Effect of electroacupuncture on ventricular structure and function in rats with myocardial ischemia-reperfusion injury. / ç”µé’ˆå¯¹å¿ƒè‚Œç¼ºè¡€å†çŒæ³¨æŸä¼¤å¤§é¼ å¿ƒå®¤ç»“æž„å’ŒåŠŸèƒ½çš„å½±å“.

OBJECTIVES: To observe the effect of electroacupuncture (EA) on changes of ventricular structure and function in rats with myocardial ischemia-reperfusion injury (MIRI), so as to explore its potential mechanisms underlying improvement of ventricular remodeling after MIRI. METHODS: Forty male SD rats were randomly divided into 4 groups：sham operation group, model group, EA group and medication (sacubactril valsartan, LCZ696) group, with 10 rats in each group. The MIRI model was established by ligation of the left anterior descending coronary artery and reperfusion. EA (2 Hz/100 Hz, 2 mA) was applied to bilateral "Neiguan" (PC6) for 20 min, once every other day for 21 d. Rats of the medication group received gavage of LCZ696 (60 mg·kg-1·d-1). After the intervention, echocardiography was used to detect the ejection fraction (EF) and fractional shortening (FS) of the left ventricle, and the contents of serum tumor necrosis factor-α(TNF-α), vascular cell adhesion molecule-1(VCAM-1) and intercellular cell adhesion molecule-1(ICAM-1) were assayed by enzyme-linked immunosorbent assay. The pathological changes of myocardial tissue were observed after HE staining. The Masson staining was used to evaluate the myocardial collagen deposition and myocardial fibrosis. The mRNA expression levels of collagen Ⅰ and Ⅲ and connective tissue growth factor (CTGF) in the myocardial tissue were detected by quantitative real-time PCR, and the expression levels of IL-1ß and IL-18 were detected by Western blot. RESULTS: In contrast to the sham operation group, the EF and FS levels of the left ventricle were ob-viously decreased (P<0.001), while the contents of serum TNF-α, VCAM-1 and ICAM-1, the proportion of myocardial fibrosis area, the mRNA expression levels of myocardial collagen Ⅰ, collagen Ⅲ and CTGF, the expression levels of IL-1ß and IL-18 were significantly increased (P<0.001, P<0.000 1, P<0.05, P<0.01) in the model group. Compared with the model group, the EF and FS levels were remarkably increased (P<0.01), whereas the contents of serum TNF-α, VCAM-1 and ICAM-1, the proportion of myocardial fibrosis area, the mRNA expression levels of myocardial collagen Ⅰ, collagen Ⅲ and CTGF, and the expression levels of IL-1ß and IL-18 were significantly down-regulated (P<0.001, P<0.01, P<0.05) in both the medication and EA groups. No significant differences were found between the EA and medication groups in all the indexes mentioned above. CONCLUSIONS: EA can improve the left-ventricular fibrosis and function, delay or reverse ventricular remodeling in MIRI rats, which may be related to its functions in down-regulating myocardial inflammatory response and mRNA expression levels of myocardial collagen Ⅰ, collagen Ⅲ and CTGF.

Experimental study on radon retardation effect of modular covering floats in radon-containing water.

Radon-containing water bodies in uranium mining areas inevitably release radon gas, polluting the surrounding environment via radiation. Thus, it is particularly important to develop devices with the ability to retard the radon release from such water bodies. Based upon theories of radon exhalation in water, a radon exhalation retardation device (RERD) with flexible, modular floats (a flexible polyvinyl chloride material module that floats on water) was designed and manufactured. To study the modular surface-covering floats' effectiveness in retarding radon release from water surfaces, an experimental setup was constructed to simulate radon release from water bodies, using a granular uranium ore sample from a uranium mine as sediment material. Closed-loop measurements were taken to determine the radon exhalation rate on the exposed surface of the water in uncovered and covered conditions. Radon retardation rates were also compared for different area coverage (29.6%, 59.1%, and 88.7%) and immersion depths (0.02 m and 0.04 m) in unperturbed and perturbed water bodies. The results show that: 1) the greater the area coverage, the greater the radon retardation rate in both unperturbed and perturbed water bodies; 2) under the same coverage conditions, the surface radon exhalation rate and the radon transfer velocity at the gas-liquid interface of the perturbed water are larger than those of the unperturbed water; 3) The immersion depth of modular surface-covering floats has a stronger effect on the radon retardation rate in unperturbed water bodies than in perturbed water bodies. The study shows that the proposed modular floats are effective in retarding radon release from both perturbed and unperturbed water bodies.

Anthraquinone metabolites isolated from the rhizosphere soil Streptomyces of Panax notoginseng (Burk.) F. H. Chen target MMP2 to inhibit cancer cell migration.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax notoginseng (Burk.) F. H. Chen belongs to the Araliaceae family. It has been used by traditional Chinese people in Northeast Asia for centuries as an antidiabetic, antioxidant, antitumor agent, etc. Endophytic or rhizospheric microorganisms play key roles in plant defense mechanisms, and they are essential in the discovery of pharmaceuticals and valuable new secondary metabolites. In particular, endophytic or rhizospheric microorganisms of traditional medicinal plants. AIM OF THE STUDY: To discover valuable new secondary metabolites from rhizosphere soil Streptomyces sp. SYP-A7185 of P. notoginseng, and to explore potential bioactivities and targets of metabolites protrusive function. MATERIALS AND METHODS: The metabolites were obtained via column chromatography and identified by multiple spectroscopic analyses. The antitumor, antioxidant, antibacterial, and antiglycosidases effects of isolated metabolites were tested using 3-[4,5-dimethythiazol-2-yl]-2,5-diphenyltetazolium bromide (MTT), 2,2-diphenyl-1-picrylhydrazyl (DPPH), 96-well turbidimetric, and α-glucosidase inhibitory assays. The potential antitumor targets were predicted through network pharmacological approaches. The interactions between metabolites and target were verified by molecular docking and biolayer interferometry (BLI) assay. The effects of cancer cells migration were detected through wound healing assays in A549 and MCF-7. Other cellular validation experiments including reverse transcription-quantitative PCR (RT‒qPCR) and western blotting (WB) were used to confirm the hypothesis of network pharmacology. RESULTS: Five different chemotypes of anthraquinone derivatives (1-10), including six new compounds (3, 6-10), were identified from Streptomyces sp. SYP-A7185. Compounds 1-6 and 9 displayed moderate to strong cytotoxicity on five human cancer cell lines (A549, HepG2, MCF-7, MDA-MD-231, and MGC-803). Moreover, matrix metalloproteinase-2 (MMP2) were predicted as a potential antitumor target of metabolites 1-6 and 9 by comprehensive network pharmacology analysis. Later, BLI assays revealed strong intermolecular interactions between MMP2 and antitumor metabolites, and molecular docking results showed the interaction of metabolites 1-6 and 9 with MMP2 was dependent on the crucial amino acid residues of LEU-83, ALA-84, LEU-117, HIS-131, PRO-135, GLY-136, ALA-140, PRO-141, TYR-143, and THR-144. These results implied that metabolites (1-6 and 9) might inhibit cancer cell migration besides cancer cell proliferation. After that, the cell wound healing assay showed that the cell migration processes were also inhibited after the treatments of compounds 1 and 3 in A549 and MCF-7 cells. In addition, the RT‒qPCR and WB results demonstrated that the gene expression levels of MMP2 were decreased after the treatment with compounds 1 and 3 in A549 and MCF-7 cells. Besides, compound 2 displayed moderate antioxidant activity (EC50, 27.43 µM), compounds 3 and 6 exhibited moderate antibacterial activity, and compound 3 inhibited α-glucosidase with an IC50 value of 13.10 µM. CONCLUSIONS: Anthraquinone metabolites, from rhizosphere soil Streptomyces sp. of P. notoginseng, possess antitumor, antioxidant, antibacterial, and antiglycosidase activities. Moreover, metabolites 1 and 3 inhibit cancer cells migration through downregulating MMP2.

[Effect of electroacupuncture combined with intradermal needling on simple obesity and serum intestinal lymphatic function-related factors].

OBJECTIVE: To assess the efficacy of the combined treatment with electroacupuncture (EA) and intradermal needling on simple obesity and explore its underlying effect mechanism. METHODS: A total number of 116 patients with simple obesity were randomized into an observation group (58 cases, 3 cases dropped off and 2 cases removed) and a control group (58 cases, 4 cases dropped off and 1 cases removed). Patients in the control group received EA at Zhongwan (CV 12), Quchi (LI 11), Zusanli (ST 36), Pishu (BL 20), Weishu (BL 21), etc., for 30 min each time. On the base of the intervention as the control group, the patients in the observation group received the intradermal needling at Tianshu (ST 25), Daheng (SP 15), Zusanli (ST 36), Shangjuxu (ST 37), Quchi (LI 11), Pishu (BL 20) and Weishu (BL 21). In each group, the intervention was given once every two days, 3 times a week, consecutively for 3 months. Before and after treatment, the obesity indexes (body mass [BW], body mass index [BMI], body fat percentage [F%], adiposity [A] and waist circumference [WC]), the serum intestinal lymphatic function-related factors (vascular endothelial growth factor C [VEGF-C], delta-like ligand 4 [DLL4], adrenomedullin [ADM]), blood lipid (total cholesterol [TC], triglyceride [TG] and low density lipoprotein-cholesterol [LDL-C]), and fasting plasma glucose (FPG), fasting insulin (FINS) and insulin resistance index (HOMA-IR) were observed in the patients of both groups; and the efficacy was assessed. RESULTS: The effective rate was 88.7% (47/53) in the observation group, higher than 71.7% (38/53) in the control group (P<0.05). After treatment, except FPG in the control group, BW, BMI, F%, A, WC, and the concentrations of serum VEGF-C, DLL4 and ADM, as well as TC, TG, LDL-C, FBG, FINS and HOMA-IR were all reduced compared with those before treatment in both groups (P<0.05). The reduction ranges of BW, BMI, F%, A, WC, and the concentrations of serum VEGF-C, DLL4 and ADM, and TC, LDL-C, FINS and HOMA-IR in the observation group were all larger than those in the control group (P<0.05). CONCLUSION: Electroacupuncture combined with intradermal needling can reduce body weight and lipid, and improve insulin resistance in treatment of simple obesity, which is achieved probably through inhibiting lymphangiogenesis and promoting lymphatic endothelial permeability.

Anti-inflammatory and PTP1B inhibitory sesquiterpenoids from the twigs and leaves of Aglaia lawii.

Twelve sesquiterpenoids with seven different carbon skeletons, including four isodaucanes (1-4), an aromadendrane (5), a guaiane (6), a cadalane (7), two eudesmanes (8 and 9), two bisabolanes (10 and 11), and a megastigmane (12), were isolated from the twigs and leaves of Aglaia lawii (Wight) C. J. Saldanha et Ramamorthy. Of these compounds, amouanglienoids A (1) and B (2) are new isodaucane sesquiterpenoids. This is the first report of isodaucanes from the genus Aglaia, and amouanglienoid A (1) represents the first isodaucane containing a Δ7(8) double bond. Their structures were discerned from extensive spectroscopic analyses, single-crystal X-ray diffraction, and comparison of the experimental and calculated ECD data. In in vitro bioassays, compounds 1, 10, and 11 showed potent inhibitory effects against lipopolysaccharide (LPS)-induced inflammation in BV-2 microglial cells, while compound 11 exhibited considerable inhibition of PTP1B with an IC50 value of 16.05 ± 1.09 µM.

Effects of resveratrol treatment on quality and antioxidant properties of postharvest strawberry fruit.

Strawberry fruit is one of people's favorite fruits. It has high nutritional value and health care effects. Strawberries lose their edible value quickly after being picked because of their thin skin, which is easily damaged. In order to find a method to maintain the quality of strawberries, the effects of resveratrol treatment on the nutritional quality and antioxidant metabolism of strawberry fruit were studied. The result indicated that 100 µM resveratrol was the optimal concentration to delay the occurrence of decay. Strawberry fruit treated with resveratrol delayed the decrease in firmness, total soluble solids (TSS), total phenolics content (TPC), total flavonoid content (TFC), vitamin C (Vc) content,1,1-diphenyl-2-picrylhydrazyl (DPPH), and 2,2'-azino-bis (3-ethylbezothi- azot-hiazoline-6-sulfonic acid) (ABTS) radical scavenging capacities. The malondialdehyde (MDA) content, hydrogen peroxide (H2 O2 ) content, and superoxide anion (O2 •- ) production of control fruit were significantly higher than those of treated fruit. Strawberry fruit treated with resveratrol also increased the activities of superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX) during storage. Therefore, resveratrol has been proved to effectively improve the nutritional quality and antioxidant properties of strawberry fruit. PRACTICAL APPLICATIONS: Strawberry fruit is rich in nutrients, which is beneficial to human health. But strawberry fruit has high water content and soft tissue, which is easy to be damaged and decayed. Therefore, it is particularly important to find a way to maintain strawberry fruit quality. In this study, resveratrol has good antioxidant, health care, and antibacterial properties. Resveratrol treatment can maintain the nutritional quality of strawberry fruit and can be used as an effective method for strawberry fruit preservation.

Shikonin Attenuates Cochlear Spiral Ganglion Neuron Degeneration by Activating Nrf2-ARE Signaling Pathway.

The molecular mechanisms that regulate the proliferation and differentiation of inner ear spiral ganglion cells (SGCs) remain largely unknown. Shikonin (a naphthoquinone pigment isolated from the traditional Chinese herbal medicine comfrey root) has anti-oxidation, anti-apoptosis and promoting proliferation and differentiation effects on neural progenitor cells. To study the protective effect of shikonin on auditory nerve damage, we isolated spiral ganglion neuron cells (SGNs) and spiral ganglion Schwann cells (SGSs) that provide nutrients in vitro and pretreated them with shikonin. We found that shikonin can reduce ouabain, a drug that can selectively destroy SGNs and induce auditory nerve damage, caused SGNs proliferation decreased, neurite outgrowth inhibition, cells apoptosis and mitochondrial depolarization. In addition, we found that shikonin can increase the expression of Nrf2 and its downstream molecules HO-1 and NQO1, thereby enhancing the antioxidant capacity of SGNs and SGSs, promoting cells proliferation, and inhibiting cells apoptosis by activating the Nrf2/antioxidant response elements (ARE) signal pathway. However, knockdown of Nrf2 rescued the protective effect of shikonin on SGNs and SGSs damage. In addition, we injected shikonin pretreatment into mouse that ouabain-induced hearing loss and found that shikonin pretreatment has a defensive effect on auditory nerve damage. In summary, the results of this study indicate that shikonin could attenuate the level of oxidative stress in SGNs and SGSs through the Nrf2-ARE signaling pathway activated, induce the proliferation and differentiation of SGNs, and thereby improve the neurological hearing damage in mice. Therefore, shikonin may be a candidate therapeutic drug for endogenous antioxidants that can be used to treat neurological deafness.

The Comparison of Therapeutic Efficacy Between Dabigatran Versus Warfarin in Patients With Nonvalvular Atrial Fibrillation.

BACKGROUND: Novel oral anticoagulants and warfarin are widely used for stroke prevention in patients with atrial fibrillation. The anticoagulation status of patients receiving warfarin or rivaroxaban has been studied. In this study, we aimed to evaluate the effect of dabigatran and warfarin on preventing thrombin generation (TG). METHODS: This retrospective study enrolled 237 nonvalvular atrial fibrillation (NVAF) subjects treated with 110 mg dabigatran etexilate twice daily and 224 NVAF patients received adjusted-dose warfarin (international normalized ratio [INR] of 2 to 3)). Coagulation assays, prothrombin fragment 1 + 2 (F1+2), calibrated automated thrombogram, and thrombin-antithrombin complex (TAT) were detected at the steady state. RESULTS: Activated partial thromboplastin time (APTT), antithrombin III activity, fibrinogen, and lag time showed no difference between the two groups. Compared to the dabigatran group, prothrombin time and INR values were higher in the warfarin group (all P < .001). Thrombin time, endogenous thrombin potential, peak TG (Cmax), F1+2, and TAT were lower in the warfarin group. The inhibition of TG was still stronger in the warfarin group when the patients were divided into subgroups. CONCLUSION: Conventional coagulation assays are suboptimal for assessing the coagulation status of dabigatran. TG could be used as supplementary assays to evaluate the anticoagulation effect of oral anticoagulants. Our results suggest that warfarin may inhibit TG more aggressively than dabigatran in patients regardless of age and kidney function.

Selenium-GPX4 axis protects follicular helper T cells from ferroptosis.

Follicular helper T (TFH) cells are a specialized subset of CD4+ T cells that essentially support germinal center responses where high-affinity and long-lived humoral immunity is generated. The regulation of TFH cell survival remains unclear. Here we report that TFH cells show intensified lipid peroxidation and altered mitochondrial morphology, resembling the features of ferroptosis, a form of programmed cell death that is driven by iron-dependent accumulation of lipid peroxidation. Glutathione peroxidase 4 (GPX4) is the major lipid peroxidation scavenger and is necessary for TFH cell survival. The deletion of GPX4 in T cells selectively abrogated TFH cells and germinal center responses in immunized mice. Selenium supplementation enhanced GPX4 expression in T cells, increased TFH cell numbers and promoted antibody responses in immunized mice and young adults after influenza vaccination. Our findings reveal the central role of the selenium-GPX4-ferroptosis axis in regulating TFH homeostasis, which can be targeted to enhance TFH cell function in infection and following vaccination.

[Pharmacokinetic study on five components in phthalide target areas of Chaxiong and its ß-CD inclusion compounds based on UPLC-MS/MS].

This study aims to establish a method for the determination of the concentration of five main components of phthalide target areas of Chaxiong(CPTA) and its inclusion of ß-CD in the plasma of rats, and determine the pharmacokinetic parameters, absolute bioavailability and relative bioavailability of CPTA/ß-CD inclusion compound in vivo. The plasma concentrations of senkyunolide A, N-butylphthalide, new osthol lactone, Z-ligustilide and butenyl phthalide were determined with UPLC-MS/MS. The content determination was conducted at the chromatographic conditions as follows: Shim-pack GIST C_(18)-AQ HP column(2.1 mm×100 mm, 3 µm), mobile phase of 0.1% formic acid solution(A)-acetonitrile(B), gradient elution, flow rate of 0.3 mL·min~(-1), column temperature of 35 ℃ and injection volume of 2 µL. The mass spectra were obtained with electrospray ion source(ESI), positive ion mode and multi reaction monitoring. CPTA/ß-CD inclusion compound was prepared by grinding method, DAS 2.0 software was used to model the data, and the absolute bioavailability of CPTA and relative bioavailability of inclusion compound were calculated. Finally, the methods for the determination of five components of senkyunolide A, N-butylphthalide, new osthol lactone, Z-ligustilide and butenyl phthalide in CPTA, were successfully established. The linear relationship among the five components was good within their respective ranges, r>0.99. The absolute bioavailability of the five components in rats was 22.30%, 16.32%, 21.90%, 10.16% and 12.43%, respectively. After CPTA/ß-CD inclusion was prepared, the relative bioavailability of the five components was 138.69%, 198.39%, 218.01%, 224.54% and 363.55%, respectively, significantly improved. This method is rapid, accurate and sensitive, so it is suitable for the pharmacokinetic study of extracts in traditional Chinese medicine and their preparations.

Based on Network Pharmacology Tools to Investigate the Mechanism of Tripterygium wilfordii Against IgA Nephropathy.

Background: Immunoglobulin A nephropathy (IgAN) is the most common primary glomerular disease and poses a global major public health burden. The preparation of Tripterygium wilfordii Hook F (TwHF) is widely applied for treating patients with Immunoglobulin A nephropathy in China, while the molecular mechanisms remain unclear. This study aimed to verify the therapeutic mechanism of TwHF on IgAN by undertaking a holistic network pharmacology strategy in combination with in vitro and in vivo experiments. Methods: TwHF active ingredients and their targets were obtained via the Traditional Chinese Medicine Systems Pharmacology Database. The collection of IgAN-related target genes was collected from GeneCards and OMIM. TwHF-IgAN common targets were integrated and visualized by Cytoscape. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to determine the predominant molecular mechanisms and pathways of TwHF on the treatment of IgAN. The protein-protein interaction network was constructed by the STRING online search tool, and hub genes were identified using R software. The expression of hub gene and related signaling were evaluated in TwHF-treated mice through immunohistochemistry and western blot and further validated in human mesangial cells (HMCs). In addition, Cell counting kit 8 (CCK8) and flow cytometry were used to detect the effects of TwHF on cell proliferation and cell cycle of mesangial cells. Results: A total of 51 active ingredients were screened from TwHF and 61 overlapping targets related to IgAN were considered potential therapeutic targets, GO functions and KEGG analyses demonstrated that these genes were primarily associated with DNA-binding transcription factor binding, lipid and atherosclerosis pathway. Genes with higher degrees including AKT1, CXCL8, MMP9, PTGS2, CASP3, JUN are hub genes of TwHF against IgAN. Verification of hub gene JUN both in vitro and in vivo showed that TwHF significantly attenuated JUN phosphorylation in the kidneys of IgAN mice and aIgA1-activated HMCs, meanwhile suppressing HMCs proliferation and arresting G1-S cell cycle progression. Conclusion: Our research strengthened the mechanisms of TwHF in treating IgAN, inhibition of JUN activation may play a pivotal role in TwHF in alleviating IgAN renal injury.

Effect of Electro-acupuncture on Expression of IRS-1/PI3K/GLUT4 Pathway in Ovarian Granulosa Cells of Infertile Patients with Polycystic Ovary Syndrome-Insulin Resistance of Phlegm-Dampness Syndrome.

OBJECTIVE: To evaluate the effect of electro-acupuncture (EA) in infertile patients with phlegm-dampness polycystic ovary syndrome-insulin resistance (PCOS-IR). METHODS: Seventy-six PCOS-IR patients who underwnet in vitro fertilization and embryo transfer (IVF-ET) were equally assigned to two groups according to a random digital table: the EA group and the control group, with 38 cases in each group. Before undergoing IVF, the two groups were treated with EA or pseudo-acupuncture, respectively, for 3 menstrual cycles. The intervention was 25 min twice a week until the day of oocyte collection. The selected acupoints were Zhongwan (RN 12), Tianshu (ST 25), Daheng (SP 15), Daimai (GB 26), Qihai (CV 6), Guanyuan (CV 4), and bilateral points including Xuehai (SP 10), Fenglong (ST 40), Zusanli (ST 36), and Yinlingquan (SP 9). Evaluation of phlegm-dampness syndrome score and IR score were carried out before and after treatment. Additionally, the number of oocytes retrieved, transplantable embryo rate, high-quality embryo rate, clinical pregnancy rate and live birth rate were compared between the two groups. Real-time polymerase chain reaction analysis was used to monitor the mRNA expression of the insulin receptor substrate (IRS-1), phosphatidylinositiol 3-kinase (PI3K) and glucose transport factor 4 (GLUT4) in ovarian granulosa cells. RESULTS: EA treatment reduced the phlegm-dampness syndrome score as well as the IR scores compared with the control group (P<0.05). No significant differences in the number of oocytes retrieved and clinical pregnancy rate between the two groups (P>0.05). Moreover, the transplantable embryo rate [49.0% (284/580) vs. 41.9% (273/652)], high-quality embryo rate [36.6% (104/284) vs. 27.8% (76/273)], and live birth rate [50% (19/38) vs. 26.3% (10/38)] in the EA group were significantly higher than in the control group (P<0.05). Gene expression analyses revealed significantly elevated IRS-1, PI3K and GLUT4 mRNA in ovarian granulosa cells of the EA group compared with the control group (P<0.05). CONCLUSIONS: EA may ameliorate the effects of phlegm-dampness syndrome and ovarian IR in PCOS-IR patients. Mechanistically, this effect might be through an upregulation of the IRS-1/PI3K/GLUT4 signaling pathway, which may result in improved oocyte quality and embryonic development potential. (Registration No. ChiCTR1800015453).

Deep eutectic solvent-based liquid-phase microextraction coupled with reversed-phase high-performance liquid chromatography for determination of α-, ß-, γ-, and δ-tocopherol in edible oils.

For simultaneous analysis of four fat-soluble tocopherols (α-, ß-, γ-, and δ-) in edible oils, an efficient and green method using deep eutectic solvent-based liquid-phase microextraction (DES-LPME) coupled with reversed-phase high-performance liquid chromatography (RP-HPLC) was developed. The DESs formed by different quaternary ammonium salts and ethanol were used as the extractants. Tetrabutylammonium chloride (TBAC)-ethanol DES at a molar ratio of 1:2 achieved the best extraction efficiency. Under the optimized conditions, the detection limits were in the range of 2.1-3.0 ng mL-1. The intra-day and inter-day repeatability were in the ranges of 3.9-5.3% and 4.8-7.1%, respectively, and the recoveries for the real samples varied from 80.7% to 105.4%. The developed method was successfully employed for the determination of all four tocopherol homologues with an RP-HPLC system containing a COSMOSIL π-NAP column in five edible oils collected locally. Graphical abstract.

[Location, selection, and comparative anatomy of "Taixi" (KI3), "Shuiquan" (KI5), "Fuliu" (KI7), "Jiaoxin" (KI8), "Zhubin" (KI9), and "Yingu"(KI10) acupoints in rabbits].

OBJECTIVE: To investigate the. METHODS: for locating and selecting the acupoints of "Taixi" (KI3), "Shuiquan" (KI5), "Fuliu" (KI7), "Jiaoxin" (KI8), "Zhubin" (KI9), and "Yingu" (KI10) and the morphological structure of these acupoints in rabbits. MethodsAccording to the WHO and national standards for human acupoints and rabbit X-ray images, acupoint locations were marked using the anatomical landmarks on body surface in 10 New Zealand rabbits. The acupoints were dissected to compare the homologous and analogous tissue between rabbits and human body and thus correct the locations of these acupoints. Potentials were measured for the 10 New Zealand rabbits at the corrected locations of the acupoints and around the acupoints, and the final locations of these acupoints were determined by comparing the anatomical results and the data of potentials. Anatomical observation was performed after marking, and the relationship between acupuncture needle and adjacent structure was observed. RESULTS: "Taixi" was located in the ankle area, at the midpoint between the prominence of the medial malleolus and the calca-neal tendon; "Shuiquan" was located in the calcaneal area below "Taixi" in the depression anterior to the calcaneal tuberosity; "Fuliu" was located at the medial side of the calf, at 2 cun above the prominence of the medial malleolus anterior to the calcaneal tendon; "Jiaoxin" was located at the medial side of the calf, at 2 cun above the prominence of the medial malleolus and in the depression posterior to the medial border of the tibia; "Zhubin" was located at the medial side of the calf, at 5 cun above the medial malleolus on the line between "Taixi" and "Yingu"; "Yingu" was located at the medial side of the knee, at the posterior-inferior border of the semitendinosus tendon on the popliteal crease. The results of skin potentials at the acupoints suggested that "Taixi", "Shuiquan", "Fuliu", and "Zhubin" were high-reliability acupoints, "Jiaoxin" was a medium-reliability acupoint, and "Yingu" was a low-reliability acupoint. CONCLUSION: Comparative anatomy combined with imaging, surface anatomy, and electrophysiological techniques of acupoints can help with the accurate localization and selection of acupoints in experimental animals, improve the reliability of acupoint location, and enrich the comparative anatomical data of acupoints.

Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease.

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is the etiological agent responsible for the global COVID-19 (coronavirus disease 2019) outbreak. The main protease of SARS-CoV-2, Mpro, is a key enzyme that plays a pivotal role in mediating viral replication and transcription. We designed and synthesized two lead compounds (11a and 11b) targeting Mpro Both exhibited excellent inhibitory activity and potent anti-SARS-CoV-2 infection activity. The x-ray crystal structures of SARS-CoV-2 Mpro in complex with 11a or 11b, both determined at a resolution of 1.5 angstroms, showed that the aldehyde groups of 11a and 11b are covalently bound to cysteine 145 of Mpro Both compounds showed good pharmacokinetic properties in vivo, and 11a also exhibited low toxicity, which suggests that these compounds are promising drug candidates.

CD13-specific ligand facilitates Xanthatin nanomedicine targeting dendritic cells for therapy of refractory allergic rhinitis.

Relapse in Allergic Rhinitis (AR) is triggered by various unclear mechanisms. Xanthium strumarium L. as a traditional folk medicine can inhibit inflammatory responses through multiple mechanisms. Xanthatin (XT) is a bioactive compound derived from Xanthium strumarium L, and we developed a polymeric micelle (PM) that is dendritic cells (DCs)-specific targeting delivery system loading XT (NGR-XT-PM) based on a cyclic peptide moiety (NGR) to render DCs maturation-resistant for therapy of refractory AR. A murine model of AR was employed to investigate the in vivo therapeutic efficiency and relapse rate compared with the commercial product Budesonide. The results showed intranasal administration of NGR-XT-PM presented significant anti-allergy effect with no recurrence, in contrast, all mice treatment with Budesonide relapsed. NGR-XT-PM could effectively reverse the Th1/Th2 imbalance by depleting the serum inflammatory levels (IgE, histamine and IL-4) and DCs surface costimulatory molecules (CD80, CD86 and I-A/I-E), and promote immune tolerance by upregulating the level of Treg cells and reducing the levels of Th2, Th9 and Th17 cells. Furthermore, we appealed to virtual screening of inflammatory targets and found XT blocking the COX-2/PGE2 signaling pathway, which is a key effector in immune responses. These indicated CD13-specific NGR could facilitate XT selectively targeting DCs for efficiently ameliorating refractory rhinitis, and NGR-XT-PM should be a potential anti-AR drug.

Three new secoiridoid glycosides from the flower buds of Lonicera japonica.

Three new secoiridoid glycosides, named lonijapoglycol A (1), aldosecolohanin C (2) and aldosecolohanin B (3), together with three known ones (4-6), have been isolated from the flower the buds of Lonicera japonica. All the structures were identified by spectroscopic analyses. Lonijapoglycol A (1) expressed significant anti-inflammatory activity to inhibit the release of ß-glu-curonidase induced by platelet-activating factor in rat polymorphonuclear leukocytes with an IC50 value of 3.76 µmol·L-1.

A meta-analysis of efficacy and safety of sorafenib versus other targeted agents for metastatic renal cell carcinoma.

BACKGROUND: Molecular targeted therapies were found to be efficacious and safer in the treatment of metastatic renal cell carcinoma (mRCC). Sorafenib is the first target agent (TA) to report a benefit in this disease and has largely established a prominent role in progression-free survival (PFS). However, there have been conflicting results across the trials that evaluated the efficacy of sorafenib. OBJECTIVE: The aim of the study was to perform a meta-analysis to compare the efficacy and safety of sorafenib in first-line treatments of mRCC. METHODS: We searched online electronic databases: PubMed, Embase, and the Cochrane Library updated on September 2017. Trials on the efficacy of sorafenib in first-line treatments of advanced RCC were included, of which the primary outcomes were objective response rate (ORR), PFS, overall survival (OS), and grade 3/4 adverse events (AEs). RESULTS: A total of 5 trials were included in this analysis. The group of AEs showed significantly improved PFS (odds ratio [OR] = 0.78, 95% confidence interval [CI] = 0.70-0.86, P < .001), as well with the ORR (OR = 1.89, 95%CI = 1.38-2.59, P < .0001) compared with sorafenib. However, there was no significant difference in OS (OR = 0.97, 95%CI = 0.78-1.22, P = .82). CONCLUSION: Sorafenib did not achieve efficacy and safety benefit in patients with mRCC compared with those treated with TAs. The role of sorafenib in first-line treatments of mRCC may change in favor of newer drugs. More research is needed to confirm whether these new TAs could replace sorafenib as the gold standard in the future.

A new indole alkaloid from the traditional Chinese medicine Chansu.

A new indole alkaloid N'-formylserotonin (1), along with five known indole alkaloids N'-methylserotonin (2), 5-hydroxy-1H-indole-3-carbaldehyde (3), N-acetylserotonin (4), 6-hydroxy-1-oxo-3,4-dihydro-ß-carboline (5), and bufoserotoin C (6), were isolated from the water extract of traditional Chinese medicine Chansu. Their structures were elucidated on the basis of spectral analyses. The cytotoxicities of 1-6 against human lung adenocarcinoma epithelial cells A549 were tested using the MTT method. Compound 6 exhibited stronger cytotoxic effect than 5-FU, and 1-5 showed no cytotoxic effects. Bufoserotonin C is one of the cytotoxic components in water-soluble extract of Chansu.

[A dosage regimen of M-receptor blocker after TURP for severe BPH with predominant urine storage symptoms].

OBJECTIVE: To study the dosage regimen of oral M-receptor blocker following transurethral resection of the prostate (TURP) for severe benign prostate hyperplasia (BPH) with predominant urine storage period symptoms (USPSs) and its clinical effect. METHODS: Severe BPH patients with predominant USPSs received oral tolterodine (2 mg q12d or 4 mg qd) 6 hours after TURP for 4 weeks. The medication continued for another 2 weeks in case of recurrence of USPSs or until the 12th week in case of repeated recurrence. Before and at 1, 4, 8 and 12 weeks after TURP, we analyzed the International Prostate Symptoms Score (IPSS), quality of life (QoL) score, maximum urinary flow rate (Qmax), and postvoid residual volume (PVR) of the patients. RESULTS: Complete clinical data were collected from 106 cases, of which 33 achieved successful drug withdrawal with no aggravation of USPSs at 4 weeks after TURP, 51 at 6－8 weeks, 13 at 10－12 weeks, and 9 needed medication after 12 weeks. Before and at 1, 4, 8 and 12 weeks after TURP, the total IPSSs were 25.33 ± 3.45, 19.33 ± 3.62, 11.56 ± 2.45, 8.38 ± 2.0 and 7.74 ± 1.87, those in the urine storage period were 11.97 ± 1.53, 10.76 ± 1.82, 6.16 ± 1.22, 4.08 ± 1.19 and 3.91 ± 1.15, those at urine voiding were 9.80 ± 1.60, 5.59 ± 1.45, 3.40 ± 0.92, 2.85 ± 0.71, and 2.61 ± 0.67, and the QoL scores were 4.70 ± 0.78, 3.92 ± 0.75, 2.55 ± 0.74, 1.83 ± 0.72 and 1.66 ± 0.75, respectively, with statistically significant differences between the baseline and the scores at 1 and 4 weeks (P <0.01) but not at 8 or 12 weeks (P >0.05). Qmax and PVR were improved progressively and significantly at 1 and 4 weeks (P <0.01) but not at 8 or 12 weeks (P >0.05). CONCLUSIONS: Four to eight weeks of oral administration of M-receptor blocker may be an effective dosage regimen for severe BPH with predominant USPSs after TURP.