[Prediction analysis of quality markers and resource evaluation of Artemisiae Argyi Folium based on chemical composition and network pharmacology].

This study is based on ultra-high-performance liquid chromatography(UPLC), gas chromatography-mass spectrometry(GC-MS), and network pharmacology methods to analyze and predict potential quality markers(Q-markers) of Artemisiae Argyi Folium. First, UPLC and GC-MS techniques were used to analyze the content of 12 non-volatile components and 8 volatile components in the leaves of 33 Artemisia argyi germplasm resources as candidate Q-markers. Subsequently, network pharmacology was employed to construct a "component-target-pathway-efficacy" network to screen out core Q-markers, and the biological activity of the markers was validated using molecular docking. Finally, cluster analysis and principal component analysis were performed on the content of Q-markers in the 33 A. argyi germplasm resources. The results showed that 18 candidate components, 60 targets, and 185 relationships were identified, which were associated with 72 pathways related to the treatment of 11 diseases and exhibited 5 other effects. Based on the combination of freedom and component specificity, six components, including eupatilin, cineole, ß-caryophyllene, dinatin, jaceosidin, and caryophyllene oxide were selected as potential Q-markers for Artemisiae Argyi Folium. According to the content of these six markers, cluster analysis divided the 33 A. argyi germplasm resources into three groups, and principal component analysis identified S14 as having the highest overall quality. This study provides a reference for exploring Q-markers of Artemisiae Argyi Folium, establishing a quality evaluation system, further studying its pharmacological mechanisms, and breeding new varieties.

[Protective effect of Liujing Toutong Tablets on rats with permanent cerebral ischemia via NF-κB signaling pathway].

This study investigated the neuroprotective effects and underlying mechanism of Liujing Toutong Tablets(LJTT) on a rat model of permanent middle cerebral artery occlusion(pMCAO). The pMCAO model was established using the suture method. Eighty-four male SPF-grade SD rats were randomly divided into a sham operation group, a model group, a nimodipine group(0.020 g·kg~(-1)), and high-, medium-, and low-dose LJTT groups(2.8, 1.4, and 0.7 g·kg~(-1)). The Longa score, adhesive removal test and laser speckle contrast imaging technique were used to evaluate the degree of neurological functional impairment and changes in local cerebral blood flow. The survival and mortality of rats in each group were recorded daily. After seven days of continuous administration following the model induction, the rats in each group were euthanized, and brain tissue and blood samples were collected for corresponding parameter measurements. Nissl staining was used to examine pathological changes in brain tissue neurons. The levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), IL-1ß, vascular endothelial growth factor(VEGF), calcitonin gene-related peptide(CGRP), beta-endorphin(ß-EP), and endogenous nitric oxide(NO) in rat serum were measured using specific assay kits. The entropy weight method was used to analyze the weights of various indicators. The protein expression levels of nuclear factor kappa-B(NF-κB), inhibitor kappaB alpha(IκBα), phosphorylated IκBα(p-IκBα), and phosphorylated inhibitor of NF-κB kinase alpha(p-IKKα) in brain tissue were determined using Western blot. Immunohistochemistry was used to detect the protein expression of chemokine-like factor 1(CKLF1) and C-C chemokine receptor 5(CCR5) in rat brain tissue. Compared with the sham operation group, the model group showed significantly higher neurological functional impairment scores, prolonged adhesive removal time, decreased cerebral blood flow, increased neuronal damage, reduced survival rate, significantly increased levels of TNF-α, IL-1ß, IL-6, CGRP, and NO in serum, significantly decreased levels of VEGF and ß-EP, significantly increased expression levels of NF-κB p65, p-IκBα/IκBα, and p-IKKα in rat brain tissue, and significantly upregulated protein expression of CKLF1 and CCR5. Compared with the model group, the high-dose LJTT group significantly improved the neurological functional score of pMCAO rats after oral administration for 7 days. LJTT at all doses significantly reduced adhesive removal time and restored cerebral blood flow. The high-and medium-dose LJTT groups significantly improved neuronal damage. The LJTT groups at all doses showed reduced levels of TNF-α, IL-1ß, IL-6, CGRP, and NO in rat serum, increased VEGF and ß-EP levels, and significantly decreased expression levels of NF-κB p65, p-IκBα/IκBα, p-IKKα, and CCR5 protein in rat brain tissue. The entropy weight analysis revealed that CGRP and ß-EP were significantly affected during the model induction, and LJTT exhibited a strong effect in reducing the release of inflammatory factors such as TNF-α and IL-1ß. LJTT may exert a neuroprotective effect on rats with permanent cerebral ischemia by reducing neuroinflammatory damage, and its mechanism may be related to the inhibition of the NF-κB signaling pathway and the regulation of the CKLF1/CCR5 axis. Additionally, LJTT may exert certain analgesic effects by reducing CGRP and NO levels and increasing ß-EP levels.

[Distinguishing between Artemisia stolonifera and A. argyi by specific PCR of leaves and non-glandular trichomes].

Artemisia stolonifera is a relative of A. argyi. The two species are difficult to be distinguished due to the similarity in leaf shape and have even less distinctive features after processing. This study aims to establish a method to quickly distinguish between them. At the same time, we examined the reasonability and applicability of the specific polymerase chain reaction(PCR) method. The C/T single nucleotide polymorphism was detected at the position 202 of the sequence, based on which specific primers were designed to identify these two species. The PCR with the specific primer JNC-F and the universal primer ITS3R produced a specific band at 218 bp for A. argyi and no band for A. stolonifera, which can be used to detect at least 3% of A. argyi samples mixed in A. stolonifera samples. The PCR with the specific primer KY-F and the universal primer ITS3R produced a specific band at 218 bp for A. stolonifera and no band for A. argyi, which can be used to detect at least 5% of A. stolonifera samples mixed with A. argyi. The limit of detection of the established method was 5 ng DNA. The established PCR method can accurately distinguish between A. stolonifera and A. argyi, which provides an experimental basis for the quality control of A. stolonifera and determines whether the herbs are adulterated.

Moxibustion attenuates liver metastasis of colorectal cancer by regulating gut microbial dysbiosis.

The liver metastasis is the primary factor attributing to the poor prognosis of colorectal cancer (CRC). Moxibustion has been used clinically against multiple malignancies. In this study, we explored the safety, efficacy, and the potential functional mechanisms of moxibustion in modulating the liver metastasis of CRC by using GFP-HCT116 cells-derived CRC liver metastasis model in Balb/c nude mice. The tumor bearing mice were randomly divided into model control and treatment groups. Moxibustion was applied to the BL18 and ST36 acupoints. CRC liver metastasis was measured by fluorescence imaging. Furthermore, feces from all mice were collected, and 16S rRNA analysis was used to assess their microbial diversity, which was analyzed for its correlation with liver metastasis. Our results indicated that the liver metastasis rate was decreased significantly by moxibustion treatment. Moxibustion treatment also caused statistically significant changes in the gut microbe population, suggesting that moxibustion reshaped the imbalanced gut microbiota in the CRC liver metastasis mice. Therefore, our findings provide new insights into the host-microbe crosstalk during CRC liver metastasis and suggest moxibustion could inhibit CRC liver metastasis by remolding the structure of destructed gut microbiota community. Moxibustion may serve as a complementary and alternative therapy for the treatment of patients with CRC liver metastasis.

Acupuncture-Neuroimaging Research Trends over Past Two Decades: A Bibliometric Analysis.

OBJECTIVE: To identify topics attracting growing research attention as well as frontier trends of acupuncture-neuroimaging research over the past two decades. METHODS: This paper reviewed data in the published literature on acupuncture neuroimaging from 2000 to 2020, which was retrieved from the Web of Science database. CiteSpace was used to analyze the publication years, countries, institutions, authors, keywords, co-citation of authors, journals, and references. RESULTS: A total of 981 publications were included in the final review. The number of publications has increased in the recent 20 years accompanied by some fluctuations. Notably, the most productive country was China, while Harvard University ranked first among institutions in this field. The most productive author was Tian J with the highest number of articles (50), whereas the most co-cited author was Hui KKS (325). Evidence-Based Complementary and Alternative Medicine (92) was the most prolific journal, while Neuroimage was the most co-cited journal (538). An article written by Hui KKS (2005) exhibited the highest co-citation number (112). The keywords "acupuncture" (475) and "electroacupuncture" (0.10) had the highest frequency and centrality, respectively. Functional magnetic resonance imaging (fMRI) ranked first with the highest citation burst (6.76). CONCLUSION: The most active research topics in the field of acupuncture-neuroimaging over the past two decades included research type, acupoint specificity, neuroimaging methods, brain regions, acupuncture modality, acupoint specificity, diseases and symptoms treated, and research type. Whilst research frontier topics were "nerve regeneration", "functional connectivity", "neural regeneration", "brain network", "fMRI" and "manual acupuncture".

[Effect of acupuncture on hypothalamic functional connectivity in patients with premature ova-rian insufficiency based on resting-state functional magnetic resonance imaging].

OBJECTIVE: To compare the differences in functional connectivity(FC) between the hypothalamus and whole brain regions in patients with premature ovarian insufficiency (POI) and healthy volunteers based on resting-state functional magnetic resonance imaging (rs-fMRI) and investigate the mechanism of acupuncture on treatment of POI. METHODS: Twelve POI patients were recruited to the acupuncture group and 12 healthy volunteers to the control group. Patients in the acupuncture group received acupuncture at two groups of acupoints alternatively, including Baihui (GV20), Zhongwan (CV12), Shenting (GV24), Shenshu (BL23), Ciliao（BL32） and so on, 30 min once time, 3 times per week for 12 weeks. The state of patients was evaluated by modified Kupperman Index (KI) and self-rating anxiety scale (SAS). Follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and anti-mullerian hormone (AMH) were tested by microparticle-based chemiluminescence. B ultrasonography was used to detect the antral follicle count (AFC). Meanwhile, POI patients and healthy volunteers underwent the rs-fMRI examination before and after acupuncture treatment and after enrollment, respectively. With hypothalamus as the region of interest, the differences in FC between the hypothalamus and other brain regions in POI patients and healthy volunteers and the changes of FC between the hypothalamus and whole brain regions in POI patients before and after acupuncture were observed. RESULTS: The SAS and KI scores of pre-treatment POI patients were higher than those in the control group （P<0.01）.In compa-rison with those pre-treatment, FSH, LH, and SAS and KI scores of POI patients decreased after treatment, while AFC increased (P<0.05). Compared with the control group, the FC of the left hypothalamus with left central sulcus, right middle occipital gyrus, and left paracentral lobule increased, but decreased with left globus pallidus of the lenticular nucleus in POI patients. Furthermore, the FC of the right hypothalamus with the left hippocampus, the left para-central lobule, and the right central sulcus increased, while the FC between the right hypothalamus and the right superior frontal gyrus decreased (P<0.05). For the acupuncture group, compared with the conditions before treatment, the FC of the right hypothalamus with the left inferior frontal gyrus, the left insula, and right inferior frontal gyrus was strengthened, but weakened with the left gyrus rectus (P<0.05). CONCLUSION: The abnormal FC between the hypothalamus and whole brain regions may be one of the central pathological factors of POI. Acupuncture can improve the ovarian function and clinical symptoms of patients with POI, which may be related to its effect in regulating the FC between the hypothalamus and multiple brain regions.

Electroacupuncture Attenuates Post-Inflammatory IBS-Associated Visceral and Somatic Hypersensitivity and Correlates With the Regulatory Mechanism of Epac1-Piezo2 Axis.

Electroacupuncture (EA) is considered to have a therapeutic effect in the relief of irritable bowel syndrome (IBS)-associated visceral hypersensitivity via the reduction of the level of 5-hydroxytryptamine (5-HT) and 5-HT3 receptors (5-HT3R). However, whether Epac1/Piezo2, as the upstream of 5-HT, is involved in this process remains unclear. We investigated whether EA at the ST36 and ST37 acupoints alleviated visceral and somatic hypersensitivity in a post-inflammatory IBS (PI-IBS) model mice via the Epac1-Piezo2 axis. In this study, we used 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced PI-IBS as a mouse model. Visceral sensitivity was assessed by the abdominal withdrawal reflex test. Somatic sensitivity was evaluated by the hind paw withdrawal threshold. Quantitative real-time PCR, immunofluorescence staining, ELISA, and Western blotting were performed to examine the expressions of Epac1, Piezo2, 5-HT, and 5-HT3R from the mouse distal colon/L5-S2 dorsal root ganglia (DRG). Our results showed that EA improved the increased visceral sensation and peripheral mechanical hyperalgesia in PI-IBS model mice, and the effects of EA were superior to the sham EA. EA significantly decreased the protein and mRNA levels of Epac1 and Piezo2, and reduced 5-HT and 5-HT3R expressions in the distal colon. Knockdown of colonic Piezo2 eliminated the effect of EA on somatic hypersensitivity. Combined knockdown of colonic Epac1 and Piezo2 synergized with EA in relieving visceral hypersensitivity and blocked the effect of EA on somatic hypersensitivity. Additionally, protein levels of Epac1 and Piezo2 were also found to be decreased in the L5-S2 DRGs after EA treatment. Taken together, our study suggested that EA at ST36 and ST37 can alleviate visceral and somatic hypersensitivity in PI-IBS model mice, which is closely related to the regulation of the Epac1-Piezo2 axis.

[Assessment of soil fertility in Artemisia argyi planting areas in Qichun county based on minimum data set].

This study aims to explore the soil fertility in the main Artemisia argyi planting areas in Qichun county.To be specific, the soil physical and chemical properties in the main planting areas of A.argyi in Qichun county were analyzed.On this basis, 12 indexes were selected for principal component analysis(PCA) which was then combined with the norm value of each index and the correlation coefficients between the indexes to establish the minimum data set(MDS).The radar map was plotted to directly demonstrate the level of each index and the comprehensive level of the sampling sites.The comprehensive index model was used to calculate the soil fertility quality index(SFQI) of the total data set(TDS) and MDS(SFQI-TDS and SFQI-MDS, respectively), and linear regression of the two was performed.The results showed that the indexes that made up the MDS for soil fertility evaluation were pH, available potas-sium, available iron, available zinc, available manganese, available copper, and available magnesium.The radar map suggested the greatest difference in soil organic matter and smallest difference in available nitrogen among the 14 sampling sites.Moreover, the overall content of available phosphorus and available iron was high, while that of available nitrogen was the lowest.The SFQI-MDS which was yielded based on the weight of each index in MDS calculated with the norm value was more sensitive and the SFQI had stronger correlation with TDS-SFQI, which can better represent TDS-SFQI.SFQI-MDS was in the range of 0.298-0.784, with the average of 0.565 and variation coefficient of 18.38%.Caohe Town had the highest average SFQI-MDS.Clustering of SFQI-MDS value suggested that the soil fertility can be classified into 4 levels: level Ⅰ(SFQI ≥ 0.677) indicated excellent soil fertility, which accounted for 11.24%(mainly in Qingshi town, Balihu, and Zhangbang town); level Ⅱ(0.571≤SFQI≤0.680) meant good fertility, which made up 43.82%(mainly in Caohe town, Hengche town, and Pengsi town); level Ⅲ(0.466≤SFQI≤0.557) indicated average fertility, which took up 32.58%(mainly in Chidong town and Zhulin town); level Ⅳ(SFQI≤0.421) suggested poor fertility, which accounted for 12.36%(mainly in Guanyao town).It is recommended that nitrogen, potassium, magnesium, and calcium fertilizers should be increased and organic ferti-lizer should be applied for the cultivation of A.argyi in Qichun county to improve soil fertility and soil physical and chemical properties.

UPLC-MS/MS method for the determination of the herb composition of Tangshen formula and the in vivo pharmacokinetics of its metabolites in rat plasma.

INTRODUCTION: Tangshen formula (TSF) is a traditional Chinese medicine composed of seven medicinal herbs including Astragalus membranaceus, Rehmannia glutinosa Libosch, Citrus aurantium L., etc. which is used to treat diabetic nephropathy III, IV qi and yin deficiency and stasis syndrome. Most of the studies on TSF are pharmacological and pharmacodynamic experiments. There are few basic studies on its chemical substances, and the effective constituents are not clear. OBJECTIVE: To analyse the main chemical components of TSF and the absorbed components in rat plasma following oral administration based on liquid chromatography tandem mass spectrometry (LC-MS/MS). Moreover, providing a rapid and valid analytical strategy for simultaneous determination of six components in rat plasma and use it in pharmacokinetic studies. RESULTS: A total of 132 components were identified in TSF, and 44 components were identified in rat plasma after oral TSF, 35 of which were prototype components and nine were metabolic components. A sensitive and reliable LC-MS/MS method was developed for simultaneous determination of six components in rat plasma. The intra-day and inter-day precision relative standard deviation (RSD) was lower than 15%; the accuracy of low, medium and high concentrations ranged from 80% to 120%. The recovery met the requirements and the RSD of the recoveries was less than 15%. CONCLUSION: A total of 132 components were identified in TSF. The LC-MS/MS quantitative method for the simultaneous determination of morroniside, loganin, notoginsenoside R1 , ginsenoside Re, ginsenoside Rb1 and astragaloside IV in rat plasma was established for the first time. The pharmacokinetic parameters are clarified, which can guide the clinical medication of TSF.

A Network Pharmacology Approach to Explore the Mechanism of HuangZhi YiShen Capsule for Treatment of Diabetic Kidney Disease.

BACKGROUND AND OBJECTIVE: HuangZhi YiShen Capsule (HZYS) is a Chinese patent herbal drug that protects kidney function in diabetic kidney disease (DKD) patients. However, the pharmacologic mechanisms of HZYS remain unclear. This study would use network pharmacology to explore the pharmacologic mechanisms of HZYS. METHODS: Chemical constituents of HZYS were obtained through the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and literature search. Potential targets of HZYS were identified by using the TCMSP and the SwissTarget Prediction databases. DKD-related target genes were collected by using the Online Mendelian Inheritance in Man, Therapeutic Target Database, GeneCards, DisGeNET, and Drugbank databases. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out to further explore the mechanisms of HZYS in treating DKD. Molecular docking was conducted to verify the potential interactions between the prime compounds and the hub genes. RESULTS: 179 active compounds and 620 target genes were obtained, and 571 common targets were considered potential therapeutic targets. The top 10 main active compounds of HZYS were heparin, quercetin, kaempferol, luteolin, methyl14-methylpentadecanoate, methyl (Z)-11-hexadecenoate, 17-hydroxycorticosterone, 4-pregnene-17α, 20ß, 21-triol-3, 11-dione, wogonin, and hydroxyecdysone. Hub signaling pathways by which HZYS treating DKD were PI3K-Akt, MAPK, AGE-RAGE in diabetic complications, TNF, and apoptosis. The top 10 target genes associated with these pathways were IL6, MAPK1, AKT1, RELA, BCL2, JUN, MAPK3, MAP2K1, CASP3, and TNF. Quercetin and Luteolin were verified to have good binding capability with the hub potential targets IL6, MAPK1, AKT1 through molecular docking. CONCLUSION: HZYS appeared to treat DKD by regulating the inflammatory, oxidative stress, apoptotic, and fibrosis signaling pathways. This study provided a novel perspective for further research of HZYS.

[Effect of cotton-moxibustion on chronic eczema and quality of life].

OBJECTIVE: To compare the therapeutic effect between cotton-moxibustion and compound flumetasone ointment, and observe the effect on quality of life in patients with chronic eczema. METHODS: A total of 66 patients with chronic eczema were randomized into an observation group (33 cases, 2 cases dropped off) and a control group (33 cases, 2 cases dropped off). In the observation group, cotton-moxibustion was adopted on target skin lesion, once a day, 3 cones a time. In the control group, external application of compound flumetasone ointment was given twice a day. The treatment for 3 weeks was required in the both groups. Before treatment and 1,2,3 weeks into treatment, scores of visual analogue scale (VAS), eczema area and severity index (EASI) and dermatology life quality index (DLQI) were observed, and the recurrence rate was evaluated in the follow-up one month after treatment. RESULTS: Compared before treatment, the VAS scores of 1,2,3 weeks into treatment, the EASI and DLQI scores of 2,3 weeks into treatment were decreased in the both groups (P<0.05), and those in the observation group were lower than the control group (P<0.05). The follow-up recurrence rate in the observation group were lower than the control group (P<0.05). CONCLUSION: Cotton-moxibustion can effectively improve the pruritus symptom, skin lesion and quality of life in the patients with chronic eczema, the therapeutic effect is superior to the external application of compound flumetasone ointment.

Magnetism and NIR dual-response polypyrrole-coated Fe3O4 nanoparticles for bacteria removal and inactivation.

Microbial contamination of water represents a great threat to the public health that has attracted worldwide attention. In this work, polypyrrole magnetic nanoparticles (Fe3O4@PPy NPs) with sterilization properties were fabricated. More specifically, the Fe3O4@PPy NPs obtained via aqueous dispersion polymerization and an in situ chemical oxidative polymerization exhibited a cationic surface and high photothermal conversion efficiency. More than 50% of bacteria adsorption can be achieved at a dosage of 100 µg/mL Fe3O4@PPy NPs under magnetic field, and high photothermal sterilization efficacy (~100%) can be obtained upon NIR exposure at the same dosage for 10 min. Noteworthy, the Fe3O4@PPy NPs can be recycled by magnetism and reused without affecting their photothermal sterilization capability. This study clearly provides experimental evidence of the great potential of Fe3O4@PPy NPs as stable and reusable nanocomposite materials for bacteria adsorption and photothermal sterilization performance. The application of Fe3O4@PPy NPs can realize enviromental-friendly bacterial contaminated water treatment as well as provide stratgies for synergistical antibacterial materials design.

Total flavonoids of Astragalus Ameliorated Bile Acid Metabolism Dysfunction in Diabetes Mellitus.

Astragalus Radix is one of the common traditional Chinese medicines used to treat diabetes. However, the underlying mechanism is not fully understood. Flavones are a class of active components that have been reported to exert various activities. Existing evidence suggests that flavones from Astragalus Radix may be pivotal in modulating progression of diabetes. In this study, total flavones from Astragalus Radix (TFA) were studied to observe its effects on metabolism of bile acids both in vivo and in vitro. C57BL/6J mice were treated with STZ and high-fat feeding to construct diabetic model, and HepG2 cell line was applied to investigate the influence of TFA on liver cells. We found a serious disturbance of bile acids and lipid metabolism in diabetic mice, and oral administration or cell incubation with TFA significantly reduced the production of total cholesterol (TCHO), total triglyceride, glutamic oxalacetic transaminase (AST), glutamic-pyruvic transaminase (ALT), and low-density lipoprotein (LDL-C), while it increased the level of high-density lipoprotein (HDL-C). The expression of glucose transporter 2 (GLUT2) and cholesterol 7α-hydroxylase (CYP7A1) was significantly upregulated on TFA treatment, and FXR and TGR5 play pivotal role in modulating bile acid and lipid metabolism. This study supplied a novel understanding towards the mechanism of Astragalus Radix on controlling diabetes.

[Mind-regulating and spleen-strengthening needling technique improves abdominal hypersensitivity and emotion by enhancing functional connectivity between hippocampus and brain regions in diarrhea-predominant irritable bowel syndrome patients].

OBJECTIVE: To compare the difference of brain functional connectivity between diarrhea-predominant irritable bowel syndrome (IBS-D) patients and healthy volunteers and changes after acupuncture intervention, so as to investigate the underlying mechanism of acupuncture in regulating functional activities of IBS-D patients by using seed point correlation analysis. METHODS: A total of 25 IBS-D patients and 25 healthy volunteers were recruited in the present study and respectively attributed to acupuncture group and control group. The IBS-D patients received manual acupuncture stimulation of Baihui (GV20), Yintang (EX-HN3), and bilateral Tianshu (ST25), Zusanli (ST36), Shangjuxu (ST37), Sanyinjiao (SP6) and Taichong (LR3) with mind-regulating and spleen-strengthening technique for 30 min, once a day, 3 days a week for 6 weeks. Before and after the intervention, the IBS symptom severity scale (IBS-SSS) was used to assess the patients' state of abdominal pain, distention and defecation, and Hamilton Anxiety Rating Scale (HAMA) employed to evaluate the patients' anxiety severity. The resting state functional magnetic resonance imaging (rs-fMRI) data were acquired and preprocessed by using SPM8 and DPARSE soft-wares. Seeds (bilate-ral hippocampus regions) to whole-brain analysis was performed to obtain the mean time series of the left and right seed regions, followed by making Pearson correlation analysis to obtain the correlation coefficient (time series from each seed region with the rest of the voxels in the brain), and making a multivariate comparative correction to get data of functional connectivity (FC) of bilateral hippocampus regions and to find the related difference in the brain regions. Then, the differences of the FC of brain regions between IBS-D patients and healthy volunteers were compared. RESULTS: Following acupuncture treatment, both the HAMA and IBS-SSS scores were significantly reduced in the acupuncture group compared with its pre-treatment (P<0.01). Compared with the healthy volunteers, there were a reduction in the functional connectivity between the left hippocampus seed region and the right inferior temporal gyrus, left fusiform gyrus and left superior gyrus, and between the right hippocampus region and the right fusiform gyrus, left inferior temporal gyrus, left inferior occipital gyrus, left rectus gyrus, left insula, left precuneus, right angular gyrus, left middle occipital gyrus, right precuneus, and the left superior temporal gyrus, and an increase in the FC between the left hippocampus and left superior temporal gyrus was increased in ISB-D patients. Self-comparison showed that after the treatment, the FC was increased between the left hippocampus seed region and the right inferior temporal gyrus, left fusiform gyrus, bilateral lingual gyrus, left amygdala, right inferior occipital gyrus, right insula, right middle frontal gyrus, left middle frontal gyrus and the left middle occipital gyrus; and between the right hippocampus seed region and the posterior inferior cerebellar lobe, left inferior temporal gyrus, left suboccipital gyrus, right fusiform gyrus, left insula, right inferior frontal gyrus, left superior temporal gyrus, left middle occipital gyrus, right middle frontal gyrus, left supplementary motor area and right supplementary motor area, and decreased between the left hippocampus region and the left anterior cingulate, paracingulate gyrus and the right posterior central gyrus in IBS-D patients. CONCLUSION: Mind-regulating and spleen-strengthening acupuncture intervention may improve the abdominal pain and distension and emotional state in IBS-D patients, which is possibly associated with its effect in enhancing FC between the hippocampus and brain regions.

A Review of Traditional Chinese Medicine in Treating Renal Interstitial Fibrosis via Endoplasmic Reticulum Stress-Mediated Apoptosis.

Renal interstitial fibrosis (RIF) is the main pathological manifestation of end-stage renal disease. Recent studies have shown that endoplasmic reticulum (ER) stress is involved in the pathogenesis and development of RIF. Traditional Chinese medicine (TCM), as an effective treatment for kidney diseases, can improve kidney damage by affecting the apoptotic signaling pathway mediated by ER stress. This article reviews the apoptotic pathways mediated by ER stress, including the three major signaling pathways of unfolded protein response, the main functions of the transcription factor C/EBP homologous protein. We also present current research on TCM treatment of RIF, focusing on medicines that regulate ER stress. A new understanding of using TCM to treat kidney disease by regulating ER stress will promote clinical application of Chinese medicine and discovery of new drugs for the treatment of RIF.

Fu-Fang-Jin-Qian-Cao herbal granules protect against the calcium oxalate-induced renal EMT by inhibiting the TGF-ß/smad pathway.

CONTEXT: Nephrolithiasis is a major public health problem worldwide and Fu-Fang-Jin-Qian-Cao granules (FFJQC) is a traditional Chinese herbal formula that is used to treat nephrolithiasis. The main component of nephrolithiasis is calcium oxalate (CaOx) and the epithelial-mesenchymal transition (EMT) shown to play a crucial role in CaOx-induced kidney injury. However, the mechanism underlying the therapeutic effect of FFJQC on the CaOx-induced renal EMT is unknown. OBJECTIVE: This study explores the therapeutic benefits and mechanism of FFJQC in oxalate-induced kidney injury. MATERIALS AND METHODS: 60 male C57BL/6 mice were used in this experiment and divided into 6 groups. A mouse kidney stone model was created by intraperitoneal injection of glyoxylate at a dose of 100 mg/kg for 6 days. The standardized FFJQC was used to treat mouse crystal kidney injury by gavage at 1.35 and 2.7 g/kg, respectively. Western blotting and immunostaining for E-cadherin, cytokeratin 18 (CK18), vimentin, smooth muscle α-actin (α-SMA) and transforming growth factor ß (TGF-ß)/Smad pathway were conducted on renal tissues. RESULTS: Following CaOx-induced kidney injury, the levels of E-cadherin and CK18 in kidney decreased, while vimentin and α-SMA levels increased. The FFJQC treatment increased the levels of E-cadherin and CK18 and decreased vimentin and α-SMA levels in varying degrees. What's more, the FFJQC reduced the expression of CaOx-induced fibrosis marker collagen II. CONCLUSION: FFJQC alleviated the CaOx-induced renal EMT and fibrosis by regulating TGF-ß/smad pathway. Therefore, the FFJQC is an important traditional Chinese medicine for the treatment of CaOx-induced renal injury and fibrosis.

[Professor SHENG Can-ruo's academic thoughts and acupoint selection experience for hot flashes].

Professor SHENG Can-ruo is a well-known national veteran doctor with over 70 years of clinical experience. He has unique academic thoughts and clinical experience for common diseases and some difficult and complicated diseases. This paper mainly introduces professor SHENG 's syndrome-differentiation thought and experience of acupoint selection for hot flashes. It is emphasized that common hot flashes, such as hot flashes and night sweats, are different between yin and yang. While regulating yin and yang, more attention should be paid to ying-wei harmony, which is not only suitable for women's perimenopausal syndrome, but also for a series of clinical diseases caused by refractory drugs such as endocrine therapy after breast cancer surgery. At the same time of acupoint selection based on syndrome differentiation, a more rational prescriptions should be made according to the duration of the disease and the experience acupoints to improve the clinical efficacy.

Sodium Butyrate Improves Liver Glycogen Metabolism in Type 2 Diabetes Mellitus.

Liver plays a central role in modulating blood glucose level. Our most recent findings suggested that supplementation with microbiota metabolite sodium butyrate (NaB) could ameliorate progression of type 2 diabetes mellitus (T2DM) and decrease blood HbA1c in db/db mice. To further investigate the role of butyrate in homeostasis of blood glucose and glycogen metabolism, we carried out the present study. In db/db mice, we found significant hypertrophy and steatosis in hepatic lobules accompanied by reduced glycogen storage, and expression of GPR43 was significantly decreased by 59.38 ± 3.33%; NaB administration significantly increased NaB receptor G-protein coupled receptor 43 (GPR43) level and increased glycogen storage in both mice and HepG2 cells. Glucose transporter 2 (GLUT2) and sodium-glucose cotransporter 1 (SGLT1) on cell membrane were upregulated by NaB. The activation of intracellular signaling Protein kinase B (PKB), also known as AKT, was inhibited while glycogen synthase kinase 3 (GSK3) was activated by NaB in both in vivo and in vitro studies. The present study demonstrated that microbiota metabolite NaB possessed beneficial effects on preserving blood glucose homeostasis by promoting glycogen metabolism in liver cells, and the GPR43-AKT-GSK3 signaling pathway should contribute to this effect.

Screening bioactive components of Glycyrrhiza uralensis Fisch. with isolated perfused lung extraction and HPLC-ESI-MSn analysis.

The isolated perfused rat lung (IPL), coupled with high performance liquid chromatography\tandem mass spectrometry analysis (HPLC-ESI-MSn), has been developed as a tool for screening bioactive components in Glycyrrhiza uralensis Fisch. (GU). First, IPL was perfused with the water extract of GU (EGU), the bioactive components in the EGU would selectively combine to the receptors or channels of lung. By changing the pH of perfused solution, the combined components were eluated and then detected by HPLC-ESI-MSn. Four compounds were detected in the desorption eluate of IPL, among these compounds, liquiritin (1), ononin (2) and glycyrrhizic acid (4) were identified by comparing with the chromatography of the standards, while licorice-saponin G2 (3) were determined by analysis of the structure clearage characterization of mass spectrometry. Then, due to the lack of compound 3 sample, compounds 1, 2 and 4 with respective concentrations of 50 µM, 5 µM, 500 nM, 50 nM and 5 nM were applied to evaluate the protective effect of pulmonary epithelial cells (PEC, A549 cell) injury induced by lipopolysaccharide (LPS) for anti-inflammatory activity assessment. The results showed that except the 5 nM group of compound 1, 5 nM and 50 nM groups of compound 2, all other groups could remarkably inhibit the PEC injury (vs LPS group, 2-500 nM groups: p < 0.05; other groups: p < 0.01), all compound showed the dose-dependent effect. In conclusion, IPL coupled with HPLC-ESI-MSn was successfully used to screen the anti-inflammatory components of GU for the first time. The application of IPL coupled with HPLC-ESI-MSn for screening bioactive components of TCMs is rapid, convenient and reliable, and the isolated perfused technology could be extended to isolated heart, liver, kidney, and so on.

Isorhamnetin protects against hypoxia/reoxygenation-induced injure by attenuating apoptosis and oxidative stress in H9c2 cardiomyocytes.

To unveil the possible protective role of isorhamnetin, an immediate 3'-O-methylated metabolite of quercetin, in cardiomyocyte under hypoxia/reoxygenation (H/R) condition and the underlying mechanisms involved, H9c2 cardiomyocytes were exposed to the vehicle or H/R for 6 h (2 h of hypoxia following by 4 h of reoxygenation) with isorhamnetin (0, 3, 6, 12, 25, 50 µM for 4 h prior to H/R exposure). Apoptosis was evaluated by TUNEL staining, flow cytometry analysis and western blot assay for cleaved caspase-3. Myocardial injure in vivo was determined by infarct size using TTC staining, histological damage using H&E staining and myocardial apoptosis. Here, we found that isorhamnetin dose-dependently protected H9c2 cardiomyocytes against H/R-induced injure, as evidenced by the reduction in lactate dehydrogenase (LDH) levels, increases in cell viability, superoxide dismutase (SOD) and catalase (CAT) activity, with the maximal effects at 25 µΜ. In addition, isorhamnetin treatment significantly inhibited apoptosis in H/R-induced H9c2 cardiomyocytes and ameliorated H/R-induced myocardial injure in vivo, concomitant with the upregulation of sirtuin 1 (SIRT1) expression. Mechanism studies demonstrated that isorhamnetin pretreatment remarkably abolished H/R-induced downregulation of Nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expressions and upregulation of NADPH oxidase-2/4 (NOX-2/4) expressions in cardiomyocytes. However, SIRT1 inhibition (Sirtinol) not only inhibited isorhamnetin-induced Nrf2/HO-1 upregulation and NOX-2/4 downregulation, but also alleviated its anti-apoptotic effects. Taken together, these data indicate that isorhamnetin can exhibit positive effect on H/R-induced injure by attenuating apoptosis and oxidative stress in H9c2 cardiomyocytes, which is partly attributable to the upregulation of SIRT1 and Nrf2/HO-1-mediated antioxidant signaling pathway.