A Retrospective Analysis of Steady-State Olanzapine Concentrations in Chinese Patients Using Therapeutic Drug Monitoring: Effects of Valproate and Other Factors.

BACKGROUND: The objective of this study was to investigate the serum concentrations of olanzapine in relation to age, sex, and other factors in Chinese patients aged between 10 and 90 years. METHODS: Data for 884 olanzapine patients, deposited between 2016 and 2017, were retrieved from the therapeutic drug monitoring database of the Affiliated Brain Hospital of Guangzhou Medical University. The effects of covariates on serum olanzapine concentration, dose-normalized concentration (C/D ratio), and normalized concentration (C/D/weight) were investigated. RESULTS: Generally, male patients had lower olanzapine concentration, C/D ratio, and C/D/weight than female patients (P < 0.001). Smoking and drinking reduced olanzapine concentration, C/D ratio, and C/D/weight (P < 0.001). Coadministration with valproate decreased olanzapine concentration, C/D ratio, and C/D/weight by about 16%, 30%, and 40%, respectively (P < 0.001). Patients younger than 60 years had higher olanzapine concentrations (P < 0.05) but lower C/D ratios and C/D/weight (P < 0.001) than patients older than 60 years. Age was correlated with olanzapine concentration (r = -0.082, P < 0.05), C/D ratio (r = 0.196, P < 0.001), and C/D/weight (r = 0.169, P < 0.001). Sample timing after dose and diagnostic factors also contributed to the olanzapine concentrations. Multiple linear regression analysis revealed significant influences of dosage, age, sex, valproate comedication, smoking, postdose interval, and schizophrenia (vs bipolar affective disorders) on serum olanzapine concentrations. CONCLUSIONS: The metabolism of olanzapine may be altered by several factors. Patients characterized with a combination of factors may benefit from therapeutic drug monitoring for the adjustment of olanzapine dose to minimize adverse reactions.

Effect of venlafaxine dosage, valproic acid concentration, sex, and age on steady state dose-corrected concentrations of venlafaxine and O-desmethylvenlafaxine: A retrospective analysis of therapeutic drug monitoring data in a Chinese population.

PURPOSE: This study aimed to investigate the influence of diagnosis, body weight, sex, age, smoking, formulations, and concomitant drugs on steady-state dose-corrected serum concentrations (C/D) of venlafaxine (VEN) and O-desmethylvenlafaxine (ODV). METHODS: A retrospective analysis of therapeutic drug monitoring (TDM) was carried out. Patients' demographic data, therapeutic regimens, and concentrations were collected. RESULTS: We included 91 verified samples from 80 patients. Females had by average 13% smaller body weight, 50% higher C/D of VEN, and VEN + ODV and 25% smaller ODV/VEN than males. Patients >60 years had by average 33-59% higher C/D levels of ODV and VEN + ODV than younger patients. The concomitant use of valproic acid caused an average 51% higher C/D of ODV and a 2.2-fold larger ODV/VEN, while clozapine was related with 40% smaller ratio of ODV/VEN and 38% lower C/D levels of ODV. Positive correlations were detected between valproic acid concentrations and the C/D of VEN and VEN + ODV. In a multiple linear regression analysis, variance in the C/D of VEN + ODV was partly attributed to the daily dose of VEN, sex, age and valproic acid concentration. CONCLUSION: Our results suggested daily dose of VEN, sex, age, and valproic acid as indicators for the C/D of VEN + ODV in Chinese patients. TDM as a valuable tool was suggested in elderly female patients and patients receiving polypharmacy.

Effects of food and grapefruit juice on single-dose pharmacokinetics of blonanserin in healthy Chinese subjects.

PURPOSE: The purpose of this study was to investigate the potential effects of a meal and grapefruit juice on the pharmacokinetics of blonanserin and its metabolite N-desethyl blonanserin in healthy Chinese volunteers. METHODS: This was a single-centre, open-label, fixed-sequence study, where 12 healthy Chinese volunteers received a single dose of 8 mg blonanserin after an overnight fast in period 1 (reference), a high-fat meal during period 2 and with co-administration of 250 mL of grapefruit juice in period 3. The washout period was 7 days. Series of plasma samples were collected after each dose to determine concentrations of blonanserin and its metabolite N-desethyl blonanserin using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were estimated by non-compartmental analysis and compared between periods by standard average bioequivalence ANOVA. Adverse events were monitored throughout the study. RESULTS: All subjects completed the study. High-fat meals significantly increased blonanserin exposure (AUCt) 2.58-fold (90% CI 2.21, 3.02), relative to the reference period. Co-administration of blonanserin with grapefruit juice remarkably prolonged elimination half-life of blonanserin (from 9.7 to 21.4 h) and significantly increased exposures to blonanserin and N-desethyl blonanserin by 5.82-fold (90% CI 4.57, 7.42) and 1.81-fold (90% CI 1.65, 1.98), respectively. CONCLUSIONS: These results suggested that blonanserin was largely metabolised in the intestinal tract before becoming systemically available, and both food and grapefruit juice enhanced exposure to blonanserin and N-desethyl blonanserin. Grapefruit juice increased bioavailability and may have reduced systemic clearance of blonanserin. Further intestinal CYP3A4 and hepatic CYP3A4 might be postulated to explain the delayed elimination of blonanserin. Dose adjustment of blonanserin is needed on the basis of co-intake of known strong CYP3A4 inhibitor. Patients taking high-dose blonanserin also need to be cautious about the ingestion of grapefruit juice.

Physicians' perceptions of generic drugs in China.

Background: In recent years, there has been a significant worldwide increase in the use of generic drugs. China has committed to a consistency evaluation of generic drugs, with the aim to improve the rate of substitution. However, there is little research on physicians' perceptions of generic drugs in China. Objective: The study aimed to explore the perceptions of physicians in China toward generic drugs. Methods: Perceptions of Chinese physicians towards generic drugs were evaluated by a cross-sectional study from June to July 2020. The online survey tool Sojump was adopted to distribute the questionnaires using convenience sampling. A total of 598 questionnaires were analyzed. Results: Perceptions of Chinese physicians towards generic drugs are generally positive. However, not all physicians appear to have sufficient knowledge about generic drugs and some of them expressed negative perceptions of generic drugs, such as perceiving generic drugs as less effective and more likely to cause side effects compared to brand-name drugs. There were significant differences in physicians' opinions about generic drugs according to age group, years in practice, educational background, clinical specialty and residential area. Conclusion: It is imperative to provide physicians with more extensive education about the consistency evaluation of generic drugs to meet the policy goal of reducing overall national medical healthcare costs.

A Simple and Sensitive HPLC-MS/MS Assay for the Quantitation of Blonanserin and N-Desethyl Blonanserin in Rat Plasma and Its Application to Pharmacokinetic Study.

A high-performance liquid chromatographic method coupled with triple quadrupole mass spectrometry (LC-MS/MS) for the analysis of blonanserin and its active metabolite, N-desethyl blonanserin, in rat plasma has been developed and validated. The biological samples were treated by simple direct protein precipitation before separation on an Agilent Eclipse Plus C18 column (4.6 × 100 mm, 3.5 µm) with a column temperature of 35°C at a flow rate of 0.5 mL/min. The mobile phase A is a mixture of methanol and water (75 : 25, v/v, 5 mM ammonium formate), and the mobile phase B is acetonitrile containing 0.1% formic acid. The ratio of mobile phase A to mobile phase B is 15 : 85. Electrospray ionization (ESI) multiple reaction monitoring modes are used for detection, which are m/z 368.10 ⟶ 296.90 (blonanserin), m/z 340.15 ⟶ 297.05(N-desethyl blonanserin), and m/z 348.15⟶ 302.05 (N-desethyl blonanserin-d8). The linear response range was 0.1-100.0 ng/mL for blonanserin and N-desethyl blonanserin. The lower limit of quantification (LLOQ), calibration curves, carryover, and matrix effects were sufficiently accurate and precise according to the National Medical Products Administration (NMPA) guidelines for bioanalytical method validation. This analytical method was successfully applied in a blonanserin-poloxamer thermosensitive gel pharmacokinetic study in rats.

[Preparation of rivastigmine liposome and its pharmacokinetics in rats after intranasal administration].

To prepare rivastigmine liposome, rivastigmine was loaded into liposome via ammonium sulfate gradient method. Its pharmacokinetic profile in rats was evaluated after intranasal administration. The size, zeta potential, entrapped efficiency and release of rivastigmine from the liposome in vitro were determined. Plasma concentration of rivastigmine was determined by high performance liquid chromatography-tandem mass spectrometry (HPLC/MS) using antipyrine as internal standard. The pharmacokinetic parameters were calculated by DAS 2.0. The entrapped efficiency of rivastigmine liposome was (33.41 +/- 6.58) %, with the mean diameter of 154-236 nm and zeta potential of (-10.47 +/- 2.41) mV. The release behavior of rivastigmine was fitting the first order equation in vitro. The pharmacokinetic studies indicated that the C(max), T(max) and AUC(0-infinity), of rivastigmine liposome were (1.50 +/- 0.15) mg x L(-1), 15 min and (89.06 +/- 8.30) mg x L(-') x min, respectively. Rivastimine liposome was absorbed rapidly, and could reach a certain concentration in rat plasma after intranasal delivery.

Analysis of influencing factors of postoperative infection in patients with colon cancer and construction of nomogram model / 中国医师进修杂志

Objective:To analyze the risk factors of postoperative infection in patients with colon cancer, and construct a nomogram model.Methods:The clinical data of 220 patients with colon cancer in Anhui Cancer Hospital from May 2019 to June 2022 were retrospectively analyzed. Among them, 55 patients developed postoperative infection (infection group), and 165 patients did not develop postoperative infection (non-infection group). The receiver operating characteristic (ROC) curve was used to analyze the efficacy of each index in predicting postoperative infection in patients with colon cancer. Multivariate Logistic regression analysis was used to analyze the independent risk factors of postoperative infection in patients with colon cancer. R language 3.5.2 software was used to construct a nomogram model for predicting postoperative infection in patients with colon cancer, and it was verified and evaluated.Results:There were no significant differences in gender composition, body mass index, tumor stage, intraoperative blood transfusion, hypertension, smoking history, alcohol consumption history, tumor diameter and hemoglobin between the two groups ( P>0.05); the age, diabetes mellitus ratio, operation time and exhaust time in the infection group were significantly higher than those in the non-infection group: (49.60 ± 4.40) years old vs. (47.20 ± 4.12) years old, 63.64% (35/55) vs. 30.30% (50/165), (197.80 ± 12.55) min vs. (192.23 ± 12.05) min and (3.42 ± 1.18) d vs. (2.60 ± 0.80) d, the albumin was significantly lower than that in the non-infected group: (28.29 ± 3.02) g/L vs. (32.80 ± 3.21) g/L, and there were statistical differences ( P<0.01). ROC curve analysis result showed that the area under the curve of age, operation time, exhaust time and albumin for predicting postoperative infection in patients with colon cancer were 0.672, 0.610, 0.706 and 0.846, and the optimal cut-off values were 49 years old, 184 min, 3 d and 30 g/L, respectively. Multivariate Logistic regression analysis result showed that age (>49 years old), diabetes mellitus, operation time (>184 min), exhaust time (>3 d) and albumin (≤30 g/L) were independent risk factors of postoperative infection in patients with colon cancer ( OR = 2.131, 1.758, 1.449, 1.841 and 2.325; 95% CI 1.269 to 2.696, 1.354 to 3.059, 1.201 to 1.965, 1.018 to 2.365 and 1.582 to 3.051; P<0.01). A nomogram model was constructed with age, diabetes mellitus, operation time, exhaust time, and albumin as predictors for predicting postoperative infection in patients with colon cancer. The correction curve of the nomogram model for predicting postoperative infection in patients with colon cancer was close to the ideal curve (C-index = 0.764, 95% CI 0.657 to 0.834); decision curve analysis result showed that the nomogram model provided clinical net benefit when the risk threshold was > 0.07; and the clinical net benefit of the model was higher than that of age, diabetes mellitus, operation time, exhaust time and albumin. Conclusions:The age (>49 years old), diabetes mellitus, operation time (>184 min), exhaust time (>3 d) and albumin (≤30 g/L) are the independent risk factors of postoperative infection in patients with colon cancer, and the nomogram model based on the above variables could predict postoperative infection.

Effects of Comedication and Genetic Factors on the Population Pharmacokinetics of Lamotrigine: A Prospective Analysis in Chinese Patients With Epilepsy.

Lamotrigine (LTG) is a second-generation anti-epileptic drug widely used for focal and generalized seizures in adults and children, and as a first-line medication in pregnant women and women of childbearing age. However, LTG pharmacokinetics shows high inter-individual variability, thus potentially leading to therapeutic failure or side effects in patients. This prospective study aimed to establish a population pharmacokinetics model for LTG in Chinese patients with epilepsy and to investigate the effects of genetic variants in uridine diphosphate glucuronosyltransferase (UGT) 1A4, UGT2B7, MDR1, ABCG2, ABCC2, and SLC22A1, as well as non-genetic factors, on LTG pharmacokinetics. The study population consisted of 89 patients with epilepsy, with 419 concentrations of LTG. A nonlinear mixed effects model was implemented in NONMEM software. A one-compartment model with first-order input and first-order elimination was found to adequately characterize LTG concentration. The population estimates of the apparent volume of distribution (V/F) and apparent clearance (CL/F) were 12.7 L and 1.12 L/h, respectively. The use of valproic acid decreased CL/F by 38.5%, whereas the co-administration of rifampicin caused an increase in CL/F of 64.7%. The CL/F decreased by 52.5% in SLC22A1-1222AA carriers. Patients with the ABCG2-34AA genotype had a 42.0% decrease in V/F, whereas patients with the MDR1-2677TT and C3435TT genotypes had a 136% increase in V/F. No obvious genetic effect of UGT enzymes was found relative to the concentrations of LTG in Chinese patients. Recommended dose regimens for patients with different gene polymorphisms and comedications were estimated on the basis of Monte Carlo simulations and the established model. These findings should be valuable for developing individualized dosage regimens in adult and adolescent Chinese patients 13-65 years of age.

Simultaneous analysis of olanzapine, fluoxetine, and norfluoxetine in human plasma using liquid chromatography-mass spectrometry and its application to a pharmacokinetic study.

Adjunctive therapy with olanzapine and fluoxetine has been shown to be beneficial in treatment-resistant depression and the depressive phase of bipolar disorder. Consensus guidelines issued by the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie strongly recommend that patients taking olanzapine undergo therapeutic drug monitoring (TDM), and suggest that TDM is useful for patients taking fluoxetine. The aim of the current study was to develop and validate a sensitive, practical, and robust liquid chromatography-tandem mass spectrometry method (LC-MS/MS) for simultaneous determination of olanzapine, fluoxetine, and norfluoxetine in human plasma for routine TDM. Simple liquid-liquid extraction using ethyl acetate was used to extract olanzapine, fluoxetine, and norfluoxetine from 200 µL of pre-basified human plasma. Analytes were separated on an Agilent Eclipse Plus C18 column (4.6 × 100 mm, 5 µm) eluted with a mobile phase consisting of methanol:20 mM ammonium formate buffer (82.5:17.5, v/v), and then quantified using an electrospray ionization source operated in positive ion multiple reaction monitoring mode. The linear range for the analytes was 0.2-25 ng/mL, covering the vast majority of levels encountered in real-life samples. A weighting factor of 1/x2 best fit the calibration curves. The mean internal standard-normalized matrix effects for all analytes were 99.5%-110%. The extraction recoveries were 75%-85% for olanzapine and olanzapine­d3, and 58%-69% for fluoxetine, norfluoxetine, and their deuterated internal standards. Accuracy and precision values also met the acceptance criteria. The stability assessments showed that QC samples containing the three analytes were stable for at least 1 d at room temperature, 21 d at -70 °C, and through three freeze-thaw cycles. Post-preparation storage for 2 d in the autosampler did not cause obvious degradation of the investigated compounds. This validated high performance LC-MS/MS method was successfully applied to a pharmacokinetic study in healthy male volunteers.

Research on rapid detection technology of airborne pathogenic organisms based on up-conversion phosphor technology / 中华预防医学杂志

Objective: To explore the application of up-conversing phosphor technology (UPT) to detect pathogenic organisms in the air. Methods: The performance of UPT was verified with Staphylococcus aureus, Yersinia pestis and Escherichia coli O157 as simulated strains, including stability, specificity, sensitivity and response time tests; Air particle sampler is used to collect air samples in the field microenvironment test chamber, and UPT is used for detection. At the same time, compared with the traditional culture method, the practicability of UPT is verified. Results: The coefficient of variation in laboratory was 9.62% and 8.02% when the concentration of 107 CFU/ml and 108 CFU/ml were detected by UPT. The results were less than the allowable target, and the detection system had good stability. The specificity of UPT was verified by Staphylococcus aureus. The results showed that no non-Staphylococcus aureus was detected, and the positive detection rate of different kinds of Staphylococcus aureus was 100%. The specificity of the detection system was good. The sensitivity of UPT for detecting Staphylococcus aureus was 104 CFU/ml. Detection sensitivity of Yersinia pestis ≥103 CFU/ml; The detection sensitivity of Escherichia coli O157 is ≥103 CFU/ml, and the response time of UPT to bacteria is within 15 min (all 10 min 15 s). The detection results of bacteria contentration in the air of the on-site microenvironment test cabin by UPT showed that when the concentration of Escherichia coli O157 in the air reached above 104 CFU/m3, the detection results of UPT were positive, and with the increase of air concentration, the numerical concentration measured by UPT showed an upward trend, which was positively correlated with the concentration of bacteria in the air. Conclusion: UPT may be feasible as a rapid method to evaluate the species and contentration of pathogenic organisms in the air.

Analysis of vaginal microecology in 23 181 cases of the gynecological female outpatients / 中华妇产科杂志

Objective:To analyze the vaginal microecological status of vaginitis population and non-vaginitis population of gynecological female outpatients.Methods:A total of 30 265 women who visited the gynecological outpatient clinic of Beijing Obstetrics and Gynecology Hospital from December 2018 to December 2020 completed vaginal microecological examination. After removing the follow-up patients, 23 181 women were divided into group with symptoms and signs of vaginitis (6 697 cases) and group without symptoms and signs of vaginitis (16 484 cases), according to whether the women with symptoms and signs of vaginitis or not. And the vaginal microecological status of the two groups was compared and analyzed.Results:(1) The total detection rate of vaginitis in the initial women was 34.87% (8 083/23 181), of which 46.10% (3 087/6 697) in group with symptoms and signs of vaginitis and 30.31% (4 996/16 484) in group without symptoms and signs of vaginitis, nearly 1/3 of the gynecological outpatients without signs and symptoms of vaginitis had vaginitis. (2) Among the types of simple vaginitis, vulvovaginal candidiasis (VVC) was the most frequent in group with symptoms and signs of vaginitis (16.01%, 1 072/6 697), followed by aerobic vaginitis (AV; 12.83%, 859/6 697), with significant differences compared with group without symptoms and signs of vaginitis (all P<0.001). There were no statistical differences between the two groups of bacterial vaginosis (BV) and trichomonal vaginitis (TV), indicating that BV and TV were more likely to be neglected (all P>0.05). (3) The proportion of various combinations of vaginitis among 2 632 cases of mixed vaginitis were, in descending order: BV+AV, VVC+AV, BV+AV+VVC, AV+TV, AV+TV+BV, BV+VVC. (4) Microecological analysis of 15 098 cases diagnosed with non-vaginitis had normal flora (including those with normal flora and those with normal flora but decreased function) in 14 013 cases (92.81%, 14 013/15 098), abnormal flora in 429 cases (2.84%, 429/15 098) and the BV intermediate in 656 cases (4.34%, 656/15 098); this indicated that the vast majority of the microecological tests were normal in the vaginal microbiota of those without vaginitis. Conclusions:Microecological examination could diagnose multiple pathogenic infections at once, and is especially important as a guide for the definitive diagnosis of mixed vaginitis and vaginitis with atypical clinical symptoms. Vaginal infections such as BV and TV that are easily overlooked should be concerned.

Dynamics of vaginal microbiota in women of reproductive age during the menstrual cycle / 中华妇产科杂志

Objective:To investigate the dynamic changes of vaginal microbiota in different phases of menstrual cycle in healthy Chinese women of childbearing age.Methods:A total of 11 healthy women of childbearing age with regular menstruation, who had physical examination in the Gynecology Clinic of Beijing Obstetrics and Gynecology Hospital from September to December 2020 were randomly selected as research subjects. Vaginal secretions were collected during menstrual phase (2nd-3rd day), mid-follicular phase (7th-8th day), and mid-luteal phase (21st-22nd day) for microbiota analysis through metagenomic sequencing.Results:(1) Vaginal microbiota species were the most diverse in menstrual phase and the least in follicular phase, observing dominant vaginal bacteria gradually changing to Lactobacillus from menstrual phase to follicular phase and then to luteal phase. (2) The dynamic evolution of vaginal microbiota from menstrual phase to follicular phase and then to luteal phase was divided into: no change in dominant bacteria, replacement of dominant bacteria, changes in the proportion of dominant bacteria, and recurrence of dominant bacteria (non-Lactobacillus-dominance appeared again in luteal phase after returning to normal Lactobacillus-dominance in follicular phase). (3) Prevotella, especially Prevotella_bivia, was significantly higher during menstrual phase.Conclusions:Healthy vaginal microbiota should be relatively stable, but also have the ability of dynamic change and self-recovery. Prevotella plays a central role among opportunistic pathogens in the vagina, whose function remains to be investigated.

Microsurgical techniques and one-stage surgical treatment of chronic osteomyelitis——concept and clinical application / 中华显微外科杂志

Chronic osteomyelitis is a serious clinical problem with repeated courses and high disability rate, which seriously affects the physical and mental health of patients. Through continuous learning and summary in the process of using traditional therapies, the innovative improvements and changes had made in the treatment of osteomyelitis: Radical debridement of lesions was performed by applying the basic principles of modern bone tumor surgery. The application of microsurgical technique to transfer composite tissue flap can provide guarantee for tissue defect repair and wound closure without tension. Combined with bone grafting, local antibiotics and bone fixation, an one-stage operation has significantly improve the therapeutic effect of chronic complex osteomyelitis.

Efficacy comparison among high risk factors questionnaire and Asia-Pacific colorectal screening score and their combinations with fecal immunochemical test in screening advanced colorectal tumor / 中华胃肠外科杂志

Objective: To investigate the effects of high risk factors questionnaire (HRFQ), Asia-Pacific colorectal screening (APCS) score and their combinations with fecal immunochemical test (FIT) in screening advanced colorectal neoplasia, in order to provide an evidence for further optimization of cancer screening program. Methods: A retrospective cohort study method was used to summarize and analyze the results of colorectal tumor screening in Jiashan County, Zhejiang Province from March 2017 to July 2018. Those with severe diseases that were not suitable for colonoscopy and those with mental and behavioral abnormalities who can not cooperate with the screening were excluded. Those who met any one or more of the followings in the HRFQ questionnaire were classified as high-risk people of HRFQ: (1) first-degree relatives with a history of colorectal cancer; (2) subjects with a history of cancer or any other malignant tumor; (3) subjects with a history of intestinal polyps; (4) those with two or more of the followings: chronic constipation (constipation lasted for more than 2 months per year in the past two years), chronic diarrhea (diarrhea lasted for more than 3 months in the past two years, and the duration of each episode was more than one week), mucus and bloody stools, history of adverse life events (occurring within the past 20 years and causing greater trauma or distress to the subject after the event), history of chronic appendicitis or appendectomy, history of chronic biliary disease or cholecystectomy. In this study, those who were assessed as high risk by HRFQ were recorded as "HRFQ (+)", and those who were not at high risk were recorded as "HRFQ (-)". The APCS questionnaire provided risk scores based on 4 risk factors including age, gender, family history and smoking: (1) age: 2 points for 50-69 years old, 3 points for 70 years old and above; (2) gender: 1 point for male, 0 point for women; (3) family history: 2 points for first-degree relatives suffering from colorectal cancer; (4) smoking: 1 point for current or past smoking, 0 point for non-smokers. The population was divided into low-risk (0-1 point), intermediate-risk (2-3 points), and high-risk (4-7 points). Those who were assessed as high risk by APCS were recorded as "APCS (+)", and those with intermediate and low risk were recorded as "APCS (-)". The hemoglobin threshold for a positive FIT was set to 100 μg/L. Those who were assessed as high risk by APCS with positive FIT were recorded as "APCS+FIT (+)". Those who were assessed as high risk by APCS with negative FIT, those who were assessed by APCS as low-middle risk with positive FIT, and those who were assessed by APCS as low-middle with negative FIT were all recorded as "APCS+FIT(-)". Observation indicators in this study were as follows: (1) the screening compliance rate of the cohort and the detection of advanced colorectal tumors; (2) positive predictive value, negative predictive value, sensitivity and specificity of HRFQ and APCS and their combination with FIT for screening advanced colorectal tumors; (3) comparison of the detection rate between HRFQ and APCS questionnaire for different colorectal lesions. Using SPSS 21.0 software, the receiver operating characteristic (ROC) curve was drawn to evaluate the clinical value of HRFQ and APCS combined with FIT in screening advanced colorectal tumors. Results: From 2017 to 2018 in Jiashan County, a total of 53 268 target subjects were screened, and 42 093 people actually completed the questionnaire, with a compliance rate of 79.02%. A total of 8145 cases underwent colonoscopy. A total of 3607 cases among HRFQ positive population (5320 cases) underwent colonoscopy, and the colonoscopy compliance rate was 67. 80%; 8 cases were diagnosed with colorectal cancer and 88 cases were advanced colorectal adenoma. A total of 2977 cases among APCS positive population (11 942 cases) underwent colonoscopy, and the colonoscopy compliance rate was 24.93%; 17 cases were diagnosed with colorectal cancer and 148 cases were advanced colorectal adenoma. The positive rate of HRFQ screening was lower than that of APCS [12.6% (5320/42 093) vs. 28.4% (11 942/42 093), χ2=3195. 547, P<0.001]. In the FIT positive population (6223 cases), a total of 4894 cases underwent colonoscopy, and the colonoscopy compliance rate was 78.64%; 34 cases were diagnosed with colorectal cancer and 224 cases were advanced adenoma. The positive predictive values of HRFQ and APCS and their combination with FIT for screening advanced colorectal tumors were 2.67%, 5.54%, 5.44%, and 8.56%; negative predictive values were 94.89%, 96.85%, 96.11% and 96.99%; sensitivity was 29.27%, 50.30%, 12.20 % and 39.02%; specificity was 55.09%, 64.03%, 91.11% and 82.51%, respectively. The ROC curves constructed by HRFQ, APCS, FIT, HRFQ+FIT and APCS+FIT indicated that APCS+FIT presented the highest efficacy in screening advanced colorectal tumors (AUC: 0.608, 95%CI: 0.574-0.642). The comparison of the detection rates of different colorectal lesions between HRFQ and APCS questionnaires showed that there were no significant differences in detection rate of inflammatory polyps and hyperplastic polyps between the two questionnaires (both P>0.05). However, as compared to HRFQ questionnaire, APCS questionnaire had higher detection rates in non-advanced adenomas [26.10% (777/2977) vs. 19.43% (701/3607), χ2=51.228, P<0.001], advanced adenoma [4.97% (148/2977) vs. 2.44% (88/3607), χ2=30.249, P<0.001] and colorectal cancer [0.57% (17 /2977) vs. 0.22% (8/3607), χ2=5.259, P=0.022]. Conclusions: APCS has a higher detection rate of advanced colorectal tumors than HRFQ. APCS combined with FIT can further improve the effectiveness of advanced colorectal tumor screening.

Safety and efficacy of trans-right-ventricular echocardiography guided percutaneous intramyocardial septal radiofrequency ablation for interventricular septal reduction: an ovine model with 1-year outcomes / 中华超声影像学杂志

Objective:To investigate the safety and efficacy of echocardiography-guided trans-right-ventricular percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) in a healthy sheep model, and to observe the pathological changes of myocardium in ablation area one year later.Methods:Twelve sheep were divided into PIMSRA group ( n=6) and sham group ( n=6). In PIMSRA group, a radiofrequency (RF) electrode was inserted to the interventricular septum (IVS) with maximum power of 80 Watts for 5 minutes. In the sham group, RF electrode tip was positioned in IVS segment but without the RF power delivery. Electrocardiogram (ECG), echocardiography, myocardial contrast echocardiography(MCE) were performed to assess the efficacy of PIMSRA at postoperative immediately, 2-week, 1-month, 2-month, 3-month, 6-month and 12-month during the follow-up. The following parameters were recorded, including the thickness of ablation area, the systolic wall thickening rate and amplitude of movement of the ablated region, left ventricular outflow tract pressure gradient (LVOT PG), and left ventricular ejection fraction (LVEF), mitral valve early diastolic peak velocity(E), late diastolic peak velocity(A) and the E/A ratio, peak velocity of early diastolic mitral annular motion(E′), peak velocity of late diastolic mitral annular motion(A′), and the E′/A′ ratio.For both groups, the myocardial biomarkers of troponin I, myoglobin and isoenzymes of creatine kinase were tested before the ablation and 3 h after the ablation, and again after 2 weeks. Tissue pathology examinations were performed at the end of study. Results:None of the animals in both groups was observed to have pericardial tamponade during perioperative period.Immediately after the procedure, septal hypokinesis was seen in all PIMSRA group animals, the systolic wall thickening rate and amplitude of movement of the ablated region were significantly decreased ( P<0.001), which was sustained until 12 months.In Sham group, there were no significant differences in the wall thickening rate and amplitude of movement of the operated region(all P>0.05).The thickness of the ablation area in the PIMSRA group was significantly increased immediately after the procedure( P<0.001), decreased to baseline level at 1-week ( P=0.931), and significantly increased at 3-month ( P<0.001).In the Sham group, the IVS thickness was significantly increased immediately after the procedure( P=0.005), decreased to baseline level at 1-week ( P=0.027), then has no further significant changes.There were no significant differences in LVEF, E/A, E′/A′ between PIMSRA and Sham group(all P>0.05).MCE showed the thickness of the ablation area was significantly decreased in the PIMSRA group 12 months after the operation.In both groups, troponin I increased significantly 3 h after the operation(all P<0.005), which decreased to baseline level 2 weeks later(all P>0.05). ECG showed that all the sheep had normal sinus rhythm. Pathological examinations revealed the tissue in the ablation area was fibrotic, having clear boundary with the surrounding normal tissue and no carbonization was observed 1 year later. Conclusions:Echocardiography-guided trans-right-ventricular PIMSRA produced precisely ablated myocardial tissues, reduced the IVS thickness significantly, preserved the global left ventricular function. All the sheep had normal sinus rhythm and without pericardial tamponade in 1 year follow-ups. Echocardiography-guided trans-right-ventricular PIMSRA is a safe and effective minimally invasive treatment for septal reduction therapy.

Evaluation of the efficacy and safety of human coagulation factor Ⅷ in the treatment of hemophilia A patients / 中国输血杂志

【Objective】 To evaluate the efficacy and safety of human coagulation factor Ⅷ developed by Shenzhen Weiguang Biological products Co, Ltd in the treatment of patients with hemophilia A. 【Methods】 A prospective, multi-center, open, single-group clinical study was conducted. A total of 65 subjects with hemophilia A were enrolled, and human coagulation factor Ⅷ(FⅧ) was injected according to the patients’ bleeding severity. The improvement score of bleeding symptoms and signs after the first infusion of the first bleeding event and the transfusion efficiency of FⅧ activity at 10 min and 1 hour after infusion were taken as the main efficacy indexes. The improvement scores of bleeding symptoms and signs after the first infusion and the increase of FⅧ activity at 10 min and 1 hour after infusion were the secondary efficacy indexes. 【Results】 The 65 subjects were enrolled in safety analysis set (SS) and full analysis set (FAS), and 58 of them were enrolled in protocol analysis set (PPS). Ten minutes and one hour after the first infusion, the level of factor Ⅷ activity in the subjects increased significantly, and the FⅧ activity increased by 100% or more in more than 79% of the subjects. The average infusion efficiency of FⅧ activity in all subjects was more than 100%. In 70% of the subjects, the pain was relieved rapidly and /or the bleeding symptoms were significantly improved 8 hours after each bleeding infusion, and the improvement rate of bleeding symptoms and signs reached 100% 72 hours after infusion. 【Conclusion】 After infusion of human coagulation factor Ⅷ, the activity level of factor Ⅷ in patients with hemophilia A significantly increased. The infusion efficiency can reach a optimal level, and the bleeding symptoms can be significantly improved.

A multicenter phase Ⅲ clinical study of human prothrombin complex concentrate in treatment of hemophilia B / 中国输血杂志

【Objective】 To evaluate the clinical efficacy and safety of one kind of human prothrombin complex concentrate in treatment of patients with hemophilia B. 【Methods】 The clinical data of 36 patients with hemophilia B treated with human prothrombin complex concentrate produced by Shenzhen Weiguang Biological Products Co. Ltd. from May 2018 to April 2019 were retrospectively analyzed, and its clinical efficacy and safety were analyzed. 【Results】 A total of 35 subjects entered the full analysis set (FAS)and safety set (SS), 33 subjects entered the per protocol Set (PPS). Thirty minutes after the first infusion of FAS subjects, the activity of coagulation factor Ⅸ increased from (3.93±0.975) IU/dL to (25.61±9.337) IU/dL, and the infusion efficiency was (96.43±22.007)%. The increased value of coagulation factor Ⅱ activity was (73.25±14.874) IU/dL. The activity of coagulation factor Ⅶ was (42.79±16.847) IU/dL. The increased value of coagulation factor Ⅹ activity was (65.29±17.042) IU/dL. The increased value of coagulation factor Ⅸ activity was (21.68±9.434%) IU/dL. Twenty-four hours after the first infusion of FAS subjects, the improvement of bleeding symptoms and signs was excellent in 21 cases (60%), improved in 14 cases (40.0%), and the effective rate was 100%. The incidence of adverse reactions was 2.9%(1/35), and there was no antibody to human coagulation factor Ⅸ and new virus infection. 【Conclusion】 Infusion of human prothrombin complex concentrate produced by Shenzhen Weiguang Biological Products Co. Ltd. in the treatment of hemophilia B has significant clinical efficacy and good safety.

Characterization of a UDP-glucose 4-epimerase from Acinetobacter Baumannii / 中国药科大学学报

@#The purpose of this article is to express the UDP-glucose 4-epimerase from Acinetobacter baumannii AB0057, characterize its enzymatic properties and analyze its structure and function.The epimerase gene was constructed into pET-28a expression vector and heterologously expressed in BL21(DE3).Enzyme activity was assayed using high performance liquid chromatography.The structure and key residues were analyzed by phylogenetic analysis, sequence alignment, homology modeling and molecular docking.Results indicated that the recombinant enzyme Gne1 was expressed at a molecular weight of 38.9 kD, with an optimum temperature of 44 °C and an optimum pH of 6.0 .Michaelis-Menten parameters KM and kcat were (1.227 ± 0.082 4) mmol/L and (82.64 ± 3.562) × 10-3?min-1, respectively.This enzyme belongs to NADB_Rossmann superfamily and UDP_G4E_1_SDR_e subgroup with typical GXGXXG and YXXXK sequence motifs.The N-terminal structural domain bound to NAD, while the C-terminal structural domain bound to substrate, and the catalytic key sites were S125 and Y150.The current work verified the epimerase activity of Gne1, explained its sequence and structural features, revealed its binding mode with substrates and cofactors, and analyzed the key residues, which provides a basis for protein engineering to improve the epimerase activity and then use biological enzymatic method to synthesize rare functional sugars.

Development and validation of an HILIC-MS/MS method by one-step precipitation for chloroquine in miniature pig plasma.

BACKGROUND: Quantification of polar compounds such as chloroquine by revered-phase LC is a challenge because of poor retention and silanol interactions with stationary phase. Strong ion-pairing reagents added to mobile phases to improve reversed-phase retention and improve peak shape can be harmful for MS. RESULTS: This new approach provides a rapid and sensitive method for the detection of chloroquine using hydrophilic interaction LC coupled to MS/MS (HILIC-MS/MS). Ammonium formate and formic acid were added to mobile phase to attain good peak shapes and the salified chloroquine as well retained in an HILIC column. Linearity, intra- and inter-day precision, accuracy, recovery, matrix effect and stability were evaluated during the validation process. CONCLUSION: The validated method has been successfully used in a PK study in miniature pigs, and paves way for future development.

Surgical treatment of traumatic osteomyelitis of extremities with MRSA infection / 中国骨伤

OBJECTIVE@#To summarize and discuss the clinical efficacy and application value of intravenous drip of linezolid combined with local targeted sustained-release of vancomycin in the treatment of traumatic osteomyelitis of extremities infected with MRSA.@*METHODS@#Thirty patients with traumatic osteomyelitis of extremities infected by MRSA from March 2015 to March 2017 were analyzed retrospectively, including 21 males and 9 females; aged 25 to 64 years old, with an average age of(47.94± 6.23) years old;the course of disease ranged from 9 to 23 months, with an average of (15.68±6.23) months. The lesions were located in tibia in 18 cases and calcaneus in 12 cases. The causes of injury were fall injury in 12 cases, trafficaccident injury in 9 cases and fall injury in 9 cases. There were 22 patients with closed fractures and 8 patients with open fractures. There were 13 cases of internal fixation. Twenty-two patients had sinustract, 8 patients had soft tissue defect with bone and internal fixation exposure, soft tissue defect area ranged from 2.0 cm × 3.0 cm to 8.2 cm × 12.3 cm;10 patients had bone defect, defect area ranged from 0.5 to 3.4 cm;bacterial culture of sinus tract or wound secretion in all patients was MRSA. On the basis of thorough debridement, calcium sulfate artificial bone loaded with vancomycin was implanted in the lesion, and linezolid and glucose injection was given intravenously during the perioperative period. The patients were followed up regularly according to the time of antibiotic use, blood routine, erythrocyte sedimentation rate, high-sensitivity C-reactive protein, liver and kidney function and other related laboratory indexes, X-ray, CT and other imaging examinations, bone healing, flap survival, joint function and McKee's osteomyelitis cure criteria.@*RESULTS@#All the patients were followed up, and the duration ranged from 3 to 6 years, with a mean of (4.23±0.76) years. No recurrence of osteomyelitis occurred. Fracture healing, infection control, wound healing and functional recovery were achieved.@*CONCLUSION@#Intravenous drip of linezolid combined with local targeted sustained-release of vancomycin for the treatment of MRSA infected traumatic osteomyelitis in limbs have significant effects and low recurrence rates.