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OBJECTIVE To identify an d analyze chemical cons tituents of Pleione yunnanensis with origin of Pleione yunnanensis. METHODS UPLC-Q-Exactive-Plus-Orbitrap-MS was adopted. The determination was performed on Hyperdil GOLD column with mobile phase consisted of 0.1％ formic acid solution-0.1％ formic acid acetonitrile solution （gradient elution ）at the flow rate of 0.3 mL/min. The column temperature was set at 40 ℃，and sample size was 2 µL. The electrospray ion source was adopted，and the scanning range was m/z 100-1 500，and the scanning mode was positive and negative ion exchange mode of full scan+ddMS2. The structure of chemical constituents were determined by using Compound Discoverer 3.1 software，comparing with mzCloud，PubChem network database and OTCML ，on the basis of reference substance and published literatures. RESULTS & CONCLUSIONS A total of 42 chemical constituents were identified （positive ion mode has 24，negative ion mode has 27）， including 13 benzyl succinate glycosides （such as dactylorhin C ，coelovirin A ，militarine），4 phenol glycosides （such as adenosine ， guanosine，gastrodin），3 alkaloids（choline，betaine，berberine），and one flavonoid （nobiletin），7 aromatics（such as DL-lysine ， DL-arginine，DL-glutamine），one sugar （sucrose），3 benzenes（shancigusin H ，shancigusin H isomer ，batatasin Ⅲ）and 10 others （such as p-methoxybenzoic acid ，monomethyl dodecanedioate ，diphenylamine）. Glucose oxybenzyl and some small mole cules are easy to be lost in the cleavage of benzyl succinate glycosides；glycosyl is easy to be lost in the cleavage of phenol glycosides；the cleavage of alkaloids mainly manifest as the cleavage and loss of small molecular substituents ；demethyla- tion reaction is occurred in most flavonoids.
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Objective:To evaluate the survival outcome and toxicity of hypofractionated radiotherapy (45 Gy/15f) in patients with locally advanced/advanced non-small cell lung cancer (NSCLC) who are ineligible for conventional fractionated radiotherapy.Methods:The early efficacy, survival and toxicity of inoperable patients ( n=64) with locally advanced/advanced NSCLC patients admitted to Cancer Hospital of Tianjin Medical University from 2014 to 2018 were retrospectively analyzed. Hypofractionated radiotherapy (45 Gy/15f) were performed by using intensity-modulated radiotherapy or volumetric-modulated arc therapy technologies on Pinnacle 9 planning system. Results:The median follow-up time was 26 months. The early efficacy was available in 58 patients: complete response for 2 cases (3%), partial response for 22(38%), stable disease for 28(44%) and progressive disease for 6(9%), respectively. The local control rate was 90%. The median time to progression (TTP) and the median overall survival (OS) for all patients was 8.2 months and 21.0 months, respectively. The 1-, 2-and 3-year TTP rate was 37%, 28%, 14% and the OS rate was 66%, 43% and 27%, respectively. The incidence of esophagitis was 17%( n=11), 19%( n=12) for radiation pneumonitis and 20%( n=13) for myelosuppression. No grade ≥3 esophagitis or pneumonia was found. Conclusion:Hypofractionated radiotherapy (45 Gy/15f) is efficacious and safe for patients with locally advanced/advanced NSCLC, which yields controllable adverse events.
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OBJECTIVE：To estab lish a method that can comprehensively and rapidly analyze the chemical compositions of Miao medicine Caesalpinia decapetala，and to providing reference for quality control and pharmacodynamic material basis study of C. decapetala . METHODS ：UPLC-Q-TOF-MS/MS was adopted . The determination was performed on Agilent SB-C 18 column with mobile phase consisted of 0.1％ formic acid solution- 0.1％ formic acid acetonitrile （gradient elution ）at the flow rate of 0.25 mL/min. The column temperature was 30 ℃，and sample size was 2 µL. ESI source was applied in negative and positive scanning ion mode and data collection range of m/z 50-1 500. The capillary voltage was 4.5 kV，the atomizing gas （nitrogen）pressure was 1.2 Bar， the solvent removal gas was nitrogen ，the flow rate of solvent removal gas was 8 L/min and the solvent removal gas temperature was 200 ℃. Data Analysis 4.2 software was adopted to analyze fragment ion information of each peak ，and identify chemica l compositions on the basis of relevant literature and mass spectograms of reference substance. RESULTS ：Under positive ion mode ， 9 chemical compounds were identified ；peak 1，2，3，4，5，6，7，8，9 were catechin ，protohematoxylin B ，epicatechin，ethyl gallate，quercetin，luteolin，3-deoxy-hematoxylin chalcone ， isoliquiritigenin and linoleic acid. Under negative ion mode ， U1812403）， totally 21 peaks were confirmed and 13 compounds were identified；peak 3，4，5，6，7，8，9，10，11，12，13，15， 21 were catechins ， brevifolin carboxylic acid ， proto- hematoxylin B ，epicatechin，ethyl gallate ，epicatechin gallate ， quercetin，resveratrol，hematoxylin，luteolin，3-deoxy-hema- toxylin， isoliquiritigenin， linoleic acid. CONCLUSIONS UPLC-Q-TOF-MS/MS method is established successfully for analysis of chemical compositions in C. decapetala .
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OBJECTIVE：To establish the HP LC fing erprints of Oxalis corniculata and to simultaneously determine the contents of isovitexin and swertisin. METHODS ：HPLC method was adopted. The determination was performed on ACE Excel- 5-C18column with mobile phase consisted of methanol- 0.1％ phosphoric acid water （gradient elution ）at the flow rate of 1 mL/min. The column temperature was 35 ℃，and detection wavelength was set at 280 nm. The sample size was 10 μL. Using isovitexin peak as reference，HPLC fingerprints of 12 batches of sample were drawn. The similarity evaluation was performed by using Similarity Evaluation System of Chromatogram Fingerprint of TCM （2012 edition）to determine common peaks. The contents of isovitexin and swertisin were determined by same method of above chromatogram. RESULTS ：There were 19 common peaks in HPLC chromatogram of 12 batches of O. corniculata ，with the similarity above 0.89. Two common peaks including isovitexin and swertisin were identified. The linear range of two components were 3.91-117.36 μg/mL（r＝0.999 4）and 9.88-118.56 μg/mL（r＝ 0.999 2），respectively. The limits of quantitation were 0.675 and 3.587 μg/mL；the limits of detection were 0.205 and 1.087 μg/mL， respectively. RSDs of precision ，stability and reproducibility tests were all lower than 2％. The recoveries were 95.46％-99.10％ （RSD＝1.23％ ，n＝6），95.34％ -101.23％（RSD＝2.74％ ，n＝6），respectively. The average contents were 0.227-1.654， 0.641-2.052 mg/g，respectively. CONCLUSIONS ：Established fingerprints can be used for the quality control of O. corniculata ； the content determination method is simple and accu rate，and can be used for simultaneous determination of two components.
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OBJECTIVE：To struc turally modify shikimic acid ，and to investigate the reversal effects of its derivatives on paclitaxel-resistant human breast cancer cells MCF- 7/PTX. METHODS ：Using shikimic acid as the lead structure ，1-position carboxyl group was structurally modified to synthesize a series of shikimic acid derivatives through esterification ，amidation， hydrogenation and reduction ，etc. Using non-drug resistant cells MCF- 7 as reference ，MTT assay was used to screen derivatives with inhibitory activity as well as half-inhibitory concentration （IC50）and reversal index （RI）of derivatives to MCF- 7/PTX. With the drug resistance-related transgelin 2 as the target ，the molecular docking of the active derivatives with the drug resistance-related protein was carried out by using Glide 1.0 computer-aided design software. RESULTS ：Totally 15 derivatives were obtained （T1-T15）， of which T 4-T15 were obtained for the first time. MTT assay showed that （3R， 4S， 5R） -N-benzyl-3， 4， 5-trihydroxy-1-cyclohexene-1-formamide（T7），（3R，4S，5R）-N-（3，4，5-trihydroxy-1-cyclohexenylmethyl）-benzylamine（T14）， （3R，4S，5R）-3，4-O-isopropyl-5-O-acetyl-1-cyclohexene-1-methyl formate （T15）inhibited MCF- 7 and MCF- 7/PTX cells to a certain extent ；IC50 values of T 7，T14 and T 15 combined with pacliaxel to MCF- 7/PTX cells were significantly lower than that in negative control （Paclitaxel alone ）group（P＜0.05）. RIs of T 14 and T 15 were higher ，and RIs of the highest dose were 8.8 and 9.3， which were equivalent to positive control verapamil （10.8）. Th e results of molecular docking showed that the hydroxyl groups at positions 3，4 of T 7 could form multiple hydrogen bonds with ； Arg625 and Asp 627 in the catalytic region of transgelin 2. In addition to the hydrogen bond mentioned above at T 7，the mail：batistuta28@126.com secondary amine side chain at position 1 of T 14 could also form hydrogen bond with Glu 657 of transgelin 2. When the hydroxyl group on the T 15 mother nucleus was derived from the donor group ，the binding of the hydroxyl group to transgelin 2 was closer and the inhibition was enhanced. CONCLUSIONS ： The derivatives T 7，T14 and T 15 have certain reverse activity to paclitaxel-resistant human breast cancer cells. The polyhydroxy structure of the mother nucleus is the main structural region of the hydrogen bond between shikimic acid and its derivatives and transgelin 2. The derivation of its power supply group or the introduction of secondary amines and hydrophobic groups into the 1-carboxyl group of shikimic acid is benifit for enhancing the drug resistance reversal effect of derivative .
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OBJECTIVE：To explore the metabolic charact eristics of Miao medicine Laportea bulbifera extract in isolated human intestinal flora. METHODS ：L. bulbifera was extracted with 70％ ethanol reflux extraction. After concentration，extraction with n-butanol and drying ，L. bulbifera extract was obtained. Taking 0.05 g/mL L. bulbifera extract 1 mL mixed with isolated human intestinal flora fluid 10 mL and cultured for 36 h in anaerobic environment （setting up blank control without drugs or human intestinal bacterial solution ），so as to simulate the metabolic process of the extract in human intestine. The metabolites were detected by UPLC-Q-TOF/MS. The determination was performed on Agilent Eclipse Plus C 18 RRHD column with mobile phase consisted of 0.01％ formic acid water solution- 0.01％ formic acid acetonitrile solution （gradient eluetion ）at the flow rate of 0.25 mL/min. The column temperature was set at 40 ℃，and the sample size was 1 µL. ESI detection was adopted and scanned by negative ion mode （ESI－）；the capillary voltage was 4.5 kV，the ion source temperature was 120 ℃，the collision energy was 15-32 V，and the scanning range was m/z 50-1 000. The “Strip”module of MassLynx V 4.1 software was used to analyze the differential chromatograms between the reaction solution and the blank control of L. bulbifera extract. Mass spectrum data and UNIFI so ftware were used to predict relative molecular weight and formula ；based on the information of substance control and related literature reports ， the structure and biotransformation pathway of L. bulbifera metabolites in isolated human intestinal flora were predicted and analyzed. RESULTS & CONCLUSIONS ： A total of 3 prototype ： products（rutin，quercetin，kaempferol-3-O-rutinoside）and 22metabolites （mainly the metabolites of quercetin ，mono- caffeoylquinic acid ，isoquercitrin，etc.） were detected after metabolized in isolated human intestinal flora. Itsbiotransformation pathway is phase Ⅰ reaction，which mainly consisted of reduction ，oxidation and hydrolysis.
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Extensive-stage small cell lung cancer (ES-SCLC) accounts for approximately two-thirds of all SCLCs. Chemotherapy is still the main treatment, supplemented with radiotherapy and other comprehensive treatments. Although sensitive to chemotherapy and radiotherapy, almost all ES-SCLCs are vulnerable to treatment resistance and have high recurrence rates. Therefore, novel therapies are needed to improve treatment efficacy. The recent advances in radiotherapy for ES-SCLC include prophylactic cranial irradiation (PCI) and thoracic radiotherapy (TRT). Moreover, immunotherapy has shown good antitumor activity, and immune-checkpoint inhibi-tors may become an important breakthrough in SCLC treatment. This article briefly reviewed the clinical research on radiotherapy and immunotherapy for advanced-stage SCLC.
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OBJECTIVE:To provide reference for rational use of antibacterial drugs in the clinic. METHODS:In retrospective study,outpatient and emergency antibacterial drugs prescriptions were randomly selected from a hospital during 2013-2014,and then analyzed statistically. DDDs of antibacterial drugs were analyzed by using DDD method. RESULTS:From 2013-2014,the ap-plication rate of antibacterial drugs in the hospital declined substantially from 13.8% to 11.9%,and the rate of irrational use dropped from 2.7% to 1.2%. The application rate of antibacterial drugs was higher in pediatric department,emergency department and urology department;drug cost per capita was higher in infectious department,nephrology department and emergency depart-ment. The application rate of antibacterial drugs in pediatric department decreased greatly in 2014,compared with 2013,maintain-ing about 40%. The application rate of antibacterial drugs in emergency department during Jan.-Sept. in 2014 was lower than corre-sponding period in 2013,and that of the hospital during Jan.-Sept. in 2014 was lower than corresponding period in 2013,but dur-ing Oct.-Dec. in 2014 was slightly higher than corresponding period in 2013. Single type of antibacterial drugs were mainly used in outpatient department,accounting for 91.50% and 90.77% of antibacterial drug prescriptions in 2013 and 2014;two-drug account-ed for 8.44% and 9.11%. The top 3 antibacterial drugs in the list of DDDs during 2013-2014 were roxithromycin,cefuroxime and cefminox. CONCLUSIONS:The use of antibacterial drugs is up to the requirements of Nation Special Rectification Actirity for Clin-ical Application of Antibacterial Drugs in 2013. The prescription comment improve the quality of antibacterial drug prescriptions and rational use index greatly in outpatient department,but the application rate of antibacterial drugs is too high in some depart-ment. There still is irrational use of antibacterial drugs.
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Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. However, at present, there are still no effective therapeutic methods for NAFLD in clinical practice. Lifestyle changes, especially changes in eating habits, play an important role in the treatment of NAFLD. This review summarizes the role of fatty acids, carbohydrates, proteins, and vitamins in the development and progression of NAFLD, and points out that a proper diet can help improve the condition of patients with NAFLD.
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Objective: To investigate the absorption and transepithelial transport characteristics of scutellarin and scutellarein in the human colonic adenocarcinoma cell (Caco-2) monolayer model. The influence factors on these two compounds' absorption were investigated, such as buffer solution, duration of culture, and inhibitors of multidrug resistance-associated protein 2 (MRP(2)), breast cancer drug resistance protein (BCRP) and P-glycoprotein (P-gp). Methods: By using Caco-2 monolayer as an intestinal epithelial cell model, the transport process was studied from apical (AP) side to basolateral (BL) side or from BL to AP. The two compounds were determined by high-performance liquid chromatography coupled with diode-array-detector detection. Transport parameters and apparent permeability coeffients (P(app)) were calculated. Results: The P(app) values of scutellarin and scutellarein were different in two buffer solutions, respectively. In phosphate buffered saline, scutellarin had no absorption from AP to BL, while its P(app) value was 0.74×10(-6) to 1.58×10(-6) cm/s from BL to AP. The P(app) values of scutellarein were 4.33×10(-6) to 6.79×10(-6) cm/s and 1.32×10(-6) to 2.56×10(-6) cm/s from AP to BL and from BL to AP, respectively. The P(app) value gradually decreased with time. The absorption of scutellarein was better than that of scutellarin. The scutellarin absorption was improved by verapamil, MK-571 and reserpine. The scutellarein absorption was improved by verapamil whereas its excretion was improved by MK-571. Conclusion: Absorption of scutellarin is difficult in Caco-2 monolayer cells, which contributes to its low bioavailability. Scutellarein absorption is better than scutellarin absorption. Scutellarein transepithelial transport is passive diffusion. The inhibitor of P-gp can improve scutellarin and scutellarein transportation. The inhibitors of MRP(2) and BCRP can promote transportation of scutellarin. The inhibitor of MRP(2) can promote efflux of scutellarein. The multidrug resistance-associated protein may be the second reason for low bioavailability of scutellarin.