Liquid chromatography-electrospray ionization tandem mass spectrometry(LC-ESI-MS)is a widely utilized technique for in vivo pharmaceutical analysis.Ionization interference within electrospray ion source,occurring between drugs and metabolites,can lead to signal variations,potentially compromising quantitative accuracy.Currently,method validation often overlooks this type of signal interference,which may result in systematic errors in quantitative results without matrix-matched calibration.In this study,we conducted an investigation using ten different groups of drugs and their corresponding me-tabolites across three LC-ESI-MS systems to assess the prevalence of signal interference.Such in-terferences can potentially cause or enhance nonlinearity in the calibration curves of drugs and metabolites,thereby altering the relationship between analyte response and concentration for quanti-fication.Finally,we established an evaluation scheme through a step-by-step dilution assay and employed three resolution methods:chromatographic separation,dilution,and stable labeled isotope internal standards correction.The above strategies were integrated into the method establishment process to improve quantitative accuracy.

Humans ; Asthma/drug therapy* ; Biological Therapy

Objective To investigate the morbidity, diagnostic profile and perinatal outcome of pregestational diabetes mellitus (PGDM) in 15 hospitals in Guangdong province. Methods A total of 41338 women delivered in the 15 hospitals during the 6 months,195 women with PGDM(PGDM group) and 195 women with normal glucose test result(control group)were recruited from these tertiary hospitals in Guangdong province from January 2016 to June 2016. The morbidity and diagnostic profile of PGDM were analyzed. The complications during pregnancy and perinatal outcomes were compared between the two groups. In the PGDM group, pregnancy outcomes were analyzed in women who used insulin treatment (n=91) and women who did not (n=104). Results (1)The incidence of PGDM was 0.472%(195/41338). Diabetes mellitus were diagnosed in 59 women (30.3%, 59/195) before pregnancy, and 136 women (69.7%,136/195) were diagnosed as PGDM after conceptions. Forty-six women (33.8%) were diagnosed by fasting glucose and glycohemoglobin (HbA1c) screening. (2) The maternal age, pre-pregnancy body mass index (BMI), prenatal BMI, percentage of family history of diabetes, incidence of macrosomia, concentration of low density lipoprotein were significantly higher in PGDM group than those in control group (all P<0.05). Women in PGDM group had significantly higher HbA1c concentration((6.3±1.3)% vs (5.2±0.4)%), fasting glucose [(6.3±2.3) vs (4.8±1.1) mmol/L], oral glucose tolerance test(OGTT)-1 h glucose((12.6±2.9) vs (7.1± 1.3) mmol/L)and OGTT-2 h glucose [(12.0±3.0) vs (6.4±1.0) mmol/L] than those in control group (P<0.01). (3)The morbidity of preterm births was significantly higher (11.3% vs 1.0%, P<0.01), and the gestational age at delivery in PGDM group was significantly smaller [(37.6±2.3) vs (39.2±1.2) weeks, P<0.01]. Cesarean delivery rate in the PGDM group (70.8% vs 29.7%) was significantly higher than the control group (P<0.01). There was significantly difference between PGDM group and control in the neonatal male/female ratio (98/97 vs 111/84, P=0.033). The neonatal birth weight in PGDM group was significantly higher((3159±700) vs (3451±423) g, P<0.01). And the incidence of neonatal hypoglycemia in the PGDM group was higher than the control group (7.7% vs 2.6%, P=0.036).(4)In the PGDM group, women who were treated with insulin had a smaller gestational age at delivery [(36.9±2.9) vs (37.9±2.5) weeks, P<0.01], and the neonates had a higher neonatal ICU(NICU)admission rate (24.2% vs 9.6% , P<0.01). Conclusions The morbidity of PGDM in the 15 hospitals in Guangdong province is 0.472%. The majority of PGDM was diagnosed during pregnancy; HbA1c and fasting glucose are reliable parameters for PGDM screening. Women with PGDM have obvious family history of diabetes and repeated pregnancy may accelerate the process of diabetes mellitus. Women with PGDM have higher risk for preterm delivery and neonatal hypoglycemia. Unsatisfied glucose control followed by insulin treatment may increase the need for NICU admission.

Diabetes, Gestational ; blood ; diagnosis ; Female ; Glucose Tolerance Test ; Humans ; Pregnancy ; World Health Organization

Ginsenoside compound K (GCK), the main metabolite of protopanaxadiol constituents of Panax ginseng, easily produces alkali metal adduct ions during mass spectrometry particularly with lithium. Accordingly, we have developed a rapid and sensitive liquid chromatography-tandem mass spectrometric method for analysis of GCK in human plasma based on formation of a lithium adduct. The analyte and paclitaxel (internal standard) were extracted from 50 µL human plasma using methyl tert-butyl ether. Chromatographic separation was performed on a Phenomenex Gemini C18 column (50 mm×2.0 mm; 5 μm) using stepwise gradient elution with acetonitrile-water and 0.2 mmol/L lithium carbonate at a flow rate of 0.5 mL/min. Detection was performed in the positive ion mode using multiple reaction monitoring of the transitions at m/z 629→449 for the GCK-lithium adduct and m/z 860→292 for the adduct of paclitaxel. The assay was linear in the concentration range 1.00-1000 ng/mL (r (2)>0.9988) with intra- and inter-day precision of ±8.4% and accuracy in the range of -4.8% to 6.5%. Recovery, stability and matrix effects were all satisfactory. The method was successfully applied to a pharmacokinetic study involving administration of a single GCK 50 mg tablet to healthy Chinese volunteers.

Objective: To investigate the effects of a Chinese herbal formula for calming liver and suppressing yang on the protein expressions of vascular tissues in spontaneously hypertensive rats (SHRs), and to explore the mechanism of efficacy. Methods: Twenty SHRs were randomly divided into model group and treatment group. Another 10 Wistar-Kyoto rats were selected as a normal control. SHRs in the treatment group were administered with the formula for calming liver and suppressing Yang for 4 weeks. During the course of treatment, blood pressure and heart rates were monitored every week and the ethology of rats, including irritability and rotation endurance was also evaluated. After treatment, thoracic aorta was obtained and its proteins were separated by 2-dimensional gel electrophoresis (2-DE). The differentially expressed proteins were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and database query. Results: The formula for calming liver and suppressing yang not only decreased the systolic blood pressure and heart rate, but also improved irritability degree and rotation endurance time of SHRs. This experiment had established the 2-DE graph of protein expressions of vascular tissues in SHRs. Compared with the normal group, the expressions of 15 proteins were down-regulated, and 12 proteins were up-regulated in vascular tissues of the model group. The formula for calming liver and suppressing yang treatment up-regulated expressions of 10 proteins in the 15 down-regulated proteins, and down-regulated 8 proteins in the 12 up-regulated proteins in vascular tissues of SHRs. After analysis, 16 obviously differentially expressed proteins were found, and 13 of them were identified. Conclusion: The formula for calming liver and suppressing yang can improve the ethology of SHRs. The mechanism is probably concerned with regulating the protein expressions of vascular tissues.

Objective To investigate the curriculum construction and evaluation of teaching effectiveness of simulation and comprehensive experiment for clinical nursing. Methods Based on the investigation of hospital, taking working progress and working task of nurses as orientation, we constructed the curriculum of simulation and comprehensive experiment for clinical nursing, and unfold in junior class (before clinical practice) for student nurses. The teaching effect was evaluated. Results Unfolding simulation and comprehensive experiment could effectively enhance the nursing students' ability to transform theoretical knowledge into clinical nursing practice, and was favorable to change the role of nurses and improve the satisfaction degree of clinical practice.Conclusions Unfolding simulation and comprehensive experiment for clinical nursing for student nurses before clinical practice is practicable and essential.

OBJECTIVETo observe the therapeutic effect of calming the liver and restraining the Yang formula in treating patients with mild or moderate degree of essential hypertension (syndrome of hyperactivity of liver-Yang), and to explore its mechanism in lowering blood pressure.

METHODThe 348 patients with EH of stage I , II were randomly divided into two groups, the 174 patients in the treated group were treated with the calming the liver and restraining the Yang formula, and the 174 patients in the control group were treated with amlodipine. The treatment course for them all was 12 weeks. The related clincial symptoms score and quality of life score estimated before and after treatment at 4th week, 8th week and 12th week were observed. Before and after treatment, the ambulatory blood pressure (AMBP), heart rate, blood lipid, serum livels of high-sensitivity C-reactive protein (Hs-CRP), Angiotensin-II (Ang II) and calcitonin gene-related peptide (CGRP) were measured respectively in 40 patients of the treared group and 40 patients of the control group.

RESULTAfter treatment, the treatment in the treated group showed an effect better than that in the control group in terms of nigh-time blood pressure reducing rate (P < 0.05). The reducing blood pressure variability and total effective rate in the treated group were no significant than that in the control group. In respect of reducing symptomatic scores on dizzy, soreness and weakness of the waist and knees, disturbed and dry and bitter of mouth, ameliorating quality of life score, decreasing the levels of heart rate, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol(HDL-C) in the treated group were showing marked improvement as compared with that in the control group (P < 0.05 or P < 0.1). The improvement in the level of Ang II , Hs-CRP and CGRP before treatment in two groups were more significant than that after treatment (P < 0.05). However There were no difference in after treatment between the treated group and the control group.

CONCLUSIONThe calming the liver and restraining the Yang formula shows favorable efficacy in lowering blood pressure on the patients with mild or moderate degree of essential hypertension. It can reduce the clincial symptoms, improve the quality of life, regulate blood lipid metabolism. Its mechanism may be related to the functional relieving inflammatory reaction and inhibition the activity of renin-angiotensin-aldosterone system (RAAS).

Adult ; Aged ; Amlodipine ; therapeutic use ; Antihypertensive Agents ; therapeutic use ; Anxiety ; chemically induced ; physiopathology ; Blood Pressure ; drug effects ; Cholesterol ; metabolism ; Cholesterol, HDL ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Heart Rate ; drug effects ; Humans ; Hypertension ; drug therapy ; physiopathology ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Phytotherapy ; Triglycerides ; metabolism

Objective To investigate the effects of alprostadil (Lipo-PGE) combined low-dose dopamine in the treatment of hepatorenal syndrome (HRS). Methods 61 patients with hepatorenal syndrome were randomly di-vided into two groups, treatment group 31 cases, 30 cases of the control group. Treatment group in the control group based on the 20μg soluble in 10% glucose infusion 100 ml in combined treatment with Lipo-PGE a day, one time,and combined with low-dose dopamine 3 μg/(kg·min) intravenous infusion, 1 week course of treatment. Result The treatment group liver function improvement in renal function are superior to the control group (P <0.01), to-ted effective rate was 67.7%. Conclusion The united alprostadil and low-dose dopamine satisfied with liver and kidney syndrome, there is synergy.

OBJECTIVETo investigate the relationship between interleukin-1 (IL-1) gene polymorphisms and the susceptibility of chronic periodontitis in Uighur minority in Xingjiang province of China.

METHODSThe buccal swabs were collected from 41 severe chronic periodontitis (CP) patients, 43 moderate CP patients, 49 mild CP patients and 92 healthy controls. DNA was extracted from these buccal swabs. Genotypes of the IL-1A-889/NcoI and IL-1B+3954/TaqI were determined by sequence specific primers-polymerase chain reaction(SSP-PCR) and PCR-restriction fragment length polymorphism(PCR-RFLP). Then distribution of genotypes for IL-1A-889 and IL-1B+3954 were compared among the different groups.

RESULTS(1) There were no significant differences in the distribution of IL-1A-889 among severe CP patients, moderate CP patients, mild CP patients and healthy controls. (2) Frequencies of allele 2 for IL-1B+3954 were higher in severe CP patients than in healthy controls, and the difference was statistically significant. But there were no such significant differences either between moderate CP patients and healthy controls or between mild CP patients and healthy controls.

CONCLUSIONThese results suggest that IL-1B+3953 allele 2 may be a risk indicator for the susceptibility to severe chronic periodontitis in Uighur minority in Xingjiang of China.

Adult ; Aged ; China ; ethnology ; Chronic Disease ; Electrophoresis, Agar Gel ; methods ; Ethnic Groups ; genetics ; Female ; Genetic Predisposition to Disease ; Humans ; Interleukin-1 ; genetics ; Male ; Middle Aged ; Periodontitis ; genetics ; immunology ; Polymorphism, Genetic