Objective To explore the pharmacokinetics/pharmacodynamics(PK/PD)parameters and influencing factors in patients with augmented renal clearance(ARC)to provide the basis for the rational use of meropenem.Methods Using the method of retrospective study,the patients with increased renal clearance who used meropenem monitored the concentration from January 2018 to December 2021.The PK/PD parameters of meropenem were analyzed,and multiple linear retrospective analyses discussed the influencing factors of meropenem valley concentration.Results A total of 58 patients were included in the study,and the trough concentration was 1.35[0.23,1.86]μg·mL-1,taking 100%fT＞MIC as PK/PD target value,the compliance rate was 20.69%.The compliance rate of daily dose＜3 g·d-1 was 8.70%,and≥3 g·d-1 was 31.43%,the difference was statistically significant.With MIC of 0.5,1,2,4,and 8 μg·mL-1,PK/PD compliance rates were 62.07%,48.28%,20.69%,8.62%and 0.Respectively.Multiple linear retrospective analyses showed that dose was an independent factor affecting meropenem valley concentration.Conclusion The PK/PD compliance rate of meropenem in patients with augmented renal clearance is low,even if MIC≤0.5 μg·mL-1,the routine dose is difficult to achieve the ideal PK/PD,so the clinical should recognize ARC and perform TDM as soon as possible,and use TDM to guide the medication regimen of meropenem for ARC patients.

Objective:To analyze factors associated with timely vaccination of pertussis-containing vaccines in children born in Shanghai from 2019 to 2023.Methods:Children born in Shanghai between 2019 and 2023 were selected using a stratified random sampling method, and their vaccination data were obtained from the Shanghai Vaccine Management and Vaccination Service Information System. The vaccination rates, timely vaccination rates, and the proportions of diphtheria-tetanus-acellular pertussis-haemophilus influenzae type b combination vaccine (DTaP-Hib) and diphtheria-tetanus-acellular pertussis-inactivated poliovirus-haemophilus influenzae type b combination vaccine (DTaP-IPV-Hib) for the substitution of diphtheria- tetanus-acellular pertussis vaccine (DTaP) were calculated. Also, the factors associated with timely vaccination rate was analyzed with multivariate logistic regression analysis.Results:The average vaccination coverage rate of pertussis-containing vaccines in children born in Shanghai from 2019 to 2023 ranged from 94.71% to 99.53%. There were significant differences in the vaccination coverage of the 1 st-4 th doses of pertussis-containing vaccines among children born in different years (all P<0.05), but no gender and area specific significant differences were observed (all P>0.05). Non-national immunization program (non-NIP) vaccines were used to substitute DTaP vaccines in some children, with the proportion of DTaP-IPV-Hib vaccine accounting for 50.11%-52.69% and the proportion of DTaP-Hib vaccine accounting for 27.22%-28.43%. The proportions of DTaP-Hib and DTaP-IPV-Hib for the substitution of DTaP had increasing trends over the years. The overall timely vaccination rate of pertussis-containing vaccine vaccination was 84.09%. Analysis on the factors affecting the timely vaccination rate showed that the rate gradually decreased with the increase of the doses. Children who received the self-paid quadrivalent or pentavalent vaccines were less likely to have vaccination delays. Birth year had a significant impact on the timely vaccination rate, while the area had less impact. Additionally, the timely vaccination rate was also influenced by the degree of non-pharmaceutical intervention measures. Conclusions:The substitution of pertussis- containing vaccines with non-NIP vaccines was common in Shanghai. The coverage and timeliness of pertussis-containing vaccine vaccination were relatively high. The timely vaccination rate was significantly associated with gender, dose, vaccine type, and the degree of non-pharmaceutical interventions. There was a certain proportions of delayed and missed vaccinations, and it is necessary to pay attention to children who are not vaccinated timely and conduct high-quality catch-up vaccination to ensure timely and complete vaccination of pertussis-containing vaccines.

Objective: To investigate the longitudinal association of plasma Irisin concentrations with changes in blood pressure (BP) levels among children,and to assess the moderating effect of physical activity (PA) or sedentary behavior (SB) on the relationship between Irisin levels and BP. Methods: Based on a cohort study, a cluster sampling method was used to select 3 651 school aged children from five schools in Guangzhou in 2017 at the baseline survey and follow up in 2019. Both at baseline and during follow up, PA and SB were assessed by validated questionnaires, and BP levels were measured by an electronic sphygmomanometer. A final sample of 521 children were enrolled based on the PA and SB at baseline. Plasma Irisin concentrations were measured by ELISA at baseline. Logistic regression analysis was recruited for exploring the associations of plasma Irisin concentrations with changes in BP. Moderating effects of PA and SB on the relationship between Irisin concentrations and BP were estimated using stratified analysis. Results: Logistic regression analysis indicated that there was no significant association between Irisin concentrations and changes in BP levels among children ( OR =0.98, P >0.05). After stratification for SB, Irisin levels in the low SB subgroup were inversely associated with changes in diastolic blood pressure ( OR=0.87, 95%CI=0.77-0.98, P =0.02). In addition, SB level had a moderating effect on the relationship between Irisin levels and the DBP changes ( P =0.01). Conclusion Increased Irisin concentration is associated with the decrease of DBP level among low SB children. Furthermore, SB level shows moderating role in the relationship between Irisin concentrations and changes in DBP levels.

Starch is the predominant compound in bulb scales, and previous studies have shown that bulblet development is closely associated with starch enrichment. However, how starch synthesis affects bulbification at the molecular level is unclear. In this study, we demonstrate that

Objective: To explore the longitudinal association of the levels of plasma irisin among children with changes in obesity related parameters and newly onset obesity, and to explore whether physical activity (PA) and sedentary behavior(SB) have regulatory effects, to provide a scientific basis for the prevention and control of childhood obesity work. Methods: Cluster random sampling method was used to select 521 children from five schools in Guangzhou in 2017 at baseline and were followed up in 2019. A based on baseline PA and SB, children who meet the following criterion were selected:moderate vigorous intensity PA≥60 min/d or <150 min/week; and gender , age specific SB≥ P 75 or SB < P 25 . Plasma irisin concentration was measured in all the selected children. Multiple linear regression and Logistic regression were conducted to analyze the association. Results: The two year cumulative incidence of obesity, overweight and obesity, and central obesity was 2.82%, 6.57%, and 6.81%, respectively. There was no statistically significant association between plasma irisin levels and changes in obesity related parameters, newly onset overweight obesity or central obesity among children ( P >0.05). After stratified by PA, the irisin concentration in the low PA group was positively associated with weight change ( B=0.229, P =0.03). After stratified by SB, the irisin concentration in the low SB group was positively associated with the height change ( B=0.210, P <0.05). In addition, PA level and SB level both had a moderating effect on the association between plasma irisin levels and the weight change ( P PA=0.01, P SB =0.05). Conclusion PA and SB show moderating effect on plasma irisin concentration and weight gain. No association of irisin concentration with newly onset overweight or obesity among children has been found.

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.
Animals ; Antiviral Agents ; pharmacology ; therapeutic use ; Betacoronavirus ; drug effects ; physiology ; Binding Sites ; drug effects ; Cell Line ; Coronavirus Infections ; drug therapy ; virology ; Crotonates ; pharmacology ; Cytokine Release Syndrome ; drug therapy ; Drug Evaluation, Preclinical ; Gene Knockout Techniques ; Humans ; Influenza A virus ; drug effects ; Leflunomide ; pharmacology ; Mice ; Mice, Inbred BALB C ; Orthomyxoviridae Infections ; drug therapy ; Oseltamivir ; therapeutic use ; Oxidoreductases ; antagonists & inhibitors ; metabolism ; Pandemics ; Pneumonia, Viral ; drug therapy ; virology ; Protein Binding ; drug effects ; Pyrimidines ; biosynthesis ; RNA Viruses ; drug effects ; physiology ; Structure-Activity Relationship ; Toluidines ; pharmacology ; Ubiquinone ; metabolism ; Virus Replication ; drug effects

Objective: To determine imaging features that may help predict the presence of placenta accreta, placenta increta or placenta percreta on prenatal MRI scanning in order to identify the most diagnostic findings. Methods: The prenatal MRI scan data of placenta accreta, placenta increta or placenta percreta (placenta implantation group, n=15) and normal placenta(placenta normal group, n=15) diagnosed and treated by surgical pathology from January 2010 to December 2017 in the People's Hospital of Huadu District were retrospectively analyzed.Two expert MRI doctors were blinded to the patients' true diagnosis and were asked to score a total of 10 MRI features of the placenta and adjacent structures.The interrater reliability was assessed using kappa statistics.The features with a moderate kappa statistic or better(kappa>0.40 ) were then compared with the true diagnosis for each observer. Results: Eight of the scored features had an interobserver reliability of kappa>0.40: placenta previa(κ=0.89); abnormal uterine bulging(κ=0.57); intraplacental hemorrhage(κ=0.45); the presence of dark intraplacental bands on T₂W imaging(κ=0.76); flow-empty blood vessels in placenta(κ=0.67); border on placenta and uterus blurring(κ=0.63); heterogeneity of signal intensity on T₂-weighted(T₂W) imaging(κ=0.53); and continuity of myometrium was interrupted(κ=0.64). Using Fisher's two-sided exact test, there were statistically significant differences between the proportion of patients with placental invasion and those without placental invasion for three of the features: abnormal uterine bulging(P=0.015, P=0.011); heterogeneity of T₂W imaging signal intensity(P=0.006, P=0.013); and presence of dark intraplacental bands on T₂W imaging(P=0.032, P=0.010). Conclusion MRI can be a useful adjunct to ultrasound in diagnosing placenta accreta prenatally.Three features that are seen on MRI in patients with placental invasion appear to be useful for diagnosis: uterine bulging; heterogeneous signal intensity within the placenta; and the presence of dark intraplacental bands on T₂W imaging.

OBJECTIVEThe research regarding the central mechanism of acupuncture (arrival of ) based on functional magnetic resonance imaging (fMRI) in recent 10 years was analyzed to summarize existing research achievements and experience.

METHODSThe literature regarding fMRI-based research published from January of 2007 through December of 2016 in CNKI and PubMed databases was collected. The research content and methods, including research design, inclusion criteria, acupoint selection and evaluation, were analyzed.

RESULTSTotally 18 articles regarding the central mechanism of acupuncture based on fMRI was included. According to research content, the literature was divided into two categories: research and sensation research. In research, the differences of and not on brain functional activity were compared to summarize the central response pattern of ; in sensation research, the differences of different sensations and intensities of on central response were compared to explore the effects of different sensations and intensities of on brain functional activity. In recent 10 years, the number of research gradually increased, and the type of design was various, mainly RCT and paired design. The majority of participants was healthy people, and single acupoint was the focus of researches, including Zusanli (ST 36), Waiguan (TE 5), Hegu (LI 4), etc. The evaluation of was based on visual analogue scale (VAS). The research contents were mainly the effects of and not and different sensations on brain function activities. The present studies confirmed that and not as well as different sensations had different impacts on brain functional effects, and different acupoints had specific activated brain areas. There was a positive correlation between the degree of and the intensity of the activation of brain regions. Furthermore, tingling sensation was not included to sensations.

CONCLUSIONThe number and quality of fMRI-based research need to be improved; the research content is simple, and research method is in exploratory stage. The results obtained in the literature are the phenomena of in the central level, and it is imperative to summarize the essential link between and the central effect through these phenomena to reveal the mechanism of . The specific impact of for brain function needs more clinical exploration.