Analysis of Chemical Composition Variations in Plantaginis Semen at Different Frying Time Based on UPLC-Q-TOF/MSE / 中国实验方剂学杂志

ObjectiveIn order to explore the changes of chemical constituents in Plantaginis Semen before and after stir-frying， ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF/MSE） was used to rapidly identify and semi-quantitatively analyze the differential components in Plantaginis Semen processed at different stir-frying time. MethodWaters ACQUITY UPLC BEH C18 column （2.1 mm×100 mm， 1.8 μm） was employed with the mobile phase of 0.1% formic acid aqueous solution （A）-acetonitrile （B） for gradient elution （0-1 min， 5%-10%B； 1-2 min， 10%-15%B； 2-10 min， 15%-20%B； 10-12 min， 20%-40%B； 12-13 min， 40%-100%B； 13-14 min， 100%-5%B； 14-15 min， 5%B）， the flow rate was 0.3 mL·min-1， the column temperature was 40 ℃， and the injection volume was 3 μL. Electrospray ionization （ESI） was applied for mass spectrometric analysis under positive and negative ion modes， and the scanning range was m/z 50-1 500. MarkerLynx 4.1 software was used to find the differential compounds， and the intensity of each ion peak in samples with different stir-frying time was compared to study the content variations of these compounds. ResultA total of 20 components with potential significant differences were found， among which 17 were identified and 3 were unknown， mainly including phenylethanoid glycosides， iridoid glycosides， alkaloids and others. After processing， the peak intensities of 7 compounds， such as sucrose， geniposidic acid， verbascoside and plantagoguanidinic acid A， in Plantaginis Semen decreased. The peak intensities of orobanchoside， dianthoside and plantain D increased first and then decreased during the stir-frying process. The peak intensities of 10 compounds （decaffeoylacteoside， calceolarioside A， isoacteoside， etc.） increased， and 9 of them were newly generated components. ConclusionThe content and composition of the chemical components in Plantaginis Semen changed significantly after stir-frying， which may be related to the reduction of laxative effect and the enhancement of antidiarrheal and diuretic activities of Plantaginis Semen after stir-frying.

Chemical Components and Mechanism of Qiling Wenshen Formula in Treating Polycystic Ovary Syndrome / 中国实验方剂学杂志

ObjectiveTo systematically analyze the chemical components of QiLing Wenshen （QLWS） formula and explore the key active components and mechanism of the formula in the treatment of polycystic ovary syndrome （PCOS）. MethodThe chemical components of QLWS formula were systematically identified by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF/MSE） combined with comparison with reference substances， literature data， and databases. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and SwissADME were employed to screen the active components for network pharmacological analysis. SwissTargetPrediction， GeneCards， DisGeNET， and DrugBank were used to obtain the potential components and targets of the formula for the treatment of PCOS. The protein-protein interaction （PPI） network was constructed via STRING database for further screening of the core targets. Gene ontology （GO） annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment of core targets were carried out with DAVID database. Molecular docking was performed in MOE 2019. ResultA total of 90 components of QLWS formula were identified， and 32 active components and 45 core targets for treating PCOS were obtained. GO annotation obtained 429 terms and KEGG pathway enrichment screened out 110 signaling pathways， mainly involving phosphatidylin-ositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， estrogen signaling pathway， and hypoxia inducible factor-1 （HIF-1） signaling pathway. The molecular docking revealed that key active components in QLWS formula were icariin， salvianolic acid A\B\C， wogonin， magnoflorine， etc.， which may play a role in treating PCOS through regulating mitogen-activated protein kinase 1 （MAPK1）， epidermal growth factor receptor （EGFR）， mitogen-activated protein kinase 3 （MAPK3）， etc. ConclusionThis study preliminarily predicted that several key active components of QLWS formula could treat PCOS via multiple targets and multiple pathways based on UPLC-Q-TOF/MSE and network pharmacology， which could provide ideas and references for the study of pharmacodynamic material basis and mechanism of action of the formula.

Analysis of Chemical Constituents in Jiechangyan Qixiao Granules Based on UPLC-Q-TOF/MSE / 中国实验方剂学杂志

Objective:In order to systematically clarify the chemical composition of Jiechangyan Qixiao granules， the main chemical components in this preparation were rapidly identified and assigned by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF/MS^E）. Method:ACQUITY UPLC BEH C₁₈ column （2.1 mm×100 mm， 1.8 μm） was employed for UPLC analysis with the mobile phase of 0.1% formic acid aqueous solution （A）-acetonitrile （B） for gradient elution （0-2 min， 5%B； 2-16 min， 5%-21%B； 16-30 min， 21%-95%B； 30-33 min， 95%B； 33-34 min， 95%-5%B； 34-37 min， 5%B）. The flow rate was 0.3 mL·min^-1， the column temperature was 30 ℃， and the volume of sample injection was 2 μL. Electrospray ionization （ESI） was applied for scanning under positive and negative ion modes with the scanning range of <italic>m</italic>/<italic>z</italic> 60-1 200. MS^E mode was used to collect mass spectral data. The ion peaks were identified by comparing with the information of control substances， literature references and self-built database. Result:A total of 102 chemical components were separated and identified in Jiechangyan Qixiao granules， including organic acids， flavonoids and its glycosides， triterpenes， phenylethanoid glycosides， tannins， iridoid glycosides and other components， among which flavonoids and its glycosides were from Drynariae Rhizoma and Crataegi Fructus， phenylethanoid glycosides and iridoid glycosides were from Plantaginis Semen， triterpenoids and tannins were from Crataegi Fructus and Chebulae Fructus. Among the identified chemical constituents， there were 28 from Drynariae Rhizoma， 31 from Plantaginis Semen， 53 from Chebulae Fructus and 58 ingredients from Crataegi Fructus. Conclusion:The established UPLC-Q-TOF/MS^E can comprehensively and rapidly analyze the chemical constituents in Jiechangyan Qixiao granules， and preliminarily elucidates the chemical composition profile of this granules， which can lay a foundation for further research on the pharmacodynamic material basis and quality control of Jiechangyan Qixiao granules.

Sulfite as the substrate of C-sulfonate metabolism of α, β-unsaturated carbonyl containing andrographolide: analysis of sulfite in rats' intestinal tract and the reaction kinetics of andrographolide with sulfite / 中国天然药物

One-sixth of the currently known natural products contain α, β-unsaturated carbonyl groups. Our previous studies reported a rare C-sulfonate metabolic pathway. Sulfonate groups were linked to the β-carbon of α, β-unsaturated carbonyl-based natural compounds through this pathway. However, the mechanism of this type of metabolism is still not fully understood, especially whether it is formed through enzyme-mediated biotransformation or direct sulfite addition. In this work, the enzyme-mediated and non-enzymatic pathways were studied. First, the sulfite content in rat intestine was determined by LC-MS/MS. The results showed that the amount of sulfite in rat intestinal contents was from 41.5 to 383 μg·g

LCMS-IT-TOF Analysis of Retention Behavior of Sanguisorbae Radix Components on D101 Macroporous Resin and Polyamide Resin / 中国实验方剂学杂志

Objective:To study on the material basis of Sanguisorbae Radix by column chromatography and liquid chromatography-ion trap-time-of-flight mass spectrometry (LCMS-IT-TOF), and analyze the distribution of different components in Sanguisorbae Radix water extract on D101 macroporous resin and polyamide resin. Method:Sanguisorbae Radix water extract was separated by D101 macroporous resin and polyamide resin, and LCMS-IT-TOF was used for detection, chromatography separation was achieved on an ACQUITY UPLC HSS T3 column (2.1 mm×100 mm, 1.8 μm) with the mobile phase consisted of water (A) and acetonitrile (B) for gradient elution (0-10 min, 5%-20%B; 10-18 min, 20%-35%B; 18-23 min, 35%-50%B; 23-28 min, 50%-90%B; 28-30 min, 90%B; 30-33 min, 90%-5%B; 33-35 min, 5%B), the flow rate was 0.3 mL·min-1, the column temperature was 30 ℃. Data acquisition was carried out in electrospray ionization (ESI) under the positive and negative ion modes, the scanning range was m/z 100-1 200. According to mass spectrometry data such as accurate molecular mass and fragment information, combined with literature, different chemical components in loading effluents and ethanol eluents of Sanguisorbae Radix water extract were identified. A heat map of the distribution of components in each fraction was drawn by extracting mass spectrum peak intensity data of each sample. The elution rules of various components were compared visually. Result:The enrichment and separation of D101 macroporous resin and polyamide resin were obvious. Tannins in Sanguisorbae Radix water extract was mainly concentrated in loading effluent of macroporous resin and its water eluent, triterpenoids were mainly distributed in the 90% ethanol eluent of macroporous resin. In the above effluents and eluents, a total of 63 compounds (including isomers) were identified. Among them, 6 compounds, ellagic acid-4-pyranoarabinoside or its isomer, 6-O-galloylnorbergerin, 3-O-galloylnorbergerin, (6-acetyloxy-5,7-dihydroxy-8-methoxy-4-oxochromen-2-yl) acetate, ethyl 2-methyl-5,6-bis (sulfooxy) benzofuran-3- carboxylate were first discovered in Sanguisorbae Radix. Conclusion:The method can quickly and accurately identify the distribution of components in aqueous extract of Sanguisorbae Radix after column chromatography, providing experimental basis for exploring the pharmacodynamic components and mechanism of Sanguisorbae Radix.

Quality of Life in Old Patients with Dysphagia and Its Related Factors / 中国康复理论与实践

objective To investigate the quality of life in old patients with dysphagia and the related factors. Methods:From January to December, 2019, 523 old inpatients were selected and investigated with Swallowing-Quality of Life Questionnaire (SWAL-QOL), Eating Assessment Tool-10 (EAT-10), videofluoroscopic swallowing study (VFSS), Nutritional Risk Screening 2002 (NRS-2002) and FRIED scale. Results:There were 160 inpatients diagnosed dysphagia (30.59%). The total score of SWAL-QOL in the inpatients with dysphagia was (45.15±13.31), and the dimension scores from low to high were appetite, social function, swallowing symptoms, mental health, sleep, eating fear, eating time, fatigue, swallowing burden and communication. For the total score of SWAL-QOL, EAT-10 score ≥ 19 was the risk factor, while good health condition and accepting swallowing treatment were the protective factors. Conclusion:The quality of life is poor for the old inpatients with dysphagia, and early screening and intervention for dysphagia are needed.

Energy Demand and Its Regulatory Mechanism during Folliculogenesis / 中国医学科学院学报

The growth and development of follicles are regulated by genes,hormones and growth factors autocrined and paracrined from granulosa cells,theca cells,and oocytes.Products of glycolysis from granulosa cells such as pyruvate and lactate are one of the main energy sources,which play an important role during folliculogenesis and follicle maturity.Studies on the changes of the products and rate-limiting enzymes during granulosa cells' glycolysis help to clarify the molecular mechanism of energy demand in folliculogenesis and guide the clinical treatment of infertility due to abnormal follicular development.This article reviews recent research advances in the energy demand and regulatory mechanism in different states of folliculogenesis.

Variations of Chemical Constituents in Gardeniae Fructus Before and After Stir-frying by LCMS-IT-TOF / 中国实验方剂学杂志

Objective: To rapidly analyze chemical compositions in raw products and stir-fried products of Gardeniae Fructus,and determine the pharmacodynamic material basis of Gardeniae Fructus Praeparatus. Method: Liquid chromatography-ion trap-time-of-flight-mass spectrometry(LCMS-IT-TOF) was performed on ACQUITY UPLC HSS T3 column(2.1 mm×100 mm,1.8 μm),mobile phase was 0.005%formic acid aqueous solution(A)-acetonitrile(B) for gradient elution(0-5 min,10%-15%B;5-8 min,15%B;8-18 min,15%-95%B;18-20 min,95%B;20-22 min,95%-10%B;22-25 min,10%B),the column temperature was 30℃ and the flow rate was 0.4 mL·min-1,volume of sample injection was 2 μL;electrospray ionization(ESI) was applied for mass spectrometric analysis under positive and negative ion mode,the scanning ranges were m/z 100-1 000.The ion peaks were identified by comparison of control substances,mass spectrometry data analysis and literature references.The peak areas of some ion peaks before and after processing were compared,the changes of chemical compositions in Gardeniae Fructus after processing were investigated. Result: Based on the mass spectral data information and references,a total of 38 compounds were identified,no new compounds were produced after processing.The ion peak areas of main compounds were investigated during the stir-frying processing,the contents of geniposide,genipin-1-β-D-gentiobioside,shanzhiside,chlorogenic acid and crocin in Gardeniae Fructus Praeparatus were decreased;the contents of geniposidic acid and crocetin were increased. Conclusion: The method can rapidly and accurately identify the chemical constituents in Gardeniae Fructus Praeparatus.The changes of iridoids and crocins in Gardeniae Fructus during the stir-frying process may be related to hemostatic activity and protection of cardiovascular and cerebrovascular.

Reaction of Chlorogenic Acid with Sulfite and Its Application in Identification of Sulfur-fumigated Herbs / 中国实验方剂学杂志

Objective: To explore the structure and reaction sites of the reaction products of chlorogenic acid and sodium sulfite,and the chemical changes of chlorogenic acid in Lonicerae Japonicae Flos after sulfur fumigating. Method: Chlorogenic acid was reacted with sodium sulfite under mild conditions. Liquid chromatography-mass spectrometry-ion trap-time-of-flight (LC-MS-IT-TOF) and 1H nuclear magnetic resonance spectroscopy (1H-NMR) detection techniques were used to detect the reaction products,and the sulfur-fumigated and unsulfurized Lonicerae Japonicae Flos water extract was detected by LC-MS-IT-TOF. Result: After analyzing the mass spectrometry data of fragment ion,molecular cleavage and accurate molecular weight,according to the results of nuclear magnetic signals of chemical shift,peak intensity and peak splitting, the products of chlorogenic acid and sodium sulfite were preliminarily identified as chlorogenic acid α,β-unsaturated carbonyl addition product:3-((3-(3,4-dihydroxyphenyl)-2-sulfopropyl)oxy)-1,4,5-trihydroxycyclohexane-1-carboxylic acid or 3-((3-(3,4-dihy droxyphenyl)-3-sulfopropyl)oxy)-1,4,5-trihydroxycyclohexane-1-carboxylic acid,and the same characteristic fragments were detected as the addition product in the sulfur fumigated Lonicerae Japonicae Flos,but not found in the unsulfurized. Conclusion: It is the first time to demonstrate the structure and reaction sites of chlorogenic acid and sulfurous acid reaction products,and detect the chlorogenic acid sulfite addition product in sulfur-fumigated Lonicerae Japonicae Flos. Although it is still unclear how the sulfite addition compound produced by sulphur Lonicerae Japonicae Flos affects the efficacy and toxicological activity of Lonicerae Japonicae Flos,we shall still pay attention to the changes of active ingredients in sulphuric medicinal materials. Besides,this study can also provide reference for the studies of chemical composition changes after sulfuration of traditional Chinese medicine containing α,β-unsaturated carbonyl structure.

Progress on AIDS drug targets and small molecule inhibitors / 药学学报

The difficulty to eradicate the HIV-1, off-target effects together with the rapid emergence of multidrug-resistant strains have created an urgent need for more potent and less toxic therapies against other targets of HIV virus. From the point of view of medicinal chemistry, we summarizes and discusses current endeavours towards the discovery and development of novel inhibitors with various scaffolds or distinct mechanisms of action, and also provides examples illustrating new methodologies in medicinal chemistry that contribute to the identification of novel antiretroviral agents.

Reverse-flow axial skin flap of the delay by minimal invasive surgery / 中华医学美学美容杂志

Objective The mechanism of delaying flap with the minimal invasive surgery was approached to understand its effects on the whole delayed survival of skin flaps thoroughly so as to provide the rationale for its clinical use.Methods 80 male or female Wistar rats were randomly subdivided into two groups:delayed by the minimal invasive surgery,and immediately transfer without delay.Flaps in each group delayed were cut at 1,2,3 and 4 weeks,respectively.The flap was designed at the lower back of rat,with the size of 5 cm × 1 cm,crossing the middle area for 2.5 cm and including stem of iliac branch from iliolumbar artery.2 weeks after second operation,the survival area,capillary density and content of lactic acid of the flaps in each group were examined,and the survival of the falps delayed by the minimal invasive surgery was compared.Results The longer delaying time,and the higher survival rate were observed in the experimental group.Delaying for 3 weeks and 4 weeks,the survival rate was (86.13 ±1.13) ％,(93.49 ± 1.15) ％,respectively,in the experimental group.While in control group,the survival rate was no more than 63％.The longer delaying time,the higher the capillary density were noted in two groups,but 3 weeks delayed group equally matched to the 4 weeks delayed group.In the experimental group,the content of lactic acid increased peaked in 1 week delayed group,then fell-down gradually,but kept steady in 3 and 4 weeks delayed group.The content of lactic acid in the control group kept steady.Conclusions The experimental model is selected as cross-area axial flap on the lower back of rats.The minimal invasive surgery plays the same role as in delaying flaps,which causes vasoconstriction,resulting in disorder of internal environment,ischemia and hypoxia,finally vasodilatation.The more ramus anastomosis,the more survival rate of the flap.

Comparison of hand-assisted laparoscopic surgery and open surgery for portal hypertension: a meta-analysis / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the clinical efficacy and safety of hand-assisted laparoscopic surgery (HALS) vs. open surgery (OS) for portal hypertension.</p><p><b>METHODS</b>Relevant literature was retrieved from databases including PubMed, EMBASE, Cochrane Library, Chinese Biomedical Literature Database, Chinese Journal Full Text Database, Chinese Vip Datebase, and Chinese Wanfang. All the relevant trials were collected and then we performed the literature screening. The quality of the included trials was assessed by Cochrane Systematic Review Handbook 5.1. Meta-analyses were conducted by RevMan 5.1 software.</p><p><b>RESULTS</b>Eight studies were involved and 435 patients were included. Meta-analysis showed that there was significant difference in intraoperative blood loss [MD = -140.95, 95% CI = (-233.58--48.32), P=0.003], total abdominal drainage volume [MD = -544.32, 95% CI= (-789.97--298.67), P<0.0001], postoperative exhaust time [MD = -28.30, 95% CI= (-41.90--14.69), P<0.0001], length of postoperative hospital stay [MD =-3.61, 95% CI= (-4.16--3.07), P<0.00001], postoperative complication [OR=0.35, 95% CI= (0.15-0.82), P=0.02] between HALS group and OS group. However, the operative time was not significantly different between these two groups [MD = -7.44, 95% CI = (-36.00 -21.12), P=0.61].</p><p><b>CONCLUSIONS</b>Compared with the traditional OS, HALS can reduce intraoperative bleeding, postoperative exhaust time, hospitalization time, surgical trauma, and postoperative complications.The patients often recover more quickly from the HALS. However, its long-term effictiveness and safety still needs to be further verified by randomized controlled trials.</p>