Objective To establish a method for determination of ciprofol and propofol in human plasma and apply it to detect the drug concentration of general anesthesia in patients plasma undergoing elective surgery.Methods Plasma samples were precipitated with acetonitrile,and Symmetry C18 column(4.6 mm x 150.0 mm,3.5 pm)was selected and the mobile phase consisted of acetonitrile(B)and 0.01％ammonia water(containing 5 mmol·L-1 ammonium acetate;A)with gradient elute.The internal standard was D6-ciprofol.Electrospray power supply and negative ionization of multi-reaction monitoring were used for mass spectrum conditions.The specificity,linearity and lower limit of quantitation,precision,recovery rate,and matrix effects of the method were investigated.Results The concentration of ciprofol in human plasma was linear in the range of 15-2 000 ng·mL-1;and the standard curve equation was y=1.94 × 10-3x+8.17 × 10-3.The concentration of propofol in human plasma was linear in the range of 30-4 000 ng·mL-1;and the standard curve equation was y=3.29 × 10-3x+6.90 × 10-2.The relative standard deviation values of ciprofol and propofol for intra-day and inter-day precision were less than 9％,and the absolute recoveries were both above 90％.The matrix effects of the analytes were within the range of±7％.The concentrations of ciprofol and propofol in plasma samples of 21 patients were 388.82-1 135.66 ng·mL-1 and 1 015.98-2 796.43 ng·mL-1,respectively.Conclusion The method established conformed to the standards for analyzing biological samples is convenient with high accuracy,and can simultaneously determine the concentrations of ciprofol and propofol in human plasma,which is suitable for clinical blood concentration monitoring and human pharmacokinetic study.

Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) was used to rapidly identify the chemical components in Dracocephalum moldavica, and UPLC was employed to determine the content of its main components. MS analysis was performed using an electrospray ionization(ESI) source and data were collected in the negative ion mode. By comparing the retention time and mass spectra of reference compounds, and using a self-built compound database and the PubChem database, 68 compounds were identified from D. moldavica, including 36 flavonoids, 22 phenylpropanoids, 4 phenols, and 6 other compounds. On this basis, a UPLC quantitative method was established to simultaneously determine 8 main components, i.e., luteolin-7-O-glucuronide, apigenin-7-O-glucuronide, rosmarinic acid, diosmetin-7-O-glucuronide, tilianin, acacetin-7-O-glucuronide, acacetin-7-O-(6″-O-malonyl)-glucoside, and acacetin. A Waters ACQUITY BEH C_(18) column(2.1 mm × 100 mm, 1.7 μm) was used, with acetonitrile and a water solution containing 0.1% formic acid and 0.1% phosphoric acid as the mobile phase for gradient elution. The detection wavelength was set at 330 nm, with a flow rate of 0.4 mL·min~(-1), and the column temperature was maintained at 35 ℃. The 8 components demonstrated good linearity(r≥0.999 9) over a wide mass concentration range(50 or 100 times). The average recovery rate ranged from 97.5% to 105.1%, and the relative standard deviations(RSDs) were 0.90% to 3.4%(n= 6), indicating that the method was simple, accurate, and reliable. In 17 batches of D. moldavica samples, the content of these 8 components ranged from 0.405 to 2.10, 0.063 to 0.342, 0.446 to 2.43, 0.415 to 1.47, 1.57 to 4.34, 0.173 to 0.386, 1.00 to 5.40, and 0.069 to 0.207 mg·g~(-1), respectively. These results indicate significant differences in the internal quality of the samples, highlighting the need for strict quality control to ensure their pharmacodynamic efficacy. This study provides a scientific basis for the rapid discovery of pharmacodynamic substances, comprehensive quality control, and the formulation or revision of quality standards for D. moldavica.
Tandem Mass Spectrometry/methods* ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Lamiaceae/chemistry* ; Flavonoids/chemistry*

Objective To establish a method for determination of ciprofol and propofol in human plasma and apply it to detect the drug concentration of general anesthesia in patients plasma undergoing elective surgery.Methods Plasma samples were precipitated with acetonitrile,and Symmetry C18 column(4.6 mm x 150.0 mm,3.5 pm)was selected and the mobile phase consisted of acetonitrile(B)and 0.01％ammonia water(containing 5 mmol·L-1 ammonium acetate;A)with gradient elute.The internal standard was D6-ciprofol.Electrospray power supply and negative ionization of multi-reaction monitoring were used for mass spectrum conditions.The specificity,linearity and lower limit of quantitation,precision,recovery rate,and matrix effects of the method were investigated.Results The concentration of ciprofol in human plasma was linear in the range of 15-2 000 ng·mL-1;and the standard curve equation was y=1.94 × 10-3x+8.17 × 10-3.The concentration of propofol in human plasma was linear in the range of 30-4 000 ng·mL-1;and the standard curve equation was y=3.29 × 10-3x+6.90 × 10-2.The relative standard deviation values of ciprofol and propofol for intra-day and inter-day precision were less than 9％,and the absolute recoveries were both above 90％.The matrix effects of the analytes were within the range of±7％.The concentrations of ciprofol and propofol in plasma samples of 21 patients were 388.82-1 135.66 ng·mL-1 and 1 015.98-2 796.43 ng·mL-1,respectively.Conclusion The method established conformed to the standards for analyzing biological samples is convenient with high accuracy,and can simultaneously determine the concentrations of ciprofol and propofol in human plasma,which is suitable for clinical blood concentration monitoring and human pharmacokinetic study.

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/MS^E） 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.

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.
Acupuncture Points ; Blood Glucose/metabolism* ; Cholesterol, LDL ; Electroacupuncture ; Humans ; Insulin Resistance ; Intestines ; Lipids ; Lymphocytes ; Obesity/therapy* ; Obesity, Morbid ; Triglycerides ; Vascular Endothelial Growth Factor C

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged ; Asian Continental Ancestry Group ; Blood Glucose/analysis* ; China/epidemiology* ; Cohort Studies ; Diabetes Mellitus/blood* ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/analysis* ; Glycemic Index ; Humans ; Male ; Middle Aged ; Uric Acid/blood*

Traditional Chinese medicines(TCMs) have certain limitations in the clinical research design in their post-marketing evaluation, so that randomized controlled programs cannot be strictly implemented in some studies, while the objective performance criteria is a reasonable external controlled research method that has been gradually recognized at home and abroad in recent years in addition to randomized controlled trial(RCT) method. It is more mature in medical devices, surgery and other research fields, but there is no relevant report in the field of post-marketing evaluation of Chinese patent medicines. In this paper, the application prospect of the objective performance criteria and the problems were discussed in the field of post-marketing evaluation of TCM. The characteristics of as TCM are more consistent with the scope of the objective performance criteria, the application of the objective performance criteria in post-marketing evaluation of Chinese patent medicines, especially in single arm research, can break through the limitations of existing conventional clinical research methods, and improve the level of evidence, with good feasibility and advantages. However, in the application process, we should pay attention to the key issues such as the selection of index, research population, follow-up period and the reference selection, to ensure the quality of research. This research group has carried out some exploration and practice in the field of post-marketing evaluation of TCM injections by using single arm combined with the objective performance criteria, hoping to establish the key technology in this field, and provide certain research and design reference for the secondary development of Chinese patent medicines.
Drugs, Chinese Herbal ; Marketing ; Medicine, Chinese Traditional ; Nonprescription Drugs ; Product Surveillance, Postmarketing ; Randomized Controlled Trials as Topic

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 m/z 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.

Background::Mounting evidence, consistent with our previous study, showed that γ-aminobutyric acid type A receptor (GABAAR) played an indispensable role in airway inflammation and mucus hypersecretion in asthma. Monocyte chemotactic protein-inducing protein 1 (MCPIP1) was a key negative regulator of inflammation. Recent studies showed that inflammation was largely suppressed by enhanced MCPIP1 expression in many inflammatory diseases. However, the role and potential mechanism of MCPIP1 in airway inflammation and mucus hypersecretion in asthma were still not well studied. This study was to explore the role of MCPIP1 in asthmatic airway inflammation and mucus hypersecretion in both mice and BEAS-2B cells, and its potential mechanism.Methods::In vivo, mice were sensitized and challenged by ovalbumin (OVA) to induce asthma. Airway inflammation and mucus secretion were analyzed. In vitro, BEAS-2B cells were chosen. Interleukin (IL)-13 was used to stimulate inflammation and mucus hypersecretion in cells. MCPIP1 Lentiviral vector (LA-MCPIP1) and plasmid-MCPIP1 were used to up-regulate MCPIP1 in lung and cells, respectively. MCP-1, thymic stromal lymphopoietin (TSLP), mucin 5AC (MUC5AC), MCPIP1, and GABAARβ2 expressions were measured in both lung and BEAS-2B cells. Immunofluorescence staining was performed to observe the expression of GABAARβ2 in cells. Results::MCPIP1 was up-regulated by LA-MCPIP1 ( P < 0.001) and plasmid-MCPIP1 ( P < 0.001) in lung and cells, respectively. OVA-induced airway inflammation and mucus hypersecretion, OVA-enhanced MCP-1, TSLP, MUC5AC, and GABAARβ2 expressions, and OVA-reduced MCPIP1 were significantly blunted by LA-MCPIP1 in mice (all P < 0.001). IL-13-enhanced MCP-1, TSLP, MUC5AC, and GABAARβ2 expressions, and IL-13-reduced MCPIP1 were markedly abrogated by plasmid-MCPIP1 in BEAS-2B cells (all P < 0.001). Conclusion::The results of this study suggested that OVA and IL-13-induced airway inflammation and mucus hypersecretion were negatively regulated by MCPIP1 in both lung and BEAS-2B cells, involving GABAAR signaling pathway.