50 %), LGG-6 (60 %), LGG-8 (50 %) groups was higher than the control group. Meanwhile, the pathological damage of the liver, spleen, head-kidney, and intestine tissues of probiotic fermentation-fed fish could be alleviated after pathogen infection. Therefore, the present work indicated that L. rhamnosus fermented A. senticosus could be regard as a potential intestine-target therapy strategy to protecting fish from pathogenic bacteria infection.

Advances in the study of endocannabinoid receptors in experimental acupuncture analgesia. / å† æºæ€§å¤§éº»ç´ å—ä½“åœ¨é’ˆåˆºé•‡ç—›æœºåˆ¶ä¸­çš„ç ”ç©¶è¿›å±•.

The endocannabinoid system, an important biological network for maintaining and balancing various functions of the human body, is involved in many physiological functions such as pain, emotion, learning and memory, etc. Among which the endocannabinoid receptors ï¼»including type I (CB1) and type II (CB2) receptorsï¼½ play an important role in the regulation of pain and have become an important target in the mechanism research of acupuncture analgesia. CB1 is mainly distributed in the central nervous system, including the spinal cord, cerebral cortex, amygdala, insular cortex, and basal ganglia, etc. CB2 is mainly distributed in peripheral immune tissues, such as spleen, bone, skin, etc. In the central and peripheral nervous systems, acupuncture can activate CB1 and CB2 receptors respectively, which is involved in the transmission of central nociceptive signals and related transmitters as well as the peri-pheral pro-nociceptive inflammatory response, thereby alleviating the nociceptive hypersensitivity in animal models. In this paper, we systematically summarize the roles of the above mechanisms in different types of animal models (inflammatory pain, neuropathological pain, visceral pain, etc.), so as to provide new ideas for the study of the underlying mechanisms of acupuncture analgesia.

Acetylenic spiroketal enol ethers from Artemisia rupestris and their synergistic antibacterial effects on methicillin-resistant Staphylococcus aureus.

Synergistic bioassay-guided isolation of the extracts of Artemisia rupestris L, which belongs to the family Asteraceae, afforded two acetylenic spiroketal enol ethers, namely rupesdiynes A (1) and B (2). Their structures were determined based on spectroscopic analysis and experimental and calculated ECD investigations. The two compounds exhibited synergistic activity and were able to reduce the minimum inhibitory concentration (MIC) of oxacillin four-fold, with a fractional inhibitory concentration index (FICI) of 0.5 in combination with oxacillin against the oxacillin-resistant EMRSA-16. Biofilm formation inhibitory and Ethidium bromide (EtBr) efflux assay were further employed to verify the possible mechanism of the synergistic antibacterial effect. Additionally, molecular docking studies were conducted to investigate the binding affinities of the two compounds with penicillin-binding protein 2a (PBP2a) of EMRSA-16. Taken together, rupesdiynes A (1) and rupesdiyne B (2) showed moderate synergistic activity against EMRSA-16 with oxacillin via inhibiting biofilm formation and efflux pump activity, respectively.

[Research progress on anti-tumor effects by traditional Chinese medicine based on "soothing" or "blockage" regulation of tumor vessels].

Regulation of tumor vessels has become one of the most common strategies for clinical anti-tumor therapy. In recent years, studies have found that the anti-tumor effect of limotherapy, which routinely inhibits tumor angiogenesis, is not ideal and may even deteriorate the tumor microenvironment, causing tumor resistance and distal metastasis and increasing the risk of tumor metastasis and recurrence. However, the proper use of anti-angiogenic drugs can promote the normalization of tumor vessels, improve the structure and function of tumor vessels, increase the number of functional vessels in the tumor, and reduce the number of ineffective vessels. It is beneficial to promote the penetration of anti-tumor drugs into the tumor, improve the microenvironment of tumor hypoxia and immunosuppression, and enhance the anti-tumor effect. Traditional Chinese medicine(TCM) has a long history of understanding the etiology and pathogenesis of tumors and has accumulated rich experience in tumor treatment, with significant clinical advantages and broad application prospects. In this study, from the perspective of bidirectional "soothing" or "blockage" regulation of tumor vessels, the commonly used molecular targets were sorted out, and the research status of anti-tumor regulation of tumor vessels by monomer-single herb-compound(herb pair) of TCM in recent years was summarized. The research on the anti-tumor effects of TCM compounds and active ingredients by regulating tumor vessels combined with other therapies was analyzed and sorted out, so as to provide ideas for the clinical application of TCM in regulating functions and anti-tumor effects of tumor vessels.

Network pharmacology identifies the inhibitory effect of Yiqiyangyinquyu prescription on salivary gland inflammation in Sjögren's syndrome.

This study aimed to explore the mode of action of Yiqiyangyinquyu prescription (YP) against Sjögren's syndrome (SS) by combining network pharmacology with molecular docking techniques. YP's active components and target proteins were identified using the BATMAN-traditional Chinese medicine database. Concurrently, targets associated with SS were extracted from databases, including Genecards, Online Mendelian Inheritance in Man, and Therapeutic Target Database. The standard targets were then imported into the STRING database to construct a protein-protein interaction network. We then conducted gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses, which were succeeded by molecular docking studies to validate core active components and key targets. Finally, in vitro experiments and molecular dynamics simulation were conducted to substantiate the therapeutic efficacy of YP in treating SS. A total of 206 intersection targets and 46 active compounds were identified. Gene ontology analysis unveiled that YP targets were primarily enriched in cellular responses to chemical stress, inflammation, and cell proliferation. Key enriched signaling pathways encompassed the interleukin 17, hypoxia-inducible factor-1, tumor necrosis factor (TNF-α), and advanced glycation end products-receptor for AGEs (AGE-RAGE) signaling pathways. Molecular docking results demonstrated high-affinity between neotanshinone C, tanshiquinone B, miltionone I, TNF-α, interleukin 1 beta (IL-1ß), and interleukin 6 (IL-6). Noteworthy, TNF-α, considered the most important gene in YP against SS, binds to YP most stably, which was further validated by molecular dynamics simulation. In vitro experiments confirmed YP's capacity to reduce TNF-α, IL-1ß, and IL-6 expression, effectively alleviating SS-related inflammation. YP demonstrated a significant anti-inflammatory effect by suppressing inflammatory cytokines (TNF-α, IL-6, and IL-1ß), providing experimental evidence for its clinical application in treating SS.

[Dead heart of pith-decayed Scutellariae Radix: a study based on multi-omics].

Dead heart is an important trait of pith-decayed Scutellariae Radix. The purpose of this study was to clarify the scientific connotation of the dead heart using multi-omics. Metabolomics and transcriptomics combined with multivariate statistical analysis such as principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA) were used to systematically compare the differences in chemical composition and gene expression among phloem, outer xylem and near-dead xylem of pith-decayed Scutella-riae Radix. The results revealed significant differences in the contents of flavonoid glycosides and aglycones among the three parts. Compared with phloem and outer xylem, near-dead xylem had markedly lowered content of flavonoid glycosides(including baicalin, norwogonin-7-O-ß-D-glucuronide, oroxylin A-7-O-ß-D-glucuronide, and wogonoside) while markedly increased content of aglycones(including 3,5,7,2',6'-pentahydroxy dihydroflavone, baicalin, wogonin, and oroxylin A). The differentially expressed genes were mainly concentrated in KEGG pathways such as phenylpropanoid metabolism, flavonoid biosynthesis, ABC transporter, and plant MAPK signal transduction pathway. This study systematically elucidated the material basis of the dead heart of pith-decayed Scutellariae Radix with multiple growing years. Specifically, the content of flavonoid aglycones was significantly increased in the near-dead xylem, and the gene expression of metabolic pathways such as flavonoid glycoside hydrolysis, interxylary cork development and programmed apoptosis was significantly up-regulated. This study provided a theoretical basis for guiding the high-quality production of pith-decayed Scutellariae Radix.

[Q-marker prediction of resin ethanol extract of Gegen Qinlian Decoction based on characteristic spectrum and network pharmacology].

The resin ethanol extract of Gegen Qinlian Decoction(GGQLD) has been found to significantly alleviate the intestinal toxicity caused by Irinotecan, but further research is needed to establish its overall quality and clinical medication standards. This study aimed to establish an HPLC characteristic fingerprint of the resin ethanol extract of GGQLD, predicted the targets and signaling pathways of its pharmacological effects based on network pharmacology, identified core compounds with pharmacological relevance, and analyzed potential quality markers(Q-markers) of the resin eluate of GGQLD for relieving Irinotecan-induced toxicity. By considering the uniqueness, measurability, and traceability of Q-markers based on the "five principles" of Q-markers and combining them with network pharmacology techniques, the overall efficacy of the resin ethanol extract of GGQLD can be characterized. Preliminary predictions suggested that the four components of puerarin, berberine, baicalin, and baicalein might serve as potential Q-markers for the resin etha-nol extract of GGQLD. This study provides a basis and references for the quality control and clinical mechanism of the resin ethanol extract of GGQLD.

Effects of Rosa roxburghii Tratt on Ulcerative Colitis: An Integrated Analysis of Network Pharmacology and Experimental Validation.

Rosa roxburghii Tratt is a traditional Chinese plant that has been used to treat different inflammatory diseases. The purpose of this study was to investigate the mechanism of action of Rosa roxburghii Tratt extract (RRTE) against ulcerative colitis (UC) using network pharmacology and experimental validation. HPLC-Q/Orbitrap MS was used to rapidly identify the substances contained in RRTE after extracting the active components from the fruit. Then, network pharmacology combined with molecular docking was used to explore the critical target and potential mechanism of RRTE against UC using the active ingredients in RRTE as the research object. Data are presented in a visual manner. Finally, the pharmacological effects of RRTE in alleviating UC were further verified using a DSS-induced UC model of NCM460. The results showed that 25 components in RRTE were identified. A total of 250 targets of the active components and 5376 targets associated with UC were collected. Furthermore, a systematic analysis of the Protein-Protein Interaction (PPI) networks suggests that epidermal growth factor receptor (EGFR), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), and serine/threonine kinase 1 (AKT1) are critical targets for RRTE in the treatment of UC. A comprehensive regulatory network analysis showed that RRTE alleviated UC through the EGFR-mediated PI3K/Akt pathway, and molecular docking showed that active components could strongly bind to EGFR, PIK3R1, and AKT1. In addition, RRTE alleviated dextran sulfate sodium salt (DSS)-induced cell injury and significantly decreased the protein expression levels of EGFR, PIK3R1, and p-AKT in NCM460 cells in vitro. Furthermore, RRTE significantly regulated the expression of the apoptosis-related proteins Apoptotic protease-activating factor 1 (Apaf1), cleaved caspase-3, B-cell lymphoma-2 (Bcl2), and Bcl2 associated X protein (Bax). In conclusion, the components of RRTE are complex, and RRTE can relieve UC through the EGFR-mediated PI3K/Akt pathway.

[Equivalence of combined decoction and mixed single decoctions of Gegen Qinlian Decoction in alleviating chemotherapy-associated diarrhea].

This study compared the chemical profiles, component content, dry paste yield, and pharmacological effects of samples obtained from the mixed single decoctions and the combined decoction of Gegen Qinlian Decoction(GQD), aiming to provide an experimental foundation for evaluating the equivalence of the two decocting methods and the suitability of TCM formula granules in clinical application. The same decoction process was used to prepare the combined decoction and mixed single decoctions of GQD. Ultra-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap MS) was employed to compare the chemical profiles between the two groups. High-performance liquid chromatography(HPLC) was used to compare the content of nine characteristic components between the two groups. Then, a delayed diarrhea mouse model induced by irinotecan was established to compare the pharmacological effects of the two groups on chemotherapy-induced diarrhea. The UPLC-Q-Exactive Orbitrap MS in ESI~+ and ESI~- modes identified 59 chemical components in the compound decoction and mixed single decoctions, which showed no obvious differences in component species. The content of baicalin and wogonoside was higher in the compound decoction, while that of puerarin, daidzein-8-C-apiosylglucoside, berberine, epiberberine, wogonin, glycyrrhizic acid, and daidzein was higher in the mixed single decoctions. Further statistical analysis revealed no significant difference in the content of the nine characteristic components between the compound decoction and the mixed single decoctions. The dry paste yield had no significant difference between the two groups. Compared with the model group, both compound decoction and mixed single decoctions alleviated the weight loss and reduced diarrhea index in mice. Both of them lowered the levels of tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), cyclooxygenase-2(COX-2), intercellular adhesion molecule-1(ICAM-1), interleukin-10(IL-10), malondialdehyde(MDA), and nitric oxide(NO) in the colon tissue. Furthermore, they significantly increased the levels of glutathione peroxidase(GSH-Px) and superoxide dismutase(SOD). Hematoxylin-eosin(HE) staining showed that colon tissue cells were tightly arranged with clear nuclei in both groups without obvious difference. The compound decoction and mixed single decoctions showed no significant differences in chemical component species, content of nine characteristic components, dry paste yield, or the pharmacological effects on alleviating chemotherapy-induced diarrhea. The findings provide a reference for evaluating the flexibility and superiority of combined or single decocting method in the preparation of TCM decoctions or formula granules.

[Nature-effect transformation mechanism of mulberry leaves and silkworm droppings based on chemical composition analysis].

Starting with the relationship between mulberry leaves and silkworm droppings as food and metabolites, this study systematically compared the chemical components, screened out differential components, and quantitatively analyzed the main differential components based on ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) and UPLC-Q-TRAP-MS combined with principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA). Moreover, the in vitro enzymatic transformation of the representative differential components was studied. The results showed that(1) 95 components were identified from mulberry leaves and silkworm droppings, among which 27 components only exist in mulberry leaves and 8 components in silkworm droppings. The main differential components were flavonoid glycosides and chlorogenic acids.(2) Nineteen components with significant difference were quantitatively analyzed, and the components with significant differences and high content were neochlorogenic acid, chlorogenic acid, and rutin.(3) The crude protease in the mid-gut of silkworm significantly metabolized neochlorogenic acid and chlorogenic acid, which may be an important reason for the efficacy change in mulberry leaves and silkworm droppings. This study lays a scientific foundation for the development, utilization, and quality control of mulberry leaves and silkworm droppings. It provides references for clarifying the possible material basis and mechanism of the pungent-cool and dispersing nature of mulberry leaves transforming into the pungent-warm and dampness-resolving nature of silkworm droppings, and offers a new idea for the study of nature-effect transformation mechanism of traditional Chinese medicine.

[Effect of transcutaneous electrical acupoint stimulation on learning and memory ability of chronic fatigue syndrome rats and its mechanisms].

OBJECTIVE: To observe the effect of transcutaneous electrical acupoint stimulation (TEAS) on the histomorphological manifestations of hippocampal CA1 region and the expression of extracellular regulatory protein kinase (ERK), cyclic adenosine response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in chronic fatigue syndrome (CFS) rats, so as to explore the mechanisms of TEAS in improving the learning and memory abilities of CFS rats. METHODS: Forty male Wistar rats were randomly divided into normal group (10 rats) and modeling group (30 rats); then after modeling, they were selected and randomly divided into model group (10 rats) and TEAS group (10 rats). CFS rats model was prepared by sleep deprivation combined with weight-bearing swimming. Rats in the TEAS group were stimulated with Han's acupoint nerve stimulator at bilateral "Zusanli" (ST36) and "Shenshu" (BL23) (2 Hz/15 Hz, 1-2 mA), 20 min each time, once a day for 4 weeks with 1 d rest every 6 d. The score of general conditions of rats was evaluated. The learning and memory ability was tested with Morris water maze. The morphology and ultrastructure of hippocampal CA1 region were observed by HE staining and transmission electron microscopy. The expression levels of ERK, CREB and BDNF mRNAs and proteins in hippocampus were detected by real time quantitative PCR and Western blot, respectively. RESULTS: Compared with the normal group, the score of general condition was increased (P<0.01); the escape latency was prolonged (P<0.05, P<0.01) and the times of crossing the original platform was decreased (P<0.05); the expression levels of ERK, CREB and BDNF mRNAs and proteins in hippocampus were decreased (P<0.05, P<0.01) in the model group. Compared with the model group, the scores of general condition on the 42nd and 49th day were decreased (P<0.05, P<0.01); the escape latency was shortened (P<0.01, P<0.05)and the times of crossing the original platform were increased (P<0.05); the expression levels of ERK, CREB and BDNF mRNAs and proteins in hippocampus were increased (P<0.01, P<0.05) in the TEAS group. The morphology of neurons in hippocampal CA1 region was normal in the normal group. In the model group, the number of neurons in hippocampal CA1 region decreased, the arrangement of nerve cells was scattered, the number of apoptotic cells increased, some nuclear structures disappeared, nuclear heterochromatin increased, the cell membrane wrinkled, the chromatin appeared empty bright area, and the crista was incomplete. Compared with the model group, the nerve cells morphology in hippocampal CA1 region was more regular, the number of apoptotic cells decreased, the chromatin and the cytoplasm were uniformly distributed, and the crista was relatively intact in the TEAS group. CONCLUSION: TEAS can improve the learning and memory ability of CFS rats, the mechanisms may be related to improving the neural structure of hippocampal CA1 region and up-regulating the expression levels of ERK/CREB/BDNF.

[Application prospect of conditional gene editing animals and viral vectors in experimental research of acupuncturology].

Conditional gene editing animals and viral vectors have been widely applied in the research fields of biology and medicine. Recently, they are also used as the effective approaches to reveal the underlying mechanism of acupuncture from the nervous system to the specific molecules. In order to further understand the application of conditional gene editing animals and viral vectors, in this article, we analyze their characteristics, advantages and recent development in the field of acupuncture research and discuss their potential roles and prospect in the future.

Electroacupuncture activated local sympathetic noradrenergic signaling to relieve synovitis and referred pain behaviors in knee osteoarthritis rats.

Introduction: Recent research has focused on the local control of articular inflammation through neuronal stimulation to avoid the systemic side effects of conventional pharmacological therapies. Electroacupuncture (EA) has been proven to be useful for inflammation suppressing and pain reduction in knee osteoarthritis (KOA) patients, yet its mechanism remains unclear. Methods: In the present study, the KOA model was established using the intra-articular injection of sodium monoiodoacetate (MIA) (1 mg/50 µL) into the knee cavity. EA was delivered at the ipsilateral ST36-GB34 acupoints. Hind paw weight-bearing and withdrawl thresholds were measured. On day 9, the histology, dep enrichment proteins, cytokines contents, immune cell population of the synovial membrane of the affected limbs were measured using HE staining, Masson staining, DIA quantitative proteomic analysis, flow cytometry, immunofluorescence staining, ELISA, and Western Blot. The ultrastructure of the saphenous nerve of the affected limb was observed using transmission electron microscopy on the 14th day after modeling. Results: The result demonstrated that EA intervention during the midterm phase of the articular inflammation alleviated inflammatory pain behaviors and cartilage damage, but not during the early phase. Mid-term EA suppressed the levels of proinflammatory cytokines TNF-α, IL-1ß, and IL-6 in the synovium on day 9 after MIA by elevating the level of sympathetic neurotransmitters Norepinephrine (NE) in the synovium but not systemic NE or systemic adrenaline. Selective blocking of the sympathetic function (6-OHDA) and ß2-adrenergic receptor (ICI 118,551) prevented the anti-inflammatory effects of EA. EA-induced increment of the NE in the synovium inhibited the CXCL1-CXCR2 dependent overexpression of IL-6 in the synovial macrophages in a ß2-adrenergic receptor (AR)-mediated manner. Discussion: These results revealed that EA activated sympathetic noradrenergic signaling to control local inflammation in KOA rats and contributed to the development of novel therapeutic neurostimulation strategies for inflammatory diseases.

Nature-effect transformation mechanism of mulberry leaves and silkworm droppings based on chemical composition analysis / 中国中药杂志

Starting with the relationship between mulberry leaves and silkworm droppings as food and metabolites, this study systematically compared the chemical components, screened out differential components, and quantitatively analyzed the main differential components based on ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) and UPLC-Q-TRAP-MS combined with principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA). Moreover, the in vitro enzymatic transformation of the representative differential components was studied. The results showed that(1) 95 components were identified from mulberry leaves and silkworm droppings, among which 27 components only exist in mulberry leaves and 8 components in silkworm droppings. The main differential components were flavonoid glycosides and chlorogenic acids.(2) Nineteen components with significant difference were quantitatively analyzed, and the components with significant differences and high content were neochlorogenic acid, chlorogenic acid, and rutin.(3) The crude protease in the mid-gut of silkworm significantly metabolized neochlorogenic acid and chlorogenic acid, which may be an important reason for the efficacy change in mulberry leaves and silkworm droppings. This study lays a scientific foundation for the development, utilization, and quality control of mulberry leaves and silkworm droppings. It provides references for clarifying the possible material basis and mechanism of the pungent-cool and dispersing nature of mulberry leaves transforming into the pungent-warm and dampness-resolving nature of silkworm droppings, and offers a new idea for the study of nature-effect transformation mechanism of traditional Chinese medicine.

Effect of Jiawei Shenqi Yixin Prescription on Cardiovascular Risk Factors in Patients with Heart Failure with Preserved Ejection Fraction and Insulin Resistance / 中国实验方剂学杂志

ObjectiveTo observe the effect of Jiawei Shenqi Yixin prescription on cardiovascular risk factors in the patients with heart failure with preserved ejection fraction and insulin resistance. MethodFrom January 2021 to January 2022， a total of 82 patients with heart failure with preserved ejection fraction were enrolled in the ward of the First Affiliated Hospital of Heilongjiang University of Chinese Medicine. The patients were randomly assigned into two groups （ 41 cases） and received the same basic treatment. The observation group was additionally treated with Jiawei Shenqi Yixin prescription for 8 weeks. The clinical efficacy， traditional Chinese medicine （TCM） efficacy， cardiac function indexes ［NT-probrain natriuretic peptide （NT-proBNP） and 6-min walking test （6MWT）］， echocardiographic parameters ［left atrial volume index （LAVI）， left ventricular mass index （LVMI）， peak early diastolic to peak late diastolic mitral flow velocity （E/A） ratio］， insulin resistance-related indexes ［fasting insulin （FINS）， fasting plasma glucose （FPG）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， homeostatic model assessment of insulin resistance （HOMA-IR）， triglyceride-glucose index （TYG）， and triglyceride to high-density lipoprotein cholesterol （TG/HDL-C） ratio］， inflammatory cytokines ［tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， adiponectin （ADP）， and C-reactive protein （CRP）］， vascular endothelial function indicators ［nitric oxide （NO）， endothelial nitric oxide synthase （eNOS）， inducible nitric oxide synthase （iNOS）， and endothelin-1 （ET-1）］， and the safety of treatment were determined. In addition， Pearson correlation analysis was performed to analyze the correlations of insulin resistance， inflammatory cytokines， and vascular endothelial factors with the mitigation of heart failure. ResultIn terms of clinical efficacy， the therapy of the observation group was significantly effective in 26 patients， effective in 12 patients， ineffective in 3 patients， with the total effective rate of 92.68%， the therapy of the control group was significantly effective in 14 patients， effective in 12 patients， and ineffective in 15 patients， with the total effective rate of 63.41%. The clinical total effective rate of the observation group was higher than that of the control group （χ2=11.6， P<0.05）. In terms of TCM efficacy， the therapy of the observation group was significantly effective in 26 patients， effective in 11 patients， and ineffective in 4 patients， with the total effective rate of 90.24%； the therapy of the control group was significantly effective in 9 patients， effective in 13 patients， and ineffective in 19 patients， with the total effective rate of 53.66%. The TCM total effective rate of the observation group was higher than that of the control group （χ2=8.19， P<0.05）. Compared with those before treatment， the levels of NT-proBNP， LAVI， LVMI， FPG， FINS， HOMA-IR， TYG， TG/HDL-C， TNF-α， IL-6， CRP， ET-1， and iNOS in two groups declined after treatment （P<0.05）， while the levels of 6MWT， E/A， ADP， NO， and eNOS elevated （P<0.05）. After treatment， the observation group had lower levels of NT-proBNP， LAVI， LVMI， FPG， FINS， HOMA-IR， TYG， TG/HDL-C， TNF-α， CRP， and ET-1 （P<0.05） and higher levels of 6MWT， E/A， ADP， and NO than the control group （P<0.05）. In addition， the increase in 6MWT after treatment was positively correlated with the increase in NO and the decrease in ET-1. The decrease in LVMI after treatment was positively correlated with the increase in NO and the decrease in FINS. The increase in left ventricular ejection fraction after treatment was positively correlated with the decreases in TNF-α and TYG （P<0.05）. Adverse reactions were observed in neither group. ConclusionJiawei Shenqi Yixin prescription can significantly mitigate the symptoms， reduce inflammation， and improve vascular endothelial function in the patients with heart failure with preserved ejection fraction and insulin resistance， being safe without causing adverse reactions.

[Effect of electroacupuncture on spontaneous pain during the synovial inflammatory response stage and allodynia at the later stage in rats with knee osteoarthritis].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on pain behavior, synovial inflammatory response and demyelination of saphenous nerve in the rats modeled with knee osteoarthritis (KOA) and explore the effect mechanism of EA for reliving allodynia. METHODS: Eighty-four male SD rats were randomly divided into a control group, a model group and an EA group, 28 rats in each one. Intra-articular injection of sodium monoiodoacetate (MIA) was administered in right knee joint of each rat in the model group and the EA group to establish the KOA model. In the EA group, separately, on day 5, 7 and 9 after modeling, EA was applied at "Zusanli" (ST 36) and "Yanglingquan" (GB 34) on the right side, with disperse-dense wave (2 Hz/15 Hz), 1 mA in current intensity, for 30 min in one intervention, once a day, and 3 interventions were required. On the 9th day after modeling, the weight-bearing rate was calculated for the affected limbs of the rats in each group, the synovial morphological changes were observed using HE and Masson staining, flow cytometry was adopted to detect the synovial immunocyte counts, and MSD multi-spot assay was used to detected the synovial inflammatory cytokine content. On the 14th day after modeling, the hind-paw mechanical withdrawal threshold was observed in each group and the ultrastructure of the saphenous nerve was observed under transmission electron microscopy. RESULTS: On the 9th day after modeling, compared with the control group, the weight-bearing rate of the affected limb was reduced (P<0.01), the synovial hyperplasia, inflammatory cell infiltration and synovial fibrosis occurred in the affected limb; the counts of synovial CD11b+ cells and M1 macrophages (CD11b+CD86+) were increased (P<0.01), the contents of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1ß, IL-10 and IL-13 in the synovial tissue were elevated (P<0.01, P<0.05) for the rats of the model group. Compared with the model group, the weight-bearing rate of the affected limb was increased (P<0.05), the synovial hyperplasia, inflammatory cell infiltration and synovial fibrosis were mitigated, the counts of CD11b+ cells and M1 macrophages (CD11b+CD86+) in the synovial tissue, and the contents of TNF-α and IL-6 were reduced (P<0.01, P<0.05) in the EA group. On the 14th day after modeling, the hind-paw mechanical withdrawal threshold was reduced in the model group when compared with the control group (P<0.01), and it was increased in the EA group when compared with the model group (P<0.05). Besides, in the model group, obviously, the myelin sheath structure was destroyed, the myelin layer was disintegrated and loosened, the axon was extruded or the layer thicken and cracked. Compared with the model group, the injury of saphenous nerve was alleviated remarkably in the EA group. CONCLUSION: The intervention with EA may attenuate the synovial inflammatory response and the injury of saphenous nerve in the affected limb of the rat with KOA, so that the spontaneous pain during the synovial inflammatory response stage and allodynia at the later stage are relieved.

[Visualization of research in treatment of vascular dementia by CiteSpace].

In light of the tremendous number of patients with vascular dementia in China, it is of great significance for the treatment of this disease to summarize related research focuses. In this study, articles on the treatment of vascular dementia, which were included in CNKI and Web of Science from January 1, 2012 to December 31, 2021, were analyzed. Specifically, CiteSpace 5.7.R2 was employed to visualize nationalities of authors, author affiliations, authors, keywords, and journals, and dissect the status quo and trend of research on the treatment of this disease. On this basis, the research focuses and evolution were elucidated. The findings are expected to serve as reference for the future research. Finally, 2 579 Chinese articles and 453 English articles were included. The annual number of published articles showed an upward trend. Authors from China published most papers and England had the highest centrality value. HU Yue-qiang and LIU Cun-zhi respectively published the most Chinese and English articles. Guangxi University of Chinese Medicine and Capital Medical University respectively topped the author affiliations in the number of published Chinese and English articles. Among the English journals, Anal Biochem and Stroke separately boasted the highest centrality value and the highest cited frequency. The analysis of keywords in the Chinese articles suggested that most studies on the treatment of vascular dementia focused on the observation of patients' mobility after treatment. Moreover, as for the therapeutic method, western medicine, as well as the Chinese medicine and acupuncture frequently attracted the attention of scholars. Basic research highlighted the oxidative stress, angiogenesis, and apoptosis. According to the analysis result of keywords in English articles on treatment of vascular dementia, the focus was the improvement of the memory function of patients with vascular dementia. As to the therapeutic method, drug therapy was frequently studied compared with other methods. The basic research focused on autophagy, nerve regeneration, and oxidative stress. This study concludes that the future research trend might be the combination of Chinese and western medicine in the treatment of vascular dementia.

Iron-catalyzed regioselective synthesis of (E)-vinyl sulfones mediated by unprotected hydroxylamines.

An Fe-catalyzed unprotected hydroxylamine mediated Heck-type coupling between sulfinic acids and alkenes for the regioselective synthesis of (E)-vinyl sulfones has been developed. Mechanism studies indicated for the first time that a radical process may be involved and that hydroxylamines play multiple roles, including those of a mild oxidant and an in situ base. It was found for the first time that this transformation not only realizes C-S bond construction promoted by unprotected hydroxylamines, but also provides a practical and complementary method for the preparation of structurally important (E)-vinyl sulfones.

Dietary supplementation of probiotics fermented Chinese herbal medicine Sanguisorba officinalis cultures enhanced immune response and disease resistance of crucian carp (Carassius auratus) against Aeromonas hydrophila.

Aeromonas hydrophila, a Gram-negative bacterium, is one of the major pathogens causing bacterial sepsis in aquatic animals due to drug resistance and pathogenicity, which could cause high mortality and serious economic losses to the aquaculture. Sanguisorba officinalis (called DiYu in Chinese, DY) is well known as herbal medicine, which could inhibit the growth of pathogenic bacteria, hemostasis and regulate the immune response. Moreover, the active ingredients in DY could remarkably reduce drug resistance. In this study, we investigated the effects of probiotic fermentation cultures on A. hydrophila through in vitro and in vivo experiments. Three lactic acid bacteria, including Lactobacillus rhamnosus (LGG), Lactobacillus casei (LC) and Lactobacillus plantarum (LP), were selected to ferment the Chinese herbal medicine DY. The assays of antagonism showed that all three fermented cultures could influence the ability of A. hydrophila growth, among which L. rhamnosus fermented DY cultures appeared to be the strongest inhibitory effect. In addition, the biofilm determination revealed that L. rhamnosus fermented DY cultures could significantly inhibit the biofilm formation of A. hydrophila compared to the other groups. Furthermore, protease, lecithinase and urease activities were found in the three fermentation cultures. Three probiotics fermented DY cultures were orally administration with crucian carp to evaluate the growth performance, immunological parameters and pathogen resistance. The results showed that the three fermentation cultures could promote the growth performance of crucian carp, and the immunoglobulins, antioxidant-related enzymes and immune-related genes were significantly enhanced. Besides, the results showed that crucian carp received L. rhamnosus (60.87%), L. casei (56.09%) and L. plantarum (41.46%) fermented DY cultures had higher survival rates compared with the control group after infection with A. hydrophila. Meanwhile, the pathological tissue results revealed that the probiotic fermented cultures could largely improve the tissues damage caused by the pathogenic bacteria. In conclusion, this study proved that the fermentation cultures of three probiotics could effectively inhibit the growth of A. hydrophila, regulate the level of immune response and improve the survival rate against A. hydrophila in crucian carp. The present data suggest that probiotic fermented Sanguisorba officinalis act as a potential gut-targeted therapy regimens to protecting fish from pathogenic bacteria infection.

Substrates, Plants, and Their Combinations for Water Purification of Urban Household Aquaponics Systems.

To make full use of urban household balcony space, an urban aquaponics system for balconies was constructed to investigate the purification effects of four different substrates (volcanic stone, ceramic pellets, ceramic rings, and nanorods) and six plants (mung bean sprouts, hollow cabbage, water celery, lettuce, leek, and water chestnut) on fish culture wastewater. Through the determination of contaminants such as nitrogen and phosphorus and through the use of 16SrDNA sequencing technology, the substrate material and plant combinations with the best purification effects were screened. The results show that volcanic stone and nanorods have strong purification capacities. Compared to the other substrate types, there were more unique bacterial species on the surface of volcanic stone, among which amoeba species were the most dominant (92.42%). Among the six tested plant species, mung bean sprouts had the highest contribution to nitrogen uptake (94.96%), and water chestnut had the highest contribution to phosphorus uptake at 12.07%. Finally, the combination of nanorods and water celery was the best at purifying the wastewater. This study provides a theoretical basis and new ideas for the construction of urban aquaponics systems on balconies, which will help to achieve green farming and the efficient utilization of water resources.