Exploration of Spectrum-effect Relationship of Zhuriheng Dropping Pills Against Macrophage Foaming Based on UPLC-Q-Exactive Orbitrap MS / 中国实验方剂学杂志

ObjectiveThrough the correlation analysis between intestinal absorption profile and inhibition of macrophage foaming， the pharmacodynamic components of Zhuriheng dripping pills（ZRH） were explored to provide a basis for establishing its quality standard. MethodIntestinal absorption fluids with 0， 5， 10， 15， 20 times clinical equivalent doses were prepared by a rat everted gut sac（EGS）， and the oxidized low density lipoprotein（ox-LDL）-induced RAW264.7 macrophage foaming model was used to investigate the effect of intestinal absorption fluid with different doses on the accumulation of lipids in RAW264.7 cells by oil red O staining and cholesterol content determination， and to screen for the optimal dose. Ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS） was used to analyze and identify intestinal absorption fractions of ZRH intestinal absorption fluids， and partial least squares-discriminant analysis（PLS-DA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were performed on different doses of ZRH intestinal absorption fluids using SIMCA 13.0 with peak area as the independent variable and the pharmacodynamic indicators as the dependent variables to screen the compounds with variable importance in the projection（VIP） value>1.0 as contributing components， and Pearson correlation analysis was used to determine the spectral effect relationship， determined the compounds and positive correlation with pharmacodynamic were as active ingredients. Molecular docking was used to verify the binding energy of peroxisome proliferator-activated receptor α（PPARα）， PPARγ， PPARβ， human retinoid X receptor α（RXRA） and nuclear transcription factor-κB（NF-κB） with the active ingredients in ZRH intestinal absorption fluids. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was performed to detect the mRNA levels of PPARγ， scavenger receptor A1（SRA1） and adenosine triphosphate-binding cassette transporter A1（ABCA1） in RAW264.7 cells， Westen blot was used to detect the expression level of PPARγ protein in RAW264.7 cells， and enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of interleukin（IL）-1β and NF-κB in RAW264.7 cells. ResultAccording to the results of oil red O staining and cholesterol content determination， the ZRH intestinal absorption fluids could significantly reduce macrophage foaming， and intestinal absorption fluids with 15， 20 times clinical equivalent doses had the best effect， the 15-fold ZRH intestinal absorption fluid was finally determined as the study subject. Spectral effect relationship showed that 52 corresponding peaks in the ZRH-containing intestinal fluid were positively correlated with the efficacy， including organic acids， phenylpropanoids， iridoids， flavonoids， bile acids， coumarins and chromones. Target validation results showed that 86.9%-96.2% of the total components processed good binding activities with the key targets of PPARα， PPARγ， PPARβ， RXRA and NF-κB， and the docking energy values were all less than -6.0 kcal·mol-1（1 cal≈4.19 J）. The results of validation showed that， compared with the normal group， the model group showed a significant increase in the levels of SRA1 and PPARγ mRNA expression， a significant decrease in ABCA1 mRNA expression， a significant increase in the level of PPARγ protein expression， and a significant increase in the levels of IL-1β and NF-κB（P<0.01）， compared with the model group， the 15-fold intestinal absorption fluid group showed a significant decrease in the levels of SRA1 and PPARγ mRNA expression（P<0.05， P<0.01）， ABCA1 mRNA expression level was significantly up-regulated， the levels of IL-1β and NF-κB were significantly reduced（P<0.01）， and PPARγ protein expression level was significantly reduced（P<0.05）. ConclusionThis study identifies 52 components and their metabolites in ZRH intestinal absorption fluid that are positively correlated with the inhibition of macrophage foaming， which may be related to the regulation of the PPARs pathway in cells and the reduction of the levels of inflammatory factors， and can provide a reference for the quality control and clinical application of ZRH.

Lipid markers and targets of coronary artery disease based on lipidomics / 药学学报

Coronary artery disease is the leading cause of death worldwide, the coronary artery stenosis or occlusion caused by atherosclerosis leads to myocardial ischemia, hypoxia, or necrosis, that is main histopathological features of coronary artery disease. Atherosclerosis relates closely to abnormal lipid regulation, chronic inflammation, and endothelial dysfunction. Cardiac enzymes and high, low-density lipoprotein are currently used to diagnose a variety of coronary artery diseases, but the evidence is inadequate. Thus, new cardioprotective therapies are required to explore sensitive molecular markers for the prediction of cardiovascular events. Lipids have an important role in maintaining the myocardial cell structure as well as cardiac function. Lipidomics is a newly emerged discipline that studies lipids on a large scale. Recent advancements in lipidomics on coronary artery disease have shown that certain lipids, such as ceramide, sphingosine, lysophosphatidic acid, oxidized lipids, and so on, are associated with the clinical classification and characteristics of coronary artery disease. In addition, recent studies of lipid profiles of the cardiac, fat, liver, and other tissue samples in animal models also have provided a novel viewpoint. Given the increasing application of lipidomics techniques for coronary artery disease, we provide a review of lipidomics technology, sensitive lipid markers, recent studies of therapeutic targets, and drug discovery for coronary artery disease.

Comparatively study of laparoscopic and open surgery for postoperative complications of acute gangrenous appendicitis / 国际外科学杂志

Objective To analyze and compare the incidence of postoperative complications of acute gangrene appendicitis after laparotomy and laparoscopic surgery.Methods This study retrospectively analyzed of 162 cases of acute gangrenous appendicitis treated in Xilin Guole Meng Hospital from January 2015 to January 2018.There were 96 male patients and 66 female patients;age (43.40 ± 16.21) years.According to different surgical methods,162 patients were divided into two groups:laparoscopic group (n =80) and open group (n =82).Laparoscopic appendectomy was performed in the laparoscopic group,and open appendectomy was performed in the open group.To compare the postoperative complications intraoperative and postoperative data between the two groups.It consists of tump fistula or bead inflammation,postoperative pneumonia,abdominal hemorrhage,deep venous thrombosis,incisional hernia,subcutaneous emphysema,incision infection,intestinal obstruction,celiac sepsis,complained of pain intensity classification method for pain score and antibiotic use time,postoperative extubation time,postoperative exhaust time,postoperative bed for the first time for the first time time,length of hospital stay.The measurement data were expressed by (Mean ± SD) and the t test was used with the groups.The counting data were expressed by the percentage or rate and the x2 test was used among the groups.When the number of single group cases was less than 10 cases,the Fisher exact probability method was used for the calibration test.Results The top three complications were incision infection,intestinal obstruction and empyema.The incidence of postoperative complications in open group and laparoscopy group was 65.9％ (54/82) and 8.8％ (7/80) respectively,and there was significant difference between the two groups (F =56.247,P=0.000).The VRS of the lapamscopic group and the open group were 53 points and 12 points for grade Ⅰ,18 points and 36 points for grade Ⅱ,and 9 points and 34 points for grade Ⅲ,The results showed that the difference between the two groups was statistically significant (x2 =2.45,P =0.01).The time of antibiotic use,postoperative tube extraction,postoperative first exhaust,postoperative first time out of bed and hospitalization in the laparoscopic group were respectively (61.2 ±24.2) d,(4.2 ± 1.2) h,(24.6 ±6.9) h,(4.6 ±2.2) h,(5.5 ±3.6) d and the open group were (72±72.6) d,(7.4 ±2.7) h,(52.2 ±4.8) h,(8.4 ±2.6) h,(13.5 ±8.2) d respectively,the differences were statistically significant (P ＜ 0.05).Conclusion The postoperative complications in laparoscopic group were lower than those in open group,so the laparoscopic group was the first choice for the treatment of acute appendicitis,while the open group was another choice for some patients.

Rapid Determination of 6 Kinds of Aconite Alkaloids in Rat Plasma by HPLC-Quadrupole/Electrostatic Field Orbitrap High Resolution Mass Spectrometry / 中国药房

OBJECTIVE:To establish HPLC-quadrupole/electrostatic field orbitrap high resolution mass spectrometry for rapid determination of aconitine,mesaconitine,hypaconitine,benzoylaconitine,benzoylmesaconine and benzoylhypacoitine in rat plasma. METHODS:Internal standard lappaconitine was added into plasma sample,and methanol precipitated protein was used for pretreatment. HPLC-quadrupole/electrostatic field orbitrap high resolution mass spectrometry was adopted. HPLC condition was as follows as Sinochrom ODS-BP C18column,mobile phase consisted of acetonitrile-1% formic acid solution(50:50,V/V),the flow rate of 0.6 mL/min,sample size of 10 μL,column temperature of 25 ℃,automatic sampler temperature of 4 ℃. Mass spectrum scanning mode was full ion monitoring model,positive ion acquisition,mass charge ratios(m/z)of ion were 646.32(aconitine), 632.30(mesaconitine),616.31(hypaconitine),604.31(benzoylaconitine),590.29(benzoylmesaconine),574.30(benzoylhypacoitine), 585.31(internal standard). Six male Wistar rats were collected and given single dose of total alkaloid extract of Aconitum carmichaeli(4 mg/kg)intragastrically. Blood samples were collected before medication(0 h)and 0.5,0.75,1.25,1.5,2,4,6, 8,10,24 h after medication. Plasma concentration was determined and pharmacokinetic parameters were calculated by using PK-Solver V2.0 software. RESULTS:The linear range of 6 kinds of aconitum alkaloids in plasma were 0.1-10 μ g/L(r>0.992). The limit of quantitation was 0.1 μ g/L. Average recovery was higher than 75%,RSDs of intra-day and inter-day,matrix effects,stability test were all lower than 15%. The tmaxof 6 kinds of aconite alkaloids were about 1.2 h;t1/2were about 10 h;cmaxof monoestertype aconite alkaloids were higher than those of diester-type aconite alkaloids. CONCLUSIONS:Established HPLC-quadrupole/electrostatic field orbitrap high resolution mass spectrometry is accurate,sensitive,simple and rapid, and can be used for plasma concentration monitoring of 6 kinds of aconitum alkaloids.

In vivo and in vitro studies of protective effect of CDPS onacute aging mouse model induced by D-galactose / 中国药理学通报

Aim To study the protective effect of CDPS on acute aging mouse model induced by D-galactose (D-gal) and its mechanism.Methods (1) The acute aging mouse model was induced by D-gal.After CDPS (25、50、100 mg·kg-1) treatment, the improving effect on learning and memory in mice was examined in vivo.(2) We also established the aging model on PC12 cells in vitro.After CDPS treatment (150、200 mg·L-1), the level of p-CREB in the nucleus was detected by Western blot, and the content of cAMP, PKA and brain derived neurotrophic factor (BDNF) levels were examined by the Elisa kits.Moreover, cAMP, PKA and BDNF were detected in PC12 cells under the condition that H89, the inhibitor of PKA, co-cultured with PC12 cells after CDPS treatment.(3) The UPLC/Q Exactive MS method was developed for determining the concentration of glutamic acid, dopamine and norepinephrine, which secreted in PC12 cells after CDPS treatment.Results (1) In vivo, CDPS significantly improved the memory impairment in aging mice induced by D-gal in the Morris assay.(2) In vitro, CDPS could significantly increase the expression of p-CREB (P<0.05), PKA, cAMP and BDNF (P<0.05).The H-89 abolished the increase of p-CREB (P<0.05), PKA, cAMP and BDNF (P<0.05) in PC12 aging cells induced by D-gal after CDPS treatment.(3) CDPS increased the release of dopamine, norepinephrine, and glutamate secreted in PC12 cells.Conclusion CDPS could significantly improve the learning and memory ability on aging mouse model in vivo, and reversed the damage in PC12 cells induced by D-gal by activating cAMP/PKA/CREB signal cascade, increase the expression of BDNF, and increasing modestly the release of excitatory neurotransmitter.

Study on the Chemical constituents of a Traditional Mogolian Medicine HERBA CLEMATIS / 世界科学技术-中医药现代化

This study was aimed to isolate and characterize of chemical constituents in a traditional Mongolian medicine HERBA CLEMATIS. Normal and reverse phase coloumn chromatography, gel filtration chromatography sephadex LH-20, and preparative HPLC were used for isolation and purification compounds from the water extraction of the arial part ofC. aethusaefoliaTurcz. The planar structures and spatial configurations of isolated compounds were identified by high resolution MS, 1D and 2D NMR, and other spectrographic methods. The chemical research on the Mongolian medicine results 6 compounds, dihydrodehydrodiconiferyl alcohol (1), syringaresinol (2), pinoresinol (3), epi-pinoresinol (4), lirioresinol B dimethyl ether (5) and loliolide (6). All the compounds were isolated from this plant for the first time.

Multi-plane hyaluronic acid injection for rhinoplasty / 中华整形外科杂志

<p><b>OBJECTIVE</b>To investigate the effect of multi-plane Hyaluronic acid (HA) injection for rhinoplasty.</p><p><b>METHODS</b>The HA was injected below or above the periosteum at the nasal bone, above the perichondrium at the cartilage portion of nose, and between the great alar cartilage at the nasal tip. The HA volume was 1-1.5 ml, according to the nose form and aesthetic assessment. Over-injection was not permitted. Touch-up injection could be performed one week after the first injection if need.</p><p><b>RESULTS</b>From Jan. 2010 to Jan. 2012, 60 cases underwent rhinoplasty with HA injection. The patients were followed up for 10-13 months with satisfactory result. The effect lasted about 9 months with the longest period as 12 months and the shortest period as 6 months.</p><p><b>CONCLUSIONS</b>Good results can be achieved with multi-plane HA injection for rhinoplasty.</p>

Correction of epicanthus by transverse incision and concurrent double-eyelid plasty / 中华医学美学美容杂志

Objective To explore epicanthus correction by transverse incision method and concurrent double-eyelid incision operation.Methods The transverse straight-line incision was performed in new inner canthus to the original canthal corner point; after the original inner canthus corner point was reached,the oblique-line parallel incision was performed along the lower eyelid so that full subcutaneous separation was obtained on the upper and lower incision; the malpositioned isomerous orbicular muscle and thickened tissue were released and excised so that the epicanthus skin was naturally restored; the superficial head of the inner canthus ligament was folded and sutured when necessary ; after small cat ears at the temporal side of the inner canthal incision was removed,routine double eyelid plasty was then performed,but the double eyelid and the inner canthus incisions were not continuous.Results The procedures were clinically applied in 258 cases and followed up for 3-18 months,showing that the epicanthus has disappeared,new inner canthus was in good appearance,the scar was not obvious,recurrence of the epicanthus was not found and double eyelids were beautiful in appearance.Conclusions The epicanthus correction by transverse incision and concurrent double-eyelid plasty is a simple and ideal approach for correction of single-edged eyelid with epicanthus and it is worthy of clinical promotion.