Study on the potential allergen and mechanism of pseudo-allergic reactions induced by combined using of Reduning injection and penicillin G injection based on metabolomics and bioinformatics / 药学学报

Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

Screening of anti-aging active ingredients and mechanism analysis based on molecular docking technology / 中国中药杂志

Dampness evil is the source of all diseases, which is easy to cause disease and promote aging, while aging could also promote the occurence and development of diseases. In this paper, the relationship between the dampness evil and aging would be discussed, to find the anti-aging active ingredients in traditional Chinese medicine (TCM), and analyze the anti-aging mechanism of dampness eliminating drug. Molecular docking technology was used, with aging-related mammalian target of rapamycin as the docking receptors, and chemical components of Fuling, Sangzhi, Mugua, Yiyiren and Houpo as the docking molecules, to preliminarily screen the anti-aging active ingredients in dampness eliminating drug. Through the comparison with active drugs already on the market (temsirolimus and everolimus), 12 kinds of potential anti-aging active ingredients were found, but their drug gability still needs further study. The docking results showed that various components in the dampness eliminating drug can play anti-aging activities by acting on mammalian target of rapamycin. This result provides a new thought and direction for the method of delaying aging by eliminating dampness.

Evaluation of Clinical Utilization of Human Serum Albumin in Surgical Inpatients in A Hospital by Interna-tional Guidance / 中国药房

OBJECTIVE:To provide reference for rational use of human serum albumin for surgical inpatients. METHODS:The utilization of human serum albumin for surgical inpatients in a hospital during Jan.-Mar. 2014 was analyzed and evaluated by UHC Guidelines for the Use of Album,Nonprotein Colloid,and Crystalloid Solutions(2010 edition)and European Immune Globu-lin and Albumin Use Recommendation. RESULTS:Among the 556 patients,totally 895 human serum albumin application were con-ducted,mainly involving development of gastrointestinal surgery(29.7%),hepatobiliary surgery(25.9%)and cardiothoracic sur-gery(13.1%). The main reasons were correcting hypoalbuminemia(62.9%),followed by albumin supplemented during major sur-gery(7.9%)and alleviating ascites in patients with cirrhosis(4.4%);only 95 applications(10.6%)were considered appropriate. The most prevalent inappropriate reason was for correcting hypoalbuminemia. CONCLUSIONS:Human serum albumin in the surgi-cal inpatients in the hospital shows a large amount,and low consistent rate between indications and guidelines. The rational stan-dardized utilization of human serum albumin should be strengthened.

Analysis of serum metabolic profile by ultra-performance liquid chromatography-mass spectrometry for biomarkers discovery: application in a pilot study to discriminate patients with tuberculosis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Tuberculosis (TB) is a chronic wasting inflammatory disease characterized by multisystem involvement, which can cause metabolic derangements in afflicted patients. Metabolic signatures have been exploited in the study of several diseases. However, the serum that is successfully used in TB diagnosis on the basis of metabolic profiling is not by much.</p><p><b>METHODS</b>Orthogonal partial least-squares discriminant analysis was capable of distinguishing TB patients from both healthy subjects and patients with conditions other than TB. Therefore, TB-specific metabolic profiling was established. Clusters of potential biomarkers for differentiating TB active from non-TB diseases were identified using Mann-Whitney U-test. Multiple logistic regression analysis of metabolites was calculated to determine the suitable biomarker group that allows the efficient differentiation of patients with TB active from the control subjects.</p><p><b>RESULTS</b>From among 271 participants, 12 metabolites were found to contribute to the distinction between the TB active group and the control groups. These metabolites were mainly involved in the metabolic pathways of the following three biomolecules: Fatty acids, amino acids, and lipids. The receiver operating characteristic curves of 3D, 7D, and 11D-phytanic acid, behenic acid, and threoninyl-γ-glutamate exhibited excellent efficiency with area under the curve (AUC) values of 0.904 (95% confidence interval [CI]: 0863-0.944), 0.93 (95% CI: 0.893-0.966), and 0.964 (95% CI: 00.941-0.988), respectively. The largest and smallest resulting AUCs were 0.964 and 0.720, indicating that these biomarkers may be involved in the disease mechanisms. The combination of lysophosphatidylcholine (18:0), behenic acid, threoninyl-γ-glutamate, and presqualene diphosphate was used to represent the most suitable biomarker group for the differentiation of patients with TB active from the control subjects, with an AUC value of 0.991.</p><p><b>CONCLUSION</b>The metabolic analysis results identified new serum biomarkers that can distinguish TB from non-TB diseases. The metabolomics-based analysis provides specific insights into the biology of TB and may offer new avenues for TB diagnosis.</p>

Study on microwave digestion of vacant gelatin capsules / 中国药学杂志

OBJECTIVE: To assure the safety and improve the efficiency of microwave digestion of vacant gelatin capsules. METHODS: Different digestion conditions were investigated by using microwave digestion system with temperature and pressure sensors to determine the optimal experimental method. RESULTS: Using high proportion of hydrogen peroxide in pre-digestion could moderate the increase of pressure in microwave digestion process and at the same time shorten time and improve the digestion efficiency. CONCLUSION: This method, which improves the experimental safety and applicability, is an effective way to solute the long pre-digestion time of the method of Ch. P(2010) and the burst with ordinary digestion tanks.

Disruption of blood brain-barrier by leukemic cells in central nervous system leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To observe the effect of leukemic cells on blood-brain barrier (BBB) in mice with central nervous system leukemia (CNSL) by establishing mice CNSL model and an in vitro BBB model and explore the mechanism of leukemic cell infiltrating central nervous system (CNS).</p><p><b>METHODS</b>After splenectomy, cytoxan intraperitoneal injection, and sublethal irradiation, 10 BALB/c nu/nu mice were transplanted intravenously with 1.2 × 10(7) of SHI-1 human monocytic leukemic cells. Mice were monitored for survival and clinical manifestation of nerve palsy. The leukemic cells engrafted were examined by RT-PCR, histopathology and bone marrow (BM) smears. Immunofluorescence analysis with laser scanning fluorescence confocal microscopy was used to determine the expression of fibrinogen and tight-junction protein ZO-1. An in vitro BBB model composed of human brain microvascular endothelial cells (BMVECs) was developed on a Matrigel-based insert. Different leukemic cell lines were seeded onto the upper compartment of transwell insert. After incubated for 24 h with BMVECs, cells that had migrated into the lower compartment were counted and analyzed.</p><p><b>RESULTS</b>(1) Paralysis with or without sight loss was developed in half the mice 30-35 d after innoculated with SHI-1 cells. Leukemic cells infiltrates were observed in BM and in different part of brain tissues including brain parenchyma. The transcriptions of human MLL/AF6 fusion gene were also detected in BM and brain tissues in paralysis mice. The fibrinogen expression and ZO-1 disruption were detected in the infiltrated tissue. (2) After 24 h incubation with leukemic cells, the BMVECs sheets were disrupted and grew singly and ZO-1 expression was down-regulated markedly. SHI-1 cells showed more injurious to BMVECs and higher invasive rate \[(40.33 ± 1.53)% vs (11.83 ± 1.44)%, P < 0.05\] than HL-60 cells did.</p><p><b>CONCLUSION</b>One of the mechanisms of leukemic cells infiltrates CNS in CNSL is injure to the BBB.</p>

Effects of valsartan on serum transforming growth factor-β1 levels in early diabetic nephropathy / 中国医师进修杂志

Objective To investigate the relationship between serum transforming growth factor- β1(TGF- β1) levels and early diabetic nephropathy and clarify whether valsartan plays a role in renal protection by reducing the level of serum TGF-β1. Methods The study subjects were divided into four groups:control group (30 cases); normal albuminuria group 1 (NA1 group with 12 cases, U MA/Cr < 10 μg/mg combined with type 2 diabetes);normal albuminuria group 2 (NA2 group with 19 cases,UMA/Cr 10-30 μg/mg combined with type 2 diabetes); microalbuminuria group ( MA group with 35 cases, U MA/Cr 31-300 μg/mg combined with type 2 diabetes). All these type 2 diabetic patients were suffering from diabetic retinopathy, and valsartan ( 80 mg/d) were medicated for those combined with hypertension. The serum TGF-β1 levels were measured by enzyme-linked immunosorbent assay in all subjects. Results Serum TGF- β1 levels in three diabetes groups were (7.41 ± 2.68 ), ( 10.52 ± 4.10), (22.98 ± 43.74) ng/L, respectively, all of which were higher than those in control group [(4.25 ± 5.82) ng/L] (P < 0.05). There were significant differences in serum TGF- β1 levels among MA group, NA2 group and NA1 group (P < 0.05 ). Serum TGF-β1 levels in NA1 group with valsartan treatment significantly decreased compared with those without valsartan treatment (P < 0.05), whereas there was no significant reduction in NA2 and MA group with valsartan treatment (P > 0.05). Conclusions High serum TGF-β1 level may be associated with type 2 diabetes and early diabetic nephropathy. Early intervention of valsartan may be delay the onset and development of diabetic nephropathy by decreasing the serum TGF-β1 level.

Prophylaxis of graft-versus-host disease in mice by chemical modification of graft and OX40-OX40L costimulatory pathway / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the prophylaxis effect of pretreatment of allograft with methoxypolyethylene glycol-succinimidyl-propionic acid ester (mPEG-SPA) and anti-OX40L monoclonal antibody (McAb) on acute graft-versus-host disease (aGVHD) after allogeneic bone marrow transplantation (allo-BMT) in mice.</p><p><b>METHODS</b>Responder splenocytes from C57BL/6 donor mice (H-2(b)) were co-cultured with stimulator splenocytes from BALB/c recipient mice (H-2(d)) for 7 days in the presence or absence of anti-OX40L McAb followed by mPEG-SPA chemical modification. Donor bone marrow cells plus the mixed culture of T-cells were then transplanted into lethally irradiated BALB/c mice. The BALB/c recipient mice were divided into four groups: group A (allo-BMT control group), group B(mPEG-SPA modification group), group C (anti-OX40L McAb pretreated group) and group D (mPEG-SPA and anti-OX40L McAb dual-treated group). Survival time and survival rate of the recipients were observed after allo-BMT. GVHD was assessed by clinical signs and histological changes of skin, liver and small intestines. Enzyme-linked immunosorbent assay (ELISA) was used to detect cytokines (IL-4, IL-10 and INF-gamma) production. Flow cytometry (FCM) analysis was used to detect allogeneic chimerism.</p><p><b>RESULTS</b>(1) The mice in group A developed typical clinical signs of aGVHD and all mice died within 17 days after BMT with an average survival time (AST) of (12.1 +/- 5.5) days. The signs of aGVHD were less evident in mice of groups B, C and D, and their AST (36.2 +/- 24.9, 32.0 +/- 24.8 and 44.3 +/- 23.2 days, respectively) were all longer than that in group A (P < 0.05). AST of group D being the longest (P < 0.05). The survival rates at day 60 post-BMT in groups B, C and D were 50%, 41.7% and 66.7%, respectively. (2) Serum IFN-gamma level was increased after BMT in group A, and peaked in day 10 to day 15 post-BMT, while the level was decreased in groups B, C and D, reached the nadir on the day 10 post-BMT, with the lowest in group D (P < 0.01). After BMT, IL-4 and IL-10 levels were slightly decreased in group A, their levels were elevated in groups B and C (P < 0.05) and even more significantly increased in group D (P < 0.01). IL-4 and IL-10 levels peaked between day 10 and 15 post-BMT. (3) The average proportion of H-2(b) positive cells in recipient mice was 95% - 100% on day 60 post-BMT, with complete donor-type implantation.</p><p><b>CONCLUSION</b>Combination of mPEG-SPA and anti-OX40L McAb can block T-cell activated antigens and co-stimulatory pathway, regulate the T cells differentiation and induce the immune shift of Th0 cells toward Th2 cells. The immune tolerance induced by this method can significantly relieve aGVHD after allo-BMT.</p>

Advances of studies on dropping pills / 中国中药杂志

From the characteristic, prepare the craft, quality control, bioavailability and clinical curative effect,etc. To do the summary to the modern research of dropping pill, analyse and is thought to dropping pill that has wide development prospects.

Preparation of solid lipid nanoparticles loaded with Xionggui powder-supercritical carbon dioxide fluid extraction and their evaluation in vitro release / 中国中药杂志

<p><b>OBJECTIVE</b>To study the preparation of solid lipid nanoparticles loaded with Xionggui powder-supercritical carbon dioxide fluid extraction and their evaluation in vitro release.</p><p><b>METHOD</b>To prepare solid lipid nanoparticles (SLN) loaded with Xionggui powder-supercritical carbon dioxide fluid extraction (XG-CO2-SFE) using a hot dispersion- ultrasonic technique, establishing the best prescription of XG-CO2-SFE-SLN through orthogonal design methods using entrapment efficiency of nanoparticles as index, and investigating their physicochemical characterizations. The invro release action of SLN was studied in different dissolution mediums using dynamic dialyse method.</p><p><b>RESULT</b>The best prescription was: phospholipid: F-68: stearie acid glyceride = 5: 2 : 1, the entrapment efficiency of nanoparticles was 96.3%, and the results revealed the nanoparticles were sphere like with the mean size of 245.8 nm, the mean Zeta potential was -33.5 mV. The in vitro release meet to Weibull distribution in physiological brine and to single-index model in pH 7.4 phosphate liquid (40% EtOH).</p><p><b>CONCLUSION</b>The preparation method of the XG-CO2-SFE-SLN was appropriate, and the XG-CO2-SFE-SLN was released completely.</p>

Study on in vitro dissolution rate of geniposide in huangqin qingfei dispersible tablet / 中国中药杂志

<p><b>OBJECTIVE</b>To study in vitro dissolution rate of geniposide in Huangqin Qingfei dispersible tablet.</p><p><b>METHOD</b>A reversed-phase HPLC method was developed for determination of geniposide. In vitro dissolution rates were compared between Huangqin Qingfei dispersible tablet and conventional tablet in the dissolution medium of pH 1.0, 2.85, 4.5, 6.8, and 8.0 accordingly. Zero-class model, single-index model, logarithm normal school model, and Weibull distributing model were used to simulate the dissolution curve.</p><p><b>RESULT</b>The dissolution rate of two tablets is not affected by pH so much, and they can dissolve within 5 to 10 minutes. Weibull distributing model is the best simulation for in vitro dissolution. Comparing with conventional tablet, dispersible tablet dissolve quickly and completely.</p><p><b>CONCLUSION</b>The in vitro dissolution rate of geniposide in Huangqin Qingfei dispersible tablet conforms to Weibull distributing model. The dispersible tablet is able to release rapidly.</p>

Studies on preparation technology of Flos Magnoliae essential oil-beta-cyclodextrin inclusion complex / 中国中药杂志

<p><b>OBJECTIVE</b>To find the best condition of the preparation technology of Flos Magnoliae essential oil-beta-cyclodextrin inclusion complex.</p><p><b>METHOD</b>L9(3(4)) table was used to examine the effects of 4 factors, and the inclusion rate of each test was determined of orthogonal test.</p><p><b>RESULT</b>The best condition was:oil:beta-cyclodextrin:water = 1:8:60 (mL:g:mL), stirring for 1 hour at 80 degrees C.</p><p><b>CONCLUSION</b>The complex prepared on the condition aforementioned is stable and stirring has a highest inclusion rate.</p>

Comparative studies on isolation and purification of Chinese medicine decoction / 中国中药杂志

<p><b>OBJECTIVE</b>To evaluate different methods by treating water-decocted liquid of 6 Chinese medical herbs and 4 co-prescription respectively with alcohol, ultrafilter, macroporousresin and clarifier.</p><p><b>METHOD</b>The contents of target component in those extracts were determined with HPLC or titration, and quantitative and qualitative determination of the impurity components, such as polysaccharide and protein, was made.</p><p><b>RESULT</b>Each method showed its advantages and disavantages.</p><p><b>CONCLUSION</b>Different method can be chosen according to the clinical and preparation demands or the characteristic of components.</p>